tbuckley/cabot-search huggingface dataset:
The effect of amlodipine on respiratory and pulmonary vascular responses to hypoxia in mountaineers
Authors: M Watt, A.j Peacock, J Newell, T McDonagh, S Grant
Journal: European Respiratory Journal (2000)

Calcium antagonists are known to reduce the incidence of high-altitude pulmonary oedema, but the mechanism is unclear. The aim of this study was to examine the effects of the calcium antagonist, amlodipine, on cardiac and respiratory responses in normoxia and hypoxia. Fourteen normal subjects aged 31+/-4 yrs who had climbed to altitudes of 5,000-7,500 m without problems were randomly assigned to a double-blind crossover trial of amlodipine versus placebo, using sea-level inspiratory hypoxia to simulate altitude. Doppler echocardiographic estimates of resting pulmonary haemodynamics and cycle ergometer test results of cardiorespiratory responses to exercise were recorded in normoxia and hypoxia. It was found that, although hypoxic pulmonary vasoconstriction (HPV) was not significantly reduced by amlodipine, the effect of the drug on HPV was inversely related to the serum level of amlodipine. Amlodipine did not alter left ventricular function measured echocardiographically. During exercise, amlodipine increased breathlessness, measured using standard scales, in both normoxia and hypoxia but had no effect on ventilatory variables. It was concluded that amlodipine has the potential to block hypoxic pulmonary vasoconstriction as evidenced by a drug concentration-related decrease in resting tricuspid regurgitation jet velocity without any change in resting myocardial contractility. However, with amlodipine, the subjects felt more breathless during exercise. The reasons for this increase in breathlessness are not clear.
An international ISHLT/ATS/ERS clinical practice guideline: diagnosis and management of bronchiolitis obliterans syndrome
Authors: Keith C. Meyer, Ganesh Raghu, Geert M. Verleden, Paul A. Corris, Paul Aurora, Kevin C. Wilson, Jan Brozek, Allan R. Glanville
Journal: European Respiratory Journal (2014)

Bronchiolitis obliterans syndrome (BOS) is a major complication of lung transplantation that is associated with poor survival. The International Society for Heart and Lung Transplantation, American Thoracic Society, and European Respiratory Society convened a committee of international experts to describe and/or provide recommendations for 1) the definition of BOS, 2) the risk factors for developing BOS, 3) the diagnosis of BOS, and 4) the management and prevention of BOS. A pragmatic evidence synthesis was performed to identify all unique citations related to BOS published from 1980 through to March, 2013. The expert committee discussed the available research evidence upon which the updated definition of BOS, identified risk factors and recommendations are based. The committee followed the GRADE (Grading of Recommendation, Assessment, Development and Evaluation) approach to develop specific clinical recommendations. The term BOS should be used to describe a delayed allograft dysfunction with persistent decline in forced expiratory volume in 1 s that is not caused by other known and potentially reversible causes of post-transplant loss of lung function. The committee formulated specific recommendations about the use of systemic corticosteroids, cyclosporine, tacrolimus, azithromycin and about re-transplantation in patients with suspected and confirmed BOS. The diagnosis of BOS requires the careful exclusion of other post-transplant complications that can cause delayed lung allograft dysfunction, and several risk factors have been identified that have a significant association with the onset of BOS. Currently available therapies have not been proven to result in significant benefit in the prevention or treatment of BOS. Adequately designed and executed randomised controlled trials that properly measure and report all patient-important outcomes are needed to identify optimal therapies for established BOS and effective strategies for its prevention.
Src promotes estrogen-dependent estrogen receptor α proteolysis in human breast cancer
Authors: Isabel Chu, Angel Arnaout, Sophie Loiseau, Jun Sun, Arun Seth, Chris McMahon, Kathy Chun, Bryan Hennessy, Gordon B. Mills, Zafar Nawaz, Joyce M. Slingerland
Journal: Journal of Clinical Investigation (2007)

