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2014

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Angiopoietin-2: A Key To Understanding Sepsis And Its Pulmonary Sequelae?, J. Y. Lee, E. J. Miller Jan 2014

Angiopoietin-2: A Key To Understanding Sepsis And Its Pulmonary Sequelae?, J. Y. Lee, E. J. Miller

Journal Articles

No abstract provided.

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B-1a Cell Diversity: Nontemplated Addition In B-1a Cell Ig Is Determined By Progenitor Population And Developmental Location, N. E. Holodick, T. Vizconde, T. L. Rothstein Jan 2014

B-1a Cell Diversity: Nontemplated Addition In B-1a Cell Ig Is Determined By Progenitor Population And Developmental Location, N. E. Holodick, T. Vizconde, T. L. Rothstein

Journal Articles

Natural Abs produced by B-1a cells are required for immediate protection against infection. The protective capacity of natural Abs is attributed to germline-like structure, which includes the relative absence of N-region addition. Previous studies have shown B-1a cell Ig from aged mice contains abundant nontemplated (N)-additions. B-1a cells have been shown to derive from a specific lineage-negative (Lin(-)) CD45R(low/-) CD19(+) progenitor found both in fetal liver and adult bone marrow. In this study, we report identification of a fetal liver population characterized phenotypically as Lin(-)CD45R(-)CD19(-), which gives rise to IgM(+)IgD(low)CD45R(low)CD5(+)Mac-1(+)CD19(high)CD43(+)CD23(low) B-1a cells upon adoptive transfer to SCID recipients. These B-1a …

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Coupling To A Glioblastoma-Directed Antibody Potentiates Antitumor Activity Of Curcumin, P. Langone, P. R. Debata, J. D. Inigo, S. Dolai, S. Mukherjee, P. Halat, K. Mastroianni, G. M. Curcio, M. R. Castellanos, K. Raja, P. Banerjee Jan 2014

Coupling To A Glioblastoma-Directed Antibody Potentiates Antitumor Activity Of Curcumin, P. Langone, P. R. Debata, J. D. Inigo, S. Dolai, S. Mukherjee, P. Halat, K. Mastroianni, G. M. Curcio, M. R. Castellanos, K. Raja, P. Banerjee

Journal Articles

Current therapies for glioblastoma are largely palliative, involving surgical resection followed by chemotherapy and radiation therapy, which yield serious side effects and very rarely produce complete recovery. Curcumin, a food component, blocked brain tumor formation but failed to eliminate established brain tumors in vivo, probably because of its poor bioavailability. In the glioblastoma GL261 cells, it suppressed the tumor-promoting proteins NF-kappa B, P-Akt1, vascular endothelial growth factor, cyclin D1 and BClXL and triggered cell death. Expression of exogenous p50 and p65 subunits of NF-kappa B conferred partial protection on transfected GL261 cells against curcumin insult, indicating that NF-kappa B played …

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Electromagnetic Interference With Implantable Cardioverter Defibrillators Causing Inadvertent Shock: Case Report And Review Of Current Literature, M. Akhtar, T. Bhat, M. Tantray, C. Lafferty, S. Faisal, S. Teli, H. Bhat, M. Raza, M. Khalid, S. Biekht Jan 2014

Electromagnetic Interference With Implantable Cardioverter Defibrillators Causing Inadvertent Shock: Case Report And Review Of Current Literature, M. Akhtar, T. Bhat, M. Tantray, C. Lafferty, S. Faisal, S. Teli, H. Bhat, M. Raza, M. Khalid, S. Biekht

Journal Articles

As the number of patients having implantable cardioverter defibrillator (ICD) devices is increasing, it is important for the physicians and patients to be aware of situations and conditions that can result in interference with normal functioning of these devices. There are multiple cases of malfunction of ICDs reported in literature and it may be of great significance to have an overview of these incidents for appropriate recognition and future prevention. Here we are reviewing the available literature as well as reporting an interesting case of electromagnetic interference (EMI) resulting from leak of current in pool water causing firing of ICD.

