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Mfg-E8 Inhibits Neutrophil Migration Through Alpha(V)Beta(3)-Integrin-Dependent Map Kinase Activation, M. Aziz, W. L. Yang, L. M. Corbo, W. W. Chaung, S. Matsuo, P. Wang Jan 2015

Mfg-E8 Inhibits Neutrophil Migration Through Alpha(V)Beta(3)-Integrin-Dependent Map Kinase Activation, M. Aziz, W. L. Yang, L. M. Corbo, W. W. Chaung, S. Matsuo, P. Wang

Journal Articles

We have previously demonstrated the involvement of milk fat globule-epidermal growth factor-factor 8 (MFG-E8) in reducing neutrophil infiltration in a murine model of acute lung injury (ALI). In the present study, we aimed to delineate the mechanisms through which MFG-E8 attenuates neutrophil migration. Recombinant human MFG-E8 (rhMFG-E8) was expressed and purified in our facility. The human differentiated neutrophil cell line, dHL-60, was treated with rhMFG-E8 and cell migration assay was performed in a Boyden chamber using recombinant interleukin-8 (IL-8) as the chemoattractant. Surface CXCR2 and intracellular G protein-coupled receptor kinase 2 (GRK2) levels were evaluated by flow cytometry or western …

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Milk Fat Globule-Egf Factor Viii Attenuates Cns Injury By Promoting Neural Stem Cell Proliferation And Migration After Cerebral Ischemia, C. Cheyuo, M. Aziz, W. L. Yang, A. Jacob, M. Zhou, P. Wang Jan 2015

Milk Fat Globule-Egf Factor Viii Attenuates Cns Injury By Promoting Neural Stem Cell Proliferation And Migration After Cerebral Ischemia, C. Cheyuo, M. Aziz, W. L. Yang, A. Jacob, M. Zhou, P. Wang

Journal Articles

The mediators in activating neural stem cells during the regenerative process of neurogenesis following stroke have not been fully identified. Milk fat globule-EGF Factor VIII (MFGE8), a secreted glycoprotein serves several cellular functions by binding to its receptor, alpha(v)beta(3)-integrin. However, its role in regulating neural stem cells after stroke has not been determined yet. We therefore, aim to reveal whether MFG-E8 promotes neural stem cell proliferation and migration during stroke. Stroke was induced in wild-type (Wt) and MFG-E8-deficinet (Mfge8(-/-)) mice by transient middle cerebral artery occlusion (tMCAO). Commercially available recombinant mouse MFG-E8 (rmMFG-E8) was used for mechanistic assays in neural …

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Blocking Cold-Inducible Rna-Binding Protein Protects Liver From Ischemia-Reperfusion Injury, A. Godwin, W. L. Yang, A. Sharma, A. Khader, Z. Wang, F. Zhang, J. Nicastro, G.F. Coppa, P. Wang Jan 2015

Blocking Cold-Inducible Rna-Binding Protein Protects Liver From Ischemia-Reperfusion Injury, A. Godwin, W. L. Yang, A. Sharma, A. Khader, Z. Wang, F. Zhang, J. Nicastro, G.F. Coppa, P. Wang

Journal Articles

Cold-inducible RNA-binding protein (CIRP) is a nuclear protein that has been recently identified as a novel inflammatory mediator in hemorrhagic shock and sepsis. We hypothesized that CIRP acts as a potent inflammatory mediator in hepatic ischemia-reperfusion (I/R), and thus blocking CIRP protects against I/R-induced liver injury. Male C57BL/6 mice were subjected to 70% hepatic ischemia by microvascular clamping of the hilum of the left and median liver lobes for 60 min, followed by reperfusion. Anti-CIRP antibody (1 mg/kg body weight) or vehicle (normal saline) in 0.2 mL was injected via the internal jugular vein at the beginning of the reperfusion. …

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Neutralization Of Osteopontin Attenuates Neutrophil Migration In Sepsis-Induced Acute Lung Injury, Y. Hirano, M. Aziz, W.L. Yang, Z. Wang, M. Zhou, M. Ochani, A. Khader, P. Wang Jan 2015

Neutralization Of Osteopontin Attenuates Neutrophil Migration In Sepsis-Induced Acute Lung Injury, Y. Hirano, M. Aziz, W.L. Yang, Z. Wang, M. Zhou, M. Ochani, A. Khader, P. Wang

