tbuckley/cabot-search huggingface dataset:
Dependence of Wall Stress in the Human Thoracic Aorta on Age and Pressure
Authors: HERMANN BADER
Journal: Circulation Research (1967)

The tangential wall stress and the tangential elasticity modulus at pressures from 0 to 200 mm Hg were calculated from pressure-volume diagrams of 27 human thoracic aortas aged 22 to 85 years. The relative volume increase of the aortas between 0 and 100 mm Hg decreased linearly from about 190% at age 20 to about 40% at age 85, whereas the elasticity modulus at 100 mm Hg increased linearly from 10 kg/cm 2 at age 20 to 42.5 kg/cm 2 at age 85. The decrease of the distensibility of the aortic wall with age was partly compensated by an increase of the internal volume of the aorta but at higher ages the distensibility was less than the theoretical values necessary for a proper buffering chamber activity. The tangential wall stress decreased linearly with age from about 2.5 kg/cm 2 at age 20 to about 1.2 kg/cm 2 at age 85. Since the pressoreceptors in the wall of the elastic vessels respond to the wall stress, this result means either that smooth muscles must increase the stress of the elastic fibers continuously, or the pressoreceptors must adapt their sensitivity throughout life to lower wall stress so that it will be kept constant. Weakness of the smooth muscles or a failure of the pressoreceptors to adapt themselves to lower stresses at higher ages may be the cause of essential hypertension.
Recent and Ancient Signature of Balancing Selection around the S-Locus in Arabidopsis halleri and A. lyrata
Authors: C. Roux, M. Pauwels, M.-V. Ruggiero, D. Charlesworth, V. Castric, X. Vekemans
Journal: Molecular Biology and Evolution (2012)

Balancing selection can maintain different alleles over long evolutionary times. Beyond this direct effect on the molecular targets of selection, balancing selection is also expected to increase neutral polymorphism in linked genome regions, in inverse proportion to their genetic map distances from the selected sites. The genes controlling plant self-incompatibility are subject to one of the strongest forms of balancing selection, and they show clear signatures of balancing selection. The genome region containing those genes (the S-locus) is generally described as nonrecombining, and the physical size of the region with low recombination has recently been established in a few species. However, the size of the region showing the indirect footprints of selection due to linkage to the S-locus is only roughly known. Here, we improved estimates of this region by surveying synonymous polymorphism and estimating recombination rates at 12 flanking region loci at known physical distances from the S-locus region boundary, in two closely related self-incompatible plants Arabidopsis halleri and A. lyrata. In addition to studying more loci than previous studies and using known physical distances, we simulated an explicit demographic scenario for the divergence between the two species, to evaluate the extent of the genomic region whose diversity departs significantly from neutral expectations. At the closest flanking loci, we detected signatures of both recent and ancient indirect effects of selection on the S-locus flanking genes, finding ancestral polymorphisms shared by both species, as well as an excess of derived mutations private to either species. However, these effects are detected only in a physically small region, suggesting that recombination in the flanking regions is sufficient to quickly break up linkage disequilibrium with the S-locus. Our approach may be useful for distinguishing cases of ancient versus recently evolved balancing selection in other systems.
Differences in the regulation of vascular resistance in guinea pigs with right and left heart failure.
Authors: P G Schmid, H E Mayer, A L Mark, D D Heistad, F M Abboud
Journal: Circulation Research (1977)

