Life Sciences Commons^™

Changes Over Time In The Incidence And Case-Fatality Rates Of Primary Ventricular Fibrillation Complicating Acute Myocardial Infarction: Perspectives From The Worcester Heart Attack Study, Craig Thompson, Jorge Yarzebski, Robert Goldberg, Darleen Lessard, Joel Gore, James Dalen

Jorge L. Yarzebski

BACKGROUND: Limited population-based data are available that describe temporal and recent trends in the incidence and case-fatality rates in patients with primary ventricular fibrillation (VF) complicating acute myocardial infarction (AMI). The purpose of this study was to describe changes over a 22-year period (1975 through 1997) in the incidence and hospital case-fatality rates of primary VF complicating AMI from a multihospital, community-wide perspective. METHODS AND RESULTS: This was an observational study of metropolitan Worcester residents hospitalized with a validated uncomplicated AMI (n = 5020) in all hospitals in the Worcester, Massachusetts, metropolitan area (1990 census population = 437,000) during 11 …

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 …

Prehospital Transport Of Patients With Acute Myocardial Infarction: A Community-Wide Perspective, Robert Goldberg, Daniel Kramer, Jorge Yarzebski, Darleen Lessard, Joel Gore

Jorge L. Yarzebski

OBJECTIVE: The objectives of this population-based study were to examine the use of emergency medical services (EMS) in greater Worcester, Massachusetts, residents (2000 census = 478,000) hospitalized with acute myocardial infarction (AMI) at all metropolitan Worcester medical centers in four biennial periods between 1997 and 2003. A secondary study aim was to describe the demographic and clinical characteristics of patients with AMI transported to metropolitan Worcester hospitals by EMS, compared with those transported by other means, and their hospital outcomes. METHODS: We reviewed the medical records of 3805 patients hospitalized for confirmed AMI at 11 greater Worcester medical centers during …

A Community-Wide Perspective Into Changing Trends In The Utilization Of Diagnostic And Interventional Procedures In Patients Hospitalized With Acute Myocardial Infarction, Jessica Hahn, Darleen Lessard, Jorge Yarzebski, Jordan Goldberg, Sean Pruell, Frederick Spencer, Joel Gore, Robert Goldberg

Jorge L. Yarzebski

BACKGROUND: Limited data are available describing contemporary trends in the utilization of diagnostic and interventional procedures in patients hospitalized with acute myocardial infarction (AMI). The objectives of our population-based investigation were to examine long-term trends (1986-2003) in the utilization of cardiac catheterization, percutaneous coronary interventions (PCI), and coronary artery bypass graft surgery (CABG) in a community sample of patients hospitalized with AMI. We examined the demographic and clinical characteristics of patients who received these diagnostic and interventional procedures and determined whether the profile of patients undergoing these procedures had changed over time. METHODS: The study sample consisted of 9422 greater …

Twenty-Two Year (1975 To 1997) Trends In The Incidence, In-Hospital And Long-Term Case Fatality Rates From Initial Q-Wave And Non-Q-Wave Myocardial Infarction: A Multi-Hospital, Community-Wide Perspective, Mark Furman, Harold Dauerman, Robert Goldberg, Jorge Yarzebski, Darleen Lessard, Joel Gore

Jorge L. Yarzebski

OBJECTIVES: The goal of this study was to examine long-term trends in the incidence, in-hospital and long-term mortality patterns in patients with an initial non-Q-wave myocardial infarction (NQWMI) as compared with those with an initial Q-wave myocardial infarction (QWMI). BACKGROUND: Limited data are available describing trends in the incidence and mortality from an initial QWMI and NQWMI from a multi-hospital community-wide perspective. METHODS: Our study was an observational study of 5,832 metropolitan Worcester, Massachusetts residents (1990 census = 437,000) hospitalized with validated initial acute MI in all greater Worcester hospitals during 11 annual periods between 1975 and 1997. RESULTS: The …

Leukocytosis And Adverse Hospital Outcomes After Acute Myocardial Infarction, Vandana Menon, Darleen Lessard, Jorge Yarzebski, Mark Furman, Joel Gore, Robert Goldberg

Jorge L. Yarzebski

An elevated white blood cell (WBC) count at the time of hospital presentation is associated with increased mortality after acute myocardial infarction (AMI). The association between WBC count and the development of clinically significant complications of AMI and death during hospitalization for AMI is, however, less clear. The objectives of this observational study were to examine the association between baseline WBC count, the development of heart failure, cardiogenic shock, and death during hospitalization for AMI from a more generalizable community-wide perspective. The study sample consisted of adult residents of all ages from the Worcester, Massachusetts, metropolitan area (1990 census estimate …

