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Full-Text Articles in Medical Sciences

Molecular Processes That Handle — And Mishandle — Dietary Lipids, Kevin Jon Williams Oct 2008

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.


The Cytoplasmic Tail Of The Rabies Virus G Protein Is An Essential Domain Controlling Death/Survival In Human Neuronal Cells, Christophe Prehaud, Mireille Lafage, Gene S. Tan, Françoise Mégret, Pauline Ménager, Matthias Schnell, Henri Buc, Monique Lafon Sep 2008

The Cytoplasmic Tail Of The Rabies Virus G Protein Is An Essential Domain Controlling Death/Survival In Human Neuronal Cells, Christophe Prehaud, Mireille Lafage, Gene S. Tan, Françoise Mégret, Pauline Ménager, Matthias Schnell, Henri Buc, Monique Lafon

Department of Microbiology and Immunology Faculty Papers

Poster presentation.


Intravenous Inoculation Of Silver-Haired Bat Rabies Virus, But Not Of A Canine Strain, Elicits Lethal Encephalophathy In Mice By Fast Brain Invasion Via Neurosecretory Hypothalamic Fibers, Mirjam Ar Preuss, Marie-Luise Faber, Gene S. Tan, Bernhard Dietzschold, Matthias J. Schnell, Eberhard Weihe Sep 2008

Intravenous Inoculation Of Silver-Haired Bat Rabies Virus, But Not Of A Canine Strain, Elicits Lethal Encephalophathy In Mice By Fast Brain Invasion Via Neurosecretory Hypothalamic Fibers, Mirjam Ar Preuss, Marie-Luise Faber, Gene S. Tan, Bernhard Dietzschold, Matthias J. Schnell, Eberhard Weihe

Department of Microbiology and Immunology Faculty Papers

No abstract provided.


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 Aug 2008

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 …


Abeta42 Mutants With Different Aggregation Profiles Induce Distinct Pathologies In Drosophila., Koichi Iijima, Hsueh-Cheng Chiang, Stephen A Hearn, Inessa Hakker, Anthony Gatt, Christopher Shenton, Linda Granger, Amy Leung, Kanae Iijima-Ando, Yi Zhong Feb 2008

Abeta42 Mutants With Different Aggregation Profiles Induce Distinct Pathologies In Drosophila., Koichi Iijima, Hsueh-Cheng Chiang, Stephen A Hearn, Inessa Hakker, Anthony Gatt, Christopher Shenton, Linda Granger, Amy Leung, Kanae Iijima-Ando, Yi Zhong

Department of Biochemistry and Molecular Biology Faculty Papers

Aggregation of the amyloid-beta-42 (Abeta42) peptide in the brain parenchyma is a pathological hallmark of Alzheimer's disease (AD), and the prevention of Abeta aggregation has been proposed as a therapeutic intervention in AD. However, recent reports indicate that Abeta can form several different prefibrillar and fibrillar aggregates and that each aggregate may confer different pathogenic effects, suggesting that manipulation of Abeta42 aggregation may not only quantitatively but also qualitatively modify brain pathology. Here, we compare the pathogenicity of human Abeta42 mutants with differing tendencies to aggregate. We examined the aggregation-prone, EOFAD-related Arctic mutation (Abeta42Arc) and an artificial mutation (Abeta42art) that …


Temporal And Functional Profile Of The Transcriptional Regulatory Network In The Early Regenerative Response To Partial Hepatectomy In The Rat., Egle Juskeviciute, Rajanikanth Vadigepalli, Jan B Hoek Jan 2008

Temporal And Functional Profile Of The Transcriptional Regulatory Network In The Early Regenerative Response To Partial Hepatectomy In The Rat., Egle Juskeviciute, Rajanikanth Vadigepalli, Jan B Hoek

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: The goal of these studies was to characterize the transcriptional network regulating changes in gene expression in the remnant liver of the rat after 70% partial hepatectomy (PHx) during the early phase response including the transition of hepatocytes from the quiescent (G0) state and the onset of the G1 phase of the cell cycle. RESULTS: The transcriptome of remnant livers was monitored at 1, 2, 4, and 6 hours after PHx using cDNA microarrays. Differentially regulated genes were grouped into six clusters according their temporal expression profiles. Promoter regions of genes in these clusters were examined for shared transcription …