We investigated neurogenic, non-neurogenic, and structural contributions to vascular resistance in hindquarters in five groups of guinea pigs after heart failure produced by (1) constriction of the pulmonary artery (RHF), (2) constriction of the ascending aorta (LHF A ), and (3) constriction of the descending thoracic aorta (LHF D ); (4) after left ventricular hypertrophy produced by mild constriction of the ascending aorta (LVH); and (5) after sham surgery.Pressure-flow curves were used to assess vascular resistance in the isolated, perfused hindquarters.In RHF and LHF A , vascular resistance tended to increase and for different reasons.In the LHF A group, sympathectomy produced the greatest vasodilation.Therefore, neurogenic influences predominated.The high neurogenic tone may have been related to reduced arterial pulse pressure (P < 0.05) and reflexes arising in arterial baroreceptors.In contrast, the LHF D group had increased arterial pressure and pulse pressure (P < 0.05) and normal neurogenic vasoconstriction.However, non-neurogenic vasoconstriction was increased probably as a result of increased vascular responsiveness to constrictor stimuli.In the RHF group, papaverine produced the greatest vasodilation (P < 0.05).Therefore, non-neurogenic influences predominated.This was attributed to both increased vascular responsiveness and to altered humoral stimuli.Similar maximal vasodilation indicated that structural factors contributed equally to vascular resistance in all the groups.These results indicate differences in the regulation of vascular resistance in anesthetized, guinea pig models of right and left heart failure.
Azithromycin for prevention of exacerbations in non-cystic fibrosis bronchiectasis (EMBRACE): a randomised, double-blind, placebo-controlled trial
Authors: Conroy Wong, Lata Jayaram, Noel Karalus, Tam Eaton, Cecilia Tong, Hans Hockey, David Milne, Wendy Fergusson, Christine Tuffery, Paul Sexton, Louanne Storey, Toni Ashton
Journal: The Lancet (2012)
Dose-Escalating and Pharmacologic Study of Oxaliplatin in Adult Cancer Patients with Impaired Hepatic Function: A National Cancer Institute Organ Dysfunction Working Group Study
Authors: Timothy W. Synold, Chris H. Takimoto, James H. Doroshow, David Gandara, Sridhar Mani, Scot C. Remick, Daniel L. Mulkerin, Anne Hamilton, Sunil Sharma, Ramesh K. Ramanathan, Heinz Josef Lenz, Martin Graham, Jeffrey Longmate, Bennett M. Kaufman, Percy Ivy
Journal: Clinical Cancer Research (2007)

Abstract Purpose: To determine the toxicities, pharmacokinetics, and maximally tolerated doses of oxaliplatin in patients with hepatic impairment and to develop formal guidelines for oxaliplatin dosing in this patient population. Experimental Design: Sixty adult cancer patients with variable hepatic function received i.v. oxaliplatin ranging from 60 to 130 mg/m2 every 3 weeks. Patients were stratified by levels of total bilirubin, aspartate aminotransferase (AST), and alkaline phosphatase (AP) into five cohorts based on the degree of hepatic dysfunction: control group A [bilirubin, AST, and AP ≤ upper limit of normal (ULN)], mild dysfunction group B (bilirubin ≤ ULN, ULN &amp;lt; AST ≤ 2.5 × ULN, or ULN &amp;lt; AP ≤ 5 × ULN), moderate dysfunction group C (ULN &amp;lt; bilirubin ≤ 3.0 mg/dL, AST &amp;gt; 2.5 × ULN, or AP &amp;gt; 5 × ULN), severe dysfunction group D (bilirubin &amp;gt; 3.0 mg/dL, any AST, and any AP), and liver transplantation group E (any bilirubin, any AST, and any AP). Doses were escalated in cohorts of three patients, and urine and plasma ultrafiltrates were assayed for platinum concentrations. Results: Dose escalation of single-agent oxaliplatin to 130 mg/m2 was well tolerated in all cohorts. Platinum clearance did not correlate with any liver function test. Two of 56 assessable patients with a diagnosis of laryngeal carcinoma and cervical adenocarcinoma experienced partial responses lasting 3 and 5.5 months. Conclusions: Oxaliplatin at 130 mg/m2 every 3 weeks was well tolerated in all patients with impaired liver function. Dose reductions of single-agent oxaliplatin are not indicated in patients with hepatic dysfunction.
Influence of hepatitis delta virus replication in the presence of hepatitis B virus DNA in peripheral blood mononuclear cells
Authors: Gloria Moraleda, Javier Bartolomé, Maria Gracia Martinez, Juan Carlos Porres, Vicente Carreño
Journal: Hepatology (1990)

