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Marc Christopher Levesque

Adjunct Associate Professor in the Department of Medicine
Medicine, Rheumatology and Immunology
Duke Box 3266, Durham, NC 27710
338 Jones Building, Box 3266, Research Drive, Durham, NC 27710

Selected Publications


CLL cell apoptosis induced by nitric oxide synthase inhibitors: correlation with lipid solubility and NOS1 dissociation constant.

Journal Article Leuk 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 ... Full text Link to item Cite

Identification of genetic polymorphisms associated with risk for pulmonary hypertension in sickle cell disease.

Journal Article Blood · 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 ... Full text Link to item Cite

Determinants of exhaled nitric oxide levels in healthy, nonsmoking African American adults.

Journal Article J Allergy Clin Immunol · February 2008 Featured Publication BACKGROUND: Asthma is a significant cause of morbidity and mortality for African Americans. Fraction of exhaled nitric oxide (FeNO) levels are increased in patients with asthma, and airway levels of nitric oxide metabolites regulate airway inflammation and ... Full text Link to item Cite

B cell-directed therapies for autoimmune disease and correlates of disease response and relapse.

Journal Article J Allergy Clin Immunol · January 2008 Recent advances have led to the development of mAbs that effectively deplete B cells in human beings and target pathways essential for B-cell development. B cell-directed therapies represent promising treatments for autoimmune disorders, although many ques ... Full text Link to item Cite

Smoking is associated with an age-related decline in exhaled nitric oxide.

Journal Article Eur Respir J · December 2007 Featured Publication Age-related declines in forced expiratory volume in one second are accelerated in smokers. Smoking is associated with decreased exhaled nitric oxide fraction (F(eNO)). The aim of the present study was to determine the impact of age on F(eNO) in otherwise h ... Full text Link to item Cite

Clinical and molecular predictors of disease severity and survival in chronic lymphocytic leukemia.

Journal Article Am J Hematol · December 2007 Featured Publication 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 ... Full text Link to item Cite

Guidelines for assessing immunocompetency in clinical trials for autoimmune diseases.

Journal Article Clin Immunol · June 2007 Clinical trials testing the safety and efficacy of immunosuppressive agents for the treatment of autoimmune diseases should also be designed to evaluate immunocompetency. The most clinically relevant outcome for assessing immunocompetency is the infection ... Full text Link to item Cite

Genetic polymorphisms associated with priapism in sickle cell disease.

Journal Article Br 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 ... Full text Link to item Cite

Progressive immunoglobulin gene mutations in chronic lymphocytic leukemia: evidence for antigen-driven intraclonal diversification.

Journal Article Blood · February 15, 2007 Featured Publication 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 ... Full text Link to item Cite

Elevated plasma phenylalanine in severe malaria and implications for pathophysiology of neurological complications.

Journal Article Infect 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 ... Full text Link to item Cite

Chronic lymphocytic leukemia cell CD38 expression and inducible nitric oxide synthase expression are associated with serum IL-4 levels.

Journal Article Leuk 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 ... Full text Link to item Cite

The dichotomous role of nitric oxide in the pathogenesis of accelerated atherosclerosis associated with systemic lupus erythematosus.

Journal Article Curr Mol Med · November 2004 Featured Publication 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 ... Full text Link to item Cite

Inducible nitric oxide synthase (NOS2) promoter CCTTT repeat polymorphism: relationship to in vivo nitric oxide production/NOS activity in an asymptomatic malaria-endemic population.

Journal Article Am 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 ... Link to item Cite

Low plasma arginine concentrations in children with cerebral malaria and decreased nitric oxide production.

Journal Article Lancet · 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 ... Full text Link to item Cite

IL-4 and interferon gamma regulate expression of inducible nitric oxide synthase in chronic lymphocytic leukemia cells.

Journal Article Leukemia · February 2003 Featured Publication 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 ... Full text Link to item Cite

Nitric oxide synthase 2 promoter polymorphisms and systemic lupus erythematosus in african-americans.

Journal Article J 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 ... Link to item Cite

A new NOS2 promoter polymorphism associated with increased nitric oxide production and protection from severe malaria in Tanzanian and Kenyan children.

Journal Article Lancet · November 9, 2002 Featured Publication 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 ... Full text Link to item Cite

Nitric oxide enhancement of fludarabine cytotoxicity for B-CLL lymphocytes.

Journal Article Leukemia · 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 ... Full text Link to item Cite

Activated T lymphocytes regulate hyaluronan binding to monocyte CD44 via production of IL-2 and IFN-gamma.

Journal Article J Immunol · January 1, 2001 Interactions of the cell surface proteoglycan CD44 with the extracellular matrix glycosaminoglycan hyaluronan (HA) are important during inflammatory immune responses. Our previous studies indicated that monocyte HA binding could be induced by TNF-alpha. Mo ... Full text Link to item Cite

CLL cell apoptosis induced by nitric oxide synthase inhibitors: correlation with lipid solubility and NOS1 dissociation constant.

