tbuckley/cabot-search huggingface dataset:
Evolution of Eukaryotic Translation Elongation and Termination Factors: Variations of Evolutionary Rate and Genetic Code Deviations
Authors: David Moreira, Stéphanie Kervestin, Olivier Jean-Jean, Hervé Philippe
Journal: Molecular Biology and Evolution (2002)

Translation is carried out by the ribosome and several associated protein factors through three consecutive steps: initiation, elongation, and termination. Termination remains the least understood of them, partly because of the nonuniversality of the factors involved. To get some insights on the evolution of eukaryotic translation termination, we have compared the phylogeny of the release factors eRF1 and eRF3 to that of the elongation factors EF-1α and EF-2, with special focus on ciliates. Our results show that these four translation proteins have experienced different modes of evolution. This is especially evident for the EF-1α, EF-2, and eRF1 ciliate sequences. Ciliates appear as monophyletic in the EF-2 phylogenetic tree but not in the EF-1α and eRF1 phylogenetic trees. This seems to be mainly because of phylogeny reconstruction artifacts (the long-branch attraction) produced by the acceleration of evolutionary rate of ciliate EF-1α and eRF1 sequences. Interaction with the highly divergent actin found in ciliates, or on the contrary, loss of interaction, could explain the acceleration of the evolutionary rate of the EF-1α sequences. In the case of ciliate eRF1 sequences, their unusually high evolutionary rate may be related to the deviations in the genetic code usage found in diverse ciliates. These deviations involve a relaxation (or even abolition) of the recognition of one or two stop codons by eRF1. To achieve this, structural changes in eRF1 are needed, and this may affect its evolutionary rate. Eukaryotic translation seems to have followed a mosaic evolution, with its different elements governed by different selective pressures. However, a correlation analysis shows that, beneath the disagreement shown by the different translation proteins, their concerted evolution can still be made apparent when they are compared with other proteins that are not involved in translation.
Artificial Hearts, Fractured Valves, and Other Problems With Medical Devices
Authors: Ram Kossowsky
Journal: JAMA (1985)

<h3>To the Editor.—</h3> Recently, two separate articles on the artificial heart program appeared simultaneously inThe Journal.<sup>1,2</sup>Both articles failed to mention important medical details on three biomedical device issues: medical device failures, thrombogenicity of silicone, and infections with percutaneous implants. With literally millions of medical devices in use, it is important for today's physician to understand the nature of the body's reaction to devices as well as the devices' reaction to long-term implantation in the body. First, the fracture of the weld of Barney Clark's Björk-Shiley heart valve on the 13th postoperative day is described as being a manifestation of Murphy's Law.<sup>2</sup>This is incorrect. The Björk-Shiley 60° convexoconcave valves have a fundamental flaw in the weld and, as of Sept 25, 1984, 107 cases of valve failure due to strut fracture have been reported; two thirds of which were estimated by Shiley to be fatal.<sup>3</sup>
Use of totally implantable central venous access ports for high-dose chemotherapy and peripheral blood stem cell transplantation: results of a monocentre series of 376 patients
Authors: R. Biffi, S. Pozzi, A. Agazzi, U. Pace, A. Floridi, S. Cenciarelli, V. Peveri, A. Cocquio, B. Andreoni, G. Martinelli
Journal: Annals of Oncology (2004)
Epigenetics and the placenta
Authors: E. C. M. Nelissen, A. P. A. van Montfoort, J. C. M. Dumoulin, J. L. H. Evers
Journal: Human Reproduction Update (2010)

BACKGROUNDThe placenta is of utmost importance for intrauterine fetal development and growth. Deregulation of placentation can lead to adverse outcomes for both mother and fetus, e.g. gestational trophoblastic disease (GTD), pre-eclampsia and fetal growth retardation. A significant factor in placental development and function is epigenetic regulation.
Comparison of Prasugrel and Ticagrelor Loading Doses in ST-Segment Elevation Myocardial Infarction Patients
Authors: Guido Parodi, Renato Valenti, Benedetta Bellandi, Angela Migliorini, Rossella Marcucci, Vincenzo Comito, Nazario Carrabba, Alberto Santini, Gian Franco Gensini, Rosanna Abbate, David Antoniucci
Journal: Journal of the American College of Cardiology (2013)
Detection in Fecal DNA of Colon Cancer–Specific Methylation of the Nonexpressed Vimentin Gene
Authors: Wei-Dong Chen, Z. James Han, Joel Skoletsky, Jeff Olson, Jerome Sah, Lois Myeroff, Petra Platzer, Shilong Lu, Dawn Dawson, Joseph Willis, Theresa P. Pretlow, James Lutterbaugh, Lakshmi Kasturi, James K. V. Willson, J. Sunil Rao, Anthony Shuber, Sanford D. Markowitz
Journal: JNCI Journal of the National Cancer Institute (2005)

