tbuckley/cabot-search huggingface dataset:
Reduction of <i>I</i> <sub>to</sub> Causes Hypertrophy in Neonatal Rat Ventricular Myocytes
Authors: Zamaneh Kassiri, Carsten Zobel, The-Tin T. Nguyen, Jeffery D. Molkentin, Peter H. Backx
Journal: Circulation Research (2002)

Prolonged action potential duration (APD) and decreased transient outward K + current ( I to ) as a result of decreased expression of K v4.2 and K v4.3 genes are commonly observed in heart disease. We found that treatment of cultured neonatal rat ventricular myocytes with Heteropoda Toxin 3 , a blocker of cardiac I to , induced hypertrophy as measured using cell membrane capacitance and 3 H-leucine uptake. To dissect the role of specific I to -encoding genes in hypertrophy, I to was selectively reduced by overexpressing mutant dominant-negative (DN) transgenes. I to amplitude was reduced equally (by about 50%) by overexpression of DN K v1.4 (K v1.4 N) or DN K v4.2 (either K v4.2 N or K v4.2 W362F), but only DN K v4.2 prolonged APD duration (at 1 Hz) and induced myocyte hypertrophy. This hypertrophy was prevented by coexpressing wild-type K v4.2 channels (K v4.2 F) with the DN K v4.2 genes, suggesting the hypertrophy is due to I to reduction and not nonspecific effects of transgene overexpression. The hypertrophy caused by reductions of K v4.x -based I to was associated with increased activity of the calcium-dependent phosphatase, calcineurin, and could be prevented by coinfection with Ad-CAIN, a specific calcineurin inhibitor. The hypertrophy and calcineurin activation induced by K v4.2 N infection were prevented by blocking Ca 2+ entry and excitability with verapamil or high [K + ] o . Our studies suggest that reductions of K v4.2/3 -based I to play a role in hypertrophy signaling by activation of calcineurin.
Stress- and Allostasis-Induced Brain Plasticity
Authors: Bruce S. McEwen, Peter J. Gianaros
Journal: Annual Review of Medicine (2010)

The brain is the key organ of stress processes. It determines what individuals will experience as stressful, it orchestrates how individuals will cope with stressful experiences, and it changes both functionally and structurally as a result of stressful experiences. Within the brain, a distributed, dynamic, and plastic neural circuitry coordinates, monitors, and calibrates behavioral and physiological stress response systems to meet the demands imposed by particular stressors. These allodynamic processes can be adaptive in the short term (allostasis) and maladaptive in the long term (allostatic load). Critically, these processes involve bidirectional signaling between the brain and body. Consequently, allostasis and allostatic load can jointly affect vulnerability to brain-dependent and stress-related mental and physical health conditions. This review focuses on the role of brain plasticity in adaptation to, and pathophysiology resulting from, stressful experiences. It also considers interventions to prevent and treat chronic and prevalent health conditions via allodynamic brain mechanisms.
Association of environmental tobacco smoking exposure with an increased risk of hospital admissions for pneumonia in children under 5 years of age in Vietnam
Authors: M Suzuki, V D Thiem, H Yanai, T Matsubayashi, L-M Yoshida, L H Tho, T T Minh, D D Anh, P E Kilgore, K Ariyoshi
Journal: Thorax (2009)

<h3>Background:</h3> The association between environmental tobacco smoking (ETS) and childhood pneumonia has not been established in developed or developing countries. A study was conducted to assess the effect and impact of ETS exposure on pneumonia among children in central Vietnam. <h3>Methods:</h3> A population-based large-scale cross-sectional survey was conducted covering all residents of 33 communes in Khanh Hoa Province, the central part of Vietnam. Information on demographics, socioeconomic status and house environment, including smoking status of each household member, was collected from householders. Hospital admissions for pneumonia among children aged &lt;5 years in each household in the previous 12 months were recorded based on caregiver's report. <h3>Results:</h3> A total of 353 525 individuals living in 75 828 households were identified in the study areas. Of these, 24 781 (7.0%) were aged &lt;5 years. The prevalence of ETS was 70.5% and the period prevalence of hospital admissions for pneumonia was 2.6%. Multiple logistic regression analysis showed that exposure to ETS was independently associated with hospital admissions for pneumonia (adjusted odds ratio 1.55, 95% CI 1.25 to 1.92). The prevalence of tobacco smoking was higher among men than women (51.5% vs 1.5%). It is estimated that 28.7% of childhood pneumonia in this community is attributable to ETS. <h3>Conclusions:</h3> Children in Vietnam are exposed to substantial levels of ETS which results in 44 000 excess hospital admissions due to pneumonia each year among children aged &lt;5 years.
Generation of suppressor cells in mice after surgical trauma.
Authors: B S Wang, E H Heacock, A V Wu, J A Mannick
Journal: Journal of Clinical Investigation (1980)

