tbuckley/cabot-search huggingface dataset:
Dual Signaling of the Fas Receptor: Initiation of Both Apoptotic and Necrotic Cell Death Pathways
Authors: Dominique Vercammen, Greet Brouckaert, Geertrui Denecker, Marc Van de Craen, Wim Declercq, Walter Fiers, Peter Vandenabeele
Journal: The Journal of Experimental Medicine (1998)

Murine L929 fibrosarcoma cells were transfected with the human Fas (APO-1/CD95) receptor, and the role of various caspases in Fas-mediated cell death was assessed. Proteolytic activation of procaspase-3 and -7 was shown by Western analysis. Acetyl-Tyr-Val-Ala-Asp-chloromethylketone and benzyloxycarbonyl-Asp(OMe)-Glu(OMe)-Val-Asp(OMe)-fluoromethylketone, tetrapeptide inhibitors of caspase-1– and caspase-3–like proteases, respectively, failed to block Fas-induced apoptosis. Unexpectedly, the broad-spectrum caspase inhibitors benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone and benzyloxycarbonyl-Asp(OMe)-fluoromethylketone rendered the cells even more sensitive to Fas-mediated cell death, as measured after 18 h incubation. However, when the process was followed microscopically, it became clear that anti-Fas–induced apoptosis of Fas-transfected L929 cells was blocked during the first 3 h, and subsequently the cells died by necrosis. As in tumor necrosis factor (TNF)-induced necrosis, Fas treatment led to accumulation of reactive oxygen radicals, and Fas-mediated necrosis was inhibited by the oxygen radical scavenger butylated hydroxyanisole. However, in contrast to TNF, anti-Fas did not activate the nuclear factor κB under these necrotic conditions. These results demonstrate the existence of two different pathways originating from the Fas receptor, one rapidly leading to apoptosis, and, if this apoptotic pathway is blocked by caspase inhibitors, a second directing the cells to necrosis and involving oxygen radical production.
Indirect evidence for cholinergic inhibition of intestinal bicarbonate absorption in humans
Authors: A Mellander, H Sjövall
Journal: Gut (1999)

BACKGROUND The aim of the study was to test the hypothesis that in the fasting state, proximal intestinal HCO 3 − absorption, which depends on villus Na + /H + exchanger activity, is tonically inhibited by a cholinergic atropine sensitive mechanism. SUBJECTS The experiments were performed in 34 healthy volunteers and in eight patients with intestinal villus atrophy. METHODS HCO 3 − absorption was measured with a modified triple lumen perfusion technique in the distal duodenum, the most proximal portion of the small intestine. The study was designed to compensate for the inhibitory effects of atropine on intestinal motor activity. RESULTS Atropine had three effects on HCO 3 − transport: it reduced HCO 3 − concentration at the proximal aspiration site, it displaced the relation between HCO 3 − concentration and HCO 3 − absorption to the left, and it induced a significant acidification of the perfusate at the distal aspiration site. The magnitude of the stimulatory effect on HCO 3 − absorption was similar to the difference between patients with intestinal villus atrophy and healthy controls. CONCLUSION The data suggest that, in the fasting state, duodenal HCO 3 − absorption, which depends on villus Na + /H + exchanger activity, may be tonically inhibited by an atropine sensitive cholinergic mechanism.
Meta-analysis of diagnostic procedures for Pneumocystis carinii pneumonia in HIV-1-infected patients
Authors: M. Cruciani, P. Marcati, M. Malena, O. Bosco, G. Serpelloni, C. Mengoli
Journal: European Respiratory Journal (2002)

Sputum induction is a simple and noninvasive procedure for Pneumocystis carinii pneumonia (PCP) diagnosis in human immunodeficiency virus-1-positive patients, although less sensitive than bronchoalveolar lavage (BAL). In order to obtain an overview of the diagnostic accuracy of sputum induction, a systematic review and meta-analysis of studies reporting the comparative sensitivity and specificity of BAL (the “gold standard”) and sputum induction was performed. The odds ratio and related 95% confidence interval were calculated using summary receiving operating characteristic curves as well as fixed-effect and random-effect models. Based on pooled data, the negative and positive predictive values were calculated for a range of PCP prevalence using a Bayesian approach. Seven prospective studies assessed the comparative accuracy of BAL and sputum induction. On the whole, sputum induction demonstrated 55.5% sensitivity and 98.6% specificity. The sensitivity of sputum induction was significantly higher with immunofluorescence than with cytochemical staining (67.1 versus 43.1%). In settings of 25–60% prevalence of PCP, the positive and negative predictive values ranged 86–96.7 and 66.2–89.8, respectively, with immunofluorescence, and 79–94.4 and 53–83.5% with cytochemical staining. In conclusion, in a setting of low prevalence of Pneumocystis carinii pneumonia, sputum induction, particularly with immunostaining, appears to be adequate for clinical decision-making.
Endotyping idiopathic pulmonary fibrosis should improve outcomes for all patients with progressive fibrotic lung disease
Authors: Gisli Jenkins
Journal: Thorax (2014)

