tbuckley/cabot-search huggingface dataset:
A Hypoxia- and α-Fetoprotein–Dependent Oncolytic Adenovirus Exhibits Specific Killing of Hepatocellular Carcinomas
Authors: Oh-Joon Kwon, Pyung-Hwan Kim, Steven Huyn, Lily Wu, Minjung Kim, Chae-Ok Yun
Journal: Clinical Cancer Research (2010)

Abstract Purpose: Oncolytic adenoviruses (Ad) constitute a new promising modality of cancer gene therapy that displays improved efficacy over nonreplicating Ads. We have previously shown that an E1B 19-kDa-deleted oncolytic Ad exhibits a strong cell-killing effect but lacks tumor selectivity. To achieve hepatoma-restricted cytotoxicity and enhance replication of Ad within the context of tumor microenvironment, we used a modified human α-fetoprotein (hAFP) promoter to control the replication of Ad with a hypoxia response element (HRE). Experimental Design: We constructed Ad-HRE6/hAFPΔ19 and Ad-HRE12/hAFPΔ19 that incorporated either 6 or 12 copies of HRE upstream of promoter. The promoter activity and specificity to hepatoma were examined by luciferase assay and fluorescence-activated cell sorting analysis. In addition, the AFP expression- and hypoxia-dependent in vitro cytotoxicity of Ad-HRE6/hAFPΔ19 and Ad-HRE12/hAFPΔ19 was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and cytopathic effect assay. In vivo tumoricidal activity on subcutaneous and liver orthotopic model was monitored by noninvasive molecular imaging. Results: Ad-HRE12/hAFPΔ19 exhibited enhanced tumor selectivity and cell-killing activity when compared with Ad-hAFPΔ19. The tumoricidal activity of Ad-HRE12/hAFPΔ19 resulted in significant inhibition of tumor growth in both subcutaneous and orthotopic models. Histologic examination of the primary tumor after treatment confirmed accumulation of viral particles near hypoxic areas. Furthermore, Ad-HRE12/hAFPΔ19 did not cause severe inflammatory immune response and toxicity after systemic injection. Conclusions: The results presented here show the advantages of incorporating HREs into a hAFP promoter–driven oncolytic virus. This system is unique in that it acts in both a tissue-specific and tumor environment–selective manner. The greatly enhanced selectivity and tumoricidal activity of Ad-HRE12/hAFPΔ19 make it a promising therapeutic agent in the treatment of liver cancers. Clin Cancer Res; 16(24); 6071–82. ©2010 AACR.
Pulmonary rehabilitation in patients with idiopathic pulmonary fibrosis: Comparison with COPD
Authors: Shinichi Arizono, Hiroyuki Taniguchi, Yasuhiro Kondoh, Tomoki Kimura, Kensuke Kataoka, Tomoya Ogawa, Fumiko Watanabe, Jun Hirasawa, Kazuyuki Tabira
Journal: European Respiratory Journal (2013)

Study objective: Pulmonary rehabilitation (PR) has been reported useful for improving exercise capacity and health status in patients with idiopathic pulmonary fibrosis (IPF). However it is reported PR demonstrated smaller exercise capacity improvements in IPF patients than in COPD patients. The purpose of the present study was to evaluate the effects of PR in IPF patients and compare their responses with COPD patients who underwent an identical PR program.

Methods: Twenty-two IPF patients (%VC: 72%) and 34 COPD patients (%FEV1: 45%) were recruited. Subjects completed a 10-week outpatient pulmonary rehabilitation program. Dyspnea (Baseline dyspnea index: BDI), health status (St. George’s Respiratory Questionnaire: SGRQ) and exercise capacity were assessed at baseline and immediately following completion of the PR program. Five kinds of exercise capacity were endurance time by constant load ergometry test, peak work rate and peak VO2 by incremental load ergometry test, the distance of 6 minutes walking test (6MWD) and incremental shuttle walking test (ISWD).