Journal Articles

INTRODUCTION: Sepsis refers to severe systemic inflammation leading to acute lung injury (ALI) and death. Introducing novel therapies can reduce the mortality in ALI. Osteopontin (OPN), a secretory glycoprotein produced by immune reactive cells, plays a deleterious role in various inflammatory diseases. However, its role in ALI caused by sepsis remains unexplored. We hypothesize that treatment with an OPN-neutralizing antibody (anti-OPN Ab) protects mice against ALI during sepsis. METHODS: Sepsis was induced in 8-week-old male C57BL/6 mice by cecal ligation and puncture (CLP). Anti-OPN Ab or non-immunized IgG as control, at a dose of 50 mug/mouse, was intravenously injected at …

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Endoplasmic Reticulum Stress In Sepsis, M. M. Khan, W.L. Yang, P. Wang Jan 2015

Endoplasmic Reticulum Stress In Sepsis, M. M. Khan, W.L. Yang, P. Wang

Journal Articles

Sepsis is an enormous public health issue and the leading cause of death in critically ill patients in intensive care units. Overwhelming inflammation, characterized by cytokine storm, oxidative threats, and neutrophil sequestration, is an underlying component of sepsis-associated organ failure. Despite recent advances in sepsis research, there is still no effective treatment available beyond the standard of care and supportive therapy. To reduce sepsis-related mortality, a better understanding of the biological mechanism associated with sepsis is essential. Endoplasmic reticulum (ER), a subcellular organelle, is responsible for the facilitation of protein folding and assembly and involved in several other physiological activities. …

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Stimulation Of Wnt/Beta-Catenin Signaling Pathway With Wnt Agonist Reduces Organ Injury After Hemorrhagic Shock, M. Kuncewitch, W.L. Yang, A. Jacob, A. Khader, M. Giangola, Jeffrey Nicastro, G. Coppa, P. Wang Jan 2015

Stimulation Of Wnt/Beta-Catenin Signaling Pathway With Wnt Agonist Reduces Organ Injury After Hemorrhagic Shock, M. Kuncewitch, W.L. Yang, A. Jacob, A. Khader, M. Giangola, Jeffrey Nicastro, G. Coppa, P. Wang

Journal Articles

BACKGROUND: Hemorrhagic shock is a leading cause of morbidity and mortality in surgery and trauma patients. Despite a large number of preclinical trials conducted to develop therapeutic strategies against hemorrhagic shock, there is still an unmet need for effective therapy for hemorrhage patients. Wnt/beta-catenin signaling controls developmental processes and cellular regeneration owing to its central role in cell survival and proliferation. We therefore hypothesized that the activation of Wnt signaling reduces systemic injury caused by hemorrhagic shock. METHODS: Adult male Sprague-Dawley rats underwent hemorrhagic shock by controlled bleeding of the femoral artery to maintain a mean arterial pressure of 30 …

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Differential Alterations Of Tissue T-Cell Subsets After Sepsis, A. Sharma, W.L. Yang, S. Matsuo, P. Wang Jan 2015

Differential Alterations Of Tissue T-Cell Subsets After Sepsis, A. Sharma, W.L. Yang, S. Matsuo, P. Wang

Journal Articles

Among immune cells in responding to sepsis, macrophages and neutrophils have been extensively studied, while the contribution of T lymphocytes and natural killer T (NKT) cells is less well characterized. Here we monitored tissue specific changes of T cell subsets in male C57BL/6 mice subjected to sham operation or cecal ligation and puncture (CLP) to induce polymicrobial sepsis. Thymus, spleen, liver, lungs and blood were processed and analyzed 20h later. Total lymphocyte count showed a significant reduction in septic thymus, spleen and blood but not in lungs and liver. The septic thymi were hypocellular with severe reduction in cell numbers …

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Human Ghrelin Mitigates Intestinal Injury And Mortality After Whole Body Irradiation In Rats, Z. M. Wang, W.L. Yang, A. Jacob, M. Aziz, P. Wang Jan 2015

Human Ghrelin Mitigates Intestinal Injury And Mortality After Whole Body Irradiation In Rats, Z. M. Wang, W.L. Yang, A. Jacob, M. Aziz, P. Wang

