tbuckley/cabot-search huggingface dataset:
Heat Shock Protein 72 Enhances Manganese Superoxide Dismutase Activity During Myocardial Ischemia-Reperfusion Injury, Associated With Mitochondrial Protection and Apoptosis Reduction
Authors: Ken Suzuki, Bari Murtuza, Ivan A. Sammut, Najma Latif, Jay Jayakumar, Ryszard T. Smolenski, Yasufumi Kaneda, Yoshiki Sawa, Hikaru Matsuda, Magdi H. Yacoub
Journal: Circulation (2002)

Heat shock protein 72 (HSP72) is known to provide myocardial protection against ischemia-reperfusion injury by its chaperoning function. Target molecules of this effect are presumed to include not only structural proteins but also other self-preservation proteins. The details, however, remain unknown. Manganese superoxide dismutase (Mn-SOD) is an enzyme that preserves mitochondria, a key organelle for cellular respiration, from reperfusion injury and limits mitochondria-related apoptosis. We hypothesized that Mn-SOD would play a role in HSP72-mediated cardioprotection.Rat hearts were transfected with human HSP72 by intra-coronary infusion of Hemagglutinating Virus of Japan-liposome, resulting in global myocardial overexpression of HSP72. After ischemia-reperfusion injury, cardiac function (left ventricular systolic pressure, maximum dP/dt, minimum dP/dt, and coronary flow) was improved in the HSP72-transfected hearts compared with control-transfected ones, corresponding with less leakage of creatine kinase and mitochondrial aspartate aminotransferase. Postischemic Mn-SOD content and activity in the HSP72-transfected hearts were enhanced in comparison with the controls (content: 96.9+/-4.1 versus 85.5+/-2.5% to the preischemic level, P=0.038; activity: 93.9+/-2.2 versus 82.2+/-3.7%, P=0.022), associated with improved mitochondrial respiratory function (postischemic percent respiratory control index; NAD(+)-linked: 81.3+/-3.8 versus 18.5+/-4.4%; FAD-linked: 71.8+/-5.5 versus 20.7+/-5.3%, P<0.001). In addition, incidence of postischemic cardiomyocyte apoptosis was attenuated in the HSP72-transfected hearts (4.0+/-1.1 versus 10.3+/-3.3%, P=0.036), correlating with an increased Bcl-2 level and reduced up-regulation of caspase-3.These data suggest that the enhanced Mn-SOD activity during ischemia-reperfusion injury, which is associated with mitochondrial protection and apoptosis reduction, is a possible mechanism of HSP72-induced cardioprotection.
Induction of fibroblast chemotaxis by fibronectin. Localization of the chemotactic region to a 140,000-molecular weight non-gelatin-binding fragment.
Authors: A E Postlethwaite, J Keski-Oja, G Balian, A H Kang
Journal: The Journal of Experimental Medicine (1981)

Plasma and cell-derived fibronectin are potent chemoattractants for human dermal fibroblasts in vitro. The chemotactic property of fibronectin resides in a major 140,000-mol wt non-gelatin-binding fragment of the native molecule. Human monocytes and neutrophils do not recognize fibronectin as a chemotactic stimulus. These findings suggest that fibronectin and perhaps certain fragments of fibronectin may function in vivo as a specific chemoattractant for fibroblasts and could, therefore, induce directional migration of fibroblasts to sites of tissue injury, remodeling or morphogenesis.
The Molecular Forms of Cholinesterase and Acetylcholinesterase in Vertebrates
Authors: J Massoulie, S Bon
Journal: Annual Review of Neuroscience (1982)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
EAACI Food Allergy and Anaphylaxis Guidelines: managing patients with food allergy in the community
Authors: A. Muraro, I. Agache, A. Clark, A. Sheikh, G. Roberts, C. A. Akdis, L. M. Borrego, J. Higgs, J. O'B. Hourihane, P. Jorgensen, A. Mazon, D. Parmigiani, M. Said, S. Schnadt, H. van Os-Medendorp, B. J. Vlieg-Boerstra, M. Wickman
Journal: Allergy (2014)

