tbuckley/cabot-search huggingface dataset:
Pulmonary venous hypertension and mechanical strain stimulate monocyte chemoattractant protein-1 release and structural remodelling of the lung in human and rodent chronic heart failure models
Authors: John E S Park, Alexander R Lyon, Dongmin Shao, Lauren R Hector, Hua Xu, Peter O'Gara, Liao Pinhu, Rachel C Chambers, S John Wort, Mark J D Griffiths
Journal: Thorax (2014)

<h3>Introduction</h3> The burden of chronic heart failure (HF) is rising owing to an increased survivorship after myocardial infarction (MI). Pulmonary structural remodelling in patients with HF may protect against oedema while causing dyspnoea, the predominant symptom associated with HF. The cellular and molecular mechanisms underlying these processes in HF are poorly understood. We hypothesised that pulmonary venous hypertension (PVH) following MI provides a mechanical stimulus for structural remodelling of the lung via monocyte chemoattractant protein-1 (MCP-1). <h3>Methods</h3> Human lung microvascular endothelial cells (HLMVEC) and Ea.Hy 926 cells exposed to cyclic mechanical strain (CMS) in vitro were analysed for MCP-1 expression and activation of signalling intermediates. HF was induced in Sprague–Dawley rats 16 weeks after MI; a cohort was rescued with AAV9.SERCA2a gene therapy to reduce PVH. <h3>Results</h3> HLMVEC and Ea.Hy 926 cells exposed to CMS upregulated MCP-1 gene expression and protein release in an extracellular-signal-regulated kinase (ERK) 1/2 dependent manner. Supernatants from these experiments stimulated fibroblast (human fetal lung fibroblast -1) and pulmonary artery smooth muscle cell proliferation and differentiation. Total lung collagen, a marker of structural remodelling, and MCP-1 gene expression were increased in the lungs of rats with post-MI HF. SERCA2a gene therapy that attenuated PVH after MI was associated with lower levels of lung collagen and MCP-1 gene expression in the lung. <h3>Conclusions</h3> Mechanical strain associated with PVH may stimulate pulmonary structural remodelling through ERK 1/2 dependent induction of MCP-1. These findings provide insights into the pathophysiology of lung remodelling in HF and highlight novel, potential therapeutic targets.
Copy Number of Chromosome 17 but Not <i>HER2</i> Amplification Predicts Clinical Outcome of Patients With Pancreatic Ductal Adenocarcinoma
Authors: Nikolas H. Stoecklein, Andreas M. Luebke, Andreas Erbersdobler, Wolfram T. Knoefel, Winfried Schraut, Pablo E. Verde, Franziska Stern, Peter Scheunemann, Matthias Peiper, Claus F. Eisenberger, Jakob R. Izbicki, Christoph A. Klein, Stefan B. Hosch
Journal: Journal of Clinical Oncology (2004)

