tbuckley/cabot-search huggingface dataset:
Promotor methylation of Bcl-2 in cigarette smoke extract-induced emphysema
Authors: Huihui Zeng, Ping Chen
Journal: European Respiratory Journal (2012)

Objective:  Abnormal apoptotic events may play an important role in emphysema. We determined whether Bcl-2, a pivotal regulator of apoptosis, participates in emphysema. Furthermore, given the methylation in promoter CpG islands causing gene silencing, and existence of CpG islands in Bcl-2 promoter. We hypothesized that the deregulation of Bcl-2 in emphysema might be caused by methylation.   Methods:  BALB/C mice were divided into four groups (n=10 per group): CSE, CSE+ 5-aza-2´-deoxycytidine(AZA, demethylation reagent), AZA, and control (phosphate buffered saline, PBS). CSE group was intraperitoneally injected with CSE once a week for 3 weeks to build emphysema models. AZA and PBS were also administered weekly as CSE. After 3 weeks of treatment, TUNEL assay was used to assess apoptotic index of pulmonary cells; western blotting or Realtime-RTPCR were used to detect expression of Bcl-2 and Cyt C in pulmonary tissue; bisulfite sequencing PCR (BSP) was used to observe the methylation status of Bcl-2 promoter.   Results: (1) The apoptotic index of pulmonary cells in CSE group[(14.2±0.6)%] was higher than CSE+AZA, AZA, Control groups[(4.9±0.5) %, (3.9±0.8)%, (4.5±0.6)%] (p   Conclusions:  The decreased anti-apoptic Bcl-2 might lead released cytoplasm Cyt C, which account for the increased apoptosis in emphysema. Furthermore, methylation might played a role in emphysema though deregulation of Bcl-2.
Component-resolved allergy diagnostics identify phenotypes in problematic severe childhood asthma
Authors: Björn Nordlund, Jon Konradsen, Inger Kull, Magnus Borres, Annica Önell, Hans Grönlund, Gunilla Hedlin
Journal: European Respiratory Journal (2011)

Aim  To analyse clinical phenotypes of problematic severe childhood asthma in relation to component-resolved allergy diagnostics.   Methods  This cross-sectional study included 56 children with problematic severe asthma, insufficiently controlled despite 800μg daily inhaled corticosteroids (budesonide or equivalents). IgE antibodies against 131 individual allergen components from inhalant and food sources were analysed using immunosolid-phase allergen chips. Airway inflammation (FeNO), lung function (FEV 1 ) and bronchial hyperresponsiveness (methacholine challenge) were assessed in all subjects, and Health-Related-Quality-of-Life (HR-QoL) questionnaires and asthma control tests were completed.   Results  IgE antibodies were detected in 80% (n=45) of children tested. Airway inflammation was greater in these children (FeNO, mean 31 ppb vs 16 ppb, p=0.039) and lung function was reduced (FEV1%, mean 79 vs 92, p=0.05) compared to children without detectable IgE (n=11, 20%). However, HR-QoL and asthma control test scores, and bronchial hyperresponsiveness, did not differ between these groups. Children (36%, n=20) with specific IgE to >3 (median value) mould/indoor components were more sensitized to specific food components (mean 5.9 vs 2.2, p=0.026) compared to 45% (n=25) of children with specific IgE to fewer mould/indoor components. Also, children with IgE to >3 mould/indoor components showed increased bronchial hyperresponsiveness (methacholine, dose-response slope, 101% vs 31%, p=0.027) and lower HR-QoL scores (5.1 versus 5.7, p=0.011).   Conclusions  Polysensitization to indoor and mould allergens based on component-resolved diagnostics identifies a more severe subgroup of childhood asthma.
Use and comparison of a fiber optic bronchoscope as an alternative to a purpose built thoracoscope
Authors: Chatura Wirasinghe, Duminda Yasarathne, Prasanna Wijerathene, Dushantha Madegedara
Journal: European Respiratory Journal (2012)

