tbuckley/cabot-search huggingface dataset:
T Cell Receptor Genotyping and <i>HOXA/TLX1</i> Expression Define Three T Lymphoblastic Lymphoma Subsets which Might Affect Clinical Outcome
Authors: Frederic Baleydier, Anne-Valerie Decouvelaere, Julie Bergeron, Philippe Gaulard, Danielle Canioni, Yves Bertrand, Stephane Lepretre, Barbara Petit, Herve Dombret, Kheira Beldjord, Thierry Molina, Vahid Asnafi, Elizabeth Macintyre
Journal: Clinical Cancer Research (2008)

Abstract Purpose: T lymphoblastic lymphomas (T-LBL) are rare disorders of immature T cells which predominantly involve the mediastinum. Their oncogenic pathways and prognostic variables are not clear. Experimental Design: We undertook a retrospective study of 41 cytoplasmic CD3+ T-LBL (nine cases aged &amp;lt;16 years) by assessing stage of maturation arrest based on T cell receptor (TCR) immunogenotyping, immunohistochemistry, and quantification of the oncogenes thought to be important in immature T cell malignancies. Results: Application of a TCR-based immunogenetic classification allowed the identification of three subcategories: 11 immature IM0/D-LBL showed no TCR or only incomplete TCRD DJ rearrangement and corresponded to cytoplasmic CD3+ precursors of uncertain lineage. Sixteen mature TCRDdel-LBL showed biallelic TCRD deletion and both TCRG and TCRB rearrangement, consistent with TCRαβ lineage restriction. Fourteen intermediate LBL (Int-LBL) showed complete TCRD VDJ and TCRG VJ rearrangement, with TCRB VDJ rearrangement in the majority. All Int-LBL expressed HOX11/TLX1 or HOXA9 transcripts and a proportion of the latter were associated with CALM-AF10 or NUP214-ABL fusion transcripts. IM0/D-LBL were restricted to adults with extrathymic disease and bone marrow involvement, whereas Int-LBL and TCRDdel-LBL were found in children and adults with predominantly thymic disease. In adults, the Int-LBL subgroup was associated with a significantly superior clinical outcome. This subgroup can be identified either by TCR immunogenotyping or HOXA9/TLX1 transcript quantification. Conclusion: Application of this molecular classification will allow the prospective evaluation of prognostic effects within pediatric and adult protocols.
Characteristics of Patients With Type 2 Diabetes in México
Authors: Carlos A. Aguilar-Salinas, Oscar Velazquez Monroy, Francisco J. Gómez-Pérez, Antonio Gonzalez Chávez, Agustin Lara Esqueda, Virginia Molina Cuevas, Juan A. Rull-Rodrigo, Roberto Tapia Conyer
Journal: Diabetes Care (2003)

OBJECTIVE—To describe the clinical characteristics of the diabetic population that formed part of a population-based survey conducted in México. RESEARCH DESIGN AND METHODS—In 2000, information was obtained from 42,886 subjects aged ≥20 years using a multistage sampling procedure. Standardized questionnaires were used. Anthropometric measurements, blood pressure, and capillary glucose concentrations were taken. RESULTS—Type 2 diabetes was found in 3,597 subjects (age-adjusted prevalence 8.18%), of which 2,878 (80%) had previously been diagnosed. The average age of the diabetic participants was 55.2 ± 13.5 years; 13% were &amp;lt;40 years of age. Nine percent had been diagnosed for &amp;gt;10 years. The average BMI was 29.2 ± 5.7 kg/m2; three-quarters of the cases had BMI &amp;gt;25 kg/m2. The average waist circumference was 102 ± 13.4 cm, and increased waist circumference was more common among women. Arterial hypertension was found in half of the cases and, of those on treatment, only one-third had a blood pressure &amp;lt;140/90 mmHg. Smoking was reported in 34% of the diabetic group, a higher rate than in the nondiabetic subjects. There was at least one modifiable coronary risk factor in 67.6% of the cases. Very few followed an exercise or dietary regimen and a small percentage used insulin. CONCLUSIONS—Diabetes affects a large proportion of Mexican adults (8.18%). This figure may be underestimated. The majority of the subjects had modifiable risk factors for the chronic complications of diabetes. Only a few achieved adequate blood pressure control and other treatment goals.
Exercise and diet in weight management: updating what works
Authors: D J Macfarlane, G N Thomas
Journal: British Journal of Sports Medicine (2009)

