tbuckley/cabot-search huggingface dataset:
Effect of cyclosporin A on the allergen-induced late asthmatic reaction
Authors: B. S. Sihra, O. M. Kon, S. R. Durham, S. Walker, N. C. Barnes, A. B. Kay
Journal: Thorax (1997)

BACKGROUND: The allergen-induced late asthmatic reaction (LAR) is associated with mucosal inflammation involving several cell types including activated T lymphocytes and eosinophils. In contrast, the early asthmatic reaction (EAR) is considered to results from rapid allergen-induced release of bronchoconstrictor mediators from IgE sensitised mast cells. Cyclosporin A has efficacy in chronic severe corticosteroid-dependent asthma and is believed to act principally by inhibiting cytokine mRNA transcription in T lymphocytes. However, it has effects on other cell types in vitro, including the inhibition of exocytosis/degranulation events in mast cells. It was therefore hypothesised that cyclosporin A would attenuate both the EAR and LAR in subjects with mild asthma. METHODS: Twelve sensitised atopic asthmatic subjects with documented dual asthmatic responses were studied in a double blind, placebo controlled, crossover trial. On two separate study visits subjects received two oral doses of either cyclosporin A or matched placebo before inhaled allergen challenges. The forced expiratory volume in one second (FEV1) was measured half hourly for eight hours and blood eosinophil counts were analysed three, six, and 24 hours after the challenge. Treatment effects on blood eosinophil counts as well as the EAR and LAR, respectively defined as the areas under the curve (AUC) of FEV1 changes from baseline between 0-1 and 4-8 hours after challenge, were compared by non-parametric crossover analysis. RESULTS: Cyclosporin A reduced both the LAR (median AUC -41.9 1.h (interquartile range -82.7 to -12.4) for cyclosporin A and -84.5 1.h (-248.9 to -39.1) for placebo; p = 0.007) and the late increase in blood eosinophils (median 0.2 x 10(9)/1 (0.15 to 0.4) for cyclosporin A and 0.4 x 10(9)/1 (0.25 to 0.55) for placebo; p = 0.024) but had no effect on the EAR. The reduction of the LAR by cyclosporin A correlated significantly with prechallenge blood concentrations of cyclosporin A (r = 0.6, p = 0.028). CONCLUSIONS: These data are consistent with the concept that cyclosporin A has anti-inflammatory actions in asthma resulting from inhibition of mRNA transcription of eosinophil-active cytokines, predominantly in T lymphocytes. Cyclosporin A, possibly in its inhaled form, or other agents which prevent cytokine gene transcription may therefore have potential in ameliorating the inflammatory component of asthma.
Posttraumatic Stress Disorder: Etiology, Epidemiology, and Treatment Outcome
Authors: Terence M. Keane, Amy D. Marshall, Casey T. Taft
Journal: Annual Review of Clinical Psychology (2006)

Posttraumatic stress disorder (PTSD) results from exposure to a traumatic event that poses actual or threatened death or injury and produces intense fear, helplessness, or horror. U.S. population surveys reveal lifetime PTSD prevalence rates of 7% to 8%. Potential reasons for varying prevalence rates across gender, cultures, and samples exposed to different traumas are discussed. Drawing upon a conditioning model of PTSD, we review risk factors for PTSD, including pre-existing individual-based factors, features of the traumatic event, and posttrauma social support. Characteristics of the trauma, particularly peritraumatic response and related cognitions, and posttrauma social support appear to confer the greatest risk for PTSD. Further work is needed to disentangle the interrelationships among these factors and elucidate the underlying mechanisms. Based upon existing treatment outcome studies, we recommend use of exposure therapies and anxiety management training as first-line treatment for PTSD. Among psychopharmacological treatments, selective serotonin reuptake inhibitors evidence the strongest treatment effects, yet these effects are modest compared with psychological treatments.
Antibodies from patients with heparin-induced thrombocytopenia/thrombosis are specific for platelet factor 4 complexed with heparin or bound to endothelial cells.
Authors: G P Visentin, S E Ford, J P Scott, R H Aster
Journal: Journal of Clinical Investigation (1994)

