tbuckley/cabot-search huggingface dataset:
A single nine-amino acid peptide induces virus-specific, CD8+ human cytotoxic T lymphocyte clones of heterogeneous serotype specificities.
Authors: J Zivny, I Kurane, A M Leporati, M Ibe, M Takiguchi, L L Zeng, M A Brinton, F A Ennis
Journal: The Journal of Experimental Medicine (1995)

It is generally accepted that virus-specific CD8+ cytotoxic T lymphocytes (CTLs) recognize nine-amino acid peptides in conjunction with HLA class I molecules. We recently reported that dengue virus-specific CD8+ CTLs of two different serotype specificities, which were established by stimulation with dengue virus, recognize a single nine-amino acid peptide of the nonstructural protein NS3 of dengue virus type 4 (D4V) in an HLA-B35-restricted fashion. To further analyze the relationships between the serotype specificities of T cells and the amino acid sequence of the recognized peptides, we examined the ability of this viral peptide D4.NS3.500-508 (TPEGIIPTL) to stimulate T lymphocytes of an HLA-B35-positive, dengue virus type 4-immune donor. Peptide stimulation of the PBMC generated dengue virus-specific, HLA-B-35-restricted CD8+ CTL clones. These clones lysed dengue virus-infected autologous cells, as well as autologous target cells pulsed with this peptide. Four patterns of dengue virus serotype specificities were demonstrated on target cells infected with dengue-vaccinia recombinant viruses or pulsed with synthetic peptides corresponding to amino acid sequences of four dengue virus serotypes. Two serotype-specific clones recognized only D4V. Three dengue virus subcomplex-specific clones recognized D1V, D3V, and D4V, and one subcomplex-specific clone recognized D2V and D4V. Three dengue virus serotype-cross-reactive clones recognized D1V-D4V. Thus, a single nine-amino acid peptide induces proliferation of a heterogeneous panel of dengue virus-specific CD8+ CTL clones that are all restricted by HLA-B35 but have a variety of serotype specificities. Peptides that contain a single amino acid substitution at each position of D4.NS3.500-508 were recognized differently by the T cell clones. These results indicate that a single epitope can be recognized by multiple CD8+ CTLs that have a variety of serotype specificities, but the manner of recognition by these multiple CTLs is heterogeneous.
Trachyonychia (rough nails)
Authors: PETER D. SAMMAN
Journal: British Journal of Dermatology (1979)

Journal Article Trachyonychia (rough nails) Get access PETER D. SAMMAN PETER D. SAMMAN Westminster Hospital, London SW1 and St John's Hospital for Diseases of the Skin, London WC2 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 101, Issue 6, 1 December 1979, Pages 701–705, https://doi.org/10.1111/j.1365-2133.1979.tb05650.x Published: 01 December 1979
Intertumor and Intratumor NY-ESO-1 Expression Heterogeneity Is Associated with Promoter-Specific and Global DNA Methylation Status in Ovarian Cancer
Authors: Anna Woloszynska-Read, Paulette Mhawech-Fauceglia, Jihnhee Yu, Kunle Odunsi, Adam R. Karpf
Journal: Clinical Cancer Research (2008)