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The Gut Microbiota Influences Blood-Brain Barrier Permeability In Mice, V. Braniste, M. Al-Asmakh, C. Kowal, F. Anuar, A. Abbaspour, M. Toth, A. Korecka, B. T. Volpe, B. Diamond, S. Pettersson, +8 Additional Authors Jan 2014

The Gut Microbiota Influences Blood-Brain Barrier Permeability In Mice, V. Braniste, M. Al-Asmakh, C. Kowal, F. Anuar, A. Abbaspour, M. Toth, A. Korecka, B. T. Volpe, B. Diamond, S. Pettersson, +8 Additional Authors

Journal Articles

Pivotal to brain development and function is an intact blood-brain barrier (BBB), which acts as a gatekeeper to control the passage and exchange of molecules and nutrients between the circulatory system and the brain parenchyma. The BBB also ensures homeostasis of the central nervous system (CNS). We report that germ-free mice, beginning with intrauterine life, displayed increased BBB permeability compared to pathogen-free mice with a normal gut flora. The increased BBB permeability was maintained in germ-free mice after birth and during adulthood and was associated with reduced expression of the tight junction proteins occludin and claudin-5, which are known to …

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Hormonal Milieu At Time Of B Cell Activation Controls Duration Of Autoantibody Response, V. Jeganathan, E. Peeva, B. Diamond Jan 2014

Hormonal Milieu At Time Of B Cell Activation Controls Duration Of Autoantibody Response, V. Jeganathan, E. Peeva, B. Diamond

Journal Articles

A strong gender bias is seen in many autoimmune diseases including systemic lupus erythematosus (SLE). To investigate the basis for the female preponderance in SLE, we have been studying BALB/c mice in which B cells express the R4A heavy chain of an anti-DNA antibody in association with an endogenous light chain repertoire (R4Atg mice). In unmanipulated mice, approximately 5% of B cells express the R4A transgene. R4Atg mice do not spontaneously develop elevated serum titers of anti-DNA antibodies. Administration of either estradiol (E2) or prolactin (Pr) results in escape from tolerance of autoreactive B cells, expressed as an increase in …

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Identification Of Stage-Specific Genes Associated With Lupus Nephritis And Response To Remission Induction In (Nzb X Nzw)F1 And Nzm2410 Mice, R. Bethunaickan, C. C. Berthier, W. J. Zhang, R. Eksi, H. D. Li, Y. F. Guan, M. Kretzler, A. Davidson Jan 2014

Identification Of Stage-Specific Genes Associated With Lupus Nephritis And Response To Remission Induction In (Nzb X Nzw)F1 And Nzm2410 Mice, R. Bethunaickan, C. C. Berthier, W. J. Zhang, R. Eksi, H. D. Li, Y. F. Guan, M. Kretzler, A. Davidson

Journal Articles

Objective. To elucidate the molecular mechanisms involved in renal inflammation during the progression, remission, and relapse of nephritis in murine lupus models using transcriptome analysis. Methods. Kidneys from (NZB x NZW)F1 (NZB/NZW) and NZM2410 mice were harvested at intervals during the disease course or after remission induction. Genome-wide expression profiles were obtained from microarray analysis of perfused kidneys. Real-time polymerase chain reaction (PCR) analysis for selected genes was used to validate the microarray data. Comparisons between groups using SAM, and unbiased analysis of the entire data set using singular value decomposition and self-organizing maps were performed. Results. Few changes in …

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Iso-66, A Novel Inhibitor Of Macrophage Migration Inhibitory Factor, Shows Efficacy In Melanoma And Colon Cancer Models, K. Ioannou, K. F. Cheng, G. V. Crichlow, A. I. Birmpilis, E. J. Lolis, O. E. Tsitsilonis, Y. Al-Abed Jan 2014

Iso-66, A Novel Inhibitor Of Macrophage Migration Inhibitory Factor, Shows Efficacy In Melanoma And Colon Cancer Models, K. Ioannou, K. F. Cheng, G. V. Crichlow, A. I. Birmpilis, E. J. Lolis, O. E. Tsitsilonis, Y. Al-Abed

Journal Articles

Macrophage migration inhibitory factor (MIF) is a pleiotropic pro-inflammatory cytokine, which possesses a contributing role in cancer progression and metastasis and, thus, is now considered a promising anticancer drug target. Many MIF-inactivating strategies have proven successful in delaying cancer growth. Here, we report on the synthesis of ISO-66, a novel, highly stable, small-molecule MIF inhibitor, an analog of ISO-1 with improved characteristics. The MIF:ISO-66 co-crystal structure demonstrated that ISO-66 ligates the tautomerase active site of MIF, which has previously been shown to play an important role in its biological functions. In vitro, ISO-66 enhanced specific and non-specific anticancer immune responses, …

