tbuckley/cabot-search huggingface dataset:
The protective effects of prostaglandin E1 in an experimental massive hepatic cell necrosis model
Authors: Yasuhiro Mizoguchi, Hiroko Tsutsui, Keiji Miyajima, Yoshihide Sakagami, Shuichi Seki, Kenzo Kobayashi, Sukeo Yamamoto, Seiji Morisawa
Journal: Hepatology (1987)

When a small amount of Gram-negative lipopolysaccharide was intravenously injected into mice which had been injected with heat-killed Propionibacterium acnes 7 days before, massive hepatic cell necrosis was induced and most of the mice died 24 hr later. However, when prostaglandin E1 was administered with lipopolysaccharide, remarkable improvements in the survival rate and in the histological changes of the liver were observed. In order to find out how prostaglandin E1 suppressed the induction of massive hepatic cell necrosis in this experimental model, we studied the effects of prostaglandin E1 on the activation of liver adherent cells, from which the cytotoxic factor is released, and on the protection of hepatocytes from the cytotoxic factor. As a result, prostaglandin E1 not only inhibited the activation of liver adherent cells and suppressed the release of the cytotoxic factor, but it also directly affected the hepatocytes and protected them from the cytotoxic factor.
Upper gastrointestinal haemorrhage and deprivation: a nationwide cohort study of health inequality in hospital admissions
Authors: Colin J Crooks, Joe West, Tim R Card
Journal: Gut (2011)

<h3>Objective</h3> Inequalities in health are well recognized in cardiovascular disease and cancer, but in comparison, we have minimal understanding for upper gastrointestinal bleeding. Since furthering our understanding of such inequality signposts preventable disease, we investigated in detail the association between upper gastrointestinal bleeding and socioeconomic status. <h3>Design</h3> Population-based cohort study. <h3>Setting</h3> All English National Health Service hospitals. <h3>Population</h3> English adult population, 1 January 2001 to 31 December 2007. <h3>Exposure measures</h3> Deprivation scores defined according to quintiles of neighbourhood areas ranked by the Indices of Multiple Deprivation for England 2007. <h3>Outcome measures</h3> Rates of all adult admissions coded with a primary diagnosis of upper gastrointestinal bleed were analysed by deprivation quintile and adjusted for age, sex, region and year using Poisson regression. <h3>Results</h3> The annual hospitalization rate for non-variceal haemorrhage was 84.6 per 100 000 population (95% CI 83.5 to 84.1; n=237 145), and for variceal haemorrhage, it was 2.83 per 100 000 population (95% CI 2.87 to 2.99; n=8291). There was a twofold increase in the hospitalization rate ratio for non-variceal haemorrhage from the most deprived areas compared to the least deprived (2.00, 95% CI 1.98 to 2.03). The ratio for variceal haemorrhage was even more pronounced (2.49, 95% CI 2.32 to 2.67). Inequality increased over the study period (non-variceal p&lt;0.0001, variceal p=0.0068), and adjusting for age and sex increased the disparity between deprived and affluent areas. Case fatality did not have a similar socioeconomic gradient. <h3>Conclusion</h3> Both variceal and non-variceal haemorrhage hospitalization rates increased with deprivation, and there was a similar gradient in all areas of the country and in all age bands. The existence of such a steep gradient suggests that there are opportunities to reduce hospitalizations down to the low rates seen in the most affluent, and thus, there is the potential to prevent almost 10 000 admissions and over 1000 deaths a year.
Overexpression of Interleukin-1 Receptor Antagonist Provides Cardioprotection Against Ischemia-Reperfusion Injury Associated With Reduction in Apoptosis
Authors: K Suzuki, B Murtuza, R T Smolenski, I A Sammut, N Suzuki, Y Kaneda, M H Yacoub
Journal: Circulation (2001)

