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Bimanual Reaching Across The Hemispace: Which Hand Is Yoked To Which?, Gavin Buckingham, Gordon Binsted, David Carey

Gavin Buckingham

When both hands perform concurrent goal-directed reaches, they become yoked to one another. To investigate the direction of this coupling (i.e., which hand is yoked to which), the temporal dynamics of bimanual reaches were compared with equivalent-amplitude unimanual reaches. These reaches were to target pairs located on either the left or right sides of space; meaning that in the bimanual condition, one hand's contralateral (more difficult) reach accompanied by the other hand's ipsilateral (easier) reach. By comparing which hand's difficult reach was improved more by the presence of the other hand's easier ipsilateral reach, we were able to demonstrate asymmetries …

Sexual Health, Risk Behaviors, And Substance Use In Heterosexual-Identified Women With Female Sex Partners: 2002 Us National Survey Of Family Growth., Greta Bauer, Jennifer Jairam, Shamara Baidoobonso

Shamara M Baidoobonso, PhD

BACKGROUND: Despite knowledge that some people engage in same-sex sexuality without espousing a sexual minority identity, this has rarely been studied in women. METHODS: Heterosexual women aged 20 to 44 who indicated one or more female sex partners in the past year were compared to those with less recent female sex partners, and to bisexual, homosexual, and exclusively heterosexual women using 2002 US National Survey of Family Growth data. RESULTS: Compared to exclusively heterosexual women, heterosexual women with a past-year female sex partner were significantly more likely to smoke tobacco (46% vs. 19%), binge drink (34% vs. 11%), use marijuana …

Distribution Of Health Care Expenditures For Hiv-Infected Patients, Ray Y. Chen, Neil A. Accortt, Andrew O. Westfall, Michael J. Mugavero, James L. Raper, Gretchen A. Cloud, Beth K. Stone, Jerome Carter, Stephanie Call, Maria Pisu, Jeroan J. Allison, Michael S. Saag

Jeroan J. Allison

BACKGROUND: Health care expenditures for persons infected with human immunodeficiency virus (HIV) in the United State determined on the basis of actual health care use have not been reported in the era of highly active antiretroviral therapy.

METHODS: Patients receiving primary care at the University of Alabama at Birmingham HIV clinic were included in the study. All encounters (except emergency room visits) that occurred within the University of Alabama at Birmingham Hospital System from 1 March 2000 to 1 March 2001 were analyzed. Medication expenditures were determined on the basis of 2001 average wholesale price. Hospitalization expenditures were determined on …

Trends In Aids-Defining And Non-Aids-Defining Malignancies Among Hiv-Infected Patients: 1989-2002, Roger Bedimo, Ray Y. Chen, Neil A. Accortt, James L. Raper, Carol Linn, Jeroan J. Allison, John Dubay, Michael S. Saag, Craig J. Hoesley

Jeroan J. Allison

In a comparison of rates of acquired immunodeficiency syndrome (AIDS)-defining malignancies (ADMs) for 1989-1996 versus 1997-2002, we found a decrease in ADMs (rate ratio, 0.31; P<.0001) and a significant increase in non-AIDS-defining malignancies (non-ADMs; rate ratio, 10.87; P<.0002). The mean CD4 cell count was lower among patients with ADMs than among those with non-ADMs. A longer duration of survival during highly active antiretroviral therapy might explain the increasing incidence of non-ADMs.

Differences In Discharge Medication After Acute Myocardial Infarction In Patients With Hmo And Fee-For-Service Medical Insurance, Danny Mccormick, Jerry Gurwitz, Judith Savageau, Jorge Yarzebski, Joel Gore, Robert Goldberg

Jorge L. Yarzebski

OBJECTIVE: To assess the impact of fee-for-service (FFS) versus HMO medical insurance coverage on receipt of aspirin, beta-blockers, and calcium channel blockers at the time of hospital discharge following an acute myocardial infarction. DESIGN: Prospective, population-based study. SETTING: All 16 community and tertiary care hospitals in the metropolitan area of Worcester, Massachusetts. PATIENTS: The study population consisted of patients under 65 years of age hospitalized with a validated acute myocardial infarction in all hospitals in the Worcester (Massachusetts) Standard Metropolitan Statistical Area (1990 census estimate, 437,000) during 1986, 1988, 1990, 1991, and 1993. MEASUREMENTS AND MAIN RESULTS: After adjustment for …