The first few years of the current millennium has seen a paradigm shift in the way people view idiopathic pulmonary fibrosis (IPF). In 2004, Raghu et al 1published the first multicentre, double blind, randomised, placebo-controlled trial in IPF. Although a negative study, it taught the field much about the natural history and conduct of clinical trials in IPF. Ultimately, this study paved the way for the Clinical Studies Assessing Pirfenidone in idiopathic pulmonary fibrosis: Research of Efficacy and Safety Outcomes (CAPACITY) studies2 that lead to the approval of Pirfenidone in Europe and eventually the Assessment of Pirfenidone to Confirm Efficacy and Safety in Idiopathic Pulmonary Fibrosis (ASCEND)3 and Prospective Observation of Fibrosis in the Lung: Clinical Endpoints (IMPULSIS)4 studies, which might lead to approval for the use of two disease-modifying drugs for the treatment of IPF in both the USA and Europe. Any thought at the turn of the century that progressive fibrotic lung disease, in the absence of inflammation, might be modifiable would have been regarded with a fair degree of scepticism. The field has come far.

However, the journey has only just begun. Extrapolating data from recent epidemiological studies would suggest there has been approximately a doubling of the incidence of IPF and associated healthcare requirements since the turn of the century.5 ,6 Furthermore, patients enrolled into clinical trials represent a unique subpopulation of patients with IPF, itself a subpopulation of patients …
Role of mesenchymal cell death in lung remodeling after injury.
Authors: V A Polunovsky, B Chen, C Henke, D Snover, C Wendt, D H Ingbar, P B Bitterman
Journal: Journal of Clinical Investigation (1993)

Repair after acute lung injury requires elimination of granulation tissue from the alveolar airspace. We hypothesized that during lung repair, signals capable of inducing the death of the two principal cellular elements of granulation tissue, fibroblasts and endothelial cells, would be present at the air-lung interface. Bronchoalveolar lavage fluid obtained from patients during lung repair induced both fibroblast and endothelial cell death, while fluid obtained at the time of injury or from patient controls did not. The mode of cell death for endothelial cells was apoptosis. Fibroblast death, while morphologically distinct from necrosis, also differed from typical apoptosis. Only proliferating cells were susceptible to the bioactivities in lavage fluid, which were trypsin sensitive and lipid insoluble. Histological examination of lung tissue from patients after lung injury revealed evidence of apoptotic cells within airspace granulation tissue. Our results suggest that cell death induced by peptide(s) present at the air-lung interface may participate in the remodeling process that accompanies tissue repair after injury.
Neutrophils and their Fc receptors are essential in a mouse model of transfusion-related acute lung injury
Authors: M. R. Looney
Journal: Journal of Clinical Investigation (2006)

Transfusion-related acute lung injury (TRALI) is the most common cause of transfusion-related mortality. To explore the pathogenesis of TRALI, we developed an in vivo mouse model based on the passive transfusion of an MHC class I (MHC I) mAb (H2Kd) to mice with the cognate antigen. Transfusion of the MHC I mAb to BALB/c mice produced acute lung injury with increased excess lung water, increased lung vascular and lung epithelial permeability to protein, and decreased alveolar fluid clearance. There was 50% mortality at a 2-hour time point after Ab administration. Pulmonary histology and immunohistochemistry revealed prominent neutrophil sequestration in the lung microvasculature that occurred concomitantly with acute peripheral blood neutropenia, all within 2 hours of administration of the mAb. Depletion of neutrophils by injection of anti-granulocyte mAb Gr-1 protected mice from lung injury following MHC I mAb challenge. FcRgamma-/- mice were resistant to MHC I mAb-induced lung injury, while adoptive transfer of wild-type neutrophils into the FcRgamma-/- animals restored lung injury following MHC I mAb challenge. In conclusion, in a clinically relevant in vivo mouse model of TRALI using an MHC I mAb, the mechanism of lung injury was dependent on neutrophils and their Fc gamma receptors.
Influence of exercise training on cardiac baroreflex sensitivity in patients with COPD
Authors: F. Costes, F. Roche, V. Pichot, J.M. Vergnon, M. Garet, J-C. Barthelemy
Journal: European Respiratory Journal (2004)

