tbuckley/cabot-search huggingface dataset:
Misclassification of smoking status among women in relation to exposure to environmental tobacco smoke
Authors: E Riboli, NJ Haley, J Tredaniel, R Saracci, S Preston-Martin, D Trichopoulos
Journal: European Respiratory Journal (1995)

In studies of the health effects of exposure to environmental tobacco smoke (ETS), misclassification of active smokers has the potential to bias the estimates of disease risk. Biochemical validation of exposure to ETS can provide objective evidence of current smoking status in epidemiological studies. Intrinsic to this effort is the establishment of appropriate cut-off points for the measurements of tobacco biomarkers. Within a collaborative study on ETS co-ordinated by the International Agency for Research on Cancer, questionnaire data and urine samples were collected from 1,369 women at 13 centres in 10 countries. Forty seven of these women had urine cotinine levels above 50 ng.mg-1 creatinine, a level used to discriminate smokers from nonsmokers in previous studies. The distributions of the subjects across cotinine values and self-reported exposure to ETS was consistent with the association, at one extreme, of moderate cotinine levels (50-150 ng.mg-1) with very high exposure to ETS, and, at the other extreme, of very high cotinine levels indicating actual use of nicotine-containing products in women with low ETS exposure. Using the cut-off point of 150 ng.mg-1, only 1.5% of the alleged nonsmokers were reclassified as current light smokers. Potential bias due to smoker misclassification is very unlikely to be responsible for the increased health risks observed in epidemiological studies on ETS.
Endothelin-1 Vasoconstriction During Swine Cardiopulmonary Resuscitation Improves Coronary Perfusion Pressures but Worsens Postresuscitation Outcome
Authors: Ronald W. Hilwig, Robert A. Berg, Karl B. Kern, Gordon A. Ewy
Journal: Circulation (2000)

Background —Vasoconstriction during cardiopulmonary resuscitation (CPR) improves coronary perfusion pressure (CPP) and thereby outcome. The combination of endothelin-1 (ET-1) plus epinephrine improved CPP during CPR compared with epinephrine alone in a canine cardiac arrest model. The effect of the combination on outcome variables, such as successful resuscitation and survival, has not been investigated. Methods and Results —Twenty-seven swine were randomly provided with 1 mg epinephrine (Epi group) or 1 mg epinephrine plus 0.1 mg ET-1 (ET-1 group) during a prolonged ventricular fibrillatory cardiac arrest. ET-1 resulted in substantially superior aortic relaxation pressure and CPP during CPR. These hemodynamic improvements tended to increase initial rates of restoration of spontaneous circulation (8 of 10 versus 8 of 17, P =0.12). However, continued intense vasoconstriction from ET-1 led to higher aortic diastolic pressure and very narrow pulse pressure after resuscitation. The mean pulse pressure 1 hour after resuscitation was 7±8 mm Hg with ET-1 versus 24±1 mm Hg with Epi, P &lt;0.01. Most importantly, the postresuscitation mortality was dramatically higher in the ET-1 group (6 of 8 versus 0 of 8 in the Epi group, P &lt;0.01). Conclusions —These data establish that administration of ET-1 during CPR can result in worse postresuscitation outcome. The intense vasoconstriction from ET-1 improved CPP during CPR but had detrimental effects in the postresuscitation period.
Severe Drug Toxicity Associated with a Single-Nucleotide Polymorphism of the <i>Cytidine Deaminase</i> Gene in a Japanese Cancer Patient Treated with Gemcitabine plus Cisplatin
Authors: Kan Yonemori, Hideki Ueno, Takuji Okusaka, Noboru Yamamoto, Masafumi Ikeda, Nagahiro Saijo, Teruhiko Yoshida, Hiroshi Ishii, Junji Furuse, Emiko Sugiyama, Su-Ryang Kim, Ruri Kikura-Hanajiri, Ryuichi Hasegawa, Yoshiro Saito, Shogo Ozawa, Nahoko Kaniwa, Jun-ichi Sawada
Journal: Clinical Cancer Research (2005)

