Journal ArticleBlood Cancer J · February 6, 2025
Despite the considerable effort to characterize the genomic landscape of chronic lymphocytic leukemia (CLL), published data have been almost exclusively derived from patients of European Ancestry (EA), with significant underrepresentation of minorities, in ...
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Journal ArticleOsteoarthritis Cartilage · August 2024
OBJECTIVE: Traumatic meniscal injuries can cause acute pain, hemarthrosis (bleeding into the joint), joint immobility, and post-traumatic osteoarthritis (PTOA). However, the exact mechanism(s) by which PTOA develops following meniscal injuries is unknown. ...
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Journal ArticleBlood Adv · May 14, 2024
High-count monoclonal B-cell lymphocytosis (HCMBL) is a precursor condition to chronic lymphocytic leukemia (CLL). We have shown that among individuals with HCMBL, the CLL-International Prognostic Index (CLL-IPI) is prognostic for time-to-first therapy (TT ...
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Journal ArticleBMJ Open Respir Res · December 20, 2023
INTRODUCTION: The genetic determinants of fractional exhalation of nitric oxide (FeNO), a marker of lung inflammation, are understudied in Black individuals. Alpha globin (HBA) restricts nitric oxide signalling in arterial endothelial cells via interaction ...
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Journal ArticleJ Geriatr Oncol · January 2023
INTRODUCTION: Chronic lymphocytic leukemia (CLL) is the most common incurable leukemia/lymphoma in the United States. Individuals with CLL are at risk for disability, frailty, and cancer-specific complications that negatively affect health-related quality ...
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Journal ArticleLeukemia · January 2022
Monoclonal B-cell lymphocytosis (MBL) is a precursor to CLL. Other than age, sex, and CLL family-history, little is known about factors associated with MBL risk. A polygenic-risk-score (PRS) of 41 CLL-susceptibility variants has been found to be associated ...
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Journal ArticleFront Oncol · 2022
Many patients with chronic lymphocytic leukemia (CLL) experience physical dysfunction and low overall fitness. It remains unknown what factors drive CLL physical dysfunction. We assessed physical function and metabolic lipoprotein panels in 106 patients wi ...
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Journal ArticleCartilage · December 2021
OBJECTIVES: The utilization of viral vectors to deliver genes of interest directly to meniscus cells and promote long-term modulation of gene expression may prove useful to enhance meniscus repair and regeneration. The objective of this study was to optimi ...
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Journal ArticleSci Rep · November 30, 2021
Chronic lymphocytic leukemia (CLL) is the most common leukemia in the USA, affecting predominantly older adults. CLL is characterized by low physical fitness, reduced immunity, and increased risk of secondary malignancies and infections. One approach to im ...
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ConferenceBlood · November 5, 2021
AbstractBackground: We need new biomarkers that manage CLL patients receiving novel chemotherapeutic agent treatments. In our earlier pilot study, we reported an association of inferior outcomes in those wit ...
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Journal ArticleJ Infect Dis · October 28, 2021
BACKGROUND: Cerebral malaria (CM) pathogenesis remains incompletely understood. Having shown low systemic levels of tetrahydrobiopterin (BH4), an enzymatic cofactor for neurotransmitter synthesis, we hypothesized that BH4 and BH4-dependent neurotransmitter ...
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Journal ArticleFASEB J · September 2021
A layer of glycocalyx covers the vascular endothelium serving important protective and homeostatic functions. The objective of this study was to determine if breakdown of the endothelial glycocalyx (eGC) occurs during malaria infection in children. Measure ...
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Journal ArticleInt J Epidemiol · August 30, 2021
BACKGROUND: Epidemiological studies have demonstrated a positive association between chronic lymphocytic leukaemia (CLL) and non-melanoma skin cancer (NMSC). We hypothesized that shared genetic risk factors between CLL and NMSC could contribute to the asso ...
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Journal ArticleCells · May 11, 2021
Chronic lymphocytic leukemia (CLL) is associated with physical dysfunction and low overall fitness that predicts poor survival following the commencement of treatment. However, it remains unknown whether higher fitness provides antioncogenic effects. We id ...
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Journal ArticleSci Rep · May 7, 2021
Degradation of the endothelial glycocalyx is associated with mortality in adult falciparum malaria. However, its role in the pathogenesis of non-falciparum malaria is unknown. In Malaysian patients with knowlesi (n = 200) and vivax (n = 61) malaria, and in ...
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Journal ArticleBlood · April 15, 2021
Chronic lymphocytic lymphoma (CLL) has one of the highest familial risks among cancers. Monoclonal B-cell lymphocytosis (MBL), the precursor to CLL, has a higher prevalence (13%-18%) in families with 2 or more members with CLL compared with the general pop ...
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Journal ArticleOsteoarthritis Cartilage · April 2021
Injury to the meniscus is common and frequently leads to the development of post-traumatic osteoarthritis (PTOA). Many times meniscus injuries occur coincident with anterior cruciate ligament (ACL) injuries and lead to a bloody joint effusion. Hemarthrosis ...
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Journal ArticleFront Cell Dev Biol · 2021
Malaria caused by Plasmodium falciparum results in over 400,000 deaths annually, predominantly affecting African children. In addition, non-falciparum species including vivax and knowlesi cause significant morbidity and mortality. Vascular dysfunction is a ...
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Journal ArticleInfect Immun · April 20, 2020
Endothelial activation and microvascular dysfunction are key pathogenic processes in severe malaria. We evaluated the early role of these processes in experimentally induced Plasmodium falciparum and P. vivax infection. Participants were enrolled in induce ...
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Journal ArticleConnect Tissue Res · 2020
Purpose: Meniscal injury and loss of meniscus tissue lead to osteoarthritis development. Therefore, novel biologic strategies are needed to enhance meniscus tissue repair. The purpose of this study was to identify a favorable culture medium for both bone m ...
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Journal ArticleInt J Mol Sci · December 19, 2019
Meniscal injuries, particularly in the avascular zone, have a low propensity for healing and are associated with the development of osteoarthritis. Current meniscal repair techniques are limited to specific tear types and have significant risk for failure. ...
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Journal ArticleFASEB J · December 2019
Cerebral malaria (CM) from Plasmodium falciparum infection is associated with endothelial dysfunction and parasite sequestration. The glycocalyx (GCX), a carbohydrate-rich layer lining the endothelium, is crucial in vascular homeostasis. To evaluate the ro ...
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Journal ArticleClin Infect Dis · October 30, 2019
BACKGROUND: Interactions between the endothelium and infected erythrocytes play a major role in the pathogenesis of falciparum malaria, with microvascular dysfunction and parasite sequestration associated with worsening outcomes. The glycocalyx is a carboh ...
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Journal ArticleBlood Cancer J · August 5, 2019
Chronic lymphocytic leukemia (CLL) and its precursor, monoclonal B-cell lymphocytosis (MBL), are heritable. Serumfree light-chain (sFLC) measures are a prognostic factor for CLL, but their role in susceptibility to CLL is not clear. We investigated differe ...
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Journal ArticleSci Rep · June 18, 2019
Meniscal tears have a poor healing capacity, and damage to the meniscus is associated with significant pain, disability, and progressive degenerative changes in the knee joint that lead to osteoarthritis. Therefore, strategies to promote meniscus repair an ...
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Journal ArticleInfect Immun · April 2019
The low bioavailability of nitric oxide (NO) and its precursor, arginine, contributes to the microvascular pathophysiology of severe falciparum malaria. To better characterize the mechanisms underlying hypoargininemia in severe malaria, we measured the pla ...
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Journal ArticleBr J Haematol · February 2019
Alteration in RNA splicing is implicated in carcinogenesis and progression. Mutations in spliceosome genes and alternative splicing of other genes have been noted in chronic lymphocytic leukaemia (CLL), a common B cell malignancy with heterogeneous outcome ...
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Journal ArticleSemin Oncol · 2019
Research in the Veterans Health Administration (VHA) has played an integral part in learning about cancer biology and treatment. Here we provide examples of past research performed in the VHA focusing on hematologic malignancies, and identify future opport ...
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Journal ArticleBr J Haematol · December 2018
Chronic lymphocytic leukaemia (CLL) is characterized by expression of CD5 on clonal B cells, and is partly driven by activated B-cell receptor (BCR) signalling. While CD5 is known to be a negative regulator of BCR signalling, it is unknown if variability i ...
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ConferenceBlood · November 29, 2018
AbstractIntroduction Exercise has potent immune enhancing and anti-inflammatory effects in healthy adults, and is increasingly recognized as a beneficial adjunct to cancer care. Inc ...
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Journal ArticleBlood · June 7, 2018
Inherited loci have been found to be associated with risk of chronic lymphocytic leukemia (CLL). A combined polygenic risk score (PRS) of representative single nucleotide polymorphisms (SNPs) from these loci may improve risk prediction over individual SNPs ...
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Internet Publication · March 29, 2018
The experimental data supports the cytotoxic mechanism of D-lactic acid dimer via the Warburg effect. ...
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ConferenceJournal of Clinical Oncology · March 1, 2017
73 Background: Hypereosinophilic syndrome (HES) is a rare hematologic disorder in which the eosinophils proliferate and infiltrate and damage multiple organs. Without treatment, the condition is fatal, usually due to cardiac dysf ...
