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Full-Text Articles in Life Sciences

Polymorphonuclear Functions In Patients With Mixed Connective Tissue Disease, E. Bodolay, Katalin Lukacs, G. Frendl, Gyongyi Szabo, G. Arato, Gyula Szegedi Apr 2010

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 …


Vsl#3 Probiotic Treatment Attenuates Fibrosis Without Changes In Steatohepatitis In A Diet-Induced Nonalcoholic Steatohepatitis Model In Mice, Arumugam Velayudham, Angela Dolganiuc, Michael Ellis, Jan Petrasek, Karen Kodys, Pranoti Mandrekar, Gyongyi Szabo Apr 2010

Vsl#3 Probiotic Treatment Attenuates Fibrosis Without Changes In Steatohepatitis In A Diet-Induced Nonalcoholic Steatohepatitis Model In Mice, Arumugam Velayudham, Angela Dolganiuc, Michael Ellis, Jan Petrasek, Karen Kodys, Pranoti Mandrekar, Gyongyi Szabo

Gyongyi Szabo

Nonalcoholic fatty liver disease (NAFLD) and its advanced stage, nonalcoholic steatohepatitis (NASH), are the most common causes of chronic liver disease in the United States. NASH features the metabolic syndrome, inflammation, and fibrosis. Probiotics exhibit immunoregulatory and anti-inflammatory activity. We tested the hypothesis that probiotic VSL#3 may ameliorate the methionine-choline-deficient (MCD) diet-induced mouse model of NASH. MCD diet resulted in NASH in C57BL/6 mice compared to methionine-choline-supplemented (MCS) diet feeding evidenced by liver steatosis, increased triglycerides, inflammatory cell accumulation, increased tumor necrosis factor alpha levels, and fibrosis. VSL#3 failed to prevent MCD-induced liver steatosis or inflammation. MCD diet, even 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 Apr 2010

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 Apr 2010

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 Apr 2010

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 …


Microrna Expression Profile In Lieber-Decarli Diet-Induced Alcoholic And Methionine Choline Deficient Diet-Induced Nonalcoholic Steatohepatitis Models In Mice, Angela Dolganiuc, Jan Petrasek, Karen Kodys, Donna Catalano, Pranoti Mandrekar, Arumugam Velayudham, Gyongyi Szabo Apr 2010

Microrna Expression Profile In Lieber-Decarli Diet-Induced Alcoholic And Methionine Choline Deficient Diet-Induced Nonalcoholic Steatohepatitis Models In Mice, Angela Dolganiuc, Jan Petrasek, Karen Kodys, Donna Catalano, Pranoti Mandrekar, Arumugam Velayudham, Gyongyi Szabo

Gyongyi Szabo

BACKGROUND: Alcoholic and nonalcoholic steatohepatitis are leading causes of liver diseases worldwide. While of different etiology, these share common pathophysiological mechanisms and feature abnormal fat metabolism, inflammation and fibrosis. MicroRNAs (miRNA) are highly conserved noncoding RNAs that control gene expression at the post-transcriptional level either via the degradation of target mRNAs or the inhibition of translation. Each miRNA controls the expression of multiple targets; miRNAs have been linked to regulation of lipid metabolism and inflammation. METHODS: We fed Lieber-DeCarli alcohol or methionine-choline-deficient (MCD) diets to C57Bl6 and analyzed livers for histopathology, cytokines by ELISA, alanine aminotransferase (ALT) by biochemical assay, …


Modulation Of Non-Alcoholic Steatohepatitis By Pattern Recognition Receptors In Mice: The Role Of Toll-Like Receptors 2 And 4, Gyongyi Szabo, Arumugam Velayudham, Laszlo Romics, Pranoti Mandrekar Apr 2010

Modulation Of Non-Alcoholic Steatohepatitis By Pattern Recognition Receptors In Mice: The Role Of Toll-Like Receptors 2 And 4, Gyongyi Szabo, Arumugam Velayudham, Laszlo Romics, Pranoti Mandrekar