We investigated single-nucleotide polymorphisms of the cytidine deaminase gene (CDA), which encodes an enzyme that metabolizes gemcitabine, to clarify the relationship between the single-nucleotide polymorphism 208G>A and the pharmacokinetics and toxicity of gemcitabine in cancer patients treated with gemcitabine plus cisplatin.Six Japanese cancer patients treated with gemcitabine plus cisplatin were examined. Plasma gemcitabine and its metabolite 2',2'-difluorodeoxyuridine were measured using an high-performance liquid chromatography method, and the CDA genotypes were determined with DNA sequencing.One patient, a 45-year-old man with pancreatic carcinoma, showed severe hematologic and nonhematologic toxicities during the first course of chemotherapy with gemcitabine and cisplatin. The area under the concentration-time curve value of gemcitabine in this patient (54.54 microg hour/mL) was five times higher than the average value for five other patients (10.88 microg hour/mL) treated with gemcitabine plus cisplatin. The area under the concentration-time curve of 2',2'-difluorodeoxyuridine in this patient (41.58 microg hour/mL) was less than the half of the average value of the five patients (106.13 microg hour/mL). This patient was found to be homozygous for 208A (Thr70) in the CDA gene, whereas the other patients were homozygous for 208G (Ala70).Homozygous 208G>A alteration in CDA might have caused the severe drug toxicity experienced by a Japanese cancer patient treated with gemcitabine plus cisplatin.
Cytokine gene polymorphisms in inflammatory bowel disease.
Authors: E Louis, J Satsangi, M Roussomoustakaki, M Parkes, G Fanning, K Welsh, D Jewell
Journal: Gut (1996)

Concordance rates in siblings and twins provide strong evidence that genetic susceptibility is important in the pathogenesis of inflammatory bowel disease. The number and identity of susceptibility genes is largely uncertain. Cytokine genes are attractive candidate loci.To study allelic frequencies of polymorphisms of the interleukin-1 receptor antagonist (IL-1RA) gene and the tumour necrosis factor alpha gene in patients with inflammatory bowel disease.One hundred and twenty nine North European caucasoid patients with ulcerative colitis, 120 patients with Crohn's disease, and 89 healthy controls.Genotyping was performed by polymerase chain reaction. A variable number of tandem repeats (VNTR) in the IL-1RA gene and a single base pair polymorphism in the TNF alpha gene promoter region (TNF-308) were analysed.No significant differences in IL-1RA VNTR allelic frequencies were noted between Crohn's disease (allele 1: 72.6%, allele 2: 24.7%, allele 3: 2.6%), ulcerative colitis (72.6%, 24.3%, 3.1%, respectively), and controls (76.9%, 20.8% and 2.3%). Some 42.4% of patients with ulcerative colitis and 43.4% patients with Crohn's disease were carriers of allele 2, compared with 34.8% healthy subjects. The TNF2 allele was modestly reduced in Crohn's disease (13.2%), compared with healthy subjects (21.3%; p = 0.04), and ulcerative colitis (21.6%).The associations demonstrated are modest: these polymorphisms are unlikely to be important determinants of overall disease susceptibility.
1012-132 Atorvastatin affects the expression of both endothelium- and liver-derived components of thrombosis/fibrinolysis system and endothelial function in patients with congestive heart failure
Authors: Dimitrios Tousoulis, Charalambos Antoniadis, Maria Kotsopoulou, Erini Bosinakou, Costas Tentolouris, Christos Pitsavos, Kyriakoula Marinou, Stella Brilli, Athanasios Trikas, Christodoulos Stefanadis
Journal: Journal of the American College of Cardiology (2004)
Adult women with mitral valve prolapse are more flexible
Authors: C G S Araújo, C P G Chaves
Journal: British Journal of Sports Medicine (2005)

