tbuckley/cabot-search huggingface dataset:
Relaxin is a potent renal vasodilator in conscious rats
Authors: Lee A. Danielson, O. David Sherwood, Kirk P. Conrad
Journal: Journal of Clinical Investigation (1999)

The kidneys and other nonreproductive organs vasodilate during early gestation; however, the "pregnancy hormones" responsible for the profound vasodilation of the renal circulation during pregnancy are unknown. We hypothesized that the ovarian hormone relaxin (RLX) contributes. Therefore, we tested whether the administration of RLX elicits renal vasodilation and hyperfiltration in conscious adult, intact female rats. After several days of treatment with either purified porcine RLX or recombinant human RLX 2 (rhRLX), effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) increased by 20%–40%. Comparable renal vasodilation and hyperfiltration was also observed in ovariectomized rats, suggesting that estrogen and progesterone are unnecessary for the renal response to rhRLX. The nitric oxide synthase inhibitor Nω-nitro-L-arginine methyl ester completely abrogated the increase in ERPF and GFR elicited by chronic administration of purified porcine RLX. In contrast, the renal vasoconstrictory response to angiotensin II was attenuated by the RLX treatment. Short-term infusion of purified porcine RLX to conscious rats over several hours failed to increase ERPF and GFR. Plasma osmolality was consistently reduced by the chronic administration of both RLX preparations. In conclusion, the renal and osmoregulatory effects of chronic RLX administration to conscious rats resemble the physiological changes of pregnancy in several respects: (a) marked increases in ERPF and GFR with a mediatory role for nitric oxide; (b) attenuation of the renal circulatory response to angiotensin II; and (c) reduction in plasma osmolality.
Vandetanib Inhibits Growth of Adenoid Cystic Carcinoma in an Orthotopic Nude Mouse Model
Authors: Sungweon Choi, Daisuke Sano, Melvina Cheung, Mei Zhao, Samar A. Jasser, Anderson J. Ryan, Li Mao, Wan-Tao Chen, Adel K. El-Naggar, Jeffrey N. Myers
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Adenoid cystic carcinoma (ACC) can often be controlled with surgery and postoperative adjuvant radiotherapy but is also characterized by late local recurrence and distant metastasis. No effective systemic therapeutic agents have been found to alter the natural history of ACC. Therefore, new therapeutic approaches are needed. In this study, we evaluated whether vandetanib (Zactima), a potent inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2) and epidermal growth factor receptor (EGFR) tyrosine kinases, had antitumor efficacy in vitro and in an orthotopic nude mouse model of human ACC. Experimental Design: The in vitro effects of vandetanib were assessed in three ACC cell lines on cell growth, apoptosis, and VEGFR-2 and EGFR phosphorylation levels. The in vivo antitumor activity of vandetanib was examined in nude mice bearing parotid gland ACC tumors. The mice were treated for 4 weeks with vandetanib (50 mg/kg/d) or placebo (control). Tumors were resected at necropsy, and immunohistochemical and immunofluorescence staining were done. Results: In vitro, vandetanib caused dose-dependent inhibition of VEGFR-2 and EGFR phosphorylation in ACC cells. Vandetanib also inhibited the cell proliferation and induced their dose-dependent apoptosis. In vivo, mice in the vandetanib group had tumor volumes significantly lower than those in the control group (P &amp;lt; 0.01). In addition, immunohistochemical staining showed a decrease in microvessel density and an increase in apoptosis of both tumor cells and endothelial cells within the tumor xenografts. Conclusion: These results suggest that vandetanib inhibits the growth of ACC in vitro and in vivo, making it a promising novel agent for the treatment of ACC.
Nuclear Receptor Coregulators and Human Disease
Authors: David M. Lonard, Rainer B. Lanz, Bert W. O’Malley
Journal: Endocrine Reviews (2007)