Heparin-induced thrombocytopenia/thrombosis (HITP) is thought to be mediated by immunoglobulins that activate platelets in the presence of pharmacologic concentrations of heparin, but the molecular basis for this relatively common and often serious complication of heparin therapy has not been established. We found that plasma from each of 12 patients with HITP contained high titer (> or = 1:200) antibodies that reacted with immobilized complexes of heparin and platelet factor 4 (PF4), a heparin-binding protein contained in platelet alpha-granules. Recombinant human PF4 behaved similarly to PF4 isolated from platelets in this assay system. Complexes formed at an apparent heparin/PF4 molecular ratio of approximately 1:2 (fresh heparin) and approximately 1:12 (outdated heparin) were most effective in binding antibody. Immune complexes consisting of PF4, heparin, and antibody reacted with resting platelets; this interaction was inhibited by a monoclonal antibody specific for the Fc gamma RII receptor and by excess heparin. Human umbilical vein endothelial cells, known to express heparin-like glycosaminoglycan molecules on their surface, were recognized by antibody in the presence of PF4 alone; this reaction was inhibited by excess heparin, but not by anti-Fc gamma RII. Antibodies reactive with heparin/PF4 were not found in normal plasma, but IgG and IgM antibodies were detected at dilutions of 1:10 (IgG) and 1:50 (IgM) in 3 of 50 patients (6%) with other types of immune thrombocytopenia. These findings indicate that antibodies associated with HITP react with PF4 complexed with heparin in solution or with glycosaminoglycan molecules on the surface of endothelial cells and provide the basis for a new hypothesis to explain the development of thrombocytopenia with thrombosis or disseminated intravascular coagulation in patients sensitive to heparin.
Non-steroidal anti-inflammatory drugs are associated with emergency admission to hospital for colitis due to inflammatory bowel disease.
Authors: J M Evans, A D McMahon, F E Murray, D G McDevitt, T M MacDonald
Journal: Gut (1997)

BACKGROUND: To evaluate the relation between non-steroidal anti-inflammatory drugs (NSAIDs) and colitis due to inflammatory bowel disease. METHODS: A case-control study was conducted using a prospectively constructed, record linkage database containing hospital event and dispensed drug data (1989-93). The study population consisted of 319,465 people resident in Tayside in January 1989, and still resident (or dead) in October 1994. RESULTS: Of the 785 patients admitted to hospital as emergencies with colitis between July 1989 and June 1993, 200 fulfilled the case criterion of colitis due to inflammatory bowel disease. A further 1198 persons were used as community controls. Odds ratios were calculated for three exposure periods (current, recent, and past exposure). The overall odds ratios (with 95% confidence intervals) for current and recent exposure to NSAIDs were 1.77 (1.01 to 3.10) and 1.93 (1.20 to 3.09) respectively. Current and recent exposure to NSAIDs was also associated for incident cases, with odds ratios of 2.96 (1.32 to 6.64) and 2.51 (1.13 to 5.55). There was a trend for recent exposure among non-incident cases. CONCLUSION: The use of NSAIDs may be associated with an increased risk of emergency admission to hospital for colitis due to inflammatory bowel disease, particularly among patients with no previous history.
ENDOCRINE FACTORS IN ACNE VULGARIS.
Authors: E. LIPMAN COHEN
Journal: British Journal of Dermatology (1941)

Journal Article ENDOCRINE FACTORS IN ACNE VULGARIS. Get access E. LIPMAN COHEN, M.B., B.Chir.Cantab. E. LIPMAN COHEN, M.B., B.Chir.Cantab. Physician to the Western Skin Hospital, London Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 53, Issue 10, 1 October 1941, Pages 269–282, https://doi.org/10.1111/j.1365-2133.1941.tb10901.x Published: 01 October 1941
Rheumatoid Arthritis with Lung Lesions
Authors: J. R. Edge, A. G. Rickards
Journal: Thorax (1957)

<b>Introduction:</b> COPD affects large numbers of people of working age. This international study measured the personal, social and economic burden of disease in this population. The age, disease severity, and co-morbidity data are presented according to employment status, to identify the characteristics of individuals across the groups. <b>Method:</b> 2426 respondents from Brazil, China, Germany, Turkey, UK, US were recruited utilising a mixed methods design. Employment status was recorded: currently employed, not working and retired due to COPD. Disease severity was assessed using MRC scores (Mild: 1-2, Mod 3-4, Severe 5). <b>Results:</b> Retirees reported greater disease severity than workers (MRC m: 4.1 v 3.1, p&lt;0.005), more co-morbidities (m: 2.5 v m: 1.1). More retirees reported anxiety and depression. 60% of retirees had mild or moderate disease v 91% in work. 64% (n 284) of early retirees retired over 4 years ago. <b>Conclusions:</b> It is possible that disease severity limits ability to work, however the trigger to retire may also be due to other factors including co-morbidities. Workers registered the lowest prevalence of psychological disorders and it is unclear whether this is due to milder disease, age or employment status. This data suggests employers and occupational health professionals have a key role in keeping people with COPD in active work for longer.
Prospects of zona pellucida glycoproteins as immunogens for contraceptive vaccine
Authors: S. Gupta
Journal: Human Reproduction Update (1997)

