Medical Sciences Commons^™

Atypical Antipsychotics And Cognitive Enhancement In Schizophrenia: The Current Status, Amresh Srivastava

Psychiatry Presentations

No abstract provided.

Cognition As An Outcome Measure In Schizophrenia, Amresh Srivastava

Psychiatry Presentations

No abstract provided.

Modulation Of Cd4 Co-Receptor Limits Spontaneous Autoimmunity When High-Affinity Transgenic Tcr Specific For Self-Antigen Is Expressed On A Genetically Resistant Background, Zsolt Illés, Hanspeter Waldner, Jay Reddy, Ana C. Anderson, Raymond A. Sobel, Vijay K. Kuchroo

Jay Reddy Publications

Myelin proteolipid protein (PLP) 139–151 is an immunodominant peptide that induces experimental autoimmune encephalomyelitis (EAE) in H-2^s SJL/J mice. While PLP 139–151-specific TCR transgenic (tg) 4E3 mice develop fulminant spontaneous disease on the susceptible SJL/J background, spontaneous EAE is dramatically reduced on the H-2^s congenic B10.S background. On this resistant background, we observed a high frequency of positively selected tg CD42CD82 (DN) thymocytes and peripheral DN tg T cells. Splenic DN tg T cells responded to anti-CD3 stimulation similarly to CD41 cells, but proliferative and cytokine responses to PLP 139–151 were blunted, implying that CD4 coreceptor down-regulation modulated …

Differential Effects Of Th1, Monocyte/Macrophage And Th2 Cytokine Mixtures On Early Gene Expression For Glial And Neural-Related Molecules In Central Nervous System Mixed Glial Cell Cultures: Neurotrophins, Growth Factors And Structural Proteins, Robert P. Lisak, Joyce A. Benjamins, Beverly Bealmear, Liljana Nedelkoska, Bin Yao, Susan Land, Diane Studzinski

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

In multiple sclerosis, inflammatory cells are found in both active and chronic lesions, and it is increasingly clear that cytokines are involved directly and indirectly in both formation and inhibition of lesions. We propose that cytokine mixtures typical of Th1 or Th2 lymphocytes, or monocyte/macrophages each induce unique molecular changes in glial cells.

Methods

To examine changes in gene expression that might occur in glial cells exposed to the secreted products of immune cells, we have used gene array analysis to assess the early effects of different cytokine mixtures on mixed CNS glia in culture. We compared the …

Age-Related Dgc Structure And Function In The F344/N X Bn Rat Heart, Sunil K. Kakarla

Theses, Dissertations and Capstones

Recent data has suggested that disruption of the dystrophin-glycoprotein complex (DGC) may be involved in mediating the progression of cardiac hypertrophy and failure. Here we examined the regulation of DGC proteins in the hearts of adult (6 months), aged (30 months), and very aged (36 months) F344/N X BN rats . Compared to adult animals, the content of α- and β-dystroglycan were 6.93 ± 5.16% and 58.36 ± 3.64% higher, respectively (P < 0.05) in very aged animals. Immunoblotting and immunhistochemical analysis suggested that aging appeared to diminish alpha-sarcoglycan, beta-sarcoglycan and delta-sarcoglycan content by 13.89 ± 3.1%,15.8 ± 2.8% and 18.63 ± 3.04%, respectively (P < 0.05). These alterations in the DGC occurred coincident with age- associated alterations in cytoplasmic anti-rat IgG immunoreactivity, TUNEL positive nuclei, alpha-fodrin cleavage, indices of caspase-3 activation and diminished AKT phosphoryation (Ser 308). Taken together, these data suggest that aging alters cardiac DGC structure and function.

Poxviral B1 Kinase Overcomes Barrier To Autointegration Factor, A Host Defense Against Virus Replication, Matthew S. Wiebe, Paula Traktman

Nebraska Center for Virology: Faculty Publications

Barrier to autointegration factor (BAF) is a DNA-binding protein found in the nucleus and cytoplasm of eukaryotic cells that functions to establish nuclear architecture during mito-sis. Herein, we demonstrate a cytoplasmic role for BAF in host defense during poxviral infections. Vaccinia is the prototypic poxvirus, a family of DNA viruses that replicate ex-clusively in the cytoplasm of infected cells. Mutations in the vaccinia B1 kinase (B1) com-promise viral DNA replication, but the mechanism by which B1 achieves this has remained elusive. We now show that BAF acts as a potent inhibitor of poxvirus replication unless its DNA-binding activity is blocked …

