tbuckley/cabot-search huggingface dataset:
Dynamical Mechanism for Subcellular Alternans in Cardiac Myocytes
Authors: Stephen A. Gaeta, Gil Bub, Geoffrey W. Abbott, David J. Christini
Journal: Circulation Research (2009)

Cardiac repolarization alternans is an arrhythmogenic rhythm disturbance, manifested in individual myocytes as a beat-to-beat alternation of action potential durations and intracellular calcium transient magnitudes. Recent experimental studies have reported "subcellular alternans," in which distinct regions of an individual cell are seen to have counterphase calcium alternations, but the mechanism by which this occurs is not well understood. Although previous theoretical work has proposed a possible dynamical mechanism for subcellular alternans formation, no direct evidence for this mechanism has been reported in vitro. Rather, experimental studies have generally invoked fixed subcellular heterogeneities in calcium-cycling characteristics as the mechanism of subcellular alternans formation.In this study, we have generalized the previously proposed dynamical mechanism to predict a simple pacing algorithm by which subcellular alternans can be induced in isolated cardiac myocytes in the presence or absence of fixed subcellular heterogeneity. We aimed to verify this hypothesis using computational modeling and to confirm it experimentally in isolated cardiac myocytes. Furthermore, we hypothesized that this dynamical mechanism may account for previous reports of subcellular alternans seen in statically paced, intact tissue.Using a physiologically realistic computational model of a cardiac myocyte, we show that our predicted pacing algorithm induces subcellular alternans in a manner consistent with theoretical predictions. We then use a combination of real-time electrophysiology and fluorescent calcium imaging to implement this protocol experimentally and show that it robustly induces subcellular alternans in isolated guinea pig ventricular myocytes. Finally, we use computational modeling to demonstrate that subcellular alternans can indeed be dynamically induced during static pacing of 1D fibers of myocytes during tissue-level spatially discordant alternans.Here we provide the first direct experimental evidence that subcellular alternans can be dynamically induced in cardiac myocytes. This proposed mechanism may contribute to subcellular alternans formation in the intact heart.
John William Bryan Palmer
Authors: D O'Brian
Journal: BMJ (2002)

Editor who raised the standards and status of the British Journal of Surgery; director of surgery in Bristol who tried to mediate as concerns about paediatric heart surgery emerged John Farndon, professor and head of surgery in Bristol, who died from a heart attack on 6 February, had a gift for medical editing and was an incisive referee.As editor of the British Journal of Surgery from 1992, he had an eye for the best material, putting together a good journal every month and moving it up the international league table until it was second only to Annals of Surgery.He chose papers that would be widely cited, increased the number of randomised controlled trials, and cut back on case reports.He was firm, fair, and strong minded.In January he stepped down as editor and was, as chairman of the British Journal of Surgery Society, to have furthered the journal's development.He wrote and edited textbooks on endocrine and breast surgery, operative surgery, and a guidebook for house surgeons.An excellent operating surgeon, his main interest was in his endocrine work, specialising in thyroid and parathyroid surgery.He improved the way in which patients with phaeochromocytoma were prepared for surgery by characterising the way in which these tumours released their hormones.He made important contributions to our understanding of the cellular biology of breast cancer, characterising those patients who would and would not respond to hormone therapy.
Local research ethics committees
Authors: K G M M Alberti
Journal: BMJ (1995)

Local research ethics committeesTime to grab several bulls by the horns Nowadays, it should be obvious to all participating in human research that ethical principles should be followed and that approval of a study by an ethics committee should always be sought.Despite the appalling lessons of the second world war this has not always been the case, and even now examples of unethical research are reported regularly, with researchers dazzled by the potential scientific rewards forgetting the moral and humane principles to which they should adhere.Ethics committees thus continue to be a vital safeguard, although their birth has been long and tortured and they continue to be criticised for their often idiosyncratic ways of operating.The main drive to the formation of ethics committees in Britain came from the World Medical Association's Declaration of Helsinki' and the publication of Pappworth's The Human Guinea Pig.2The British Medical Research Council reported in 1963 on the responsibility of researchers for the wellbeing of their subjects, and in 1967 the Royal College of Physicians recommended that all research should be subjected to ethical review.3In 1968 the Department of Health recommended that hospitals should establish ethics review boards but on an informal basis.Guidelines on how they should function appeared from the royal college in 1984 and in 1989 from the Department of Health.4But it was not until 1991 that the Department of Health formally required every health district to have a local research ethics committee and gave more detailed guidance on the composition of these committees and how they should function.5
Asbestos bodies in bronchoalveolar lavage reflect lung asbestos body concentration
Authors: P De Vuyst, P Dumortier, E Moulin, N Yourassowsky, P Roomans, P de Francquen, J C Yernault
Journal: European Respiratory Journal (1988)