Immunoincompetency is often seen in patients after various types of trauma and is associated with increased morbidity and mortality from infectious complications. To understand better the immunologic impairment associated with trauma, we have studied this phenomenon in an animal model. Splenocytes from mice traumatized by amputation of their right hind limbs were consistently shown to have a diminished capacity to proliferate in response to alloantigens and to form alloreactive cytolytic cells in mixed lymphocyte cultures. Anesthesia itself had no effect in this system. The immunoincompetency was detected from 2 h to 6 d after surgical trauma and was completely reversed by removing adherent and phagocytic cells from the splenocytes. Furthermore, addition of splenocytes from traumatized mice to mixed lymphocyte cultures from normal mice prevented normal lymphocytes from responding to alloantigens, suggesting the existence of suppressor cells. The suppressor cells were found to adhere to glass and to nylon wool columns, and were contained within an esterase-positive cell population. They were insensitive to treatment with anti-Thy 1.2 and anti-Ig sera in the presence of complement. Therefore, the present results suggest that a Thy 1.2-negative, Ig-negative, esterase-positive cell population capable of adhering to glass and nylon wool, presumably macrophages, was responsible for the inhibition of the responsiveness of lymphocytes to alloantigens in traumatized animals.
Antibiotics for chronic bronchitis: a meta-analysis that speaks only four languages
Authors: M. Miravitlles, B. Celli, A. Anzueto
Journal: European Respiratory Journal (2007)

To the Editors: 

We have read with interest the meta-analysis by Siempos et al . 1 evaluating the use of different antibiotics for exacerbations of chronic bronchitis. We are puzzled by the criteria used to select the studies that were included in the analysis. The authors utilised a well-established methodology and quality criteria for the selection of randomised clinical trials, but only studies written in English, French, German or Italian …
Histamine-2 Receptor Antagonists vs Proton Pump Inhibitors on Gastrointestinal Tract Hemorrhage and Infectious Complications in the Intensive Care Unit
Authors: Robert MacLaren, Paul M. Reynolds, Richard R. Allen
Journal: JAMA Internal Medicine (2014)

