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Salvatore Vincent Pizzo

Distinguished Professor of Pathology, in the School of Medicine
Pathology
Rm 3059 Duke South Hospital, Duke Box 3712, Durham, NC 27710
Rm 3059 Duke South Hospital, Durham, NC 27710

Selected Publications


Serum Pro-N-Cadherin Is a Marker of Subclinical Heart Failure in the General Population.

Journal Article J Am Heart Assoc · March 21, 2023 Background We recently reported aberrant processing and localization of the precursor PNC (pro-N-cadherin) protein in failing heart tissues and detected elevated PNC products in the plasma of patients with heart failure. We hypothesize that PNC mislocaliza ... Full text Link to item Cite

Physiological Roles of the Autoantibodies to the 78-Kilodalton Glucose-Regulated Protein (GRP78) in Cancer and Autoimmune Diseases.

Journal Article Biomedicines · May 24, 2022 The 78 kDa glucose-regulated protein (GRP78), a member of the 70 kDa heat-shock family of molecular chaperones (HSP70), is essential for the regulation of the unfolded protein response (UPR) resulting from cellular endoplasmic reticulum (ER) stress. During ... Full text Link to item Cite

Pathologic Proteolytic Processing of N-Cadherin as a Marker of Human Fibrotic Disease.

Journal Article Cells · January 4, 2022 Prior research has implicated the involvement of cell adhesion molecule N-cadherin in tissue fibrosis and remodeling. We hypothesize that anomalies in N-cadherin protein processing are involved in pathological fibrosis. Diseased tissues associated with fib ... Full text Link to item Cite

Activated Alpha 2-Macroglobulin Is a Novel Mediator of Mesangial Cell Profibrotic Signaling in Diabetic Kidney Disease.

Journal Article Biomedicines · August 30, 2021 Diabetic kidney disease (DKD) is caused by the overproduction of extracellular matrix proteins (ECM) by glomerular mesangial cells (MCs). We previously showed that high glucose (HG) induces cell surface translocation of GRP78 (csGRP78), mediating PI3K/Akt ... Full text Link to item Cite

Cell surface GRP78 signaling: An emerging role as a transcriptional modulator in cancer.

Journal Article J Cell Physiol · April 2021 Cancer cells acquire dysregulated gene expression to establish specific transcriptional dependencies and their underlying mechanisms that are ultimately responsible for this addictions have not been fully elucidated. Glucose-regulated protein 78 (GRP78) is ... Full text Link to item Cite

Targeting cell surface GRP78 enhances pancreatic cancer radiosensitivity through YAP/TAZ protein signaling.

Journal Article J Biol Chem · September 20, 2019 Ionizing radiation (IR) can promote migration and invasion of cancer cells, but the basis for this phenomenon has not been fully elucidated. IR increases expression of glucose-regulated protein 78kDa (GRP78) on the surface of cancer cells (CS-GRP78), and t ... Full text Open Access Link to item Cite

Adipose stem cell crosstalk with chemo-residual breast cancer cells: implications for tumor recurrence.

Journal Article Breast Cancer Res Treat · April 2019 PURPOSE: Most triple-negative breast cancer (TNBC) patients exhibit an incomplete response to neoadjuvant chemotherapy, resulting in chemo-residual tumor cells that drive tumor recurrence and patient mortality. Accordingly, strategies for eliminating chemo ... Full text Link to item Cite

Serum cholesterol levels and tumor growth in a PTEN-null transgenic mouse model of prostate cancer.

Journal Article Prostate Cancer Prostatic Dis · June 2018 BACKGROUND: Some, but not all, epidemiologic evidence supports a role for cholesterol, the precursor for steroid hormone synthesis, in prostate cancer. Using a PTEN-null transgenic mouse model of prostate cancer, we tested the effect of modifying serum cho ... Full text Link to item Cite

Preface

Book · March 22, 2018 Full text Cite

The Endoplasmic Reticulum Chaperone GRP78 Also Functions as a Cell Surface Signaling Receptor

Chapter · January 1, 2018 The Glucose Regulated Protein 78,000 (GRP78) is a member of the heat shock protein family in the endoplasmic reticulum to regulate protein quality control and degradation. We and others demonstrated that GRP78 is preferentially translocated onto the cell s ... Full text Cite

Novel Cell Surface Targets for the Plasminogen Activating System in the Brain: Implications for Human Disease

Chapter · January 1, 2018 The plasminogen (Pg) activator system plays an important role in the central nervous system (CNS), including processes of neuronal migration, neurite outgrowth, and neuronal plasticity. Pg and tissue-type plasminogen activator (t-PA) are primarily involved ... Full text Cite

An Historical Perspective: Cell Surface GRP78, a New Paradigm in Signal Transduction Biology

Chapter · January 1, 2018 This chapter will present a historical perspective with respect to the presence of Glucose Regulated Protein 78,000 (GRP78) on the cell surface. Its presence there was completely unexpected since this protein normally functions as a molecular chaperone wit ... Full text Cite

Cell Surface GRP78, a New Paradigm in Signal Transduction Biology

Book · January 1, 2018 Cell Surface GRP78, a New Paradigm in Signal Transduction Biology presents a new paradigm that has emerged in the past decade with the discovery that various intracellular proteins may acquire new functions as cell surface receptors. Two very prominent exa ... Full text Cite

Autoantibodies against the cell surface-associated chaperone GRP78 stimulate tumor growth via tissue factor.

Journal Article J Biol Chem · December 22, 2017 Tumor cells display on their surface several molecular chaperones that normally reside in the endoplasmic reticulum. Because this display is unique to cancer cells, these chaperones are attractive targets for drug development. Previous epitope-mapping of a ... Full text Link to item Cite

Cell surface GRP78 promotes tumor cell histone acetylation through metabolic reprogramming: a mechanism which modulates the Warburg effect.

Journal Article Oncotarget · December 8, 2017 Acetyl coenzyme A (acetyl-CoA) is essential for histone acetylation, to promote cell proliferation by regulating gene expression. However, the underlying mechanism(s) governing acetylation remains poorly understood. Activated α2-Macroglobulin (α2M*) signal ... Full text Link to item Cite

ROS-independent Nrf2 activation in prostate cancer.

Journal Article Oncotarget · September 2017 In prostate cancer, oxidative stress and the subsequent Nrf2 activation promote the survival of cancer cells and acquired chemoresistance. Nrf2 links prostate cancer to endoplasmic reticulum stress, an event that triggers the unfolded protein response, aim ... Full text Cite

Myelin basic protein stimulates plasminogen activation via tissue plasminogen activator following binding to independent l-lysine-containing domains.

Journal Article Biochem Biophys Res Commun · August 26, 2017 Myelin basic protein (MBP) is a key component of myelin, the specialized lipid membrane that encases the axons of all neurons. Both plasminogen (Pg) and tissue-type plasminogen activator (t-PA) bind to MBP with high affinity. We investigated the kinetics a ... Full text Link to item Cite

ROS-independent Nrf2 activation in prostate cancer.

Journal Article Oncotarget · June 28, 2017 In prostate cancer, oxidative stress and the subsequent Nrf2 activation promote the survival of cancer cells and acquired chemoresistance. Nrf2 links prostate cancer to endoplasmic reticulum stress, an event that triggers the unfolded protein response, aim ... Full text Link to item Cite

Serum Pro-N-Cadherin Is a Marker of Subclinical Heart Failure in the General Population.

Journal Article J Am Heart Assoc · March 21, 2023 Background We recently reported aberrant processing and localization of the precursor PNC (pro-N-cadherin) protein in failing heart tissues and detected elevated PNC products in the plasma of patients with heart failure. We hypothesize that PNC mislocaliza ... Full text Link to item Cite

Physiological Roles of the Autoantibodies to the 78-Kilodalton Glucose-Regulated Protein (GRP78) in Cancer and Autoimmune Diseases.

Journal Article Biomedicines · May 24, 2022 The 78 kDa glucose-regulated protein (GRP78), a member of the 70 kDa heat-shock family of molecular chaperones (HSP70), is essential for the regulation of the unfolded protein response (UPR) resulting from cellular endoplasmic reticulum (ER) stress. During ... Full text Link to item Cite

Pathologic Proteolytic Processing of N-Cadherin as a Marker of Human Fibrotic Disease.

Journal Article Cells · January 4, 2022 Prior research has implicated the involvement of cell adhesion molecule N-cadherin in tissue fibrosis and remodeling. We hypothesize that anomalies in N-cadherin protein processing are involved in pathological fibrosis. Diseased tissues associated with fib ... Full text Link to item Cite

Activated Alpha 2-Macroglobulin Is a Novel Mediator of Mesangial Cell Profibrotic Signaling in Diabetic Kidney Disease.

Journal Article Biomedicines · August 30, 2021 Diabetic kidney disease (DKD) is caused by the overproduction of extracellular matrix proteins (ECM) by glomerular mesangial cells (MCs). We previously showed that high glucose (HG) induces cell surface translocation of GRP78 (csGRP78), mediating PI3K/Akt ... Full text Link to item Cite

Cell surface GRP78 signaling: An emerging role as a transcriptional modulator in cancer.

Journal Article J Cell Physiol · April 2021 Cancer cells acquire dysregulated gene expression to establish specific transcriptional dependencies and their underlying mechanisms that are ultimately responsible for this addictions have not been fully elucidated. Glucose-regulated protein 78 (GRP78) is ... Full text Link to item Cite

Targeting cell surface GRP78 enhances pancreatic cancer radiosensitivity through YAP/TAZ protein signaling.

Journal Article J Biol Chem · September 20, 2019 Ionizing radiation (IR) can promote migration and invasion of cancer cells, but the basis for this phenomenon has not been fully elucidated. IR increases expression of glucose-regulated protein 78kDa (GRP78) on the surface of cancer cells (CS-GRP78), and t ... Full text Open Access Link to item Cite

Adipose stem cell crosstalk with chemo-residual breast cancer cells: implications for tumor recurrence.

Journal Article Breast Cancer Res Treat · April 2019 PURPOSE: Most triple-negative breast cancer (TNBC) patients exhibit an incomplete response to neoadjuvant chemotherapy, resulting in chemo-residual tumor cells that drive tumor recurrence and patient mortality. Accordingly, strategies for eliminating chemo ... Full text Link to item Cite

Serum cholesterol levels and tumor growth in a PTEN-null transgenic mouse model of prostate cancer.

Journal Article Prostate Cancer Prostatic Dis · June 2018 BACKGROUND: Some, but not all, epidemiologic evidence supports a role for cholesterol, the precursor for steroid hormone synthesis, in prostate cancer. Using a PTEN-null transgenic mouse model of prostate cancer, we tested the effect of modifying serum cho ... Full text Link to item Cite

Preface

Book · March 22, 2018 Full text Cite

The Endoplasmic Reticulum Chaperone GRP78 Also Functions as a Cell Surface Signaling Receptor

Chapter · January 1, 2018 The Glucose Regulated Protein 78,000 (GRP78) is a member of the heat shock protein family in the endoplasmic reticulum to regulate protein quality control and degradation. We and others demonstrated that GRP78 is preferentially translocated onto the cell s ... Full text Cite

Novel Cell Surface Targets for the Plasminogen Activating System in the Brain: Implications for Human Disease

Chapter · January 1, 2018 The plasminogen (Pg) activator system plays an important role in the central nervous system (CNS), including processes of neuronal migration, neurite outgrowth, and neuronal plasticity. Pg and tissue-type plasminogen activator (t-PA) are primarily involved ... Full text Cite

An Historical Perspective: Cell Surface GRP78, a New Paradigm in Signal Transduction Biology

Chapter · January 1, 2018 This chapter will present a historical perspective with respect to the presence of Glucose Regulated Protein 78,000 (GRP78) on the cell surface. Its presence there was completely unexpected since this protein normally functions as a molecular chaperone wit ... Full text Cite

Cell Surface GRP78, a New Paradigm in Signal Transduction Biology

Book · January 1, 2018 Cell Surface GRP78, a New Paradigm in Signal Transduction Biology presents a new paradigm that has emerged in the past decade with the discovery that various intracellular proteins may acquire new functions as cell surface receptors. Two very prominent exa ... Full text Cite

Autoantibodies against the cell surface-associated chaperone GRP78 stimulate tumor growth via tissue factor.

Journal Article J Biol Chem · December 22, 2017 Tumor cells display on their surface several molecular chaperones that normally reside in the endoplasmic reticulum. Because this display is unique to cancer cells, these chaperones are attractive targets for drug development. Previous epitope-mapping of a ... Full text Link to item Cite

Cell surface GRP78 promotes tumor cell histone acetylation through metabolic reprogramming: a mechanism which modulates the Warburg effect.

Journal Article Oncotarget · December 8, 2017 Acetyl coenzyme A (acetyl-CoA) is essential for histone acetylation, to promote cell proliferation by regulating gene expression. However, the underlying mechanism(s) governing acetylation remains poorly understood. Activated α2-Macroglobulin (α2M*) signal ... Full text Link to item Cite

ROS-independent Nrf2 activation in prostate cancer.

Journal Article Oncotarget · September 2017 In prostate cancer, oxidative stress and the subsequent Nrf2 activation promote the survival of cancer cells and acquired chemoresistance. Nrf2 links prostate cancer to endoplasmic reticulum stress, an event that triggers the unfolded protein response, aim ... Full text Cite

Myelin basic protein stimulates plasminogen activation via tissue plasminogen activator following binding to independent l-lysine-containing domains.

Journal Article Biochem Biophys Res Commun · August 26, 2017 Myelin basic protein (MBP) is a key component of myelin, the specialized lipid membrane that encases the axons of all neurons. Both plasminogen (Pg) and tissue-type plasminogen activator (t-PA) bind to MBP with high affinity. We investigated the kinetics a ... Full text Link to item Cite

ROS-independent Nrf2 activation in prostate cancer.

Journal Article Oncotarget · June 28, 2017 In prostate cancer, oxidative stress and the subsequent Nrf2 activation promote the survival of cancer cells and acquired chemoresistance. Nrf2 links prostate cancer to endoplasmic reticulum stress, an event that triggers the unfolded protein response, aim ... Full text Link to item Cite

Evidence for Feedback Regulation Following Cholesterol Lowering Therapy in a Prostate Cancer Xenograft Model.

Journal Article Prostate · April 2017 BACKGROUND: Epidemiologic data suggest cholesterol-lowering drugs may prevent the progression of prostate cancer, but not the incidence of the disease. However, the association of combination therapy in cholesterol reduction on prostate or any cancer is un ... Full text Link to item Cite

Upregulation of autophagy genes and the unfolded protein response in human heart failure.

Journal Article Int J Clin Exp Med · 2017 The cellular environment of the mammalian heart constantly is challenged with environmental and intrinsic pathological insults, which affect the proper folding of proteins in heart failure. The effects of damaged or misfolded proteins on the cell can be pr ... Link to item Cite

Chemotherapy enriches for an invasive triple-negative breast tumor cell subpopulation expressing a precursor form of N-cadherin on the cell surface.

Journal Article Oncotarget · December 20, 2016 BACKGROUND: Although most triple-negative breast cancer (TNBC) patients initially respond to chemotherapy, residual tumor cells frequently persist and drive recurrent tumor growth. Previous studies from our laboratory and others' indicate that TNBC is hete ... Full text Link to item Cite

Proteolysis in the interstitial space

Book · August 19, 2016 Most clinical laboratory tests utilize interstitial and extravascular such as blood, urine, cerebral spinal fluid (CSF), and saliva. For example, CSF is monitored in the context of cancer for both diagnostic and therapeutic reasons. And yet, our understand ... Full text Cite

Activated α2-Macroglobulin Regulates Transcriptional Activation of c-MYC Target Genes through Cell Surface GRP78 Protein.

Journal Article J Biol Chem · May 13, 2016 Activated α2-macroglobulin (α2M*) signals predominantly through cell surface GRP78 (CS-GRP78) to promote proliferation and survival of cancer cells; however, the molecular mechanism remains obscure. c-MYC is an essential transcriptional regulator that cont ... Full text Link to item Cite

Actions of thrombin in the interstitium.

Journal Article J Thromb Haemost · January 2016 Thrombin is a pleiotropic enzyme best known for its contribution to fibrin formation and platelet aggregation during vascular hemostasis. There is increasing evidence to suggest a role for thrombin in the development of interstitial fibrosis, but interstit ... Full text Link to item Cite

BRG1 and BRM SWI/SNF ATPases redundantly maintain cardiomyocyte homeostasis by regulating cardiomyocyte mitophagy and mitochondrial dynamics in vivo.

Journal Article Cardiovasc Pathol · 2016 There has been an increasing recognition that mitochondrial perturbations play a central role in human heart failure. Mitochondrial networks, whose function is to maintain the regulation of mitochondrial biogenesis, autophagy ('mitophagy') and mitochondria ... Full text Link to item Cite

Catalytic autoantibodies against myelin basic protein (MBP) isolated from serum of autistic children impair in vitro models of synaptic plasticity in rat hippocampus.

Journal Article J Neuroimmunol · October 15, 2015 Autoantibodies from autistic spectrum disorder (ASD) patients react with multiple proteins expressed in the brain. One such autoantibody targets myelin basic protein (MBP). ASD patients have autoantibodies to MBP of both the IgG and IgA classes in high tit ... Full text Link to item Cite

Abstract POSTER-THER-1420: Ascites drives ovarian cancer stem-like cell growth: therapeutic opportunities

Conference Clinical Cancer Research · August 15, 2015 AbstractBackground: A significant literature suggests that cancer stem-like cells drive the aggressive behavior of ovarian cancer. Cancer stem-like cells are distinct from bulk tumor cells in possessing self ... Full text Cite

Nuclear basic fibroblast growth factor regulates triple-negative breast cancer chemo-resistance.

Journal Article Breast Cancer Res · July 4, 2015 INTRODUCTION: Chemotherapy remains the only available treatment for triple-negative (TN) breast cancer, and most patients exhibit an incomplete pathologic response. Half of patients exhibiting an incomplete pathologic response die within five years of trea ... Full text Link to item Cite

Activated α2-macroglobulin binding to human prostate cancer cells triggers insulin-like responses.

Journal Article J Biol Chem · April 10, 2015 Ligation of cell surface GRP78 by activated α2-macroglobulin (α2M*) promotes cell proliferation and suppresses apoptosis. α2M*-treated human prostate cancer cells exhibit a 2-3-fold increase in glucose uptake and lactate secretion, an effect similar to ins ... Full text Link to item Cite

Syngeneic Murine Ovarian Cancer Model Reveals That Ascites Enriches for Ovarian Cancer Stem-Like Cells Expressing Membrane GRP78.

Journal Article Mol Cancer Ther · March 2015 Patients with ovarian cancer are generally diagnosed at FIGO (International Federation of Gynecology and Obstetrics) stage III/IV, when ascites is common. The volume of ascites correlates positively with the extent of metastasis and negatively with prognos ... Full text Link to item Cite

Ascites Increases Expression/Function of Multidrug Resistance Proteins in Ovarian Cancer Cells.

Journal Article PLoS One · 2015 Chemotherapy resistance is the major reason for the failure of ovarian cancer treatment. One mechanism behind chemo-resistance involves the upregulation of multidrug resistance (MDR) genes (ABC transporters) that effectively transport (efflux) drugs out of ... Full text Link to item Cite

Nuclear basic fibroblast growth factor regulates triple-negative breast cancer chemo-resistance

Journal Article Breast Cancer Research · 2015 © 2015 Li et al.Introduction: Chemotherapy remains the only available treatment for triple-negative (TN) breast cancer, and most patients exhibit an incomplete pathologic response. Half of patients exhibiting an incomplete pathologic response die within fi ... Full text Cite

Binding of tissue-type plasminogen activator to the glucose-regulated protein 78 (GRP78) modulates plasminogen activation and promotes human neuroblastoma cell proliferation in vitro.

Journal Article J Biol Chem · September 5, 2014 The glucose-regulated protein 78 (GRP78) is a plasminogen (Pg) receptor on the cell surface. In this study, we demonstrate that GRP78 also binds the tissue-type plasminogen activator (t-PA), which results in a decrease in K(m) and an increase in the V(max) ... Full text Link to item Cite

Activated α2-macroglobulin binding to cell surface GRP78 induces T-loop phosphorylation of Akt1 by PDK1 in association with Raptor.

Journal Article PLoS One · 2014 PDK1 phosphorylates multiple substrates including Akt by PIP3-dependent mechanisms. In this report we provide evidence that in prostate cancer cells stimulated with activated α2-macroglobulin (α2M*) PDK1 phosphorylates Akt in the T-loop at Thr(308) by usin ... Full text Link to item Cite

Model of tumor dormancy/recurrence after short-term chemotherapy.

Journal Article PLoS One · 2014 Although many tumors regress in response to neoadjuvant chemotherapy, residual tumor cells are detected in most cancer patients post-treatment. These residual tumor cells are thought to remain dormant for years before resuming growth, resulting in tumor re ... Full text Link to item Cite

The monomeric receptor binding domain of tetrameric α2-macroglobulin binds to cell surface GRP78 triggering equivalent activation of signaling cascades.

Journal Article Biochemistry · June 11, 2013 α2-Macroglobulin (α2M) is a broad spectrum proteinase inhibitor that when activated by proteinases (α2M*) undergoes a major conformational change exposing receptor recognition sites in each of its four subunits. These complexes bind to two distinct recepto ... Full text Link to item Cite

Resveratrol worsens survival in SCID mice with prostate cancer xenografts in a cell-line specific manner, through paradoxical effects on oncogenic pathways.

Journal Article Prostate · May 2013 BACKGROUND: Resveratrol increases lifespan and decreases the risk of many cancers. We hypothesized resveratrol will slow the growth of human prostate cancer xenografts. METHODS: SCID mice were fed Western diet (40% fat, 44% carbohydrate, 16% protein by kca ... Full text Link to item Cite

Abstract 3698: Inhibition of cholesterol uptake with ezetimibe reduces intra-tumoral testosterone levels and slows tumor growth in transgenic mouse models of prostate cancer.

Conference Cancer Research · April 15, 2013 AbstractIntroduction: Western countries have 6 fold higher incidence of prostate cancer (PC). Dietary composition, in addition to other factors, may contribute to this geographic disparity. Cholesterol, the ... Full text Cite

The effect of carbohydrate restriction on prostate cancer tumor growth in a castrate mouse xenograft model.

Journal Article Prostate · April 2013 BACKGROUND: No- and low-carbohydrate diets delay tumor growth compared to western diet (WD) in prostate cancer (PCa) xenograft studies. The effect of these diets in concert with androgen deprivation is unknown. METHODS: A total of 160 male SCID mice were i ... Full text Link to item Cite

The voltage-dependent anion channel (VDAC) binds tissue-type plasminogen activator and promotes activation of plasminogen on the cell surface.

Journal Article J Biol Chem · January 4, 2013 The voltage-dependent anion channel (VDAC), a major pore-forming protein in the outer membrane of mitochondria, is also found in the plasma membrane of a large number of cells where in addition to its role in regulating cellular ATP release and volume cont ... Full text Link to item Cite

In vitro and in vivo evaluation of resveratrol and 3,5-dihydroxy-4'-acetoxy-trans-stilbene in the treatment of human prostate carcinoma and melanoma.