The presence of hepatitis B virus DNA was studied in peripheral blood mononuclear cell samples from 259 HBsAg carriers (229 anti-hepatitis delta negative, 30 anti-hepatitis delta positive), 16 anti-HBc-positive HBsAg-negative patients and 30 patients without hepatitis B virus markers. Hepatitis B virus DNA sequences were detected in peripheral blood mononuclear cell from 115 (44.4%) of the chronic HBsAg carriers and from two (12%) of the anti-HBc-positive, HBsAg-negative patients. In anti-hepatitis delta-negative patients, viral DNA was positive in peripheral blood mononuclear cell from 74 (46%) and from 24 (35.5%) with and without serum HBV-DNA, respectively. With respect to anti-hepatitis delta-positive patients, viral DNA was found in peripheral blood mononuclear cell in 8 of 13 (61.5%) of the patients with circulating hepatitis delta virus RNA and in 9 of 17 (53%) of the hepatitis delta virus RNA-negative subjects. Regarding hepatitis B virus DNA in serum and peripheral blood mononuclear cell, 71% (5 of 7) of the patients with serum hepatitis B virus DNA had this marker in peripheral blood mononuclear cell, whereas 52% (12 of 23) of the patients without serum hepatitis B virus DNA had hepatitis B virus DNA in peripheral blood mononuclear cell. A Southern blot analysis was also carried out on peripheral blood mononuclear cell samples from 30 patients. Hepatitis B virus DNA was detected in 16 patients as free forms, in 12 patients as dimers and free forms and as free circular together with free linear forms in the remaining two patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Influence of Aortic Coarctation on Pulsatile Hemodynamics in the Proximal Aorta
Authors: MICHAEL F. O'ROURKE, TIMOTHY B. CARTMILL
Journal: Circulation (1971)

Pressure and flow were recorded in the ascending aorta of three dogs with aortic coarctation, induced surgically 3 months previously, and in three control litter mates. From these data were derived input impedance of the systemic circulation, pulsatile and steady components of external heart work, aortic systolic pressure-time index, and mean systolic and mean diastolic pressures. Results were correlated with intraoperative measurements of aortic pressure in three young patients with aortic coarctation and with records taken in another 24 patients during diagnostic catheterization. Distinctive changes in aortic impedance with coarctation were explained in terms of altered peripheral reflection. Such changes were responsible for characteristic alteration in central aortic pressure pulse contour and for change in other parameters, indicating impaired arterial function in accepting pulsatile flow from the heart. Such changes in the cushioning function appear responsible for many clinical features and complications of aortic coarctation. Surgery is probably justified for restoration of the normal cushioning function of the arterial system as well as for reduction of resistance and mean arterial pressure.
An Initial Strategy of Intensive Medical Therapy Is Comparable to That of Coronary Revascularization for Suppression of Scintigraphic Ischemia in High-Risk But Stable Survivors of Acute Myocardial Infarction
Authors: John J. Mahmarian, Habib A. Dakik, Neil G. Filipchuk, Leslee J. Shaw, Sherif S. Iskander, Terrence D. Ruddy, Felix Keng, Milena J. Henzlova, Adel Allam, Lemuel A. Moyé, Craig M. Pratt
Journal: Journal of the American College of Cardiology (2006)
The Health of Latino Children
Authors: Glenn Flores, Elena Fuentes-Afflick, Oxiris Barbot, Olivia Carter-Pokras, Luz Claudio, Marielena Lara, Jennie A McLaurin, Lee Pachter, Francisco J Ramos-Gomez, Fernando Mendoza, R Burciaga Valdez, Antonia M Villarruel, Ruth E Zambrana, Robert Greenberg, Michael Weitzman, Francisco J Ramos Gomez
Journal: JAMA (2002)

