tbuckley/cabot-search huggingface dataset:
Course and Predictors of Cognitive Function in Patients With Prostate Cancer Receiving Androgen-Deprivation Therapy: A Controlled Comparison
Authors: Brian D. Gonzalez, Heather S.L. Jim, Margaret Booth-Jones, Brent J. Small, Steven K. Sutton, Hui-Yi Lin, Jong Y. Park, Philippe E. Spiess, Mayer N. Fishman, Paul B. Jacobsen
Journal: Journal of Clinical Oncology (2015)

Men receiving androgen-deprivation therapy (ADT) for prostate cancer may be at risk for cognitive impairment; however, evidence is mixed in the existing literature. Our study examined the impact of ADT on impaired cognitive performance and explored potential demographic and genetic predictors of impaired performance.Patients with prostate cancer were assessed before or within 21 days of starting ADT (n = 58) and 6 and 12 months later. Age- and education-matched patients with prostate cancer treated with prostatectomy only (n = 84) and men without prostate cancer (n = 88) were assessed at similar intervals. Participants provided baseline blood samples for genotyping. Mean-level cognitive performance was compared using mixed models; cognitive impairment was compared using generalized estimating equations.ADT recipients demonstrated higher rates of impaired cognitive performance over time relative to all controls (P = .01). Groups did not differ at baseline (P > .05); however, ADT recipients were more likely to demonstrate impaired performance within 6 and 12 months (P for both comparisons < .05). Baseline age, cognitive reserve, depressive symptoms, fatigue, and hot flash interference did not moderate the impact of ADT on impaired cognitive performance (P for all comparisons ≥ .09). In exploratory genetic analyses, GNB3 single-nucleotide polymorphism rs1047776 was associated with increased rates of impaired performance over time in the ADT group (P < .001).Men treated with ADT were more likely to demonstrate impaired cognitive performance within 6 months after starting ADT relative to matched controls and to continue to do so within 12 months after starting ADT. If confirmed, findings may have implications for patient education regarding the risks and benefits of ADT.
Disturbances in the A-V Conduction System in Chagas' Myocarditis in the Dog
Authors: ALFONSO ANSELMI, ORLANDO GURDIEL, JOSé ANGEL SUAREZ, GERARDO ANSELMI
Journal: Circulation Research (1967)

Atrioventricular (A-V) conduction and the functional refractory period (FRP) of the A-V system were studied in 13 dogs chronically infected by T. cruzi that had ECG disturbances indicative of myocarditis. Histopathologic findings at the A-V node and the bundle of His were correlated with the FRP and with conduction times of the A-V propagation system. Retarded conduction was related to inflammatory and fibrotic processes localized at the bundle of His. At relatively slow rates of stimulation, conduction time was prolonged, but the ventricle was capable of following high atrial rates. With augmented FRP, mononuclear cell infiltrates were observed in the A-V node or in the septal muscle around the node. This suggests that the node was included in the inflammatory process. No correlation was found between inflammatory infiltrates of the bundle of His and changes in the FRP. At relatively slow rates of stimulation, normal A-V conduction time corresponded to prolonged FRP. A-V conduction became slow as the atrial rate increased. A point was reached when the ventricle could not follow the moderately increased atrial rates. Excitability of cardiac tissues was so markedly altered in 5 dogs with severe inflammatory infiltrates that a similar study of the A-V system could not be made.
Exercise in patients with chronic obstructive pulmonary disease.
Authors: M J Belman
Journal: Thorax (1993)

Sporadic visits to the local doctor followed sometimes by changes in oral and inhaled bronchodilators and occasionally by the addition of steroids frequently does little to significantly improve symptoms and function in the disabled patient with COPD. As in other chronic diseases, the management of these patients is facilitated by a team approach in conjunction with general rehabilitation principles. The rationale and practical implementation of such a programme has recently been outlined by the American Association of Cardiopulmonary Rehabilitation. These are multifaceted programmes but a key component, as outlined above, is exercise training. In this brief review the various approaches available have been described. Controversy still reigns regarding the optimal modes of training and there are important differences among the several approaches. Two main groups can be delineated. One emphasises the detailed definition of the impaired physiology with therapeutic measures targeted to specific defects. There is good documentation that, conversely, unstructured programmes that use treadmill and free range walking and cycling also improve endurance for walking. Upper extremity training is of additional benefit. Programmes with as little as three sessions per week of 1-2 hours of low intensity activity have achieved success so we know that simple programmes can be helpful. Moreover, without the necessity for complex testing and training methods these programmes can be implemented with relatively low costs. Future investigations to examine the relationship between improved exercise capacity for walking and arm exercise on the one hand, and the ease of performance of activities of daily living on the other, will help to reinforce the effectiveness of exercise programmes.
A Systematic Screen for CDK4/6 Substrates Links FOXM1 Phosphorylation to Senescence Suppression in Cancer Cells
Authors: Lars Anders, Nan Ke, Per Hydbring, Yoon J. Choi, Hans R. Widlund, Joel M. Chick, Huili Zhai, Marc Vidal, Stephen P. Gygi, Pascal Braun, Piotr Sicinski
Journal: Cancer Cell (2011)
Inferring the Evolutionary History of IncP-1 Plasmids Despite Incongruence among Backbone Gene Trees
Authors: Diya Sen, Celeste J. Brown, Eva M. Top, Jack Sullivan
Journal: Molecular Biology and Evolution (2012)

