tbuckley/cabot-search huggingface dataset:
Blockade of Kv1.3 channels ameliorates radiation-induced brain injury
Authors: Ying Peng, Kui Lu, Zichen Li, Yaodong Zhao, Yiping Wang, Bin Hu, Pengfei Xu, Xiaolei Shi, Bin Zhou, Michael Pennington, K. George Chandy, Yamei Tang
Journal: Neuro-Oncology (2013)

Tumors affecting the head, neck, and brain account for significant morbidity and mortality. The curative efficacy of radiotherapy for these tumors is well established, but radiation carries a significant risk of neurologic injury. So far, neuroprotective therapies for radiation-induced brain injury are still limited. In this study we demonstrate that Stichodactyla helianthus (ShK)–170, a specific inhibitor of the voltage-gated potassium (Kv)1.3 channel, protected mice from radiation-induced brain injury. Mice were treated with ShK-170 for 3 days immediately after brain irradiation. Radiation-induced brain injury was assessed by MRI scans and a Morris water maze. Pathophysiological change of the brain was measured by immunofluorescence. Gene and protein expressions of Kv1.3 and inflammatory factors were measured by quantitative real-time PCR, reverse transcription PCR, ELISA assay, and western blot analyses. Kv currents were recorded in the whole-cell configuration of the patch-clamp technique. Radiation increased Kv1.3 mRNA and protein expression in microglia. Genetic silencing of Kv1.3 by specific short interference RNAs or pharmacological blockade with ShK-170 suppressed radiation-induced production of the proinflammatory factors interleukin-6, cyclooxygenase-2, and tumor necrosis factor–α by microglia. ShK-170 also inhibited neurotoxicity mediated by radiation-activated microglia and promoted neurogenesis by increasing the proliferation of neural progenitor cells. The therapeutic effect of ShK-170 is mediated by suppression of microglial activation and microglia-mediated neurotoxicity and enhanced neurorestoration by promoting proliferation of neural progenitor cells.
A Ca <sup>2+</sup> -Dependent Transgenic Model of Cardiac Hypertrophy
Authors: James N. Muth, Ilona Bodi, William Lewis, Gyula Varadi, Arnold Schwartz
Journal: Circulation (2001)

Background —Calcium imbalances have been implicated as an underlying mechanism of human cardiac dysfunction. The voltage-dependent calcium channel plays a critical role in calcium regulation in the heart. Thus, aberrant calcium signaling arising from this channel could initiate the calcium imbalances observed in heart failure. In the present study, we used a transgenic mouse with an increased number of L-type calcium channels to identify the role of an increased, sustained ingress of calcium as an initiator of hypertrophy. Methods and Results —Whole-heart histology and electrophysiology in isolated cardiomyocytes identified calcium-channel overexpression in the hearts of transgenic mice. Calcium-channel density was increased in 2-, 4-, and 8-month-old transgenic cardiomyocytes. Ventricular fibrosis, damage, and remodeling became more pronounced as the transgenic mice aged. Apoptosis was also present in transgenic hearts at 8 months of age. Increased protein kinase Cα activation was elevated before the development of hypertrophy and failure. Conclusions —Transgenic mice developed hypertrophy and severe cardiomyopathy as a function of age, thus confirming that changes in channel density are sufficient to induce disease. The small, sustained increase in the ingress of Ca 2+ through the calcium channel elevated protein kinase Cα before the development of hypertrophy, suggesting that protein kinase Cα plays an important role in triggering hypertrophy.
Adeno-associated Virus Gene Therapy With Cholesterol 24-Hydroxylase Reduces the Amyloid Pathology Before or After the Onset of Amyloid Plaques in Mouse Models of Alzheimer's Disease
Authors: Eloise Hudry, Debby Van Dam, Wim Kulik, Peter P De Deyn, Femke S Stet, Ornella Ahouansou, Abdellatif Benraiss, André Delacourte, Pierre Bougnères, Patrick Aubourg, Nathalie Cartier
Journal: Molecular Therapy (2009)

