tbuckley/cabot-search huggingface dataset:
Interleukin 17A Exacerbates Atherosclerosis by Promoting Fatty Acid-Binding Protein 4–Mediated ER Stress in Macrophages
Authors: Qi Gao, Yang Jiang, Shen Dai, Bo Wang, Fei Gao, Chun Guo, Faliang Zhu, Qun Wang, Xiaoyan Wang, Jining Wang, Yongyu Shi, Yun Zhang, Wanjun Chen, Lining Zhang
Journal: Circulation Research (2012)

Apoptosis and fatty acid-binding protein-4 (FABP4) induced-endoplasmic reticulum (ER) stress in macrophage is an important pathological process in several vascular occlusive diseases, including atherosclerosis, both of which are accelerated by lipids or inflammatory cytokines.To determine whether interleukin 17A (IL-17A) accelerates atherosclerosis through activating FABP4-mediated ER stress in macrophage.We show here that IL-17A induced ER stress in both murine and human-derived macrophages in vitro, and in the atherosclerotic lesions of ApoE-/- mice. Treating ApoE-/- mice with a chemical chaperone alleviated IL-17A-mediated ER stress and macrophage apoptosis, which was accompanied by recovered atherogenesis. Mechanistically, IL-17A up-regulated the expression of FABP4 (aP2), a cytosolic lipid chaperone that is able to promote lipid-induced macrophage ER stress, through NF-κB and ERK/p38 mitogen-activated protein kinase (MAPK) pathways in macrophages. The inhibition of aP2 expression with a specific chemical inhibitor significantly blocked IL-17A-accelerated ER stress and apoptosis in plaque, and partially rescued IL17A-induced atherogenesis.The data collectively establish a previously unrecognized link between IL-17A and ER stress through cytosolic lipid chaperone aP2 in macrophages and provide a new insight for understanding the role of IL-17A in atherosclerosis.
Shortage of academics threatens rise in number of doctors
Authors: Z. Kmietowicz
Journal: BMJ (2001)

Plans to boost the number of doctors working in the NHS are under threat from a shortage of medical academics at universities in the United Kingdom, the BMA has warned.

There are currently fewer than 1000 clinical academic doctors working in the health service, and 79 professorships at medical schools are unfilled, representing a quarter of all posts funded by the government's higher education funding council.

Professor …
Chronic Renal Allograft Dysfunction
Authors: Helen Robertson, Simi Ali, Benjamin J. McDonnell, Alastair D. Burt, John A. Kirby
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. Chronic graft dysfunction is now the leading clinical problem after renal transplantation. The principal histopathologic lesion seen in this disease is tubular loss with concurrent interstitial fibrosis. Although the severity of acute rejection often correlates with that of subsequent chronic dysfunction, a direct link between these processes has remained elusive. This study was designed to test the hypothesis that intraepithelial T cells recruited to the renal tubules during acute rejection can directly induce fibrosis by causing tubular epithelial cells to undergo transformation to produce a motile population of activated fibroblasts. A study of renal allograft tissue sections showed the presence of the S100A4 marker of epithelial to mesenchymal transition in some tubular epithelial cells; the expression of this antigen was heterogeneous both within and between individual tubular cross-sections. Significantly, S100A4-expressing epithelial cells were frequently associated with infiltrating CD8+ T cells, and many coexpressed the Ki67 marker of proliferation. A parallel study of human renal cortical epithelial cells in primary culture demonstrated that S100A4 was induced by stimulation for 72 h with TGF-β1 and by direct contact with membrane-associated TGF-β on MOLT-16 cells, a model intraepithelial T-cell line. Further experiments demonstrated that induction of transition coincided with a significantly increased potential for human renal epithelial cells to invade the tubular basement membrane. These data are consistent with a model in which intratubular T cells can present TGF-β and directly induce adjacent tubular epithelial cells to transform to proliferating fibroblasts that migrate across the tubular basement membrane, producing fibrotic lesions within the renal interstitium.
Combined TAB Vaccine
Authors: S. B. Werner
Journal: JAMA (1973)