Background: Increased DNA methylation is an epigenetic alteration that is common in human cancers and is often associated with transcriptional silencing. Aberrantly methylated DNA has also been proposed as a potential tumor marker. However, genes such as vimentin, which are transcriptionally silent in normal epithelium, have not until now been considered as targets for cancer-associated aberrant methylation and for use as cancer markers. Methods: We applied methylation-specific polymerase chain reaction to the vimentin gene, which is transcriptionally silent in normal colonocytes, and compared methylation of vimentin exon 1 in cancer tissues and in fecal DNA from colon cancer patients versus control samples from healthy subjects. Results: Vimentin exon-1 sequences were unmethylated in 45 of 46 normal colon tissues. In contrast, vimentin exon-1 sequences were methylated in 83% (38 of 46) and 53% (57 of 107) of tumors from two independently collected groups of colon cancer patients. When evaluated as a marker for colon cancer detection in fecal DNA from another set of colon cancer patients, aberrant vimentin methylation was detected in fecal DNA from 43 of 94 patients, for a sensitivity of 46% (95% confidence interval [CI] = 35% to 56%). The sensitivity for detecting stage I and II cancers was 43% (26 of 60 case patients) (95% CI = 31% to 57%). Only 10% (20 of 198 case patients) of control fecal DNA samples from cancer-free individuals tested positive for vimentin methylation, for a specificity of 90% (95% CI = 85% to 94%). Conclusions : Aberrant methylation of exon-1 sequences within the nontranscribed vimentin gene is a novel molecular biomarker of colon cancer and can be successfully detected in fecal DNA to identify nearly half of individuals with colon cancer.
The contribution of preintervention blood pressure, VO<sub>2</sub>max, BMI, autonomic function and gender to exercise-induced changes in heart rate variability
Authors: Catharina C Grant, Dina C Janse van Rensburg
Journal: British Journal of Sports Medicine (2013)

Introduction The quantification of heart rate variability (HRV) is a tool to assess the interaction between exercise and autonomic control, as well as the pathophysiology of diseases affecting autonomic function. Little is known about the influence of genetically influenced physiology on exercise-induced changes in autonomic cardiac regulation. It was theorised that preintervention values for blood pressure, VO 2 max, body mass index (BMI), autonomic function and gender contribute significantly to the exercise-induced changes in HRV. Methods A 12-week, medium-to-high intensity exercise intervention was completed by 183 volunteers (18–22 years). Data were sampled at baseline and after 12 weeks. Standard time domain, frequency domain and Poincaré HRV quantification techniques were implemented. Regression analysis was performed to determine the influences of the predictors (baseline values for low frequency (LF), high frequency (HF), BMI, VO 2 max, gender, blood pressure) on the exercise-induced response of the dependent variables (changes in HRV-indicator values). Results Parameters found to be significant (p&lt;0.05) predictors of exercise-induced changes were LF, HF and systolic blood pressure in, respectively, 10, 5 and 2 of the 12 regressions performed. The results indicated that the independent variables contribute between 12.83% and 29.82%, depending on the specific HRV indicator, to the exercise-induced changes in the autonomic nervous system. Conclusions Preintervention autonomic status, as represented specifically by LF, is the most important determinant of cardiac autonomic response to an exercise intervention in a healthy study population. Baseline autonomic function could thus be a significant confounder in the outcome of exercise study results.
If the pope can change his mind on condoms, why not emergency contraceptives?
Authors: Sara Carrillo de Albornoz
Journal: BMJ (2010)

In November Pope Benedict XVI declared the use of condoms acceptable in certain cases.1 In comments quoted in the Vatican newspaper L’Osservatore Romano he said, “There can be single cases of justified use of condoms—for example, when a prostitute uses a condom—and this can be the first step towards moralisation, the first act of responsibility to develop awareness that not everything is allowed and that we cannot do everything we want. However, this is not the true and appropriate way to fight HIV infection.”