Results: Age, BDI, SGRQ and exercise capacity at baseline were no different between the two groups. Significant improvements in BDI and SGRQ were observed in both groups (p < 0.05). Endurance time, peak work rate, 6MWD and ISWD were improved significantly after 10-weeks (p<0.05), whereas peak VO2 was not improved, in both groups. The magnitude of improvement in all outcomes was no difference in IPF and COPD patients.

Conclusions: PR in IPF produced improvements in exercise capacity, dyspnea and health status, as well as in COPD patients.
Indoor exposure to molds and allergic sensitization.
Authors: Beate Jacob, Beate Ritz, Ulrike Gehring, Andrea Koch, Wolfgang Bischof, H E Wichmann, Joachim Heinrich
Journal: Environmental Health Perspectives (2002)

Evidence that indoor dampness and mold growth are associated with respiratory health has been accumulating, but few studies have been able to examine health risks in relation to measured levels of indoor mold exposure. In particular, little is known about the contribution of indoor molds to the development of allergic sensitization. As a part of an ongoing study examining the effects of ambient air pollutants on respiratory health and atopic diseases in German school children, we examined the relation between viable mold levels indoors and allergic sensitization in 272 children. We examined whether allergic sensitization in children is associated with higher fungal spore count in settled house dust sampled from living room floors. Adjusting for age, sex, parental education, region of residency, and parental history of atopy, we found that mold spore counts for Cladosporium and Aspergillus were associated with an increased risk of allergic sensitization. Sensitized children exposed to high levels of mold spores (> 90th percentile) were more likely to suffer from symptoms of rhinoconjunctivitis. We conclude that elevated indoor concentrations of molds in wintertime might play a role in increasing the risk of developing atopic symptoms and allergic sensitization not only to molds but also to other common, inhaled allergens. These effects were strongest in the group of children who had lived in the same home since birth.
Effect of 3 weeks' rehabilitation on neutrophil surface antigens and lung function in cystic fibrosis
Authors: W.H. Nikolaizik, H-U. Simon, P. Iseli, K. Blaser, M.H Schoni
Journal: European Respiratory Journal (2000)

Neutrophil leukocytes have been shown to be the predominant cells in inflammatory airway infiltrates of cystic fibrosis (CF) patients. The aim of this study was to investigate the effect of rehabilitation on neutrophil surface antigen expression and lung function in healthy controls and stable CF patients with moderately severe disease. The absolute number of neutrophils and the level of surface marker expression on neutrophils were elevated in 12 CF patients compared with eight healthy controls. The level of neutrophil surface marker expression was similar in bronchoalveolar lavage fluid from CF patients who underwent bronchoscopy for diagnostic or therapeutic reasons. After 3 weeks9 rehabilitation, there was a significant reduction in the expression of CD11b (complement receptor type 3), CD13 (aminopeptidase N), CD32 (low-affinity Fc gamma chain receptor II), and CD35 (complement receptor type 1) in only the CF patients. At the same time, lung function improved significantly. The increase in forced vital capacity correlated significantly with the decrease in CD32 level. These results demonstrate that rehabilitation in a specialized clinic can reduce the neutrophil-dominated inflammation and improve the lung function of stable CF patients with moderately severe disease even without changing any medications.
Outcome of Recent Thromboembolic Occlusions of Limb Arteries Treated with Streptokinase
Authors: A. Amery, W. Deloof, J. Vermylen, M. Verstraete
Journal: BMJ (1970)

