tbuckley/cabot-search huggingface dataset:
Asthma from childhood at age 21: the patient and his disease.
Authors: A J Martin, L I Landau, P D Phelan
Journal: BMJ (1982)

Information was obtained from 336 21-year-olds who had begun wheezing before the age of 7 about their knowledge of asthma and its effect on their current life style. Two-thirds of the subjects were still symptomatic. A control group of 62 subjects was available for comparison. Knowledge about asthma was poor, particularly among those with less troublesome symptoms. Half of those with frequent episodic asthma and one-third with persistent asthma did not regard excess use of bronchodilator aerosols as potentially dangerous. Over three-quarters of those with persistent asthma were not receiving adequate treatment. One-third of third of those with persistent asthma were missing substantial time from work because of respiratory illness, and a similar proportion were restricting sporting activities. The incidence of smoking was disturbingly high in all asthma groups. The higher the number of cigarettes ever smoked and the higher the current tobacco consumption the less satisfactory was the progress of asthma. Both cigarette smoking and severity of asthma contributed to chronic production of sputum. Children and teenagers with asthma should be educated to seek more appropriate medical help and thereby reduce morbidity.
1033 SERPIN-B3 INDUCES HIF2a NUCLEAR TRANSLOCATION IN HEPATIC CANCER CELLS: A PARACRINE LOOP ABLE TO AFFECT CANCER CELL BEHAVIOUR
Authors: S. Cannito, C. Turato, C. Paternostro, S. Quarta, E. Novo, G. Villano, S. Colombatto, E. David, P. Pontisso, M. Parola
Journal: Journal of Hepatology (2013)
Telomere biology in cardiovascular disease: the TERC-/- mouse as a model for heart failure and ageing
Authors: L. S.M. Wong, H. Oeseburg, R. A. de Boer, W. H. van Gilst, D. J. van Veldhuisen, P. van der Harst
Journal: Cardiovascular Research (2008)

Atherosclerosis and heart failure are major causes of morbidity and mortality in Western countries. Recent studies are suggesting involvement of telomere biology in the development and progression of age-associated conditions, including hypertension, atherosclerosis, and heart failure. Whether any of these reported associations are based on causal relationships remains to be elucidated. The construction of telomerase-deficient (telomerase RNA component, TERC−/−) mice might provide a potential instrumental model to study the involvement of telomere biology in cardiovascular disease. Here, we review the current available information from all studies performed in TERC−/− mice providing information on the cardiovascular phenotypic characteristics. Although this mouse model has proven its value in the understanding of the role of telomere biology in cancer, stem cell, and basic telomere research, only few studies were specifically designed to answer cardiovascular-related questions. The TERC−/− mice provide exciting opportunities to expand our knowledge of telomere biology in cardiovascular disease and the potential identification of novel targets of treatment.
Blunted sensation of dyspnoea and near fatal asthma
Authors: D.J. Eckert, P.G. Catcheside, R.D. McEvoy
Journal: European Respiratory Journal (2004)

Asthmatic patients who experience an acute, severe attack requiring hospitalisation, intensive care admission or who die as a result of the attack make up a relatively small percentage of the total asthma population 1. However, they contribute disproportionately to the human and economic cost of this disease. It has long been held that it should be possible to identify such individuals ahead of time in order to focus therapeutic efforts in their direction to reduce morbidity and mortality. Despite substantial research effort, this goal remains elusive. The impediments to progress in this area are considerable. First, there are no universally agreed diagnostic criteria for near fatal asthma (NFA) 1. Perhaps not surprisingly therefore there have been no large scale prospective multicentre studies in unselected clinical populations to define the incidence of NFA and its relationship tofatal asthma 1. Secondly, it appears from case control studies that multiple risk factors are likely involved. These include psychological and socioeconomic factors, poor asthma control, suppressed respiratory sensation and blunted chemoreceptor sensitivity 1–6. Prior near-miss episodes are also predictive of subsequent NFA episodes and fatalities 7. Thus far no reliable predictive equation or screening tool has been developed to identify patients at risk of NFA. Initial findings reported in this issue by Barreiro et al. 8 offer some promise that assessment of dyspnoea at maximal exercise capacity could prove useful in this respect.