Latinos recently became the largest racial/ethnic minority group of US children. The Latino Consortium of the American Academy of Pediatrics Center for Child Health Research, consisting of 13 expert panelists, identified the most important urgent priorities and unanswered questions in Latino child health. Conclusions were drawn when consensus was reached among members, with refinement through multiple iterations. A consensus statement with supporting references was drafted and revised. This article summarizes the key issues, including lack of validated research instruments, frequent unjustified exclusion from studies, and failure to analyze data by pertinent subgroups. Latino children are at high risk for behavioral and developmental disorders, and there are many unanswered questions about their mental health needs and use of services. The prevalence of dental caries is disproportionately higher for Latino children, but the reasons for this disparity are unclear. Culture and language can profoundly affect Latino children's health, but not enough cultural competency training of health care professionals and provision of linguistically appropriate care occur. Latinos are underrepresented at every level of the health care professions. Latino children are at high risk for school dropout, environmental hazards, obesity, diabetes mellitus, asthma, lack of health insurance, nonfinancial barriers to health care access, and impaired quality of care, but many key questions in these areas remain unanswered. This article suggests areas in which more research is needed and ways to improve research and care of Latino children.
Association Between Cigarette Smoking and Metabolic Syndrome
Authors: Maria Masulli, Olga Vaccaro
Journal: Diabetes Care (2006)

In the August 2005 issue of Diabetes Care , Oh et al. (1) reported that, in a representative population-based sample of 3,452 Korean men, cigarette smoking is associated with the metabolic syndrome. They also show a dose-dependent effect, with prevalence of the syndrome progressively increasing with the number of cigarettes smoked. Of the components of the syndrome, dyslipidemia (high triglycerides and low HDL cholesterol) and abdominal …
Schizophrenia as a Specific Biologic Disease
Authors: ROBERT G. HEATH, IRIS M. KRUPP
Journal: American Journal of Psychiatry (1968)

Previous work from the Tulane laboratories showed that a psychosis-inducing gamma globulin fraction in sera of schizophrenic patients, designated taraxein, was demonstrable by passive transfer in volunteer nonpsychotic recipients and in rhesus monkeys. In this study the authors found that the presence of taraxein in the sera of schizophrenic patients is specifically related to acute psychotic episodes and that serum fractions of patients with psychotic symptoms from diseases other than schizophrenia produced negative results. They conclude that taraxein is specifically related to schizophrenia.
Induction of immune tolerance to coagulation factor IX antigen by in vivo hepatic gene transfer
Authors: Federico Mingozzi, Yi-Lin Liu, Eric Dobrzynski, Antje Kaufhold, Jian Hua Liu, YuQin Wang, Valder R. Arruda, Katherine A. High, Roland W. Herzog
Journal: Journal of Clinical Investigation (2003)

Gene replacement therapy is an attractive approach for treatment of genetic disease, but may be complicated by the risk of a neutralizing immune response to the therapeutic gene product. There are examples of humoral and cellular immune responses against the transgene product as well as absence of such responses, depending on vector design and the underlying mutation in the dysfunctional gene. It has been unclear, however, whether transgene expression can induce tolerance to the therapeutic antigen. Here, we demonstrate induction of immune tolerance to a secreted human coagulation factor IX (hF.IX) antigen by adeno-associated viral gene transfer to the liver. Tolerized mice showed absence of anti-hF.IX and substantially reduced in vitro T cell responses after immunization with hF.IX in adjuvant. Tolerance induction was antigen specific, affected a broad range of Th cell subsets, and was favored by higher levels of transgene expression as determined by promoter strength, vector dose, and mouse strain. Hepatocyte-derived hF.IX expression induced regulatory CD4+ T cells that can suppress anti-hF.IX formation after adoptive transfer. With a strain-dependent rate of success, tolerance to murine F.IX was induced in mice with a large F.IX gene deletion, supporting the relevance of these data for treatment of hemophilia B and other genetic diseases.
Conservation of Essential Design Features in Coiled Coil Silks
Authors: T. D. Sutherland, S. Weisman, H. E. Trueman, A. Sriskantha, J. W. H. Trueman, V. S. Haritos
Journal: Molecular Biology and Evolution (2007)

