tbuckley/cabot-search huggingface dataset:
Relation between intracellular sodium and twitch tension in sheep cardiac Purkinje strands exposed to cardiac glycosides.
Authors: J A Wasserstrom, D J Schwartz, H A Fozzard
Journal: Circulation Research (1983)

Changes in intracellular sodium ion activity (aiNa) produced by several cardiac glycosides were correlated with twitch tension in sheep cardiac Purkinje strands. Simultaneous measurements of aiNa and twitch tension were obtained through the use of Na-sensitive intracellular microelectrodes (ETH 227) in Purkinje preparations stimulated at a frequency of 1 Hz. All concentrations of ouabain, acetylstrophanthidin, and actodigin that were tested caused an increase in aiNa immediately before, or coincident with, a positive inotropic effect. No fall in aiNa was observed at any positive inotropic concentration of digitalis in these beating fibers. In all cases, the onset and washout of the positive inotropic effect were paralleled by the rise and fall in aiNa, respectively. No dissociation between changes in aiNa and twitch tension occurred at any concentration of any of the agents used. The relation between changes in aiNa and twitch tension was linear with 1 mM increase in aiNa producing about a 100% increase in the twitch magnitude. Propranolol did not significantly alter this relationship. The increase in aiNa with digitalis was also associated with a reduction in the maximum depolarization rate of the action potential, presumably as a consequence of a reduction in the transmembrane Na electrochemical gradient. These results indicate that the positive inotropic action of digitalis in sheep Purkinje strands is always associated with a rise in aiNa secondary to inhibition of the Na pump. This increase in aiNa could increase calcium available for contraction via the Na-Ca equilibrium exchange process. In addition, the increase in aiNa reduces Vmax, as a consequence of decreasing the electrochemical gradient for Na.
Primary Plague Pneumonia Contracted From a Domestic Cat at South Lake Tahoe, Calif
Authors: S. Benson Werner
Journal: JAMA (1984)

Primary plague pneumonia occurred in a 47-year-old South Lake Tahoe woman shortly after face-to-face exposure to her plague pneumonia-infected cat. Both died. Field investigation revealed a recent plague epizootic in squirrels and chipmunks around the patient's home. Control measures included active surveillance and chemoprophylaxis of 197 contacts to the victim, a community alert on methods of self- and pet protection, and application of insecticide to reduce rodent flea populations. No secondary cases occurred.
A double-blind, randomized, placebo-controlled trial of prostaglandinE1 in liver transplantation
Authors: Keith S. Henley, Michael R. Lucey, Daniel P. Normolle, Robert M. Merion, Ian D. McLaren, Bruce A. Crider, Donald S. Mackie, Victoria L. Shieck, Timothy T. Nostrant, Kimberly A. Brown, Darrell A. Campbell, John M. Ham, Henry D. Appelman, Jeremiah G. Turcotte
Journal: Hepatology (1995)

A double-blind placebo-controlled trial of intravenous prostaglandin PGE1 (40 micrograms/h) was conducted in adult orthotopic liver transplant recipients. Infusion was started intraoperatively and continued for up to 21 days. Patients were followed up for 180 days postoperatively. Among 172 patients eligible for treatment in the study, 160 could be evaluated (78 PGE1; 82 placebo). Patient and graft survival were similar (PGE1: 16 deaths, 9 retransplantations [7 survivors]; controls: 15 deaths, 6 retransplantations [3 survivors]). In patients with surviving grafts, however, PGE1 administration resulted in a 23% shorter mean duration of hospitalization following transplantation (PGE1: 24.4 days; controls: 31.8 days; P = .02) and a 40% shorter length of time postoperatively in the intensive care unit (PGE1: 8.2 days; controls 13.7 days; P = .05). Reduced needs for renal support (P = .03) or surgical intervention other than retransplantation (P = .02) were also noted with PGE1 use. Further, PGE1 administration resulted in a trend toward improved survival rates in patients with mild renal impairment (preoperative serum creatinine 1.5 mg percent or greater; P = .08). Neither the incidence of acute cellular rejection nor of primary nonfunction was significantly different in the two groups. Phlebitis was the only complication that was more common during PGE1 administration, (PGE1: 9; controls: 4). These results suggest that PGE1 use in hepatic allograft recipients reduces morbidity and may result in sizable cost reductions.
Randomized Controlled Trial of Collaborative Care Management of Depression Among Low-Income Patients With Cancer
Authors: Kathleen Ell, Bin Xie, Brenda Quon, David I. Quinn, Megan Dwight-Johnson, Pey-Jiuan Lee
Journal: Journal of Clinical Oncology (2008)

