tbuckley/cabot-search huggingface dataset:
A CASP-8 Mutation Recognized by Cytolytic T Lymphocytes on a Human Head and Neck Carcinoma
Authors: Susanna Mandruzzato, Francis Brasseur, Guy Andry, Thierry Boon, Pierre van der Bruggen
Journal: The Journal of Experimental Medicine (1997)

Of the antigens recognized on human tumors by autologous cytolytic T lymphocytes, all those defined thus far have been identified on melanoma or renal cell carcinoma. We report here the identification of an antigen recognized by autologous cytolytic T lymphocytes on a human squamous cell carcinoma of the oral cavity. The antigen is encoded by a mutated form of the CASP-8 gene. This gene, also named FLICE or MACH, codes for protease caspase-8, which is required for induction of apoptosis through the Fas receptor and tumor necrosis factor receptor-1. The mutation, which was found in the tumor cells but not in the normal cells of the patient, modifies the stop codon and adds an Alu repeat to the coding region, thereby lengthening the protein by 88 amino acids. The ability of the altered protein to trigger apoptosis appears to be reduced relative to the normal caspase-8. The antigenic peptide is a nonamer presented by HLA-B*3503. The five last amino acids are encoded by the extension of the reading frame caused by the mutation. This, together with previous observations of CDK4 and β-catenin mutations, suggests that a significant fraction of the point mutations generating a tumor antigen also play a role in the tumoral transformation or progression.
Reduced Representation Genome Sequencing Suggests Low Diversity on the Sex Chromosomes of Tonkean Macaque Monkeys
Authors: Ben J. Evans, Kai Zeng, Jacob A. Esselstyn, Brian Charlesworth, Don J. Melnick
Journal: Molecular Biology and Evolution (2014)

In species with separate sexes, social systems can differ in the relative variances of male versus female reproductive success. Papionin monkeys (macaques, mangabeys, mandrills, drills, baboons, and geladas) exhibit hallmarks of a high variance in male reproductive success, including a female-biased adult sex ratio and prominent sexual dimorphism. To explore the potential genomic consequences of such sex differences, we used a reduced representation genome sequencing approach to quantifying polymorphism at sites on autosomes and sex chromosomes of the tonkean macaque (Macaca tonkeana), a species endemic to the Indonesian island of Sulawesi. The ratio of nucleotide diversity of the X chromosome to that of the autosomes was less than the value (0.75) expected with a 1:1 sex ratio and no sex differences in the variance in reproductive success. However, the significance of this difference was dependent on which outgroup was used to standardize diversity levels. Using a new model that includes the effects of varying population size, sex differences in mutation rate between the autosomes and X chromosome, and GC-biased gene conversion (gBGC) or selection on GC content, we found that the maximum-likelihood estimate of the ratio of effective population size of the X chromosome to that of the autosomes was 0.68, which did not differ significantly from 0.75. We also found evidence for 1) a higher level of purifying selection on genic than nongenic regions, 2) gBGC or natural selection favoring increased GC content, 3) a dynamic demography characterized by population growth and contraction, 4) a higher mutation rate in males than females, and 5) a very low polymorphism level on the Y chromosome. These findings shed light on the population genomic consequences of sex differences in the variance in reproductive success, which appear to be modest in the tonkean macaque; they also suggest the occurrence of hitchhiking on the Y chromosome.
HIV-associated pityriasis rubra pilaris responsive to triple antiretroviral therapy
Authors: A González-López, E Velasco, T Pozo, A Del Villar
Journal: British Journal of Dermatology (1999)

HIV-associated pityriasis rubra pilaris (PRP) or PRP type VI designates a new distinctive entity reported in HIV patients. It is characterized by cutaneous lesions of PRP and variable association with lesions of acne conglobata, hidradenitis suppurativa and lichen spinulosus. We report a patient with HIV-associated PRP which was treated by triple antiretroviral therapy (zidovudine, lamivudin and saquinavir) with complete response. The patient has remained free from symptoms for 20 months of follow-up. We review the clinical features, pathology, evolution, treatment and possible aetiology of this recently described entity.
Microenvironment Determines Lineage Fate in a Human Model of MLL-AF9 Leukemia
Authors: Junping Wei, Mark Wunderlich, Catherine Fox, Sara Alvarez, Juan C. Cigudosa, Jamie S. Wilhelm, Yi Zheng, Jose A. Cancelas, Yi Gu, Michael Jansen, Jorge F. DiMartino, James C. Mulloy
Journal: Cancer Cell (2008)
THE REGULATION AND PHARMACOLOGY OF ENDOTHELIAL NITRIC OXIDE SYNTHASE
Authors: David M. Dudzinski, Junsuke Igarashi, Daniel Greif, Thomas Michel
Journal: The Annual Review of Pharmacology and Toxicology (2005)