Purpose To determine the frequency and the potential clinical use of HER2 (17q21) gene amplification and chromosome 17 aneuploidy in pancreatic ductal adenocarcinoma (PDAC). Materials and Methods Serial tissue sections of 50 resected PDACs were analyzed with chromogenic in situ hybridization using locus-specific HER2 probes and centromeric probes for chromosome 17. Centromeric probes for chromosome 7 and 8 were hybridized to confirm ploidy levels. Expression of HER2 protein was assessed by immunohistochemistry. Correlations of experimental findings with clinical and follow-up data were tested. Results The HER2 gene locus was frequently (24%) amplified in PDAC and the rate of overexpression (2+ and 3+) was 10%, but no prognostic significance was found. Copy number analysis of chromosomes 7, 8, and 17 revealed disomic (40%), trisomic (36%), and hypertetrasomic (24%) tumors. Compared with patients with disomic tumors, patients with hypertetrasomic tumors exhibited a significantly decreased relapse-free and overall survival (5.0 v 13.0 months, P = .0144 and 7.0 v 20.0 months, P = .0099, respectively). Multivariate analysis confirmed the independent prognostic significance of hypertetrasomy. Conclusion Tumor ploidy levels correlate with prognosis of PDAC patients, indicating characteristic biologic properties of PDAC with high chromosomal instability. In contrast, no prognostic influence on patient outcome was found for the amplification of the HER2 oncogene or p185 HER2 overexpression. Therefore, evaluation of ploidy levels offers new opportunities for patient stratification in clinical trials and enables novel approaches to study the well-known aggressiveness of PDAC.
Low Prevalence of Psychoses Among the Hutterites, an Isolated Religious Community
Authors: Vishwajit L. Nimgaonkar, T. Mary Fujiwara, Mrinal Dutta, Joel Wood, Koren Gentry, Selma Maendel, Kenneth Morgan, Joseph Eaton
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: The authors estimated the prevalence of psychoses among the Hutterites in Manitoba, Canada, who lived in 102 communal farms or colonies. The study stemmed from an earlier epidemiological survey of North American Hutterite colonies (1950–1953), in which a low prevalence of psychoses was documented.METHOD: Psychiatrically ill individuals identified during the previous survey were rediagnosed with DSM-IV criteria. A current provincial health insurance claims database was queried anonymously for the period June 1992–May 1997, and the prevalence rate of disease among Hutterites, identified by distinctive surnames and unique postal addresses, was compared with the rate in the entire population of the province of Manitoba and in a comparison group of persons with Hutterite surnames but with addresses outside the Hutterite colonies.RESULTS: The annual prevalence of schizophrenia among the communal Hutterites, estimated from the database search by using ICD-9 criteria, was consistent with the prevalence found in the prior epidemiological survey (annual mean of 1.2/1,000 population, compared with 1.3/1,000 in the prior survey). The database search yielded a significantly lower prevalence for schizophrenia and other functional psychoses among communal Hutterites as well as among the comparison group, compared to the total Manitoba population. There was also lower prevalence for affective psychoses and adjustment reaction disorders among the communal Hutterites, compared to the total Manitoba population. Rates for neurotic disorders were elevated both among the communal Hutterites and the comparison group.CONCLUSIONS: The prevalence of specific psychoses was reduced among the Hutterites, although neurotic disorders were more prevalent. These findings suggest some specificity, although possible artifacts such as ascertainment bias must be considered. Further research is needed to examine genetic and environmental factors that may contribute to reduced prevalence of specific psychoses among the Hutterites.
Synaptic inhibition of Purkinje cells mediates consolidation of vestibulo-cerebellar motor learning
Authors: Peer Wulff, Martijn Schonewille, Massimiliano Renzi, Laura Viltono, Marco Sassoè-Pognetto, Aleksandra Badura, Zhenyu Gao, Freek E Hoebeek, Stijn van Dorp, William Wisden, Mark Farrant, Chris I De Zeeuw
Journal: Nature Neuroscience (2009)
Energy expenditure in adolescents playing new generation computer games
Authors: Lee Graves, Gareth Stratton, N D Ridgers, N T Cable
Journal: BMJ (2008)

To compare the energy expenditure of adolescents when playing sedentary and new generation active computer games.Cross sectional comparison of four computer games. Setting Research laboratories.Six boys and five girls aged 13-15 years.Participants were fitted with a monitoring device validated to predict energy expenditure. They played four computer games for 15 minutes each. One of the games was sedentary (XBOX 360) and the other three were active (Wii Sports).Predicted energy expenditure, compared using repeated measures analysis of variance.Mean (standard deviation) predicted energy expenditure when playing Wii Sports bowling (190.6 (22.2) kl/kg/min), tennis (202.5 (31.5) kl/kg/min), and boxing (198.1 (33.9) kl/kg/min) was significantly greater than when playing sedentary games (125.5 (13.7) kl/kg/min) (P<0.001). Predicted energy expenditure was at least 65.1 (95% confidence interval 47.3 to 82.9) kl/kg/min greater when playing active rather than sedentary games.Playing new generation active computer games uses significantly more energy than playing sedentary computer games but not as much energy as playing the sport itself. The energy used when playing active Wii Sports games was not of high enough intensity to contribute towards the recommended daily amount of exercise in children.
High-Flow Nasal Cannulae in Very Preterm Infants after Extubation
Authors: Brett J. Manley, Louise S. Owen, Lex W. Doyle, Chad C. Andersen, David W. Cartwright, Margo A. Pritchard, Susan M. Donath, Peter G. Davis
Journal: New England Journal of Medicine (2013)

