tbuckley/cabot-search huggingface dataset:
A Phase IIa Trial of the New Tuberculosis Vaccine, MVA85A, in HIV- and/or <i>Mycobacterium tuberculosis</i>–infected Adults
Authors: Thomas J. Scriba, Michele Tameris, Erica Smit, Linda van der Merwe, E. Jane Hughes, Blessing Kadira, Katya Mauff, Sizulu Moyo, Nathaniel Brittain, Alison Lawrie, Humphrey Mulenga, Marwou de Kock, Lebohang Makhethe, Esme Janse van Rensburg, Sebastian Gelderbloem, Ashley Veldsman, Mark Hatherill, Hendrik Geldenhuys, Adrian V. S. Hill, Anthony Hawkridge, Gregory D. Hussey, Willem A. Hanekom, Helen McShane, Hassan Mahomed
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Novel tuberculosis (TB) vaccines should be safe and effective in populations infected with Mycobacterium tuberculosis (M.tb) and/or HIV for effective TB control.To determine the safety and immunogenicity of MVA85A, a novel TB vaccine, among M.tb- and/or HIV-infected persons in a setting where TB and HIV are endemic.An open-label, phase IIa trial was conducted in 48 adults with M.tb and/or HIV infection. Safety and immunogenicity were analyzed up to 52 weeks after intradermal vaccination with 5 × 10(7) plaque-forming units of MVA85A. Specific T-cell responses were characterized by IFN-γ enzyme-linked immunospot and whole blood intracellular cytokine staining assays.MVA85A was well tolerated and no vaccine-related serious adverse events were recorded. MVA85A induced robust and durable response of mostly polyfunctional CD4(+) T cells, coexpressing IFN-γ, tumor necrosis factor-α, and IL-2. Magnitudes of pre- and postvaccination T-cell responses were lower in HIV-infected, compared with HIV-uninfected, vaccinees. No significant effect of antiretroviral therapy on immunogenicity of MVA85A was observed.MVA85A was safe and immunogenic in persons with HIV and/or M.tb infection. These results support further evaluation of safety and efficacy of this vaccine for prevention of TB in these target populations.
The sequence of the gorilla fetal globin genes: evidence for multiple gene conversions in human evolution.
Authors: A F Scott, P Heath, S Trusko, S H Boyer, W Prass, M Goodman, J Czelusniak, L Y Chang, J L Slightom
Journal: Molecular Biology and Evolution (1984)

Two fetal globin genes (G gamma and A gamma) from one chromosome of a lowland gorilla (Gorilla gorilla gorilla) have been sequenced and compared to three human loci (a G gamma-gene and two A gamma-alleles). A comparison of regions of local homology among these five sequences indicates that long after the duplication that produced the two nonallelic gamma-globin loci of catarrhine primates, about 35 million years (Myr) ago, at least one gene conversion event occurred between these loci. This conversion occurred not long before the ancestral divergence (about 6 Myr ago) of Homo and Gorilla. After this ancestral divergence, a minimum of three more gene conversion events occurred in the human lineage. Each human A gamma-allele shares specific sequence features with the gorilla A gamma-gene; one such distinctive allelic feature involves the simple repeated sequence in IVS 2. This suggests that early in the human lineage the A gamma-genes may have undergone a crossing-over event mediated by this simple repeated sequence. The DNA sequences from coding regions of both G gamma- and A gamma-loci, a comparison of 292 codons in the corresponding gorilla and human genes, show an unusually low evolutionary rate, with only two nonsilent differences and, surprisingly, not even one silent substitution. The two nonsynonymous substitutions observed predict a glycine at codon 73 and an arginine at codon 104 in the gorilla A gamma-sequence rather than aspartic acid and lysine, respectively, in human A gamma. Because only arginine has been found at position 104 in gamma-chains of Old World monkeys, it may represent the ancestral residue lost in gorilla and human G gamma-chains and in the human A gamma-chain. Possibly the arginine codon (AGG) was replaced by the lysine codon (AAG) in the G gamma-gene of a common ancestor of Homo and Gorilla and then was transferred to the A gamma-gene by subsequent conversions in the human lineage. DNA sequence conversions, similar to that attributed to the fetal gamma-globin genes, appear to be relatively frequent phenomena and, if widespread throughout the genome, may have profound evolutionary consequences.
Withdrawal of Clopidogrel in Active Gastric Bleeding
Authors: Jean-Jacques Mourad
Journal: Annals of Internal Medicine (2010)