<h3>Importance</h3> Histamine-2 receptor antagonists (H<sub>2</sub>RAs) and proton pump inhibitors (PPIs) are commonly used to prevent gastrointestinal tract (GI) hemorrhage in critically ill patients. The stronger acid suppression of PPIs may reduce the rate of bleeding but enhance infectious complications, specifically pneumonia and<i>Clostridium difficile</i>infection (CDI). <h3>Objective</h3> To evaluate the occurrence and risk factors for GI hemorrhage, pneumonia, and CDI in critically ill patients. <h3>Design, Setting, and Participants</h3> A pharmacoepidemiological cohort study was conducted of adult patients requiring mechanical ventilation for 24 hours or more and administered either an H<sub>2</sub>RA or PPI for 48 hours or more while intubated across 71 hospitals between January 1, 2003, and December 31, 2008. Propensity score–adjusted and propensity-matched multivariate regression models were used to control for confounders. <h3>Main Outcomes and Measures</h3> Primary outcomes were secondary diagnoses of<i>International Classification of Diseases, Ninth Revision </i>(<i>ICD-9</i>)–coded GI hemorrhage, pneumonia, and CDI occurring 48 hours or more after initiating invasive ventilation. <h3>Results</h3> Of 35 312 patients, 13 439 (38.1%) received H<sub>2</sub>RAs and 21 873 (61.9%) received PPIs. Gastrointestinal hemorrhage (2.1% vs 5.9%;<i>P</i> &lt; .001), pneumonia (27% vs 38.6%;<i>P</i> &lt; .001), and CDI (2.2% vs 3.8%;<i>P</i> &lt; .001) occurred less frequently in the H<sub>2</sub>RA group. After adjusting for propensity score and covariates, odds ratios of GI hemorrhage (2.24; 95% CI, 1.81-2.76), pneumonia (1.2; 95% CI, 1.03-1.41), and CDI (1.29; 95% CI, 1.04-1.64) were greater with PPIs. Similar results were obtained in the propensity-matched models of 8799 patients in each cohort. <h3>Conclusions and Relevance</h3> Proton pump inhibitors are associated with greater risks of GI hemorrhage, pneumonia, and CDI than H<sub>2</sub>RAs in mechanically ventilated patients. Numerous other risk factors are apparent. These data warrant confirmation in comparative prospective studies.
Development of a New Isogenic Cell-Xenograft System for Evaluation of NAD(P)H:Quinone Oxidoreductase-Directed Antitumor Quinones
Authors: Donna L. Dehn, Shannon L. Winski, David Ross
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The purpose of our study was to develop and validate an isogenic cell line pair that differs only in the expression of NAD(P)H:quinone oxidoreductase (NQO1) that can be used to examine the in vitro and in vivo role of NQO1 in the bioactivation of the antitumor quinone RH1 (2,5-diaziridinyl-3-(hydroxymethyl)-6-methyl-1,4-benzoquinone), a compound currently in Phase I clinical trials. Experimental Design: MDA-MB-468 (MDA468) human breast adenocarcinoma cells, homozygous for a polymorphism in NQO1 (NQO1*2/*2) and with low levels of NQO1 activity, were stably transfected with human NQO1 to generate a clone (NQ16) expressing very high NQO1 activity. We examined levels of other reductases and looked at biochemical systems that might influence response to antitumor quinones to validate that the isogenic cell line pair differed only in the expression of NQO1. The 3-(4,5-dimethylthiazol-2,5-diphenyl)tetrazolium (MTT) assay was used to determine the differential toxicity of various quinones, including the most recent NQO1-directed antitumor quinone, RH1, between the two cell lines. Human tumor xenografts were established from both MDA468 and NQ16 cells, and the antitumor activity of RH1 was evaluated. Results: Levels of cytochrome P450 reductase, cytochrome b5 reductase, soluble thiols, and superoxide dismutase in the NQ16 line were unchanged from the parental line. The functional significance of wild-type NQO1 expression was confirmed by measurement of the differential toxicity of compounds activated or deactivated by NQO1 in the two cell lines. The toxicity of the NQO1-directed antitumor quinones RH1 and streptonigrin were markedly greater and the toxicity of menadione, which is detoxified by NQO1, was ameliorated in the NQ16 line. High levels of NQO1 expression were observed throughout xenograft tumors established from the NQ16 cell line. RH1 treatment was effective at statistically reducing tumor volume in NQ16 xenografts at all of the doses tested [0.1, 0.2, 0.4 mg/kg every day for 5 days), whereas only the highest dose of RH1 resulted in a significant reduction in tumor volume in MDA468 xenografts. Conclusions: The MDA468/NQ16 isogenic cell line pair is a useful model system for evaluating the role of NQO1 in the bioactivation of antitumor quinones in both cell lines and xenografts. In addition, our data demonstrate that the novel antitumor quinone RH1, is effectively activated by NQO1 both in vitro and in vivo.
Two ways to feel the pressure: an endothelial Ca2+ entry channel with dual mechanosensitivity
Authors: K Groschner
Journal: Cardiovascular Research (2002)

One impressive function of the vascular endothelium is its ability to adjust the release of vasoactive mediators such as NO and PGI2 almost instantaneously to changes in blood flow or blood pressure. Besides this fast feedback response to hemodynamic alterations, the endothelium is subject to long-term adaptations that are crucial for prevention of pathological processes such as atherogenesis. Among the various signals that are sensed by endothelial cells, mechanical forces which arise from pulsatile blood flow are probably most important for fast as well as long-term control of blood vessel function by the endothelium.
INDUCTION OF SKIN RESISTANCE TO VACCINIA VIRUS IN RABBITS BY VACCINIA-SOLUBLE EARLY ANTIGENS
Authors: Y. Ueda, I. Tagaya
Journal: The Journal of Experimental Medicine (1973)

