tbuckley/cabot-search huggingface dataset:
The antagonism of histamine <scp>H</scp>1 and <scp>H</scp>4 receptors ameliorates chronic allergic dermatitis via anti‐pruritic and anti‐inflammatory effects in <scp>NC</scp>/<scp>N</scp>ga mice
Authors: Y. Ohsawa, N. Hirasawa
Journal: Allergy (2012)

Although histamine H1 receptor (H1R) antagonists are commonly used to treat atopic dermatitis, the treatment is not always effective. The histamine H4 receptor (H4R) was recently described as important to the pruritus in dermatitis. Here, we investigated whether the combination of a H1R antagonist plus a H4R antagonist attenuates chronic dermatitis in NC/Nga mice.Chronic dermatitis was developed by repeated challenges with picryl chloride on the dorsal back and ear lobes. The therapeutic effects of the H1R antagonist olopatadine and H4R antagonist JNJ7777120 on scratching and the severity of dermatitis were evaluated. In addition, the mechanisms responsible for the anti-allergic effects of H1R and/or H4R antagonism were examined using bone marrow-derived mast cells (BMMC) and keratinocytes.JNJ7777120 attenuated scratching behavior after a single administration and improved dermatitis, as assessed with clinical scores, pathology, and cytokine levels in skin lesions when administered repeatedly. These effects were augmented by combined treatment with olopatadine, having a similar therapeutic efficacy to prednisolone. JNJ7777120 inhibited dose-dependently the production of thymus and activation-regulated chemokine/CCL17 and macrophage-derived chemokine/CCL22 from antigen-stimulated BMMC. In addition, olopatadine reversed the histamine-induced reduction of semaphorin 3A mRNA in keratinocytes.Combined treatment with H1R and H4R antagonists may have a significant therapeutic effect on chronic dermatitis through the synergistic inhibition of pruritus and skin inflammation.
COMPARATIVE CORONARY REVASCULARIZATION RATES FOLLOWING FRACTIONAL FLOW RESERVE AMONGST MEN AND WOMEN IN THE UNITED STATES
Authors: Vladimir Lakhter, Yevgeniy Brailovsky, Chad J. Zack, John Gaughan, Alfred A. Bove, Howard A. Cohen, Riyaz Bashir
Journal: Journal of the American College of Cardiology (2013)
Circulating IgA and IgE autoantibodies in antilaminin-332 mucous membrane pemphigoid
Authors: K. Natsuga, W. Nishie, S. Shinkuma, R. Moriuchi, M. Shibata, M. Nishimura, T. Hashimoto, H. Shimizu
Journal: British Journal of Dermatology (2009)

Journal Article Circulating IgA and IgE autoantibodies in antilaminin‐332 mucous membrane pemphigoid Get access K. Natsuga, K. Natsuga Department of Dermatology, Hokkaido University Graduate School of Medicine, North 15 West 7, Sapporo 060‐8638, Japan Ken Natsuga. E‐mail: natsuga@med.hokudai.ac.jp Search for other works by this author on: Oxford Academic Google Scholar W. Nishie, W. Nishie Department of Dermatology, Hokkaido University Graduate School of Medicine, North 15 West 7, Sapporo 060‐8638, Japan Search for other works by this author on: Oxford Academic Google Scholar S. Shinkuma, S. Shinkuma Department of Dermatology, Hokkaido University Graduate School of Medicine, North 15 West 7, Sapporo 060‐8638, Japan Search for other works by this author on: Oxford Academic Google Scholar R. Moriuchi, R. Moriuchi Department of Dermatology, Hokkaido University Graduate School of Medicine, North 15 West 7, Sapporo 060‐8638, Japan Search for other works by this author on: Oxford Academic Google Scholar M. Shibata, M. Shibata Department of Dermatology, Hokkaido University Graduate School of Medicine, North 15 West 7, Sapporo 060‐8638, Japan Search for other works by this author on: Oxford Academic Google Scholar M. Nishimura, M. Nishimura Department of Dermatology, Hokkaido University Graduate School of Medicine, North 15 West 7, Sapporo 060‐8638, Japan Search for other works by this author on: Oxford Academic Google Scholar T. Hashimoto, T. Hashimoto Department of Dermatology, Kurume University School of Medicine, Kurume, Japan Search for other works by this author on: Oxford Academic Google Scholar H. Shimizu H. Shimizu Department of Dermatology, Hokkaido University Graduate School of Medicine, North 15 West 7, Sapporo 060‐8638, Japan Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 162, Issue 3, 1 March 2010, Pages 513–517, https://doi.org/10.1111/j.1365-2133.2009.09508.x Published: 01 March 2010
UK encourages unrealistic expectations among overseas applicants for training
Authors: M K Sridhar
Journal: BMJ (1998)

