tbuckley/cabot-search huggingface dataset:
Carbon in airway macrophages from children with asthma
Authors: Rossa E Brugha, Naseem Mushtaq, Thomas Round, Dev H Gadhvi, Isobel Dundas, Erol Gaillard, Lee Koh, Louise J Fleming, Daniel J Lewis, Marek Sanak, Helen E Wood, Benjamin Barratt, Ian S Mudway, Frank J Kelly, Christopher J Griffiths, Jonathan Grigg
Journal: Thorax (2014)

<h3>Background</h3> Airway macrophage (AM) phagocytosis is impaired in severe asthma. Prostaglandin (PG) E<sub>2</sub> and D<sub>2</sub> are increased in severe asthma and suppress AM phagocytic function in vitro. In this study, we sought evidence for PG-mediated impairment of phagocytosis of inhalable carbonaceous particulate matter (PM) by AM in children with severe asthma compared with mild asthmatics and healthy controls. <h3>Methods</h3> AM were obtained from children with asthma and healthy controls using induced sputum. AM carbon area (μm<sup>2</sup>) was assessed by image analysis. In a subgroup of asthmatics, urinary PGE<sub>2</sub> and PGD<sub>2</sub> metabolites were measured by high-performance liquid chromatography, and PM exposure at the home address was modelled. Phagocytosis of PM by human monocyte-derived macrophages and rat AM was assessed in vitro by image analysis. <h3>Results</h3> AM carbon was 51% lower in children with moderate-to-severe asthma (n=36) compared with mild asthmatics (n=12, p&lt;0.01) and healthy controls (n=47, p&lt;0.01). There was no association between modelled PM exposure and AM carbon in 33 asthmatics who had a urine sample, but there was an inverse association between AM carbon and urinary metabolites of PGE<sub>2</sub> and D<sub>2</sub> (n=33, rs=−0.40, p&lt;0.05, and rs=−0.44, p&lt;0.01). PGE<sub>2</sub> 10<sup>−6</sup> M, but not PGD<sub>2</sub> 10<sup>−6</sup> M, suppressed phagocytosis of PM<sub>10</sub> by human macrophages in vitro (p&lt;0.05 vs control). PGE<sub>2</sub> 10<sup>−6</sup> M also suppressed phagocytosis of PM<sub>10</sub> by rat AM in vitro (p&lt;0.01 vs control). <h3>Conclusions</h3> Phagocytosis of inhaled carbonaceous PM by AMs is impaired in severe asthma. PGE<sub>2</sub> may contribute to impaired AM phagocytic function in severe asthma.
Major histocompatibility complex-controlled, antigen-presenting cell-expressed specificity of T cell antigen recognition. Identification of a site of interaction and its relationship to Ir genes.
Authors: D Hansburg, E Heber-Katz, T Fairwell, E Appella
Journal: The Journal of Experimental Medicine (1983)

In previous work (5,6), we have reported studies on a T lymphocyte hybridoma clone and the peritoneal exudate T cells (PETLES) from B10.A(5R) mice primed with the cytochrome c carboxyl terminal peptide (residues 81-103) of the tobacco horn worm moth (Manducca sextus). As expected, since B10.A(5R) is a low responder to pigeon fragment 81-104, it was found that the B10.A(5R) lymphocytes were unable to respond to the pigeon cytochrome c 81-104 fragment presented on syngeneic B10.A(5R) antigen-presenting cells (APC). However, these same T lymphocytes did respond to the pigeon fragment when presented on B10.A APC. Thus, some structural difference between the pigeon and moth peptides had prevented B10.A(5R) APC from effectively presenting the pigeon fragment to moth-primed B10.A(5R) lymphocytes. This structural difference was found to be the deletion of an alanine at position -103 (Ala103) from the pigeon sequence in the moth peptide. Two additional T cell specificities were created by changing residue-99. These T cell populations from the B10.A(5R) showed an identical dependence on the Ala103 deletion when B10.A and B10.A(5R) APC were compared. The relationship of APC-expressed antigen specificity and MHC-linked immune responsiveness differences was also examined. The B10.A(5R) was found to be a high responder to each of three peptides that lack Ala103 but not to the Ala103-containing analogues. B10.A mice, in contrast, respond to both types of peptides. Utilizing allogeneic antigen-presentation to B10.A PETLES by pulsed APC, it was shown that the poor response of the B10.A(5R) to the Ala103-containing peptides was, in two of three cases, not associated with any differences in T cell repertoires but due to two different APC capabilities of B10.A and B10.A(5R). The exception apparently represents a case of T cell repertoire polymorphism between B10.A and B10.A(5R) that can also affect immune responsiveness.
Prevalence and prognosis of unclassifiable interstitial lung disease
Authors: Lauren Troy, Ian Glaspole, Nicole Goh, Chris Zappala, Peter Hopkins, Margaret Wilsher, Yuben Moodley, Tamera Corte
Journal: European Respiratory Journal (2014)