Journal Article J Surg Res · January 2013 BACKGROUND: Resveratrol (RESV) is a naturally occurring compound that may possess anticancer capabilities in both prostate carcinoma and melanoma. METHODS: The in vitro and in vivo cytotoxic activity of RESV and 3,5-dihydroxy-4'-acetoxy-trans-stilbene (4-A ... Full text Link to item Cite

Evidence for a pro-proliferative feedback loop in prostate cancer: the role of Epac1 and COX-2-dependent pathways.

Journal Article PLoS One · 2013 OBJECTIVE: In human prostate cancer cells, a selective Epac agonist, 8-CPT-2Me-cAMP, upregulates cell proliferation and survival via activation of Ras-MAPK and PI- 3-kinase-Akt-mTOR signaling cascades. Here we examine the role of inflammatory mediators in ... Full text Link to item Cite

Catabolism of exogenous lactate reveals it as a legitimate metabolic substrate in breast cancer.

Journal Article PLoS One · 2013 Lactate accumulation in tumors has been associated with metastases and poor overall survival in cancer patients. Lactate promotes angiogenesis and metastasis, providing rationale for understanding how it is processed by cells. The concentration of lactate ... Full text Link to item Cite

Carbohydrate restriction and lactate transporter inhibition in a mouse xenograft model of human prostate cancer.

Journal Article BJU Int · October 2012 UNLABELLED: What's known on the subject? and What does the study add? It is known that both lactate inhibition and carbohydrate restriction inhibit tumour growth. What is unknown is whether the two work synergistically together. This study adds that though ... Full text Link to item Cite

The Escherichia coli subtilase cytotoxin A subunit specifically cleaves cell-surface GRP78 protein and abolishes COOH-terminal-dependent signaling.

Journal Article J Biol Chem · September 21, 2012 GRP78, a molecular chaperone with critical endoplasmic reticulum functions, is aberrantly expressed on the surface of cancer cells, including prostate and melanoma. Here it functions as a pro-proliferative and anti-apoptotic signaling receptor via NH(2)-te ... Full text Link to item Cite

A murine monoclonal antibody directed against the carboxyl-terminal domain of GRP78 suppresses melanoma growth in mice.

Journal Article Melanoma Res · June 2012 The HSP70 family member GRP78 is a selective tumor marker upregulated on the surface of many tumor cell types, including melanoma, where it acts as a growth factor receptor-like protein. Receptor-recognized forms of the proteinase inhibitor α2-macroglobuli ... Full text Link to item Cite

Upregulation of mTORC2 activation by the selective agonist of EPAC, 8-CPT-2Me-cAMP, in prostate cancer cells: assembly of a multiprotein signaling complex.

Journal Article J Cell Biochem · May 2012 Ligation of cell surface-associated GRP78 by activated α(2) -macroglobulin triggers pro-proliferative cellular responses. In part, this results from activation of adenylyl cyclase leading to an increase in cAMP. We have previously employed the cAMP analog ... Full text Link to item Cite

Abstract 3220: The effects of cholesterol treatment drugs alone and in combination on prostate tumor xenograft growth

Journal Article Cancer Research · April 15, 2012 AbstractBackground: Epidemiologic data suggest cholesterol-lowering drugs may prevent the progression of prostate cancer (PC), but not the incidence of the disease. This may occur by lowering levels of low-d ... Full text Cite

Anti-inflammatory and vasoprotective activity of a retroviral-derived peptide, homologous to human endogenous retroviruses: endothelial cell effects.

Journal Article PloS one · January 2012 Malignant and inflammatory tissues sometimes express endogenous retroviruses or their proteins. A highly-conserved sequence from retroviral transmembrane (TM) proteins, termed the "immunosuppressive domain (ID)", is associated with inhibition of immune and ... Full text Cite

Receptor-recognized α₂-macroglobulin binds to cell surface-associated GRP78 and activates mTORC1 and mTORC2 signaling in prostate cancer cells.

Journal Article PLoS One · 2012 OBJECTIVE: Tetrameric α(2)-macroglobulin (α(2)M), a plasma panproteinase inhibitor, is activated upon interaction with a proteinase, and undergoes a major conformational change exposing a receptor recognition site in each of its subunits. Activated α(2)M ( ... Full text Link to item Cite

Changes in oligosaccharide chains of autoantibodies to GRP78 expressed during progression of malignant melanoma stimulate melanoma cell growth and survival.

Journal Article Melanoma Res · August 2011 A correlation between expression of the glucose-regulated protein of 78 kDa (GRP78) in malignant melanoma tumors and poor patient survival is well established. In this study, in addition to demonstrating the expression of GRP78 in tumor tissue, we investig ... Full text Link to item Cite

Loss of cell surface TFII-I promotes apoptosis in prostate cancer cells stimulated with activated α₂ -macroglobulin.

Journal Article J Cell Biochem · June 2011 Receptor-recognized forms of α₂ -macroglobulin (α₂ M) bind to cell surface-associated GRP78 and initiate pro-proliferative and anti-apoptotic signaling. Ligation of GRP78 with α₂ M also upregulates TFII-I, which binds to the GRP78 promoter and enhances GRP ... Full text Link to item Cite

Abstract 4602: Cholesterol and ezetimibe: Effects on tumor growth and survival outcomes: An interim analysis

Journal Article Cancer Research · April 15, 2011 AbstractIntroduction and Objectives: Prostate cancer (PC) is affected by cholesterol metabolism and cholesterol-mediating medications. Ezetimibe, a gut cholesterol-uptake inhibitor, inhibits angiogenesis in ... Full text Cite

Autoantibodies against cell surface GRP78 promote tumor growth in a murine model of melanoma.

Journal Article Melanoma Res · February 2011 Autoantibodies that react with GRP78 expressed on the cell-surface of many tumor cell lines occur in the sera of patients with prostate cancer, melanoma, and ovarian cancer. These autoantibodies are a negative prognostic factor in prostate cancer and, when ... Full text Link to item Cite

Ligation of prostate cancer cell surface GRP78 activates a proproliferative and antiapoptotic feedback loop: a role for secreted prostate-specific antigen.

Journal Article J Biol Chem · January 14, 2011 GRP78, a well characterized chaperone in the endoplasmic reticulum, is critical to the unfolded protein response. More recently, it has been identified on the cell surface, where it has many roles. On cancer cells, it functions as a signaling receptor coup ... Full text Link to item Cite

The modified Patient and Observer Scar Assessment Scale: a novel approach to defining pathologic and nonpathologic scarring.

Journal Article Plast Reconstr Surg · January 2011 BACKGROUND: Scarring is a highly prevalent and multifactorial process, yet no studies to date have attempted to distinguish pathologic from nonpathologic scarring. METHODS: This article defines and proposes methods of classifying pathologic scarring as it ... Full text Link to item Cite

Modulation of the unfolded protein response by GRP78 in prostate cancer.

Journal Article Methods Enzymol · 2011 The unfolded protein response (UPR) is an adaptive survival mechanism through which cells can weather the stress of misfolded protein accumulation induced by a wide variety of pathophysiologic and pharmacologic insults. The ER chaperone GRP78 is a central ... Full text Link to item Cite

Cell surface ATP synthase: A potential target for anti-angiogenic therapy

Journal Article · December 1, 2010 Since the presence of F1F0 adenosine triphosphate (ATP) synthase was discovered on the surface of human cells, numerous studies have elucidated new functions for this molecule that classically functions as part of the electron transport chain in mitochondr ... Full text Cite

Re-examination of CD91 function in GRP94 (glycoprotein 96) surface binding, uptake, and peptide cross-presentation.

Journal Article J Immunol · December 1, 2010 GRP94 (gp96)-peptide complexes can be internalized by APCs and their associated peptides cross-presented to yield activation of CD8(+) T cells. Investigations into the identity (or identities) of GRP94 surface receptors have yielded conflicting results, pa ... Full text Link to item Cite

Antibodies against the voltage-dependent anion channel (VDAC) and its protective ligand hexokinase-I in children with autism.

Journal Article J Neuroimmunol · October 8, 2010 Autistic children show elevated serum levels of autoantibodies to several proteins essential for the function of normal brains. The voltage-dependent anion channel (VDAC) and hexokinase-I, a VDAC protective ligand, were identified as targets of this autoim ... Full text Link to item Cite

Binding of anti-GRP78 autoantibodies to cell surface GRP78 increases tissue factor procoagulant activity via the release of calcium from endoplasmic reticulum stores.

Journal Article J Biol Chem · September 10, 2010 The increased risk of venous thromboembolism in cancer patients has been attributed to enhanced tissue factor (TF) procoagulant activity (PCA) on the surface of cancer cells. Recent studies have shown that TF PCA can be modulated by GRP78, an endoplasmic r ... Full text Link to item Cite

LMP-420: a novel purine nucleoside analog with potent cytotoxic effects for CLL cells and minimal toxicity for normal hematopoietic cells.

Journal Article Leukemia · September 2010 B-cell chronic lymphocytic leukemia (CLL) is characterized by slow accumulation of malignant cells, which are supported in the microenvironment by cell-cell interactions and soluble cytokines such as tumor necrosis factor (TNF). We evaluated the effect of ... Full text Link to item Cite

Low-carbohydrate diets and prostate cancer: how low is "low enough"?

Journal Article Cancer Prev Res (Phila) · September 2010 Previous studies indicate that carbohydrate intake influences prostate cancer biology, as mice fed a no-carbohydrate ketogenic diet (NCKD) had significantly smaller xenograft tumors and longer survival than mice fed a Western diet. As it is nearly impossib ... Full text Link to item Cite

Inhibition of NF-kappaB1 and NF-kappaB2 activation in prostate cancer cells treated with antibody against the carboxyl terminal domain of GRP78: effect of p53 upregulation.

Journal Article Biochem Biophys Res Commun · February 19, 2010 Ligation of cancer cell surface GRP78 by activated alpha2-macroglobulin (alpha2M*) triggers pro-proliferative and anti-apoptotic signaling pathways. Cancer patients who develop autoantibodies to the alpha2M* binding site in GRP78 have a poor prognosis sinc ... Full text Link to item Cite

Modulation of the unfolded protein response in prostate cancer cells by antibody-directed against the carboxyl-terminal domain of GRP78.

Journal Article Apoptosis · February 2010 Receptor-recognized forms of alpha(2)-macroglobulin (alpha(2)M*) bind to cancer cell surface GRP78, which functions as a signaling receptor promoting proliferation and survival. Patients with prostate, ovary, and skin cancer may develop auto-antibodies to ... Full text Link to item Cite

PFT-alpha inhibits antibody-induced activation of p53 and pro-apoptotic signaling in 1-LN prostate cancer cells.

Journal Article Biochem Biophys Res Commun · January 1, 2010 Antibodies against the COOH-terminal domain of cell surface GRP78 induce apoptosis in cancer cell lines via activation of p53 signaling. We now have studied the effects of PFT-alpha, an inhibitor of p53-mediated apoptotic pathways, on anti-GRP78 antibody-i ... Full text Link to item Cite

Ligation of cell surface GRP78 with antibody directed against the COOH-terminal domain of GRP78 suppresses Ras/MAPK and PI 3-kinase/AKT signaling while promoting caspase activation in human prostate cancer cells.

Journal Article Cancer Biol Ther · January 2010 We have previously shown that treatment of prostate cancer and melanoma cells expressing GRP78 on their cell surface with antibody directed against the COOH-terminal domain of GRP78 upregulates and activates p53 causing decreased cell proliferation and upr ... Full text Open Access Link to item Cite

Patterns of GRP78 and MTJ1 expression in primary cutaneous malignant melanoma.

Journal Article Mod Pathol · January 2010 Cell surface expression of glucose-regulated protein 78 (GRP78) occurs in several types of cancer; however, its role in the behavior of primary cutaneous melanoma is not well studied. The association of cell surface GRP78 with other proteins such as MTJ1 s ... Full text Link to item Cite

Epac1-induced cellular proliferation in prostate cancer cells is mediated by B-Raf/ERK and mTOR signaling cascades.

Journal Article J Cell Biochem · November 1, 2009 cAMP-dependent, PKA-independent effects on cell proliferation are mediated by cAMP binding to EPAC and activation of Rap signaling. In this report, we employed the analogue 8-CPT-2-O-Me-cAMP to study binding to EPAC and subsequent activation of B-Raf/ERK a ... Full text Link to item Cite

Antigen delivery by alpha(2)-macroglobulin enhances the cytotoxic T lymphocyte response.

Journal Article J Leukoc Biol · November 2009 alpha(2)M* targets antigens to APCs for rapid internalization, processing, and presentation. When used as an antigen-delivery vehicle, alpha(2)M* amplifies MHC class II presentation, as demonstrated by increased antibody titers. Recent evidence, however, s ... Full text Link to item Cite

GRP78: a multifunctional receptor on the cell surface.

Journal Article Antioxid Redox Signal · September 2009 The 78 kDa glucose-regulated protein (GRP78) is an endoplasmic reticulum chaperone, whose function is generally thought to be restricted to controlling the structural maturation of nascent glycoproteins. However, GRP78 also is expressed on the cell surface ... Full text Link to item Cite

The antitumorigenic trifecta.

Journal Article Blood · August 27, 2009 The laboratory of Judah Folkman identified the potent endogenous antiangiogenic protein angiostatin in 1994.(1) In this issue of Blood, Lee and colleagues propose 2 new mechanisms of action for angiostatin that may represent promising targets for new cance ... Full text Link to item Cite

Prion protein paralog doppel protein interacts with alpha-2-macroglobulin: a plausible mechanism for doppel-mediated neurodegeneration.

Journal Article PLoS One · June 18, 2009 Doppel protein (Dpl) is a paralog of the cellular form of the prion protein (PrP(C)), together sharing common structural and biochemical properties. Unlike PrP(C), which is abundantly expressed throughout the central nervous system (CNS), Dpl protein expre ... Full text Link to item Cite

The effects of varying dietary carbohydrate and fat content on survival in a murine LNCaP prostate cancer xenograft model.

Journal Article Cancer Prev Res (Phila) · June 2009 PURPOSE: Numerous dietary factors elevate serum levels of insulin and insulin-like growth factor I (IGF-I), both potent prostate cancer mitogens. We tested whether varying dietary carbohydrate and fat, without energy restriction relative to comparison diet ... Full text Link to item Cite

Ligation of cancer cell surface GRP78 with antibodies directed against its COOH-terminal domain up-regulates p53 activity and promotes apoptosis.

Journal Article Mol Cancer Ther · May 2009 Featured Publication Binding of activated α(2)-macroglobulin to GRP78 on the surface of human prostate cancer cells promotes proliferation by activating signaling cascades. Autoantibodies directed against the activated α(2)-macroglobulin binding site in the NH(2)-terminal doma ... Full text Link to item Cite

RESVERATROL ALTERS PROSTATE CANCER XENOGRAFT GROWTH

Journal Article Journal of Urology · April 2009 Full text Cite

Transcription factor TFII-I causes transcriptional upregulation of GRP78 synthesis in prostate cancer cells.

Journal Article J Cell Biochem · February 15, 2009 Receptor-recognized forms of alpha(2)-macroglobulin (alpha(2)M*) bind to cell surface-associated GRP78 and induce proliferative and survival signaling in prostate cancer cells. As part of the cellular response to alpha(2)M*, GRP78 expression is itself upre ... Full text Link to item Cite

GRP78: a chaperone with diverse roles beyond the endoplasmic reticulum.

Journal Article Histol Histopathol · November 2008 Glucose-regulated protein 78 (GRP78) is a well-characterized molecular chaperone that is ubiquitously expressed in mammalian cells. GRP78 is best known for binding to hydrophobic patches on nascent polypeptides within the endoplasmic reticulum (ER) and for ... Full text Link to item Cite

Can you tBID on it?

Journal Article Cancer Biol Ther · November 2008 Full text Link to item Cite

Targeting cell surface F1F0 ATP synthase in cancer therapy

Journal Article Cancer Biology and Therapy · November 1, 2008 Cite

Amyloid precursor protein and amyloid beta-peptide bind to ATP synthase and regulate its activity at the surface of neural cells.

Journal Article Mol Psychiatry · October 2008 Featured Publication Amyloid precursor protein (APP) and amyloid beta-peptide (Abeta) have been implicated in a variety of physiological and pathological processes underlying nervous system functions. APP shares many features with adhesion molecules in that it is involved in n ... Full text Link to item Cite

The cAMP-activated GTP exchange factor, Epac1 upregulates plasma membrane and nuclear Akt kinase activities in 8-CPT-2-O-Me-cAMP-stimulated macrophages: Gene silencing of the cAMP-activated GTP exchange Epac1 prevents 8-CPT-2-O-Me-cAMP activation of Akt activity in macrophages.

Journal Article Cell Signal · August 2008 cAMP regulates a wide range of processes through its downstream effectors including PKA, and the family of guanine nucleotide exchange factors. Depending on the cell type, cAMP inhibits or stimulates growth and proliferation in a PKA-dependent or independe ... Full text Link to item Cite

Murine low-density lipoprotein receptor-related protein 1 (LRP) is required for phagocytosis of targets bearing LRP ligands but is not required for C1q-triggered enhancement of phagocytosis.

Journal Article J Immunol · July 1, 2008 Featured Publication C1q and members of the defense collagen family are pattern recognition molecules that bind to pathogens and apoptotic cells and trigger a rapid enhancement of phagocytic activity. Candidate phagocytic cell receptors responsible for the enhancement of phago ... Full text Link to item Cite

Mast cell activators: a new class of highly effective vaccine adjuvants.

Journal Article Nat Med · May 2008 Featured Publication Mast cells (MCs) have recently received recognition as prominent effectors in the regulation of immune cell migration to draining lymph nodes and lymphocyte activation. However, their role in the development of humoral immune responses is not clear. Here, ... Full text Link to item Cite

Heterotrimeric Galphaq11 co-immunoprecipitates with surface-anchored GRP78 from plasma membranes of alpha2M*-stimulated macrophages.

Journal Article J Cell Biochem · May 1, 2008 We have previously shown that a fraction of newly expressed GRP78 is translocated to the cell surface in association with the co-chaperone MTJ-1. Proteinase and methylamine-activated alpha(2)M (alpha(2)M*) bind to cell surface-associated GRP78 activating p ... Full text Link to item Cite

Annexin 2/factor xa-mediated signal transduction.

Journal Article Circ Res · February 29, 2008 Full text Link to item Cite

Alpha 2-macroglobulin binds CpG oligodeoxynucleotides and enhances their immunostimulatory properties by a receptor-dependent mechanism.

Journal Article J Leukoc Biol · February 2008 Featured Publication CpG oligodeoxynucleotides (ODN) stimulate the immune system and are under evaluation as treatments and vaccine adjuvants for infectious diseases, cancer, and immune system disorders. Although they have shown promising results in numerous clinical trials, t ... Full text Link to item Cite

Probing the stability of native and activated forms of alpha2-macroglobulin.

Journal Article Int J Biol Macromol · January 1, 2008 alpha2-Macroglobulin (alpha2M) is a 718 kDa homotetrameric proteinase inhibitor which undergoes a large conformational change upon activation. This conformational change can occur either by proteolytic attack on an approximately 40 amino acid stretch, the ... Full text Link to item Cite

Carbohydrate restriction, prostate cancer growth, and the insulin-like growth factor axis.

Journal Article Prostate · January 1, 2008 BACKGROUND: Recent evidence suggests carbohydrate intake may influence prostate cancer biology. We tested whether a no-carbohydrate ketogenic diet (NCKD) would delay prostate cancer growth relative to Western and low-fat diets in a xenograft model. METHODS ... Full text Link to item Cite

Interaction between TCL1 and Epac1 in the activation of Akt kinases in plasma membranes and nuclei of 8-CPT-2-O-Me-cAMP-stimulated macrophages.

Journal Article Cell Signal · January 2008 Epac1 is a cAMP-stimulated guanine exchange factor that activates Rap1. The protein product of the T cell leukemia 1 (TCL1) proto-oncogene binds to Akt enhancing its kinase activity. TCL1 and Epac promote cellular proliferation because of their activating ... Full text Link to item Cite

Dipeptidyl peptidase IV (DPP IV/CD26) is a cell-surface plasminogen receptor.

Journal Article Front Biosci · January 1, 2008 Binding of plasminogen (Pg) to cell-surface receptors colocalized with plasminogen activators promotes Pg activation and enables cells to utilize the proteolytic activity of plasmin (Pm). Proteolysis by Pm is necessary in several physiological and patholog ... Full text Link to item Cite

Targeting cell surface F1F0 ATP synthase in cancer therapy

Journal Article Cancer Biology and Therapy · 2008 Cite

Plasminogen structural domains exhibit different functions when associated with cell surface GRP78 or the voltage-dependent anion channel.

Journal Article J Biol Chem · November 9, 2007 Featured Publication Both the voltage-dependent anion channel and the glucose-regulated protein 78 have been identified as plasminogen kringle 5 receptors on endothelial cells. In this study, we demonstrate that kringle 5 binds to a region localized in the N-terminal domain of ... Full text Link to item Cite

Incorporation of low molecular weight molecules into alpha(2)-macroglobulin by nucleophilic exchange.

Journal Article Biochem Biophys Res Commun · June 1, 2007 alpha(2)-Macroglobulin (alpha(2)M) is a proteinase inhibitor that functions by a trapping mechanism which has been exploited such that the receptor-recognized, activated form (alpha(2)M( *)) can be employed to target antigens to antigen-presenting cells. A ... Full text Link to item Cite

Angiostatin-like activity of a monoclonal antibody to the catalytic subunit of F1F0 ATP synthase.

Journal Article Cancer Res · May 15, 2007 The antiangiogenic protein angiostatin inhibits ATP synthase on the endothelial cell surface, blocking cellular proliferation. To examine the specificity of this interaction, we generated monoclonal antibodies (mAb) directed against ATP synthase. mAb direc ... Full text Link to item Cite

Upregulation of AKT1 protein expression in forskolin-stimulated macrophage: evidence from ChIP analysis that CREB binds to and activates the AKT1 promoter.

Journal Article J Cell Biochem · March 1, 2007 Recently, we reported that silencing CREB gene expression by RNAi significantly attenuates forskolin-induced activation of Akt1. We now provide evidence that forskolin-treatment causes transcriptional and translational upregulation of Akt1 in macrophages. ... Full text Link to item Cite

Prostate cancer cell proliferation in vitro is modulated by antibodies against glucose-regulated protein 78 isolated from patient serum.

Journal Article Cancer Res · December 1, 2006 Featured Publication Circulating autoantibodies against the glucose-regulated protein of 78 kDa (GRP78) are present at high levels in prostate cancer patients and are a biomarker of aggressive tumor behavior. We purified the anti-GRP78 IgGs and examined their effect on 1-LN, P ... Full text Link to item Cite

Activation and cross-talk between Akt, NF-kappaB, and unfolded protein response signaling in 1-LN prostate cancer cells consequent to ligation of cell surface-associated GRP78.

Journal Article J Biol Chem · May 12, 2006 Featured Publication Binding of activated forms of the proteinase inhibitor alpha2-macroglobulin (alpha2M*) to cell surface-associated GRP78 on 1-LN human prostate cancer cells causes their proliferation. We have now examined the interplay between Akt activation, regulation of ... Full text Link to item Cite

LMP-420, a small-molecule inhibitor of TNF-alpha, reduces replication of HIV-1 and Mycobacterium tuberculosis in human cells.

Journal Article AIDS Res Ther · March 31, 2006 BACKGROUND: Co-infections of human immunodeficiency virus (HIV) and Mycobacterium tuberculosis (M. Tb) are steadily increasing and represent a major health crisis in many developing countries. Both pathogens individually stimulate tumor necrosis factor-alp ... Full text Link to item Cite

Angiostatin is directly cytotoxic to tumor cells at low extracellular pH: a mechanism dependent on cell surface-associated ATP synthase.