Editor—The current situation regarding overseas graduates and training posts in the United Kingdom is unsatisfactory. I recently went through 147 applications for four senior house officer posts in medicine at the district general hospital where I work. Of these, four were from British nationals (two of whom were graduates of British universities). Most applicants were graduates from India (77), with the others being from African countries (16), Germany (9), Greece (8), the Middle East (6), Myanmar (3), Pakistan (3), and Sri Lanka (3). …
Regulation of memory B-cell survival by the BH3-only protein Puma
Authors: Cyril Clybouw, Silke Fischer, Marie Thérèse Auffredou, Patricia Hugues, Catherine Alexia, Philippe Bouillet, Martine Raphael, Gérald Leca, Andreas Strasser, David M. Tarlinton, Aimé Vazquez
Journal: Blood (2011)
Control of Pancreatic β Cell Regeneration by Glucose Metabolism
Authors: Shay Porat, Noa Weinberg-Corem, Sharona Tornovsky-Babaey, Rachel Schyr-Ben-Haroush, Ayat Hija, Miri Stolovich-Rain, Daniela Dadon, Zvi Granot, Vered Ben-Hur, Peter White, Christophe A. Girard, Rotem Karni, Klaus H. Kaestner, Frances M. Ashcroft, Mark A. Magnuson, Ann Saada, Joseph Grimsby, Benjamin Glaser, Yuval Dor
Journal: Cell Metabolism (2011)
Screening of Anaplastic Lymphoma Kinase Rearrangement by Immunohistochemistry in Non-small Cell Lung Cancer: Correlation with Fluorescence In Situ Hybridization
Authors: Jin Ho Paik, Gheeyoung Choe, Hyojin Kim, Ji-Young Choe, Hyun Ju Lee, Choon-Taek Lee, Jong Seok Lee, Sanghoon Jheon, Jin-Haeng Chung
Journal: Journal of Thoracic Oncology (2011)
Morphine-Prostigmin Test Effect on Tc-99m DISIDA Cholescintigraphy
Authors: RODOLFO E. LIM, EVA V. DUBOVSKY, LEONARD OU TIM, W NEWLON TAUXE
Journal: Clinical Nuclear Medicine (1982)

LIM, RODOLFO E. M.D.*; DUBOVSKY, EVA V. M.D.*; TIM, LEONARD OU M.D.†; TAUXE, W NEWLON M.D.* Author Information
Riding for people with disability
Authors: G Peacock
Journal: BMJ (1994)

reported by Super and colleagues, one had completed their family and another five did not request parental diagnosis.This contrasts with the 12 heterozygous couples detected through our antenatal screening programmes,23 all of whom have requested prenatal diagnosis.It is impossible to measure the theoretical effectiveness of cascade testing by simple extrapolation.It is necessary to create models with family size distributions and alternative testing strategies.Our projections, using such modelling, suggest that less than 25% of heterozygous couples be detected by cascading to the second cousin level.4In contrast, we have already shown that over 50% of heterozygous couples can be detected by either of the two major forms of antenatal screening.
Quantifying the Impact of Protein Tertiary Structure on Molecular Evolution
Authors: S. C. Choi, A. Hobolth, D. M. Robinson, H. Kishino, J. L. Thorne
Journal: Molecular Biology and Evolution (2007)

