tbuckley/cabot-search huggingface dataset:
Adrenomedullin inhibits ovalbumin-induced bronchoconstriction and airway microvascular leakage in guinea-pigs
Authors: H Ohbayashi, H Suito, N Yoshida, Y Ilto, H Kume, K Yamaki
Journal: European Respiratory Journal (1999)

Human adrenomedullin is a potent vasodilator with bronchodilation properties. The effects of adrenomedullin on antigen-induced bronchoconstriction and airway microvascular leakage in guinea-pigs was investigated. The portion of the adrenomedullin molecule possessing these pulmonary active profiles was also examined, using two truncated adrenomedullin molecules: adrenomedullin (1-25) and adrenomedullin (22-52). Four weeks after sensitization with ovalbumin (0.1 mg x k(-1)), the guinea-pigs were anaesthetized and mechanically ventilated. Respiratory resistance, dynamic compliance and arterial blood pressure were monitored. Airway microvascular leakage was evaluated by extravasation of 20 mg x kg(-1) Evans blue into airway interstitial tissue. In order to enhance the pulmonary effects of adrenomedullin, the active production of endogenous nitric oxide was inhibited by coadministration of a nitric oxide synthase inhibitor, L-N(G)-nitroarginine methethyl ester (10 mg x kg(-1)). Intravenous pretreatment with adrenomedullin (10, 30 and 100 microg x mL(-1)) dose-dependently inhibited ovalbumin-induced bronchoconstriction and airway microvascular leakage in all airway segments. Inhaled adrenomedullin (100 microg.mL(-1), 1 min) also significantly inhibited pulmonary changes induced by ovalbumin inhalation (3 mg x mL (-1) , 3 min). These pulmonary profiles of adrenomedullin were enhanced by inhibiting the active production of endogenous nitric oxide. In conclusion, adrenomedullin has inhibitory effects on antigen-induced microvascular leakage and bronchoconstriction in guinea-pigs. These beneficial effects strongly related to its unique ring structure and N-terminal segment, making it a potential anti-asthma.
Influenza vaccination in Europe: an inventory of strategies to reach target populations and optimise vaccination uptake
Authors: M Kroneman, W J Paget, G A van Essen
Journal: Eurosurveillance (2003)

A study was undertaken to assess influenza vaccine uptake in risk groups and to get insight into vaccination practices in European countries. Questionnaires were completed by national influenza experts from 26 countries. Only 14 were able to provide uptake rates for the elderly. For the other risk groups, even fewer could provide data. Vaccines are usually administrated by GPs. Financial incentives for physicians and patients might work as a strategy to increase uptake rates, but due to the small amount of data, it was not possible to carry out thorough multivariate analyses. The development of a uniform influenza vaccination monitoring method was recommended to allow for comparison of uptake data in Europe.
Tirapazamine with cisplatin in patients with advanced non-small-cell lung cancer: a phase II study.
Authors: J Treat, E Johnson, C Langer, C Belani, B Haynes, R Greenberg, R Rodriquez, P Drobins, W Miller, L Meehan, A McKeon, J Devin, R von Roemeling, J Viallet
Journal: Journal of Clinical Oncology (1998)

PURPOSE A phase II study was conducted to evaluate the safety and efficacy of tirapazamine combined with cisplatin for the treatment of patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Forty-four patients with stage IIIB/IV NSCLC were treated with a combination of tirapazamine and cisplatin. Patients received tirapazamine 260 mg/m2 administered intravenously over 2 hours, followed 1 hour later by cisplatin 75 mg/m2 administered over an additional hour, repeated every 21 days. The duration of therapy was meant to be limited to four cycles for nonresponders and eight cycles for responders. RESULTS Ten of 44 patients (23%) showed a partial response. The estimated median survival for all patients was 37 weeks. Toxicities were treatable and included grade 3 nausea or vomiting (25%), fatigue (27.3%), and muscle cramps (4.5%). No dose reductions were necessary. CONCLUSION The results show that tirapazamine can safely be added to cisplatin. Both the median survival and response rate observed strongly suggest that tirapazamine with cisplatin is more active than cisplatin alone.
Gene–environment interaction between <i>HLA-DRB1</i> shared epitope and heavy cigarette smoking in predicting incident rheumatoid arthritis
Authors: E W Karlson, S-C Chang, J Cui, L B Chibnik, P A Fraser, I De Vivo, K H Costenbader
Journal: Annals of the Rheumatic Diseases (2009)