Purpose To determine the effectiveness of the Alleviating Depression Among Patients With Cancer (ADAPt-C) collaborative care management for major depression or dysthymia. Patients and Methods Study patients included 472 low-income, predominantly female Hispanic patients with cancer age ≥ 18 years with major depression (49%), dysthymia (5%), or both (46%). Patients were randomly assigned to intervention (n = 242) or enhanced usual care (EUC; n = 230). Intervention patients had access for up to 12 months to a depression clinical specialist (supervised by a psychiatrist) who offered education, structured psychotherapy, and maintenance/relapse prevention support. The psychiatrist prescribed antidepressant medications for patients preferring or assessed to require medication. Results At 12 months, 63% of intervention patients had a 50% or greater reduction in depressive symptoms from baseline as assessed by the Patient Health Questionnaire-9 (PHQ-9) depression scale compared with 50% of EUC patients (odds ratio [OR] = 1.98; 95% CI, 1.16 to 3.38; P = .01). Improvement was also found for 5-point decrease in PHQ-9 score among 72.2% of intervention patients compared with 59.7% of EUC patients (OR = 1.99; 95% CI, 1.14 to 3.50; P = .02). Intervention patients also experienced greater rates of depression treatment (72.3% v 10.4% of EUC patients; P &lt; .0001) and significantly better quality-of-life outcomes, including social/family (adjusted mean difference between groups, 2.7; 95% CI, 1.22 to 4.17; P &lt; .001), emotional (adjusted mean difference, 1.29; 95% CI, 0.26 to 2.22; P = .01), functional (adjusted mean difference, 1.34; 95% CI, 0.08 to 2.59; P = .04), and physical well-being (adjusted mean difference, 2.79; 95% CI, 0.49 to 5.1; P = .02). Conclusion ADAPt-C collaborative care is feasible and results in significant reduction in depressive symptoms, improvement in quality of life, and lower pain levels compared with EUC for patients with depressive disorders in a low-income, predominantly Hispanic population in public sector oncology clinics.
Signal transduction by immunoglobulin is mediated through Ig alpha and Ig beta.
Authors: M Sanchez, Z Misulovin, A L Burkhardt, S Mahajan, T Costa, R Franke, J B Bolen, M Nussenzweig
Journal: The Journal of Experimental Medicine (1993)

Immunoglobulin (Ig) antigen receptors are composed of a noncovalently-associated complex of Ig and two other proteins, Ig alpha and Ig beta. The cytoplasmic domain of both of these Ig associated proteins contains a consensus sequence that is shared with the signaling proteins of the T cell and Fc receptor. To test the idea that Ig alpha-Ig beta heterodimers are the signaling components of the Ig receptor, we have studied Ig mutations that interfere with signal transduction. We find that specific mutations in the transmembrane domain of Ig that inactivate Ca2+ and phosphorylation responses also uncouple IgM from Ig alpha-Ig beta. These results define amino acid residues that are essential for the assembly of the Ig receptor. Further, receptor activity can be fully reconstituted in Ca2+ flux and phosphorylation assays by fusing the cytoplasmic domain of Ig alpha with the mutant Igs. In contrast, fusion of the cytoplasmic domain of Ig beta to the inactive Ig reconstitutes only Ca2+ responses. Thus, Ig alpha and Ig beta are both necessary and sufficient to mediate signal transduction by the Ig receptor in B cells. In addition, our results suggest that Ig alpha and Ig beta can activate different signaling pathways.
Aberrant dimerization of von Willebrand factor as the result of mutations in the carboxy-terminal region: identification of 3 mutations in members of 3 different families with type 2A (phenotype IID) von Willebrand disease
Authors: M. Said Enayat, Andrea M. Guilliatt, Gurcharan K. Surdhar, P. Vincent Jenkins, K. John Pasi, Cheng Hock Toh, Michael D. Williams, Frank G. H. Hill
Journal: Blood (2001)
Posterior cortical atrophy
Authors: Sebastian J Crutch, Manja Lehmann, Jonathan M Schott, Gil D Rabinovici, Martin N Rossor, Nick C Fox
Journal: The Lancet Neurology (2012)