To investigate the evolutionary impact of protein structure, the experimentally determined tertiary structure and the protein-coding DNA sequence were collected for each of 1,195 genes. These genes were studied via a model of sequence change that explicitly incorporates effects on evolutionary rates due to protein tertiary structure. In the model, these effects act via the solvent accessibility environments and pairwise amino acid interactions that are induced by tertiary structure. To compare the hypotheses that structure does and does not have a strong influence on evolution, Bayes factors were estimated for each of the 1,195 sequences. Most of the Bayes factors strongly support the hypothesis that protein structure affects protein evolution. Furthermore, both solvent accessibility and pairwise interactions among amino acids are inferred to have important roles in protein evolution. Our results also indicate that the strength of the relationship between tertiary structure and evolution has a weak but real correlation to the annotation information in the Gene Ontology database. Although their influences on rates of evolution vary among protein families, we find that the mean impacts of solvent accessibility and pairwise interactions are about the same.
Notch2 Receptor Signaling Controls Functional Differentiation of Dendritic Cells in the Spleen and Intestine
Authors: Kanako L. Lewis, Michele L. Caton, Milena Bogunovic, Melanie Greter, Lucja T. Grajkowska, Dennis Ng, Apostolos Klinakis, Israel F. Charo, Steffen Jung, Jennifer L. Gommerman, Ivaylo I. Ivanov, Kang Liu, Miriam Merad, Boris Reizis
Journal: Immunity (2011)
Gastrointestinal symptoms during the first week of intensive care are associated with poor outcome: a prospective multicentre study
Authors: Annika Reintam Blaser, Martijn Poeze, Manu L. N. G. Malbrain, Martin Björck, Heleen M. Oudemans-van Straaten, Joel Starkopf
Journal: Intensive Care Medicine (2013)

The study aimed to develop a gastrointestinal (GI) dysfunction score predicting 28-day mortality for adult patients needing mechanical ventilation (MV). 377 adult patients from 40 ICUs with expected duration of MV for at least 6 h were prospectively studied. Predefined GI symptoms, intra-abdominal pressures (IAP), feeding details, organ dysfunction and treatment were documented on days 1, 2, 4 and 7. The number of simultaneous GI symptoms was higher in nonsurvivors on each day. Absent bowel sounds and GI bleeding were the symptoms most significantly associated with mortality. None of the GI symptoms alone was an independent predictor of mortality, but gastrointestinal failure (GIF)—defined as three or more GI symptoms—on day 1 in ICU was independently associated with a threefold increased risk of mortality. During the first week in ICU, GIF occurred in 24 patients (6.4 %) and was associated with higher 28-day mortality (62.5 vs. 28.9 %, P = 0.001). Adding the created subscore for GI dysfunction (based on the number of GI symptoms) to SOFA score did not improve mortality prediction (day 1 AUROC 0.706 [95 % CI 0.647–0.766] versus 0.703 [95 % CI 0.643–0.762] in SOFA score alone). An increasing number of GI symptoms independently predicts 28 day mortality with moderate accuracy. However, it was not possible to develop a GI dysfunction score, improving the performance of the SOFA score either due to data set limitations, definition problems, or possibly indicating that GI dysfunction is often secondary and not the primary cause of other organ failure.
Pergolide for the Treatment of Pituitary Tumors Secreting Prolactin or Growth Hormone
Authors: David L. Kleinberg, Aubrey E. Boyd, Sharon Wardlaw, Andrew G. Frantz, Ajax George, Nick Bryan, Sadek Hilal, Joanne Greising, Dale Hamilton, Terry Seltzer, Cynda J. Sommers
Journal: New England Journal of Medicine (1983)

We gave pergolide mesylate, a new long-acting ergot derivative with dopaminergic properties, to 47 patients with hypersecretion of prolactin or growth hormone. Single doses produced long-lasting reductions of serum prolactin levels; after 24 hours, the values remained depressed at a mean of 28.8 per cent of the base-line value. Among 41 patients (22 women and 19 men) with hyperprolactinemia who took pergolide for three months or more, prolactin levels fell to normal in 37 and remained slightly elevated in 2. In the two patients in whom the levels fell to only 38 to 52 per cent of base line, treatment was regarded as a failure. The level of growth hormone fell to a mean of 52.8 per cent of base line in patients with acromegaly who were taking 100 μg of pergolide per day. Among patients for whom adequate CT scans were available, definite tumor shrinkage occurred in 10 of 13 with macroadenomas and definite or probable shrinkage in 5 of 9 with microadenomas. Menses returned in 76 per cent of treated women and testosterone levels rose in 10 of 14 men. We conclude that pergolide reduces hypersecretion and shrinks most prolactin-secreting macroadenomas. In some patients long-term pergolide therapy may be superior to surgery and x-ray treatment. (N Engl J Med 1983; 309:704–9.)
931. Refractory Period Prolongation by Fibroblasts Overexpressing the Mutant Kv1.3 H401W Channel in Computer Simulation and Pig Hearts
Authors: Ariel Shabtay, Tal Bresler, Lior Yankelson, Lior Gepstein, Shimon Marom, Yair Feld
Journal: Molecular Therapy (2005)