The development of Alzheimer's disease (AD) is closely connected with cholesterol metabolism. Cholesterol increases the production and deposition of amyloid-beta (Abeta) peptides that result in the formation of amyloid plaques, a hallmark of the pathology. In the brain, cholesterol is synthesized in situ but cannot be degraded nor cross the blood-brain barrier. The major exportable form of brain cholesterol is 24S-hydroxycholesterol, an oxysterol generated by the neuronal cholesterol 24-hydroxylase encoded by the CYP46A1 gene. We report that the injection of adeno-associated vector (AAV) encoding CYP46A1 in the cortex and hippocampus of APP23 mice before the onset of amyloid deposits markedly reduces Abeta peptides, amyloid deposits and trimeric oligomers at 12 months of age. The Morris water maze (MWM) procedure also demonstrated improvement of spatial memory at 6 months, before the onset of amyloid deposits. AAV5-wtCYP46A1 vector injection in the cortex and hippocampus of amyloid precursor protein/presenilin 1 (APP/PS) mice after the onset of amyloid deposits also reduced markedly the number of amyloid plaques in the hippocampus, and to a less extent in the cortex, 3 months after the injection. Our data demonstrate that neuronal overexpression of CYP46A1 before or after the onset of amyloid plaques significantly reduces Abeta pathology in mouse models of AD.
Cell-Mediated Immunity after Bacterial Infection of the Lower Respiratory Tract
Authors: J. Robert Cantey, W. Lee Hand, Carl G. Hughes, Mary E. Lund, Neva L. King
Journal: Journal of Clinical Investigation (1974)

Lower respiratory tract and systemic cell-mediated immunity have been studied in rabbits after infection with Listeria monocytogenes or Diplococcus pneumoniae. Respiratory tract cell-mediated immunity was evaluated by direct and indirect assays of migration inhibitory factor (MIF) production. Systemic delayed hypersensitivity was determined by means of intradermal testing with appropriate antigens. Aerosol exposure to listeria was followed by markedly increased numbers of free lower respiratory tract cells. These cells manifested antigen-stimulated inhibition of migration (mean inhibition of migration = 30.4%). Pneumococcal pneumonia was associated with similar but less dramatic changes. Intravenous administration of organisms was uncommonly followed by inhibition of lower respiratory tract cells in direct migration assays. Fractionated MIF, as well as crude supernates of antigen-stimulated lower respiratory tract and lymph node lymphocytes from animals exposed to listeria aerosols, caused inhibition of normal alveolar macrophage migration. MIF, produced by lymph node lymphocytes, has a molecular weight of approximately 65,000 and is inactivated by chymotrypsin or neuraminidase. Delayed dermal hypersensitivity to listeria antigen was observed in 54 of 55 animals exposed to listeria aerosols and in all 9 animals infected by the intravenous route. Delayed dermal reactions to pneumococcal sonicate antigen (but not capsular polysaccharide) followed D. pneumoniae respiratory tract infection in 19 of 28 animals, and was elicited in 5 of 6 animals after intravenous infection. Both local (macrophage migration inhibition) and systemic delayed hypersensitivity followed bacterial infection of the lower respiratory tract. MIF activity was shown to be one mechanism for inhibition of alveolar macrophage migration.
Deletion or insertion in the first immunoglobulin-plexin-transcription (IPT) domain differentially regulates expression and tumorigenic activities of RON receptor Tyrosine Kinase
Authors: Qi Ma, Kun Zhang, Sunny Guin, Yong-Qing Zhou, Ming-Hai Wang
Journal: Molecular Cancer (2010)