Journal Articles

Widespread use of ionizing radiation has led to the realization of the danger associated with radiation exposure. Although studies in radiation countermeasures were initiated a half century ago, an effective therapy for a radiomitigator has not been identified. Ghrelin is a gastrointestinal hormone, and administration of ghrelin is protective in animal models of injuries including radiation combined injury. To test whether ghrelin can be protective in whole body irradiaton (WBI) alone, male Sprague Dawley (SD) rats were treated with human ghrelin (20 nmol/rat) daily for 6 days starting at either 24 h or 48 h after 10 Gray (Gy) WBI …

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Combination Of Adrenomedullin With Its Binding Protein Accelerates Cutaneous Wound Healing, J. P. Idrovo, W. L. Yang, A. Jacob, M. A. Ajakaiye, C. Cheyuo, Z. M. Wang, J. M. Prince, J. Nicastro, G.F. Coppa, P. Wang Jan 2015

Combination Of Adrenomedullin With Its Binding Protein Accelerates Cutaneous Wound Healing, J. P. Idrovo, W. L. Yang, A. Jacob, M. A. Ajakaiye, C. Cheyuo, Z. M. Wang, J. M. Prince, J. Nicastro, G.F. Coppa, P. Wang

Journal Articles

Cutaneous wound continues to cause significant morbidity and mortality in the setting of diseases such as diabetes and cardiovascular diseases. Despite advances in wound care management, there is still an unmet medical need exists for efficient therapy for cutaneous wound. Combined treatment of adrenomedullin (AM) and its binding protein-1 (AMBP-1) is protective in various disease conditions. To examine the effect of the combination treatment of AM and AMBP-1 on cutaneous wound healing, full-thickness 2.0-cm diameter circular excision wounds were surgically created on the dorsum of rats, saline (vehicle) or AM/AMBP1 (96/320 mu g kg BW) was topically applied to the …

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Combining Task-Evoked And Spontaneous Activity To Improve Pre-Operative Brain Mapping With Fmri, M. D. Fox, T. Qian, J. R. Madsen, D. Wang, M. Ge, H. C. Zuo, D. M. Groppe, A. D. Mehta, B. Hong, H. Liu, +1 Additional Author Jan 2015

Combining Task-Evoked And Spontaneous Activity To Improve Pre-Operative Brain Mapping With Fmri, M. D. Fox, T. Qian, J. R. Madsen, D. Wang, M. Ge, H. C. Zuo, D. M. Groppe, A. D. Mehta, B. Hong, H. Liu, +1 Additional Author

Journal Articles

Noninvasive localization of brain function is used to understand and treat neurological disease, exemplified by pre-operative fMRI mapping prior to neurosurgical intervention. The principal approach for generating these maps relies on brain responses evoked by a task and, despite known limitations, has dominated clinical practice for over 20years. Recently, pre-operative fMRI mapping based on correlations in spontaneous brain activity has been demonstrated, however this approach has its own limitations and has not seen widespread clinical use. Here we show that spontaneous and task-based mapping can be performed together using the same pre-operative fMRI data, provide complimentary information relevant for functional …

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Galantamine Attenuates Type 1 Diabetes And Inhibits Anti-Insulin Antibodies In Non-Obese Diabetic Mice, W. M. Hanes, P. S. Olofsson, K. Kwan, L. K. Hudson, S. S. Chavan, V. A. Pavlov, K. J. Tracey Jan 2015

Galantamine Attenuates Type 1 Diabetes And Inhibits Anti-Insulin Antibodies In Non-Obese Diabetic Mice, W. M. Hanes, P. S. Olofsson, K. Kwan, L. K. Hudson, S. S. Chavan, V. A. Pavlov, K. J. Tracey

Journal Articles

Type 1 diabetes in mice is characterized by autoimmune destruction of insulin-producing pancreatic beta cells. Disease pathogenesis involves invasion of pancreatic islets by immune cells, including macrophages and T cells, and production of antibodies to self-antigens, including insulin. Activation of the inflammatory reflex, the neural circuit that inhibits inflammation, culminates on cholinergic receptor signals on immune cells to attenuate cytokine release and inhibit B cell antibody production. Here, we show that galantamine, a centrally acting acetylcholinesterase inhibitor and an activator of the inflammatory reflex, attenuates murine experimental type 1 diabetes. Administration of galantamine to animals immunized with keyhole limpet hemocyanin …

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Damp Signaling Is A Key Pathway Inducing Immune Modulation After Brain Injury, A. Liesz, A. Dalpke, E. Mracsko, D. J. Antoine, S. Roth, W. Zhou, H. Yang, P. P. Nawroth, K. J. Tracey, R. Veltkamp, +4 Additional Authors Jan 2015