Abstract Purpose: The cancer/germline antigen NY-ESO-1 is variably expressed in epithelial ovarian cancer (EOC), with most tumors showing low or heterogeneous expression, which limits patient responses to NY-ESO-1 vaccine therapy. We tested the hypothesis that promoter and global genomic DNA methylation status correlates with intertumor and intratumor NY-ESO-1 expression status in EOC. Experimental Design: We utilized 78 EOC tumors and 10 normal ovary controls for quantitative DNA methylation analyses and NY-ESO-1 expression analysis by immunohistochemistry (IHC) and quantitative reverse transcriptase PCR. A subset of EOC tumors were used to perform microdissections of NY-ESO-1 IHC-positive and NY-ESO-1 IHC-negative tissue regions, followed by DNA methylation analyses. EOC cell lines were treated in vitro with decitabine to determine the functional contribution of DNA methylation to NY-ESO-1 gene regulation in EOC. Results: Compared with normal ovary, bulk EOC tissues display increased NY-ESO-1 expression, reduced NY-ESO-1 promoter methylation, and reduced LINE-1 DNA methylation. However, NY-ESO-1 expression is not significantly associated with NY-ESO-1 promoter methylation status in bulk tumors. We hypothesized that this resulted from heterogeneous intratumor NY-ESO-1 expression. Supporting this idea, experiments using microdissected material revealed that intertumor and intratumor NY-ESO-1 expression heterogeneity is significantly correlated with promoter and global DNA methylation status in EOC. Moreover, decitabine treatment functionally restored NY-ESO-1 expression in nonexpressing EOC cell lines. Conclusion: DNA methylation status is associated with both intertumor and intratumor NY-ESO-1 expression status in EOC. These findings support a novel chemoimmunotherapy approach using decitabine to augment NY-ESO-1 vaccine therapy for treatment of recurrent EOC.
p53 deletion impairs clearance of chromosomal-instable stem cells in aging telomere-dysfunctional mice
Authors: Yvonne Begus-Nahrmann, André Lechel, Anna C Obenauf, Kodandaramireddy Nalapareddy, Elvira Peit, Eva Hoffmann, Falk Schlaudraff, Birgit Liss, Peter Schirmacher, Hans Kestler, Esther Danenberg, Nick Barker, Hans Clevers, Michael R Speicher, K Lenhard Rudolph
Journal: Nature Genetics (2009)
Seizures in 204 comatose children: incidence and outcome
Authors: Fenella J. Kirkham, Angela M. Wade, Fiona McElduff, Stewart G. Boyd, Robert C. Tasker, Melinda Edwards, Brian G. R. Neville, Norbert Peshu, Charles R. J. C. Newton
Journal: Intensive Care Medicine (2012)

Seizures are common in comatose children, but may be clinically subtle or only manifest on continuous electroencephalographic monitoring (cEEG); any association with outcome remains uncertain.cEEG (one to three channels) was performed for a median 42 h (range 2-630 h) in 204 unventilated and ventilated children aged ≤15 years (18 neonates, 61 infants) in coma with different aetiologies. Outcome at 1 month was independently determined and dichotomized for survivors into favourable (normal or moderate neurological handicap) and unfavourable (severe handicap or vegetative state).Of the 204 patients, 110 had clinical seizures (CS) before cEEG commenced. During cEEG, 74 patients (36%, 95% confidence interval, 95% CI, 32-41%) had electroencephalographic seizures (ES), the majority without clinical accompaniment (non-convulsive seizures, NCS). CS occurred before NCS in 69 of the 204 patients; 5 ventilated with NCS had no CS observed. Death (93/204; 46%) was independently predicted by admission Paediatric Index of Mortality (PIM; adjusted odds ratio, aOR, 1.027, 95% CI 1.012-1.042; p < 0.0005), Adelaide coma score (aOR 0.813, 95% CI 0.700-0.943; p = 0.006), and EEG grade on admission (excess slow with >3% fast, aOR 5.43, 95% CI 1.90-15.6; excess slow with <3% fast, aOR 8.71, 95% CI 2.58-29.4; low amplitude, 10th centile <9 µV, aOR 3.78, 95% CI 1.23-11.7; and burst suppression, aOR 10.68, 95% CI 2.31-49.4) compared with normal cEEG, as well as absence of CS at any time (aOR 2.38, 95% CI 1.18-4.81). Unfavourable outcome (29/111 survivors; 26%) was independently predicted by the presence of ES (aOR 15.4, 95% CI 4.7-49.7) and PIM (aOR 1.036, 95% CI 1.013-1.059).Seizures are common in comatose children, and are associated with an unfavourable outcome in survivors. cEEG allows the detection of subtle CS and NCS and is a prognostic tool.
New perspectives on community-acquired pneumonia in 388 406 patients. Results from a nationwide mandatory performance measurement programme in healthcare quality
Authors: S Ewig, N Birkner, R Strauss, E Schaefer, J Pauletzki, H Bischoff, P Schraeder, T Welte, G Hoeffken
Journal: Thorax (2009)