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Journal ArticlePLoS One · 2017
Rituximab therapy for B cell chronic lymphocytic leukemia (B-CLL) has met with mixed success. Among several factors to which resistance can be attributed is failure to activate complement dependent cytotoxicity (CDC) due to protective complement regulatory ...
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Journal ArticleOpen Forum Infect Dis · 2017
Microvascular function and oxygen consumption affect oxygen homeostasis but have not been assessed in African children with malaria. Microvascular function in Tanzanian children with severe malaria (SM) or uncomplicated malaria were 39% and 72%, respective ...
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ConferenceBlood · December 2, 2016
AbstractIntroduction: Hypereosinophilic syndrome (HES) is a rare hematologic disorder in which the eosinophils proliferate and infiltrate and damage multiple organs. Without treatment, the condition is fatal ...
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ConferenceBlood · December 2, 2016
AbstractINTRODUCTION:Conventional treatment of acute myeloid leukemia (AML) remains largely unchanged for over thirty years. With poor overall survival and disease cure rates ...
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ConferenceBlood · December 2, 2016
AbstractIntroduction: Chronic Lymphocytic Leukemia (CLL) is a malignancy characterized by B-lymphocytes with aberrant expression of CD5. In normal T-lymphocytes, CD5 is an important regulator of T-cell recep ...
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Journal ArticleJ Infect Dis · November 15, 2016
BACKGROUND: Pathogenesis of severe Plasmodium vivax malaria is poorly understood. Endothelial dysfunction and reduced nitric oxide (NO) bioavailability characterize severe falciparum malaria, but have not been assessed in severe vivax malaria. METHODS: In ...
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Journal ArticleJ Immunol · September 15, 2016
Leukemia can promote T cell dysfunction and exhaustion that contributes to increased susceptibility to infection and mortality. The treatment-independent mechanisms that mediate leukemia-associated T cell impairments are poorly understood, but metabolism t ...
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Journal ArticleSci Rep · July 7, 2016
We earlier established that nitric oxide (NO) is protective against severe malaria and that arginine and NO levels are reduced in malaria patients. We now show that an M2-like blood monocyte phenotype is significantly associated with hypoargininemia, NO in ...
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Journal ArticleAm J Hematol · July 2016
Monocyte-derived cells, constituents of the cancer microenvironment, support chronic lymphocytic leukemia (CLL) cell survival in vitro via direct cell-cell interaction and secreted factors. We hypothesized that circulating absolute monocyte count (AMC) ref ...
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Journal ArticleJ Psychosom Res · April 2016
OBJECTIVE: Posttraumatic stress disorder (PTSD) has been linked to chronic inflammation, a condition that poses a risk for cardiovascular disease. Attenuated vagal activity has been proposed as a potential mediator of PTSD and inflammation, although associ ...
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Journal ArticleNat Commun · March 9, 2016
Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide associatio ...
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ConferenceClinical Cancer Research · September 1, 2015
AbstractBackground: The PI3K pathway is a central pro-survival mechanism in chronic lymphocytic leukemia (CLL). While the delta isoform of PI3K is largely associated with B-cell signaling, gamma is involved ...
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Journal ArticlePLoS Pathog · March 2015
Tetrahydrobiopterin (BH₄) is a co-factor required for catalytic activity of nitric oxide synthase (NOS) and amino acid-monooxygenases, including phenylalanine hydroxylase. BH4 is unstable: during oxidative stress it is non-enzymatically oxidized to dihydro ...
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Journal ArticlePLoS Pathog · March 2015
Decreased bioavailability of nitric oxide (NO) is a major contributor to the pathophysiology of severe falciparum malaria. Tetrahydrobiopterin (BH4) is an enzyme cofactor required for NO synthesis from L-arginine. We hypothesized that systemic levels of BH ...
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Journal ArticleJ Infect Dis · November 15, 2014
Endothelial nitric oxide (NO) bioavailability, microvascular function, and host oxygen consumption have not been assessed in pediatric malaria. We measured NO-dependent endothelial function by using peripheral artery tonometry to determine the reactive hyp ...
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ConferenceCancer Research · October 1, 2014
AbstractBackground: The PI3K pathway is a central pro-survival mechanism in chronic lymphocytic leukemia (CLL), with expression of the delta isoform of PI3K largely restricted to lymphocytes. Clinical evalua ...
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Journal ArticleJ Infect Dis · September 15, 2014
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BACKGROUND: Nitric oxide (NO) bioavailability is impaired in children and adults with severe falciparum malaria (SM). Asymmetric-dimethylarginine (ADMA) limits NO production by inhibiting NO synthase and is increased in adult SM. The role of ADMA in the pa ...
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Journal ArticleAm J Trop Med Hyg · September 2014
A cerebrospinal fluid (CSF) biomarker for cerebral malaria (CM) has not been validated. We examined the detection, semiquantification, and clinical use of the Plasmodium falciparum histidine-rich protein-2 (PfHRP-2) as a parasite antigen biomarker for CM. ...
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Journal ArticleCrit Care · August 1, 2014
INTRODUCTION: Impaired T cell function in sepsis is associated with poor outcome, but the mechanisms are unclear. In cancer, arginase-expressing myeloid derived suppressor cells (MDSCs) deplete arginine, impair T cell receptor CD3 zeta-chain expression and ...
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Journal ArticleLeuk Lymphoma · May 2014
Abstract Because of the importance of the phosphoinositide 3-kinase (PI3K)/AKT pathway in chronic lymphocytic leukemia (CLL), we evaluated in vitro cytotoxicity induced by perifosine, an AKT inhibitor, in CLL lymphocytes and found that the mean 50% effecti ...
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Journal ArticleClin Chem Lab Med · April 2014
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BACKGROUND: The pathophysiology of sepsis is incompletely understood. Impaired bioavailability of L-arginine, the substrate for NO synthesis, is linked to sepsis severity, and plasma arginase has been linked to hypoargininemia in other disease states. Circ ...
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ConferenceBlood · November 15, 2013
AbstractIntroductionVitamin D deficiency is common in the general population. Approximately 25-50% of adult patients seen at routine v ...
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Journal ArticleNat Genet · August 2013
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Genome-wide association studies (GWAS) have previously identified 13 loci associated with risk of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL). To identify additional CLL susceptibility loci, we conducted the largest meta-analysis for C ...
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Journal ArticleCancer Epidemiol Biomarkers Prev · March 2013
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BACKGROUND: Our genome-wide association study (GWAS) of chronic lymphocytic leukemia (CLL) identified 4 highly correlated intronic variants within the IRF8 gene that were associated with CLL. These results were further supported by a recent meta-analysis o ...
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Journal ArticleLeukemia · January 2013
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Chronic lymphocytic leukemia (CLL) can be immunosuppressive in humans and mice, and CLL cells share multiple phenotypic markers with regulatory B cells that are competent to produce interleukin (IL)-10 (B10 cells). To identify functional links between CLL ...
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Journal ArticlePLoS One · 2013
BACKGROUND: Chronic lymphocytic leukemia (CLL) is typically regarded as an indolent B-cell malignancy. However, there is wide variability with regards to need for therapy, time to progressive disease, and treatment response. This clinical variability is du ...
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Journal ArticleBiomaterials · December 2012
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Tissue-engineered constructs designed to treat large cartilage defects or osteoarthritic lesions may be exposed to significant mechanical loading as well as an inflammatory environment upon implantation in an injured or diseased joint. We hypothesized that ...
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Journal ArticleBr J Haematol · December 2012
A recent meta-analysis of three genome-wide association studies of chronic lymphocytic leukaemia (CLL) identified two common variants at the 6p21.31 locus that are associated with CLL risk. To verify and further explore the association of these variants wi ...
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ConferenceBlood · November 16, 2012
AbstractAbstract 4576Background:Chronic lymphocytic leukemia (CLL) has a highly variable clinical cou ...
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ConferenceBlood · November 16, 2012
AbstractAbstract 1785Background:Chronic lymphocytic leukemia (CLL), the most common hematopoietic mal ...
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Journal ArticleLeuk Lymphoma · November 2012
Chronic lymphocytic leukemia (CLL) is the most prevalent leukemia in the United States with almost 4390 attributable deaths per year. Epidemiologic data compiled by the Surveillance, Epidemiology and End Results (SEER) program identifies important differen ...
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Journal ArticleBlood · August 23, 2012
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The incidence of chronic lymphocytic leukemia (CLL) is significantly lower in African Americans than whites, but overall survival is inferior. The biologic basis for these observations remains unexplored. We hypothesized that germline genetic predispositio ...
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Journal ArticleBlood · July 26, 2012
We performed a meta-analysis of 3 genome-wide association studies to identify additional common variants influencing chronic lymphocytic leukemia (CLL) risk. The discovery phase was composed of genome-wide association study data from 1121 cases and 3745 co ...
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Journal ArticleLeuk Lymphoma · February 2012
Patients with chronic lymphocytic leukemia (CLL) with deletion or mutation of TP53 have exceedingly poor clinical outcomes. Cenersen, an oligonucleotide targeting TP53, has been shown to abrogate the activity of TP53 gain-of-function mutants and to increas ...