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Magnesium Protects Against Cisplatin-Induced Acute Kidney Injury By Regulating Platinum Accumulation, M. H. Solanki, P. K. Chatterjee, M. Gupta, X. Y. Xue, A. Plagov, M. H. Metz, R. Mintz, P. C. Singhal, C. N. Metz Jan 2014

Magnesium Protects Against Cisplatin-Induced Acute Kidney Injury By Regulating Platinum Accumulation, M. H. Solanki, P. K. Chatterjee, M. Gupta, X. Y. Xue, A. Plagov, M. H. Metz, R. Mintz, P. C. Singhal, C. N. Metz

Journal Articles

Despite its success as a potent antineoplastic agent, similar to 25% of patients receiving cisplatin experience acute kidney injury (AKI) and must discontinue therapy. Impaired magnesium homeostasis has been linked to cisplatin-mediated AKI, and because magnesium deficiency is widespread, we examined the effect of magnesium deficiency and replacement on cisplatin-induced AKI in physiologically relevant older female mice. Magnesium deficiency significantly increased cisplatin-associated weight loss and markers of renal damage (plasma blood urea nitrogen and creatinine), histological changes, inflammation, and renal cell apoptosis and modulated signaling pathways (e.g., ERK1/2, p53, and STAT3). Conversely, these damaging effects were reversed by magnesium. Magnesium …

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Measures Of User Experience In A Streptococcal Pharyngitis And Pneumonia Clinical Decision Support Tools, D. Mann, M. Knaus, L. Mccullagh, A. Sofianou, L. Rosen, T. Mcginn, J. Kannry Jan 2014

Measures Of User Experience In A Streptococcal Pharyngitis And Pneumonia Clinical Decision Support Tools, D. Mann, M. Knaus, L. Mccullagh, A. Sofianou, L. Rosen, T. Mcginn, J. Kannry

Journal Articles

Objective: To understand clinician adoption of CDS tools as this may provide important insights for the implementation and dissemination of future CDS tools. Materials and Methods: Clinicians (n=168) at a large academic center were randomized into intervention and control arms to assess the impact of strep and pneumonia CDS tools. Intervention arm data were analyzed to examine provider adoption and clinical workflow. Electronic health record data were collected on trigger location, the use of each component and whether an antibiotic, other medication or test was ordered. Frequencies were tabulated and regression analyses were used to determine the association of tool …

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Mif: Mood Improving/Inhibiting Factor?, J. Bloom, Y. Al-Abed Jan 2014

Mif: Mood Improving/Inhibiting Factor?, J. Bloom, Y. Al-Abed

Journal Articles

Although major depressive disorder imposes a serious public health burden and affects nearly one in six individuals in developed countries over their lifetimes, there is still no consensus on its pathophysiology. Inflammation and cytokines have emerged as a promising new avenue in depression research, and, in particular, macrophage migration inhibitory factor (MIF) has been shown to be significant in depression physiology. In this review we summarize current research on MIF and depression. We highlight the arguments for MIF as a pro-and antidepressant species and discuss the potential implications for therapeutics.

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Modulation Of Renin Angiotensin System Predominantly Alters Sclerotic Phenotype Of Glomeruli In Hivan, A. Plagov, X. Q. Lan, P. Rai, D. Kumar, R. Lederman, S. Rehman, A. Malhotra, G. H. Ding, P. N. Chander, P. C. Singhal Jan 2014

Modulation Of Renin Angiotensin System Predominantly Alters Sclerotic Phenotype Of Glomeruli In Hivan, A. Plagov, X. Q. Lan, P. Rai, D. Kumar, R. Lederman, S. Rehman, A. Malhotra, G. H. Ding, P. N. Chander, P. C. Singhal

Journal Articles

HIV-associated nephropathy (HIVAN) is a common complication of HIV-1 infection in patients with African ancestry in general and with APOL1 gene risk variants in particular. Although collapsing glomerulopathy is considered a hallmark of HIVAN, significant numbers of glomeruli in patients with HIVAN also display other variants of focal segmental glomerulosclerosis (FSGS). We propose that collapsed glomeruli as well as glomeruli with other variants of FSGS are manifestations of HIVAN and their prevalence depends on associated host factors. We explored the role of the renin-angiotensin system (RAS) in the manifestation of any specific glomerular phenotype in HIVAN. To evaluate the role …