Journal Article Cancer Res · January 15, 2006 Featured Publication Angiostatin, a proteolytic fragment of plasminogen, is a potent angiogenesis inhibitor able to suppress tumor growth and metastasis through inhibition of endothelial cell proliferation and migration. Previously, we showed that angiostatin binds and inhibit ... Full text Link to item Cite

Cell surface F1Fo ATP synthase: a new paradigm?

Journal Article Ann Med · 2006 The mitochondrial F1Fo adenosine triphosphate (ATP) synthase is one of the most thoroughly studied enzyme complexes known. Yet, a number of new observations suggesting that the enzyme is also located on the cell surface necessitate further investigation. W ... Full text Link to item Cite

Chaperones and disease.

Journal Article N Engl J Med · December 29, 2005 Link to item Cite

Cytokine profiling for prediction of symptomatic radiation-induced lung injury.

Journal Article Int J Radiat Oncol Biol Phys · December 1, 2005 PURPOSE: To analyze plasma cytokine profiles before the initiation of radiation therapy to define a cytokine phenotype that correlates with risk of developing symptomatic radiation-induced lung injury (SRILI). METHODS AND MATERIALS: Symptomatic radiation-i ... Full text Link to item Cite

Coordinate regulation of forskolin-induced cellular proliferation in macrophages by protein kinase A/cAMP-response element-binding protein (CREB) and Epac1-Rap1 signaling: effects of silencing CREB gene expression on Akt activation.

Journal Article J Biol Chem · November 18, 2005 Featured Publication In this study, we have examined the role of two cAMP downstream effectors protein kinase A (PKA) and Epac, in forskolin-induced macrophage proliferation. Treatment of macrophages with forskolin enhanced [(3)H]thymidine uptake and increased cell number, and ... Full text Link to item Cite

The properties of rabbit alpha1-macroglobulin upon activation are distinct from those of rabbit and human alpha2-macroglobulins.

Journal Article J Biochem · November 2005 We have characterized native and activated forms of rabbit alpha1M and compared them to rabbit and human alpha2M. Similar to human alpha2M, rabbit alpha1M is a tetramer associated via disulfide bonds and non-covalent interactions that exhibits autolysis in ... Full text Link to item Cite

Anti-tumor necrosis factor-alpha therapy augments dipeptidyl peptidase IV activity and decreases autoantibodies to GRP78/BIP and phosphoglucose isomerase in patients with rheumatoid arthritis.

Journal Article J Rheumatol · November 2005 OBJECTIVE: To assess the enzymatic activity and biochemical status of dipeptidyl peptidase IV (DPP IV), an enzyme that participates in the degradation of proinflammatory molecules, in sera from a group of patients with rheumatoid arthritis (RA; n = 15) tre ... Link to item Cite

Angiostatin's molecular mechanism: aspects of specificity and regulation elucidated.

Journal Article J Cell Biochem · October 1, 2005 Tumor growth requires the development of new vessels that sprout from pre-existing normal vessels in a process known as "angiogenesis" [Folkman (1971) N Engl J Med 285:1182-1186]. These new vessels arise from local capillaries, arteries, and veins in respo ... Full text Link to item Cite

Ligation of cell surface-associated glucose-regulated protein 78 by receptor-recognized forms of alpha 2-macroglobulin: activation of p21-activated protein kinase-2-dependent signaling in murine peritoneal macrophages.

Journal Article J Immunol · August 15, 2005 Featured Publication Previous studies of the plasma proteinase inhibitor alpha2-macroglobulin (alpha2M) demonstrated that alpha2M-proteinase complexes (alpha2M*) modulate immune responses and promotes macrophage locomotion and chemotaxis. Alpha2M* binds to cell surface-associa ... Full text Link to item Cite

Association of plasminogen with dipeptidyl peptidase IV and Na+/H+ exchanger isoform NHE3 regulates invasion of human 1-LN prostate tumor cells.

Journal Article J Biol Chem · July 22, 2005 Featured Publication Binding of plasminogen type II (Pg 2) to dipeptidyl peptidase IV (DPP IV) on the surface of the highly invasive 1-LN human prostate tumor cell line induces an intracellular Ca2+ ([Ca2+]i) signaling cascade accompanied by a rise in intracellular pH (pHi). I ... Full text Link to item Cite

Binding of activated alpha2-macroglobulin to its cell surface receptor GRP78 in 1-LN prostate cancer cells regulates PAK-2-dependent activation of LIMK.

Journal Article J Biol Chem · July 15, 2005 Featured Publication Two characteristics of highly malignant cells are their increased motility and secretion of proteinases allowing these cells to penetrate surrounding basement membranes and metastasize. Activation of 21-kDa activated kinases (PAKs) is an important mechanis ... Full text Link to item Cite

Up-regulation of GRP78 and antiapoptotic signaling in murine peritoneal macrophages exposed to insulin.

Journal Article J Leukoc Biol · July 2005 The unfolded protein response pathway (UPR) compensates for excessive protein accumulation in the endoplasmic reticulum (ER). As insulin induces global protein synthesis, it may cause accumulation of unfolded proteins in the ER, thus triggering UPR. We ass ... Full text Link to item Cite

Soluble alpha2-macroglobulin receptor is increased in endotracheal aspirates from infants and children after cardiopulmonary bypass.

Journal Article J Thorac Cardiovasc Surg · May 2005 OBJECTIVE: Cytokine dysregulation contributes to the systemic inflammatory response after cardiopulmonary bypass. Clearance of cytokine binding proteins may be important in the resolution of inflammation. Our aim was to determine whether the cytokine bindi ... Full text Link to item Cite

The role of MTJ-1 in cell surface translocation of GRP78, a receptor for alpha 2-macroglobulin-dependent signaling.

Journal Article J Immunol · February 15, 2005 Featured Publication MTJ-1 associates with a glucose-regulated protein of Mr approximately 78,000(GRP78) in the endoplasmic reticulum and modulates GRP78 activity as a chaperone. GRP78 also exists on the cell surface membrane, where it is associated with a number of functions. ... Full text Link to item Cite

Angiostatin directly inhibits human prostate tumor cell invasion by blocking plasminogen binding to its cellular receptor, CD26.

Journal Article Exp Cell Res · February 1, 2005 Previous studies demonstrate that one of the six plasminogen type 2 glycoforms, plasminogen 2epsilon, enhances invasiveness of the 1-LN human prostate tumor cell line in an in vitro model. Binding of plasminogen 2epsilon to CD26 on the cell surface induces ... Full text Link to item Cite

An Inhibitor of the F1 subunit of ATP synthase (IF1) modulates the activity of angiostatin on the endothelial cell surface.

Journal Article J Biol Chem · January 21, 2005 Featured Publication Angiostatin binds to endothelial cell (EC) surface F(1)-F(0) ATP synthase, leading to inhibition of EC migration and proliferation during tumor angiogenesis. This has led to a search for angiostatin mimetics specific for this enzyme. A naturally occurring ... Full text Link to item Cite

Behçet's disease patients present high levels of deglycosylated anti-lipoteichoic acid IgG and high IL-8 production after lipoteichoic acid stimulation.

Journal Article Clin Exp Rheumatol · 2005 OBJECTIVES: Lipoteichoic acid (LTA), induces some of the clinical symptoms of Behçet's disease (BD) in a rat animal model. These results led to the hypothesis that LTA may also trigger BD in humans. We investigated the humoral and cellular immune response ... Link to item Cite

SREC-I, a type F scavenger receptor, is an endocytic receptor for calreticulin.

Journal Article J Biol Chem · December 3, 2004 Featured Publication Calreticulin and gp96 (GRP94) traffic associated peptides into the major histocompatibility complex class-I cross-presentation pathway of antigen-presenting cells (APCs). Efficient accession of the cross-presentation pathway requires APC receptor-mediated ... Full text Link to item Cite

Activation of Akt/PDK signaling in macrophages upon binding of receptor-recognized forms of alpha2-macroglobulin to its cellular receptor: effect of silencing the CREB gene.

Journal Article J Cell Biochem · November 15, 2004 Macrophage binding of receptor-recognized forms of alpha2-macrogobulin (alpha2M*) significantly increases cAMP, CREB, and activated CREB. We have now examined the participation of the PI 3-kinase/PDK/Akt/p70s6k signaling cascade in alpha2M*-induced cellula ... Full text Link to item Cite

A novel receptor function for the heat shock protein Grp78: silencing of Grp78 gene expression attenuates alpha2M*-induced signalling.

Journal Article Cell Signal · August 2004 The activated proteinase inhibitor alpha2-macroglobulin (alpha2M*) binds to two receptors, the low density lipoprotein receptor-related protein (LRP-1) and the alpha2M* signalling receptor (alpha2MSR). Silencing LRP-1 gene expression in macrophages by RNA ... Full text Link to item Cite

Endothelial cell surface ATP synthase-triggered caspase-apoptotic pathway is essential for k1-5-induced antiangiogenesis.

Journal Article Cancer Res · May 15, 2004 We have recently reported the identification of kringle 1-5 (K1-5) of plasminogen as a potent and specific inhibitor of angiogenesis and tumor growth. Here, we show that K1-5 bound to endothelial cell surface ATP synthase and triggered caspase-mediated end ... Full text Link to item Cite

Cell surface adenosine deaminase binds and stimulates plasminogen activation on 1-LN human prostate cancer cells.

Journal Article J Biol Chem · May 14, 2004 Adenosine deaminase (ADA) is expressed intracellularly by all cells, but in some tissues, it is also associated with the cell surface multifunctional glycoprotein CD26/dipeptidyl peptidase IV. By modulating extracellular adenosine, this "ecto-ADA" may regu ... Full text Link to item Cite

Potentiation of signal transduction mitogenesis and cellular proliferation upon binding of receptor-recognized forms of alpha2-macroglobulin to 1-LN prostate cancer cells.

Journal Article Cell Signal · April 2004 The alpha2-macroglobulin signalling receptor is upregulated in highly metastatic 1-LN prostate cancer cells. Stimulation of 1-LN cells with activated alpha2-macroglobulin (alpha2M*) caused a two- to threefold increase in [3H]thymidine uptake and cell numbe ... Full text Link to item Cite

Angiostatin and anti-angiogenic therapy in human disease.

Journal Article Recent Prog Horm Res · 2004 Many diseases have abnormal quality and/or quantity of vascularization as a characteristic feature. Cancer cells elicit the growth of new capillaries during neovascularization in a process termed angiogenesis. In diabetics, pathologic angiogenesis in vario ... Full text Link to item Cite

A CD91-positive subset of CD11c+ blood dendritic cells: characterization of the APC that functions to enhance adaptive immune responses against CD91-targeted antigens.

Journal Article J Immunol · January 1, 2004 Featured Publication Dendritic cells (DC) and other APCs rely on a number of specialized receptors to facilitate the uptake and intracellular accumulation of Ags. In this capacity, APCs use receptor-mediated endocytosis to enhance Ag presentation and the stimulation of Ag-spec ... Full text Link to item Cite

Mast cell-derived tumor necrosis factor induces hypertrophy of draining lymph nodes during infection.

Journal Article Nat Immunol · December 2003 Featured Publication Palpable swelling of regional lymph nodes is a common sequela of microbial infections but the mechanism responsible for the sequestration and subsequent coordination of lymphocyte responses within these dynamic structures remains poorly understood. Here we ... Full text Link to item Cite

Scavenger receptor-A mediates gp96/GRP94 and calreticulin internalization by antigen-presenting cells.

Journal Article EMBO J · November 17, 2003 Featured Publication gp96 (GRP94) elicits antigen-presenting cell (APC) activation and can direct peptides into the cross- presentation pathways of APC. These responses arise through interactions of gp96 with Toll-like (APC activation) and endocytic (cross-presentation) recept ... Full text Link to item Cite

Induction of mitogenic signalling in the 1LN prostate cell line on exposure to submicromolar concentrations of cadmium+.

Journal Article Cell Signal · November 2003 Cadmium exposure increases the risk of prostate cancer. We now describe the effects of Cd2+ on signalling and proliferation in 1LN prostate cells. Cd2+ increased [3H]thymidine uptake and cell number twofold. Cd2+ elevated intracellular IP3, cytosolic-free ... Full text Link to item Cite

Characterization of the interaction between alpha2-macroglobulin and fibroblast growth factor-2: the role of hydrophobic interactions.

Journal Article Biochem J · August 15, 2003 Basic fibroblast growth factor (FGF-2) is important in development, wound healing and angiogenesis. The human plasma proteinase inhibitor alpha2-macroglobulin (alpha2M) binds to and regulates the biological activity of various growth factors, including FGF ... Full text Link to item Cite

The voltage-dependent anion channel is a receptor for plasminogen kringle 5 on human endothelial cells.

Journal Article J Biol Chem · July 18, 2003 Featured Publication Human plasminogen contains structural domains that are termed kringles. Proteolytic cleavage of plasminogen yields kringles 1-3 or 4 and kringle 5 (K5), which regulate endothelial cell proliferation. The receptor for kringles 1-3 or 4 has been identified a ... Full text Link to item Cite

Protease-activated receptor-2 signaling triggers dendritic cell development.

Journal Article Am J Pathol · June 2003 Dendritic cells (DC) are potent antigen-presenting cells that govern the effector cell responses of the immune system. DC are thought to continuously develop from circulating progenitors in a process that is accelerated by inflammatory stimuli. However, th ... Full text Link to item Cite

Streptokinase promotes development of dipeptidyl peptidase IV (CD26) autoantibodies after fibrinolytic therapy in myocardial infarction patients.

Journal Article Clin Diagn Lab Immunol · November 2002 Dipeptidyl peptidase IV (DPP IV) (CD26) plays a critical role in the modulation and expression of autoimmune and inflammatory diseases. We recently reported that sera from patients with rheumatoid arthritis and systemic lupus erythematosus contained low le ... Full text Link to item Cite

The role of Grp 78 in alpha 2-macroglobulin-induced signal transduction. Evidence from RNA interference that the low density lipoprotein receptor-related protein is associated with, but not necessary for, GRP 78-mediated signal transduction.

Journal Article J Biol Chem · November 1, 2002 The low density lipoprotein receptor-related protein (LRP) is a scavenger receptor that binds to many proteins, some of which trigger signal transduction. Receptor-recognized forms of alpha(2)-Macroglobulin (alpha(2)M*) bind to LRP, but the pattern of sign ... Full text Link to item Cite

The role of cAMP-dependent signaling in receptor-recognized forms of alpha 2-macroglobulin-induced cellular proliferation.

Journal Article J Biol Chem · September 27, 2002 Ligation of alpha(2)-macroglobulin receptors by receptor-recognized forms of alpha(2)-macroglobulin (alpha(2)M*) activates various signaling cascades and promotes cell proliferation. It also elevates cAMP in murine peritoneal macrophages. We now report tha ... Full text Link to item Cite

New member of the trefoil factor family of proteins is an alpha-macroglobulin protease inhibitor.

Journal Article Biochim Biophys Acta · July 29, 2002 The amino acid sequence of the monomeric alpha-macroglobulin (alphaM) from the American bullfrog, Rana catesbiana, was determined. The mature protein consisted of 1469 amino acid residues and shared sequence identity with other members of the alphaM family ... Full text Link to item Cite

Tissue factor is the receptor for plasminogen type 1 on 1-LN human prostate cancer cells.

Journal Article Blood · June 15, 2002 Tissue factor (TF), the initiator of the extrinsic pathway of coagulation, binds plasminogen (Pg) with high affinity through an interaction between kringles 1-3 of Pg and the extracellular domain of TF. We investigated the binding of Pg type 1 (Pg 1) and P ... Full text Link to item Cite

Increased immunogenicity of HIV envelope subunit complexed with alpha2-macroglobulin when combined with monophosphoryl lipid A and GM-CSF.

Journal Article Vaccine · May 22, 2002 Critical to the success of HIV-1 subunit vaccines is the development of strategies to augment vaccine immunogenicity. Successful adjuvants must not only improve immunogenicity above current adjuvant levels, but must also decrease the dose of immunogen requ ... Full text Link to item Cite

Cutting edge: CD91-independent cross-presentation of GRP94(gp96)-associated peptides.

Journal Article J Immunol · May 1, 2002 GRP94(gp96) elicits CD8(+) T cell responses against its bound peptides, a process requiring access of its associated peptides into the MHC class I cross-presentation pathway of APCs. Entry into this pathway requires receptor-mediated endocytosis, and CD91 ... Full text Link to item Cite

Cadmium-induced DNA synthesis and cell proliferation in macrophages: the role of intracellular calcium and signal transduction mechanisms.

Journal Article Cell Signal · April 2002 Cd(2+) exposure increases the risk of cancer in humans and animals. In this report, we have studied the effect of Cd(2+) on signal transduction and Ca(2+) mobilization in murine macrophages. At micromolar concentrations, Cd(2+) significantly increased cell ... Full text Link to item Cite

The mechanism of action of angiostatin: can you teach an old dog new tricks?

Journal Article Thromb Haemost · March 2002 What is angiostatin? In 1994, Folkman and colleagues published a landmark paper describing anti-tumor effects in mice with a purified fragment of plasminogen they named angiostatin (1). Although many papers have been published describing activities of cryp ... Link to item Cite

Beryllium fluoride-induced cell proliferation: a process requiring P21(ras)-dependent activated signal transduction and NF-kappaB-dependent gene regulation.

Journal Article J Leukoc Biol · March 2002 We studied the effect of beryllium fluoride on murine peritoneal macrophages and determined its effects on signal transduction and genetic regulation. At low concentration (1-5 nM), BeF(2) caused an approximate twofold increase in [(3)H]thymidine uptake an ... Link to item Cite

Regulation of cytosolic phospholipase A2 activity in macrophages stimulated with receptor-recognized forms of alpha 2-macroglobulin: role in mitogenesis and cell proliferation.

Journal Article J Biol Chem · February 8, 2002 Macrophages exposed to receptor-recognized forms of alpha(2)-macroglobulin (alpha(2)M*) demonstrate increased DNA synthesis and cell division. In the current study, we have probed the role of cytosolic phospholipase A(2) (cPLA(2)) activity in the cellular ... Full text Link to item Cite

Receptor-associated protein binding blocks ubiquitinylation of the low density lipoprotein receptor-related protein.

Journal Article Arch Biochem Biophys · December 1, 2001 The low density lipoprotein receptor-related protein (LRP) consists of two subunits, M(r) approximately 515,000 and 85,000. LRP is a receptor for activated alpha2-macrogobulin (alpha2M*), Pseudomonas exotoxin A, and many other proteins. We now report that ... Full text Link to item Cite

Covalent complexes of antigen and alpha(2)-macroglobulin: evidence for dramatically-increased immunogenicity.

Journal Article Vaccine · November 12, 2001 A safe, effective, more potent adjuvant than currently available would be beneficial in developing new therapeutics and diagnostic reagents. We report here a technique for the rapid, efficient incorporation of non-proteolytic antigens into alpha(2)-macrogl ... Full text Link to item Cite

Kinetics of nonproteolytic incorporation of a protein ligand into thermally activated alpha 2-macroglobulin: evidence for a novel nascent state.

Journal Article J Biol Chem · November 9, 2001 We have previously shown that antigens complexed to the receptor-recognized form of alpha(2)-macroglobulin (alpha(2)M*) demonstrate enhanced immune responsiveness mediated by the low density lipoprotein receptor-related protein LRP/CD91. Recently, we devel ... Full text Link to item Cite

Induction of cyclooxygenase-2 synthesis by ligation of the macrophage alpha(2)-macroglobulin signalling receptor.

Journal Article Cell Signal · November 2001 We have studied the induction of cyclooxygenase-2 (COX-2) in macrophages consequent to ligating the alpha(2)-macroglobulin (alpha(2)M) signalling receptor (alpha(2)MSR) with receptor-recognized forms of alpha(2)M (alpha(2)M*). Macrophage stimulation with a ... Full text Link to item Cite

Apolipoprotein E and mimetic peptide initiate a calcium-dependent signaling response in macrophages.

Journal Article J Leukoc Biol · October 2001 Apolipoprotein E (ApoE) is a 34-kDa cholesterol transport protein that also possesses immunomodulatory properties. In this study, we demonstrate that ApoE initiates a signaling cascade in murine peritoneal macrophages that leads to increased production of ... Link to item Cite

alpha(2)-Macroglobulin from rheumatoid arthritis synovial fluid: functional analysis defines a role for oxidation in inflammation.

Journal Article Arch Biochem Biophys · July 1, 2001 A hallmark of inflammation is the release of oxidants, proteinases, and cytokines, all important mediators of the inflammatory cascade. alpha(2)-Macroglobulin (alpha(2)M) is a high-affinity, broad-specificity proteinase inhibitor that also binds and regula ... Full text Link to item Cite

Endothelial cell surface F1-F0 ATP synthase is active in ATP synthesis and is inhibited by angiostatin.

Journal Article Proc Natl Acad Sci U S A · June 5, 2001 Featured Publication Angiostatin blocks tumor angiogenesis in vivo, almost certainly through its demonstrated ability to block endothelial cell migration and proliferation. Although the mechanism of angiostatin action remains unknown, identification of F(1)-F(O) ATP synthase a ... Full text Link to item Cite

Differential regulation of the fibroblast growth factor (FGF) family by alpha(2)-macroglobulin: evidence for selective modulation of FGF-2-induced angiogenesis.

Journal Article Blood · June 1, 2001 The fibroblast growth factor (FGF) family has an important role in processes such as angiogenesis, wound healing, and development in which precise control of proteinase activity is important. The human plasma proteinase inhibitor alpha(2)-macroglobulin (al ... Full text Link to item Cite

Interaction of plasminogen with dipeptidyl peptidase IV initiates a signal transduction mechanism which regulates expression of matrix metalloproteinase-9 by prostate cancer cells.

Journal Article Biochem J · April 15, 2001 Both plasminogen (Pg) activation and matrix metalloproteinases (MMPs) are involved in the proteolytic degradation of extracellular matrix components, a requisite event for malignant cell metastasis. The highly invasive 1-LN human prostate tumour cell line ... Full text Link to item Cite

Ligation of the alpha2M* signaling receptor regulates synthesis of cytosolic phospholipase A2.

Journal Article Arch Biochem Biophys · February 15, 2001 We have studied the regulation of cytosolic phospholipase A2 (cPLA2) synthesis in macrophages stimulated with receptor-recognized forms of alpha2-macroglobulin (alpha2M*). [35S]methionine-labeled cells were stimulated with alpha2M* and [35S]cPLA2 was immun ... Full text Link to item Cite

Characterization of human serum dipeptidyl peptidase IV (CD26) and analysis of its autoantibodies in patients with rheumatoid arthritis and other autoimmune diseases.

Journal Article Clin Exp Rheumatol · 2001 OBJECTIVES: To assess the serum levels, specific activity and other characteristics of dipeptidylpeptidase IV (DPP IV/CD26), an ectoenzyme that plays a critical role in the modulation and expression of autoimmune and inflammatory diseases, from patients wi ... Link to item Cite

Inducible expression of the alpha2-macroglobulin signaling receptor in response to antigenic stimulation: a study of second messenger generation.

Journal Article J Cell Biochem · 2001 Thioglycollate (TG)-elicited murine, peritoneal macrophages express two receptors for activated forms of the proteinase inhibitor alpha2-macroglobulin (alpha2M*)--namely, the low density lipoprotein receptor-related protein (LRP) and the alpha2M signaling ... Full text Link to item Cite

Downregulation of microglial activation by apolipoprotein E and apoE-mimetic peptides.