Temporal Trends And Factors Associated With Extent Of Delay To Hospital Arrival In Patients With Acute Myocardial Infarction: The Worcester Heart Attack Study, Jorge Yarzebski, Robert Goldberg, Joel Gore, Joseph Alpert

Jorge L. Yarzebski

Factors associated with delay to hospital arrival after the onset of symptoms suggestive of acute myocardial infarction (AMI) were examined in the late 1960s and 1970s, but recent data concerning these characteristics are limited. The purpose of the present study was to examine overall and temporal distributions of the extent of patients' delay from the time of onset of AMI symptoms to hospital arrival and factors associated with delay in seeking medical care from a multihospital, population-based perspective. Review of medical records was undertaken of patients hospitalized with a discharge diagnosis of AMI in 16 teaching and community hospitals in …

Patient Delay And Receipt Of Thrombolytic Therapy Among Patients With Acute Myocardial Infarction From A Community-Wide Perspective, Robert Goldberg, Jerry Gurwitz, Jorge Yarzebski, J. Landon, Joel Gore, Joseph Alpert, P. Dalen, James Dalen

Jorge L. Yarzebski

The duration of patient delay from the time of onset of symptoms of acute myocardial infarction (AMI) to hospital presentation, and the relation of delay time and various patient characteristics to receipt of thrombolytic therapy were examined as part of a community-based study of patients hospitalized with AMI in the Worcester, Massachusetts, metropolitan area. In all, 800 patients with validated AMI hospitalized at 16 hospitals in the Worcester metropolitan area in 1986 and 1988 constituted the study sample. Patients delayed on average 4 hours between noting symptoms suggestive of AMI and presenting to area-wide emergency departments with no significant change …

Sex Differences In 2-Year Mortality After Hospital Discharge For Myocardial Infarction, Viola Vaccarino, Harlan Krumholz, Jorge Yarzebski, Joel Gore, Robert Goldberg

Jorge L. Yarzebski

BACKGROUND: An interaction between sex and age is thought to affect hospital mortality after myocardial infarction; younger, but not older, women have been shown to have higher mortality rates than men. It is currently unknown whether findings are similar after hospital discharge. OBJECTIVE: To determine whether an interaction between sex and age affects 2-year mortality after myocardial infarction. DESIGN: Community-based prospective cohort study. SETTING: 16 community hospitals serving the Worcester, Massachusetts, metropolitan area. PATIENTS: 6826 patients who survived hospitalization for acute myocardial infarction during ten 1-year periods between 1975 and 1995. MEASUREMENTS: Mortality 2 years after hospital discharge. RESULTS: The …

Pilot Study Of The Characteristics Of Acute Stroke Events In Patients Discharged From The Carolina University Hospital, Puerto Rico In 2007, Juan Carlos Zevallos, Juan Gonzalez, Fernando Santiago, Rafael Rodriguez, Ada Rivera, Ana Michelle Garcia, Felixa Flecha, Marielys Colon, Jorge L. Yarzebski

Jorge L. Yarzebski

BACKGROUND: Stroke is the third leading cause of death in Puerto Rico. We examined the pre-hospital phase, management and case-fatality-rates (CFR) of patients discharged with acute stroke from the Carolina University of Puerto Rico Hospital during 2007.

METHODS: Trained personnel collected information on demographics, delay-time, mode-of-transportation, management, and mortality from all medical records. STATAa was utilized to conduct univariate comparison of demographics, mode-of-transportation, therapeutics and diagnostic characteristics. Logistic regression analysis assessed cohort effect and controlled for confounders.

RESULTS: The average age was 69.1 years, and 53% were males. The average delay between onset of symptoms suggestive of stroke and arrival …

A Two-Decades (1975 To 1995) Long Experience In The Incidence, In-Hospital And Long-Term Case-Fatality Rates Of Acute Myocardial Infarction: A Community-Wide Perspective, Robert Goldberg, Jorge Yarzebski, Darleen Lessard, Joel Gore

Jorge L. Yarzebski

OBJECTIVES: The purpose of the present study is to describe changes over two decades (1975 to 1995) in the incidence, in-hospital and long-term case-fatality rates associated with acute myocardial infarction (AMI) from a multihospital community-wide perspective.

