tbuckley/cabot-search huggingface dataset:
A Disintegrin and Metalloprotease 33 Polymorphisms and Lung Function Decline in the General Population
Authors: Cleo C. van Diemen, Dirkje S. Postma, Judith M. Vonk, Marcel Bruinenberg, Jan P. Schouten, H. Marike Boezen
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

A disintegrin and metalloprotease 33 (ADAM33) has been identified as a susceptibility gene for asthma and single nucleotide polymorphisms (SNPs) in this gene have been associated with excessive decline of lung function in individuals with asthma.To assess whether SNPs in ADAM33 are associated with accelerated lung function loss in the general population and with chronic obstructive pulmonary disease (COPD).DNA was collected from subjects of the Vlagtwedde-Vlaardingen cohort participating in the last survey in 1989-1990 after a follow-up of 25 years. Information was collected every 3 years, including lung function measurements. We defined COPD as GOLD stage 2 or higher at the last survey. A total of 1,390 subjects from the cohort was genotyped for the following SNPs in ADAM33: F+1, Q-1, S_1, S_2, T_1, T_2, V_4, and ST+5. Differences in prevalence of SNPs were analyzed with chi(2) tests. Linear mixed effects models were used to analyze FEV(1) decline according to genotype.In the whole population, mean adjusted decline was 18.7 and 12.7 ml/year in females and males, respectively. Individuals homozygous for minor alleles of SNPs S_2 and Q-1 and heterozygous for SNP S_1 had a significantly accelerated decline in FEV(1) of, respectively, 4.9, 9.6, and 3.6 ml/year compared with wild type. We found a significantly higher prevalence of SNPs F+1, S_1, S_2, and T_2 in subjects with COPD.We demonstrated that SNPs in ADAM33 are associated with accelerated lung function decline in the general population. These SNPs are also risk factors for COPD.
Cost-effectiveness of a primary care based physical activity intervention in 45-74 year old men and women: a randomised controlled trial.
Authors: W Stevens, M Hillsdon, M Thorogood, D McArdle
Journal: British Journal of Sports Medicine (1998)

To assess the cost-effectiveness of a primary care based intervention aimed at increasing levels of physical activity in inactive people aged 45-74.A total of 714 inactive people aged 45-74, taken from two west London general practices, were randomised into two groups. Intervention subjects were invited to a consultation with an exercise development officer, and offered a personalised 10 week programme to increase their level of regular physical activity, combining leisure centre and home based activities. Control subjects were sent information on local leisure centres. All subjects were followed up at eight months.There was a net 10.6% (95% confidence interval 4.5 to 16.9%) reduction in the proportion of people classified as sedentary in the intervention group compared with the control group, eight months after the intervention. The intervention group also reported an increase in the mean number of episodes of physical activity per week, as compared with the control group (an additional 1.52 episodes (95% confidence interval 1.14 to 1.95)). The cost of moving a person out of the sedentary group was shown to be less than 650 Pounds. The cost of moving someone to the now commonly recommended level was estimated at almost 2500 Pounds.Moderate physical activity can be successfully encouraged in previously sedentary men and women aged 45-74 through a primary care based intervention. The process of recruitment was the most important variable cost. A high uptake rate would maximise cost-effectiveness, and sensitivity analysis suggests that unit costs could be halved with a more effective recruitment strategy.
Direct immunofluorescence of plucked hair for evaluation of immunologic remission in pemphigus vulgaris
Authors: Maryam Daneshpazhooh, Zahra S. Naraghi, Ali Ramezani, Alireza Ghanadan, Nafiseh Esmaili, Cheyda Chams-Davatchi
Journal: Journal of the American Academy of Dermatology (2011)
Inhibition of miR-15 Protects Against Cardiac Ischemic Injury
Authors: Thomas G. Hullinger, Rusty L. Montgomery, Anita G. Seto, Brent A. Dickinson, Hillary M. Semus, Joshua M. Lynch, Christina M. Dalby, Kathryn Robinson, Christianna Stack, Paul A. Latimer, Joshua M. Hare, Eric N. Olson, Eva van Rooij
Journal: Circulation Research (2011)