Nuclear receptor (NR) coregulators (coactivators and corepressors) are essential elements in regulating nuclear receptor-mediated transcription. In a little more than a decade since their discovery, these proteins have been studied mechanistically and reveal that the regulation of transcription is a highly controlled and complex process. Because of their central role in regulating NR-mediated transcription and in coordinating intercompartmental metabolic processes, disruptions in coregulator biology can lead to pathological states. To date, the extent to which they are involved in human disease has not been widely appreciated. In a complete literature survey, we have identified nearly 300 distinct coregulators, revealing that a great variety of enzymatic and regulatory capabilities exist for NRs to regulate transcription and other cellular events. Here, we substantiate that coregulators are broadly implicated in human pathological states and will be of growing future interest in clinical medicine.
RET Gene and Its Implications for Cancer
Authors: P. J. Goodfellow, S. A. Wells
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article RET Gene and Its Implications for Cancer Get access Paul J. Goodfellow, Paul J. Goodfellow Department of Surgery, Washington University School of MedicineSt. Louis, MO Search for other works by this author on: Oxford Academic PubMed Google Scholar Samuel A. Wells, Jr. Samuel A. Wells, Jr. * Department of Surgery, Washington University School of MedicineSt. Louis, MO *Correspondence to : Samuel A. Wells, Jr., M.D., Department of Surgery, Washington University School of Medicine, Campus Box 8109, 660 South Euclid, St. Louis, MO 63110. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 20, 18 October 1995, Pages 1515–1523, https://doi.org/10.1093/jnci/87.20.1515 Published: 18 October 1995 Article history Received: 23 March 1995 Revision received: 11 July 1995 Accepted: 18 July 1995 Published: 18 October 1995
Bochdalek hernia: a rare cause of pleural empyema
Authors: LH Steenhuis, A RT Tjon Tham, FW Smeenk
Journal: European Respiratory Journal (1994)

This case report describes pleural empyema, caused by an intrathoracic ruptured stomach, in an adult patient with Bochdalek hernia. The possible complications and difficulties in diagnosing Bochdalek hernia in the adult are discussed.
Human infections with the emerging avian influenza A H7N9 virus from wet market poultry: clinical analysis and characterisation of viral genome
Authors: Yu Chen, Weifeng Liang, Shigui Yang, Nanping Wu, Hainv Gao, Jifang Sheng, Hangping Yao, Jianer Wo, Qiang Fang, Dawei Cui, Yongcheng Li, Xing Yao, Yuntao Zhang, Haibo Wu, Shufa Zheng, Hongyan Diao, Shichang Xia, Yanjun Zhang, Kwok-Hung Chan, Hoi-Wah Tsoi, Jade Lee-Lee Teng, Wenjun Song, Pui Wang, Siu-Ying Lau, Min Zheng, Jasper Fuk-Woo Chan, Kelvin Kai-Wang To, Honglin Chen, Lanjuan Li, Kwok-Yung Yuen
Journal: The Lancet (2013)
Simultaneous measurement of gastric acid and duodenal alkali secretion by in situ titration in health and disease.
Authors: P Dubey, S Nundy
Journal: Gut (1983)

We have devised a technique for simultaneously measuring the acid secretion into the stomach and alkali into the duodenum by in situ titration using a modification of the technique of Fordtran and Walsh. Using this technique, the results of acid and alkali secretion measured simultaneously were identical with those obtained using the conventional aspiration method on separate days. In response to stimulation with pentagastrin acid output was 17.2 +/- 1.4 vs 15.4 +/- 1.9 mmol/h and alkali response with secretin was 16.0 +/- 0.8 vs 14.4 +/- 1.5 mmol/h. The response to food was measured in 10 control subjects, 10 patients with duodenal ulcer, and 10 patients with pancreatitis. In controls, the acid and alkaline secretion were similar (15.8 +/- 1.7 vs 18.2 +/- 1.3 mmol/h), in patients with duodenal ulcer acid secretion was significantly greater than alkaline secretion (31.9 +/- 2.2 vs 21.9 +/- 1.7 mmol/h), and in patients with pancreatitis the alkali secretion was significantly less than acid (19.8 +/- 1.9 mmol/h acid vs 11.4 +/- 0.6 mmol/h alkali). It can, therefore, be concluded that in response to food the patients with duodenal ulcer are significant hypersecretors of acid (DU acid greater than DU alkali output) and patients with pancreatitis are significant hyposecretors of alkali (pancreatitis-alkaline output less than acid output) and normal subjects secrete equal amounts of acid and alkali.
Airway epithelial cell apoptosis and inflammation in COPD, smokers and nonsmokers
Authors: David M. Comer, Joseph C. Kidney, Madeleine Ennis, J. Stuart Elborn
Journal: European Respiratory Journal (2012)

