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Association Of Ubqln1 Mutation With Brown-Vialetto-Van Laere Syndrome But Not Typical Als, Paloma Gonzalez-Perez, Yubing Lu, Ru-Ju Chian, Peter Sapp, Rudolph Tanzi, Lars Bertram, Diane Mckenna-Yasek, Fen-Biao Gao, Robert Brown Dec 2012

Association Of Ubqln1 Mutation With Brown-Vialetto-Van Laere Syndrome But Not Typical Als, Paloma Gonzalez-Perez, Yubing Lu, Ru-Ju Chian, Peter Sapp, Rudolph Tanzi, Lars Bertram, Diane Mckenna-Yasek, Fen-Biao Gao, Robert Brown

Dr Robert Brown

Genetic variants in UBQLN1 gene have been linked to neurodegeneration and mutations in UBQLN2 have recently been identified as a rare cause of amyotrophic lateral sclerosis (ALS). OBJECTIVE: To test if genetic variants in UBQLN1 are involved in ALS. METHODS: 102 and 94 unrelated patients with familial and sporadic forms of ALS were screened for UBQLN1 gene mutations. Single nucleotide variants were further screened in a larger set of sporadic ALS (SALS) patients and unrelated control subjects using high-throughput Taqman genotyping; variants were further assessed for novelty using the 1000Genomes and NHLBI databases. In vitro studies tested the effect of …


Awareness, Acceptability And Uptake Of Human Papilloma Virus Vaccine Among Cameroonian School-Attending Female Adolescents, Claudine Ayissi, Richard Wamai, Geofrey Oduwo, Stacey Perlman, Edith Welty, Simon Manga, Javier Ogembo Nov 2012

Awareness, Acceptability And Uptake Of Human Papilloma Virus Vaccine Among Cameroonian School-Attending Female Adolescents, Claudine Ayissi, Richard Wamai, Geofrey Oduwo, Stacey Perlman, Edith Welty, Simon Manga, Javier Ogembo

Richard G. Wamai

The purpose of this study is to assess awareness, knowledge and beliefs about HPV, cervical cancer HPV vaccine and willingness to vaccinate among adolescent females aged 12-26 years at clinics and schools in the North West Region of Cameroon where the Cameroon Baptist Convention Health Services (CBCHS) conducted a sensitization and education campaign. A questionnaire survey was administered among female adolescents in schools and clinics. Descriptive statistics including frequencies, percentages and proportions were generated for independent variables and bivariate analyses (Chi square test) were used to assess the relationship between independent and outcome variables. Data were analyzed using SAS Version …


Recent Trends In Post-Discharge Mortality Among Patients With An Initial Acute Myocardial Infarction, Andrew Coles, Kimberly Fisher, Chad Darling, David Mcmanus, Oscar Maitas, Jorge Yarzebski, Joel Gore, Darleen Lessard, Robert Goldberg Nov 2012

Recent Trends In Post-Discharge Mortality Among Patients With An Initial Acute Myocardial Infarction, Andrew Coles, Kimberly Fisher, Chad Darling, David Mcmanus, Oscar Maitas, Jorge Yarzebski, Joel Gore, Darleen Lessard, Robert Goldberg

Jorge L. Yarzebski

The objectives of this study were to describe contemporary postdischarge death rates of patients hospitalized at all Worcester, Massachusetts, hospitals after initial acute myocardial infarctions (AMIs) and to examine factors associated with a poor prognosis. The medical records of patients discharged from 11 central Massachusetts medical centers after initial AMIs during 2001, 2003, 2005, and 2007 were reviewed, identifying 2,452 patients. This population was composed of predominantly older patients, men (58%), and whites. Overall, the 3-month, 1-year, and 2-year all-cause death rates were 8.9%, 16.4%, and 23.4%, respectively. Over time, reductions in postdischarge mortality were observed in crude as well …


Living With Significant Other Is Associated With Lower Risk For Emergency Readmission After Unstable Angina & Non-St Elevation Myocardial Infarction. [Abstract], Patricia Harris, Barbara J. Drew Nov 2012

Living With Significant Other Is Associated With Lower Risk For Emergency Readmission After Unstable Angina & Non-St Elevation Myocardial Infarction. [Abstract], Patricia Harris, Barbara J. Drew

Patricia Harris

Patients who are diagnosed with unstable angina (UA) or non-ST elevation myocardial infarction (non-STEMI) are at risk for repeated acute cardiac episodes resulting in emergent rehospitalization. American Heart Association/American College of Cardiology practice guidelines recommend use of risk stratification prior to hospital discharge; however, the importance of identifying patients’ social support for follow-up planning is not emphasized.


