tbuckley/cabot-search huggingface dataset:
Relationship between respiratory muscle function and quality of life in sarcoidosis
Authors: RM Wirnsberger, M Drent, N Hekelaar, MH Breteler, S Drent, EF Wouters, PN Dekhuijzen
Journal: European Respiratory Journal (1997)

In sarcoidosis, pulmonary and general symptoms often do not correlate with radiographic stage and routinely performed lung function tests. Asymptomatic muscle involvement in sarcoidosis is common, but little is known about respiratory muscle involvement. The aim of this study was to investigate any relationships between persistent complaints and/or quality of life and respiratory muscle strength and endurance, respectively. Measurements of maximal inspiratory and expiratory mouth pressures (PI,max and PE,max), respiratory muscle endurance and routine lung function were made in 18 patients with sarcoidosis. To assess health status and quality of life, patients completed the Sickness Impact Profile (SIP). Respiratory muscle strength and endurance time were lower in the patient group than in a group of healthy controls (p=0.05). Compared to a general population, the patients with sarcoidosis were found to be limited in physical and psychosocial functioning. The respiratory muscle endurance time correlated with the SIP subscales "mobility" (r=-0.56; p<0.01), and "body care and movement" (r=-0.79; p<0.001). The total lung capacity (TLC), inspiratory vital capacity (IVC) and forced expiratory volume in one second (FEV1) were normal in all subjects. In conclusion, patients with sarcoidosis and normal lung function showed reduced respiratory muscle strength and endurance time. Correlations were found between these indices and both symptoms and certain Sickness Impact Profile domains. Therefore, we suggest inclusion of measurements of respiratory muscle strength in the assessment and follow-up of patients with sarcoidosis.
A functional platelet fibrinogen receptor with a deletion in the cysteine-rich repeat region of the β3 integrin: the Oea alloantigen in neonatal alloimmune thrombocytopenia
Authors: Sentot Santoso, Volker Kiefel, Ina G. Richter, Ulrich J. H. Sachs, Abdul Rahman, Bettina Carl, Harmut Kroll
Journal: Blood (2002)
Urine proteomic analysis differentiates cholangiocarcinoma from primary sclerosing cholangitis and other benign biliary disorders
Authors: Jochen Metzger, Ahmed A Negm, Ruben R Plentz, Tobias J Weismüller, Jochen Wedemeyer, Tom H Karlsen, Mohammed Dakna, William Mullen, Harald Mischak, Michael P Manns, Tim O Lankisch
Journal: Gut (2012)

Diagnosis and curative treatment of cholangiocarcinoma (CC) often comes too late due to the lack of reliable tumour markers especially in patients with primary sclerosing cholangitis (PSC). The authors recently introduced bile proteomic analysis for CC diagnosis. Nevertheless, bile collection depends on invasive endoscopic retrograde cholangiography. The authors therefore evaluated urine proteomic analysis for non-invasive CC diagnosis.Using capillary electrophoresis mass spectrometry the authors established a CC-specific peptide marker model based on the distribution of 42 peptides in 14 CC, 13 PSC and 14 benign biliary disorder (BBD) patients.In cross-sectional validation of 123 patients, the urine peptide marker model correctly classified 35 of 42 CC patients and 64 of 81 PSC and BBD patients with an area under the curve value of 0.87 (95% CI 0.80 to 0.92, p=0.0001, 83% sensitivity, 79% specificity). Evaluation of 101 normal controls resulted in 86% specificity. All 10 patients with CC on top of PSC were correctly classified. The majority of sequence-identified peptides are fragments of interstitial collagens with some of them also detected in blood indicating their extra-renal origin. Immunostaining of liver sections for matrix metallopeptidase 1 indicated increased activity of the interstitial collagenase in liver epithelial cells of CC patients.The urine test differentiates CC from PSC and other BBD and may provide a new diagnostic non-invasive tool for PSC surveillance and CC detection.
EFFECT OF INTENSE SONIC VIBRATIONS ON ELEMENTARY BODIES OF VACCINIA
Authors: Thomas M. Rivers, Joseph E. Smadel, Leslie A. Chambers
Journal: The Journal of Experimental Medicine (1937)

Thoroughly washed elementary bodies of vaccinia were inactivated by sonic vibrations with a frequency of about 8900 cycles per second; the inactivation was not accompanied by a disruption of the bodies. Adventitious substances, notably protein, prevented or hindered the inactivation. There is some evidence that oxidation might have played a rôle in the inactivation.
FitSNPs: highly differentially expressed genes are more likely to have variants associated with disease
Authors: Rong-Rong Chen, Alex A. Morgan, Joel T Dudley, Tarangini Deshpande, Li Li, Keiichi Kodama, Annie P Chiang, Atul J Butte
Journal: Genome biology (2008)

