tbuckley/cabot-search huggingface dataset:
Regulation of hypoxic pulmonary vasoconstriction: basic mechanisms
Authors: N. Sommer, A. Dietrich, R. T. Schermuly, H. A. Ghofrani, T. Gudermann, R. Schulz, W. Seeger, F. Grimminger, N. Weissmann
Journal: European Respiratory Journal (2008)

Hypoxic pulmonary vasoconstriction (HPV), also known as the von Euler-Liljestrand mechanism, is a physiological response to alveolar hypoxia which distributes pulmonary capillary blood flow to alveolar areas of high oxygen partial pressure. Impairment of this mechanism may result in hypoxaemia. Under conditions of chronic hypoxia generalised vasoconstriction of the pulmonary vasculature in concert with hypoxia-induced vascular remodelling leads to pulmonary hypertension. Although the principle of HPV was recognised decades ago, its exact pathway still remains elusive. Neither the oxygen sensing process nor the exact pathway underlying HPV is fully deciphered yet. The effector pathway is suggested to include L-type calcium channels, nonspecific cation channels and voltage-dependent potassium channels, whereas mitochondria and nicotinamide adenine dinucleotide phosphate oxidases are discussed as oxygen sensors. Reactive oxygen species, redox couples and adenosine monophosphate-activated kinases are under investigation as mediators of hypoxic pulmonary vasoconstriction. Moreover, the role of calcium sensitisation, intracellular calcium stores and direction of change of reactive oxygen species is still under debate. In this context the present article focuses on the basic mechanisms of hypoxic pulmonary vasoconstriction and also outlines differences in current concepts that have been suggested for the regulation of hypoxic pulmonary vasoconstriction.
Prescribing of Thyroxine
Authors: J. H. Wetherill
Journal: BMJ (1971)

<h3>Background</h3> Understanding the mechanism of injury is necessary for the development of effective injury prevention strategies. Video analysis of injuries provides valuable information on the playing situation and athlete-movement patterns, which can be used to formulate these strategies. Therefore, we conducted a video analysis of the mechanism of concussion injury in junior-level rugby union and compared it with a representative and matched non-injury sample. <h3>Methods</h3> Injury reports for 18 concussion events were collected from the 2011 to 2013 under-18 Craven Week tournaments. Also, video footage was recorded for all 3 years. On the basis of the injury events, a representative ‘control’ sample of matched non-injury events in the same players was identified. The video footage, which had been recorded at each tournament, was then retrospectively analysed and coded. 10 injury events (5 tackle, 4 ruck, 1 aerial collision) and 83 non-injury events were analysed. <h3>Results</h3> All concussions were a result of contact with an opponent and 60% of players were unaware of the impending contact. For the measurement of <i>head position on contact</i>, 43% had a ‘down’ position, 29% the ‘up and forward’ and 29% the ‘away’ position (n=7). The speed of the injured tackler was observed as ‘slow’ in 60% of injurious tackles (n=5). In 3 of the 4 rucks in which injury occurred (75%), the concussed player was acting defensively either in the capacity of ‘support’ (n=2) or as the ‘jackal’ (n=1). <h3>Conclusions</h3> Training interventions aimed at improving peripheral vision, strengthening of the cervical muscles, targeted conditioning programmes to reduce the effects of fatigue, and emphasising safe and effective playing techniques have the potential to reduce the risk of sustaining a concussion injury.
Quantification of myocardial infarct size after coronary reperfusion by serum cardiac myosin light chain II in conscious dogs.
Authors: M Isobe, R Nagai, K Yamaoki, H Nakaoka, F Takaku, Y Yazaki
Journal: Circulation Research (1989)