Mitral valve prolapse (MVP) is common in women. Other clinical features such as flexibility and hyperlaxity are often associated with MVP, as there is a common biochemical and histological basis for collagen tissue characteristics, range of joint motion, and mitral leaflet excursion.To confirm whether adult women with MVP are more flexible and hypermobile than those without.Data from 125 women (mean age 50 years), 31 of them with MVP, were retrospectively analysed with regard to clinical and kinanthropometric aspects. Passive joint motion was evaluated in 20 body movements using Flexitest and three laxity tests. Flexitest individual movements (0 to 4) and overall Flexindex scores were obtained in all subjects by the same investigator.Women with MVP were lighter, less endomorphic and mesomorphic, and more linear. The Flexindex was significantly higher in the women with MVP, both absolute (48 (1.6) v 41 (1.3); p<0.01) and centile for age (67 v 42; p<0.01) values. In 13 out of 20 movements, the Flexitest scores were significantly higher for the women with MVP. Signs of hyperlaxity were about five times more common in these women: 74% v 16% (p<0.01). Scores of 0 and 1 in elbow extension, absence of hyperlaxity, and a Flexindex centile below 65 were almost never found in women with MVP.Flexitest, alone or combined with hyperlaxity tests, may be useful in the assessment of adult women with MVP.
Lateral Gene Transfer of a Multigene Region from Cyanobacteria to Dinoflagellates Resulting in a Novel Plastid-Targeted Fusion Protein
Authors: Ross F. Waller, Claudio H. Slamovits, Patrick J. Keeling
Journal: Molecular Biology and Evolution (2006)

The number of cases of lateral or horizontal gene transfer in eukaryotic genomes is growing steadily, but in most cases, neither the donor nor the recipient is known, and the biological implications of the transfer are not clear. We describe a relatively well-defined case of transfer from a cyanobacterial source to an ancestor of dinoflagellates that diverged before Oxyrrhis but after Perkinsus. This case is also exceptional in that 2 adjacent genes, a paralogue of the shikimate biosynthetic enzyme AroB and an O-methyltransferase (OMT) were transferred together and formed a fusion protein that was subsequently targeted to the dinoflagellate plastid. Moreover, this fusion subsequently reverted to 2 individual genes in the genus Karlodinium, but both proteins maintained plastid localization with the OMT moiety acquiring its own plastid-targeting peptide. The presence of shikimate biosynthetic enzymes in the plastid is not unprecedented as this is a plastid-based pathway in many eukaryotes, but this species of OMT has not been associated with the plastid previously. It appears that the OMT activity was drawn into the plastid simply by virtue of its attachment to the AroB paralogue resulting from their cotransfer and once in the plastid performed some essential function so that it remained plastid targeted after it separated from AroB. Gene fusion events are considered rare and likely stable, and such an event has recently been used to argue for a root of the eukaryotic tree. Our data, however, show that exact reversals of fusion events do take place, and hence gene fusion data are difficult to interpret without knowledge of the phylogeny of the organisms—therefore their use as phylogenetic markers must be considered carefully.
Follow-up standards and treatment targets in rheumatoid arthritis: results of a questionnaire at the EULAR 2008
Authors: Monika Schoels, Daniel Aletaha, Josef S Smolen, Johannes W J Bijlsma, Gerd Burmester, Ferdinand C Breedveld, Maurizio Cutolo, Bernard Combe, Maxime Dougados, Paul Emery, Joachim Kalden, Edward C Keystone, Tore K Kvien, Emilio Martin-Mola, Carlomaurizio Montecucco, Maarten De Wit
Journal: Annals of the Rheumatic Diseases (2009)