Dietary Behaviors And Anthropometric Measurements Of Mexican Women And Second Generation Mexican American Women, Liane Fernyhough

Undergraduate Honors Theses

Risk for chronic diseases is higher among Mexican Americans than in the general American population. A high percentage of central Washington Mexican Americans (CWMAs) immigrated from Michoacan, Mexico. The purpose of this study was to determine if dietary behaviors differ between women living in these areas and if these differences were associated with physiological differences. Sixty-one women (ages 18-50) in Morelia Michoacan and 26 second-generation CWMA women (ages 18-50) participated. Body mass index tended to be higher in the CWMA women (32±7 vs. 29±6, p≤0.06) as was waist circumference (39±7 vs 36±5 inches, p≤0.06). those surveyed in both Michoacan and …

Role Of Protein Kinase Phosphorylation On Sert Oligomerization: A Novel Mechanistic View, Eric Richard Buck

MUSC Theses and Dissertations

The serotonin transporter (SERT) is the primary mechanism for the termination of synaptic signaling. It is of clinical relevance because it is a high-affinity target for therapeutics such as anti-depressants (SSRIs) and drugs of abuse such as cocaine, amphetamine, and 3,4 methylenedioxymethamphetamine (ecstasy). It is also seen as a protein potentially involved in the etiology underlying disorders such as clinical depression, autism, anxiety-related disorders, obsessive compulsive disorder, and anorexia nervosa among others. SERT has also been found to be a target of protein kinases that exert their effects through phosphorylation. For example, activation of protein kinase C (PKC) decreases SERT …

Ribosome Recycling: An Essential Process Of Protein Synthesis, Michael C. Kiel, Hideko Kaji, Akira Kaji

Department of Biochemistry and Molecular Biology Faculty Papers

A preponderance of textbooks outlines cellular protein synthesis (translation) in three basic steps: initiation, elongation, and termination. However, researchers in the field of translation accept that a vital fourth step exists; this fourth step is called ribosome recycling. Ribosome recycling occurs after the nascent polypeptide has been released during the termination step. Despite the release of the polypeptide, ribosomes remain bound to the mRNA and tRNA. It is only during the fourth step of translation that ribosomes are ultimately released from the mRNA, split into subunits, and are free to bind new mRNA, thus the term "ribosome recycling." This step …

Inhibition Of Antiassociation Activity Of Translation Initiation Factor 3 By Paromomycin, Go Hirokawa, Hideko Kaji, Akira Kaji

Department of Biochemistry and Molecular Biology Faculty Papers

The effect of paromomycin on the interaction of ribosomal subunits was studied. Paromomycin inhibited the antiassociation activity of initiation factor 3 (IF3). Furthermore, ribosomal subunits were associated to form 70S ribosomes by paromomycin even in the presence of 1 mM Mg(2+). Paromomycin did not inhibit the binding of IF3 to the 30S ribosomal subunits. On the other hand, IF3 bound to the 30S subunits was expelled by paromomycin-induced subunit association (70S formation). These results indicate that the stabilization of 70S ribosomes by paromomycin may in part be responsible for its inhibitory effects on translocation and ribosome recycling.

Letter To The Editor: Further Efforts To Redce The Incidence Of Neural Tube Defects, Robert L. Brent

The Selected Works of Robert Brent

No abstract provided.

Triumph And/Or Tragedy: The Present Food And Drug Administration Program Of Enriching Grains With Folic Acid., Robert L. Brent

The Selected Works of Robert Brent

No abstract provided.

Developmental Toxicology Drugs, And Fetal Teratogenesis, Robert L. Brent

The Selected Works of Robert Brent

No abstract provided.

Robert Warwick Miller: In Memoriam., Robert L. Brent

The Selected Works of Robert Brent

No abstract provided.

How Does The Physician Avoid Prescribong Drugs And Medical Procedures That Have Reproductive And Developmental Risks?, Robert L. Brent

The Selected Works of Robert Brent

No abstract provided.