The effects of early coronary artery reperfusion on the relation between the extent of myocardial infarction and serum levels of cardiac myosin light chain II or plasma creatine kinase levels were evaluated in the conscious dog. Hydraulic occluders were placed on the left anterior descending arteries of 38 dogs. Seven to 10 days later, myocardial infarction was produced. Coronary reperfusion was performed 3 hours (group A1, n = 13) and 6 hours (group A2, n = 12) after the occlusion. In the other 13 dogs, coronary occlusion was sustained throughout the course of the experiment (group B). Seven days after the occlusion, the heart was cut from the apex to the base into 4-mm slices, and infarct size was determined macroscopically. Rapid appearance and early peaking of creatine kinase were observed in group A. Cumulative release of creatine kinase significantly correlated with infarct size in group A (infarct size ranged from 0.1 to 20.1 g, r = 0.90) and group B (from 0.6 to 26.8 g, r = 0.91). However, since creatine kinase release in group A was greater in comparison with that from infarcts of the same size in group B, the slope of the regression line for group A was significantly steeper (p less than 0.05). Cardiac myosin light chain II appeared as early as creatine kinase did and continued to be elevated for 7 days. A very close relation was observed between infarct size and total cardiac myosin light chain II release (r = 0.87 for group A, and r = 0.88 for group B) or peak level of light chain II (r = 0.85 for group A, and r = 0.81 for group B). In addition, the slopes of the regression lines for infarct size and both peak and total release of light chain II did not differ between group A and group B. On histological examination, viable myocardium was frequently observed in the epicardium of the ischemic area in group A1; therefore, infarct size was greater in group B than in group A1 (p less than 0.05). Also, myocardial creatine kinase content in the epicardium of the center of the ischemic area in group A1 was greater than that in group B. Cardiac myosin light chain II release in group A1 was less than that in group B, whereas no difference was found in plasma creatine kinase release among groups A1, A2, and B.(ABSTRACT TRUNCATED AT 250 WORDS)
A B Cell Superantigen–Induced Persistent “Hole” in the B-1 Repertoire
Authors: Gregg J. Silverman, Stephen P. Cary, Denise C. Dwyer, Linda Luo, Raymond Wagenknecht, Virginia E. Curtiss
Journal: The Journal of Experimental Medicine (2000)

The bacterial toxin protein A from Staphylococcus aureus (SpA) interacts with B cell antigen receptors encoded by variable region heavy chain (V(H)) clan III genes via a V region framework surface that has been highly conserved during the evolution of the adaptive immune system. We have investigated the consequences of exposure to this prototypic B cell superantigen, and found that treatment of neonates or adults induces a T cell-independent deletion of a large supraclonal set of susceptible B cells that includes clan III/V(H) S107 family-expressing lymphocytes. In studies of different SpA forms, the magnitude of the induced deletion directly correlated with the V(H)-specific binding affinity/avidity. Upon cessation of SpA exposure, the representation of conventional splenic (B-2 subset) lymphocytes normalized; however, we found that the V(H) family-restricted deficit of peritoneal B-1 cells persisted. SpA treatment also induced a persistent loss of splenic S107-mu transcripts, with a loss of certain natural antibodies and specific tolerance to phosphorylcholine immunogens that normally recruit protective antimicrobial responses dominated by the S107-expressing B-1 clone, T15. These studies illustrate how a B cell superantigen can exploit a primordial Achilles heel in the immune system, for which B-1 cells, an important source of natural antibodies and host immune responses, have special susceptibility.
Charles David Marsden Headley Boardman John Leslie Boldero William Howard Kenneth Carpenter Edward Gordon Crookes Jack Neville Phillips Davies John Clifford Denmark Ivan Joffe Iain Kerr Alistair Donald MacKenzie
Authors: N. Quinn, J B Vergano, J. L. Boldero, P K Carpenter, R P Slatcher, M. Hutt, B. T Monteiro, D. Boomla, D. B. Kelly, J. Mackie, P. H Setna
Journal: BMJ (1998)
Vagal stimulation and prevention of sudden death in conscious dogs with a healed myocardial infarction.
Authors: E Vanoli, G M De Ferrari, M Stramba-Badiale, S S Hull, R D Foreman, P J Schwartz
Journal: Circulation Research (1991)

