tbuckley/cabot-search huggingface dataset:
Essence of education in dermatology
Authors: S. Chua, M. Pitts, J. Li
Journal: British Journal of Dermatology (2015)

Journal Article Essence of education in dermatology Get access S. Chua, S. Chua Duke NUS Graduate Medical School Singapore City SingaporeSchool of Medicine Duke University Durham NC U.S.A Search for other works by this author on: Oxford Academic Google Scholar M. Pitts, M. Pitts Pritzker School of Medicine University of Chicago Chicago IL U.S.A Search for other works by this author on: Oxford Academic Google Scholar J. Li J. Li Department of Rheumatology Jiangsu University Affiliated Hospital Jiangsu China Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 173, Issue 3, 1 September 2015, Page 864, https://doi.org/10.1111/bjd.13739 Published: 01 September 2015
Epidemiological data and correlation with bronchoscopic findings in first diagnosis of lung cancer in the last 3 years in a tertiary Greek hospital
Authors: Marousa Kouvela, Evangelos Balis, Nikolaos Tatsis, Marios Kougias, Stavroula Boulia, Vasiliki Lazarou, Georgios Boulbasakos, Georgios Tatsis
Journal: European Respiratory Journal (2012)

Introduction: Lung cancer remains in Europe the second most frequent type of malignancy. In Greece, even though the incidence of lung cancer continues to grow, there is not enough epidemiological data. Our aim was to conduct a retrospective epidemiological study using the large pool of data from our Bronchoscopic Unit.  Methods: In a total of 235 patients, diagnosed with lung cancer by histological and/or cytological bronchoscopic findings(2009-2011), we conducted a correlation between demographic and medical data at the time of diagnosis with the type of lung cancer.  Results: The mean age of first diagnosis was between 60-70 years (33%) and the male to female ratio was 3.8:1. There was no significant difference between the three most common histological types (ADLC -24%, SqCLC-21%, SCLC-22%), and 1/4 of the patients were found to have distal locations at the time of diagnosis. The smoking history of the patients had the strongest correlation with all lung cancer types.The most common first symptom was persistent cough for ADCL (18%), haemoptysis for SqCLC (21%) and symptoms of advanced disease in SCLC (25%). In all types of cancer, the most common radiologic finding was lung nodule (60%),the main endobronchial finding was a mass causing obstruction of the bronchus (45%) and almost half of the patients (45%) had lymphnodes hyperplasia.  Discussion: In contrast with European data, the SCLC retains a high percentage between all histological types of lung cancer. Smoking is confirmed to have the strongest correlation with all lung cancer types. The mean age of first diagnosis is lower than expected from studies conducted in the US.
SUPPRESSION OF ANTIBODY SYNTHESIS AND PROLONGATION OF HOMOGRAFT SURVIVAL BY CHLORAMPHENICOL
Authors: Austin S. Weisberger, Thomas M. Daniel, Allan Hoffman
Journal: The Journal of Experimental Medicine (1964)

Chloramphenicol suppresses primary antibody synthesis in vivo without affecting the ability to develop a normal anamnestic response. Chloramphenicol also prolongs homograft survival in rabbits. The survival of homografts is related to the duration as well as to the amount of chloramphenicol administered. The mechanism of action of chloramphenicol in suppressing immune responses is correlated with its ability to inhibit protein synthesis in proliferating mammalian cells. These observations suggest that the inhibitory effect of chloramphenicol on protein synthesis may be applicable to mammalian cells in vivo as well as to cell-free systems and to intact mammalian cells in vivo.
AN INHERITED X-LINKED SERUM SYSTEM IN MAN
Authors: Kåre Berg, Alexander G. Bearn
Journal: The Journal of Experimental Medicine (1966)

The detection of an inherited X-linked serum system in man, disclosed by a heteroantisenim made specific by absorption, is described. These studies suggest that the antigen, demonstrated by the specific antiserum, resides in the alpha(2)-macroglobulin fraction of serum. The system has been named the Xm system, where X refers to the localization of the gene on the X chromosome, and the m indicates that the antigen is part of the alpha(2)-macroglobulin fraction. The distribution of phenotypes in unrelated individuals from 4 populations, as well as studies performed in families are consistent with an X-linked dominant mode of inheritance. One Xm(a-) daughter was found in a family where the father was Xm(a+). This finding is discussed with particular reference to the possible influence of sex and age on the development of the phenotype. This common X-linked marker is likely to prove useful in mapping the human X chromosome.
The nature of medical evidence and its inherent uncertainty for the clinical consultation: qualitative study
Authors: Frances Griffiths, Eileen Green, Maria Tsouroufli
Journal: BMJ (2005)

