tbuckley/cabot-search huggingface dataset:
Preterminal host dendritic cells in irradiated mice prime CD8+ T cell–mediated acute graft-versus-host disease
Authors: Yi Zhang, Jean-Pierre Louboutin, Jiang Zhu, Adam J. Rivera, Stephen G. Emerson
Journal: Journal of Clinical Investigation (2002)

To understand the relationship between host antigen-presenting cells (APCs) and donor T cells in initiating graft-versus-host disease (GVHD), we followed the fate of host dendritic cells (DCs) in irradiated C57BL/6 (B6) recipient mice and the interaction of these cells with minor histocompatibility antigen- (miHA-) mismatched CD8+ T cells from C3H.SW donors. Host CD11c+ DCs were rapidly activated and aggregated in the T cell areas of the spleen within 6 hours of lethal irradiation. By 5 days after irradiation, <1% of host DCs were detectable, but the activated donor CD8+ T cells had already undergone as many as seven divisions. Thus, proliferation of donor CD8+ T cells preceded the disappearance of host DCs. When C3H.SW donor CD8+ T cells were primed in vivo in irradiated B6 mice or ex vivo by host CD11c+ DCs for 24–36 hours, they were able to proliferate and differentiate into IFN-γ–producing cells in β2-microglobulin–deficient (β2m–/–) B6 recipients and to mediate acute GVHD in β2m–/– → B6 chimeric mice. These results indicate that, although host DCs disappear rapidly after allogeneic bone marrow transplantation, they prime donor T cells before their disappearance and play a critical role in triggering donor CD8+ T cell–mediated GVHD.
Relationship between physical fitness, physical activity and body mass index of adolescents
Authors: C Cruz, S Sequeira, H Gomes, D Pinto, A Marques
Journal: British Journal of Sports Medicine (2011)

The aim of this study was to examine the relationship between physical fitness (PF), physical activity (PA), and body mass index (BMI) among adolescents who attended secondary school. A total of 131 healthy students (49 boys, 82 girls) age 14 to 18 years (M=16±1) participated in the study. PA was assessed by a questionnaire based on the practice of organised and non-organised PA on a regular basis. PF level was determined by the Pacer test and allowed to label the individuals as ‘not fit' or ‘fit' according to the Fitnessgram. The individuals were also profiled according to their fat levels as ‘not fat' or ‘fat' also based on the Fitnessgram. Qui-square and t-test were performed to analyse the relationship between PF, PA, and BMI. Boys and girls were analysed separately. 66% of the boys and 38% of the girls were considered fit based on PF test. Still the majority of students did not meet the recommended 1 h/day of MVPA. The average time spent doing PA was 2.9±2.2 h/day for the boys and 1.8±1.5 h/day for the girls. The difference in PA participation levels was significant between boys and girls ( p =0.005). Almost all students were considered fit based on BMI (84% boys, 79% girls) and no differences were found between genders ( p =0.531). Although the most active boys and girls performed better on PF test, a relationship between PF and PA was not found (boys p =0.069, girls p =0.079). For both genders, students with lower BMI had better results on the PF test, however only for the boys the results were significant ( p =0.009). Additionally, there was no relationship between the practice of PA and BMI for boys ( p =0.883) and girls ( p =149). There are no relationships between PF, PA and BMI. The only exception was observed for the boys; those with lower BMI had better results on the PF test.
Activity-Dependent Changes in Extracellular Ca2+ and K+ Reveal Pacemakers in the Spinal Locomotor-Related Network
Authors: Frédéric Brocard, Natalia A. Shevtsova, Mouloud Bouhadfane, Sabrina Tazerart, Uwe Heinemann, Ilya A. Rybak, Laurent Vinay
Journal: Neuron (2013)
Cardiac Events in 735 Type 2 Diabetic Patients Who Underwent Screening for Unknown Asymptomatic Coronary Heart Disease
Authors: Ezio Faglia, Fabrizio Favales, Patrizia Calia, Felice Paleari, Giovanni Segalini, Pier Luigi Gamba, Alberto Rocca, Nicoletta Musacchio, Arturo Mastropasqua, Gianpaolo Testori, Pietro Rampini, Flavia Moratti, Anna Braga, Alberto Morabito
Journal: Diabetes Care (2002)