Journal Article Exp Neurol · January 2001 Apolipoprotein E plays an important role in recovery from acute brain injury and risk of developing Alzheimer's disease. We demonstrate that biologically relevant concentrations of apoE suppress microglial activation and release of TNFalpha and NO in a dos ... Full text Link to item Cite

Selective upregulated expression of the alpha2-macroglobulin signaling receptor in highly metastatic 1-LN prostate carcinoma cells.

Journal Article Arch Biochem Biophys · November 1, 2000 Cellular binding of receptor-recognized forms of alpha2-macroglobulin (alpha2M*) is mediated by the low-density lipoprotein receptor related protein (LRP) and the alpha2M signaling receptor (alpha2MSR). In nonmalignant cells, ligation of alpha2MSR promotes ... Full text Link to item Cite

The conformation-dependent interaction of alpha 2-macroglobulin with vascular endothelial growth factor. A novel mechanism of alpha 2-macroglobulin/growth factor binding.

Journal Article J Biol Chem · September 1, 2000 Featured Publication alpha(2)-Macroglobulin (alpha(2)M) is a highly conserved proteinase inhibitor present in human plasma at high concentration (2-4 mg/ml). alpha(2)M exists in two conformations, a native form and an activated, receptor-recognized form. While alpha(2)M binds ... Full text Link to item Cite

Cytosolic phospholipase A(2) activity associated with nuclei is not inhibited by arachidonyl trifluoromethyl ketone in macrophages stimulated with receptor-recognized forms of alpha(2)-macroglobulin.

Journal Article Arch Biochem Biophys · July 1, 2000 We have studied the translocation of cytosolic phospholipase A(2) (cPLA(2)) to nuclei in macrophages stimulated with receptor-recognized forms of alpha(2)-macroglobulin (alpha(2)M*). Translocation of phosphorylated cPLA(2) to nuclei was determined by immun ... Full text Link to item Cite

Potentiation of calcium levels by extracellular arachidonic acid in nuclei isolated from macrophages stimulated with receptor-recognized forms of alpha(2)-macroglobulin.

Journal Article Cell Signal · February 2000 Featured Publication Ligation of macrophage alpha(2)-macroglobulin signalling receptors (alpha(2)MSR) with activated alpha(2)-macroglobulin (alpha(2)M*) increases intracellular Ca(2+), and cytosolic phospholipase A(2) (cPLA(2)) and phospholipase D activities. In view of the re ... Full text Link to item Cite

Ligation of low-density lipoprotein receptor-related protein with antibodies elevates intracellular calcium and inositol 1,4, 5-trisphosphate in macrophages.

Journal Article Arch Biochem Biophys · December 15, 1999 We have probed the signaling characteristics of the macrophage low-density lipoprotein receptor-related protein (LRP) with monoclonal antibody 8G1, its Fab and F(ab')(2) fragments directed against the ligand binding heavy chain, and monoclonal antibody 5A6 ... Full text Link to item Cite

Mechanism of hypochlorite-mediated inactivation of proteinase inhibition by alpha 2-macroglobulin.

Journal Article Biochemistry · October 19, 1999 Featured Publication The proteinase-proteinase inhibitor balance plays an important role in mediating inflammation-associated tissue destruction. alpha 2-Macroglobulin (alpha 2M) is a high-affinity, broad-spectrum proteinase inhibitor found abundantly in plasma and interstitia ... Full text Link to item Cite

Coordinate regulation of the alpha(2)-macroglobulin signaling receptor and the low density lipoprotein receptor-related protein/alpha(2)-macroglobulin receptor by insulin.

Journal Article J Biol Chem · September 3, 1999 Featured Publication We have studied insulin-dependent regulation of macrophage alpha(2)-macroglobulin signaling receptors (alpha(2)MSR) and low density lipoprotein receptor-related protein/alpha(2)M receptors (LRP/alpha(2)MR) employing cell binding of (125)I-alpha(2)M*, inhib ... Full text Link to item Cite

Incorporation of non-proteolytic proteins by murine alpha2-macroglobulin.

Journal Article Biochim Biophys Acta · June 15, 1999 Human alpha2-macroglobulin is a tetrameric glycoprotein with a molecular weight of 718 kDa that is present in human plasma at high concentrations. Murine alpha2-macroglobulin is homologous to human alpha2-macroglobulin but it undergoes post-translational c ... Full text Link to item Cite

Exposure of cultured murine peritoneal macrophages to low concentrations of beryllium induces increases in intracellular calcium concentrations and stimulates DNA synthesis.

Journal Article J Leukoc Biol · June 1999 Exposure of humans to beryllium dusts can induce a specific form of chronic pneumonitis that consists mainly of noncaseating granulomas in the lungs. Multiple studies have documented both genetic and immune components of chronic berylliosis. Much work has ... Full text Link to item Cite

Angiostatin binds ATP synthase on the surface of human endothelial cells.

Journal Article Proc Natl Acad Sci U S A · March 16, 1999 Featured Publication Angiostatin, a proteolytic fragment of plasminogen, is a potent antagonist of angiogenesis and an inhibitor of endothelial cell migration and proliferation. To determine whether the mechanism by which angiostatin inhibits endothelial cell migration and/or ... Full text Link to item Cite

Upregulation of macrophage plasma membrane and nuclear phospholipase D activity on ligation of the alpha2-macroglobulin signaling receptor: involvement of heterotrimeric and monomeric G proteins.

Journal Article Arch Biochem Biophys · March 1, 1999 The effect of ligating the alpha2-macroglobulin signaling receptor (alpha2MSR) with receptor-recognized forms of alpha2M (alpha2M*) was studied with respect to phospholipase D (PLD) activity in murine macrophages, their plasma membranes, and nuclei. PLD ac ... Full text Link to item Cite

Cyclosporin A inhibits inositol 1,4,5-trisphosphate binding to its receptors and release of calcium from intracellular stores in peritoneal macrophages.

Journal Article J Immunol · December 1, 1998 We have studied the effects of the immunosuppressive drug cyclosporin A (CsA) on the generation of inositol 1,4,5-trisphosphate (IP3) and intracellular Ca2+ levels elicited upon ligation of murine macrophage receptors for alpha2-macroglobulin, bradykinin, ... Link to item Cite

APOE3 and APOE4 binding to macrophages triggers inositol (1,4,5-) triphosphate-mediated increases in intracellular calcium

Journal Article FASEB Journal · December 1, 1998 Apolipoprotein E (apoE) is a 34 kDa protein that mediates binding of lipopro teins to the LDL and LRP receptors- Apart from maintaining plasma cholesterol homeostasis, apoE may participate in mobilization and redistribution of lipids during normal developm ... Cite

Upregulation of a2m signalling receptor by insulin in macrophages

Journal Article FASEB Journal · December 1, 1998 In 1984 this laboratory showed that the treatment of adipocytes and fibrob lasts with insulin enhanced the binding of 125I-a2M-methylamine by about 2-3 fold and its slowed receptor-mediated degradation. We have recently reported the presence of a novel ojM ... Cite

Secretion of MMP-9 by 1-LN human prostate tumor cells is modulated via a signaling mechanism initiated by interaction between plasminogen carbohydrate chains and DPP IV (CD26) on the cell surface

Journal Article FASEB Journal · December 1, 1998 Remodeling of the extracellular matrix (ECM), which occurs during metastatic processes, is one of the requisite events for cellular invasion. Both the plasminogen (Pg) activation system and matrix metalloproteinases (MMPs) are involved in proteolytic degra ... Cite

Oxidized alpha2-macroglobulin (alpha2M) differentially regulates receptor binding by cytokines/growth factors: implications for tissue injury and repair mechanisms in inflammation.

Journal Article J Immunol · October 15, 1998 Alpha2M binds specifically to TNF-alpha, IL-1beta, IL-2, IL-6, IL-8, basic fibroblast growth factor (bFGF), beta-nerve growth factor (beta-NGF), platelet-derived growth factor (PDGF), and TGF-beta. Since many of these cytokines are released along with neut ... Link to item Cite

Alterations in calcium metabolism in murine macrophages by the benzene metabolite 1,4-benzoquinone.

Journal Article Toxicol Appl Pharmacol · July 1998 Exposure of murine peritoneal macrophages to very low concentrations of 1,4-benzoquinone (BQ) induced immediate increases in intracellular Ca2+ concentrations ([Ca2+]i). Increases in [Ca2+]i were induced by concentrations as low as 5 nM and the response wa ... Full text Link to item Cite

Ligation of the alpha2M signalling receptor elevates the levels of p21Ras-GTP in macrophages.

Journal Article Cell Signal · June 1998 Ligation of the alpha2-macroglobulin signalling receptor (alpha2MSR) with alpha2-macroglobulin (alpha2M)-methylamine or a cloned and expressed receptor binding fragment (RBF) stimulates DNA synthesis. To examine the possible role of the Ras pathway in the ... Full text Link to item Cite

Binding of receptor-recognized forms of alpha2-macroglobulin to the alpha2-macroglobulin signaling receptor activates phosphatidylinositol 3-kinase.

Journal Article J Biol Chem · May 29, 1998 Ligation of the alpha2-macroglobulin (alpha2M) signaling receptor by receptor-recognized forms of alpha2M (alpha2M*) initiates mitogenesis secondary to increased intracellular Ca2+. We report here that ligation of the alpha2M signaling receptor also causes ... Full text Link to item Cite

Nonproteolytic incorporation of protein ligands into human alpha 2-macroglobulin: implications for the binding mechanism of alpha 2-macroglobulin.

Journal Article Biochemistry · April 28, 1998 alpha 2-Macroglobulin (alpha 2M) is a complex tetrameric protein of 718 kDa. In native alpha 2M, each of the four subunits contains a thiol ester between the side chains of Cys949 and Gln952. Cleavage of the thiol ester with small nucleophiles destabilizes ... Full text Link to item Cite

Ligation of the alpha2M signaling receptor with receptor-recognized forms of alpha2-macroglobulin initiates protein and DNA synthesis in macrophages. The effect of intracellular calcium.

Journal Article Biochim Biophys Acta · January 2, 1998 We have previously reported that receptor-recognized forms of the proteinase inhibitor alpha2-macroglobulin (alpha2M) bind to a distinct receptor (alpha2MSR), Kd approximately 50-100 pM, activating a signaling cascade, triggering tyrosine phosphorylation o ... Full text Link to item Cite

Oxidized α2-macroglobulin differentially regulates receptor binding by cytokines/growth factors

Journal Article FASEB Journal · 1998 α2-Macroglobulin (α2M) is a highly conserved, homotetrameric, broad-spectrum plasma and inflammatory fluid proteinase inhibitor that also binds to a wide variety of cytokines and growth factors such as TNF-α, IL-1β, IL-2, IL-6, IL-8, bFGF, βNGF, PDGF, and ... Cite

Dipeptidyl peptidase IV (CD26) is a receptor for streptokinase on rheumatoid synovial fibroblasts

Journal Article Fibrinolysis and Proteolysis · January 1, 1998 Plasminogen (Pg) binds to synovial fibroblasts from patients with rheumatoid arthritis with a very high affinity and in a dose-dependent manner. The Pg receptor in these cells is composed of a glycoprotein IIb/IIIa related protein (α(IIIb)β3) in associatio ... Full text Cite

Plasmin(ogen) carbohydrate chains mediate binding to dipeptidyl peptidase IV (CD 26) in rheumatoid arthritis human synovial fibroblasts

Journal Article Fibrinolysis and Proteolysis · January 1, 1998 Objective: To assess the reactivity between dipeptidyl peptidase IV (DPP IV) and the α2,3-linked sialic acid of the plasminogen (Pg)Thr345 O- linked carbohydrate chain as the mechanism enabling plasmin (Pm) to induce intracellular Ca2+ via DPP IV on rheuma ... Full text Cite

Isolation of an angiostatin receptor from the membranes of human umbilical vein endothehal cells

Journal Article Fibrinolysis and Proteolysis · December 1, 1997 Angiostatin, a kringle-containing fragment of plasminogen, is a potent antagonist of angiogenesis, resulting from its ability to inhibit endothelial cell migration and proliferation. To test the hypothesis that alteration of the biologic properties of endo ... Cite

Cyclosporin a inhibits ip,-mediated release of calcium from intracellu lar stores in macrophages

Journal Article FASEB Journal · December 1, 1997 Cycloporin A (CsA) and FKöOfi interteie wiHi Ca2+ -nnsimc T-cell sigtial l raii-duct ion pathways, preventing 'he activation of specific transcription fulors involved in lymphokine gene expression. CsA find FK">Oli act by interaction witii (ornate intracel ... Cite

Activation of ARF- But not RHO-dependent nuclear phospholipase D in murine peritoneal macrophages on ligation of cvM signaling receptor

Journal Article FASEB Journal · December 1, 1997 Activation of phospholipase D (PLD) is a receptor-mediated event revolved m signal transduction, ntembrane trafficking, cell proliferation, and phagocytosis Phosphatidic acid (PA). the prmary lipid product of PLD, possesses growth factors-like properties a ... Cite

Nickel inhibits binding of alpha2-macroglobulin-methylamine to the low-density lipoprotein receptor-related protein/alpha2-macroglobulin receptor but not the alpha2-macroglobulin signaling receptor.

Journal Article Biochemistry · October 14, 1997 A previous study demonstrated that activated alpha2-macroglobulin (alpha2M*) binding to the low-density receptor-related protein/alpha2-macroglobulin receptor (LRP/alpha2MR) is blocked by Ni2+ [Hussain, M. M., et al. (1995) Biochemistry 34, 16074-16081]. W ... Full text Link to item Cite

Aspirin inhibits tumor necrosis factoralpha gene expression in murine tissue macrophages.

Journal Article Mol Pharmacol · September 1997 Aspirin has been reported to inhibit the activation of nuclear factor-kappaB (NF-kappaB) through stabilization of inhibitor kappaB (IkappaB). This observation led us to investigate the role of aspirin in suppressing the activation of the NF-kappaB-regulate ... Full text Link to item Cite

The binding of receptor-recognized alpha2-macroglobulin to the low density lipoprotein receptor-related protein and the alpha2M signaling receptor is decoupled by oxidation.

Journal Article J Biol Chem · August 15, 1997 Receptor-recognized forms of alpha2-macroglobulin (alpha2M*) bind to two classes of cellular receptors, a high affinity site comprising approximately 1500 sites/cell and a lower affinity site comprising about 60,000 sites/cell. The latter class has been id ... Full text Link to item Cite

Molecular abnormalities of human plasminogen isolated from synovial fluid of rheumatoid arthritis patients.

Journal Article J Mol Med (Berl) · May 1997 Plasminogen (Pg) in the synovial fluid of patients with acute inflammatory disease, including rheumatoid arthritis, osteoarthritis, and gout, was purified by affinity chromatography techniques. The Pg isolated from patients with osteoarthritis and gout has ... Link to item Cite

Evidence for a novel O-linked sialylated trisaccharide on Ser-248 of human plasminogen 2.

Journal Article J Biol Chem · March 14, 1997 Human plasminogen, the inactive precursor of plasmin, exists in two major glycoforms. Plasminogen 1 contains an N-linked oligosaccharide at Asn-289 and an O-linked oligosaccharide at Thr-345. Plasminogen 2 is known to contain only an O-linked oligosacchari ... Full text Link to item Cite

Chloroquine, quinine and quinidine inhibit calcium release from macrophage intracellular stores by blocking inositol 1,4,5-trisphosphate binding to its receptor.

Journal Article J Cell Biochem · February 1997 The binding of many ligands to cellular receptors induces a signaling cascade which generates inositol 1,4,5-trisphosphate (IP3). IP3 binding to its receptors in various internal compartments causes a rapid Ca2+ efflux into the cytosol. We now demonstrate ... Full text Link to item Cite

Up-regulation of the alpha2-macroglobulin signaling receptor on rheumatoid synovial fibroblasts.

Journal Article J Biol Chem · January 3, 1997 In the present study, we demonstrate that the alpha2-macroglobulin (alpha2M) signaling receptor is up-regulated on rheumatoid synovial fibroblasts. In rheumatoid cells, 125I-alpha2M-methylamine bound to two sites; namely, one of high affinity (Kd approxima ... Full text Link to item Cite

The potential role of alpha 2-macroglobulin in the control of cysteine proteinases (gingipains) from Porphyromonas gingivalis.

Journal Article J Periodontal Res · January 1997 Porphyromonas gingivalis is closely associated with the development of some forms of periodontitis. The major cysteine proteinases released by this bacterium hydrolyze peptide bonds only after arginyl (gingipain R) or lysyl residues (gingipain K). No targe ... Full text Link to item Cite

Maleylated-BSA induces hydrolysis of PIP2, fluxes of Ca2+, NF-kappaB binding, and transcription of the TNF-alpha gene in murine macrophages.

Journal Article J Leukoc Biol · December 1996 The interaction of altered lipids or proteins with the several scavenger receptors (SR) on macrophages can lead to disparate results in both gene expression and cell function. However, the molecular bases of signaling induced by SR ligation have remained o ... Full text Link to item Cite

Identification of residues in alpha-macroglobulins involved in activation of the alpha 2-macroglobulin signaling receptor.

Journal Article Biochim Biophys Acta · October 17, 1996 Site-directed mutagenesis of residues in the receptor binding fragment of rat alpha 1-macroglobulin identify residues 1377 and 1378 (human numbering) as crucial for interaction with the alpha 2M signaling receptor on murine macrophages. Secondary structure ... Full text Link to item Cite

Evidence for preferential adhesion of ovarian epithelial carcinoma cells to type I collagen mediated by the alpha2beta1 integrin.

Journal Article Int J Cancer · September 4, 1996 Epithelial ovarian carcinoma, the leading cause of gynecologic cancer death, is characterized by widespread intra-abdominal metastases mediated primarily by surface shedding of tumor cells and peritoneal implantation. Whereas hematogenous metastasis is kno ... Full text Link to item Cite

Structural and functional analysis of the spontaneous re-formation of the thiol ester bond in human alpha 2-macroglobulin, rat alpha 1-inhibitor-3 and chemically modified derivatives.

Journal Article Biochem J · September 1, 1996 The alpha-macroglobulins are proteinase inhibitors that form part of a superfamily along with components of the complement system. Internal beta-cysteinyl-gamma-glutamyl thiol ester bonds are an important structural feature of most alpha-macroglobulins and ... Full text Link to item Cite

Characterization of alpha 2-macroglobulin binding to human trabecular meshwork cells: presence of the alpha 2-macroglobulin signaling receptor.

Journal Article Arch Biochem Biophys · September 1, 1996 Direct binding of receptor-recognized alpha 2-macroglobulin (alpha 2M*) or a cloned receptor binding fragment from rat alpha 1-macroglobulin (RBF) to human trabecular meshwork cells demonstrated two classes of cell surface binding sites. One class has an a ... Full text Link to item Cite

Analysis of autoantibodies to plasminogen in the serum of patients with rheumatoid arthritis.

Journal Article J Mol Med (Berl) · August 1996 Sera from patients with rheumatoid arthritis containing high titers of anti-streptokinase antibodies were found to contain anti-plasminogen antibodies of the IgG and IgA classes. High titers of anti-plasminogen autoantibodies of the IgA class were also fou ... Full text Link to item Cite

Characterization of gelatinases linked to extracellular matrix invasion in ovarian adenocarcinoma: purification of matrix metalloproteinase 2.

Journal Article Gynecol Oncol · July 1996 Substantial evidence indicates that proteolytic degradation of the extracellular matrix is necessary for invasion and metastasis by cancer cells. Our previous work has demonstrated elevated secretion by cultured ovarian adenocarcinoma cells of two gelatino ... Full text Link to item Cite

Selective mutations in cloned and expressed alpha-macroglobulin receptor binding fragment alter binding to either the alpha2-macroglobulin signaling receptor or the low density lipoprotein receptor-related protein/alpha2-macroglobulin receptor.

Journal Article J Biol Chem · June 14, 1996 alpha2-Macroglobulin (alpha2M) activated with methylamine binds to two distinct cell-surface receptors: low density-lipoprotein receptor-related protein/alpha2M receptors and alpha2M signaling receptors. Binding to lipoprotein receptor-related protein/alph ... Full text Link to item Cite

Activated human plasma carboxypeptidase B is retained in the blood by binding to alpha2-macroglobulin and pregnancy zone protein.

Journal Article J Biol Chem · May 31, 1996 A 66-kDa glycosylated carboxypeptidase, plasma pro-carboxypeptidase B (pro-plasma CPB), has recently been identified in human blood (Eaton, D. L., Malloy, B. E., Tsai, S. P., Henzel, W., and Drayna, D. (1991) J. Biol. Chem. 266, 21833-21838). The pro-enzym ... Full text Link to item Cite

Career characteristics of graduates of a Medical Scientist Training Program, 1970-1990.

Journal Article Acad Med · May 1996 PURPOSE: To describe the career characteristics of the graduates of the Medical Scientist Training Program (MSTP) at Duke University School of Medicine. METHOD: Surveys and information at administrative offices were used to collect data on all the 1970-199 ... Full text Link to item Cite

Ligation of the alpha 2-macroglobulin signaling receptor on macrophages induces synthesis of platelet activating factor.

Journal Article J Cell Biochem · April 1996 The binding of receptor-recognized forms of alpha 2-macroglobulin (alpha 2M) to macrophage alpha 2M signaling receptors increases inositol-1,4,5-triphosphate synthesis and induces Ca2+ mobilization. In this report, we demonstrate that ligation of the macro ... Full text Link to item Cite

Binding of rat alpha 1-inhibitor-3-methylamine to the alpha 2-macroglobulin signaling receptor induces second messengers.

Journal Article J Cell Biochem · April 1996 Binding of receptor-recognized forms of tetrameric human alpha 2-macroglobulin (alpha 2M*) to a macrophage signaling receptor induces cAMP synthesis, increases in inositol 1,4,5-triphosphate (IP3) synthesis, and a concomitant rise in cytosolic free calcium ... Full text Link to item Cite

Altered interaction of Cis-dichlorodiammineplatinum(II)--modified alpha 2-macroglobulin (alpha 2M) with the low density lipoprotein receptor-related protein/alpha 2M receptor but not the alpha 2M signaling receptor.

Journal Article J Clin Invest · March 1, 1996 Receptor-recognized forms of alpha 2-macroglobulin (alpha 2M*) bind to two macrophage receptors: an endocytic receptor, the low density lipoprotein receptor-related protein/alpha 2M receptor (LRP/alpha 2MR), and a G protein-coupled receptor, the alpha 2M s ... Full text Link to item Cite

Human trabecular meshwork cells possess two distinct receptors for receptor-recognized forms of α2macroglobulin

Journal Article Investigative Ophthalmology and Visual Science · February 15, 1996 Purpose. α2-macro-globulin(α2M*) has been found to stimulate growth, regulate the synthesis and secretion of proteases and other compounds, and enhance antigen presentation in cells. We wanted to investigate the binding of receptor-recognized forms of α2M* ... Cite

Low-density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor on murine peritoneal macrophages mediates the binding and catabolism of low-density lipoprotein.