All our patients with a recent thromboembolic occlusion of limb arteries treated with streptokinase have been reviewed retrospectively. Clearing of the main artery, as judged by arteriography or reappearance of arterial pulsations, occurred more often when treatment was started early. If only patients with an iliac, femoral, or popliteal artery occlusion are considered, those who received a lower initial dose had a significantly higher clearing rate and a significantly lower mortality than those who received a high initial dose (500,000 units of streptokinase or more). Therefore an initial standard dose of 1,200,000 units of streptokinase is no longer recommended in these conditions, and even an individually titrated initial dose of more than half a million units could be hazardous. If no neurological abnormalities were present on admission amputation was never necessary, even if clearing of the main artery did not occur. If there was sensory loss of at least part of a limb, amputation was avoided only if the pulsations returned in at least one artery of hand or foot.
Transcriptome Sequencing Reveals <i>PCAT5</i> as a Novel ERG-Regulated Long Noncoding RNA in Prostate Cancer
Authors: Antti Ylipää, Kati Kivinummi, Annika Kohvakka, Matti Annala, Leena Latonen, Mauro Scaravilli, Kimmo Kartasalo, Simo-Pekka Leppänen, Serdar Karakurt, Janne Seppälä, Olli Yli-Harja, Teuvo L.J. Tammela, Wei Zhang, Tapio Visakorpi, Matti Nykter
Journal: Cancer Research (2015)

Abstract Castration-resistant prostate cancers (CRPC) that arise after the failure of androgen-blocking therapies cause most of the deaths from prostate cancer, intensifying the need to fully understand CRPC pathophysiology. In this study, we characterized the transcriptomic differences between untreated prostate cancer and locally recurrent CRPC. Here, we report the identification of 145 previously unannotated intergenic long noncoding RNA transcripts (lncRNA) or isoforms that are associated with prostate cancer or CRPC. Of the one third of these transcripts that were specific for CRPC, we defined a novel lncRNA termed PCAT5 as a regulatory target for the transcription factor ERG, which is activated in approximately 50% of human prostate cancer. Genome-wide expression analysis of a PCAT5-positive prostate cancer after PCAT5 silencing highlighted alterations in cell proliferation pathways. Strikingly, an in vitro validation of these alterations revealed a complex integrated phenotype affecting cell growth, migration, invasion, colony-forming potential, and apoptosis. Our findings reveal a key molecular determinant of differences between prostate cancer and CRPC at the level of the transcriptome. Furthermore, they establish PCAT5 as a novel oncogenic lncRNA in ERG-positive prostate cancers, with implications for defining CRPC biomarkers and new therapeutic interventions. Cancer Res; 75(19); 4026–31. ©2015 AACR.
Cardiovascular outcomes in patients with locally advanced and metastatic prostate cancer treated with luteinising-hormone-releasing-hormone agonists or transdermal oestrogen: the randomised, phase 2 MRC PATCH trial (PR09)
Authors: Ruth E Langley, Fay H Cafferty, Abdulla A Alhasso, Stuart D Rosen, Subramanian Kanaga Sundaram, Suzanne C Freeman, Philip Pollock, Rachel C Jinks, Ian F Godsland, Roger Kockelbergh, Noel W Clarke, Howard G Kynaston, Mahesh KB Parmar, Paul D Abel
Journal: The Lancet Oncology (2013)