The zona pellucida (ZP) surrounding a mammalian oocyte mediates the initial recognition and binding of spermatozoon to oocyte in a relatively species-specific manner and plays an important role in the subsequent activation events during the fertilization process. The ZP comprises three biochemically and immunologically distinct glycoproteins termed ZP1, ZP2 and ZP3. The critical role of ZP glycoproteins in reproduction together with their tissue-specific nature have led to their being considered as potential candidate antigens for immunocontraception. Immunization of females with ZP glycoproteins leads to a block of fertility in several animal models. However, it is invariably associated with either a transient or an irreversible alteration in the cyclicity, hormonal profile and follicular development in the ovary. To overcome these problems, attempts are being made to delineate relevant `B' cell epitopes on ZP proteins so as to design immunocontraceptive vaccines based on synthetic peptides devoid of oophoritogenic `T' cell epitopes. Monoclonal antibodies capable of inhibiting the gamete interaction are being employed to delineate such regions. Additionally, DNA-recombinant technology has made it feasible to obtain, in reasonably large quantities, the ZP glycoproteins from human and non-human primates. Availability of sequence information of these zona proteins and the availability of recombinant antigens (devoid of other ovarian-associated proteins) will further help in understanding more precisely their functions during fertilization and make it feasible to undertake immunization studies to determine their prospects as immunogens for fertility regulation.
The renin–angiotensin system in a rat model of hepatic fibrosis: Evidence for a protective role of Angiotensin-(1–7)
Authors: Regina Maria Pereira, Robson Augusto Souza dos Santos, Mauro Martins Teixeira, Virginia Hora Rios Leite, Lincoln Paiva Costa, Filipi Leles da Costa Dias, Lucíola S. Barcelos, Guilherme Birchal Collares, Ana Cristina Simões e Silva
Journal: Journal of Hepatology (2006)
Testicular Damage by Microcirculatory Disruption and Colonization of an Immune-Privileged Site during <i>Borrelia crocidurae</i> Infection
Authors: Alireza Shamaei-Tousi, Ola Collin, Anders Bergh, Sven Bergström
Journal: The Journal of Experimental Medicine (2001)

The agent of African relapsing fever, Borrelia crocidurae, causes reversible multiple organ damage. We hypothesize that this damage is caused when the spirochete forms aggregate with erythrocytes in vivo, creating rosettes that plug the microcirculatory system. To test this hypothesis, we compared testicular microcirculation over an extended time period in two groups of rats: one experimentally inoculated with B. crocidurae, the other with the nonerythrocyte rosette–forming Borrelia hermsii. In the B. crocidurae group, erythrocyte rosettes formed during spiro-chetemia blocked precapillary blood vessels and reduced the normal pattern of microcirculatory blood flow. After spirochetemia, erythrocyte rosettes disappeared and flow was normalized. Decreased blood flow and focal vascular damage with increased permeability and interstitial bleeding adjacent to the erythrocyte microemboli induced cell death in seminiferous tubules. Interestingly, we found that B. crocidurae could penetrate the tubules and remain in the testis long after the end of spirochetemia, suggesting that the testis can serve as a reservoir for this bacteria in subsequent relapses. The group infected with B. hermsii displayed normal testicular blood flow and vasomotion at all selected time points, and suffered no testicular damage. These results confirmed our hypothesis that the erythrocyte rosettes produce vascular obstruction and are the main cause of histopathology seen in model animal and human infections.
Change in Disability After Hospitalization or Restricted Activity in Older Persons
Authors: Thomas M. Gill, Heather G. Allore, Evelyne A. Gahbauer, Terrence E. Murphy
Journal: JAMA (2010)