Estrogen drives both transcriptional activation and proteolysis of estrogen receptor alpha (ER alpha; encoded by ESR1). Here we observed variable and overlapping ESR1 mRNA levels in 200 ER alpha-negative and 50 ER alpha-positive primary breast cancers examined, which suggests important posttranscriptional ER alpha regulation. Our results indicate that Src cooperates with estrogen to activate ER alpha proteolysis. Inducible Src stimulated ligand-activated ER alpha transcriptional activity and reduced ER alpha t(1/2). Src and ER alpha levels were inversely correlated in primary breast cancers. ER alpha-negative primary breast cancers and cell lines showed increased Src levels and/or activity compared with ER alpha-positive cancers and cells. ER alpha t(1/2) was reduced in ER alpha-negative cell lines. In both ER alpha-positive and -negative cell lines, both proteasome and Src inhibitors increased ER alpha levels. Src inhibition impaired ligand-activated ER alpha ubiquitylation and increased ER alpha levels. Src siRNA impaired ligand-activated ER alpha loss in BT-20 cells. Pretreatment with Src increased ER alpha ubiquitylation and degradation in vitro. These findings provide what we believe to be a novel link between Src activation and ER alpha proteolysis and support a model whereby crosstalk between liganded ER alpha and Src drives ER alpha transcriptional activity and targets ER alpha for ubiquitin-dependent proteolysis. Oncogenic Src activation may promote not only proliferation, but also estrogen-activated ER alpha loss in a subset of ER alpha-negative breast cancers, altering prognosis and response to therapy.
Microarray-Based Response Prediction in Esophageal Adenocarcinoma
Authors: Matthias Schauer, Klaus-Peter Janssen, Caroline Rimkus, Matthias Raggi, Marcus Feith, Helmut Friess, Joerg Theisen
Journal: Clinical Cancer Research (2009)

In locally advanced (uT(3), N(+)) adenocarcinomas of the esophagus, neoadjuvant chemotherapy improves patient outcome. However, only a subgroup of patients responds. Therefore, in the present study, we evaluated whether the response to neoadjuvant chemotherapy can be predicted by a pretreatment tumor biopsy analysis.Biopsies of 47 patients with locally advanced (uT(3), N(+)) adenocarcinoma of the esophagus were obtained during primary staging. All patients underwent neoadjuvant chemotherapy with cisplatin, 5-fluorouracil, and leucovorin and subsequent resection of the esophagus. Biopsies were used for microarray analysis. The predominance of tumor cells within the specimens was >70%. Affymetrix U133 plus 2.0 gene chips with 54675 probe sets were used. A statistical comparison of patients responding to chemotherapy versus nonresponding patients was done. All patients were examined with immunohistology against Ephrin B3 receptor and Ki-67.A total of 86 genes were at least 2-fold differentially regulated comparing responding with nonresponding adenocarcinomas of the esophagus. The predominant genes encoded for the regulation of the cell cycle, transduction, translation, cell-cell interaction, cytoskeleton, and the signal transduction. The strongest difference was seen for the Ephrin B3 receptor. This result could be confirmed by immunhistology. A statistical significant correlation between the Ephrin B3 receptor, chemotherapy response, pathologic staging, and grading could be shown.There were significant differences in the gene profile between patients with adenocarcinoma of the esophagus responding to neoadjuvant chemotherapy compared with nonresponding patients. This suggests that it could be possible to characterize patients responding to chemotherapy even before starting the treatment using customized microarray analysis.
Relationship between osteoporosis and adipose tissue leptin and osteoprotegerin in patients with chronic obstructive pulmonary disease
Authors: Pavol Pobeha, Jozef Ukropec, Pavol Joppa, Barbara Ukropcova, Peter Skyba, Martin Javorsky, Daniela Gasperikova, Ruzena Tkacova
Journal: European Respiratory Journal (2011)

Introduction:  The role of fat-bone interactions in the pathogenesis of osteoporosis in chronic obstructive pulmonary disease (COPD) is poorly understood. We investigated adipose tissue (AT) expressions of leptin and osteoprotegerin (OPG) and their relationships to osteoporosis in COPD.   Methods:  In 39 patients with stable COPD, bone mineral density (BMD) and body composition was assessed by DEXA. Serum leptin and β-crosslaps were determined by electrochemiluminiscence immunoassays. Subcutaneous AT samples were analyzed using real-time PCR.   Results:  Twenty-one patients without, and 18 with osteoporosis were enrolled (35 men; age 62.2±7.3 years). Compared to patients without osteoporosis, those with the disease had lower serum levels and AT expressions of leptin, and increased serum β-crosslaps (p=0.028, p=0.034, p=0.022, resp.). Log AT leptin was inversely related to serum β-crosslaps (p=0.015), and directly to leptin (p R  2 adj  =0.383; p=0.008,  R  2 adj  =0.301, resp.). Introducing body or fat mass index into these models eliminated independent predictive value of leptin and OPG expressions.   Conclusion:  Our results suggest that adipose tissue leptin and OPG expressions are related to osteoporosis in patients with COPD, and appear to act as mediators between fat mass and BMD.  Support: APVV-0122-06, VEGA-1/0227/11 and VVGS 36/10-11.
Immunologic basis for allopurinol-induced severe cutaneous adverse reactions: HLA-B*58:01-restricted activation of drug-specific T cells and molecular interaction
Authors: Chia-Hsien Lin, Jung-Kuei Chen, Tai-Ming Ko, Chun-Yu Wei, Jer-Yuarn Wu, Wen-Hung Chung, Shih-Yang Chen, You-Di Liao, Shuen-Iu Hung, Yuan-Tsong Chen
Journal: Journal of Allergy and Clinical Immunology (2014)
Noninvasive ventilation in children
Authors: O. Norregaard
Journal: European Respiratory Journal (2002)