To the Editor: 

We read with interest the recent article by Ryerson et al. [1], describing the prevalence and characteristics of patients with unclassifiable interstitial lung disease (ILD) presenting to a specialist centre. This study is the first to target specifically this newly defined disease category, in parallel with publication of the updated American Thoracic Society/European Respiratory Society classification of the idiopathic interstitial pneumonias (IIPs) [2]. The authors identified 10% of their ILD patient population as having unclassifiable ILD following multidisciplinary discussion (MDD). The major reasons for diagnostic uncertainty related to either inability or unwillingness of the patient to undergo surgical lung biopsy, or inadequacy of the tissue specimen sampled. Only a minority of cases remained ambiguous after a reasonable tissue sample had been obtained.

The study detailed the clinical characteristics of this hybrid group, with many of the mean baseline demographics and disease behaviours falling between the two reference groups of patients with confirmed idiopathic pulmonary fibrosis (IPF) and non-IPF diagnoses. Multivariate analysis revealed low diffusing capacity of …
RESISTANCE TO PNEUMOCOCCUS INFECTION IN RABBITS FOLLOWING IMMUNIZING INJECTIONS OF HEAT-KILLED PNEUMOCOCCUS SUSPENSIONS
Authors: Ernest G. Stillman, Kenneth Goodner
Journal: The Journal of Experimental Medicine (1933)

The degree and duration of the active resistance against pneumococcus infection have been determined in rabbits which received intravenous injections of a heat-killed suspension of pneumococci of the three principal types. The resistance induced by the immunization procedure varied in degree and in duration with each type of Pneumococcus.
A Schizophrenia Gene Locus on Chromosome 17q21 in a New Set of Families of Mexican and Central American Ancestry: Evidence From the NIMH Genetics of Schizophrenia in Latino Populations Study
Authors: Michael Escamilla, Elizabeth Hare, Albana M. Dassori, Juan Manuel Peralta, Alfonso Ontiveros, Humberto Nicolini, Henriette Raventós, Rolando Medina, Ricardo Mendoza, Alvaro Jerez, Rodrigo Muñoz, Laura Almasy
Journal: American Journal of Psychiatry (2009)

Objective: The present study investigated a new set of families of Latin American ancestry in order to detect the location of genes predisposing to schizophrenia and related psychotic disorders. Method: A genome-wide scan was performed for 175 newly recruited families with at least two siblings suffering from a psychotic disorder. Best-estimate consensus procedures were used to arrive at diagnoses, and nonparametric allele-sharing statistics were calculated to detect linkage. Results: Genome-wide significant evidence for linkage for the phenotype of DSM-IV schizophrenia or schizoaffective disorder was found in a region on chromosome 17q21 (lod score, 3.33). A region on chromosome 15q22-23 showed suggestive evidence of linkage with this same phenotype (lod score, 2.11). Analyses using a broader model (any psychosis) yielded evidence of suggestive linkage for the 17q21 region only, and no region achieved genome-wide significance of linkage. Conclusions: The new set of 175 families of Mexican and Central American ancestry delineates two new loci likely to harbor predisposition genes for schizophrenia and schizoaffective disorder. The region with the strongest support for linkage in this sample, 17q21, has been implicated in meta-analyses of schizophrenia genome screens, but the authors found no previous reports of it as a locus for schizophrenia in specific population- or family-based studies, and it may represent the location of a schizophrenia predisposition gene (or genes) of special relevance in Mexican and Central American populations.
Prognostic Factors for Survival of Patients with Stage IV Renal Cell Carcinoma
Authors: Robert J. Motzer, Jennifer Bacik, Madhu Mazumdar
Journal: Clinical Cancer Research (2004)