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Journal ArticlePLoS One · 2012
Plasma Plasmodium falciparum histidine-rich protein-2 (PfHRP-2) concentrations, a measure of parasite biomass, have been correlated with malaria severity in adults, but not yet in children. We measured plasma PfHRP-2 in Tanzanian children with uncomplicate ...
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Journal ArticleBlood · October 13, 2011
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B-cell chronic lymphocytic leukemia (CLL), an incurable leukemia, is characterized by defective apoptosis. We found that the SET oncoprotein, a potent inhibitor of the protein phosphatase 2A (PP2A) tumor suppressor, is overexpressed in primary CLL cells an ...
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Journal ArticleLeukemia · September 2011
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Monoclonal B-cell lymphocytosis (MBL) is a hematologic condition wherein small B-cell clones can be detected in the blood of asymptomatic individuals. Most MBL have an immunophenotype similar to chronic lymphocytic leukemia (CLL), and 'CLL-like' MBL is a p ...
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Journal ArticleLeuk Lymphoma · July 2011
During B lymphocyte maturation, a subset of B cells undergo class switch recombination (CSR), a process wherein the heavy chain constant region is changed to a different immunoglobulin isotype without introduction of variable region mutations. CSR thus all ...
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Journal ArticleImmunol Res · April 2011
Monoclonal B-cell lymphocytosis (MBL) is a preclinical hematologic condition wherein small numbers of clonal B cells can be detected in the blood of otherwise healthy individuals. Most MBL have a surface immunophenotype nearly identical to that of chronic ...
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Journal ArticleBlood · February 10, 2011
Prior genome-wide association (GWA) studies have identified 10 susceptibility loci for risk of chronic lymphocytic leukemia (CLL). To identify additional loci, we performed a GWA study in 407 CLL cases (of which 102 had a family history of CLL) and 296 con ...
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Journal ArticleArthritis Res Ther · 2011
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INTRODUCTION: Interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α) are up-regulated in injured and osteoarthritic knee joints. IL-1 and TNF-α inhibit integrative meniscal repair; however, the mechanisms by which this inhibition occurs are not fully und ...
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Journal ArticleBlood · December 2, 2010
A role for microRNA (miRNA) has been recognized in nearly every biologic system examined thus far. A complete delineation of their role must be preceded by the identification of all miRNAs present in any system. We elucidated the complete small RNA transcr ...
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Journal ArticleMalar J · October 29, 2010
BACKGROUND: Severe malaria (SM) syndromes caused by Plasmodium falciparum infection result in major morbidity and mortality each year. However, only a fraction of P. falciparum infections develop into SM, implicating host genetic factors as important deter ...
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Journal ArticleBr J Haematol · October 2010
Monoclonal B-cell lymphocytosis (MBL) is an asymptomatic haematological condition characterized by low absolute levels of B-cell clones with a surface immunophenotype similar to that of chronic lymphocytic leukaemia (CLL). In the general population, MBL in ...
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Journal ArticleLeukemia · September 2010
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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 ArticleLeuk Lymphoma · August 2010
Monoclonal B lymphocytosis (MBL) is an asymptomatic clinical syndrome wherein small B cell clones are detectable in the peripheral blood. MBL is common in the adult population, with an estimated prevalence of greater than 3% among individuals over age 50. ...
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Journal ArticleNat Genet · August 2010
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To identify susceptibility loci for non-Hodgkin lymphoma subtypes, we conducted a three-stage genome-wide association study. We identified two variants associated with follicular lymphoma at 6p21.32 (rs10484561, combined P = 1.12 x 10(-29) and rs7755224, c ...
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Journal ArticleJ Infect Dis · July 1, 2010
BACKGROUND: Age and host genetics are important determinants of malaria severity. Lymphotoxin-alpha (LTalpha) has been associated with the development of cerebral malaria (CM) and other severe malaria (SM) syndromes. Mutations in genes regulating LTalpha p ...
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Journal ArticleOsteoarthritis Cartilage · June 2010
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OBJECTIVE: Meniscal tears are a common knee injury and increased levels of interleukin-1 (IL-1) have been measured in injured and degenerated joints. Studies have shown that IL-1 decreases the shear strength, cell accumulation, and tissue formation in meni ...
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Journal ArticleAm J Clin Pathol · May 2010
We describe a simple and robust flow cytometry assay for ZAP-70 and CD38 expression. The steps required to validate this assay in a clinical flow cytometry laboratory are described. Two criteria were used to characterize ZAP-70 expression into positive, ne ...
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Journal ArticlePLoS Pathog · April 22, 2010
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Asymmetrical dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), is a predictor of mortality in critical illness. Severe malaria (SM) is associated with decreased NO bioavailability, but the contribution of ADMA to the pathogen ...
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Journal ArticleCancer Epidemiol Biomarkers Prev · April 2010
BACKGROUND: There is strong and consistent evidence that a genetic component contributes to the etiology of chronic lymphocytic leukemia (CLL). A recent genome-wide association study of CLL identified seven genetic variants that increased the risk of CLL w ...
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Journal ArticleHum Genet · February 2010
Nitric oxide (NO) mediates host resistance to severe malaria and other infectious diseases. NO production and mononuclear cell expression of the NO producing enzyme-inducible nitric oxide synthase (NOS2) have been associated with protection from severe fal ...
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Journal ArticleLeukemia · January 2010
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Monoclonal B-cell lymphocytosis (MBL) is a preclinical hematologic syndrome characterized by small accumulations of CD5(+) B lymphocytes. Most MBL share phenotypic characteristics with chronic lymphocytic leukemia (CLL). Although some MBL progress to CLL, ...
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Journal ArticlePLoS Pathogens · 2010
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Asymmetrical dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), is a predictor of mortality in critical illness. Severe malaria (SM) is associated with decreased NO bioavailability, but the contribution of ADMA to the pathogen ...
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Journal ArticleCytometry B Clin Cytom · 2010
Monoclonal B Cell Lymphocytosis (MBL) refers to clones of CLL-like cells that exhibit CLL characteristics that fall short of the numbers required for CLL diagnosis. Data from large CLL kindreds document increased prevalence of MBL suggesting a genetic cont ...
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ConferenceBlood · November 20, 2009
AbstractAbstract 802Background and Significance:Even though we have treatments for CLL, it remains an ...
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Journal ArticleClin Cancer Res · November 15, 2009
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PURPOSE: Chronic lymphocytic leukemia (CLL) is a B-cell malignancy characterized by a variable clinical course. Several parameters have prognostic capabilities but are associated with altered response to therapy in only a small subset of patients. EXPERIME ...
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Journal ArticleJ Infect Dis · November 15, 2009
BACKGROUND: Hemolysis causes anemia in falciparum malaria, but its contribution to microvascular pathology in severe malaria (SM) is not well characterized. In other hemolytic diseases, release of cell-free hemoglobin causes nitric oxide (NO) quenching, en ...
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Journal ArticleHum Genet · November 2009
Tuberculosis (TB) has substantial mortality worldwide with 5-10% of those exposed progressing to active TB disease. Studies in mice and humans indicate that the inducible nitric oxide synthase (iNOS) molecule plays an important role in immune response to T ...
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Journal ArticleFree Radic Biol Med · June 15, 2009
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Cobalamins are important cofactors for methionine synthase and methylmalonyl-CoA mutase. Certain corrins also bind nitric oxide (NO), quenching its bioactivity. To determine if corrins would inhibit NO synthase (NOS), we measured their effects on -L-[(14)C ...
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Journal ArticleClin Orthop Relat Res · June 2009
Damage or injury of the meniscus is associated with onset and progression of knee osteoarthritis (OA). The intrinsic repair capacity of the meniscus is inhibited by inflammatory cytokines, such as interleukin-1 (IL-1). Using an in vitro meniscal repair mod ...
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Journal ArticleBlood · May 7, 2009
Mature B-cell differentiation provides an important mechanism for the acquisition of adaptive immunity. Malignancies derived from mature B cells constitute the majority of leukemias and lymphomas. These malignancies often maintain the characteristics of th ...
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Journal ArticleJ Biol Inorg Chem · January 2009
Intraprotein electron transfer (IET) from flavin mononucleotide (FMN) to heme is essential in NO synthesis by NO synthase (NOS). Our previous laser flash photolysis studies provided a direct determination of the kinetics of the FMN-heme IET in a truncated ...
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Journal ArticleLeukemia · December 2008
Survival of chronic lymphocytic leukemia (CLL) cells requires sustained activation of the antiapoptotic PI-3-K/Akt pathway, and many therapies for CLL cause leukemia cell death by triggering apoptosis. Blood lipoprotein particles are either pro- or antiapo ...
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Journal ArticleCurr Opin Infect Dis · October 2008
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PURPOSE OF REVIEW: Parasiticidal therapy of severe falciparum malaria improves outcome, but up to 30% of these patients die despite best therapy. Nitric oxide is protective against severe disease, and both nitric oxide and arginine (the substrate for nitri ...