Myocardial infarction (MI) is a leading cause of death worldwide. Because endogenous cardiac repair mechanisms are not sufficient for meaningful tissue regeneration, MI results in loss of cardiac tissue and detrimental remodeling events. MicroRNAs (miRNAs) are small, noncoding RNAs that regulate gene expression in a sequence dependent manner. Our previous data indicate that miRNAs are dysregulated in response to ischemic injury of the heart and actively contribute to cardiac remodeling after MI.This study was designed to determine whether miRNAs are dysregulated on ischemic damage in porcine cardiac tissues and whether locked nucleic acid (LNA)-modified anti-miR chemistries can target cardiac expressed miRNAs to therapeutically inhibit miR-15 on ischemic injury.Our data indicate that the miR-15 family, which includes 6 closely related miRNAs, is regulated in the infarcted region of the heart in response to ischemia-reperfusion injury in mice and pigs. LNA-modified chemistries can effectively silence miR-15 family members in vitro and render cardiomyocytes resistant to hypoxia-induced cardiomyocyte cell death. Correspondingly, systemic delivery of miR-15 anti-miRs dose-dependently represses miR-15 in cardiac tissue of both mice and pigs, whereas therapeutic targeting of miR-15 in mice reduces infarct size and cardiac remodeling and enhances cardiac function in response to MI.Oligonucleotide-based therapies using LNA-modified chemistries for modulating cardiac miRNAs in the setting of heart disease are efficacious and validate miR-15 as a potential therapeutic target for the manipulation of cardiac remodeling and function in the setting of ischemic injury.
Roflumilast-N-oxide exerts anti-remodelling potencies in COPD patients in vitro
Authors: Christopher Lambers, Michael Roth, Hermann Tenor, Elisabeth Hofbauer, Venzel Petkov, Lutz-Henning Block
Journal: European Respiratory Journal (2012)

COPD is characterised by progressive airway remodelling and peribronchiolar fibrosis. The origin of pathologic remodelling in COPD is unknown and may result from local hypoxia and increased growth factor expression, including transforming growth factor-beta (TGF-β). TGF-β increases the synthesis of collagen1A1, connective tissue growth factor (CTGF), alpha smooth muscle actin (SMA). This study explores whether the phosphodiesterase-4 (PDE4) inhibitor roflumilast N-oxide (RNO), the active metabolite of roflumilast in use for severe COPD modifies TGF-β induced ECM composition.

Methods:

Lung fibroblasts from patients with COPD (GOLD II-III) (n=3) were isolated and cultured using standard protocols. Cells were preincubated with RNO (1µM), Budesonide (BUD, 100nM), or vehicle (0.1% DMSO) and stimulated with TGF-β (1 or 2ng/ml) for 24 hours. CTGF, Collagen (Col) 1A1, and SMA mRNA expression were measured by quantitative RT-PCR (18S mRNA served as reference gene) and results were depicted as relative expression.

Results:

In COPD lung fibroblasts, TGF-β induced CTGF (1.2 fold/ SD±0.19/ p=0.0069), Col1A1 (1.51/±0.41/p=0.003) and SMA (1.6/±0.15/p=0.0028) significantly, key modulators of extracellular matrix composition in vitro . The addition of RNO significantly reversed this induction after 24 hours for all parameters (CTGF:-21%, Col1A1:-23%, α-SMA:-30%), whereas BUD did not exert such an inhibitory effect for SMA and CTGF.