The world is facing major problems associated with the rapid increase in levels of overweight and obesity. Solving this problem via appropriate modifications to exercise habits and/or diet appears easy, but in practice it is inordinately difficult and only a small percentage manage to maintain their weight loss over the long term. However, a number of strategies can be used to increase the chances of success. Medical doctors, dieticians and other allied health professionals are potentially well placed to provide guidance to those at risk of overweight/obesity. This review is aimed at supporting major initiatives targeting an increase in community physical activity to help reduce the prevalence of overweight/obesity, such as the "Change4Life" campaign in the UK (http://www.nhs.uk/change4life) and the "Exercise is Medicine" campaign in the USA (http://www.exerciseismedicine.org). By providing a concise summary of the evidence-based research that can be easily understood by a wide range of health professionals, this review hopes to provide a useful document that can be used to enhance preventive counselling by promoting appropriate changes in lifestyle that will ultimately increase levels of physical activity, as well as reduce levels of overweight/obesity and other associated chronic hypokinetic conditions.
Food‐induced cutaneous adverse reactions
Authors: B. Wüthrich
Journal: Allergy (1998)

The skin is the most frequently affected target organ in allergy or intolerance of food and food additives. The most common manifestation is acute urticaria (with or without angioedema), accounting for 40-60% of patients with IgE-mediated food allergy, whereas food additives rather aggravate chronic urticaria (intolerance provocation). The role of food allergy in the pathogenesis of atopic dermatitis is still controversial; however, there is no doubt that, particularly in infants and young children, food allergens can induce atopic dermatitis or aggravate skin lesions. In adults, food allergy as a cause or a trigger of atopic dermatitis is very rare. However, in food-allergic patients with atopic dermatitis, the ingestion of the food item can provoke the whole spectrum of IgE-mediated symptoms, from oral allergy syndrome to severe anaphylaxis. Skin symptoms can also be induced not only after food ingestion in sensitized people, but also after direct skin contact, as lipophilic food allergens can penetrate the skin via the hair follicles or when the skin barrier function is defective. Immediate contact reactions of the skin are a heterogeneous group: they include not only contact urticaria (contact urticaria syndrome) on an immunologic or nonimmunologic basis, but also allergic or nonallergic eczematous reactions caused by food proteins (protein contact dermatitis). A prototype is baker's eczema in a restricted sense with immediate-type sensitization to flour. Atopic eczema provoked by direct contact of the skin with food must also be taken into consideration. Finally, very rarely, allergic contact dermatitis that is due to type IV sensitization to food or food additives (positive delayed type reaction in the patch tests) can occur. The oral ingestion of these foods may provoke in these patients a generalized eczematous rash or dyshidrosiform reactions (vesicles) of the fingers, palms, and soles.
Recovery from Cardiac Bypass and Elective Cardiac Arrest
Authors: DAVID J. HEARSE, DAVID A. STEWART, ERNST B. CHAIN
Journal: Circulation Research (1974)

Isolated perfused working rat hearts were subjected to elective cardiac arrest for 20 or 30 minutes. Various methods of arrest, either singly or in combination and with or without coronary perfusion, were studied. The functional recovery of the heart following the termination of arrest was related to the concentration of adenosine triphosphate (ATP) and creatine phosphate in the myocardium at the end of the period of arrest. In turn, these concentrations depended on the method used to induce arrest. Normothermic ischemic arrest or electrical fibrillation led to a marked reduction in high-energy phosphates and a poor functional recovery. In contrast, coronary perfusion with hypothermic solutions or solutions containing high concentrations of potassium induced arrest without depleting ATP or creatine phosphate. These procedures conferred considerable protection on the myocardium and thus permitted good recovery. The energy status and the recovery associated with ischemic arrest were improved by combining the ischemia with potassium-induced arrest, intermittent coronary perfusion, or hypothermia. In the latter instance, a time- and temperature-dependent relationship was demonstrated. The results stress the importance of maintaining ATP and creatine phosphate levels during arrest; such maintenance requires the provision of a continuous supply of oxygen and nutrient, which may perhaps be best achieved by ensuring continuous and adequate coronary perfusion.
HLA-Dw2: a genetic marker for human immune response to short ragweed pollen allergen Ra5. I. Response resulting primarily from natural antigenic exposure.
Authors: D G Marsh, S H Hsu, M Roebber, E Ehrlich-Kautzky, L R Freidhoff, D A Meyers, M K Pollard, W B Bias
Journal: The Journal of Experimental Medicine (1982)