Asbestos body (AB) countings on both bronchoalveolar lavage (BAL) fluids and digested lung tissue samples were performed in one hundred consecutive subjects submitted to a thoracotomy procedure, mostly for lung carcinoma. A good correlation (r = 0.73) was found between the two groups of values for the total group of subjects. When restrictive selection criteria were taken into account, such as lavage homolateral to the analysed lung, performed by the same trained physician, this correlation improved (r = 0.82). Absence of AB's or low AB counts (less than 1 AB/ml) in BAL corresponded in about 70% of cases to concentrations of less than 1,000 AB/gm and in 100% of cases to concentrations less than 10,000 AB/gm. In subjects with BAL containing more than 1 AB/ml, the lung tissues of 85% contained more than 1,000 AB/gm and the tissues of 44% contained more than 10,000 AB/gm. Above 10 AB/ml BAL, all lung tissues contained more than 10,000 AB/gm. Since lung tissue is not readily available in patients undergoing assessment of their asbestos exposure, BAL fluid analysis seems to be a useful tool to evaluate lung AB concentrations. This technique cannot be performed, however, in patients with severe lung impairment which does not allow sufficient recovery of BAL fluid.
Molecular Analysis of Clinical Isolates of Mycobacterium tuberculosis Collected from Patients with Persistent Disease in the Khartoum Region of Sudan
Authors: G.S. Sharaf-Eldin, N.S. Saeed, M.E. Hamid, A.M. Jordaan, G.D. Van der Spuy, R.M. Warren, P.D. Van Helden, T.C. Victor
Journal: Journal of Infection (2002)
Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer
Authors: Laufey Amundadottir, Peter Kraft, Rachael Z Stolzenberg-Solomon, Charles S Fuchs, Gloria M Petersen, Alan A Arslan, H Bas Bueno-de-Mesquita, Myron Gross, Kathy Helzlsouer, Eric J Jacobs, Andrea LaCroix, Wei Zheng, Demetrius Albanes, William Bamlet, Christine D Berg, Franco Berrino, Sheila Bingham, Julie E Buring, Paige M Bracci, Federico Canzian, Françoise Clavel-Chapelon, Sandra Clipp, Michelle Cotterchio, Mariza de Andrade, Eric J Duell, John W Fox Jr, Steven Gallinger, J Michael Gaziano, Edward L Giovannucci, Michael Goggins, Carlos A González, Göran Hallmans, Susan E Hankinson, Manal Hassan, Elizabeth A Holly, David J Hunter, Amy Hutchinson, Rebecca Jackson, Kevin B Jacobs, Mazda Jenab, Rudolf Kaaks, Alison P Klein, Charles Kooperberg, Robert C Kurtz, Donghui Li, Shannon M Lynch, Margaret Mandelson, Robert R McWilliams, Julie B Mendelsohn, Dominique S Michaud, Sara H Olson, Kim Overvad, Alpa V Patel, Petra H M Peeters, Aleksandar Rajkovic, Elio Riboli, Harvey A Risch, Xiao-Ou Shu, Gilles Thomas, Geoffrey S Tobias, Dimitrios Trichopoulos, Stephen K Van Den Eeden, Jarmo Virtamo, Jean Wactawski-Wende, Brian M Wolpin, Herbert Yu, Kai Yu, Anne Zeleniuch-Jacquotte, Stephen J Chanock, Patricia Hartge, Robert N Hoover
Journal: Nature Genetics (2009)
Flying Under the Radar: The Immunobiology of Hepatitis C
Authors: Lynn B. Dustin, Charles M. Rice
Journal: Annual Review of Immunology (2006)