Conclusion:

Roflumilast N-oxide diminished TGF-β-induced gene transcription of different markers of remodelling (Col1A1, SMA, CTGF) in isolated human primary fibroblasts of COPD patients. These findings may support the notion of roflumilast N-oxide mitigating a fibrotic response in COPD.
Cloning and Characterization of DULP, a Novel Ubiquitin-Like Molecule from Human Dendritic Cells
Authors: Guoyan Liu, Shuxun Liu, Ping Li, Ling Tang, Yanmei Han, Huazhang An, Jiangyan Li, Xiankun Dai, Nan Li, Xuetao Cao, Yizhi Yu
Journal: Cellular and Molecular Immunology (2009)
Xena, a Full-Length Basal Retroelement from Tetraodontid Fish
Authors: Damian E. Dalle Nogare, Melody S. Clark, Greg Elgar, Ian G. Frame, Russell T. M. Poulter
Journal: Molecular Biology and Evolution (2002)

Mobile genetic elements are ubiquitous throughout the eukaryote superkingdom. We have sequenced a highly unusual full-length retroelement from the Fugu fish, Takifugu rubripes. This element, which we have named Xena, is similar in structure and sequence to the Penelope retroelement from Drosophila virilis and consists of a single long open reading frame containing a reverse transcriptase domain flanked by identical direct long terminal repeat (LTR) sequences. These LTRs show an organization similar to the terminal repeats already described in the Penelope retrotransposon of Drosophila but are structurally and functionally distinct from the LTRs carried by LTR-retrotransposons. In view of their distinctness, we refer to these repeats as PLTRs (Penelope-LTRs). Whereas the element contains a reverse transcriptase, no other domains or motifs commonly associated with retroelements are present. In the full-length Fugu element, the 5′ direct PLTR is preceded by an inverted PLTR fragment. Additional elements, many showing various degrees of deletion, are described from the Fugu genome and from that of the freshwater pufferfish Tetraodon nigroviridis. Many of these additional elements are also preceded by inverted PLTR sequences. Xena-like elements are also described from the genomes of several other organisms. The Penelope-Xena lineage is apparently a basal group within the retrotransposons and therefore represents an evolutionarily important class of retroelement.
Coeliac disease: how much of what is toxic to whom?
Authors: C F FEIGHERY
Journal: Gut (1998)

See article on page 190 

The cause of coeliac disease remained an enigma until the early 1950s when the Dutch paediatrician, W K Dicke made his seminal observation that gluten, the major storage protein of wheat cereal, is essential to the pathogenesis of the disease.1 Removal of gluten from the diet permits virtually complete recovery of the intestinal mucosa and reversal of the clinical and laboratory abnormalities. The precise mechanism whereby gluten causes damage to certain susceptible individuals has still to be elucidated. Many features of the disorder are in keeping with central involvement of the immune response, displaying a delayed-type hypersensitivity reaction to gluten. However, other features are in keeping with a so called autoimmune disease: these include a notable association with MHC class II genes (in particular HLA-DQ2), a female preponderance of approximately 3 to 1, and the presence of an autoantibody, the anti-endomysial antibody. Thus, coeliac disease could represent an unique example of autoimmune disease, where the disease process is absolutely dependent on continued exposure to an exogenous, dietary protein.

In 1983, Chorzelski and colleagues reported the association between gluten sensitive disease and circulating IgA anti-endomysial antibodies.2 In 1997, the nature of the endomysial antigen was discovered to be tissue transglutaminase3 and this gave an intriguing insight into the link between gluten and anti-endomysial antibodies: …
Brain Malignancy Steering Committee clinical trials planning workshop: Report from the Targeted Therapies Working Group
Authors: B. M. Alexander, E. Galanis, W. K. A. Yung, K. V. Ballman, J. M. Boyett, T. F. Cloughesy, J. F. Degroot, J. T. Huse, B. Mann, W. Mason, I. K. Mellinghoff, T. Mikkelsen, P. S. Mischel, B. P. O'Neill, M. D. Prados, J. N. Sarkaria, A. Tawab-Amiri, L. Trippa, X. Ye, K. L. Ligon, D. A. Berry, P. Y. Wen
Journal: Neuro-Oncology (2014)