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Nf-Kappa B-To-Ap-1 Switch: A Mechanism Regulating Transition From Endothelial Barrier Injury To Repair In Endotoxemic Mice, G. Liu, X. B. Ye, E. J. Miller, S. F. Liu Jan 2014

Nf-Kappa B-To-Ap-1 Switch: A Mechanism Regulating Transition From Endothelial Barrier Injury To Repair In Endotoxemic Mice, G. Liu, X. B. Ye, E. J. Miller, S. F. Liu

Journal Articles

Endothelial barrier disruption is a hallmark of multiple organ injury (MOI). However, mechanisms governing the restoration of endothelial barrier function are poorly understood. Here, we uncovered an NF-kappa B-to-AP-1 switch that regulates the transition from barrier injury to repair following endotoxemic MOI. Endothelial NF-kappa B mediates barrier repair by inhibiting endothelial cell (EC) apoptosis. Blockade of endothelial NF-kappa B pathway activated the activator protein (AP)-1 pathway (NF-kappa B-to-AP-1 switch), which compensated for the anti-apoptotic and barrier-repair functions of NF-kappa B. The NF-kappa B-to-AP-1 switch occurred at 24 hours (injury to repair transition phase), but not at 48 hours (repair phase) …

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A Novel Mechanism Of B Cell-Mediated Immune Suppression Through Cd73 Expression And Adenosine Production, H. Kaku, K. F. Cheng, Y. Al-Abed, T. L. Rothstein Jan 2014

A Novel Mechanism Of B Cell-Mediated Immune Suppression Through Cd73 Expression And Adenosine Production, H. Kaku, K. F. Cheng, Y. Al-Abed, T. L. Rothstein

Journal Articles

Immune suppression by regulatory T cells and regulatory B cells is a critical mechanism to limit excess inflammation and autoimmunity. IL-10 is considered the major mediator of B cell induced immune suppression. We report a novel mechanism for immune suppression through adenosine generation by B cells. We identified a novel population of B cells that expresses CD73 as well as CD39, two ectoenzymes that together catalyze the extracellular dephosphorylation of adenine nucleotides to adenosine. Whereas CD39 expression is common among B cells, CD73 expression is not. Approximately 30-50% of B-1 cells (B220(+)CD23(-)) and IL-10 producing B (B10) cells (B220(+)CD5(+)CD1d(hi)) are …

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An Obligatory Role Of Nf-Kappa B In Mediating Bone Marrow Derived Endothelial Progenitor Cell Recruitment And Proliferation Following Endotoxemic Multiple Organ Injury In Mice, S. Z. Mao, X. B. Ye, G. Liu, D. M. Song, S. F. Liu Jan 2014

An Obligatory Role Of Nf-Kappa B In Mediating Bone Marrow Derived Endothelial Progenitor Cell Recruitment And Proliferation Following Endotoxemic Multiple Organ Injury In Mice, S. Z. Mao, X. B. Ye, G. Liu, D. M. Song, S. F. Liu

Journal Articles

Background: Recruitment of bone marrow derived endothelial progenitor cells (BMDEPCs) alleviates multiple organ injury (MOI) and improves outcomes. However, mechanisms mediating BMDEPC recruitment following septic MOI remain largely unknown. This study characterized the kinetics of BMDEPC recruitment and proliferation and defined the role of NF-kappa B in regulating BMDEPC recruitment and proliferation. Methods and Main Findings: Chimeric mice with an intact or disrupted NF-kappa B p50 gene and BMDEPC-restricted expression of green fluorescent protein were created and injected with LPS (2 mg/kg, i.p.). BMDEPC recruitment and proliferation in multiple organs were quantified. BMDEPC recruitment and proliferation are highly organ-dependent. Lungs …

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Pleural Innate Response Activator B Cells Protect Against Pneumonia Via A Gm-Csf-Igm Axis, G. F. Weber, B. G. Chousterman, I. Hilgendorf, C. S. Robbins, I. Theurl, L. M. S. Gerhardt, Y. Iwamoto, T. D. Quach, T. L. Rothstein, F. K. Swirski, +4 Additional Authors Jan 2014

Pleural Innate Response Activator B Cells Protect Against Pneumonia Via A Gm-Csf-Igm Axis, G. F. Weber, B. G. Chousterman, I. Hilgendorf, C. S. Robbins, I. Theurl, L. M. S. Gerhardt, Y. Iwamoto, T. D. Quach, T. L. Rothstein, F. K. Swirski, +4 Additional Authors