▪ Abstract Nitric oxide (NO) is a small, diffusible, lipophilic free radical gas that mediates significant and diverse signaling functions in nearly every organ system in the body. The endothelial isoform of nitric oxide synthase (eNOS) is a key source of NO found in the cardiovascular system. This review summarizes the pharmacology of NO and the cellular regulation of endothelial NOS (eNOS). The molecular intricacies of the chemistry of NO and the enzymology of NOSs are discussed, followed by a review of the biological activities of NO. This information is then used to develop a more global picture of the pharmacological control of NO synthesis by NOSs in both physiologic conditions and pathophysiologic states.
Duration of length of stay in pneumonia: influence of clinical factors and hospital type
Authors: R. Menéndez, M.J. Cremades, E. Martínez-Moragón, J.J. Soler, S. Reyes, M. Perpiñá
Journal: European Respiratory Journal (2003)

Length of stay (LOS) in hospital for community-acquired pneumonia depends on the characteristics of the patient and hospital. The present study sought to identify these variables within the first 24 h of hospitalisation. Patients hospitalised for pneumonia in four hospitals (one teaching and three general hospitals) had their data analysed by univariate and multivariate statististics. The variables entered were LOS, demographical characteristics, referral source, comorbidity, initial severity of illness, laboratory analyses, initial radiograph findings and antibiotic treatment regimens. The study sample included 425 patients. The overall mortality was 8.2% and the median LOS was 9 days. Using LOS as a dependent variable, three multivariate linear regression analyses were performed with: 1) the whole cohort; 2) the low-risk classes (categories I and II of Fine); and 3) the high-risk classes (categories III, IV and V of Fine). The mathematical model identified hypoxemia, low diastolic pressure, pleural effusion, multi-lobe involvement and hypoalbuminaemia as associated with longer stays in risk classes III–V, while in the low-risk patients (I–II) only hypoxemia and pleural effusion appeared in the equation. Following adjustment for these clinical variables, the LOS remained lower in some hospitals. Several independent clinical factors increased the pneumonia-associated length of stay with significant differences between hospitals. Hypoxemia and pleural effusions were the predictive variables of length of stay in low-risk patients and, additionally, diastolic blood pressure, multi-lobe involvement and hypoalbuminaemia were significant in the higher-risk classes III–V.
An analysis of the physiological strain of submaximal exercise in patients with chronic obstructive bronchitis.
Authors: S G Spiro, H L Hahn, R H Edwards, N B Pride
Journal: Thorax (1975)

An increasing work rate was performed by 40 patients with chronic obstructive bronchitis, split into two groups according to FEV1 (group M, mean FEV1 1-451. and group S, mean FEV1 0-621.), and by 20 normal, non-athletic men of similar age to the patients. Values for cardiac frequency and ventilation were interpolated to standard oxygen uptakes of 0-75, 1-0, and, where possible, 1-5 min-1. The tidal volume at a ventilation of 20 and 30 1 min-1 was also determined. The cardiac frequencies at oxygen uptake of 0-75 and 1-01 min-1 were significantly higher in the patient groups than in the normal men, and were highest in patient group S. The cardiac output when related to the oxygen uptake was in the normal range in all three groups of subjects, so that the patients had smaller stroke volumes than the normal men. Ventilation at oxygen uptakes of 0-75 and 1-01 min-1 was significantly higher in both patient groups than in the normal subjects; there were no significant differences between the two patient groups, Values for dead space/tidal volume ration, alveolar-arterial oxygen gradient, and the percent venous admixture measured during a constant work rate test were significantly greater than normal in the patient groups. Possible factors limiting exercise tolerance in these patients were assessed by extending the increasing work rate test from submaximum to maximum exercise. Changes in blood gas tensions and blood lactate concentrations from resting levels were small, and probably did not limit exercise performance. Measurements at maximum exercise did not add appreciably to the analysis of the disturbed cardiopulmonary function. This study has shown that major disturbances in cardiopulmonary function can be demonstrated without the need for stressing a patient to the limit of his effort tolerance.
Exploring Postinfarction Reentrant Ventricular Tachycardia With Entrainment Mapping
Authors: William G Stevenson, Peter L Friedman, Philip T Sager, Leslie A Saxon, Dusan Kocovic, Tomoo Harada, Isaac Wiener, Hafiza Khan
Journal: Journal of the American College of Cardiology (1997)