Gene And Stem Cell Therapies For Treating Epilepsy., Janice Naegele, Xu Maisano Nov 2012

Gene And Stem Cell Therapies For Treating Epilepsy., Janice Naegele, Xu Maisano

Janice R Naegele

No abstract provided.


Age At Diagnosis Of Diabetes In Appalachia, Lawrence Barker, Robert Gerzoff, Richard Crespo, Molly Shrewsberry Nov 2012

Age At Diagnosis Of Diabetes In Appalachia, Lawrence Barker, Robert Gerzoff, Richard Crespo, Molly Shrewsberry

Richard Crespo

Background Appalachia is a region of the United States noted for the poverty and poor health outcomes of its residents. Residents of the poorest Appalachian counties have a high prevalence of diabetes and risk factors (obesity, low income, low education, etc.) for type 2 diabetes. However, diabetes prevalence exceeds what these risk factors alone explain. Based on this, the history of poor health outcomes in Appalachia, and personally observed high rates of childhood obesity and lack of concern about prediabetes, we speculated that people in Appalachia with diagnosed diabetes might tend to be diagnosed younger than their non-Appalachian counterparts. Methods …


Residence In A Distressed County In Appalachia As A Risk Factor For Diabetes, Behavioral Risk Factor Surveillance System, 2006-2007, Lawrence Barker, Richard Crespo, Robert Gerzoff, Sharon Denham, Molly Shrewsberry, Darrlyn Cornelius-Averhart Nov 2012

Residence In A Distressed County In Appalachia As A Risk Factor For Diabetes, Behavioral Risk Factor Surveillance System, 2006-2007, Lawrence Barker, Richard Crespo, Robert Gerzoff, Sharon Denham, Molly Shrewsberry, Darrlyn Cornelius-Averhart

Richard Crespo

Introduction We compared the risk of diabetes for residents of Appalachian counties to that of residents of non-Appalachian counties after controlling for selected risk factors in states containing at least 1 Appalachian county. Methods We combined Behavioral Risk Factor Surveillance System data from 2006 and 2007 and conducted a logistic regression analysis, with self-reported diabetes as the dependent variable. We considered county of residence (5 classifications for Appalachian counties, based on economic development, and 1 for non-Appalachian counties), age, sex, race/ethnicity, education, household income, smoking status, physical activity level, and obesity to be independent variables. The classification “distressed” refers to …


Dendritic Cells In Hepatitis C Infection: Can They (Help) Win The Battle, Angela Dolganiuc, Gyongyi Szabo Oct 2012

Dendritic Cells In Hepatitis C Infection: Can They (Help) Win The Battle, Angela Dolganiuc, Gyongyi Szabo

Gyongyi Szabo

Infection with hepatitis C virus (HCV) is a public health problem; it establishes a chronic course in ~85% of infected patients and increases their risk for developing liver cirrhosis, hepatocellular carcinoma, and significant extrahepatic manifestations. The mechanisms of HCV persistence remain elusive and are largely related to inefficient clearance of the virus by the host immune system. Dendritic cells (DCs) are the most efficient inducers of immune responses; they are capable of triggering productive immunity and maintaining the state of tolerance to self- and non-self antigens. During the past decade, multiple research groups have focused on DCs, in hopes of …


Inflammasomes In Liver Diseases, Gyongyi Szabo, Timea Csak Oct 2012

Inflammasomes In Liver Diseases, Gyongyi Szabo, Timea Csak

Gyongyi Szabo

Inflammation is a common element in the pathogenesis of most chronic liver diseases that lead to fibrosis and cirrhosis. Inflammation is characterized by activation of innate immune cells and production of pro-inflammatory cytokines IL-1alpha, IL-1beta, and TNFalpha. Inflammasomes are intracellular multiprotein complexes expressed in both parenchymal and non-parenchymal cells of the liver that in response to cellular danger signals activate caspase-1, and release IL-1beta and IL-18. The importance of inflammasome activation in various forms of liver diseases in relation to liver damage, steatosis, inflammation and fibrosis is discussed in this review. Elsevier B.V. All rights reserved.