We hypothesised that primary bronchial epithelial cells (PBECs) from subjects with chronic obstructive pulmonary disease (COPD) respond differently to Pseudomonas aeruginosa lipopolysaccharide (LPS) after cigarette smoke extract (CSE) exposure than PBECs obtained from smokers without airflow obstruction and nonsmokers. PBECs from 16 COPD subjects, 10 smokers without airflow obstruction and nine nonsmokers were cultured at air-liquid interface. Cultures were incubated with CSE prior to stimulation with P. aeruginosa LPS. Interleukin (IL)-6 and IL-8 were measured by ELISA and Toll-like receptor (TLR)-4 expression by fluorescence-activated cell sorter. Activation of nuclear factor (NF)-κB was determined by Western blotting and ELISA, and MAPK and caspase-3 activity by Western blotting. Apoptosis was evaluated using Annexin-V staining and the terminal transferase-mediated dUTP nick end-labelling methods. Constitutive release of IL-8 and IL-6 was greatest from the COPD cultures. However, CSE pretreatment followed by P. aeruginosa LPS stimulation reduced IL-8 release from COPD PBECs, but increased it from cells of smokers without airflow obstruction and nonsmokers. TLR-4 expression, MAPK and NF-κB activation in COPD cultures were reduced after CSE treatment, but not in the smokers without airflow obstruction or nonsmoker groups, which was associated with increased apoptosis. CSE attenuates inflammatory responses to LPS in cells from people with COPD but not those from nonsmoking individuals and those who smoke without airflow obstruction.
Health Services Utilization in Jerusalem Under Terrorism
Authors: Itzhak Levav, Ilya Novikov, Alexander Grinshpoon, Joseph Rosenblum, Alexander Ponizovsky
Journal: American Journal of Psychiatry (2006)

Objective: The authors explored the effects of an escalation of terrorism on the help-seeking behavior of the general population in Jerusalem, a city that offers an adequate supply of medical and psychiatric services. Method: Time-series analyses were applied to examine the utilization of health services (primary medical care and ambulance calls) and mental health services (clinics, hospitals, and telephone hotlines) by Jerusalem residents before and during part of the current intifada. The authors assessed seasonality, general linear trends (from factors such as health education and increased access), short-term intifada impact (reflecting reactions that peaked at the third month and ended 1 year thereafter), and long-term impact (starting at the intifada outbreak and reflecting a more stable population behavior). Results: Adult psychiatric outpatient visits did not change except for the elderly in ongoing care who had both short- and long-term increases. The proportion of recorded ICD-10 diagnoses reflecting intifada-related reactions remained generally stable. Short-term effects included an increase in psychiatric readmissions. First contacts to substance abuse clinics remained unchanged. While long-term effects included a decrease in new psychiatric hospitalizations, the rate of monthly general practitioner visitors and the number of monthly ambulance and hotline calls increased. Conclusions: Except for the elderly and previously hospitalized persons, Jerusalem residents did not increase their use of psychiatric services but did increase their use of some other health services. These results suggest that this terrorism-affected population did not perceive their mental and social suffering as requiring specialized intervention.
Is sputum eosinophilia a good or poor predictor of benefit from inhaled corticosteroid therapy in asthma?
Authors: M.M.M. Pizzichini
Journal: European Respiratory Journal (2002)

Sputum eosinophilia was first described as a feature of asthma by Gollasch 1 more than a century ago. Thirty-years later, eosinophils were found to be a part of the pathological process that characterises asthma 2. Since then, much work has been undertaken to understand the precise role of eosinophils in mediating airway inflammation, tissue damage and repair in asthma pathogenesis. There is now strong evidence supporting the association of airway eosinophilic inflammation and symptomatic asthma. Although central, sputum eosinophils and their pro-inflammatory mediators are only a part of the heterogeneous inflammatory response that distinguishes asthma from other airway diseases. There is now increasing evidence that other inflammatory mechanisms may be involved in producing the two prominent clinical features of asthma: increased bronchial responsiveness and reversible airflow limitation 3.

