Medicine and Health Sciences Commons^™

Beyond Bmi: The “Metabolically Healthy Obese” Phenotype & Its Association With Clinical/Subclinical Cardiovascular Disease And All-Cause Mortality -- A Systematic Review, Lara L. Roberson, Ehimen C. Aneni, Wasim Maziak, Arthur Agatston, Theodore Feldman, Maribeth Rouseff, Thinh Tran, Michael J. Blaha, Raul D. Santos, Andrei Sposito, Mouaz H. Al-Mallah, Ron Blankenstein, Matthew J. Budoff, Khurram Nasir

HWCOM Faculty Publications

Background

A subgroup has emerged within the obese that do not display the typical metabolic disorders associated with obesity and are hypothesized to have lower risk of complications. The purpose of this review was to analyze the literature which has examined the burden of cardiovascular disease (CVD) and all-cause mortality in the metabolically healthy obese (MHO) population.

Methods

Pubmed, Cochrane Library, and Web of Science were searched from their inception until December 2012. Studies were included which clearly defined the MHO group (using either insulin sensitivity and/or components of metabolic syndrome AND obesity) and its association with either all cause …

Cocaine Enhances Hiv-1 Infectivity In Monocyte Derived Dendritic Cells By Suppressing Microrna-155, Jessica Napuri, Sudheesh Pilakka-Kanthikeel, Andrea Raymond, Marisela Agudelo, Adriana Yndart-Arias, Madhavan Nair, Shailendra K. Saxena

HWCOM Faculty Publications

Cocaine and other drugs of abuse increase HIV-induced immunopathogenesis; and neurobiological mechanisms of cocaine addiction implicate a key role for microRNAs (miRNAs), single-stranded non-coding RNAs that regulate gene expression and defend against viruses. In fact, HIV defends against miRNAs by actively suppressing the expression of polycistronic miRNA cluster miRNA-17/92, which encodes miRNAs including miR-20a. IFN-g production by natural killer cells is regulated by miR-155 and this miRNA is also critical to dendritic cell (DC) maturation. However, the impact of cocaine on miR-155 expression and subsequent HIV replication is unknown. We examined the impact of cocaine on two miRNAs, miR-20a and …

Specific Increase In Mdr1 Mediated Drug-Efflux In Human Brain Endothelial Cells Following Co-Exposure To Hiv-1 And Saquinavir, Upal Roy, Christine Bulot, Kerstin Honer Zu Bentrup, Debasis Mondal

HWCOM Faculty Publications

Persistence of HIV-1 reservoirs within the Central Nervous System (CNS) remains a significant challenge to the efficacy of potent anti-HIV-1 drugs. The primary human Brain Microvascular Endothelial Cells (HBMVEC) constitutes the Blood Brain Barrier (BBB) which interferes with anti-HIV drug delivery into the CNS. The ATP binding cassette (ABC) transporters expressed on HBMVEC can efflux HIV-1 protease inhibitors (HPI), enabling the persistence of HIV-1 in CNS. Constitutive low level expression of several ABC-transporters, such as MDR1 (a.k.a. P-gp) and MRPs are documented in HBMVEC. Although it is recognized that inflammatory cytokines and exposure to xenobiotic drug substrates (e.g HPI) can …

Novel Nr5a1 Missense Mutation In Premature Ovarian Failure: Detection In Han Chinese Indicates Causation In Different Ethnic Groups, Xue Jiao, Yingying Qin, Guangyu Li, Shidou Zhao, Li You, Jinlong Ma, Joe Leigh Simpson, Zi-Jiang Chen

HWCOM Faculty Publications

Background

The etiology of most premature ovarian failure (POF) cases is usually elusive. Although genetic causes clearly exist and a likely susceptible region of 8q22.3 has been discovered, no predominant explanation exists for POF. More recently, evidences have indicated that mutations in NR5A1 gene could be causative for POF. We therefore screened for mutations in the NR5A1 gene in a large cohort of Chinese women with non-syndromic POF.

Methods

Mutation screening of NR5A1 gene was performed in 400 Han Chinese women with well-defined 46,XX idiopathic non-syndromic POF and 400 controls. Subsequently, functional characterization of the novel mutation identified was evaluated …

Notch1 Gain Of Function In Germ Cells Causes Failure Of Spermatogenesis In Male Mice, Zaohua Huang, Bryan Rivas, Alexander I. Agoulnik

HWCOM Faculty Publications

NOTCH1 is a member of the NOTCH receptor family, a group of single-pass trans-membrane receptors. NOTCH signaling is highly conserved in evolution and mediates communication between adjacent cells. NOTCH receptors have been implicated in cell fate determination, as well as maintenance and differentiation of stem cells. In the mammalian testis expression of NOTCH1 in somatic and germ cells has been demonstrated, however its role in spermatogenesis was not clear. To study the significance of NOTCH1 in germ cells, we applied a cre/loxP approach in mice to induce NOTCH1 gain- or loss-of function specifically in male germ cells. Using a Stra8-icre …