Replication Fork Regression In Vitro By The Werner Syndrome Protein (Wrn): Holliday Junction Formation, The Effect Of Leading Arm Structure And A Potential Role For Wrn Exonuclease Activity, Amrita Machwe, Liren Xiao, Robert G Lloyd, Edward Bolt, David K. Orren

Toxicology and Cancer Biology Faculty Publications

The premature aging and cancer-prone disease Werner syndrome stems from loss of WRN protein function. WRN deficiency causes replication abnormalities, sensitivity to certain genotoxic agents, genomic instability and early replicative senescence in primary fibroblasts. As a RecQ helicase family member, WRN is a DNA-dependent ATPase and unwinding enzyme, but also possesses strand annealing and exonuclease activities. RecQ helicases are postulated to participate in pathways responding to replication blockage, pathways possibly initiated by fork regression. In this study, a series of model replication fork substrates were used to examine the fork regression capability of WRN. Our results demonstrate that WRN catalyzes …

Fa2h Dependent Fatty Acid 2-Hydroxylation In The Mammalian Nervous System, Nathan Lance Alderson

MUSC Theses and Dissertations

Myelin is formed by oligodendrocytes in the central nervous system and Schwann cells in the peripheral nervous system. This unique membrane is comprised of approximately 70% lipid and 30% protein. The high lipid content is thought to be vital for its insulatory function. Galactosylceramide (GaICer) and sulfatide make up approximately 30% of total myelin lipids, with more than half of these galactolipids containing fatty acids hydroxylated at the C[subscript 2] position (2-hydroxy fatty acids). Despite their high abundance, very little is know about the biosynthesis of these 2-hydroxy galactolipids, and specific functions of the 2-hydroxyl group in myelin galactolipids remain …

Sustained Il-6/Stat-3 Signaling In Cholangiocarcinoma Cells Due To Socs-3 Epigenetic Silencing., Hajime Isomoto, Justin L. Mott, Shogo Kobayashi, Nathan W. Werneburg, Steve F. Bronk, Serge Haan, Gregory J. Gores

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND & AIMS: Interleukin 6 (IL-6)-mediated signal transducers and activators of transcription 3 (STAT-3) phosphorylation (activation) is aberrantly sustained in cholangiocarcinoma cells resulting in enhanced myeloid cell leukemia 1 (Mcl-1) expression and resistance to apoptosis. Because suppressor of cytokine signaling 3 (SOCS) controls the IL-6/STAT-3 signaling pathway by a classic feedback loop, the aims of this study were to examine SOCS-3 regulation in human cholangiocarcinoma.

METHODS: SOCS-3 expression was assessed in human cholangiocarcinoma tissue and the Mz-ChA-1 and CCLP1 human cholangiocarcinoma cell lines.

RESULTS: An inverse correlation was observed between phospho-STAT-3 and SOCS-3 protein expression in cholangiocarcinoma. In those cancers …

Telomerase Inhibition And Sensitization Of Breast Tumor Cells, Kennon R. Poynter

Theses and Dissertations

Telomerase, a ribonucleoprotein enzyme minimally composed of an RNA template (hTR) and a catalytically active protein subunit (hTERT), synthesizes telomeric repeats onto chromosome ends and is obligatory for continuous tumor cell proliferation, as well as malignant progression of breast cancer cells. Telomerase is an attractive anticancer therapeutic target because its activity is present in over 90% of human cancers, including more than 95% of breast carcinomas, but undetectable in most somatic cells. Traditions chemo- and radio-therapies lack the ability to effectively control and cure breast cancer, in part because residual cells are or become resistant to DNA damaging modalities.While various …

Single Nucleotide Polymorphisms (Snps) Distinguish Indian-Origin And Chinese-Origin Rhesus Macaques (Macaca Mulatta), Betsy Ferguson, Summer L. Street, Hollis Wright, Carlo Pearson, Yibing Jia, Shaun L. Thompson, Patrick Allibone, Christopher J. Dubay, Eliot Spindel, Robert B. Norgren

Journal Articles: Genetics, Cell Biology & Anatomy

BACKGROUND: Rhesus macaques serve a critical role in the study of human biomedical research. While both Indian and Chinese rhesus macaques are commonly used, genetic differences between these two subspecies affect aspects of their behavior and physiology, including response to simian immunodeficiency virus (SIV) infection. Single nucleotide polymorphisms (SNPs) can play an important role in both establishing ancestry and in identifying genes involved in complex diseases. We sequenced the 3' end of rhesus macaque genes in an effort to identify gene-based SNPs that could distinguish between Indian and Chinese rhesus macaques and aid in association analysis.

