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Articles 12181 - 12210 of 15661
Full-Text Articles in Entire DC Network
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
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 …
Stimulation Of Brain Amp-Activated Protein Kinase Attenuates Inflammation And Acute Lung Injury In Sepsis, N. Mulchandani, W.L. Yang, M. M. Khan, F. Zhang, P. Marambaud, J. Nicastro, G.F. Coppa, P. Wang
Stimulation Of Brain Amp-Activated Protein Kinase Attenuates Inflammation And Acute Lung Injury In Sepsis, N. Mulchandani, W.L. Yang, M. M. Khan, F. Zhang, P. Marambaud, J. Nicastro, G.F. Coppa, P. Wang
Journal Articles
Sepsis and septic shock are enormous public health problems with astronomical financial repercussions on health systems worldwide. The central nervous system (CNS) is closely intertwined in the septic process but the underlying mechanism is still obscure. AMP-activated protein kinase (AMPK) is a ubiquitous energy sensor enzyme and plays a key role in regulation of energy homeostasis and cell survival. In this study, we hypothesized that activation of AMPK in the brain would attenuate inflammatory responses in sepsis, particularly in the lungs. Adult C57BL/6 male mice were treated with 5-aminoimidazole-4-carboxamide riboneucleotide (AICAR, 20 ng), an AMPK activator, or vehicle (normal saline) …
Differential Alterations Of Tissue T-Cell Subsets After Sepsis, A. Sharma, W.L. Yang, S. Matsuo, P. Wang
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 …
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
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 …
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
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 …
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
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 …
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
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, …
Neutrophil Trafficking In Pulmonary Inflammation: Monitoring Migration And Blockade With 111in-Labeled Leukocytes, C. Palestro, H. M. Linge, K. J. Nichols, K. Ochani, K. Bhargava, E. J. Miller
Neutrophil Trafficking In Pulmonary Inflammation: Monitoring Migration And Blockade With 111in-Labeled Leukocytes, C. Palestro, H. M. Linge, K. J. Nichols, K. Ochani, K. Bhargava, E. J. Miller
Journal Articles
No abstract provided.
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
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. …
A Review Of The Nonpressor And Nonantidiuretic Actions Of The Hormone Vasopressin, G. P. Mavani, M. V. Devita, M. F. Michelis
A Review Of The Nonpressor And Nonantidiuretic Actions Of The Hormone Vasopressin, G. P. Mavani, M. V. Devita, M. F. Michelis
Journal Articles
The pressor and antidiuretic actions of arginine vasopressin (AVP) have been well documented. This review focuses on the less widely appreciated actions of AVP which also have important physiologic functions and when better understood may provide important insights into common disease states. These actions include effects on pain perception and bone structure as well as important relationships to the varied components of metabolic syndrome. These include effects on blood glucose, lipid levels, and blood pressure. AVP may also play a role in the progression of chronic kidney disease and effect physiologic changes relating to aging, abnormal social behavior, and cognitive …
Vitamin D Receptor And Epigenetics In Hiv Infection And Drug Abuse, N. Chandel, A. Malhotra, P. C. Singhal
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; …
Lps Down-Regulates Specificity Protein 1 Activity By Activating Nf-Kappab Pathway In Endotoxemic Mice, X. Ye, H. Liu, Y. S. Gong, S. F. Liu
Lps Down-Regulates Specificity Protein 1 Activity By Activating Nf-Kappab Pathway In Endotoxemic Mice, X. Ye, H. Liu, Y. S. Gong, S. F. Liu
Journal Articles
BACKGROUND: Specificity protein (Sp) 1 mediates the transcription of a large number of constitutive genes encoding physiological mediators. NF-kappaB mediates the expression of hundreds of inducible genes encoding pathological mediators. Crosstalk between Sp1 and NF-kappaB pathways could be pathophysiologically significant, but has not been studied. This study examined the crosstalk between the two pathways and defined the role of NF-kappaB signaling in LPS-induced down-regulation of Sp1 activity. METHODS AND MAIN FINDINGS: Challenge of wild type mice with samonelia enteritidis LPS (10 mg/kg, i.p.) down-regulated Sp1 binding activity in lungs in a time-dependent manner, which was concomitantly associated with an increased …
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
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 …
Hepatic Manifestations Of Non-Steroidal Inflammatory Bowel Disease Therapy, R. Hirten, K. Sultan, A. Thomas, D. E. Bernstein
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.