Glioblastoma is the most common primary brain malignancy and is associated with poor prognosis despite aggressive local and systemic therapy, which is related to a paucity of viable treatment options in both the newly diagnosed and recurrent settings. Even so, the rapidly increasing number of targeted therapies being evaluated in oncology clinical trials offers hope for the future. Given the broad range of possibilities for future trials, the Brain Malignancy Steering Committee convened a clinical trials planning meeting that was held at the Udvar-Hazy Center in Chantilly, Virginia, on September 19 and 20, 2013. This manuscript reports the deliberations leading up to the event from the Targeted Therapies Working Group and the results of the meeting.
Antireticulin antibody: Incidence and diagnostic significance
Authors: P. P. Seah, L. Fry, E. J. Holborow, M. A. Rossiter, W. F. Doe, A. F. Magalhaes, A. V. Hoffbrand
Journal: Gut (1973)

Sera from 101 patients with adult coeliac disease, 46 patients with childhood coeliac disease, 50 patients with dermatitis herpetiformis, and 479 patients with various other diseases, including skin, gastrointestinal, haematological, and immunological disorders, have been tested for the presence of the antireticulin antibody. Positive sera were retested at higher dilutions. Antireticulin antibody was only found in a significant proportion of patients with three diseases, ie, coeliac disease, dermatitis herpetiformis, and Crohn's disease. Antireticulin antibody was present in 38 out of 101 patients (38%) with adult coeliac disease, 27 out of 46 patients (59%) with childhood coeliac disease, 11 out of 50 patients (22%) with dermatitis herpetiformis, and nine out of 38 patients (24%) with Crohn's disease. In the 434 other patients with various disorders the antireticulin antibody was present in only six 1.4%) (two patients were pregnant, one had vitiligo, one had tropical sprue, one had reticulum cell sarcoma, and one had pernicious anaemia). In patients with gluten-sensitive enteropathy, ie, coeliac disease and dermatitis herpetiformis, there was a significantly higher incidence in patients taking a normal diet compared with those on a gluten-free diet. The presence of antireticulin antibody would appear to be particularly helpful in diagnosing childhood coeliac disease as it was found in 22 out of 26 patients (85%) taking a normal diet.
Sympathetic Activity Is Increased in Polycystic Kidney Disease and Is Associated with Hypertension
Authors: INGE H. H. T. KLEIN, GERRY LIGTENBERG, P. LIAM OEY, HEIN A. KOOMANS, PETER J. BLANKESTIJN
Journal: Journal of the American Society of Nephrology (2001)

Hypertension is common in patients with polycystic kidney disease (PKD). This study addresses the hypothesis that sympathetic activity is enhanced in hypertensive PKD patients, not only when renal function is impaired but also when renal function is still normal. Muscle sympathetic nerve activity (MSNA, peroneal nerve), plasma renin activity (PRA), heart rate, and BP were studied in PKD patients with normal and with impaired renal function and in matched controls. In hypertensive patients with normal renal function, MSNA and mean arterial pressure (MAP) were higher than in normotensive patients (23 ± 5 versus 15 ± 7 bursts/min; 110 ± 10 versus 90 ± 3 mmHg; P < 0.05), whereas PRA and heart rate did not differ. In PKD with chronic renal failure (CRF) (creatinine clearance rate, 39 ± 19 ml/min), MAP, MSNA and PRA were higher than in controls (resp, 116 ± 7 versus 89 ± 9 mmHg; 34 ± 14 versus 19 ± 9 bursts/min; 405 [20 to 1640] versus 120 [40 to 730] fmol/L per sec; all P < 0.05). Heart rate in PKD CRF did not differ from controls. MSNA correlated with MAP (r = 0.42; P = 0.01) and age with MSNA (r = 0.45; P < 0.01). Regression line of age and MSNA in patients was steeper than that in controls. This study indicates that MSNA is increased in hypertensive PKD patients regardless of renal function. The data support the idea that sympathetic hyperactivity contributes to the pathogenesis of hypertension in PKD.
Relaxin improves TNF-α-induced endothelial dysfunction: the role of glucocorticoid receptor and phosphatidylinositol 3-kinase signalling
Authors: Thomas Dschietzig, Anna Brecht, Cornelia Bartsch, Gert Baumann, Karl Stangl, Konstantin Alexiou
Journal: Cardiovascular Research (2012)