RESULTS: We surveyed the …

Modulation Of Retroviral Restriction And Proteasome Inhibitor-Resistant Turnover By Changes In The Trim5Α B-Box 2 Domain, Felipe Diaz-Griffero, Alak Kar, Michel Perron, Shi-Hua Xiang, Hassan Javanbakht, Xing Li, Joseph Sodroski

Nebraska Center for Virology: Faculty Publications

An intact B-box 2 domain is essential for the antiretroviral activity of TRIM5α. We modeled the structure of the B-box 2 domain of TRIM5α based on the existing three-dimensional structure of the B-box 2 domain of human TRIM29. Using this model, we altered the residues predicted to be exposed on the surface of this globular structure. Most of the alanine substitutions in these residues exerted little effect on the antiretroviral activity of human TRIM5αhu or rhesus monkey TRIM5α_rh. However, alteration of arginine 119 of TRIM5α_hu or the corresponding arginine 121 of TRIM5α_rh diminished the abilities of …

Functional Interplay Between The B-Box 2 And The B30.2(Spry) Domains Of Trim5Α, Xi Ling, Byeongwoon Song, Shi-Hua Xiang, Joseph Sodroski

Nebraska Center for Virology: Faculty Publications

The retroviral restriction factors, TRIM5α and TRIMCyp, consist of RING and B-box 2 domains separated by a coiled coil from carboxy-terminal domains. These carboxy-terminal domains (the B30.2(SPRY) domain in TRIM5α and the cyclophilin A domain in TRIMCyp) recognize the retroviral capsid. Here we show that some B-box 2 changes in TRIM5α, but not in TRIMCyp, resulted in decreased human immunodeficiency virus (HIV-1) capsid binding. The phenotypic effects of these B-box 2 changes on the restriction of retroviral infection depended on the potency of restriction and the affinity of the TRIM5α interaction with the viral capsid, two properties specified by the …

Characterization Of Human Immunodeficiency Virus Type 1 Monomeric And Trimeric Gp120 Glycoproteins Stabilized In The Cd4-Bound State: Antigenicity, Biophysics, And Immunogenicity, Barna Dey, Marie Pancera, Krisha Svehla, Yuuei Shu, Shi-Hua Xiang, Jeffrey Vainshtein, Yuxing Li, Joseph Sodroski, Peter D. Kwong, John R. Mascola, Richard Wyatt

Nebraska Center for Virology: Faculty Publications

The human immunodeficiency virus type 1 exterior gp120 envelope glycoprotein is highly flexible, and this flexibility may contribute to the inability of monomeric gp120 immunogens to elicit broadly neutralizing antibodies. We previously showed that an S375W modification of a critical interfacial cavity central to the primary receptor binding site, the Phe43 cavity, stabilizes gp120 into the CD4-bound state. However, the immunological effects of this cavity-altering replacement were never tested. Subsequently, we screened other mutations that, along with the S375W alteration, might further stabilize the CD4-bound state. Here, we define a selected second cavity-altering replacement, T257S, and analyze the double mutations …

Georgeoral Immunization Of Rhesus Macaques With Adenoviral Hiv Vaccines Using Enteric-Coated Capsules, George T. Mercier, Pramod N. Nehete, Marco F. Passeri, Bharti N. Nehete, Eric A. Weaver, Nancy Smyth Templeton, Kimberly Schluns, Stephanie S. Buchl, K. Jagannadha Sastry, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

Targeted delivery of vaccine candidates to the gastrointestinal (GI) tract holds potential for mucosal immunization, particularly against mucosal pathogens like the human immunodeficiency virus (HIV). Among the different strategies for achieving targeted release in the GI tract, namely the small intestine, pH sensitive enteric coating polymers have been shown to protect solid oral dosage forms from the harsh digestive environment of the stomach and dissolve relatively rapidly in the small intestine by taking advantage of the luminal pH gradient. We developed an enteric polymethacrylate formulation for coating hydroxy-propyl-methyl-cellulose (HPMC) capsules containing lyophilized Adenoviral type 5 (Ad5) vectors expressing HIV-1 gag …

Autoregulation Of Gld-2 Cytoplasmic Poly(A) Polymerase, Labib Rouhana, Marvin Wickens