Transcriptome Analysis Reveals New Insights Into The Modulation Of Endometrial Stromal Cell Receptive Phenotype By Embryo-Derived Signals Interleukin-1 And Human Chorionic Gonadotropin: Possible Involvement In Early Embryo Implantation, Amélie Bourdiec, Ezequiel Calvo, C. V. Rao, Ali Akoum

HWCOM Faculty Publications

The presence of the conceptus in uterine cavity necessitates an elaborate network of interactions between the implanting embryo and a receptive endometrial tissue. We believe that embryo-derived signals play an important role in the remodeling and the extension of endometrial receptivity period. Our previous studies provided original evidence that human Chorionic Gonadotropin (hCG) modulates and potentiates endometrial epithelial as well as stromal cell responsiveness to interleukin 1 (IL1), one of the earliest embryonic signals, which may represent a novel pathway by which the embryo favors its own implantation and growth within the maternal endometrial host. The present study was designed …

Targeted Brain Derived Neurotropic Factors (Bdnf) Delivery Across The Blood-Brain Barrier For Neuro-Protection Using Magnetic Nano Carriers: An In-Vitro Study, Sudheesh Pilakka-Kanthikeel, Venkata Subba Rao Atluri, Vidya Sagar, Shailendra K. Saxena, Madhavan Nair

HWCOM Faculty Publications

Parenteral use of drugs; such as opiates exert immunomodulatory effects and serve as a cofactor in the progression of HIV-1 infection, thereby potentiating HIV related neurotoxicity ultimately leading to progression of NeuroAIDS. Morphine exposure is known to induce apoptosis, down regulate cAMP response element-binding (CREB) expression and decrease in dendritic branching and spine density in cultured cells. Use of neuroprotective agent; brain derived neurotropic factor (BDNF), which protects neurons against these effects, could be of therapeutic benefit in the treatment of opiate addiction. Previous studies have shown that BDNF was not transported through the blood brain barrier (BBB) in-vivo.; …

Human Synaptic Plasticity Gene Expression Profile And Dendritic Spine Density Changes In Hiv-Infected Human Cns Cells: Role In Hiv-Associated Neurocognitive Disorders (Hand), Venakata Subba Rao Alturi, Sudheesh P. Kanthikeel, Pichili V.B. Reddy, Adriana Yndart, Madhavan P.N. Nair

HWCOM Faculty Publications

HIV-associated neurocognitive disorders (HAND) is characterized by development of cognitive, behavioral and motor abnormalities, and occur in approximately 50% of HIV infected individuals. Our current understanding of HAND emanates mainly from HIV-1 subtype B (clade B), which is prevalent in USA and Western countries. However very little information is available on neuropathogenesis of HIV-1 subtype C (clade C) that exists in Sub-Saharan Africa and Asia. Therefore, studies to identify specific neuropathogenic mechanisms associated with HAND are worth pursuing to dissect the mechanisms underlying this modulation and to prevent HAND particularly in clade B infection. In this study, we have investigated …

Reduced Androgen Receptor Expression Accelerates The Onset Of Erbb2 Induced Breast Tumors In Female Mice, Myles C. Hodgson, Garrett Vanostran, Sarah Alghamdi, Robert J. Poppiti, Alexander I. Agoulnik, Irina U. Agoulnik

HWCOM Faculty Publications

Androgen receptor (AR) is commonly expressed in both the epithelium of normal mammary glands and in breast cancers. AR expression in breast cancers is independent of estrogen receptor alpha (ERα) status and is frequently associated with overexpression of the ERBB2 oncogene. AR signaling effects on breast cancer progression may depend on ERα and ERBB2 status. Up to 30% of human breast cancers are driven by overactive ERBB2 signaling and it is not clear whether AR expression affects any steps of tumor progression in this cohort of patients. To test this, we generated mammary specific Ar depleted mice (MARKO) by combining …

Living With Uncertainty: Acting In The Best Interests Of Women, Erica Gollub, Zena Stein

HWCOM Faculty Publications

A recent multi-country study on hormonal contraceptives (HC) and HIV acquisition and transmission among African HIV-serodiscordant couples reported a statistically significant doubling of risk for HIV acquisition among women as well as transmission from women to men for injectable contraceptives. Together with a prior cohort study on African women seeking health services, these data are the strongest yet to appear on the HC-HIV risk. This paper will briefly review the Heffron study strengths and relevant biological and epidemiologic evidence; address the futility of further trials; and propose instead an alternative framework for next steps. The weight of the evidence calls …

