tbuckley/cabot-search huggingface dataset:
A comparison of six different ways of expressing the bronchodilating response in asthma and COPD; reproducibility and dependence of prebronchodilator FEV1
Authors: E Dompeling, CP van Schayck, J Molema, R Akkermans, H Folgering, PM van Grunsven, C van Weel
Journal: European Respiratory Journal (1992)

Various indices are used to express the bronchodilating response. It is unclear, however, which index is most informative. The aim of this study was to compare six expressions of the bronchodilating response and to examine: 1) the independence of the prebronchodilator forced expiratory volume in one second (FEV1); and 2) the reproducibility of the bronchodilating response. Bronchodilating responses (increases in FEV1 60 min after salbutamol 400 micrograms and ipratropium bromide 80 micrograms) on six test occasions, during two years, of 183 patients (72 asthma, 111 chronic obstructive pulmonary disease (COPD)) from a large bronchodilator intervention study were used. The dependence of the prebronchodilator FEV1 was investigated both between patients (cross-sectional analysis) and within patients (longitudinal analysis) by means of linear regression analysis. The reproducibility of the bronchodilating response was calculated by means of the coefficients of variation (CVs) of the six bronchodilating responses during two years. The CVs of the six expression indices were compared by analysis of variance (ANOVA). No index was independent of the prebronchodilator FEV1. However, some indices were significantly more dependent on the prebronchodilator lung function and, therefore, less reproducible than others. The "% initial" index (change as a percentage of the prebronchodilator value) was the most dependent on the prebronchodilator lung function and had the worst reproducibility (CV ranged from 50-61%). The "% possible" (change as a percentage of the predicted minus prebronchodilator value) and "% achievable" (change as a percentage of the maximal postbronchodilator minus prebronchodilator value) indices were the least dependent on the prebronchodilator value and had the highest reproducibility (CV ranging from 34-53%).(ABSTRACT TRUNCATED AT 250 WORDS)
C reactive protein and chronic obstructive pulmonary disease: a Mendelian randomisation approach
Authors: M. Dahl, J. Vestbo, J. Zacho, P. Lange, A. Tybjaerg-Hansen, B. G. Nordestgaard
Journal: Thorax (2010)

<h3>Background</h3> It is unclear whether elevated plasma C reactive protein (CRP) is causally related to chronic obstructive pulmonary disease (COPD). The authors tested the hypothesis that genetically elevated plasma CRP causes COPD using a Mendelian randomisation design. <h3>Methods</h3> The authors measured high-sensitivity CRP in plasma, genotyped for four single nucleotide polymorphisms in the CRP gene, and screened for spirometry-defined COPD and hospitalisation due to COPD in 7974 individuals from the Copenhagen City Heart Study and in 32 652 individuals from the Copenhagen General Population Study. <h3>Results</h3> Elevated plasma CRP &gt;3 mg/l compared with &lt;1 mg/l was associated with risk estimates of 1.8 and 2.8 for spirometry-based COPD and of 1.6 and 1.8 for hospitalisation due to COPD in the Copenhagen City Heart Study and the Copenhagen General Population Study, respectively. Genotype combinations of the four CRP polymorphisms were associated with up to a 62% increase in plasma CRP. However, these genotype combinations did not associate with increased risk of COPD or hospitalisation due to COPD in either cohort or in the two cohorts combined. On instrumental variable analysis, a doubling of plasma CRP versus a doubling of genetically elevated CRP resulted in ORs for COPD of 1.27 (95% CI 1.25 to 1.30) versus 1.01 (0.81 to 1.26) and for COPD hospitalisation of 1.47 (1.43 to 1.51) versus 0.82(0.59 to 1.13). <h3>Conclusion</h3> Although elevated CRP is related to both a diagnosis of COPD and subsequent hospital admission, genetically elevated plasma CRP is not associated with an increased risk of clinical COPD. This suggests that the association between CRP levels and COPD is not causal.
The CD4/CD8 ratio in BAL fluid is highly variable in sarcoidosis
Authors: SP Kantrow, KC Meyer, P Kidd, G Raghu
Journal: European Respiratory Journal (1997)