Letters18 May 2010Withdrawal of Clopidogrel in Active Gastric BleedingJean-Jacques Mourad, MD, PhDJean-Jacques Mourad, MD, PhDFrom Avicenne University Hospital, AP-HP, 93000 Bobigny, France.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-152-10-201005180-00012 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Sung and colleagues (1) provided important results on a very frequent clinical situation: withdrawal of aspirin in active gastric bleeding. We were surprised by the unusually high incidence of mortality at 1 month (9%). Could this be explained by any other factor related to study design, namely, the withdrawal of clopidogrel? The authors stated that they “did not exclude patients who received clopidogrel in conjunction with aspirin, but [they] discontinued clopidogrel therapy after randomization … ” The indications for dual antiplatelet blockade are few and include percutaneous coronary interventions. Discontinuation of therapy with clopidogrel in patients treated ...Reference1. Sung JJ, Lau JY, Ching JY, Wu JC, Lee YT, Chiu PW, et al. Continuation of low-dose aspirin therapy in peptic ulcer bleeding: a randomized trial. Ann Intern Med. 2010;152:1-9. [PMID: 19949136] LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From Avicenne University Hospital, AP-HP, 93000 Bobigny, France.Disclosures: None disclosed. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoContinuation of Low-Dose Aspirin Therapy in Peptic Ulcer Bleeding Joseph J.Y. Sung , James Y.W. Lau , Jessica Y.L. Ching , Justin C.Y. Wu , Yuk T. Lee , Philip W.Y. Chiu , Vincent K.S. Leung , Vincent W.S. Wong , and Francis K.L. Chan Withdrawal of Clopidogrel in Active Gastric Bleeding Joseph J.Y. Sung Metrics 18 May 2010Volume 152, Issue 10Page: 685KeywordsConflicts of interestDrug therapyHeart rateHemorrhageMorbidityPercutaneous coronary interventionStent implantationThrombosis ePublished: 18 May 2010 Issue Published: 18 May 2010 Copyright & PermissionsCopyright © 2010 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Frequency-Dependent Activation of a Constitutive Nitric Oxide Synthase and Regulation of Contractile Function in Adult Rat Ventricular Myocytes
Authors: David M. Kaye, Stephen D. Wiviott, Jean-Luc Balligand, William W. Simmons, Thomas W. Smith, Ralph A. Kelly
Journal: Circulation Research (1996)

Abstract Cardiac myocytes have recently been shown to express a constitutive Ca 2+ -sensitive isoform of NO synthase (NOS3), although the mechanism(s) responsible for activation of NOS3 and its physiological function remain to be determined. Since the activity of NOS3 is known to be regulated in part by the intracellular Ca 2+ activity ([Ca 2+ ] i ) in endothelial cells, we determined whether increasing myocyte [Ca 2+ ] i by uniform electric field pacing was accompanied by an increase in NOS3 activity, detected as nitrite accumulation in the medium. A higher [Ca 2+ ] i with increasing pacing frequencies was shown to be accompanied by a time-dependent accumulation of nitrite in medium that bathed adult rat ventricular myocytes stimulated at 3 Hz. Nitrite release by paced cells was significantly attenuated by treatment with either the NO synthase inhibitor nitro- l- arginine (L-NA, 1 mmol/L) or the intracellular Ca 2+ chelator BAPTA-AM (20 μmol/L). Paced myocytes also exhibited a frequency- and time-dependent increase in intracellular cGMP content that could be inhibited significantly by either L-NA or the soluble guanylate cyclase inhibitor LY83583 (5 μmol/L). To determine whether the increase in NOS3 activity with pacing affected contractile function, myocytes were sequentially paced at frequencies from 0.5 to 3 Hz. Methylene blue, L-NA, and LY83583 all increased the amplitude of shortening of myocytes paced at 3 Hz. Furthermore, a significantly greater positive inotropic response to high extracellular Ca 2+ (3 mmol/L) was demonstrated by myocytes pretreated with L-NA compared with control cells. These data indicate that myocyte NOS3 activity is regulated in part by [Ca 2+ ] i , whether induced by changes in pacing frequency or [Ca 2+ ] o , and depresses myocyte contractile responsiveness to higher stimulation frequencies.
A Phase 2 Study of Rituximab in Combination with Recombinant Interleukin-2 for Rituximab-Refractory Indolent Non-Hodgkin's Lymphoma
Authors: Khuda D. Khan, Christos Emmanouilides, Don M. Benson, Deborah Hurst, Pablo Garcia, Glenn Michelson, Sandra Milan, Amy K. Ferketich, Lawrence Piro, John P. Leonard, Pierluigi Porcu, Charles F. Eisenbeis, Amy L. Banks, Lei Chen, John C. Byrd, Michael A. Caligiuri
Journal: Clinical Cancer Research (2006)

