tbuckley/cabot-search huggingface dataset:
Diet, lung function, and lung function decline in a cohort of 2512 middle aged men
Authors: B. K Butland
Journal: Thorax (2000)

<h3>BACKGROUND</h3> A prospective cohort study of 2512 Welshmen aged 45–59 living in Caerphilly in 1979–1983 was used to investigate associations between diet and lung function. <h3>METHODS</h3> At baseline (phase I) and at five year follow up (phase II), forced expiratory volume in one second (FEV<sub>1</sub>) was measured using a McDermott spirometer and dietary data were obtained using a semi-quantitative food frequency questionnaire. <h3>RESULTS</h3> Good lung function, indicated by high maximum FEV<sub>1</sub> given age and height, was associated with high intakes of vitamin C, vitamin E, β-carotene, citrus fruit, apples, and the frequent consumption of fruit juices/squashes. Lung function was inversely associated with magnesium intake but there was no evidence of an association with fatty fish. Following adjustment for confounders including body mass index, smoking history, social class, exercise, and total energy intake, only the associations with vitamin E and apples persisted, with lung function estimated to be 39 ml (95% confidence interval (CI) 9 to 69) higher for vitamin E intakes one standard deviation (SD) apart and 138 ml higher (95% CI 58 to 218) for those eating five or more apples per week compared with non-consumers. Decline in lung function between phases was not significantly associated with the changing intakes of apples or vitamin E. An association between high average apple consumption and slow decline in lung function lost significance after adjustment for confounders. <h3>CONCLUSIONS</h3> A strong positive association is seen between lung function and the number of apples eaten per week cross sectionally, consistent with a protective effect of hard fruit rather than soft/citrus fruit. The recent suggestion that such effects are reversible was not supported by our longitudinal analysis.
Uric Acid and Survival in Chronic Heart Failure
Authors: Stefan D. Anker, Wolfram Doehner, Mathias Rauchhaus, Rakesh Sharma, Darrel Francis, Christoph Knosalla, Constantinos H. Davos, Mariantonietta Cicoira, Waqar Shamim, Michel Kemp, Robert Segal, Karl Josef Osterziel, Francisco Leyva, Roland Hetzer, Piotr Ponikowski, Andrew J.S. Coats
Journal: Circulation (2003)

Background— Serum uric acid (UA) could be a valid prognostic marker and useful for metabolic, hemodynamic, and functional (MFH) staging in chronic heart failure (CHF). Methods and Results— For the derivation study, 112 patients with CHF (age 59±12 years, peak oxygen consumption [V̇ o 2 ] 17±7 mL/kg per minute) were recruited. In separate studies, we validated the prognostic value of UA (n=182) and investigated the relationship between MFH score and the decision to list patients for heart transplantation (n=120). In the derivation study, the best mortality predicting UA cutoff (at 12 months) was 565 μmol/L (9.50 mg/dL) (independently of age, peak V̇ o 2 , left ventricular ejection fraction, diuretic dose, sodium, creatinine, and urea; P &lt;0.0001). In the validation study, UA ≥565 μmol/L predicted mortality (hazard ratio, 7.14; P &lt;0.0001). In 16 patients (from both studies) with UA ≥565 μmol/L, left ventricular ejection fraction ≤25% and peak V̇ o 2 ≤14 mL/kg per min (MFH score 3), 12-month survival was lowest (31%) compared with patients with 2 (64%), 1 (77%), or no (98%, P &lt;0.0001) risk factor. In an independent study, 51% of patients with MFH score 2 and 81% of patients with MFH score 3 were listed for transplantation. The positive predictive value of not being listed for heart transplantation with an MFH score of 0 or 1 was 100%. Conclusions— High serum UA levels are a strong, independent marker of impaired prognosis in patients with moderate to severe CHF. The relationship between serum UA and survival in CHF is graded. MFH staging of patients with CHF is feasible.
Role of insulin in the intermediary metabolism of the activated thymic-derived lymphocyte.
Authors: J H Helderman
Journal: Journal of Clinical Investigation (1981)