Posterior cortical atrophy (PCA) is a neurodegenerative syndrome that is characterised by progressive decline in visuospatial, visuoperceptual, literacy, and praxic skills. The progressive neurodegeneration affecting parietal, occipital, and occipitotemporal cortices that underlies PCA is attributable to Alzheimer's disease in most patients. However, alternative underlying causes, including dementia with Lewy bodies, corticobasal degeneration, and prion disease, have also been identified, and not all patients with PCA have atrophy on clinical imaging. This heterogeneity has led to inconsistencies in diagnosis and terminology and difficulties in comparing studies from different centres, and has restricted the generalisability of findings from clinical trials and investigations of factors that drive phenotypic variability. Important challenges remain, including the identification of factors associated not only with the selective vulnerability of posterior cortical regions but also with the young age of onset of PCA. Greater awareness of the syndrome and agreement over the correspondence between syndrome-level and disease-level classifications are needed to improve diagnostic accuracy, clinical management, and the design of research studies.
The effects of intra-arterial and intraportal injections of vasopressin on the simultaneously perfused hepatic arterial and portal venous vascular beds of the dog.
Authors: P D Richardson, P G Withrington
Journal: Circulation Research (1978)

The hepatic arterial and hepatic portal venous vascular beds of the chloralose-urethane anesthetized dog were perfused simultaneously in situ. Vasopressin (10 mU = 1 unit) was injected in graded increasing doses into the hepatic artery and into the portal vein. Both intra-arterial and intraportal vasopressin elicited both hepatic arterial vasoconstriction and hepatic venous dilation; the delay in onset of both hepatic vascular effects was significantly shorter than that for any succeeding systemic effects (a rise in systemic arterial pressure and fall in heart rate), showing that they were not attributable to recirculation or to arterial baroreceptor reflexes. Injections of vasopressin into the inferior vena cava at the level of the hepatic veins consistently produced smaller hepatic vascular effects than either intra-arterial or intraportal injections of the same doses. The results are discussed in the context of the therapeutic role of vasopressin in controlling gastrointestinal bleeding and portal hypertension.
Systemic activity of inhaled corticosteroid treatment in asthmatic children: corticotrophin releasing hormone test
Authors: L Pescollderungg
Journal: Thorax (2003)

A study was undertaken to assess the function of the hypothalamic-pituitary-adrenal axis (HPA) in a group of asthmatic children before and after treatment with inhaled corticosteroids.Thirty prepubertal patients of mean (SD) age 6.7 (1.8) years were treated with inhaled corticosteroids. All children underwent a corticotrophin releasing hormone (CRH) test with evaluation of serum cortisol and adrenocorticotrophin hormone (ACTH) levels before and after 3 months of treatment. Twenty four hour urine samples were also collected to measure free cortisol (UFC) excretion.Subjects showed no difference between basal serum cortisol levels (mean change -18; 95% CI -41 to 5; p=0.118) and delta (peak minus basal) levels (mean change -13; 95% CI -38 to 12; p=0.308) before and after treatment, whereas the peak cortisol level (mean change -31; 95% CI -55 to -7; p=0.013) and area under the curve (AUC) (mean change -175; 95% CI -288 to -63; p=0.003) after CRH were significantly lower following treatment. Basal, peak and AUC ACTH were significantly lower after treatment (p<0.05, p=0.004 and p=0.003, respectively), while delta ACTH was similar before and after treatment ((mean change -12; 95% CI - 31 to -7; p=0.199). No significant reduction in 24 hour UFC was observed after the treatment period (before 14.9 (7.1), after 15.0 (11.6); mean change 0.1, 95% CI -5.2 to 5.4; p=0.967). No correlation was found between UFC and any of the parameters of cortisol excretion following the CRH test, either before or after treatment.These data suggest that, at the dosage and for the treatment period used, inhaled steroids do not seem to suppress the HPA axis in the majority of patients. The CRH test may be more sensitive than 24 hour UFC and morning plasma cortisol levels in evaluating systemic activity of inhaled corticosteroid treatment.
Determinants of Impaired Fasting Glucose Versus Glucose Intolerance in Polycystic Ovary Syndrome
Authors: Sidika E. Karakas, Kyoungmi Kim, Antoni J. Duleba
Journal: Diabetes Care (2010)