The use of high-flow nasal cannulae is an increasingly popular alternative to nasal continuous positive airway pressure (CPAP) for noninvasive respiratory support of very preterm infants (gestational age, <32 weeks) after extubation. However, data on the efficacy or safety of such cannulae in this population are lacking.In this multicenter, randomized, noninferiority trial, we assigned 303 very preterm infants to receive treatment with either high-flow nasal cannulae (5 to 6 liters per minute) or nasal CPAP (7 cm of water) after extubation. The primary outcome was treatment failure within 7 days. Noninferiority was determined by calculating the absolute difference in the risk of the primary outcome; the margin of noninferiority was 20 percentage points. Infants in whom treatment with high-flow nasal cannulae failed could be treated with nasal CPAP; infants in whom nasal CPAP failed were reintubated.The use of high-flow nasal cannulae was noninferior to the use of nasal CPAP, with treatment failure occurring in 52 of 152 infants (34.2%) in the nasal-cannulae group and in 39 of 151 infants (25.8%) in the CPAP group (risk difference, 8.4 percentage points; 95% confidence interval, -1.9 to 18.7). Almost half the infants in whom treatment with high-flow nasal cannulae failed were successfully treated with CPAP without reintubation. The incidence of nasal trauma was significantly lower in the nasal-cannulae group than in the CPAP group (P=0.01), but there were no significant differences in rates of serious adverse events or other complications.Although the result for the primary outcome was close to the margin of noninferiority, the efficacy of high-flow nasal cannulae was similar to that of CPAP as respiratory support for very preterm infants after extubation. (Funded by the National Health and Medical Research Council; Australian New Zealand Clinical Trials Network number, ACTRN12610000166077.).
The role of adherence in tuberculosis HIV‐positive patients treated in ambulatory regimen
Authors: M. Rocha, S. Pereira, L. Ferreira, H. Barros
Journal: European Respiratory Journal (2003)

Adherence to antituberculosis treatment, a major determinant of outcome, is of special concern in human immunodeficiency virus (HIV)‐positive patients. However, tuberculosis death in HIV‐positive patients remains higher than in HIV‐negative patients, regardless of adherence. To assess determinants for an unfavourable tuberculosis outcome (defined as no cure or death), and determinants for nonadherence to antituberculosis treatment, 70 HIV‐positive patients with tuberculosis referred to an outpatient centre were studied. Patient outcome was compared according to HIV risk factors, other opportunistic diseases, antiretroviral drugs use, current i.v. drugs use, a methadone programme participation, tuberculosis features, treatment characteristics and adherence. Adherent and nonadherent patient characteristics were also compared. An unfavourable outcome occurred in 22.9% of patients and 32.9% were nonadherent with therapy. Nonadherence was the only independent determinant for an unfavourable outcome. Adherence was independently associated with current i.v. drug use, treatment complications and use of methadone. This study confirms that human immunodeficiency virus-infected patients, treated as outpatients, have high rates of nonadherence and that adherence is the strongest determinant for tuberculosis outcome. Independently of the current use of drugs, a methadone programme improves adherence to treatment.
Trace Element Transport in the Mammary Gland
Authors: Bo Lönnerdal
Journal: Annual Review of Nutrition (2007)

The mammary gland has a remarkable capacity to adapt to maternal deficiency or excess of iron, copper, and zinc and to homeostatically control milk concentrations of these essential nutrients. Similarly, it can regulate changes in concentrations of iron, copper, and zinc change during lactation. For iron, this regulation is achieved by transferrin receptor, DMT1, and ferroportin, whereas mammary gland copper metabolism is regulated by Ctr1, ATP7A, and ATP7B. Zinc homeostasis is complex, involving both zinc importers (Zip3) and zinc exporters (ZnT-1, ZnT-2, and ZnT-4). Both transcriptional and post-translational regulation can affect protein abundance and cellular localization of these transporters, finely orchestrating uptake, intracellular trafficking, and secretion of iron, copper, and zinc. The control of mammary gland uptake and milk secretion of iron, copper, and zinc protects both the mammary gland and the breast-fed infant against deficiency and excess of these nutrients.
Screening for Hearing Loss in Older Adults: U.S. Preventive Services Task Force Recommendation Statement
Authors: Virginia A. Moyer
Journal: Annals of Internal Medicine (2012)

Description: Update of the 1996 U.S. Preventive Services Task Force (USPSTF) recommendation statement on screening for hearing impairment in older adults. Methods: The USPSTF reviewed evidence published between 1950 and January 2010 on screening for age-related sensorineural hearing impairment in adults aged 50 years or older without diagnosed hearing loss in the primary care setting. Population: This recommendation applies to asymptomatic adults aged 50 years or older. It does not apply to persons seeking evaluation for perceived hearing problems or for cognitive or affective symptoms that may be related to hearing loss. Recommendation: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for hearing loss in asymptomatic adults aged 50 years or older (I statement).
Histamine induced bronchoconstriction and end tidal inspiratory activity in man.
Authors: N. E. Meessen, C. P. van der Grinten, S. C. Luijendijk, H. T. Folgering
Journal: Thorax (1996)