Luteinising-hormone-releasing-hormone agonists (LHRHa) to treat prostate cancer are associated with long-term toxic effects, including osteoporosis. Use of parenteral oestrogen could avoid the long-term complications associated with LHRHa and the thromboembolic complications associated with oral oestrogen.In this multicentre, open-label, randomised, phase 2 trial, we enrolled men with locally advanced or metastatic prostate cancer scheduled to start indefinite hormone therapy. Randomisation was by minimisation, in a 2:1 ratio, to four self-administered oestrogen patches (100 μg per 24 h) changed twice weekly or LHRHa given according to local practice. After castrate testosterone concentrations were reached (1·7 nmol/L or lower) men received three oestrogen patches changed twice weekly. The primary outcome, cardiovascular morbidity and mortality, was analysed by modified intention to treat and by therapy at the time of the event to account for treatment crossover in cases of disease progression. This study is registered with ClinicalTrials.gov, number NCT00303784.85 patients were randomly assigned to receive LHRHa and 169 to receive oestrogen patches. All 85 patients started LHRHa, and 168 started oestrogen patches. At 3 months, 70 (93%) of 75 receiving LHRHa and 111 (92%) of 121 receiving oestrogen had achieved castrate testosterone concentrations. After a median follow-up of 19 months (IQR 12-31), 24 cardiovascular events were reported, six events in six (7·1%) men in the LHRHa group (95% CI 2·7-14·9) and 18 events in 17 (10·1%) men in the oestrogen-patch group (6·0-15·6). Nine (50%) of 18 events in the oestrogen group occurred after crossover to LHRHa. Mean 12-month changes in fasting glucose concentrations were 0·33 mmol/L (5·5%) in the LHRHa group and -0·16 mmol/L (-2·4%) in the oestrogen-patch group (p=0·004), and for fasting cholesterol were 0·20 mmol/L (4·1%) and -0·23 mmol/L (-3·3%), respectively (p<0·0001). Other adverse events reported by 6 months included gynaecomastia (15 [19%] of 78 patients in the LHRHa group vs 104 [75%] of 138 in the oestrogen-patch group), hot flushes (44 [56%] vs 35 [25%]), and dermatological problems (10 [13%] vs 58 [42%]).Parenteral oestrogen could be a potential alternative to LHRHa in management of prostate cancer if efficacy is confirmed. On the basis of our findings, enrolment in the PATCH trial has been extended, with a primary outcome of progression-free survival.Cancer Research UK, MRC Clinical Trials Unit.
Variation in hydrogen cyanide production between different strains of Pseudomonas aeruginosa
Authors: F.J. Gilchrist, A. Alcock, J. Belcher, M. Brady, A. Jones, D. Smith, P. Španĕl, K. Webb, W. Lenney
Journal: European Respiratory Journal (2011)

There is increasing interest in using the cyanogenic properties of Pseudomonas aeruginosa to develop a nonmicrobiological method for its detection. Prior to this, the variation in cyanide production between different P. aeruginosa strains needs to be investigated. Hydrogen cyanide (HCN) released into the gas phase by 96 genotyped P. aeruginosa samples was measured using selected ion flow tube-mass spectrometry after 24, 48, 72 and 96 h of incubation. The HCN produced by a range of non- P. aeruginosa cultures and incubated blank plates was also measured. All P. aeruginosa strains produced more HCN than the control samples, which generated extremely low levels. Analysis across all time-points demonstrated that nonmucoid samples produced more HCN than the mucoid samples (p=0.003), but this relationship varied according to strain. There were clear differences in the headspace HCN concentration for different strains. Multivariate analysis of headspace HCN for the commonest strains (Liverpool, Midlands_1 and Stoke-on-Trent, UK) revealed a significant effect of strain (p&lt;0.001) and a borderline interaction of strain and phenotype (p=0.051). This evidence confirms that all P. aeruginosa strains produce HCN but to varying degrees and generates interest in the possible future clinical applications of the cyanogenic properties of P. aeruginosa .
Lung function and exercise capacity in thalassaemia major
Authors: C Cracowski, B Wuyam, V Klein, P Levy
Journal: European Respiratory Journal (1998)