<h3>To the Editor.—</h3> In a brief discussion of salmonellosis in the MEDICAL NEWS section ofThe Journal(222:1117, 1972), the following statement is made: "There is no<i>Salmonella</i>vaccine for humans except<i>S typhi</i>, paratyphoid A and B." This statement leaves the erroneous impression that the combined typhoid and paratyphoid (TAB) vaccine is available. At present, typhoid vaccines are no longer combined with paratyphoid A and B. The effectiveness of paratyphoid A vaccine has never been established and field trials have shown that the small amount of paratyphoid B vaccine present in previous TAB vaccines was not effective.<sup>1</sup>Consequently, and because paratyphoid A and B antigens are believed to increase the risk of vaccine reaction with typhoid vaccine, these were deleted from formulations of typhoid vaccine in the last few years. In addition to the difficulties with the combined vaccine, the need for protection against paratyphoid A and B
Dexamethasone But Not Tadalafil Improves Exercise Capacity in Adults Prone to High-Altitude Pulmonary Edema
Authors: Manuel Fischler, Marco Maggiorini, Lorenz Dorschner, Johann Debrunner, Alain Bernheim, Stephanie Kiencke, Heimo Mairbäurl, Konrad E. Bloch, Robert Naeije, Hans Peter Brunner-La Rocca
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Whether pulmonary hypertension at high altitude limits exercise capacity remains uncertain.To gain further insight into the pathophysiology of hypoxia induced pulmonary hypertension and the resulting reduction in exercise capacity, we investigated if the reduction in hypoxic pulmonary vasoconstrictive response with corticosteroids or phosphodiesterase-5 inhibition improves exercise capacity.A cardiopulmonary exercise test and echocardiography to estimate systolic pulmonary artery pressure were performed in 23 subjects with previous history of high altitude pulmonary edema, known to be associated with enhanced hypoxic vasoconstriction. Subjects were randomized to dexamethasone 8 mg twice a day, tadalafil 10 mg twice a day, or placebo (double-blinded), starting the day before ascent.Measurements were performed at low and high (i.e., 4,559 m) altitude. Altitude exposure decreased maximum oxygen uptake and oxygen saturation, increased pulmonary artery pressure, and altered oxygen uptake kinetics. Compared with placebo, dexamethasone improved maximum oxygen uptake (% predicted 74 +/- 13%; tadalafil 63 +/- 13%, placebo 61 +/- 11%; P < 0.05), oxygen kinetics (mean response time 41 +/- 13 s; tadalafil 46 +/- 6 s, placebo 45 +/- 10 s; P < 0.05), and reduced the ventilatory equivalent for CO(2) (42 +/- 4; tadalafil 49 +/- 4, placebo 50 +/- 5; P < 0.01). Peak oxygen saturation did not differ significantly between the three groups (dexamethasone 66 +/- 7%, placebo 62 +/- 7%, tadalafil 69 +/- 5%; P = 0.08). During echocardiography at low-intensity exercise (40% of peak power), dexamethasone compared with placebo resulted in lower pulmonary artery pressure (47 +/- 9 mm Hg; tadalafil 57 +/- 11 mm Hg, placebo 68 +/- 23 mm Hg; P = 0.05) and higher oxygen saturation (74 +/- 7%; tadalafil 67 +/- 3%, placebo 61 +/- 20; P < 0.02).Corticosteroids, but not phosphodiesterase-5 inhibition, partially prevented the limitation of exercise capacity in subjects with intense hypoxic pulmonary vasoconstriction at high altitude.
Characterization of the sodium current in single human atrial myocytes.
Authors: Y Sakakibara, J A Wasserstrom, T Furukawa, H Jia, C E Arentzen, R S Hartz, D H Singer
Journal: Circulation Research (1992)