Abstract Purpose: The incidence of non-Hodgkin's lymphoma (NHL), the fifth most common malignancy in the United States, has increased over 70% in the last 30 years. Fifty percent to 75% of patients with low-grade or follicular NHL respond to rituximab therapy. However, responses are generally of limited duration, and complete responses are rare. Preclinical work suggests that human recombinant interleukin-2 (rIL-2; aldesleukin, Proleukin) enhances rituximab efficacy. Antibody-dependent cellular cytotoxicity (ADCC) is an important mechanism of action of rituximab. rIL-2 induces expansion and activation of Fc receptor (FcR)–bearing cells, thereby enhancing ADCC. Therefore, a large, multicenter phase 2 trial to assess the effects of rIL-2 on rituximab therapy in patients with rituxumab-refractory low-grade NHL was conducted. Experimental Design: The combination of rituximab and rIL-2 was studied in 57 patients with rituximab-refractory low-grade NHL (i.e., patients must have received a single-agent course of rituximab and showed no tumor response, or had a response lasting &amp;lt;6 months). I.V. rituximab was given at 375 mg/m2 (weeks 1-4). S.C. rIL-2 was given thrice a week at 14 MIU (weeks 2-5) and at 10 MIU (weeks 6-9). Results: Rituximab plus rIL-2 combination therapy was safe and generally well tolerated, but responses were low. Fifty-seven patients were enrolled with 54 evaluable for response; however, only five responses (one complete and four partial) were observed. Correlative data indicate that rIL-2 expanded FcR-bearing cells and enhanced ADCC. However, other factors, such as FcγR polymorphisms in patients refractory to single-agent rituxumab and heterogeneous tumor biology, may have influenced the lack of clinical efficacy seen with this combination therapy. Conclusions: rIL-2 expands FcR-bearing cellular subsets in vivo and enhances in vitro ADCC of rituxumab. However, these findings do not directly translate into meaningful clinical benefit for patients with rituxumab-refractory NHL.
Longer term effects of very low energy diet on obstructive sleep apnoea in cohort derived from randomised controlled trial: prospective observational follow-up study
Authors: K. Johansson, E. Hemmingsson, R. Harlid, Y. Trolle Lagerros, F. Granath, S. Rossner, M. Neovius
Journal: BMJ (2011)

Objective To determine whether initial improvements in obstructive sleep apnoea after a very low energy diet were maintained after one year in patients with moderate to severe obstructive sleep apnoea. Design Single centre, prospective observational follow-up study. Setting Outpatient obesity clinic in a university hospital in Stockholm, Sweden. Participants 63 men aged 30-65 with body mass index (BMI) 30-40 and moderate to severe obstructive sleep apnoea defined as an apnoea-hypopnoea index ≥15 (events/hour), all treated with continuous positive airway pressure. Intervention A one year weight loss programme, consisting of an initial very low energy diet for nine weeks (seven weeks of 2.3 MJ/day and two weeks of gradual introduction of normal food) followed by a weight loss maintenance programme. Main outcome measure Apnoea-hypopnoea index, the main index for severity of obstructive sleep apnoea. Data from all patients were analysed (baseline carried forward for missing data). Results Of 63 eligible patients, 58 completed the very low energy diet period and started the weight maintenance programme and 44 completed the full programme; 49 had complete measurements at one year. At baseline the mean apnoea-hypopnoea index was 36 events/hour. After the very low energy diet period, apnoea-hypopnoea index was improved by −21 events/hour (95% confidence interval −17 to −25) and weight by −18 kg (−16 to −19; both P<0.001). After one year the apnoea-hypopnoea index had improved by −17 events/hour (−13 to −21) and body weight by −12 kg (−10 to −14) compared with baseline (both P<0.001). Patients with severe obstructive sleep apnoea at baseline had greater improvements in apnoea-hypopnoea index (−25 events/hour) compared with patients with moderate disease (−7 events/hour, P<0.001). At one year, 30/63 (48%, 95% confidence interval 35% to 60%) no longer required continuous positive airway pressure and 6/63 (10%, 2% to 17%) had total remission of obstructive sleep apnoea (apnoea-hypopnoea index <5 events/hour). There was a dose-response association between weight loss and apnoea-hypopnoea index at follow-up (β=0.50 events/kg, 0.11 to 0.88; P=0.013). Conclusion Initial improvements in obstructive sleep apnoea after treatment with a very low energy diet can be maintained after one year in obese men with moderate to severe disease. Those who lose the most weight or have severe sleep apnoea at baseline benefit most. Trial registration Current Controlled Trials 70090382.
Common Abnormalities and Disorder-Specific Compensation During Implicit Regulation of Emotional Processing in Generalized Anxiety and Major Depressive Disorders
Authors: Amit Etkin, Alan F. Schatzberg
Journal: American Journal of Psychiatry (2011)

