Medical Genetics Commons^™

Molecular Processes That Handle — And Mishandle — Dietary Lipids, Kevin Jon Williams

Department of Medicine Faculty Papers

Overconsumption of lipid-rich diets, in conjunction with physical inactivity, disables and kills staggering numbers of people worldwide. Recent advances in our molecular understanding of cholesterol and triglyceride transport from the small intestine to the rest of the body provide a detailed picture of the fed/fasted and active/sedentary states. Key surprises include the unexpected nature of many pivotal molecular mediators, as well as their dysregulation — but possible reversibility — in obesity, diabetes, inactivity, and related conditions. These mechanistic insights provide new opportunities to correct dyslipoproteinemia, accelerated atherosclerosis, insulin resistance, and other deadly sequelae of overnutrition and underexertion.

Pegylated Interferon 2a And 2b In Combination With Ribavirin For The Treatment Of Chronic Hepatitis C In Hiv Infected Patients., Ravinder Dhillon, Simona Rossi, Steven K Herrine

Department of Medicine Faculty Papers

Coinfection with hepatitis C virus (HCV) and HIV is an increasingly recognized clinical dilemma, particularly since the advent of highly active antiretroviral therapy. Several studies of this population have demonstrated both more rapid progression of liver disease and poorer overall prognosis compared to HCV monoinfected patients. Consensus guidelines, based primarily on the results of 4 major randomized trials, recommend treatment with peginterferon and ribavirin for 48 weeks in coinfected patients. However, this current standard of care is associated with lower response rates to therapy than those seen in monoinfected patients. Important predictors of response include HCV genotype, pretreatment HCV RNA …

Beta3 Integrin Haplotype Influences Gene Regulation And Plasma Von Willebrand Factor Activity, Katie E. Payne, Paul F. Bray, Peter J. Grant, Angela M. Carter

Department of Medicine Faculty Papers

The Leu33Pro polymorphism of the gene encoding beta(3) integrin (ITGB3) is associated with acute coronary syndromes and influences platelet aggregation. Three common promoter polymorphisms have also been identified. The aims of this study were to (1) investigate the influence of the ITGB3 -400C/A, -425A/C and -468G/A promoter polymorphisms on reporter gene expression and nuclear protein binding and (2) determine genotype and haplotype associations with platelet alpha(IIb)beta(3) receptor density. Promoter haplotypes were introduced into an ITGB3 promoter-pGL3 construct by site directed mutagenesis and luciferase reporter gene expression analysed in HEL and HMEC-1 cells. Binding of nuclear proteins was assessed by electrophoretic …

Primary Care Physicians And Insulin Initiation: Multiple Barriers, Lack Of Knowledge Or Both?, Serge Jabbour, Md, Facp, Face

Department of Medicine Faculty Papers

Primary care physicians (PCPs) provide diabetes care for 82% of patients with type 2 diabetes (1). Many patients with type 2 diabetes will eventually need insulin. The UKPDS (2) showed that ß-cell failure is progressive. From 50% of normal ß-cell function present at diagnosis, there is a steady decline with almost complete loss of ß-cell mass within 10-15 years, even earlier in some patients. On average, as many as 40-80% of patients with type 2 diabetes will need insulin within 10 years after diagnosis (1,2). These statistics can vary between patients and depending on the different agents used after the …

Solid Serous Adenoma Of The Pancreas: A Rare Form Of Serous Cystadenoma, Madhusudhan R. Sanaka, Thomas E. Kowalski, Corey Brotz, Charles J. Yeo, Peter Mccue, Juan Palazzo

Department of Medicine Faculty Papers

Serous cystadenomas (SC) of the pancreas are uncommon benign cystic neoplasms that were first differentiated from mucinous cystadenomas in 1978 by Compagno and Oertel (1-3). Serous cystadenomas characteristically have a spongy gross appearance and are composed of innumerable tiny cysts lined by flattened cuboidal or polygonal cells with clear to pale eosinophilic cytoplasm atop of thin fibrous septae. Since 1978, five unique SC subtypes have been identified (4-5). Here we report a case of a solid serous adenoma, a rare serous cystadenoma subtype.