Patients with pulmonary sarcoidosis frequently have increased numbers of lymphocytes and a high ratio of CD4+ to CD8+ T-lymphocytes (CD4/CD8 ratio) in bronchoalveolar lavage (BAL) fluid. Some investigators have suggested that these parameters can be used to distinguish sarcoidosis from other types of interstitial lung disease with a high degree of reliability. However, we hypothesized that the BAL CD4/CD8 ratio measured during the initial diagnostic evaluation of patients with biopsy-proven sarcoidosis is highly variable. BAL lymphocytes were analysed via flow cytometry to determine the CD4/CD8 ratio in a population of 86 patients with histological and clinical evidence of sarcoidosis, who underwent BAL as part of their initial diagnostic evaluation. In these patients, the CD4/CD8 ratio ranged 0.5-37.3, with a median value of 3.35 (mean 6.49). The CD4/CD8 ratio was greater than 4 in only 36 (42%) subjects. Ten patients (12%) had a CD4/CD8 ratio less than 1. The distribution of CD4/CD8 ratios was similar in the presence or absence of BAL lymphocytosis. In conclusion, the CD4/CD8 ratio in bronchoalveolar lavage fluid is highly variable in biopsy-proven sarcoidosis. Bronchoalveolar lavage lymphocyte subset determination is a diagnostic test with low sensitivity for this disease.
Multiple actuations of salbutamol MDI into a spacer device reduce the amount of drug recovered in the respirable range
Authors: PW Barry, C O'Callaghan
Journal: European Respiratory Journal (1994)

We wanted to determine the amount of salbutamol available in respirable particles from the Volumatic spacer device after one, two or five actuations of a metered-dose inhaler into the spacer prior to analysis. A glass multistage liquid impinger was used to determine particle size. Aerosol was sampled after one, two or five actuations from a metered-dose inhaler into a Volumatic spacer. Each experiment was repeated four times. The amount of salbutamol recovered per actuation in particles less than 5 microns (mean and 95% confidence intervals) was: 54.3 micrograms (48.3-60.1) after one actuation; 42.4 micrograms (38.2-46.5) after two actuations, and 20.7 micrograms (17.5-23.9) after five actuations. We conclude that multiple actuations of salbutamol into the Volumatic spacer do not linearly increase the amount of drug available for inhalation. To maximize drug delivery, single actuations should be used prior to inhalation. In comparative studies of drugs and dosages, it must be remembered that the amount of drug delivered is not the same as that administered.
Effects of Type 2 Diabetes on 12-Year Cognitive Change
Authors: Peggy J.J. Spauwen, Sebastian Köhler, Frans R.J. Verhey, Coen D.A. Stehouwer, Martin P.J. van Boxtel
Journal: Diabetes Care (2012)

OBJECTIVE To examine the effects of baseline and incident diabetes on change in cognitive function over 12 years. RESEARCH DESIGN AND METHODS A sample of 1,290 individuals aged ≥40 years at baseline, participating in the Maastricht Aging Study, were cognitively tested at baseline, after 6 years, and after 12 years. Of these, 68 participants had type 2 diabetes at baseline, and 54 and 57 had incident diabetes at the 6- and 12-year follow-up, respectively. Changes in performance on tests of information-processing speed, executive function, and verbal memory from baseline to 6- and 12-year follow-up were compared between groups using linear mixed models. Effects of diabetes on cognitive decline were adjusted for demographic variables, history of smoking, alcohol intake, and comorbid conditions, including hypertension, cardiovascular disease, BMI, and depression. RESULTS Participants with baseline diabetes showed larger decline in information-processing speed (estimate −7.64; P &amp;lt; 0.01), executive function (21.82; P &amp;lt; 0.01), and delayed word recall (−1.35; P &amp;lt; 0.05) over the 12-year follow-up compared with control subjects. No significant difference in decline was observed for immediate word recall. Compared with control subjects, participants with incident diabetes showed subtle early decline in information-processing speed only. Interestingly, they did not show larger decline in any other cognitive domain. CONCLUSIONS Individuals with baseline type 2 diabetes show accelerated cognitive decline, particularly in information-processing speed and executive function, compared with individuals without diabetes. In incident diabetes, decline in speed becomes detectable first, and cognitive decline seems to increase with increasing exposure time.
Repetitive Weekly Cycles of Interleukin-2. II. Clinical and Immunologic Effects of Dose, Schedule, and Addition of Indomethacin
Authors: J. A. Sosman, P. C. Kohler, J. A. Hank, K. H. Moore, R. Bechhofer, B. Storer, P. M. Sonde
Journal: JNCI Journal of the National Cancer Institute (1988)