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Journal ArticleJ Infect Dis · August 15, 2008
BACKGROUND: Severe malaria is characterized by microvascular obstruction, endothelial dysfunction, and reduced levels of L-arginine and nitric oxide (NO). L-Arginine infusion improves endothelial function in moderately severe malaria. Neither the longitudi ...
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Journal ArticleLeuk Res · July 2008
Nitric oxide synthase (NOS) inhibitors induce chronic lymphocytic leukemia (CLL) cell apoptosis and have potential as CLL therapeutics. We determined the half-maximal concentration (ED(50)) of 22 NOS inhibitors that induced CLL cell death in vitro. There w ...
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Journal ArticleBlood · June 15, 2008
Up to 30% of adult patients with sickle cell disease (SCD) will develop pulmonary hypertension (pHTN), a complication associated with significant morbidity and mortality. To identify genetic factors that contribute to risk for pHTN in SCD, we performed ass ...
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Journal ArticlePLoS One · June 11, 2008
BACKGROUND: L-arginine infusion improves endothelial function in malaria but its safety profile has not been described in detail. We assessed clinical symptoms, hemodynamic status and biochemical parameters before and after a single L-arginine infusion in ...
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Journal ArticleOsteoarthritis Cartilage · May 2008
OBJECTIVE: Osteoarthritis (OA) is associated with increased levels of reactive nitrogen and oxygen species and pro-inflammatory cytokines, such as interleukin-1 (IL-1). Nitric oxide (NO) can mediate a number of the catabolic effects of IL-1 in articular ca ...
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Journal ArticleJ Orthop Res · April 2008
Damage or loss of the meniscus is associated with progressive osteoarthritic degeneration of the knee joint. Injured and degenerative joints are characterized by elevated levels of the pro-inflammatory cytokine interleukin-1 (IL-1), which with prolonged ex ...
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Journal ArticleAm J Hematol · December 2007
Several parameters may predict disease severity and overall survival in chronic lymphocytic leukemia (CLL). The purpose of our study of 190 CLL patients was to compare immunoglobulin heavy chain variable region (IgV(H)) mutation status, cytogenetic abnorma ...
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ConferenceBlood · November 16, 2007
AbstractChronic Lymphocytic Leukemia (CLL) is notable for variation in aggressiveness of disease. Many patients with low-risk disease at diagnosis can be followed expectantly, while others rapidly require th ...
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ConferenceBlood · November 16, 2007
AbstractB cell chronic lymphocytic leukemia (CLL), the most common subtype of leukemia in the United States of America and in Europe, is treatable but incurable. New drugs are needed for its management. Phos ...
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ConferenceBlood · November 16, 2007
AbstractSurvival of CLL cells requires sustained activation of the anti-apoptotic PI-3-kinase/Akt pathway, and many therapies for CLL cause leukemia cell death by triggering apoptosis. Blood lipoprotein part ...
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ConferenceBlood · November 16, 2007
AbstractBackground: Monoclonal B cell lymphocytosis (MBL) is a pre-clinical syndrome characterized by small accumulations of monoclonal B lymphocytes in the peripheral blood. MBL have an immunophenotype simi ...
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ConferenceBlood · November 16, 2007
AbstractBackground: Although most malignancies are associated with decreased numbers of circulating T cells, in CLL they are elevated 2 to 4 times normal. Rather than promoting an anti-tumor response, this i ...
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ConferenceBlood · November 16, 2007
AbstractBackground: Segregation analyses suggest that CLL has one of the highest inherited risks among all types of cancer. However, no common germline mutations that confer an inherited predisposition to CL ...
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Journal ArticleJ Exp Med · October 29, 2007
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Severe falciparum malaria (SM) is associated with tissue ischemia related to cytoadherence of parasitized erythrocytes to microvascular endothelium and reduced levels of NO and its precursor, l-arginine. Endothelial function has not been characterized in S ...
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Journal ArticleArthritis Rheum · September 2007
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OBJECTIVE: To examine the hypotheses that increasing concentrations of interleukin-1 (IL-1) or tumor necrosis factor alpha (TNFalpha) inhibit the integrative repair of the knee meniscus in an in vitro model system, and that inhibitors of these cytokines wi ...
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Journal ArticleOsteoarthritis Cartilage · September 2007
OBJECTIVE: Injury or removal of the knee meniscus leads to progressive joint degeneration, and current surgical therapies for meniscal tears seek to maximally preserve meniscal structure and function. However, the factors that influence intrinsic repair of ...
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Journal ArticleBiochem Biophys Res Commun · July 13, 2007
Injury or loss of the knee meniscus is associated with altered joint stresses that lead to progressive joint degeneration. The goal of this study was to determine if dynamic mechanical compression influences the production of inflammatory mediators by meni ...
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Journal ArticleThe American journal of tropical medicine and hygiene · June 2007
Plasmodium falciparum malaria is one of the leading causes of childhood morbidity and mortality in sub-Saharan Africa. The host immune response to P. falciparum is a critical determinant of malarial pathogenesis and disease outcomes. Macrophage migration i ...
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Journal ArticleAm J Trop Med Hyg · June 2007
Plasmodium falciparum malaria is one of the leading causes of childhood morbidity and mortality in sub-Saharan Africa. The host immune response to P. falciparum is a critical determinant of malarial pathogenesis and disease outcomes. Macrophage migration i ...
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Journal ArticleAm J Sports Med · May 2007
BACKGROUND: The menisci are essential intra-articular structures that contribute to knee function, and meniscal injury or loss is associated with joint degeneration. Tears of the outer vascularized zone have a greater potential for repair than do tears in ...
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Journal ArticleBr J Haematol · May 2007
Priapism occurs in 30-45% of male patients with sickle cell disease (SCD), but the possible influence of genetic risk factors on the incidence of priapism is not well understood. We examined genetic polymorphisms in 199 unrelated, adult (>18 years), male p ...
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Journal ArticleEur Cell Mater · April 11, 2007
Molecular oxygen is required for the production of nitric oxide (NO), a pro-inflammatory mediator that is associated with osteoarthritis and rheumatoid arthritis. To date there has been little consideration of the role of oxygen tension in the regulation o ...
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Journal ArticleBlood · February 15, 2007
Somatic mutations of immunoglobulin genes characterize mature memory B cells, and intraclonal B-cell diversification is typically associated with expansion of B-cell clones with greater affinity for antigen (antigen drive). Evidence for a role of antigen i ...
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Journal ArticleJ Rheumatol · February 2007
OBJECTIVE: Osteoarthritis is characterized by the degradation of articular cartilage. The catabolic activity of chondrocytes is partly regulated by nitric oxide (NO), which with superoxide (O2-) leads to the formation of peroxynitrite (OONO-), a potentiall ...
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Journal ArticleSubcell Biochem · 2007
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Rheumatoid arthritis and osteoarthritis are painful and debilitating diseases with complex pathophysiology. There is growing evidence that pro-inflammatory cytokines (e.g., interleukin-1 and tumor necrosis factor alpha) and mediators (e.g., prostaglandins, ...
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Journal ArticleProc Natl Acad Sci U S A · August 22, 2006
Alzheimer's disease is characterized by two primary pathological features: amyloid plaques and neurofibrillary tangles. The interconnection between amyloid and tau aggregates is of intense interest, but mouse models have yet to reveal a direct interrelatio ...
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Journal ArticleInfect Immun · June 2006
Cerebral malaria is associated with decreased production of nitric oxide and decreased levels of its precursor, l-arginine. Abnormal amino acid metabolism may thus be an important factor in malaria pathogenesis. We sought to determine if other amino acid a ...
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Journal ArticleJ Biol Chem · May 19, 2006
Mammalian nitric-oxide synthases are large modular enzymes that evolved from independently expressed ancestors. Calmodulin-controlled isoforms are signal generators; calmodulin activates electron transfer from NADPH through three reductase domains to an ox ...
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Journal ArticleJ Infect Dis · May 15, 2006
Cytokines and effector molecules are important immunoregulatory molecules in human malaria. Tumor necrosis factor (TNF)-alpha limits malaria parasitemia but also promotes pathogenesis at high concentrations, whereas prostaglandin E2 (PGE2) inhibits TNF-alp ...
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Journal ArticleClin Immunol · May 2006
Plasmodium falciparum malaria remains one of the most frequently lethal diseases affecting children in sub-Saharan Africa, yet the immune mediators that regulate pathogenesis are only partially defined. Since macrophage migration inhibitory factor (MIF) is ...
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Journal ArticleMCB Molecular and Cellular Biomechanics · January 1, 2006
A study was performed to examine the hypotheses that increasing concentrations of the pro-inflammatory cytokines interleukin-1 (IL-1) or tumor necrosis factor-alpha (TNF) inhibit integrative repair of the knee meniscus in an in vitro model system and that ...
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Journal ArticleLeuk Res · January 2006
B cell chronic lymphocytic leukemia (CLL) CD38 expression is variable and may predict outcome. Inducible nitric oxide synthase (NOS2) expression regulates CLL cell apoptosis. IL-4 and IFN-gamma regulate B cell CD38 expression and NOS2 expression. We compar ...