Journal Article Leuk 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 ... Full text Link to item Cite

Identification of genetic polymorphisms associated with risk for pulmonary hypertension in sickle cell disease.

Journal Article Blood · 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 ... Full text Link to item Cite

Determinants of exhaled nitric oxide levels in healthy, nonsmoking African American adults.

Journal Article J Allergy Clin Immunol · February 2008 Featured Publication BACKGROUND: Asthma is a significant cause of morbidity and mortality for African Americans. Fraction of exhaled nitric oxide (FeNO) levels are increased in patients with asthma, and airway levels of nitric oxide metabolites regulate airway inflammation and ... Full text Link to item Cite

B cell-directed therapies for autoimmune disease and correlates of disease response and relapse.

Journal Article J Allergy Clin Immunol · January 2008 Recent advances have led to the development of mAbs that effectively deplete B cells in human beings and target pathways essential for B-cell development. B cell-directed therapies represent promising treatments for autoimmune disorders, although many ques ... Full text Link to item Cite

Smoking is associated with an age-related decline in exhaled nitric oxide.

Journal Article Eur Respir J · December 2007 Featured Publication Age-related declines in forced expiratory volume in one second are accelerated in smokers. Smoking is associated with decreased exhaled nitric oxide fraction (F(eNO)). The aim of the present study was to determine the impact of age on F(eNO) in otherwise h ... Full text Link to item Cite

Clinical and molecular predictors of disease severity and survival in chronic lymphocytic leukemia.

Journal Article Am J Hematol · December 2007 Featured Publication 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 ... Full text Link to item Cite

Guidelines for assessing immunocompetency in clinical trials for autoimmune diseases.

Journal Article Clin Immunol · June 2007 Clinical trials testing the safety and efficacy of immunosuppressive agents for the treatment of autoimmune diseases should also be designed to evaluate immunocompetency. The most clinically relevant outcome for assessing immunocompetency is the infection ... Full text Link to item Cite

Genetic polymorphisms associated with priapism in sickle cell disease.

Journal Article Br 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 ... Full text Link to item Cite

Progressive immunoglobulin gene mutations in chronic lymphocytic leukemia: evidence for antigen-driven intraclonal diversification.

Journal Article Blood · February 15, 2007 Featured Publication 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 ... Full text Link to item Cite

Elevated plasma phenylalanine in severe malaria and implications for pathophysiology of neurological complications.

Journal Article Infect 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 ... Full text Link to item Cite

Chronic lymphocytic leukemia cell CD38 expression and inducible nitric oxide synthase expression are associated with serum IL-4 levels.

Journal Article Leuk 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 ... Full text Link to item Cite

The dichotomous role of nitric oxide in the pathogenesis of accelerated atherosclerosis associated with systemic lupus erythematosus.

Journal Article Curr Mol Med · November 2004 Featured Publication 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 ... Full text Link to item Cite

Inducible nitric oxide synthase (NOS2) promoter CCTTT repeat polymorphism: relationship to in vivo nitric oxide production/NOS activity in an asymptomatic malaria-endemic population.

Journal Article Am 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 ... Link to item Cite

Low plasma arginine concentrations in children with cerebral malaria and decreased nitric oxide production.

Journal Article Lancet · 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 ... Full text Link to item Cite

IL-4 and interferon gamma regulate expression of inducible nitric oxide synthase in chronic lymphocytic leukemia cells.

Journal Article Leukemia · February 2003 Featured Publication 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 ... Full text Link to item Cite

Nitric oxide synthase 2 promoter polymorphisms and systemic lupus erythematosus in african-americans.

Journal Article J 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 ... Link to item Cite

A new NOS2 promoter polymorphism associated with increased nitric oxide production and protection from severe malaria in Tanzanian and Kenyan children.

Journal Article Lancet · November 9, 2002 Featured Publication 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 ... Full text Link to item Cite

Nitric oxide enhancement of fludarabine cytotoxicity for B-CLL lymphocytes.

Journal Article Leukemia · 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 ... Full text Link to item Cite

Activated T lymphocytes regulate hyaluronan binding to monocyte CD44 via production of IL-2 and IFN-gamma.

Journal Article J Immunol · January 1, 2001 Interactions of the cell surface proteoglycan CD44 with the extracellular matrix glycosaminoglycan hyaluronan (HA) are important during inflammatory immune responses. Our previous studies indicated that monocyte HA binding could be induced by TNF-alpha. Mo ... Full text Link to item Cite

Serum levels of soluble CD44 in primary Sjögren's syndrome.

Journal Article J Rheumatol · June 2000 OBJECTIVE: To determine whether elevated soluble CD44 (sCD44) levels serve as a marker of inflammation and lymphoproliferation in primary Sjögren's syndrome (SS). METHODS: We measured sCD44 levels by ELISA in serum samples from a cross section of healthy i ... Link to item Cite

Nitric oxide synthase type 2 promoter polymorphisms, nitric oxide production, and disease severity in Tanzanian children with malaria.

Journal Article J 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 ... Full text Link to item Cite

TNFalpha and IL-4 regulation of hyaluronan binding to monocyte CD44 involves posttranslational modification of CD44.