This is hardly a revolutionary stand on the use of contraceptives and on the fight against HIV, as Vatican spokesmen have hurriedly assured us, but we can only hope that it opens the way to wider discussion, adjustment of the Catholic church to the 21st century, and a change of stance on birth control. The time has come for the church to learn from science and take a step forward in improving women’s lives. Women should …
Effects of the neutrophil-activating peptide NAP-2, platelet basic protein, connective tissue-activating peptide III and platelet factor 4 on human neutrophils.
Authors: A Walz, B Dewald, V von Tscharner, M Baggiolini
Journal: The Journal of Experimental Medicine (1989)

Platelet basic protein (PBP), connective tissue-activating peptide III (CTAP-III), and platelet factor 4 (PF-4) were purified from human platelet release supernatants by heparin-Sepharose ion-exchange and reversed-phase HPLC, and their neutrophil-activating effects were compared with those of NAP-2, a peptide of 70 amino acids corresponding to part of the sequence of PBP (1) and with sequence homology to NAF/NAP-1. NAP-2-induced elastase release and a rise in cytosolic free Ca2+ at concentrations between 0.3 and 100 nM, and neutrophil chemotaxis at concentrations between 0.03 and 10 nM. It was half as potent as NAF/NAP-1 in inducing exocytosis but showed the same activity in the other responses. By contrast, only minimal if any effects were obtained with PBP, CTAP-III, and PF-4 up to 100 nM. NAP-2 thus appears to behave like a typical chemotactic receptor agonist. It could be generated from PBP and/or CTAP-III released from activated platelets and lead to the accumulation of neutrophils in platelet aggregates.
Cardiac Valve Calcification as an Important Predictor for All-Cause Mortality and Cardiovascular Mortality in Long-Term Peritoneal Dialysis Patients
Authors: Angela Yee-Moon Wang, Mei Wang, Jean Woo, Christopher Wai-Kei Lam, Philip Kam-Tao Li, Siu-Fai Lui, John E. Sanderson
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Calcification complications are frequent among long-term dialysis patients. However, the prognostic implication of cardiac valve calcification in this population is not known. This study aimed to determine if cardiac valve calcification predicts mortality in long-term dialysis patients. Baseline echocardiography was performed in 192 patients (mean ± SD age, 55 ± 12 yr) on continuous ambulatory peritoneal dialysis (mean ± SD duration of dialysis, 39 ± 31 mo) to screen for calcification of the aortic valve, mitral valve, or both. Valvular calcification was present in 62 patients. During the mean follow-up of 17.9 mo (range, 0.6 to 33.9 mo), 46 deaths (50% of cardiovascular causes) were observed. Overall 1-yr survival was 70% and 93% for patients with and without valvular calcification (P < 0.0001, log-rank test). Cardiovascular mortality was 22% and 3% for patients with and without valvular calcification (P < 0.0001). Multivariable Cox regression analysis showed that cardiac valve calcification was predictive of an increased all-cause mortality (hazard ratio [HR], 2.50; 95% CI, 1.32 to 4.76; P = 0.005) and cardiovascular death (HR 5.39; 95% CI, 2.16 to 13.48; P = 0.0003) independent of age, male gender, dialysis duration, C-reactive protein, diabetes, and atherosclerotic vascular disease. Eighty-nine percent of patients with both valvular calcification and atherosclerotic vascular disease, 23% of patients with valvular calcification only, 21% of patients with atherosclerotic vascular disease only, and 13% of patients with neither complication died at 1-yr (P < 0.0005). The cardiovascular death rate was 85% for patients with both complications, 13% for patients with valvular calcification only, 14% for patients with atherosclerotic vascular disease only, and 5% for those with neither complication (P < 0.0005). The number of calcified valves was associated with all-cause mortality (P < 0.0005) and cardiovascular death (P < 0.0005). One-year all-cause mortality was 57% for patients with both aortic and mitral valves calcified, 40% for those with either valve calcified, and 15% for those with neither valve calcified. In conclusion, cardiac valve calcification is a powerful predictor for mortality and cardiovascular deaths in long-term dialysis patients. Valvular calcification by itself has similar prognostic importance as the presence of atherosclerotic vascular disease. Its coexistence with other atherosclerotic complications indicates more severe disease and has the worst outcome. E-mail: [email protected]
Anticlonotypic monoclonal antibodies induce proliferation of clonotype-positive T cells in peripheral blood human T lymphocytes. Evidence for a phenotypic (T4/T8) heterogeneity of the clonotype-positive proliferating cells.
Authors: A Moretta, G Pantaleo, M Lopez-Botet, M C Mingari, L Moretta
Journal: The Journal of Experimental Medicine (1985)