The use of noninvasive ventilation (NIV)/ventilatory assistance has in its modern form experienced a resurgence during the last two decades, primarily in the adult population. During the last few years, NIV, predominantly in the form of positive-pressure ventilation/ventilatory assistance, has also become an option in the paediatric population. Although the technique is increasingly being applied, data in this often very heterogeneous group of patients are still very limited, and are usually derived from case series and not randomised controlled studies. Available experience indicates that the technique is useful for children with a wide spectrum of hypercapnic and/or hypoxaemic respiratory disorders, in the acute as well as in the chronic setting. Results have shown improvements in survival and arterial blood gases, and have indicated better quality of life. Adverse effects are generally minor, although the impact on facial bony structures should be monitored closely during long-term ventilation. Considering the paucity of data, the area badly needs research, which preferentially should include: 1) short- and long-term effects and adverse effects in various conditions and age groups; 2) techniques, in particular interfaces and triggering mechanisms; 3) comprehensive plans for training of attendants, discharge and follow-up; and 4) quality of life measurements. As many of the conditions suited for noninvasive ventilation are very rare, much of the research would probably benefit from multicentre studies, or even studies on a European level.
PROPERDIN FACTOR D: CHARACTERIZATION OF ITS ACTIVE SITE AND ISOLATION OF THE PRECURSOR FORM
Authors: Douglas T. Fearon, K. Frank Austen, Shaun Ruddy
Journal: The Journal of Experimental Medicine (1974)

The activity of properdin factor D was measured by the generation of the hemolytically active cellular intermediate, EAC43B(D), bearing the C3b-dependent alternate pathway C3 convertase. Treatment of factor D with DFP prevented formation of EAC43B(D); thus, a serine esterase is essential for the generation of the alternate pathway C3 convertase, a situation analogous to the role of C1 in the formation of the classical C3 convertase, C42. The definition of factor D as a serine esterase prompted a search for its proenzyme form, and resulted in the chromatographic isolation from plasma of a single peak of trypsin-inducible factor D activity, distinct from activated factor D. Analytical gel filtration indicated an apparent mol wt of 25,000. This protein from which trypsin elaborated factor D activity, as assessed by the formation of EAC43B(D), the generation of the CoVF-dependent C3 convertase, and the cleavage of factor B in the presence of C3b, was designated "precursor factor D." The DFP resistance of precursor factor D, and the susceptibility of its trypsin-activated form to inactivation by DFP is analogous to the behavior of other plasma serine esterases, including C1.
A longitudinal psycho-physiological study of active and inactive men.
Authors: R M Reid, I McGowan
Journal: British Journal of Sports Medicine (1986)

After an interval of ten years, physically active and inactive male university teachers were re-examined across four measures; predicted maximum oxygen uptake, percentage body fat, personality and attitudes towards physical activity. Both groups showed a decrease in predicted oxygen uptake and an increase in body fat although the active subjects continued to possess higher predicted maximum oxygen uptake values and have a lower percentage body fat than the inactive subjects. In general the psychological assessments revealed no major changes but minor shifts in attitudes towards physical activity were noted.
Natural history of rheumatoid cervical luxations.
Authors: P H Smith, R T Benn, J Sharp
Journal: Annals of the Rheumatic Diseases (1972)