Damp Signaling Is A Key Pathway Inducing Immune Modulation After Brain Injury, A. Liesz, A. Dalpke, E. Mracsko, D. J. Antoine, S. Roth, W. Zhou, H. Yang, P. P. Nawroth, K. J. Tracey, R. Veltkamp, +4 Additional Authors

Journal Articles

Acute brain lesions induce profound alterations of the peripheral immune response comprising the opposing phenomena of early immune activation and subsequent immunosuppression. The mechanisms underlying this brain-immune signaling are largely unknown. We used animal models for experimental brain ischemia as a paradigm of acute brain lesions and additionally investigated a large cohort of stroke patients. We analyzed release of HMGB1 isoforms by mass spectrometry and investigated its inflammatory potency and signaling pathways by immunological in vivo and in vitro techniques. Features of the complex behavioral sickness behavior syndrome were characterized by homecage behavior analysis. HMGB1 downstream signaling, particularly with RAGE, …

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Regulation Of Post-Translational Modifications Of Hmgb1 During Immune Responses, B. Lu, Y. Tang, X. Zhao, D. Antoine, X. Xiao, H. Wang, U. Andersson, T. Billiar, K. J. Tracey Jan 2015

Regulation Of Post-Translational Modifications Of Hmgb1 During Immune Responses, B. Lu, Y. Tang, X. Zhao, D. Antoine, X. Xiao, H. Wang, U. Andersson, T. Billiar, K. J. Tracey

Journal Articles

SIGNIFICANCE: High mobility group protein 1 (HMGB1) is an evolutionarily conserved and multi-functional protein. The biological function of HMGB1 depends on its cellular locations, binding partners, and redox states. Extracellular HMGB1 is a mediator of inflammation during infection or tissue injury. Immune cells actively release HMGB1 in response to infection, which in turn orchestrates both innate and adaptive immune responses. RECENT ADVANCES: Hyperacetylation of HMGB1 within its nuclear localization sequences mobilizes HMGB1 from the nucleus to the cytoplasm and subsequently promotes HMGB1 release. The redox states of the cysteines in position 23, 45 and 106 determine the biological activity of …

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Resident Endothelial Cells And Endothelial Progenitor Cells Restore Endothelial Barrier Function After Inflammatory Lung Injury, S. Z. Mao, X. B. Ye, G. Liu, D. M. Song, S. F. Liu Jan 2015

Resident Endothelial Cells And Endothelial Progenitor Cells Restore Endothelial Barrier Function After Inflammatory Lung Injury, S. Z. Mao, X. B. Ye, G. Liu, D. M. Song, S. F. Liu

Journal Articles

Objective Disruption of endothelial barrier integrity is a characteristic of many inflammatory conditions. However, the origin and function of endothelial cells (ECs) restoring endothelial barrier function remain unknown. This study defined the roles of resident ECs (RECs) and bone marrow-derived endothelial progenitor cells (BMDEPCs) in endothelial barrier restoration after endotoxemic lung injury. Approach and Results We generated mice that enable to quantify proliferating RECs or BMDEPCs and also to study the causal link between REC or BMDEPC proliferation and endothelial barrier restoration. Using these mouse models, we showed that endothelial barrier restoration was associated with increased REC and BMDEPC proliferation. …

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Tubular Cell Phenotype In Hiv-Associated Nephropathy: Role Of Phospholipid Lysophosphatidic Acid, K. R. Ayasolla, P. Rai, S. Rahimipour, M. Hussain, A. Malhotra, P. C. Singhal Jan 2015

Tubular Cell Phenotype In Hiv-Associated Nephropathy: Role Of Phospholipid Lysophosphatidic Acid, K. R. Ayasolla, P. Rai, S. Rahimipour, M. Hussain, A. Malhotra, P. C. Singhal

Journal Articles

Collapsing glomerulopathy and microcysts are characteristic histological features of HIV-associated nephropathy (HIVAN). We have previously reported the role of epithelial mesenchymal transition (EMT) in the development of glomerular and tubular cell phenotypes in HIVAN. Since persistent tubular cell activation of NF kappa B has been reported in HIVAN, we now hypothesize that HIV may be contributing to tubular cell phenotype via lysophosphatidic acid (LPA) mediated downstream signaling. Interestingly, LPA and its receptors have also been implicated in the tubular interstitial cell fibrosis (TIF) and cyst formation in autosomal dominant polycystic kidney disease (PKD). Primary human proximal tubular cells (HRPTCs) were …