To report the cardiac events in type 2 diabetic outpatients screened for unknown asymptomatic coronary heart disease (CHD) and followed for 5 years.During 1993, 925 subjects aged 40-65 years underwent an exercise treadmill test (ETT). If it was abnormal, the subjects then underwent an exercise scintigraphy. Of the 925 subjects, 735 were followed for 5 years and cardiac events were recorded.At the entry of the study, 638 of the 735 followed subjects had normal ETT, 45 had abnormal ETT with normal scintigraphy, and 52 had abnormal ETT and abnormal scintigraphy. The 52 subjects with abnormal scintigraphy and ETT underwent a cardiological and diabetological follow-up; the subjects with just abnormal ETT had a diabetological follow-up only. During the follow-ups, 42 cardiac events occurred: 1 fatal myocardial infarction (MI), 20 nonfatal MIs, and 10 cases of angina in the 638 subjects with normal ETT; 1 fatal MI in the 45 subjects with normal scintigraphy; and 1 fatal MI and 9 cases of angina in the 52 subjects with abnormal scintigraphy. In these 52 subjects all cardiac events were significantly more frequent (chi(2) = 21.40, P < 0.0001) but the ratio of major (cardiac death and MI) to minor (angina) cardiac events was significantly lower (P = 0.002). Scintigraphy abnormality (hazard ratio 5.47; P < 0.001; 95% CI 2.43-12.29), diabetes duration (1.06; P = 0.021; 1.008-1.106), and diabetic retinopathy (2.371; P = 0.036; 1.059-5.307) were independent predictors of cardiac events on multivariate analysis.The low ratio of major to minor cardiac events in the positive scintigraphy group may suggest, although it does not prove, that the screening program followed by appropriate management was effective for the reduction of risk of major cardiac events.
SLAM Family Receptors and SAP Adaptors in Immunity
Authors: Jennifer L. Cannons, Stuart G. Tangye, Pamela L. Schwartzberg
Journal: Annual Review of Immunology (2011)

The signaling lymphocyte activation molecule (SLAM)-associated protein, SAP, was first identified as the protein affected in most cases of X-linked lymphoproliferative (XLP) syndrome, a rare genetic disorder characterized by abnormal responses to Epstein-Barr virus infection, lymphoproliferative syndromes, and dysgammaglobulinemia. SAP consists almost entirely of a single SH2 protein domain that interacts with the cytoplasmic tail of SLAM and related receptors, including 2B4, Ly108, CD84, Ly9, and potentially CRACC. SLAM family members are now recognized as important immunomodulatory receptors with roles in cytotoxicity, humoral immunity, autoimmunity, cell survival, lymphocyte development, and cell adhesion. In this review, we cover recent findings on the roles of SLAM family receptors and the SAP family of adaptors, with a focus on their regulation of the pathways involved in the pathogenesis of XLP and other immune disorders.
Effects of long-term retinoic acid treatment on epidermal differentiation <i>in vivo</i> : specific modifications in the programme of terminal differentiation
Authors: R. EICHNER, G.J. GENDIMENICO, M. KAHN, J.P. MALLON, R.J. CAPETOLA, J.A. MEZICK
Journal: British Journal of Dermatology (1996)

To investigate the effects of long-term all-trans-retinoic acid (RA) treatment on epidermal differentiation in vivo, rhino mice were treated topically with 0.005% RA, and their epidermis was analysed histologically and biochemically after 5, 13 and 26 weeks of treatment. Effects of RA were observed first in the living layers of the epidermis, and then in the non-viable stratum corneum. Five weeks of topical RA led to thickening of the spinous and granular compartments, induction of keratins K6, K16 and K17, and suppression of filaggrin expression. After 13 and 26 weeks of RA treatment, the number of anucleate cornified cell layers remained similar to controls, but additional changes in histology and protein expression were observed. The results showed that prolonged administration of topical RA induced epidermal hyperproliferation, but did not suppress differentiation, in contrast to results observed in keratinocyte cultures. However, the distinct histological and biochemical changes observed in the spinous, granular and cornified layers of RA-treated skin after 26 weeks of treatment, suggested that the progeny of RA-treated basal cells undergo a modified programme of terminal differentiation. Considering the present data together with results of previous in vivo studies, we propose that long-term topical RA treatment retards, or specifically modulates, the later stages in epidermal differentiation, or programmed cell death.
AMH and AMH receptor defects in persistent Müllerian duct syndrome
Authors: Nathalie Josso, Corinne Belville, Nathalie di Clemente, Jean-Yves Picard
Journal: Human Reproduction Update (2005)

