Journal articleJACC Adv · July 23, 2026
BACKGROUND: The delayed effects of radiation exposure on the heart often manifest as cardiac fibrosis and diastolic dysfunction, which can develop years after exposure. However, no Food and Drug Administration-approved serological biomarker is available to ...
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Journal articleJCI Insight · December 22, 2025
We recently showed that cell surface translocation of the endoplasmic reticulum-resident protein GRP78, when bound by activated α 2-macroglobulin (α2M*), induces pro-fibrotic responses in glomerular mesangial cells in response to high glucose and regulates ...
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Journal articleJ Cell Biochem · May 2023
Glucose-regulated protein-78 (Grp78) is an endoplasmic reticulum chaperone, which is secreted by cells and associates with cell surfaces, where it functions as a receptor for activated α2 -macroglobulin (α2 M) and tissue-type plasminogen activator (tPA). I ...
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Journal articleJ 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 ...
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Journal articleBiomedicines · 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 ...
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Journal articleCells · 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 ...
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Journal articleBiomedicines · 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 ...
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Journal articleIUBMB Life · June 2021
The 78 kDa glucose-regulated protein (GRP78) is an endoplasmic reticulum (ER)-resident molecular chaperone. GRP78 is a member of the 70 kDa heat shock family of proteins involved in correcting and clearing misfolded proteins in the ER. In response to cellu ...
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Journal articleJ 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 ...
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Journal articleSci Rep · June 15, 2020
The villous cytotrophoblastic cells have the ability to fuse and differentiate, forming the syncytiotrophoblast (STB). The syncytialisation process is essential for placentation. Nevertheless, the mechanisms involved in cell fusion and differentiation are ...
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Journal articleJ 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 ...
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Journal articleBreast 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 ...
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Journal articleProstate cancer and prostatic diseases · June 2018
BackgroundSome, 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 se ...
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Journal articleJ 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 ...
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Journal articleOncotarget · 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 ...
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Journal articleOncotarget · September 15, 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 ...
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Journal articleBiochem 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 ...
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Journal articleOncotarget · 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 ...
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Journal articleProstate · 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 ...
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Journal articleInt 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 ...
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Journal articleOncotarget · 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 ...
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Journal articleJ 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 ...
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Journal articleJ 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 ...
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Journal articleCardiovasc 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 ...
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Journal articleJ 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 ...
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Journal articleBreast 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 ...
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Journal articleJ 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 ...
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Journal articleMol 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 ...
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Journal articlePLoS 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 ...
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Journal articleJ 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) ...
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Journal articlePLoS 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 ...
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Journal articlePLoS 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 ...
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Journal articleBiochemistry · 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 ...
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Journal articleProstate · 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 ...
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Journal articleProstate · 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 ...
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Journal articleJ 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 ...
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Journal articleJ 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 ...
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Journal articlePLoS 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 ...
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Journal articlePLoS 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 ...
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Journal articleBJU 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 ...
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Journal articleJ 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 ...
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Journal articleMelanoma 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 ...
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Journal articleJ 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 ...
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Journal articleCancer 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 ...
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Journal articlePLoS One · 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 ...
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Journal articlePLoS 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 ( ...
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Journal articleMelanoma 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 ...
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Journal articleJ 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 ...
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Journal articleCancer 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 ...
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Journal articleMelanoma 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 ...
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Journal articleJ 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 ...
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Journal articlePlast 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 ...
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Journal articleMethods 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 ...
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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 transpo ...
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Journal articleJ 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 ...
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Journal articleJ 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 ...
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Journal articleJ 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 ...
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Journal articleLeukemia · 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 ...
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Journal articleCancer 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 ...
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Journal articleBiochem 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 ...
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Journal articleApoptosis · 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 ...
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Journal articleBiochem 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 ...
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Journal articleCancer 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 ...
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Journal articleMod 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 ...
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Journal articleJ 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 ...
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Journal articleJ 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 ...
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Journal articleAntioxid 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 ...
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Journal articleBlood · 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 ...
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Journal articlePLoS 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 ...
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Journal articleCancer 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 ...
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Journal articleMol Cancer Ther · May 2009
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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 ...
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Journal articleJ 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 ...
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Journal articleHistol 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 ...
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Journal articleMol Psychiatry · October 2008
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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 ...
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Journal articleCell 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 ...
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Journal articleJ Immunol · July 1, 2008
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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 ...
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Journal articleNat Med · May 2008
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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, ...
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Journal articleJ 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 ...