Journal Article Repetitive Weekly Cycles of Interleukin-2. II. Clinical and Immunologic Effects of Dose, Schedule, and Addition of Indomethacin Get access Jeff A. Sosman, Jeff A. Sosman 3Departments of Human Oncology, University of Wisconsin Medical SchoolMadison, WI Search for other works by this author on: Oxford Academic PubMed Google Scholar Peter C. Kohler, Peter C. Kohler 4Department of MedicineMadison General Hospital, Madison, WL3Departments of Human Oncology, University of Wisconsin Medical SchoolMadison, WI Search for other works by this author on: Oxford Academic PubMed Google Scholar Jacquelyn A. Hank, Jacquelyn A. Hank 3Departments of Human Oncology, University of Wisconsin Medical SchoolMadison, WI Search for other works by this author on: Oxford Academic PubMed Google Scholar Karen H. Moore, Karen H. Moore 3Departments of Human Oncology, University of Wisconsin Medical SchoolMadison, WI Search for other works by this author on: Oxford Academic PubMed Google Scholar Robin Bechhofer, Robin Bechhofer 3Departments of Human Oncology, University of Wisconsin Medical SchoolMadison, WI3Department of Pediatrics, University of Wisconsin Medical SchoolMadison, WI Search for other works by this author on: Oxford Academic PubMed Google Scholar Barry Storer, Barry Storer 3Departments of Human Oncology, University of Wisconsin Medical SchoolMadison, WI3Department of Pediatrics, University of Wisconsin Medical SchoolMadison, WI Search for other works by this author on: Oxford Academic PubMed Google Scholar Paul M. Sonde Paul M. Sonde * 3Departments of Human Oncology, University of Wisconsin Medical SchoolMadison, WI3Department of Pediatrics, University of Wisconsin Medical SchoolMadison, WI3Department of Statistics, University of Wisconsin Medical SchoolMadison, WI3Department of Genetics, University of Wisconsin Medical SchoolMadison, WI *Correspondence to: Dr. P. Sondel, Room K4/448, Clinical Science Center, University of Wisconsin, 600 Highland Ave., Madison, WI 53792. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 80, Issue 18, 16 November 1988, Pages 1451–1461, https://doi.org/10.1093/jnci/80.18.1451 Published: 16 November 1988 Article history Received: 12 July 1988 Revision received: 24 August 1988 Accepted: 24 August 1988 Published: 16 November 1988
Therapeutic IMC-C225 Antibody Inhibits Breast Cancer Cell Invasiveness via Vav2-Dependent Activation of RhoA GTPase
Authors: Poonam R. Molli, Liana Adam, Rakesh Kumar
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Abnormalities in the expression and signaling pathways downstream of epidermal growth factor receptor (EGFR) contribute to progression, invasion, and maintenance of the malignant phenotype in human cancers. Accordingly, biological agents, such as the EGFR-blocking antibody IMC-C225 have promising anticancer potential and are currently in various stages of clinical development. Because use of IMC-C225 is limited, at present, only for treatment of cancer with high EGFR expression, the goal of the present study was to determine the effect of IMC-C225 on the invasiveness of breast cancer cells with high and low levels of EGFR expression. Experimental Design: The effect of IMC-C225 on invasion was studied using breast cancer cell lines with high and low levels of EGFR expression. Results: The addition of EGF led to progressive stress fiber dissolution. In contrast, cells treated with IMC-C225 showed reduced invasiveness and increased stress-fiber formation. Interestingly, IMC-C225 pretreatment was accompanied by EGFR phosphorylation, as detected using an anti–phosphorylated tyrosine antibody (PY99), which correlated with phosphorylation of Vav2 guanine nucleotide exchange factor and activation of RhoA GTPase irrespective of EGFR level, and Vav2 interacted with EGFR only in IMC-C225–treated cells. The underlying mechanism involved an enhanced interaction between β1 integrins and EGFR upon IMC-C225 treatment. Conclusion: Here, we defined a new mechanism for IMC-C225 that cross-links integrins with EGFR, leading to activation of RhoA and inhibition of breast cancer cell invasion irrespective of the level of EGFR in the cells, thus providing a rationale for using IMC-C225 in the metastatic setting independent of the levels of EGFR.
Vertebral end-plate lesions (Schmorl's nodes) in the dorsolumbar spine.
Authors: R C Hilton, J Ball, R T Benn
Journal: Annals of the Rheumatic Diseases (1976)