Anti-Müllerian hormone (AMH) produced by fetal Sertoli cells is responsible for regression of Müllerian ducts, the anlage for uterus and Fallopian tubes, during male sex differentiation. A member of the transforming growth factor-beta superfamily, AMH signals through two transmembrane receptors, type II which is specific and type I receptors, shared with the bone morphogenetic protein family. Mutations of the AMH and AMH receptor type II (AMHR-II) genes lead to persistence of the uterus and Fallopian tubes in males. Both conditions are transmitted according to a recessive autosomal pattern and are symptomatic only in males. Affected individuals are otherwise normally virilized, undergo normal male puberty; and may be fertile if testes, tightly attached to the Fallopian tubes, can be replaced in the scrotum. Approximately 85% of the cases are due, in similar proportions, to mutations of the AMH or AMHR-II gene. The genetic background does not influence the phenotype, the only difference is the level of circulating AMH which is normal for age in AMHR-II mutants and usually low or undetectable in AMH gene defects. This is due to lack of secretion, explained by the localization of the mutations in critical regions, based on the assumed 3D structure of the molecule. Similarly, lack of translocation to the surface membrane is responsible for the inactivity of AMHR-II molecules bearing mutations in the extracellular domain. In 15% of cases, the cause of the persistent Mullerian duct syndrome is unknown and could be related to complex malformations of the urogenital region, unrelated to AMH physiology.
Echo‐Doppler and clinical evaluations to define hemodynamic profile in patients with chronic heart failure: accuracy and influence on therapeutic management
Authors: Soccorso Capomolla, Monica Ceresa, GianDomenico Pinna, Roberto Maestri, Maria Teresa La Rovere, Oreste Febo, Angelo Rossi, Vincenzo Paganini, Angelo Caporotondi, Giampaolo Guazzotti, Marco Gnemmi, Andrea Mortara, Franco Cobelli
Journal: European Journal of Heart Failure (2004)
Effects of the Early ACE Inhibition in Diabetic Nonthrombolyzed Patients With Anterior Acute Myocardial Infarction
Authors: Claudio Borghi, Stefano Bacchelli, Daniela Degli Esposti, Ettore Ambrosioni
Journal: Diabetes Care (2003)

OBJECTIVE—The aim of the present study was to evaluate the clinical efficacy of the ACE inhibitor zofenopril in a cohort of diabetic patients with nonthrombolyzed anterior acute myocardial infarction who were enrolled in the Survival of Myocardial Infarction Long-Term Evaluation (SMILE) trial. RESEARCH DESIGN AND METHODS—Among the overall population of 1,512 patients, 303 (20.0%) had diabetes. The primary end point of this study was the effect of treatment on the 6-week combined occurrence of death and severe congestive heart failure (CHF). Secondary end points included the evaluation of the 6-week rate of major cardiovascular events as well as the 1-year survival rate. RESULTS—After 6 weeks of double-blind treatment, zofenopril significantly reduced both the incidence of the primary end point (8.6 vs. 18.3%; P = 0.019) and the 6-week incidence of severe CHF (0 vs. 7.3%; P = 0.001) in diabetic patients, and the effect was greater than that observed in nondiabetic patients. Conversely, 1-year mortality was significantly reduced among nondiabetic patients (9.1 vs. 13.8%; P = 0.010), whereas in the diabetic population, the decrease did not reach statistical significance (13.7 vs. 16.5%; P = 0.52). CONCLUSIONS—The present data suggest that the clinical outcome of patients with diabetes and myocardial infarction can be significantly improved by early treatment with zofenopril. The lesser effect on 1-year mortality seems to suggest that long-term treatment is probably needed to maintain the benefits of the early ACE inhibition in patients with diabetes.
Breast Cancer Growth Prevention by Statins
Authors: Michael J. Campbell, Laura J. Esserman, Yamei Zhou, Mark Shoemaker, Margaret Lobo, Elizabeth Borman, Frederick Baehner, Anjali S. Kumar, Kelly Adduci, Corina Marx, Emanuel F. Petricoin, Lance A. Liotta, Mary Winters, Stephen Benz, Christopher C. Benz
Journal: Cancer Research (2006)