The hypothesis that a role for insulin in the metabolism of T cells would be evident after cell activation when receptors appear was tested to validate the T cell model and to analyze the mechanism by which insulin may function in immunoregulation. Measuring the flux rates of 3-O-[methyl-3H]-D-glucose and aminoisobutyric acid, alpha-[1-14C], lactate production and oxidation, and glucose oxidation from carbon 1- and carbon 6-labeled substrates, it was determined that (a) mitogens such as phytohemagglutinin enhance basal T lymphocyte intermediary metabolism, (b) physiologic concentrations of insulin have no impact on the metabolism of unstimulated, cultured, receptor-negative lymphocytes, and (c) insulin provided to receptor bearing lymphocytes augments intermediary metabolism above mitogen stimulated levels. The importance of the pentose phosphate shunt pathway for energy metabolism in the stimulated lymphocyte was confirmed. These studies demonstrate that insulin has a classical physiologic role to play in the activated lymphocyte further validating the use of this cell to examine potential receptor defects in disorders of carbohydrate metabolism. By enhancing energy metabolism of stimulated lymphocytes, insulin serves biologic economy and thus may perform its immunoregulatory role.
Institute of Neurology
Authors: G. de M. Rudolf
Journal: BMJ (1966)

p. 1482) questions the factual basis for my tentative conclusion (21 May, p. 1301) that general practice may be the most appropriate setting for conducting clinical trials.Two types of defaulting in respect of adherence to treatment schedules must be distinguished, and perhaps should have been distinguished in my original letter.The first group are the " overt defaulters," and the second the " occult defaulters."The former fail to complete the trial for reasons which are obvious to the doctor-for example, volunteering that they have stopped the tab- lets, leaving the district, failing to reattend, etc. Being readily identifiable, their presence can be allowed for in the final assessment.It is the " occult defaulters " who may, and probably usually do, invalidate a trial.This group, having persevered, may appear to the unwary to have been entirely consonant to the treatment schedule, but in fact they have been dissonant.If my figures are examined, bearing in mind this distinction, then it can be seen that out of 29 " completers " 22 (76%) were available for assessment, and that only three of these patients were suspected as being definite defaulters.Can these figures be matched by any hospital outpatient trial ?I am, etc., Camberley,
A multicentre, randomised phase III trial comparing protracted venous infusion (PVI) 5-fluorouracil (5-FU) with PVI 5-FU plus mitomycin C in patients with inoperable oesophago-gastric cancer
Authors: N.C. Tebbutt, A. Norman, D. Cunningham, T. Iveson, M. Seymour, T. Hickish, P. Harper, N. Maisey, K. Mochlinski, Y. Prior, M. Hill
Journal: Annals of Oncology (2002)
Hydrolysis of diadenosine 5',5''-P',P''-triphosphate (Ap3A) by porcine aortic endothelial cells.
Authors: S J Goldman, E L Gordon, L L Slakey
Journal: Circulation Research (1986)

Diadenosine triphosphate is present in platelet-dense granules and released quantitatively on platelet aggregation. We have found that intact porcine aortic endothelial cells can efficiently hydrolyze extracellular diadenosine triphosphate. The products of diadenosine triphosphate hydrolysis are adenosine monophosphate and adenosine diphosphate. Adenosine diphosphate is a potent stimulus of platelet aggregation. Since platelet-dense granules contain high concentrations of adenosine triphosphate and adenosine diphosphate, we examined endothelial cell hydrolysis of a mixture of diadenosine triphosphate and adenosine triphosphate. We find that the presence of adenosine triphosphate severely inhibits the hydrolysis of diadenosine triphosphate. Thus, although endothelial cells can rapidly clear extracellular diadenosine triphosphate, during platelet aggregation the hydrolysis of diadenosine triphosphate may be slow due to the presence of high concentrations of other adenine nucleotides. This phenomenon may be important physiologically if, as current evidence implies, diadenosine triphosphate is involved in the maintenance of hemostasis.
Progress Study of 590 Consecutive Nonsurgical Cases of Coronary Disease Followed 5-9 Years
Authors: ALBERT V. G. BRUSCHKE, WILLIAM L. PROUDFIT, F. MASON SONES
Journal: Circulation (1973)

The clinical progress was studied in a series of 590 patients documented to have significant obstructive disease by coronary arteriography. Ventriculographic findings, age, history, cigarette smoking, hypertension, serum cholesterol, and diabetes were correlated with prognosis. In categories separated on the basis of left ventricular angiogram the 5-year cardiac mortality rates ranged from 25% among patients with normal left ventricles to 69% among patients with dilated and generally poorly contracting left ventricles. Combining the results of coronary and left ventricular angiography yielded a better prediction than either method separately. Most of the other parameters studied were related to a certain extent to mortality, but their predictive power was limited and could partly or entirely be explained by the associated obstructions of the coronary arteries or the condition of the left ventricle. The most significant clinical determinants were the history, the electrocardiogram, and the presence of diabetes mellitus. Particularly high mortality was found in patients with congestive heart failure or electrocardiographic conduction disturbances.
Significant increase of CD57+ cells in pulmonary lymphoid follicles of COPD patients
Authors: J. Olloquequi, J.F. Montes, A. Prats, E. Rodríguez, M.A. Montero, J. García-Valero, J. Ferrer
Journal: European Respiratory Journal (2010)