BACKGROUND: Despite the magnitude of, and mortality associated with acute myocardial infarction (AMI), relatively limited population-based data are available to describe recent and temporal trends in the attack and case-fatality rates associated with AMI from a representative population-based perspective.

METHODS: The community-based study included 5,270 residents of the Worcester, Massachusetts, metropolitan area hospitalized with confirmed initial AMI in all metropolitan Worcester, Massachusetts, hospitals (1990 …

Recent Trends In The Incidence Rates Of And Death Rates From Atrial Fibrillation Complicating Initial Acute Myocardial Infarction: A Community-Wide Perspective, Robert Goldberg, Jorge Yarzebski, Darleen Lessard, Jacqueline Wu, Joel Gore

Jorge L. Yarzebski

BACKGROUND: Limited information is available about recent trends in the incidence and death rates from atrial fibrillation (AF) complicating acute myocardial infarction (AMI). The purpose of this study was to examine the impact and trends over time of AF complicating initial AMI. METHODS: We conducted a longitudinal study of 2596 residents of the Worcester, Massachusetts, metropolitan area with initial AMI and without previous AF who were hospitalized at all area hospitals in 5 annual periods between 1990 and 1997. RESULTS: A total of 13% of hospitalized patients developed AF. There was a marked decrease in the proportion of patients who …

Health Insurance Coverage And Outcome Following Acute Myocardial Infarction. A Community-Wide Perspective, Silvia Kreindel, Ronald Rosetti, Robert Goldberg, Judith Savageau, Jorge Yarzebski, Joel Gore, Arthur Russo, Carol Bigelow

Jorge L. Yarzebski

BACKGROUND: Several studies have suggested that type of medical insurance coverage is associated with hospital utilization rates and receipt of selected diagnostic or treatment approaches. To our knowledge no studies, however, have examined the relation between medical insurance coverage and short-term outcomes following acute myocardial infarction (AMI) from a multihospital, community-wide perspective. OBJECTIVE: To examine the association between medical insurance coverage and in-hospital case-fatality rates as well as length of hospital stay following AMI. METHODS: The study sample consisted of 3735 residents of the Worcester, Mass, metropolitan area hospitalized with validated AMI during 1986, 1988, 1990, 1991, and 1993 at …

Aberrations In Post-Trauma Monocyte (Mo) Subpopulation: Role In Septic Shock Syndrome, Carol Miller-Graziano, Gyongyi Szabo, Karen Kodys, Katherine Griffey

Gyongyi Szabo

Appearance of increased proportions of monocytes bearing the 72kd(FcRI) receptor for IgG correlated to aberrant monocyte (MO) functions, depressed immune functions, and poor clinical outcome. The trauma patients' FcRI+ MO subpopulation produced the majority of their elevated IL-6, TNF alpha, TGF beta, and PGE2. IgG stimulation of patients' MO through FcRI not only stimulated TNF alpha, IL-6, and PGE2 levels, but also greatly augmented the levels of these monokines produced after subsequent bacterial challenge. Post-trauma increased IL-6 levels can lead to polyclonal B-cell activation and high levels of circulating, nonspecific IgG as seen in trauma patients. This nonspecific IgG triggers …

Dibutyryl-Camp Modulation Of Receptor Expression And Antigen Presentation Capacity In Monocyte Subpopulations, Gyongyi Szabo, Karen Kodys, Carol Miller-Graziano

Gyongyi Szabo

Monocyte phenotype heterogeneity is often associated with functional differences between the distinguished Mphi subpopulations. We have previously demonstrated that the Mphi subpopulation separated and stimulated by rosetting Mphi via the Type I Fc gamma R (CD64) are poor antigen presenting cells but can be induced to greater production of TNF alpha, IL-6 and PGE2 than the Fc gamma RI- Mphi population. Here we demonstrate that the Fc gamma RI- Mphi represent the major antigen presenting Mphi population and that APC capacity of the FcRI- Mphi can be further increased by elevating intracellular cAMP levels. Treatment of the Fc gamma RI+ …