In fact, several recent cross-sectional studies using the examination of bronchial biopsies tissue from bronchial biopsies, bronchoalveolar lavage fluid or samples of induced sputum 4–12 have demonstrated the presence of noneosinophilic inflammation in patients with symptomatic asthma. The prevalence of noneosinophilic inflammation in asthma is variable and this may be due, in part, to differences in subject characteristics such as the severity 5–7, 11 and control 4–6 of asthma, smoking 13, dose of corticosteroid treatment 6, 7, concurrent infection 9 and recent exposure to aggravating environmental allergens 14 or pollutants 15, 16. Nevertheless, these studies highlighted the heterogeneity of airway inflammation in asthma and this cannot always be anticipated from clinical parameters 17.

Therefore, it seems reasonable to assume that knowing the characteristics of airway inflammation of symptomatic or uncontrolled asthmatics would be of interest in accessing the effects of different asthma treatments. This is particularly relevant in relation to corticosteroid treatment, as not all asthmatics respond …
Ins(1,4,5)P3 and cardiac dysfunction
Authors: Elizabeth A Woodcock, Scot J Matkovich, Ofer Binah
Journal: Cardiovascular Research (1998)

Time for primary review 33 days. 

Cardiac related death occurs rapidly via the development of arrhythmias or more slowly by a progressive decline in mechanical performance reflecting decreased contractile activity as well as loss of viable myocytes. Pathological conditions such as myocardial ischaemia, inflammatory heart diseases and various forms of heart failure are associated with both sudden death and also with a more progressive decrease in cardiac function. Electrophysiological disturbances leading to malignant ventricular arrhythmias are the usual cause of sudden cardiac death, whereas a gradual loss of functional myocytes, or a decline in their performance, underlies heart failure ultimately leading to cardiac decompensation. The mechanisms initiating these scenarios are complex and multifactorial, involving both extracellular and intracellular factors. However, given the continued major contribution of cardiac deaths to overall mortality, understanding the processes which initiate these pathological events is of prime importance. The current review will focus on changes in the intracellular milieu and in particular the potential role of the Ca2+-releasing second messenger inositol(1,4,5) tris phosphate [Ins(1,4,5)P3] in initiating arrhythmias and cell death in cardiac pathologies.

Ins(1,4,5)P3 is generated along with sn -1,2-diacylglycerol following the activation of either G protein-coupled receptors and phospholipase C-β (PLC-β) isoforms or receptor tyrosine kinases and PLC-γ isoforms [1]. The Ins(1,4,5)P3 which is rapidly released into the cytoplasm, especially after activation of G protein-coupled receptors, activates Ins(1,4,5)P3 receptors on Ca2+ stores in the endoplasmic reticulum [sarcoplasmic reticulum (SR) in muscle cells] causing a rapid and quantal release of Ca2+ [2]. In most non-cardiac cell types, this Ins(1,4,5)P3-initiated Ca2+ response can be perpetuated by the process of Ca2+-induced Ca2+ release mediated by either the Ins(1,4,5)P3 receptors or the related family of ryanodine receptors, the overall effect … 

* Corresponding author. Tel.: +61-3-9522-4387; Fax: +61-3-9521-1362; E-mail: liz.woodcock@baker.edu.au
Trimethoprim-sulfamethoxazole versus trimethoprim-sulfamethoxazole plus doxycycline as oral eradicative treatment for melioidosis (MERTH): a multicentre, double-blind, non-inferiority, randomised controlled trial
Authors: Ploenchan Chetchotisakd, Wirongrong Chierakul, Wipada Chaowagul, Siriluck Anunnatsiri, Kriangsak Phimda, Piroon Mootsikapun, Seksan Chaisuksant, Jiraporn Pilaikul, Bandit Thinkhamrop, Sunchai Phiphitaporn, Wattanachai Susaengrat, Chalongchai Toondee, Surasakdi Wongrattanacheewin, Vanaporn Wuthiekanun, Narisara Chantratita, Janjira Thaipadungpanit, Nicholas P Day, Direk Limmathurotsakul, Sharon J Peacock
Journal: The Lancet (2013)

