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Full-Text Articles in Medicine and Health Sciences

Histone Deacetylase Inhibitor Valproic Acid Suppresses The Growth And Increases The Androgen Responsiveness Of Prostate Cancer Cells., Yu-Wei Chou, Nagendra K. Chaturvedi, Shougiang Ouyang, Fen-Fen Lin, Dharam Kaushik, Jue Wang, Isaac Kim, Ming-Fong Lin Dec 2011

Histone Deacetylase Inhibitor Valproic Acid Suppresses The Growth And Increases The Androgen Responsiveness Of Prostate Cancer Cells., Yu-Wei Chou, Nagendra K. Chaturvedi, Shougiang Ouyang, Fen-Fen Lin, Dharam Kaushik, Jue Wang, Isaac Kim, Ming-Fong Lin

Journal Articles: Biochemistry & Molecular Biology

We identified the molecular target by histone deacetylase (HDAC) inhibitors for exploring their potential prostate cancer (PCa) therapy. Upon HDAC inhibitors-treatment, LNCaP cell growth was suppressed, correlating with increased cellular prostatic acid phosphatase (cPAcP) expression, an authentic protein tyrosine phosphatase. In those cells, ErbB-2 was dephosphorylated, histone H3/H4 acetylation and methylation increased and cyclin proteins decreased. In PAcP shRNA-transfected C-81 cells, valproic acid (VPA) efficacy of growth suppression was diminished. Further, VPA pre-treatment enhanced androgen responsiveness of C-81, C4-2 and MDA PCa2b-AI cells. Thus, cPAcP expression is involved in growth suppression by HDAC inhibitors in PCa cells, and VPA pre-treatments …


The Raf/Mek/Extracellular Signal-Regulated Kinase 1/2 Pathway Can Mediate Growth Inhibitory And Differentiation Signaling Via Androgen Receptor Downregulation In Prostate Cancer Cells., Seung-Keun Hong, Jin-Hwan Kim, Ming-Fong Lin, Jong-In Park Nov 2011

The Raf/Mek/Extracellular Signal-Regulated Kinase 1/2 Pathway Can Mediate Growth Inhibitory And Differentiation Signaling Via Androgen Receptor Downregulation In Prostate Cancer Cells., Seung-Keun Hong, Jin-Hwan Kim, Ming-Fong Lin, Jong-In Park

Journal Articles: Biochemistry & Molecular Biology

Upregulated ERK1/2 activity is correlated with androgen receptor (AR) downregulation in certain prostate cancer (PCa) that exhibits androgen deprivation-induced neuroendocrine differentiation, but its functional relevance requires elucidation. We found that sustained ERK1/2 activation using active Raf or MEK1/2 mutants is sufficient to induce AR downregulation at mRNA and protein levels in LNCaP. Downregulation of AR protein, but not mRNA, was blocked by proteasome inhibitors, MG132 and bortezomib, indicating that the pathway regulation is mediated at multiple points. Ectopic expression of a constitutively active AR inhibited Raf/MEK/ERK-mediated regulation of the differentiation markers, neuron-specific enolase and neutral endopeptidase, and the cyclin-dependent kinase …


Pathobiological Implications Of Muc16 Expression In Pancreatic Cancer., Dhanya Haridas, Subhankar Chakraborty, Moorthy P. Ponnusamy, Imayavaramban Lakshmanan, Satyanarayana Rachagani, Eric Cruz, Sushil Kumar, Srustidhar Das, Subodh M. Lele, Judy M. Anderson, Uwe A. Wittel, Michael A. Hollingsworth, Surinder K. Batra Oct 2011

Pathobiological Implications Of Muc16 Expression In Pancreatic Cancer., Dhanya Haridas, Subhankar Chakraborty, Moorthy P. Ponnusamy, Imayavaramban Lakshmanan, Satyanarayana Rachagani, Eric Cruz, Sushil Kumar, Srustidhar Das, Subodh M. Lele, Judy M. Anderson, Uwe A. Wittel, Michael A. Hollingsworth, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

MUC16 (CA125) belongs to a family of high-molecular weight O-glycosylated proteins known as mucins. While MUC16 is well known as a biomarker in ovarian cancer, its expression pattern in pancreatic cancer (PC), the fourth leading cause of cancer related deaths in the United States, remains unknown. The aim of our study was to analyze the expression of MUC16 during the initiation, progression and metastasis of PC for possible implication in PC diagnosis, prognosis and therapy. In this study, a microarray containing tissues from healthy and PC patients was used to investigate the differential protein expression of MUC16 in PC. MUC16 …