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Vascular Smooth Muscle Cells Contribute To Apol1-Induced Podocyte Injury In Hiv Milieu, X. Lan, H. Wen, M. A. Saleem, J. Mikulak, A. Malhotra, K. Skorecki, P. C. Singhal Jan 2015

Vascular Smooth Muscle Cells Contribute To Apol1-Induced Podocyte Injury In Hiv Milieu, X. Lan, H. Wen, M. A. Saleem, J. Mikulak, A. Malhotra, K. Skorecki, P. C. Singhal

Journal Articles

Clinical reports have demonstrated that higher rates of non-diabetic glomerulosclerosis in African Americans can be attributed to two coding sequence variants (G1 and G2) in the APOL1 gene; however, the underlying mechanism is still unknown. Kidney biopsy data suggest enhanced expression of APOL1/APOL1 variants (Vs) in smooth muscle cells (SMCs) of renal vasculature. Since APOL1 is a secretory protein of relatively low molecular weight (41kDa), SMCs may be a contributory endocrine/paracrine source of APOL1 wild type (WT)/APOL1Vs in the glomerular capillary perfusate percolating podocytes. In the present study, we tested the hypothesis that an HIV milieu stimulated secretion of APOL1 …

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Vitamin D Receptor And Epigenetics In Hiv Infection And Drug Abuse, N. Chandel, A. Malhotra, P. C. Singhal Jan 2015

Vitamin D Receptor And Epigenetics In Hiv Infection And Drug Abuse, N. Chandel, A. Malhotra, P. C. Singhal

Journal Articles

Illicit drug abuse is highly prevalent and serves as a powerful co-factor for HIV exacerbation. Epigenetic alterations in drug abuse and HIV infection determine expression of several critical genes such as vitamin D receptor (VDR), which participates in proliferation, differentiation, cell death under both physiological and pathological conditions. On that account, active vitamin D, the ligand of VDR, is used as an adjuvant therapy to control infection, slow down progression of chronic kidney diseases, and cancer chemotherapy. Interestingly, vitamin D may not be able to augment VDR expression optimally in several instances where epigenetic contributes to down regulation of VDR; …

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Non-Small-Cell Lung Cancer Clinicopathologic Features And Survival Outcomes In Asian Pacific Islanders Residing In The United States: A Seer Analysis, M. S. Hamid, R. Shameem, K. Gafoor, J. George, B. Mina, K. Sullivan Jan 2015

Non-Small-Cell Lung Cancer Clinicopathologic Features And Survival Outcomes In Asian Pacific Islanders Residing In The United States: A Seer Analysis, M. S. Hamid, R. Shameem, K. Gafoor, J. George, B. Mina, K. Sullivan

Journal Articles

Background. The objective of our study was to ascertain racial/ethnic disparities in Asian/Pacific Islanders (API) for non-small-cell lung cancer (NSCLC) clinicopathologic features and survival outcomes based on various tumor characteristics and treatment modalities. Method. SEER database identified invasive NSCLC cases from 2004 to 2010. Variables included American Joint Committee on Cancer (AJCC) stage 7, tumor grade, tumor size, histology, age, marital status, radiation, surgery, and reason for no surgery. The Kruskall-Wallis test and the Z test were used to examine differences between races/ethnicities and the referent, non-Hispanic white (NHW). Multivariate Cox proportional analyses were used to establish the weight of …

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Patient Considerations In The Management Of Ulcerative Colitis - Role Of Vedolizumab, M. Kothari, P. Mudireddy, A. Swaminath Jan 2015

Patient Considerations In The Management Of Ulcerative Colitis - Role Of Vedolizumab, M. Kothari, P. Mudireddy, A. Swaminath

Journal Articles

Ulcerative colitis (UC) is a subtype of inflammatory bowel disease which causes inflammation of the large intestine and affects approximately 7.6-24.6 per 100,000 persons. The therapeutic goal for UC patients is inducing remission, maintaining remission, and ideally, obtaining mucosal healing. Vedolizumab, approved by the US Food and Drug Administration in May 2014 for the treatment of moderate-to-severe UC and Crohn's disease, is a newly developed anti-integrin therapy. This review focuses on the preclinical development of vedolizumab and data from early trials, and details the results of the landmark trails that led to its approval in the USA with a specific …