Patch-clamp recording techniques have permitted measurement of the fast Na+ current (INa) in isolated cardiac cells from a number of species in recent years. However, there is still only very little information concerning human cardiac INa. The purpose of this study was to describe the kinetics of INa in normal-appearing, Ca(2+)-tolerant, enzymatically isolated human atrial myocytes using whole-cell voltage-clamp techniques. Atrial specimens were obtained from 46 patients undergoing open heart surgery. Cs+ was substituted for K+ in both pipette and external solutions and F- was added to the former. The reversal potential of the rapid inward current varied approximately 57 mV at 17 +/- 1 degrees C with a 10-fold change in [Na+]o, and the current was completely blocked by 100 microM tetrodotoxin, findings typical of the fast cardiac Na+ current. The tetrodotoxin dose-response curve was best fitted by an equation describing binding to high- and low-affinity sites. INa was activated at a voltage threshold of -70 to -60 mV, and peak inward current was obtained at approximately -30 mV (holding potential, -140 mV). The inactivation time course was voltage dependent and was fitted best by the sum of two exponentials. The relation between voltage and steady-state availability (h infinity) was sigmoidal with the half-inactivation at -95.8 +/- 0.9 mV and a slope factor of 5.3 +/- 0.1 mV (n = 46), and we did not observe a significant difference with disease and age. The overlap of the h infinity and activation curves suggested the presence of a Na+ "window" current. Recovery from inactivation also was voltage dependent and best fitted by a model describing the sum of two exponentials. Recovery occurred after an initial delay at potentials positive to -140 mV, suggesting that inactivation of human atrial INa is a multistate process. We conclude that INa of normal-appearing, Ca(2+)-tolerant human atrial myocytes is similar to that of other mammalian cardiac cells with the possible exception of having two tetrodotoxin binding sites.
Acute pancreatitis: the substantial human and financial costs
Authors: J P NEOPTOLEMOS, M RARATY, M FINCH, R SUTTON
Journal: Gut (1998)

A greater understanding of the natural history of acute pancreatitis combined with greatly improved radiological imaging has led to improvement in the hospital mortality from acute pancreatitis, from around 25-30% to 6-10% in the past 30 years. Moreover, it is now recognised that the first phase of severe acute phase pancreatitis is a systemic inflammatory response syndrome (SIRS), during which multiple organ failure and death often supervene. Survival into the second phase may be accompanied by local complications, such as infected pancreatic necrosis, which may be prevented by prophylactic antibiotics and treated by judicious surgery. Intensive care unit costs can be substantial, but might be justified because of the excellent quality of life of survivors. Reduction in multiple organ failure by agents such as lexipafant, an antagonist of platelet activating factor (PAF) (which plays a critical role in generating the SIRS), may contribute to intensive care unit cost containment, as well as reducing the incidence of local complications and deaths from acute pancreatitis. A further improvement in the human and financial costs also requires the centralisation of the management of patients with severe acute pancreatitis, to single hospital units whose concentrated expertise equips them to intervene most effectively in what is still recognised as a highly complex disease.
Obliterative bronchiolitis and alveolitis associated with sulphamethoxypyridazine (Lederkyn) therapy for linear IgA disease of adults
Authors: K.M. Godfrey, F. Wojnarowska, J.S. Friedland
Journal: British Journal of Dermatology (1990)