OBJECTIVE To determine insulin resistance and response in patients with polycystic ovary syndrome (PCOS) and normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance, and combined glucose intolerance (CGI). RESEARCH DESIGN AND METHODS In this cross-sectional study, 143 patients with PCOS (diagnosed on the basis of National Institutes of Health criteria) underwent oral glucose tolerance testing (OGTT), and 68 patients also had frequently sampled intravenous glucose tolerance tests. Changes in plasma glucose, insulin, cardiovascular risk factors, and androgens were measured. RESULTS Compared with patients with NGT, those with both IFG and CGI were significantly insulin resistant (homeostasis model assessment 3.3 ± 0.2 vs. 6.1 ± 0.9 and 6.4 ± 0.5, P &amp;lt; 0.0001) and hyperinsulinemic (insulin area under the curve for 120 min 973 ± 69 vs. 1,470 ± 197 and 1,461 ± 172 pmol/l, P &amp;lt; 0.0001). Insulin response was delayed in patients with CGI but not in those with IFG (2-h OGTT, insulin 1,001 ± 40 vs. 583 ± 45 pmol/l, P &amp;lt; 0.0001). Compared with the NGT group, the CGI group had a lower disposition index (1,615 ± 236 vs. 987 ± 296, P &amp;lt; 0.0234) and adiponectin level (11.1 ± 1.1 vs. 6.2 ± 0.8 ng/ml, P &amp;lt; 0.0096). Compared with the insulin-resistant tertile of the NGT group, those with IFG had a reduced insulinogenic index (421 ± 130 vs. 268 ± 68, P &amp;lt; 0.05). Compared with the insulin-sensitive tertile of the NGT group, the resistant tertile had higher triglyceride and high-sensitivity C-reactive protein (hs-CRP) and lower HDL cholesterol and sex hormone–binding globulin (SHBG). In the entire population, insulin resistance correlated directly with triglyceride, hs-CRP, and the free androgen index and inversely with SHBG. CONCLUSIONS Patients with PCOS develop IFG and CGI despite having significant hyperinsulinemia. Patients with IFG and CGI exhibit similar insulin resistance but very different insulin response patterns. Increases in cardiac risk factors and free androgen level precede overt glucose intolerance.
Continuity between pre- and post-demographic transition populations with respect to grandparental investment
Authors: Brad R. Huber
Journal: Behavioral and Brain Sciences (2010)

Abstract This commentary suggests that there is more continuity in pre- and post-demographic transition populations with respect to grandparental investments than is assumed by Coall &amp; Hertwig (C&amp;H). Recent research employing high-quality data supports the claim that sex-biased grandparental investments are likely to exist in industrialized societies, and that the economic status of grandparents is related to their long-term fitness.
Transduction of Renal Cells in Vitro and in Vivo by Adeno-Associated Virus Gene Therapy Vectors
Authors: MICHAEL S. LIPKOWITZ, BASIL HANSS, NATALIE TULCHIN, PATRICIA D. WILSON, JESSICA C. LANGER, MICHAEL D. ROSS, GARY J. KURTZMAN, PAUL E. KLOTMAN, MARY E. KLOTMAN
Journal: Journal of the American Society of Nephrology (1999)

Abstract. There has been an increasing interest recently in the possibility of treating renal diseases using gene therapy. The ability to pursue gene therapy for renal diseases has been limited by the availability of an adequate system for gene delivery to the kidney. Adeno-associated virus (AAV) is a defective virus of the parvovirus family that has a number of properties attractive for renal gene delivery: recombinant AAV contains no viral genes; expression of genes delivered by these vectors does not activate cell-mediated immunity; the virus is able to transduce nondividing as well as dividing cells; and both wild-type and recombinant AAV integrate into the host chromosome resulting in long-term gene expression. Studies were performed to determine whether AAV can deliver reporter genes to kidney cells in vitro and in vivo . These studies show that AAV can deliver reporter genes with approximately equal efficiency to human mesangial, proximal tubule, thick ascending limb, collecting tubule, and renal cell carcinoma cells in primary culture. Immortalized mouse mesangial cells are transduced at a much greater efficiency. Transduction can be enhanced by pharmaceutical agents up to sevenfold in primary cells (transducing up to 20% of primary cells per well) and as much as 400-fold in immortalized mesangial cells. AAV delivered in vivo by intraparenchymal injection results in at least 3 mo of reporter gene expression in tubular epithelial, but not glomerular or vascular, cells at the injection site. These data indicate that AAV can deliver genes to renal cells both in vitro and in vivo resulting in prolonged gene expression, and thus AAV can be a useful tool for renal gene delivery.
Two classes of germline genes both derived from the VH1 family direct the formation of human antibodies that recognize distinct antigenic sites in the C2 domain of factor VIII
Authors: Edward N. van den Brink, Wendy S. Bril, Ellen A. M. Turenhout, Marleen Zuurveld, Niels Bovenschen, Marjolein Peters, Thynn Thynn Yee, Koen Mertens, Deborah A. Lewis, Thomas L. Ortel, Pete Lollar, Dorothea Scandella, Jan Voorberg
Journal: Blood (2002)
Transient Receptor Potential Channels in Cardiovascular Function and Disease
Authors: Ryuji Inoue, Lars Jørn Jensen, Juan Shi, Hiromitsu Morita, Motohiro Nishida, Akira Honda, Yushi Ito
Journal: Circulation Research (2006)