To describe how clinicians deal with the uncertainty inherent in medical evidence in clinical consultations.Qualitative study.Clinical consultations related to hormone replacement therapy, bone densitometry, and breast screening in seven general practices and three secondary care clinics in the UK NHS.Women aged 45-64.45 of the 109 relevant consultations included sufficient discussion for analysis. The consultations could be categorised into three groups: focus on certainty for now and this test, with slippage into general reassurance; a coherent account of the medical evidence for risks and benefits, but blurring of the uncertainty inherent in the evidence and giving an impression of certainty; and acknowledging the inherent uncertainty of the medical evidence and negotiating a provisional decision.Strategies health professionals use to cope with the uncertainty inherent in medical evidence in clinical consultations include the use of provisional decisions that allow for changing priorities and circumstances over time, to avoid slippage into general reassurance from a particular test result, and to avoid the creation of a myth of certainty.
MHC Class II DRB Variability and Parasite Load in the Striped Mouse (Rhabdomys pumilio) in the Southern Kalahari
Authors: Götz Froeschke, Simone Sommer
Journal: Molecular Biology and Evolution (2005)

Major histocompatibility complex (MHC) variability is believed to be maintained by pathogen-driven selection, mediated either through heterozygous advantage or frequency-dependent selection. However, empirical support for these hypotheses under natural conditions is rare. In this study, we investigated the genetic constitution of the functionally important MHC class II gene (DRB exon 2) and the parasite load in a population of the striped mouse (Rhabdomys pumilio) in the Southern Kalahari. Fifty-eight individuals were genetically examined and the endoparasite load was quantified by counting fecal helminth eggs by using a modified McMaster technique. Thirty-four animals (58.6%) were infected. We identified 20 different MHC alleles with high levels of sequence divergence between alleles. Particularly, the antigen-binding sites revealed a significant higher rate of nonsynonymous substitutions (dN) than synonymous substitutions (dS), giving strong evidence of balancing selection. Heterozygosity did influence the infection status (being infected or not) and the individual fecal egg count (FEC) value with significantly higher values observed in homozygous individuals. Furthermore, a positive relationship was found between specific alleles and parasite load. The allele Rhpu-DRB*1 significantly occurred more frequently in infected individuals and in individuals with high FEC values (high parasite load). Individuals with the allele Rhpu-DRB*1 had a 1.5-fold higher chance of being infected than individuals without this allele (odds ratio test, P < 0.05). Contrarily, the allele Rhpu-DRB*8 significantly occurred more frequent in individuals with low FEC values. Our results support the hypotheses that MHC polymorphism in R. pumilio is maintained through pathogen-driven selection acting by both heterozygosity advantage and frequency-dependent selection.
Circulating catecholamines in exercise and hyperventilation induced asthma.
Authors: P J Barnes, M J Brown, M Silverman, C T Dollery
Journal: Thorax (1981)

Plasma noradrenaline, adrenaline, and cyclic 3959 AMP (cAMP) were measured in seven asthmatic patients with known exercise-induced bronchospasm and six matched non-atopic control subjects during a standard treadmill exercise test and then during matched isocapnic hyperventilation. Normal subjects showed a 5.5 fold rise in noradrenaline and a 3.2 fold rise in adrenaline during exercise compared with a 2.1 fold rise in noradrenaline and no significant rise in adrenaline in asthmatics who all developed bronchoconstriction after exercise (mean fall in peak flow rate 28.4 +/- 5.8%). Plasma cAMP rose 1.4 fold in controls but showed no significant rise in asthmatics. This reduced sympatho-adrenal response to exercise in asthmatics is difficult to explain. The failure of circulating catecholamines to rise and stimulate beta adrenoceptors on the mast cell may facilitate the release of bronchoconstrictor mediators. Matched hyperventilation produced bronchospasm in asthmatics (mean fall in peak flow rate 29.0 +/- 4.4%) but no change in catecholamines in either group suggesting that circulating catecholamines have no direct role in exercise-induced bronchospasm but may play a permissive role via the mast cell.
Cyclooxygenase-2 Inhibition Does Not Improve the Reduction in Ductal Carcinoma <i>In situ</i> Proliferation with Aromatase Inhibitor Therapy: Results of the ERISAC Randomized Placebo-Controlled Trial
Authors: Nigel J. Bundred, Angela Cramer, Julie Morris, Lorna Renshaw, Kwok-Leung Cheung, Pamela Flint, Rachael Johnson, Oliver Young, Göran Landberg, Sue Grassby, Lorraine Turner, Andrew Baildam, Lester Barr, J. Michael Dixon
Journal: Clinical Cancer Research (2010)