The interest for the antifibrillatory effect of vagal stimulation has been largely limited by the fact that this concept seemed restricted to acute experiments in anesthetized animals. To explore the potentially protective role of vagal stimulation in conscious animals we developed a chronically implantable device to be placed around the cervical right vagus. An anterior myocardial infarction was produced in 161 dogs; 1 month later an exercise stress test was performed on the 105 survivors. Toward the end of the test the circumflex coronary artery was occluded for 2 minutes. Fifty-nine (56%) dogs developed ventricular fibrillation and, before this test was repeated, were assigned either to a control group (n = 24) or to be instrumented with the vagal device (n = 35). Five dogs were excluded because of electrode malfunction. Compared with the heart rate level attained after 30 seconds of occlusion during exercise in the control test, vagal stimulation led to a decrease of approximately 75 beats/min (from 255 +/- 33 to 170 +/- 36 beats/min, p less than 0.001). In the control group 22 (92%) of 24 dogs developed ventricular fibrillation during the second exercise and ischemia test. By contrast, during vagal stimulation ventricular fibrillation occurred in only 3 (10%) of the 30 dogs tested and recurred in 26 (87%) during an additional exercise and ischemia test in the control condition (p less than 0.001 versus the vagal stimulation test; internal control analysis). Combined analysis of the tests performed in the control condition showed that ventricular fibrillation was reproducible in 48 (89%) of the 54 dogs tested. The protective effect of vagal stimulation was also significant in the group comparison analysis and even after exclusion of those four dogs in which ventricular fibrillation was not reproducible (92% versus 11.5%, control versus vagal stimulation, p less than 0.001). When heart rate was kept constant by atrial pacing, the vagally mediated protection was still significant (p = 0.015) as five (55%) of nine dogs survived the test. This study shows that vagal stimulation, performed shortly after the onset of an acute ischemic episode in conscious animals with a healed myocardial infarction, can effectively prevent ventricular fibrillation. This striking result seems to depend on multiple mechanisms having a synergistic action. The decrease in heart rate is an important but not always essential protective mechanism. The electrophysiological effects secondary to the vagally mediated antagonism of the sympathetic activity on the heart are likely to play a major role.
Mortality Risk in Patients With Dementia Treated With Antipsychotics Versus Other Psychiatric Medications
Authors: Helen C. Kales, Marcia Valenstein, H. Myra Kim, John F. McCarthy, Dara Ganoczy, Francesca Cunningham, Frederic C. Blow
Journal: American Journal of Psychiatry (2007)

Mortality rates in the year following new antipsychotic medication starts for neuropsychiatric symptoms of dementia were compared with rates after starts of other psychiatric medications.The retrospective, cohort study used national data from the Department of Veterans Affairs (fiscal years 2001-2005) on patients older than 65 years who began outpatient treatment with psychiatric medication following a dementia diagnosis (N=10,615). Twelve-month mortality rates were compared in patients taking antipsychotics and those taking other psychiatric medications. The authors controlled for confounding by using multivariate models and propensity-scoring methods. Secondary analyses included a no-medication group and examination of mortality causes.All groups taking antipsychotics had significantly higher mortality rates (22.6%-29.1%) than patients taking nonantipsychotic medications (14.6%). Adjusted mortality risks for atypicals and for combined atypical and conventional antipsychotics were similar to those for conventional antipsychotics. The mortality risk was significantly lower for nonantipsychotic medications than conventional antipsychotics. Except for anticonvulsants, the adjusted risks for all individual classes of nonantipsychotics were significantly lower than the risk for antipsychotics. Mortality risks did not change over 12 months. The proportions of patients taking antipsychotics who died from cerebrovascular, cardiovascular, or infectious causes were not higher than rates for those taking nonantipsychotic psychiatric medications.Antipsychotic medications taken by patients with dementia were associated with higher mortality rates than were most other medications used for neuropsychiatric symptoms. The association between mortality and antipsychotics is not well understood and may be due to a direct medication effect or the pathophysiology underlying neuropsychiatric symptoms that prompt antipsychotic use.
Use of an Automated, Load-Distributing Band Chest Compression Device for Out-of-Hospital Cardiac Arrest Resuscitation
Authors: Marcus Eng Hock Ong, Joseph P. Ornato, David P. Edwards, Harinder S. Dhindsa, Al M. Best, Caesar S. Ines, Scott Hickey, Bryan Clark, Dean C. Williams, Robert G. Powell, Jerry L. Overton, Mary Ann Peberdy
Journal: JAMA (2006)