Accurate recognition of asthma symptoms is essential for prompting individuals with acute severe asthma to increase medication or seek medical assistance. Any factor that inhibits this process has the potential to increase asthma morbidity and mortality 3, 4. Perception of dyspnoea and the underlying mechanisms for its genesis are complex and incompletely understood 9, 10. Multiple sensory pathways and brain …
Human intestinal epithelial cell-induced CD8+ T cell activation is mediated through CD8 and the activation of CD8-associated p56lck.
Authors: Y Li, X Y Yio, L Mayer
Journal: The Journal of Experimental Medicine (1995)

The activation of CD8+ suppressor T cells by normal intestinal epithelial cells in antigen-specific or allogeneic mixed cell culture systems has significant implications for the regulation of mucosal immune responses. In this study, we found that the capacity of epithelial cells to induce CD8+ suppressor T cell activation appeared to be linked to the binding of CD8 molecules on the T cell surface. This appears to be mediated by a non-class I molecule expressed on the epithelial cell surface, which binds to CD8 and results in the activation of the CD8-associated src-like tyrosine kinase, p56lck. Epithelial cell-stimulated p56lck activation is an early event (in contrast to monocytes) and is essential for T cell activation, since proliferation could be completely abrogated by pretreatment of T cells with genestein or herbamycin, both of which are protein tyrosine kinase inhibitors. Pretreatment of T cells with anti-CD8 or of intestinal epithelial cells with an anti-epithelial cell mAb B9 inhibited p56lck activation and further confirmed that CD8 on the T cell and a CD8 ligand on the epithelial cell were involved in this T cell activation event. The specificity of this reaction was confirmed in experiments in which murine transfectants 3G4 and 3G8, expressing CD4 or CD8, respectively, were used. Coculture of 3G8 with epithelial cells but not with monocytes activated p56lck in this cell line, whereas p56lck was preferentially activated in 3G4 cells when monocytes were used as the stimulator cells. Although stimulation through CD8- and CD8-associated p56lck was important for epithelial cell-induced T cell activation, T cell proliferation could not be induced by cross-linking CD8 alone with monoclonal antibody anti-CD8. These data suggest that a second signal, possibly through the T cell antigen receptor since activation of the T cell receptor-associated kinase fyn was also seen, is required for epithelial cell-driven T cell proliferation.
Expression of p21 Protein Predicts Clinical Outcome in DLBCL Patients Older than 60 Years Treated with R-CHOP but not CHOP: A Prospective ECOG and Southwest Oncology Group Correlative Study on E4494
Authors: Jane N. Winter, Shuli Li, Vikas Aurora, Daina Variakojis, Beverly Nelson, Maryla Krajewska, Lijun Zhang, Thomas M. Habermann, Richard I. Fisher, William R. Macon, Mukesh Chhanabhai, Raymond E. Felgar, Eric D. Hsi, L. Jeffrey Medeiros, James K. Weick, Edie A. Weller, Ari Melnick, John C. Reed, Sandra J. Horning, Randy D. Gascoyne
Journal: Clinical Cancer Research (2010)

To prospectively investigate the prognostic significance of p21 and p53 expression in diffuse large B-cell lymphoma in the context of the U.S. Intergroup trial comparing conventional cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy to rituximab-CHOP (R-CHOP) induction, with or without maintenance rituximab.Immunohistochemical staining of 197 paraffin-embedded biopsy specimens was scored by an independent panel of experts.The cyclin-dependent kinase inhibitor, p21, was expressed in 55% of cases examined. In a multivariable analysis adjusting for International Prognostic Index score and BCL2 status, p21 expression was a significant, independent, favorable predictive factor for failure-free survival (relative risk, 0.3; P = 0.001) and overall survival (relative risk, 0.3; P = 0.003) for patients treated with R-CHOP. Expression of p21 was not predictive of outcome for CHOP-treated patients. Only p21-positive cases benefited from the addition of rituximab to CHOP. Among p21-positive patients, treatment with R-CHOP was associated with a higher failure-free survival rate at 5 years compared with CHOP (61% versus 24%; P = 0.01). In contrast, no significant differences were detected in failure-free survival according to treatment arm for p21-negative patients. Expression of p53, alone or in combination with p21, did not predict for outcome in univariable or multivariable analyses.In this study, p21 protein expression emerged as an important independent predictor of a favorable clinical outcome when rituximab was added to CHOP therapy. These data suggest that rituximab-related effects on lymphoma survival pathways may be functionally linked to p21 activity.
Mechanisms of the pro- and anti-oxidant actions of nitric oxide in atherosclerosis
Authors: R Patel
Journal: Cardiovascular Research (2000)