Hypoxia And Hypoxia Inducible Factors: Diverse Roles In Liver Diseases, Bharath Nath, Gyongyi Szabo Oct 2012

Hypoxia And Hypoxia Inducible Factors: Diverse Roles In Liver Diseases, Bharath Nath, Gyongyi Szabo

Gyongyi Szabo

Hypoxia has been shown to have a role in the pathogenesis of several forms of liver disease. The hypoxia inducible factors (HIFs) are a family of evolutionarily conserved transcriptional regulators that affect a homeostatic response to low oxygen tension and have been identified as key mediators of angiogenesis, inflammation, and metabolism. In this review we summarize the evidence for a role of HIFs across a range of hepatic pathophysiology. We describe regulation of the HIFs and review investigations that demonstrate a role for HIFs in the development of liver fibrosis, activation of innate immune pathways, hepatocellular carcinoma, as well as …


Mitochondrial Antiviral Signaling Protein Defect Links Impaired Antiviral Response And Liver Injury In Steatohepatitis In Mice, Timea Csak, Angela Dolganiuc, Karen Kodys, Bharath Nath, Jan Petrasek, Shashi Bala, Dora Lippai, Gyongyi Szabo Oct 2012

Mitochondrial Antiviral Signaling Protein Defect Links Impaired Antiviral Response And Liver Injury In Steatohepatitis In Mice, Timea Csak, Angela Dolganiuc, Karen Kodys, Bharath Nath, Jan Petrasek, Shashi Bala, Dora Lippai, Gyongyi Szabo

Gyongyi Szabo

Mitochondrial dysfunction is a pathogenic feature of nonalcoholic steatohepatitis (NASH). NASH complicates hepatotropic viral disease. The mitochondrial antiviral signaling protein (MAVS) is the adapter of helicase receptors involved in sensing double-stranded RNA (dsRNA). We hypothesized that impaired MAVS function may contribute to insufficient antiviral response and liver damage in steatohepatitis. We identified reduced MAVS protein levels and increased MAVS association with the proteasome subunit alpha type 7 (PSMA7) in livers from mice given a methionine-choline-deficient (MCD) diet. Decreased association of MAVS with mitochondria and increased cytosolic cytochrome c indicated mitochondrial damage in steatohepatitis. In vivo administration of the synthetic dsRNA …


The Presence Of P47phox In Liver Parenchymal Cells Is A Key Mediator In The Pathogenesis Of Alcoholic Liver Steatosis, Ivan Levin, Jan Petrasek, Gyongyi Szabo Oct 2012

The Presence Of P47phox In Liver Parenchymal Cells Is A Key Mediator In The Pathogenesis Of Alcoholic Liver Steatosis, Ivan Levin, Jan Petrasek, Gyongyi Szabo

Gyongyi Szabo

BACKGROUND: Reactive oxygen species contribute to steatosis and inflammation in alcoholic liver disease (ALD). Here, we evaluated the selective contribution of p47phox, a critical subunit of nicotinamide adenine dinucleotide phosphate oxidase (NADPH) oxidase complex, in liver parenchymal cells and in bone marrow (BM)-derived cells. METHODS: Female C57Bl/6 wild type [WT], total body p47phox-deficient knockout [KO] or p47phox chimera mice generated by BM transplantation of p47phox-KO-BM into irradiated WT mice (WT/p47phox-KO-BM mice) received 5% Lieber-DeCarli alcohol or control (pair feeding) diet for 4 weeks. RESULTS: Alcohol-induced liver steatosis as measured by Oil Red O staining and serum triglyceride up-regulation were prevented …


Ethanol Facilitates Hcv Replication Via Upregulation Of Gw182 And Hsp90 In Human Hepatoma Cells, Terence Bukong, Wei Hou, Karen Kodys, Gyongyi Szabo Oct 2012

Ethanol Facilitates Hcv Replication Via Upregulation Of Gw182 And Hsp90 In Human Hepatoma Cells, Terence Bukong, Wei Hou, Karen Kodys, Gyongyi Szabo

Gyongyi Szabo

Alcohol use and hepatitis C virus (HCV) infection synergize to cause liver damage and microRNA-122 (miR-122) appears to play a key role in this process. Argonaute 2 (Ago2), a key component of the RNA-induced silencing complex, has been shown to be important in modulating miR-122 function during HCV infection. However, GW182, a critical component of processing bodies (GW-bodies) that is recruited by Ago2 to target mRNA has not been assessed in HCV infection. To characterize the role of GW182 in the pathogenesis of HCV infection, we determined its transcription and protein expression in an HCV J6/JFH1 culture system. Here we …