Decreased spontaneous cardiac baroreflex sensitivity (BRS), which could lead to the onset of cardiovascular events, has been demonstrated in chronic obstructive pulmonary disease patients. This study evaluates the effects of an exercise training programme on BRS. Twenty-one chronic obstructive pulmonary disease patients (mean±sd age 62±9 yrs; forced expiratory volume in one second 43.6±18.1% of the predicted value) with mild hypoxaemia (arterial oxygen tension 8.96±1.18 kPa) were compared to 18 healthy age-matched subjects. BRS was calculated as the slope of the baroreflex sequences between spontaneous changes in systolic blood pressure and subsequent consecutive relative risk deviation length, and was measured in the supine position and following head-up tilt for sympathetic stimulation. Pulmonary function test results and blood gas levels, measured only in patients, did not change after the training programme. Exercise training increased the maximal sustained workload (16.5%) and peak oxygen consumption (20.5%). Before training, BRS was lower in patients than in controls (2.7±1.5 versus 7.8±4.9 ms·mmHg −1 ) and tilting induced a smaller reduction in BRS (13 versus 34%). After training, BRS increased to 3.4±2.6 ms·mmHg −1 in patients but remained lower than in controls. The response to the tilt test remained unchanged after training. It is concluded that, in chronic obstructive pulmonary disease patients, exercise training is associated with a gain in spontaneous baroreflex sensitivity, reflecting cardiovascular benefits.
Incidence and causes of tenosynovitis of the wrist extensors in long distance paddle canoeists.
Authors: P du Toit, G Sole, P Bowerbank, T D Noakes
Journal: British Journal of Sports Medicine (1999)

OBJECTIVES: To investigate the incidence and causes of acute tenosynovitis of the forearm of long distance canoeists. METHOD: A systematic sample of canoeists competing in four canoe marathons were interviewed. The interview included questions about the presence and severity of pain in the forearm and average training distances. Features of the paddles and canoes were determined. RESULTS: An average of 23% of the competitors in each race developed this condition. The incidence was significantly higher in the dominant than the nondominant hand but was unrelated to the type of canoe and the angle of the paddle blades. Canoeists who covered more than 100 km a week for eight weeks preceding the race had a significantly lower incidence of tenosynovitis than those who trained less. Environmental conditions during racing, including fast flowing water, high winds, and choppy waters, and the paddling techniques, especially hyperextension of the wrist during the pushing phase of the stroke, were both related to the incidence of tenosynovitis. CONCLUSION: Tenosynovitis is a common injury in long distance canoeists. The study suggests that development of tenosynovitis is not related to the equipment used, but is probably caused by difficult paddling conditions, in particular uneven surface conditions, which may cause an altered paddling style. However, a number of factors can affect canoeing style. Level of fitness and the ability to balance even a less stable canoe, thereby maintaining optimum paddling style without repeated eccentric loading of the forearm tendons to limit hyperextension of the wrist, would seem to be important.
Domiciliary nebulised salbutamol solution in severe chronic airway obstruction.
Authors: R S Wilson, S J Connellan
Journal: Thorax (1980)

Nine patients with severe chronic airway obstruction secondary to chronic bronchitis and emphysema all preferred nebulised salbutamol solution to placebo in a double-blind controlled trial. Four of the patients who had previously received domiciliary nebulised salbutamol failed to complete the placebo period, though all completed the active period. Five others improved subjectively on active therapy, and showed a significant improvement in morning and evening peak flows. Symptom scores for breathlessness, wheezing, and sputum production were lower in the active treatment period and standard aerosol usage fell, although these changes might have been due to chance. Patients with severe chronic airway obstruction who do not respond to conventional bronchodilator therapy should be considered for this form of treatment.
Dr antigen positive monocyte‐macrophages control granulocyte‐macrophage colony‐stimulating activity and burst promoting activity elaboration in man
Authors: D. S. Verma, G. Spitzer, M. Beran
Journal: American Journal of Hematology (1982)