Human Rna Polymerase Ii-Association Factor 1 (Hpaf1/Pd2) Regulates Histone Methylation And Chromatin Remodeling In Pancreatic Cancer., Parama Dey, Moorthy P. Ponnusamy, Shonali Deb, Surinder K. Batra Oct 2011

Human Rna Polymerase Ii-Association Factor 1 (Hpaf1/Pd2) Regulates Histone Methylation And Chromatin Remodeling In Pancreatic Cancer., Parama Dey, Moorthy P. Ponnusamy, Shonali Deb, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

Change in gene expression associated with pancreatic cancer could be attributed to the variation in histone posttranslational modifications leading to subsequent remodeling of the chromatin template during transcription. However, the interconnected network of molecules involved in regulating such processes remains elusive. hPaf1/PD2, a subunit of the human PAF-complex, involved in the regulation of transcriptional elongation has oncogenic potential. Our study explores the possibility that regulation of histone methylation by hPaf1 can contribute towards alteration in gene expression by nucleosomal rearrangement. Here, we show that knockdown of hPaf1/PD2 leads to decreased di- and tri-methylation at histone H3 lysine 4 residues in …


Cardiovascular Magnetic Resonance Myocardial Feature Tracking Detects Quantitative Wall Motion During Dobutamine Stress., Andreas Schuster, Shelby Kutty, Asif Padiyath, Victoria Parish, Paul Gribben, David A. Danford, Marcus R. Makowski, Boris Bigalke, Philipp Beerbaum, Eike Nagel Oct 2011

Cardiovascular Magnetic Resonance Myocardial Feature Tracking Detects Quantitative Wall Motion During Dobutamine Stress., Andreas Schuster, Shelby Kutty, Asif Padiyath, Victoria Parish, Paul Gribben, David A. Danford, Marcus R. Makowski, Boris Bigalke, Philipp Beerbaum, Eike Nagel

Journal Articles: Pediatrics

BACKGROUND: Dobutamine stress cardiovascular magnetic resonance (DS-CMR) is an established tool to assess hibernating myocardium and ischemia. Analysis is typically based on visual assessment with considerable operator dependency. CMR myocardial feature tracking (CMR-FT) is a recently introduced technique for tissue voxel motion tracking on standard steady-state free precession (SSFP) images to derive circumferential and radial myocardial mechanics.We sought to determine the feasibility and reproducibility of CMR-FT for quantitative wall motion assessment during intermediate dose DS-CMR.

METHODS: 10 healthy subjects were studied at 1.5 Tesla. Myocardial strain parameters were derived from SSFP cine images using dedicated CMR-FT software (Diogenes MRI prototype; …


Microarray-Based Cancer Prediction Using Single Genes., Xiaosheng Wang, Richard Simon Oct 2011

Microarray-Based Cancer Prediction Using Single Genes., Xiaosheng Wang, Richard Simon

Journal Articles: Genetics, Cell Biology & Anatomy

BACKGROUND: Although numerous methods of using microarray data analysis for cancer classification have been proposed, most utilize many genes to achieve accurate classification. This can hamper interpretability of the models and ease of translation to other assay platforms. We explored the use of single genes to construct classification models. We first identified the genes with the most powerful univariate class discrimination ability and then constructed simple classification rules for class prediction using the single genes.

RESULTS: We applied our model development algorithm to eleven cancer gene expression datasets and compared classification accuracy to that for standard methods including Diagonal Linear …


The Meaning Of Breast Cancer Risk For African American Women., Janice Phillips, Marlene Z. Cohen Sep 2011

The Meaning Of Breast Cancer Risk For African American Women., Janice Phillips, Marlene Z. Cohen

Journal Articles: College of Nursing

PURPOSE: To describe African American women's experience of being at high risk for breast cancer.

DESIGN: A hermeneutic phenomenological approach was used to guide in-depth interviews and analysis. Methods to ensure trustworthiness and rigor were included.

METHODS: Open interviews were conducted with 20 African American women who were at high risk for breast cancer (family history, personal history, genetic mutation). They were recruited from a cancer risk clinic and community-based settings. Data were transcribed verbatim, and themes were labeled among and between all interviews.