Processing deficits were observed in the ventral anterior cingulate and amygdala of patients with major depression and/or generalized anxiety disorder, but those with depression only had compensatory prefrontal activity.
Concentrated swine feeding operations and public health: a review of occupational and community health effects.
Authors: D Cole, L Todd, S Wing
Journal: Environmental Health Perspectives (2000)

Recent industry changes in swine-management practices have resulted in a growing controversy surrounding the environmental and public health effects of modern swine production. The numerous wastes produced by intensive swine production not only pose a significant challenge to effective environmental management but also are associated with decreased air quality in confinement houses, potentially transferable antimicrobial resistance patterns, and several infectious agents that can be pathogenic to humans. Published studies have documented a variety of contaminants, microbial agents, and health effects in those occupationally exposed to swine, and these have provided the groundwork for an increasing body of research to evaluate possible community health effects. Nonetheless, several factors limit our ability to define and quantify the potential role of intensive swine-rearing facilities in occupational and community health. Our incomplete understanding and ability to detect specific exposures; the complicated nature of disease etiology; pathogenesis; and surveillance; and the inherent difficulties associated with study design all contribute to the inadequate level of knowledge that currently prevails. However; an evaluation of the published literature; and a recognition of the elements that may be compromising these studies; provides the foundation from which future studies may develop.
PMN migration in psoriasis
Authors: E. Christophers, A. Langer
Journal: British Journal of Dermatology (1988)

Journal Article PMN migration in psoriasis Get access E. Christophers, E. Christophers Department of Dermatology and Venerology Christian‐Albrechts University, Schittenhelmstr. 7, 2300 Kiel, Germany Search for other works by this author on: Oxford Academic Google Scholar A. Langer A. Langer Department of Dermatology, Warsaw Academy of Sciences, Warsaw, Poland Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 118, Issue 4, 1 April 1988, Pages 586–587, https://doi.org/10.1111/j.1365-2133.1988.tb02478.x Published: 01 April 1988
The use of liver biopsy evaluation in discrimination of idiopathic autoimmune hepatitis versus drug-induced liver injury
Authors: Ayako Suzuki, Elizabeth M. Brunt, David E. Kleiner, Rosa Miquel, Thomas C. Smyrk, Raul J. Andrade, Isabel M. Lucena, Agustin Castiella, Keith Lindor, Einar Björnsson
Journal: Hepatology (2011)

Distinguishing drug-induced liver injury (DILI) from idiopathic autoimmune hepatitis (AIH) can be challenging. We performed a standardized histologic evaluation to explore potential hallmarks to differentiate AIH versus DILI. Biopsies from patients with clinically well-characterized DILI [n = 35, including 19 hepatocellular injury (HC) and 16 cholestatic/mixed injury (CS)] and AIH (n = 28) were evaluated for Ishak scores, prominent inflammatory cell types in portal and intra-acinar areas, the presence or absence of emperipolesis, rosette formation, and cholestasis in a blinded fashion by four experienced hepatopathologists. Histologic diagnosis was concordant with clinical diagnosis in 65% of cases; but agreement on final diagnosis among the four pathologists was complete in only 46% of cases. Interface hepatitis, focal necrosis, and portal inflammation were present in all evaluated cases, but were more severe in AIH (P &lt; 0.05) than DILI (HC). Portal and intra-acinar plasma cells, rosette formation, and emperiopolesis were features that favored AIH (P &lt; 0.02). A model combining portal inflammation, portal plasma cells, intra-acinar lymphocytes and eosinophils, rosette formation, and canalicular cholestasis yielded an area under the receiver operating characteristic curve (AUROC) of 0.90 in predicting DILI (HC) versus AIH. All Ishak inflammation scores were more severe in AIH than DILI (CS) (P ≤ 0.05). The four AIH-favoring features listed above were consistently more prevalent in AIH, whereas portal neutrophils and intracellular (hepatocellular) cholestasis were more prevalent in DILI (CS) (P &lt; 0.02). The combination of portal inflammation, fibrosis, portal neutrophils and plasma cells, and intracellular (hepatocellular) cholestasis yielded an AUC of 0.91 in predicting DILI (CS) versus AIH. Conclusion: Although an overlap of histologic findings exists for AIH and DILI, sufficient differences exist so that pathologists can use the pattern of injury to suggest the correct diagnosis. (Hepatology 2011;)
The Complete Sequence of the Mitochondrial Genome of Buteo buteo (Aves, Accipitridae) Indicates an Early Split in the Phylogeny of Raptors
Authors: E Haring, L Kruckenhauser, A Gamauf, M J Riesing, W Pinsker
Journal: Molecular Biology and Evolution (2001)