An Essential Role For Monocyte Chemoattractant Protein-1 In Alcoholic Liver Injury: Regulation Of Proinflammatory Cytokines And Hepatic Steatosis In Mice, Pranoti Mandrekar, Aditya Ambade, Arlene Lim, Gyongyi Szabo, Donna Catalano Oct 2012

An Essential Role For Monocyte Chemoattractant Protein-1 In Alcoholic Liver Injury: Regulation Of Proinflammatory Cytokines And Hepatic Steatosis In Mice, Pranoti Mandrekar, Aditya Ambade, Arlene Lim, Gyongyi Szabo, Donna Catalano

Gyongyi Szabo

The importance of chemokines in alcoholic liver injury has been implicated. The role of the chemokine, monocyte chemoattractant protein-1 (MCP-1), elevated in patients with alcoholic liver disease is not yet understood. Here, we evaluated the pathophysiological significance of MCP-1 and its receptor, chemokine (C-C motif) receptor 2 (CCR2), in alcoholic liver injury. The Leiber-DeCarli diet containing alcohol or isocaloric control diets were fed to wild-type (WT) and MCP-1-deficient knockout (KO) mice for 6 weeks. In vivo and in vitro assays were performed to study the role of MCP-1 in alcoholic liver injury. MCP-1 was increased in Kupffer cells (KCs) as …


Microrna Silencing And The Development Of Novel Therapies For Liver Disease, Gyongyi Szabo, Peter Sarnow, Shashi Bala Oct 2012

Microrna Silencing And The Development Of Novel Therapies For Liver Disease, Gyongyi Szabo, Peter Sarnow, Shashi Bala

Gyongyi Szabo

In recent years microRNAs have emerged as crucial small non-coding RNA molecules with diverse roles in various diseases including diseases of the liver. In this review, we highlight the latest advances in the field of microRNA biology and their potential as emerging therapeutic targets in liver disease. Elsevier B.V. All rights reserved.


Reduction In Hepatic Inflammation Is Associated With Less Fibrosis Progression And Fewer Clinical Outcomes In Advanced Hepatitis C, Chihiro Morishima, Mitchell Shiffman, Jules Dienstag, Karen Lindsay, Gyongyi Szabo, Gregory Everson, Anna Lok, Adrian Di Bisceglie, Marc Ghany, Deepa Naishadham, Timothy Morgan, Elizabeth Wright Oct 2012

Reduction In Hepatic Inflammation Is Associated With Less Fibrosis Progression And Fewer Clinical Outcomes In Advanced Hepatitis C, Chihiro Morishima, Mitchell Shiffman, Jules Dienstag, Karen Lindsay, Gyongyi Szabo, Gregory Everson, Anna Lok, Adrian Di Bisceglie, Marc Ghany, Deepa Naishadham, Timothy Morgan, Elizabeth Wright

Gyongyi Szabo

OBJECTIVES:During the Hepatitis C Antiviral Long-term Treatment against Cirrhosis Trial, 3.5 years of maintenance peginterferon-alfa-2a therapy did not affect liver fibrosis progression or clinical outcomes among 1,050 previous interferon nonresponders with advanced fibrosis or cirrhosis. We investigated whether reduced hepatic inflammation was associated with clinical benefit in 834 patients with a baseline and follow-up biopsy 1.5 years after randomization to peginterferon or observation. METHODS:Relationships between change in hepatic inflammation (Ishak hepatic activity index, (HAI)) and serum alanine aminotransferase level, fibrosis progression and clinical outcomes after randomization, and hepatitis C virus (HCV) RNA decline before and after randomization were evaluated. Histological …


Cd81/Cd9 Tetraspanins Aid Plasmacytoid Dendritic Cells In Recognition Of Hcv-Infected Cells And Induction Of Ifnalpha, Shuye Zhang, Karen Kodys, Gregory Babcock, Gyongyi Szabo Oct 2012

Cd81/Cd9 Tetraspanins Aid Plasmacytoid Dendritic Cells In Recognition Of Hcv-Infected Cells And Induction Of Ifnalpha, Shuye Zhang, Karen Kodys, Gregory Babcock, Gyongyi Szabo