Background   Mechanical failure of (fiber optic thoracoscope) FOT at our unit, which was an established investigation in pleural disease led to a search for an alternative.   Objective   To demonstrate the use of a fiber optic bronchoscope (FOB) for local anesthetic thoracoscopy and to compare it with a purpose build thoracoscope.   Methodology   The new procedure was similar to standard local anesthetic thoracoscopy with the difference being an 8mm internal diameter endotracheal tube used as the trochar thorough which FOB was inserted. 22 patients with undiagnosed unilateral plural effusion underwent the procedure from July to November 2011. Their results were compared to those obtained using purpose built FOT in 22 consecutive patients from January 2011.   Results   Modified FOB thoracoscopy was successful in 77% of patients while purpose built FOT was successful in 86%. All failures were attributed to lungs not collapsing due to adhesions. Time taken to empty fluid from the pleural cavity and total procedure times were longer with FOB. The biopsy size using FOB was smaller. Histological diagnosis of malignancy was made in 27% (6) in FOB group and in FOT group it was 32% (7). Histological evidence of TB was obtained 22%(5) in FOB group and 27%(6) in the FOT group. A universal complication in both groups was post procedure pain which was relieved with use of simple analgesics. Other procedure related complications were not encountered in both groups.   Conclusion   A modified procedure with FOB can be used safely with a reasonable success rate to investigate pleural disease by experienced operators although there are limitations.
Mitochondrial Biogenesis as a Pharmacological Target: A New Approach to Acute and Chronic Diseases
Authors: Ryan M. Whitaker, Daniel Corum, Craig C. Beeson, Rick G. Schnellmann
Journal: The Annual Review of Pharmacology and Toxicology (2015)

Mitochondrial dysfunction is a key pathophysiological component of many acute and chronic diseases. Maintenance of mitochondrial homeostasis through the balance of mitochondrial turnover, fission and fusion, and generation of new mitochondria via mitochondrial biogenesis is critical for tissue health. Pharmacological activation of mitochondrial biogenesis can enhance oxidative metabolism and tissue bioenergetics, and improve organ function in conditions characterized by mitochondrial dysfunction. However, owing to the complexity of mitochondrial assembly and maintenance, identification of specific activators of mitochondrial biogenesis has been difficult. This review provides an overview of the role of mitochondrial dysfunction in acute and chronic diseases, details the current state of therapeutics for the stimulation of mitochondrial biogenesis and their effects on disease outcomes, describes new screening methodologies to identify novel stimulators and noncanonical pathways of mitochondrial biogenesis, and discusses potential hurdles of mitochondrial biogenesis as a therapeutic strategy.
Comparison of Oral Capecitabine Versus Intravenous Fluorouracil Plus Leucovorin as First-Line Treatment in 605 Patients With Metastatic Colorectal Cancer: Results of a Randomized Phase III Study
Authors: Paulo M. Hoff, Rafat Ansari, Gerald Batist, John Cox, Walter Kocha, Mario Kuperminc, Jean Maroun, David Walde, Charles Weaver, Evelyn Harrison, Hans U. Burger, Bruno Osterwalder, Alfred O. Wong, Ralf Wong
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To compare the response rate, efficacy parameters, and toxicity profile of oral capecitabine with bolus intravenous (IV) fluorouracil plus leucovorin (5-FU/LV) as first-line treatment in patients with metastatic colorectal cancer. PATIENTS AND METHODS: We prospectively randomized 605 patients to treatment with oral capecitabine for 14 days every 3 weeks or 5-FU/LV by rapid IV injection daily for 5 days in 4-week cycles. RESULTS: The overall objective tumor response rate among all randomized patients was significantly higher in the capecitabine group (24.8%) than in the 5-FU/LV group (15.5%; P = .005). In the capecitabine and 5-FU/LV groups, median times to disease progression were 4.3 and 4.7 months (log-rank P = .72), median times to treatment failure were 4.1 and 3.1 months (P = .19), and median overall survival times were 12.5 and 13.3 months (P = .974), respectively. Capecitabine, compared with bolus 5-FU/LV treatment, produced a significantly lower incidence (P &lt; .0002) of diarrhea, stomatitis, nausea, and alopecia. Patients treated with capecitabine also displayed lower incidences of grade 3/4 stomatitis and grade 3/4 neutropenia (P &lt; .0001) leading to significantly less neutropenic fever/sepsis. Grade 3 hand-foot syndrome (P &lt; .00001) and grade 3/4 hyperbilirubinemia were the only toxicities more frequently associated with capecitabine than with 5-FU/LV treatment. CONCLUSION: Oral capecitabine was more active than 5-FU/LV in the induction of objective tumor responses. Time to disease progression and survival were at least equivalent for capecitabine compared with the 5-FU/LV arm. Capecitabine also demonstrated clinically meaningful benefits over bolus 5-FU/LV in terms of tolerability.
Frequency and pathogenicity of rhinovirus associated pulmonary exacerbations in patients with cystic fibrosis
Authors: Amna Shah, Michael Connolly, Lucy Clasper, Chloe McIntyre, Heli Harvala, Antony Hale, Paul Whitaker, Peter Simmonds, Daniel Peckham
Journal: European Respiratory Journal (2013)