Plasmids of the incompatibility group IncP-1 can transfer and replicate in many genera of the Proteobacteria.They are composed of backbone genes that encode a variety of essential functions and accessory genes that have implications for human health and environmental remediation.Although it is well understood that the accessory genes are transferred horizontally between plasmids, recent studies have also provided examples of recombination in the backbone genes of IncP-1 plasmids.As a consequence, phylogeny estimation based on backbone genes is expected to produce conflicting gene tree topologies.The main goal of this study was therefore to infer the evolutionary history of IncP-1 plasmids in the presence of both vertical and horizontal gene transfer.This was achieved by quantifying the incongruence among gene trees and attributing it to known causes such as 1) phylogenetic uncertainty, 2) coalescent stochasticity, and 3) horizontal inheritance.Topologies of gene trees exhibited more incongruence than could be attributed to phylogenetic uncertainty alone.Species-tree estimation using a Bayesian framework that takes coalescent stochasticity into account was well supported, but it differed slightly from the maximum-likelihood tree estimated by concatenation of backbone genes.After removal of the gene that demonstrated a signal of intergroup recombination, the concatenated tree was congruent with the species-tree estimate, which itself was robust to inclusion/exclusion of the recombinant gene.Thus, in spite of horizontal gene exchange both within and among IncP-1 subgroups, the backbone genome of these IncP-1 plasmids retains a detectable vertical evolutionary history.
A CASE OF PITYRIASIS LICHENOIDES ET VARIOLIFORMIS ACUTA
Authors: H. W. BARBER
Journal: British Journal of Dermatology (1931)

Journal Article A CASE OF PITYRIASIS LICHENOIDES ET VARIOLIFORMIS ACUTA Get access H. W. BARBER, M.B., F.R.C.P. H. W. BARBER, M.B., F.R.C.P. Physician in Charge of Skin Department, Guy's Hospital Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 43, Issue 3, 1 March 1931, Pages 126–129, https://doi.org/10.1111/j.1365-2133.1931.tb09477.x Published: 01 March 1931
Idiotype connectance in the immune system. II. A heavy chain variable region idiotope that dominates the antibody response to the p-azobenzenearsonate group is a minor idiotope in the response to trinitrophenyl group.
Authors: P V Hornbeck, G K Lewis
Journal: The Journal of Experimental Medicine (1985)

We describe the recurrence of a cross-reactive idiotope (CRIAD8) in antibody responses to different epitopes, and explore factors leading to its dominance in some responses, but not others. Serological and genomic DNA analyses showed that CRIAD8 is a marker of the CRIa heavy chain variable region (VH) that encodes the majority of anti-p-azobenzenearsonate (anti-ABA) antibodies. The independence of CRIAD8 from any particular light chain or antigen specificity was underscored by the fact that we could isolate hybridomas that secrete antitrinitrophenyl (TNP) antibodies expressing CRIAD8, with lambda 1 light chains. CRIAD8 is dominant in anti-ABA responses, recurrent but nondominant in anti-TNP and anti-chicken gammaglobulin responses, and is virtually absent in other antihapten responses, including that to p-azobenzenephosphonate (ABP), which contains an ABA-cross-reactive component (approximately 5-40%). Dominance in the anti-TNP response could not be achieved by immunization with doubly haptenated TNP-ABA-KLH (keyhole limpet hemocyanin), where the anti-ABA response was dominated by CRIAD8. These observations suggest that, while the CRIAD8 VH region is necessary for idiotypic dominance, it is not sufficient. Apparently, an additional specificity is required. Since immunization with ABA calls up anti-ABP antibodies that express CRIAD8, but not vice versa, it is possible that the additional specificity is ABA itself. This possibility imposes a new constraint on the specificity of the putative idiotype-specific regulation that may establish dominance in the CRIa system.
Nuclear localization and characterization of alkaline phosphatase in neutrophils from normal controls and pregnant women
Authors: Henri A. Vergnes, Andrée Brisson‐Lougarre, Jean G. Grozdea, Claude J. Blum, Y. Kihn, J. Sevely
Journal: American Journal of Hematology (1992)