FINDINGS: Five themes were identified: (a) life-changing experience; (b) relationships: fears, support, and concerns; (c) the …


Monoclonal Antibodies Recognizing The Non-Tandem Repeat Regions Of The Human Mucin Muc4 In Pancreatic Cancer., Maneesh Jain, Ganesh Venkatraman, Nicolas Moniaux, Sukhwinder Kaur, Sushil Kumar, Subhankar Chakraborty, Grish C. Varshney, Surinder K. Batra Aug 2011

Monoclonal Antibodies Recognizing The Non-Tandem Repeat Regions Of The Human Mucin Muc4 In Pancreatic Cancer., Maneesh Jain, Ganesh Venkatraman, Nicolas Moniaux, Sukhwinder Kaur, Sushil Kumar, Subhankar Chakraborty, Grish C. Varshney, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

The MUC4 mucin is a high molecular weight, membrane-bound, and highly glycosylated protein. It is a multi-domain protein that is putatively cleaved into a large mucin-like subunit (MUC4α) and a C-terminal growth-factor like subunit (MUC4β). MUC4 plays critical roles in physiological and pathological conditions and is aberrantly overexpressed in several cancers, including those of the pancreas, cervix, breast and lung. It is also a potential biomarker for the diagnosis, prognosis and progression of several malignancies. Further, MUC4 plays diverse functional roles in cancer initiation and progression as evident from its involvement in oncogenic transformation, proliferation, inhibition of apoptosis, motility and …


Tgfb1 Disrupts The Angiogenic Potential Of Microvascular Endothelial Cells Of The Corpus Luteum., Dulce Maroni, John S. Davis Jul 2011

Tgfb1 Disrupts The Angiogenic Potential Of Microvascular Endothelial Cells Of The Corpus Luteum., Dulce Maroni, John S. Davis

Journal Articles: Obstetrics & Gynecology

Cyclical formation and regression of the ovarian corpus luteum is required for reproduction. During luteal regression, the microvasculature of the corpus luteum is extensively disrupted. Prostaglandin F2α, a primary signal for luteal regression, induces the expression of transforming growth factor β1 (TGFB1) in the corpus luteum. This study determined the actions of TGFB1 on microvascular endothelial cells isolated from the bovine corpus luteum (CLENDO cells). We hypothesized that TGFB1 participates in the disruption of the microvasculature during luteal regression. TGFB1 activated the canonical SMAD signaling pathway in CLENDO cells. TGFB1 (1 ng/ml) significantly reduced both basal and fetal-calf-serum-stimulated DNA synthesis, …


Marital Status And Survival In Pancreatic Cancer Patients: A Seer Based Analysis., Michael J. Baine, Freshta Sahak, Chi Lin, Subhankar Chakraborty, Surinder K. Batra, Elizabeth R. Lyden Jun 2011

Marital Status And Survival In Pancreatic Cancer Patients: A Seer Based Analysis., Michael J. Baine, Freshta Sahak, Chi Lin, Subhankar Chakraborty, Surinder K. Batra, Elizabeth R. Lyden

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND: Recent findings suggest that marital status affects survival in patients with different types of cancer. However, its role in the survival of patients with pancreatic ductal adenocarcinoma is unknown. In this study, we investigated whether there was an association between marital status and overall survival (OS) in patients with pancreatic ductal adenocarcinoma (PDAC).

METHODS: Adult patients diagnosed with PDAC between 1998 and 2003 with known marital statuses were identified from the Surveillance, Epidemiology, and End Results registry of the National Cancer Institute. OS for these patients was plotted using the Kaplan-Meier method. Comparative risks of mortality were evaluated by …


Tnfα Enhances The Motility And Invasiveness Of Prostatic Cancer Cells By Stimulating The Expression Of Selective Glycosyl- And Sulfotransferase Genes Involved In The Synthesis Of Selectin Ligands., Prakash Radhakrishnan, Vishwanath Chachadi, Ming-Fong Lin, Rakesh Singh, Reiji Kannagi, Pi-Wan Cheng Jun 2011

Tnfα Enhances The Motility And Invasiveness Of Prostatic Cancer Cells By Stimulating The Expression Of Selective Glycosyl- And Sulfotransferase Genes Involved In The Synthesis Of Selectin Ligands., Prakash Radhakrishnan, Vishwanath Chachadi, Ming-Fong Lin, Rakesh Singh, Reiji Kannagi, Pi-Wan Cheng