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Journal articleJ Leukoc Biol · February 2008
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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 ...
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Journal articleInt 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 ...
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Journal articleProstate · 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 ...
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Journal articleCell 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 ...
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Journal articleFront 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 ...
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Journal articleJ Biol Chem · November 9, 2007
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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 ...
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Journal articleBiochem 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 ...
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Journal articleCancer 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 ...
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Journal articleJ 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. ...
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Journal articleCancer Res · December 1, 2006
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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 ...
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Journal articleJ Biol Chem · May 12, 2006
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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 ...
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Journal articleAIDS 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 ...
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Journal articleCancer Res · January 15, 2006
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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 ...
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Journal articleAnn 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 ...
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Journal articleInt 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 ...
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Journal articleJ Biol Chem · November 18, 2005
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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 ...
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Journal articleJ 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 ...
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Journal articleJ 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 ...
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Journal articleJ 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 ...
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Journal articleJ Immunol · August 15, 2005
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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 ...
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Journal articleJ Biol Chem · July 22, 2005
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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 ...
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Journal articleJ Biol Chem · July 15, 2005
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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 ...
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Journal articleJ 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 ...
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Journal articleJ 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 ...
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Journal articleJ Immunol · February 15, 2005
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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. ...
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Journal articleExp 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 ...
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Journal articleJ Biol Chem · January 21, 2005
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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 ...
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Journal articleClin 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 ...
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Journal articleJ Biol Chem · December 3, 2004
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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 ...
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Journal articleJ 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 ...
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Journal articleCell 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 ...
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Journal articleCancer 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 ...
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Journal articleJ 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 ...
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Journal articleCell 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 ...
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Journal articleRecent 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 ...
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Journal articleJ Immunol · January 1, 2004
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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 ...
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Journal articleNat Immunol · December 2003
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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 ...
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Journal articleEMBO J · November 17, 2003
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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 ...
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Journal articleCell 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 ...
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Journal articleBiochem 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 ...
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Journal articleJ Biol Chem · July 18, 2003
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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 ...
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Journal articleAm 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 ...
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Journal articleClin 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 ...
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Journal articleJ 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 ...
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Journal articleJ 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 ...
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Journal articleBiochim 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 ...
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Journal articleBlood · 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 ...
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Journal articleVaccine · 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 ...
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Journal articleJ 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 ...
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Journal articleCell 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 ...
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Journal articleThromb 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 ...
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Journal articleJ 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 ...
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Journal articleJ 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 ...
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Journal articleArch 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 ...
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Journal articleVaccine · 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 ...
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Journal articleJ 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 ...
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Journal articleCell 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 ...
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Journal articleJ 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 ...
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Journal articleArch 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 ...
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Journal articleProc Natl Acad Sci U S A · June 5, 2001
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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 ...
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Journal articleBlood · 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 ...
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Journal articleBiochem 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 ...
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Journal articleArch 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 ...
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Journal articleClin 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 ...
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Journal articleJ 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 ...
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Journal articleExp 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 ...
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Journal articleArch 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 ...
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Journal articleJ 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 ...
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Journal articleArch 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 ...
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Journal articleCell Signal · February 2000
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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 ...
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Journal articleArch 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 ...
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Journal articleBiochemistry · October 19, 1999
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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 ...
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Journal articleJ Biol Chem · September 3, 1999
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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 ...
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Journal articleBiochim 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 ...
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Journal articleJ 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 ...
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Journal articleProc Natl Acad Sci U S A · March 16, 1999
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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 ...
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Journal articleArch 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 ...
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Journal articleJ 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, ...
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Journal articleFASEB 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 ...
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Journal articleFASEB 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 ...
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Journal articleFASEB 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 ...
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Journal articleJ 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 ...
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Journal articleToxicol 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 ...
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Journal articleCell 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 ...
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Journal articleJ 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 ...
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Journal articleBiochemistry · 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 ...
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Journal articleBiochim 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 ...
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Journal articleFASEB 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 ...
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Journal articleFibrinolysis 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 ...
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Journal articleFibrinolysis 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+
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Journal articleFibrinolysis 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 ...
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Journal articleFASEB 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 (orna ...
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Journal articleFASEB 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 ...
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Journal articleBiochemistry · 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 ...
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Journal articleMol 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 ...
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Journal articleJ 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 ...
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Journal articleJ 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 ...
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Journal articleJ 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 ...
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Journal articleJ 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 ...
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Journal articleJ 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 ...
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Journal articleJ 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 ...