The association of nitric oxide (NO) with cardiovascular disease has long been recognized and the extensive research on this topic has revealed both pro- and anti-atherosclerotic effects. While these contradictory findings were initially perplexing recent studies offer molecular mechanisms for the integration of these data in the context of our current understanding of the biochemistry of NO. The essential findings are that the biochemical properties of NO allow its exploitation as both a cell signaling molecule, through its interaction with redox centers in heme proteins, and an extremely rapid reaction with other biologically relevant free radicals. The direct reaction of NO with free radicals can have either pro- or antioxidant effects. In the cell, antioxidant properties of NO can be greatly amplified by the activation of signal transduction pathways that lead to the increased synthesis of endogenous antioxidants or down regulate responses to pro-inflammatory stimuli. These findings will be discussed in the context of atherosclerosis.
Darbepoetin Alfa and History of Thromboembolic Events
Authors: Gianluigi Ferretti, Alessandra Felici, Francesco Cognetti
Journal: Journal of Clinical Oncology (2009)

In their pooled analysis of individual patientlevel data from all randomized double-blind placebo-controlled trials in patients with chemotherapy-induced anemia receiving darbopoetin alfa or placebo, Ludwig et al 1 do not report whether the proportion of patients with a history of thromboembolic events was well balanced between the two study arms.In another analysis comparing epoetin or darbopoetin plus RBC transfusions as necessary, 2 patients with cancer and previous thromboembolic events being treated with erythropoiesis-stimulating agents (ESAs) seemed to be protected against an increase in mortality associated with ESAs, even though the cumulative results of this meta-analysis showed that treatment with ESAs in patients with cancer increased mortality during active study periods and worsened overall survival.Prophylactic anticoagulation during cancer treatment in these patients might have protected them against the thrombogenic effects of ESAs. 2 It has been reported that critically ill patients receiving heparin did not have an increased risk of developing thromboembolic complications when treated with ESAs. 3 In addition, Ludwig et al 1 do not specify whether ESAs were eventually given to patients undergoing chemotherapy concomitantly with radiotherapy: whether ESAs are safer in patients given chemotherapy than in those undergoing chemoradiotherapy is still controversial.
Authorities in India ban use of stem cells in patients except in clinical trials
Authors: S. Bagcchi
Journal: BMJ (2014)

The Indian Council of Medical Research and the Department of Biotechnology, both based in New Delhi, have issued new guidelines for stem cell research in India. The guidelines stated that stem cells in India can be used as “therapy” only in the context of a clinical trial.1

The council and the department had jointly released guidelines for stem cell research and therapy in 2007, but they have now issued a revised form of the guidelines to highlight new findings that have significantly changed the scope of research related to stem cells and their possible translation.

“There is no conclusive proof of safety or therapeutic efficacy of stem cells in any condition yet,” said the revised …
Profound Apoptosis-Mediated Regional Myocyte Loss and Compensatory Hypertrophy in Pigs With Hibernating Myocardium
Authors: Hajin Lim, James A. Fallavollita, Robert Hard, Christopher W. Kerr, John M. Canty
Journal: Circulation (1999)