Abstract There were controversial data concerning localization of alkaline phosphatase (AP) in neutrophil nuclei under physiological conditions. In this context, the AP pattern has been determined on nuclei preparations from normal human neutrophils. Blood cells were isolated from 10 healthy adults and from 3 women in the third trimester of an uncomplicated pregnancy. Purity of nuclear suspension was checked by electron microscopy and assay of organelle marker enzymes. Electron microscope cytochemistry and immunocytochemistry studies were carried out on WBC. Enzyme characterization was performed by the usual biochemical procedures. AP was found in nuclear preparations from four of ten normal controls. When present, AP was detected in approximately two‐thirds of the nuclei examined, representing an average of 20% of the total cell activity. Conversely, a large amount of nucleus‐bound enzyme (55% of total AP activity) was recognized in all pregnant women samples. Biochemical and immunological characteristics clearly differentiate AP forms in the two groups of subjects. Normal controls have an heterogeneous enzyme pattern. AP positive preparations contain a mixture of isoenzymes: a prominent heat labile form and a relatively heat stable minor component. The heat stable fraction displays some properties similar to those previously described in leukocyte AP. Pregnant women express a unique very heat labile isoenzyme identical in its main characteristics to the early placental type. © 1992 Wiley‐Liss, Inc.
Frequency and determinants of exaggerated bronchoconstriction during shortened methacholine challenge tests in epidemiological and clinical set-ups
Authors: S Troyanov, J-L Malo, A Cartier, D Gautrin
Journal: European Respiratory Journal (2000)

The European Respiratory Society guidelines on bronchial provocation testing have proposed time-saving procedures, which may lead to unwanted exaggerated responses. The frequency and determinants of exaggerated bronchoconstriction in response to methacholine inhalation testing in clinical and epidemiological settings have not been assessed. The authors evaluated: 1) the prevalence of exaggerated bronchoconstriction, 2) its relation to time-saving measures (starting methacholine concentration and skipping concentrations); and 3) associations between such reactions and risk factors, respiratory symptoms and/or lung function parameters. Clinical (n=408) and epidemiological (n=711) groups were included. Exaggerated bronchoconstriction was defined as either a fall &gt; or =20% following saline or a &gt; or =30% fall in forced expiratory volume in one second (FEV1) after methacholine inhalations. Cases were compared with two groups of subjects: 1) with measurable bronchial responsiveness (MBR); and 2) without MBR. In the epidemiological group, 84 subjects (12%) presented exaggerated bronchoconstriction. Skipped concentrations accounted for an exaggerated bronchoconstriction in 18 of these. In the clinical group, 41 subjects (10%) experienced exaggerated reactions. Skipped concentrations accounted for an exaggerated bronchoconstriction in five of these. The provocative concentration of methacholine causing a 20% fall in FEV1 values were marginally lower in subjects with exaggerated bronchoconstriction. Questionnaire analysis in epidemiological subjects showed some symptoms of asthma and rhinitis to be more prevalent in cases than in subjects without MBR. In conclusion, methacholine inhalation tests with time-saving measures result in a 10% risk of exaggerated bronchoconstriction as defined in this study and bronchial responsiveness is more prominent in subjects with exaggerated bronchoconstriction.
Biomarker Analysis of Neoadjuvant Doxorubicin/Cyclophosphamide Followed by Ixabepilone or Paclitaxel in Early-Stage Breast Cancer
Authors: Christine E. Horak, Lajos Pusztai, Guan Xing, Ovidiu C. Trifan, Cristina Saura, Ling-Ming Tseng, Stephen Chan, Rosanne Welcher, David Liu
Journal: Clinical Cancer Research (2013)