Silks are strong protein fibers produced by a broad array of spiders and insects. The vast majority of known silks are large, repetitive proteins assembled into extended β-sheet structures. Honeybees, however, have found a radically different evolutionary solution to the need for a building material. The 4 fibrous proteins of honeybee silk are small (∼30 kDa each) and nonrepetitive and adopt a coiled coil structure. We examined silks from the 3 superfamilies of the Aculeata (Hymenoptera: Apocrita) by infrared spectroscopy and found coiled coil structure in bees (Apoidea) and in ants (Vespoidea) but not in parasitic wasps of the Chrysidoidea. We subsequently identified and sequenced the silk genes of bumblebees, bulldog ants, and weaver ants and compared these with honeybee silk genes. Each species produced orthologues of the 4 small fibroin proteins identified in honeybee silk. Each fibroin contained a continuous predicted coiled coil region of around 210 residues, flanked by 23–160 residue length N- and C-termini. The cores of the coiled coils were unusually rich in alanine. There was extensive sequence divergence among the bee and ant silk genes (<50% similarity between the alignable regions of bee and ant sequences), consistent with constant and equivalent divergence since the bee/ant split (estimated to be 155 Myr). Despite a high background level of sequence diversity, we have identified conserved design elements that we propose are essential to the assembly and function of coiled coil silks.
T2 Blockade of intraalveolar p55 TNF-receptor signalling by a domain antibody decreases inflammation and oedema in an in vivo mouse model of ventilator-induced lung injury
Authors: S. Bertok, M. R. Wilson, P. J. Morley, R. de Wildt, A. Bayliffe, M. Takata
Journal: Thorax (2010)

<h3>Introduction and Objectives</h3> Tumour necrosis factor (TNF) alpha is transiently up-regulated within the alveolar space during ventilator-induced lung injury (VILI). We previously found that the two TNF receptors play opposing roles during VILI in knock-out mice, with p55 promoting but p75 preventing pulmonary oedema. This suggests that specific blockade of p55 receptor signalling within the alveolar space may be beneficial in VILI. Domain antibodies (dAbs) are the smallest antigen-binding fragments of the IgG molecule, which may have advantages over complete antibodies due to their small size and monovalent binding (mAbs often have agonist activity due to receptor cross-linking). In this study we tested the effects of an intratracheally (i.t.) delivered dAb that binds to and inhibits the murine p55 receptor (Biopharmaceutical R&amp;D, GlaxoSmithKline), on pulmonary oedema and inflammation in mouse models of VILI. <h3>Methods</h3> C57BL6 mice were ventilated with a high-stretch protocol (standardised by plateau pressure at 12.5–13.5 cm H<sub>2</sub>O; tidal volume 20–22 ml/kg, PEEP 3 cm H<sub>2</sub>O, O<sub>2</sub> with 2–4% CO<sub>2</sub>). Mice then received an i.t. bolus of either non-specific ‘dummy’ dAb or p55-specific dAb (25 μg in 50 μl), and were ventilated for up to 4 h (1-hit model). As a 2-hit model, 20 ng LPS were included in the dAb bolus. Development of lung injury was assessed by respiratory elastance and blood gases, and protein level in bronchoalveolar lavage fluid (BALF) at termination. In the 2-hit model, neutrophil infiltration into BALF, the activation state of alveolar macrophages, and neutrophil margination within lung vasculature were all assessed by flow cytometry. <h3>Results</h3> High stretch ventilation produced deteriorations in elastance and PO<sub>2</sub> and high BALF protein in both models. Treatment with the p55-specific dAb substantially attenuated all of these changes in the 1-hit model (Abstract T2 Table 1). In the 2-hit model, p55 blockade prevented deteriorations in elastance and oxygenation, and significantly decreased neutrophil margination, intraalveolar neutrophil infiltration and ICAM-1 expression on alveolar macrophages. <h3>Conclusions</h3> Use of dAbs to selectively inhibit intra-alveolar p55 TNF receptor signalling may open new therapeutic approaches for ventilated patients with acute lung injury. This study was supported by Biopharmaceutical R&amp;D, GlaxoSmithKline.
Short Communication: Oxidative Posttranslational Modifications Mediate Decreased SERCA Activity and Myocyte Dysfunction in Gαq-Overexpressing Mice
Authors: Steve Lancel, Fuzhong Qin, Shannon L. Lennon, Jingmei Zhang, XiaoYong Tong, Michael J. Mazzini, Y. James Kang, Deborah A. Siwik, Richard A. Cohen, Wilson S. Colucci
Journal: Circulation Research (2010)