Luxation of the cervical spine, if looked for, is commonly observed at some stage during the longterm care of patients with rheumatoid arthritis.At the atlanto-axial level up to a quarter of patients admitted to hospital with rheumatoid arthritis can be expected to have luxations and about half will have subaxial luxations at two or more levels (Sharp and Purser, 1961; Conlon, Isdale, and Rose, 1966; Sharp, 1964).Pain and stiffness in the neck may be present but are frequently absent and often the luxations cause no symptoms or disability.Occasionally the presenting symptoms are transient blackouts, tetraplegia, sudden death, or other neurological complications resulting from damage to the cervical cord or interference with the flow of the vertebral arteries (Ball and Sharp, 1971).In this paper we report the results of a study of the natural history of cervical luxation in patients with rheumatoid arthritis, with particular reference to the development of dangerous neurological complications. Patients studiedBetween the years 1955 and 1964 all patients with rheuma- toid arthritis who were admitted to the beds of the Table IA Age, sex, and incidence of luxations in 962 hospital in-patients with rheumatoid arthritis Sex Male Female
Circulating TNF Receptors 1 and 2 Predict ESRD in Type 2 Diabetes
Authors: Monika A. Niewczas, Tomohito Gohda, Jan Skupien, Adam M. Smiles, William H. Walker, Florencia Rosetti, Xavier Cullere, John H. Eckfeldt, Alessandro Doria, Tanya N. Mayadas, James H. Warram, Andrzej S. Krolewski
Journal: Journal of the American Society of Nephrology (2012)

Levels of proinflammatory cytokines associate with risk for developing type 2 diabetes but whether chronic inflammation contributes to the development of diabetic complications, such as ESRD, is unknown. In the 1990s, we recruited 410 patients with type 2 diabetes for studies of diabetic nephropathy and recorded their characteristics at enrollment. During 12 years of follow-up, 59 patients developed ESRD (17 per 1000 patient-years) and 84 patients died without ESRD (24 per 1000 patient-years). Plasma markers of systemic inflammation, endothelial dysfunction, and the TNF pathway were measured in the study entry samples. Of the examined markers, only TNF receptors 1 and 2 (TNFR1 and TNFR2) associated with risk for ESRD. These two markers were highly correlated, but ESRD associated more strongly with TNFR1. The cumulative incidence of ESRD for patients in the highest TNFR1 quartile was 54% after 12 years but only 3% for the other quartiles (P<0.001). In Cox proportional hazard analyses, TNFR1 predicted risk for ESRD even after adjustment for clinical covariates such as urinary albumin excretion. Plasma concentration of TNFR1 outperformed all tested clinical variables with regard to predicting ESRD. Concentrations of TNFRs moderately associated with death unrelated to ESRD. In conclusion, elevated concentrations of circulating TNFRs in patients with type 2 diabetes at baseline are very strong predictors of the subsequent progression to ESRD in subjects with and without proteinuria.
The FEF<sub>25–75</sub>/FVC Ratio Is Associated with Methacholine Airway Responsiveness
Authors: AUGUSTO A. LITONJUA, DAVID SPARROW, SCOTT T. WEISS
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Airway responsiveness is known to be partly explained by geometric and anatomic factors. This cross-sectional investigation was undertaken to determine whether FEF25–75/FVC as a surrogate measure of airway size relative to lung size is associated with airway responsiveness to methacholine. Posteroanterior chest radiographs and spirometry were performed on a group of 929 middle aged and older men from an ongoing longitudinal study, the Normative Aging Study, who returned for their regularly scheduled examination between 1984 and 1989. Subjects had a mean age of 60.5 ± 7.7 yr. FEV1, FEF25–75, and FVC were taken from spirometric results and FEF25–75/FVC ratios were obtained. Main bronchus (MB) and tracheal (TR) diameters and lung area (LA) were obtained from chest radiographs, and ratios of MB/LA and TR/LA were calculated for each subject and compared with FEF25–75/ FVC as measures of airway size relative to lung size. In a multiple linear regression model adjusting for age, height, initial FEV1, smoking, eosinophil count, and IgE level, FEF25–75/FVC was significantly related to the degree of methacholine airway responsiveness as measured by Log10 dose response slope ( β = − 0.37, p < 0.001). Controlling for the same variables, both MB/LA ( β = − 149.07, p < 0.001) and TR/LA ( β = − 125.87, p < 0.001) were significant predictors of the degree of bronchial responsiveness in separate regression models; however, their effects were greatly attenuated when FEF25–75/ FVC was present in the same model. Similar results were obtained after excluding subjects with FEV1/ FVC ⩽ 0.70 and subjects who had any smoking history. We conclude that FEF25–75/FVC as a surrogate measure of airway size relative to lung size is significantly associated with airway responsiveness.
Naturally Occurring Bone Tumors in C57BL/lcrf Mice
Authors: L. M. Franks, C. Rowlatt, F. C. Chesterman
Journal: JNCI Journal of the National Cancer Institute (1973)