Journal Article Arch Biochem Biophys · February 1, 1996 Low-density lipoprotein receptor-related protein (LRP)/alpha 2-macroglobulin receptor is a member of the low-density lipoprotein receptor family. It is known to bind a wide variety of unrelated ligands including alpha 2-macroglobulin-proteinase complexes, ... Full text Link to item Cite

ATP-regulated activity of the plasmin-streptokinase complex: a novel mechanism involving phosphorylation of streptokinase.

Journal Article Biochem J · January 1, 1996 Streptokinase, an extracellular protein produced by Streptococci, is capable of activating the human fibrinolytic zymogen plasminogen. The rate of amidolytic activity of the plasminogen-streptokinase complex is greatly diminished by micromolar concentratio ... Full text Link to item Cite

Potential pathogenicity of deglycosylated IgG cross reactive with streptokinase and fibronectin in the serum of patients with rheumatoid arthritis.

Journal Article J Rheumatol · January 1996 OBJECTIVE: Fibronectin (FN) and the streptococcal plasminogen activator streptokinase (SK) share the epitope LTSRPA. This epitope is not reactive in native FN and it reacts with anti-SK antibodies only after plasmin digestion of the protein. To investigate ... Link to item Cite

Role of adhesion and proteolysis in epithelial ovarian carcinoma dissemination

Journal Article Fibrinolysis · January 1, 1996 Metastatic spread of epithelial ovarian carcinoma (OV CA) is mediated primarily by surface shedding of tumor cells and peritoneal implantation; however the role of adhesion and proteolysis in OV CA remains unclear. We have previously shown that OV CA cells ... Full text Cite

Plasmin(ogen) carbohydrate chains mediate binding to dipeptidyl peptidase iv (cd 26) on rheumatoid artrhitis human synovial fibroblasts

Journal Article Fibrinolysis · January 1, 1996 Both plasminogen (Pg) and the streptococcal plasminogen activator streptokinase (SK) bind to synovial fibroblasts from patients with rheumatoid arthritis (RA) with a very high affinity and in a dose-dependent manner. The receptor for both proteins has been ... Full text Cite

Interaction of human plasminogen kringles 1-3 (angiostatin) with human umbilical vein endothelial cells (huvec): binding properties and effects on cell proliferation

Journal Article Fibrinolysis · January 1, 1996 Receptors which bind plasminogen (Pg) have previously been demonstrated in HUVEC. To determine whether the mechanism by which the Pg fragment, angiostatin, inhibits endothelial cell migralion and/or proliferation involves interaction with the Pg receptor, ... Full text Cite

The role of carbohydrate in the activation of plasminogen 2 glycoforms by streptokinase

Journal Article Fibrinolysis · January 1, 1996 Plasminogen 2 has six glycoforms that differ in their sialic acid content. In this study we have examined the effect that this differential sialylation has on activation of these glycoforms by streptokinase (SK). We find that increases in sialic acid conte ... Full text Cite

Dipeptidyl Peptidase IV(CD 26) is a Receptor for Streptokinase and Fibronectin on Rheumatoid Arthritis Human Synovial Fibroblasts

Journal Article Fibrinolysis · January 1, 1996 Streptokinase (SK), a potent non-proteolytic plasminogen (Pg) activator, binds to synovial fibroblasts derived from patients with rheumatoid arthritis(RA) at very high affinity (Kd= 77 nM) either directly or via a complex with Pg. By contrast, SK does not ... Full text Cite

Activated alpha 2-macroglobulin promotes mitogenesis in rat vascular smooth muscle cells by a mechanism that is independent of growth-factor-carrier activity.

Journal Article Eur J Biochem · December 15, 1995 Vascular smooth muscle cell (vSMC) proliferation is important in atherosclerosis. We previously demonstrated that methylamine-activated alpha 2-macroglobulin (alpha 2M) and transforming growth factor beta 1 (TGF-beta 1) cause a synergistic proliferative re ... Full text Link to item Cite

Ligation of the alpha 2-macroglobulin signalling receptor on macrophages induces protein phosphorylation and an increase in cytosolic pH.

Journal Article Biochem J · July 1, 1995 We have recently described an alpha 2-macroglobulin (alpha 2M) signalling receptor which is distinct from the low-density lipoprotein-related protein/alpha 2M receptor (LRP/alpha 2MR). Ligation of the macrophage signalling receptor by alpha 2M-methylamine ... Full text Link to item Cite

Sodium dodecyl sulfate-stable complexes between serpins and active or inactive proteinases contain the region COOH-terminal to the reactive site loop.

Journal Article J Biol Chem · June 23, 1995 Recently inhibitors of the serpin family were shown to form complexes with dichloroisocoumarine (DCI)-inactivated proteinases under native conditions (Enghild, J. J., Valnickova, Z., Thøgersen I., and Pizzo, S. V. (1994) J. Biol. Chem. 269, 20159-20166). T ... Full text Link to item Cite

Specific binding of urinary-type plasminogen activator (u-PA) to vitronectin and its role in mediating u-PA-dependent adhesion of U937 cells.

Journal Article Biochem J · May 1, 1995 The present paper described interactions of urinary-type plasminogen activator (u-PA) with isolated protein components of the extracellular matrix (ECM) using kinetic and ligand-blotting analyses, as well as adhesion studies with u-PA-saturated U937 monocy ... Full text Link to item Cite

Sialic acid content of plasminogen 2 glycoforms as a regulator of fibrinolytic activity. Isolation, carbohydrate analysis, and kinetic characterization of six glycoforms of plasminogen.

Journal Article J Biol Chem · March 17, 1995 Six glycoforms of plasminogen 2 were isolated using a combination of lectin affinity chromatography and chromatofocussing, and the sialic acid content of each glycoform was determined. The kinetics of activation of each glycoform by tissue-type plasminogen ... Full text Link to item Cite

alpha 1-Microglobulin destroys the proteinase inhibitory activity of alpha 1-inhibitor-3 by complex formation.

Journal Article J Biol Chem · March 3, 1995 The immunoregulatory plasma protein alpha 1-microglobulin (alpha 1-m) and the proteinase inhibitor alpha 1-inhibitor-3 (alpha 1I3) form a complex in rat plasma. In the present work, it was demonstrated that the alpha 1I3.alpha 1-m complex has no inhibitory ... Full text Link to item Cite

Oxidized low density lipoprotein suppresses activation of NF kappa B in macrophages via a pertussis toxin-sensitive signaling mechanism.

Journal Article J Biol Chem · February 24, 1995 The interaction of oxidized low density lipoprotein (ox-LDL) and macrophages is generally believed to be a significant inductive step in atherogenesis. Endocytosis of ox-LDL by scavenger receptors (SR) on macrophages is one result of this interaction, as i ... Full text Link to item Cite

A plasma membrane-associated component of ovarian adenocarcinoma cells enhances the catalytic efficiency of matrix metalloproteinase-2.

Journal Article J Biol Chem · January 20, 1995 Several recent investigations have demonstrated that matrix metalloproteinase-2 (MMP-2) binds to the cell surface and undergoes zymogen activation via a plasma membrane-associated activity. The purpose of this study was to determine if association of MMP-2 ... Full text Link to item Cite

Lipoprotein (a) in the regulation of fibrinolysis.

Journal Article J Atheroscler Thromb · 1995 Elevated plasma levels of lipoprotein(a) [LP(a)] are associated with increased an risk of developing atherosclerosis. This increased risk may be due to an Lp(a)-mediated depression of fibrinolytic activity. Lp(a) regulates fibrinolysis by controlling the a ... Full text Link to item Cite

α1-Microglobulin destroys the proteinase inhibitory activity of α1-inhibitor-3 by complex formation

Journal Article Journal of Biological Chemistry · 1995 The immunoregulatory plasma protein α1-microglobulin (α1-m) and the proteinase inhibitor α1-inhibitor-3 (α1I3) form a complex in rat plasma. In the present work, it was demonstrated that the α1I3·α1-m complex has no inhibitory activity, the bait region was ... Cite

Comparison of plasminogen binding and activation on extracellular matrices produced by vascular smooth muscle and endothelial cells.

Journal Article Eur J Biochem · December 15, 1994 Plasminogen is the zymogen form of the serine proteinase plasmin. Although plasmin functions primarily as a fibrinolytic enzyme, recent evidence from numerous laboratories indicates that plasmin is also active in extracellular-matrix (ECM) proteolysis. The ... Full text Link to item Cite

Life-long bleeding diathesis: effect of orthotopic liver transplantation.

Journal Article Am J Clin Pathol · December 1994 Proper regulation of the fibrinolytic system is critical to the prevention of both thrombosis and hemorrhage. Patients with inherited or acquired excess fibrinolysis may have a bleeding tendency, usually characterized by delayed and posttrauma or postopera ... Full text Link to item Cite

Alpha 2-macroglobulin: a sensor for proteolysis.

Journal Article Ann N Y Acad Sci · September 10, 1994 Full text Link to item Cite

Complexes between serpins and inactive proteinases are not thermodynamically stable but are recognized by serpin receptors.

Journal Article J Biol Chem · August 5, 1994 The serpin mechanism of action may resemble the "standard mechanism" described for small protein inhibitors of serine proteinases. Since these inhibitors are able to bind active site-modified target proteinases, we have investigated the interactions betwee ... Link to item Cite

The relationship between low density lipoprotein-related protein/alpha 2-macroglobulin (alpha 2M) receptors and the newly described alpha 2M signaling receptor.

Journal Article J Biol Chem · July 15, 1994 alpha 2-Macroglobulin (alpha 2M)-methylamine binding to macrophages appears to involve two receptors. Binding of alpha 2M-methylamine to low density lipoprotein-related protein (LRP) results in cellular uptake and degradation, while binding to a newly desc ... Link to item Cite

Coordinate expression of urinary-type plasminogen activator and its receptor accompanies malignant transformation of the ovarian surface epithelium.

Journal Article Am J Obstet Gynecol · May 1994 OBJECTIVE: Because elevated expression and cell surface association of urinary-type plasminogen activator have been linked to invasive potential in certain tumor types, we examined the expression of urinary-type plasminogen activator and urinary-type plasm ... Full text Link to item Cite

Evidence for a second alpha 2-macroglobulin receptor.

Journal Article J Biol Chem · April 29, 1994 alpha 2-Macroglobulin (alpha 2M)-methylamine binds to purified low density lipoprotein receptor-related protein (LRP), and it is assumed that LRP functions as the alpha 2M receptor in vivo. Binding of alpha 2M-methylamine to macrophage receptors elevates i ... Link to item Cite

Secretion of extracellular matrix-degrading proteinases is increased in epithelial ovarian carcinoma.

Journal Article Int J Cancer · February 15, 1994 The biochemical events associated with tumor invasion involve localized degradation of the basement membrane by tumor-associated proteinases. In this study, we have characterized the proteinase secretion profiles of 5 ovarian epithelial carcinoma cell line ... Full text Link to item Cite

The effect of substituted laminin A chain-derived peptides on the conformation and activation kinetics of plasminogen.

Journal Article Arch Biochem Biophys · February 15, 1994 Conversion of the zymogen plasminogen (Pg) to the active enzyme plasmin is catalyzed by proteinases such as tissue-type plasminogen activator (t-PA). Interaction of Pg with small ligands such as lysine or macromolecular ligands such as fibrin induces a dra ... Full text Link to item Cite

Adjuvant-free in vivo targeting. Antigen delivery by alpha 2-macroglobulin enhances antibody formation.

Journal Article J Immunol · February 15, 1994 The proteinase "inhibitor" alpha 2-macroglobulin (alpha 2M) is able to entrap and form covalent linkages with diverse proteins during a transient proteinase-activated state. These complexes are rapidly endocytosed after binding to receptors present on macr ... Link to item Cite

Characterization of the plasminogen receptors of normal and rheumatoid arthritis human synovial fibroblasts.

Journal Article J Biol Chem · February 11, 1994 Plasminogen (Pg) activation on the surface of rheumatoid arthritis (RA) synovial fibroblasts by the urinary-type Pg activator induced a significant increase in cytosolic free Ca2+ concentration. This response was not observed in normal synovial fibroblasts ... Link to item Cite

Oxidative dissociation of human alpha 2-macroglobulin tetramers into dysfunctional dimers.

Journal Article J Biol Chem · February 11, 1994 Human alpha 2-macroglobulin is a broad-spectrum, homotetrameric antiproteinase that can maximally bind up to two proteinase molecules in a ternary complex. Proteinases cleave the inhibitor within a peptide stretch termed the bait region and induce the emer ... Link to item Cite

Lipoprotein (a) regulates plasmin generation and inhibition.

Journal Article Chem Phys Lipids · January 1994 The relationship between lipoprotein (a) (Lp(a)) and atherosclerosis has been appreciated for a number of years. Only in recent years, however, has the structural relationship of Lp(a) to plasminogen resulted in studies of the effect of this lipoprotein on ... Full text Link to item Cite

Heparin as an hyperbolic modulator of plasminogen activation by t-PA

Journal Article Fibrinolysis and Proteolysis · January 1, 1994 The effect of heparin on plasminogen activation, by t-PA, was re-exmamined using the Botts-Morales scheme for hyperbolic modulation. The modulation was found to be either positive, negative or non-existent depending on the presence of fibrin and the concen ... Full text Cite

The physiologic role of antithrombin III as an anticoagulant

Journal Article Seminars in Hematology · January 1, 1994 Cite

Plasminogen activation stimulates an increase in intracellular calcium in human synovial fibroblasts.

Journal Article J Biol Chem · October 5, 1993 Both plasminogen (Pg) and urinary-type Pg activator (u-PA), but not tissue-type Pg activator (t-PA), bind to normal and rheumatoid arthritis (RA) human synovial fibroblasts in culture with high affinity and in a dose-dependent manner. Single cell intracell ... Link to item Cite

The extracellular matrix proteins laminin and fibronectin contain binding domains for human plasminogen and tissue plasminogen activator.

Journal Article J Biol Chem · September 5, 1993 This study describes the binding of plasminogen and tissue-type plasminogen activator (t-PA) to the extracellular matrix proteins fibronectin and laminin. Plasminogen bound specifically and saturably to both fibronectin and laminin immobilized on microtite ... Link to item Cite

Modulation of tissue plasminogen activator-catalyzed plasminogen activation by synthetic peptides derived from the amino-terminal heparin binding domain of fibronectin.

Journal Article J Biol Chem · September 5, 1993 Fibronectin is a multidomain adhesive glycoprotein found in plasma, interstitial connective tissue, and basement membrane. Diverse biological activities have been associated with the fibronectin molecule including cell adhesion, cell migration, wound heali ... Link to item Cite

An examination of the inhibitory mechanism of serpins by analysing the interaction of trypsin and chymotrypsin with alpha 2-antiplasmin.

Journal Article Biochem J · May 1, 1993 Human alpha 2-antiplasmin (alpha 2-AP) has previously been shown to possess overlapping inhibitory sites for trypsin and chymotrypsin [Potempa, Shieh and Travis (1988) Science 241, 699-700]. Since this is currently unique among active-site-directed inhibit ... Full text Link to item Cite

Modulation of murine B16F10 melanoma plasminogen activator production by a synthetic peptide derived from the laminin A chain.

Journal Article Cancer Res · May 1, 1993 Laminin is a large multidomain protein with diverse biological activities. We previously demonstrated that intact laminin as well as an A chain synthetic peptide (LamA2091-2108) stimulate tissue plasminogen activator (t-PA)-catalyzed plasminogen activation ... Link to item Cite

Presence of the protein-glycosaminoglycan-protein covalent cross-link in the inter-alpha-inhibitor-related proteinase inhibitor heavy chain 2/bikunin.

Journal Article J Biol Chem · April 25, 1993 HC2/bikunin is a human plasma proteinase inhibitor composed of two polypeptide chains that resist dissociation under reducing conditions in SDS-polyacrylamide gel electrophoresis. This observation suggests that a nondisulfide cross-link is responsible for ... Link to item Cite

Electron microscopy studies of alpha 2-macroglobulin subunit association after limited reduction with dithiothreitol.

Journal Article Arch Biochem Biophys · April 1993 The subunits of human alpha 2-macroglobulin (alpha 2M) were dissociated by treatment with reductant (0.5 mM dithiothreitol) under mild conditions. Intact tetramers, half-molecules (subunit dimers), and monomers were identified by chromatography on Superose ... Full text Link to item Cite

Receptor-recognized alpha 2-macroglobulin-methylamine elevates intracellular calcium, inositol phosphates and cyclic AMP in murine peritoneal macrophages.

Journal Article Biochem J · March 15, 1993 Human plasma alpha 2-macroglobulin (alpha 2M) is a tetrameric proteinase inhibitor, which undergoes a conformational change upon reaction with either a proteinase or methylamine. As a result, a receptor recognition site is exposed on each subunit of the mo ... Full text Link to item Cite

Identification of monomeric alpha-macroglobulin proteinase inhibitors in birds, reptiles, amphibians and mammals, and purification and characterization of a monomeric alpha-macroglobulin proteinase inhibitor from the American bullfrog Rana catesbeiana.

Journal Article Biochem J · February 15, 1993 The alpha-macroglobulins are classified as broad-spectrum inhibitors because of their ability to entrap proteinases of different specificities and catalytic class. Tetrameric and dimeric alpha-macroglobulins have been identified in a wide variety of organi ... Full text Link to item Cite

Streptokinase and human fibronectin share a common epitope: implications for regulation of fibrinolysis and rheumatoid arthritis.

Journal Article Biochim Biophys Acta · January 22, 1993 Rheumatoid arthritis is a disease characterized by a destructive inflammatory process in joints. Fibronectin (FN) is present at a high concentration in rheumatoid synovial tissue and it is a chemoattractant for inflammatory cells. FN fragments also play si ... Full text Link to item Cite

Protein-glycosaminoglycan-protein Covalent Cross-link in Heavy Chain 2-Bikunin

Journal Article Trends in Glycoscience and Glycotechnology · January 1, 1993 Full text Cite

Receptor-mediated antigen delivery into macrophages. Complexing antigen to alpha 2-macroglobulin enhances presentation to T cells.

Journal Article J Immunol · January 1, 1993 Macrophages secrete alpha 2-macroglobulin (alpha 2M), a protein that may facilitate early Ag handling. alpha 2M is able to entrap and form covalent linkages with diverse proteins during a transient proteinase-activated state. The resulting complexes are ra ... Link to item Cite

Expression of a functional alpha-macroglobulin receptor binding domain in Escherichia coli.

Journal Article FEBS Lett · November 23, 1992 We have expressed receptor-binding domains of human alpha 2-macroglobulin and rat alpha 1-macroglobulin in Escherichia coli. Expression levels of both recombinants were quite high, but the human one was insoluble, probably forming inclusion bodies. The rat ... Full text Link to item Cite

Why is lipoprotein(a) relevant to thrombosis?

Journal Article Am J Clin Nutr · October 1992 Full text Link to item Cite

Lipoprotein (a) promotes plasmin inhibition by alpha 2-antiplasmin.

Journal Article Biochem J · August 15, 1992 Plasmin inhibition by alpha 2-antiplasmin (alpha 2AP) is regulated by the vascular components fibrin(ogen) fragments, plasminogen and lipoprotein (a). Kinetic analysis demonstrates that CNBr-derived fibrinogen fragments completely protect plasmin from alph ... Full text Link to item Cite

Ionic modulation of the effects of heparin on plasminogen activation by tissue plasminogen activator: the effects of ionic strength, divalent cations, and chloride.

Journal Article Arch Biochem Biophys · August 1, 1992 Ionic strength, divalent cations, and Cl- modulate the ability of the glycosaminoglycan heparin to stimulate the activation of human plasminogen (Pg) by tissue-type Pg activator. Kinetic analysis of Pg activation indicates that heparin is inhibitory, stimu ... Full text Link to item Cite

Purification and characterization of an alpha-macroglobulin proteinase inhibitor from the mollusc Octopus vulgaris.

Journal Article Biochem J · July 15, 1992 The cell-free haemolymph of the mollusc Octopus vulgaris inhibited the proteolytic activity of the thermolysin against the high-molecular-mass substrate hide powder azure. The purified inhibitor was a glycoprotein composed of two identical 180 kDa disulphi ... Full text Link to item Cite

Binding of human plasminogen to basement-membrane (type IV) collagen.

Journal Article Biochem J · May 15, 1992 Plasminogen, the zymogen form of the serine proteinase plasmin, has been implicated in numerous physiological and pathological processes involving extracellular-matrix remodelling. We have previously demonstrated that the activation of plasminogen catalyse ... Full text Link to item Cite

Effect of desialylation on the biological properties of human plasminogen.

Journal Article Biochem J · May 15, 1992 There are two major isoenzymes of plasminogen (Pg) in human plasma, designated Pg1 and Pg2. Both Pg forms have an identical primary structure, but differ in their extent of glycosylation. Removal of the oligosaccharide chains alters the normal physiologica ... Full text Link to item Cite

Lipoprotein(a) inhibits plasminogen activation in a template-dependent manner.

Journal Article Blood Coagul Fibrinolysis · December 1991 Lipoprotein(a) [Lp(a)] is a low density lipoprotein whose plasma levels strongly correlate with the occurrence of atherosclerotic disease. Structural studies have demonstrated that Lp(a) contains two disulphide bonded subunits, one of which has structural ... Full text Link to item Cite

Heparin oligosaccharides enhance tissue-type plasminogen activator: a correlation between oligosaccharide length and stimulation of plasminogen activation.

Journal Article Biochemistry · November 12, 1991 The rate of plasminogen (Pg) activation by tissue-type Pg activator (t-PA) is enhanced by heparin-derived oligosaccharides. Kinetic analysis of the effects of heparin oligosaccharides, ranging in size from di- to dodecasaccharides, on Pg activation demonst ... Full text Link to item Cite

Kinetics and physiologic relevance of the inactivation of alpha 1-proteinase inhibitor, alpha 1-antichymotrypsin, and antithrombin III by matrix metalloproteinases-1 (tissue collagenase), -2 (72-kDa gelatinase/type IV collagenase), and -3 (stromelysin).

Journal Article J Biol Chem · August 25, 1991 Serpins encompass a superfamily of proteinase inhibitors that regulate many of the serine proteinases involved in inflammation and hemostasis. In vitro, many serpins are catalytically inactivated by proteinases that they do not inhibit, leading to the conc ... Link to item Cite

The exposure of murine macrophages to alpha 2-macroglobulin 'fast' forms results in the rapid secretion of eicosanoids.

Journal Article Biochim Biophys Acta · July 10, 1991 The exposure of [3H]arachidonate-radiolabelled murine peritoneal macrophages to alpha 2-macroglobulin-methylamine or alpha 2-macroglobulin-trypsin but not native alpha 2-macroglobulin (alpha 2M) results in the rapid secretion of [3H]eicosanoids. Resident p ... Full text Link to item Cite

Limited proteolysis of the alpha-macroglobulin rat alpha 1-inhibitor-3. Implications for a domain structure.

Journal Article J Biol Chem · June 15, 1991 Rat alpha 1-inhibitor-3 is a 180-kDa monomeric proteinase inhibitor found in high concentration in rat plasma. By several criteria it has been shown to be a member of the family of alpha-macroglobulin proteinase inhibitors often exemplified by the tetramer ... Link to item Cite

Kinetic analysis of the effects of glycosaminoglycans and lipoproteins on urokinase-mediated plasminogen activation.

Journal Article Biochem J · June 15, 1991 The glycosaminoglycans (GAGs) heparin, heparan sulphate and chondroitin 6-sulphate stimulate the rate of urokinase activation of human plasminogen. Kinetic analysis of plasminogen activation demonstrates that heparin, heparan sulphate and chondroitin 6-sul ... Full text Link to item Cite

Plasmin binding to the plasminogen receptor enhances catalytic efficiency and activates the receptor for subsequent ligand binding.

