tbuckley/cabot-search huggingface dataset:
Apoptosis of Tubular Epithelial Cells in Donor Kidney Biopsies Predicts Early Renal Allograft Function
Authors: RAINER OBERBAUER, MANUELA ROHRMOSER, HEINZ REGELE, FERDINAND MÜHLBACHER, GERT MAYER
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Acute renal failure (ARF) is a serious complication in the early postoperative period after kidney transplantation. In an effort to identify subjects at risk, several donor-, recipient-, and procedure-related factors have been studied. Because no morphologic parameter predictive of delayed graft function has been identified to date, this study was conducted to determine whether the number of apoptotic cells in donor biopsies obtained before engraftment is predictive of the development of posttransplant ARF. Donor biopsies of patients with “biopsyproven” acute tubular damage but no signs of rejection ( n = 23) showed significantly higher counts of apoptotic tubular epithelial cells when compared to patients with immediate transplant function ( n = 44) or early rejection ( n = 22). In all groups, a significantly higher percentage of apoptotic cells was found in the distal compared to the proximal tubule. The expression of bcl-2 and proliferating cell nuclear antigen was not different among the groups. Late allograft function was not affected by early ARF as serum creatinine values were similar in all three groups after 6 mo. These data suggest that the number of apoptotic renal tubular epithelial cells in donor biopsies before engraftment is predictive of the early postoperative course in patients undergoing kidney transplantation.
Association of a non-synonymous functional variant of the ITGAM gene with systemic sclerosis
Authors: F. D. Carmona, C. P. Simeon, L. Beretta, P. Carreira, M. C. Vonk, R. Rios-Fernandez, G. Espinosa, N. Navarrete, E. Vicente-Rabaneda, L. Rodriguez-Rodriguez, C. Tolosa, F. J. Garcia-Hernandez, I. Castellvi, M. V. Egurbide, V. Fonollosa, M. A. Gonzalez-Gay, M. Rodriguez-Carballeira, F. Diaz-Gonzalez, L. Saez-Comet, R. Hesselstrand, G. Riemekasten, T. Witte, A. E. Voskuyl, A. J. Schuerwegh, R. Madhok, P. Shiels, C. Fonseca, C. Denton, A. Nordin, O. Palm, A.-M. Hoffmann-Vold, P. Airo, R. Scorza, C. Lunardi, J. M. van Laar, N. Hunzelmann, A. Kreuter, A. Herrick, J. Worthington, B. P. C. Koeleman, T. R. D. J. Radstake, J. Martin
Journal: Annals of the Rheumatic Diseases (2011)

Systemic sclerosis (SSc) is a chronic fibrotic autoimmune disease of complex aetiology which shares genetic similarities with systemic lupus erythematosus (SLE).1 2 One of the novel risk loci that have been recently associated with SLE is the integrin α M ( ITGAM ) gene, which encodes the α subunit of the αMβ2-integrin.3 4 The most likely causal polymorphism that best explains this association is a non-synonymous single-nucleotide polymorphism (SNP) at the exon 3, rs1143679, which changes the 77th amino acid residue arginine to histidine (R77H). This functional SNP represents one of the highest associated signals with SLE and is predicted to alter the structure and function of the integrin.4 5 To determine whether ITGAM rs1143679 is also associated with SSc susceptibility and clinical manifestations, we genotyped a total of 3735 SSc patients and 3930 matched healthy individuals from seven independent European cohorts of Caucasian origin (Spain, Germany, The Netherlands, Italy, Norway, Sweden and UK) using a predesigned TaqMan® assay (ID: C\__\_|2847895\_1_) in an ABI 7900HT (both from Applied Biosystems, Foster City, California, USA). Case …
Functional immunoglobulin light chain genes are replaced by ongoing rearrangements of germline V kappa genes to downstream J kappa segment in a murine B cell line.
Authors: S Levy, M J Campbell, R Levy
Journal: The Journal of Experimental Medicine (1989)

