tbuckley/cabot-search huggingface dataset:
Properties of the antigen-specific suppressive T-cell factor in the regulation of antibody response of the mouse. IV. Special subregion assignment of the gene(s) that codes for the suppressive T-cell factor in the H-2 histocompatibility complex.
Authors: T Tada, M Taniguchi, C S David
Journal: The Journal of Experimental Medicine (1976)

The locus of the gene that codes for the antigen-specific suppressive T-cell factor was determined to be in a new subregion "I-J" which locates between I-B and I-C subregions in the H-2 histocompatibility complex. This was shown by two different lines of evidence: (a) The absorbing capacity for the suppressive T-cell factor of several alloantisera against restricted I subregions did not correlate with their specificity for previously known Ia molecules which are coded for by genes in I-A and I-C subregions, but was associated with the specificity for the products of genes putatively present between I-B and I-C subregions. By the occurrence of special recombinant strains, i.e. B10.A(5R), B10.A(3R), B10.S(9R), and B10.HTT, which differ with respect to the I-J subregion, we were able to produce alloantisera which distinguish I-J subregion gene products. The absorption studies using these special alloantisera directed to I-J subregion clearly indicated that the suppressive T-cell factor is a product of I-J subregion gene(s), and that the molecule is distinct from known Ia molecules expressed on splenic B cells. (b) Taking advantage of the fact that there is a strict histocompatibility requirement for the effective suppression between the donor and recipient strains of the suppressive T-cell factor, we were able to determine the required identities of the genes in the H-2 complex existing among those present between I-B and I-C. Again, utilizing the T-cell factors obtained from special recombinant strains, i.e. B10.A(4R) and B10.A(5R), we were able to locate the gene that codes for the suppressive T-cell factor reactive only with relevant haplotype strains between I-B and I-C subregions. These results are most reasonably explained by the presence of a new subregion I-J which is specialized in coding for the suppressive T-cell factor as a different molecule from previously known Ia molecules.
A Subgroup of Metastatic Colorectal Cancer Patients with Very Prolonged Disease Control Under Maintenance Therapy with the TLR-9 Agonist MGN1703
Authors: J. Riera-Knorrenschild, H.G. Kopp, F. Mayer, D. Nitsche, J. Kuhlmann, R. Ziebermayr, J. Andel, D. Arnold, M. Schmidt, W. Scheithauer, H.J. Schmoll
Journal: Annals of Oncology (2014)
Incidence and progression of osteoarthritis in women with unilateral knee disease in the general population: the effect of obesity.
Authors: T D Spector, D J Hart, D V Doyle
Journal: Annals of the Rheumatic Diseases (1994)

OBJECTIVES--The natural history of knee osteoarthritis (OA) is poorly understood. The principal aim was to assess the rate of contralateral knee OA in middle aged women in the general population with existing unilateral disease and to identify the major factors that influence this rate. METHODS--Fifty eight women aged (45-64) from a general population study cohort were identified with unilateral knee OA diagnosed radiologically (Kellgren and Lawrence 2+) (K&amp;L). Follow up AP films were obtained at 24 months and compared with the baseline for K&amp;L grade and individual features of osteophytes and joint space. RESULTS--Twenty women (34%) developed incident disease in the contralateral knee (based on K&amp;L 2+ or osteophyte changes) and 22.4% (n = 13) of women progressed radiologically in the index joint. Obesity at baseline was the most important factor related to incident disease, 47% of women in the top BMI tertile developed OA, compared with 10% in the lowest tertile: relative risk 4.69 (063-34.75). No clear effect was seen for age, physical activity, trauma or presence of hand OA. CONCLUSIONS--Over one third of middle aged women with unilateral disease will progress to bilateral knee OA within two years and a fifth will progress in the index joint. Obesity is a strong and important risk factor in the primary and secondary prevention of OA. These natural history data provide a useful estimate for planning therapeutic intervention trials.
PUNCTIFORM HAEMORRHAGES OF THE BRAIN IN GAS POISONING
Authors: F. W. Mott
Journal: BMJ (1917)

THE subject of punctiform haemorrhages in the brain in gas poisoning has awakened new interest on account of its existence in fatal cases of shell shock with burial, and in cases of death from inhalation of poisonous gases, either as a result of their liberation by explosives in confined spaces, such as mines, trenches, and dug-outs, or as a
A call for inspiration
Authors: Kamran Abbasi
Journal: Journal of the Royal Society of Medicine (2012)

What inspires you? What was the moment that turned your mind to medicine? Whose influence cast a spell that set your future course? Perhaps it's hard to pinpoint an event or an experience that galvanized you? Medicine is a career of variety and unexpected paths, and this month I'll be speaking to sixth form and GCSE students in the hope of offering some inspiration as they consider a life of doctoring.

