tbuckley/cabot-search huggingface dataset:
Role of transcription factors in inflammatory lung diseases
Authors: I. Rahman, W. MacNee
Journal: Thorax (1998)

Acute and chronic alveolar and/or bronchial inflammation is thought to be central to the pathogenesis of many lung disorders such as asthma, chronic obstructive pulmonary disease (COPD), adult respiratory distress syndrome (ARDS), and idiopathic pulmonary fibrosis (IPF). The site and specific characteristics of the inflammatory responses may be different in each of these diseases, but all are characterised by the recruitment to the lungs and activation of immune and inflammatory cells. These activated cells produce cytokines, oxidants and many other mediators which are involved in inflammation.1 2 Recent data indicate that, in addition, airway epithelial cells are able to act as immune effector cells by secreting pro-inflammatory mediators, oxidants, and cytokines.3 Once triggered, an inappropriate chronic inflammatory response persists in these conditions and is presumed to result in lung injury. The intracellular molecular mechanisms in response to environmental signals, leading to increased gene expression and biosynthesis of proinflammatory mediators by airspace inflammatory and epithelial cells, are of considerable current interest. It is now recognised that there are gene specific factors which regulate the transcription of particular genes by affinity binding to specific recognition motifs, which are usually located in the upstream (5′) promoter region of the gene. These factors, which are usually located in the cytosol, can translocate to the cell nucleus and, by binding to specific consensus sites, can upregulate the rate of transcription of the gene and therefore increase the formation of messenger RNA (mRNA) and the protein of an inflammatory mediator. Some transcription factors are cell specific, but others are ubiquitous. Their activity can be modulated by environmental signals and they may play a key role in immune and inflammatory responses. The transcription factors about which there is most information in immune and inflammatory responses are nuclear factor-kappa (κ)B (NF-κB) and activator protein 1 (AP-1). …
VIRUSES OF CLASSICAL AND MILD FORMS OF HAEMORRHAGIC FEVER WITH RENAL SYNDROME ISOLATED IN CHINA HAVE SIMILAR BUNYAVIRUS-LIKE MORPHOLOGY
Authors: Hung Tao, Xia Se-Mau, Song Gan, Liao Hua-Xin, Chao Tung-Xin, Chou Zing-Yi, Hang Chang-Shou
Journal: The Lancet (1983)
Randomised controlled trial of behavioural infant sleep intervention to improve infant sleep and maternal mood
Authors: H Hiscock
Journal: BMJ (2002)

<h3>Objective</h3> Two randomized phase III trials demonstrated the efficacy and safety of combining bevacizumab with front-line carboplatin/paclitaxel for advanced ovarian cancer. The OSCAR (NCT01863693) study assessed the impact of front-line bevacizumab-containing therapy on safety and oncologic outcomes in patients with advanced ovarian cancer in the UK. <h3>Methods</h3> Between May 2013 and April 2015, patients with high-risk stage IIIB–IV advanced ovarian cancer received bevacizumab (7.5 or 15 mg/kg every 3 weeks, typically for ≤12 months, per UK clinical practice) combined with front-line chemotherapy, with bevacizumab continued as maintenance therapy. Co-primary endpoints were progression-free survival and safety (NCI-CTCAE v4.0). Patients were evaluated per standard practice/physician's discretion. <h3>Results</h3> A total of 299 patients received bevacizumab-containing therapy. The median age was 64 years (range 31–83); 80 patients (27%) were aged ≥70 years. Surgical interventions were primary debulking in 21%, interval debulking in 36%, and none in 43%. Most patients (93%) received bevacizumab 7.5 mg/kg with carboplatin/paclitaxel. Median duration of bevacizumab was 10.5 months(range &lt;0.1–41.4); bevacizumab and chemotherapy were given in combination for a median of three cycles (range 1–10). Median progression-free survival was 15.4 (95% CI 14.5 to 16.9) months. Subgroup analyses according to prior surgery showed median progression-free survival of 20.8, 16.1, and 13.6 months in patients with primary debulking, interval debulking, and no surgery, respectively. Median progression-free survival was 16.1 vs 14.8 months in patients aged &lt;70 versus ≥70 years, respectively. The 1-year overall survival rate was 94%. Grade 3/4 adverse events occurred in 54% of patients, the most common being hypertension (16%) and neutropenia (5%). Thirty-five patients (12%) discontinued bevacizumab for toxicity (most often for proteinuria (2%)). <h3>Conclusions</h3> Median progression-free survival in this study was similar to that in the high-risk subgroup of the ICON7 phase III trial. Median progression-free survival was shortest in patients who did not undergo surgery.
Mechanism of Induction of Ovarian Tumors in the Mouse by 7,12-Dimethylbenz[&lt;italic&gt;a&lt;/italic&gt;]anthracene. VII. Relative Activities of Parent Hydrocarbon and Some of Its Metabolites&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: J. W. Jull, A. Russell
Journal: JNCI Journal of the National Cancer Institute (1970)