Three previously selected monoclonal antibodies (mAb) directed against the clonotypic structure of a variant (termed JA3) of the interleukin 2 (IL-2)-producing Jurkat leukemia cell line (anti-JTi1-3 mAb) were found to induce an adherent cell-dependent proliferation of peripheral blood T cells in 20 different donors. Unlike the early cell proliferation induced by anti-T3 mAb, anti-JTi mAb-induced proliferation was detectable at day 5-6 of culture and reached peak levels at day 7-9. Less than 1% JTi+ cells were consistently detected in the starting peripheral blood lymphocytes or in control cultures in which cells were stimulated with anti-T3, phytohemagglutinin, or allogeneic cells. However, JTi+ cells were found in increasing proportions after culture with anti-JTi mAb and they were mostly represented by large blast cells expressing either the T4 or the T8 antigen, together with typical activation antigens including HLA-DR, IL-2 receptor, and 4F2. Immunoprecipitation experiments and sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that anti-JTi-reactive molecules present on antibody-stimulated lymphocytes or on JA3 cells were similar, disulphide-linked heterodimeric structures.
Natural history and outcome in 32 Swedish patients with small duct primary sclerosing cholangitis (PSC)
Authors: Ulrika Broomé, Hans Glaumann, Eva Lindstöm, Lars Lööf, Sven Almer, Hanne Prytz, Hanna Sandberg-Gertzén, Stefan Lindgren, Frans-Thomas Fork, Gunnar Järnerot, Rolf Olsson
Journal: Journal of Hepatology (2002)
Loss of Human Immunodeficiency Virus Type 1 (HIV-I) Antibodies with Evidence of Viral Infection in Asymptomatic Homosexual Men
Authors: H Farzadegan, M A Polis, S M Wolinsky, C R Rinaldo, J J Sninsky, S Kwok, R L Griffith, R A Kaslow, J P Phair, B F Polk
Journal: Annals of Internal Medicine (1988)

Four asymptomatic homosexual men reverted from positive to negative serologic results for the human immunodeficiency virus, type 1 (HIV-I) over 2.5 years, as shown by enzyme-linked immunosorbent assay (ELISA) and Western blot. Antibody bands in the Western blot from three men were undetectable 6 to 12 months after being positive; gradual fading of the number and intensity of bands was seen in the other man. No HIV-1-p24 antigenemia was detected; cryopreserved peripheral blood mononuclear cells were negative for HIV-1 by standard culture assay. Polymerase chain reaction (gene amplification) assays were done on peripheral blood mononuclear cells and showed the HIV-1 provirus in all subjects 6 to 18 months after the last positive antibody test. Serum specimens from each participant were genetically identical. Polymerase chain reaction showed that peripheral blood mononuclear cells from one subject at different times matched by HLA DNA typing. Clinical and laboratory features of these four men were similar to those of other seronegative subjects. Rare, asymptomatic persons seropositive for HIV-1 may not remain seropositive, but may remain latently infected with HIV-1.
Docetaxel plus nintedanib versus docetaxel plus placebo in patients with previously treated non-small-cell lung cancer (LUME-Lung 1): a phase 3, double-blind, randomised controlled trial
Authors: Martin Reck, Rolf Kaiser, Anders Mellemgaard, Jean-Yves Douillard, Sergey Orlov, Maciej Krzakowski, Joachim von Pawel, Maya Gottfried, Igor Bondarenko, Meilin Liao, Claudia-Nanette Gann, José Barrueco, Birgit Gaschler-Markefski, Silvia Novello
Journal: The Lancet Oncology (2014)
Ectopic cutaneous schistosomiasis and schistosomal ocular inflammatory disease
Authors: A. MILLIGAN, D.A. BURNS
Journal: British Journal of Dermatology (1988)