The distribution of end-plate lesions (Schmorl's nodes) and their relationship to bone density and disc degeneration have been studied in 50 post-mortem spines below D9 in subjects aged 13-96 years. Lesions were present in 76% of cases with a predominance in males. They were found more frequently in the lower than in the upper vertebral end-plate. They were also more common and more severe in the dorsolumbar (D10-L1) region than in the lower lumbar (L2-L5 region). In adults they were unrelated to age and bone density. Lesions were significantly related to disc degeneration in the D10-L1 region but not in the L2-L5 region. It is suggested that end-plate lesions arising in adolescence (or before) may predispose the dorsolumbar spine to disc degeneration in later life.
Small intestinal absorption of amino acids and a dipeptide in pancreatic insufficiency.
Authors: P J Milla, A Kilby, U B Rassam, R Ersser, J T Harries
Journal: Gut (1983)

In this study a perfusion technique has been used to investigate in vivo jejunal absorption and transmural potential difference evoked by the neutral amino acids phenylalanine (56 or 20 mmol/l) and glycine (20 mmol/l), the dibasic amino acid lysine (56 or 5 mmol/l), and a dipeptide glycyl-l-phenylalanine (20 mmol/l) in 11 children with pancreatic insufficiency due to cystic fibrosis and in three children with other causes of exocrine pancreatic insufficiency. Net absorption and potential difference evoked by phenylalanine in both cystic fibrosis and pancreatic insufficiency, and net absorption of glycine in cystic fibrosis were significantly reduced; but the absorption of lysine and glycyl-l-phenylalanine was normal. Absorption of the constituent amino acids from the dipeptide was normal or increased in cystic fibrosis. Thus, these studies show a defect in active absorption of neutral amino acids in cystic fibrosis with pancreatic insufficiency and exocrine pancreatic insufficiency. We speculate that pancreatic factors participate in neutral amino acid absorption.
Chlamydia pneumoniae immunoglobulin A reactivation and airway inflammation in acute asthma
Authors: P.A.B. Wark, S.L. Johnston, J.L. Simpson, M.J. Hensley, P.G. Gibson
Journal: European Respiratory Journal (2002)

Infection with Chlamydia pneumoniae can trigger acute asthma and is associated with severe chronic asthma. The aim of the present study was to examine the relationship between airway inflammation and serological response to C. pneumoniae in acute severe asthma. Subjects (n=54) were recruited within 4 h of presentation to the emergency department with an acute exacerbation of asthma. Clinical history taking, sputum induction (0.9% saline), spirometry and acute and convalescent serology for C. pneumoniae immunoglobulins A and G were performed. At presentation, 47% of subjects had antibodies directed against C. pneumoniae , and 38% (20) demonstrated an increase in C. pneumoniae antibody levels, with 15 demonstrating a rise in immunoglobulin A concentration. C. pneumoniae responders exhibited significantly higher sputum neutrophil levels (4.6×10 6 cells·mL −1 ) compared to nonresponders (1.2×10 6 cells·mL −1 , p=0.02) and elevated sputum eosinophil cationic protein concentration (3,981 versus 1,122 ng·mL −1 , p=0.02). An acute antibody response to Chlamydia pneumoniae is common in exacerbations of asthma. The serological features suggest that Chlamydia pneumoniae reactivation may trigger neutrophilic airway inflammation in acute asthma.
Status of upper airways in exacerbation of COPD
Authors: Evgeny Gilifanov, Vera Nevsorova, Tatyana Tilik, Valentina Kudryavtseva, Elena Samoilenko, Sergey Klimov, Boris Lepeiko, Yulia Lepeiko
Journal: European Respiratory Journal (2012)

Environmental tobacco smoke is the most significant factor of development and progression of COPD. Besides the pathological effects of environmental tobacco smoke on upper airways cannot be excluded.  Purpose of our study was to study the condition of upper airways at exacerbation of COPD. Twenty patients (twelve men and eight women) with the second and third stages of COPD have been examined, index of a smoker was 29.3 ± 1.2. Average age of patients was 57.9. Control group included twenty non-smokers comparable in age and sex, not having respiratory disease.  Study of condition of upper airways included the anterior active rhinomanometry, ransport time of the saccharin, endoscopic examination of nasal cavity, X-ray computed tomography scans paranasal sinus, videostroboscopy, fibrolaryngoscopy, estimation of acoustic analysis of voice.  Changes in paranasal sinus were characterized by appearance of thickening of mucosa on the X-ray computed tomography have been determined for sixteen patients with COPD. According to Lund-Mackay scale the average index was 3.5 ± 0.2; p  Thus we determined frequent occurrence of upper airways pathology in the form of edema of paranasal sinus mucosa, elongation of transport time of the saccharin of nasal mucosa, changes in vocal cords in the form of Reinke9s space edema in patients with exacerbation of COPD.
Functional consequences of somatic mutations in cancer using protein pocket-based prioritization approach
Authors: Huy Vuong, Feixiong Cheng, Chen-Ching Lin, Zhongming Zhao
Journal: Genome Medicine (2014)