Ultra-pure short ragweed pollen allergen Ra5 (5,000 mol wt) was used to investigate the relationship between human leukocyte antigen (HLA) type and IgE and IgG antibody (Ab) responses to Ra5 in two groups of Caucasian subjects, totaling 447 people. Using highly sensitive radioimmunoassay procedures to measure serum IgE and IgG Ab, qualitative responses to Ra5 in both groups were found to be strongly associated with HLA-Dw2 (P less than 0.0001). For example, 95% of 38 people with IgE Ab vs. 22% of 139 ragweed-allergic persons having no detectable IgE Ab to Ra5 were Dw2+. Quantitative log [IgE Ab] and log[IgG Ab] responses to Ra5 were highly correlated with Dw2 (P = 10(-5) to 10(-14)) in four separate multiple regression analyses, examining the relationship between HLA type (and other variables) and Ab levels in the two study groups. Further studies showed that the primary association of Ra5 response was with Dw2 rather than DR2 and that various combinations of A3, B7, and Dw2 were less strongly associated than Dw2 alone.
Anti-Scl-70 antibodies detected by immunoblotting in progressive systemic sclerosis: specificity and clinical correlations.
Authors: A Aeschlimann, O Meyer, P Bourgeois, T Haim, N Belmatoug, E Palazzo, M F Kahn
Journal: Annals of the Rheumatic Diseases (1989)

One hundred and forty five serum samples from patients with a connective tissue disease and 30 serum samples from healthy blood donors were analysed by immunoblotting. The presence of anti-Scl-70, which seems to discriminate between progressive systemic sclerosis (PSS) and the CREST (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia) syndrome, was found in 31/64 (48%) patients with PSS, in 6/55 (11%) patients with systemic lupus erythematosus, in 2/26 (8%) patients with mixed connective tissue disease, and in none of 30 healthy blood donors. These data resulted in a specificity of 93% for this antibody in systemic sclerosis. For patients with PSS the duration of disease was significantly shorter in those with anti-Scl-70 antibodies than in those without, whereas the presence of anti-Scl-70 did not correlate with severity of disease. An 82% prevalence of anticentromere antibodies in patients with the CREST variant compared with a 4% prevalence in patients with PSS or with overlap syndrome confirms the high diagnostic value of this autoantibody for the CREST variant of PSS.
Pacemaker Therapy in Patients With Neurally Mediated Syncope and Documented Asystole
Authors: Michele Brignole, Carlo Menozzi, Angel Moya, Dietrich Andresen, Jean Jacques Blanc, Andrew D. Krahn, Wouter Wieling, Xulio Beiras, Jean Claude Deharo, Vitantonio Russo, Marco Tomaino, Richard Sutton
Journal: Circulation (2012)