Journal Articles

Pneumonia is a major cause of mortality worldwide and a serious problem in critical care medicine, but the immunophysiological processes that confer either protection or morbidity are not completely understood. We show that in response to lung infection, B1a B cells migrate from the pleural space to the lung parenchyma to secrete polyreactive emergency immunoglobulin M ( IgM). The process requires innate response activator (IRA) B cells, a transitional B1a-derived inflammatory subset which controls IgM production via autocrine granulocyte/macrophage colony-stimulating factor (GM-CSF) signaling. The strategic location of these cells, coupled with the capacity to produce GM-CSF-dependent IgM, ensures effective early …

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A Rare Case Of Double-Chambered Right Ventricle Associated With Ventricular Septal Defect And Congenital Absence Of The Pulmonary Valve, G. Khoueiry, T. Bhat, M. Tantray, M. Meghani, N. Abi Rafeh, M. Abdallah, W. Hoyek Jan 2014

A Rare Case Of Double-Chambered Right Ventricle Associated With Ventricular Septal Defect And Congenital Absence Of The Pulmonary Valve, G. Khoueiry, T. Bhat, M. Tantray, M. Meghani, N. Abi Rafeh, M. Abdallah, W. Hoyek

Journal Articles

Double-chambered right ventricle (DCRV) is a rare congenital heart disorder involving 2 different right ventricle (RV) pressure compartments that is often associated with ventricular septal defect (VSD). Usually, the obstruction is caused by an anomalous muscle bundle crossing the RV from the interventricular septum to the RV free wall. We are reporting a case of double-chambered right ventricle associated with ventricular septal defect and congenital absence of the pulmonary valve, a rare form of congenital infundibular pulmonary stenosis. In addition to ventricular septal defect, our patient had congenital absence of the pulmonary valve, which is very unusual and has never …

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Renin Angiotensin System Modulates Mtor Pathway Through At2r In Hivan, P. Rai, R. Lederman, S. Hague, S. Rehman, V. Kumar, K. Sataranatrajan, A. Malhotra, B. S. Kasinath, P. C. Singhal Jan 2014

Renin Angiotensin System Modulates Mtor Pathway Through At2r In Hivan, P. Rai, R. Lederman, S. Hague, S. Rehman, V. Kumar, K. Sataranatrajan, A. Malhotra, B. S. Kasinath, P. C. Singhal

Journal Articles

Mammalian target of rapamycin (mTOR) has been reported to contribute to the development of HIV-associated nephropathy (HI VAN). We hypothesized that HIV may be activating renal tissue mTOR pathway through renin angiotensin system (RAS) via Angiotensin Receptor Type II receptor (AT2R). Renal tissues of Vpr transgenic and Tg26 (HIVAN) mice displayed enhanced phosphorylation of mTOR and p70S6K. Aliskiren, a renin inhibitor attenuated phosphotylation of both mTOR and p70S6K in renal tissues of HIVAN mice. Interestingly, Angiotensin Receptor Type I (AT1R) blockade did not modulate renal tissue phosphorylation of mTOR in HIVAN mice; on the other hand, AT2R blockade attenuated renal …

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Splenic B-1a Cells Expressing Cd138 Spontaneously Secrete Large Amounts Of Immunoglobulin In Naive Mice, N. E. Holodick, T. Vizconde, T. L. Rothstein Jan 2014

Splenic B-1a Cells Expressing Cd138 Spontaneously Secrete Large Amounts Of Immunoglobulin In Naive Mice, N. E. Holodick, T. Vizconde, T. L. Rothstein

Journal Articles

B-1a cells constitutively secrete natural antibody that provides immediate protection against microbial pathogens and functions homeostatically to speed removal of apoptotic cell debris. Although B-1a cells are especially prominent in the peritoneal and pleural cavities, some B-1a cells reside in the spleen. A small subset of splenic B-1a cells in naive, unimmunized mice express CD138, a recognized plasma cell antigen, whereas the bulk of splenic B-1a cells are CD138 negative. Splenic B-1a cells in toto have been shown to generate much more antibody per cell than peritoneal B-1a cells; however, specific functional information regarding CD138(+) splenic B-1a cells has been …

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Structure And Function Of Renal Macrophages And Dendritic Cells From Lupus-Prone Mice, R. Sahu, R. Bethunaickan, S. Singh, A. Davidson Jan 2014

Structure And Function Of Renal Macrophages And Dendritic Cells From Lupus-Prone Mice, R. Sahu, R. Bethunaickan, S. Singh, A. Davidson