Gyongyi Szabo

Recognition of hepatitis C virus (HCV)-infected hepatocyes and interferon (IFN) induction are critical in antiviral immune response. We hypothesized that cell-cell contact between plasmacytoid dendritic cells (pDCs) and HCV-infected cells was required for IFNalpha induction via involvement of cell surface molecules. Co-culture of human peripheral blood mononuclear cells (PBMCs) with genotype 1a full length HCV genomic replicon cells (FL) or genotype 2a JFH-1 virus infected hepatoma cells (JFH-1), not with uninfected hepatoma cells (Huh7.5), induced IFNalpha production. Depletion of pDCs from PBMCs attenuated IFNalpha release and purified pDCs produced high levels of IFNalpha after co-culture with FL replicons or JFH-1 …


Hepatocyte-Specific Hypoxia-Inducible Factor-1alpha Is A Determinant Of Lipid Accumulation And Liver Injury In Alcohol-Induced Steatosis In Mice, Bharath Nath, Ivan Levin, Timea Csak, Jan Petrasek, Christian Mueller, Karen Kodys, Donna Catalano, Pranoti Mandrekar, Gyongyi Szabo Oct 2012

Hepatocyte-Specific Hypoxia-Inducible Factor-1alpha Is A Determinant Of Lipid Accumulation And Liver Injury In Alcohol-Induced Steatosis In Mice, Bharath Nath, Ivan Levin, Timea Csak, Jan Petrasek, Christian Mueller, Karen Kodys, Donna Catalano, Pranoti Mandrekar, Gyongyi Szabo

Gyongyi Szabo

Chronic alcohol causes hepatic steatosis and liver hypoxia. Hypoxia-regulated hypoxia-inducible factor 1-alpha, (HIF-1alpha) may regulate liporegulatory genes, but the relationship of HIF-1 to steatosis remains unknown. We investigated HIF-1alpha in alcohol-induced hepatic lipid accumulation. Alcohol administration resulted in steatosis, increased liver triglyceride levels, and increased serum alanine aminotransferase (ALT) levels, suggesting liver injury in wild-type (WT) mice. There was increased hepatic HIF-1alpha messenger RNA (mRNA), protein, and DNA-binding activity in alcohol-fed mice compared with controls. Mice engineered with hepatocyte-specific HIF-1 activation (HIF1dPA) had increased HIF-1alpha mRNA, protein, and DNA-binding activity, and alcohol feeding in HIF1dPA mice increased hepatomegaly and hepatic …


Induction Of Bcl-3 By Acute Binge Alcohol Results In Toll-Like Receptor 4/Lps Tolerance, Shashi Bala, Alexander Tang, Donna Catalano, Jan Petrasek, Odette Taha, Karen Kodys, Gyongyi Szabo Oct 2012

Induction Of Bcl-3 By Acute Binge Alcohol Results In Toll-Like Receptor 4/Lps Tolerance, Shashi Bala, Alexander Tang, Donna Catalano, Jan Petrasek, Odette Taha, Karen Kodys, Gyongyi Szabo

Gyongyi Szabo

Acute alcohol binge results in immunosuppression and impaired production of proinflammatory cytokines, including TNF-alpha. TNF-alpha production is induced by LPS, a TLR4 ligand, and is tightly regulated at various levels of the signaling cascade, including the NF-kappaB transcription factor. Here, we hypothesized that acute alcohol induces TLR4/LPS tolerance via Bcl-3, a nuclear protein and member of the NF-kappaB family. We found that acute alcohol pretreatment resulted in the same attenuating effect as LPS pretreatment on TLR4-induced TNF-alpha production in human monocytes and murine RAW 264.7 macrophages. Acute alcohol-induced Bcl-3 expression and IP studies revealed increased association of Bcl-3 with NF-kappaB …


Novel Developmental Biology-Based Protocol Of Embryonic Stem Cell Differentiation To Morphologically Sound And Functional Yet Immature Hepatocytes, Terence Bukong, Tracie Lo, Gyongyi Szabo, Angela Dolganiuc Oct 2012

Novel Developmental Biology-Based Protocol Of Embryonic Stem Cell Differentiation To Morphologically Sound And Functional Yet Immature Hepatocytes, Terence Bukong, Tracie Lo, Gyongyi Szabo, Angela Dolganiuc