Sustained elevation in the intracellular Ca2+ concentration via Ca2+ influx, which is activated by a variety of mechanisms, plays a central regulatory role for cardiovascular functions. Recent molecular biological research has disclosed an unexpectedly diverse array of Ca(2+-entry channel molecules involved in this Ca2+ influx. These include more than ten transient receptor potential (TRP) superfamily members such as TRPC1, TRPC3-6, TRPV1, TRPV2, TRPV4, TRPM4, TRPM7, and polycystin (TRPP2). Most of them appear to be multimodally activated or modulated and show relevant features to both acute hemodynamic control and long-term remodeling of the cardiovascular system, and many of them have been found to respond not only to receptor stimulation but also to various forms of stimuli. There is good evidence to implicate TRPC1 in neointimal hyperplasia after vascular injury via store-depletion-operated Ca2+ entry. TRPC6 likely contributes to receptor-operated and mechanosensitive Ca2+ mobilizations, being involved in vasoconstrictor and myogenic responses and pulmonary arterial proliferation and its associated disease (idiopathic pulmonary arterial hypertension). Considerable evidence has also been accumulated for unique involvement of TRPV1 in blood flow/pressure regulation via sensory vasoactive neuropeptide release. New lines of evidence suggest that TRPV2 may act as a Ca2+-overloading pathway associated with dystrophic cardiomyopathy, TRPV4 as a mediator of endothelium-dependent hyperpolarization, TRPM7 as a proproliferative vascular Mg2+ entry channel, and TRPP2 as a Ca2+-entry channel requisite for vascular integrity. This review attempts to provide an overview of the current knowledge on TRP proteins and discuss their possible roles in cardiovascular functions and diseases.
Spain is planning to introduce restrictions on abortion
Authors: A. Garcia Rada
Journal: BMJ (2013)

The conservative government of the People’s Party is planning to change Spain’s current law on abortion, passed by the previous socialist government in 2010,1 to make it more restrictive.

The current law established the right to abortion on demand up to 14 weeks of gestation and, under certain circumstances, up to the 22nd week, similar to the law in many other European Union countries. Despite the liberalisation of the law in 2010 the number of abortions fell by 5% from 2011 to 2012 (from 118 359 to 112 390), show data from the Ministry of Health, Social Affairs and Equality.

The draft of the new law, which has …
MHC Heterozygote Advantage in Simian Immunodeficiency Virus–Infected Mauritian Cynomolgus Macaques
Authors: Shelby L. O’Connor, Jennifer J. Lhost, Ericka A. Becker, Ann M. Detmer, Randall C. Johnson, Caitlin E. MacNair, Roger W. Wiseman, Julie A. Karl, Justin M. Greene, Benjamin J. Burwitz, Benjamin N. Bimber, Simon M. Lank, Jennifer J. Tuscher, Edward T. Mee, Nicola J. Rose, Ronald C. Desrosiers, Austin L. Hughes, Thomas C. Friedrich, Mary Carrington, David H. O’Connor
Journal: Science Translational Medicine (2010)

The importance of a broad CD8 T lymphocyte (CD8-TL) immune response to HIV is unknown. Ex vivo measurements of immunological activity directed at a limited number of defined epitopes provide an incomplete portrait of the actual immune response. We examined viral loads in simian immunodeficiency virus (SIV)-infected major histocompatibility complex (MHC)-homozygous and MHC-heterozygous Mauritian cynomolgus macaques. Chronic viremia in MHC-homozygous macaques was 80 times that in MHC-heterozygous macaques. Virus from MHC-homozygous macaques accumulated 11 to 14 variants, consistent with escape from CD8-TL responses after 1 year of SIV infection. The pattern of mutations detected in MHC-heterozygous macaques suggests that their epitope-specific CD8-TL responses are a composite of those present in their MHC-homozygous counterparts. These results provide the clearest example of MHC heterozygote advantage among individuals infected with the same immunodeficiency virus strain, suggesting that broad recognition of multiple CD8-TL epitopes should be a key feature of HIV vaccines.
Is the Glu298Asp polymorphism of Endothelial Nitric Oxide Synthesis Increase the Risk of Stent Thrombosis ?
Authors: Ahmet Arif Yalçın, Sinem Özyılmaz, İbrahim Faruk Aktürk, Veysel Sabri Hançer, Ömer Çelik, Fatih Uzun, Mehmet Ertürk, Ali Birand, Ender Öner, Ali Kemal Kalkan
Journal: Journal of the American College of Cardiology (2013)