JRSM readers with children of that age will know that preparations begin early in these competitive times. Gone are the days of a last minute impulse on a university application form. Today's students mount a four-year campaign to gain a place at medical school, armed with entry criteria, exam preparation, interview training, and work experience. When sixth form principals advise sagely on the difficulties of students winning an Oxbridge place, their one consolation is: “It could be worse, you could be applying for medical school.”

What most medical students don't realise is that they are entering a career of infinity possibilities. Medicine's multi-specialty nature means that there is a medical career to suit all personalities. Your degree is merely the key to an Aladdin's cave of opportunity, a blessing that is hard to appreciate on a thankless night on call or in the middle of a disastrous ward round. Many doctors are fortunate to experience a variety of specialities as they find the one that they were destined for.

Nor is variety confined to medicine. The broad experiences of a doctor's life help many people turn to second careers as managers, business people, writers, performers, politicians, and revolutionaries. Add in foreign travel and the international nature of many specialties, and medical school becomes more than a passport to a career.

But how can you know that when you fill in your university application? How do you know what it takes to be a cardiologist, an orthopaedic surgeon, a microbiologist, a clinical director, or even a journal editor? How do you know that medicine, a career that might seem glamorous from the way the media portrays doctors, is the right career for you? For amid the myriad of exciting opportunities lie as many avenues of misery, hurt, and disillusionment.

Imagine you are sitting in front of a hall full of sixth form students or young doctors on graduation day. What would you say to them about what inspires you? What was the moment that transformed your career? Share that inspiration and that moment with JRSM readers by sending in a submission for our Podium section. In these days of demoralization, a little inspiration is a welcome pleasure.
Mechanism of Metabolic Advantages After Bariatric Surgery
Authors: Filip K. Knop, Roy Taylor
Journal: Diabetes Care (2013)

The acute glucose-lowering effect of certain bariatric procedures—before any significant weight loss has occurred—has been known for decades (1). In a comprehensive meta-analysis by Buchwald et al. (2), type 2 diabetes remission rates after the most common bariatric procedure, Roux-en-Y gastric bypass (RYGB), were reported to be 80%. Applying the 2009 consensus criteria for the definition of diabetes remission has been reported to show complete remission of diabetes in “only” 41% of 160 RYGB-treated obese patients with type 2 diabetes (3). Importantly, bariatric surgery seems to improve several components of the metabolic syndrome, and type 2 diabetes–specific mortality rates have been demonstrated to be up to 90% lower in RYGB-treated subjects compared with nontreated control subjects (2,4). In comparison with medical therapy alone, recent clinical trials have shown that RYGB or biliopancreatic diversion resulted in better glucose control (5), RYGB achieved glycemic control in significantly more patients (6), and sleeve gastrectomy resolved the diabetic state more effectively (7). Thus, it is well established that bariatric procedures improve glycemic control or even resolve the type 2 diabetic state. However, the mechanisms by which these operations bring about their glucose-lowering effects remain much debated. Obviously, the body weight–lowering effect of these operations contributes to the long-term improvements in glucose metabolism (primarily via increased hepatic and peripheral insulin sensitivity [8]), but it is striking that amelioration of hyperglycemia after bariatric surgery occurs within days of the surgery, pointing to immediate, weight loss–independent mechanisms possibly related to surgery-induced changes in food intake (caloric restriction), gastrointestinal (GI) anatomy, or transit of nutrients.