Abstract Background Activation of the RON receptor tyrosine kinase, a member of the c-MET family, regulates tumorigenic phenotypes. The RON extracellular domains are critical in regulating these activities. The objective of this study was to determine the role of the first IPT domain in regulating RON-mediated tumorigenic activities and the underlying mechanisms. Results Two RON variants, RON160 and RON E5/6in with deletion and insertion in the first IPT domain, respectively, were molecularly cloned. RON160 was a splicing variant generated by deletion of 109 amino acids encoded by exons 5 and 6. In contrast, RON E5/6in was derived from a transcript with an insertion of 20 amino acids between exons 5 and 6. Both RON160 and RON E5/6in were proteolytically matured into two-chain receptor and expressed on the cell surface. RON160 was constitutively active with tyrosine phosphorylation. However, activation of RON E5/6in required ligand stimulation. Deletion resulted in the resistance of RON160 to proteolytic digestion by cell associated trypsin-like enzymes. RON160 also resisted anti-RON antibody-induced receptor internalization. These features contributed to sustained intracellular signaling cascades. On the other hand, RON E5/6in was highly susceptible to protease digestion, which led to formation of a truncated variant known as RONp110. RON E5/6in also underwent rapid internalization upon anti-RON antibody treatment, which led to signaling attenuation. Although ligand-induced activation of RON E5/6in partially caused epithelial to mesenchymal transition (EMT), it was RON160 that showed cell-transforming activities in cell focus formation and anchorage-independent growth. RON160-mediated EMT is also associated with increased motile/invasive activity. Conclusions Alterations in the first IPT domain in extracellular region differentially regulate RON mediated tumorigenic activities. Deletion of the first IPT results in formation of oncogenic variant RON160. Enhanced degradation and internalization with attenuated signaling cascades could be the mechanisms underlying non-tumorigenic features of RON E5/6in .
BITES BY RUSSELL'S VIPER (VIPERA RUSSELLI SIAMENSIS) IN BURMA: HAEMOSTATIC, VASCULAR, AND RENAL DISTURBANCES AND RESPONSE TO TREATMENT
Authors: None Myint-Lwin, RodneyE. Phillips, None Tun-Pe, DavidA. Warrell, None Tin-Nu-SWE, None Maung-Maung-Lay
Journal: The Lancet (1985)
Adiponectin antagonizes the oncogenic actions of leptin in hepatocellular carcinogenesis
Authors: Dipali Sharma, Jason Wang, Ping P. Fu, Shvetank Sharma, Arumugam Nagalingam, Jamie Mells, Jeffrey Handy, Andrew J. Page, Cynthia Cohen, Frank A. Anania, Neeraj K. Saxena
Journal: Hepatology (2010)

Obesity is rapidly becoming a pandemic and is associated with increased carcinogenesis. Obese populations have higher circulating levels of leptin in contrast to low concentrations of adiponectin. Hence, it is important to evaluate the dynamic role between adiponectin and leptin in obesity-related carcinogenesis. Recently, we reported the oncogenic role of leptin including its potential to increase tumor invasiveness and migration of hepatocellular carcinoma (HCC) cells. In the present study we investigated whether adiponectin could antagonize the oncogenic actions of leptin in HCC. We employed HCC cell lines HepG2 and Huh7, the nude mice-xenograft model of HCC, and immunohistochemistry data from tissue-microarray to demonstrate the antagonistic role of adiponectin on the oncogenic actions of leptin. Adiponectin treatment inhibited leptin-induced cell proliferation of HCC cells. Using scratch-migration and electric cell-substrate impedance-sensing-based migration assays, we found that adiponectin inhibited leptin-induced migration of HCC cells. Adiponectin treatment effectively blocked leptin-induced invasion of HCC cells in Matrigel invasion assays. Although leptin inhibited apoptosis in HCC cells, we found that adiponectin treatment induced apoptosis even in the presence of leptin. Analysis of the underlying molecular mechanisms revealed that adiponectin treatment reduced leptin-induced Stat3 and Akt phosphorylation. Adiponectin also increased suppressor of cytokine signaling (SOCS3), a physiologic negative regulator of leptin signal transduction. Importantly, adiponectin significantly reduced leptin-induced tumor burden in nude mice. In HCC samples, leptin expression significantly correlated with HCC proliferation as evaluated by Ki-67, whereas adiponectin expression correlated significantly with increased disease-free survival and inversely with tumor size and local recurrence. Conclusion: Collectively, these data demonstrate that adiponectin has the molecular potential to inhibit the oncogenic actions of leptin by blocking downstream effector molecules. (Hepatology 2010
US military medical support continues as future of United Nations in former Yugoslavia is debated
Authors: P. Gundy
Journal: JAMA (1995)