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Protein Domains Of Apol1 And Its Risk Variants, X. Q. Lan, H. X. Wen, R. Lederman, A. Malhotra, J. Mikulak, W. Popik, K. Skorecki, P. C. Singhal Jan 2015

Protein Domains Of Apol1 And Its Risk Variants, X. Q. Lan, H. X. Wen, R. Lederman, A. Malhotra, J. Mikulak, W. Popik, K. Skorecki, P. C. Singhal

Journal Articles

Increasing lines of evidence have demonstrated that the development of higher rates of non-diabetic glomerulosclerosis (GS) in African Americans can be attributed to two coding sequence variants (G1 and G2) in the Apolipoprotein L1 (APOL) gene. Recent studies indicate that the gene products of these APOL1 risk variants have augmented toxicity to kidney cells. However, the biological characteristics of APOL1 and its risk variants are not well elucidated. The APOL1 protein can be divided into several functional domains, including signal peptide (SP), pore forming domain (PFD), membrane address domain (MAD), and SEA-interacting domain. To investigate the relative contribution of each …

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A Randomized, Phase 2 Trial Of Docetaxel With Or Without Px-866, An Irreversible Oral Phosphatidylinositol 3-Kinase Inhibitor, In Patients With Relapsed Or Metastatic Head And Neck Squamous Cell Cancer, A. Jimeno, J. E. Bauman, C. Weissman, D. Adkins, I. Schnadig, P. Beauregard, D. W. Bowles, A. Spira, B. Levy, N. Seetharamu, D. Hausman, L. Walker, C. M. Rudin, K. Shirai Jan 2015

A Randomized, Phase 2 Trial Of Docetaxel With Or Without Px-866, An Irreversible Oral Phosphatidylinositol 3-Kinase Inhibitor, In Patients With Relapsed Or Metastatic Head And Neck Squamous Cell Cancer, A. Jimeno, J. E. Bauman, C. Weissman, D. Adkins, I. Schnadig, P. Beauregard, D. W. Bowles, A. Spira, B. Levy, N. Seetharamu, D. Hausman, L. Walker, C. M. Rudin, K. Shirai

Journal Articles

INTRODUCTION: The phosphotidylinositol-3 kinase (PI3K)/serine-threonine kinase (AKT)/mammalian target of rapamycin (mTOR) signaling pathway is frequently altered in head and neck squamous cell cancer (HNSCC). PX-866 is an oral, irreversible, pan-isoform inhibitor of PI3K. Preclinical models revealed synergy with docetaxel and a phase 1 trial demonstrated tolerability of this combination. This randomized phase 2 study evaluated PX-866 combined with docetaxel in patients with advanced, refractory HNSCC. METHODS: Patients with locally advanced, recurrent or metastatic HNSCC who had received at least one and no more than two prior systemic treatment regimens were randomized (1:1) to a combination of docetaxel (75mg/m(2) IV every …

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Epigenetic Modulation Of Human Podocyte Vitamin D Receptor In Hiv Milieu, N. Chandel, K. S. Ayasolla, X. Lan, M. Sultana-Syed, A. Chawla, R. Lederman, V. Vethantham, M. A. Saleem, A. Malhotra, P. C. Singhal, +1 Additional Author Jan 2015

Epigenetic Modulation Of Human Podocyte Vitamin D Receptor In Hiv Milieu, N. Chandel, K. S. Ayasolla, X. Lan, M. Sultana-Syed, A. Chawla, R. Lederman, V. Vethantham, M. A. Saleem, A. Malhotra, P. C. Singhal, +1 Additional Author

Journal Articles

HIV (human immunodeficiency virus) has been reported to induce podocyte injury through down regulation of vitamin D receptor (VDR) and activation of renin angiotensin system; however, the involved mechanism is not clear. Since HIV has been reported to modulate gene expression via epigenetic phenomena, we asked whether epigenetic factors contribute to down regulation of VDR. Kidney cells in HIV transgenic mice and HIV-infected podocytes (HIV/HPs) displayed enhanced expression of SNAIL, a repressor of VDR. To elucidate the mechanism, we studied the effect of HIV on expression of molecules involved in SNAIL repressor complex formation and demonstrated that HIV enhances expression …