Journal Articles: Biochemistry & Molecular Biology

Sialyl Lewis x (sLe(x)) plays an important role in cancer metastasis. But, the mechanism for its production in metastatic cancers remains unclear. The objective of current study was to examine the effects of a proinflammatory cytokine on the expression of glycosyltransferase and sulfotransferase genes involved in the synthesis of selectin ligands in a prostate cancer cell line. Androgen-independent human lymph node-derived metastatic prostate cancer cells (C-81 LNCaP), which express functional androgen receptor and mimic the castration-resistant advanced prostate cancer, were used. TNFα treatment of these cells increased their binding to P-, E- and L-selectins, anti-sLe(x) antibody, and anti-6-sulfo-sialyl Lewis x …


Inhibition Of Phosphorylated C-Met In Rhabdomyosarcoma Cell Lines By A Small Molecule Inhibitor Su11274., Jinxuan Hou, Jixin Dong, Lijun Sun, Liying Geng, J. Wang, Jialin C. Zheng, Yan Li, Julia A. Bridge, Steven H. Hinrichs, Shi-Jian Ding May 2011

Inhibition Of Phosphorylated C-Met In Rhabdomyosarcoma Cell Lines By A Small Molecule Inhibitor Su11274., Jinxuan Hou, Jixin Dong, Lijun Sun, Liying Geng, J. Wang, Jialin C. Zheng, Yan Li, Julia A. Bridge, Steven H. Hinrichs, Shi-Jian Ding

Journal Articles: Pathology and Microbiology

BACKGROUND: c-Met is a receptor tyrosine kinase (RTK) that is over-expressed in a variety of cancers and involved in cell growth, invasion, metastasis and angiogenesis. In this study, we investigated the role of c-Met in rhabdomyosarcoma (RMS) using its small molecule inhibitor SU11274, which has been hypothesized to be a potential therapeutic target for RMS.

METHODS: The expression level of phosphorylated c-Met in RMS cell lines (RD, CW9019 and RH30) and tumor tissues was assessed by phospho-RTK array and immunohistochemistry, respectively. The inhibition effects of SU11274 on RMS cells were studied with regard to intracellular signaling, cell proliferation, cell cycle …


Myd88 Is Pivotal For Immune Recognition Of Citrobacter Koseri And Astrocyte Activation During Cns Infection., Shuliang Liu, Tammy Kielian Apr 2011

Myd88 Is Pivotal For Immune Recognition Of Citrobacter Koseri And Astrocyte Activation During Cns Infection., Shuliang Liu, Tammy Kielian

Journal Articles: Pathology and Microbiology

Citrobacter koseri (C. koseri) is a Gram-negative bacterium that can cause a highly aggressive form of neonatal meningitis, which often progresses to establish multi-focal brain abscesses. The roles of Toll-like receptor 4 (TLR4) and its signaling adaptor MyD88 during CNS C. koseri infection have not yet been examined, which is important since recent evidence indicates that innate immune responses are tailored towards specific pathogen classes. Here TLR4 WT (C3H/FeJ) and TLR4 mutant (C3H/HeJ) mice as well as MyD88 KO animals were infected intracerebrally with live C. koseri, resulting in meningitis and ventriculitis with accompanying brain abscess formation. MyD88 KO mice …


Activated Krasg¹²D Is Associated With Invasion And Metastasis Of Pancreatic Cancer Cells Through Inhibition Of E-Cadherin., Satyanarayana Rachagani, S Senapati, S Chakraborty, Moorthy P. Ponnusamy, Sushil Kumar, Lynette Smith, Maneesh Jain, Surinder K. Batra Mar 2011

Activated Krasg¹²D Is Associated With Invasion And Metastasis Of Pancreatic Cancer Cells Through Inhibition Of E-Cadherin., Satyanarayana Rachagani, S Senapati, S Chakraborty, Moorthy P. Ponnusamy, Sushil Kumar, Lynette Smith, Maneesh Jain, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND: Pancreatic cancer (PC) harbours an activated point mutation (Kras(G12D)) in the Kras proto-oncogene that has been demonstrated to promote the development of PC.

METHODS: This study was designed to investigate the effect of the oncogenic Kras(G12D) allele on aggressiveness and metastatic potential of PC cells. We silenced the oncogenic Kras(G12D) allele expression in CD18/HPAF and ASPC1 cell lines by stable expression of shRNA specific to the Kras(G12D)allele.