Ventricular tachycardia late after myocardial infarction is usually due to reentry in the infarct region. These reentry circuits can be large, complex and difficult to define, impeding study in the electrophysiology laboratory and making catheter ablation difficult. Pacing through the electrodes of the mapping catheter provides a new approach to mapping. When pacing stimuli capture the effects on the tachycardia depend on the location of the pacing site relative to the reentry circuit. The effects observed allow identification of various portions of the reentry circuit, without the need for locating the entire circuit. Isthmuses where relatively small lesions produced by radiofrequency catheter ablation can interrupt reentry can often be identified. A classification that divides reentry circuits into one or more functional components helps to conceptualize the reentry circuit and predicts the likelihood that heating with radiofrequency current will terminate tachycardia. These methods are helping to define human reentry circuits. (J Am Coll Cardiol 1997;29:1180–9)
What forces keep the air spaces of the lung dry?
Authors: B A Hills
Journal: Thorax (1982)

<h3>Abstract</h3> Recombinant AAV (rAAV) vectors have been developed for therapeutic treatment of genetic diseases. Nevertheless, current rAAV vectors administered to patients often contain non-vector related DNA contaminants. Here, we present a thorough molecular analysis of the configuration of non-standard AAV genomes generated during rAAV production. In addition to the sub-vector genomic size particles containing incomplete AAV genomes, our results found that rAAV preparations were contaminated with multiple categories of subgenomic particles with either snapback genomes or vector genomes with deletions in the mid regions. Through CRISPR and restriction enzyme-based in vivo and in vitro modeling, we identified that the main mechanism leading to the formation of non-canonical genome particles occurred through nonhomologous end joining of fragmented vector genomes caused by genome lesions or DNA breaks that were generated by the host cell/environment. The results of this study advance our understanding of AAV vectors and provide new clues on improving vector efficiency and safety profile for use in human gene therapy.
Serial Analysis of Gene Expression Identifies Connective Tissue Growth Factor Expression as a Prognostic Biomarker in Gallbladder Cancer
Authors: Hector Alvarez, Alejandro Corvalan, Juan C. Roa, Pedram Argani, Francisco Murillo, Jennifer Edwards, Robert Beaty, Georg Feldmann, Seung-Mo Hong, Michael Mullendore, Ivan Roa, Luis Ibañez, Fernando Pimentel, Alfonso Diaz, Gregory J. Riggins, Anirban Maitra
Journal: Clinical Cancer Research (2008)

Gallbladder cancer (GBC) is an uncommon neoplasm in the United States, but one with high mortality rates. This malignancy remains largely understudied at the molecular level such that few targeted therapies or predictive biomarkers exist.We built the first series of serial analysis of gene expression (SAGE) libraries from GBC and nonneoplastic gallbladder mucosa, composed of 21-bp long-SAGE tags. SAGE libraries were generated from three stage-matched GBC patients (representing Hispanic/Latino, Native American, and Caucasian ethnicities, respectively) and one histologically alithiasic gallbladder. Real-time quantitative PCR was done on microdissected epithelium from five matched GBC and corresponding nonneoplastic gallbladder mucosa. Immunohistochemical analysis was done on a panel of 182 archival GBC in high-throughput tissue microarray format.SAGE tags corresponding to connective tissue growth factor (CTGF) transcripts were identified as differentially overexpressed in all pairwise comparisons of GBC (P < 0.001). Real-time quantitative PCR confirmed significant overexpression of CTGF transcripts in microdissected primary GBC (P < 0.05), but not in metastatic GBC, compared with nonneoplastic gallbladder epithelium. By immunohistochemistry, 66 of 182 (36%) GBC had high CTGF antigen labeling, which was significantly associated with better survival on univariate analysis (P = 0.0069, log-rank test).An unbiased analysis of the GBC transcriptome by SAGE has identified CTGF expression as a predictive biomarker of favorable prognosis in this malignancy. The SAGE libraries from GBC and nonneoplastic gallbladder mucosa are publicly available at the Cancer Genome Anatomy Project web site and should facilitate much needed research into this lethal neoplasm.
Involvement of large plasma von Willebrand factor (vWF) multimers and unusually large vWF forms derived from endothelial cells in shear stress-induced platelet aggregation.
Authors: J L Moake, N A Turner, N A Stathopoulos, L H Nolasco, J D Hellums
Journal: Journal of Clinical Investigation (1986)