Journal Article Obliterative bronchiolitis and alveolitis associated with sulphamethoxypyridazine (Lederkyn) therapy for linear IgA disease of adults Get access K.M. Godfrey, K.M. Godfrey Department of Dermatology, The Slade Hospital, Headington, Oxford OX37JH Search for other works by this author on: Oxford Academic Google Scholar F. Wojnarowska, F. Wojnarowska Department of Dermatology, The Slade Hospital, Headington, Oxford OX37JH Search for other works by this author on: Oxford Academic Google Scholar J.S. Friedland J.S. Friedland Nuffield Department of Medicine, John Radcliffe Hospital, Headington, Oxford OX39DU, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 123, Issue 1, 1 July 1990, Pages 125–131, https://doi.org/10.1111/j.1365-2133.1990.tb01833.x Published: 01 July 1990
Prophylaxis with GM-CSF mouthwashes does not reduce frequency and duration of severe oral mucositis in patients with solid tumors undergoing high-dose chemotherapy with autologous peripheral blood stem cell transplantation rescue: a double blind, randomized, placebo-controlled study
Authors: C. Dazzi, A. Cariello, P. Giovanis, M. Monti, B. Vertogen, M. Leoni, A. Tienghi, D. Turci, G. Rosti, O. Nanni, C. Rondoni, M. Marangolo
Journal: Annals of Oncology (2003)
The random inactivation of the X chromosome carrying the defective gene responsible for X-linked hyper IgM syndrome (X-HIM) in female carriers of HIGM1.
Authors: D Hollenbaugh, L H Wu, H D Ochs, S Nonoyama, L S Grosmaire, J A Ledbetter, R J Noelle, H Hill, A Aruffo
Journal: Journal of Clinical Investigation (1994)

The molecular origin of X-linked hyper IgM syndrome has recently been identified as a defect in the ligand of CD40, gp39, a protein expressed on the surface of activated T cells.The availability of detailed pedigrees for three families with affected males allowed assessment of the random or nonran- dom nature of the inactivation of the defective X chromo- some as well as a determination of the origin of the mutation.X chromosome inactivation was studied because of the rele- vance to the ability to detect carriers of HIGM1 and the potential for phenotypic effect in the carriers.Using immu- nostaining, PCR, and DNA sequencing, we found that the defective gene for gp39 is not selectively inactivated.Even in the presence of extremely skewed inactivation, normal levels of serum Ig were found.In carriers in which the defective gene is predominantly expressed, staining alone revealed the carrier status reliably while cloning and se- quencing of the cDNA was necessary when the normal gene was predominantly expressed.Unlike some other X-linked defects where extreme Lyonization may lead to disease, a small population of cells expressing the wild-type gp39 is sufficient to maintain normal humoral immtuniy and pre- vent the clinical symptoms of X-HIM.(
Asthma following occupational exposure to Lycopodium clavatum in condom manufacturers.
Authors: P Cullinan, J Cannon, D Sheril, A Newman Taylor
Journal: Thorax (1993)

Abstract Occupational asthma in two women employed in the manufacture of condoms is reported. The spores of Lycopodium clavatum, used as a rubber dusting agent, were identified as the causative agent.
The Distinctive Nature of HER2-Positive Breast Cancers
Authors: Harold J. Burstein
Journal: New England Journal of Medicine (2005)

Breast cancer is not a single disease but a group of several important tumor subtypes, each with a different natural history and each requiring a different treatment. Overexpression of HER2 (which derives its name from human epidermal growth factor receptor 2) defines one of these unique subtypes. The HER2/neu gene is a member of a family of genes encoding transmembrane receptors for growth factors, including the epidermal growth factor receptor (EGFR), HER2, HER3, and HER4. The intracellular domain of HER2 has tyrosine kinase activity that regulates important aspects of the physiology, growth, and differentiation of cells.1,2 Extracellular domains of . . .
Specific and Generalized Neuropsychological Deficits: A Comparison of Patients With Various First-Episode Psychosis Presentations
Authors: Jolanta Zanelli, Abraham Reichenberg, Kevin Morgan, Paul Fearon, Eugenia Kravariti, Paola Dazzan, Craig Morgan, Caroline Zanelli, Arsime Demjaha, Peter B Jones, Gillian A Doody, Shitij Kapur, Robin M Murray
Journal: American Journal of Psychiatry (2009)