Background —Myocyte apoptosis is seen in ischemic heart disease, but whether it can occur after reversible ischemia or independent of necrosis and replacement fibrosis is unknown. Methods and Results —Pigs were instrumented with a stenosis of the left anterior descending coronary artery to chronically reduce coronary flow reserve over a period of 3 months. At this time, there was viable dysfunctional myocardium having the physiological features of hibernating myocardium. Resting subendocardial perfusion was reduced to 0.65±0.08 (mean±SEM) mL · min −1 · g −1 in hibernating myocardium of instrumented pigs compared with 0.98±0.14 mL · min −1 · g −1 in myocardium of sham-operated pigs ( P &lt;0.05). There was a critical limitation in subendocardial flow during vasodilation to 0.78±0.20 mL · min −1 · g −1 in instrumented pigs versus 3.24±0.50 mL · min −1 · g −1 in sham-operated pigs ( P &lt;0.001). Histology revealed a regional reduction in myocyte nuclear density to 995±100 nuclei/mm 2 in hibernating myocardium from the instrumented group versus 1534±65 nuclei/mm 2 in myocardium from the sham-operated group ( P &lt;0.05), regional myocyte hypertrophy (myocyte volume per nucleus, 14 183±2594 in the instrumented group versus 9130±1301 μm 3 in the sham group; P &lt;0.05), and minimal increases in connective tissue (5.8±0.9% in the instrumented group versus 3.0±0.2% in the sham group, P &lt;0.05). Necrosis was not identified, but apoptosis was increased from 30±9 myocytes per 10 6 myocyte nuclei in myocardium from the sham group to 220±77 myocytes per 10 6 myocyte nuclei in hibernating myocardium ( P &lt;0.05). Conclusions —These findings indicate that reversible ischemia in an area of chronically reduced coronary flow reserve induces regional myocyte loss via an apoptotic mechanism. This may contribute to the progression of chronic coronary disease to heart failure and explain the lack of complete functional recovery after revascularization in hibernating myocardium.
Chemoprevention of Prostate Cancer by <scp>d</scp>,<scp>l</scp>-Sulforaphane Is Augmented by Pharmacological Inhibition of Autophagy
Authors: Avani R. Vyas, Eun-Ryeong Hahm, Julie A. Arlotti, Simon Watkins, Donna Beer Stolz, Dhimant Desai, Shantu Amin, Shivendra V. Singh
Journal: Cancer Research (2013)

There is a preclinical evidence that the oral administration of d,l-sulforaphane (SFN) can decrease the incidence or burden of early-stage prostate cancer [prostatic intraepithelial neoplasia (PIN)] and well-differentiated cancer (WDC) but not late-stage poorly differentiated cancer (PDC). Because SFN treatment induces cytoprotective autophagy in cultured human prostate cancer cells, the present study tested the hypothesis that chemopreventive efficacy of SFN could be augmented by the pharmacologic inhibition of autophagy using chloroquine (CQ). Incidence of PDC characterized by prostate weight of more than 1 g was significantly lower in the SFN + CQ group than in control (P = 0.004), CQ group (P = 0.026), or SFN group (P = 0.002 by Fisher exact test). Average size of the metastatic lymph node was lower by about 42% in the SFN + CQ group than in control (P = 0.043 by Wilcoxon test). On the other hand, the SFN + CQ combination was not superior to SFN alone with respect to inhibition of incidence or burden of microscopic PIN or WDC. SFN treatment caused in vivo autophagy as evidenced by transmission electron microscopy. Mechanistic studies showed that prevention of prostate cancer and metastasis by the SFN + CQ combination was associated with decreased cell proliferation, increased apoptosis, alterations in protein levels of autophagy regulators Atg5 and phospho-mTOR, and suppression of biochemical features of epithelial-mesenchymal transition. Plasma proteomics identified protein expression signature that may serve as biomarker of SFN + CQ exposure/response. This study offers a novel combination regimen for future clinical investigations for prevention of prostate cancer in humans.
Bronchiolitis in Kartagener's syndrome
Authors: S Homma, M Kawabata, K Kishi, E Tsuboi, K Narui, T Nakatani, S Saiki, K Nakata
Journal: European Respiratory Journal (1999)