Recent And Temporal Trends (1975 To 1999) In The Treatment, Hospital, And Long-Term Outcomes Of Hispanic And Non-Hispanic White Patients Hospitalized With Acute Myocardial Infarction: A Population-Based Perspective, Jorge Yarzebski, Carmen Bujor, Darleen Lessard, Joel Gore, Robert Goldberg

Jorge L. Yarzebski

BACKGROUND: Extremely limited population-based data are available describing recent and temporal trends in the characteristics, treatment, and outcomes of Hispanic and non-Hispanic white patients hospitalized with acute myocardial infarction (AMI).

METHODS: This was a community-based, observational study of 9649 greater Worcester residents hospitalized in all hospitals serving the Worcester, Massachusetts, metropolitan area in 12 one-year periods between 1975 and 1999. In the total study sample, 171 (2%) patients were Hispanic. Hispanic patients were matched with 395 non-Hispanic white patients on the basis of age, sex, and year of hospitalization.

RESULTS: Hispanics were more likely to present to greater Worcester hospitals …

Delays In Seeking Medical Care In Hospitalized Patients With Decompensated Heart Failure, Robert Goldberg, Jordan Goldberg, Sean Pruell, Jorge Yarzebski, Darleen Lessard, Frederick Spencer, Joel Gore

Jorge L. Yarzebski

PURPOSE: The magnitude of, and factors associated with, prolonged delay in seeking medical care in patients with acute myocardial infarction has been well described. It is unknown, however, what the extent of, and factors associated with, prehospital delay are in patients hospitalized with acute heart failure. The purpose of this study was to examine patterns of prehospital delay, and factors associated with delay in seeking medical care, in patients hospitalized with acute heart failure at all 11 medical centers in the Worcester, Massachusetts metropolitan area. METHODS: The medical records of 2587 greater Worcester residents with decompensated heart failure who were …

Trends In The Use Of Echocardiography And Left Ventriculography To Assess Left Ventricular Ejection Fraction In Patients Hospitalized With Acute Myocardial Infarction, Samuel Joffe, Armen Chalian, Dennis Tighe, Gerard Aurigemma, Jorge Yarzebski, Joel Gore, Darleen Lessard, Robert Goldberg

Jorge L. Yarzebski

BACKGROUND: Although current guidelines strongly recommend the measurement of ejection fraction (EF) in all patients hospitalized with acute myocardial infarction (AMI), there are limited data available describing trends in the use of diagnostic modalities to assess EF in these patients. The purpose of this study was to evaluate trends in the use of ventriculography and echocardiography to measure EF in a community sample of patients hospitalized with AMI. METHODS: The medical records of 5,380 residents of the Worcester (MA) metropolitan area hospitalized with AMI at 11 greater Worcester medical centers between 1997 and 2005 were reviewed. RESULTS: Between 1997 and …

Gender Differences In The Treatment Of Patients With Acute Myocardial Infarction. A Multihospital, Community-Based Perspective, Paul Pagley, Jorge Yarzebski, Robert Goldberg, Z. Chen, David Chiriboga, Priscilla Dalen, Jerry Gurwitz, Joseph Alpert, Joel Gore

Jorge L. Yarzebski

OBJECTIVE: As part of a community-wide study examining temporal trends in the incidence and survival rates of acute myocardial infarction, we examined differences between the sexes in overall utilization rates and changes over time, therein, of various therapies used in the management of acute myocardial infarction. DESIGN: Nonconcurrent prospective study. PATIENTS: Three thousand three hundred sixty-one men and 2119 women hospitalized with validated acute myocardial infarction in 16 hospitals in the Worcester, Mass, metropolitan area during 1975, 1978, 1981, 1984, 1986, 1988, and 1990. RESULTS: After controlling, by means of a logistic regression analysis, for a variety of patient-related factors …

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 …

Temporal Trends In Cardiogenic Shock Complicating Acute Myocardial Infarction, Robert J. Goldberg, Navid A. Samad, Jorge L. Yarzebski, Jerry H. Gurwitz, Carol Bigelow, Joel M. Gore