ability in essential activities of daily living, such as bathing, dressing, walking, and transferring, is common and associated with increased mortality, institutionalization, and greater use of formal and informal home services. 1Active life expectancy, a metric that is often used by policy makers to forecast the functional health of older persons, is based on disability. 2,3ccording to several conceptual models, 4,5 disability is thought to arise when a vulnerable host is exposed to a new or worsening insult or intervening event.Supporting this theoretical framework, we have shown that intervening events, including illnesses and injuries leading to either hospitalization or restricted activity, are strongly associated with the development of disability in activities of daily living. 6These results, however, were based solely on the initial onset of disability.We have subsequently demonstrated that disability is a complex and highly dynamic process, with high rates of recovery and frequent transitions between states of disability. 7,8The role of intervening events on these transitions is uncertain.The objectives of the current study were to evaluate the association of intervening events with transitions between states of no disability, mild dis-ability, severe disability, and death and to determine the association of physical frailty, the vulnerability factor with the strongest epidemiologic link to disability, 9,10 with these transitions.To ac
Hepatic Imaging: Positron Emission Tomography, Digital Angiography, and Nuclear Magnetic Resonance Imaging
Authors: Alex M. Aisen, William Martel, Gary M. Glazer, Paul L. Carson
Journal: Hepatology (2007)

Major advances in diagnostic imaging of the human body have been made in recent years. Positron emission tomography, a technique founded on advances in radiopharmaceuticals and radionuclide imaging apparatus, permits imaging regional metabolism, metabolite distribution, and flow. Thus far, its major applications have been in the study of the brain, and to a lesser extent, the heart; however, it is also finding a role in the study of the liver. Digital angiography is being applied to fluoroscopic systems which permits visualization of relatively low doses of intravascular iodinated radiographic contrast media. Imaging of the major arteries is possible using simple intravenously administered contrast media; digital techniques also increase the diagnostic yield in intraarterial studies. Nuclear magnetic resonance (NMR) imaging is an outgrowth of laboratory NMR spectroscopy; the interaction of radiofrequency signals with nuclei in strong magnetic fields permits imaging the distribution and certain chemical properties of various isotopes. Hydrogen NMR imaging is proving most useful for clinical diagnosis. The techniques used to image hydrogen are also being applied to NMR spectroscopy in vivo of various isotopes, including carbon-13, phosphorus-31, and hydrogen-1.
CaM Kinase II-dependent pathophysiological signalling in endothelial cells
Authors: H. Cai, D. Liu, J. G.N. Garcia
Journal: Cardiovascular Research (2007)

Calcium/calmodulin-dependent protein kinase II (CaM Kinase II) is a known modulator of cardiac pathophysiology. The present review uniquely focuses on novel CaM Kinase II-mediated endothelial cell signalling which, under pathophysiological conditions, may indirectly modulate cardiac functions via alterations in endothelial or endocardial responses. CaM Kinase II has four different isoforms and various splicing variants for each isoform. The endothelial cell CaM Kinase II isoforms are sensitive to KN93 and a threonine 286-mutated inhibitory peptide. In macrovascular endothelial cells derived from aortas, CaM Kinase II mediates redox-sensitive upregulation of endothelial nitric oxide synthase (eNOS) gene expression by hydrogen peroxide (H2O2) and oscillatory shear stress, and a rapid activation of eNOS in response to bradykinin. In endothelial cells derived from lung microvessels, CaM Kinase II mediates barrier dysfunction, particularly when activated by thrombin. In brain capillary endothelial cells, CaM Kinase II lies upstream of voltage-gated potassium channels and hypoxia-induced cell swelling. In both macrovascular and microvascular endothelial cells, CaM Kinase II mediates actin cytoskeleton reorganization via distinct p38 MAPK/HSP27 and ERK1/2/MLCK signalling pathways, respectively. Although understanding of endothelium-specific CaM Kinase II signalling is nascent, data accumulated so far have demonstrated a potentially significant role of CaM Kinase II in endothelial cell pathophysiology.
UK endoscopy trainees provide a significant quantity of service delivery
Authors: L. P. Griffiths, K. Dowler, R. Valori, P. Dunckley
Journal: Gut (2011)