A murine B cell lymphoma (38C13) was subjected to immunoselection with mAbs directed against the idiotypic determinants of its cell surface Ig. Variants emerged with altered Ig receptors containing identical heavy chains but different light chains. The functional light chain genes in these variants were composed of V kappa segments drawn from the V kappa Ox-1 family, which had replaced the V kappa gene expressed by the parental tumor by rearranging to downstream J kappa segments. Rearrangement at the kappa locus continued to occur spontaneously, giving rise to secondary and tertiary variants at a rate of 1.9 x 10(-4) per cell per generation. Variants were isolated that had ceased production of surface Ig but went on to rearrange again and to become surface Ig+. The Ig- state may be an intermediate step providing a stimulus for continued rearrangement. This process provides an additional mechanism for generating diversity within B cell clones and expands the use of the available repertoire of Ig genes.
Chemoradiotherapy With or Without AE-941 in Stage III Non–Small Cell Lung Cancer: A Randomized Phase III Trial
Authors: Charles Lu, J. Jack Lee, Ritsuko Komaki, Roy S. Herbst, Lei Feng, William K. Evans, Hak Choy, Pierre Desjardins, Benjamin T. Esparaz, Mylene T. Truong, Scott Saxman, Joseph Kelaghan, Archie Bleyer, Michael J. Fisch
Journal: JNCI Journal of the National Cancer Institute (2010)

BackgroundAE-941 is a standardized aqueous shark cartilage extract with antiangiogenic properties that has previously been evaluated in phase I and II clinical trials. Our objective was to determine the effect of adding AE-941 to chemoradiotherapy on overall survival of patients with unresectable stage III non–small cell lung cancer (NSCLC).
Cells with Defective p53-p21-pRb Pathway Are Susceptible to Apoptosis Induced by p84N5 via Caspase-6
Authors: Elizabeth Garner, Fabio Martinon, Jurg Tschopp, Peter Beard, Kenneth Raj
Journal: Cancer Research (2007)

Adeno-associated virus (AAV) infection triggers a DNA damage response in the cell. This response is not induced by viral proteins but by virtue of the structure of AAV ssDNA being recognized by the cell as damaged DNA. The consequence of this is the killing of cells lacking p53 activity. We have observed that cells that lack p21 or pRb activity are also sensitive to AAV-induced cell death. We report that cells respond to AAV infection by activating two DNA damage signaling cascades. The first activates the p84N5 protein, which in turn activates caspase-6, leading to cell death. The second cascade activates the p53-21-pRb pathway, which inhibits activation of the p84N5 protein and thus prevents cell death. The result of the antagonistic interaction between these two pathways is that cells that do not exhibit functional p53-p21-pRb signaling undergo apoptosis as a consequence of AAV infection. Cells with a functional p53-21-pRb pathway are refractory to AAV-induced cell death. These results show that p53, although a proapoptotic protein, together with pRb and p21 proteins, is a member of an antiapoptotic cellular mechanism. As such, these experiments reveal features that may be exploited to specifically kill cells that lack the p53-p21-pRb pathway, such as cancer cells. The use of AAV to expose these subtle characteristics of intracellular signaling further highlights the advantages of using viruses as precision tools with which to address questions of cell biology.
Myocardial Infarction Mortality Risk After Treatment for Hodgkin Disease: A Collaborative British Cohort Study
Authors: Anthony J. Swerdlow, Craig D. Higgins, Paul Smith, David Cunningham, Barry W. Hancock, Alan Horwich, Peter J. Hoskin, Andrew Lister, John A. Radford, Ama Z. S. Rohatiner, David C. Linch
Journal: JNCI Journal of the National Cancer Institute (2007)

Myocardial infarction is a major cause of excess long-term mortality in survivors of Hodgkin disease, but limited information exists on the effects of specific chemotherapy regimens used to treat these patients on their risk of death from myocardial infarction.We followed a cohort of 7033 Hodgkin disease patients who were treated in Britain from November 1, 1967, through September 30, 2000, and compared their risk of myocardial infarction mortality with that in the general population of England and Wales. All statistical tests were two-sided.A total of 166 deaths from myocardial infarction occurred in the cohort, statistically significantly more than expected (standardized mortality ratio [SMR] = 2.5, 95% confidence interval [CI] = 2.1 to 2.9), with an absolute excess risk of 125.8 per 100,000 person-years. Standardized mortality ratios decreased sharply with older age at first treatment, but absolute excess risks of death from myocardial infarction increased with older age up to age 65 years at first treatment. The statistically significantly increased risk of myocardial infarction mortality persisted through to 25 years after first treatment. Risks were increased statistically significantly and independently for patients who had been treated with supradiaphragmatic radiotherapy, anthracyclines, or vincristine. Risk was particularly high for patients treated with the doxorubicin, bleomycin, vinblastine, and dacarbazine regimen (SMR = 9.5, 95% CI = 3.5 to 20.6). Risk at 20 or more years after first treatment was particularly great for patients who had received supradiaphragmatic radiotherapy and vincristine without anthracyclines (SMR = 14.8, 95% CI = 4.8 to 34.5).The risk of death from myocardial infarction after treatment for Hodgkin disease remains high for at least 25 years. The increased risks are related to supradiaphragmatic radiotherapy but may also be related to anthracycline and vincristine treatment.
"Sentinel lines"--an unusual sign of lower lobe contraction.
Authors: B Strickland
Journal: Thorax (1976)