Objective Overwhelming evidence suggests that compromised neuropsychological function is frequently observed in schizophrenia. Neurocognitive dysfunction has often been reported in other psychotic disorders, although there are inconsistencies in the literature. In the context of four distinct diagnostic groups, the authors compared neuropsychological performance among patients experiencing their first psychotic episode. Method Data were derived from a population-based, case-control study of patients with first-episode psychosis. A neuropsychological test battery was administered to patients with a diagnosis of schizophrenia (N=65), bipolar disorder or mania (N=37), depressive psychosis (N=39), or other psychotic disorders (N=46) following index presentation, as well as to healthy comparison subjects (N=177). The presence of specific and generalized cognitive deficits was examined. Results The schizophrenia group presented widespread neuropsychological impairments and performed significantly worse than healthy comparison subjects on most neuropsychological measures. Patients with other psychotic disorders and depressive psychosis also demonstrated widespread impairments. Deficits in patients with bipolar disorder or mania were less pervasive but evident in performance scores on verbal memory and fluency tests. Differences between the four patient groups and healthy comparison subjects and among the patient groups were attenuated after controlling for differences in general cognitive ability (IQ). Conclusions Early in their course, cognitive deficits are present in all psychotic disorders but are most severe and pervasive in schizophrenia and least pervasive in bipolar disorder and mania.
Treatment of Symptomatic Polyneuropathy With Actovegin in Type 2 Diabetic Patients
Authors: Dan Ziegler, Lusine Movsesyan, Boris Mankovsky, Irina Gurieva, Zhangentkhan Abylaiuly, Igor Strokov
Journal: Diabetes Care (2009)

OBJECTIVE To evaluate the efficacy and safety of actovegin in patients with diabetic polyneuropathy. RESEARCH DESIGN AND METHODS In this multicenter, randomized, double-blind trial, 567 patients with type 2 diabetes received 20 intravenous infusions of actovegin (2,000 mg/day) (n = 281) or placebo (n = 286) once daily followed by three tablets of actovegin (1,800 mg/day) or placebo three times daily for 140 days. Total symptom score (TSS) of the lower limbs and vibration perception threshold (VPT) were used as coprimary outcome measures, computed as the area under the curve (AUC) from repeated scores and divided by duration of exposure. Secondary end points included individual TSS symptoms, neuropathy impairment score of the lower limbs (NIS-LL), and quality of life (short form [SF]-36). RESULTS TSS was significantly improved during actovegin treatment compared with placebo, as assessed by AUC (−0.56 points [95% CI −0.85 to −0.27]; P = 0.0003), and from baseline to 160 days (−0.86 points [−1.22 to −0.50]; P &amp;lt; 0.0001). VPT (five sites per foot) decreased by 3% (95% CI 0–6; P = 0.084) with actovegin than placebo, as assessed by AUC, and by 5% (1–9; P = 0.017) after 160 days. NIS-LL sensory function, as assessed by AUC, was significantly improved with actovegin versus placebo (−0.25 [95% CI −0.46 to −0.04]; P = 0.021), as was the SF-36 mental health domain. There were no differences in the incidence of adverse events between the groups. CONCLUSIONS Sequential intravenous and oral actovegin treatment over 160 days improved neuropathic symptoms, VPT, sensory function, and quality of life in type 2 diabetic patients with symptomatic polyneuropathy.
High Rate of Infectivity and Liver Disease in Blood Donors with Antibodies to Hepatitis C Virus
Authors: J I Esteban, J C López-Talavera, J Genescà, P Madoz, L Viladomiu, E Muñiz, C Martin-Vega, M Rosell, H Allende, X Vidal
Journal: Annals of Internal Medicine (1991)