Only 1% to 8% of adults with out-of-hospital cardiac arrest survive to hospital discharge.To compare resuscitation outcomes before and after an urban emergency medical services (EMS) system switched from manual cardiopulmonary resuscitation (CPR) to load-distributing band (LDB) CPR.A phased, observational cohort evaluation with intention-to-treat analysis of 783 adults with out-of-hospital, nontraumatic cardiac arrest. A total of 499 patients were included in the manual CPR phase (January 1, 2001, to March 31, 2003) and 284 patients in the LDB-CPR phase (December 20, 2003, to March 31, 2005); of these patients, the LDB device was applied in 210 patients.Urban EMS system change from manual CPR to LDB-CPR.Return of spontaneous circulation (ROSC), with secondary outcome measures of survival to hospital admission and hospital discharge, and neurological outcome at discharge.Patients in the manual CPR and LDB-CPR phases were comparable except for a faster response time interval (mean difference, 26 seconds) and more EMS-witnessed arrests (18.7% vs 12.6%) with LDB. Rates for ROSC and survival were increased with LDB-CPR compared with manual CPR (for ROSC, 34.5%; 95% confidence interval [CI], 29.2%-40.3% vs 20.2%; 95% CI, 16.9%-24.0%; adjusted odds ratio [OR], 1.94; 95% CI, 1.38-2.72; for survival to hospital admission, 20.9%; 95% CI, 16.6%-26.1% vs 11.1%; 95% CI, 8.6%-14.2%; adjusted OR, 1.88; 95% CI, 1.23-2.86; and for survival to hospital discharge, 9.7%; 95% CI, 6.7%-13.8% vs 2.9%; 95% CI, 1.7%-4.8%; adjusted OR, 2.27; 95% CI, 1.11-4.77). In secondary analysis of the 210 patients in whom the LDB device was applied, 38 patients (18.1%) survived to hospital admission (95% CI, 13.4%-23.9%) and 12 patients (5.7%) survived to hospital discharge (95% CI, 3.0%-9.3%). Among patients in the manual CPR and LDB-CPR groups who survived to hospital discharge, there was no significant difference between groups in Cerebral Performance Category (P = .36) or Overall Performance Category (P = .40). The number needed to treat for the adjusted outcome survival to discharge was 15 (95% CI, 9-33).Compared with resuscitation using manual CPR, a resuscitation strategy using LDB-CPR on EMS ambulances is associated with improved survival to hospital discharge in adults with out-of-hospital nontraumatic cardiac arrest.
Is Oxytocin a Player in Antidiuresis?
Authors: Sei Sasaki
Journal: Journal of the American Society of Nephrology (2008)

The nonpeptide hormone oxytocin does not receive much thought from the renal community compared with its colleague, vasopressin. These two hormones display close similarities in chemical structure (differing by only two amino acids), their genes cluster at the same locus (20p13), and they are
Reperfusion induced enzyme release: washout effect or manifestation of reperfusion damage?
Authors: R W MOHANLAL, I MAUVE, A C M ZOET, A v. d. LAARSE
Journal: Cardiovascular Research (1988)

Isolated isovolumically contracting rat hearts were subjected to ischaemia and subsequent reperfusion to determine whether reperfusion induced release of lactate dehydrogenase from the heart was due to washout of previously unperfused areas by reflow or a manifestation of myocardial damage occurring during reperfusion. Hearts were exposed to 2 h of ischaemia alone or to 2 h of ischaemia followed by reperfusion for at least 2 h. Below an ischaemic coronary flow rate of 40% of the preischaemic value drainage of enzymes liberated from irreversibly damaged myocytes was impaired owing to the presence of unperfused myocardium. The lactate dehydrogenase activity released during 2 h of ischaemia was maximally 60 U per heart and during 2 h of reperfusion maximally 251 U per heart (comprising together 89% of cardiac lactate dehydrogenase content). Lactate dehydrogenase activity released during reperfusion correlated with ischaemic coronary flow rate (r = -0.93). Reperfusion induced reflow of previously unperfused regions resulted in washout of liberated but trapped lactate dehydrogenase, predominantly responsible for lactate dehydrogenase release if ischaemia was severe (ischaemic flow rate below 40%). After the onset of reperfusion there was partial initial recovery of left ventricular developed pressure, with a gradual decline thereafter. In experiments in which ischaemia induced unperfused areas could be excluded--that is, at ischaemic flow rates of 40% or higher--reperfusion gave rise to lactate dehydrogenase release closely associated in time with the decline of left ventricular developed pressure. It is concluded that in this rat heart preparation reperfusion --takes place in previously underperfused (low flow) myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)
Premenstrual asthma: still poorly understood
Authors: B. J. O'Connor
Journal: Thorax (1997)