Of the various densities occurring in the lower zones of the standard postero-anterior chest radiograph, one sign has been ignored. Coarse linear densities at the bases may be due to adjacent lower lobe contraction. The cause is related to bending or kinking of the lower zone bronchi, usually the superior and inferior branches of the lingular bronchi. The densities are probably due to mucus-filled bronchi or alveolar atelectasis distal to the kink. resulting from poor bronchial drinage, and may indicate more extensive disease. The left lower lobe collapse may not be visible on the chest radiograph but the presence of these densities should alert the observer to the more important associated abnormality.
A Randomized Trial of Low-Dose Aspirin in the Prevention of Clinical Type 2 Diabetes in Women
Authors: Aruna D. Pradhan, Nancy R. Cook, JoAnn E. Manson, Paul M. Ridker, Julie E. Buring
Journal: Diabetes Care (2008)

Subclinical inflammation is linked with the development of type 2 diabetes, and epidemiologic data suggest that this association may be stronger in women. Although small clinical studies have shown a prominent hypoglycemic effect of short-term high-dose aspirin, no randomized trials have directly evaluated the efficacy of aspirin in diabetes prevention at doses acceptable for use in routine clinical practice. We evaluated whether chronic low-dose aspirin prevents the development of clinical diabetes among initially healthy American women.Subjects were enrolled in the Women's Health Study, a 10-year randomized double-blind, placebo-controlled trial of aspirin and vitamin E for primary prevention of cardiovascular disease and cancer. Between 1992 and 1995, 38,716 women aged > or =45 years and free of clinical diabetes were randomly assigned to either low-dose aspirin or placebo (median follow-up 10.2 years). Documented clinical type 2 diabetes was prospectively evaluated throughout the trial.Among women randomly assigned to receive aspirin (n = 19,326) or placebo (n = 19,390), there was no statistically significant difference in the incidence of type 2 diabetes. There were 849 cases of diabetes in the aspirin group and 847 in the placebo group (rate ratio 1.01 [95% CI 0.91-1.11]). Stratification by diabetes risk factors including age, BMI, family history of diabetes, physical activity, A1C, and high-sensitivity C-reactive protein did not support a modulating effect of these variables. Analyses accounting for treatment duration and adherence similarly found no beneficial effects.These data suggest that long-term low-dose aspirin does not prevent the development of clinical type 2 diabetes in initially healthy women.
Implication of a Rare Deletion at Distal 16p11.2 in Schizophrenia
Authors: Saurav Guha, Elliott Rees, Ariel Darvasi, Dobril Ivanov, Masashi Ikeda, Sarah E. Bergen, Patrik K. Magnusson, Paul Cormican, Derek Morris, Michael Gill, Sven Cichon, Jeffrey A. Rosenfeld, Annette Lee, Peter K. Gregersen, John M. Kane, Anil K. Malhotra, Marcella Rietschel, Markus M. Nöthen, Franziska Degenhardt, Lutz Priebe, René Breuer, Jana Strohmaier, Douglas M. Ruderfer, Jennifer L. Moran, Kimberly D. Chambert, Alan R. Sanders, Jianxin Shi, Kenneth Kendler, Brien Riley, Tony O’Neill, Dermot Walsh, Dheeraj Malhotra, Aiden Corvin, Shaun Purcell, Pamela Sklar, Nakao Iwata, Christina M. Hultman, Patrick F. Sullivan, Jonathan Sebat, Shane McCarthy, Pablo V. Gejman, Douglas F. Levinson, Michael John Owen, Michael Conlon O'Donovan, Todd Lencz, George Kirov
Journal: JAMA Psychiatry (2013)