Prolongation of the refractory period is one of the therapeutical strategies for the treatment of cardiac arrhythmias. The Kv1.3 channel have a long tail current causing it to be attractive as a potential modulator of cardiac effective refractory period (ERP) when overexpressed by cardiomyocytes or other cells electrically coupled with cardiomyocytes. It was previously demonstrated that Kv1.3 channel in which the histidine at position 401 was replaced by tryptophan (Kv1.3 H401W) introduced a rapid inactivation property to the channel. Preliminary analysis suggested that the effect of the mutation is caused by slowing down of the recovery rate from inactivation. In this channel recovery from inactivation involved passing through the open state. It was therefore expected that the mutant channel will have extremely long tail current. In this work the possibility of prolonging the refractory period of pig hearts at specific loci by transplantation of fibroblasts overexpressing GFP, the wild type (WT) Kv1.3 channel, and the Kv1.3 H401W was evaluated by computer simulation and in vivo experiments.
Apurinic Endonuclease Activity in Adult Gliomas and Time to Tumor Progression after Alkylating Agent-Based Chemotherapy and after Radiotherapy
Authors: Michael S. Bobola, Mary J. Emond, A. Blank, Elizabeth H. Meade, Douglas D. Kolstoe, Mitchel S. Berger, Robert C. Rostomily, Daniel L. Silbergeld, Alexander M. Spence, John R. Silber
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Apurinic/apyrimidinic endonuclease (Ap endo) is a key DNA repair enzyme that cleaves DNA at cytotoxic abasic sites caused by alkylating agents and radiation. We have observed that human glioma cells deficient in Ap endo activity are hypersensitive to clinically used alkylators (Silber et al., Clin Cancer Res 2002;8:3008.). Here we examine the association of glioma Ap endo activity with clinical response after alkylating agent-based chemotherapy or after radiotherapy. Experimental Design: Cox proportional hazards regression models were used to analyze the relationship of Ap endo activity with time to tumor progression (TTP). Results: In a univariate model with Ap endo activity entered as a continuous variable, the hazard ratio (HR) for progression after alkylator therapy in 30 grade III gliomas increased by a factor of 1.061 for every 0.01 increase in activity (P = 0.013). Adjusting for age, gender, extent of resection, and prior treatment strengthened slightly the association (HR = 1.094; P = 0.003). Similarly, the HR for progression after radiotherapy in 44 grade II and III tumors increased by a factor of 1.069 (P = 0.008). Adjusting for the aforementioned variables had little effect on the association. In contrast, we observed no association between activity and TTP in grade IV gliomas after either alkylator therapy in 34 tumors or radiotherapy in 26 tumors. Conclusions: Our data suggest that Ap endo activity mediates resistance to alkylating agents and radiation and may be a useful predictor of progression after adjuvant therapy in a subset of gliomas.
An Outbreak of Acute Gastroenteritis among Troops in a Large Training Area
Authors: A. H. D. Smith, D. J. Davies
Journal: BMJ (1941)

MIEDIC AL JOURNAL cases are the response of the tissues (anergy or allergy) to a tuberCulous invader, but it is more than likely that the second stage in infection is a non-specific one, and that the appearances of disease of a common sort are only produLced when the balance between attack and defence is so disturbed as to allow of the development of the pro- liferative lesions of the third stage of' disease, with the characteristic tissuie immunity.Summary An unusLual case of sarcoidosis is described, with visceral- ization" in the nervous system, producing Adie's syndrome.Episcleritis and Luveo-parotitis oCCLerred later in the same patient.A general discussion of the possible mechanisms of infection is attempted, and it is maintained that conditions such as sarcoiditis represent a non-specific second stage of disease.
Effects of acidosis and hypoxia on the response of isolated ferret cardiac muscle to inotropic agents
Authors: N Than, N Shah, J White, J A Lee, C H Orchard
Journal: Cardiovascular Research (1994)