Previous studies have reported an interaction between ever cigarette smoking and the presence of the human leukocyte antigen (HLA)-DRB1 shared epitope (SE) genotype and rheumatoid arthritis (RA) risk. To address the effect of dosage, a case-control study nested within two prospective cohorts to determine the interaction between heavy smoking and the HLA-SE was conducted.Blood was obtained from 32 826 women in the Nurses' Health Study and 29 611 women in the Nurses' Health Study II. Incident RA diagnoses were validated by chart review. Controls were matched for age, menopausal status and postmenopausal hormone use. High-resolution HLA-DRB1 genotyping was performed for SE alleles. HLA-SE, smoking, HLA-SE* smoking interactions and RA risk, were assessed using conditional logistic regression models, adjusted for age and reproductive factors. Additive and multiplicative interactions were tested.In all, 439 Caucasian matched pairs were included. Mean age at RA diagnosis was 55.2 years; 62% of cases were seropositive. A modest additive interaction was observed between ever smoking and HLA-SE in seropositive RA risk. A strong additive interaction (attributable proportion due to interaction (AP) = 0.50; p<0.001) and significant multiplicative interaction (p = 0.05) were found between heavy smoking (>10 pack-years) and any HLA-SE in seropositive RA risk. The highest risk was in heavy smokers with double copy HLA-SE (odds ratio (OR) 7.47, 95% CI 2.77 to 20.11).A strong gene-environment interaction was observed between HLA-SE and smoking when stratifying by pack-years of smoking rather than by ever smoking. Future studies should assess cumulative exposure to cigarette smoke when testing for gene-smoking interactions.
Alterations in hepatic glucose and energy metabolism as a result of calorie and carbohydrate restriction
Authors: Jeffrey D. Browning, Brian Weis, Jeannie Davis, Santhosh Satapati, Matthew Merritt, Craig R. Malloy, Shawn C. Burgess
Journal: Hepatology (2008)

Abstract Carbohydrate restriction is a common weight-loss approach that modifies hepatic metabolism by increasing gluconeogenesis (GNG) and ketosis. Because little is known about the effect of carbohydrate restriction on the origin of gluconeogenic precursors (GNG from glycerol [GNGglycerol] and GNG from lactate/amino acids [GNGphosphoenolpyruvate {PEP}]) or its consequence to hepatic energy homeostasis, we studied these parameters in a group of overweight/obese subjects undergoing weight-loss via dietary restriction. We used 2H and 13C tracers and nuclear magnetic resonance spectroscopy to measure the sources of hepatic glucose and tricarboxylic acid (TCA) cycle flux in weight-stable subjects (n = 7) and subjects following carbohydrate restriction (n = 7) or calorie restriction (n = 7). The majority of hepatic glucose production in carbohydrate restricted subjects came from GNGPEP. The contribution of glycerol to GNG was similar in all groups despite evidence of increased fat oxidation in carbohydrate restricted subjects. A strong correlation between TCA cycle flux and GNGPEP was found, though the reliance on TCA cycle energy production for GNG was attenuated in subjects undergoing carbohydrate restriction. Together, these data imply that the TCA cycle is the energetic patron of GNG. However, the relationship between these two pathways is modified by carbohydrate restriction, suggesting an increased reliance of the hepatocyte on energy generated outside of the TCA cycle when GNGPEP is maximal. Conclusion: Carbohydrate restriction modifies hepatic GNG by increasing reliance on substrates like lactate or amino acids but not glycerol. This modification is associated with a reorganization of hepatic energy metabolism suggestive of enhanced hepatic β-oxidation. (Hepatology 2008;48:1487–1496.)
Expression of FOXP3, CD68, and CD20 at Diagnosis in the Microenvironment of Classical Hodgkin Lymphoma Is Predictive of Outcome
Authors: Paul Greaves, Andrew Clear, Rita Coutinho, Andrew Wilson, Janet Matthews, Andrew Owen, Milensu Shanyinde, T. Andrew Lister, Maria Calaminici, John G. Gribben
Journal: Journal of Clinical Oncology (2012)