Large genomic copy number variations have been implicated as strong risk factors for schizophrenia. However, the rarity of these events has created challenges for the identification of further pathogenic loci, and extremely large samples are required to provide convincing replication.To detect novel copy number variations that increase the susceptibility to schizophrenia by using 2 ethnically homogeneous discovery cohorts and replication in large samples.Genetic association study of microarray data.Samples of DNA were collected at 9 sites from different countries.Two discovery cohorts consisted of 790 cases with schizophrenia and schizoaffective disorder and 1347 controls of Ashkenazi Jewish descent and 662 parent-offspring trios from Bulgaria, of which the offspring had schizophrenia or schizoaffective disorder. Replication data sets consisted of 12,398 cases and 17,945 controls.Statistically increased rate of specific copy number variations in cases vs controls.One novel locus was implicated: a deletion at distal 16p11.2, which does not overlap the proximal 16p11.2 locus previously reported in schizophrenia and autism. Deletions at this locus were found in 13 of 13,850 cases (0.094%) and 3 of 19,954 controls (0.015%) (odds ratio, 6.25 [95% CI, 1.78-21.93]; P = .001, Fisher exact test).Deletions at distal 16p11.2 have been previously implicated in developmental delay and obesity. The region contains 9 genes, several of which are implicated in neurological diseases, regulation of body weight, and glucose homeostasis. A telomeric extension of the deletion, observed in about half the cases but no controls, potentially implicates an additional 8 genes. Our findings add a new locus to the list of copy number variations that increase the risk for development of schizophrenia.
Antipeptic activity of antacids
Authors: J. T. Kuruvilla
Journal: Gut (1971)

An in vitro experiment based on the digestion of haemoglobin with pepsin was carried out to test the claim made by some manufacturers that the antacids used in their proprietary preparations had an intrinsic antipeptic activity independent of the change brought about by alteration of pH. In no case could these claims be substantiated.
Localization of anionic sites in normal and psoriatic epidermis: the effect of enzyme digestion on these anionic sites
Authors: K. SAGA, M. TAKAHASHI
Journal: British Journal of Dermatology (2006)

Cell surface anionic charge is known to be related to various cellular functions. Therefore, we ultrastructurally localized anionic sites in normal and psoriatic human epidermis, using poly-l-lysine-gold complex (cationic gold), to assess their possible participation in the differentiation of keratinocytes and the pathogenesis of psoriasis. In normal and psoriatic epidermis, the cell membrane of keratinocytes showed positive staining at pH 2.0. At pH 7.4 the cytoplasm and nucleus were diffusely stained, in addition to the cell membrane. In normal epidermis, the intensity of labelling on the cell membrane at pH 2.0 was strong in the basal layer and lower stratum spinosum, and decreased in parallel with differentiation of keratinocytes. In psoriatic epidermis, the intensity of labelling on the cell membrane at pH 2.0 was stronger than in normal epidermis. In normal epidermis, heparitinase digested 63% and chondroitinase ABC digested 80% of cationic labelling. This suggests that heparan sulphate and chondroitin sulphate (and/or dermatan sulphate) constitute anionic sites in normal epidermis. In psoriatic epidermis, chondroitinase ABC-sensitive anionic sites were greatly increased, whereas heparitinase-sensitive anionic sites were the same, when compared with normal epidermis. This suggests that chondroitin sulphate and/or dermatan sulphate constitute anionic sites which are increased in psoriatic epidermis.
Effect of eight weeks of treatment with salmeterol on bronchoalveolar lavage inflammatory indices in asthmatics.
Authors: P V Gardiner, C Ward, H Booth, A Allison, D J Hendrick, E H Walters
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

Using BAL, we studied the effects of 8 wk of treatment with salmeterol on airway inflammation in nine asthmatic subjects in a double-blind crossover placebo-controlled protocol. The study patients were all receiving regular inhaled corticosteroid therapy (400 to 1,000 micrograms beclomethasone dipropionate per day) and inhaled albuterol for symptomatic relief, i.e., subjects who might be considered suitable for treatment with salmeterol. The asthmatic group had significant differences in numbers of epithelial cells and eosinophils in BAL compared with a group of 15 normal control subjects (p < 0.01). During salmeterol treatment mean morning and evening peak flow rates were increased (p < 0.05). There was no significant change in BAL cell profile and no change in percentages of CD4 and CD8 lymphocytes or proportion of lymphocytes expressing HLA-DR after salmeterol. In conclusion, we were unable to demonstrate any significant anti-inflammatory effect of regular salmeterol therapy on airway inflammation using BAL in these asthmatic patients. At the same time, there was equally no evidence of a deterioration in the underlying inflammatory disease process.
Review of exercise studies in breast cancer survivors: attention to principles of exercise training
Authors: Kristin L Campbell, Sarah E Neil, Kerri M Winters-Stone
Journal: British Journal of Sports Medicine (2012)