Gyongyi Szabo

Toll-like receptors (TLR) recognize pathogen-derived molecules and induce downstream activation of inflammatory pathways. Fatty liver has been shown to result in increased sensitivity to lipopolysaccharide (LPS), a TLR4 ligand. In this study, we investigated the roles of TLR2 and TLR4 in liver damage and on cytokine induction in a methionine-choline deficient (MCD) diet-induced model of nonalcoholic steatohepatitis. We found that mice with nonalcoholic fatty liver had increased liver injury and inflammatory cytokine induction after challenge with a TLR4 but not with a TLR2 ligand. TLR2 deficient mice were not protected against the development of steatohepatitis after MCD diet feeding. On …


Acute Ethanol Treatment Modulates Toll-Like Receptor-4 Association With Lipid Rafts, Angela Dolganiuc, Genadyi Bakis, Karen Kodys, Pranoti Mandrekar, Gyongyi Szabo Apr 2010

Acute Ethanol Treatment Modulates Toll-Like Receptor-4 Association With Lipid Rafts, Angela Dolganiuc, Genadyi Bakis, Karen Kodys, Pranoti Mandrekar, Gyongyi Szabo

Gyongyi Szabo

BACKGROUND: Alcohol, a substance that is most frequently abused, suppresses innate immune responses to microbial pathogens. The host senses pathogens via Toll-like receptors (TLRs). Recent studies indicate that alcohol affects TLR signaling. METHODS: Here, we hypothesized that acute alcohol treatment may interfere with early steps of membrane-associated TLR2 and TLR4 signaling at the level of lipid rafts. Human monocytes and Chinese hamster ovary (CHO) cells, transfected with human TLR2, TLR4, or CD14, were stimulated with peptidoglycan (PGN, TLR2 ligand) or lipopolysaccharide (LPS, TLR4 ligand) with or without alcohol (50 mM) and analyzed for cytokine production (enzyme-linked immunosorbent assay), nuclear factor-kappaB …


Acceptance Of An Abo-Incompatible Mismatched (Ab(+) To O(+)) Liver Allograft With The Use Of Daclizumab And Mycophenolate Mofetil, W. Fang, John Saltzman, Sarah Rososhansky, Gyongyi Szabo, Stephen Heard, Barbara Banner, Ravi Chari, Eliezer Katz Apr 2010

Acceptance Of An Abo-Incompatible Mismatched (Ab(+) To O(+)) Liver Allograft With The Use Of Daclizumab And Mycophenolate Mofetil, W. Fang, John Saltzman, Sarah Rososhansky, Gyongyi Szabo, Stephen Heard, Barbara Banner, Ravi Chari, Eliezer Katz

Gyongyi Szabo

Liver allograft survival rates of 50% to 60% are reported in blood group A, group B, group O (ABO)-incompatible mismatched grafts even when aggressive immunosuppressive protocols, including plasmapheresis, OKT(3), cyclophosphamide, cyclosporine, prostaglandin E(1), and steroids, are used. A 59-year-old woman, blood type O(+), required emergency retransplantation posttransplantation day 2 because of primary nonfunction of the liver allograft. A blood type AB(+) allograft was used. Induction immunosuppressive therapy included tacrolimus, mycophenolate mofetil, OKT(3) (muromonab-CD(3)), steroids, and prostaglandin E(1). In addition, plasmapheresis was performed daily for 9 days. OKT(3) and prostaglandin E(1) were also discontinued postoperative day 9. Biopsy-proven acute cellular rejection …


Decarboxylation Of L-Dopa And 5-Hydroxytryptophan In Dispersed Rat Pancreas Acinar Cells, E. Yu, L. Stern, A. Tenenhouse Oct 2009

Decarboxylation Of L-Dopa And 5-Hydroxytryptophan In Dispersed Rat Pancreas Acinar Cells, E. Yu, L. Stern, A. Tenenhouse

Edward Yu

Amino acid decarboxylation activity in dispersed rat pancreas acinar cells and fractions derived by differential centrifugation of homogenate of these cells was studied. The rate of decarboxylation was measured by determining the rate of production of the [3H]-amine from [3H]-amino acid or the rate of production of 14CO2 from the [14C]-carboxy-labelled amino acid. Only the hydroxylated amino acids L-dopa and 5-hydroxytryptophan are decarboxylated by intact dispersed pancreas acinar cells or cell homogenates at all pH values and amino acid concentrations tested. The decarboxylase activity is located exclusively in the cell cytosol. Each substrate competitively inhibits the decarboxylation of the other …