Objectives:  Human rhinovirus (HRV) is associated with pulmonary exacerbations in patients with CF. With sensitive RT-PCR techniques HRV is readily detected and new strains are being identified. In asthma, children with HRV group C have been shown to have more severe exacerbations. The aim of this project was to establish the frequency of each HRV group during exacerbations and to assess whether any HRV group is more pathogenic.   Methods:  Viral throat swabs were taken on all adult exacerbations between Dec 2008 and May 2011. Positive HRV samples were stored and typed in more detail. Date matched non-CF samples positive for HRV were used as community controls. To allow typing the extracted viral RNA was transcribed into cDNA. The resulting cDNA underwent two rounds of nested PCR reaction to produce amplicons of the VP4/VP2 region. This was then sequenced to allow genetic typing of the specimens. The HRV groups were then compared using demographic and clinical data obtained from patient records.   Conclusion:  HRV was identified in 7% of pulmonary exacerbations. 126 positive samples were stored and typing was possible in 104 of the isolates. HRV group A was identied in 57 (55%) of isolates, group B in 23 (22%), and group C in 24 (23%). The frequency of HRV group A was higher than that seen in community (55% vs 40%). Some patients had viral persistence for several weeks with the same serotype. Virus associated exacerbations had significantly greater impact on lung function, length of treatment, and time to next exacerbation compared to matched patients without a virus. However, no individual HRV group appeared more pathogenic and the detrimental effects were seen with all groups.
Elevated protein arginine methyltransferase 1 expression contributes to the pathogenesis of pulmonary fibrosis
Authors: Dariusz Zakrzewicz, Anna Zakrzewicz, Miroslava Didiasova, Klaus T. Preissner, Malgorzata Wygrecka
Journal: European Respiratory Journal (2014)

Objectve:  Idiopathic pulmonary fibrosis (IPF) is characterized by epithelial cell injury, fibroblast activation, proliferation, migration and excessive extracellular matrix deposition. Protein arginine methyltransferases (PRMTs) catalyze the methylation of protein arginine residues thereby controlling cellular activities. The impact of PRMT1 expression on the development of IPF has not been addressed so far.   Results:  Expression of PRMT1 was elevated in the lung homogenates from IPF patients as compared to donors. Significant upregulation of PRMT1 expression was also observed in lung samples of bleomycin-treated mice on day 5, 10 and 18 days post application. In the lungs of bleomycin-challenged mice strong PRMT1 immunostaining was associated with recruiting inflammatory cells and fibrotic regions. In IPF lungs PRMT1 immunoreactivity was attributed to alveolar epithelial type II cells (AECII), pulmonary arterial smooth muscle cells (PASMC) and fibroblasts. IPF fibroblasts demonstrated enhanced PRMT1 expression compared to donor fibroblasts. Overexpression of PRMT1 in human fibroblasts resulted in a significant increase in fibroblast migration and proliferation. This effect was reversed by PRMT1 knockdown and by pharmacological inhibitor of PRMT activity AMI-1. Interestingly, reduced expression of profibrotic markers ( Col1a1, MMP2 ) was only observed in PRMT1 siRNA-treated fibroblasts. Neither PRMT1 siRNA, nor AMI-1 treatment influenced  Col3a1  and  MMP9  expression in human lung fibroblasts.   Conclusions:  Dysregulated PRMT1 expression in human lung fibroblasts may influence fibroblast behavior by both methylation of target proteins or by regulation of gene expression.
Front-line treatment of advanced non-small-cell lung cancer with MTA (LY231514, Pemetrexed disodium, ALIMTA™ and cisplatin: A multicenter phase II trial
Authors: C. Manegold, U. Gatzemeier, J. von Pawel, R. Pirker, R. Malayeri, J. Blatter, K. Krejcy
Journal: Annals of Oncology (2000)
Dissemination and Growth of Transplanted Isologous Murine Lymphoma Cells2
Authors: W. R. Bruce, B. E. Meeker
Journal: JNCI Journal of the National Cancer Institute (1964)