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Journal ArticleConnect Tissue Res · 2006
During knee joint loading, the fibrocartilaginous menisci experience significant spatial variations in mechanical stimuli. Meniscus cells also exhibit significant variations in biosynthesis and gene expression depending on their location within the tissue. ...
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Journal ArticleArthritis Res Ther · 2006
Nitric oxide (NO) may play important roles in rheumatoid arthritis (RA). RA is an inflammatory disease involving joints and other systems including salivary glands. To assess NO production in RA patients, we compared levels of serum, urine, and salivary ni ...
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ConferenceBlood · November 16, 2005
AbstractCobalamins (Cbl) serve as important co-factors for methionine synthase and methylmalonyl-coA mutase. They also can block the activities of nitric oxide (NO), as the cobalt binds NO and quenches its b ...
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Journal ArticleOsteoarthritis Cartilage · October 2005
OBJECTIVES: Articular cartilage is an avascular tissue that exists at low oxygen tension. Oxygen tension can influence the production of the pro-inflammatory mediators nitric oxide (NO) and prostaglandin E2 (PGE(2)) in cartilage, which are increased in ost ...
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Journal ArticleInfect Immun · July 2005
Chemokines regulate the host immune response to a variety of infectious pathogens. Since the role of chemokines in regulating host immunity in children with Plasmodium falciparum malaria has not previously been reported, circulating levels of beta-chemokin ...
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Journal ArticleInfect Immun · June 2005
The cytokine gamma interferon (IFN-gamma) is critical for resistance to Toxoplasma gondii. IFN-gamma strongly activates macrophages and nonphagocytic host cells to limit intracellular growth of T. gondii; however, the cellular factors that are required for ...
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Journal ArticleJ Biol Chem · May 13, 2005
One of the phenotypes of mice with targeted disruption of the uncoupling protein-2 gene (Ucp2-/-) is greater macrophage phagocytic activity and free radical production, resulting in a striking resistance to infectious microorganisms. In this study, the mol ...
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Journal ArticleJ Infect Dis · May 1, 2005
Prostaglandins (PGs) are important mediators of macrophage activity, vascular permeability, fever, erythropoiesis, and proinflammatory responses to infection. Our recent studies have shown that plasma levels of bicyclo-PGE2 (a stable end product of PGE2 me ...
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Journal ArticleInfect Immun · December 2004
Individuals in areas of intense malaria transmission exhibit resistance (or tolerance) to levels of parasitemia in their blood that would normally be associated with febrile illness in malaria-naive subjects. The resulting level of parasitemia associated w ...
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Journal ArticleOsteoarthritis Cartilage · December 2004
OBJECTIVES: Cells of the knee meniscus respond to changes in their biochemical and biomechanical environments with alterations in the biosynthesis of matrix constituents and inflammatory mediators. Tumor necrosis factor alpha (TNF-alpha) is a pro-inflammat ...
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Journal ArticleCurr Mol Med · November 2004
Atherosclerosis is an inflammatory disorder, and the inflammation associated with systemic lupus erythematosus (SLE) accelerates the development of atherosclerosis. Nitric oxide (NO) is an important mediator of inflammation including the inflammation assoc ...
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Journal ArticleJ Biol Chem · August 6, 2004
The interactions of neuronal nitric-oxide synthase (nNOS) with calmodulin (CaM) and mutant forms of CaM, including CaM-troponin C chimeras, have been previously reported, but there has been no comparable investigation of CaM interactions with the other con ...
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Journal ArticleInfect Immun · August 2004
Experiments outlined here investigate the role of nitric oxide (NO) in the pathogenesis of Plasmodium falciparum-induced malarial anemia (MA). The results show that ex vivo and in vitro NO synthase (NOS) activity in peripheral blood mononuclear cells (PBMC ...
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Journal ArticleClin Orthop Relat Res · June 2004
Osteoarthritis is a painful and debilitating disease characterized by progressive degenerative changes in the articular cartilage and other joint tissues. Biomechanical factors play a critical role in the initiation and progression of this disease, as evid ...
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Journal ArticleJ Biol Chem · April 30, 2004
The three mammalian nitric-oxide synthases produce NO from arginine in a reaction requiring 3 electrons per NO, which are supplied to the catalytic center from NADPH through reductase domains incorporating FAD and FMN cofactors. The isoforms share a common ...
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Journal ArticleMol Med · 2004
Molecular immunologic determinants of disease severity during Plasmodium falciparum malaria are largely undetermined. Our recent investigations showed that peripheral blood mononuclear cell (PBMC) cyclooxygenase-2 (COX-2) gene expression and plasma prostag ...
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Journal ArticleAm J Trop Med Hyg · December 2003
Polymorphisms in the inducible nitric oxide synthase gene (NOS2) promoter have been associated with clinical outcome from malaria. These include a CCTTT repeat (CCTTTn) 2.5 kilobases upstream from the NOS2 transcription start site, and two single nucleotid ...
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Journal ArticleInfect Immun · November 2003
Interleukin-12 (IL-12) has been inversely associated with disease severity in human and murine malaria, and a polymorphism in the IL-12 p40 subunit gene (IL12B) has been associated with susceptibility to human cerebral malaria and reduced nitric oxide (NO) ...
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Journal ArticleInfect Immun · July 2003
Individuals living in regions of intense malaria transmission exhibit natural immunity that allows them to be without fever and other symptoms for most of the time despite frequent parasitization. Although this tolerance of parasitemia appears to be more e ...
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Journal ArticleJ Appl Physiol (1985) · July 2003
The meniscus is an intra-articular fibrocartilaginous structure that serves essential biomechanical roles in the knee. With injury or arthritis, the meniscus may be exposed to significant changes in its biochemical and biomechanical environments that likel ...
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Journal ArticleLancet · February 22, 2003
Nitric oxide (NO) production and mononuclear cell NO synthase 2 (NOS2) expression are high in healthy Tanzanian children but low in those with cerebral malaria. Factors that downregulate NOS2 also diminish factors involved in cellular uptake and biosynthes ...
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Journal ArticleLeukemia · February 2003
Chronic lymphocytic leukemia (B-CLL) is characterized by the accumulation of long-lived non-dividing CD5(+) B cells. Nitric oxide (NO) is an important regulator of apoptosis, and the viability of cultured B-CLL cells may be dependent on the autocrine produ ...
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Journal ArticleJ Rheumatol · January 2003
OBJECTIVE: Systemic lupus erythematosus (SLE) is an autoimmune disease in which morbidity and mortality are higher in African-Americans. The etiology of this racial disparity is unknown. A genetic predisposition to enhanced nitric oxide (NO) production may ...
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Journal ArticleLancet · November 9, 2002
BACKGROUND: Nitric oxide (NO) is a mediator of immunity to malaria, and genetic polymorphisms in the promoter of the inducible NO synthase gene (NOS2) could modulate production of NO. We postulated that NOS2 promoter polymorphisms would affect resistance t ...
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Journal ArticleGenes Immun · November 2002
Interleukin-12 (IL-12) is an important regulatory cytokine in infection and immunity. Administration of IL-12 may reduce complications of severe malaria in rodents. Polymorphisms in IL12B, the gene encoding the IL-12 p40 subunit, influence the secretion of ...
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Journal ArticleOsteoarthritis Cartilage · October 2002
OBJECTIVE: Biomechanical signals play important roles in regulating the homeostasis of articular cartilage, but under abnormal conditions may be a critical factor in the onset and progression of arthritis. Prostaglandin E(2) (PGE(2)) and nitric oxide (NO), ...
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Journal ArticleLancet · August 24, 2002
BACKGROUND: The ability of T cells, acting independently of antibodies, to control malaria parasite growth in people has not been defined. If such was shown to be effective, an additional vaccine strategy could be pursued. Our aim was to ascertain whether ...
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Journal ArticleArthritis Rheum · April 2002
OBJECTIVE: Articular cartilage is an avascular tissue that functions at a lower oxygen tension than do most tissues. With mobilization, arthritic joints may undergo cycles of hypoxia and reoxygenation. The goal of this study was to determine the effects of ...
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Journal ArticleFertil Steril · January 2002
OBJECTIVE: Determine whether peritoneal macrophages from women with endometriosis-associated infertility express more inducible nitric oxide synthase (NOS2) and produce more NO than fertile controls. DESIGN: Unblinded clinical study. PATIENT(S): Nine infer ...
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Journal ArticleLeukemia · December 2001
Fludarabine is active but not curative in the treatment of chronic lymphocytic leukemia (B-CLL). Nitric oxide (NO) supplied from exogenous, NO-donating pro-drugs can also induce apoptosis and death of acute leukemia cells. This study investigated combinati ...
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Journal ArticleInfect Immun · December 2001
Depending on sequence, bacterial and synthetic DNAs can activate the host immune system and influence the host response to infection. The purpose of this study was to determine the abilities of various phosphorothioate oligonucleotides with cytosine-guanos ...
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Journal ArticleArthritis Rheum · September 2001
OBJECTIVE: In osteoarthritis (OA), a combination of biochemical and biomechanical factors may damage both menisci and articular cartilage. Nitric oxide (NO) and prostaglandin E2 (PGE2) have been implicated as mediators of inflammation in OA. The goals of t ...