Jorge L. Yarzebski

BACKGROUND: Limited information is available on trends in the incidence of and mortality due to cardiogenic shock complicating acute myocardial infarction. We studied the incidence of cardiogenic shock complicating acute myocardial infarction and in-hospital death rates among patients with this condition in a single community from 1975 through 1997. METHODS: We conducted an observational study of 9076 residents of metropolitan Worcester, Massachusetts, who were hospitalized with confirmed acute myocardial infarction in all local hospitals during 11 one-year periods between 1975 and 1997. Our study included periods before and after the advent of reperfusion therapy. RESULTS: The incidence of cardiogenic shock …

Changing Trends In The Evaluation Of Ejection Fraction In Patients Hospitalized With Acute Myocardial Infarction: The Worcester Heart Attack Study, Paul Santolucito, Dennis Tighe, Darleen Lessard, Rovshan Ismailov, Joel Gore, Jorge Yarzebski, Robert Goldberg

Jorge L. Yarzebski

BACKGROUND: Extent of left ventricular dysfunction in patients with acute myocardial infarction (AMI) is an important predictor of subsequent morbidity and mortality. It is unclear, however, how often ejection fraction (EF) findings are evaluated in the setting of AMI, and the characteristics of patients who do not have their EF evaluated, particularly from the more generalizable perspective of a population-based investigation.

PURPOSE: The purpose of this study was to examine nearly 3 decade long trends (1975-2003) in the evaluation of EF in patients admitted with confirmed AMI (n = 12,760) to all greater Worcester (Massachusetts) hospitals during 14 annual periods. …

Age-Specific Differences In The Use Of Thrombolytic Therapy And Hospital Outcomes In Patients With Acute Myocardial Infarction: A Community-Wide Perspective, Omar Ali, Immad Sadiq, Robert Goldberg, Jorge Yarzebski, Darleen Lessard, Jerry Gurwitz, Joel Gore

Jorge L. Yarzebski

BACKGROUND: Relatively limited information is available about recent, and trends over time, use of thrombolytic therapy in patients of different ages hospitalized with acute myocardial infarction and the association between use of thrombolytic therapy and hospital outcomes. METHODS: We conducted an observational study of 5601 residents of the Worcester, Massachusetts, metropolitan area (1990 census = 437,000) with confirmed acute myocardial infarction in all local hospitals during 6 one-year periods between 1990 and 1999. RESULTS: Despite relatively stable use of thrombolytic therapy between 1990 and 1995, decreases in the use of thrombolytic therapy in all patients with acute myocardial infarction were …

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 …

Declining Length Of Hospital Stay For Acute Myocardial Infarction And Postdischarge Outcomes: A Community-Wide Perspective, Frederick Spencer, Darleen Lessard, Joel Gore, Jorge Yarzebski, Robert Goldberg

Jorge L. Yarzebski

BACKGROUND: The objectives of this population-based study were to describe trends of more than a decade (1986-1999) in duration of hospitalization after acute myocardial infarction (AMI), patient characteristics associated with varying lengths of stay, and the impact of declining length of stay on postdischarge mortality. METHODS: The study sample consisted of 4551 patients discharged after AMI from all greater Worcester, Mass, hospitals in 8 annual periods during the study period. Regression models were used to examine the influence of demographic, clinical, and treatment variables on length of stay and the association between declining length of hospital stay and postdischarge mortality. …

Use Of Do-Not-Resuscitate Orders In Patients With Kidney Disease Hospitalized With Acute Myocardial Infarction, Joline Chen, Jonathan Sosnov, Darleen Lessard, Jorge Yarzebski, Joel Gore, Robert Goldberg

Jorge L. Yarzebski

BACKGROUND: Patients with kidney disease are at increased risk for adverse health outcomes in comparison to patients without kidney disease. Therefore, patients with kidney disease may have greater use of do-not-resuscitate (DNR) orders than patients without kidney disease in the setting of an acute illness. We examined the association between advanced kidney disease and use of DNR orders in patients admitted with an acute myocardial infarction (AMI) to all greater Worcester, MA, hospitals as part of an epidemiological study.