Predictive biomarkers offer the potential to improve the benefit:risk ratio of a therapeutic agent. Ixabepilone achieves comparable pathologic complete response (pCR) rates to other active drugs in the neoadjuvant setting. This phase II trial was designed to investigate potential biomarkers that differentiate response to this agent.Women with untreated, histologically confirmed primary invasive breast adenocarcinoma received neoadjuvant doxorubicin/cyclophosphamide, followed by 1:1 randomization to ixabepilone (n = 148) or paclitaxel (n = 147). Rates of pCR were compared between treatment arms based on predefined biomarker sets: TUBB3, TACC3, and CAPG gene expression, a 20- and 26-gene expression model, MDR1 protein expression, and other potential markers of sensitivity. βIII-tubulin protein expression is reported separately but is referred to here for completeness. All patients underwent a core needle biopsy of the primary cancer for molecular marker analysis before chemotherapy. Gene expression profiling data were used for molecular subtyping.There was no significant difference in the rate of pCR in both treatment arms in βIII-tubulin-positive patients. Higher pCR rates were observed among βIII-tubulin-positive patients than in βIII-tubulin-negative patients. Furthermore, no correlation was evident between TUBB3, TACC3, and CAPG gene expression, MDR1 protein expression, multi-gene expression models, and the efficacy of ixabepilone or paclitaxel, even within the estrogen receptor-negative subset.These results indicate that βIII-tubulin protein and mRNA expression, MDR1 protein expression, TACC3 and CAPG gene expression, and multigene expression models (20- and 26-gene) are not predictive markers for differentiating treatment benefit between ixabepilone and paclitaxel in early-stage breast cancer.
Use of Methodological Standards in Diagnostic Test Research
Authors: M. Carrington Reid
Journal: JAMA (1995)

To determine the frequency and temporal changes in application of seven accepted methodological standards for the evaluation of diagnostic tests.A search of the MEDLINE database yielded 1302 articles about diagnostic test studies, during a 16-year secular interval, 1978 through 1993, in four prominent general medical journals.In the 112 eligible studies, the test was intended for clinical use, indexes of accuracy (sensitivity and specificity or likelihood ratios) were provided, and more than 10 patients were enrolled.Although each study was critically reviewed by one primary observer, a subset was independently evaluated for interrater consistency.The percentage of studies that fulfilled criteria for each of the seven methodological standards are as follows: (1) specify spectrum of evaluated patients, 27%; (2) report test indexes for clinical subgroups, 8%; (3) avoid workup bias, 46%; (4) avoid review bias, 38%; (5) provide numerical precision for test indexes, 11%; (6) report frequency and management of indeterminate results when calculating test indexes, 22%; and (7) specify test reproducibility, 23%. Secular increases were found for six of the seven standards in ranges of use from 14% to 31% during 1978-1981 to 1990-1993. Nevertheless, only one standard, avoidance of workup bias, was fulfilled by more than 50% of studies in the most recent secular interval.These results indicate that most diagnostic tests are still inadequately appraised. The routine demand for methodological standards could raise the quality of diagnostic test information, and the careful predissemination evaluation of diagnostic tests could eliminate useless tests before they receive widespread application.
Early versus delayed initiation of highly active antiretroviral therapy for HIV-positive adults with newly diagnosed pulmonary tuberculosis (TB-HAART): a prospective, international, randomised, placebo-controlled trial
Authors: Sayoki G Mfinanga, Bruce J Kirenga, Duncan M Chanda, Beatrice Mutayoba, Thuli Mthiyane, Getnet Yimer, Oliver Ezechi, Cathy Connolly, Vincent Kapotwe, Catherine Muwonge, Julius Massaga, Edford Sinkala, Wanze Kohi, Lucinda Lyantumba, Grace Nyakoojo, Henry Luwaga, Basra Doulla, Judith Mzyece, Nathan Kapata, Mahnaz Vahedi, Peter Mwaba, Saidi Egwaga, Francis Adatu, Alex Pym, Moses Joloba, Roxana Rustomjee, Alimuddin Zumla, Philip Onyebujoh
Journal: The Lancet Infectious Diseases (2014)
Surgical adjuvant therapy of rectal carcinoma: a controlled evaluation of leucovorin, 5-fluorouracil and radiation therapy with or without interferon-α2b
Authors: C. Gennatas, C. Dardoufas, D. Mouratidou, N. Tsavaris, A. Pouli, G. Androulakis, M. Philippakis, D. Voros, T. Batalis, S. Besbeas, G. Hatzistylianos, J. Katsos, V. Komporozos, N. Legakis, H. Mallas, G. Peros, A. Photopoulos, C. Pisiotis, G. Polymeneas, G. Retalis, L. Samanidis, V. Smyrniotis, A. Stamatiadis, J. Vasiliou, H. Andreadis, J. Papadimitriou
Journal: Annals of Oncology (2003)
Phagocyte enzymes in bronchoalveolar lavage from patients with pulmonary sarcoidosis and collagen vascular disorders
Authors: Y Sibille, JB Martinot, LL Polomski, B Wallaert, M Demusis, JA Rankin, C Voisin, JB Gee
Journal: European Respiratory Journal (1990)