Journal Article Arch Biochem Biophys · May 1, 1991 Specific cell surface receptors for plasminogen (Pg) are expressed by a wide variety of cell types. The colocalization of receptors for Pg and its activators restricts plasmin (Pm) activity to specific sites and serves to promote fibrinolysis and local Pg ... Full text Link to item Cite

The inhibition of tissue type plasminogen activator by plasminogen activator inhibitor-1. The effects of fibrinogen, heparin, vitronectin, and lipoprotein(a).

Journal Article J Biol Chem · April 25, 1991 Plasminogen activator inhibitor-1 (PAI-1) regulates fibrinolysis by inhibiting tissue type plasminogen activator (t-PA). Fibrinogen, heparin, and vitronectin enhance the rate of inhibition of t-PA by PAI-1. Kinetic studies indicate that both fibrinogen and ... Link to item Cite

Modulation of plasminogen activation and type IV collagenase activity by a synthetic peptide derived from the laminin A chain.

Journal Article Biochemistry · February 26, 1991 Laminin is a large multidomain glycoprotein with diverse biological activities which include stimulation of neurite outgrowth, enhancement of tumor metastasis, and promotion of cell growth, adhesion, and differentiation. A 19 amino acid synthetic peptide d ... Full text Link to item Cite

Characterization of human alpha 2-macroglobulin monomers obtained by reduction with dithiothreitol.

Journal Article Biochemistry · February 12, 1991 We compared the physicochemical characteristics of alpha 2-macroglobulin (alpha 2M) monomers produced by limited reduction and carboxamidomethylation to those of the naturally occurring monomeric alpha-macroglobulin homologue rat alpha 1-inhibitor 3 (alpha ... Full text Link to item Cite

Analysis of the plasma elimination kinetics and conformational stabilities of native, proteinase-complexed, and reactive site cleaved serpins: comparison of alpha 1-proteinase inhibitor, alpha 1-antichymotrypsin, antithrombin III, alpha 2-antiplasmin, angiotensinogen, and ovalbumin.

Journal Article Biochemistry · February 12, 1991 Proteinase inhibitors of the serpin superfamily may exist in one of three distinct conformations: the native form, a fully active protein with the reactive site loop intact; the proteolytically modified form in which inhibitory capacity is abolished; and t ... Full text Link to item Cite

Mechanism of insulin incorporation into alpha 2-macroglobulin: implications for the study of peptide and growth factor binding.

Journal Article Biochemistry · February 12, 1991 In recent years, many studies have suggested a direct role for alpha 2-macroglobulin (alpha 2M), a plasma proteinase inhibitor, in growth factor regulation. When coincubated in the presence of either trypsin, pancreatic elastase, human neutrophil elastase, ... Full text Link to item Cite

Chondroitin 4-sulfate covalently cross-links the chains of the human blood protein pre-alpha-inhibitor.

Journal Article J Biol Chem · January 15, 1991 The human blood protein pre-alpha-inhibitor is composed of one heavy and one light protein chain. The chains are covalently linked to each other by a structure that has not previously been described, which we designate a protein-glycosaminoglycan-protein ( ... Link to item Cite

Releasable tissue plasminogen activators in ischemic stroke.

Journal Article J Stroke Cerebrovasc Dis · 1991 To determine if patients who suffer atherothrombotic ischemic stroke have altered release of tissue plasminogen activator (t-PA), we measured levels in 22 patients within 24 h of onset of symptoms and 1-2 months later. t-PA levels were measured in blood sa ... Full text Link to item Cite

The effect of divalent cations on the conformation and function of human plasminogen.

Journal Article Arch Biochem Biophys · January 1991 The activation of native human plasminogen (Glu1-Pg) by tissue plasminogen activator, urinary plasminogen activator (u-PA), and streptokinase is inhibited by the divalent cations Ca2+, Mg2+, and Mn2+. This inhibition is accompanied by a conformational chan ... Full text Link to item Cite

Preparation, in vivo properties and proposed clinical use of polyoxyethylene-modified tissue plasminogen activator and streptokinase

Journal Article Advanced Drug Delivery Reviews · January 1, 1991 Fibrinolytic agents such as tissue plasminogen activator (tPA) and streptokinase (SK) are important drugs for the treatment of thromboembolic disease including myocardial infarction. Both agents show short half-lives and, since it is a bacterial protein, S ... Full text Cite

Lipoprotein (a): The link between impaired fibrinolysis and atherosclerosis

Journal Article Fibrinolysis and Proteolysis · January 1, 1991 Full text Cite

Regulation of tissue plasminogen activator in sickle cell anemia.

Journal Article Am J Hematol · November 1990 Evidence of activation of the clotting system in individuals with sickle cell anemia (SCA) has been observed by several investigators. It has been suggested that the clotting and fibrinolytic systems may play a role in the pathophysiology of vaso-occlusion ... Full text Link to item Cite

Alpha-macroglobulin from Limulus polyphemus exhibits proteinase inhibitory activity and participates in a hemolytic system.

Journal Article Biochemistry · October 30, 1990 Significant primary sequence homology between the alpha-macroglobulin family of proteinase inhibitors and the complement components C3, C4, and C5 implies that these proteins arose from a common ancestor. Hemolymph from the ancient invertebrate Limulus pol ... Full text Link to item Cite

The role of carbohydrate in the function of human plasminogen: comparison of the protein obtained from molecular cloning and expression in Escherichia coli and COS cells.

Journal Article Biochim Biophys Acta · July 6, 1990 A cDNA library was constructed in the phage lambda gt11 from human liver mRNA enriched for plasminogen mRNA by chromatography on Sepharose 4B. A full-length cDNA clone of human plasminogen was isolated. The 2.7 kb cDNA encoded the entire plasminogen molecu ... Full text Link to item Cite

Catabolism of streptokinase and polyethylene glycol-streptokinase: evidence for transport of intact forms through the biliary system in the mouse.

Journal Article Blood · July 1, 1990 The catabolism of streptokinase (SK) and polyethylene glycol derivatives of SK (PEG-SK) were studied in mice. The clearance and catabolism of SK:plasmin (SK:Pm) and PEG-SK:Pm activator complexes were also investigated. Native 125I-SK cleared rapidly (t1/2 ... Link to item Cite

Neonatal plasminogen displays altered cell surface binding and activation kinetics. Correlation with increased glycosylation of the protein.

Journal Article J Clin Invest · July 1990 Plasminogen isolated from 60 full-term newborns differs from adult plasminogen in carbohydrate composition, kinetic activation constants, and cell binding. Amino acid composition and amino-terminal sequence analysis data indicate that the plasminogens of n ... Full text Link to item Cite

Evaluation of the rapid plasma elimination of recombinant alpha 1-proteinase inhibitor: synthesis of polyethylene glycol conjugates with improved therapeutic potential.

Journal Article J Lab Clin Med · July 1990 Plasma-derived alpha 1-proteinase inhibitor (alpha 1PlI) is used for replacement therapy in patients with emphysema who have a deficiency of the protein. Future therapy with alpha 1PI with reactive site mutants of this inhibitor will probably require the u ... Link to item Cite

Kinetic analysis of the effects of heparin and lipoproteins on tissue plasminogen activator mediated plasminogen activation.

Journal Article Biochemistry · June 26, 1990 Heparin sulfate and the less sulfated glycosaminoglycan heparan sulfate enhance human plasminogen (Pg) conversion to plasmin by tissue-type plasminogen activator (t-PA). Kinetic studies indicate that both heparin and heparan increase the kcat of t-PA-media ... Full text Link to item Cite

Regulation of plasminogen activation by components of the extracellular matrix.

Journal Article Biochemistry · May 22, 1990 The kinetics of activation of Glu-plasminogen (Glu-Pg) and Lys77-Pg by two-chain recombinant tissue plasminogen activator (t-PA) were determined in the presence of isolated protein components of the extracellular matrix (ECM) and compared to activation in ... Full text Link to item Cite

Effect of interferon-gamma and human alpha 2-macroglobulin on peritoneal macrophage morphology and Ia antigen expression.

Journal Article Biochim Biophys Acta · February 19, 1990 While the primary role of the plasma protein alpha 2-macroglobulin (alpha 2M) appears to be related to its proteinase inhibitory activity, alpha 2M has been reported to regulate the immune response in vitro. Previous studies have demonstrated that, althoug ... Full text Link to item Cite

Papillary adenocarcinoma of the renal pelvis in a child: case report and brief review of the literature.

Journal Article Med Pediatr Oncol · 1990 Tumors of the renal pelvis are not common in adults and are extremely rare in children. Forty-eight cases of adenocarcinoma of the renal pelvis have been reported, with only one patient under 32 years of age. We report the youngest patient (an 11 year old ... Full text Link to item Cite

Analysis of inter-alpha-trypsin inhibitor and a novel trypsin inhibitor, pre-alpha-trypsin inhibitor, from human plasma. Polypeptide chain stoichiometry and assembly by glycan.

Journal Article J Biol Chem · September 25, 1989 The polypeptide chain composition of protein material referred to in the literature as "inter-alpha-trypsin inhibitor" was investigated. The material was found to consist of distinct proteins of 125,000 and 225,000 Da, each of which contained more than one ... Link to item Cite

Independent analysis of bait region cleavage dependent and thiolester bond cleavage dependent conformational changes by cross-linking of alpha 2-macroglobulin with cis-dichlorodiammineplatinum(II) and dithiobis(succinimidyl propionate).

Journal Article Biochemistry · September 19, 1989 Treatment of the human plasma proteinase inhibitor alpha 2-macroglobulin (alpha 2M) with proteinase results in conformational changes in the inhibitor and subsequent activation and cleavage of the internal thiolester bonds of alpha 2M. Previous studies fro ... Full text Link to item Cite

Serpin receptor 1: a hepatic receptor that mediates the clearance of antithrombin III-proteinase complexes.

Journal Article Am J Med · September 11, 1989 Antithrombin III (ATIII) clearance from blood occurs by redistribution into the extravascular compartment and by binding to the endothelial surface. When, however, ATIII reacts with a proteinase such as alpha-thrombin, the complex is rapidly cleared from t ... Full text Link to item Cite

Functional inactivation and structural disruption of human alpha 2-macroglobulin by neutrophils and eosinophils.

Journal Article J Biol Chem · August 15, 1989 Human alpha 2-macroglobulin (alpha 2M) rapidly lost functional and structural integrity in the course of a short-term incubation with either triggered neutrophils or eosinophils. In contrast to native alpha 2M, the modified antiproteinase was unable to bin ... Link to item Cite

Proteinase binding and inhibition by the monomeric alpha-macroglobulin rat alpha 1-inhibitor-3.

Journal Article J Biol Chem · July 5, 1989 The inhibitory capacity of the alpha-macroglobulins resides in their ability to entrap proteinase molecules and thereby hinder the access of high molecular weight substrates to the proteinase active site. This ability is thought to require at least two alp ... Link to item Cite

Elevated urokinase-type plasminogen activator level and bleeding in amyloidosis: case report and literature review.

Journal Article Am J Hematol · May 1989 Hyperfibrinolytic states are reported to be a cause of bleeding in patients with amyloidosis. We reviewed the literature on excessive fibrinolysis in association with amyloidosis and report our findings from a patient with idiopathic amyloidosis who develo ... Full text Link to item Cite

Lipoprotein a inhibits streptokinase-mediated activation of human plasminogen.

Journal Article Biochemistry · March 21, 1989 Lipoprotein a [Lp(a)] inhibits human plasminogen (Pg) conversion to plasmin (Pm) by streptokinase- (SK-) mediated activation. Kinetic and binding studies indicate that Lp(a) inhibits Pg activation by competitive and uncompetitive inhibition. Lp(a) competes ... Full text Link to item Cite

Further characterization of the cellular plasminogen binding site: evidence that plasminogen 2 and lipoprotein a compete for the same site.

Journal Article Biochemistry · March 21, 1989 Specific cell surface receptors for plasminogen (Pg) are expressed by a wide variety of cell types and serve to promote fibrinolysis and local Pg proteolysis. Pg types 1 and 2, separated by chromatography on concanavalin A-Sepharose, were utilized to deter ... Full text Link to item Cite

A conserved region in alpha-macroglobulins participates in binding to the mammalian alpha-macroglobulin receptor.

Journal Article Biochemistry · February 7, 1989 Efforts to characterize the receptor recognition domain of alpha-macroglobulins have primarily focused on human alpha 2-macroglobulin (alpha 2M). In the present work, the structure and function of the alpha-macroglobulin receptor recognition site were inve ... Full text Link to item Cite

Inflammatory cells degrade inter-alpha inhibitor to liberate urinary proteinase inhibitors.

Journal Article J Leukoc Biol · January 1989 The relationship between inter-alpha inhibitor (I alpha I) and urinary proteinase inhibitor (UPI) was examined by comparing purified UPI with a proteolytic fragment of I alpha I (I'), and by demonstrating that inflammatory cells produce similar fragments u ... Full text Link to item Cite

Comparison of α2-macroglobulin receptors from human, baboon, rat and mouse liver

Journal Article Biochemical Archives · January 1, 1989 Cite

Alpha 2 macroglobulin-proteinase complexes stimulate prostaglandin E2 synthesis by peritoneal macrophages.

Journal Article Agents Actions · December 1988 alpha 2-Macroglobulin is a proteinase inhibitor which is converted from its native form into an electrophoretically "fast" form by reaction with a proteinase or methylamine. All alpha 2M "fast" forms bind to a specific high-affinity receptor on macrophages ... Full text Link to item Cite

In vivo catabolism of alpha 1-antichymotrypsin is mediated by the Serpin receptor which binds alpha 1-proteinase inhibitor, antithrombin III and heparin cofactor II.

Journal Article Biochim Biophys Acta · November 17, 1988 The in vivo catabolism of 125I-labeled alpha 1-antichymotrypsin was studied in our previously described mouse model. Native alpha 1-antichymotrypsin cleared with an apparent t1/2 of 85 min, but alpha 1-antichymotrypsin in complex with chymotrypsin or cathe ... Full text Link to item Cite

Analysis of thiolester bond cleavage-dependent conformational changes in binary alpha 2-macroglobulin-proteinase complexes.

Journal Article Arch Biochem Biophys · November 15, 1988 The structures of the two proteinase-binding sites in human alpha 2-macroglobulin (alpha 2M) were probed by treatment of alpha 2M with the serine proteinases thrombin and plasmin. Each proteinase forms an equimolar complex with alpha 2M (a binary alpha 2M- ... Full text Link to item Cite

Primary undifferentiated sarcoma of the thoracic aorta.

Journal Article Histopathology · November 1988 A case of a primary undifferentiated sarcoma of the descending thoracic aorta in a 75-year-old man is reported. Intraluminal growth and occlusion produced congestive heart failure and renal failure. The thoracic aorta was relatively normal on chest radiogr ... Full text Link to item Cite

Symmetry of the inhibitory unit of human alpha 2-macroglobulin.

Journal Article Biochemistry · October 4, 1988 Human alpha 2-macroglobulin (alpha 2M) of Mr approximately 720,000 is a proteinase inhibitor whose four identical subunits are arranged to form two adjacent inhibitory units. At present, the spatial arrangement of the two subunits which form one inhibitory ... Full text Link to item Cite

Defective release of tissue plasminogen activator in patients with sickle cell anemia.

Journal Article Am J Hematol · September 1988 Recent studies suggest that intravascular coagulation occurs in sickle cell anemia. There is also some evidence that decreased fibrinolytic activity may be associated with the disorder. In the current study we measured tissue plasminogen activator levels ( ... Full text Link to item Cite

Modification of the tandem reactive centres of human inter-alpha-trypsin inhibitor with butanedione and cis-dichlorodiammineplatinum(II).

Journal Article Biochem J · August 15, 1988 Human inter-alpha-trypsin inhibitor (I alpha I) is a plasma proteinase inhibitor active against cathepsin G, leucocyte elastase, trypsin and chymotrypsin. It owes its broad inhibitory specificity to tandem Kunitz-type inhibitory domains within an N-termina ... Full text Link to item Cite

Electron microscopic identification of exposed plasmin epitopes in alpha 2-macroglobulin-plasmin complex using monoclonal antibody-colloidal gold adducts.

Journal Article J Biol Chem · August 5, 1988 Monoclonal antibodies 10-F-1, directed against the K4 region of plasminogen, and 10-V-1, directed against the K1-3 region of plasminogen, were adducted to colloidal gold. These antibody-gold adducts bound specifically to alpha 2-macroglobulin (alpha 2M)-pl ... Link to item Cite

Preparation of polyethylene glycol-tissue plasminogen activator adducts that retain functional activity: characteristics and behavior in three animal species.

Journal Article Blood · June 1988 Conditions were defined for the derivatization of recombinant tissue plasminogen activator (rt-PA) with polyethylene glycol (PEG) so as to retain functional activity as a possible means of producing a t-PA species with a prolonged circulating lifetime. Der ... Link to item Cite

Use of anti-idiotypic antibodies to establish that monoclonal antibody 7H11D6 binds to the alpha 2-macroglobulin receptor recognition site.

Journal Article J Biol Chem · May 15, 1988 Studies were performed to determine if monoclonal antibody 7H11D6 binds to the region of alpha 2-macroglobulin (alpha 2M) that interacts with cell-surface receptors. F(ab')2 fragments prepared from this antibody delayed the in vivo clearance of alpha 2M-tr ... Link to item Cite

Evidence that the platinum-reactive methionyl residue of the alpha 2-macroglobulin receptor recognition site is not in the carboxyl-terminal receptor binding domain.

Journal Article J Biol Chem · May 15, 1988 Digestion of human alpha 2-macroglobulin-methylamine (alpha 2M-CH3NH2) with papain prior to gel filtration resulted in the resolution of three distinct peaks. The material in peak I (Mr approximately 600,000) and peak II (Mr approximately 55,000) did not h ... Link to item Cite

Selectivity and stereospecificity of the reactions of dichlorodiammineplatinum(II) with three purified plasma proteins.

Journal Article J Inorg Biochem · May 1988 The reactions of cis- and trans-dichlorodiammineplatinum(II) (cis- and trans-DDP) with albumin and two plasma proteinase inhibitors were compared. Reaction with alpha 2-macroglobulin (alpha 2M) resulted in subunit crosslinking and loss of proteinase bindin ... Full text Link to item Cite

The role of endothelium in factor Xa regulation: the effect of plasma proteinase inhibitors and hirudin.

Journal Article Blood · May 1988 The role of endothelium in the inhibition of human factor Xa was studied in a plasma environment. Human factor Xa can bind to and function on bovine aortic endothelium in a manner similar to that of bovine factor Xa. Approximately 70% of the bound factor X ... Link to item Cite

Clearance and distribution of recombinant murine gamma-interferon in mice.

Journal Article Cancer Res · April 15, 1988 Recombinant murine gamma-interferon (rIFN-gamma) was radiolabeled by a novel procedure which does not require the use of preiodinated Bolton-Hunter reagent (specific activities of 0.5-3.0 microCi/micrograms). Gel filtration chromatography of the radiolabel ... Link to item Cite

In vivo catabolism of heparin cofactor II and its complex with thrombin: evidence for a common receptor-mediated clearance pathway for three serine proteinase inhibitors.

Journal Article Arch Biochem Biophys · April 1988 The plasma clearance of 125I-labeled human heparin cofactor II and its complex with thrombin was studied in mice to determine whether a specific mechanism exists for the catabolism of the inhibitor-proteinase complex. Initial studies demonstrated that muri ... Full text Link to item Cite

Methionine sulfoxide and the oxidative regulation of plasma proteinase inhibitors.

Journal Article J Leukoc Biol · April 1988 The sensitivity of methionine residues to oxidation is a mechanism by which many proteins, including plasma proteinase inhibitors, may be oxidatively inactivated. Much evidence suggests that methionine oxidation and concurrent losses of protein activity no ... Full text Link to item Cite

Characterization of the fibrin polymer structure that accelerates thrombin cleavage of plasma factor XIII.

Journal Article Arch Biochem Biophys · April 1988 The effect of plasmin-derived fibrin(ogen) degradation products on alpha-thrombin cleavage of plasma Factor XIII was studied to identify the fibrin polymer structure that promotes Factor XIIIa formation. Fibrin polymers derived from fibrinogen and Fragment ... Full text Link to item Cite

Intersubunit cross-linking by cis-dichlorodiammineplatinum(II) stabilizes an alpha 2-macroglobulin "nascent" state: evidence that thiol ester bond cleavage correlates with receptor recognition site exposure.

Journal Article Biochemistry · January 26, 1988 Treatment of human alpha 2-macroglobulin (alpha 2M) with proteinase results in cleavage of the alpha 2M subunits and subsequently in a conformational change in the inhibitor. This change irreversibly traps the proteinase and is accompanied by the generatio ... Full text Link to item Cite

cis-dichlorodiammineplatinum (II) as a selective modifier of the oxidation-sensitive reactive-center methionine in alpha 1-antitrypsin.

Journal Article J Biol Chem · January 5, 1988 Methionine 358 in the plasma protein alpha 1-antitrypsin (alpha 1AT) is an oxidation-sensitive reactive-center residue critical for proteinase-inhibitory activity. Reaction of alpha 1AT with 20 microM to 1.67 mM cis-dichlorodiammineplatinum (II) (cis-DDP) ... Link to item Cite

Large scale purification of factor X by hydrophobic chromatography.

Journal Article Prep Biochem · 1988 Factor X is a critical enzyme in the blood coagulation cascade, however, in recent years the coagulation zymogen factor X has received additional interest as a selective proteinase to allow production of functional eukaryotic proteins in a prokaryotic expr ... Full text Link to item Cite

Photoreactivation of Irreversibly Inhibited Serine Proteinases

Journal Article Journal of the American Chemical Society · January 1, 1988 The p-amidinophenyl ester of o-hydroxy-α-methylcinnamic acid has been synthesized and characterized. This compound irreversibly inhibits thrombin, Factor Xa, and trypsin. Inhibition by this derivative is, however, reversible (80-100%) upon irradiation of t ... Full text Cite

Carbohydrate recognition systems in amphibians: primitive alpha 2-macroglobulin receptors.

Journal Article Biochem Int · December 1987 Two alpha-macroglobulins were isolated from the plasma of the frog. Murine clearance studies were performed with these proteins after they were reacted with proteinase. These studies indicated that clearance behavior was more complex than observed with avi ... Link to item Cite

The role of inter-alpha-trypsin inhibitor and other proteinase inhibitors in the plasma clearance of neutrophil elastase and plasmin.

Journal Article Arch Biochem Biophys · November 1, 1987 The plasma clearance of neutrophil elastase, plasmin, and their complexes with human inter-alpha-trypsin inhibitor (I alpha I) was examined in mice, and the distribution of the proteinases among the plasma proteinase inhibitors was quantified in mixtures o ... Full text Link to item Cite

Modulation of mouse peritoneal macrophage Ia and human peritoneal macrophage HLA-DR expression by alpha 2-macroglobulin "fast" forms.

Journal Article J Immunol · September 15, 1987 alpha 2-Macroglobulin (alpha 2M) is converted from its native form into electrophoretically "fast" forms by reaction with proteinases or with methylamine. The "fast" forms both bind to specific receptors on macrophages (MP). We have previously shown that a ... Link to item Cite

Effects of bacterial lipopolysaccharide on the hydrolysis of phosphatidylinositol-4,5-bisphosphate in murine peritoneal macrophages.