<h3>Background:</h3> The database of the German programme for quality in healthcare including data of every hospitalised patient with community-acquired pneumonia (CAP) during a 2-year period (n = 388 406 patients in 2005 and 2006) was analysed. <h3>Methods:</h3> End points of the analysis were: (1) incidence; (2) outcome; (3) performance of the CRB-65 (C, mental confusion; R, respiratory rate ⩾30/min; B, systolic blood pressure &lt;90 mm Hg or diastolic blood pressure ⩽60 mm Hg; 65, age ⩾65 years) score in predicting death; and (4) lack of ventilatory support as a possible indicator of treatment restrictions. The CRB-65 score was calculated, resulting in three risk classes (RCs). <h3>Results:</h3> The incidence of hospitalised CAP was 2.75 and 2.96 per 1000 inhabitants/year in 2005 and 2006, respectively, higher for males (3.21 vs 2.52), and strongly age related, with an incidence of 7.65 per 1000 inhabitants/year in patients aged ⩾60 years over 2 years. Mortality (13.72% and 14.44%) was higher than reported in previous studies. The CRB-65 RCs accurately predicted death in a three-class pattern (mortality 2.40% in CRB-65 RC 1, 13.43% in CRB-65 RC 2 and 34.39% in CRB-65 RC 3). The first days after admission were consistently associated with the highest risk of death throughout all risk classes. Only a minority of patients who died had received mechanical ventilation during hospitalisation (15.74%). <h3>Conclusions:</h3> Hospitalised CAP basically is a condition of the elderly associated with a higher mortality than previously reported. It bears a considerable risk of early mortality, even in low risk patients. CRB-65 is a simple and powerful tool for the assessment of CAP severity. Hospitalised CAP is a frequent terminal event in chronic debilitated patients, and a limitation of treatment escalation is frequently applied.
Evidence for double resistance to permethrin and malathion in head lice
Authors: None Downs, None Stafford, None Harvey, None Coles
Journal: British Journal of Dermatology (1999)

A rising prevalence of head lice among school children and rising sales of insecticides with anecdotal evidence of their treatment failure, led us to examine whether head lice in Bristol and Bath were resistant to the insecticides available for treating head lice. Ten schools in Bristol and Bath were visited to collect field samples of head lice. A comparison was made of the survival rates of fully sensitive laboratory reared body lice and field samples of head lice on insecticide exposure. To confirm the in vitro relevance of these tests we performed supervised treatments of affected subjects with malathion or permethrin. There were significant differences (P < 10−6 Fishers exact test) between head and body lice survival for malathion and permethrin exposure, but not for carbaryl. There was an 87% failure rate for permethrin and a 64% failure rate for malathion with the topical treatment of a selected number of infested school children. We conclude that there is a high resistance to permethrin and malathion, but head lice remain fully sensitive to carbaryl. This is the first report of doubly resistant head lice. As permethrin, phenothrin (a very similar synthetic pyrethroid) or malathion are the active ingredients in all the over-the-counter head lice treatments in the U.K., then it is likely that head lice prevalence will continue to increase. The resistance against permethrin employed by the head louse is probably the kdr (knockdown resistance) mechanism, and an enzyme-mediated malathion-specific esterase is the likely mechanism against malathion.
The Transcription Factor ZNF217 Is a Prognostic Biomarker and Therapeutic Target during Breast Cancer Progression
Authors: Laurie E. Littlepage, Adam S. Adler, Hosein Kouros-Mehr, Guiqing Huang, Jonathan Chou, Sheryl R. Krig, Obi L. Griffith, James E. Korkola, Kun Qu, Devon A. Lawson, Qing Xue, Mark D. Sternlicht, Gerrit J.P. Dijkgraaf, Paul Yaswen, Hope S. Rugo, Colleen A. Sweeney, Colin C. Collins, Joe W. Gray, Howard Y. Chang, Zena Werb
Journal: Cancer Discovery (2012)