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Journal articleJ 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 ...
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Journal articleBiochim 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 ...
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Journal articleInt 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 ...
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Journal articleBiochem 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 ...
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Journal articleArch 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 ...
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Journal articleJ 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 ...
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Journal articleGynecol 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 ...
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Journal articleJ 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 ...
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Journal articleJ 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 ...
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Journal articleAcad 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 ...
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Journal articleJ 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 ...
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Journal articleJ 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 ...
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Journal articleJ 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 ...
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Journal articleInvestigative 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-re ...
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Journal articleArch 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, ...
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Journal articleBiochem 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 ...
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Journal articleJ 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 ...
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Journal articleFibrinolysis · 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 ...
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Journal articleFibrinolysis · 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 ...
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Journal articleFibrinolysis · 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, ...
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Journal articleFibrinolysis · 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 ...
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Journal articleFibrinolysis · 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 ...
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Journal articleEur 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 ...
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Journal articleBiochem 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 ...
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Journal articleJ 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 ...
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Journal articleBiochem 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 ...
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Journal articleJ 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 ...
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Journal articleJ 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 ...
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Journal articleJ 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 ...
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Journal articleJ 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 ...
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Journal articleJ 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 ...
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Journal articleJournal 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 ...
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Journal articleEur 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 ...
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Journal articleAm 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 ...
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Journal articleJ 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 ...
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Journal articleJ 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 ...
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Journal articleAm 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 ...
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Journal articleJ 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 ...
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Journal articleInt 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 ...
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Journal articleArch 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 ...
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Journal articleJ 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 ...
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Journal articleJ 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 ...
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Journal articleJ 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 ...
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Journal articleChem 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 ...
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Journal articleFibrinolysis 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 ...
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Journal articleJ 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 ...
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Journal articleJ 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 ...
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Journal articleJ 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 ...
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Journal articleBiochem 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 ...
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Journal articleCancer 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 ...
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Journal articleJ 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 ...
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Journal articleArch 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 ...
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Journal articleBiochem 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 ...
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Journal articleBiochem 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 ...
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Journal articleBiochim 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 ...
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Journal articleJ 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 ...
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Journal articleFEBS 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 ...
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Journal articleBiochem 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 ...
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Journal articleArch 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 ...
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Journal articleBiochem 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 ...
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Journal articleBiochem 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 ...
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Journal articleBiochem 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 ...
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Journal articleBlood 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 ...
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Journal articleBiochemistry · 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 ...
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Journal articleJ 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 ...
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Journal articleBiochim 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 ...
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Journal articleJ 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 ...
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Journal articleBiochem 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 ...
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Journal articleArch 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 ...
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Journal articleJ 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 ...
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Journal articleBiochemistry · 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 ...
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Journal articleBiochemistry · 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 ...
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Journal articleBiochemistry · 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 ...
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Journal articleBiochemistry · 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, ...
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Journal articleJ 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 ( ...
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Journal articleJ 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 ...
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Journal articleArch 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 ...
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Journal articleAdvanced 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 ...
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Journal articleAm 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 ...
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Journal articleBiochemistry · 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 ...
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Journal articleBiochim 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 ...
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Journal articleBlood · 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 ...
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Journal articleJ 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 ...
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Journal articleJ 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 ...
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Journal articleBiochemistry · 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 ...
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Journal articleBiochemistry · 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 ...
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Journal articleBiochim 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 ...
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Journal articleMed 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 ...
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Journal articleJ 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 ...
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Journal articleBiochemistry · 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 ...
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Journal articleAm 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 ...
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Journal articleJ 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 ...
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Journal articleJ 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 ...
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Journal articleAm 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 ...
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Journal articleBiochemistry · 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 ...
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Journal articleBiochemistry · 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 ...
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Journal articleBiochemistry · 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 ...
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Journal articleJ 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 ...
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Journal articleAgents 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 ...
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Journal articleBiochim 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 ...
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Journal articleArch 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- ...
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Journal articleHistopathology · 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 ...
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Journal articleBiochemistry · 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 ...
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Journal articleAm 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 ( ...
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Journal articleBiochem 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 ...
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Journal articleJ 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 ...
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Journal articleBlood · 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 ...
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Journal articleJ 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 ...
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Journal articleJ 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 ...
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Journal articleJ 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 ...
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Journal articleBlood · 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 ...
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Journal articleCancer 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 ...
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Journal articleArch 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 ...
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Journal articleJ 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 ...
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Journal articleArch 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 ...