BACKGROUND: End tidal inspiratory activity (ETIA) in diaphragm and parasternal intercostal muscles can be evoked in man and in animals by administration of histamine. Exacerbations of asthma and administration of histamine are often accompanied by hyperinflation. The aims of the study were to determine (1) the magnitude of ETIA in response to histamine in man, (2) the relative contributions of chemical and mechanical stimulation of airway receptors to ETIA, and (3) the importance of ETIA to hyperinflation. METHODS: The effects of inhalation of histamine on the electrical activities of the diaphragm and parasternal intercostal muscles measured with surface electrodes were studied in 21 subjects. The experiments were repeated after inhalation of 600 micrograms of salbutamol to prevent histamine induced bronchoconstriction and concomitant mechanical stimulation of airway receptors. Subjects were connected to a closed breathing circuit to measure the changes in functional residual capacity (FRC) for the different experiments. RESULTS: The mean values of histamine induced ETIA were 60.6% and 46.9% of peak inspiratory activities during control conditions for the diaphragm and intercostal muscles, respectively. After salbutamol histamine induced ETIA was reduced to about one quarter of pre-salbutamol values. FRC increased by 427 ml as a result of inhalation of histamine, but after salbutamol this increase was only 53 ml. The data for ETIA and FRC were interpreted as indicating that the contributions of airflow limitation and ETIA to histamine induced hyperinflation are comparable. CONCLUSIONS: Histamine is a forceful stimulus for inducing ETIA. Both chemical and mechanical stimulation of airway receptors contribute to evoke ETIA, of which the contribution of mechanical stimulation is the more important one. ETIA contributes substantially to histamine induced hyperinflation.
Cystatin C and Prognosis for Cardiovascular and Kidney Outcomes in Elderly Persons without Chronic Kidney Disease
Authors: Michael G. Shlipak, Ronit Katz, Mark J. Sarnak, Linda F. Fried, Anne B. Newman, Catherine Stehman-Breen, Stephen L. Seliger, Brian Kestenbaum, Bruce Psaty, Russell P. Tracy, David S. Siscovick
Journal: Annals of Internal Medicine (2006)

Background: Cystatin C is an alternative measure of kidney function that may have prognostic importance among elderly persons who do not meet standard criteria for chronic kidney disease (estimated glomerular filtration rate [GFR] ≥60 mL/min per 1.73 m2). Objective: To evaluate cystatin C as a prognostic biomarker for death, cardiovascular disease, and incident chronic kidney disease among elderly persons without chronic kidney disease. Design: Cohort study. Setting: The Cardiovascular Health Study, a population-based cohort recruited from 4 communities in the United States. Participants: 4663 elderly persons. Measurements: Measures of kidney function were creatinine-based estimated GFR by using the Modification of Diet in Renal Disease equation and cystatin C concentration. Outcomes were death, cardiovascular death, noncardiovascular death, heart failure, stroke, myocardial infarction, and incident chronic kidney disease during follow-up (median, 9.3 years). Results: At baseline, 78% of participants did not have chronic kidney disease (estimated GFR ≥60 mL/min per 1.73 m2) and mean cystatin C concentration, creatinine concentration, and estimated GFR were 1.0 mg/L, 79.6 µmol/L (0.9 mg/dL), and 83 mL/min per 1.73 m2, respectively. Cystatin C concentrations (per SD, 0.18 mg/L) had strong associations with death (hazard ratio, 1.33 [95% CI, 1.25 to 1.40]), cardiovascular death (hazard ratio, 1.42 [CI, 1.30 to 1.54]), noncardiovascular death (hazard ratio, 1.26 [CI, 1.17 to 1.36]), incident heart failure (hazard ratio, 1.28 [CI, 1.17 to 1.40]), stroke (hazard ratio, 1.22 [CI, 1.08 to 1.38]), and myocardial infarction (hazard ratio, 1.20 [CI, 1.06 to 1.36]) among these participants. Serum creatinine concentrations had much weaker associations with each outcome and only predicted cardiovascular death. Participants without chronic kidney disease who had elevated cystatin C concentrations (≥1.0 mg/L) had a 4-fold risk for progressing to chronic kidney disease after 4 years of follow-up compared with those with cystatin C concentrations less than 1.0 mg/L. Limitations: Because this study did not directly measure GFR or albuminuria, the extent to which cystatin C may be influenced by nonrenal factors was not determined and participants with albuminuria might have been misclassified as having no kidney disease. Conclusions: Among elderly persons without chronic kidney disease, cystatin C is a prognostic biomarker of risk for death, cardiovascular disease, and chronic kidney disease. In this setting, cystatin C seems to identify a “preclinical” state of kidney dysfunction that is not detected with serum creatinine or estimated GFR.
UPDATED KIEL CLASSIFICATION FOR LYMPHOMAS
Authors: A.G. Stansfeld, J. Diebold, Y. Kapanci, G. Kelényi, K. Lennert, O. Mioduszewska, H. Noel, F. Rilke, C. Sundstrom, J.A.M. Van Unnik, D.H. Wright
Journal: The Lancet (1988)
THE EFFECT OF PASSIVELY ADMINISTERED ANTIBODY ON ANTIBODY SYNTHESIS
Authors: Frank J. Dixon, Hubert Jacot-Guillarmod, Patricia J. McConahey
Journal: The Journal of Experimental Medicine (1967)