Background— The efficacy of cardiac pacing for prevention of syncopal recurrences in patients with neurally mediated syncope is controversial. We wanted to determine whether pacing therapy reduces syncopal recurrences in patients with severe asystolic neurally mediated syncope. Methods and Results— Double-blind, randomized placebo-controlled study conducted in 29 centers in the Third International Study on Syncope of Uncertain Etiology (ISSUE-3) trial. Patients were ≥40 years, had experienced ≥3 syncopal episodes in the previous 2 years. Initially, 511 patients, received an implantable loop recorder; 89 of these had documentation of syncope with ≥3 s asystole or ≥6 s asystole without syncope within 12±10 months and met criteria for pacemaker implantation; 77 of 89 patients were randomly assigned to dual-chamber pacing with rate drop response or to sensing only. The data were analyzed on intention-to-treat principle. There was syncope recurrence during follow-up in 27 patients, 19 of whom had been assigned to pacemaker OFF and 8 to pacemaker ON. The 2-year estimated syncope recurrence rate was 57% (95% CI, 40–74) with pacemaker OFF and 25% (95% CI, 13–45) with pacemaker ON (log rank: P =0.039 at the threshold of statistical significance of 0.04). The risk of recurrence was reduced by 57% (95% CI, 4–81). Five patients had procedural complications: lead dislodgment in 4 requiring correction and subclavian vein thrombosis in 1 patient. Conclusions— Dual-chamber permanent pacing is effective in reducing recurrence of syncope in patients ≥40 years with severe asystolic neurally mediated syncope. The observed 32% absolute and 57% relative reduction in syncope recurrence support this invasive treatment for the relatively benign neurally mediated syncope. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00359203.
PSMD9 expression predicts radiotherapy response in breast cancer
Authors: Fiona E Langlands, David Dodwell, Andrew M Hanby, Kieran Horgan, Rebecca A Millican-Slater, Valerie Speirs, Eldo T Verghese, Laura Smith, Thomas A Hughes
Journal: Molecular Cancer (2014)

Abstract Background More than 50% of cancer patients are recommended to receive radiotherapy. Recommendations are based mainly on clinical and pathological factors and not intrinsic tumour radio-sensitivity. Use of radiotherapy according to predictive markers would potentially reduce costly over-treatment, and improve the treatment risk-benefit ratio and cancer outcomes. Tumour expression of the 26S proteasome has been reported to predict radiotherapy response: low expression was associated with higher rates of local recurrence after radiotherapy, suggesting that low proteasome expression and activity was associated with radio-resistance. However, this conclusion is at odds with the emerging use of proteasome inhibitors as radio-sensitizers. Our aim was to further analyse the relevance of 26S proteasome expression, focussing specifically on the PSMD9 subunit, in the largest clinical cohort to date, and to investigate the functional role of PSMD9 in radio-sensitivity in breast cancer cell lines. Methods We examined expression of PSMD9 using immunohistochemistry in a cohort of 157 breast cancer patients, including 32 cases (20.4%) that subsequently developed local recurrences. The value of expression as a prognostic or radiotherapy predictive marker was tested using Kaplan-Meier and Cox regression analyses. PSMD9 function was examined in breast cancer cell lines MCF7 and MDA-MB-231 using siRNA knock-downs and colony forming assays after irradiation. Results Low tumour PSMD9 expression was significantly associated with a reduced incidence of local recurrence in patients receiving adjuvant radiotherapy (univariate log rank p = 0.02; multivariate regression p = 0.009), but not in those treated without radiotherapy, suggesting that low PSMD9 expression was associated with relative tumour radio-sensitivity. In support of this, reduction of PSMD9 expression using siRNA in breast cancer cell lines in vitro sensitized cells to radiotherapy. Conclusions We conclude that PSMD9 expression may predict radiotherapy benefit, with low expression indicative of relative radio-sensitivity, the opposite of previous reports relating to 26S proteasome expression. Our conclusion is compatible with use of proteasome inhibitors as radio-sensitizers, and highlights PSMD9 as a potential target for radio-sensitizing drugs.
GENETIC AND BIOCHEMICAL CORRELATES OF ALCOHOL PREFERENCE IN MICE
Authors: KURT SCHLESINGER
Journal: American Journal of Psychiatry (1966)