Abstract Prospective identification of patients with stage IV renal cell carcinoma more likely to benefit from cytokine therapy could be used as a stratification factor in Phase III trials and in risk-directed therapy. The relationship between pretreatment clinical features and survival was evaluated in patients treated in Phase II and III clinical trials for metastatic renal cell carcinoma at the Memorial Sloan-Kettering Cancer Center. The first analysis was performed in 670 patients treated with cytokines or chemotherapy, and a multivariate model was created to predict survival. Studies that followed addressed four topics: (1) the survival of patients given interferon α as first-line therapy, (2) a comparison of survival for patients treated with chemotherapy versus cytokine therapy, (3) survival of patients with nonclear cell histologic features, and (4) survival of patients treated with a second-line therapy. Prognostic models based on pretreatment clinical and laboratory variables can help identify patients more likely to benefit from standard therapies, as well as assist in the interpretation of drug effectiveness in Phase II clinical trials. Investigations into new prognostic factors based on tumor biology are needed and of high priority.
Ten year follow up of pulmonary function in patients with primary Sjogren's syndrome
Authors: B K S Davidson, C A Kelly, I D Griffiths
Journal: Annals of the Rheumatic Diseases (2000)

<h3>OBJECTIVES</h3> To follow up a previous report on the lung function of patients with primary Sjögren9s syndrome (SS), and describe the findings having followed up this cohort for a median duration of 10 years (range 8–12 years). <h3>METHODS</h3> 30 patients fulfilling Fox9s criteria for definite or probable primary SS were assessed within six months of diagnosis and after a median duration of four and then 10 years by a clinical examination, chest radiograph, and lung function studies (FEV<sub>1</sub>, FVC, Tlco, and Kco). <h3>RESULTS</h3> At baseline, symptomatic dyspnoea was a common finding, reported by 13/30 patients, of whom two had evidence of fibrosing alveolitis on plain chest radiograph. Five patients had a carbon monoxide transfer factor (Tlco) more than two standardised residuals below the predicted value. After four years9 follow up two further patients developed radiological fibrotic changes and there were significant reductions in Tlco (p&lt;0.02) and transfer coefficient (Kco) (p&lt;0.02) compared with the baseline measurements. At 10 years9 follow up four patients had died and four were lost to follow up. One patient with fibrosing alveolitis had died from chest disease. There were no further cases of pulmonary fibrosis identified on plain chest radiograph. The lung function studies showed no further deterioration from the results found at year four with significant improvements in both Tlco (p&lt;0.001) and Kco(p&lt;0.001). Those patients who were anti-Ro antibody positive had significantly lower transfer factors than patients with primary SS without this serological marker (p&lt;0.02). <h3>CONCLUSION</h3> This long term follow up of lung disease in primary SS is reassuring, and suggests that most patients do not develop progressive lung disease. Pulmonary disease occurs predominantly in anti-Ro antibody positive patients and presents early in the course of the disease.
Exposure to farming environments in childhood and asthma and wheeze in rural populations: A systematic review with meta-analysis
Authors: Jon Genuneit
Journal: European Respiratory Journal (2012)

Background: Particularly strong associations with asthma and allergic diseases have been described for exposure to farming environments in childhood. The aim of this systematic review was to update and extend existing narrative reviews, test for heterogeneity across studies, and conduct a meta-analysis.

Methods: Published literature was searched through PubMed including all articles added before September 1, 2011. Articles were included if they reported an epidemiological study on the exposure to a farming environment in childhood and subsequent wheeze or asthma. Heterogeneity of effect measures was evaluated using Cochran's Q and I2. Effect measures were summarized by random-effects meta-analysis for various outcome definitions.

Results: In total, 357 retrieved abstracts revealed 52 articles from 39 studies with data considered for the meta-analysis. Most studies were conducted among children or on childhood onset of disease. Most data was on doctor diagnosed asthma or current wheeze. The meta-analysis showed substantial heterogeneity across studies with similar outcome definitions. Nonetheless, the combined effects were statistically significant and showed an approximate 25% lower asthma prevalence among exposed subjects compared to unexposed subjects.