The hepatitis C virus (HCV) is a remarkably successful pathogen, establishing persistent infection in more than two-thirds of those who contract it. Its success is related to its abilities to blunt innate antiviral pathways and to evade adaptive immune responses. These two themes may be related. We propose that HCV takes advantage of the impaired innate response to delay the organization of an effective adaptive immune attack. The tolerogenic liver environment may provide cover, prolonging this delay. HCV's error-prone replication strategy permits rapid evolution under immune pressure. Persistent high levels of viral antigens may contribute to immune exhaustion. Finally, the virus may benefit from the efficient enlistment of memory T and B cells in the pursuit of a moving target.
Organotypic slice cultures of human glioblastoma reveal different susceptibilities to treatments
Authors: Felicitas Merz, Frank Gaunitz, Faramarz Dehghani, Christof Renner, Jürgen Meixensberger, Angelika Gutenberg, Alf Giese, Kosta Schopow, Christian Hellwig, Michael Schäfer, Manfred Bauer, Horst Stöcker, Gisela Taucher-Scholz, Marco Durante, Ingo Bechmann
Journal: Neuro-Oncology (2013)

Glioblastoma multiforme is the most common lethal brain tumor in human adults, with no major therapeutic breakthroughs in recent decades. Research is based mostly on human tumor cell lines deprived of their organotypic environment or inserted into immune-deficient animals required for graft survival. Here, we describe how glioblastoma specimens obtained from surgical biopsy material can be sectioned and transferred into cultures within minutes. Slices were kept in 6-well plates, allowing direct observation, application of temozolomide, and irradiation. At the end of experiments, slice cultures were processed for histological analysis including hematoxylin-eosin staining, detection of proliferation (Ki67), apoptosis/cell death (cleaved caspase 3, propidium iodide), DNA double-strand breaks (γH2AX), and neural subpopulations. First clinical trials employed irradiation with the heavy ion carbon for the treatment of glioblastoma patients, but the biological effects and most effective dose regimens remain to be established. Therefore, we developed an approach to expose glioblastoma slice cultures to 12C and X-rays. We found preservation of the individual histopathology over at least 16 days. Treatments resulted in activation of caspase 3, inhibition of proliferation, and cell loss. Irradiation induced γH2AX. In line with clinical observations, individual tumors differed significantly in their susceptibility to temozolomide (0.4%–2.5% apoptosis and 1%–15% cell loss). Glioblastoma multiforme slice cultures provide a unique tool to explore susceptibility of individual tumors for specific therapies including heavy ions, thus potentially allowing more personalized treatments plus exploration of mechanisms of (and strategies to overcome) tumor resistance.
Convergent Evolution of Head Crests in Two Domesticated Columbids Is Associated with Different Missense Mutations in<i>EphB2</i>
Authors: Anna I. Vickrey, Eric T. Domyan, Martin P. Horvath, Michael D. Shapiro
Journal: Molecular Biology and Evolution (2015)

Head crests are important display structures in wild bird species and are also common in domesticated lineages.Many breeds of domestic rock pigeon (Columba livia) have crests of reversed occipital feathers, and this recessive trait is associated with a nonsynonymous coding mutation in the intracellular kinase domain of EphB2 (Ephrin receptor B2).The domestic ringneck dove (Streptopelia risoria) also has a recessive crested morph with reversed occipital feathers, and interspecific crosses between crested doves and pigeons produce crested offspring, suggesting a similar genetic basis for this trait in both species.We therefore investigated EphB2 as a candidate for the head crest phenotype of ringneck doves and identified a nonsynonymous coding mutation in the intracellular kinase domain that is significantly associated with the crested morph.This mutation is over 100 amino acid positions away from the crest mutation found in rock pigeons, yet both mutations are predicted to negatively affect the function of ATP-binding pocket.Furthermore, bacterial toxicity assays suggest that "crest" mutations in both species severely impact kinase activity.We conclude that head crests are associated with different mutations in the same functional domain of the same gene in two different columbid species, thereby representing striking evolutionary convergence in morphology and molecules.
Effects of corticosteroids on epithelial structure and smooth muscle function of rat trachea
Authors: D Pavlovic, N Viires, C Zedda, M Fournier, M Aubier
Journal: European Respiratory Journal (1998)