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Fungal Infections In Renal Transplant Patients, A. Khan, E. El-Charabaty, S. El-Sayegh Jan 2015

Fungal Infections In Renal Transplant Patients, A. Khan, E. El-Charabaty, S. El-Sayegh

Journal Articles

Organ transplantation has always been considered to be the standard therapeutic interventions in patients with end-stage organ failure. In 2008, more than 29,000 organ transplants were performed in US. Survival rates among transplant recipients have greatly improved due to better understanding of transplant biology and more effective immunosuppressive agents. After transplant, the extent of the immune response is influenced by the amount of interleukin 2 (IL-2) being produced by the T-helper cells. Transplant immunosuppressive therapy primarily targets T cell-mediated graft rejection. Calcineurin inhibitor, which includes cyclosporine, pimecrolimus and tacrolimus, impairs calcineurin-induced up-regulation of IL-2 expression, resulting in increased susceptibility to …

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Hepatic Manifestations Of Non-Steroidal Inflammatory Bowel Disease Therapy, R. Hirten, K. Sultan, A. Thomas, D. E. Bernstein Jan 2015

Hepatic Manifestations Of Non-Steroidal Inflammatory Bowel Disease Therapy, R. Hirten, K. Sultan, A. Thomas, D. E. Bernstein

Journal Articles

Inflammatory bowel disease (IBD) is composed of Crohn's disease and ulcerative colitis and is manifested by both bowel-related and extraintestinal manifestations. Recently the number of therapeutic options available to treat IBD has dramatically increased, with each new medication having its own mechanism of action and side effect profile. A complete understanding of the hepatotoxicity of these medications is important in order to distinguish these complications from the hepatic manifestations of IBD. This review seeks to evaluate the hepatobiliary complications of non-steroid based IBD medications and aide providers in the recognition and management of these side-effects.

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The Onion Sign In Neovascular Age-Related Macular Degeneration Represents Cholesterol Crystals, C. E. Pang, J. D. Messinger, E. C. Zanzottera, K. B. Freund, C. A. Curcio Jan 2015

The Onion Sign In Neovascular Age-Related Macular Degeneration Represents Cholesterol Crystals, C. E. Pang, J. D. Messinger, E. C. Zanzottera, K. B. Freund, C. A. Curcio

Journal Articles

PURPOSE: To investigate the frequency, natural evolution, and histologic correlates of layered, hyperreflective, subretinal pigment epithelium (sub-RPE) lines, known as the onion sign, in neovascular age-related macular degeneration (AMD). DESIGN: Retrospective observational cohort study and experimental laboratory study. PARTICIPANTS: Two hundred thirty eyes of 150 consecutive patients with neovascular AMD and 40 human donor eyes with histopathologic diagnosis of neovascular AMD. METHODS: Spectral-domain optical coherence tomography (SD OCT), near-infrared reflectance (NIR), color fundus images, and medical charts were reviewed. Donor eyes underwent multimodal ex vivo imaging, including SD OCT, before processing for high-resolution histologic analysis. MAIN OUTCOME MEASURES: Presence of …

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Outer Retinal Tubulation In Advanced Age-Related Macular Degeneration: Optical Coherence Tomographic Findings Correspond To Histology, K. B. Schaal, K. B. Freund, K. M. Litts, Y. Zhang, J. D. Messinger, C. A. Curcio Jan 2015

Outer Retinal Tubulation In Advanced Age-Related Macular Degeneration: Optical Coherence Tomographic Findings Correspond To Histology, K. B. Schaal, K. B. Freund, K. M. Litts, Y. Zhang, J. D. Messinger, C. A. Curcio

Journal Articles

PURPOSE: To compare optical coherence tomography (OCT) and histology of outer retinal tubulation (ORT) secondary to advanced age-related macular degeneration in patients and in postmortem specimens, with particular attention to the basis of the hyperreflective border of ORT. METHOD: A private referral practice (imaging) and an academic research laboratory (histology) collaborated on two retrospective case series. High-resolution OCT raster scans of 43 eyes (34 patients) manifesting ORT secondary to advanced age-related macular degeneration were compared to high-resolution histologic sections through the fovea and superior perifovea of donor eyes (13 atrophic age-related macular degeneration and 40 neovascular age-related macular degeneration) preserved

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Image Artifacts In Optical Coherence Tomography Angiography, R. F. Spaide, J. G. Fujimoto, N. K. Waheed Jan 2015