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Journal ArticleProc Natl Acad Sci U S A · August 28, 2001
Human inducible nitric oxide synthase (iNOS) is active as a dimer of two identical subunits. Each subunit has an amino-terminal oxygenase domain that binds the substrate l-Arg and the cofactors heme and tetrahydrobiopterin and a carboxyl-terminal reductase ...
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Journal ArticleBiochem Biophys Res Commun · July 20, 2001
Nitric oxide (NO) and leukotrienes regulate a variety of processes in joint tissues and are frequently elevated in arthritis. Mechanical stress can induce biochemical and functional changes in cartilage that may influence mediator production. To investigat ...
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Journal ArticleJ Orthop Res · July 2001
Nitric oxide (NO) production and NO synthase (NOS) expression are increased in osteoarthritis and rheumatoid arthritis, suggesting that NO may play a role in the destruction of articular cartilage. To test the hypothesis that mechanical stress may increase ...
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Journal ArticleOsteoarthritis Cartilage · July 2001
OBJECTIVE: The menisci play an important role in the biomechanics of the knee, and loss of meniscal function has been associated with progressive degenerative changes of the joint in rheumatoid arthritis as well as in osteoarthritis. However, little is kno ...
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Journal ArticleJ Infect Dis · January 1, 2001
Prostaglandins (PGs) derived from inducible cyclooxygenase (COX)-2 are important proinflammatory mediators of the host-immune response to infection. Since the role of host-derived PG in human malaria is unknown, plasma bicyclo-PGE2 (a stable catabolite of ...
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Journal ArticleSepsis · January 1, 2001
Significant variability exists in host responses to malaria in different human populations. These epidemiological data have prompted a search for genetic variations that determine host responses to malaria. This review focuses on polymorphisms in the promo ...
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Journal ArticleBlood · December 1, 2000
Prostaglandins (PG) derived from inducible cyclooxygenase (COX-2) are important pro-inflammatory mediators of the host-immune response to infection. Since the role of host-derived PG in human malaria is unknown, plasma bicyclo-PGE2 (a stable catabolite of ...
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Journal ArticleBlood · December 1, 2000
Chronic lymphocytic leukemia (B-CLL) is a malignancy of a mantle zone-based subpopulation of anergic, self-reactive, activated CD5+ B lymphocytes devoted to the production of polyreactive natural autoantibodies. B-CLL is characterized by the accumulation o ...
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Journal ArticleBlood · December 1, 2000
Malaria is extremely important, with approximately 500 million people infected and 1.5 to 2.7 million dying from the disease each year. Deaths are usually related to cerebral malaria and malarial anemia. Malarial anemia is a multifactorial anemia related t ...
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Journal ArticleInfect Immun · July 2000
We compared interleukin-12 (IL-12) and other cytokine activities during and after an acute clinical episode in a matched-pair case-control study of young African children who presented with either mild or severe Plasmodium falciparum malaria. The acute-pha ...
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Journal ArticleImmunol Res · 2000
Nitric oxide (NO) and prostaglandin (PG) E2 produced by NO synthase type 2 (NOS2) and cyclooxygenase type 2 (COX2), respectively, are important mediators in inflammation. There is much information regarding their roles in models of inflammation in mice and ...
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Journal ArticleJ Infect Dis · December 1999
Nitric oxide (NO) plays an important role in host resistance to infection with a variety of organisms. Two recent reports from Gabon and Gambia identified associations of malaria disease severity with the inducible NO synthase (NOS2) promoter G-954C and sh ...
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Journal ArticleInfect Immun · September 1999
Plasmodium falciparum malaria is an important cause of morbidity and mortality in children. Factors that determine the development of mild versus severe malaria are not fully understood. Since host-derived nitric oxide (NO) has antiplasmodial properties, w ...
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Journal ArticleAm J Trop Med Hyg · August 1999
The cause of the anemia associated with chronic, intermittent, asymptomatic, low-level parasitemia in children in malaria-endemic endemic areas is not well understood. Nitric oxide (NO) decreases erythropoiesis, and it is likely an important mediator of an ...
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Journal ArticleAm J Trop Med Hyg · August 1999
Age appears to influence not only the acquisition of clinical immunity to malaria but also the susceptibility to and clinical manifestations of severe malaria. Asymptomatic malaria-exposed Tanzanian children have high production of nitric oxide (NO) and un ...
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Journal ArticleArthritis Rheum · March 1999
Human interferon-alpha (IFNalpha) and IFNbeta are administered for treatment of several diseases, including viral infections, malignancies, and multiple sclerosis (MS). IFNalpha therapy has been associated with the production of autoantibodies and the deve ...
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Journal ArticleArthritis Rheum · December 1998
OBJECTIVE: Peripheral blood mononuclear cells (PBMC) from patients with rheumatoid arthritis (RA) have increased expression of nitric oxide synthase type 2 (NOS2) protein and enhanced formation of nitric oxide (NO) that correlate with disease activity. NO ...
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Journal ArticleEnviron Health Perspect · October 1998
Nitric oxide (.NO) may exhibit proinflammatory features. .NO synthase type 2 (NOS2) is overexpressed and .NO overproduced in rodent models of induced inflammation. Blockage of .NO production by administration of NOS inhibitors prevents or reduces various t ...
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Journal ArticleLeukemia · September 1998
Nitric oxide (NO) has potent antiproliferative properties. In previous work we have shown that NO inhibits growth, induces differentiation and modulates gene expression in acute nonlymphocytic leukemia (ANLL) cells. The goal of this work was to determine w ...
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Journal ArticleBiochem Biophys Res Commun · May 19, 1998
Our prior studies showed that certain cobalamins inhibit productive HIV-1 infection of primary cultures of blood lymphocytes and monocytes. We demonstrate here that this antiviral activity may be mediated by an inhibition of HIV-1 integrase, an enzyme requ ...
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Journal ArticleFree Radic Biol Med · January 1, 1998
MRL-lpr/lpr mice spontaneously develop manifestations of autoimmunity including arthritis, vasculitis, and glomerulonephritis. The paramagnetic molecule nitric oxide has been implicated as an effector molecule in initiation and propagation of these inflamm ...
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Journal ArticleJ Exp Med · November 3, 1997
Although researchers have noted high level activation of rodent mononuclear phagocytes for nitric oxide (NO) synthase type 2 (S2) expression and NO production with a variety of agents such as interferon (IFN) gamma and endotoxin, it has been difficult to d ...
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Journal ArticleJ Exp Med · August 4, 1997
Nitric oxide (NO) is an important mediator of the inflammatory response. MRL-lpr/lpr mice overexpress inducible nitric oxide synthase (NOS2) and overproduce NO in parallel with the development of an autoimmune syndrome with a variety of inflammatory manife ...
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Journal ArticleOral Dis · May 1997
Saliva contains factors that inhibit infection with the human immunodeficiency virus type 1 (HIV-1) in vitro. One of these factors was recently identified as secretory leukocyte protease inhibitor (SLPI), a salivary protein which blocked HIV-1 infectivity ...
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Journal ArticleBlood · September 1, 1996
Nitric oxide (NO) is a paramagnetic gas that has been implicated in a wide range of biologic functions. The common pathway to evoke the functional response frequently involves the formation of an iron-nitrosyl complex in a target (heme) protein. In this st ...
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Journal ArticleJ Exp Med · September 1, 1996
Nitric oxide (NO) is an important inflammatory mediator in nonhuman animal models of rheumatoid arthritis (RA). The purpose of the present study was to determine whether blood mononuclear cells from patients with active RA (as compared to control subjects) ...
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Journal ArticleJ Exp Med · August 1, 1996
Nitric oxide (NO)-related activity has been shown to be protective against Plasmodium falciparum in vitro. It has been hypothesized, however, that excess NO production contributes to the pathogenesis of cerebral malaria. The purpose of this study was to co ...
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Journal ArticleAIDS Res Hum Retroviruses · June 10, 1996
The HIV-1 genome encodes a protease that is required for viral processing of the precursor polyproteins Pr55gag and Pr160gag-pol. Interference with this process in human lymphocytes inhibits production of infectious virus. We tested the ability of several ...
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Journal ArticleBlood · February 1, 1996
Nitric oxide (NO) is a reactive molecule with numerous physiologic and pathophysiologic roles affecting the nervous, cardiovascular, and immune systems. In previous work, we have demonstrated that NO inhibits the growth and induces the monocytic differenti ...
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Journal ArticleBlood · August 15, 1995
Various cobalamins act as important enzyme cofactors and modulate cellular function. We investigated cobalamins for their abilities to modify productive human immunodeficiency virus-1 (HIV-1) infection of hematopoietic cells in vitro. We show that hydroxoc ...
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Journal ArticleBlood · August 1, 1995
Nitric oxide (NO) is produced by numerous different cell types, and it is an important regulator and mediator of many processes including smooth muscle relaxation, neurotransmission, and murine macrophage-mediated cytotoxicity for microbes and tumor cells. ...
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Journal ArticleFertil Steril · August 1995
OBJECTIVE: To determine the effect of nitric oxide (NO) on sperm motility in vitro. DESIGN: Normal human sperm separated by centrifugation through a discontinuous Percoll gradient and subsequent swim-up were incubated for up to 24 hours with NO donors, wit ...