Corticosteroids, efficient drugs for the treatment of severe asthma, may have numerous side effects. We investigated the effects of 7 days of treatment with triamcinolone (1.2 mg x kg(-1) x day(-1)) on the epithelial structure, tracheal smooth muscle cross-sectional area and contractility in the rat. The corticosteroid-injected rats were compared to pair-fed, and pair-weighed animals. Histological studies were performed on transverse sections of glutaraldehyde-fixed tracheal blocks embedded in plastic. In the preparations taken from corticosteroid-injected, pair-fed and pair-weighed animals, pharmacological stimulation with single (10(-3) M) or cumulative (10(-8)-10(-3) M) concentrations of carbachol (in corticosteroid-injected and pair-fed animals), either inside (In) or outside (Out) of the tracheal lumen, was performed and contractions of the tracheal smooth muscle were recorded. We found that triamcinolone administration: 1) reduced the number of epithelial cells and the tracheal smooth muscle cross-sectional area; 2) induced a decrease in maximal tension (Tmax (g); Out: 2.42+/-0.17, 1.03+/-0.1 in pair-fed and corticosteroid-injected, respectively; In: 2.55+/-0.16, 1.1+/-0.16, respectively) without affecting the sensitivity of the tracheal smooth muscle; and 3) reduced the time required to reach 50% Tmax in carbachol (In) preparations. We conclude that the observed changes resulted from atrophy of tracheal smooth muscle induced by undernutrition and atrophy of tracheal smooth muscle and tracheal epithelium induced by corticosteroid treatment.
Coronary Driving Pressure and Vasomotor Tonus as Determinants of Coronary Blood Flow
Authors: CECIL E. CROSS, P. ANDRE RIEBEN, PETER F. SALISBURY
Journal: Circulation Research (1961)

A method is described that measures the contribution of coronary vasomotor tonus and extracoronary factors in the regulation of coronary blood flow. Coronary flow was measured from the bypassed right heart when the left ventricle pumped the entire systemic flow (method "A") and when a heart-lung machine generated systemic pressure (method "B"). In method "B," the mechanical activity and the oxygen consumption of the heart could be dissociated from systemic pres sure by the use of a balloon in the ventricle. Control measurements were performed in "uninjured" hearts; when a balloon was inflated to a left ventricular diastolic pressure of 15 mm. Hg or more, a state of "cardiac injury" supervened. The arterial oxygen content was kept above 20 to 21 vol. per cent, but the cardiac oxygen consumption varied over a wide range. Whenever hemodynamic factors changed, coronary flow was a highly correlated, straight-line function of the difference between the aortic pressure and the left ventricular pressure, which we call the "coronary driving pressure." In "injured" hearts this linearity and high correlation persisted, but the slope of the regression line increased. We conclude that coronary flow is determined by the integrated difference between the propulsive force (the fluctuating pressure head at the coronary ostia) and opposing forces (intramyocardial pressure, which is known to oppose local coronary flow whenever and wherever it exceeds intravascular pressures). Cardiac oxygen consumption and coronary blood flow were not significantly related and were, therefore, coordinated by purely mechanical pressure differentials and not by changes of coronary vasomotor tonus. However, coronary vasomotor tonus decreased markedly during arterial anoxia or after various types of cardiac injury; it increased after Pitressin.
Reduction in renal blood flow following acute increase in the portal pressure: evidence for the existence of a hepatorenal reflex in man?
Authors: R Jalan, E H Forrest, D N Redhead, J F Dillon, P C Hayes
Journal: Gut (1997)