Suppression of the primary response of rabbits to intravenously administered KLH can be achieved with very small amounts of hyperimmune anti-KLH administered a day later since the rabbit apparently rapidly eliminates most of the KLH by nonimmunologic means. The amount of passive anti-KLH needed to achieve immunosuppression was directly proportional to the dose of injected antigen. Antibody passively administered as much as 6–8 days after antigen still can be strongly immunosuppressive, which suggests that the antibody must be reacting with immunogen in or on responding cells or perhaps in the process of transfer between cells. There was no evidence that the presence of passively administered hyperimmune anti-KLH prior to the injection of antigen had any immunosuppressive action beyond the direct neutralization of the injected antigen. When KLH was injected in Freund adjuvant, anti-KLH incorporated with the KLH in the adjuvant was much more efficient in causing immunosuppression than anti-KLH given intravenously. The primary responses to 2 mg KLH given intravenously and 2 µg given in adjuvant reached approximately equal peaks and were suppressible by comparable amounts of intravenously administered anti-KLH. Two observations suggest that passive antibody neutralizes the immunogenic stimulus at the level of individual antigenic determinants and not merely by aggregating or precipitating entire antigenic molecules. First, anti-abalone hemocyanin (AH) which cross-reacts approximately 50% with KLH was only partially immunosuppressive even in extremely large amounts, i.e., amounts which could react with and precipitate much more KLH than could the smaller but more suppressive doses of anti-KLH. Second, when KLH and anti-KLH were given together in adjuvant, effective immunosuppression was achieved only with amounts of anti-KLH sufficient to saturate or cover virtually all available antigenic determinants. The immunosuppressive quality of passive antibody increases with time after immunization and with repeated immunization of the donor. In view of their relatively weak immunosuppressive properties, antibodies formed in the first weeks of a primary response may not contribute significantly to the turning off of the antibody response. In any event, results obtained by passive transfer of hyperimmune antibody to animals early in a primary response cannot be applied to the natural events in a primary response.
Zonula occludens toxin modulates tight junctions through protein kinase C-dependent actin reorganization, in vitro.
Authors: A Fasano, C Fiorentini, G Donelli, S Uzzau, J B Kaper, K Margaretten, X Ding, S Guandalini, L Comstock, S E Goldblum
Journal: Journal of Clinical Investigation (1995)

The intracellular signaling involved in the mechanism of action of zonula occludens toxin (ZOT) was studied using several in vitro and ex vivo models. ZOT showed a selective effect among various cell lines tested, suggesting that it may interact with a specific receptor, whose surface expression on various cells differs. When tested in IEC6 cell monolayers, ZOT-containing supernatants induced a redistribution of the F-actin cytoskeleton. Similar results were obtained with rabbit ileal mucosa, where the reorganization of F-actin paralleled the increase in tissue permeability. In endothelial cells, the cytoskeletal rearrangement involved a decrease of the soluble G-actin pool (-27%) and a reciprocal increase in the filamentous F-actin pool (+22%). This actin polymerization was time- and dose-dependent, and was reversible. Pretreatment with a specific protein kinase C inhibitor, CGP41251, completely abolished the ZOT effects on both tissue permeability and actin polymerization. In IEC6 cells ZOT induced a peak increment of the PKC-alpha isoform after 3 min incubation. Taken together, these results suggest that ZOT activates a complex intracellular cascade of events that regulate tight junction permeability, probably mimicking the effect of physiologic modulator(s) of epithelial barrier function.