A fluid shear stress of 180 dyn/cm2 was applied for 0.5 and 5 min to platelets in citrated plasma or blood in a cone and plate viscometer with minimal platelet-surface interactions. Platelets aggregated in the shear field if large von Willebrand Factor (vWF) multimers were present. Aggregation did not require ristocetin, other exogenous agents, or desialation of vWF. Unusually large vWF multimers produced by human endothelial cells were functionally more effective than the largest plasma vWF forms in supporting shear-induced aggregation. Shear-induced aggregation was inhibited by monoclonal antibodies to platelet glycoprotein Ib or the IIb/IIIa complex, but was little affected by the absence of fibrinogen. vWF-dependent platelet aggregation under elevated shear stress in partially occluded vessels of the arterial microcirculation may contribute to thrombosis, especially if unusually large vWF multimers are released locally from stimulated or disrupted endothelial cells.
Host determinants for the development of allergy in apprentices exposed to laboratory animals
Authors: D. Gautrin, H. Ghezzo, C. Infante-Rivard, J-L. Malo
Journal: European Respiratory Journal (2001)

The aim of this study was to evaluate whether determinants of work-related symptoms, skin sensitization and diseases differ between atopic and nonatopic subjects starting a career with exposure to laboratory animals (LA). A cohort of 417 apprentices in animal-health technology was prospectively followed during 32 or 44 months. The effect on the study outcomes of variables derived from questionnaire, skin reactivity, and lung function assessments at baseline were compared in atopic (n=212) and nonatopic (n=183) subjects. Eighty-five incident cases of sensitization to a LA-derived allergen were identified, 67 among atopic and 18 among nonatopic subjects. Baseline rhinitis symptoms in contact with pets and skin sensitization to pets were associated with the development of work-related rhinoconjunctivitis (RC) symptoms in atopic subjects, whereas perannual rhinitis symptoms and having a PC 20 (provocative concentration causing a 20% fall in forced expiratory volume in one second) ≤32 mg·mL −1 were associated in nonatopic subjects. Baseline rhinitis symptoms on contact with pets and a PC 20 value ≤32 mg·mL −1 were significant determinants for developing sensitization to a specific allergen in atopic subjects only. Finally, baseline rhinitis symptoms in contact with pets and perannual rhinitis symptoms were associated with the development of occupational RC in atopic subjects, whereas in nonatopic subjects this was associated with having a PC 20 value ≤32 mg·mL −1 . In conclusion, the determinants for the development of specific skin sensitization, symptoms and disease are different between atopic and nonatopic apprentices starting occupational exposure to laboratory-animal-derived allergens.
Results of a prospective dose-intensive regimen in 27 patients with small cell carcinoma of the ovary of the hypercalcemic type
Authors: P. Pautier, V. Ribrag, P. Duvillard, A. Rey, I. Elghissassi, I. Sillet-Bach, P. Kerbrat, F. Mayer, A. Lesoin, B. Brun, H. Crouet, J.C. Barats, P. Morice, C. Lhommé
Journal: Annals of Oncology (2007)