Dissemination and Growth of Transplanted Isologous Murine Lymphoma Cells Get access W. R. Bruce, W. R. Bruce Ontario Cancer Institute, and the Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar B. E. Meeker B. E. Meeker Ontario Cancer Institute, and the Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 32, Issue 5, May 1964, Pages 1145–1159, https://doi.org/10.1093/jnci/32.5.1145 Published: 01 May 1964 Article history Received: 01 November 1963 Published: 01 May 1964
Targeting Central Nervous System B Cells in Progression of Multiple Sclerosis
Authors: Mahboobeh Fereidan-Esfahani, Wolfgang Brück, Martin S. Weber
Journal: JAMA Neurology (2015)

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Central centrifugal cicatricial alopecia severity is associated with cowhage-induced itch
Authors: G. A. Bin Saif, A. McMichael, S. G. Kwatra, Y. H. Chan, Gil Yosipovitch
Journal: British Journal of Dermatology (2012)

Background Patients with central centrifugal cicatricial alopecia (CCCA) often suffer from varying degrees of itch, pain and burning sensations. However, the neural component of these skin sensations has not been assessed. Objective To conduct a comprehensive analysis of C nerve fibre function relating to itch and pain perception in patients with CCCA using thermosensory testing and experimental itch models. Methods Fifteen healthy African-American women and 16 African-American female patients with CCCA participated in the study and underwent quantitative computerized thermosensory testing to assess warmth and heat pain thresholds. Itch was induced using histamine iontophoresis and application of cowhage spicules, and the intensity of each itch was assessed. The association between itch intensity and CCCA severity score was examined. Results A positive correlation between CCCA severity score and peak itch ratings of cowhage on the lesional scalp (crown) was observed (P = 0·023, r = 0·562). Notably, the histamine peak itch rating was not found to have a significant correlation with CCCA severity score (P = 0·913). The crown also had significantly higher warmth and pain thresholds than the occiput in both healthy subjects and patients with CCCA. Conclusions Our results suggest a putative role for the protease-activated receptor (PAR)-2, which is activated by cowhage, in the pathogenesis of CCCA. Future studies should examine PAR-2-directed therapeutics for patients with CCCA. Examining for itch and other dysaesthesias in patients with CCCA is of vital importance to dermatologists in assessing disease severity.
Munchausen syndrome by proxy presenting as unexplained hemoptysis: A report of two cases
Authors: Suleyman Tolga Yavuz, Guzin Cinel, Ugur Ozcelik, Ebru Yalcin, Deniz Dogru, Nural Kiper
Journal: European Respiratory Journal (2012)