Seven bone tumors were found in a colony of C57BL/lcrf mice. All occurred in females. Histologically these were osteosarcomas. Lymph node metastases were present in 1 mouse. Transplants from 2 primary tumors were bone forming. The ultrastructure of 1 of these is described.
Declining Rates of Hospitalization for Nontraumatic Lower-Extremity Amputation in the Diabetic Population Aged 40 Years or Older: U.S., 1988–2008
Authors: Yanfeng Li, Nilka Ríos Burrows, Edward W. Gregg, Ann Albright, Linda S. Geiss
Journal: Diabetes Care (2012)

OBJECTIVE To assess trends in rates of hospitalization for nontraumatic lower-extremity amputation (NLEA) in U.S. diabetic and nondiabetic populations and disparities in NLEA rates within the diabetic population. RESEARCH DESIGN AND METHODS We calculated NLEA hospitalization rates, by diabetes status, among persons aged ≥40 years on the basis of National Hospital Discharge Survey data on NLEA procedures and National Health Interview Survey data on diabetes prevalence. We used joinpoint regression to calculate the annual percentage change (APC) and to assess trends in rates from 1988 to 2008. RESULTS The age-adjusted NLEA discharge rate per 1,000 persons among those diagnosed with diabetes and aged ≥40 years decreased from 11.2 in 1996 to 3.9 in 2008 (APC −8.6%; P &amp;lt; 0.01), while rates among persons without diagnosed diabetes changed little. NLEA rates in the diabetic population decreased significantly from 1996 to 2008 in all demographic groups examined (all P &amp;lt; 0.05). Throughout the entire study period, rates of diabetes-related NLEA were higher among persons aged ≥75 years than among those who were younger, higher among men than women, and higher among blacks than whites. CONCLUSIONS From 1996 to 2008, NLEA discharge rates declined significantly in the U.S. diabetic population. Nevertheless, NLEA continues to be substantially higher in the diabetic population than in the nondiabetic population and disproportionately affects people aged ≥75 years, blacks, and men. Continued efforts are needed to decrease the prevalence of NLEA risk factors and to improve foot care among certain subgroups within the U.S. diabetic population that are at higher risk.
Deficient glucocorticoid induction of anti-inflammatory genes in nasal polyp fibroblasts of asthmatic patients with and without aspirin intolerance
Authors: Laura Fernández-Bertolín, Joaquim Mullol, Mireya Fuentes-Prado, Isam Alobid, Jordi Roca-Ferrer, César Picado, Laura Pujols
Journal: Journal of Allergy and Clinical Immunology (2013)
CONCORDANT SEGREGATION OF THE EXPRESSION OF SV40 T ANTIGEN AND HUMAN CHROMOSOME 7 IN MOUSE-HUMAN HYBRID SUBCLONES
Authors: Carlo M. Croce, Hilary Koprowski
Journal: The Journal of Experimental Medicine (1974)

Subcloning of Simian virus 40 (SV40) T antigen-positive mouse-human hybrids, derived from the fusion of mouse cells deficient in thymidine kinase with SV40-transformed Lesch Nyhan fibroblasts, resulted in their segregation into T antigen-positive and negative subclones. Positive correlation between the presence of human chromosome 7 and the expression of SV40 T antigen was established in the subclones examined. These results negate the possibility of a transfer of the SV40 genome to a mouse chromosome.
Phase I study of the novel, fully synthetic epothilone sagopilone (ZK-EPO) in patients with solid tumors
Authors: P. Schmid, P. Kiewe, K. Possinger, A. Korfel, S. Lindemann, M. Giurescu, S. Reif, H. Wiesinger, E. Thiel, D. Kühnhardt
Journal: Annals of Oncology (2009)
TWO CASES OF WITHDRAWAL FROM ETHCHLORVYNOL
Authors: JOHN B. AYCRIGG
Journal: American Journal of Psychiatry (1964)

Two cases of withdrawal from chronic addiction to ethchlorvynol are reported. The withdrawal syndrome is characterized by a latent period of 6 to 10 days and by a delirium which, in addition to the classical characteristics of delirium, has many features suggestive of a schizophrenic reaction. Clearing of the schizophreniform symptoms occurs first followed by clearing of the confusion.
Detection of sharing by descent, long-range phasing and haplotype imputation
Authors: Augustine Kong, Gisli Masson, Michael L Frigge, Arnaldur Gylfason, Pasha Zusmanovich, Gudmar Thorleifsson, Pall I Olason, Andres Ingason, Stacy Steinberg, Thorunn Rafnar, Patrick Sulem, Magali Mouy, Frosti Jonsson, Unnur Thorsteinsdottir, Daniel F Gudbjartsson, Hreinn Stefansson, Kari Stefansson
Journal: Nature Genetics (2008)