Interleukin-1 (IL-1) plays a role in mediating acute inflammation during ischemia-reperfusion (I/R) injury in the heart, which leads to both necrosis and apoptosis of cardiomyocytes. IL-1 receptor antagonist (IL-1ra) is known to inhibit the effects of IL-1alpha and IL-1beta, resulting in attenuated inflammatory injury, and to protect cells from IL-1beta-induced apoptosis in vitro. We hypothesized that IL-1ra overexpression would provide cardioprotection by reducing inflammation-mediated myocardial damage including apoptosis after I/R injury in vivo.Rat hearts were transfected with human secreted-type IL-1ra gene by intracoronary infusion of Hemagglutinating Virus of Japan liposome and were heterotopically transplanted. IL-1ra overexpression in these hearts was confirmed by enzyme immunoassay and immunohistochemistry. Myocardial tolerance of the transplanted heart was evaluated with the use of a novel system in which the heart, existing within the recipient's abdomen, was given 30 minutes of ischemia by left coronary artery occlusion and 24 hours of reperfusion. Consequently, infarct size was decreased in IL-1ra-transfected hearts compared with control-transfected ones (26.9+/-3.2% versus 46.2+/-3.0%, P=0.001), corresponding to lower myocardial myeloperoxidase activity (2.20+/-0.69 versus 6.82+/-1.19 U/g wet wt, P<0.001) and decreased neutrophil infiltration in histological study. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling and DNA-laddering studies demonstrated that cardiomyocyte apoptosis was attenuated in IL-1ra-transfected hearts (21.4+/-3.3 versus 41.4+/-3.4%, P=0.002), correlating with reduced post I/R upregulation of Bax, Bak, and caspase-3.IL-1ra introduced by gene transfection protected myocardium from I/R injury by attenuating the inflammatory response, which was associated with decreased apoptosis. This suggests a potentially important role of IL-1/IL-1ra in myocardial I/R injury and the value of IL-1ra-gene therapy for myocardial preservation.
Effect of ondansetron, a 5-HT3 receptor antagonist, on fatigue in chronic hepatitis C: a randomised, double blind, placebo controlled study
Authors: T Piche
Journal: Gut (2005)

<b>Background and aims:</b> There are no available effective therapies for fatigue associated with chronic hepatitis C (CHC). The serotonin antagonist ondansetron has been shown to be effective in the chronic fatigue syndrome. In this randomised, placebo controlled, double blind trial, we investigated the effect of orally administered ondansetron on fatigue in CHC. <b>Methods:</b> Thirty six patients with CHC were included if fatigue was their predominant symptom and they scored more than 4 on a visual analogue scale (0–10). During the study, fatigue and depression were measured on days 0, 15, 30, and 60 using a validated self report questionnaire (fatigue impact scale and Beck depression inventory). Patients were randomised to receive ondansetron tablets 4 mg twice daily or placebo for one month followed by an additional four weeks of observation. <b>Results:</b> Fatigue score was 85.4 (28.2) and 98.2 (26.9) in the ondansetron and placebo groups, respectively (NS). Ondansetron significantly reduced the fatigue score with more than 30% improvement on day 15 (57.1 (38.9); p&lt;0.01), day 30 (54.5 (37.6); p&lt;0.01), and day 60 (60.8 (37.3); p&lt;0.01) whereas placebo did not. Overall, the reduction in fatigue was significantly higher with ondansetron compared with placebo (ANOVA for repeated measurements) for the whole follow up period (p = 0.03) or for the treatment period only (p = 0.04). Ondansetron also significantly reduced depression scores. <b>Conclusions:</b> The 5-hydroxytryptamine receptor type 3 antagonist ondansetron had a significant positive effect on fatigue in CHC. These observations support the concept that fatigue involves serotoninergic pathways and may encourage further evaluations of the efficacy of ondansetron on fatigue in chronic liver diseases.
Gastric rupture associated with use of the laryngeal mask airway during cardiopulmonary resuscitation
Authors: Nathaniel Haslam, G Claire Campbell, John E Duggan
Journal: BMJ (2004)

The laryngeal mask airway has revolutionised airway management in anaesthesia and seems set to do so for resuscitation. Its appeal is based largely on less need for skill and training than with either facemask or an endotracheal tube.1 All paramedic crews and emergency departments have the laryngeal mask as standard equipment, and its popularity in hospital resuscitation is growing. Gas leak and gastric inflation are well recognised complications of positive pressure ventilation with the laryngeal mask.2 3 We present a case in which the use of a laryngeal mask during an out of hospital cardiac arrest led to massive gastric dilation, gastric rupture, and a tension pneumoperitoneum.