Image Artifacts In Optical Coherence Tomography Angiography, R. F. Spaide, J. G. Fujimoto, N. K. Waheed

Journal Articles

PURPOSE: To describe image artifacts of optical coherence tomography (OCT) angiography and their underlying causative mechanisms. To establish a common vocabulary for the artifacts observed. METHODS: The methods by which OCT angiography images are acquired, generated, and displayed are reviewed as are the mechanisms by which each or all of these methods can produce extraneous image information. A common set of terminology is proposed and used. RESULTS: Optical coherence tomography angiography uses motion contrast to image blood flow and thereby images the vasculature without the need for a contrast agent. Artifacts are very common and can arise from the OCT …

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Effects Of Wharton's Jelly-Derived Mesenchymal Stem Cells On Neonatal Neutrophils, I. Khan, L. Zhang, M. Mohammed, F. E. Archer, J. Abukharmah, Z. Yuan, S. S. Rizvi, M. G. Melek, B. Weinberger, A. M. Vetrano, +2 Additional Authors Jan 2015

Effects Of Wharton's Jelly-Derived Mesenchymal Stem Cells On Neonatal Neutrophils, I. Khan, L. Zhang, M. Mohammed, F. E. Archer, J. Abukharmah, Z. Yuan, S. S. Rizvi, M. G. Melek, B. Weinberger, A. M. Vetrano, +2 Additional Authors

Journal Articles

BACKGROUND: Mesenchymal stem cells (MSCs) have been proposed as autologous therapy for inflammatory diseases in neonates. MSCs from umbilical cord Wharton's jelly (WJ-MSCs) are accessible, with high proliferative capacity. The effects of WJ-MSCs on neutrophil activity in neonates are not known. We compared the effects of WJ-MSCs on apoptosis and the expression of inflammatory, oxidant, and antioxidant mediators in adult and neonatal neutrophils. METHODS: WJ-MSCs were isolated, and their purity and function were confirmed by flow cytometry. Neutrophils were isolated from cord and adult blood by density centrifugation. The effects of neutrophil/WJ-MSC co-culture on apoptosis and gene and protein expression …

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The Erythroblastic Island As An Emerging Paradigm In The Anemia Of Inflammation, J. Hom, B. M. Dulmovits, N. Mohandas, L. Blanc Jan 2015

The Erythroblastic Island As An Emerging Paradigm In The Anemia Of Inflammation, J. Hom, B. M. Dulmovits, N. Mohandas, L. Blanc

Journal Articles

Terminal erythroid differentiation occurs in the bone marrow, within specialized niches termed erythroblastic islands. These functional units consist of a macrophage surrounded by differentiating erythroblasts and have been described more than five decades ago, but their function in the pathophysiology of erythropoiesis has remained unclear until recently. Here we propose that the central macrophage in the erythroblastic island contributes to the pathophysiology of anemia of inflammation. After introducing erythropoiesis and the interactions between the erythroblasts and the central macrophage within the erythroblastic islands, we will discuss the immunophenotypic characterization of this specific subpopulation of macrophages. We will then integrate these …

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Mutations In Ddx3x Are A Common Cause Of Unexplained Intellectual Disability With Gender-Specific Effects On Wnt Signaling, L. Snijders Blok, E. Madsen, J. Juusola, C. Gilissen, D. Baralle, M. R. Reijnders, H. Venselaar, J. Fox, J. Mclaughlin, T. Kleefstra, +73 Additional Authors Jan 2015

Mutations In Ddx3x Are A Common Cause Of Unexplained Intellectual Disability With Gender-Specific Effects On Wnt Signaling, L. Snijders Blok, E. Madsen, J. Juusola, C. Gilissen, D. Baralle, M. R. Reijnders, H. Venselaar, J. Fox, J. Mclaughlin, T. Kleefstra, +73 Additional Authors

Journal Articles

Intellectual disability (ID) affects approximately 1%-3% of humans with a gender bias toward males. Previous studies have identified mutations in more than 100 genes on the X chromosome in males with ID, but there is less evidence for de novo mutations on the X chromosome causing ID in females. In this study we present 35 unique deleterious de novo mutations in DDX3X identified by whole exome sequencing in 38 females with ID and various other features including hypotonia, movement disorders, behavior problems, corpus callosum hypoplasia, and epilepsy. Based on our findings, mutations in DDX3X are one of the more common …

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