Purpose The immune microenvironment is key to the pathophysiology of classical Hodgkin lymphoma (CHL). Twenty percent of patients experience failure of their initial treatment, and others receive excessively toxic treatment. Prognostic scores and biomarkers have yet to influence outcomes significantly. Previous biomarker studies have been limited by the extent of tissue analyzed, statistical inconsistencies, and failure to validate findings. We aimed to overcome these limitations by validating recently identified microenvironment biomarkers (CD68, FOXP3, and CD20) in a new patient cohort with a greater extent of tissue and by using rigorous statistical methodology. Patients and Methods Diagnostic tissue from 122 patients with CHL was microarrayed and stained, and positive cells were counted across 10 to 20 high-powered fields per patient by using an automated system. Two statistical analyses were performed: a categorical analysis with test/validation set-defined cut points and Kaplan-Meier estimated outcome measures of 5-year overall survival (OS), disease-specific survival (DSS), and freedom from first-line treatment failure (FFTF) and an independent multivariate analysis of absolute uncategorized counts. Results Increased CD20 expression confers superior OS. Increased FOXP3 expression confers superior OS, and increased CD68 confers inferior FFTF and OS. FOXP3 varies independently of CD68 expression and retains significance when analyzed as a continuous variable in multivariate analysis. A simple score combining FOXP3 and CD68 discriminates three groups: FFTF 93%, 62%, and 47% (P &lt; .001), DSS 93%, 82%, and 63% (P = .03), and OS 93%, 82%, and 59% (P = .002). Conclusion We have independently validated CD68, FOXP3, and CD20 as prognostic biomarkers in CHL, and we demonstrate, to the best of our knowledge for the first time, that combining FOXP3 and CD68 may further improve prognostic stratification.
Intravitreal Triamcinolone plus Sequential Grid Laser versus Triamcinolone or Laser Alone for Treating Diabetic Macular Edema
Authors: Dennis S.C. Lam, Carmen K.M. Chan, Shaheeda Mohamed, Timothy Y.Y. Lai, Vincent Y.W. Lee, David T.L. Liu, Kenneth K.W. Li, Patrick S.H. Li, Mahesh P. Shanmugam
Journal: Ophthalmology (2007)
Tie2 lineage deletion of 6 integrin: endothelial and haematopoietic cells in neovascularization
Authors: V. W. M. van Hinsbergh
Journal: Cardiovascular Research (2012)

This editorial refers to ‘Tie2-dependent knockout of α6 integrin subunit in mice reduces post-ischaemic angiogenesis’ by C. Bouvard et al ., pp. 39–47, this issue. 

The metabolic demand of a mature tissue determines the degree of blood and oxygen supply, which normally is controlled by vasoregulation at the level of arteriolar resistance vessels. However, in specific conditions such as inflammation and excessive tissue growth including tumours, the metabolic demand exceeds the supply by autoregulation and therefore requires neovascularization. The need for additional blood supply and neovascularization becomes urgent after an acute vascular occlusion. Rapid formation of collaterals is then required, while the distal hypoxic tissue simultaneously shifts to the production of pro-angiogenic factors, in particular vascular endothelial growth factor, which subsequently induces sprouting angiogenesis in an attempt to connect to other perfused vessels and to restore oxygen and nutrient supply to the ischaemic tissue.

In addition, circulating monocytes and endothelial progenitor cells (EPCs) are recruited to the sites of structural arterial widening (arteriogenesis) and sprouting angiogenesis. Monocytes and circulating angiogenic cells (monocyte-lineage cells that acquire several endothelial markers, also called early outgrowth EPCs) support the vascular adaptation in a paracrine manner.1 Furthermore, endothelial colony-forming cells (ECFCs, also called late outgrowth EPCs), which are present in small numbers …
Gabapentin Combined With Naltrexone for the Treatment of Alcohol Dependence
Authors: Raymond F. Anton, Hugh Myrick, Tara M. Wright, Patricia K. Latham, Alicia M. Baros, L. Randolph Waid, Patrick K. Randall
Journal: American Journal of Psychiatry (2011)