AIR FORCE medical personnel from an Ohio base are replacing their California-based counterparts at the United Nations (UN) hospital, Zagreb, Croatia. This is the seventh US military medical team to staff the UN facility since November 1992. As the situation in the former Yugoslavia continues to deteriorate, there is speculation that the hospital may be withdrawn along with the peacekeepers it serves. The newest team to staff the Zagreb hospital is from Wright-Patterson Air Force Base (AFB), northeast of Dayton, Ohio. The 128-member team, commanded by John A. Bishop, MD, a colonel, replaces the 145 US Air Force medical personnel (commanded by Col David Boggs, DDS, from Travis AFB, Fairfield, Calif), who began their 179-day deployment in early February. Army medical units staffed the hospital initially from November 10, 1992, until October 8, 1993. A US Air Force medical unit stationed in England then took over until March 16, 1994,
An Official American Thoracic Society Systematic Review: Insurance Status and Disparities in Lung Cancer Practices and Outcomes
Authors: Christopher G. Slatore, David H. Au, Michael K. Gould
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Section:ChooseTop of pageAbstract <<CONTENTSMETHODSRESULTSDISCUSSIONReferencesCITING ARTICLES
Oligomeric amyloid-β peptide disrupts phosphatidylinositol-4,5-bisphosphate metabolism
Authors: Diego E Berman, Claudia Dall'Armi, Sergey V Voronov, Laura Beth J McIntire, Hong Zhang, Ann Z Moore, Agniezka Staniszewski, Ottavio Arancio, Tae-Wan Kim, Gilbert Di Paolo
Journal: Nature Neuroscience (2008)
Malignant mesothelioma following radiation exposure.
Authors: K H Antman, J M Corson, F P Li, J Greenberger, A Sytkowski, D E Henson, L Weinstein
Journal: Journal of Clinical Oncology (1983)

Mesothelioma developed in proximity to the field of therapeutic radiation administered 10-31 years previously in four patients. In three, mesothelioma arose within the site of prior therapeutic radiation for another cancer. Mesothelioma in the fourth patient developed adjacent to the site of cosmetic radiation to a thyroidectomy scar. None of these four patients recalled an asbestos exposure or had evidence of asbestosis on chest roentgenogram. Lung tissue in one patient was negative for ferruginous bodies, a finding considered to indicate no significant asbestos exposure. Five other patients with radiation-associated mesothelioma have been reported previously, suggesting that radiation is an uncommon cause of human mesothelioma. Problems in the diagnosis of radiation-associated mesotheliomas are considered.
Female Children and Adolescents With Type 1 Diabetes Have More Pronounced Early Echocardiographic Signs of Diabetic Cardiomyopathy
Authors: Bert E. Suys, Nienke Katier, Raoul P.A. Rooman, Dirk Matthys, Lieve Op De Beeck, Mark V.L. Du Caju, Daniel De Wolf
Journal: Diabetes Care (2004)

OBJECTIVE—This study was designed to assess whether children and adolescents with type 1 diabetes have early echocardiographic signs of subclinical cardiac dysfunction and whether sex, state of metabolic control, and diabetes duration are of influence. RESEARCH DESIGN AND METHODS—Systolic and diastolic blood pressure in supine and upright positions and echocardiographic parameters, including tissue Doppler measurements of the septal mitral annulus, were evaluated in 80 children and adolescents with stable type 1 diabetes and 52 age- and sex-matched control subjects. A possible correlation was examined for age, sex, HbA1c, and diabetes duration with univariate and multivariate regression analysis. RESULTS—Female diabetic patients showed significantly larger left ventricular wall dimensions (left ventricular posterior wall in diastole 0.54 ± 0.08 vs. 0.48 ± 0.11 cm) and signs of significant diastolic filling abnormalities on conventional and tissue Doppler echocardiography (mitral valve-atrial contraction velocity 0.47 ± 0.12 vs. 0.40 ± 0.09 m/s; tricuspid valve-atrial contraction velocity 0.35 ± 0.09 vs. 0.30 ± 0.07 m/s; early filling velocity/myocardial velocity during early filling 7.15 ± 1.47 vs. 6.17 ± 1.07; isovolumetric relaxation time [IVRT] 66 ± 8 vs. 58 ± 8 ms) compared with female control subjects, suggesting delayed myocardial relaxation. Male diabetic patients only differed significantly from their control subjects for IVRT (66 ± 9 vs. 59 ± 8 ms). The measured parameters showed an expected correlation with age and BMI standard deviation scores in the control group. This correlation was significantly weaker in the diabetic population; only a weak influence was found for diabetes duration and glycosylated hemoglobin levels. CONCLUSIONS—Young diabetic patients already have significant changes in left ventricular dimensions and myocardial relaxation, with the girls clearly being more affected. Tissue Doppler proved to have additional value in the evaluation of ventricular filling in this population. Almost no correlation was found for diabetes duration and HbA1c with the cardiovascular changes.
Treating axial and peripheral spondyloarthritis, including psoriatic arthritis, to target: results of a systematic literature search to support an international treat-to-target recommendation in spondyloarthritis
Authors: M M Schoels, J Braun, M Dougados, P Emery, O Fitzgerald, A Kavanaugh, T K Kvien, R Landewé, T Luger, P Mease, I Olivieri, J Reveille, C Ritchlin, M Rudwaleit, J Sieper, J S Smolen, M de Wit, D van der Heijde
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Current recommendations for the management of axial spondyloarthritis (SpA) and psoriatic arthritis are to monitor disease activity and adjust therapy accordingly. However, treatment targets and timeframes of change have not been defined. An international expert panel has been convened to develop 'treat-to-target' recommendations, based on published evidence and expert opinion. <h3>Objective</h3> To review evidence on targeted treatment for axial and peripheral SpA, as well as for psoriatic skin disease. <h3>Methods</h3> We performed a systematic literature search covering Medline, Embase and Cochrane, conference abstracts and studies in http://www.clinicaltrials.gov. <h3>Results</h3> Randomised comparisons of targeted versus routine treatment are lacking. Some studies implemented treatment targets before escalating therapy: in ankylosing spondylitis, most trials used a decrease in Bath Ankylosing Spondylitis Disease Activity Index; in psoriatic arthritis, protocols primarily considered a reduction in swollen and tender joints; in psoriasis, the Modified Psoriasis Severity Score and the Psoriasis Area and Severity Index were used. Complementary evidence correlating these factors with function and radiographic damage at follow-up is sparse and equivocal. <h3>Conclusions</h3> There is a need for randomised trials that investigate the value of treat-to-target recommendations in SpA and psoriasis. Several trials have used thresholds of disease activity measures to guide treatment decisions. However, evidence on the effect of these data on long-term outcome is scarce. The search data informed the expert committee regarding the formulation of recommendations and a research agenda.
The Effect of Oral Glucosamine Sulfate on Insulin Sensitivity in Human Subjects
Authors: Joseph G. Yu, Sarah M. Boies, Jerrold M. Olefsky
Journal: Diabetes Care (2003)