Gyongyi Szabo

BACKGROUND/AIMS: Liver diseases are common in the United States and often require liver transplantation; however, donated organs are limited and thus alternative sources for liver cells are in high demand. Embryonic stem cells (ESC) can provide a continuous and readily available source of liver cells. ESC differentiation to liver cells is yet to be fully understood and comprehensive differentiation protocols are yet to be defined. Here, we aimed to achieve human (h)ESC differentiation into mature hepatocytes using defined recombinant differentiation factors and metabolites. METHODS: Embryonic stem cell H1 line was sub-cultured on feeder layer. We induced hESCs into endodermal differentiation …


Circulating Micrornas In Exosomes Indicate Hepatocyte Injury And Inflammation In Alcoholic, Drug-Induced, And Inflammatory Liver Diseases, Shashi Bala, Jan Petrasek, Shiv Mundkur, Donna Catalano, Ivan Levin, Jeanine Ward, Hawau Alao, Karen Kodys, Gyongyi Szabo Oct 2012

Circulating Micrornas In Exosomes Indicate Hepatocyte Injury And Inflammation In Alcoholic, Drug-Induced, And Inflammatory Liver Diseases, Shashi Bala, Jan Petrasek, Shiv Mundkur, Donna Catalano, Ivan Levin, Jeanine Ward, Hawau Alao, Karen Kodys, Gyongyi Szabo

Gyongyi Szabo

MicroRNAs are fine tuners of diverse biological responses and are expressed in various cell types of the liver. Here we hypothesized that circulating microRNAs (miRNAs) may serve as biomarkers of liver damage and inflammation. We studied miRNA-122, which is abundant in hepatocytes, and miR-155, -146a, and -125b, which regulate inflammation in immune cells in mouse models of alcoholic liver disease (ALD), drug (acetaminophen, APAP)-induced liver injury (DILI), and Toll-like receptor (TLR) 9+4 ligand-induced inflammatory cell-mediated liver damage. We found that serum/plasma miR-122 correlated with alanine aminotransferase (ALT) increases in the liver damage caused by alcohol, APAP, and TLR9 (CpG)+4 (LPS) …


Fatty Acid And Endotoxin Activate Inflammasomes In Mouse Hepatocytes That Release Danger Signals To Stimulate Immune Cells, Timea Csak, Michal Ganz, Justin Pespisa, Karen Kodys, Angela Dolganiuc, Gyongyi Szabo Oct 2012

Fatty Acid And Endotoxin Activate Inflammasomes In Mouse Hepatocytes That Release Danger Signals To Stimulate Immune Cells, Timea Csak, Michal Ganz, Justin Pespisa, Karen Kodys, Angela Dolganiuc, Gyongyi Szabo

Gyongyi Szabo

The pathogenesis of nonalcoholic steatohepatitis (NASH) and inflammasome activation involves sequential hits. The inflammasome, which cleaves pro-interleukin-1beta (pro-IL-1beta) into secreted IL-1beta, is induced by endogenous and exogenous danger signals. Lipopolysaccharide (LPS), a toll-like receptor 4 ligand, plays a role in NASH and also activates the inflammasome. In this study, we hypothesized that the inflammasome is activated in NASH by multiple hits involving endogenous and exogenous danger signals. Using mouse models of methionine choline-deficient (MCD) diet-induced NASH and high-fat diet-induced NASH, we found up-regulation of the inflammasome [including NACHT, LRR, and PYD domains-containing protein 3 (NALP3; cryopyrin), apoptosis-associated speck-like CARD-domain containing …


Hepatocyte-Specific Hypoxia-Inducible Factor-1alpha Is A Determinant Of Lipid Accumulation And Liver Injury In Alcohol-Induced Steatosis In Mice, Bharath Nath, Ivan Levin, Timea Csak, Jan Petrasek, Christian Mueller, Karen Kodys, Donna Catalano, Pranoti Mandrekar, Gyongyi Szabo Oct 2012

Hepatocyte-Specific Hypoxia-Inducible Factor-1alpha Is A Determinant Of Lipid Accumulation And Liver Injury In Alcohol-Induced Steatosis In Mice, Bharath Nath, Ivan Levin, Timea Csak, Jan Petrasek, Christian Mueller, Karen Kodys, Donna Catalano, Pranoti Mandrekar, Gyongyi Szabo