After oral administration of 7,12-dimethylbenz[a]anthracene to donor CNZ mice and transplantation of the ovaries to ovariectomized recipients, granulosa cell tumors developed in the transplanted ovaries. No tumors were found in similar transplants from mice receiving 7-hydroxymethyl-12-methylbenz[a]anthracene or 7,12-dihydroxymethylbenz[a]anthracene. When ovaries in organ culture were exposed to 7,12-dimethylbenz[a]-anthracene or 12-hydroxymethyl-7-methylbenz[a]anthracene for 4 days and then reimplanted subcutaneously into the same mouse, granulosa cell tumors arose in these implants; similar results were obtained in strains CNZ, C3H, and CAF1 mice. After the exposure of ovaries in organ culture to 7-hydroxymethyl-12-methylbenz[a]anthracene, 7,12-dihydroxymethylbenz[a]anthracene, or culture medium alone before reimplantation, no ovarian tumors developed.
The role of glutathione in detoxication
Authors: Brian Ketterer, Brian Coles, David J. Meyer
Journal: Environmental Health Perspectives (1983)

Glutathione (GSH) is a strong nucleophile which reacts well with soft electrophiles, but poorly with both weak and strong electrophiles. Weak electrophiles have low reactivity with all nucleophiles while strong electrophiles react well with weak nucleophiles including superabundant H2O. There are enzymes, the GSH transferases, which catalyze GSH conjugation with all the types of electrophiles described above. In order to deal with the wide variety of potential substrates, a multiplicity of GSH transferases exists—each tissue having its own collection and each enzyme having a different substrate specificity. These enzymes are often very abundant, e.g., in the rat liver cytosol, their concentration is 0.2 mM. The following substrates are considered in some detail: 1-chloro-2,4-dinitrobenzene, the electrophile derived metabolically from paracetamol N-acetyliminoquinone?), benzo(a)pyrene-4-5-oxide, cholesterol-5α,6α-oxide, benzo(a)pyrene-7,8-diol-9,10-oxide and the electrophiles derived metabolically from aflatoxin B1 (the 2,3-oxide?). According to the substrate, optimal enzyme rates vary over seven orders of magnitude from 10−5 to 10−12 mole/min/mg. Despite the wide embrace of the GSH transferases, not all metabolically produced electrophiles are substrates. We know of the following examples: N-methylol-4-aminoazobenzene and its 4′-hydroxy derivative (these are soft electrophiles and react well with GSH noncatalytically), N-sulfonyloxy-N-methyl-4-aminoazobenzene, N-sulfonyloxy-N-acetyl-2-aminofluorene (these are strong electrophiles which do not react selectively with GSH) and N-hydroxy-2-aminofluorene which appears to react only slowly with GSH. It is of interest in the present context that all these compounds are derived from either arylamine or arylamide carcinogens. Whether the reaction be enzymic or nonenzymic, conjugation with GSH is a very important means of detoxication accounting in some cases for up to 60% of the biliary metabolites. As seen in the example of aflatoxin B1, very low enzymic rates observed in vitro are sufficient to account for apparently high rates of biliary excretion of GSH conjugates. GSH transferases have evolved other functions apart from the catalysis of GSH conjugation. GSH transferase B participates in the hepatic uptake of bilirubin and the intracellular distribution of the heme prosthetic group. It also has GSH peroxidase activity which suggests that it might participate in the detoxication of by-products of oxygen utilization including those produced by the action of cytochrome P-450. It is shown that GSH transferase B inhibits lipid peroxidation in vitro.
High-dose (2000-μg) intravitreous ganciclovir in the treatment of cytomegalovirus retinitis11The authors have no financial interest in the drugs or methods described in this article.
Authors: Stephanie Young, Nigel Morlet, Gilberto Besen, Clayton A Wiley, Philip Jones, Julian Gold, Yueming Li, William R Freeman, Minas T Coroneo
Journal: Ophthalmology (1998)
Genome-Wide Analysis Reveals Origin of Transfer RNA Genes from tRNA Halves
Authors: Zhixiang Zuo, Duo Peng, Xiujuan Yin, Xiang Zhou, Hanhua Cheng, Rongjia Zhou
Journal: Molecular Biology and Evolution (2013)