Inner Segment Remodeling And Mitochondrial Translocation In Cone Photoreceptors In Age-Related Macular Degeneration With Outer Retinal Tubulation, K. M. Litts, J. D. Messinger, K. B. Freund, Y. Zhang, C. A. Curcio
Inner Segment Remodeling And Mitochondrial Translocation In Cone Photoreceptors In Age-Related Macular Degeneration With Outer Retinal Tubulation, K. M. Litts, J. D. Messinger, K. B. Freund, Y. Zhang, C. A. Curcio
Journal Articles
PURPOSE: To quantify impressions of mitochondrial translocation in degenerating cones and to determine the nature of accumulated material in the subretinal space with apparent inner segment (IS)-like features by examining cone IS ultrastructure. METHODS: Human donor eyes with advanced age-related macular degeneration (AMD) were screened for outer retinal tubulation (ORT) in macula-wide, high-resolution digital sections. Degenerating cones inside ORT (ORT cones) and outside ORT (non-ORT cones) from AMD eyes and unaffected cones in age-matched control eyes were imaged using transmission electron microscopy. The distances of mitochondria to the external limiting membrane (ELM), cone IS length, and cone IS width at …
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
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 …
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
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
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
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 …
The Erythroblastic Island As An Emerging Paradigm In The Anemia Of Inflammation, J. Hom, B. M. Dulmovits, N. Mohandas, L. Blanc
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 …
Effects Of Levodopa On Regional Cerebral Metabolism And Blood Flow, J. H. Ko, R. P. Lerner, D. Eidelberg
Effects Of Levodopa On Regional Cerebral Metabolism And Blood Flow, J. H. Ko, R. P. Lerner, D. Eidelberg
Journal Articles
Levodopa (l-dopa) has been at the forefront of antiparkinsonian therapy for a half century. Recent advances in functional brain imaging have contributed substantially to the understanding of the effects of l-dopa and other dopaminergic treatment on the activity of abnormal motor and cognitive brain circuits in Parkinson's disease patients. Progress has also been made in understanding the functional pathology of dyskinesias, a common side effect of l-dopa treatment, at both regional and network levels. Here, we review these studies, focusing mainly on the new mechanistic insights provided by metabolic brain imaging and network analysis. (c) 2014 International Parkinson and Movement …
Reproducibility Of A Parkinsonism-Related Metabolic Brain Network In Non-Human Primates: A Descriptive Pilot Study With Fdg Pet, Y. L. Ma, T. H. Johnston, S. C. Peng, C. T. Zuo, J. B. Koprich, S. H. Fox, Y. H. Guan, D. Eidelberg, J. M. Brotchie
Reproducibility Of A Parkinsonism-Related Metabolic Brain Network In Non-Human Primates: A Descriptive Pilot Study With Fdg Pet, Y. L. Ma, T. H. Johnston, S. C. Peng, C. T. Zuo, J. B. Koprich, S. H. Fox, Y. H. Guan, D. Eidelberg, J. M. Brotchie
Journal Articles
Background: We have previously defined a parkinsonism-related metabolic brain network in rhesus macaques using a high-resolution research positron emission tomography camera. This brief article reports a descriptive pilot study to assess the reproducibility of network activity and regional glucose metabolism in independent parkinsonian macaques using a clinical positron emission tomography/CT camera. Methods: [F-18]fluorodeoxyglucose PET scans were acquired longitudinally over 3 months in three drug-naive parkinsonian and three healthy control cynomolgus macaques. Group difference and test-retest stability in network activity and regional glucose metabolism were evaluated graphically, using all brain images from these macaques. Results: Comparing the parkinsonian macaques with the …
The Visual Perception Of Natural Motion: Abnormal Task-Related Neural Activity In Dyt1 Dystonia, W. Sako, K. Fujita, A. Vo, J. C. Rucker, J. R. Rizzo, M. Niethammer, M. Carbon, S. B. Bressman, A. M. Ulug, D. Eidelberg
The Visual Perception Of Natural Motion: Abnormal Task-Related Neural Activity In Dyt1 Dystonia, W. Sako, K. Fujita, A. Vo, J. C. Rucker, J. R. Rizzo, M. Niethammer, M. Carbon, S. B. Bressman, A. M. Ulug, D. Eidelberg
Journal Articles
Although primary dystonia is defined by its characteristic motor manifestations, non-motor signs and symptoms have increasingly been recognized in this disorder. Recent neuroimaging studies have related the motor features of primary dystonia to connectivity changes in cerebello-thalamo-cortical pathways. It is not known, however, whether the non-motor manifestations of the disorder are associated with similar circuit abnormalities. To explore this possibility, we used functional magnetic resonance imaging to study primary dystonia and healthy volunteer subjects while they performed a motion perception task in which elliptical target trajectories were visually tracked on a computer screen. Prior functional magnetic resonance imaging studies of …