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Journal ArticleLeuk Res · August 1995
Freshly isolated acute non-lymphocytic leukemia (ANLL) cells were treated with the nitric oxide (NO)-liberating compounds sodium nitroprusside or S-nitrosoacetyl penicillamine and analyzed for viability, growth, and differentiation at 3-5 days. NO decrease ...
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Journal ArticleJ Virol · July 1995
CD4 is the predominant cell membrane protein that binds human immunodeficiency virus type 1 (HIV-1) gp120 and facilitates HIV-1 infection, but other membrane-associated molecules may be involved in determining HIV-1 cellular infection. Our prior work had s ...
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Journal ArticleCancer Lett · January 6, 1995
Laminin is a component of the extracellular matrix and is associated with tumor cell metastasis. Present studies show that the ovarian cancer cell lines produce significant amounts of laminin (54-140 ng/ml) in culture. Since ovarian cancer is associated wi ...
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Journal ArticleJ Leukoc Biol · November 1994
Neopterin is a pteridine produced by human mononuclear phagocytes, usually in response to interferon-gamma (IFN-gamma) stimulation. Increasing serum levels of neopterin correlate with clinical progression to AIDS in HIV-infected people, but the factors tha ...
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Journal ArticleJ Exp Med · February 1, 1994
MRL-lpr/lpr mice spontaneously develop various manifestations of autoimmunity including an inflammatory arthropathy and immune complex glomerulonephritis. This study examines the role of nitric oxide, a molecule with proinflammatory actions, in the pathoge ...
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Journal ArticleClin Infect Dis · September 1993
Despite widespread use of trimethoprim-sulfamethoxazole (TMP-SMZ) for prophylaxis in neutropenic patients, questions remain regarding its efficacy, toxicity, the risk of selection of resistant isolates, and the relation of its activity to selective decolon ...
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Journal ArticleImmunol Invest · July 1993
Macrophages are normal constituents of synovial tissue, and in inflammatory synovitis the number of synovial macrophages increases. Synovial macrophages and their secretory products are important in initiating, propagating, and maintaining the synovial inf ...
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Journal ArticleBlood · October 15, 1992
Nitric oxide (NO) functions as an intercellular messenger molecule in such varied contexts as neurotransmission, immune regulation, and the control of vascular tone. We report that NO, delivered as purified gas or released from the pharmacologic NO donors ...
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Journal ArticleJ Clin Immunol · September 1992
Rheumatoid arthritis is a complex inflammatory disease of unknown cause. Although various laboratory and clinical measurements are useful in managing these patients, there is a need for better tests to quantitatively assess disease activity. The purpose of ...
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Journal ArticleJ Clin Invest · July 1992
The nuclear factor (NF)-kappa B transcription factor system is composed of at least four inducible nucleoprotein adducts termed p50, p55 (NF-kappa B p50), p75 (NF-kappa B p65), and p85 (c-Rel). These proteins are expressed in the nuclei of activated T cell ...
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Journal ArticleBlood · June 15, 1992
We have previously noted that the glutamine antagonist acivicin (alpha S,5S-alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid) induces monocytoid differentiation of freshly isolated human myeloid leukemia cells and cells of the myeloid leukemia cell ...
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Journal ArticleJ Leukoc Biol · May 1992
Dichlorofluorescein (DCFH) oxidation assay measures hydrogen peroxide (H2O2), which is a derivative of superoxide anion. We found that a calmodulin antagonist, W-13, which is known to inhibit superoxide anion generation enhanced the capacity of human neutr ...
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Journal ArticleAm J Obstet Gynecol · March 1992
OBJECTIVE: We investigated whether monocyte-derived factors could stimulate the growth of ovarian cancer cells. STUDY DESIGN: Human peripheral blood monocytes or human monocyte-like cell lines THP-1 and U-937 were cultured with or without macrophage colony ...
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Journal ArticleBlood · December 15, 1991
Thrombomodulin is an essential cofactor for the activation of the anticoagulant protein C by thrombin. We have identified the expression of thrombomodulin messenger RNA (mRNA) and protein in peripheral blood monocytes. While untreated monocytes expressed t ...
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Journal ArticleJ Exp Med · December 1, 1991
Human immunodeficiency virus type 1 (HIV-1) infection of T lymphocytes requires cellular proliferation and DNA synthesis. Human monocytes were shown to have low DNA synthesis rates, yet the monocytotropic BaL isolate of HIV-1 was able to infect these cells ...
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Journal ArticleFertil Steril · September 1991
OBJECTIVE: We tested the hypothesis that menstrual debris from ectopic endometrium is the stimulus responsible for eliciting the peritoneal fluid (PF) inflammation observed in infertile women with endometriosis. DESIGN, SETTING, PATIENTS: The extent of end ...
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Journal ArticleJ Virol · August 1991
The influence of human anti-human immunodeficiency virus type 1 (HIV-1) antibody on HIV-1 infection of freshly isolated normal human peritoneal macrophages and blood monocytes was examined. Each of 14 HIV antibody-positive human serum samples was found to ...
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Journal ArticleBlood · July 15, 1991
The peritoneal fluid (PF) of women with infertility (especially in the presence of endometriosis) contains increased numbers of leukocytes, 90% to 95% of which are macrophages. The high numbers of peritoneal macrophages presumably result from an influx of ...
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Journal ArticleAm Rev Respir Dis · December 1990
Human alveolar macrophages (HAM) from 28 normal volunteers were found to inhibit replication of Cryptococcus neoformans. Conditions under which fungistasis occurred were different than those required for mouse peritoneal macrophage-mediated fungistasis. In ...
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Journal ArticleGynecol Oncol · February 1990
CA 125 was measured in peritoneal fluid from 200 patients with primary ovarian malignancies (35) and benign gynecologic conditions (165). In 86 patients CA 125 was measured both in peritoneal fluid and in serum. Patients with ovarian cancer had markedly gr ...
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Journal ArticleJ Biol Chem · November 5, 1989
Tissue factor is a lipoprotein, expressed on the surface of cells, which binds coagulation Factor VII or VIIa, leading to activation of Factors X and IX with subsequent fibrin generation. Cellular tissue factor activity is important in pathophysiologic pro ...
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Journal ArticleBlood · October 1989
Previously we showed that starvation of HL-60 promyelocytic leukemia cells for a single essential amino acid induced irreversible differentiation into more mature monocyte-like cells. Although not an essential amino acid, glutamine is important in the grow ...
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Journal ArticleThromb Res · July 1, 1989
The physiologic function of the monocyte transglutaminases is not known. In this study, we detected Factor XIII A-subunit antigen and "tissue" transglutaminase antigen in human monocytes by polyacrylamide gel electrophoresis and immunoblotting techniques. ...
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Journal ArticleBlood · April 1989
In this study we examine the effects of amino acid deprivation on the growth and differentiation of the human HL-60 myeloid leukemia cell line. The HL-60 cell line was chosen for study because of its ability to differentiate along either a granulocytic or ...
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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 ArticleOral Surg Oral Med Oral Pathol · December 1988
Anticoagulation therapy is used to treat patients with a variety of hemostatic disorders in an attempt to prevent thrombus formation. A thorough understanding of the patient's medical history is essential before dental treatment that may require alteration ...
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Journal ArticleFertil Steril · July 1988
Alpha 2-macroglobulin (alpha 2M) is a plasma protein with proteinase inhibitor and immune modulatory capabilities. The amounts of alpha 2M in peritoneal fluid (PF) from women with endometriosis and women with noninflammatory gynecologic conditions were ana ...
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Journal ArticleBlood · July 1988
The induction of procoagulant activity (PCA) by human recombinant tumor necrosis factor (rTNF) was studied in human monoblastic leukemia cell line U937 and human peripheral blood monocytes. Using a one-step recalcificating clotting assay, PCA in cell lysat ...
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Journal ArticleAm J Med · July 1988
PURPOSE: Human adult T-cell leukemia-lymphoma is a malignant, proliferative disease of CD4+ lymphocytes associated with infection with human T-cell lymphotropic virus type I (HTLV-I). Following the presentation of a patient who was infected with the virus, ...
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Journal ArticleBlood · April 1988
We studied the effect of tumor necrosis factor (TNF) and gamma interferon (IFN-gamma), alone and in combination, on the expression of chemotactic peptide receptors, stimulus-induced actin polymerization, hydrogen peroxide production (H2O2), and expression ...
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Journal ArticleArch Intern Med · April 1988
An improved anemia classification may be available by combining measures of red blood cell size variability with mean corpuscular volume. Visual inspection of the peripheral blood film allows semiquantitative description of anisocytosis while quantitative ...
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Journal ArticleBiochem Biophys Res Commun · February 29, 1988
Human promyelocytic leukemia cells (HL-60) differentiate along a monocytoid pathway in response to recombinant human tumor necrosis factor or recombinant human interferon gamma. Together, these agents act synergistically to induce phenotypic differentiatio ...