Statins are cholesterol-lowering drugs with pleiotropic activities including inhibition of isoprenylation reactions and reduction of signals driving cell proliferation and survival responses. The objectives of this study were to examine the effects of statins on breast cancer cells, both in vitro and in vivo, and to begin to determine their mechanism of action. We evaluated the effects of statins on breast cancer cell growth, phosphoprotein signaling intermediates, survival/apoptosis regulators, cell cycle regulators, and activated transcription factors. We also examined the in vivo effect of statin administration in a mouse ErbB2(+) breast cancer model. Only lipophilic statins had direct anticancer activity in vitro. Breast cancer cells with activated Ras or ErbB2 pathways seemed to be more sensitive than those overexpressing estrogen receptor, and this correlated with endogenous levels of activated nuclear factor kappaB (NF-kappaB). Key intermediates regulating cell survival by NF-kappaB activation, as well as cell proliferation by the mitogen activated protein kinase cascade, were among the earliest phosphoproteins influenced by statin treatment. These early effects were followed by declines in activator protein-1 and NF-kappaB activation and concordant changes in other mediators of proliferation and apoptosis. In vivo results showed that oral dosing of statins significantly inhibited the growth of a mouse mammary carcinoma. Lipophilic statins can exert direct anticancer activity in vitro by reducing proliferation and survival signals in susceptible breast cancer phenotypes. Tumor growth inhibition in vivo using a clinically relevant statin dose also seems to be associated with reduced tumor cell proliferation and survival. These findings provide supporting rationale for future statin trials in breast cancer patients.
Epirubicin in malignant mesothelioma: a phase II study of the European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group.
Authors: K Mattson, G Giaccone, A Kirkpatrick, D Evrard, L Tammilehto, F J van Breukelen, H T Planteydt, N van Zandwijk
Journal: Journal of Clinical Oncology (1992)

PURPOSE The doxorubicin analog, epirubicin (EPI), was tested in patients with malignant mesothelioma. PATIENTS AND METHODS Sixty-three patients with malignant mesothelioma were given EPI 110 mg/m2 every 3 weeks. Histology was reviewed and confirmed by a pathology panel. On the basis of unconvincing or wrong histology, insufficient material or cytology only, nine cases were considered ineligible for the study. None of the patients had received prior chemotherapy. RESULTS The main side effects were myelosuppression, alopecia, and gastrointestinal toxicity. Tumor response, assessed by computed tomographic (CT) scans, was assessable in 48 patients. Seven patients (15%) achieved a partial response that lasted a median of 37 weeks; 19 patients had stable disease, and 22 patients progressed on treatment. Median survival time was 40 weeks from the start of chemotherapy, and the median survival of responding patients was 87 weeks. One responding patient is still alive and free of relapse 4 years from the start of chemotherapy. CONCLUSION We conclude that further testing of EPI in malignant mesothelioma is warranted.
Exposure to cobalt chromium dust and lung disorders in dental technicians.
Authors: A I Selden, B Persson, S I Bornberger-Dankvardt, L E Winstrom, L S Bodin
Journal: Thorax (1995)

Dental technician's pneumoconiosis is a dust-induced fibrotic lung disease of fairly recent origin. This study was carried out to estimate its occurrence in Sweden.Thirty seven dental technicians in central and south eastern Sweden with at least five years of exposure to dust from cobalt chromium molybdenum (CoCrMo) alloys, identified by postal survey, agreed to undergo chest radiography and assessment of lung function and exposure to inorganic dust.Six subjects (16%; 95% confidence interval 6% to 23%) showed radiological evidence of dental technician's pneumoconiosis. The lung function of the study group was reduced compared with historical reference material. With local exhaust ventilation dust levels were generally low, whereas in dental laboratories without such equipment high levels of dust, particularly cobalt, were found.Pneumoconiosis may result from exposure to inorganic dust in the manufacturing of CoCrMo-based dental constructions. It is possible to reduce this hazard substantially by local exhaust ventilation.
Regulation of the Phosphorylation of Human Pharyngeal Cell Proteins by Group A Streptococcal Surface Dehydrogenase: Signal Transduction between Streptococci and Pharyngeal Cells
Authors: Vijaykumar Pancholi, Vincent A. Fischetti
Journal: The Journal of Experimental Medicine (1997)