Conclusions: The protective 'farm-effect' on asthma was reported in numerous studies. Its underlying factors ought to be studied and promising efforts have been already made. However, the heterogeneity of the effect across studies should also be investigated because whatever causes it is a potential threat to valid synthesis of evidence and to the detection of specific protective factors.
Observer agreement in evaluating coronary angiograms.
Authors: K M Detre, E Wright, M L Murphy, T Takaro
Journal: Circulation (1975)

The reliability of interpretation of coronary arteriography as a diagnostic tool was investigated in a sub-study of the VA Cooperative Study of Surgical Treatment for Coronary Arterial Occlusive Disease. Twenty-two physicians with varying levels of experience read 13 cine angiograms -- blind -- on two different occasions. Analysis of inter- and intraobserver variability showed that angiographic items about which observers were most inconsistent from one reading to the other had the largest interobserver disagreement as well. They were the distal portions of the left anterior descending and left circumflex arteries. Among the items on which there was most consistent agreement -- namely, the right main coronary artery and presence of ventricular aneurysm -- there was most often agreement between observers as well. When individual readers were evaluated, some observers were far more consistent in their own readings of all the angiographic items than others. This intraobserver agreement in turn correlated fairly well with how often they agreed with the other observers and with how much experience they reported having in reading coronary cineangiograms.
Evolutionary Conservation of Drosophila Polycystin-2 as a Calcium-Activated Cation Channel
Authors: Charles J. Venglarik, Zhiqian Gao, Xiangyi Lu
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. Mutations in the PKD2 gene cause autosomal dominant polycystic kidney disease (ADPKD) in humans. The protein encoded by PKD2 has similarity to voltage-sensitive cation channels and TRP channels and was named polycystin-2 (PC2). In agreement with this structural information, expression of PC2 in Xenopus oocytes or reconstitution of human PC2 in planar lipid bilayers produced Ca2+-activated cation channels. Although these studies provided a basic description of the biophysical, regulatory, and pharmacologic properties of the PC2-induced channels, it is still unknown how defective PC2 activity leads to cyst formation and expansion in ADPKD patients. To establish a genetic model for studying PC2 function and regulation, the authors identified and cloned a Drosophila PC2 (DmPC2). It is here shown that expression of DmPKD2 in Drosophila S2 cells produced a novel channel. On the basis of the similarity of this channel’s properties to mammalian PKD2-induced channels, this Drosophila channel is expected to provide a convenient genetic model for dissecting the mechanisms underlying ADPKD.
THE INCIDENCE OF BLACKHEAD AND OCCURRENCE OF HETERAKIS PAPILLOSA IN A FLOCK OF ARTIFICIALLY REARED TURKEYS
Authors: H. W. Graybill
Journal: The Journal of Experimental Medicine (1921)

In a flock of artificially reared turkeys originally consisting of 85 birds and reduced during the summer and fall by deaths and withdrawals for experimental purposes to 42 birds, five cases of blackhead occurred. These appeared during the months of July, September, and October. In four, Heterakis was searched for and found. In 38 birds from this flock killed for food during November and December, five harbored no Heterakis, and the rest carried light infestations. Of sixteen healthy birds withdrawn from the above flock during July and placed with a flock of older birds which had passed through this disease in former seasons, all contracted blackhead and fourteen died of the disease. The infestation with Heterakis was, as a rule, high, reaching a hundred specimens in some cases. In general, it appears that a high infestation with Heterakis is correlated with a high incidence of blackhead, a relation that had already been inferred in feeding experiments. In both of these groups no other species of worm was found in the ceca, and in instances in which examinations for coccidia were made none was found. Pheasants have been incriminated as a source of infestation with Heterakis papillosa in artificially reared flocks. In an artificially reared flock 38 birds that had never been ill, when killed in November and December, failed to show lesions of blackhead or evidence in the nature of scars that they had passed through an attack of the disease. Infectious soil that had remained unoccupied by turkeys and chickens for a period of 5 months beginning in the depth of a severe winter still harbored viable ova of Heterakis and proved highly dangerous to young poults. These experiments and observations fail to throw any light on the source of the protozoan parasite (Amoeba meleagridis) which causes the fatal lesions of blackhead.
Whole-genome sequencing of the snub-nosed monkey provides insights into folivory and evolutionary history
Authors: Xuming Zhou, Boshi Wang, Qi Pan, Jinbo Zhang, Sudhir Kumar, Xiaoqing Sun, Zhijin Liu, Huijuan Pan, Yu Lin, Guangjian Liu, Wei Zhan, Mingzhou Li, Baoping Ren, Xingyong Ma, Hang Ruan, Chen Cheng, Dawei Wang, Fanglei Shi, Yuanyuan Hui, Yujing Tao, Chenglin Zhang, Pingfen Zhu, Zuofu Xiang, Wenkai Jiang, Jiang Chang, Hailong Wang, Zhisheng Cao, Zhi Jiang, Baoguo Li, Guang Yang, Christian Roos, Paul A Garber, Michael W Bruford, Ruiqiang Li, Ming Li
Journal: Nature Genetics (2014)