The evaluation of first-line intensive combination therapy in small cell carcinoma of the ovary (SCCO).Debulking surgery; four to six cycles of chemotherapy with cisplatin (P) 80 mg/m(2) day 1, adriamycin (A) 40 mg/m(2) day 1, vepeside (V) 75 mg/m(2)/day days 1-3, cyclophosphamide (EP) 300 mg/m(2)/day days 1-3, every 3 weeks and granulocyte colony-stimulating factor with, in case of a complete remission, high-dose chemotherapy with carboplatin, vepeside, cyclophosphamide and stem-cell support.Twenty-seven patients (median age 25 years); International Federation of Gynecology and Obstetrics stage: five I, four IIC, 17 IIIC-IV and one unknown. Twenty patients underwent complete surgery. Eight patients progressed under chemotherapy. Among 18 patients in complete response (CR), 10 received high-dose chemotherapy (CT) (three stem-cell collection failures, two protocol violations, two disease progression and one refusal). The main grade 3-4 toxic effects were hematologic. There were eight relapses among the 18 CR, four of which were pelvic alone. Among the 27 patients, 13 died and 10 patients are in CR1, three in CR2. The median follow-up is 37 months (8-166) and the median duration of the 18 CR is 30 months (5-111). Overall survival at 1 and 3 years is 58% [confidence interval (CI) 40% to 75%] and 49% (CI 30% to 67%).Initial dose-intensive therapy achieves interesting overall survival in SCCO.
PRESYMPTOMATIC DIAGNOSIS OF FAMILIAL ADENOMATOUS POLYPOSIS BY BRIDGING DNA MARKERS
Authors: C.M.J Tops, G Griffioen, H.F.A Vasen, C Breukel, H.M Van Der Klift, J.Th Wijnen, I.S.J.V Leeuwen, F.C.A Den Hartog Jager, F.M Nagengast, C.B.H.W Lamers, P.Meera Khan
Journal: The Lancet (1989)
The Bw4 public epitope of HLA-B molecules confers reactivity with natural killer cell clones that express NKB1, a putative HLA receptor.
Authors: J E Gumperz, V Litwin, J H Phillips, L L Lanier, P Parham
Journal: The Journal of Experimental Medicine (1995)

Although inhibition of natural killer (NK) cell-mediated lysis by the class I HLA molecules of target cells is an established phenomenon, knowledge of the features of class I molecules which induce this effect remains rudimentary. Using class I alleles HLA-B*1502 and B*1513 which differ only at residues 77-83 which define the Bw4 and Bw6 serological epitopes, we tested the hypothesis that the presence of the Bw4 epitope on class I molecules determines recognition by NKB1+ NK cells. HLA-B*1513 possesses the Bw4 epitope, whereas B*1502 has the Bw6 epitope. Lysis by NKB1+ NK cell clones of transfected target cells expressing B*1513 as the only HLA-A, -B, or -C molecule was inhibited, whereas killing of transfectants expressing B*1502 was not. Addition of an an anti-NKB1 monoclonal antibody reconstituted lysis of the targets expressing B*1513, but did not affect killing of targets bearing B*1502. The inhibitory effect of B*1513 could be similarly prevented by the addition of an anti-class I monoclonal antibody. These results show that the presence of the Bw4 epitope influences recognition of HLA-B molecules by NK cells that express NKB1, and suggest that the NKB1 molecule may act as a receptor for Bw4+ HLA-B alleles. Sequences outside of the Bw4 region must also affect recognition by NKB1+ NK cells, because lysis of transfectants expressing HLA-A*2403 or A*2501, which possess the Bw4 epitope but are in other ways substantially different from HLA-B molecules, was not increased by addition of the anti-NKB1 antibody. Asparagine 86, the single site of N-linked glycosylation on class I molecules, is in close proximity to the Bw4/Bw6 region. The glycosylation site of the Bw4-positive molecule B*5801 was mutated, and the mutant molecules tested for inhibition of NKB1+ NK cells. Inhibition that could be reversed by addition of the anti-NKB1 monoclonal antibody was observed, showing the presence of the carbohydrate moiety is not essential for class I recognition by NKB1+ NK cell clones.
Effect of Dietary Fiber on Azoxymethane-Induced Intestinal Carcinogenesis in Rats&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: N D Nigro, A W Bull, B A Klopfer, M S Pak, R L Campbell
Journal: JNCI Journal of the National Cancer Institute (1979)

The effect of alfalfa, bran, and cellulose on intestinal tumor formation and fecal billary steroid levels was studied in male Sprague-Dawley rats given injections of azoxymethane (AOM). Animals received weekly injections of 8 mg AOM/kg and were fed diets containing 10% fiber (wt/wt) and 35% beef fat or 20 or 30% fiber and about 6% beef fat. Control animals in each instance were fed fiber-free diets. The addition of 10% fiber to the high-fat diet did not significantly reduce the intestinal tumor frequency (average No. of tumors/rat). However, addition of 20 or 30% fiber to the 6% fat diet significantly reduced the intestinal tumor frequency. The concentration of fecal biliary steroids (mg/g dry feces) was significantly lowered in the groups with reduced tumor frequencies, whereas the total excretion of fecal biliary steroids (mg/day) did not show a similar correlation. These observations suggest that intestinal tumor frequency can be reduced by increased dietary fiber only when fat intake is not at a high level. The effect of fiber may be due to dilution of promoters and/or carcinogens in the intestinal tract.