Journal Article J Immunol · July 15, 1987 LPS and lipid A initiated enhanced hydrolysis of PIP2 in macrophages. When murine peritoneal macrophages were labeled with [2-3H]myoinositol and stimulated with either LPS or lipid A, a rapid (within 10 sec) rise in Ins(1,4,5)P3 was observed. The breakdown ... Link to item Cite

The role of histidyl residues in zinc-induced precipitation of alpha 2-macroglobulin-proteinase complexes.

Journal Article Arch Biochem Biophys · July 1987 When alpha 2-macroglobulin (alpha 2M) is reacted with proteinases including trypsin, plasmin, alpha-thrombin, or with CH3NH2, each resulting alpha 2M derivative is precipitated by Zn2+ in a similar manner. By contrast, unreacted alpha 2M is not precipitate ... Full text Link to item Cite

Mechanism of action of inter-alpha-trypsin inhibitor.

Journal Article Biochemistry · May 19, 1987 Inter-alpha-trypsin inhibitor (I alpha I) is a unique proteinase inhibitor that can be proteolyzed by the same enzymes that are inhibited, to generate smaller inhibitors. This study examines the reactions of I alpha I with trypsin, chymotrypsin, plasmin, a ... Full text Link to item Cite

The temperature-dependent reaction between alpha 2-macroglobulin and streptokinase-plasmin(ogen) complex.

Journal Article J Biol Chem · March 15, 1987 The reactions of alpha 2-macroglobulin (alpha 2M) with plasmin or streptokinase-plasmin(ogen) (SkPl) were studied as a function of temperature. alpha 2M and plasmin reacted relatively rapidly at all temperatures. The initial rates of reaction were identica ... Link to item Cite

Pregnancy-induced changes in the fibrinolytic balance: evidence for defective release of tissue plasminogen activator and increased levels of the fast-acting tissue plasminogen activator inhibitor.

Journal Article Am J Obstet Gynecol · March 1987 Pregnancy is accompanied by an increased risk of thromboembolic disease. One contributing factor to such disease in the nonpregnant patient is disordered fibrinolysis. It has been suggested that defective fibrinolysis may occur in pregnancy, but this defec ... Full text Link to item Cite

Defective release of tissue plasminogen activator in systemic and cutaneous vasculitis.

Journal Article Am J Med · March 1987 The fibrinolytic system in a group of 23 patients with vasculitis and 10 patients with the cutaneous vasculitis atrophie blanche were studied. These patients were found to have markedly suppressed release of vascular tissue plasminogen activator (t-PA) sto ... Full text Link to item Cite

Photochemical Activation of Acylated α-Thrombin

Journal Article Journal of the American Chemical Society · February 1, 1987 Full text Cite

Characterization of alpha 2-macroglobulin-plasmin complexes: complete subunit cleavage alters receptor recognition in vivo and in vitro.

Journal Article Biochemistry · January 27, 1987 When human alpha 2-macroglobulin (alpha 2M) binds proteinases, it undergoes subunit cleavage. Binding of small proteinases such as trypsin results in proteolysis of each of the four subunits of the inhibitor. By contrast, previous studies suggest that reac ... Full text Link to item Cite

Evaluation of p-amidinophenyl esters as potential antithrombotic agents.

Journal Article Thromb Haemost · December 15, 1986 Three p-amidinophenyl esters have been synthesized and characterized as irreversible inhibitors of the vitamin-K dependent proteinases; factors IXa, Xa and thrombin (Turner et al. [4]).+ In the present report we describe the in vitro and in vivo effects of ... Link to item Cite

Partial purification and characterization of a murine glioma-associated antigen defined by syngeneic rat monoclonal antibodies.

Journal Article J Neuroimmunol · December 1986 A glioma-associated antigen was previously identified on an avian sarcoma virus-induced F-344 rat astrocytoma cell line S69-c15 by four rat monoclonal antibodies (7G4, 9F1, 10E3 and 10E7) produced after syngeneic immunization. Earlier data suggested all fo ... Full text Link to item Cite

Specificity of alpha 2-macroglobulin covalent cross-linking for the active domain of proteinases.

Journal Article Biol Chem Hoppe Seyler · November 1986 The reaction of alpha 2-macroglobulin (alpha 2M) with the two-chain enzyme plasma kallikrein results in covalent bond formation between the catalytic subunit and the inhibitor. We have recently published a model of alpha 2M which suggests that this phenome ... Full text Link to item Cite

Oral contraceptives and thromboembolic disease.

Journal Article West J Med · September 1986 Link to item Cite

p-Amidino esters as irreversible inhibitors of factors IXa and Xa and thrombin.

Journal Article Biochemistry · August 26, 1986 A number of inhibitors of thrombin and factor Xa have been described; however, only one inhibitor of factor IXa has been reported. This compound, dansyl-Glu-Gly-Arg chloromethyl ketone (DEGER), inhibits porcine factor IXa with a second-order rate constant ... Full text Link to item Cite

Further characterization of the platinum-reactive component of the alpha 2-macroglobulin-receptor recognition site.

Journal Article Biochem J · August 15, 1986 alpha 2-Macroglobulin (alpha 2M)-methylamine that had been allowed to react with cis-dichlorodiammineplatinum(II) (cis-DDP) bound with greatly reduced affinity to specific alpha 2M receptors, as determined by macrophage binding studies in vitro and plasma- ... Full text Link to item Cite

In vivo metabolism of inter-alpha-trypsin inhibitor and its proteinase complexes: evidence for proteinase transfer to alpha 2-macroglobulin and alpha 1-proteinase inhibitor.

Journal Article Arch Biochem Biophys · August 1, 1986 Inter-alpha-trypsin inhibitor was purified by a modification of published procedures which involved fewer steps and resulted in higher yields. The preparation was used to study the clearance of the inhibitor and its complex with trypsin from the plasma of ... Full text Link to item Cite

A three-dimensional model of a unique proteinase inhibitor: alpha 2-macroglobulin.

Journal Article Semin Thromb Hemost · July 1986 alpha 2-Macroglobulin inhibits many proteinases by a unique mechanism termed "trapping" depicted in Figure 3A,B. This article details a mechanism by which a large proteinase, such as plasmin, binds in a molar ratio between 1 and 2 to 1 proteinase to inhibi ... Full text Link to item Cite

The binding of fucose-containing glycoproteins by hepatic lectins. Re-examination of the clearance from blood and the binding to membrane receptors and pure lectins.

Journal Article J Biol Chem · June 5, 1986 The nature of the hepatic receptors that bind glycoproteins through fucose at the non-reducing termini of oligosaccharides in glycoproteins has been examined by three different approaches. First, the clearance from blood of intravenously injected glycoprot ... Link to item Cite

Atrophie blanche. A disorder associated with defective release of tissue plasminogen activator.

Journal Article Arch Pathol Lab Med · June 1986 Atrophie blanche is a skin disorder characterized by recurrent ulceration and fibrosis. It is one of a group of cutaneous vasculitides associated with decreased blood fibrinolytic activity. We examined pre- and post-venous occlusion plasma from eight patie ... Link to item Cite

Characterization of murine peritoneal macrophage receptors for fibrin(ogen) degradation products.

Journal Article Blood · May 1986 The binding of human fibrinogen degradation fragments D1, E, X, and Y, as well as fibrin fragment D1 dimer, to mouse peritoneal macrophages was examined. A Scatchard plot of fragment D1 binding was biphasic, suggesting two classes of receptors. Fragments D ... Link to item Cite

Purification and characterization of human alpha 2-macroglobulin conformational variants by non-ideal high performance size-exclusion chromatography.

Journal Article Biochem J · April 15, 1986 Human alpha 2-macroglobulin (alpha 2M) was eluted as a single nondispersed peak from a TSK-G4000SW size exclusion chromatography column equilibrated in 20 mM-sodium phosphate/100 mM-NaCl, pH 7.2 (PBS). The void volume and total accessible volume of the col ... Full text Link to item Cite

The macrophage-mediated regulation of hepatocyte synthesis of antithrombin III and alpha 1-proteinase inhibitor.

Journal Article Thromb Res · March 1, 1986 Antithrombin III (ATIII) is an anticoagulant protein which binds and inactivates thrombin and other serine proteinases. Little is known about regulation of its synthesis. We confirm that ATIII is synthesized by isolated rat hepatocytes, and that its synthe ... Full text Link to item Cite

Purification and characterization of a "half-molecule" alpha 2-macroglobulin from the southern grass frog: absence of binding to the mammalian alpha 2-macroglobulin receptor.

Journal Article Biochemistry · February 11, 1986 An alpha-macroglobulin (alpha 2M), which is a dimer consisting of two non-disulfide-bonded subunits, was identified and purified from frog plasma by Ni2+ chelate affinity chromatography. This frog "half-molecule" alpha-macroglobulin migrated as an alpha 2- ... Full text Link to item Cite

Defective release of vascular plasminogen activator in patients with gynecologic malignancies.

Journal Article Gynecol Oncol · February 1986 Vascular plasminogen activator release was measured in 176 women with gynecologic malignancies and 92 normal women. Releasable plasminogen activator was considerably decreased in the patients (P less than 0.00001 by Wilcoxon's rank sum test) with 59.1% rel ... Full text Link to item Cite

The biochemistry of haemostasis.

Journal Article Clin Lab Haematol · 1986 Full text Link to item Cite

Release of tissue plasminogen activator and its fast-acting inhibitor in defective fibrinolysis.

Journal Article Arch Intern Med · January 1986 Releasable tissue plasminogen activator (t-PA) and the fast inhibitor of t-PA were measured in 18 controls and a pedigree with venous thrombosis. The functional assay was performed by a technique that destroys the t-PA inhibitor when blood is drawn. It was ... Link to item Cite

Releasable vascular plasminogen activator and thrombotic strokes.

Journal Article Am J Med · October 1985 Releasable vascular plasminogen activator was measured in 28 patients (14 males and 14 females) with a history of thrombotic strokes documented by computed tomographic scanning. Levels were compared with those in a control population of 126 healthy subject ... Full text Link to item Cite

Model of alpha 2-macroglobulin structure and function.

Journal Article Proc Natl Acad Sci U S A · September 1985 A model of alpha 2-macroglobulin is presented that is compatible with previous structural, functional, and phylogenetic studies of the protein. The model of the molecule resembles a hollow cylinder and is comprised of two identical functional halves with t ... Full text Link to item Cite

Binding and endocytosis of alpha 2-macroglobulin-plasmin complexes.

Journal Article Biochemistry · August 13, 1985 The clearance of 125I-labeled alpha 2-macroglobulin-plasmin complexes (125I-alpha 2M-PM) from mouse circulation is slower than that of 125I-labeled alpha 2M-methylamine complexes (125I-alpha 2M-CH3NH2). In addition, clearance of 125I-alpha 2M-PM is biphasi ... Full text Link to item Cite

Precipitation of fibrinogen, fibrinogen degradation products and fibrin monomer by histone H3.

Journal Article Thromb Res · July 1, 1985 Incubation of histone H3 with normal citrated plasma resulted in the formation of insoluble aggregates, as determined by turbidity measurements. The precipitate was subjected to sodium dodecyl sulfate polyacrylamide gel electrophoresis, confirming that fib ... Full text Link to item Cite

Purification and characterization of frog alpha-macroglobulin: receptor recognition of an amphibian glycoprotein.

Journal Article Biochemistry · May 7, 1985 Frog alpha-macroglobulin was purified to apparent homogeneity by Ni2+ chelate affinity chromatography. Frog alpha-macroglobulin migrated as an alpha 1-globulin in cellulose acetate electrophoresis. A molecular weight of 730 000 was obtained by equilibrium ... Full text Link to item Cite

In vitro preparation of nonenzymatically glucosylated human transferrin, alpha 2-macroglobulin, and fibrinogen with preservation of function.

Journal Article Diabetes · May 1985 Human transferrin, alpha 2-macroglobulin, and fibrinogen were incubated with [3H]-glucose. After a 7-day, 37 degrees C incubation at 20 mM glucose, transferrin incorporated 1.1 mol of glucose/mol protein; alpha 2-macroglobulin, 10 mol of glucose/mol; and f ... Full text Link to item Cite

Binding of alpha 2-macroglobulin to hepatocytes: mechanism of in vivo clearance.

Journal Article Biochem Biophys Res Commun · April 30, 1985 The binding of 125I-labeled human alpha 2-macroglobulin-methylamine to adult rat hepatocytes in primary culture was studied at 4 degrees C. Cells which had been in culture for 4 hours exhibited steady state ligand binding after 1 hour, a receptor number of ... Full text Link to item Cite

In vitro effects of acetaminophen and its analogues on human platelet aggregation and thromboxane B2 synthesis.

Journal Article Thromb Res · April 1, 1985 We examined the effect of acetaminophen and the structural analogues 2,6-dimethylacetaminophen, 3,5-dimethylacetaminophen, and N-acetyl-p-benzoquinone imine on human platelet aggregation, 14C-serotonin secretion, and thromboxane B2 synthesis. Preincubation ... Full text Link to item Cite

Catabolism of human tissue plasminogen activator in mice.

Journal Article Blood · March 1985 The catabolism of human tissue plasminogen activator (t-PA) was studied in mice. The clearance of t-PA labeled with iodine 125 was rapid (t1/2). The clearance of phenylmethylsulfonyl-125I-t-PA, which is active site-inhibited, was identical to the active en ... Link to item Cite

A nonantigenic covalent streptokinase-polyethylene glycol complex with plasminogen activator function.

Journal Article J Clin Invest · February 1985 A series of new, covalent polyethylene glycol (PEG)-streptokinase adducts were synthesized and characterized. PEGs with average molecular weights of 2,000, 4,000, and 5,000 were activated with carbonyldiimidazole and coupled to the protein under standardiz ... Full text Link to item Cite

Trypanosoma brucei gambiense: growth in vitro of bloodstream forms inhibited by dichlorodiammineplatinum (II) compounds and hypolipidemic drugs.

Journal Article Exp Parasitol · February 1985 Infectious bloodstream forms of Trypanosoma brucei gambiense were grown in microcultures of murine bone marrow cells in 96-well tissue culture plates. Limiting dilution studies showed that fewer than 10 cultured trypanosomes developed into populations of a ... Full text Link to item Cite

Immunochemical and biochemical characterization of a glioma-associated extracellular matrix glycoprotein.

Journal Article J Cell Biochem · 1985 A novel human glioma-associated extracellular matrix (ECM) glycoprotein has been identified by murine monoclonal antibody 81C6. The glycoprotein, designated GMEM, is expressed in the ECM of glioma and mesenchymal cell cultures, in the perivascular matrix o ... Full text Link to item Cite

Microassay for the photometric quantitation of cell-associated plasminogen activator using a chromogenic tripeptide substrate.

Journal Article J Immunol Methods · December 31, 1984 Plasminogen activator (PA), a neutral protease whose primary function is to convert plasminogen to plasmin, is produced by various cells including macrophages, monocytes, endothelial cells, and tumor cells. This study reports the use of the chromogenic tri ... Full text Link to item Cite

Fluorescent probes as a measure of conformational alterations induced by nucleophilic modification and proteolysis of bovine alpha 2-macroglobulin.

Journal Article Biochemistry · December 18, 1984 Conformational alterations occurring in bovine alpha 2-macroglobulin (alpha 2M) resulting from proteolysis and nucleophilic modification have been monitored by UV difference spectra, circular dichroism, and changes in the fluorescence of 6-(p-toluidino)-2- ... Full text Link to item Cite

The effect of zinc and other divalent cations on the structure and function of human alpha 2-macroglobulin.

Journal Article Biochim Biophys Acta · December 7, 1984 Zinc binding to human alpha 2-macroglobulin was studied to assess its involvement in the structure and function alpha 2-macroglobulin. Equilibrium dialysis experiments indicated multiple classes of zinc-binding sites, the one of highest affinity having a s ... Full text Link to item Cite

Effects of diethyldithiocarbamate and nine other nucleophiles on the intersubunit protein cross-linking and inactivation of purified human alpha 2-macroglobulin by cis-diamminedichloroplatinum(II).

Journal Article Cancer Res · December 1984 The cross-linking and inactivation of the plasma protein alpha 2-macroglobulin by cis-diamminedichloroplatinum(II) (cisplatin; Gonias, S. L., and Pizzo, S. V. J. Biol. Chem., 256: 12478-12484, 1981) was used to study platinum(II)-protein binding in the pre ... Link to item Cite

Effects of Diethyldithiocarbamate and Nine Other Nucleophiles on the Intersubunit Protein Cross-Linking and Inactivation of Purified Human α2-Macroglobulin by cis-Diamminedichloroplatinum(ll)

Journal Article Cancer Research · December 1, 1984 The cross-linking and inactivation of the plasma protein αz-macroglobulin by cis-diamminedichloroplatinum(ll) (cisplatin; Gonias, S. L., and Pizzo, S. V. J. Biol. Chem., 256: 12478-12484,1981) was used to study platinum(ll)-protein binding in the presence ... Cite

Comparison of the binding of chicken alpha-macroglobulin and ovomacroglobulin to the mammalian alpha 2-macroglobulin receptor.

Journal Article Arch Biochem Biophys · November 15, 1984 Chicken alpha-macroglobulin (alpha M) and ovomacroglobulin were purified by Ni+2 chelate chromatography. These proteins had similar subunit structure as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Chicken alpha M bound 1.0 mol ... Full text Link to item Cite

Circular dichroic spectroscopy of non-human alpha-macroglobulins.

Journal Article Biochem Biophys Res Commun · September 17, 1984 Bovine, chicken and frog alpha-macroglobulins and ovomacroglobulin were studied by circular dichroic spectroscopy over the region 205-250 nm. All four spectra exhibited negative ellipticity with minima at about 215 nm similar to that reported for human alp ... Full text Link to item Cite

Conformation-specific precipitation of human alpha 2-macroglobulin by divalent zinc or calf thymus histone H3.

Journal Article Arch Biochem Biophys · September 1984 Highly purified native alpha 2-macroglobulin (alpha 2M), alpha 2M-trypsin, and alpha 2M-methylamine were compared in experiments designed to study protein precipitation. Significant turbidity developed within 30 min in solutions containing histone H3 and e ... Full text Link to item Cite

Increased releasable vascular plasminogen activator and a bleeding diathesis.

Journal Article Am J Med · September 1984 A 66-year-old man with metastatic prostatic carcinoma treated with high-dose (5 mg) diethylstilbestrol therapy underwent orchiectomy to allow discontinuation of estrogen. An extensive ecchymosis developed postoperatively in an area covered by elastic dress ... Full text Link to item Cite

Vascular plasminogen activator levels and thromboembolic disease in patients with gynecologic malignancies.

Journal Article Am J Obstet Gynecol · August 15, 1984 Vascular plasminogen activator levels were measured preoperatively in 66 women with gynecologic malignancies. These levels were compared to levels in a matched control group of 84 women and to the incidence of postoperative venous thromboembolic disease in ... Full text Link to item Cite

Changes in the binding of "fast"-form alpha 2-macroglobulin to 3T3-L1 cells after differentiation to adipocytes.

Journal Article Biochemistry · July 17, 1984 Human alpha 2-macroglobulin (alpha 2M)-CH3NH2 specifically binds to 3T3-L1 fibroblasts and adipocytes with an apparent Kd of 0.3 nM at 4 degrees C. Binding to fibroblasts follows first-order kinetics only for the first 20-30 min of reaction, k1 = 160 micro ... Full text Link to item Cite

Regulation of factor IXa in vitro in human and mouse plasma and in vivo in the mouse. Role of the endothelium and the plasma proteinase inhibitors.

Journal Article J Clin Invest · June 1984 The regulation of human Factor IXa was studied in vitro in human and mouse plasma and in vivo in the mouse. In human plasma, approximately 60% of the 125I-Factor IXa was bound to antithrombin III (ATIII) by 2 h, with no binding to alpha 2-macroglobulin or ... Full text Link to item Cite

Identification of "embryonin" as bovine alpha 2-macroglobulin.

Journal Article J Biol Chem · April 10, 1984 Pedersen fetuin contains a contaminant, previously named "embryonin" that exhibits immuno-cross reactivity with human alpha2-macroglobulin (alpha2Mh). In the present study, it is demonstrated that this protein coelutes with alpha2Mh in gel filtration chrom ... Link to item Cite

Effect of methylamine and plasmin on the conformation of human alpha 2-macroglobulin as revealed by differential scanning calorimetric analysis.

Journal Article Biophys J · April 1984 Differential scanning calorimetric analysis was used as a probe of the conformational alteration in human alpha 2-macroglobulin (AM) upon its complex formation with methylamine and with the protease, human plasmin. The slow electrophoretic form of AM displ ... Full text Link to item Cite

Hepatocyte uptake of alpha 1-proteinase inhibitor-trypsin complexes in vitro: evidence for a shared uptake mechanism for proteinase complexes of alpha 1-proteinase inhibitor and antithrombin III.

Journal Article J Cell Biochem · 1984 In vivo clearance studies have indicated that the clearance of proteinase complexes of the homologous serine proteinase inhibitors alpha 1-proteinase inhibitor and antithrombin III occurs via a specific and saturable pathway located on hepatocytes. In vitr ... Full text Link to item Cite

Hepatocyte receptors for antithrombin III-proteinase complexes.

Journal Article J Cell Biochem · 1984 The in vivo clearance of antithrombin III-proteinase complexes occurs via a specific and saturable pathway located on hepatocytes. We now report studies of the catabolism of antithrombin III-proteinase complexes in vitro using rat hepatocytes in primary cu ... Full text Link to item Cite

Conformation and protease binding activity of binary and ternary human alpha 2-macroglobulin-protease complexes.

Journal Article J Biol Chem · December 10, 1983 Human alpha 2-macroglobulin (alpha 2M) undergoes a conformational change after reaction with proteases. In this report, it is shown that although two trypsin molecules may bind simultaneously to each alpha 2M, only one trypsin is necessary to induce alpha ... Link to item Cite

Regulation of factor Xa in vitro in human and mouse plasma and in vivo in mouse. Role of the endothelium and plasma proteinase inhibitors.

Journal Article J Clin Invest · December 1983 The regulation of human Factor Xa was studied in vitro in human and mouse plasma, and in vivo in mouse. In human plasma, 125I-Factor Xa bound to alpha 1-proteinase inhibitor, antithrombin III, and alpha 2-macroglobulin in a ratio of 4.9:1.9:1 as determined ... Full text Link to item Cite

Alpha 2-macroglobulin 'fast' forms inhibit superoxide production by activated macrophages.

Journal Article Biochim Biophys Acta · November 8, 1983 Mouse peritoneal macrophages activated by bacillus Calmette-Guerin (BCG) were incubated with human alpha 2-macroglobulin converted to its 'fast' form with either trypsin or methylamine before being stimulated with phorbol myrystate acetate. Both alpha 2-ma ... Full text Link to item Cite

Reaction of human alpha 2-macroglobulin half-molecules with plasmin as a probe of protease binding site structure.

Journal Article Biochemistry · October 11, 1983 Human alpha 2-macroglobulin (alpha 2M) half-molecules were prepared by limited reduction and alkylation of the native protein. Reaction with plasmin resulted in nearly quantitative cleavage of the half-molecule Mr approximately 180000 subunits into Mr appr ... Full text Link to item Cite

Mesenteric vein thrombosis and vascular plasminogen activator.