Candidate single nucleotide polymorphisms (SNPs) from genome-wide association studies (GWASs) were often selected for validation based on their functional annotation, which was inadequate and biased. We propose to use the more than 200,000 microarray studies in the Gene Expression Omnibus to systematically prioritize candidate SNPs from GWASs. We analyzed all human microarray studies from the Gene Expression Omnibus, and calculated the observed frequency of differential expression, which we called differential expression ratio, for every human gene. Analysis conducted in a comprehensive list of curated disease genes revealed a positive association between differential expression ratio values and the likelihood of harboring disease-associated variants. By considering highly differentially expressed genes, we were able to rediscover disease genes with 79% specificity and 37% sensitivity. We successfully distinguished true disease genes from false positives in multiple GWASs for multiple diseases. We then derived a list of functionally interpolating SNPs (fitSNPs) to analyze the top seven loci of Wellcome Trust Case Control Consortium type 1 diabetes mellitus GWASs, rediscovered all type 1 diabetes mellitus genes, and predicted a novel gene (KIAA1109) for an unexplained locus 4q27. We suggest that fitSNPs would work equally well for both Mendelian and complex diseases (being more effective for cancer) and proposed candidate genes to sequence for their association with 597 syndromes with unknown molecular basis. Our study demonstrates that highly differentially expressed genes are more likely to harbor disease-associated DNA variants. FitSNPs can serve as an effective tool to systematically prioritize candidate SNPs from GWASs.
Primary care opportunities and threats Developing professional knowledge: Making primary care education and research more relevant
Authors: P. Pearson, K. Jones
Journal: BMJ (1997)

The trio of recent government white papers heralds a new world for primary care. Many changes in the education of future primary health care professionals and in the research ethos of the discipline will be needed to realise this vision. New skills and attitudes, not least in multidisciplinary working; lifelong learning; and greater understanding of and participation in primary care research will have to emerge from educational efforts in the next few years.
Gimema Registry of Conception/Pregnancy in Adult Patients Diagnosed with Chronic Myeloid Leukemia (CML) Treated with Tyrosine Kinase Inhibitors (TKIs)
Authors: Elisabetta Abruzzese, Anna Rita Scortechini, Gabriele Gugliotta, Ivana Pierri, Caterina Musolino, Alessandra Iurlo, Lucia Mastrullo, Clementina Caracciolo, Ester Orlandi, Sara Galimberti, Marzia Salvucci, Paolo Avanzini, Simona Sica, Giuliana Alimena, Monica Bocchia, Patrizia Pregno, Anna D'Emilio, Carlo Gambacorti-Passerini, Fabio Stagno, Domenico Santorsola, Fausto Castagnetti, Alessio Pio Perrotti, Paolo de Fabritiis, Michele Baccarani
Journal: Blood (2014)
KRAS-Mutation Positive, Metastatic Tonsil Carcinoma With Cancer Stem-Like Cell Features and Long-Term Response to Gefitinib: A Case Report and Review of the Literature
Authors: Sandra Gottschling, Roland Penzel, Tanja Pelz, Esther Herpel, Philipp A. Schnabel, Gerhard Dyckhoff, Michael Thomas, Thomas Kuhnt
Journal: Journal of Clinical Oncology (2011)
Insulin Detemir Is Associated With More Predictable Glycemic Control and Reduced Risk of Hypoglycemia Than NPH Insulin in Patients With Type 1 Diabetes on a Basal-Bolus Regimen With Premeal Insulin Aspart
Authors: Philippe Vague, Jean-Louis Selam, Svein Skeie, Ivo De Leeuw, Jan W.F. Elte, Hanne Haahr, Allan Kristensen, Eberhard Draeger
Journal: Diabetes Care (2003)