A 71 year old man with a history of angina and hypertension developed chest pain and collapsed in a shopping centre. A bystander performed cardiopulmonary resuscitation for about seven minutes until a paramedic unit arrived. A paramedic inserted a laryngeal mask airway and started hand ventilation at a rate of 12 breaths/min with a 1600 ml self inflating resuscitation bag with reservoir and oxygen supply set to 12 litres per minute. Normal chest movement and auscultation of the chest confirmed correct placement of the mask. The paramedic then resumed chest compression at a rate of 100 per minute synchronous with ventilation. Three lead electrocardiography showed ventricular fibrillation. A single DC shock of 200 J restored sinus rhythm, with a good cardiac output after about five minutes of the paramedic starting cardiopulmonary resuscitation. The patient was then transferred to our emergency department; although some respiratory effort was noted, this was considered inadequate by the paramedic, who ventilated the patient by hand throughout the 25 minute journey to hospital. The paramedic saw no episodes of retching, coughing, or vomiting.

On the patient's arrival in the emergency department, doctors noted the following in the …
Re-tuning bone formation
Authors: Gerard Karsenty
Journal: The Journal of Experimental Medicine (2015)

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Insight from Gerard Karsenty



Fibrillin-1 (FBN1) is a structural component of microfibrils in the extracellular matrix that plays a role in tissue development. Genetic defects in FBN1 are associated with a number of clinical conditions including systemic sclerosis (SSc)/
Residual ovarian activity during oral steroid contraception
Authors: A. M. van Heusden
Journal: Human Reproduction Update (2002)

Steroid drugs with contraceptive properties have been available in the clinical setting for over four decades and are still subject to improvement. Estrogens, progestins and anti-progestins have been used alone or in various combinations, regimens and routes of administration to favour the balance between efficacy and undesirable effects. One of the most important changes in this respect is the gradual lowering of steroid dosage in commercially available contraceptives. Current steroid contraceptive pills still achieve the goal of suppression of pituitary-ovarian activity, but the margins for error are minimal. In this review the available data on modes of action and the effects on suppressing pituitary-ovarian activity by different forms of oral contraception are reassessed. Although pregnancy rates provide a crude measure of contraceptive efficacy, no benchmark for pituitary-ovarian inhibition is available to test the suppressive potential of contraceptive drugs. Consequently, many studies provide incomplete and/or incomparable results. For the further study of those forms of steroid contraception that rely predominantly on suppression of ovarian activity, prevention of dominant follicles selection should be the objective.
PREPARATION FROM HUMAN RED CELLS OF A SUBSTANCE INHIBITING VIRUS HEMAGGLUTINATION
Authors: Patrick M. deBurgh, Pen-Chung Yu, Calderon Howe, Max Bovarnick
Journal: The Journal of Experimental Medicine (1948)

Methods have been described for the extraction and purification of an agent inhibiting the hemagglutination of red cells by influenza (PR8) and mumps viruses. Human red cells have served as the chief source of the inhibitor but the latter has also been found in human lung. The active extracts have been purified to the extent that 0.1 gamma of material suffices to inhibit one hemagglutinating dose of virus. Incomplete chemical characterization of the most highly purified fractions available indicates the presence of 2.6 per cent nitrogen, at least 50 per cent of polysaccharide, and no phosphorus. In the ultracentrifuge the purified preparation behaves as a polydisperse macromolecular substance. The active material can be obtained from red cell stroma in an ether- and chloroform-soluble form which, on further treatment, can be converted into chloroform-insoluble material. It is possible that the former represents more closely the virus receptor as it exists in the red cell. The purified inhibitor is inactivated on incubation with the virus at 37 degrees C. The nature of this effect is being investigated.
MCRS1 overexpression, which is specifically inhibited by miR-129*, promotes the epithelial-mesenchymal transition and metastasis in non-small cell lung cancer
Authors: Min-Xia Liu, Ke-Cheng Zhou, Yi Cao
Journal: Molecular Cancer (2014)