The balance between proteases and antiproteases in the lower respiratory tract is believed to play a role in the outcome of interstitial lung diseases. In this cross-sectional study, we measure several phagocyte derived enzymes, namely plasminogen activator, neutrophil elastase and an ill-defined protease active on the trialanine chromophore substrate succinyl-alanine3-nitroanilide (SLAPN) in bronchoalveolar lavage (BAL) fluid from 42 patients with pulmonary sarcoidosis and from 43 patients with collagen vascular disease (CVD), 22 without lung disease (group I) and 21 associated with parenchymal lung disease (group II). The results show: a) that sarcoidosis is associated with increased plasminogen activator activity and with the presence of enzymatic activity against SLAPN corresponding at least in part to a metalloprotease; b) that CVD in the absence of radiographic lung disease is associated with an increase of plasminogen activator activity and increased levels of alpha 1-antiprotease-neutrophil elastase complexes; c) that the majority of untreated CVD (group II) patients have detectable levels of neutrophil elastase activity. These data show that patients with pulmonary sarcoidosis and CVD have different enzymatic profiles in their lower respiratory tract as assessed by BAL. Thus, sarcoidosis (mostly lymphocytic) is associated with enhanced macrophage-derived proteolytic activity in BAL, while CVD patients both with and without lung disease have increased neutrophil counts and neutrophil elastase complexed to alpha 1-protease inhibitor and presumably inactive in BAL. Finally, only BAL from untreated CVD patients with interstitial lung disease contain neutrophil elastase activity. This latter activity could contribute to the lung lesions frequently observed in these disorders.
CD4+CD45RBHi T cell transfer induced colitis in mice is accompanied by osteopenia which is treatable with recombinant human osteoprotegerin
Authors: F R Byrne
Journal: Gut (2004)

Transfer of CD4+CD45RBHi T cells into semi syngeneic immunodeficient mice represents a model of inflammatory bowel disease (IBD). As patients with IBD often suffer from osteopenia, we studied if this T cell transfer in mice results in osteopenia in addition to colitis, and if treatment with osteoprotegerin (OPG) has effects on the bone mineral density of T cell transferred mice. We also investigated whether osteopenia was due to malabsorption as a result of a dysregulated digestive tract or as a consequence of the inflammatory process.CD4+CD45RBHi or CD4+CD45RBLo T cells (4 x 10(5)) were sorted from CB6F1 and transferred into C.B.17 scid/scid mice. Recipient mice were treated with human IgG1 Fc (control) or Fc-OPG three times per week in a prophylactic regimen as well as a therapeutic regimen (after 10% body weight loss) and were evaluated for osteopenia and colitis.Mice that received CD4+CD45RBHi T cells developed osteopenia (as indicated by decreased bone density accompanied by decreased osteoblasts and increased osteoclasts) and colitis (as indicated by histological changes in the large intestine). Mice that received CD4+CD45RBLo T cells developed neither osteopenia nor colitis. All animals consumed, on average, the same amount of food and water over the course of the study. Prophylactic treatment with Fc-OPG increased bone density in mice that received either CD4+CD45RBHi or CD4+CD45RBLo T cells but had no effects on the gastrointestinal tract. Fc-OPG treatment of osteopenic mice with established IBD caused the normalisation of bone density. Osteopenia in CD4+CD45RBHi T cell recipients was accompanied by hypoparathyroidism that was partially normalised by treatment with Fc-OPG. CD4+CD45RBHi T cell recipients also had a bone marrow inflammatory cell infiltrate expressing tumour necrosis factor alpha which was unaffected by treatment with Fc-OPG.CD4+CD45RBHi T cell transfer results in osteopenia in addition to colitis. Evidence suggests that this osteopenia was induced by inflammatory cell infiltration and not by malabsorption of calcium. Recombinant human osteoprotegerin effectively treated the osteopenia. OPG may be a useful therapeutic option for treating osteopenia in patients with IBD.