The association of diffuse bronchiolitis in patients with Kartagener's syndrome (KS) has not been reported previously. The aim of this study was to present the morphological characteristics of bronchiolitis in patients with KS. Eight patients (four males, four females; mean age 37.9+/-18.7 yrs), clinically diagnosed as KS with the classical triad of chronic pansinusitis, bronchiectasis and situs in versus with dextrocardia, were evaluated. Routine chest radiography showed bronchiectasis and dextrocardia in all patients. Chest computed tomography (CT) showed diffuse centrilobular small nodules up to 2 mm in diameter throughout both lungs in six out of eight patients. Pulmonary function tests revealed marked obstructive impairment in all patients (forced expiratory volume in one second 57.0+/-11.3%, residual volume/total lung capacity 45.+/-12.7%, maximum midexpiratory flow 0.92+/-0.72 L x s(-1), forced vital capacity 74.1+/-12.2% (all mean +/- SD)). The examination of cilial movement of the bronchus revealed immotility in all of the five patients examined. The ultrastructure showed ciliary dynein arm defects in all patients. Histopathological examination of lung specimens obtained at autopsy or by video-assisted thoracoscopic surgery showed obliterative thickening of the walls of the membranous bronchioli with infiltration of lymphocytes, plasma cells and neutrophils, but most of the distal respiratory bronchioli were spared and alveolar spaces were overinflated. Pathologically, the diffuse centrilobular small nodules on the chest CT mainly corresponded to membranous bronchiolitis. This is the first report demonstrating that the association of diffuse bronchiolitis might be one of the characteristic features of the lung in Kartagener's syndrome.
Active Length-Tension Relations Compared in Isometric, Afterloaded and Isotonic Contractions of Cat Papillary Muscle
Authors: ROGER R. TAYLOR, Peter Burrows
Journal: Circulation Research (1970)

Isometric, afterloaded and isotonic contractions of cat right ventricular papillary muscle were studied in vitro at 30°C or 37°C. The length to which muscle contracted under a given total load varied directly with initial muscle length. The discrepancies between contracted muscle lengths depended upon load and the inotropic state of the muscle. In control contractions at 12/min, the maximum discrepancy occurred at a load of 0.5 g or 1 g and averaged 0.47 ± 0.04 ( SD ) mm while after acetylstrophanthidin (0.75 µg/ml) the maximum discrepancy occurred between 3- and 5-g load and averaged 0.62 ± 0.07 mm ( P &lt; 0.001). At low loads acetylstrophanthidin decreased the discrepancy at 0.5-g load from 0.41 ± 0.08 mm to 0.22 ± 0.05 mm ( P &lt; 0.001). Acetylstrophanthidin increased developed tension at optimum muscle length by 71 ± 23% ( P &lt; 0.001). Increasing frequency of contraction from 12/min to 60/min induced greater decrease in time to peak tension than occurred with acetylstrophanthidin (30% vs. 15%) but produced little change in either isotonic or isometric contracted length-tension relations. Since the differences between contracted length-tension relations were not influenced by abbreviation of active state induced by frequency changes, it is unlikely that the lesser abbreviation with acetylstrophanthidin was responsible for the changes it produced. Rather, they may be related to the intensity and duration of active state reflecting increased energy release in the contractile process.
A randomised, double blind, placebo controlled study of celecoxib, a selective cyclooxygenase 2 inhibitor, on duodenal polyposis in familial adenomatous polyposis
Authors: R K S Phillips
Journal: Gut (2002)

<b>Background:</b> Non-selective cyclooxygenase (COX) inhibitors (non-steroidal anti-inflammatory drugs) inhibit large bowel carcinogenesis in patients with familial adenomatous polyposis (FAP). Their role in the duodenum of these patients is less certain. The disease modifying activity of specific COX-2 inhibitors has not been explored in humans. <b>Patients and methods:</b> This was a randomised, double blind, placebo controlled study of celecoxib (100 mg twice daily (n=34) or 400 mg twice daily (n=32)) versus placebo (n=17), given orally twice daily for six months to patients with FAP. Efficacy was assessed qualitatively by blinded review of shuffled endoscopy videotapes comparing the extent of duodenal polyposis at entry and at six months and quantitatively by measurement of the percentage change in duodenal area covered by discrete and plaque-like adenomas from photographs of high and low density polyposis. <b>Results:</b> Shuffled and blinded video review showed a statistically significant effect of 400 mg twice daily celecoxib compared with placebo treatment (p=0.033) with all five independent observers scoring a beneficial effect. Overall, patients taking celecoxib 400 mg twice daily showed a 14.5% reduction in involved areas compared with a 1.4% for placebo (p=0.436). However, patients with clinically significant disease at baseline (greater than 5% covered by polyps) showed a 31% reduction in involved areas with celecoxib 400 mg twice daily compared with 8% on placebo (p=0.049). <b>Conclusions:</b> A panel of five endoscopists found a significant reduction in duodenal polyposis after six months of treatment with celecoxib 400 mg twice daily. COX-2 inhibition may help this otherwise untreatable condition.