Although tumor invasion and metastasis are both classical hallmarks of cancer malignancy and the major causes of poor clinical outcomes among cancer patients, the underlying master regulators of invasion and metastasis remain largely unknown. In this study, we observed that an overexpression of microspherule protein 1 (MCRS1) promotes the invasion and metastasis of non-small cell lung cancer (NSCLC) cells. Furthermore, we sought to systematically investigate the pathophysiological functions and related mechanisms of MCRS1. Retrovirus-mediated RNA interference was employed to knockdown MCRS1 expression in NSCLC cell lines. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot respectively were used to measure levels of mRNA and protein. Further cell permeability assessment, invasion and proliferation assays were conducted to evaluate MCRS1 functions in vitro while nude mice experiments were performed to examine metastatic capability in vivo. Microarray analysis and microRNA (miRNA) sequencing were respectively carried out for mRNA and miRNA expression profiling, while chromatin immunoprecipitation (ChIP), luciferase reporter assay, and miRNA transfection were used to investigate the interaction between MCRS1 and miRNAs. MCRS1 knockdown induced morphological alterations, increased monolayer integrity, decreased cellular invasion and metastasis, and attenuated stemness and drug resistance among tested NSCLC cells. The levels of MCRS1 expression were likewise correlated with tumor metastasis among NSCLC patients. We identified differentially expressed genes after MCRS1 silencing, which included cell junction molecules, such as ZO-1, Occludin, E-cadherin, and DSG2. However, these differentially expressed genes were not directly recognized by a transcriptional complex containing MCRS1. Furthermore, we found that MCRS1 binds to the miR-155 promoter and regulates its expression, as well as MCRS1 promotes epithelial-mesenchymal transition (EMT), invasion, and metastasis through the up-regulation of miR-155. Systematic investigations ultimately showed that MCRS1 was directly and negatively regulated by the binding of miR-129* to its 3'-UTR, with miR-129* overexpression suppressing the growth and invasion of NSCLC cells. MiR-129* down-regulation induced MCRS1 overexpression, which promotes EMT and invasion/metastasis of NSCLC cells through both the up-regulation of miR-155 and down-regulation of cell junction molecules. This miR-129*/MCRS1/miR-155 axis provides a new angle in understanding the basis for the invasion and metastasis of lung cancer.
Raised CRP levels mark metabolic and functional impairment in advanced COPD
Authors: R Broekhuizen
Journal: Thorax (2005)

C-reactive protein (CRP) is often used as a clinical marker of acute systemic inflammation. Since low grade inflammation is evident in chronic diseases such as chronic obstructive pulmonary disease (COPD), new methods have been developed to enhance the sensitivity of CRP assays in the lower range. A study was undertaken to investigate the discriminative value of high sensitivity CRP in COPD with respect to markers of local and systemic impairment, disability, and handicap.Plasma CRP levels, interleukin 6 (IL-6) levels, body composition, resting energy expenditure (REE), exercise capacity, health status, and lung function were determined in 102 patients with clinically stable COPD (GOLD stage II-IV). The cut off point for normal versus raised CRP levels was 4.21 mg/l.CRP levels were raised in 48 of 102 patients. In these patients, IL-6 (p<0.001) and REE (adjusted for fat-free mass, p = 0.002) were higher while maximal (p = 0.040) and submaximal exercise capacity (p = 0.017) and 6 minute walking distance (p = 0.014) were lower. The SGRQ symptom score (p = 0.003) was lower in patients with raised CRP levels, as were post-bronchodilator FEV1 (p = 0.031) and reversibility (p = 0.001). Regression analysis also showed that, when adjusted for FEV1, age and sex, CRP was a significant predictor for body mass index (p = 0.044) and fat mass index (p = 0.016).High sensitivity CRP is a marker for impaired energy metabolism, functional capacity, and distress due to respiratory symptoms in COPD.
Rehabilitation of sports injuries: scientific basis
Authors: M E Batt
Journal: British Journal of Sports Medicine (2005)

Edited by Walter R Frontera. London: Blackwell, 2003, £65.00, pp 326, hardcover. ISBN 0632058137

Do not buy this book if you are seeking the latest word on hamstring rehabilitation or current concepts in the management of multidirectional instability of the shoulder in athletes. As the title implies, this book addresses the scientific basis of the rehabilitation of sports injuries. As such it …
Arrest Defective 1 Autoacetylation Is a Critical Step in Its Ability to Stimulate Cancer Cell Proliferation
Authors: Ji Hae Seo, Jong-Ho Cha, Ji-Hyeon Park, Chul-Ho Jeong, Zee-Yong Park, Hye-Suk Lee, Seung Hyun Oh, Ju-Hee Kang, Se Won Suh, Kyoung Hoon Kim, Jun Yong Ha, Sang Hee Han, Se-Hee Kim, Ji-Won Lee, Jeong Ae Park, Joo-Won Jeong, Kong-Joo Lee, Goo Taeg Oh, Mi-Ni Lee, Sung Won Kwon, Seung-Ki Lee, Kwang-Hoon Chun, Su-Jae Lee, Kyu-Won Kim
Journal: Cancer Research (2010)