Lung function abnormalities in thalassaemia major are various and complex; however, patients still die from cardiac lesions. This study aimed to investigate pulmonary and cardiac involvement at an early stage in thalassaemic patients and study their respective implications at rest and during exercise. Ten patients (five adults and five children) with thalassaemia major were investigated by echocardiography, lung function and exercise testing a few days after transfusion. All have had regular transfusions and chelation with deferoxamine and none had chronic pulmonary disease symptoms. Minor lung function abnormalities were found: two patients had moderate obstructive syndrome and two had a decreased carbon monoxide transfer factor. Hypoxaemia was never found at rest and no desaturation was observed at the end of exercise. Echocardiographic abnormalities were also moderate. Peak oxygen consumption (V'O2) was decreased in three adults and was lower in adults than children (means 27.7+/-4.6 and 41.1+/-4.8 mL.kg(-1).min(-2) respectively). The V'O2/cardiac frequency slope was lower in adults than children (0.25+/-0.06 versus 0.42+/-0.10 mL.kg(-1).min(-2)), whereas end-exercise breathing reserve was >40% maximal voluntary ventilation for all patients. In conclusion, none of the patients had ventilatory limitations but older patients had cardiac limitations assessed by the relationship between oxygen consumption and cardiac frequency. Exercise testing may detect cardiac impairment in thalassaemia major earlier than investigations at rest.
Prevalence of anxiety and depressive illness and help seeking behaviour in African Caribbeans and white Europeans: two phase general population survey Commentary: Counting heads may mask cultural and social factors
Authors: C M Shaw, F Creed, B Tomenson, L Riste, J K Cruickshank, G. Rait
Journal: BMJ (1999)

# Prevalence of anxiety and depressive illness and help seeking behaviour in African Caribbeans and white Europeans: two phase general population survey {#article-title-2} Objective : To determine the prevalence of common mental disorders (anxiety and depression) and help seeking behaviour in African Caribbeans and white Europeans. Design : Two phase survey in a general population sample. The first phase comprised screening with the 12 item general health questionnaire; the second phase was standardised psychiatric assessment and interview about help seeking. Setting : People registered with four general practices in central Manchester. Participants : Of 1467 people randomly selected from family health services authority lists, 864 were still resident. 337 African Caribbeans and 275 white Europeans completed the screening phase (response rate 71%); 127 African Caribbeans and 103 white Europeans were interviewed in the second phase. Main outcome measures : One month period prevalence of anxiety and depressive disorders in each ethnic group. Results : 13% of African Caribbeans (95% confidence interval 10% to 16%) and 14% (10% to 18%) of white Europeans had one or more disorder. Anxiety disorders were significantly less common among African Caribbeans (3% (1% to 5%) v 9% (6% to 12%) in white Europeans). Depressive disorders were significantly more common among African Caribbean women than white women (difference 8% (1% to 15%)). Medical help seeking was similar in the two groups, but African Caribbeans with mental disorders were more likely to seek additional help from non-medical sources (12/29 v 5/29, P=0.082). Conclusions : In an inner city setting the prevalence of common mental disorders is similar in these two ethnic groups. # Commentary: Counting heads may mask cultural and social factors {#article-title-12}
Propulsion (mass movements) in the human colon and its relationship to meals and somatic activity
Authors: D. J. Holdstock, J. J. Misiewicz, T. Smith, E. N. Rowlands
Journal: Gut (1970)

Propulsive activity of the human colon was measured with radiopaque markers (shapes), radiotelemetering capsules, Perspex capsules containing (51)Cr, or with free (51)Cr sodium chromate. Propulsive activity can be readily detected by these techniques, none of which requires the use of radiological contrast media. With capsules containing (51)Cr or with free (51)Cr repeated observations can be made in the same patient without recourse to radiography. The patient can remain normally active during the test with encapsulated (51)Cr. Repeated observations may also be made with shapes, if films exposed at low mA are used. It was found that colonic intraluminal pressure activity rises markedly during and after food, but that in the resting patient this increase is rarely associated with propulsive activity. In physically active patients propulsion of colonic contents was significantly increased after meals. When colonic propulsion takes place, it does so by a series of mass movements. These results suggest that somatic activity is an important factor in the control of colonic transit in health or disease.
Fatigue in COPD: association with functional status and hospitalisations
Authors: Johanna Susan Paddison, Tanya W. Effing, Stephen Quinn, Peter A. Frith
Journal: European Respiratory Journal (2012)