The predominant hypotheses on the physiological background for the metabolic advantages (specifically, the glucose-lowering effects) after bariatric surgery include changed release of GI hormones (increased secretion of hormones with antidiabetes properties and reduced secretion of “diabetogenic” hormones) and surgery-induced …
Pregnancy outcomes following first-trimester exposure to topical retinoids: a systematic review and meta-analysis
Authors: Y.C. Kaplan, J. Ozsarfati, F. Etwel, C. Nickel, I. Nulman, G. Koren
Journal: British Journal of Dermatology (2015)

Evaluation of human data regarding the outcomes of topical-retinoid-exposed pregnancies is important in terms of counselling pregnant women with inadvertent exposure. The objective of this study was thus to determine whether exposure to topical retinoids leads to an increase in the risk of adverse pregnancy outcomes. We carried out a search using the Medline, Embase, Web of Science and Cochrane Central Register of Controlled Trials databases from inception to 4 December 2014. The selection, review and quality assessment of the studies were carried out by two independent reviewers according to predetermined inclusion criteria. Odds ratios (ORs) were calculated by the random effects method. This meta-analysis, including a total of 654 pregnant women who were exposed to topical retinoids, and 1375 unexposed control pregnant women, did not detect significant increases in rates of major congenital malformations [OR 1·22, 95% confidence interval (CI) 0·65-2·29], spontaneous abortions (OR 1·02, 95% CI 0·64-1·63), stillbirth (OR 2·06, 95% CI 0·43-9·86), elective termination of pregnancy (OR 1·89, 95% CI 0·52-6·80), low birthweight (OR 1·01, 95% CI, 0·31-3·27) or prematurity (OR 0·69, 95% CI 0·39-1·23). No significant heterogeneity was detected among the studies for the evaluated outcomes. The present meta-analysis ruled out a major increase in the rates of major congenital malformations, spontaneous abortions, low birthweight and prematurity. This result may be used primarily in reassuring women who were inadvertently exposed to topical retinoids during their pregnancy. However, the statistical power is not adequate to justify the use of topical retinoids during pregnancy.
Patupilone (epothilone B) inhibits growth and survival of multiple myeloma cells in vitro and in vivo
Authors: Boris Lin, Laurence Catley, Richard LeBlanc, Constantine Mitsiades, Renate Burger, Yu-Tzu Tai, Klaus Podar, Markus Wartmann, Dharminder Chauhan, James D. Griffin, Kenneth C. Anderson
Journal: Blood (2004)
Pediatric lung transplantation at St. Louis Children's Hospital, 1990-1995.
Authors: S C Sweet, T L Spray, C B Huddleston, E Mendeloff, C E Canter, D T Balzer, N D Bridges, A H Cohen, G B Mallory
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Although accepted therapy in adults, lung transplantation in children is less well established. Reports from the few existing pediatric centers have involved relatively small patient number. Seventy-nine patients underwent 88 lung transplant procedures at St. Louis Children's Hospital between June 1990 and August 1995. Twenty-one transplants (24%) were done in 19 infants and children under the age of 3 yr. Twelve-, 24-, and 48-mo actuarial survival for the primary transplants was 69%, 67%, and 60%, respectively. Survival improved over the course of the program: 12-mo survival for patients transplanted during the first 18 mo was 42% compared with 78% for those transplanted after December 1991. Survival of children transplanted at younger than 3 yr of age was comparable to older children and adults. However, younger children had a lower incidence of acute rejection; none developed bronchiolitis obliterans. Both graft growth and linear growth occurred. Risk factors for early mortality included presence of aortopulmonary collateral vessels and prior thoracic surgery. Risk factors for survival duration included requiring assisted ventilation at the time of transplant, continuous supplemental oxygen requirement, and presence of aortopulmonary collateral vessels. The major late complication was bronchiolitis obliterans, which occurred in 27% of patients and played a role in 64% of late deaths. Investigation of the lower incidence of acute rejection and bronchiolitis obliterans in younger versus older children may reveal important information about the etiology of this disease. The ultimate long-term success of lung transplantation will depend on identification and treatment of the mechanisms responsible. A multicenter data registry would facilitate further clinical studies of pediatric lung transplantation.
Amelioration of collagen-induced arthritis by thrombin inhibition
Authors: Ingrid Marty, Veronique Péclat, Gailute Kirdaite, Roberto Salvi, Alexander So, Nathalie Busso
Journal: Journal of Clinical Investigation (2001)