Role Of Elevated Monocyte Transforming Growth Factor Beta (Tgf Beta) Production In Posttrauma Immunosuppression, Carol Miller-Graziano, Gyongyi Szabo, Katherine Griffey, Bela Mehta, Karen Kodys, Donna Catalano

Gyongyi Szabo

We previously reported that increased production of prostaglandin E2 by monocytes is a pivotal mechanism in posttrauma immunopathology. Here we characterize monocyte levels of transforming growth factor beta and examine the effects of elevated transforming growth factor beta on prostaglandin E2 release by patients' monocytes. Trauma patients' and normals' monocyte supernates (+/- stimulation with muramyl dipeptide) were acid treated and assayed for transforming growth factor beta using the mink lung-cell bioassay. Alternatively, human transforming growth factor beta was added to patients' and normals' monocytes and prostaglandin E2 production assayed. Significantly elevated transforming growth factor beta levels (median = 181.7 pmol/10(6) …

Reduced Alloreactive T-Cell Activation After Alcohol Intake Is Due To Impaired Monocyte Accessory Cell Function And Correlates With Elevated Il-10, Il-13, And Decreased Ifngamma Levels, Gyongyi Szabo, Pranoti Mandrekar, Angela Dolganiuc, Donna Catalano, Karen Kodys

Gyongyi Szabo

BACKGROUND: Immunosuppression associated with chronic alcohol use is characterized by reduced antigen-specific T-cell response and impaired delayed type hypersensitivity. Increasing evidence suggests in chronic alcohol consumption models that reduced antigen-specific T-cell proliferation is due to insufficient accessory cell function. Accessory cell function, a critical step in recognition of viral antigens, is reduced in chronic hepatitis C. The severity of hepatitis C is increased by alcohol consumption. Thus, we investigated the effects of alcohol consumption on accessory cell activity of monocytes in supporting alloreactive T-cell proliferation. METHODS: Alloreactive T-cell proliferation was evaluated in a one-way mixed lymphocyte reaction (MLR). Mononuclear cells …

Elevated Tumor Necrosis Factor Alpha Production Concomitant To Elevated Prostaglandin E2 Production By Trauma Patients' Monocytes, Thomas Takayama, Carol Miller-Graziano, Gyongyi Szabo

Gyongyi Szabo

The level of tumor necrosis factor alpha (TNF alpha), a monokine implicated in mediating septic shock, is elevated in the blood of some patients with sepsis. Monocytes from 11 trauma patients and 11 burn patients were suboptimally stimulated with interferon gamma and muramyl dipeptide, an analogue of bacterial wall products. The patients with sepsis showed significantly greater total TNF alpha levels (secreted in combination with cell-associated) 3 days before septic episodes, as compared with normal controls (32.38 to 2231.76 ng/10(6) monocytes per milliliter, median = 121.03 ng/10(6) monocytes per milliliter; normal control: 0.00 to 18.20 ng/10(6) monocytes per milliliter, median …

Regulation Of Human Monocyte Functions By Acute Ethanol Treatment: Decreased Tumor Necrosis Factor-Alpha, Interleukin-1 Beta And Elevated Interleukin-10, And Transforming Growth Factor-Beta Production, Gyongyi Szabo, Pranoti Mandrekar, Linda Girouard, Donna Catalano

Gyongyi Szabo

We and others have previously shown that even acute ethanol exposure has the capacity to modulate immune functions, particularly monocyte functions. Herein, we tested the hypothesis that acute ethanol treatment inhibits inflammatory, while increasing inhibitory cytokine production in human blood monocytes that, in turn, could contribute to the overall immune abnormalities seen after alcohol use. Our data show that in vitro treatment of blood monocytes with a physiologically relevant dose of alcohol (25 mM) results in significantly decreased induction of tumor necrosis factor-alpha (TNF alpha) and interleukin (IL)-1 beta by bacterial stimulation of either Gram-positive [staphylococcal enterotoxin B (SEB), 1 …