The transcription factor ZNF217 is a candidate oncogene in the amplicon on chromosome 20q13 that occurs in 20% to 30% of primary human breast cancers and that correlates with poor prognosis. We show that Znf217 overexpression drives aberrant differentiation and signaling events, promotes increased self-renewal capacity, mesenchymal marker expression, motility, and metastasis, and represses an adult tissue stem cell gene signature downregulated in cancers. By in silico screening, we identified candidate therapeutics that at low concentrations inhibit growth of cancer cells expressing high ZNF217. We show that the nucleoside analogue triciribine inhibits ZNF217-induced tumor growth and chemotherapy resistance and inhibits signaling events [e.g., phospho-AKT, phospho-mitogen-activated protein kinase (MAPK)] in vivo. Our data suggest that ZNF217 is a biomarker of poor prognosis and a therapeutic target in patients with breast cancer and that triciribine may be part of a personalized treatment strategy in patients overexpressing ZNF217. Because ZNF217 is amplified in numerous cancers, these results have implications for other cancers.This study finds that ZNF217 is a poor prognostic indicator and therapeutic target in patients with breast cancer and may be a strong biomarker of triciribine treatment efficacy in patients. Because previous clinical trials for triciribine did not include biomarkers of treatment efficacy, this study provides a rationale for revisiting triciribine in the clinical setting as a therapy for patients with breast cancer who overexpress ZNF217.
COPD in never smokers: a significant problem?
Authors: S Grundy
Journal: Thorax (2006)

▴ Celli BR, Halbert RJ, Nordyke RJ, et al . Airway obstruction in never smokers: results from the Third National Health and Nutrition Examination Survey. Am J Med2005;118:1364–72 [OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] Chronic obstructive pulmonary disease (COPD) is rarely considered in people who have never smoked. This paper reviews the results of a large US survey which involved a detailed questionnaire, physical examination, and spirometric testing. It looks particularly at airways obstruction in lifelong non-smokers. A total of 10 276 … [1]: {openurl}?query=rft.jtitle%253DThe%2BAmerican%2Bjournal%2Bof%2Bmedicine%26rft.stitle%253DAm%2BJ%2BMed%26rft.aulast%253DCelli%26rft.auinit1%253DB.%2BR.%26rft.volume%253D118%26rft.issue%253D12%26rft.spage%253D1364%26rft.epage%253D1372%26rft.atitle%253DAirway%2Bobstruction%2Bin%2Bnever%2Bsmokers%253A%2Bresults%2Bfrom%2Bthe%2BThird%2BNational%2BHealth%2Band%2BNutrition%2BExamination%2BSurvey.%26rft_id%253Dinfo%253Adoi%252F10.1016%252Fj.amjmed.2005.06.041%26rft_id%253Dinfo%253Apmid%252F16378780%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1016/j.amjmed.2005.06.041&link_type=DOI [3]: /lookup/external-ref?access_num=16378780&link_type=MED&atom=%2Fthoraxjnl%2F61%2F4%2F283.1.atom [4]: /lookup/external-ref?access_num=000234157700012&link_type=ISI
Association of Hydroxyethyl Starch Administration With Mortality and Acute Kidney Injury in Critically Ill Patients Requiring Volume Resuscitation
Authors: Ryan Zarychanski, Ahmed M. Abou-Setta, Alexis F. Turgeon, Brett L. Houston, Lauralyn McIntyre, John C. Marshall, Dean A. Fergusson
Journal: JAMA (2013)