AimsHuman relaxin-2 influences renal and cardiovascular functions. We investigated its effects on experimental endothelial dysfunction.
Factors associated with hospital mortality in community-acquired legionellosis in France
Authors: C. Chidiac, D. Che, S. Pires-Cronenberger, S. Jarraud, C. Campèse, A. Bissery, P. Weinbreck, C. Brun-Buisson, J-P. Sollet, R. Ecochard, J-C. Desenclos, J. Etienne, P. Vanhems
Journal: European Respiratory Journal (2011)

The aims of this study were to describe the clinical, biological and radiological features of community-acquired (CA) Legionnaires' disease (LD) and identify the predictors of mortality in hospitalised patients. Demographic data, risk factors, clinical and biological features, medical management, complications, and outcome from 540 hospitalised patients with confirmed CA LD were prospectively recorded. 8.1% of patients (44 out of 540) died. The predictors of survival after Kaplan-Meier analysis were male sex (p = 0.01), age <60 yrs (p = 0.02), general symptoms (p = 0.006), intensive care unit (ICU) stay (p<0.001), and class II-III Pneumonia Severity Index score (p = 0.004). Six predictors of death were identified by multivariate analysis: age (per 10-yr increment) (relative hazard (RH) 1.50, 95% CI 1.21-1.87), female sex (RH 2.00, 95% CI 1.08-3.69), ICU admission (RH 3.31, 95% CI 1.67-6.56), renal failure (RH 2.73, 95% CI 1.42-5.27), corticosteroid therapy (RH 2.54, 95% CI 1.04-6.20) and C-reactive protein (CRP) >500 mg · L(-1) (RH 2.14, 95% CI 1.02-4.48). Appropriate antibiotic therapy was prescribed for 70.8% (292 out of 412) of patients after admission and for 99.8% (537 out of 538) of patients after diagnosis confirmation. In conclusion, female sex, age, ICU stay, renal failure, corticosteroid treatment and increased level of CRP are significant risk factors for mortality in CA LD.
IP-10 as a biomarker for rhinoviral infections in asthma
Authors: Jennifer K Quint
Journal: Thorax (2008)

Asthma exacerbations are most commonly triggered by viruses, particularly rhinovirus. There is currently no biomarker that can be used to predict that a virus has triggered an exacerbation.

This group studied bronchial epithelial cells (BECs) obtained by bronchoscopy from 10 healthy controls and 10 patients with asthma who had never received inhaled corticosteroids. The epithelial cells were cultured and exposed to rhinovirus …
Unsuspected Chronic Glaucoma
Authors: W. M. Walker
Journal: BMJ (1963)

MEDICBJOURNA1947, but the mass at the transverse colon was much larger than before and a biopsy only was taken, which showed the presence of anaplastic adenocarcinoma.The patient made a good recovery and was discharged home on December 20, 1947.She attended my follow-up clinic for some years and I last saw her about 10 years ago."On October 2, 1963, the patient was admitted to New Cross Hospital in a con- fused senile state associated with hyperten- sion, blood-pressure 220/130, and severe bronchopneumonia from which she died on October 7.At necropsy there was an encysted empyema between the middle and lower lobes of the right lung, the lower lobe showing bronchopneumonia.The left lung was congested.The heart weighed 430 g. and the coronary arteries were atheromatous.The gastro-intesti nal tract showed no evidence of growth.The omentum and mesentery appeared normal.No glands were present.Sections were examined from post- mortem tissues and no evidence of carcinoma was demonstrated.
Comparison of cervical magnetic stimulation and bilateral percutaneous electrical stimulation of the phrenic nerves in normal subjects
Authors: S Wragg, R Aquilina, J Moran, M Ridding, C Hamnegard, T Fearn, M Green, J Moxham
Journal: European Respiratory Journal (1994)