Christian Mueller

Chronic alcohol causes hepatic steatosis and liver hypoxia. Hypoxia-regulated hypoxia-inducible factor 1-alpha, (HIF-1alpha) may regulate liporegulatory genes, but the relationship of HIF-1 to steatosis remains unknown. We investigated HIF-1alpha in alcohol-induced hepatic lipid accumulation. Alcohol administration resulted in steatosis, increased liver triglyceride levels, and increased serum alanine aminotransferase (ALT) levels, suggesting liver injury in wild-type (WT) mice. There was increased hepatic HIF-1alpha messenger RNA (mRNA), protein, and DNA-binding activity in alcohol-fed mice compared with controls. Mice engineered with hepatocyte-specific HIF-1 activation (HIF1dPA) had increased HIF-1alpha mRNA, protein, and DNA-binding activity, and alcohol feeding in HIF1dPA mice increased hepatomegaly and hepatic …


Vasoactive Neuropeptides In Autoimmune Diseases, Ekua Brenu, Lotti Tajouri, Donald Staines, Sonya Marshall-Gradisnik Oct 2012

Vasoactive Neuropeptides In Autoimmune Diseases, Ekua Brenu, Lotti Tajouri, Donald Staines, Sonya Marshall-Gradisnik

Sonya Marshall-Gradisnik

Extract:Neuropeptides are a class of regulatory peptides with effects in nearly all physiological systems and processes. They are important in facilitating neuroendocrine immune interactions. Bi-directional communication between these two systems in both the central nervous system (CNS) and the periphery are arbitrated by the presence of these peptidergic innervations. These innervations interacting through unique ligand receptor binding complexes have immunomodulatory effects that preserve neuroendocrine and neuroimmune health.


Mechanism Of Autoimmunity In Pregnancy - The Good And The Bad, Lotti Tajouri, Ekua Brenu, Donald Staines, Sonya Marshall-Gradisnik Oct 2012

Mechanism Of Autoimmunity In Pregnancy - The Good And The Bad, Lotti Tajouri, Ekua Brenu, Donald Staines, Sonya Marshall-Gradisnik

Sonya Marshall-Gradisnik

Extract:In humans, female’s humoral and cellular immunity are actually stronger than men (Nalbandian & Kovats, 2005) and present a higher antibody serum titration than men (Giron-Gonzalez et al., 2000) which could logically and possibly explain their gender predisposition and susceptibility to autoimmunity. Holding an autoimmune disease and becoming pregnant is a serious matter for a woman and knowledge of the course of the condition during pregnancy is essential. Relational variations exist between types of autoimmuny during pregnancy and consequently proper advices from physicians are provided accordingly. In Systemic lupus erythematosus, all advices provided to the patients are meant to dissuade …


Factors Associated With Inadequate Colorectal Cancer Screening With Flexible Sigmoidoscopy, Adeyinka Laiyemo, Chyke Doubeni, Paul Pinsky, V. Paul Doria-Rose, Andrew Sanderson, Robert Bresalier, Joel Weissfeld, Robert Schoen, Pamela Marcus, Phillip Prorok, Christine Berg Oct 2012

Factors Associated With Inadequate Colorectal Cancer Screening With Flexible Sigmoidoscopy, Adeyinka Laiyemo, Chyke Doubeni, Paul Pinsky, V. Paul Doria-Rose, Andrew Sanderson, Robert Bresalier, Joel Weissfeld, Robert Schoen, Pamela Marcus, Phillip Prorok, Christine Berg

Chyke A. Doubeni

BACKGROUND AND STUDY AIM: Inadequate colorectal cancer screening wastes limited endoscopic resources. We examined patients factors associated with inadequate flexible sigmoidoscopy (FSG) screening at baseline screening and repeat screening 3-5 years later in 10 geographically-dispersed screening centers participating in the ongoing Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

METHODS: A total of 64,554 participants (aged 55-74) completed baseline questionnaires and underwent FSG at baseline. Of these, 39,385 participants returned for repeat screening. We used logistic regression models to assess factors that are associated with inadequate FSG (defined as a study in which the depth of insertion of FSG was …


Contribution Of Behavioral Risk Factors And Obesity To Socioeconomic Differences In Colorectal Cancer Incidence, Chyke Doubeni, Jacqueline Major, Adeyinka Laiyemo, Mario Schootman, Ann Zauber, Albert Hollenbeck, Rashmi Sinha, Jeroan Allison Oct 2012

Contribution Of Behavioral Risk Factors And Obesity To Socioeconomic Differences In Colorectal Cancer Incidence, Chyke Doubeni, Jacqueline Major, Adeyinka Laiyemo, Mario Schootman, Ann Zauber, Albert Hollenbeck, Rashmi Sinha, Jeroan Allison

Chyke A. Doubeni

BACKGROUND:Health behaviors are known risk factors for colorectal cancer and are more common in low socioeconomic status (SES) populations. We evaluated the extent to which behavioral risk factors and body mass index (BMI) explain SES disparities in colorectal cancer incidence, overall and by tumor location.