Hemoptysis is a serious symptom in early childhood and further investigation may be required in some cases. Munchausen syndrome by Proxy (MSBP) must be kept in mind particularly when suspicious behaviors of the supervisors are observed.  Case 1: A thirteen-month-old boy was admitted with recurrent hemoptysis. He was hospitalized because of persisting symptoms for four months, however no reason was found and he was subsequently discharged. Detailed history revealed that hemoptysis had occurred only in times when he was alone with his mother. Despite comprehensive diagnostic evaluation including laryngoscopy, Computerized Tomography, bronchoscopy and endoscopy, no definitive etiology was diagnosed. During his hospitalization, the mother reported new bleedings of the child and blood stained clothes were noticed. Examination of security footage revealed that the mother was sneakily obtaining the blood samples of another patient and deceiving medical staff.  Case 2: An-eight-month old girl was admitted with a history of having vomited blood for two months. Reluctance of her mother was noticed by the physician during history taking. Upper endoscopic investigation revealed linear hemorrhagic lesions at pharynx and tonsils. No definitive etiology was diagnosed despite comprehensive investigations. During hospitalization, the doctor witnessed that her mother was injuring the child with her finger and making her bleed. She was warned about security footage of the room and her complaints resolved spontaneously.  Munchausen syndrome by proxy is an unusual and difficult to identify cause of child abuse. It must be taken into consideration particularly in conditions with secondary gain of family members.
Clonal dissemination of a toxin-A-negative/toxin-B-positive Clostridium difficile strain from patients with antibiotic-associated diarrhea in Poland
Authors: H. Pituch, N. van den Braak, W. van Leeuwen, A. van Belkum, G. Martirosian, P. Obuch-Woszczatyński, M. Łuczak, F. Meisel-Mikołajczyk
Journal: Clinical Microbiology and Infection (2001)
Inspiratory Muscle Training in Patients with Chronic Obstructive Pulmonary Disease
Authors: Alba Ramírez-Sarmiento, Mauricio Orozco-Levi, Rosa Güell, Esther Barreiro, Nuria Hernandez, Susana Mota, Merce Sangenis, Joan M. Broquetas, Pere Casan, Joaquim Gea
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

The present study was aimed at evaluating the effects of a specific inspiratory muscle training protocol on the structure of inspiratory muscles in patients with chronic obstructive pulmonary disease. Fourteen patients (males, FEV1, 24 ± 7% predicted) were randomized to either inspiratory muscle or sham training groups. Supervised breathing using a threshold inspiratory device was performed 30 minutes per day, five times a week, for 5 consecutive weeks. The inspiratory training group was subjected to inspiratory loading equivalent to 40 to 50% of their maximal inspiratory pressure. Biopsies from external intercostal muscles and vastus lateralis (control muscle) were taken before and after the training period. Muscle samples were processed for morphometric analyses using monoclonal antibodies against myosin heavy chain isoforms I and II. Increases in both the strength and endurance of the inspiratory muscles were observed in the inspiratory training group. This improvement was associated with increases in the proportion of type I fibers (by approximately 38%, p < 0.05) and in the size of type II fibers (by approximately 21%, p < 0.05) in the external intercostal muscles. No changes were observed in the control muscle. The study demonstrates that inspiratory training induces a specific functional improvement of the inspiratory muscles and adaptive changes in the structure of external intercostal muscles.
Value of an Anal Dilator after Anal Stretch for Haemorrhoids
Authors: F Greca, E Nevah, M Hares, M R B Keighley
Journal: Journal of the Royal Society of Medicine (1981)

A prospective randomized trial compared anal stretch with or without continued dilatation for three months in 89 consecutive patients with haemorrhoids. Complications of therapy occurred in only 4 patients, 3 of whom had transient incontinence of flatus. When patients were reviewed four months after treatment, only 4 of 44 patients (9%) who used a dilator had not been improved and required additional therapy, compared with 15 of 42 patients (36%) who had anal stretch alone (P &lt;0.02). It is concluded that the use of an anal dilator improves the results of anal stretch.
Metronidazole: Effect on Radiosensitivity of Tumor and Normal Tissues in Mice2
Authors: Helen B. Stone, H. Rodney Withers
Journal: JNCI Journal of the National Cancer Institute (1975)

Local control of a mammary carcinoma in air-breathing C3H mice was enhanced by giving metronidazole before radiotherapy. When 0.5–1.0 mg metronidazole/g body weight was given ip 10 minutes before irradiation, the dose required for local control of 50% of the tumors (TC050) was reduced by a factor of 1.37–1.38. The TCD50 was reduced by a factor of 1.48–1.50 when tumors were irradiated 30–60 minutes after 1.0 mg/g. Metronidazole alone, at a dose of 1.0 mg/g, only slightly inhibited tumor growth. The acute skin response of the leg, as determined by the radiation dose required to produce complete moist desquamation in 50% of the animals (DD50), was enhanced by a factor of 1.26 when mice were irradiated 10 minutes after a dose of 1.0 mg metronidazole/g. Clonogenic cells in the jejunal epithelium were not sensitized after metronidazole administration in either air-breathing mice or those irradiated in O2 30 pounds per square inch, but the drug appeared to exert a slight protective effect at higher doses of radiation.