The immunological role of vaccinia-soluble early antigen was examined in rabbits. The antigens were prepared from HeLa cells infected with a conditional lethal mutant of vaccinia virus, which induces in these cells early antigens including those responsible for surface immunofluorescence of infected cells, but not viral DNA and late protein syntheses. Immunization of rabbits with the antigens in Freund's complete adjuvant induced complement-fixing antibody but neither detectable circulating neutralizing antibody nor any detectable level of inhibitory substance or interferon in the skin of the animals. When immunized animals were inoculated intradermally with vaccinia virus, multiplication of virus in the skin was greatly inhibited, being accompanied by an earlier appearance as well as an accelerated wane of the local reactions. The resistance could not be transferred passively by the serum of immunized animals to normal rabbits. Immunization of rabbits with the antigens without the adjuvant not only failed to inhibit but, contrariwise, enhanced the multiplication of intradermally inoculated vaccinia virus, inducing heavy skin lesions and exalted virus multiplication.
Phase II trial of gemcitabine concurrent with radiation for locally advanced squamous cell carcinoma of the head and neck
Authors: J. Aguilar-Ponce, M. Granados-García, V. Villavicencio, A. Poitevin-Chacón, D. Green, A. Dueñas-González, Á. Herrera-Gómez, K. Luna-Ortiz, A. Alvarado, H. Martínez-Said, C. Castillo-Henkel, B. Segura-Pacheco, J. De la Garza
Journal: Annals of Oncology (2004)
Comparison of Nomograms With Other Methods for Predicting Outcomes in Prostate Cancer: A Critical Analysis of the Literature
Authors: Shahrokh F. Shariat, Pierre I. Karakiewicz, Nazareno Suardi, Michael W. Kattan
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Accurate estimates of risk are essential for physicians if they are to recommend a specific management to patients with prostate cancer. Accurate risk estimates are also required for clinical trial design, to ensure homogeneous patient groups. Because there is more than one model available for prediction of most outcomes, model comparisons are necessary for selection of the best model. We describe the criteria based on which to judge predictive tools, describe the limitations of current predictive tools, and compare the different predictive methodologies that have been used in the prostate cancer literature. Experimental Design: Using MEDLINE, a literature search was done on prostate cancer decision aids from January 1966 to July 2007. Results: The decision aids consist of nomograms, risk groupings, artificial neural networks, probability tables, and classification and regression tree analyses. The following considerations need to be applied when the qualities of predictive models are assessed: predictive accuracy (internal or ideally external validation), calibration (i.e., performance according to risk level or in specific patient subgroups), generalizability (reproducibility and transportability), and level of complexity relative to established models, to assess whether the new model offers advantages relative to available alternatives. Studies comparing decision aids have shown that nomograms outperform the other methodologies. Conclusions: Nomograms provide superior individualized disease-related risk estimations that facilitate management-related decisions. Of currently available prediction tools, the nomograms have the highest accuracy and the best discriminating characteristics for predicting outcomes in prostate cancer patients.
Mammary tumors and mammary tumor virus expression in hybrid mice of strains C57BL and GR.
Authors: W E Heston, W P Parks
Journal: The Journal of Experimental Medicine (1977)

Mammary tumorigenesis in genetic crosses between the high mammary tumor incidence GR and the low incidence C57BL mouse strains is highly correlated with murine mammary tumor virus expression in milk. Although the F1 and first backcross females had a mammary tumor incidence which was consistent with a single dominant gene segregation, the tumor incidence in the critical second backcross segregants disproved the single gene hypothesis. Genetic factors were clearly involved in regulation of virus expression which in turn correlated with both tumor incidence and tumor latency; these complex phenotypes are however best explained as threshold or quasicontinuous characters. As predicted from this model, the age specific incidence of mammary tumors showed a broad peak at 14-19 mo of age with no evidence of an early or late phase. Hematopoietic tumors showed no correlation with virus expression or mammary tumorigenesis suggesting different etiologies for these tumors.
Effects of indomethacin, renal denervation, and propranolol on plasma renin activity in conscious dogs with chronic thoracic caval constriction.
Authors: S F Echtenkamp, J O Davis, J M DeForrest, B P Rowe, R H Freeman, A A Seymour, J R Dietz
Journal: Circulation Research (1981)