As glucosamine is presently in wide use due to its purported beneficial effects in patients with osteoarthritis, it seemed important to consider its possible adverse effects on glucose metabolism. Many subjects who take glucosamine for osteoarthritis are obese, insulin resistant, diabetic, or at risk for the development of diabetes, and it is established that glucosamine induces insulin resistance in rats and mice. Hypotheses suggest that glucosamine causes insulin resistance by directly entering the hexosamine biosynthetic pathway. It has been proposed that this provides a model for glucotoxicity-induced defects in insulin action and secretion (1), since, under hyperglycemic conditions, a larger amount of glucose flux is metabolized through the hexosamine pathway. Therefore, we undertook this study to determine if glucosamine, taken at recommended doses for the treatment of osteoarthritis, had any detrimental …
A COMPARATIVE HISTOLOGIC AND IMMUNOLOGIC STUDY IN RABBITS OF INDUCED HYPERSENSITIVITY OF THE SERUM SICKNESS TYPE
Authors: Frederick G. Germuth
Journal: The Journal of Experimental Medicine (1953)

A histologic and quantitative immunologic study was made on a large group of rabbits injected intravenously with a single dose of crystallized bovine albumin and bled and sacrificed at various intervals after injection. Both cardiovascular and renal lesions were encountered in high incidence. The various stages in the development of these lesions were observed from their first appearance until their complete regression. The cardiac, vascular, and renal alterations were morphologically similar to those of rheumatic fever, polyarteritis nodosa, and acute glomerulonephritis, respectively, in man. In addition to those tissue changes ordinarily attributed to hypersensitivity, peculiar granulomatous lesions consisting of epithelioid and foreign body giant cells were encountered in the follicles of the spleen and in the lymph nodes of a large proportion of the animals receiving the antigen. Similar granulomas in the spleen and lymph nodes as well as in other tissues have been described in polyarteritis nodosa. The present experimental demonstration that an epithelioid and giant cell reaction may result from hypersensitivity provides evidence for the allergic origin of those cases of polyarteritis nodosa of unknown etiology containing this type of lesion. In the present study the time of development of the cardiovascular, renal, and granulomatous lesions was determined in relation to the blood clearance of antigen and the time of appearance of circulating antibody. All the tissue lesions developed during the "immune" phase of antigen elimination and regressed after the antigen had been completely eliminated and free antibody had appeared in the circulation. These temporal relationships indicate that the tissue lesions which occur after the intravenous administration of foreign protein are the result of antigen-antibody combination.