RESULTS: The Kras(G12D) knockdown cells exhibited a significant decrease in motility (P

CONCLUSIONS: The results of this study suggest that the Kras(G12D) allele promotes metastasis in PC cells partly through the downregulation …


Renal Thrombotic Microangiopathy In Mice With Combined Deletion Of Endocytic Recycling Regulators Ehd3 And Ehd4., Manju George, Mark A. Rainey, Mayumi Naramura, Kirk W. Foster, Melissa S. Holzapfel, Laura L. Willoughby, Guoguang Ying, Rasna M. Goswami, Channabasavaiah B. Gurumurthy, Vimla Band, Simon C. Satchell, Hamid Band Mar 2011

Renal Thrombotic Microangiopathy In Mice With Combined Deletion Of Endocytic Recycling Regulators Ehd3 And Ehd4., Manju George, Mark A. Rainey, Mayumi Naramura, Kirk W. Foster, Melissa S. Holzapfel, Laura L. Willoughby, Guoguang Ying, Rasna M. Goswami, Channabasavaiah B. Gurumurthy, Vimla Band, Simon C. Satchell, Hamid Band

Journal Articles: Eppley Institute

Eps15 Homology Domain-containing 3 (EHD3), a member of the EHD protein family that regulates endocytic recycling, is the first protein reported to be specifically expressed in the glomerular endothelium in the kidney; therefore we generated Ehd3(-/-) mice and assessed renal development and pathology. Ehd3(-/-) animals showed no overt defects, and exhibited no proteinuria or glomerular pathology. However, as the expression of EHD4, a related family member, was elevated in the glomerular endothelium of Ehd3(-/-) mice and suggested functional compensation, we generated and analyzed Ehd3(-/-); Ehd4(-/-) mice. These mice were smaller, possessed smaller and paler kidneys, were proteinuric and died between …


Loss Of Neuronal Integrity During Progressive Hiv-1 Infection Of Humanized Mice., Prasanta Dash, Santhi Gorantla, Howard Gendelman, Jaclyn Knibbe, George P. Casale, Edward Makarov, Adrian A. Epstein, Harris A. Gelbard, Michael D. Boska, Larisa Y. Poluektova Mar 2011

Loss Of Neuronal Integrity During Progressive Hiv-1 Infection Of Humanized Mice., Prasanta Dash, Santhi Gorantla, Howard Gendelman, Jaclyn Knibbe, George P. Casale, Edward Makarov, Adrian A. Epstein, Harris A. Gelbard, Michael D. Boska, Larisa Y. Poluektova

Journal Articles: Radiology

Neuronal damage induced by ongoing human immunodeficiency virus type 1 (HIV-1) infection was investigated in humanized NOD/scid-IL-2Rγ(c)(null) mice transplanted at birth with human CD34-positive hematopoietic stem cells. Mice infected at 5 months of age and followed for up to 15 weeks maintained significant plasma viral loads and showed reduced numbers of CD4(+) T-cells. Prospective serial proton magnetic resonance spectroscopy tests showed selective reductions in cortical N-acetyl aspartate in infected animals. Diffusion tensor imaging revealed structural changes in cortical gray matter. Postmortem immunofluorescence brain tissue examinations for neuronal and glial markers, captured by multispectral imaging microscopy and quantified by morphometric and …


Hedgehog Inhibition Promotes A Switch From Type Ii To Type I Cell Death Receptor Signaling In Cancer Cells., Satoshi Kurita, Justin L. Mott, Sophie C. Cazanave, Christian D. Fingas, Maria E. Guicciardi, Steve F. Bronk, Lewis R. Roberts, Martin E. Fernandez-Zapico, Gregory J. Gores Mar 2011

Hedgehog Inhibition Promotes A Switch From Type Ii To Type I Cell Death Receptor Signaling In Cancer Cells., Satoshi Kurita, Justin L. Mott, Sophie C. Cazanave, Christian D. Fingas, Maria E. Guicciardi, Steve F. Bronk, Lewis R. Roberts, Martin E. Fernandez-Zapico, Gregory J. Gores

Journal Articles: Biochemistry & Molecular Biology

TRAIL is a promising therapeutic agent for human malignancies. TRAIL often requires mitochondrial dysfunction, referred to as the Type II death receptor pathway, to promote cytotoxicity. However, numerous malignant cells are TRAIL resistant due to inhibition of this mitochondrial pathway. Using cholangiocarcinoma cells as a model of TRAIL resistance, we found that Hedgehog signaling blockade sensitized these cancer cells to TRAIL cytotoxicity independent of mitochondrial dysfunction, referred to as Type I death receptor signaling. This switch in TRAIL requirement from Type II to Type I death receptor signaling was demonstrated by the lack of functional dependence on Bid/Bim and Bax/Bak, …