The deleterious role of fibrin deposition in arthritic joints prompted us to explore the effect of the thrombin inhibition on the course of collagen-induced arthritis (CIA) in the mouse. CIA was induced in male DBA/1J mice using native chicken type II collagen. The thrombin inhibitor polyethyleneglycol-hirudin (PEG-hirudin) was given for 16 days, starting 20 days after the first immunization (preventive treatment) or at the onset of clinical signs of arthritis (curative treatment). All the mice treated with PEG-hirudin had a significantly prolonged clotting time compared with control mice. PEG-hirudin, administered in a preventive way, led to significantly reduced incidence and severity of CIA during most of the treatment period, as assessed by clinical scoring. Accordingly, histological features showed a significant diminution of synovial hyperplasia in PEG-hirudin–treated mice compared with untreated mice. There was also a significant downmodulation of the synovial proinflammatory IL-1β and IL-12p35 cytokine mRNAs in treated mice. Intra-articular fibrin, evaluated by immunohistochemistry, was significantly reduced in treated mice compared with control mice and correlated with both clinical and histological scorings. Most importantly, once arthritis was established, PEG-hirudin also showed a curative effect. In conclusion, PEG-hirudin can both prevent the onset of CIA in a dose-dependent manner and ameliorate established arthritis, suggesting that thrombin inhibition may offer a new therapeutic approach in arthritis.
Variations in the prevalence across countries of chronic bronchitis and smoking habits in young adults
Authors: I. Cerveri, S. Accordini, G. Verlato, A. Corsico, M.C. Zoia, L. Casali, P. Burney, R. de Marco
Journal: European Respiratory Journal (2001)

The present work aims to assess the international variation in the prevalence of chronic bronchitis and its main risk factor, smoking habits, in young adults of 35 centres from 16 countries. Respiratory symptoms and pulmonary function were assessed in 17,966 subjects (20–44 yrs), randomly selected from the general population, in the frame of the European Community Respiratory Health Survey. The median prevalence of chronic bronchitis was 2.6%, with wide variations across countries (p&lt;0.001; 0.7–9.7%). The prevalence of current smokers ranged 20.1–56.9% (p&lt;0.001) with a median value of 40%. Current smoking was the major risk factor for chronic bronchitis, especially in males. Its effect increased according to number of pack-yrs: in males, the odds ratio of chronic bronchitis was 3.51 (95% confidence interval (CI) 2.31–5.32) in 1–14 pack-yrs smokers and increased to 17.32 (9.97–30.11) in ≥45 pack-yrs smokers with respect to nonsmokers. Only 30% of the geographical variability in prevalence could be explained by differences in smoking habits, suggesting that other environmental and/or genetic factors may play an important role. In conclusion, chronic bronchitis is a substantial health problem even in young adults. The impressive prevalence in current smokers in most countries highlights the need to improve the quality of prevention.
Interferon gamma and tumor necrosis factor have a role in tumor regressions mediated by murine CD8+ tumor-infiltrating lymphocytes.
Authors: R J Barth, J J Mulé, P J Spiess, S A Rosenberg
Journal: The Journal of Experimental Medicine (1991)

We have investigated the mechanisms whereby adoptively transferred murine CD8+ lymphocytes mediate tumor regressions. Noncytolytic, CD8+ tumor-infiltrating lymphocytes (TIL) eradicated established lung tumors in irradiated mice. Many cytolytic and noncytolytic CD8+ TIL cultures specifically secreted interferon gamma (IFN-gamma) and tumor necrosis factor when stimulated with tumor cells in vitro. The effectiveness of TIL when adoptively transferred to mice bearing micrometastases correlated better with their ability to specifically secrete lymphokines than with their cytotoxicity in vitro. In 14 of 15 tests, therapeutically effective TIL specifically secreted IFN-gamma in vitro, whereas only 1 of 11 ineffective TIL specifically secreted IFN-gamma. In contrast, only 8 of 15 therapeutically effective TIL were cytolytic. Antibodies to TNF inhibited the effectiveness of two adoptively transferred TIL cultures. In five experiments, antibodies to IFN-gamma abrogated the ability of four different CD8+ TIL cultures to mediate tumor regressions, indicating that secretion of IFN-gamma is an essential part of the mechanism of action of TIL.
Association Between Use of Lung-Protective Ventilation With Lower Tidal Volumes and Clinical Outcomes Among Patients Without Acute Respiratory Distress Syndrome
Authors: Ary Serpa Neto, Sérgio Oliveira Cardoso, José Antônio Manetta, Victor Galvão Moura Pereira, Daniel Crepaldi Espósito, Manoela de Oliveira Prado Pasqualucci, Maria Cecília Toledo Damasceno, Marcus J. Schultz
Journal: JAMA (2012)