▪Objective: To determine the epidemiologic, clinical, serologic, and histologic importance of antibodies to hepatitis C virus (anti-HCV) in blood donors. ▪Design: Cross-sectional identification and prospective evaluation of seropositive donors; retrospective assessment of infectivity; and nested case-control study for risk factors. ▪Setting: Liver unit of a referral-based university hospital. ▪Subjects: Of 30 231 consecutive donors, 368 (1. 2%) were found to be anti-HCV-reactive by enzyme-linked immunosorbent assay (ELISA). Two hundred and fifty-four of these 368 donors were evaluated for risk factors by comparison with 284 age- and sex-matched controls. Eighty-six spouses of seropositive donors were also evaluated. ▪Measurements and Main Results: Twenty-four percent of the seropositive donors had a history of percutaneous exposure to blood. This rate increased to 45% when only those donors confirmed to be anti-HCV positive by a second-generation recombinant immunoblot assay (RIBA-2) were considered. A family history of liver disease (odds ratio, 2.8; 95% Cl, 1.6 to 4.8), previous blood transfusion (odds ratio, 6.1; 95% Cl, 3 to 12.5), and a history of tattooing or intravenous drug abuse (odds ratio, 8.4; 95% Cl, 2.3 to 31) were associated with anti-HCV seropositivity. An elevated alanine aminotransferase (ALT) level was found in 58% of the seropositive donors. Of the 150 donors tested, 104 (69%; Cl, 62% to 77%) were confirmed by RIBA-2 to be anti-HCV positive. Of the 105 donors who had a biopsy, 16% had normal histologic findings, 11 % had minimal changes, 21% had chronic persistent hepatitis, 45% had chronic active hepatitis, and 7% had active cirrhosis. All 77 donors with RIBA-2-confirmed seropositivity had histologic abnormalities. Of 43 donors evaluated in an infectivity study, 82% were implicated in previous HCV transmission. Only 2.3% of the spouses were anti-HCV positive. The ELISA, RIBA-2, and ALT results correlated with infectivity and abnormal histologic findings. ▪Conclusions: In our geographic area, almost 70% of donors who are anti-HCV positive by ELISA are confirmed to be positive by RIBA-2; most of these donors appear to be chronic carriers of HCV and have substantial liver disease.
Viral regulation of inflammatory cytokines in epithelial cells: an alternative signalling pathway
Authors: I S Patel
Journal: Thorax (2003)

▴ Meusel TR, Imani F. Viral induction of inflammatory cytokines in human epithelial cells follows a p38 mitogen-activated protein kinase-dependent but NF-κB-independent pathway. J Immunol2003;171:3768–74 [OpenUrl][1][Abstract/FREE Full Text][2] Respiratory viruses primarily target the bronchial epithelium and induce the expression of several inflammatory cytokines and chemokines. These include tumour necrosis factor alpha (TNF-α) and interleukin 1β (IL-1β) which are key regulatory factors in the early induction of inflammation and Th1/Th2 immune responses. A number of cellular signalling pathways are thought to play a role in this context including nuclear factor-κB (NF-κB), a ubiquitous transcription factor which … [1]: {openurl}?query=rft.jtitle%253DThe%2BJournal%2Bof%2BImmunology%26rft.stitle%253DJ.%2BImmunol.%26rft.issn%253D0022-1767%26rft.aulast%253DMeusel%26rft.auinit1%253DT.%2BR.%26rft.volume%253D171%26rft.issue%253D7%26rft.spage%253D3768%26rft.epage%253D3774%26rft.atitle%253DViral%2BInduction%2Bof%2BInflammatory%2BCytokines%2Bin%2BHuman%2BEpithelial%2BCells%2BFollows%2Ba%2Bp38%2BMitogen-Activated%2BProtein%2BKinase-Dependent%2Bbut%2BNF-%257Bkappa%257DB-Independent%2BPathway%26rft_id%253Dinfo%253Adoi%252F10.4049%252Fjimmunol.171.7.3768%26rft_id%253Dinfo%253Apmid%252F14500677%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/ijlink?linkType=ABST&journalCode=jimmunol&resid=171/7/3768&atom=%2Fthoraxjnl%2F58%2F12%2F1019.atom