Journal Article Arch Pathol Lab Med · October 1983 A 60-year-old woman with livedo reticularis was examined for defective release of vascular plasminogen activator by a newly described chromogenic assay. Her activator level was only 0.007 Committee on Thrombolytic Agents (CTA) units/mL, compared with a mea ... Link to item Cite

Down regulation of macrophage mannose/N-acetylglucosamine receptors by elevated glucose concentrations.

Journal Article Biochim Biophys Acta · September 13, 1983 The binding of the 125I-induced neoglycoprotein mannosyl-bovine serum albumin (Man-albumin) to peptone-elicited murine peritoneal macrophages was examined. Binding studies demonstrated that the extent of receptor activity for Man-albumin depended upon the ... Full text Link to item Cite

In vitro binding and in vivo clearance of human alpha 2-macroglobulin after reaction with endoproteases from four different classes.

Journal Article Biochem Biophys Res Commun · July 29, 1983 The binding of human alpha 2-macroglobulin complexed with trypsin, papain, thermolysin and cathepsin-D to murine macrophages was studied at 4 degrees C. Similar dissociation constants (0.4 nM) were determined for all of the complexes except alpha 2-macrogl ... Full text Link to item Cite

The role of ligand-ligand interactions in competition by fibrinogen and fibrin degradation products for fibrinogen binding to human platelets.

Journal Article Biochim Biophys Acta · June 9, 1983 Binding to human platelets of radioiodinated human fibrinogen and fragments X, Y, D, D1 dimer and E was studied to determine the domain of the fibrinogen molecule responsible for binding to the platelet receptor. Although the fragments did not bind, some w ... Full text Link to item Cite

Clearance and binding of native and defucosylated lactoferrin.

Journal Article Biochem J · May 15, 1983 These studies explore the role of carbohydrate recognition systems and the direct involvement of terminal alpha 1-3-linked fucose in the clearance of lactoferrin from the murine circulation and in the specific binding of lactoferrin to receptors on murine ... Full text Link to item Cite

A new procedure for the synthesis of polyethylene glycol-protein adducts; effects on function, receptor recognition, and clearance of superoxide dismutase, lactoferrin, and alpha 2-macroglobulin.

Journal Article Anal Biochem · May 1983 A new, simplified technique for the synthesis of polyethylene glycol (PEG) derivatives of proteins utilizing 1,1'-carbonyldiimidazole for PEG activation, is described. PEG derivatives of superoxide dismutase, alpha 2-macroglobulin, alpha 2-macroglobulin-tr ... Full text Link to item Cite

The clearance of human fibrinogen fragments X and Y in mice: a process mediated by the fragment D receptor.

Journal Article Thromb Haemost · April 28, 1983 The clearance of radiolabeled human fibrinogen fragments X and Y was studied in the mouse model. Fragment X cleared rapidly from the circulation with less than 10% of the ligand remaining in the circulation at 4 hr. The clearance of fragment Y was somewhat ... Link to item Cite

In vivo metabolism of reversibly inhibited alpha-thrombin.

Journal Article Biochem Pharmacol · February 15, 1983 Full text Link to item Cite

Venous thrombosis in a family with defective release of vascular plasminogen activator and elevated plasma factor VIII/von Willebrand's factor.

Journal Article Am J Med · January 1983 A family is described in which venous thrombosis developed in five members as early as 14 years of age. Routine coagulation studies, plasma antithrombin III, factor V, plasminogen, beta-thromboglobulin, fibrinopeptide A, prothrombin fragment F1+2, and thro ... Full text Link to item Cite

Ligand binding, conformational change and plasma elimination of human, mouse and rat alpha-macroglobulin proteinase inhibitors.

Journal Article Biochem J · January 1, 1983 Rat alpha 1-macroglobulin (alpha 1M), rat alpha 2-macroglobulin (alpha 2M) migrated as single bands on non-denaturing gels when purified by the methods described. All three proteins demonstrated increased mobility after reaction with trypsin. A single satu ... Full text Link to item Cite

α2-macroglobulin 'fast' forms inhibit superoxide production by activated macrophages

Journal Article BBA - General Subjects · 1983 Mouse peritoneal macrophages activated by bacillus Calmette-Guerin (BCG) were incubated with human α2-macroglobulin converted to its 'fast' form with either trypsin or methylamine before being stimulated with phorbol myrystate acetate. Both α2-macroglobuli ... Cite

Evaluation of embolization distal to arterial occlusion by transcatheter electrocoagulation (TCEC) and Gianturco coils.

Journal Article Invest Radiol · 1983 A technique was developed to evaluate the degree of embolization distal to arterial occlusion by transcatheter electrocoagulation (TCEC) and Gianturco coils. The kidneys of mongrel dogs were used to collect emboli distal to conventional TCEC or Gianturco c ... Full text Link to item Cite

Venous and arterial thromboembolic disease in women using oral contraceptives.

Journal Article Am J Obstet Gynecol · December 1, 1982 Vascular plasminogen activator was measured by means of a new chromogenic assay in 24 women who had suffered from oral contraceptive-associated thrombotic disease and was compared to that in a control group of 78 premenopausal women. Vascular plasminogen a ... Full text Link to item Cite

Fibrinolysis and fibrinogenolysis by Val442-plasmin.

Journal Article Biochim Biophys Acta · November 9, 1982 Elastase cleavage of Lys77-plasmin results in the formation of Val442-plasmin. This result suggests that small, active plasmin fragments can be produced even under conditions of high plasminogen activator levels such as occur in vivo. We examined the effec ... Full text Link to item Cite

Receptors for maleylated proteins regulate secretion of neutral proteases by murine macrophages.

Journal Article Science · November 5, 1982 Receptors for maleylated or acetylated proteins as well as for alpha-2-macroglobulin-protease complexes on macrophages serve as scavengers by mediating the uptake of macromolecules from the extracellular compartment. Described in this report is a novel fun ... Full text Link to item Cite

Immunohistochemical studies of cell differentiation in a juxtaglomerular tumor.

Journal Article Arch Pathol Lab Med · November 1982 A renal tumor removed from a 29-year-old woman, who recently had had onset of primary hypertension, showed the histologic and ultrastructural features of a renin-secretory juxtaglomerular cell tumor. The expression of Factor VIII-related antigen (FVIII-RAG ... Link to item Cite

A unique pathway for the plasma elimination of alpha 2-antiplasmin-protease complexes in mice.

Journal Article Thromb Haemost · October 29, 1982 Radiolabeled alpha 2-antiplasmin cleared slowly from the circulation of mice. Complex formation with either plasmin or trypsin resulted in a significant increase in the plasma elimination rate of the protease inhibitor. Approximately 20 min and 14 min were ... Link to item Cite

The clearance of human fibrinogen fragments D1, D2, D3 and fibrin fragment D1 dimer in mice.

Journal Article Biochim Biophys Acta · October 8, 1982 The clearance of human fibrinogen fragments D1, D2, D3 and fibrin fragment D1 dimer were studied in the mouse model. Clearance of these fragments is a complex process involving clearance from blood into three other compartments. The overall clearance of fr ... Full text Link to item Cite

Immunohistochemical detection of factor VIII/von Willebrand factor in hyperplastic endothelial cells in glioblastoma multiforme and mixed glioma-sarcoma.

Journal Article J Neuropathol Exp Neurol · September 1982 The sarcomatous components of most glioma-sarcomas are thought to arise from the neoplastic transformation of hyperplastic endothelial and adventitial vascular cells in a preexisting glioblastoma multiforme. The expression of factor VIII/von Willebrand fac ... Link to item Cite

Physical properties of human alpha 2-macroglobulin following reaction with methylamine and trypsin.

Journal Article Biochim Biophys Acta · August 10, 1982 Circular dichroism spectroscopy, sedimentation velocity and ultraviolet difference spectroscopy were used to compare alpha 2-macroglobulin, alpha 2-macroglobulin-trypsin complex and alpha 2-macroglobulin-methylamine complex. The circular dichroic spectrum ... Full text Link to item Cite

Catabolic pathways for streptokinase, plasmin, and streptokinase activator complex in mice. In vivo reaction of plasminogen activator with alpha 2-macroglobulin.

Journal Article J Clin Invest · August 1982 The catabolic pathways of streptokinase, plasmin, and activator complex prepared with human plasminogen were studied in mice. (125)I-streptokinase clearance occurred in the liver and was 50% complete in 15 min. Incubation with mouse plasma had no effect on ... Full text Link to item Cite

Purification of an almond emulsin fucosidase on Cibacron blue-sepharose and demonstration of its activity toward fucose-containing glycoproteins.

Journal Article J Biol Chem · July 25, 1982 The almond emulsin fucosidase that specifically hydrolyzes fucose in alpha (1-3) linkage to N-acetylglucosamine has been purified 1250-fold. The purification procedure includes ion exchange chromatography on sulfopropyl-Sephadex C-25, gel filtration on Sep ... Link to item Cite

In vivo catabolism of alpha 1-proteinase inhibitor-trypsin, antithrombin III-thrombin and alpha 2-macroglobulin-methylamine.

Journal Article Biochim Biophys Acta · May 27, 1982 The clearances of 125I-labeled alpha 1-proteinase inhibitor-trypsin, antithrombin III-thrombin and alpha 2-macroglobulin-methylamine (CH3NH2) were compared in our previously described mouse model. alpha 1-Proteinase inhibitor-trypsin cleared with a t 1/2 o ... Full text Link to item Cite

A colorimetric assay for releasable plasminogen activator.

Journal Article Clin Chem · May 1982 We describe an equilibrium assay for measuring release of plasminogen activator form blood-vessel walls and report data from 125 individuals free of overt thromboembolic disease. Excess human plasminogen is added to the euglobulin fraction of plasma obtain ... Link to item Cite

Specificity and sensitivity of immunohistochemical detection of factor VIII/von Willebrand factor antigen in formalin-fixed paraffin-embedded tissue.

Journal Article J Histochem Cytochem · April 1982 The immunohistochemical detection of factor VIII/von Willebrand factor antigen (FVIII/vWF-AG) in formalin-fixed paraffin-embedded tissues was investigated using the peroxidase-antiperoxidase (PAP) method. Highly purified human FVIII/vWF was used to raise r ... Full text Link to item Cite

Effect of increasing current and decreasing blood flow for transcatheter electrocoagulation (TCEC).

Journal Article Invest Radiol · 1982 Arterial occlusion by direct-current transcatheter electrocoagulation (TCEC) has been developed experimentally and used successfully in clinical situations. The major shortcoming of the technique has been the lengthy time necessary for occlusion of larger ... Full text Link to item Cite

Experimental pulmonary infarction in dogs: a comparison of chest radiography and computed tomography.

Journal Article Invest Radiol · 1982 Transcatheter electrocoagulation of the pulmonary artery was used to successfully create experimental pulmonary infarcts in 15 to 16 dogs. The animals were evaluated from one to 13 weeks by chest radiography, computed tomography (CT), angiography, and path ... Link to item Cite

Localization of factor VIII/von Willebrand factor and glial fibrillary acidic protein in the hemangioblastoma: implications for stromal cell histogenesis.

Journal Article Acta Neuropathol · 1982 The histogenesis of hemangioblastoma stromal cells is unresolved. Ultrastructural observations suggest that the stromal cells, endothelial cells, and pericytes that compose this neoplasm are all derived from angiogenic mesenchyme. The expression of factor ... Full text Link to item Cite

The clearance of human fibrinogen fragments D1, D2, D3 and fibrin fragment D1 dimer in mice

Journal Article BBA - General Subjects · 1982 The clearance of human fibrinogen fragments D1, D2, D3 and fibrin fragment D1 dimer were studied in the mouse model. Clearance of these fragments is a complex process involving clearance from blood into three other compartments. The overall clearance of fr ... Cite

Inactivation of the plasma protease inhibitor alpha 2-macroglobulin by the antitumor drug cis-dichlorodiamineplatinum(II).

Journal Article J Biol Chem · December 10, 1981 The plasma protease inhibitor alpha 2-macroglobulin (alpha 2M) was reacted in vitro with cis-dichlorodiamineplastinum(II) (cis-DDP). Following the reaction, alpha 2M demonstrated a significantly decreased ability to bind trypsin as determined by esterase a ... Link to item Cite

Altered clearance of human alpha 2-macroglobulin complexes following reaction with cis-dichlorodiamineplatinum(II).

Journal Article Biochim Biophys Acta · December 4, 1981 Clearance studies were performed in mice using alpha 2-macroglobulin (alpha 2M), alpha 2M-trypsin complex and alpha 2M-CH3NH2 complex. All three species were incubated with cis-dichlorodiamine platinum(II) (cis-DDPt) at concentrations between 9.0 microM an ... Full text Link to item Cite

Simple and sensitive assay employing stable reagents for quantification of plasminogen activator.

Journal Article Am J Clin Pathol · October 1981 A simple and sensitive indirect assay for quantifying plasminogen activator using [3H]-casein as substrate is described. The assay has been used to measure plasminogen activators from various sources including bacteria, cultured cells, and human plasma. Th ... Full text Link to item Cite

Reducing the risk of oral contraceptive-induced thrombosis.

Journal Article Drug Ther (NY) · September 1981 Link to item Cite

Clearance and binding of two electrophoretic "fast" forms of human alpha 2-macroglobulin.

Journal Article J Biol Chem · August 10, 1981 These studies explore the role of conformational change and exposed carbohydrate residues in the clearance of alpha 2-macroglobulin-trypsin (alpha 2M-T) complexes in the mouse. Human alpha 2-macroglobulin (alpha 2M) was purified and demonstrated to be homo ... Link to item Cite

The clearance of glycoproteins in diabetic mice.

Journal Article Biochem Biophys Res Commun · July 30, 1981 Full text Link to item Cite

Endothelial cell surface expression and binding of factor VIII/von Willebrand factor.

Journal Article Am J Pathol · May 1981 Factor VIII/von Willebrand factor (FVIII/vWF), a glycoprotein molecular complex found in human plasma, has been demonstrated by cell membrane fluorescence to be present on the surface of cultured human umbilical cord vein endothelial cells. The endothelial ... Link to item Cite

A radioreceptor assay for quantitating plasma factor VIII/von Willebrand's protein.

Journal Article Blood · March 1981 A sensitive and precise radioreceptor assay for determining plasma levels of human factor VIII/von Willebrand's factor (FVIII/vWF) has been developed by taking advantage of the FVIII/vWF receptor sites on human platelets. Paraformaldehyde-fixed platelets, ... Link to item Cite

Fibrinolytic response and oral contraceptive associated thromboembolism.

Journal Article Contraception · February 1981 A case-control study of fibrinolytic activity was conducted comparing 12 women with a recent history of thromboembolism while taking oral contraceptives and 28 matched female controls without a history of thromboembolism. All subjects had stopped using ora ... Full text Link to item Cite

Receptors on hepatocytes that bind ligands containing fucosyl α1,3 N-acetylglucosamine linkages

Journal Article Birth Defects: Original Article Series · January 1, 1981 Cite

Evaluation of the anode and cathode for transcatheter electrocoagulation.

Journal Article Acta Radiol Diagn (Stockh) · 1981 The effect of changing the size and position of the anode and cathode during direct current Transcatheter Electrocoagulation (TCEC) was evaluated in dogs. The results showed that there was no difference in the time required for vessel occlusion when the si ... Full text Link to item Cite

Transcatheter electrocoagulation of the pulmonary artery: an experimental model in dogs for studying pulmonary thrombosis.

Journal Article Invest Radiol · 1981 Transcatheter electrocoagulation (TCEC) has been shown to produce permanent arterial occlusion. This study was performed to evaluate the potential of using TCEC of the pulmonary artery as an experimental model of pulmonary thromboembolism. Fourteen lobar o ... Full text Link to item Cite

Membrane protein mediation of thromboxane A2-induced platelet aggregation.

Journal Article Biochem Biophys Res Commun · November 17, 1980 Full text Link to item Cite

Physical conditioning and fibrinolysis.

Journal Article N Engl J Med · September 25, 1980 Full text Link to item Cite

Blood coagulation and idiopathic thromboembolism among fertile women.

Journal Article Contraception · August 1980 A case-control study of fibrinolytic activity and antithrombin-III (AT-III) was conducted comparing 16 women within the childbearing ages who had a recent history of idiopathic thromboembolism to 29 age- and race-matched female controls without a history o ... Full text Link to item Cite

Physical conditioning augments the fibrinolytic response to venous occlusion in healthy adults.

Journal Article N Engl J Med · May 1, 1980 The effects of a 10-week physical-conditioning program on fibrinolytic activity at rest and after stimulation by venous occlusion were studied in 69 healthy adults 25 to 69 years old. Physical conditioning was documented by treadmill performance, and fibri ... Full text Link to item Cite

Renal carcinosarcoma. Ultrastructure and transplantation into athymic mice.

Journal Article Arch Pathol Lab Med · May 1980 An adult renal carcinosarcoma was studied by light and transmission electron microscopy. A portion of the tumor was transplanted and serially passed in athymic mice. The neoplasm consisted in part of typical renal cell carcinoma. The sarcomatous portion sh ... Link to item Cite

Vessel occlusion with transcatheter electrocoagulation: initial clinical experience.

Journal Article Radiology · November 1979 Transcatheter electrocoagulation (TCEC) was used for vessel occlusion in combination with embolization by Gelfoam and/or Ivalon in six patients in whom other interventional or surgical techniques were considered dangerous or unfeasible. The technique was e ... Full text Link to item Cite

Platelet receptors for human Factor VIII/von Willebrand protein: functional correlation of receptor occupancy and ristocetin-induced platelet aggregation.

Journal Article Proc Natl Acad Sci U S A · October 1979 Previous studies of von Willebrand disease indicate that a deficiency of blood clotting Factor VIII/von Willebrand factor (FVIII/vWF) activity is responsible for the failure of platelets to participate fully in the initial stages of hemostasis. We have rec ... Full text Link to item Cite

Demonstration and characterization of specific binding sites for factor VIII/von Willebrand factor on human platelets.

Journal Article J Clin Invest · April 1979 The presence of specific Factor VIII/von Willebrand factor (FVIII/vWF) binding sites on human platelets has been demonstrated by using 125I-FVIII/vWF and washed human platelets. Binding is ristocetin-dependent and increases in proportion to the concentrati ... Full text Link to item Cite

Transcatheter electrocoagulation: experimental evaluation of the anode.

Journal Article Invest Radiol · 1979 Transcatheter electrocoagulation using direct current has been shown to be an effective method for vessel occlusion. To date, the stainless steel anode has not been entirely satisfactory. Thus, an evaluation of bipolar platinum electrodes and a comparison ... Full text Link to item Cite

Carbohydrate on human factor VIII/von Willebrand factor. Impairment of function by removal of specific galactose residues.

Journal Article J Biol Chem · October 25, 1978 Human factor VIII/von Willebrand factor protein containing 120 +/- 12 nmol of sialic acid and 135 +/- 13 nmol of galactose/mg of protein was digested with neuraminidase. The affinity of native factor VIII/von Willebrand factor and its asialo form for the h ... Link to item Cite

Miliary aspergillosis associated with alcoholism.

Journal Article AJR Am J Roentgenol · October 1978 Full text Link to item Cite

Clinical use of transcatheter electrocoagulation.

Journal Article Radiology · October 1978 Transcatheter electrocoagulation is an effective method of experimental vessel occlusion even in the presence of thrombocytopenia and heparinization. This technique was used to occlude 13 arteries in 3 patients. In vitro testing suggests that intra-arteria ... Full text Link to item Cite

Hepatic receptor that specifically binds oligosaccharides containing fucosyl alpha1 leads to 3 N-acetylglucosamine linkages.

Journal Article Proc Natl Acad Sci U S A · May 1978 Evidence is presented suggesting that hepatocytes contain a receptor that binds glycoproteins specifically through fucose in alpha1-->3 linkage to N-acetylglucosamine. Human lactoferrin, which contains this type of linkage, is rapidly cleared from the circ ... Full text Link to item Cite

Necrosis of the colon secondary to pancreatitis

Journal Article The American Journal of Digestive Diseases · January 1, 1978 This case is the sixth report of colonic necrosis developing secondary to acute pancreatitis. In the previous cases there was no roentgen evidence of colonic inflammation or necrosis prior to surgery or autopsy. The initial radiographic findings in this 56 ... Full text Cite

The effect of drug-induced thrombocytopenia on direct-current transcatheter electrocoagulation.

Journal Article Radiology · September 1977 Direct-current transcatheter electrocoagulation in vitro produced substantial clots in thrombocytopenic blood in dogs. The splenic artery was occluded in 3 dogs following ristocetin-induced thrombocytopenia. This procedure may produce effective vessel occl ... Full text Link to item Cite

Transcatheter electrocoagulation: a therapeutic angiographic technique for vessel occlusion.

Journal Article Invest Radiol · 1977 Previous work has shown that localized electrocoagulation of blood vessels using direct current applied by catheter placed electrodes is feasible. In vitro and in vivo experiments showed that clot size and thrombosis of vessels are directly related to the ... Full text Link to item Cite

Severe combined immunodeficiency with leukopenia (reticular dysgenesis) in siblings: immunologic and histopathologic findings.

Journal Article J Pediatr · September 1976 The hematologic and histologic features of two, nontwin, male siblings with severe combined immunodeficiency and variable granulocytopenia are compared to the four previously reported cases of reticular dysgenesis. These sibs died at 50 and 3 days of age, ... Full text Link to item Cite

Comparison of ancrod and heparin as anticoagulants following endarterectomy in the dog.

Journal Article Ann Surg · August 1976 An experimental model of surgically-induced arterial thrombosis was devised using the femoral arteries of dogs. Within 7 days, 67% of the arteries became completely thrombosed and only 12% remained compeletly patent. In the group of dogs that received low- ... Full text Link to item Cite

Characterization of fragment E from fibrinogen and cross-linked fibrin.

Journal Article J Biol Chem · March 25, 1976 Fragment E, a terminal plasmin digestion product of fibrinogen or fibrin, contains portions of the alpha, beta, and gamma chains linked by disulfide bonds. In this study, Fragment E from fibrinogen and fully cross-linked fibrin were purified by gel filtrat ... Link to item Cite

The subunit structure of normal and hemophilic factor VIII.

Journal Article J Clin Invest · September 1973 Human factor VIII from normals and hemophiliacs was partially purified by ethanol and polyethylene glycol precipitations. Final purification was achieved by gel filtration on 2 or 4% agarose or ion exchange chromatography on diethylaminoethyl cellulose. Co ... Full text Link to item Cite

Cross-linking of fibrin by fibrin=stabilizing factor.

Journal Article Ann N Y Acad Sci · December 8, 1972 Full text Link to item Cite

Mechanism of ancrod anticoagulation. A direct proteolytic effect on fibrin.

Journal Article J Clin Invest · November 1972 Fibrin formed in response to ancrod, reptilase, or thrombin was reduced by beta-mercaptoethanol and examined by sodium dodecyl sulfate polyacrylamide gel electrophoresis. It was found that ancrod progressively and totally digested the alpha-chains of fibri ... Full text Link to item Cite

Minimal brain dysfunction and methylphenidate.

Journal Article N Engl J Med · July 29, 1971 Link to item Cite

The effect of fibrin-stabilizing factor on the subunit structure of human fibrin.

Journal Article J Clin Invest · July 1971 The formation of human fibrin from fibrinogen has been examined by polyacrylamide gel electrophoresis in sodium dodecyl sulfate, a method which separates a mixture of proteins on the basis of differences in molecular weight. It has been found that the plas ... Full text Link to item Cite