Cervical magnetic stimulation is a new technique for stimulating the phrenic nerves, and may offer an alternative to percutaneous electrical stimulation for assessing diaphragmatic strength in normal subjects and patients in whom electrical stimulation is technically difficult or poorly tolerated. We compared cervical magnetic stimulation with conventional supramaximal bilateral percutaneous electrical stimulation in nine normal subjects. We measured oesophageal pressure (Poes), gastric pressure (Pgas) and transdiaphragmatic pressure (Pdi). The maximal relaxation rate (MRR) was also measured. The mean magnetic twitch Pdi was 36.5 cmH2O (range 27-48 cmH2O), significantly larger than electrical twitch Pdi, mean 29.7 cmH2O (range 22-40 cmH2O). The difference in twitch Pdi was explained entirely by twitch Poes, and it is possible that the magnetic technique stimulates some of the nerves to the upper chest wall muscles as well as the phrenic nerves. We compared bilateral, rectified, integrated, diaphragm surface electromyographic (EMG) responses in three subjects and found results within 10% in each subject, indicating similar diaphragmatic activation. The within occasion coefficient of variation, i.e. same subject/same session, was 6.7% both for magnetic and electrical twitch Pdi. The between occasion coefficient of variation, i.e. same subject/different days, was 6.6% for magnetic stimulation and 8.8% for electrical. There was no difference between relaxation rates measured with either technique. We conclude that magnetic stimulation is a reproducible and acceptable technique for stimulating the phrenic nerves, and that it provides a potentially useful alternative to conventional electrical stimulation as a nonvolitional test of diaphragm strength.
Outcome of Patients With Residual Germ Cell or Non-Germ Cell Malignancy After Resection of Primary Mediastinal Nonseminomatous Germ Cell Cancer
Authors: Bryan P. Schneider, Kenneth A. Kesler, Jo Ann Brooks, Constantin Yiannoutsos, Lawrence H. Einhorn
Journal: Journal of Clinical Oncology (2004)

Purpose To identify prognostic variables and outcomes in patients with primary mediastinal nonseminomatous germ cell tumor (PMNSGCT) with postchemotherapy resection of persistent cancer. Patients and Methods Forty-seven consecutive patients with residual cancer after resection of PMNSGCT were retrospectively reviewed. Univariate comparisons were performed. Results At diagnosis, 43 patients had elevated serum tumor markers (STMs), and 20 had extramediastinal disease. At resection, 21 patients had elevated STMs. After resection, 26 patients had germ cell tumors (GCT), 12 had malignant transformation of teratoma with elements of non-GCT, and nine had both GCT and non-GCT. Sixteen of 47 patients continuously have no evidence of disease (NED). This includes eight of 26 patients with GCT histology and two of 12 patients with non-GCT histology. Of 27 patients with mediastinal-only disease at presentation, 14 have continuously NED. Of 20 patients with extramediastinal disease at presentation, two have continuously NED. Seven of 21 patients with elevated STMs at time of resection have continuously NED. Sixteen patients received adjuvant chemotherapy, and seven have continuously NED. Overall, 16 of 47 patients have continuously NED, an additional four patients have NED with further therapy (currently NED), two patients are alive with disease, 23 patients died of disease, and two patients died postoperatively. Conclusion The presence of elevated STMs at resection does not appear to alter outcome if residual disease is completely resected. In this poor-risk patient population, surgical resection of persistent cancer, even in the presence of elevated STMs, can still achieve long-term survival.