The N-acetyltransferase arrest defective 1 (ARD1) is an important regulator of cell growth and differentiation that has emerged recently as a critical molecule in cancer progression. However, the regulation of the enzymatic and biological activities of human ARD1 (hARD1) in cancer is presently poorly understood. Here, we report that hARD1 undergoes autoacetylation and that this modification is essential for its functional activation. Using liquid chromatography-tandem mass spectrometry and site-directed mutational analyses, we identified K136 residue as an autoacetylation target site. K136R mutation abolished the ability of hARD1 to promote cancer cell growth in vitro and tumor xenograft growth in vivo. Mechanistic investigations revealed that hARD1 autoacetylation stimulated cyclin D1 expression through activation of the transcription factors beta-catenin and activator protein-1. Our results show that hARD1 autoacetylation is critical for its activation and its ability to stimulate cancer cell proliferation and tumorigenesis.
MD-Logic Artificial Pancreas System
Authors: Eran Atlas, Revital Nimri, Shahar Miller, Eli A. Grunberg, Moshe Phillip
Journal: Diabetes Care (2010)

OBJECTIVE Current state-of-the-art artificial pancreas systems are either based on traditional linear control theory or rely on mathematical models of glucose-insulin dynamics. Blood glucose control using these methods is limited due to the complexity of the biological system. The aim of this study was to describe the principles and clinical performance of the novel MD-Logic Artificial Pancreas (MDLAP) System. RESEARCH DESIGN AND METHODS The MDLAP applies fuzzy logic theory to imitate lines of reasoning of diabetes caregivers. It uses a combination of control-to-range and control-to-target strategies to automatically regulate individual glucose levels. Feasibility clinical studies were conducted in seven adults with type 1 diabetes (aged 19–30 years, mean diabetes duration 10 ± 4 years, mean A1C 6.6 ± 0.7%). All underwent 14 full, closed-loop control sessions of 8 h (fasting and meal challenge conditions) and 24 h. RESULTS The mean peak postprandial (overall sessions) glucose level was 224 ± 22 mg/dl. Postprandial glucose levels returned to &amp;lt;180 mg/dl within 2.6 ± 0.6 h and remained stable in the normal range for at least 1 h. During 24-h closed-loop control, 73% of the sensor values ranged between 70 and 180 mg/dl, 27% were &amp;gt;180 mg/dl, and none were &amp;lt;70 mg/dl. There were no events of symptomatic hypoglycemia during any of the trials. CONCLUSIONS The MDLAP system is a promising tool for individualized glucose control in patients with type 1 diabetes. It is designed to minimize high glucose peaks while preventing hypoglycemia. Further studies are planned in the broad population under daily-life conditions.
Complete reversal of acid-induced acute lung injury by blocking of platelet-neutrophil aggregation
Authors: Alexander Zarbock, Kai Singbartl, Klaus Ley
Journal: Journal of Clinical Investigation (2006)

Acute lung injury (ALI) causes high mortality, but its molecular mechanisms are poorly understood. Acid aspiration is a frequent cause of ALI, leading to neutrophil sequestration, increased permeability, and deterioration of gas exchange. We investigated the role of platelet-neutrophil interactions in a murine model of acid-induced ALI. Acid aspiration induced P-selectin–dependent platelet-neutrophil interactions in blood and in lung capillaries. Reducing circulating platelets or blocking P-selectin halted the development of ALI. Bone marrow chimeras showed that platelet, not endothelial, P-selectin was responsible for the injury. The interaction of platelets with neutrophils and endothelia was associated with TXA2 formation, with detrimental effects on permeability and tissue function. Activated platelets induced endothelial expression of ICAM-1 and increased neutrophil adhesion. Inhibition of platelet-neutrophil aggregation improved gas exchange, reduced neutrophil recruitment and permeability, and prolonged survival. The key findings were confirmed in a sepsis-induced model of ALI. These findings may translate into improved clinical treatments for ALI.