Journal Articles

Objective. To characterize renal macrophages and dendritic cells (DCs) in 2 murine models of lupus nephritis. Methods. We used a bead-based enrichment step followed by cell sorting to isolate populations of interest from young mice and nephritic mice. Cell morphology was examined by microscopy. Arginase and nitrite production was examined using biochemical assays. The antigen-presenting functions of the cells were determined using mixed lymphocyte reactions. Selected cytokine, chemokine, and Toll-like receptor (TLR) profiles were examined using real-time quantitative polymerase chain reaction. Results. We identified 2 populations of macrophages and 3 populations of DCs in both of our murine models of …

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Critical Periods Of Increased Fetal Vulnerability To A Maternal High Fat Diet, M. D. Plata, L. Williams, Y. Seki, K. Hartil, H. Kaur, C. L. Lin, A. Fiallo, A. S. Glenn, E. B. Katz, P. M. Vuguin, +2 Additional Authors Jan 2014

Critical Periods Of Increased Fetal Vulnerability To A Maternal High Fat Diet, M. D. Plata, L. Williams, Y. Seki, K. Hartil, H. Kaur, C. L. Lin, A. Fiallo, A. S. Glenn, E. B. Katz, P. M. Vuguin, +2 Additional Authors

Journal Articles

Background: Fetal adaptations to high fat (HF) diet in utero (IU) that may predispose to Metabolic Syndrome (MetS) in adulthood include changes in fetal hepatic gene expression. Studies were performed to determine whether maternal exposure to HF diet at different stages during pregnancy had different effects on the fetus, including hepatic gene expression. Methods: Female wild type mice were fed either a HF or breeding chow (C) for 2 wks prior to mating. The experimental groups were composed of embryonic day (e) 18.5 fetuses obtained from WT female mice that were fed HF (HF, 35.5% fat) or breeding chow (C, …

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In Utero Exposure To A Maternal High-Fat Diet Alters The Epigenetic Histone Code In A Murine Model, M. A. Suter, J. Ma, P. M. Vuguin, K. Hartil, A. Fiallo, R. A. Harris, M. J. Charron, K. M. Aagaard Jan 2014

In Utero Exposure To A Maternal High-Fat Diet Alters The Epigenetic Histone Code In A Murine Model, M. A. Suter, J. Ma, P. M. Vuguin, K. Hartil, A. Fiallo, R. A. Harris, M. J. Charron, K. M. Aagaard

Journal Articles

OBJECTIVE: Data from animal models show that in utero exposure to a maternal high-fat diet (HFD) renders susceptibility of these offspring to the adult onset of metabolic syndrome. We and others have previously shown that epigenetic modifications to histones may serve as a molecular memory of the in utero exposure, rendering the risk of adult disease. Because mice heterozygous for the Glut4 gene (insulin sensitive glucose transporter) born to wild-type (WT) mothers demonstrate exacterbated metabolic syndrome when exposed to an HFD in utero, we sought to analyze the genome-wide epigenetic changes that occur in the fetal liver in susceptible offspring. …

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P53-Independent Cell Cycle And Erythroid Differentiation Defects In Murine Embryonic Stem Cells Haploinsufficient For Diamond Blackfan Anemia-Proteins: Rps19 Versus Rpl5, S. A. Singh, T. A. Goldberg, A. L. Henson, S. Husain-Krautter, A. Nihrane, L. Blanc, S. R. Ellis, J. M. Lipton, J. M. Liu Jan 2014

P53-Independent Cell Cycle And Erythroid Differentiation Defects In Murine Embryonic Stem Cells Haploinsufficient For Diamond Blackfan Anemia-Proteins: Rps19 Versus Rpl5, S. A. Singh, T. A. Goldberg, A. L. Henson, S. Husain-Krautter, A. Nihrane, L. Blanc, S. R. Ellis, J. M. Lipton, J. M. Liu

Journal Articles

Diamond Blackfan anemia (DBA) is a rare inherited bone marrow failure syndrome caused by ribosomal protein haploinsufficiency. DBA exhibits marked phenotypic variability, commonly presenting with erythroid hypoplasia, less consistently with non-erythroid features. The p53 pathway, activated by abortive ribosome assembly, is hypothesized to contribute to the erythroid failure of DBA. We studied murine embryonic stem (ES) cell lines harboring a gene trap mutation in a ribosomal protein gene, either Rps19 or Rpl5. Both mutants exhibited ribosomal protein haploinsufficiency and polysome defects. Rps19 mutant ES cells showed significant increase in p53 protein expression, however, there was no similar increase in the …