Tamoxifen reduces risk of recurrence after breast conservation surgery for ductal carcinoma in situ (DCIS), but no data exists on the effectiveness of aromatase inhibitors for DCIS. Cyclooxygenase-2 (COX-2) is overexpressed in DCIS, representing another potential therapeutic target. The aim of the study was to determine the effect of aromatase and/or COX-2 inhibition on epithelial proliferation and apoptosis in a presurgical study of estrogen receptor (ER)-positive DCIS.Postmenopausal women with ER-positive DCIS diagnosed by core biopsy were randomized to a 2 x 2 design of either 14 days of exemestane or placebo and celecoxib, or placebo immediately before surgery. Paired baseline and end point biopsies were analyzed for proliferation (Ki67), apoptosis, human epidermal growth factor receptor 2 (HER2), COX-2, and progesterone receptor (PR) expression by immunohistochemistry. The primary end point was a decrease in Ki67 between diagnosis and surgical excision.Ninety women were randomized: all were ER positive, 49 (54%) had grade III tumors, and 29 (32%) were HER2 positive (3+). Exemestane reduced proliferation compared with placebo with a median reduction of 9% (95% confidence interval, 6-14; P < 0.001). Progesterone receptor was reduced by exemestane (mean decrease, 19%; 95% confidence interval, 9-28; P = 0.011). The effect of exemestane on proliferation was seen regardless of grade, HER2, or PR expression. Celecoxib had no effect on proliferation or apoptosis alone, or in combination with exemestane.Exemestane reduces proliferation in ER-positive DCIS. Aromatase inhibition is a potential alternative to tamoxifen in patients who have undergone breast conservation for ER-positive DCIS.
Immunosuppressive factor(s) specific for L-glutamic acid50-L-tyrosine50 (GT). III. Generation of suppressor T cells by a suppressive extract derived from GT-primed lymphoid cells.
Authors: C Waltenbaugh, J Thèze, J A Kapp, B Benacerraf
Journal: The Journal of Experimental Medicine (1977)

Injection of mice with L-glutamic acid50-L-tyrosine50 (GT)- or L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT)-specific suppressor T-cell factor (GT-TsF or GAT-TsF) up to 5 wk before antigenic challenge challenge suppresses GT-methylated bovine serum albumin (MBSA) and GAT-MBSA plaque-forming cells responses. T suppressor cells are responsible for the suppression induced by the suppressive extract as demonstrated by adoptive transfer and sensitivity to anti-Thy-1 and complement treatment. We conclude that suppressive extract induces specific suppressor T cells. The material responsible for generation of suppressor T cells is a product of the I subregion of the H-2 complex. We have excluded that suppressive quantities of antigens are present in the extract. A/J mice, which can neither be suppressed by GT nor make GT-TsF can be suppressed by BALB/c GT-tsf. Spleen cells from BALB/c GT TsF-primed A/J mice can adoptively transfer suppression to normal syngeneic recipients. A/J mice appear to be genetically defective in cells involved in factor production. These results are discussed in the light of a two-step model for induction of antigen-specific suppressor cells.
Functional crosstalk between cardiac fibroblasts and adult cardiomyocytes by soluble mediators
Authors: James E. Cartledge, Christopher Kane, Priyanthi Dias, Meron Tesfom, Lucy Clarke, Benjamin Mckee, Samha Al Ayoubi, Adrian Chester, Magdi H. Yacoub, Patrizia Camelliti, Cesare M. Terracciano
Journal: Cardiovascular Research (2015)