The European Academy of Allergy and Clinical Immunology (EAACI) Food Allergy and Anaphylaxis Guidelines, managing patients with food allergy (FA) in the community, intend to provide guidance to reduce the risk of accidental allergic reactions to foods in the community. This document is intended to meet the needs of early-childhood and school settings as well as providers of non-prepackaged food (e.g., restaurants, bakeries, takeaway, deli counters, and fast-food outlets) and targets the audience of individuals with FA, their families, patient organizations, the general public, policymakers, and allergists. Food allergy is the most common trigger of anaphylaxis in the community. Providing children and caregivers with comprehensive information on food allergen avoidance and prompt recognition and management of allergic reactions are of the utmost importance. Provision of adrenaline auto-injector devices and education on how and when to use these are essential components of a comprehensive management plan. Managing patients at risk of anaphylaxis raises many challenges, which are specific to the community. This includes the need to interact with third parties providing food (e.g., school teachers and restaurant staff) to avoid accidental exposure and to help individuals with FA to make safe and appropriate food choices. Education of individuals at risk and their families, their peers, school nurses and teachers as well as restaurant and other food retail staff can reduce the risk of severe/fatal reactions. Increased awareness among policymakers may improve decision-making on legislation at local and national level.
Survival from high-grade localised extremity osteosarcoma: combined results and prognostic factors from three European Osteosarcoma Intergroup randomised controlled trials
Authors: J.S. Whelan, R.C. Jinks, A. McTiernan, M.R. Sydes, J.M. Hook, L. Trani, B. Uscinska, V. Bramwell, I.J. Lewis, M.A. Nooij, M. van Glabbeke, R.J. Grimer, P.C.W. Hogendoorn, A.H.M. Taminiau, H. Gelderblom
Journal: Annals of Oncology (2011)
A high proportion of T lymphocytes that infiltrate H-2-incompatible heart allografts in vivo express genes encoding cytotoxic cell-specific serine proteases, but do not express the MEL-14-defined lymph node homing receptor.
Authors: C Mueller, H K Gershenfeld, C G Lobe, C Y Okada, R C Bleackley, I L Weissman
Journal: The Journal of Experimental Medicine (1988)

The role of cytotoxic cells in in vivo immune functions such as allograft rejection is unknown. To begin to assess the function of cytolytic cells in vivo we have begun with cytolytic cell-specific functional molecules: we have isolated and characterized cytolytic cell-specific cDNA clones from cytolytic T cell clones, both encoding distinct serine esterases. The HF gene encodes a trypsin-like enzyme while the C11 gene encodes an enzyme with likely specificity for acidic residues. Here we demonstrate, using in situ hybridization with RNA probe, that both genes are expressed selectively in a subset of T lymphocytes that have infiltrated cardiac allografts. The phenotype of these cells is consistent with the most frequent phenotype of active CTL raised in vitro: they are predominantly CD4-, CD8+, MEL-14- T cell blasts. Thus the expression of these genes, each of which encodes serine esterase found in killer cell granules in vitro, is a valid marker for these cells in vivo as well. The kinetics of their accumulation is consistent with, but not proof of, a putative role in allograft rejection. It is likely that HF and C11 gene expression will be of diagnostic value.
Prefrontal Function and Activation in Bipolar Disorder and Schizophrenia
Authors: Andrew M. McIntosh, Heather C. Whalley, James McKirdy, Jeremy Hall, Jessika E. D. Sussmann, Prakash Shankar, Eve C. Johnstone, Stephen M. Lawrie
Journal: American Journal of Psychiatry (2008)