Transcriptional Profiling Of Peripheral Blood Mononuclear Cells In Pancreatic Cancer Patients Identifies Novel Genes With Potential Diagnostic Utility., Michael J. Baine, Subhankar Chakraborty, Lynette M. Smith, Kavita Mallya, Aaron R. Sasson, Randall E. Brand, Surinder K. Batra Feb 2011

Transcriptional Profiling Of Peripheral Blood Mononuclear Cells In Pancreatic Cancer Patients Identifies Novel Genes With Potential Diagnostic Utility., Michael J. Baine, Subhankar Chakraborty, Lynette M. Smith, Kavita Mallya, Aaron R. Sasson, Randall E. Brand, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND: It is well known that many malignancies, including pancreatic cancer (PC), possess the ability to evade the immune system by indirectly downregulating the mononuclear cell machinery necessary to launch an effective immune response. This knowledge, in conjunction with the fact that the trancriptome of peripheral blood mononuclear cells has been shown to be altered in the context of many diseases, including renal cell carcinoma, lead us to study if any such alteration in gene expression exists in PC as it may have diagnostic utility.

METHODS AND FINDINGS: PBMC samples from 26 PC patients and 33 matched healthy controls were …


Aberrant Promoter Cpg Methylation Is A Mechanism For Impaired Phd3 Expression In A Diverse Set Of Malignant Cells., Trenton L. Place, Matthew P. Fitzgerald, Sujatha Venkataraman, Sabine U. Vorrink, Adam J. Case, Melissa L.T. Teoh, Frederick E. Domann Jan 2011

Aberrant Promoter Cpg Methylation Is A Mechanism For Impaired Phd3 Expression In A Diverse Set Of Malignant Cells., Trenton L. Place, Matthew P. Fitzgerald, Sujatha Venkataraman, Sabine U. Vorrink, Adam J. Case, Melissa L.T. Teoh, Frederick E. Domann

Journal Articles: Cellular & Integrative Physiology

BACKGROUND: The prolyl-hydroxylase domain family of enzymes (PHD1-3) plays an important role in the cellular response to hypoxia by negatively regulating HIF-α proteins. Disruption of this process can lead to up-regulation of factors that promote tumorigenesis. We observed decreased basal expression of PHD3 in prostate cancer tissue and tumor cell lines representing diverse tissues of origin. Furthermore, some cancer lines displayed a failure of PHD3 mRNA induction when introduced to a hypoxic environment. This study explores the mechanism by which malignancies neither basally express PHD3 nor induce PHD3 under hypoxic conditions.

METHODOLOGY/PRINCIPAL FINDINGS: Using bisulfite sequencing and methylated DNA enrichment …


Steroids Up-Regulate P66shc Longevity Protein In Growth Regulation By Inhibiting Its Ubiquitination., Santosh Kumar, Satyendra Kumar, Mythilypriya Rajendran, Syed Mahfuzul Alam, Fen-Fen Lin, Pi-Wan Cheng, Ming-Fong Lin Jan 2011

Steroids Up-Regulate P66shc Longevity Protein In Growth Regulation By Inhibiting Its Ubiquitination., Santosh Kumar, Satyendra Kumar, Mythilypriya Rajendran, Syed Mahfuzul Alam, Fen-Fen Lin, Pi-Wan Cheng, Ming-Fong Lin

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND: p66Shc, an isoform of Shc adaptor proteins, mediates diverse signals, including cellular stress and mouse longevity. p66Shc protein level is elevated in several carcinomas and steroid-treated human cancer cells. Several lines of evidence indicate that p66Shc plays a critical role in steroid-related carcinogenesis, and steroids play a role in its elevated levels in those cells without known mechanism.