Hydroxyethyl starch is commonly used for volume resuscitation yet has been associated with serious adverse events, including acute kidney injury and death. Clinical trials of hydroxyethyl starch are conflicting. Moreover, multiple trials from one investigator have been retracted because of scientific misconduct.To evaluate the association of hydroxyethyl starch use with mortality and acute kidney injury.Randomized controlled trials from MEDLINE, EMBASE, CENTRAL, Global Health, HealthStar, Scopus, Web of Science, the International Clinical Trials Registry Platform (inception to October 2012), reference lists of relevant articles, and gray literature.Two reviewers independently identified randomized controlled trials comparing hydroxyethyl starch with other resuscitation fluids in critically ill patients receiving acute volume resuscitation.Two reviewers independently extracted trial-level data including population characteristics, interventions, outcomes, and funding sources. Risk of bias was assessed using the risk of bias tool; the strength of evidence was adjudicated using the GRADE methodology.We included 38 eligible trials comparing hydroxyethyl starch to crystalloids, albumin, or gelatin. The majority of trials were categorized as having an unclear risk or high risk of bias. For the 10,880 patients in studies contributing mortality data, the risk ratio (RR) for death among patients randomized to receive hydroxyethyl starch was 1.07 (95% CI, 1.00 to 1.14; I2, 0%; absolute risk [AR], 1.20%; 95% CI, -0.26% to 2.66%). This summary effect measure included results from 7 trials performed by an investigator whose subsequent research had been retracted because of scientific misconduct. When we excluded these 7 trials that involved 590 patients, hydroxyethyl starch was found to be associated with increased mortality among 10,290 patients (RR, 1.09; 95% CI, 1.02 to 1.17; I2, 0%; AR, 1.51%; 95% CI, 0.02% to 3.00%), increased renal failure among 8725 patients (RR, 1.27; 95% CI, 1.09 to 1.47; I2, 26%; AR, 5.45%; 95% CI, 0.44% to 10.47%), and increased use of renal replacement therapy among 9258 patients (RR, 1.32; 95% CI, 1.15 to 1.50; I2, 0%; AR, 3.12%; 95% CI, 0.47% to 5.78%).In critically ill patients requiring acute volume resuscitation, use of hydroxyethyl starch compared with other resuscitation solutions was not associated with a decrease in mortality. Moreover, after exclusion of 7 trials performed by an investigator whose research has been retracted because of scientific misconduct, hydroxyethyl starch was associated with a significant increased risk of mortality and acute kidney injury. Clinical use of hydroxyethyl starch for acute volume resuscitation is not warranted due to serious safety concerns.
High dose androgen therapy in male pseudohermaphroditism due to 5 alpha-reductase deficiency and disorders of the androgen receptor.
Authors: P Price, J A Wass, J E Griffin, M Leshin, M O Savage, D M Large, D E Bu'Lock, D C Anderson, J D Wilson, G M Besser
Journal: Journal of Clinical Investigation (1984)

We describe the clinical and biochemical features of six men with male pseudohermaphroditism due to androgen resistance. Each of the subjects had male-gender behavior but incomplete virilization. The underlying defects in androgen metabolism were defined by studies of the 5 alpha-reductase enzyme and the androgen receptor in fibroblasts cultured from biopsies of genital skin. Four of the six have 5 alpha-reductase deficiency, and two have defects of the androgen receptor (the Reifenstein syndrome). The responses of these men to androgen treatment were assessed by monitoring nitrogen balance, plasma luteinizing hormone (LH) values, and clinical parameters of virilization including penile growth, potency and ejaculatory volume, muscle bulk, and growth of body and facial hair. In all of the subjects with 5 alpha-reductase deficiency and one man with the Reifenstein syndrome significant response occurred, as evidence by nitrogen retention, lowered plasma LH levels, and improved virilization, with doses of parenteral testosterone esters that raised plasma testosterone levels above the normal male range and brought plasma dihydrotestosterone levels into the normal male range. The subject who did not respond with clinical virilization nevertheless showed nitrogen retention in response to acute testosterone administration. This patient had a profound deficiency of the androgen receptor, whereas the man with a receptor defect who did respond clinically to therapy had normal amounts of a qualitatively abnormal receptor. We conclude that high dose androgen therapy may be of benefit in improving virilization, self-image, and sexual performance in subjects with 5 alpha-reductase deficiency who have male-gender behavior and in some subjects with defects of the androgen receptor.
Developing an In-Training Examination for Fellows: The Experience of the American Society of Clinical Oncology
Authors: Frances A. Collichio, Karen M. Kayoumi, Kenneth R. Hande, Richard E. Hawkins, Janine L. Hawley, David J. Adelstein, Jean M. D'Angelo, James A. Stewart
Journal: Journal of Clinical Oncology (2009)