The role of renal prostaglandins and the adrenergic nervous system in the control of renin release was studied in conscious dogs with thoracic caval constriction. Indomethacin reduced plasma renin activity (PRA) in intact animals with thoracic caval constriction by 43% but failed to change PRA after surgical renal denervation and during chronic propranolol administration; adrenergic blockade reduced the initial control level of PRA before indomethacin from 15 to 4 ng angiotensin I/ml per hr. Renal hemodynamic function was markedly reduced by indomethacin both before and after adrenergic blockade. These observations indicate that prostaglandins are involved in the control of renin release, but they appear to have a more important role in the control of renal arterial resistance. The adrenergic nervous system also plays a role in the hyperreninemia of caval constriction and, possibly, a greater role than the renal prostaglandins. In the first experimental design, surgical renal denervation and daily oral propranolol administration in dogs with caval constriction reduced PRA to normal in two of seven dogs and a natriuresis occurred. In four of the five remaining animals, PRA fell, but not to normal, and renal sodium excretion failed to increase. In a second experimental design, the kidneys were denervated and propranolol was given before the dogs were subjected to caval constriction and propranolol was continued for 5 days; PRA increased markedly, sodium retention occurred, and ascites formed. Under these circumstances, compensatory mechanisms secondary to caval constriction led to increased PRA in spite of adrenergic blockade.
Autologous non-myeloablative haematopoietic stem cell transplantation for refractory systemic vasculitis
Authors: L Statkute, Y Oyama, W G Barr, R Sufit, S Ho, L Verda, Y Loh, K Yaung, K Quigley, R K Burt
Journal: Annals of the Rheumatic Diseases (2007)

For patients with systemic vasculitis (SV) refractory to conventional therapy, new treatment strategies aimed at aggressive induction of remission and relapse prevention are being sought. We herein report our single-centre experience in treating four patients with refractory SV employing non-myeloablative autologous haematopoietic stem cell transplantation (HSCT).Four patients with refractory SV (two with neurovascular Behcet disease, one with neurovascular Sjögren syndrome, and one with Wegener granulomatosis) were involved in an Institutional Review Board (IRB) and US Food and Drug Administration (FDA) approved phase I clinical trial of high dose chemotherapy and autologous HSCT. Peripheral blood stem cells were mobilised with cyclophosphamide (Cy) and granulocyte-colony stimulating factor (G-CSF). Conditioning regimen consisted of Cy 200 mg/kg and rabbit anti-thymocyte globulin 5.5 mg/kg intravenously (iv).All four patients tolerated HSCT well without transplant related mortality or any significant toxicity. At median follow-up of 28 (range 22-36) months all patients were alive. Three patients (one with Behcet disease, one with Sjögren syndrome, and one with Wegener granulomatosis) entered a sustained remission at 6, 6 and 24 months, respectively, after transplant. They had significant decrease in disease activity and disease or treatment related damage, as measured by the Birmingham Vasculitis Activity Score and Vasculitis Damage Index, respectively. All three patients who achieved remission discontinued immunosuppressive therapy at the time of transplant and have not required treatment since. One patient with Behcet disease and positive for human leukocyte antigen (HLA)-B51 has not improved after HSCT.We suggest non-myeloablative autologous HSCT is an alternative therapy for select patients with SV refractory to conventional immunosuppressive therapies.
Concentrations of Thrombopoietin in Bone Marrow in Normal Subjects and in Patients With Idiopathic Thrombocytopenic Purpura, Aplastic Anemia, and Essential Thrombocythemia Correlate With Its mRNA Expression of Bone Marrow Stromal Cells
Authors: Yasuo Hirayama, Sumio Sakamaki, Takuya Matsunaga, Takashi Kuga, Hiroyuki Kuroda, Toshiro Kusakabe, Katsunori Sasaki, Koshi Fujikawa, Junji Kato, Katsuhisa Kogawa, Ryuzo Koyama, Yoshiro Niitsu
Journal: Blood (1998)