Crosstalk between cardiomyocytes and fibroblasts in physiological conditions and during disease remains poorly defined. Previous studies have shown that fibroblasts and myocytes interact via paracrine communication, but several experimental confounding factors, including the use of immature myocytes and the induction of alpha-smooth muscle actin (α-SMA) expression in fibroblasts by prolonged culture, have hindered our understanding of this phenomenon. We hypothesize that fibroblasts and myofibroblasts differentially affect cardiomyocytes viability, volume, and Ca2+ handling via soluble mediators. More specifically here: (i) we compare the effects of freshly isolated fibroblasts and cultured fibroblasts from normal rat hearts on adult cardiomyocytes; (ii) we compare the effects of (freshly isolated) normal fibroblasts and myofibroblasts from pressure-overloaded hearts; and (iii) we study the contribution of TGF-β and the importance of the crosstalk between the two cell types. We used co-culture methods and conditioned medium to investigate paracrine interaction between fibroblasts and cardiomyocytes. All fibroblast types reduce cardiomyocyte viability and increase cardiomyocyte volume but α-SMA-negative fibroblasts increase cardiomyocyte Ca2+ transient amplitude, whereas cultured fibroblasts and myofibroblasts from pressure-overloaded hearts decrease Ca2+ transient amplitude. In turn, cardiomyocytes release soluble mediators that affect fibroblast proliferation. Using SB431542 to block TGF-β type 1 receptors, we determined that TGF-β directly causes cardiomyocyte hypertrophy and participates in bi-directional regulatory signalling between fibroblasts and cardiomyocytes. Fibroblasts have different roles during physiology and disease in regulating myocardial function via soluble mediators. A crosstalk between fibroblasts and cardiomyocytes, controlled by TGF-β, is crucial in this interaction.
Measuring health status in chronic airflow limitation
Authors: G Guyatt
Journal: European Respiratory Journal (1988)

A health status instrument for use in clinical trials must be valid (measuring what it is supposed to measure) and responsive (able to detect clinically important change). Approaches to measuring health status in clinical trials include using a battery of instruments, a general instrument which provides a profile of the patient's health, an instrument that generates a health utility, or an instrument that focuses on the problems associated with a particular disease. Disease-specific instruments have been used in clinical trials in chronic airflow limitation (CAL). The Oxygen Cost Diagram is simple and easy to administer, but responsiveness and validity are unproven. The Transition Dyspnoea Index is valid and responsive, but is difficult to use in trials in which multiple measurements are desired. The Chronic Respiratory Disease Questionnaire has proved valid and responsive in controlled trials in CAL patients. Health status measures should be included in all clinical trials in CAL.
TREX1 gene variant in neuropsychiatric systemic lupus erythematosus
Authors: B de Vries, G M Steup-Beekman, J Haan, E L Bollen, J Luyendijk, R R Frants, G M Terwindt, M A van Buchem, T W J Huizinga, A M J M van den Maagdenberg, M D Ferrari
Journal: Annals of the Rheumatic Diseases (2009)

Systemic lupus erythematosus (SLE) is an autoimmune disorder with a complex genetic background. Some 14–75% of SLE patients report neurological and psychiatric symptoms and are diagnosed with neuropsychiatric-SLE (NPSLE).1 Many of these patients also have cerebral white matter hyperintensities (WMH). The aetiology and genetic background of NPSLE is largely unknown.

In 2007, mutations in the TREX1 gene, encoding the major mammalian 3′-5′ DNA exonuclease, were identified in nine out of 417 SLE patients.2 In addition, TREX1 has been associated with disorders that are often associated with cerebral WMH, migraine(-like symptoms) and other manifestations of brain disease.3 4 Consequently, we considered TREX1 an excellent candidate for NPSLE. We scanned genomic DNA of 60 NPSLE patients (table 1) for exonic TREX1 mutations using direct sequencing,5 and identified a novel heterozygous p.Arg128His mutation in one NPSLE patient. This patient was admitted to our hospital …
Regulation of pancreatic PC1 and PC2 associated with increased glucagon-like peptide 1 in diabetic rats
Authors: Ying Nie, Masahiro Nakashima, Patricia L. Brubaker, Qiao-Ling Li, Riccardo Perfetti, Erik Jansen, Yasmeen Zambre, Daniel Pipeleers, Theodore C. Friedman
Journal: Journal of Clinical Investigation (2000)

The pancreatic processing enzymes, PC1 and PC2, convert proinsulin to insulin and convert proglucagon to glucagon and glucagon-like peptide 1 (GLP-1). We examined the effect of streptozotocin (STZ) treatment on the regulation of these enzymes and the production of insulin, glucagon, and GLP-1 in the rat. Pancreatic PC1 and PC2 mRNA increased >2-fold and >4-fold, respectively, in rats receiving intraperitoneal STZ (50 mg/kg) daily for 5 days. Immunocytochemistry revealed that, although pancreatic islet cells in the STZ-treated rats were sparse and atrophic PC1, PC2, glucagon, and GLP-1 immunoreactivity increased dramatically in the remaining islet cells. Heightened PC1 and PC2 expression was seen in cells expressing glucagon but not in insulin-expressing cells. Furthermore, in STZ-treated rats, bioactive GLP-17–36 amide accumulated in pancreatic extracts and serum 3- and 2.5-fold, respectively, over control animals. This treatment also caused a 2-fold increase in the ratio of amidated forms of GLP-1 immunoreactivity to total glucagon immunoreactivity in the pancreas but did not affect the ratio of proinsulin to insulin. We conclude that hyperglycemic rats have an increased expression of prohormone converting enzymes in islet α cells, leading to an increase in amidated GLP-1, which can then exert an insulinotropic effect on the remaining β cells.
β <sub>2</sub> -Adrenergic Receptor Gene Delivery to the Endothelium Corrects Impaired Adrenergic Vasorelaxation in Hypertension
Authors: Guido Iaccarino, Ersilia Cipolletta, Antonia Fiorillo, Mario Annecchiarico, Michele Ciccarelli, Vincenzo Cimini, Walter J. Koch, Bruno Trimarco
Journal: Circulation (2002)