Multiple Forms Of Atypical Rearrangements Generating Supernumerary Derivative Chromosome 15., Nicholas J Wang, Alexander S Parokonny, Karen N Thatcher, Jennette Driscoll, Barbara M Malone, Naghmeh Dorrani, Marian Sigman, Janine M Lasalle, N Carolyn Schanen Jan 2008

Multiple Forms Of Atypical Rearrangements Generating Supernumerary Derivative Chromosome 15., Nicholas J Wang, Alexander S Parokonny, Karen N Thatcher, Jennette Driscoll, Barbara M Malone, Naghmeh Dorrani, Marian Sigman, Janine M Lasalle, N Carolyn Schanen

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Maternally-derived duplications that include the imprinted region on the proximal long arm of chromosome 15 underlie a complex neurobehavioral disorder characterized by cognitive impairment, seizures and a substantial risk for autism spectrum disorders1. The duplications most often take the form of a supernumerary pseudodicentric derivative chromosome 15 [der(15)] that has been called inverted duplication 15 or isodicentric 15 [idic(15)], although interstitial rearrangements also occur. Similar to the deletions found in most cases of Angelman and Prader Willi syndrome, the duplications appear to be mediated by unequal homologous recombination involving low copy repeats (LCR) that are found clustered in the …


A Comprehensive Analysis Of The Naturally Occurring Polymorphisms In Hiv-1 Vpr: Potential Impact On Ctl Epitopes., Alagarsamy Srinivasan, Velpandi Ayyavoo, Sundarasamy Mahalingam, Aarthi Kannan, Anne Boyd, Debduti Datta, Vaniambadi S Kalyanaraman, Anthony Cristillo, Ronald G Collman, Nelly Morellet, Bassel E Sawaya, Ramachandran Murali Jan 2008

A Comprehensive Analysis Of The Naturally Occurring Polymorphisms In Hiv-1 Vpr: Potential Impact On Ctl Epitopes., Alagarsamy Srinivasan, Velpandi Ayyavoo, Sundarasamy Mahalingam, Aarthi Kannan, Anne Boyd, Debduti Datta, Vaniambadi S Kalyanaraman, Anthony Cristillo, Ronald G Collman, Nelly Morellet, Bassel E Sawaya, Ramachandran Murali

Department of Microbiology and Immunology Faculty Papers

The enormous genetic variability reported in HIV-1 has posed problems in the treatment of infected individuals. This is evident in the form of HIV-1 resistant to antiviral agents, neutralizing antibodies and cytotoxic T lymphocytes (CTLs) involving multiple viral gene products. Based on this, it has been suggested that a comprehensive analysis of the polymorphisms in HIV proteins is of value for understanding the virus transmission and pathogenesis as well as for the efforts towards developing anti-viral therapeutics and vaccines. This study, for the first time, describes an in-depth analysis of genetic variation in Vpr using information from global HIV-1 isolates …


Hiv-1 Tat And Aids-Associated Cancer: Targeting The Cellular Anti-Cancer Barrier?, Giuseppe Nunnari, Johanna A Smith, René Daniel Jan 2008

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 …


Inhibition Of Oncogene-Induced Inflammatory Chemokines Using A Farnesyltransferase Inhibitor., Katharine C Degeorge, Brent R Degeorge, James S Testa, Jay L Rothstein Jan 2008

Inhibition Of Oncogene-Induced Inflammatory Chemokines Using A Farnesyltransferase Inhibitor., Katharine C Degeorge, Brent R Degeorge, James S Testa, Jay L Rothstein

Department of Microbiology and Immunology Faculty Papers

ABSTRACT: BACKGROUND: Farnesyltransferase inhibitors (FTI) are small molecule agents originally formulated to inhibit the oncogenic functions of Ras. Although subsequent analysis of FTI activity revealed wider effects on other pathways, the drug has been demonstrated to reduce Ras signaling by direct measurements. The purpose of the current study was to determine if FTI could be used to inhibit the inflammatory activities of a known Ras-activating human oncoprotein, RET/PTC3. RET/PTC3 is a fusion oncoprotein expressed in the thyroid epithelium of patients afflicted with thyroid autoimmune disease and/or differentiated thyroid carcinoma. Previous studies have demonstrated that RET/PTC3 signals through Ras and can …


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 Jan 2008

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 …