Distinctive patterns of speech and language abnormalities are associated with bipolar disorder and schizophrenia. It is, however, unclear whether the associated patterns of neural activation are diagnosis specific. The authors sought to determine whether there are differences in language-associated prefrontal activation that discriminate bipolar disorder and schizophrenia.Forty-two outpatients with bipolar I disorder, 27 outpatients with schizophrenia, and 37 healthy comparison subjects were recruited. Differences in blood oxygen level-dependent activity were evaluated using the Hayling Sentence Completion Test and analyzed in Statistical Parametric Mapping (SPM) 2. Differences in activation were estimated from a sentence completion versus rest contrast and from a contrast of decreasing sentence constraint. Regional activations were related to clinical variables and performance on a set shifting task and evaluated for their ability to differentiate among the three groups.Patients with bipolar disorder showed differences in insula and dorsal prefrontal cortex activation, which differentiated them from patients with schizophrenia. Patients with bipolar disorder recruited the orbitofrontal cortex and ventral striatum to a greater extent relative to healthy comparison subjects on the parametric contrast of increasing difficulty. The gradient of ventral striatal and prefrontal activation was significantly associated with reversal errors in bipolar disorder patients.Brain activations during the Hayling task differentiated patients with bipolar disorder from comparison subjects and patients with schizophrenia. Patients with bipolar disorder showed abnormalities in frontostriatal systems associated with performance on a set shifting task. This finding suggests that bipolar disorder patients engaged emotional brain areas more than comparison subjects while performing the Hayling task.
MicroRNA-21 Is an Antiapoptotic Factor in Human Glioblastoma Cells
Authors: Jennifer A. Chan, Anna M. Krichevsky, Kenneth S. Kosik
Journal: Cancer Research (2005)

Abstract MicroRNAs (miRNAs) are small noncoding RNA molecules that regulate protein expression by targeting the mRNA of protein-coding genes for either cleavage or repression of translation. The roles of miRNAs in lineage determination and proliferation as well as the location of several miRNA genes at sites of translocation breakpoints or deletions has led to the speculation that miRNAs could be important factors in the development or maintenance of the neoplastic state. Here we show that the highly malignant human brain tumor, glioblastoma, strongly overexpresses a specific miRNA, miR-21. Our studies show markedly elevated miR-21 levels in human glioblastoma tumor tissues, early-passage glioblastoma cultures, and in six established glioblastoma cell lines (A172, U87, U373, LN229, LN428, and LN308) compared with nonneoplastic fetal and adult brain tissues and compared with cultured nonneoplastic glial cells. Knockdown of miR-21 in cultured glioblastoma cells triggers activation of caspases and leads to increased apoptotic cell death. Our data suggest that aberrantly expressed miR-21 may contribute to the malignant phenotype by blocking expression of critical apoptosis-related genes.
Changing heat-related mortality in the United States.
Authors: Robert E Davis, Paul C Knappenberger, Patrick J Michaels, Wendy M Novicoff
Journal: Environmental Health Perspectives (2003)

Heat is the primary weather-related cause of death in the United States. Increasing heat and humidity, at least partially related to anthropogenic climate change, suggest that a long-term increase in heat-related mortality could occur. We calculated the annual excess mortality on days when apparent temperatures--an index that combines air temperature and humidity--exceeded a threshold value for 28 major metropolitan areas in the United States from 1964 through 1998. Heat-related mortality rates declined significantly over time in 19 of the 28 cities. For the 28-city average, there were 41.0 +/- 4.8 (mean +/- SE) excess heat-related deaths per year (per standard million) in the 1960s and 1970s, 17.3 +/- 2.7 in the 1980s, and 10.5 +/- 2.0 in the 1990s. In the 1960s and 1970s, almost all study cities exhibited mortality significantly above normal on days with high apparent temperatures. During the 1980s, many cities, particularly those in the typically hot and humid southern United States, experienced no excess mortality. In the 1990s, this effect spread northward across interior cities. This systematic desensitization of the metropolitan populace to high heat and humidity over time can be attributed to a suite of technologic, infrastructural, and biophysical adaptations, including increased availability of air conditioning.
Randomized controlled trials in frontotemporal dementia: cognitive and behavioral outcomes
Authors: Justin B Miller, Sarah J Banks, Gabriel C Léger, Jeffrey L Cummings
Journal: Translational Neurodegeneration (2014)