Certain strains of mice prefer alcohol to water in preference tests whereas others avoid alcohol. This is the behavior which we are trying to explain, and we have formulated several explanatory hypotheses: 1. It was hypothesized that animals of high preference strains metabolize alcohol more quickly than animals of low preference strains. This hypothesis was confirmed. 2. We have asked the question whether there are differences in the activity of liver ADH, the enzyme which catalyzes the rate limiting reaction in alcohol metabolism. We have found that the activity of this enzyme is significantly greater in high than in low preference strains. 3. We have asked whether there are differences in the rate of accumulation of acetaldehyde in high and low preference strains. Tests indicated that significantly greater amounts of blood acetaldehyde accumulate during alcohol metabolism in low than in high preference strains. 4. We have asked whether there are differences in aldehyde dehydrogenase which might account for this differential acetaldehyde accumulation in high and low preference strains. Only an indirect answer is available, but it was found that Antabuse, an inhibitor of aldehyde dehydrogenase, acts differently in high and low preference strains. 5. We have asked whether Antabuse will decrease voluntary consumption of alcohol in normally high or intermediate preference strains. Antabuse was found to decrease voluntary alcohol intake in all strains tested. 6. We have asked whether in mice which show a decrease in alcohol preference with age, liver ADH activity also decreases with time. The answer to this question was affirmative. 7. It was hypothesized that mice which are selectively bred for high and low alcohol preference show a correlated selection response in terms of liver ADH activity. The answer to this question was affirmative; mice selected for high alcohol preference have higher liver ADH activity than mice selected for low alcohol preference. A number of questions were asked about the metabolism of alcohol in different strains of mice in attempting to discover the underlying biochemical reasons for these differences in alcohol preference behavior. In every case the answers make it appear as if we are heading in the right direction. No one, of course, can say whether these differences which we have described are the real answer to why certain mice drink alcohol and others do not. What can be said, however, is that a good start in that direction has been made.
SPINAL ANAESTHESIA: A STUDY OF 250 CONSECUTIVE CASES
Authors: A. W. Adams
Journal: BMJ (1931)

COMMENTARYOperations in old patients, therefore, take a very secondarv place compared with primary mechanical treat- ment.The cases left for operation are usuially neglected ones.Un-united and mal-united fractures occurring in the virile-for which reconstructive operations are needed- without benefit.On January-9th, 1931, he was definitely wTorse, and, aided by two sticks, walked with great dlifficulty.On that date liver treatment was begun.Patient reported on March 25th.He stated that he was immensely better, and that he had been working four hours a day for over a month.
Personality Factors Associated With Dissociation: Temperament, Defenses, and Cognitive Schemata
Authors: Daphne Simeon, Orna Guralnik, Margaret Knutelska, James Schmeidler
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: The purpose of this study was to investigate temperamental, psychodynamic, and cognitive factors associated with dissociation. METHOD: Fifty-three subjects with DSM-IV-defined depersonalization disorder and 22 healthy comparison subjects were administered the Dissociative Experiences Scale, the Tridimensional Personality Questionnaire, the Defense Style Questionnaire, and the Schema Questionnaire. RESULTS: Subjects with depersonalization disorder demonstrated significantly greater harm-avoidant temperament, immature defenses, and overconnection and disconnection cognitive schemata than comparison subjects. Within the group of subjects with depersonalization disorder, dissociation scores significantly correlated with the same variables. CONCLUSIONS: Particular personality factors may render individuals more vulnerable to dissociative symptoms. Risk factors associated with dissociative disorders merit further study.
Selenium and sulindac are synergistic to inhibit intestinal tumorigenesis in Apc/p21 mice
Authors: Xiuli Bi, Nicole Pohl, Huali Dong, Wancai Yang
Journal: Journal of Hematology & Oncology (2013)

Abstract Background Both selenium and non-steroidal anti-inflammatory drug (NSAID) sulindac are effective in cancer prevention, but their effects are affected by several factors including epigenetic alterations and gene expression. The current study was designed to determine the effects of the combination of selenium and sulindac on tumor inhibition and the underlying mechanisms. Results We fed the intestinal tumor model Apc/p21 mice with selenium- and sulindac-supplemented diet for 24 weeks, and found that the combination of selenium and sulindac significantly inhibited intestinal tumorigenesis, in terms of reducing tumor incidence by 52% and tumor multiplicities by 80% (p&lt;0.01). Mechanistic studies revealed that the combination of selenium and sulindac led to the significant induction of the expression of p27 and p53 and JNK1 phosphorylation, and led to the suppression of β-catenin and its downstream targets. Impressively, the data also showed that demythelation on p21 promoter was associated with tumor inhibition by the combination of selenium and sulindac. Conclusions The selenium is synergistic with sulindac to exert maximal effects on tumor inhibition. This finding provides an important chemopreventive strategy using combination of anti-cancer agents, which has a great impact on cancer prevention and has a promising translational potential.