Ming Li, Ruiqiang Li and colleagues report the whole-genome sequencing of a male golden snub-nosed monkey, Rhinopithecus roxellana, as well as its relatives Rhinopithecus bieti, Rhinopithecus brelichi and Rhinopithecus strykeri. Their analysis provides insights into primate evolution and adaptation to a diet consisting primarily of leaves and seeds. Colobines are a unique group of Old World monkeys that principally eat leaves and seeds rather than fruits and insects. We report the sequencing at 146× coverage, de novo assembly and analyses of the genome of a male golden snub-nosed monkey (Rhinopithecus roxellana) and resequencing at 30× coverage of three related species (Rhinopithecus bieti, Rhinopithecus brelichi and Rhinopithecus strykeri). Comparative analyses showed that Asian colobines have an enhanced ability to derive energy from fatty acids and to degrade xenobiotics. We found evidence for functional evolution in the colobine RNASE1 gene, encoding a key secretory RNase that digests the high concentrations of bacterial RNA derived from symbiotic microflora. Demographic reconstructions indicated that the profile of ancient effective population sizes for R. roxellana more closely resembles that of giant panda rather than its congeners. These findings offer new insights into the dietary adaptations and evolutionary history of colobine primates.
Cost Effectiveness and Screening Interval of Lipid Screening in Hodgkin's Lymphoma Survivors
Authors: Aileen B. Chen, Rinaa S. Punglia, Karen M. Kuntz, Peter M. Mauch, Andrea K. Ng
Journal: Journal of Clinical Oncology (2009)

Survivors of Hodgkin's lymphoma (HL) who received mediastinal irradiation have an increased risk of coronary heart disease. We evaluated the cost effectiveness of lipid screening in survivors of HL and compared different screening intervals.We developed a decision-analytic model to evaluate lipid screening in a hypothetical cohort of 30-year-old survivors of HL who survived 5 years after mediastinal irradiation. We compared the following strategies: no screening, and screening at 1-, 3-, 5-, or 7-year intervals. Screen-positive patients were treated with statins. Markov models were used to calculate life expectancy, quality-adjusted life expectancy, and lifetime costs. Baseline probabilities, transition probabilities, and utilities were derived from published studies and US population data. Costs were estimated from Medicare fee schedules and the medical literature. Sensitivity analyses were performed.Using an incremental cost-effectiveness ratio (ICER) threshold of $100,000 per quality-adjusted life-year (QALY) saved, lipid screening at every interval was cost effective relative to a strategy of no screening. When comparing screening intervals, a 3-year interval was cost effective relative to a 5-year interval, but annual screening, relative to screening every 3 years, had an ICER of more than $100,000/QALY saved. Factors with the most influence on the results included risk of cardiac events/death after HL, efficacy of statins in reducing cardiac events/death, and costs of statins.Lipid screening in survivors of HL, with statin therapy for screen-positive patients, improves survival and is cost effective. A screening interval of 3 years seems reasonable in the long-term follow-up of survivors of HL.
Absence of γ-Interferon–inducible Lysosomal Thiol Reductase in Melanomas Disrupts T Cell Recognition of Select Immunodominant Epitopes
Authors: M. Azizul Haque, Ping Li, Sheila K. Jackson, Hassane M. Zarour, John W. Hawes, Uyen T. Phan, Maja Maric, Peter Cresswell, Janice S. Blum
Journal: The Journal of Experimental Medicine (2002)

Long-lasting tumor immunity requires functional mobilization of CD8+ and CD4+ T lymphocytes. CD4+ T cell activation is enhanced by presentation of shed tumor antigens by professional antigen-presenting cells (APCs), coupled with display of similar antigenic epitopes by major histocompatibility complex class II on malignant cells. APCs readily processed and presented several self-antigens, yet T cell responses to these proteins were absent or reduced in the context of class II+ melanomas. T cell recognition of select exogenous and endogenous epitopes was dependent on tumor cell expression of γ-interferon–inducible lysosomal thiol reductase (GILT). The absence of GILT in melanomas altered antigen processing and the hierarchy of immunodominant epitope presentation. Mass spectral analysis also revealed GILT's ability to reduce cysteinylated epitopes. Such disparities in the profile of antigenic epitopes displayed by tumors and bystander APCs may contribute to tumor cell survival in the face of immunological defenses.