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Journal articleBiochemistry · 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 ...
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Journal articleJ 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) ...
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Journal articlePrep 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 ...
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Journal articleJournal 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 ...
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Journal articleBiochem 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 ...
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Journal articleArch 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 ...
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Journal articleJ 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 ...
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Journal articleJ 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 ...
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Journal articleArch 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 ...
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Journal articleBiochemistry · 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 ...
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Journal articleJ 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 ...
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Journal articleAm 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 ...
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Journal articleAm 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 ...
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Journal articleBiochemistry · 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 ...
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Journal articleThromb 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 ...
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Journal articleJ 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 ...
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Journal articleBiol 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 ...
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Journal articleBiochemistry · 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 ...
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Journal articleBiochem 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- ...
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Journal articleArch 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 ...
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Journal articleSemin 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 ...
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Journal articleJ 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 ...
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Journal articleArch 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 ...
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Journal articleBlood · 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 ...
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Journal articleBiochem 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 ...
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Journal articleThromb 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 ...
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Journal articleBiochemistry · 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- ...
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Journal articleGynecol 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 ...
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Journal articleArch 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 ...
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Journal articleAm 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 ...
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Journal articleProc 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 ...
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Journal articleBiochemistry · 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 ...
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Journal articleThromb 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 ...
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Journal articleBiochemistry · 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 ...
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Journal articleDiabetes · 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 ...
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Journal articleBiochem 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 ...
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Journal articleThromb 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 ...
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Journal articleBlood · 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 ...
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Journal articleJ 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 ...
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Journal articleExp 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 ...
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Journal articleJ 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 ...
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Journal articleJ 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 ...
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Journal articleBiochemistry · 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- ...
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Journal articleBiochim 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 ...
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Journal articleCancer 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 ...
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Journal articleCancer 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 ...
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Journal articleArch 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 ...
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Journal articleBiochem 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 ...
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Journal articleArch 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 ...
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Journal articleAm 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 ...
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Journal articleAm 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 ...
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Journal articleBiochemistry · 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 ...
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Journal articleJ 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 ...
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Journal articleJ 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 ...
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Journal articleBiophys 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 ...
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Journal articleJ 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 ...
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Journal articleJ 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 ...
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Journal articleJ 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 ...
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Journal articleJ 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 ...
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Journal articleBiochim 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 ...
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Journal articleBiochemistry · 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 ...
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Journal articleArch 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 ...
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Journal articleBiochim 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 ...
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Journal articleBiochem 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 ...
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Journal articleBiochim 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 ...
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Journal articleBiochem 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 ...
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Journal articleAnal 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 ...
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Journal articleThromb 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 ...
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Journal articleAm 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 ...
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Journal articleBiochem 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 ...
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Journal articleBBA - 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 ...
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Journal articleInvest 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 ...
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Journal articleAm 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 ...
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Journal articleBiochim 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 ...
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Journal articleScience · 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 ...
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Journal articleArch 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 ...
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Journal articleThromb 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 ...
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Journal articleBiochim 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 ...
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Journal articleJ 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 ...
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Journal articleBiochim 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 ...
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Journal articleJ 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 ...
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Journal articleJ 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 ...
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Journal articleBiochim 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 ...
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Journal articleClin 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 ...
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Journal articleJ 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 ...
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Journal articleInvest 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 ...
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Journal articleInvest 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 ...
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Journal articleActa 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 ...
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Journal articleBBA - 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 ...
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Journal articleJ 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 ...
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Journal articleBiochim 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 ...
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Journal articleAm 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 ...
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Journal articleJ 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 ...
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Journal articleAm 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 ...
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Journal articleBlood · 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, ...
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Journal articleContraception · 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 ...
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Journal articleActa 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 ...
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Journal articleInvest 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 ...
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Journal articleContraception · 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 ...
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Journal articleN 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 ...
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Journal articleArch 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 ...
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Journal articleRadiology · 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 ...
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Journal articleProc 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 ...
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Journal articleJ 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 ...
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Journal articleInvest 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 ...
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Journal articleJ 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 ...
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Journal articleRadiology · 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 ...
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Journal articleProc 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 ...
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Journal articleAmerican 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 ...
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Journal articleRadiology · 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 ...
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Journal articleInvest 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 ...
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Journal articleJ 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, ...
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Journal articleAnn 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- ...
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Journal articleJ 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 ...
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Journal articleJ 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 ...
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Journal articleJ 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 ...
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Journal articleJ 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 ...
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