METHODS AND FINDINGS: In this study, we investigated the molecular mechanism by which steroid hormones up-regulate p66Shc protein level. In steroid-treated human prostate and ovarian cancer cells, p66Shc protein levels were elevated, correlating with increased cell proliferation. These steroid effects on …


Neuroinflammation Leads To Region-Dependent Alterations In Astrocyte Gap Junction Communication And Hemichannel Activity., Nikolay Karpuk, Maria Burkovetskaya, Teresa Fritz, Amanda Angle, Tammy Kielian Jan 2011

Neuroinflammation Leads To Region-Dependent Alterations In Astrocyte Gap Junction Communication And Hemichannel Activity., Nikolay Karpuk, Maria Burkovetskaya, Teresa Fritz, Amanda Angle, Tammy Kielian

Journal Articles: Pathology and Microbiology

Inflammation attenuates gap junction (GJ) communication in cultured astrocytes. Here we used a well-characterized model of experimental brain abscess as a tool to query effects of the CNS inflammatory milieu on astrocyte GJ communication and electrophysiological properties. Whole-cell patch-clamp recordings were performed on green fluorescent protein (GFP)-positive astrocytes in acute brain slices from glial fibrillary acidic protein-GFP mice at 3 or 7 d after Staphylococcus aureus infection in the striatum. Astrocyte GJ communication was significantly attenuated in regions immediately surrounding the abscess margins and progressively increased to levels typical of uninfected brain with increasing distance from the abscess proper. Conversely, …


Prerequisites In Behavioral Science And Business: Opportunities For Dental Education., David G. Dunning, Brian M. Lange, Robert D. Madden, Koko K. Tacha Jan 2011

Prerequisites In Behavioral Science And Business: Opportunities For Dental Education., David G. Dunning, Brian M. Lange, Robert D. Madden, Koko K. Tacha

Journal Articles: College of Dentistry

There is increasing pressure on recent dental school graduates to understand and successfully utilize patient management and business management strategies to run a productive dental office. Dental schools are faced with the dilemma to either add more credit hours in their already crowded curriculum or adjust predental school requirements. All fifty-nine U.S. dental schools were assessed online to determine admission requirements in the areas of behavioral science and business education. Results show that only 11.9 percent of the schools require prerequisite course work in behavioral science and no school requires prerequisite course work in business. However, 64.4 percent and 30.5 …


Safety And Efficacy Of Abt-089 In Pediatric Attention-Deficit/Hyperactivity Disorder: Results From Two Randomized Placebo-Controlled Clinical Trials., Timothy E. Wilens, Laura M. Gault, Ann Childress, Christopher J. Kratochvil, Lindsey Bensman, Coleen M. Hall, Evelyn Olson, Weining Z. Robieson, Tushar S. Garimella, Walid M. Abi-Saab, George Apostol, Mario D. Saltarelli Jan 2011

Safety And Efficacy Of Abt-089 In Pediatric Attention-Deficit/Hyperactivity Disorder: Results From Two Randomized Placebo-Controlled Clinical Trials., Timothy E. Wilens, Laura M. Gault, Ann Childress, Christopher J. Kratochvil, Lindsey Bensman, Coleen M. Hall, Evelyn Olson, Weining Z. Robieson, Tushar S. Garimella, Walid M. Abi-Saab, George Apostol, Mario D. Saltarelli

Journal Articles: Psychiatry

OBJECTIVE: To assess the safety and efficacy of ABT-089, a novel α(4)β(2) neuronal nicotinic receptor partial agonist, vs. placebo in children with attention-deficit/hyperactivity disorder (ADHD).

METHOD: Two multicenter, randomized, double-blind, placebo-controlled, parallel-group studies of children 6 through 12 years of age were conducted. Study 1 (n = 274) assessed six treatment groups over 8 weeks: 4 once-daily (QD) ABT-089 doses (0.085-0.700 mg/kg), QD atomoxetine, and placebo. Study 2 (n = 119) assessed three treatment groups over 6 weeks: 2 QD ABT-089 doses (0.7 mg/kg, 1.4 mg/kg) and placebo. The primary efficacy variable was the investigator-administered Attention-Deficit/Hyperactivity Disorder Rating Scale-IV: Home …


Web-Based Interventions For Weight Loss And Weight Maintenance Among Rural Midlife And Older Women: Protocol For A Randomized Controlled Trial., Patricia A. Hageman, Carol H. Pullen, Melody Hertzog, Linda S, Boeckner, Susan Noble Walker Jan 2011

Web-Based Interventions For Weight Loss And Weight Maintenance Among Rural Midlife And Older Women: Protocol For A Randomized Controlled Trial., Patricia A. Hageman, Carol H. Pullen, Melody Hertzog, Linda S, Boeckner, Susan Noble Walker

Journal Articles: Physical Therapy

BACKGROUND: Weight loss is challenging and maintenance of weight loss is problematic among midlife and older rural women. Finding effective interventions using innovative delivery methods that can reach underserved and vulnerable populations of overweight and obese rural women is a public health challenge.