Risk Factors Associated With Intracranial Hemorrhage In Neonates With Persistent Pulmonary Hypertension On Ecmo, S. Doymaz, M. Zinger, T. Sweberg
Risk Factors Associated With Intracranial Hemorrhage In Neonates With Persistent Pulmonary Hypertension On Ecmo, S. Doymaz, M. Zinger, T. Sweberg
Journal Articles
BACKGROUND: Up to 40% of infants with persistent pulmonary hypertension (PPHN) remains refractory to conventional therapies, and extracorporeal membrane oxygenation (ECMO) is offered as an effective support for this group. However, ECMO is a highly invasive and risky procedure with devastating complications such as intracranial hemorrhage (ICH). In this study, we aimed to determine the risk factors for ICH in infants with PPHN. METHODS: A case-control study of patients admitted to the pediatric intensive care unit (PICU) with PPHN requiring ECMO support was conducted. The study was carried out at a 25-bed PICU in large urban tertiary care children's hospital. …
Antigen-Based Immunotherapy For Autoimmune Disease: Current Status, D. L. Hirsch, P. Ponda
Antigen-Based Immunotherapy For Autoimmune Disease: Current Status, D. L. Hirsch, P. Ponda
Journal Articles
Autoimmune diseases are common chronic disorders that not only have a major impact on the quality of life but are also potentially life-threatening. Treatment modalities that are currently favored have conferred signifcant clinical benefts, but they may have considerable side effects. An optimal treatment strategy for autoimmune disease would specifcally target disease-associated antigens and limit systemic side effects. Similar to allergen-specifc immunotherapy for allergic rhinitis, antigen-specifc immunotherapy for autoimmune disease aims to induce immune deviation and promote tolerance to specifc antigens. In this review, we present the current status of studies and clinical trials in both human and animal hosts …
Calhm1 Ion Channel Elicits Amyloid-Beta Clearance By Insulin-Degrading Enzyme In Cell Lines And In Vivo In The Mouse Brain, V. Vingtdeux, P. Chandakkar, H. Zhao, L. Blanc, S. Ruiz, P. Marambaud
Calhm1 Ion Channel Elicits Amyloid-Beta Clearance By Insulin-Degrading Enzyme In Cell Lines And In Vivo In The Mouse Brain, V. Vingtdeux, P. Chandakkar, H. Zhao, L. Blanc, S. Ruiz, P. Marambaud
Journal Articles
Alzheimer's disease is characterized by amyloid-beta (Abeta) peptide accumulation in the brain. CALHM1, a cell-surface Ca(2+) channel expressed in brain neurons, has anti-amyloidogenic properties in cell cultures. Here, we show that CALHM1 controls Abeta levels in vivo in the mouse brain through a previously unrecognized mechanism of regulation of Abeta clearance. Using pharmacological and genetic approaches in cell lines, we found that CALHM1 ion permeability and extracellular Ca(2+) were required for the Abeta-lowering effect of CALHM1. Abeta level reduction by CALHM1 could be explained by an increase in extracellular Abeta degradation by insulin-degrading enzyme (IDE), extracellular secretion of which was …
Chronic Hiv Infection Is Associated With Upregulation Of Proinflammatory Cytokine And Chemokine And Alpha Defensin Gene Expression In Colorectal Mucosa, J. Mait-Kaufman, E. Fakioglu, P. M. Mesquita, J. Elliott, Y. Lo, R. P. Madan
Chronic Hiv Infection Is Associated With Upregulation Of Proinflammatory Cytokine And Chemokine And Alpha Defensin Gene Expression In Colorectal Mucosa, J. Mait-Kaufman, E. Fakioglu, P. M. Mesquita, J. Elliott, Y. Lo, R. P. Madan
Journal Articles
HIV may induce gastrointestinal (GI) mucosal immune dysregulation similar to inflammation observed in ulcerative colitis (UC). Colorectal biopsies from healthy controls (N=12) and from participants with HIV (N=20) or UC (N=9) were subjected to real time (RT)-PCR for selected cytokines, chemokines, antimicrobial peptides, Toll-like receptors, and inflammatory signaling and epithelial barrier proteins. HIV long terminal repeat relative copy number (RCN) in HIV participant biopsies was quantified by RT-PCR. Mean interleukin (IL)-6 mRNA levels did not differ significantly between HIV and UC participants (p=0.48) but were significantly higher relative to control mRNA levels only for HIV participants (p=0.03). Mean IL-8 and …
Xanomeline Suppresses Excessive Pro-Inflammatory Cytokine Responses Through Neural Signal-Mediated Pathways And Improves Survival In Lethal Inflammation, M. Rosas-Ballina, S. I. Valdes-Ferrer, M. E. Dancho, M. Ochani, D. Katz, K. F. Cheng, P. S. Olofsson, S. S. Chavan, Y. Al-Abed, K. J. Tracey, V. A. Pavlov