Monocytes, Alcohol Use, And Altered Immunity, Gyongyi Szabo

Gyongyi Szabo

The immunomodulatory capacity of acute, moderate alcohol consumption was investigated in this study in nonalcoholic volunteers after 2 ml of vodka/kg body weight of alcohol consumption. There was a significant, transient increase in interleukin-12 and interferon-gamma (IFNgamma) levels in whole blood samples collected 4 hr after alcohol consumption in response to an ex vivo bacterial challenge with lipopolysaccharide (p < 0.02). However, decreased IFNgamma levels were produced by mononuclear cells collected later after alcohol consumption (16 hr), suggesting that acute alcohol consumption has a biphasic effect on IFNgamma inducibility. Furthermore, isolated blood monocytes collected 16 hr after alcohol consumption showed significantly …

Mechanisms Of Altered Monocyte Prostaglandin E2 Production In Severely Injured Patients, Carol Miller-Graziano, Mitchell Fink, Jia-Yan Wu, Gyongyi Szabo, Karen Kodys

Gyongyi Szabo

Monocytes from immunosuppressed trauma (11 patients) and burn (12 patients) patients stimulated with muramyl dipeptide, a potent prostaglandin E2 (PGE2) secretagogue, showed twofold greater PGE2 production compared with normal controls or immunocompetent patients. Monocyte plasminogen activator production was markedly depressed and inversely correlated to patients' monocyte hyper PGE2 production. Levels of the PGE2-producing monocyte subset (selected as high-affinity Fc+ receptors) were progressively elevated after injury in immunosuppressed patients, reaching 65% to 80% of the total monocyte population (39% for normal controls). Although early T-suppressor (Ts) lymphocytes did not augment monocyte PGE2 secretion, Ts lymphocytes that appeared late (greater than 12 …

Polymorphonuclear Functions In Patients With Mixed Connective Tissue Disease, E. Bodolay, Katalin Lukacs, G. Frendl, Gyongyi Szabo, G. Arato, Gyula Szegedi

Gyongyi Szabo

Polymorphonuclear leukocytes (PMNs) from 29 patients with mixed connective tissue disease (MCTD) were studied "in vitro" for their phagocytic and chemotactic function as well as for granulocyte alkaline phosphatase (GAP) activity. Fc-receptor expression detected by EA-rosette formation was comparable to the control. Yeast-phagocytosis, C3b-receptor mediated phagocytosis and chemotaxis of PMNs, however, significantly decreased in MCTD. At the same time, photometric measure of alkaline phosphatase activity indicated a nearly two fold increase in PMNs from patients with MCTD. Although no correlation was found between PMN functions and the activity of the disease, PMN disorders may play a role in pathogenesis of …

Acute Alcohol Consumption Attenuates Interleukin-8 (Il-8) And Monocyte Chemoattractant Peptide-1 (Mcp-1) Induction In Response To Ex Vivo Stimulation, Gyongyi Szabo, Sangeeta Chavan, Pranoti Mandrekar, Donna Catalano

Gyongyi Szabo

No abstract provided.

Monocyte Functions In Patients With Mixed Connective Tissue Disease, E. Bodolay, Katalin Lukacs, Gyongyi Szabo, G. Frendl, T. Ben, Gyula Szegedi

Gyongyi Szabo

The authors investigated the number and functions of peripheral blood monocytes in patients with mixed connective tissue disease. Moderate monocytopenia was detected in the active stage of the disease. There was a close correlation between the sensitized sheep red blood cell binding capacity of monocytes and the elevated levels of circulating immune complexes. The yeast phagocytosis of monocytes and the chemotactic activity were normal in patients with mixed connective tissue disease. C3b receptor mediated phagocytosis of monocytes decreased in the active and inactive stages of the disease. This study suggests that the decreased function of C3b receptors of monocytes is …

Acute Ethanol Consumption Synergizes With Trauma To Increase Monocyte Tumor Necrosis Factor Alpha Production Late Postinjury, Gyongyi Szabo, Pranoti Mandrekar, Bikash Verma, Ann Isaac, Donna Catalano