METHODS/DESIGN: This Women Weigh-In for Wellness (The WWW study) randomized-controlled trial is designed to compare the effectiveness of theory-based behavior-change interventions using (1) website only, (2) website with peer-led support, or (3) website with professional email-counseling to facilitate initial weight loss (baseline to 6 months), guided continuing weight loss and maintenance (7-18 months) and self-directed weight maintenance …


The Roles Of Conserved And Nonconserved Cysteinyl Residues In The Oligomerization And Function Of Mammalian Prestin, Benjamin Currall, Danielle Rossino, Heather Jensen Smith, Richard Hallworth Jan 2011

The Roles Of Conserved And Nonconserved Cysteinyl Residues In The Oligomerization And Function Of Mammalian Prestin, Benjamin Currall, Danielle Rossino, Heather Jensen Smith, Richard Hallworth

Journal Articles: Eppley Institute

The creation of several prestin knockout and knockin mouse lines has demonstrated the importance of the intrinsic outer hair cell membrane protein prestin to mammalian hearing. However, the structure of prestin remains largely unknown, with even its major features in dispute. Several studies have suggested that prestin forms homo-oligomers that may be stabilized by disulfide bonds. Our phylogenetic analysis of prestin sequences across chordate classes suggested that the cysteinyl residues could be divided into three groups, depending on the extent of their conservation between prestin orthologs and paralogs or homologs. An alanine scan functional analysis was performed of all nine …


Microrna-183 Family Expression In Hair Cell Development And Requirement Of Micrornas For Hair Cell Maintenance And Survival, Michael D. Weston, Marsha L. Pierce, Heather Jensen Smith, Bernd Fritzsch, Sonia Rocha-Sanchez, Kirk W. Beisel, Garrett A. Soukup Jan 2011

Microrna-183 Family Expression In Hair Cell Development And Requirement Of Micrornas For Hair Cell Maintenance And Survival, Michael D. Weston, Marsha L. Pierce, Heather Jensen Smith, Bernd Fritzsch, Sonia Rocha-Sanchez, Kirk W. Beisel, Garrett A. Soukup

Journal Articles: Eppley Institute

MicroRNAs (miRNAs) post-transcriptionally repress complementary target gene expression and can contribute to cell differentiation. The coordinate expression of miRNA-183 family members (miR-183, miR-96, and miR-182) has been demonstrated in sensory cells of the mouse inner ear and other vertebrate sensory organs. To further examine hair cell miRNA expression in the mouse inner ear, we have analyzed miR-183 family expression in wild type animals and various mutants with defects in neurosensory development. miR-183 family member expression follows neurosensory cell specification, exhibits longitudinal (basal-apical) gradients in maturating cochlear hair cells, and is maintained in sensory neurons and most hair cells into adulthood. …


Medical Encounter Characteristics Of Hiv Seroconverters In The Us Army And Air Force, 2000–2004, Shilpa Hakre, David Brett-Major, Darrell E. Singer, Robert J. O'Connell, Warren B. Sateren, Jose L. Sanchez, Brian K. Agan, Nelson L. Michael, Paul T. Scott Jan 2011

Medical Encounter Characteristics Of Hiv Seroconverters In The Us Army And Air Force, 2000–2004, Shilpa Hakre, David Brett-Major, Darrell E. Singer, Robert J. O'Connell, Warren B. Sateren, Jose L. Sanchez, Brian K. Agan, Nelson L. Michael, Paul T. Scott

Journal Articles: Epidemiology

BACKGROUND AND METHODS: Active duty US Army and Air Force military personnel undergo mandatory biennial HIV antibody screening. We compared pre- and post-HIV seroconversion health status by conducting a case-control study, which evaluated all medical encounters and sociodemographic factors among incident HIV seroconverters and HIV-negative controls from June 2000 through February 2004.

RESULTS: A total of 274 HIV seroconverters and 6205 HIV-negative personnel were included. In multivariate analysis restricted to male personnel (cases = 261, controls = 5801), single marital status (adjusted odds ratio [AOR] = 14.37), clinical indicators or symptoms within four years of HIV diagnosis (AOR = 6.22), …


Naming Global Health, David Brett-Major Jan 2011

Naming Global Health, David Brett-Major

Journal Articles: Epidemiology

No abstract provided.