<h3>ABSTRACT</h3> Accurate characterization of the tropical moist forests changes is needed to support conservation policies and to better quantify their contribution to global carbon fluxes. We document - at pantropical scale - the extent of these forests and their changes (degradation, deforestation and recovery) over the last three decades. We estimate that 17% of the tropical moist forests have disappeared since 1990 with a remaining area of 1060 million ha in 2019, from which 8.5% are degraded. Our study underlines the importance of the degradation process in such ecosystems, in particular as precursor of deforestation and in the recent increase of the tropical moist forest disturbances. Without reduction of the present disturbance rates, undisturbed forests will disappear entirely in large tropical humid regions by 2050. Our study suggests reinforcing actions to prevent the first disturbance scar that leads to forest clearance in 45% of the cases.
In Vivo Assessment of Embryonic Cardiovascular Dimensions and Function in Day-10.5 to -14.5 Mouse Embryos
Authors: Bradley B. Keller, Megan J. MacLennan, Joseph P. Tinney, Masaaki Yoshigi
Journal: Circulation Research (1996)

Embryonic cardiovascular function has been extensively studied in vivo in the chick embryo. However, the geometry of mammalian and avian hearts differs; the mammalian cardiovascular system is coupled to both yolk sac and placental circulations, and unique murine genetic models associated with structural and functional cardiovascular defects are now available. We therefore adapted techniques validated for the chick embryo to define cardiovascular dimensions and function in the mouse embryo. We bred C3HeB female and C57Bl/J6 male mice and ICR pairs for experiments on embryonic days (EDs) 10.5 to 14.5 (n=130 dams). After maternal anesthesia (pentobarbital, 60 mg/kg IP), laparotomy, and sequential regional hysterotomy, we exposed and then imaged individual embryos at 60 Hz (video) in the ventral and/or left anterior oblique views while maintaining uteroplacental continuity. We measured epicardial chamber dimensions and then calculated right and left ventricular elliptical volumes from areas. In addition, we measured pulsed-Doppler blood velocity across the atrioventricular cushions and ventricular outflow tract. We maintained embryonic temperature with a heated surgical platform, topical oxygenated and warmed buffer, and warming lamps. Embryonic heart rate increased from 124.7±5.2 to 194.3±13.2 bpm from EDs 10.5 to 14.5 ( P &lt;.01). Right and left ventricular end-diastolic and end-systolic dimensions increased ( P &lt;.05 by ANOVA for each). Maximal ventricular mean inflow and outflow velocities increased from 62.33±4.06 to 106.23±11.59 and from 55.79±6.11 to 91.61±6.93 mm/s, respectively ( P &lt;.05 by ANOVA for each). Thus, as has been done for chick and rat embryos, the maturation of murine embryonic cardiovascular function can be quantified in vivo, setting the stage for the investigation of structure-function relations in mouse models of cardiovascular development and disease.
Frequent epigenetic inactivation of RASSF2 in thyroid cancer and functional consequences
Authors: Undraga Schagdarsurengin, Antje M Richter, Juliane Hornung, Cornelia Lange, Katrin Steinmann, Reinhard H Dammann
Journal: Molecular Cancer (2010)

Abstract Background The Ras association domain family (RASSF) encodes for distinct tumor suppressors and several members are frequently silenced in human cancer. In our study, we analyzed the role of RASSF2, RASSF3, RASSF4, RASSF5A, RASSF5C and RASSF6 and the effectors MST1, MST2 and WW45 in thyroid carcinogenesis. Results Frequent methylation of the RASSF2 and RASSF5A CpG island promoters in thyroid tumors was observed. RASSF2 was methylated in 88% of thyroid cancer cell lines and in 63% of primary thyroid carcinomas. RASSF2 methylation was significantly increased in primary thyroid carcinoma compared to normal thyroid, goiter and follicular adenoma (0%, 17% and 0%, respectively; p &lt; 0.05). Patients which were older than 60 years were significantly hypermethylated for RASSF2 in their primary thyroid tumors compared to those younger than 40 years (90% vs. 38%; p &lt; 0.05). RASSF2 promoter hypermethylation correlated with its reduced expression and treatment with a DNA methylation inhibitor reactivated RASSF2 transcription. Over-expression of RASSF2 reduced colony formation of thyroid cancer cells. Functionally our data show that RASSF2 interacts with the proapoptotic kinases MST1 and MST2 and induces apoptosis in thyroid cancer cell lines. Deletion of the MST interaction domain of RASSF2 reduced apoptosis significantly (p &lt; 0.05). Conclusion These results suggest that RASSF2 encodes a novel epigenetically inactivated candidate tumor suppressor gene in thyroid carcinogenesis.