Recently, a number of large-scale cancer genome sequencing projects have generated a large volume of somatic mutations; however, identifying the functional consequences and roles of somatic mutations in tumorigenesis remains a major challenge. Researchers have identified that protein pocket regions play critical roles in the interaction of proteins with small molecules, enzymes, and nucleic acid. As such, investigating the features of somatic mutations in protein pocket regions provides a promising approach to identifying new genotype-phenotype relationships in cancer.In this study, we developed a protein pocket-based computational approach to uncover the functional consequences of somatic mutations in cancer. We mapped 1.2 million somatic mutations across 36 cancer types from the COSMIC database and The Cancer Genome Atlas (TCGA) onto the protein pocket regions of over 5,000 protein three-dimensional structures. We further integrated cancer cell line mutation profiles and drug pharmacological data from the Cancer Cell Line Encyclopedia (CCLE) onto protein pocket regions in order to identify putative biomarkers for anticancer drug responses.We found that genes harboring protein pocket somatic mutations were significantly enriched in cancer driver genes. Furthermore, genes harboring pocket somatic mutations tended to be highly co-expressed in a co-expressed protein interaction network. Using a statistical framework, we identified four putative cancer genes (RWDD1, NCF1, PLEK, and VAV3), whose expression profiles were associated with overall poor survival rates in melanoma, lung, or colorectal cancer patients. Finally, genes harboring protein pocket mutations were more likely to be drug-sensitive or drug-resistant. In a case study, we illustrated that the BAX gene was associated with the sensitivity of three anticancer drugs (midostaurin, vinorelbine, and tipifarnib).This study provides novel insights into the functional consequences of somatic mutations during tumorigenesis and for anticancer drug responses. The computational approach used might be beneficial to the study of somatic mutations in the era of cancer precision medicine.
8q Gain Is an Independent Predictor of Poor Survival in Diagnostic Needle Biopsies from Prostate Cancer Suspects
Authors: Franclim R. Ribeiro, Carmen Jerónimo, Rui Henrique, Daniel Fonseca, Jorge Oliveira, Ragnhild A. Lothe, Manuel R. Teixeira
Journal: Clinical Cancer Research (2006)

Abstract Purpose: The main procedure to confirm a suspected diagnosis of prostate cancer is histologic analysis of ultrasound-guided sextant prostate biopsies. As it is difficult to reliably assess tumor stage and grade in such minute samples, the clinical significance of some tumor foci remains unclear. Genetic markers that could augment pretreatment prognostic information would improve the clinical management of the disease. Experimental Design: We have analyzed by comparative genomic hybridization a consecutive series of prostate needle biopsies obtained prospectively from 100 prostate cancer suspects. For 25 of these patients, a second independent biopsy core was analyzed to assess possible tumor heterogeneity. Additionally, a three-color fluorescent in situ hybridization assay was done in paraffin-embedded biopsy cores to validate the comparative genomic hybridization findings and to confirm their prognostic value. Results: Sixty-one of 100 biopsy samples had morphologic evidence of prostate cancer and 41 (67%) of these displayed genomic copy number changes as opposed to none of the morphologically normal biopsies. The presence of losses, amplifications, and the total number of genomic imbalances were significantly associated with poorly differentiated tumors. Kaplan-Meier curves with log-rank test showed that patients whose tumors displayed 8q gains had a significantly worse survival even when tumor grade was taken into account (P = 0.008). Restricting the analysis to cases with Gleason score 7, the most troublesome category in terms of prognostic information, gains at 8q were still significantly associated with poor survival (P = 0.011), something that was confirmed by fluorescent in situ hybridization in an independent series of biopsies with much longer follow-up time (P = 0.023). Conclusions: We show that whole genomic information can be obtained from minute needle biopsies of prostate cancer suspects and that genetic data can provide additional prognostic information before a therapeutic decision is taken.