Gyongyi Szabo

The hypothesis that acute ethanol uptake plus trauma can synergize to increase immunosuppression was tested. We found that, unlike non-alcohol-exposed patients, patients with acute alcohol use prior to trauma have a transient decrease in monocyte tumor necrosis factor alpha (TNF alpha) production during the very early postinjury (0-3 days) period. However, TNF alpha production by these alcohol-exposed patients' monocytes (M0) became hyperelevated late postinjury (> 9 days). Consequently, these massively elevated M0 TNF alpha levels can contribute to posttrauma immunosuppression after acute alcohol use. We also demonstrate that normal monocyte activation with the superantigen, Staphylococcus enterotoxin B (SEB), results in …

Regulation Of Monocyte Interleukin-12 Production By Acute Alcohol: A Role For Inhibition By Interleukin-10, Linda Girouard, Pranoti Mandrekar, Donna Catalano, Gyongyi Szabo

Gyongyi Szabo

Acute ethanol treatment results in decreased antigen presentation capacity (Th1-type immunity) and elevated interleukin IL-10 (Th2 cytokine) production in human monocytes. Monocytes can contribute to both Th1 (IL-12) and Th2 (IL-10) immune responses via production of IL-12 and IL-10, respectively. Thus, we tested the hypothesis that acute alcohol treatment might affect Th1/Th2 immune balance by altering monocyte production of IL-12 and IL-10. Neither acute ethanol treatment alone (25 to 100 mM) nor its combination with a bacterial challenge Staphylococcal enterotoxin B (SEB) induced IL-12 production in isolated blood monocytes. In contrast, the same physiological alcohol concentrations increased monocyte IL-10 levels, …

Inhibition Of Antigen-Presenting Cell Functions By Alcohol: Implications For Hepatitis C Virus Infection, Gyongyi Szabo, Angela Dolganiuc, Pranoti Mandrekar, Bernadette White

Gyongyi Szabo

The mechanisms of alcohol-induced immunosuppression include defects in innate and adaptive immune responses. Monocytes and dendritic cells (DCs) link innate and adaptive immune responses as they recognize viral antigens and induce antigen-specific T-cell activation. We investigated the effects of alcohol on antigen-presenting cell functions. Acute alcohol consumption by healthy volunteers (vodka, 2 ml/kg) resulted in significantly reduced antigen-presenting cell function of monocyte-derived DCs. Reduced allostimulatory capacity of DCs treated with alcohol in vitro correlated with decreased co-stimulatory molecule (B7.1 and B7.2) expression, as well as with reduced interleukin (IL)-12 and increased IL-10 concentrations, in mixed lymphocyte cultures. Dendritic cells recognize …

Regulation Of Monocyte Il-12 Production: Augmentation By Lymphocyte Contact And Acute Ethanol Treatment, Inhibition By Elevated Intracellular Camp, Gyongyi Szabo, Linda Girouard, Pranoti Mandrekar, Donna Catalano

Gyongyi Szabo

IL-12, a monocyte-derived cytokine, is pivotal in activation of cellular immune response and inflammation. Both inflammatory response and cellular immunity are impaired by acute ethanol consumption. Here, we found that in vitro acute ethanol treatment (25-100 mM) results in a dose-dependent and significant increase of IL-12 in IFN-gamma (100 U/ml) plus Staphylococcal enterotoxin B (SEB; 1 microg/ml) stimulated monocytes and mononuclear cells but not in unstimulated cells from non-alcoholic blood donors. There was significantly greater IL-12 production in the MNC population compared to isolated Mphi (P < 0.001). Prevention of monocyte surface contact with either purified T lymphocytes or monocyte-depleted MNC resulted in a significant, 65+/-20%, decrease in IL-12 production regardless of IFN-gamma, SEB or ethanol stimulation suggesting that Mphi T-cell surface contact provides an additional signal for IL-12 production. In addition to cell surface contact, soluble mediators, particularly IL-10 and PGE2 may regulate IL-12 production. The cyclooxygenase inhibitor, Indomethacin (10(-6)M), augmented both IL-12 and IL-10 levels in isolated monocytes and mononuclear cells whether induced by medium, SEB or SEB plus 25 mM ethanol suggesting that regulation of IL-12 production via the cyclooxygenase pathway is independent of IL-10. Finally, elevation of intracellular cAMP levels by dbcAMP treatment consistently inhibited IL-12 as well as IL-10 production in monocytes induced by IFN-gamma or IFN-gamma plus 25 mM ethanol. These data suggest that augmentation of monocyte IL-12 by acute ethanol is not mediated via the cAMP pathway.