Xanomeline Suppresses Excessive Pro-Inflammatory Cytokine Responses Through Neural Signal-Mediated Pathways And Improves Survival In Lethal Inflammation, M. Rosas-Ballina, S. I. Valdes-Ferrer, M. E. Dancho, M. Ochani, D. Katz, K. F. Cheng, P. S. Olofsson, S. S. Chavan, Y. Al-Abed, K. J. Tracey, V. A. Pavlov
Journal Articles
Inflammatory conditions characterized by excessive immune cell activation and cytokine release, are associated with bidirectional immune system-brain communication, underlying sickness behavior and other physiological responses. The vagus nerve has an important role in this communication by conveying sensory information to the brain, and brain-derived immunoregulatory signals that suppress peripheral cytokine levels and inflammation. Brain muscarinic acetylcholine receptor (mAChR)-mediated cholinergic signaling has been implicated in this regulation. However, the possibility of controlling inflammation by peripheral administration of centrally-acting mAChR agonists is unexplored. To provide insight we used the centrally-acting M1 mAChR agonist xanomeline, previously developed in the context of Alzheimer's disease …
Developments In Intervertebral Disc Disease Research: Pathophysiology, Mechanobiology, And Therapeutics, K. T. Weber, T. D. Jacobsen, R. Maidhof, J. Virojanapa, C. Overby, O. Bloom, S. Quraishi, M. Levine, N. O. Chahine
Developments In Intervertebral Disc Disease Research: Pathophysiology, Mechanobiology, And Therapeutics, K. T. Weber, T. D. Jacobsen, R. Maidhof, J. Virojanapa, C. Overby, O. Bloom, S. Quraishi, M. Levine, N. O. Chahine
Journal Articles
Low back pain is a leading cause of disability worldwide and the second most common cause of physician visits. There are many causes of back pain, and among them, disc herniation and intervertebral disc degeneration are the most common diagnoses and targets for intervention. Currently, clinical treatment outcomes are not strongly correlated with diagnoses, emphasizing the importance for characterizing more completely the mechanisms of degeneration and their relationships with symptoms. This review covers recent studies elucidating cellular and molecular changes associated with disc mechanobiology, as it relates to degeneration and regeneration. Specifically, we review findings on the biochemical changes in …
Selective Impairment Of Spatial Cognition Caused By Autoantibodies To The N-Methyl-D-Aspartate Receptor, E. H. Chang, B. T. Volpe, M. Mackay, C. Aranow, C. Kowal, P. Mattis, R. Berlin, S. Mader, T. S. Huerta, P. T. Huerta, B. Diamond, +3 Additional Authors
Selective Impairment Of Spatial Cognition Caused By Autoantibodies To The N-Methyl-D-Aspartate Receptor, E. H. Chang, B. T. Volpe, M. Mackay, C. Aranow, C. Kowal, P. Mattis, R. Berlin, S. Mader, T. S. Huerta, P. T. Huerta, B. Diamond, +3 Additional Authors
Journal Articles
Patients with systemic lupus erythematosus (SLE) experience cognitive abnormalities in multiple domains including processing speed, executive function, and memory. Here we show that SLE patients carrying antibodies that bind DNA and the GluN2A and GluN2B subunits of the N-methyl-d-aspartate receptor (NMDAR), termed DNRAbs, displayed a selective impairment in spatial recall. Neural recordings in a mouse model of SLE, in which circulating DNRAbs penetrate the hippocampus, revealed that CA1 place cells exhibited a significant expansion in place field size. Structural analysis showed that hippocampal pyramidal cells had substantial reductions in their dendritic processes and spines. Strikingly, these abnormalities became evident at …
Postnatal Neurodevelopmental Expression And Glutamate-Dependent Regulation Of The Znf804a Rodent Homologue, E. H. Chang, A. Kirtley, T. S. Chandon, P. Borger, S. Husain-Krautter, V. Vingtdeux, A. Malhotra
Postnatal Neurodevelopmental Expression And Glutamate-Dependent Regulation Of The Znf804a Rodent Homologue, E. H. Chang, A. Kirtley, T. S. Chandon, P. Borger, S. Husain-Krautter, V. Vingtdeux, A. Malhotra
Journal Articles
The zinc finger protein ZNF804A rs1344706 variant is a replicated genome-wide significant risk variant for schizophrenia and bipolar disorder. While its association with altered brain structure and cognition in patients and healthy risk allele carriers is well documented, the characteristics and function of the gene in the brain remains poorly understood. Here, we used in situ hybridization to determine mRNA expression levels of the ZNF804A rodent homologue, Zfp804a, across multiple postnatal neurodevelopmental time points in the rat brain. We found changes in Zfp804a expression in the rat hippocampus, frontal cortex, and thalamus across postnatal neurodevelopment. Zfp804a mRNA peaked at postnatal …