Biological Sciences Faculty Publications

Cytoplasmic polyadenylation regulates mRNA stability and translation and is required for early development and synaptic plasticity. The GLD-2 poly(A) polymerase catalyzes cytoplasmic polyadenylation in the germline of metazoa. Among vertebrates, the enzyme is encoded by two isoforms of mRNA that differ only in the length of their 3′-UTRs. Here we focus on regulation of vertebrateGLD-2 mRNA. We show that the 3′-UTR of GLD-2 mRNA elicits its own polyadenylation and translational activation during frog oocyte maturation. We identify the sequence elements responsible for repression and activation, and demonstrate that CPEB and PUF proteins likely mediate repression in the resting oocyte. …

Differential Engagement Of Tim-1 During Activation Can Positively Or Negatively Costimulate T Cell Expansion And Effector Function, Vijay K. Kuchroo, Sheng Xiao, Nader Najafian, Jay Reddy, Monica Albin, Chen Zhu, Eric Jensen, Jaimie Imitola, Thomas Korn, Ana C. Anderson, Zheng Zhang, Cristina Gutierrez, Thomas Moll, Raymond A. Sobel, Dale T. Umetsu, Hideo Yagita, Hisaya Akiba, Terry Strom, Mohamed H. Sayegh, Rosemarie H. Dekruyff, Samia J. Khoury

School of Veterinary and Biomedical Sciences: Faculty Publications

It has been suggested that T cell immunoglobulin mucin (Tim)-1 expressed on T cells serves to positively costimulate T cell responses. However, crosslinking of Tim-1 by its ligand Tim-4 resulted in either activation or inhibition of T cell responses, thus raising the issue of whether Tim-1 can have a dual function as a costimulator. To resolve this issue, we tested a series of monoclonal antibodies specifi c for Tim-1 and identifi ed two antibodies that showed opposite functional effects. One anti–Tim-1 antibody increased the frequency of antigen-specifi c T cells, the production of the proinfl ammatory cytokines IFN-γ and IL-17, …

Synthesis And Antifungal Properties Of Alpha-Methoxy And Alpha-Hydroxyl Substituted 4-Thiatetradecanoic Acids, Nestor Carballeira, Rosann O'Neill, Keykavous Parang

Pharmacy Faculty Articles and Research

4-Thiatetradecanoic acid exhibited weak antifungal activities against Candida albicans (ATCC 60193), Cryptococcus neoformans (ATCC 6603 1), and Aspergillus niger (ATCC 16404) (MIC = 4.8-12.7 mM). It has been demonstrated that alpha-methoxylation efficiently blocks P-oxidation and significantly improve the antifungal activities of fatty acids. We examined whether antifungal activity of 4-thiatetradecanoic acid can be improved by a-substitution. The unprecedented (+/-)-2-tiydroxy-4-thiatetradecanoic acid was synthesized in four steps (20% overall yield), while the (+/-)-2-methoxy-4-thiatetradecanoic acid was synthesized in five steps (14% overall yield) starting from 1-decanethiol. The key step in the synthesis was the hydrolysis of a trimethylsilyloxynitrile. In general, the novel (+/-)-2-methoxy-4-thiatetradecanoic …

Update - January 2007, Loma Linda University Center For Christian Bioethics

Update

In this issue:

-- Stem Cells, Embryos, and Ethics: Is There a Way Forward?
-- Editorial
-- 2006 Contributor's Convocation "Present Day Health Care: Collaborate or Close the Door"

The Folate Debate., Robert L. Brent

The Selected Works of Robert Brent

No abstract provided.

A Comparision Of Delta-9-Tetrahydrocannabinol Dependence In C57bl/6j Mice And Fatty Acid Amide Hydrolase Knock Out Mice, Brittany Leigh Alice Carlson

Theses and Dissertations

The idea that humans and laboratory animals can become physically dependent on marijuana or its primary psychoactive constituent, delta-9-tetrahydrocannabinol (THC), is gaining acceptance. However, there are no currently approved pharmacotherapies to treat cannabinoid withdrawal. The objective of this thesis was to evaluate whether elevating endogenous anandamide levels using mice lacking fatty acid amide hydrolase (FAAH), the enzyme responsible for anandamide metabolism, would ameliorate THC dependence. Mice were treated subchronically with a low or high THC dosing regimen and challenged with the CB1 receptor antagonist, rimonabant, to precipitate withdrawal. Following subchronic THC treatment, rimonabant precipitated a significant increase in paw flutters …