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User Centered Clinical Decision Support Tools: Adoption Across Clinician Training Level, L. J. Mccullagh, A. Sofianou, J. Kannry, D. M. Mann, T. G. Mcginn Jan 2014

User Centered Clinical Decision Support Tools: Adoption Across Clinician Training Level, L. J. Mccullagh, A. Sofianou, J. Kannry, D. M. Mann, T. G. Mcginn

Journal Articles

BACKGROUND: Dissemination and adoption of clinical decision support (CDS) tools is a major initiative of the Affordable Care Act's Meaningful Use program. Adoption of CDS tools is multipronged with personal, organizational, and clinical settings factoring into the successful utilization rates. Specifically, the diffusion of innovation theory implies that 'early adopters' are more inclined to use CDS tools and younger physicians tend to be ranked in this category. OBJECTIVE: This study examined the differences in adoption of CDS tools across providers' training level. PARTICIPANTS: From November 2010 to 2011, 168 residents and attendings from an academic medical institution were enrolled into …

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Bisphenol A Exposure Is Associated With Decreased Lung Function, A. J. Spanier, E. K. Fiorino, L. Trasande Jan 2014

Bisphenol A Exposure Is Associated With Decreased Lung Function, A. J. Spanier, E. K. Fiorino, L. Trasande

Journal Articles

Objective To examine the associations of bisphenol A (BPA) exposure with lung function measures and exhaled nitric oxide (FeNO) in children. Study design We performed a cross-sectional analysis of a subsample of US children age 6-19 years who participated in the 2007-2010 National Health and Nutrition Examination Survey. We assessed univariate and multivariable associations of urinary BPA concentration with the predicted pulmonary function measures for age, sex, race/ethnicity and height (forced expiratory volume in 1 second [FEV1], forced vital capacity [FVC], forced expiratory flow 25%-75%, and FEV1 divided by FVC) and with FeNO. Results Exposure and outcome data were available …

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Maternal Magnesium Deficiency In Mice Leads To Maternal Metabolic Dysfunction And Altered Lipid Metabolism With Fetal Growth Restriction, M. Gupta, M. H. Solanki, P. K. Chatterjee, X. Y. Xue, A. Roman, N. Desai, B. Rochelson, C. N. Metz Jan 2014

Maternal Magnesium Deficiency In Mice Leads To Maternal Metabolic Dysfunction And Altered Lipid Metabolism With Fetal Growth Restriction, M. Gupta, M. H. Solanki, P. K. Chatterjee, X. Y. Xue, A. Roman, N. Desai, B. Rochelson, C. N. Metz

Journal Articles

Inadequate magnesium (Mg) intake is a widespread problem, with over 50% of women of reproductive age consuming less than the Recommended Dietary Allowance (RDA). Because pregnancy increases the requirement for Mg and the beneficial effects of magnesium sulfate for preeclampsia/eclampsia and fetal neuroprotection are well described, we examined the outcomes of Mg deficiency during pregnancy. Briefly, pregnant Swiss Webster mice were fed either control or Mg-deficient diets starting on gestational day (GD) 6 through euthanasia on GD17. Mg-deficient dams had significantly reduced weight gain and higher plasma adipokines, in the absence of inflammation. Livers of Mg-deficient dams had significantly higher …

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Regional Brain Metabolism In A Murine Systemic Lupus Erythematosus Model, An Vo, B. T. Volpe, C. C. Tang, W. K. Schiffer, C. Kowal, P. T. Huerta, A. M. Ulug, S. L. Dewey, D. Eidelberg, B. Diamond Jan 2014

Regional Brain Metabolism In A Murine Systemic Lupus Erythematosus Model, An Vo, B. T. Volpe, C. C. Tang, W. K. Schiffer, C. Kowal, P. T. Huerta, A. M. Ulug, S. L. Dewey, D. Eidelberg, B. Diamond