Although the presence of pulmonary lymphoid follicles (LFs) has been associated with the progression of chronic obstructive pulmonary disease (COPD), there is no information regarding the pattern of vascularisation, expression of addressins or inflammatory cell densities within these structures in COPD. Histological and immunohistochemical techniques were used to assess the prevalence, structure, localisation, vascularisation and cell proliferation/apoptosis of LFs, as well as the follicular density of B- and T-lymphocytes, macrophages, dendritic cells and CD57 + cells, in lung tissue of nine nonsmokers, 18 smokers without COPD, 16 smokers with moderate COPD and 16 patients with very severe COPD. The density of CD57 + cells within LFs of COPD patients was significantly increased compared to that of nonsmokers and smokers without COPD (p&lt;0.05). Moreover, the percentage of LF profiles with cell apoptosis was also significantly higher in COPD patients (p = 0.03). By contrast, no significant differences among groups were observed in the follicular densities of other inflammatory cells, nor in the distribution of blood and lymphatic vessels within LFs. Since CD57 + cells are important effectors of cytotoxicity and immune regulation, an increase in their follicular density supports the hypothesis of local immune dysfunction in COPD.
The effects of osmotic challenge on bronchial responsiveness to methacholine in non-asthmatic subjects
Authors: D Antoniou, G Pavlakou, PJ Rees
Journal: European Respiratory Journal (1990)

We have measured the airway responses to methacholine on three days in sixteen non-asthmatic subjects. On the first day the methacholine challenge alone was performed. The other two days were randomized between pretreatment with distilled water or hypertonic saline administered by ultrasonic nebulizer. Distilled water and hypertonic saline did not affect baseline specific conductance (sGaw). Provocative dose producing a 35% fall in sGaw (PD35sGaw) was slightly reduced by both distilled water and hypertonic saline (15.83 to 8.55 mumol with distilled water and to 11.80 mumol with hypertonic saline). Six out of 16 subjects reached a plateau of maximal response with methacholine. The level of this plateau was not affected by pretreatment with distilled water or hypertonic saline. These results show that distilled water and 3.6% saline produced small increases in non-specific reactivity in normal subjects and confirm that substantial osmotic challenge does not change airway calibre in non-asthmatic subjects.
HABER'S SYNDROME. Familial Rosacea-Like Eruption with Intraepidermal Epithelioma.
Authors: K. V. SANDERSON, H. T. H. WILSON
Journal: British Journal of Dermatology (1965)

Journal Article HABER'S SYNDROME. Familial Rosacea‐Like Eruption with Intraepidermal Epithelioma. Get access K. V. SANDERSON, K. V. SANDERSON St. George's Hospital, London, S.W.I Search for other works by this author on: Oxford Academic Google Scholar H. T. H. WILSON H. T. H. WILSON Mount Vernon Hospital, Northwood, Middlesex Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 77, Issue 1, 1 January 1965, Pages 1–8, https://doi.org/10.1111/j.1365-2133.1965.tb14558.x Published: 01 January 1965
p130Cas mediates the transforming properties of the anaplastic lymphoma kinase
Authors: Chiara Ambrogio, Claudia Voena, Andrea D. Manazza, Roberto Piva, Ludovica Riera, Laura Barberis, Carlotta Costa, Guido Tarone, Paola Defilippi, Emilio Hirsch, Elisabetta Boeri Erba, Shabaz Mohammed, Ole N. Jensen, Giorgio Palestro, Giorgio Inghirami, Roberto Chiarle
Journal: Blood (2005)
Evolutionary Balancing Is Critical for Correctly Forecasting Disease-Associated Amino Acid Variants
Authors: L. Liu, S. Kumar
Journal: Molecular Biology and Evolution (2013)