Transfer RNAs (tRNAs) play an important role linking mitochondrial RNA and amino acids during protein biogenesis. Four types of tRNA genes have been identified in living organisms. However, the evolutionary origin of tRNAs remains largely unknown. In this article, we conduct a deep sequence analysis of diverse genomes that cover all three domains of life to unveil the evolutionary history of tRNA genes from tRNA halves. tRNA half homologs were detected in diverse organisms, and some of them were expressed in mouse tissues. Continuous tRNA genes have a conserved pattern similar to indels, which is, more closely flanking regions have higher single nucleotide substitution rates, whereas tRNA half homologs do not have this pattern. In addition, tRNAs tend to break into tRNA halves when tissues are incubated in vitro, the tendency of tRNA to break into tRNA halves may be a "side-effect" of tRNA genes evolving from tRNA halves. These results suggest that modern tRNAs originated from tRNA halves through a repeat element-mediated mechanism. These findings provide insight into the evolutionary origin of tRNA genes.
ECOSEP: bringing the European SEM family together
Authors: Liam West, Nikos Malliaropoulos, Suzan de Jonge
Journal: British Journal of Sports Medicine (2014)

Advancing the field of Sport and Exercise Medicine (SEM) requires organisations and societies to collaborate. Common scientific and educational standards need to be developed to promote attainment of high levels of practical skills within SEM. We feel that the best practice is pan-European and not limited to one nation's view alone. Our personal experience is that the smaller the country, the better the international collaboration, while countries with larger populations, all speaking the same language, are under less pressure to cooperate internationally. This can lead to researchers opting to publish in a national journal written in their native language and losing out on global reach. This slows international knowledge exchange and clinical progress.

ECOSEP—the European College of Sports and Exercise Physicians—was founded with the aim of advancing the competency of sports physicians and, thus, facilitating optimal care for their own and, more broadly, the citizens of Europe. It was to achieve this by providing continuing education, publishing research, collaborating with other sports medicine organisations …
Plasma l-[3H]norepinephrine, d-[14C]norepinephrine, and d,l-[3H]isoproterenol kinetics in essential hypertension.
Authors: D S Goldstein, D Horwitz, H R Keiser, R J Polinsky, I J Kopin
Journal: Journal of Clinical Investigation (1983)

We infused tracer-labeled l-[3H]-norepinephrine, d-[14C]norepinephrine, and d,l-[3H]-isoproterenol simultaneously into patients with essential hypertension and into normotensive control subjects, in order to determine whether abnormalities in the disappearance kinetics of these substances characterized the hypertensive patients. The mean preinfusion venous plasma norepinephrine concentration was somewhat higher in the hypertensive group (260 vs. 194 pg/ml, P = 0.06), but the groups did not differ in the disappearance kinetics of l- or d-norepinephrine or of isoproterenol. Preinfusion plasma norepinephrine was significantly positively correlated with calculated spillover rates in both the hypertensive and normotensive groups, but not with norepinephrine clearances. The d/l ratio in plasma norepinephrine was the same as in the infusate during and after the infusion, even after pretreatment with the neuronal norepinephrine uptake blocker, desipramine. Because isoproterenol is not taken up by nerve endings, the ratio of [3H]isoproterenol to l-[3H]norepinephrine increased after the infusion ended. This increase was almost completely abolished by pretreatment with desipramine. These results indicate that (a) increased plasma norepinephrine levels seen in some patients with essential hypertension result from increased sympathetic neural activity and not from decreased clearance of norepinephrine, (b) changes in the isoproterenol/norepinephrine ratio after simultaneous infusion of both provide an index of neuronal norepinephrine uptake in man, and (c) neuronal norepinephrine uptake is not stereospecific.
Effect of Ether Anesthesia on the Cardiac Output, Blood Pressure, and Distribution of Blood Flow in the Albino Rat
Authors: DONALD G. VIDT, ANTONIE BREDEMEYER, ELIZABETH SAPIRSTEIN, LEO A. SAPIRSTEIN
Journal: Circulation Research (1959)