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Journal ArticleBiol Reprod · December 1987
The role of reproductive tract macrophages in contraception and reproductive failure has become widely recognized. However, in vitro analysis of sperm phagocytosis by macrophages has relied upon a semi-quantitative method of sperm counting that is of limit ...
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Journal ArticleJ Leukoc Biol · December 1987
It has recently been shown that tumor necrosis factor (TNF) induces increased Ia antigen expression on a malignant murine macrophage cell line, and that TNF is synergistic with gamma interferon (IFN) in inducing Ia expression. This finding raises the possi ...
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Journal ArticleFertil Steril · November 1987
An intraperitoneal inflammatory process has been associated with infertility in women without anatomic distortion of the pelvic viscera, particularly with endometriosis. This phenomenon was investigated by measuring peritoneal fluid (PF) and serum levels o ...
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Journal ArticleJ Leukoc Biol · November 1987
1 alpha,25 dihydroxyvitamin D3 (1,25 D3) is known to interact with hematopoietic cells. The purpose of this study was to determine the effect of 1,25 D3 on hydrogen peroxide (H2O2) production and tumor cell killing by mouse peritoneal macrophages and human ...
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Journal ArticleBlood · October 1987
Human myeloid leukemia cells respond to various signals by differentiating to more mature cells. This study was designed to evaluate the effects of a mononuclear phagocyte-derived factor, tumor necrosis factor/cachectin (TNF), on the proliferation and diff ...
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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 · March 15, 1987
To assess the role of macrophages (MAC) in the pathogenesis of systemic lupus erythematosus, we investigated functional aspects of peritoneal MAC obtained from autoimmune MRL/MpJ-lpr/lpr (MRL-lpr) mice. MRL-lpr and control C3H/HeN MAC were obtained from un ...
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Journal ArticleBlood · February 1987
Patients with syndromes of autoantibody-mediated hematocytopenias may manifest signs of increased cell destruction and/or decreased cell production, depending on the maturity of the target cell and the effects of antibody binding. The purpose of this study ...
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Journal ArticleJ Clin Invest · January 1987
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hematopoietic stem cell disorder in which the blood cells demonstrate aberrant interactions with serum complement. In part, this is due to the absence of the complement regulatory protein, decay acce ...
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Journal ArticleJ Immunol Methods · December 4, 1986
Mononuclear phagocytes (monocytes and macrophages) are widely distributed throughout the body. Indium-111 (111In) oxine has been a useful radioactive label in studies of in vivo cellular kinetics and distribution. In preparation for in vivo monocyte invest ...
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Journal ArticleExp Hematol · February 1986
Various agents induce differentiation of human leukemia cells in vitro. Most of these agents cause myeloid differentiation, but phorbol diesters, 1-alpha,25-dihydroxyvitamin D3 (1,25[OH2]D3), and certain lymphokines cause differentiation to monocyte-like c ...
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Journal ArticleBlood · December 1985
Multinucleated giant cells of mononuclear phagocyte origin (monocyte or macrophage polykaryons [MPs] ) are seen in numerous different normal and pathologic states. We have previously shown that gamma interferon (IFN-gamma) induces fusion of uninuclear mono ...
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Journal ArticleFertil Steril · December 1985
Increased numbers of peritoneal macrophages have been repeatedly associated with infertility. Because the factors contributing to this intraperitoneal exudate are unknown, this study was carried out to determine which anatomic or endocrinologic abnormaliti ...
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Journal ArticleArch Pathol Lab Med · April 1985
We describe a patient with acute myelomonoblastic leukemia, jaundice, and ascites. The ascitic fluid contained leukemic cells comparable with those of the blood and bone marrow. Treatment with cytarabine (cytosine arabinoside) caused a decrease in the peri ...
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Journal ArticleFertil Steril · February 1985
The mechanism by which antisperm antibodies inhibit fertility is not completely understood. Macrophages may play a role in mediating infertility by interacting with sperm and destroying gametes. Experiments were conducted evaluating the effect of antisperm ...
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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 ArticleCancer research · December 1984
Various human and mouse myeloid leukemia cell lines can differentiate to mature myeloid or monocytoid cells in response to different agents. The myeloblastic leukemia of the RFM/Un mouse (the RF.AML line) was studied here to determine its ability to differ ...
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Journal ArticleFertil Steril · December 1984
To evaluate the functional status of endometriotic implants, a luteal secretory product of endometrium, PRL, was measured in the PF of 27 infertile women with endometriosis, 13 infertile women without endometriosis, and 11 fertile women undergoing elective ...
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Journal ArticleCancer Res · December 1984
Various human and mouse myeloid leukemia cell lines can differentiate to mature myeloid or monocytoid cells in response to different agents. The myeloblastic leukemia of the RFM/Un mouse (the RF.AML line) was studied here to determine its ability to differ ...
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Journal ArticleProc Natl Acad Sci U S A · July 1984
Monocyte or macrophage polykaryons (MP) are seen in different tissues in various inflammatory states and in normal bone (osteoclasts). The factors controlling the formation and the function of MP are not completely understood. This study was designed to ev ...
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Journal ArticleFertil Steril · June 1984
No single test to detect the presence of antisperm antibodies has correlated precisely with subsequent fertility. The purpose of this study was to determine whether heterogeneous effects of antibodies could potentially explain this observation. The effects ...
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Journal ArticleBlood · February 1984
Freshly isolated human leukemia cells have been shown in the past to display varying in vitro responses to phorbol diesters, depending on their cell type. Specific receptors for the phorbol diesters have been demonstrated on numerous different cells. This ...
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Journal ArticleInfect Immun · October 1983
Various microbial products are known to influence the function of mouse peritoneal macrophages. Lipopolysaccharide (LPS) and certain lipid A-associated proteins are known to enhance the tumoricidal effects of macrophages. The purpose of this study was to d ...
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Journal ArticleCell Immunol · September 1983
Mouse peritoneal macrophages respond to environmental stimuli in different ways depending on their state of differentiation. Macrophages from mice with bacillus Calmette--Guerin (BCG) infection produced large amounts of H2O2 in response to phorbol diesters ...
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Journal ArticleJ Natl Cancer Inst · June 1983
Human mononuclear phagocytes (monocytes and macrophages) act as effectors in the destruction of tumor cells. Peritoneal macrophages from normal or infertile women killed a variety of tumor cells in vitro more efficiently than did blood monocytes from the s ...
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Journal ArticleFertil Steril · March 1983
Human peritoneal macrophages have previously been shown to phagocytize normal sperm. We had hypothesized that if macrophages were present in the distal oviducts, they could interfere with fertilization by phagocytizing sperm in vivo. The present study was ...
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Journal ArticleAm J Pathol · February 1983
Peritoneal macrophages from mice that have received two separate intraperitoneal injections of the sterile, soluble oxidant NaIO4 form macrophage polykaryons (MPs) in vitro, but peritoneal macrophage from untreated, peptone-treated, or mice infected with b ...
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Journal ArticleAm J Obstet Gynecol · November 1, 1982
The mechanism of infertility in women with endometriosis is unknown, but it is independent of mechanical factors that affect fallopian tube function. Increased numbers of peritoneal macrophages are present in women with endometriosis and have access to the ...
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Journal ArticleJ Clin Invest · October 1982
The tumor promoting phorbol diesters elicit a variety of responses from normal and leukemic blood cells in vitro by apparently interacting with cellular receptors. The biologically active ligand [20-(3)H] phorbol 12,13-dibutyrate ([(3)H]PDBu) bound specifi ...
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Journal ArticleJ Clin Invest · September 1981
Monocytes, macrophages, and neutrophils will demonstrate several important cellular functions in response to synthetic formylated oligopeptides. N-formyl-norleucyl-leucyl-phenylalanyl-norleucyl-tyrosyl-lysine (fNLPNTL) was a potent chemoattractant for huma ...
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Journal ArticleScience · August 7, 1981
The tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate causes differentiation of cells of the human leukemia cell line HL60 to nondividing macrophage-like cells. These differentiated cells are cytotoxic for tumor cells (including parent, untreated HL60 c ...
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Journal ArticleAm J Med Genet · 1980
Elliptocytosis, multiple lipomatosis, and biological false-postive serological test for syphilis (BFPSTS) were found in a single individual. One hundred eighty relatives were tested for the three diseases: 74 were typed for seven blood group antigens, and ...
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Journal ArticleCancer Immunology Immunotherapy · January 1, 1980
NaIO4 treatment of mouse adherent peritoneal cells or lymphocyte-free cloned macrophages enhances their cytotoxic and tumoricidal activity. 5×10-3 M NaIO4 treatment of nontumoricidal BCG-activated macrophages renders them c ...
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Journal ArticleAm J Clin Pathol · February 1979
A patient with acute leukemia and an IgM, kappa (IgMkappa) monoclonal gammopathy, Bence-Jones proteinuria, and blasts containing intracytoplasmic vacuoles with peroxidase-positive inclusions is discussed. Special stains, immunofluorescence, and electron mi ...
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Journal ArticleScience · July 15, 1977
Tumor killing by activated macrophages is not a highly determined biologic event, but a relative capability influenced by the local environment. An intrinsic macrophage cytotoxic effector system is modulated by serum and other environmental factors that ca ...
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