Computational predictions have become indispensable for evaluating the disease-related impact of nonsynonymous single-nucleotide variants discovered in exome sequencing. Many such methods have their roots in molecular evolution, as they use information derived from multiple sequence alignments. We show that the performance of current methods (e.g., PolyPhen-2 and SIFT) is improved significantly by optimizing their statistical models on evolutionarily balanced training data, where equal numbers of positive and negative controls within each evolutionary conservation class are used. Evolutionary balancing significantly reduces the false-positive rates for variants observed at highly conserved sites and false-negative rates for variants observed at fast evolving sites. Use of these improved methods enables more accurate forecasting when concordant diagnosis from multiple methods is regarded as a more reliable indicator of the prediction. Applied to a large exome variation data set, we find that the current methods produce concordant predictions for less than half of the population variants. These advances are implemented in a web resource for use in practical applications (www.mypeg.info, last accessed March 13, 2013).
Actions of adenosine and isoproterenol on isolated mammalian ventricular myocytes.
Authors: L Belardinelli, G Isenberg
Journal: Circulation Research (1983)

We investigated the effects of adenosine and isoproterenol on enzymatically dispersed ventricular myocytes from bovine and guinea pig hearts. Intracellular stimulation of relaxed myocytes with regular striation patterns and normal resting potential resulted in action potentials with full plateaus accompanied by contractions. Adenosine in concentrations up to 0.2 mM had no significant effect on any of the action potential parameters or on the basal contractility. In contrast, in the same cells, adenosine effectively antagonized the stimulatory effect of isoproterenol. Isoproterenol (1-10 nM) prolonged the action potentials by 34-41%, displaced the plateau to more positive potentials, and caused a 3-fold increase in the extent of myocyte sarcomere shortening. In the presence of adenosine (5-50 microM), isoproterenol increased the action potential duration by only 8-9%, the shift of the plateau was nearly abolished, and the increase in the extent of myocyte sarcomere shortening was less than 10%. In some of the myocytes, isoproterenol (1-10 nM) induced depolarizing afterpotentials accompanied by aftercontractions. The afterdepolarizations occasionally reached threshold resulting in triggered sustained rhythmic activity. Adenosine (20-50 microM) not only reduced the amplitude of the afterdepolarizations and aftercontractions, but also abolished the sustained rhythmic activity. We conclude, first, that isolated ventricular myocytes respond to isoproterenol and adenosine; second, that adenosine has no direct effect, but effectively antagonizes the stimulatory actions of isoproterenol; third, that findings are consistent with the ones reported for multicellular ventricular preparations; fourth, that adenosine concentrations required to attenuate the actions of isoproterenol are in the range of adenosine concentrations released by cardiac cells when oxygen availability is limited and/or demand is increased; and fifth, that endogenously released adenosine may modulate the electrophysiological and contractile effects of catecholamines.
Connexin43 regulates sodium current; ankyrin-G modulates gap junctions: the intercalated disc exchanger
Authors: M. Delmar
Journal: Cardiovascular Research (2011)

Intercalated disc structures have conventionally been considered to be independent. Recent work shows that molecules initially thought of as belonging to one complex can actually affect another. Here, I focus on the cross-talk between connexin43 (Cx43, 'the gap junction protein') and the sodium channel complex and, conversely, on ankyrin-G (AnkG, a 'component of the sodium channel complex') and gap junctions. I speculate as to the possibility that one molecule affects the function of the other by regulating its trafficking into the intercalated disc.
EGFR-TKI Resistance Due to <i>BIM</i> Polymorphism Can Be Circumvented in Combination with HDAC Inhibition
Authors: Takayuki Nakagawa, Shinji Takeuchi, Tadaaki Yamada, Hiromichi Ebi, Takako Sano, Shigeki Nanjo, Daisuke Ishikawa, Mitsuo Sato, Yoshinori Hasegawa, Yoshitaka Sekido, Seiji Yano
Journal: Cancer Research (2013)