OBJECTIVE—Insulin detemir is a soluble basal insulin analog with a unique mechanism of protracted action designed to reduce the variability associated with conventional basal insulins. This trial compared the glycemic control, risk of hypoglycemia, and effect on body weight of insulin detemir and NPH insulin in patients with type 1 diabetes treated with rapid-acting insulin aspart at meals. RESEARCH DESIGN AND METHODS—This study was a 6-month multinational open parallel-group comparison conducted at 46 centers in five countries and included 448 patients with type 1 diabetes randomized 2:1 to insulin detemir or NPH insulin, respectively. RESULTS—After 6 months, comparable HbA1c levels were found between the two treatment groups. Fasting plasma glucose tended to be lower in patients treated with insulin detemir, but this difference was not statistically significant (−0.76 mmol/l, P = 0.097). Within-subject variation in self-measured fasting blood glucose was lower with insulin detemir than with NPH insulin (SD 3.37 vs. 3.78 mmol/l, P &amp;lt; 0.001). Risk of hypoglycemia was 22% lower with insulin detemir than with NPH insulin (P &amp;lt; 0.05) and 34% lower for nocturnal (2300–0600) hypoglycemia (P &amp;lt; 0.005). Nightly plasma glucose profiles were smoother and more stable with insulin detemir (P = 0.05). Body weight was significantly lower with insulin detemir at the end of the trial (P &amp;lt; 0.001). CONCLUSIONS—Treatment with insulin detemir resulted in more predictable glycemic control, with smoother plasma glucose profiles than NPH insulin and a significant reduction in the risk of hypoglycemia. The reduction in body weight with insulin detemir is a potential additional advantage. Regimens optimized for insulin detemir may be able to improve glycemic control beyond that possible with NPH insulin.
Smoking cessation in patients with respiratory diseases: a high priority, integral component of therapy
Authors: P. Tønnesen, L. Carrozzi, K. O. Fagerström, C. Gratziou, C. Jimenez-Ruiz, S. Nardini, G. Viegi, C. Lazzaro, I. A. Campell, E. Dagli, R. West
Journal: European Respiratory Journal (2007)

Smoking cessation is the one of the most important ways to improve the prognosis of patients with respiratory disease. The Task Force on guidelines for smoking cessation in patients with respiratory diseases was convened to provide evidence-based recommendations on smoking cessation interventions in respiratory patients. Based on the currently available evidence and the consensus of an expert panel, the following key recommendations were made. 1) Patients with respiratory disease have a greater and more urgent need to stop smoking than the average smoker, so respiratory physicians must take a proactive and continuing role with all smokers in motivating them to stop and in providing treatment to aid smoking cessation. 2) Smoking cessation treatment should be integrated into the management of the patient's respiratory condition. 3) Therapies should include pharmacological treatment ( i . e . nicotine replacement therapy, bupropion or varenicline) combined with behavioural support. 4) Respiratory physicians should receive training to ensure that they have the knowledge, attitudes and skills necessary to deliver these interventions or to refer to an appropriate specialist. 5) Although the cost of implementing these recommendations will partly be offset by a reduction in attendance for exacerbations, etc ., a budget should be established to enable implementation. Research is needed to establish optimum treatment strategies specifically for respiratory patients.
Estrogen Inhibits Cell Proliferation through <i>In situ</i> Production in Human Thymoma
Authors: Hironori Ishibashi, Takashi Suzuki, Satoshi Suzuki, Takuya Moriya, Chika Kaneko, Taisuke Nakata, Makoto Sunamori, Masashi Handa, Takashi Kondo, Hironobu Sasano
Journal: Clinical Cancer Research (2005)

We showed previously estrogen receptor (ER) alpha as an independent prognostic marker in human thymoma. Estrogen sulfotransferase (EST), steroid sulfatase (STS), 17beta-hydroxysteroid dehydrogenase (17beta-HSD), and aromatase are considered to play important roles in hormone metabolism of estrogen-dependent tumors.We examined estrogen production using primary cultures of human thymoma epithelial cells (TEC), intratumoral estradiol (E(2)) concentrations, and status of these enzymes above using immunohistochemistry or semiquantitative reverse transcription-PCR. We then correlated these findings with clinicopathologic variables and/or clinical outcome in 132 patients.E(2) inhibited cell proliferation via ERalpha in TEC, which synthesized estrone and E(2). Intratumoral E(2) concentrations were inversely correlated with EST, positively correlated with STS or 17beta-HSD type 1, and significantly higher in lower-grade or early-stage thymoma. EST status was positively correlated with tumor size, clinical stage, histologic differentiation, and Ki-67 labeling index and significantly associated with adverse clinical outcome and turned out to be a potent independent prognostic factor. STS and/or 17beta-HSD type 1 status was inversely correlated with Ki-67 labeling index and associated with lower histologic grade or early clinical stages.E(2) inhibits proliferation of TEC through ERalpha, which suggests that E(2) may be effective in treatment of thymoma, especially inoperable tumor, possibly through suppressing its cell proliferation activity. EST status is a potent prognostic factor in thymoma through inactivating estrogens. In situ estrogen synthesis through intracrine mechanism therefore may play important roles in tumorigenesis and/or development of thymoma through regulation of cell proliferation in an intracrine manner.
Intraluminal crawling of neutrophils to emigration sites: a molecularly distinct process from adhesion in the recruitment cascade
Authors: Mia Phillipson, Bryan Heit, Pina Colarusso, Lixin Liu, Christie M. Ballantyne, Paul Kubes
Journal: The Journal of Experimental Medicine (2006)