METHODS: We analyzed prospective National Institutes of Health-AARP Diet and Health Study data on 506 488 participants who were recruited in 1995-1996 from six US states and two metropolitan areas and followed through 2006. Detailed baseline data on risk factors for colorectal cancer, including health behaviors, were obtained using questionnaires. SES was measured by self-reported …


Socioeconomic Status, Healthcare Density, And Risk Of Prostate Cancer Among African American And Caucasian Men In A Large Prospective Study, Jacqueline Major, M. Oliver, Chyke Doubeni, Albert Hollenbeck, Barry Graubard, Rashmi Sinha Oct 2012

Socioeconomic Status, Healthcare Density, And Risk Of Prostate Cancer Among African American And Caucasian Men In A Large Prospective Study, Jacqueline Major, M. Oliver, Chyke Doubeni, Albert Hollenbeck, Barry Graubard, Rashmi Sinha

Chyke A. Doubeni

OBJECTIVES: The purpose of this study was to separately examine the impact of neighborhood socioeconomic deprivation and availability of healthcare resources on prostate cancer risk among African American and Caucasian men. METHODS: In the large, prospective NIH-AARP Diet and Health Study, we analyzed baseline (1995-1996) data from adult men, aged 50-71 years. Incident prostate cancer cases (n = 22,523; 1,089 among African Americans) were identified through December 2006. Lifestyle and health risk information was ascertained by questionnaires administered at baseline. Area-level socioeconomic indicators were ascertained by linkage to the US Census and the Area Resource File. Multilevel Cox models were …


Variation Of Adenoma Prevalence By Age, Sex, Race, And Colon Location In A Large Population: Implications For Screening And Quality Programs, Douglas Corley, Christopher Jensen, Amy Marks, Wei Zhao, Jolanda De Boer, Theodore Levin, Chyke Doubeni, Bruce Fireman, Charles Quesenberry Oct 2012

Variation Of Adenoma Prevalence By Age, Sex, Race, And Colon Location In A Large Population: Implications For Screening And Quality Programs, Douglas Corley, Christopher Jensen, Amy Marks, Wei Zhao, Jolanda De Boer, Theodore Levin, Chyke Doubeni, Bruce Fireman, Charles Quesenberry

Chyke A. Doubeni

BACKGROUND and AIMS: Reliable community-based colorectal adenoma prevalence estimates are needed to inform colonoscopy quality standards and to estimate patient colorectal cancer risks; however, minimal data exist from populations with large numbers of diverse patients and examiners. METHODS: We evaluated the prevalence of adenomas detected by sex, age, race/ethnicity, and colon location among 20,792 Kaiser Permanente Northern California members >/=50 years of age who received a screening colonoscopy exam (102 gastroenterologists, years 2006-2008). RESULTS: Prevalence of detected adenomas increased more rapidly with age in the proximal colon (adjusted odds ratio [OR], 2.39; 95% confidence interval [CI], 2.05-2.80; 70-74 vs 50-54 …


Vasoactive Neuropeptides In Autoimmune Diseases, Ekua Brenu, Lotti Tajouri, Donald Staines, Sonya Marshall-Gradisnik Oct 2012

Vasoactive Neuropeptides In Autoimmune Diseases, Ekua Brenu, Lotti Tajouri, Donald Staines, Sonya Marshall-Gradisnik

Lotti Tajouri

Extract:Neuropeptides are a class of regulatory peptides with effects in nearly all physiological systems and processes. They are important in facilitating neuroendocrine immune interactions. Bi-directional communication between these two systems in both the central nervous system (CNS) and the periphery are arbitrated by the presence of these peptidergic innervations. These innervations interacting through unique ligand receptor binding complexes have immunomodulatory effects that preserve neuroendocrine and neuroimmune health.