Viral And Host Factors Induce Macrophage Activation And Loss Of Toll-Like Receptor Tolerance In Chronic Hcv Infection, Angela Dolganiuc, Oxana Norkina, Karen Kodys, Donna Catalano, Gennadiy Bakis, Christopher Marshall, Pranoti Mandrekar, Gyongyi Szabo

Gyongyi Szabo

BACKGROUND and AIMS: Persistent inflammation contributes to progression of liver damage in chronic HCV (cHCV) infection. Repeated exposure to toll-like receptor (TLR) ligands results in tolerance, a protective mechanism aimed at limiting inflammation.

METHODS: Monocytes/macrophages were repeatedly stimulated via proinflammatory cytokine-inducing TLRs and evaluated for activation markers.

RESULTS: Unlike monocytes of controls or patients with nonalcoholic steatohepatitis, the monocytes of cHCV patients were hyperresponsive and failed to show homo- or heterotolerance to TLR ligands, manifested by elevated tumor necrosis factor (TNF)-alpha production. Serum levels of interferon (IFN)-gamma, endotoxin (TLR4 ligand), and HCV core protein (TLR2 ligand) were elevated in cHCV …

Down-Regulation Of Tumor Necrosis Factor Alpha Activity By Acute Ethanol Treatment In Human Peripheral Blood Monocytes, Bikash Verma, Miklos Fogarasi, Gyongyi Szabo

Gyongyi Szabo

As the most commonly used drug that can modulate both metabolic and immune pathways, ethanol is evaluated in this report as a regulator of tumor necrosis factor alpha (TNF alpha) production in human peripheral blood monocytes (M phi) in combination with a variety of stimuli. While acute ethanol treatment did not induce TNF alpha in M phi, it was a potent down-regulator of M phi TNF alpha production whether induced by the combination of interferon-gamma plus muramyl dipeptide (MDP) (P < 0.001), lipopolysaccharide (LPS) alone (P < 0.01), or interferon-gamma plus LPS. Down-regulation of M phi TNF alpha by ethanol was dose dependent and statistically significant in the biologically relevant, 25-150 mM, ethanol concentration range. We also demonstrate that these ethanol concentrations did not affect M phi viability. TNF alpha down-regulation by ethanol was most effective when ethanol was administered 4 hr prior to MDP stimulation; however, it was also effective--though to a lesser extent--if it was added at the time of MDP stimulation. Furthermore, ethanol also down-regulated TNF alpha production of the in vivo preactivated M phi of trauma patients, which produce hyperelevated levels of TNF alpha. We have previously shown that the majority of posttrauma elevated M phi TNF alpha is produced by the M phi subpopulation expressing high-affinity type I Fc gamma receptors (Fc gamma RI). When the Fc gamma RI cross-linking-stimulated M phi subpopulation was treated with acute ethanol, TNF alpha production was suppressed again both in in vivo preactivated M phi of trauma patients and in M phi of normal controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Alcohol Consumption Inhibits Accessory Cell Function Of Monocytes And Dendritic Cells, Gyongyi Szabo, Donna Catalano, Bernadette White, Pranoti Mandrekar

Gyongyi Szabo

BACKGROUND: Alcohol affects both innate and acquired immune responses. Chronic alcoholics have reduced delayed-type hypersensitivity response and increased susceptibility to infections. In contrast, recent studies suggest that acute, moderate alcohol consumption has protective effects on mortality. Monocytes and dendritic cells (DC) play a central role in coordination of innate and adaptive immune responses and are pivotal in activation of T lymphocytes in an antigen-specific manner. In this study, we investigated the effects of acute, moderate alcohol consumption on antigen presenting cell function of blood monocytes and monocyte-derived myeloid dendritic cells. METHODS: Accessory cell function of human blood monocytes was tested …