Progress has been made in understanding the genetics and molecular biology of frontotemporal dementia (FTD). Targets for intervention have been identified, therapies are being developed, and clinical trials are advancing. A major challenge for FTD research is that multiple underlying pathologies can be associated with heterogeneous phenotypes. The neuropsychological profiles associated with FTD spectrum disorders often include executive dysfunction, language impairments and behavioral disturbance. Behavioral variant FTD is characterized by an initial presentation of changes in personality, behavior and/or emotion, which are often difficult to objectively capture using traditional neuropsychological measures. The two principal language variants of FTD are Progressive Nonfluent Aphasia (PNFA) with predominant agrammatic/non-fluent impairments and Semantic Dementia (SD) with semantic impairments and visual agnosia. Selection of appropriate endpoints for clinical trials is critical to ensure that the measures are adequately sensitive to detect change, yet specific enough to isolate signal from noise, and acceptable to regulatory agencies. Given the anticipated potential for small effect sizes, measures must be able to identify small incremental changes over time. It is also imperative that the measures provide adequate coverage of the constructs or behaviors of interest. Selected outcome measures should be suitable for repeat administration, yet relatively robust to practice effects to ensure that observed changes reflect true signal variance and not residual effects due to repeated measurement or poor reliability. To facilitate widespread adoption as an endpoint, measures should be readily accessible. We provide several examples of potential global, composite, and individual cognitive measures, as well as behavioral measures promising for FTD trials. Development and application of appropriate trial outcomes is critically important to success in advancing new treatments for FTD patients.
PORCINE CONTAGIOUS PLEUROPNEUMONIA
Authors: David C. White, Grace Leidy, James D. Jamieson, Richard E. Shope
Journal: The Journal of Experimental Medicine (1964)

Hemophilus pleuropneumoniae, the causative agent of porcine contagious pleuropneumonia (PCP) is an encapsulated organism that has the metabolic features of the parainfluenza group of Hemophilus in that it requires DPN but not hemin for growth. Its formation of nitrate reductase cytochrome a1 and non-physiologically reducible cytochrome c1 in the stationary phase, together with its requirement of electron transport through oxidases for growth are typical of non-hemin-requiring Hemophilus species. It has the closest genetic homology, judged from the capacity of its DNA to induce transformation to streptomycin resistance, with H. parasuis but can be differentiated from this organism on the basis of its growth in defined medium and its marked and characteristic pathogenicity for swine.
Hypoglycemia: An unrecognized problem in cystic fibrosis (CF) patients unmasked by continues glucose monitorisation (CGM)
Authors: Belma Haliloglu, Yasemin Gokdemir, Zeynep Atay, Saygin Abali, Tulay Guran, Fazilet Karakoc, Refika Ersu, Bulent Karadag, Serap Turan, Abdullah Bereket
Journal: European Respiratory Journal (2014)

Cystic Fibrosis Related Diabetes (CFRD) is one of the factors associated with increased mortality in CF. CGM has the potential to diagnose glucose abnormalities earlier than OGTT.

Aim:To compare CGM vs standard OGTT in determining diabetes and other glucose abnormalities.

Methods: 44 CF patients underwent OGTT followed by CGM for three days.

The patients were classified according to OGTT categories and the CGM results.

CGM results were grouped as hypoglycemia, hyperglycemia and both hypo and hyperglycemia.

View this table:

OGTT and CGM results





Results: In 26 patients who had normal OGTT, CGM showed hyperglycemia in 7, both hypo-and hyperglycemia in 6, and hypoglycemia only in 1 patient. The frequency of hypoglycemia in OGTT was %13.6.

Conclusion:CGM is a useful tool especially to determine hypoglycemia in CF patients which might be missed by OGTT. We suggest that CF patients should be evaluated by CGM especially if they are to be started/or on insulin treatment to detect and prevent hypoglycemia appropriately.
Contraction of Vascular Smooth Muscle in Response to Plasma
Authors: DAVID F. BOHR, BÖRJE JOHANSSON
Journal: Circulation Research (1966)