The American Society of Clinical Oncology (ASCO) developed its own test—the Medical Oncology In-Training Examination (MedOnc ITE)—as a tool to assess trainees' knowledge of the clinical oncology subspecialty, establish consistency in educational standards across training programs, identify areas of strength and weakness in individual programs, and stimulate intraprogrammatic reading and discussion. The Accreditation Council for Graduate Medical Education Outcome Project provided additional incentive for ASCO to develop an ITE. The examination was developed in 4 years. The concept of the examination and the budget were approved by the ASCO governing board. The National Board of Medical Examiners was selected to work with ASCO. Fellowship programs were contacted to determine if they had the information technology support to hold the examination. A blueprint for the examination was developed. The test format, including the number of questions and the selection of case-based single best answers, was determined. Physician volunteers to write the questions were solicited from among program directors, various ASCO committees, and disease experts. A workshop was held to teach volunteers how to write proper case-based questions. From this pool, a smaller group of physicians was selected to develop the test and review all test questions. The final examination was developed and administered in February 2008, with scores provided to fellows and program directors in April 2008. Feedback received after the examination will be helpful for developing future MedOnc ITEs. The process ASCO went through to develop the MedOnc ITE serves as a model for other subspecialties interested in developing their own ITEs.
Fusion of Human Hematopoietic Progenitor Cells and Murine Cardiomyocytes Is Mediated by α4β1 Integrin/Vascular Cell Adhesion Molecule-1 Interaction
Authors: Sui Zhang, Elizabeth Shpall, James T. Willerson, Edward T.H. Yeh
Journal: Circulation Research (2007)

Fusion of transplanted stem cells and host cells has been proposed as a major mechanism for the generation of hepatocytes, Purkinje neurons, and cardiomyocytes. However, the mechanism of cell fusion has not been precisely defined. Furthermore, the consequence of cell fusion remains unclear. We have previously shown that adult peripheral blood CD34-positive cells injected into severe combined immune deficiency (SCID) mice can transform into cardiomyocytes, endothelial cells, and smooth muscle cells following experimentally induced myocardial infarction and that most of the newly formed cardiomyocytes result from cell fusion. We therefore undertook this study to define the mechanism and consequences of cell fusion. Here we show that hypoxia and cytokines increase fusion of human peripheral blood CD34-positive cells and murine cardiomyocytes in vitro by up to 7-fold, and this is blocked by anti-α4β1 or anti–vascular cell adhesion molecule (VCAM)-1. In vivo, fusion of progenitor cells and cardiomyocytes can also be blocked by anti-α4β1 or anti–VCAM-1, but not by anti–vascular endothelial growth factor. On the other hand, generation of human-derived endothelial cells is blocked by anti–vascular endothelial growth factor but not by anti-α4β1 antibodies. Two months following transplant, a high percentage of fused cells expressed cyclin B1 and incorporated bromodeoxyuridine. Thus, hematopoietic progenitor cell and cardiomyocyte fusion is mediated by α4β1/VCAM-1 interaction, leading to cell cycle reentry and cellular proliferation.