Rats anesthetized with ethyl ether were compared with rats anesthetized with sodium pentobarbital from the standpoint of cardiac output, peripheral resistance and regional blood flow. Cardiac output was measured by the indicator-dilution technic; regional blood flow was determined by the indicator-fractionation technic employing Rb 86 or I 131 -antipyrine. The cardiac output is one and a half times as great in ether anesthesia as in pentobarbital anesthesia; the peripheral resistance is about two-thirds as great with ether. Compared to pentobarbital, ether increases myocardial, cerebral, and carcass blood flow, while decreasing renal, splanchnic and cutaneous blood flow. The pronounced difference in the cardiovascular effects of the two agents indicates the need for caution in the interpretation of experiments in which cardiovascular measurements are made under anesthesia.
Eosinophilic enterocolitis diagnosed by means of technetium-99m albumin scintigraphy and treated with budesonide (CIR).
Authors: M G Russel, R N Zeijen, R J Brummer, A P de Bruine, M J van Kroonenburgh, R W Stockbrugger
Journal: Gut (1994)

A patient with a 15 year history of diarrhoea of unknown origin is described. Scintigraphy with technetium-99m labelled albumin suggested albumin loss at the terminal ileum and caecum; subsequent colonoscopic biopsies of these macroscopically normal looking areas showed abundant infiltration with eosinophils. A diagnosis of eosinophilic enterocolitis was made. Treatment with prednisolone had good results, but had to be stopped because of severe side effects. Oral cromoglycate and mesalazine were not effective. Budesonide (CIR), a new topically active corticosteroid with very little systemic effects, was at least as effective as prednisolone without producing side effects.
Treatment Issues in Type 2 Diabetes
Authors: Zachary T. Bloomgarden
Journal: Diabetes Care (2002)

This is the fifth in a series of reports on the American Diabetes Association (ADA) 61st Scientific Sessions held in Philadelphia, PA, in June 2001. It covers topics related to the treatment of type 2 diabetes.

Alan Cherrington, Nashville, TN, examined the effect of insulin to inhibit hepatic glucose production. Using a dog preparation with somatostatin to block insulin and glucagon production and administration of insulin and glucagon into the portal vein, decreasing portal insulin to levels similar to those in the arterial circulation immediately increased hepatic glucose production via glycogenolysis, which was sustained over a period of several hours, with consequent hyperglycemia. There is a steep inverse dose-response curve of hepatic glucose production versus hepatic sinusoidal insulin levels. Tripling insulin quickly turns off hepatic glucose production. Glucose utilization by the liver in response to increasing insulin levels has a longer time course, taking several hours to reach maximal levels. This response is much less sensitive to changes in insulin levels than hepatic glucose production, and normal basal hepatic glucose utilization is very low. Muscle is less sensitive on a molar basis than in the liver, so that a tripling of insulin levels causes only a 50% increase in glucose utilization, compared with the more than sixfold increase in glucose uptake under maximal stimulation.

Comparing the effects of first-phase and second-phase insulin release in response to glucagon, the former more potently inhibits glucose production. Insulin levels show similar first- and second-phase responses to a hyperglycemic clamp, and elimination of the first-phase insulin response leads to much greater hepatic glucose production, although it has little effect on glucose utilization. A recent study with nateglinide similarly showed a rapid insulin response and marked lessening of postprandial hyperglycemia (1). When intraduodenal glucose is given with dogs having somatostatin and portal catheters, a first-phase …
Comparison of the Instructional Efficacy of Internet-Based CME With Live Interactive CME Workshops
Authors: Michael Fordis, Jason E King, Christie M Ballantyne, Peter H Jones, Katharine H Schneider, Stephen J Spann, Stephen B Greenberg, Anthony J Greisinger
Journal: JAMA (2005)