Rosai-Dorfrman Disease Of The Colon, Rahul A. Nathwani, Lawrence Kenyon, Thomas E. Kowalski

Department of Medicine Faculty Papers

Rosai-Dorfman disease (RDD), formerly referred to as "sinus histiocytosis with massive lymphadenopathy," was first described by Rosai and Dorfman in 1969. Initially believed to be a disease limited to the lymph nodes, RDD is now recognized as involving a variety of organs. Although GI involvement has been reported, it remains rare. To our knowledge, there have been no cases of RDD reported in the gastroenterology literature and no cases evaluated with EUS.

The Yin And Yang Of Fcγ Receptors In Itp, Steven E. Mckenzie

Department of Medicine Faculty Papers

The Fcγ receptors contribute to the susceptibility to autoimmune diseases such as ITP in several ways: (1) they modulate dendritic cell antigen processing and presentation, (2) they modulate antibody production by B cells, and (3) they participate in effector cell functions, such as phagocytosis, antibody-dependent cellular cytotoxicity, and mediator release. The key finding in recent years has been the appreciation that the activating Fcγ receptors, encoded by FCGR2A, -2C, -3A, and -3B, compete with the inhibitory Fcγ receptor, encoded by FCGR2B, to determine cellular responses to immune complexes and antibody-coated cells.

Eosinophilic Fasciitis: Demographics, Disease Pattern And Response To Treatment: Report Of 12 Cases And Review Of The Literature, Lindsay Bischoff, Chris T. Derk

Department of Medicine Faculty Papers

BACKGROUND:
Eosinophilic fasciitis is a rare scleroderma-like illness. The clinical spectrum of the disease has evolved since its initial description.

METHODS:
We identified all patients diagnosed with eosinophilic fasciitis over the past 10 years at our scleroderma clinic. Demographics, disease pattern, serologies, tissue pathology and reponse to treatment were all recorded.

RESULTS:
Twelve patients with eosinophilic fasciitis were identified in our clinic over the past 10 years. The mean age at diagnosis was 49.8 +/- 9.8 years, with nine female and three male patients. The first symptoms were noticed at an average of 8.8 +/- 6.1 months before diagnosis. The …

Hiv-1 Tat Protein Alter The Tight Junction Integrity And Function Of Retinal Pigment Epithelium: An In Vitro Study., Ling Bai, Zhenping Zhang, Hui Zhang, Xiumei Li, Qiurong Yu, Haotian Lin, Wenhui Yang

Department of Medicine Faculty Papers

BACKGROUND: How HIV-1 enter into the eyes remains obscure. We postulated that HIV-1 Tat protein can alter the expression of specific tight-junction proteins and disturb the blood retinal barrier, and contributes to HIV trafficking into the eyes. This study is to determine the effects of HIV-1 Tat proteins on the barrier function and tight-junction protein expression of retinal pigment epithelial cell (RPE). METHODS: A human RPE cell line (D407) cultured on microporous filter-supports was used. After treating with HIV-1 Tat protein, transepithelial electrical resistance (TER) of confluent RPE cells was measured by epithelial voltmeter. The permeability of the RPE cells …

Hiv-1 Tat And Aids-Associated Cancer: Targeting The Cellular Anti-Cancer Barrier?, Giuseppe Nunnari, Johanna A Smith, René Daniel

Department of Medicine Faculty Papers

The acquired immunodeficiency syndrome (AIDS) is accompanied by a significant increase in the incidence of neoplasms. Several causative agents have been proposed for this phenomenon. These include immunodeficiency and oncogenic DNA viruses and the HIV-1 protein Tat. Cancer in general is closely linked to genomic instability and DNA repair mechanisms. The latter maintains genomic stability and serves as a cellular anti-cancer barrier. Defects in DNA repair pathway are associated with carcinogenesis. This review focuses on newly discovered connections of the HIV-1 protein Tat, as well as cellular co-factors of Tat, to double-strand break DNA repair. We propose that the Tat-induced …