Research supports the use of exercise to improve quality of life and reduce the side effects of breast cancer treatment, such as fatigue and decreased aerobic capacity. Previously published reviews have focused on reporting the outcomes of exercise interventions, but have not critically examined the exercise prescriptions. The purpose of this review is to evaluate the application of the principles of exercise training in the exercise prescriptions reported in intervention studies for breast cancer survivors.Databases were searched for randomised controlled trials of exercise in women diagnosed with breast cancer. Data were extracted to evaluate the application of the principles of exercise training, the reporting of the components of the exercise prescription and the reporting of adherence to the exercise prescription.Of the 29 papers included, none applied all principles of exercise training. Specificity was applied by 64%, progression by 41%, overload by 31%, initial values by 62% and diminishing returns and reversibility by 7% of trials. No study reported all components of the exercise prescription.The application of the principles of exercise training varied greatly, and reporting of the exercise prescribed and completed was incomplete. When principles of exercise training are applied to the development of exercise protocols, there is greater confidence that non-significant findings reflect lack of efficacy of exercise rather than deficiencies in the prescription. Incomplete reporting of the exercise prescription and adherence to the prescription limits the reproducibility of the intervention, and the ability to determine the dose of exercise received by participants.
Supportive evidence is lacking for report on animal studies
Authors: P. Pound
Journal: BMJ (2002)

EDITOR—As Dobson notes, the House of Lords Select Committee on Animals in Scientific Procedures concluded that animal experiments were necessary but that more needs to be done to develop and promote alternative methods.1

Although it is clear that the committee sought the views and opinions of a wide range of experts, we were struck throughout by the lack of published, peer reviewed evidence to support one of its important conclusions: “On balance, we are convinced that experiments on animals have contributed greatly …
Discrimination of the toxic potential of chemically differing topical glucocorticoids using a neutral red release assay with human keratinocytes and fibroblasts
Authors: H. C. KORTING, E. HÜLSEBUS, M. KERSCHER, R. GREBER, M. SCHÄFER-KORTING
Journal: British Journal of Dermatology (2006)

In inflammatory skin disease, hydrocortisone and prednisolone double esters are about equipotent to conventional medium potency topical glucocorticoids, such as betamethasone valerate. Local adverse effects, in particular skin atrophy, are a potential problem with topical glucocorticoids. Recently, cell cultures have shown promise as a means of assessing local tolerance. To investigate the toxic potential of hydrocortisone, hydrocortisone-17-butyrate, hydrocortisone aceponate, prednicarbate, triamcinolone acetonide, betamethasone valerate and desoximethasone, human keratinocytes and fibroblasts were exposed to these agents in vitro, using a modified neutral red release assay. In addition, the morphology of these cells was assessed by light microscopy. Although all the topical glucocorticoids tested proved toxic to both cell types, there were major differences between glucocorticoids in their effect on fibroblasts. Hydrocortisone and the non-halogenated double-ester-type glucocorticoids were less toxic than the conventional medium potency topical glucocorticoids tested (betamethasone valerate and desoximethasone). In particular, hydrocortisone aceponate was less toxic than betamethasone valerate (P < or = 0.05). In general, the effect of topical glucocorticoids on the cells, based on neutral red release, was more marked with keratinocytes than with fibroblasts. Although the ranking order with respect to the toxic potential was similar, a clear-cut difference was not observed between non-halogenated double-ester-type glucocorticoids and betamethasone valerate. Morphological changes due to glucocorticoid exposure followed the same pattern with both keratinocytes and fibroblasts. The neutral red release assay is able to discriminate between the cytotoxic effects of chemically differing topical glucocorticoids on human keratinocytes and fibroblasts.(ABSTRACT TRUNCATED AT 250 WORDS)