Despite evidence that a variety of continuing medical education (CME) techniques can foster physician behavioral change, there have been no randomized trials comparing performance outcomes for physicians participating in Internet-based CME with physicians participating in a live CME intervention using approaches documented to be effective.To determine if Internet-based CME can produce changes comparable to those produced via live, small-group, interactive CME with respect to physician knowledge and behaviors that have an impact on patient care.Randomized controlled trial conducted from August 2001 to July 2002. Participants were 97 primary care physicians drawn from 21 practice sites in Houston, Tex, including 7 community health centers and 14 private group practices. A control group of 18 physicians from these same sites received no intervention.Physicians were randomly assigned to an Internet-based CME intervention that could be completed in multiple sessions over 2 weeks, or to a single live, small-group, interactive CME workshop. Both incorporated similar multifaceted instructional approaches demonstrated to be effective in live settings. Content was based on the National Institutes of Health National Cholesterol Education Program--Adult Treatment Panel III guidelines.Knowledge was assessed immediately before the intervention, immediately after the intervention, and 12 weeks later. The percentage of high-risk patients who had appropriate lipid panel screening and pharmacotherapeutic treatment according to guidelines was documented with chart audits conducted over a 5-month period before intervention and a 5-month period after intervention.Both interventions produced similar and significant immediate and 12-week knowledge gains, representing large increases in percentage of items correct (pretest to posttest: 31.0% [95% confidence interval {CI}, 27.0%-35.0%]; pretest to 12 weeks: 36.4% [95% CI, 32.2%-40.6%]; P<.001 for all comparisons). Chart audits revealed high baseline screening rates in all study groups (> or =93%) with no significant postintervention change. However, the Internet-based intervention was associated with a significant increase in the percentage of high-risk patients treated with pharmacotherapeutics according to guidelines (preintervention, 85.3%; postintervention, 90.3%; P = .04).Appropriately designed, evidence-based online CME can produce objectively measured changes in behavior as well as sustained gains in knowledge that are comparable or superior to those realized from effective live activities.
Autoimmune hepatitis experimental model based on adenoviral infections
Authors: Pascal Lapierre, Kathie Béland, Fernando Alvarez
Journal: Hepatology (2013)

We read with great interest the article by Hardtke-Wolenski et al.1 describing the development of an animal model of autoimmune hepatitis based on a self-limited adenoviral infection. The adenovirus administered encoded for formiminotransferase cyclodeaminase (FTCD), a targeted liver antigen in type 2 autoimmune hepatitis (AIH), identified in 1999. This report confirms our previously published findings that a self-limited adenoviral infection, with a virus encoding for FTCD, can lead to the development of an AIH in mice.2 The researchers state that “danger signals” are necessary for the initiation of an autoimmune response against the liver based on adenoviral infections and hydrodynamic transfection experiments with an observation period of 12 weeks. These results are in contrast with previous findings in models of AIH generated by DNA vaccination3 or adoptive transfer,4 where a peripheral activation of T-cell specific to a liver autoantigen, in the absence of inflammation (danger signals), led to an active autoimmune response. The researchers describe the development of fibrosis in their model, but it is solely based on silver staining of liver sections. It should be remembered that silver staining of reticulin proteins mainly reflects changes in the liver structure (as in Fig. 2C), where mild alterations are observed. These can be interpreted as the result of hepatocyte lysis secondary to the lymphocyte infiltration. Trichrome staining would have allowed one to visualize collagen deposition, the hallmark of liver fibrosis. The researchers bring up an interesting point when they discuss the need for a predisposing genetic background (nonobese diabetes, in this case) for the development of an AIH in mice, an observation we previously reported on in our model of type 2 AIH. However, the complete absence of an AIH in C57BL/6 and FVB/N mice in their model is rather puzzling. We2 and others5 found that AIH can be triggered in both these mouse strains. This could be attributed to the duration of the observation period, which is critical in view of the fact that we observed the development of AIH as late as 8 months after adenoviral infection.2 In the article, it is not clear whether the C57BL/6 and FVB/N mice were followed for more than 12 weeks. It could also be the result of the plaque-forming units of adenovirus used, an important factor in the outcome of an adenoviral infection or their adenovirus construction, because our vector encoded for CYP2D6 in addition to FTCD,2 whereas Holdener et al. used an adenoviral vector encoding for CYP2D6.5 Pascal Lapierre, Ph.D.1 Kathie Béland, M.Sc.2 Fernando Alvarez, M.D.2 1Department of Immunovirology, INRS-Institut Armand-Frappier, Laval, Quebec, Canada 2Department of Gastroenterology, Hepatology, and Nutrition, CHU Sainte-Justine, Montréal, Quebec, Canada