Naltrexone, an efficacious medication for alcohol dependence, does not work for everyone. Symptoms such as insomnia and mood instability that are most evident during early abstinence might respond better to a different pharmacotherapy. Gabapentin may reduce these symptoms and help prevent early relapse. This clinical trial evaluated whether the combination of naltrexone and gabapentin was better than naltrexone alone and/or placebo during the early drinking cessation phase (first 6 weeks), and if so, whether this effect persisted.A total of 150 alcohol-dependent individuals were randomly assigned to a 16-week course of naltrexone alone (50 mg/day [N=50]), naltrexone (50 mg/day) with gabapentin (up to 1,200 mg/day [N=50]) added for the first 6 weeks, or double placebo (N=50). All participants received medical management.During the first 6 weeks, the naltrexone-gabapentin group had a longer interval to heavy drinking than the naltrexone-alone group, which had an interval similar to that of the placebo group; had fewer heavy drinking days than the naltrexone-alone group, which in turn had more than the placebo group; and had fewer drinks per drinking day than the naltrexone-alone group and the placebo group. These differences faded over the remaining weeks of the study. Poor sleep was associated with more drinking in the naltrexone-alone group but not in the naltrexone-gabapentin group, while a history of alcohol withdrawal was associated with better response in the naltrexone-gabapentin group.The addition of gabapentin to naltrexone improved drinking outcomes over naltrexone alone during the first 6 weeks after cessation of drinking. This effect did not endure after gabapentin was discontinued.
The magnitude of early response to methotrexate therapy predicts long-term outcome of patients with juvenile idiopathic arthritis
Authors: M Bartoli, M Taro, S Magni-Manzoni, A Pistorio, F Traverso, S Viola, A Magnani, C Gasparini, A Martini, A Ravelli
Journal: Annals of the Rheumatic Diseases (2007)

To investigate the relationship between the magnitude of clinical response in the first 6 months of methotrexate (MTX) therapy and long-term outcome in children with juvenile idiopathic arthritis (JIA).The clinical charts of 125 JIA patients who were started with MTX and then followed for at least 5 years were reviewed. Based on the level of American College of Rheumatology (ACR) Pediatric response at 6 months, patients were divided in four mutually exclusive groups: (1) non-responders, (2) responders at 30%, (3) responders at 50%, and (4) responders at 70%. The long-term outcome in each response group was evaluated by calculating the percentage change in active and restricted joint counts from baseline to 1, 2 and 5 years and the frequency of inactive disease at 5 years.At 6 months, 42 patients were classified as non-responders, 24 as 30% responders, 26 as 50% responders, and 33 as 70% responders. Patients who had achieved a 70% response showed a significantly greater percentage improvement in active joint count between baseline to 5 years compared with non-responders and 30% responders, and a significantly greater percentage improvement in restricted joint count between baseline to 5 years compared with 30% responders. The 70% responders also had a greater frequency of inactive disease at 5 years compared with 30% responders,Our results show that the achievement of an ACR Pediatric 70 response at 6 months after start of MTX therapy predicts a more favorable long-term outcome of patients with JIA.
Anaerobic bacteraemia in a patient with necrotising pancreatitis
Authors: M-L Han, H-F Lin, K-L Liu, T-H Lee, W-C Liao
Journal: Gut (2008)

An 83-year-old woman was admitted to our hospital with fever and hypotension. She had been admitted to another hospital 3 months prior to this admission for biliary pancreatitis, and pancreatic pseudocyst was diagnosed by CT 1 month before this admission. Observation …
Hepatocyte proliferation and hepatomegaly induced by phenobarbital and 1,4-bis [2-(3,5-dichloropyridyloxy)] benzene is suppressed in hepatocyte-targeted glypican 3 transgenic mice
Authors: Chih-Wen Lin, Wendy M. Mars, Shirish Paranjpe, Shashikiran Donthamsetty, Vishakha S. Bhave, Liang-I Kang, Anne Orr, William C. Bowen, Aaron W. Bell, George K. Michalopoulos
Journal: Hepatology (2011)