Addition of plasma to the physiologic salt solution in which helical strips of vascular smooth muscle were suspended caused the muscle to contract. The plasma was obtained from dog arterial blood which, extracorporeally, had been in contact only with siliconized polyethylene in the cold. The strips were from large and small vessels from several sites in rabbit and dog. The contractions were reproducible and dose dependent. Threshold concentrations for contraction ranged from 2% to 30% depending on the source of the smooth muscle. In concentrations too low to produce contraction, plasma potentiated tension developed in response to stimulation by epinephrine, angiotensin, and KC1. The response of the strips to plasma was compared with their response to the several known vasoactive agents of plasma: epinephrine, norepinephrine, serotonin, angiotensin, vasopressin, bradykinin and histamine. Important differences were found. It is possible that in normal plasma there is an as yet undefined vasoactive component which in situ may play a role in the maintenance of vascular tone.
HLA-DRA variants predict penicillin allergy in genome-wide fine-mapping genotyping
Authors: Jean-Louis Guéant, Antonino Romano, Jose-Antonio Cornejo-Garcia, Abderrahim Oussalah, Celine Chery, Natalia Blanca-López, Rosa-Maria Guéant-Rodriguez, Francesco Gaeta, Pierre Rouyer, Thomas Josse, Gabriella Canto, F. David Carmona, Lara Bossini-Castillo, Javier Martin, Jose-Julio Laguna, Javier Fernandez, Francisco Feo, David A. Ostrov, Pablo C. Plasencia, Cristobalina Mayorga, Maria-Jose Torres, Miguel Blanca
Journal: Journal of Allergy and Clinical Immunology (2014)
Long-term Efficacy and Safety of a Calcineurin Inhibitor-free Regimen in Live-Donor Renal Transplant Recipients
Authors: Ahmed F. Hamdy, Mohamed A. Bakr, Mohamed A. Ghoneim
Journal: Journal of the American Society of Nephrology (2008)

Calcineurin inhibitor (CNI) nephrotoxicity is a major concern after renal transplantation. To investigate the safety and efficacy of a CNI-free immunosuppressive regimen, 132 live-donor renal transplant recipients were included in a prospective, randomized controlled trial. All patients received induction therapy with basiliximab and steroids. The patients were randomized to a maintenance immunosuppression regimen that included steroids, sirolimus, and either low-dose tacrolimus or mycophenolate mofetil (MMF). Over a mean follow-up period of approximately 5 yr, patient and graft survival did not significantly differ between the two maintenance regimens. Patient survival was 93.8% and 98.5% in the tacrolimus/sirolimus and MMF/sirolimus groups, respectively, and graft survival was 83% and 88%, respectively. However, the MMF/sirolimus group had significantly better renal function, calculated by Cockcroft-Gault, from the second year post-transplant until the last follow-up. In addition, this group was less likely to require a change in their primary immunosuppression regimen than the tacrolimus/sirolimus group (20.8% versus 53.8%, P = 0.001). The safety profile was similar between groups. In summary, after long-term follow-up, a CNI-free maintenance regimen consisting of sirolimus, MMF, and steroids was both safe and efficacious among low to moderate immunologic risk renal transplant recipients.
Identification of the Genes Up- and Down-Regulated by the High Mobility Group A1 (HMGA1) Proteins
Authors: Josefina Martinez Hoyos, Monica Fedele, Sabrina Battista, Francesca Pentimalli, Mogens Kruhoffer, Claudio Arra, Torben F. Orntoft, Carlo Maria Croce, Alfredo Fusco
Journal: Cancer Research (2004)

High mobility group A (HMGA) proteins are chromatinic proteins that do not have transcriptional activity per se, however, by interacting with the transcription machinery, they regulate, negatively or positively, the expression of several genes. We searched for genes regulated by HMGA1 proteins using microarray analysis in embryonic stem (ES) cells bearing one or two disrupted hmga1 alleles. We identified 87 transcripts increased and 163 transcripts decreased of at least 4-fold in hmga1-/- ES cells. For some of them, a HMGA1-dose dependency was observed, because an intermediate level was observed in the heterozygous ES cells. When the expression analysis of these genes was extended to embryonic fibroblasts and adult tissues such as heart, spleen, and liver from hmga1-knockout mice, contrasting results were obtained. In fact, aside some genes showing the same HMGA1 regulation observed in ES cells, there were some genes that did not modify their expression, and others showing a HMGA1-mediated regulation but in an opposite direction. These results clearly indicate that HMGA1-mediated gene regulation depends on the cellular context. Finally for a couple of analyzed HMGA1-regulated genes, electrophoretic mobility shift assay and chromatin immunoprecipitation revealed a direct binding of HMGA1 proteins to their promoters, suggesting a HMGA1-direct regulation of their expression.