This study aimed to examine the importance of fatigue as a clinical indicator in chronic obstructive pulmonary disease (COPD), by analysing its relationship with COPD severity and ability to predict risk of hospitalisation, and by comparing the intensity of fatigue in stable COPD patients with levels of fatigue reported by patients with other chronic conditions. We studied 100 consecutive patients attending assessment clinics before pulmonary rehabilitation. Both questionnaire and physiological data were collected. Partial correlations, multiple linear regressions and Cox proportional hazard models/negative binomial regressions were used to address the research questions. A significant relationship existed between fatigue and COPD severity. Fatigue reports predicted future hospitalisation risk. Compared to the lowest third of patients, the third of patients reporting the most intense fatigue showed a 10-fold increase in risk of hospitalisation (fatigue experiences hazard ratio (HR) 10.2, 95% CI 2.66-38.86; fatigue impacts HR 10.7, 95% CI 2.76-41.65). Our COPD sample reported fatigue scores of similar intensity to colorectal cancer patients and HIV-positive patients. While fatigue is significantly related to COPD functional severity, fatigue data also capture independent information. Fatigue reports can contribute to predictions of hospitalisation risk.
G-CSF prevents the suppression of bone marrow hematopoiesis induced by IL-12 and augments its antitumor activity in a melanoma model in mice
Authors: I. Gołąb, T. Stokłosa, R. Zagożdżon, A. Kaca, A. Giermasz, Z. Pojda, E. Machaj, A. Dąbrowska, W. Feleszko, W. Lasek, A. Iwan-Osiecka, M. Jakóbisiak
Journal: Annals of Oncology (1998)
Mycobacterial hypersensitivity pneumonitis requires TLR9-MyD88 in lung CD11b+ CD11c+ cells
Authors: H. Daito, T. Kikuchi, T. Sakakibara, K. Gomi, T. Damayanti, J. Zaini, N. Tode, M. Kanehira, S. Koyama, S. Fujimura, M. Ebina, K.J. Ishii, S. Akira, T. Takai, A. Watanabe, T. Nukiwa
Journal: European Respiratory Journal (2011)

Mycobacteria are among the most common causes of hypersensitivity pneumonitis (HP), but controversy persists with regard to the involvement of the infectious potency of the organism in mycobacterial HP (hot tub lung). This study aimed to establish a mouse model of hot tub lung to clarify its pathophysiology. Mice were exposed intranasally to formalin-killed Mycobacterium avium from a patient with hot tub lung (HP strain) or chronic pulmonary infection (non-HP strain), and bronchoalveolar lavage fluids and lung tissues were evaluated for allergic inflammation. Dead M. avium HP strain, but not non-HP strain, elicited marked HP-like pulmonary inflammation in wild-type mice. Although the inflammation was induced in mice lacking CD4 or CD8, the induction of HP-like responses was prevented in mice lacking myeloid differentiation factor (MyD)88 or Toll-like receptor (TLR)9. Cultured lung CD11c+ cells responded to M. avium in a TLR9-dependent manner, and reconstitution of TLR9-/- mice with lung CD11c+ cells from wild-type mice restored the inflammatory responses. Further investigation revealed that pulmonary exposure to M. avium HP strain increased the number of lung CD11b+ CD11c+ cells (dendritic cells) through TLR9 signalling. Our results provide evidence that hot tub lung develops via the mycobacterial engagement of TLR9–MyD88 signalling in lung CD11b+ dendritic cells independent of the mycobacterial infectious capacity.
Biweekly high-dose gemcitabine alone or in combination with capecitabine in patients with metastatic pancreatic adenocarcinoma: a randomized phase II trial
Authors: W. Scheithauer, B. Schüll, H. Ulrich-Pur, K. Schmid, M. Raderer, K. Haider, W. Kwasny, D. Depisch, B. Schneeweiss, F. Lang, G.V. Kornek
Journal: Annals of Oncology (2002)