Abstract To investigate the mechanisms that modulate granulocyte‐macrophage colony‐stimulating activity (GM‐CSA) and burst promoting activity (BPA) elaboration, we studied human peripheral blood‐derived monocyte‐macrophage (MØ) and T‐lymphocyte (TL) interaction. Coincubation of live MØ with autologous TL at a 1:3 ratio in the presence of 1% phytohemagglutinin synergistically increased GM‐CSA (6 of 6 experiments) and BPA (4 of 6 experiments) (P &lt;0.002). Prior treatment of MØ with cycloheximide or actinomycin D significantly (P &lt; 0.002) diminished this MØ's capacity to collaborate with TL. Mitomycin C treatment did not. Live MØ also enhanced TL‐derived GM‐CSA (P &lt;0.002) and BPA (P &lt;0.001). This enhancement was again compromised by prior cycloheximide or actinomycin D treatment, but not by mitomycin C treatment. Further experiments in which we blocked DR antigen on MØ membrane with monoclonal anti‐DR antibodies suggested that MØ required their membrane DR antigen to collaborate with TL in elaborating GM‐CSA and BPA.
Frequent Silencing of <b> <i>Low Density Lipoprotein Receptor-Related Protein 1B (LRP1B</i> </b>) Expression by Genetic and Epigenetic Mechanisms in Esophageal Squamous Cell Carcinoma
Authors: Itaru Sonoda, Issei Imoto, Jun Inoue, Tatsuhiro Shibata, Yutaka Shimada, Koei Chin, Masayuki Imamura, Teruo Amagasa, Joe W. Gray, Setsuo Hirohashi, Johji Inazawa
Journal: Cancer Research (2004)

Abstract Low-density lipoprotein receptor-related protein 1B (LRP1B) is frequently deleted in tumors of various types, but its status and expression in esophageal squamous cell carcinomas (ESCs) have never been reported. In the course of a program to screen ESC cell lines for copy-number aberrations using array-based comparative genomic hybridization, we identified a homozygous deletion of LRP1B. Genomic PCR experiments revealed homozygous deletions of LRP1B in additional ESC cell lines (total, 6 of 43; 14.0%) and in primary esophageal tumors (30 of 70; 42.9%). Moreover, expression of LRP1B mRNA was frequently silenced in ESC lines without homozygous deletions (14 of 37; 37.8%). Using bisulfite-PCR analysis and sequencing, we found that LRP1B-nonexpressing cells without homozygous deletions were highly methylated at a CpG island of LRP1B, a sequence possessing promoter activity. Treatment with 5-aza-2′-deoxycytidine restored expression of LRP1B in those ESC lines. Histone acetylation status correlated directly with expression of LRP1B and inversely with the methylation status of the CpG island. Methylation of LRP1B was also detected in primary esophageal tumors. Restoration of LRP1B expression in ESC cells reduced colony formation. These results suggest that loss of LRP1B function in esophageal carcinogenesis most often occurs either by homozygous deletion or by transcriptional silencing through hypermethylation of its CpG island.
No Delay in Glucose Change at Antecubital Skin in Hypoglycemia of Normal Subjects
Authors: Kyohei Nonaka, Fukimi Ono, Miyuki Ishibashi, Nobumitsu Okita
Journal: Diabetes Care (2003)

In the July 2001 issue of Diabetes Care , Jungheim and Koschinsky (1) reported that capillary blood glucose values at forearm lagged behind those at fingertip by maximum 30 min in their particular type 1 diabetic patient rendered to hypoglycemia. They warned that this might result in delay of hypoglycemia detection in diabetic patients and endangered their lives. They hypothesized that this was a physiological phenomenon rather than a pathological delay.

We investigated if their observation was physiological. We had 10 nondiabetic healthy volunteers (8 males and 2 females aged 35.0 ± 11.2 years with a BMI of 22.2 ± 3.0 kg/m2) who were hypoglycemic with intravenous bolus injection of human insulin 0.1 unit/kg body wt. Blood glucose levels were monitored …
A 16-week comparison of the novel insulin analog insulin glargine (HOE 901) and NPH human insulin used with insulin lispro in patients with type 1 diabetes.
Authors: P Raskin, L Klaff, R Bergenstal, J P Hallé, D Donley, T Mecca
Journal: Diabetes Care (2000)