To investigate the relation between changes in portal haemodynamics and renal blood flow (RBF) in patients with cirrhosis.Twenty patients with cirrhosis and transjugular intrahepatic portosystemic stent-shunts were divided into two groups which were well matched. At routine portography, either changes in unilateral RBF (group I) or changes in cardiac output (group II) before and after shunt occlusion were studied. Blood was obtained from the renal and systemic circulations for the measurement of neurohumoral factors before and after shunt occlusion in group I patients.After shunt occlusion, there was a progressive reduction in unilateral RBF from a mean (SD) of 289 (32) to 155 (25) (-43.5%) (p < 0.001). These changes correlated significantly with the changes in the portal atrial gradient (p < 0.001). There was no significant change in heart rate, mean arterial pressure and right atrial pressure. No significant changes were found in the concentrations of the various neurohumoral factors measured. There was a less notable but significant reduction in the cardiac output (-10.9%) (p = 0.02) unaccompanied by significant reduction in the pulmonary capillary wedge pressure or mean arterial pressure.These results suggest the existence of hepatorenal reflex in man which is important in the regulation of RBF, although other mechanisms may also be contributory.
Association between early life history of respiratory disease and morbidity and mortality in adulthood
Authors: B Galobardes, P McCarron, M Jeffreys, G Davey Smith
Journal: Thorax (2008)

<h3>Background:</h3> Early life exposure to respiratory diseases is associated with lung impairment in adulthood. The objective of this study was to investigate morbidity, and respiratory and other cause specific mortality, among people who reported a medical history of bronchitis, pneumonia and asthma early in life. <h3>Methods:</h3> We studied an historical cohort of male students who attended Glasgow University between 1948 and 1968 and for whom long term follow-up and cause specific mortality were available (9544 students, 1553 deaths). A medical history of respiratory diseases, including bronchitis, pneumonia and asthma, along with other disease risk factors and socioeconomic conditions, were collected during university health examinations. A subsample responded to a postal follow-up in adulthood (n = 4044), which included respiratory and other chronic disease questions. <h3>Results:</h3> A medical history of a respiratory disease (bronchitis, pneumonia and asthma) in early life was associated with a 57% greater risk of overall respiratory disease mortality in adulthood and a more than twofold increase in chronic obstructive pulmonary disease mortality (fully adjusted hazard ratio (HR) 2.37; 95% CI 1.16, 4.83). In addition, students reporting a history of bronchitis had a 38% higher risk of cardiovascular disease mortality (95% CI 1.06, 1.80). Respiratory disease in early life was also associated with a higher risk in adulthood of chronic phlegm, dyspnoea and doctor's diagnosis of asthma, bronchitis and emphysema (adjusted odds ratios ranging from 1.40 to 6.95 for these outcomes). <h3>Conclusion:</h3> An early life history of respiratory diseases is associated with higher mortality and morbidity risk in adulthood in men, the associations being seen particularly for respiratory related and cardiovascular deaths among those with a history of bronchitis. All early life respiratory diseases appeared to be negatively associated with later adult respiratory health.
Correlation of right ventricular echocardiographic parameters with hemodynamic factors in pulmonary hypertension
Authors: Hajime Kasai, Akane Matsumura, Toshihiko Sugiura, Ayako Shigeta, Ryogo Ema, Yoriko Sakurai, Yukiko Matsuura, Misuzu Yahaba, Naoko Kawata, Seiichiro Sakao, Yasunori Kasahara, Nobuhiro Tanabe, Koichiro Tatsumi
Journal: European Respiratory Journal (2014)

Background: In pulmonary hypertension, various echocardiographic parameters are measured for the evaluation of pulmonary hemodynamics. There are a few reports that evaluate how these parameters reflect pulmonary hemodynamics.  Materials and Methods: 42 subjects (20 with chronic thromboembolic pulmonary hypertension (CTEPH), 22 with pulmonary arterial hypertension (PAH)) underwent echocardiography and right heart catheterization (RHC). We measured tricuspid annular plane systolic excursion (TAPSE), systolic excursion velocity of tricuspid annulus of the right ventricular free wall side (S´) and right ventricular Tei-Index (RV Tei-Index) by echocardiography. And then, the correlation of these echocardiographic parameters and hemodynamic data by RHC were evaluated.  Results: There was no significant difference in pulmonary hemodynamic data by RHC between CTEPH and PAH, while S´ was significantly lower in CTEPH. In all subjects, S´ significantly correlated with pulmonary vascular resistance (PVR), mean pulmonary arterial pressure (mPAP) and cardiac output (CO) (r = -0.52, p   Conclusion: S´ is a noninvasive useful parameter reflecting pulmonary hemodynamics in pulmonary hypertension.