METHODS: Use of DNR orders in 4,033 Worcester residents hospitalized with AMI at 11 greater Worcester medical centers during 1997, 1999, …

Treatment Practices And Outcomes Of Patients With Established Peripheral Arterial Disease Hospitalized With Acute Myocardial Infarction In A Community Setting, Frederick Spencer, Darleen Lessard, Chyke Doubeni, Jorge Yarzebski, Joel Gore, Robert Goldberg

Jorge L. Yarzebski

BACKGROUND: There are little contemporary data available describing the hospital and long-term outcomes of patients with peripheral arterial disease (PAD) who are hospitalized with acute myocardial infarction (AMI). The objectives of our population-based study were to examine the hospital and long-term outcomes, as well as the use of different treatment practices, among patients with established PAD who were hospitalized with AMI. METHODS: The study sample consisted of 4480 patients hospitalized with AMI at all Worcester, Mass, medical centers in 4 alternate years between 1997 and 2003. RESULTS: Among the metropolitan Worcester residents hospitalized with AMI, 13.5% had a history of …

Trends (1986 To 1999) In The Incidence And Outcomes Of In-Hospital Stroke Complicating Acute Myocardial Infarction (The Worcester Heart Attack Study), Frederick Spencer, Joel Gore, Jorge Yarzebski, Darleen Lessard, Elizabeth Jackson, Robert Goldberg

Jorge L. Yarzebski

Although stroke is an infrequent hospital complication of acute myocardial infarction (AMI), limited contemporary data are available about the incidence and death rates associated with this serious complication. The objective of this population-based study was to examine temporal trends (1986 to 1999) in the risk of stroke and associated hospital outcomes in patients hospitalized with AMI. This was an observational study of 6,325 metropolitan Worcester, Massachusetts, residents hospitalized with validated AMI and without prior stroke at all greater Worcester hospitals during 8 one-year periods between 1986 and 1999. Overall, 1.5% of patients (n = 92) with confirmed AMI developed an …

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) …

Effect Of Ethanol On Inflammatory Responses. Implications For Pancreatitis, Gyongyi Szabo, Pranoti Mandrekar, Shilpa Oak, Julia Mayerle

Gyongyi Szabo

BACKGROUND/AIMS: Alcohol use alters inflammatory cell responses. While alcohol has direct effects on pancreatic acinar cells, activation of inflammatory cells is a major component of the pathology of alcoholic pancreatitis.

METHODS: The effects of acute or chronic alcohol exposure were evaluated in human monocytes on the production of TNFalpha or IL-10 production, pro-inflammatory gene and nuclear factor-kappaB (NF-kappaB) activation.

RESULTS: Moderate, acute alcohol consumption or equivalent doses of alcohol in vitro had anti-inflammatory effects on monocyte activation via inhibition of pro-inflammatory genes and NF-kappaB activation, inhibition of TNFalpha production and augmentation of the anti-inflammatory cytokine, IL-10. In contrast, acute alcohol …

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 …

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 …

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 …

Ethanol-Mediated Regulation Of Transcription Factors In Immunocompetent Cells, Gyongyi Szabo, Pranoti Mandrekar

Gyongyi Szabo

The immunomodulatory effects of acute and chronic alcohol use are characterized by impaired antigen-specific immune activation and by increased susceptibility to infections due to alterations in innate immune responses and inflammatory mediator production. The central feature of cellular responses to inflammatory and stress signals is the activation of the nuclear regulatory kappa B/Rel family of transcriptional factors via various surface receptor systems in immunocompetent cells. Activation of NF-kappa B, however, is regulated at multiple levels including I-kappa B degradation, nuclear translocation, and by interaction of NF-kappa B/Rel with other transcription factors. Data from our and other laboratories demonstrate that acute …

The Critical Role Of Toll-Like Receptor (Tlr) 4 In Alcoholic Liver Disease Is Independent Of The Common Tlr Adapter Myd88, Istvan Hritz, Pranoti Mandrekar, Arumugam Velayudham, Donna Catalano, Angela Dolganiuc, Karen Kodys, Evelyn Kurt-Jones, Gyongyi Szabo

Gyongyi Szabo

The Toll-like receptor 4 (TLR4) that recognizes endotoxin, a trigger of inflammation in alcoholic liver disease (ALD), activates two signaling pathways utilizing different adapter molecules: the common TLR adapter, myeloid differentiation factor 88 (MyD88), or Toll/interleukin immune-response-domain-containing adaptor inducing interferon (IFN)-beta. The MyD88 pathway induces proinflammatory cytokine activation, a critical mediator of ALD. Here we evaluated the role of MyD88 in alcohol-induced liver injury in wild-type, TLR2-deficient, TLR4-deficient, or MyD88-deficient (knockout [KO]) mice after administration of the Lieber-De-Carli diet (4.5% volume/volume ethanol) or an isocaloric liquid control diet for 5 weeks. Alcohol feeding resulted in a significant increase in serum …