Objective: The aim was to study the effects of acidosis and hypoxia on the response of cardiac muscle to inotropic agents which (a) act predominantly by increasing intracellular [Ca2+] (raising extracellular [Ca2+], noradrenaline, isoprenaline) and (b) act partly (phenylephrine) or predominantly (EMD 57033) by increasing myofilament calcium sensitivity. Methods: The experiments were performed on isometrically contracting, isolated ferret papillary muscles (n = 45). For each intervention dose-response curves were performed in control solution (pH 7.35), in hypercapnic acidosis (pH 6.85), and in hypoxia (produced by replacing O2 with N2 in the superfusing solution). In some experiments, the photoprotein aequorin was microinjected into superficial cells of the preparation in order to measure intracellular [Ca2+] as well as force. Results: The results were broadly similar for both classes of inotropic agent. Acidosis caused a shift of the pCa-tension curve to the right (desensitisation of the myofilaments to calcium), but had no significant effect on maximum force. A sufficient inotropic stimulus supplied by either class of inotropic agent could completely reverse the negative inotropic effects of acidosis. The main difference between the two inotropic mechanisms was that the enhanced force produced by calcium sensitisers was associated with a reduction in calcium transient amplitude, while the other inotropes increased the amplitude. The main effect of hypoxia was to decrease maximum force. All the inotropes tested were relatively ineffective in reversing the force depression due to hypoxia. Conclusions: The negative inotropic effects of acidosis can be reversed by a sufficiently large inotropic stimulus. Since calcium transient amplitude is already increased in acidosis, the results suggest that calcium sensitisers are likely to be less arrhythmogenic in this situation. The relative ineffectiveness of the inotropes in hypoxia indicates that the main mechanisms causing reduced force in this situation lie downstream of the mechanisms of action of the inotropic agents tested. Cardiovascular Research 1994;28:1209-1217
INTRAVASCULAR ULTRASOUND MORPHOLOGY OF CULPRIT LESIONS AND CLINICAL DEMOGRAPHICS IN PATIENTS WITH ACUTE CORONARY SYNDROME IN RELATION TO LOW-DENSITY LIPOPROTEIN CHOLESTEROL LEVELS AT ONSET
Authors: Kenichi Tsujita, Naoko Takaoka, Koichi Kaikita, Seiji Hokimoto, Tadasuke Chitose, Takamichi Ono, Michio Mizobe, Eiji Horio, Koji Sato, Naoki Nakayama, Shinji Tayama, Seigo Sugiyama, Sunao Nakamura, Hisao Ogawa
Journal: Journal of the American College of Cardiology (2012)
Relative lack of coronary blood flow during closed-chest resuscitation in dogs.
Authors: R V Ditchey, J V Winkler, C A Rhodes
Journal: Circulation (1982)

Recent studies have shown that blood flow during closed-chest cardiopulmonary resuscitation (CPR) results primarily from generalized changes in intrathoracic pressure rather than direct compression of the heart. Since ascending aortic and right atrial pressures rise and fall synchronously and to comparable levels during CPR, we hypothesized that the absence of a pressure difference across the coronary vascular bed during CPR precludes coronary blood flow. To test this hypothesis, we compared high-fidelity ascending aortic and right atrial pressures and carotid and coronary blood flow (electromagnetic flowmeters) during closed-chest CPR in 12 fibrillating dogs. Chest compression force was increased from 40 to 140 pounds in 20-pound increments using a pneumatic chest compression device. Although ascending aortic and right atrial pressures were always similar, high-compression-force CPR produced small mean pressure differences across the coronary vascular bed (5.6 +/- 0.8 mm Hg [+/- SEM] at 140 pounds). These pressure differences were accompanied by low levels of coronary blood flow. However, coronary flow was less than 1% control (prearrest) values whenever chest compression force was less than 100 pounds, and carotid flow exceeded coronary flow under all conditions (carotid and coronary flows at 140 pounds = 26.2 +/- 6.4% and 4.3 +/- 2.0% of prearrest values, respectively, p less than 0.01). We conclude that generalized changes in intrathoracic vascular pressures during closed-chest CPR promote carotid but not coronary blood flow. High-compression-force CPR produces small pressure differences across the coronary vascular bed, allowing low levels of coronary flow. However, even high-compression-force CPR is over six times more effective in maintaining carotid flow than coronary flow.
Partial belief as a solution to the logical problem of holding simultaneous, contrary beliefs in self-deception research
Authors: Keith Gibbins
Journal: Behavioral and Brain Sciences (1997)

A major worry in self-deception research has been the implication that people can hold a belief that something is true and false at the same time: a logical as well as a psychological impossibility. However, if beliefs are held with imperfect confidence, voluntary self-deception in the sense of seeking evidence to reject an unpleasant belief becomes entirely plausible and demonstrably real.