Background — Impaired β-adrenergic receptor (AR)–mediated vasorelaxation in hypertension plays a role in increased peripheral vascular resistance and blood pressure. Because the β 2 AR is the most abundant vascular AR subtype, we sought to enhance βAR vasorelaxation by overexpressing β 2 ARs via adenoviral-mediated gene transfer (ADβ 2 AR) to the vascular endothelium of the carotid artery. Methods and Results — In normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats, we exposed the right common carotid artery to ADβ 2 AR in situ for 15 minutes by injection into the lumen while the blood flow was interrupted. Control carotids received an empty vector (ADempty). Three days later, transgene expression and selective endothelial localization were confirmed in infected vessels. Vasoregulation after β 2 AR overexpression (2-fold) was studied in isolated organ baths. ADβ 2 AR carotid responses to α 1 AR and α 2 AR agonists were not affected, whereas responses to epinephrine were altered and βAR-mediated vasorelaxation was enhanced after β 2 AR overexpression. As expected, βAR-mediated vasodilatation in control carotids of SHR rats was significantly less than in similar control WKY carotid arteries. ADβ 2 AR treatment enhanced βAR vasorelaxation in SHR to levels similar to those seen in ADβ 2 AR WKY carotids. Conclusions — Our results demonstrate a critical role for the endothelium in βAR-mediated vasorelaxation and suggest that impaired βAR signaling may account for dysfunctional βAR vasorelaxation in hypertension rather than impaired endothelium-dependent nitric oxide metabolism.
Efficacy of prednisone 1-4 mg/day in patients with rheumatoid arthritis: a randomised, double-blind, placebo controlled withdrawal clinical trial
Authors: T Pincus, C J Swearingen, G Luta, T Sokka
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Objective:</h3> A randomised double-blind placebo controlled withdrawal clinical trial of prednisone versus placebo in patients with rheumatoid arthritis (RA), treated in usual clinical care with 1–4 mg/day prednisone, withdrawn to the same dose of 1 mg prednisone or identical placebo tablets. <h3>Methods:</h3> All patients were from one academic setting and all trial visits were conducted in usual clinical care. Patients were taking stable doses of 1–4 mg prednisone with stable clinical status, documented quantitatively by patient questionnaire scores. The protocol included three phases: (1) equivalence: 1–4 study prednisone 1 mg tablets taken for 12 weeks to ascertain their efficacy compared with the patient's usual tablets before randomisation; (2) transfer: substitution of a 1 mg prednisone or identical placebo tablet every 4 weeks (over 0–12 weeks) to the same number as baseline prednisone; (3) comparison: observation over 24 subsequent weeks taking the same number of either placebo or prednisone tablets as at baseline. The primary outcome was withdrawal due to patient-reported lack of efficacy versus continuation in the trial for 24 weeks. <h3>Results:</h3> Thirty-one patients were randomised, 15 to prednisone and 16 to placebo, with three administrative discontinuations. In "intent-to-treat" analyses, 3/15 prednisone and 11/16 placebo participants withdrew (p = 0.03). Among participants eligible for the primary outcome, 3/13 prednisone and 11/15 placebo participants withdrew for lack of efficacy (p = 0.02). No meaningful adverse events were reported, as anticipated. <h3>Conclusion:</h3> Efficacy of 1–4 mg prednisone was documented. Evidence of statistically significant differences with only 31 patients may suggest a robust treatment effect.
Clinical tests in shoulder examination: how to perform them
Authors: Maarten Hendrik Moen, Robert-Jan de Vos, Todd S Ellenbecker, Adam Weir
Journal: British Journal of Sports Medicine (2010)

Background This article describes the best clinical tests of shoulder function and injury as identified in a recent systematic review published in the British Journal of Sports Medicine . Discussion A description of the different tests is given, with photographs of the exact test procedure.