Journal Articles

Systemic lupus erythematosus (SLE) is characterized by multiorgan inflammation, neuropsychiatric disorders (NPSLE), and antinuclear antibodies. We previously identified a subset of anti-DNA antibodies (DNRAb) cross-reactive with the N-methyl-D-aspartate receptor, present in 30% to 40% of patients, able to enhance excitatory post-synaptic potentials and trigger neuronal apoptosis. DNRAb + mice exhibit memory impairment or altered fear response, depending on whether the antibody penetrates the hippocampus or amygdala. Here, we used 18F-fluorodeoxyglucose (FDG) microPET to plot changes in brain metabolism after regional blood-brain barrier (BBB) breach. In DNRAb + mice, metabolism declined at the site of BBB breach in the first 2 …

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Hyperglycemia Enhances Kidney Cell Injury In Hivan Through Down-Regulation Of Vitamin D Receptors, P. Rai, T. Singh, R. Lederman, A. Chawla, D. Kumar, K. Cheng, G. Valecha, P. W. Mathieson, M. A. Saleem, A. Malhotra, P. C. Singhal Jan 2014

Hyperglycemia Enhances Kidney Cell Injury In Hivan Through Down-Regulation Of Vitamin D Receptors, P. Rai, T. Singh, R. Lederman, A. Chawla, D. Kumar, K. Cheng, G. Valecha, P. W. Mathieson, M. A. Saleem, A. Malhotra, P. C. Singhal

Journal Articles

In the present study, we evaluated the effect of short term hyperglycemia on renal lesions in a mouse model (Tg26) of HIV-associated nephropathy (HIVAN). Control and Tg26 mice in groups (n=6) were administered either normal saline (FVBN or Tg) or streptozotocin (FVBN+STZ or Tg26+STZ). After two weeks, biomarkers were collected and kidneys were harvested. FVBN+ STZ and Tg26+STZ displayed elevated serum glucose levels when compared to FVBN and Tg26 respectively. Tg26+STZ displayed elevated (P

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Brain Region-Specific Alterations In The Gene Expression Of Cytokines, Immune Cell Markers And Cholinergic System Components During Peripheral Endotoxin-Induced Inflammation, H. A. Silverman, M. Dancho, A. Regnier-Golanov, M. Nasim, M. Ochani, P. S. Olofsson, M. Ahmed, E. J. Miller, S. S. Chavan, E. Golanov, C. Metz, K. J. Tracey, V. A. Pavlov Jan 2014

Brain Region-Specific Alterations In The Gene Expression Of Cytokines, Immune Cell Markers And Cholinergic System Components During Peripheral Endotoxin-Induced Inflammation, H. A. Silverman, M. Dancho, A. Regnier-Golanov, M. Nasim, M. Ochani, P. S. Olofsson, M. Ahmed, E. J. Miller, S. S. Chavan, E. Golanov, C. Metz, K. J. Tracey, V. A. Pavlov

Journal Articles

Inflammatory conditions characterized by excessive peripheral immune responses are associated with diverse alterations in brain function, and brain-derived neural pathways regulate peripheral inflammation. Important aspects of this bidirectional peripheral immune - brain communication, including the impact of peripheral inflammation on brain region-specific cytokine responses, and brain cholinergic signaling (which plays a role in controlling peripheral cytokine levels) remain unclear. To provide insight, we studied gene expression of cytokines, immune cell markers and brain cholinergic system components in the cortex, cerebellum, brainstem, hippocampus, hypothalamus, striatum, and thalamus in mice following an intraperitoneal lipopolysaccharide injection. Endotoxemia was accompanied by elevated serum levels …

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Laser-Assisted Zona Pellucida Thinning Does Not Facilitate Hatching And May Disrupt The In Vitro Hatching Process: A Morphokinetic Study In The Mouse, T. Schimmel, J. Cohen, H. Saunders, M. Alikani Jan 2014

Laser-Assisted Zona Pellucida Thinning Does Not Facilitate Hatching And May Disrupt The In Vitro Hatching Process: A Morphokinetic Study In The Mouse, T. Schimmel, J. Cohen, H. Saunders, M. Alikani

Journal Articles

STUDY QUESTION: Does laser-assisted zona thinning of cleavage stage mouse embryos facilitate hatching in vitro? SUMMARY ANSWER: No, unlike laser zona opening, zona thinning does not facilitate embryo hatching. WHAT IS KNOWN ALREADY: Artificial opening of the zona pellucida facilitates hatching of mouse and human embryos. Laser-assisted zona thinning has also been used for the purpose of assisted hatching of human embryos but it has not been properly investigated in an animal model; thinning methods have produced inconsistent clinical results. STUDY DESIGN, SIZE, DURATION: Time-lapse microscopy was used to study the hatching process in the mouse after zona opening and …

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