The complete sequence of the mitochondrial (mt) genome of Buteo buteo was determined. Its gene content and nucleotide composition are typical for avian genomes. Due to expanded noncoding sequences, Buteo possesses the longest mt genome sequenced so far (18,674 bp). The gene order comprising the control region and neighboring genes is identical to that of Falco peregrinus, suggesting that the corresponding rearrangement occurred before the falconid/accipitrid split. Phylogenetic analyses performed with the mt sequence of Buteo and nine other mt genomes suggest that for investigations at higher taxonomic levels (e.g., avian orders), concatenated rRNA and tRNA gene sequences are more informative than protein gene sequences with respect to resolution and bootstrap support. Phylogenetic analyses indicate an early split between Accipitridae and Falconidae, which, according to molecular dating of other avian divergence times, can be assumed to have taken place in the late Cretaceous 65–83 MYA.
The Predictive Value of Exhaled Nitric Oxide Measurements in Assessing Changes in Asthma Control
Authors: STUART L. JONES, JOHN KITTELSON, JAN O. COWAN, ERIN M. FLANNERY, ROBERT J. HANCOX, CHRISTENE R. MCLACHLAN, D. ROBIN TAYLOR
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Exhaled nitric oxide (eNO) levels are increased in untreated or unstable asthma and measurements can be made easily. Our aim was to assess the usefulness of eNO for diagnosing and predicting loss of control (LOC) in asthma following steroid withdrawal. Comparisons were made against sputum eosinophils and airway hyperresponsiveness (AHR) to hypertonic saline (4.5%). Seventy-eight patients with mild/moderate asthma had their inhaled steroid therapy withdrawn until LOC occurred or for a maximum of 6 wk. Sixty (77.9%) developed LOC. There were highly significant correlations between the changes in eNO and symptoms (p < 0.0001), FEV1 (p < 0.002), sputum eosinophils (p < 0.0002), and saline PD15 (p < 0.0002), and there were significant differences between LOC and no LOC groups. Both single measurements and changes of eNO (10 ppb, 15 ppb, or an increase of > 60% over baseline) had positive predictive values that ranged from 80 to 90% for predicting and diagnosing LOC. These values were similar to those obtained using sputum eosinophils and saline PD15 measurements. We conclude that eNO measurements are as useful as induced sputum analysis and AHR in assessing airway inflammation, with the advantage that they are easy to perform.
Reliability and validity testing of a single-item physical activity measure
Authors: K Milton, F C Bull, A Bauman
Journal: British Journal of Sports Medicine (2010)

Objective To develop and test a new single-item physical activity screening tool, suitable for assessing respondents' eligibility for behaviour change interventions. Design Two single-item assessment tools were developed, one using a “past week” recall period, the other using a “past month” recall period. A quota sampling system was used to recruit 480 adults from across England, Scotland and Wales. Half the sample completed the past-week question and half completed the past-month version. Test–retest reliability was assessed over a 2- to 5-day period. Concurrent validity was assessed using the Global Physical Activity Questionnaire and the UK Active People Survey. All surveys were completed via telephone interviews. Results Both versions of the single-item instrument demonstrated strong reproducibility (r=0.72–0.82), using Spearman's rank correlation coefficients. The past-week recall question showed strong agreement in the classification of respondents meeting the current physical activity recommendation (kappa=0.63, 95% CI 0.54 to 0.72).Concurrent validity over the past week compared to the Global Physical Activity Questionnaire was modest (r=0.53) and slightly weaker for the past month compared to the Active People Survey (r=0.33–0.48). Conclusion Both versions of the new single-item measure performed as well as other short physical activity tools in terms of reliability and concurrent validity. Criterion validity testing of the single-item measure is recommended to establish its ability to assess objectively measured physical activity levels. In addition, further research to assess the responsiveness of the single-item measure in detecting changes in physical activity will inform its usefulness in programme evaluation.