Whether cell-to-cell communication results when group A streptococci interact with their target cells is unknown. Here, we report that upon contact with cultured human pharyngeal cells, both whole streptococci and purified streptococcal surface dehydrogenase (SDH) activate pharyngeal cell protein tyrosine kinase as well as protein kinase C, thus regulating the phosphorylation of cellular proteins. SDH, a major surface protein of group A streptococci, has both glyceraldehyde-3-phosphate dehydrogenase and ADP-ribosylating enzyme activities that may relate to early stages of streptococcal infection. Intact streptococci and purified SDH induce a similar protein phosphorylation pattern with the de novo tyrosine phosphorylation of a 17-kD protein found in the membrane/particulate fraction of the pharyngeal cells. However, this phosphorylation required the presence of cytosolic components. NH2-terminal amino acid sequence analysis identified the 17-kD protein as nuclear core histone H3. Both phosphotyrosine and phosphoserine-specific monoclonal antibodies reacted with the 17-kD protein by Western blot, suggesting that the binding of SDH to these pharyngeal cells elicits a novel signaling pathway that ultimately leads to activation of histone H3–specific kinases. Genistein-inhibitable phosphorylation of histone H3 indicates that tyrosine kinase plays a key role in this event. Treatment of pharyngeal cells with protein kinase inhibitors such as genistein and staurosporine significantly inhibited streptococcal invasion of pharyngeal cells. Therefore, these data indicated that streptococci/SDH-mediated phosphorylation plays a critical role in bacterial entry into the host cell. To identify the membrane receptor that elicits these signaling events, we found that SDH bound specifically to 30- and 32-kD membrane proteins in a direct ligand-binding assay. These findings clearly suggest that SDH plays an important role in cellular communication between streptococci and pharyngeal cells that may be important in host cell gene transcription, and hence in the pathogenesis of streptococcal infection.
Sir Harry Platt: 100 not out.
Authors: R Smith
Journal: BMJ (1986)

One of  proud claims of Sir Harry Platt, Britain's first orthopaedic professor, who is 100 this month, is that he won  Ashes for England in 1932. He was summoned to Old Trafford from his popular Tuesday afternoon teaching session at Ancoats Hospital. At  cricket ground  north was playing  south in  selection match and Harold Larwood was having trouble with his knee. Sir Harry examined Larwood in  professional changing room (players were, of course, separated from gentlemen in those days), and then was summoned to give his verdict to  selec? tors,  chairman of whom was P F Warner. His recom? mendation was that if Lar? wood rested for  next match he would be fit to tour Australia. Warner said, Put that in writing, and we'll send you your fee, which, Sir Harry says, was a miser? able four guineas. So Larwood went on  famous bodyline tour, and England came home with  Ashes. Sir Harry still feels strongly that  idea that Larwood was bowling at  body was quite wrong and grossly exaggerated by  Times cricket correspon? dent _ He was simply bowling at  leg stump. Sir Harry was particularly incensed by last year's Australian television series on  tour?he described it as the worst television I've ever seen. Nor is he much fonder of modern cricket, in which, he says,  bowling is much more vicious than anything Lar? wood ever bowled: The game's spoilt for me by  way  players hug each other?they look like copulating frogs. Cricket is one of  few subjects that still provokes  fire for which Sir Harry was once famous. I spent  quiet and relaxing day with him in  summer, but he admitted that irascible had been  fair word to use about him when he was younger. Apocryphal was, however, how he described  story about  theatre sister getting back at him for kicking buckets in  operating theatre by filling one with plaster of Paris. But it was his determination and need for perfection that took him to  heights of  profession: after being  first in Britain to organise  fracture clinic he became  first secretary of  British Orthopaedic Association,  first orthopaedic surgeon to become president of  Royal College of Surgeons of England, and  first president of  International Federation of Surgical Colleges. ?i 2 ? lg B ?JMaW M ? y ^^MaaaaaWaSlfl^& ' '^S'^aP-'
Diagnosis and Treatment of Postpartum Obsessions and Compulsions That Involve Infant Harm
Authors: Robert Hudak, Katherine L. Wisner
Journal: American Journal of Psychiatry (2012)

For women who develop intrusive thoughts of harming their infants and rituals that result in avoidance of their babies, differential diagnosis includes postpartum major mood disorders, obsessive-compulsive disorder, and psychosis with infanticidal thoughts. Rapid onset in the postpartum period of anxiety and obsession is common. Insight into the obsessive unreality of rituals to avoid harm is a key diagnostic feature. Treatment includes serotonergic drugs, psychoeducation to help the woman understand that she is unlikely to harm her infant, and exposure with response prevention therapy.