The prevailing view is that the β2-integrins Mac-1 (αMβ2, CD11b/CD18) and LFA-1 (αLβ2, CD11a/CD18) serve similar biological functions, namely adhesion, in the leukocyte recruitment cascade. Using real-time and time-lapse intravital video-microscopy and confocal microscopy within inflamed microvessels, we systematically evaluated the function of Mac-1 and LFA-1 in the recruitment paradigm. The chemokine macrophage inflammatory protein-2 induced equivalent amounts of adhesion in wild-type and Mac-1−/− mice but very little adhesion in LFA-1−/− mice. Time-lapse video-microscopy within the postcapillary venules revealed that immediately upon adhesion, there is significant intraluminal crawling of all neutrophils to distant emigration sites in wild-type mice. In dramatic contrast, very few Mac-1−/− neutrophils crawled with a 10-fold decrease in displacement and a 95% reduction in velocity. Therefore, Mac-1−/− neutrophils initiated transmigration closer to the initial site of adhesion, which in turn led to delayed transmigration due to movement through nonoptimal emigration sites. Interestingly, the few LFA-1−/− cells that did adhere crawled similarly to wild-type neutrophils. Intercellular adhesion molecule-1 but not intercellular adhesion molecule-2 mediated the Mac-1–dependent crawling. These in vivo results clearly delineate two fundamentally different molecular mechanisms for LFA-1 and Mac-1 in vivo, i.e., LFA-1–dependent adhesion followed by Mac-1–dependent crawling, and both steps ultimately contribute to efficient emigration out of the vasculature.
Impairment of mitochondrial acetoacetyl CoA thiolase activity in the colonic mucosa of patients with ulcerative colitis
Authors: S. Santhanam, A. Venkatraman, B. S Ramakrishna
Journal: Gut (2007)

Butyrate oxidation by colonocytes is impaired in ulcerative colitis. This study examined the activity of enzymes involved in butyrate oxidation in ulcerative colitis.Activities of mitochondrial acetoacetyl coenzyme A (CoA) thiolase, crotonase and beta-hydroxy butyryl CoA dehydrogenase were estimated spectrophotometrically in rectosigmoid mucosal biopsies from patients with ulcerative colitis and Crohn's colitis, and control subjects undergoing colonoscopy for colon cancer or rectal bleeding.The activity of mitochondrial acetoacetyl CoA thiolase was decreased by 80% in ulcerative colitis (3.4 (0.58) mumol/min/g wet weight, n = 30) compared with control (16.9 (3.5), n = 18) and with Crohn's colitis (17.6 (3.1), n = 12) (p<0.0001). The activity of two other mitochondrial butyrate oxidation enzymes--crotonase and beta-hydroxy butyryl CoA dehydrogenase--as well as of cytoplasmic thiolase was normal in ulcerative colitis. Mitochondrial thiolase activity in ulcerative colitis did not correlate with clinical, endoscopic or histological indices of disease severity. Mitochondrial thiolase activity was reduced in the normal right colon mucosa of patients with left-sided ulcerative colitis. Enzyme kinetic studies revealed a lowered V(max), suggesting inhibition at a site distinct from the catalytic site. Reduced thiolase activity in ulcerative colitis was returned to normal by exposure to 0.3 mM beta-mercaptoethanol, a reductant. Using normal colon mucosal biopsies, redox modulation of thiolase activity by hydrogen peroxide, a mitochondrial oxidant, could be shown. A significant increase in hydrogen peroxide formation was observed in ulcerative colitis biopsies.A defect of mitochondrial acetoacetyl CoA thiolase occurs in ulcerative colitis. Increased reactive oxygen species generation in mitochondria of epithelial cells in ulcerative colitis may underlie this defect.
Allogeneic suppressive effects of pregnancy sera on monocytes of responding cells in human mixed lymphocyte reactions.
Authors: M Nieda, T Juji, S Imao
Journal: Journal of Clinical Investigation (1985)