BIM (BCL2L11) is a BH3-only proapoptotic member of the Bcl-2 protein family. BIM upregulation is required for apoptosis induction by EGF receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKI) in EGFR-mutant forms of non-small cell lung cancer (NSCLC). Notably, a BIM deletion polymorphism occurs naturally in 12.9% of East Asian individuals, impairing the generation of the proapoptotic isoform required for the EGFR-TKIs gefitinib and erlotinib and therefore conferring an inherent drug-resistant phenotype. Indeed, patients with NSCLC, who harbored this host BIM polymorphism, exhibited significantly inferior responses to EGFR-TKI treatment than individuals lacking this polymorphism. In an attempt to correct this response defect in the resistant group, we investigated whether the histone deacetylase (HDAC) inhibitor vorinostat could circumvent EGFR-TKI resistance in EGFR-mutant NSCLC cell lines that also harbored the BIM polymorphism. Consistent with our clinical observations, we found that such cells were much less sensitive to gefitinib-induced apoptosis than EGFR-mutant cells, which did not harbor the polymorphism. Notably, vorinostat increased expression in a dose-dependent manner of the proapoptotic BH3 domain-containing isoform of BIM, which was sufficient to restore gefitinib death sensitivity in the EGFR mutant, EGFR-TKI-resistant cells. In xenograft models, while gefitinib induced marked regression via apoptosis of tumors without the BIM polymorphism, its combination with vorinostat was needed to induce marked regression of tumors with the BIM polymorphism in the same manner. Together, our results show how HDAC inhibition can epigenetically restore BIM function and death sensitivity of EGFR-TKI in cases of EGFR-mutant NSCLC where resistance to EGFR-TKI is associated with a common BIM polymorphism.
Community-acquired pneumonia as medical emergency: predictors of early deterioration
Authors: Martin Kolditz, Santiago Ewig, Benjamin Klapdor, Hartwig Schütte, Johannes Winning, Jan Rupp, Norbert Suttorp, Tobias Welte, Gernot Rohde
Journal: Thorax (2015)

<h3>Background</h3> Early organ dysfunction determines the prognosis of community-acquired pneumonia (CAP), and recognition of CAP as a medical emergency has been advocated. <h3>Objective</h3> To characterise patients with 'emergency CAP' and evaluate predictors for very early organ failure or death. <h3>Methods</h3> 3427 prospectively enrolled patients of the CAPNETZ cohort were included. Emergency CAP was defined as requirement for mechanical ventilation or vasopressor support (MV/VS) or death within 72 h and 7 days after hospital admission, respectively. To determine independent predictors, multivariate Cox regression was employed. The ATS/IDSA 2007 minor criteria were evaluated for prediction of emergency CAP in patients without immediate need of MV/VS. <h3>Results</h3> 140 (4%) and 173 (5%) patients presented with emergency CAP within 3 and 7 days, respectively. Hospital mortality of patients presenting without immediate need of MV/VS was highest. Independent predictors of emergency CAP were the presence of focal chest signs, home oxygen therapy, multilobar infiltrates, altered mental status and altered vital signs (hypotension, raised respiratory or heart rate, hypothermia). The ATS/IDSA 2007 minor criteria showed a high sensitivity and negative predictive value, whereas the positive predictive value was low. Reduction to 6 minor criteria did not alter accuracy. <h3>Conclusions</h3> Emergency CAP is a rare but prognostic relevant condition, mortality is highest in patients presenting without immediate need of MV/VS. Vital sign abnormalities and parameters indicating acute organ dysfunction are independent predictors, and the ATS/IDSA 2007 minor criteria show a high negative predictive value.
Computer Three-Dimensional Reconstruction of the Atrioventricular Node
Authors: Jue Li, Ian D. Greener, Shin Inada, Vladimir P. Nikolski, Mitsuru Yamamoto, Jules C. Hancox, Henggui Zhang, Rudi Billeter, Igor R. Efimov, Halina Dobrzynski, Mark R. Boyett
Journal: Circulation Research (2008)

Because of its complexity, the atrioventricular node (AVN), remains 1 of the least understood regions of the heart. The aim of the study was to construct a detailed anatomic model of the AVN and relate it to AVN function. The electric activity of a rabbit AVN preparation was imaged using voltage-dependent dye. The preparation was then fixed and sectioned. Sixty-five sections at 60- to 340-microm intervals were stained for histology and immunolabeled for neurofilament (marker of nodal tissue) and connexin43 (gap junction protein). This revealed multiple structures within and around the AVN, including transitional tissue, inferior nodal extension, penetrating bundle, His bundle, atrial and ventricular muscle, central fibrous body, tendon of Todaro, and valves. A 3D anatomically detailed mathematical model (approximately 13 million element array) of the AVN and surrounding atrium and ventricle, incorporating all cell types, was constructed. Comparison of the model with electric activity recorded in experiments suggests that the inferior nodal extension forms the slow pathway, whereas the transitional tissue forms the fast pathway into the AVN. In addition, it suggests the pacemaker activity of the atrioventricular junction originates in the inferior nodal extension. Computer simulation of the propagation of the action potential through the anatomic model shows how, because of the complex structure of the AVN, reentry (slow-fast and fast-slow) can occur. In summary, a mathematical model of the anatomy of the AVN has been generated that allows AVN conduction to be explored.