Journal Article Cell Immunol · May 1, 1999 Our previous studies have identified TNFalpha as a positive regulator and IL-4 as a negative regulator of human monocyte CD44-HA binding. In order to determine the mechanisms of IL-4- and TNFalpha-mediated regulation of monocyte HA binding, we measured HA ... Full text Link to item Cite

Interferon-beta1A-induced polyarthritis in a patient with the HLA-DRB1*0404 allele.

Journal Article Arthritis 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 ... Full text Link to item Cite

Recombinant acyl-CoA:cholesterol acyltransferase-1 (ACAT-1) purified to essential homogeneity utilizes cholesterol in mixed micelles or in vesicles in a highly cooperative manner.

Journal Article J Biol Chem · December 25, 1998 Acyl-coenzyme A:cholesterol acyltransferase (ACAT) is an integral membrane protein located in the endoplasmic reticulum. It catalyzes the formation of cholesteryl esters from cholesterol and long-chain fatty acyl coenzyme A. The first gene encoding the enz ... Full text Link to item Cite

Cytokine-regulated expression of activated leukocyte cell adhesion molecule (CD166) on monocyte-lineage cells and in rheumatoid arthritis synovium.

Journal Article Arthritis Rheum · December 1998 OBJECTIVE: To determine whether monocyte/macrophage expression of the CD6 ligand, activated leukocyte cell adhesion molecule (ALCAM) (CD166), is regulated by cytokines during inflammation in rheumatoid arthritis (RA). METHODS: We used flow cytometry to tes ... Full text Link to item Cite

Cytokine induction of the ability of human monocyte CD44 to bind hyaluronan is mediated primarily by TNF-alpha and is inhibited by IL-4 and IL-13.

Journal Article J Immunol · December 15, 1997 Ligation of CD44 by hyaluronan (HA) is a key proinflammatory event that regulates lymphocyte and monocyte adhesion and cytokine production. While most immune cells express CD44, few immune cells constitutively bind HA. We have previously shown that monocyt ... Link to item Cite

Expression of CD44 and variant isoforms in cultured human retinal pigment epithelial cells.

Journal Article Invest Ophthalmol Vis Sci · September 1997 PURPOSE: CD44 is a major hyaluronic acid receptor that exists as a number of isoforms, generated by alternative splicing of 9 "variant" exons in humans (v2 to v10) and 10 exons in rodents. Little is known about the expression and function of CD44 in human ... Link to item Cite

Clinical, biochemical and pathological predictors of poor response to intravenous cyclophosphamide in patients with proliferative lupus nephritis.

Journal Article Clin Nephrol · September 1996 BACKGROUND: Reports in the literature on the outcome of lupus nephritis (LN) treated with intravenous (i.v.) cyclophosphamide have varied considerably. Previous studies have suggested that less than 25% of patients with LN will progress to end stage renal ... Link to item Cite

A blood group-related polymorphism of CD44 abolishes a hyaluronan-binding consensus sequence without preventing hyaluronan binding.

Journal Article J Biol Chem · March 22, 1996 CD44 is a widely expressed integral membrane protein that acts as a receptor for hyaluronan (HA) and is proposed to be important to cell-extracellular matrix interaction. The Indian (In) blood group antigens reside on CD44, and most individuals express the ... Full text Link to item Cite

In vitro culture of human peripheral blood monocytes induces hyaluronan binding and up-regulates monocyte variant CD44 isoform expression.

Journal Article J Immunol · February 15, 1996 CD44 is a cell surface proteoglycan homologous to cartilage link protein that serves as a receptor for hyaluronan (HA). CD44 isoforms include an unspliced 80- to 90-kDa standard form (CD44S) and isoforms derived from alternative splicing of nine CD44 varia ... Link to item Cite

N-terminal and central regions of the human CD44 extracellular domain participate in cell surface hyaluronan binding.

Journal Article J Immunol · October 15, 1995 CD44 molecules are cell surface receptors for hyaluronan (HA). To define regions of the extracellular domain of CD44 that are important for HA binding, we have studied the ability of HA-blocking CD44 mAbs to bind to CD44 from a variety of sources. Five CD4 ... Link to item Cite

Regulation of human CD44H and CD44E isoform binding to hyaluronan by phorbol myristate acetate and anti-CD44 monoclonal and polyclonal antibodies.

Journal Article J Immunol · December 1, 1993 CD44 molecules are comprised of multiple alternatively spliced forms and are associated with diverse functions such as mediation of carcinoma metastasis and T cell coactivation. To study the function of individual CD44 isoforms, we have transfected CD44 is ... Link to item Cite

Preparation and characterization of unilamellar vesicles from cholate-phospholipid micelle treated with cholestyramine.

Journal Article Anal Biochem · September 1986 Cholestyramine, a well-known bile-salt sequestrant, can be used effectively to remove cholate or deoxycholate from a solution of phosphatidylcholine-bile salt mixed micelle. Upon removal of the bile salt, unilamellar phospholipid vesicles form essentially ... Full text Link to item Cite