Lung-protective mechanical ventilation with the use of lower tidal volumes has been found to improve outcomes of patients with acute respiratory distress syndrome (ARDS). It has been suggested that use of lower tidal volumes also benefits patients who do not have ARDS.To determine whether use of lower tidal volumes is associated with improved outcomes of patients receiving ventilation who do not have ARDS.MEDLINE, CINAHL, Web of Science, and Cochrane Central Register of Controlled Trials up to August 2012.Eligible studies evaluated use of lower vs higher tidal volumes in patients without ARDS at onset of mechanical ventilation and reported lung injury development, overall mortality, pulmonary infection, atelectasis, and biochemical alterations.Three reviewers extracted data on study characteristics, methods, and outcomes. Disagreement was resolved by consensus.Twenty articles (2822 participants) were included. Meta-analysis using a fixed-effects model showed a decrease in lung injury development (risk ratio [RR], 0.33; 95% CI, 0.23 to 0.47; I2, 0%; number needed to treat [NNT], 11), and mortality (RR, 0.64; 95% CI, 0.46 to 0.89; I2, 0%; NNT, 23) in patients receiving ventilation with lower tidal volumes. The results of lung injury development were similar when stratified by the type of study (randomized vs nonrandomized) and were significant only in randomized trials for pulmonary infection and only in nonrandomized trials for mortality. Meta-analysis using a random-effects model showed, in protective ventilation groups, a lower incidence of pulmonary infection (RR, 0.45; 95% CI, 0.22 to 0.92; I2, 32%; NNT, 26), lower mean (SD) hospital length of stay (6.91 [2.36] vs 8.87 [2.93] days, respectively; standardized mean difference [SMD], 0.51; 95% CI, 0.20 to 0.82; I2, 75%), higher mean (SD) PaCO2 levels (41.05 [3.79] vs 37.90 [4.19] mm Hg, respectively; SMD, -0.51; 95% CI, -0.70 to -0.32; I2, 54%), and lower mean (SD) pH values (7.37 [0.03] vs 7.40 [0.04], respectively; SMD, 1.16; 95% CI, 0.31 to 2.02; I2, 96%) but similar mean (SD) ratios of PaO2 to fraction of inspired oxygen (304.40 [65.7] vs 312.97 [68.13], respectively; SMD, 0.11; 95% CI, -0.06 to 0.27; I2, 60%). Tidal volume gradients between the 2 groups did not influence significantly the final results.Among patients without ARDS, protective ventilation with lower tidal volumes was associated with better clinical outcomes. Some of the limitations of the meta-analysis were the mixed setting of mechanical ventilation (intensive care unit or operating room) and the duration of mechanical ventilation.
Guidelines
Authors: K.E. Harman, S. Albert, M.M. Black
Journal: British Journal of Dermatology (2003)

These guidelines for management of pemphigus vulgaris have been prepared for dermatologists on behalf of the British Association of Dermatologists. They present evidence-based guidance for treatment, with identification of the strength of evidence available at the time of preparation of the guidelines, and a brief overview of epidemiological aspects, diagnosis and investigation.
Impaired renal conservation of sodium and chloride during sustained correction of systemic acidosis in patients with type 1, classic renal tubular acidosis.
Authors: A Sebastian, E McSherry, R C Morris
Journal: Journal of Clinical Investigation (1976)

In 10 patients with classic renal tubular acidosis in whom correction of acidosis was sustained with orally administered potassium bicarbonate, renal conservation of sodium was evaluated when dietary intake of sodium was restricted to 9--13 meq/day. In five patients, renal conservation of sodium was impaired by at least one criterion of impairment. In the remaining patients, renal conservation of sodium appeared to be relatively well-maintained, but an impairment could not be excluded. In each of six patients studied during induced water diuresis, including two in whom renal conservation of sodium was not unequivocally impaired, the minimal urinary concentrations of sodium were inappropriately high and the urinary excretion rates of sodium were flow-dependent. These results provide direct evidence that an abnormality in renal transport of sodium can occur in classic renal tubular acidosis, and compel a reconsideration of the pathophysiology of disordered renal transport of sodium in this disorder. The results indicate that in at least some patients with classic renal tubular acidosis impaired renal conservation of sodium is not exclusively a reversible consequence of the renal acidification defect. These findings raise the question whether renal transport of sodium is unimpaired in any patients with classic renal tubular acidosis. In the presently studied patients, the impairment in renal conservation of sodium appeared to be in part the consequence of an impaired ability of the vasopressin-responsive segments of the distal nephron to generate and maintain appropriately steep transepithelial sodium concentration gradients.