Magneto-Electric Nano-Particles For Non-Invasive Brain Stimulation, Kun Yue, Rakesh Guduru, Jeongmin Hong, Ping Liang, Madhavan Nair, Sakhrat Khizroev

HWCOM Faculty Publications

This paper for the first time discusses a computational study of using magneto-electric (ME) nanoparticles to artificially stimulate the neural activity deep in the brain. The new technology provides a unique way to couple electric signals in the neural network to the magnetic dipoles in the nanoparticles with the purpose to enable a non-invasive approach. Simulations of the effect of ME nanoparticles for non-invasively stimulating the brain of a patient with Parkinson’s Disease to bring the pulsed sequences of the electric field to the levels comparable to those of healthy people show that the optimized values for the concentration of …

Review Of The History And Current Status Of Cell-Transplant Approaches For The Management Of Neuropathic Pain, Mary J. Eaton, Yerko Berrocal, Stacey Q. Wolfe, Eva Widerström-Noga

HWCOM Faculty Publications

Treatment of sensory neuropathies, whether inherited or caused by trauma, the progress of diabetes, or other disease states, are among the most difficult problems in modern clinical practice. Cell therapy to release antinociceptive agents near the injured spinal cord would be the logical next step in the development of treatment modalities. But few clinical trials, especially for chronic pain, have tested the transplant of cells or a cell line to treat human disease. The history of the research and development of useful cell-transplant-based approaches offers an understanding of the advantages and problems associated with these technologies, but as an adjuvant …

Potential For Cell-Transplant Therapy With Human Neuronal Precursors To Treat Neuropathic Pain In Models Of Pns And Cns Injury: Comparison Of Hnt2.17 And Hnt2.19 Cell Lines, Mary J. Eaton, Yerko Berrocal, Stacey Q. Wolfe

HWCOM Faculty Publications

Effective treatment of sensory neuropathies in peripheral neuropathies and spinal cord injury (SCI) is one of the most difficult problems in modern clinical practice. Cell therapy to release antinociceptive agents near the injured spinal cord is a logical next step in the development of treatment modalities. But few clinical trials, especially for chronic pain, have tested the potential of transplant of cells to treat chronic pain. Cell lines derived from the human neuronal NT2 cell line parentage, the hNT2.17 and hNT2.19 lines, which synthesize and release the neurotransmitters gamma-aminobutyric acid (GABA) and serotonin (5HT), respectively, have been used to evaluate …

Postmortem Demonstration Of The Source Of Pulmonary Thromboembolism: The Importance Of The Autopsy, Gina Elhammady, Andrew T. Schubeck, Vicky El-Najjar, Morton J. Robinson

HWCOM Faculty Publications

Periprostatic or paravaginal venous thromboses are rarely considered clinically as sites of clot origin in patients with pulmonary thromboembolism. The majority of emboli have been demonstrated to originate in the veins of the legs. This report raises awareness of pelvic vein thrombosis as a potential source of pulmonary embolism that is rarely considered or detected clinically, and which usually requires postmortem examination for recognition. It also reviews the possible routes emboli may take to reach the lungs.

Arsenic Transport By Zebrafish Aquaglyceroporins, Mohamad Hamdi, Marco A. Sanchez, Lauren C. Beene, Qianyong Liu, Scott M. Landfear, Barry P. Rosen, Zijuan Liu

HWCOM Faculty Publications

Background

Arsenic is one of the most ubiquitous toxins and endangers the health of tens of millions of humans worldwide. It is a mainly a water-borne contaminant. Inorganic trivalent arsenic (As^III) is one of the major species that exists environmentally. The transport of As^III has been studied in microbes, plants and mammals. Members of the aquaglyceroporin family have been shown to actively conduct As^III and its organic metabolite, monomethylarsenite (MAs^III). However, the transport of As^III and MAs^III in in any fish species has not been characterized.

Results

In this study, five members …

Comparative Transcriptome Analyses Of Pseudomonas Aeruginosa, Deepak Balasubramanian, Kalai Mathee

HWCOM Faculty Publications

One of the hallmarks of bacterial survival is their ability to adapt rapidly to changing environmental conditions. Niche adaptation is a response to the signals received that are relayed, often to regulators that modulate gene expression. In the post-genomic era, DNA microarrays are used to study the dynamics of gene expression on a global scale. Numerous studies have used Pseudomonas aeruginosa--a Gram-negative environmental and opportunistic human pathogenic bacterium--as the model organism in whole-genome transcriptome analysis. This paper reviews the transcriptome studies that have led to immense advances in our understanding of the biology of this intractable human pathogen. Comparative …