The purified human monocytes of a responding donor preincubated with heat-inactivated serum T1264 or T1295 derived from pregnant women for 30 min at 37 degrees C expressed allogeneic suppressive effects on the proliferative response of the lymphocytes from the same donor in the allogeneic mixed lymphocyte reaction (MLR). The pregnancy serum in our experiments was found not to contain any antibodies to DR and DQ antigens on monocytes of the responding donor. Accordingly, the suppressive effects mediated by monocytes were not based on the blocking of DR and DQ antigens on monocytes of the responding donor by DR and DQ antibodies in the serum. These highly reproducible allogeneic suppressive effects by monocytes of the responding donor were demonstrated in the MLR specific for DRw9-positive stimulating cells, whereas no inhibition was seen in the cultures with other stimulating cells of different DR phenotypes. Additionally, these suppressive effects appeared on the monocytes of a DR2-positive responding donor, but not on the monocytes of a DR2-negative responding donor. These suppressive effects were abolished when the absorbed pregnancy serum by monocytes of the DR2-positive responding donor was used. In this suppression phenomenon that we discovered, monocytes of the responding donor appear to act as regulatory cells on the proliferative response of the allogeneic MLR. This regulatory function of monocytes could be expressed through the specific molecules distinct from DR and DQ determinants on monocytes in cooperation with antibodies (IgG class) in the pregnancy serum.
Thunderstorm-associated asthma in an inland town in south-eastern Australia. Who is at risk?
Authors: S.T. Girgis, G.B. Marks, S.h Downs, A Kolbe, G.n Car, R Paton
Journal: European Respiratory Journal (2000)

The aim of the study was to characterize patients at risk of asthma exacerbation during spring thunderstorms and identify potential measures to ameliorate the impact of those events. A case-control study was conducted among patients aged 7-60 yrs, who attended Wagga Hospital (NSW, Australia) for asthma during the period of 1 June 1997 to 31 October 1997. One hundred and eighty-three patients who attended on 30 and 31 October 1997 were the cases and the remaining 121 patients were the controls. Questionnaire data were obtained from 148 (81%) cases and 91 (75%) controls. One hundred and thirty-eight (95%) cases who attended during the thunderstorm gave a history of hayfever prior to the event compared to 66 (74%) controls who attended at other times (odds ratio (OR) 6.01, 95% confidence interval (CI) 2.55-14.15); 111 (96%) cases were allergic to rye grass pollen compared to 47 (64%) controls (OR 23.6, 95% CI 6.6-84.3). Among subjects with a prior diagnosis of asthma (64% cases and 82% controls), controls (56%) were more likely to be taking inhaled steroids at time of the thunderstorm than cases (27%, OR 0.3, 95% CI 0.16-0.57). History of hayfever and allergy to rye grass are strong predictors for asthma exacerbation during thunderstorms in spring. The lower rate of inhaled steroid use in thunderstorm cases suggests that this treatment may be effective in preventing severe attacks during thunderstorms.
Perceived hyperoxia: Oxygen-induced remodeling of the reoxygenated heart
Authors: C SEN, S KHANNA, S ROY
Journal: Cardiovascular Research (2006)

Focal coronary artery blockage followed by further reperfusion injury is commonly involved in myocardial infarction. The injured heart has some inherent reparative responses. Although such natural healing mechanisms seem to be inefficient, a clear understanding of the underlying principles of myocardial healing holds the key to successful therapy. Under normoxic conditions, pO(2) ranges from 90 to <3 Torr in mammalian organs with the heart at approximately 35 Torr (5%) and arterial blood at approximately 100 Torr. Thus, "normoxia" for cells is an adjustable variable. In response to chronic moderate hypoxia, cells lower their normoxia set-point such that reoxygenation-dependent relative elevation of pO(2) (+DeltapO(2)) results in perceived hyperoxia. Perceived hyperoxia induces differentiation of cardiac fibroblasts to myofibroblasts in the peri-infarct region and represents a significant factor supporting myocardial healing. The oxygen-sensitive signaling pathways involved have been characterized and point towards a central role of p21, TGFbeta and p38MAPK. That low oxygen ambience serves as a cue to trigger angiogenesis is a well-accepted notion. Studies related to perceived hyperoxia establish that the sensing of oxygen environment is not limited to hypoxia. It demonstrates that in addition to being a trigger for injury as is widely recognized, reoxygenation insult has a built-in component of tissue remodeling in the peri-infarct region induced by perceived hyperoxia. Understanding of the underlying mechanisms of this and other myocardial healing responses should prove to be instrumental in developing productive therapeutic approaches to mend the infarcted heart.