OBJECTIVE: To determine the safety and efficacy of the long-acting insulin analog, insulin glargine, as a component of basal bolus therapy in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: Patients with type 1 diabetes receiving basal-bolus insulin treatment with NPH human insulin and insulin lispro were randomized to receive insulin glargine (HOE 901), a long-acting basal insulin analog, once a day (n = 310) or NPH human insulin (n = 309) as basal treatment with continued bolus insulin lispro for 16 weeks in an open-label study NPH insulin patients maintained their prior schedule of administration once or twice a day, whereas insulin glargine patients received basal insulin once a day at bedtime. RESULTS: Compared with all NPH insulin patients, insulin glargine patients had significant decreases in fasting blood glucose measured at home (means +/- SEM, -42.0 +/- 4.7 vs. -12.4 +/- 4.7 mg/dl [-2.33 +/- 0.26 vs. -0.69 +/- 0.26 mmol/l]; P = 0.0001). These differences were evident early and persisted throughout the study More patients in the insulin glargine group (29.6%) than in the NPH group (16.8%) reached a target fasting blood glucose of 119 mg/dl (&amp;lt; 6.6 mmol/l). However, there were no differences between the groups with respect to change in GHb. Insulin glargine treatment was also associated with a significant decrease in the variability of fasting blood glucose values (P = 0.0124). No differences in the occurrence of symptomatic hypoglycemia, including nocturnal hypoglycemia, were observed. Overall, adverse events were similar in the two treatment groups with the exception of injection site pain, which was more common in the insulin glargine group (6.1%) than in the NPH group (0.3%). Weight gain was 0.12 kg in insulin glargine patients and 0.54 kg in NPH insulin patients (P = 0.034). CONCLUSIONS: Basal insulin therapy with insulin glargine once a day appears to be as safe and at least as effective as using NPH insulin once or twice a day in maintaining glycemic control in patients with type 1 diabetes receiving basal-bolus insulin treatment with insulin lispro.
Early change in thermal perception is not a driver of anticipatory exercise pacing in the heat
Authors: Martin James Barwood, Jo Corbett, Danny White, Jason James
Journal: British Journal of Sports Medicine (2011)

Initial power output declines significantly during exercise in hot conditions on attaining a rapid increase in skin temperature when exercise commences. It is unclear whether this initial reduced power is mediated consciously, through thermal perceptual cues, or is a subconscious process. The authors tested the hypothesis that improved thermal perception (feeling cooler and more comfortable) in the absence of a change in thermal state (ie, similar deep-body and skin temperatures between spray conditions) would alter pacing and 40 km cycling time trial (TT) performance.Eleven trained participants (mean (SD): age 30 (8.1) years; height 1.78 (0.06) m; mass 76.0 (8.3) kg) completed three 40 km cycling TTs in standardised conditions (32°C, 50% RH) with thermal perception altered prior to exercise by application of cold-receptor-activating menthol spray (MENTHOL SPRAY), in contrast to a separate control spray (CONTROL SPRAY) and no spray control (CON). Thermal perception, perceived exertion, thermal responses and cycling TT performance were measured.MENTHOL SPRAY induced feelings of coolness and improved thermal comfort before and during exercise. Skin temperature profile at the start of exercise was similar between sprays (CON-SPRAY 33.3 (1.1)°C and MENTHOL SPRAY 33.4 (0.4)°C, but different to CON 34.5 (0.5)°C), but there was no difference in the pacing strategy adopted. There was no performance benefit using MENTHOL SPRAY; cycling TT completion time for CON is 71.58 (6.21) min, for CON-SPRAY is 70.94 (6.06) min and for MENTHOL SPRAY is 71.04 (5.47) min.The hypothesis is rejected. Thermal perception is not a primary driver of early pacing during 40 km cycling TT in hot conditions in trained participants.
Gene expression predicts overall survival in paraffin-embedded tissues of diffuse large B-cell lymphoma treated with R-CHOP
Authors: Lisa M. Rimsza, Michael L. LeBlanc, Joseph M. Unger, Thomas P. Miller, Thomas M. Grogan, Daniel O. Persky, Ralph R. Martel, Constantine M. Sabalos, Bruce Seligmann, Rita M. Braziel, Elias Campo, Andreas Rosenwald, Joseph M. Connors, Laurie H. Sehn, Nathalie Johnson, Randy D. Gascoyne
Journal: Blood (2008)
BTS guidelines for the investigation of a unilateral pleural effusion in adults
Authors: N A Maskell
Journal: Thorax (2003)

These guidelines have been replaced by BTS Pleural Disease Guideline 2010  Superseded By BTS Pleural Disease Guideline 2010: BTS Guidelines for the Management of Pleural Disease. Thorax 2003 May; 58(Suppl 2): 1–59.
Phase II Study of Clofarabine in Pediatric Patients With Refractory or Relapsed Acute Lymphoblastic Leukemia
Authors: Sima Jeha, Paul S. Gaynon, Bassem I. Razzouk, Janet Franklin, Richard Kadota, Violet Shen, Lori Luchtman-Jones, Michael Rytting, Lisa R. Bomgaars, Susan Rheingold, Kim Ritchey, Edythe Albano, Robert J. Arceci, Stewart Goldman, Timothy Griffin, Arnold Altman, Bruce Gordon, Laurel Steinherz, Steven Weitman, Peter Steinherz
Journal: Journal of Clinical Oncology (2006)

To determine the efficacy and safety of clofarabine in pediatric patients with refractory or relapsed acute myeloid leukemia (AML).