We describe a patient with unilateral ectopic cutaneous schistosomiasis as a feature of Schistosoma mansoni infection. In addition to skin lesions he also suffered from schistosomal ocular inflammatory disease. The infection appeared to have been acquired during a visit to Tanzania. Ectopic cutaneous lesions usually affect the perineal area or trunk, and our patient is unusual in the localization of his skin lesions to the forehead.
Leptin-dependent neuronal NO signaling in the preoptic hypothalamus facilitates reproduction
Authors: Nicole Bellefontaine, Konstantina Chachlaki, Jyoti Parkash, Charlotte Vanacker, William Colledge, Xavier d’Anglemont de Tassigny, John Garthwaite, Sebastien G. Bouret, Vincent Prevot
Journal: Journal of Clinical Investigation (2014)

The transition to puberty and adult fertility both require a minimum level of energy availability. The adipocyte-derived hormone leptin signals the long-term status of peripheral energy stores and serves as a key metabolic messenger to the neuroendocrine reproductive axis. Humans and mice lacking leptin or its receptor fail to complete puberty and are infertile. Restoration of leptin levels in these individuals promotes sexual maturation, which requires the pulsatile, coordinated delivery of gonadotropin-releasing hormone to the pituitary and the resulting surge of luteinizing hormone (LH); however, the neural circuits that control the leptin-mediated induction of the reproductive axis are not fully understood. Here, we found that leptin coordinated fertility by acting on neurons in the preoptic region of the hypothalamus and inducing the synthesis of the freely diffusible volume-based transmitter NO, through the activation of neuronal NO synthase (nNOS) in these neurons. The deletion of the gene encoding nNOS or its pharmacological inhibition in the preoptic region blunted the stimulatory action of exogenous leptin on LH secretion and prevented the restoration of fertility in leptin-deficient female mice by leptin treatment. Together, these data indicate that leptin plays a central role in regulating the hypothalamo-pituitary-gonadal axis in vivo through the activation of nNOS in neurons of the preoptic region.
Lymphocyte subsets of the nasal mucosa in perennial allergic rhinitis.
Authors: R U Pawankar, M Okuda, K Okubo, C Ra
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

T cells have been considered to play a primary role in IgE-mediated atopic diseases, yet little is known about the T-cell subsets in the nasal mucosa of patients with perennial allergic rhinitis. To elucidate the characteristics of T cells at the site of allergic inflammation, we analyzed the proportions, phenotypes, stages of differentiation, and distribution of T-cell subsets in the nasal mucosa of 15 patients with house-dust-mite perennial allergic rhinitis (PAR) and 14 patients with chronic infective rhinitis (CIR), using flow cytometry and immunohistochemistry. We also examined the T-cell subsets in the peripheral blood (PBL) in conjunction with those of the nasal mucosa in 10 patients with PAR and in nine patients with CIR. Our results revealed no obvious difference in the percentage of nasal CD3+ T cells, CD8+ T cells, and alpha beta T cells in the PAR and CIR patients. In contrast, CD4+ T cells (p < 0.05), CD3+4-8- double-negative T cells, (p < 0.01), and gamma delta T cells (p < 0.01) were significantly increased in the nasal mucosa of PAR patients. A majority of the CD4+ T cells in the nasal mucosa of PAR patients coexpressed the CD45RO surface molecule, and a predominant proportion of CD4+ T cells in the nasal coexpressed the CD45RO surface molecule, and a predominant proportion of CD4+ T cells in the nasal epithelium were CD45RO+. The ratio of CD4+ CD45RO+:CD4+ CD45RA+ T cells in the allergic patients' nasal mucosa was significantly greater than that in autologous peripheral blood (p < 0.01). The proportion and stages of activation and differentiation of T-cell subsets in the allergic patients' nasal mucosa were independent of those in the peripheral blood. An increase in the proportion of natural killer (NK) cells was observed in the nasal mucosa of CIR patients. Taken together, our results suggest that nasal T cells exhibit distinct patterns of distribution, differentiation, and activation in different inflammatory conditions of the nose. PAR is characterized by a selective increase in CD4+ memory T cells, CD3+4-8- double-negative T cells, B cells, and gamma delta T cells in the nasal mucosa. The increase in CD4+ memory T cells in the allergic nasal epithelium may have critical implications in the pathogenesis of PAR.