Glypican 3 (GPC3) is a family of glycosylphosphatidylinositol-anchored, cell-surface heparan sulfate proteoglycans. Loss-of-function mutations of GPC3 cause Simpson-Golabi-Behmel syndrome characterized by overgrowth of multiple organs, including liver. Our previous study showed that in GPC3 transgenic (TG) mice, hepatocyte-targeted overexpression of GPC3 suppresses hepatocyte proliferation and liver regeneration after partial hepatectomy and alters gene expression profiles and potential cell cycle-related proteins. This study investigates the role of GPC3 in hepatocyte proliferation and hepatomegaly induced by the xenobiotic mitogens phenobarbital (PB) and TCPOBOP (1, 4-bis [2-(3, 5-dichloropyridyloxy)] benzene). Wildtype (WT) and GPC3 TG mice were given 0.1% PB in drinking water for 10 days or a single dose of TCPOBOP (3 mg/kg) by oral gavage. At day 5 the WT mice showed a 2.2- and 3.0-fold increase in liver weight, whereas the GPC3 TG mice showed a 1.3- and 1.6-fold increase in liver weight after PB and TCPOBOP administration, respectively. There was a significant suppression of proliferative response in the GPC3 TG mice, as assessed by percent of Ki67-positive hepatocyte nuclei. Moreover, gene array analysis showed a panel of changes in the gene expression profile of TG mice, both before and after administration of the xenobiotic mitogens. Expression of cell cycle-related genes in the TG mice was also decreased compared to the WT mice. Conclusion: Our results indicate that in GPC3 TG mice, hepatocyte-targeted overexpression of GPC3 plays an important role for regulation of liver size and termination of hepatocyte proliferation induced by the xenobiotic mitogens PB and TCPOBOP, comparable to the effects seen in the GPC3 TG mice during liver regeneration after partial hepatectomy. (Hepatology 2011;)
Molecular Evolution of Nuclear Genes in Cupressacea, a Group of Conifer Trees
Authors: Junko Kusumi, Yoshihiko Tsumura, Hiroshi Yoshimaru, Hidenori Tachida
Journal: Molecular Biology and Evolution (2002)

We surveyed the molecular evolutionary characteristics of 11 nuclear genes from 10 conifer trees belonging to the Taxodioideae, the Cupressoideae, and the Sequoioideae. Comparisons of substitution rates among the lineages indicated that the synonymous substitution rates of the Cupressoideae lineage were higher than those of the Taxodioideae. This result parallels the pattern previously found in plastid genes. Likelihood-ratio tests showed that the nonsynonymous-synonymous rate ratio did not change significantly among lineages. In addition, after adjustments for lineage effects, the dispersion indices of synonymous and nonsynonymous substitutions were considerably reduced, and the latter was close to 1. These results indicated that the acceleration of evolutionary rates in the Cupressoideae lineage occurred in both the nuclear and plastid genomes, and that generally, this lineage effect affected synonymous and nonsynonymous substitutions similarly. We also investigated the relationship of synonymous substitution rates with the nonsynonymous substitution rate, base composition, and codon bias in each lineage. Synonymous substitution rates were positively correlated with nonsynonymous substitution rates and GC content at third codon positions, but synonymous substitution rates were not correlated with codon bias. Finally, we tested the possibility of positive selection at the protein level, using maximum likelihood models, assuming heterogeneous nonsynonymous-synonymous rate ratios among codon (amino acid) sites. Although we did not detect strong evidence of positively selected codon sites, the analysis suggested that significant variation in nonsynonymous-synonymous rate ratio exists among the sites. The most likely sites for action of positive selection were found in the ferredoxin gene, which is an important component of the apparatus for photosynthesis.
Analysis of T cell receptor V alpha polymorphisms in rheumatoid arthritis
Authors: M Ibberson, V Péclat, P A Guerne, J M Tiercy, P Wordsworth, J Lanchbury, J Camilleri, A K So
Journal: Annals of the Rheumatic Diseases (1998)

<h3>OBJECTIVE</h3> To test for association of T cell receptor (TCR) V alpha polymorphisms and rheumatoid arthritis (RA) in British and Swiss white populations. <h3>METHODS</h3> TCRAV polymorphisms were analysed in RA patients and controls by single strand conformational polymorphism (SSCP) analysis. Associations were sought between defined genotypes and RA, and the effect of HLA-DR4 status analysed. Putative associations were then retested further in new groups of patients and controls. Overall, 360 RA patients and 197 controls were studied. <h3>RESULTS</h3> No association between TCRAV5S1, V6S1, V8S1, V17S1 or V21S1 polymorphisms and RA were observed in the initial population screened. Stratification for DR4 status showed an increase of V5S1*01/*01 in DR4 positive versus DR4 negative patients (χ<sup>2</sup> = 7.19, p=0.028 (2df), p=0.14 after correction for multiple comparisons). This putative association was tested in three further patient groups, none of which showed significant increase of V5S1*01/*01 in DR4 positive patients, although an overall trend towards an increase in V5S1*01/*01 was observed. <h3>CONCLUSION</h3> No evidence was found for a strong association of TCRAV genes and RA in a white population. However, these results suggest a weak association of V5S1*01/*01 with DR4 positive RA, although this requires confirmation using larger groups of patients and controls.