Melioidosis, an infectious disease caused by the Gram-negative bacillus Burkholderia pseudomallei, is difficult to cure. Antimicrobial treatment comprises intravenous drugs for at least 10 days, followed by oral drugs for at least 12 weeks. The standard oral regimen based on trial evidence is trimethoprim-sulfamethoxaxole (TMP-SMX) plus doxycycline. This regimen is used in Thailand but is associated with side-effects and poor adherence by patients, and TMP-SMX alone is recommended in Australia. We compared the efficacy and side-effects of TMP-SMX with TMP-SMX plus doxycycline for the oral phase of melioidosis treatment.
Vitamin A supplements for preventing mortality, illness, and blindness in children aged under 5: systematic review and meta-analysis
Authors: E. Mayo-Wilson, A. Imdad, K. Herzer, M. Y. Yakoob, Z. A. Bhutta
Journal: BMJ (2011)

<b>Objective</b> To determine if vitamin A supplementation is associated with reductions in mortality and morbidity in children aged 6 months to 5 years. <b>Design</b> Systematic review and meta-analysis. Two reviewers independently assessed studies for inclusion. Data were double extracted; discrepancies were resolved by discussion. Meta-analyses were performed for mortality, illness, vision, and side effects. <b>Data sources</b> Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, Medline, Embase, Global Health, Latin American and Caribbean Health Sciences, metaRegister of Controlled Trials, and African Index Medicus. Databases were searched to April 2010 without restriction by language or publication status. <b>Eligibility criteria for selecting studies</b> Randomised trials of synthetic oral vitamin A supplements in children aged 6 months to 5 years. Studies of children with current illness (such as diarrhoea, measles, and HIV), studies of children in hospital, and studies of food fortification or β carotene were excluded. <b>Results</b> 43 trials with about 215 633 children were included. Seventeen trials including 194 483 participants reported a 24% reduction in all cause mortality (rate ratio=0.76, 95% confidence interval 0.69 to 0.83). Seven trials reported a 28% reduction in mortality associated with diarrhoea (0.72, 0.57 to 0.91). Vitamin A supplementation was associated with a reduced incidence of diarrhoea (0.85, 0.82 to 0.87) and measles (0.50, 0.37 to 0.67) and a reduced prevalence of vision problems, including night blindness (0.32, 0.21 to 0.50) and xerophthalmia (0.31, 0.22 to 0.45). Three trials reported an increased risk of vomiting within the first 48 hours of supplementation (2.75, 1.81 to 4.19). <b>Conclusions</b> Vitamin A supplementation is associated with large reductions in mortality, morbidity, and vision problems in a range of settings, and these results cannot be explained by bias. Further placebo controlled trials of vitamin A supplementation in children between 6 and 59 months of age are not required. However, there is a need for further studies comparing different doses and delivery mechanisms (for example, fortification). Until other sources are available, vitamin A supplements should be given to all children at risk of deficiency, particularly in low and middle income countries.
Counterpoint: Intensive Glucose Control and Mortality in ACCORD—Still Looking for Clues
Authors: Matthew C. Riddle
Journal: Diabetes Care (2010)

Early cessation of the intensive glycemic treatment arm of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial because of a 22% excess of all-cause mortality compared with the standard arm (1) came as an unpleasant surprise to many observers. Since then, considerable discussion of the significance of this result has ensued along with various theories as to why it occurred. In the companion article, a respected statistician, John Lachin, proposes yet another hypothesis: that the finding was due to the play of chance (2). In response, this article will address three related issues: 1 ) Dr. Lachin's hypothesis; 2 ) a review of findings of post hoc analyses of the ACCORD data seeking support or lack of support for the other main theories; and 3 ) my own opinions on why continued study of the ACCORD data are needed, including a reformulation of one of the original theories regarding the cause of excess mortality.

### The play-of-chance hypothesis

“How often have I said to you that when you have eliminated the impossible, whatever remains, however improbable, must be the truth?” asked Sherlock Holmes of Dr. Watson in The Sign of the Four (1890).

Dr. Lachin's exposition of the theory that the apparent excess of mortality in ACCORD was due to the play of chance is very welcome. This possibility has not previously been given enough attention. The excess of deaths with the intensive glycemic treatment strategy was indeed not large, a 22% relative increase from 1.1 to 1.4% of participants affected per year (1). In absolute terms, it was 257 versus 203 deaths or an excess of 54 among 10,251 study participants. Had this been the primary end point, a direct comparison would have shown the level of statistical significance generally regarded as conclusive. But it was not the primary end point and repeated measurements …