Myocyte contractile dysfunction occurs in pathological remodeling in association with abnormalities in calcium regulation. Mice with cardiac myocyte-specific overexpression of Galphaq develop progressive left ventricular failure associated with myocyte contractile dysfunction and calcium dysregulation.
Cellular and Molecular Basis of Pulmonary Arterial Hypertension
Authors: Nicholas W. Morrell, Serge Adnot, Stephen L. Archer, Jocelyn Dupuis, Peter Lloyd Jones, Margaret R. MacLean, Ivan F. McMurtry, Kurt R. Stenmark, Patricia A. Thistlethwaite, Norbert Weissmann, Jason X.-J. Yuan, E. Kenneth Weir
Journal: Journal of the American College of Cardiology (2009)
MUNCHAUSEN ZOLLINGER-ELLISON SYNDROME
Authors: M.J. Daly, E.A. Forret, N.J.H. Carroll, K.R.W. Gillon, F.S. Plaat, D.A. Persoff, T.V.T. Isitt, D.C. Wilkins, S.M. Knight, J. Nightingale, D.A. Burke, H. Mitchison, S. O'Brian, A. Rich, M.B. Clague
Journal: The Lancet (1989)
CORRELATIONS OF BEHAVIOR AND NEUROPATHOLOGY IN A CASE OF CEREBRAL PALSY FROM BIRTH INJURY
Authors: Arnold Gesell, Harry M. Zimmerman
Journal: American Journal of Psychiatry (1937)

1. A first detailed study, correlating behavioral data with neuropathologic findings in a case of cerebral palsy is presented. 2. The psychological development and behavior characteristics of A. C. were investigated by repeated observations, cinema records, and a training program, until his death at the age of 14 years. 3. Necropsy showed an uncomplicated lesion of the basal ganglia, of the classic status marmoratus type. 4. A tabular summary lists the neuropathological and behavioral findings and brings normal and observed functions into comparison. 5. The cinema records of A. C. at 7, 10 and 13 years were subjected to frame by frame analysis to ascertain evidences of pattern in the apparently erratic movements of his double athetosis. 6. This cinemanalysis revealed temporal and spatial pattern characteristics similar to those of the spontaneous supine activity and the tonic neck reflex of normal infancy. Eleven comparable pattern phases in A. C. and a normal four weeks old infant are identified and delineated. 7. The psychological characteristics of A. C. are interpreted in relation to his autonomic, sensori-motor, intellectual and social behavior. The limitations of motor theories of mental life and of mental growth are pointed out. 8. In spite of the paucity and disfigurement of kinesthetic experience, A. C. showed remarkable integration of personality and significant approximations to normal mentality. 9. Considerable maturation takes place in unimpaired cerebral areas even when they are cut off from normal tactile motor communications. 10. The blemish of behavior patterning is not commensurate with the destruction of the primary sensory and motor mechanisms. Mental growth tends toward an optimum organization.