<h3>Introduction</h3> In September 2009, the JAG Endoscopy Training System (JETS) e-portfolio was launched. Since its release, over 75% of UK trusts have set the system up and over 70 000 procedures logged by trainees. Within the JETS e-portfolio, trainees record their data under pre-defined lists. These are dedicated service lists (reduced points and/or tailored case mix), ad-hoc training lists (training occurring on a standard service list) or service lists. With the European Working Time Directive, trainees have less opportunity for endoscopy training. Furthermore, in a cash-strapped NHS, training may become a low priority over service delivery. We studied the proportion of endoscopies performed on each of the list types by trainees to assess when trainees start to provide service lists within the NHS. <h3>Methods</h3> All endoscopy data from the JETS e-portfolio from September 2009 to 30 October 2010 were analysed. <h3>Results</h3> There were 70 499 procedures from 16 433 procedure lists. All non-trainee roles were then excluded, leaving 60 124 endoscopies performed by trainees, and of these, 22 358 (37%) were on service lists. 34 186 endoscopies were performed by registrar-level doctors and 9726 (28%) of these were on service lists. Of these, gastroenterology registrars did 29 876, of which 8686 on service lists (29%) and GI surgical registrars did 4310, of which 1040 were on service lists (24%) (Figure 1). The remaining 25 938 endoscopies, of which 12 632 were service (47%), were performed by others such as associate specialists and nurse endoscopists. <h3>Conclusion</h3> UK trainee endoscopists contribute towards a large volume of service provision; in fact by year 5, gastroenterology registrars perform the majority of their endoscopies on service lists. This data shows that hospital trusts should prioritise endoscopy training. High quality training will result in competent, experienced, independent trainee endoscopists who can support the service of the trust in which they work and gain further valuable experience.
MicroRNA-148a regulates LDL receptor and ABCA1 expression to control circulating lipoprotein levels
Authors: Leigh Goedeke, Noemi Rotllan, Alberto Canfrán-Duque, Juan F Aranda, Cristina M Ramírez, Elisa Araldi, Chin-Sheng Lin, Norma N Anderson, Alexandre Wagschal, Rafael de Cabo, Jay D Horton, Miguel A Lasunción, Anders M Näär, Yajaira Suárez, Carlos Fernández-Hernando
Journal: Nature Medicine (2015)
Histone Deacetylase Inhibition Blunts Ischemia/Reperfusion Injury by Inducing Cardiomyocyte Autophagy
Authors: Min Xie, Yongli Kong, Wei Tan, Herman May, Pavan K. Battiprolu, Zully Pedrozo, Zhao V. Wang, Cyndi Morales, Xiang Luo, Geoffrey Cho, Nan Jiang, Michael E. Jessen, John J. Warner, Sergio Lavandero, Thomas G. Gillette, Aslan T. Turer, Joseph A. Hill
Journal: Circulation (2014)

Reperfusion accounts for a substantial fraction of the myocardial injury occurring with ischemic heart disease. Yet, no standard therapies are available targeting reperfusion injury. Here, we tested the hypothesis that suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor approved for cancer treatment by the US Food and Drug Administration, will blunt reperfusion injury.Twenty-one rabbits were randomly assigned to 3 groups: (1) vehicle control, (2) SAHA pretreatment (1 day before and at surgery), and (3) SAHA treatment at the time of reperfusion only. Each arm was subjected to ischemia/reperfusion surgery (30 minutes coronary ligation, 24 hours reperfusion). In addition, cultured neonatal and adult rat ventricular cardiomyocytes were subjected to simulated ischemia/reperfusion to probe mechanism. SAHA reduced infarct size and partially rescued systolic function when administered either before surgery (pretreatment) or solely at the time of reperfusion. SAHA plasma concentrations were similar to those achieved in patients with cancer. In the infarct border zone, SAHA increased autophagic flux, assayed in both rabbit myocardium and in mice harboring an RFP-GFP-LC3 transgene. In cultured myocytes subjected to simulated ischemia/reperfusion, SAHA pretreatment reduced cell death by 40%. This reduction in cell death correlated with increased autophagic activity in SAHA-treated cells. RNAi-mediated knockdown of ATG7 and ATG5, essential autophagy proteins, abolished SAHA's cardioprotective effects.The US Food and Drug Administration-approved anticancer histone deacetylase inhibitor, SAHA, reduces myocardial infarct size in a large animal model, even when delivered in the clinically relevant context of reperfusion. The cardioprotective effects of SAHA during ischemia/reperfusion occur, at least in part, through the induction of autophagic flux.