Background Therapeutic approaches to rheumatoid arthritis (RA) have undergone significant changes. The importance of tight control and early treatment, rapidly altered if goals are not achieved, is supported by evidence. However, it is unknown to what extent these insights are accepted by practitioners in clinical practice. Objective To obtain information about standard follow-up and treatment practices, and rheumatologists' aims in the care of patients with RA. Methods A survey conducted at the 2008 EULAR Congress. Results Most specialists, who were mainly from Europe and Latin America, were well-informed about recent concepts: two-thirds specified remission as a major goal. The experts attempted to reach treatment aims within 12–14 weeks, altering treatment otherwise. Disease activity assessment by composite measures is performed by a majority, although one-third preferentially relied upon their judgment. Conclusion These results suggest the acceptance of ambitious treatment concepts in practice. Although voluntary surveys have limitations, the answers reflect widespread adoption of desirable standards of care.
Identification of a W Variant Outbreak of &lt;EMPH TYPE="ITAL"&gt;Mycobacterium tuberculosis&lt;/EMPH&gt; via Population-Based Molecular Epidemiology
Authors: Pablo J. Bifani
Journal: JAMA (1999)

ContextTyping of Mycobacterium tuberculosis could provide a more sensitive means of identifying outbreaks than use of conventional surveillance techniques alone. Variants of the New York City W strain of M tuberculosis were identified in New Jersey.ObjectiveTo describe the spread of the W family of M tuberculosis strains in New Jersey identified by molecular typing and surveillance data.DesignPopulation-based cross-sectional study.Setting and SubjectsAll incident culture-positive tuberculosis cases reported in New Jersey from January 1996 to September 1998, for which the W family was defined by insertion sequence (IS) IS6110 DNA fingerprinting, polymorphic GC-rich repetitive sequence (PGRS) typing, spacer oligotyping (spoligotyping), and variable number tandem repeat (VNTR) analysis.Main Outcome MeasureIdentification and characterization of W family clones supplemented by surveillance data.ResultsIsolates from 1207 cases were analyzed, of which 68 isolates (6%) belonged to the W family based on IS6110 and spoligotype hybridization patterns. The IS6110 hybridization patterns or fingerprints revealed that 43 patients (designated group A) shared a unique banding motif not present in other W family isolates. Strains collected from the remaining 25 patients (designated group B), while related to W, displayed a variety of IS6110 patterns and did not share this motif. The PGRS and VNTR typing confirmed the division of the W family into groups A and B and again showed group A strains to be closely related and group B strains to be more diverse. The demographic characteristics of individuals from groups A and B were specific and defined. Group A patients were more likely than group B patients to be US born (91% vs 24%, P<.001), black (76% vs 16%, P<.001), human immunodeficiency virus positive (40% vs 0%, P = .007), and residents of urban northeast New Jersey counties (P<.001). Patients with group B strains were primarily non-US born, of Asian descent, and more dispersed throughout New Jersey. No outbreak had been detected using conventional surveillance alone.ConclusionsThe implementation of multiple molecular techniques in conjunction with surveillance data enabled us to identify a previously undetected outbreak in a defined geographical setting. The outbreak isolates comprise members of a distinct branch of the W family phylogenetic lineage. The use of molecular strain typing provides a proactive approach that may be used to initiate, and not just augment, traditional surveillance outbreak investigations.
Low virological response and high relapse rates in hepatitis C genotype 1 patients with advanced fibrosis despite adequate therapeutic dosing
Authors: Wendy S.C. Cheng, Stuart K. Roberts, Geoffrey McCaughan, William Sievert, Martin Weltman, Darrell Crawford, William Rawlinson, Philippa S. Marks, James Thommes, Bishoy Rizkalla, Motoko Yoshihara, Gregory J Dore
Journal: Journal of Hepatology (2010)
AT-25 * A PHASE I STUDY OF CONVECTION-ENHANCED DELIVERY OF LIPOSOMAL-IRINOTECAN USING REAL-TIME IMAGING WITH GADOLINIUM IN PATIENTS WITH RECURRENT HIGH GRADE GLIOMA
Authors: S. Han, A. Martin, M. Berger, M. Prados, S. Chang, J. Clarke, K. Bankiewicz, N. Butowski
Journal: Neuro-Oncology (2014)

BACKGROUND: Chemotherapy for high grade glioma (HGG) is limited by the blood brain barrier. Convection enhanced delivery (CED) improves chemotherapy delivery by utilizing fluid convection obviating the challenges of crossing the BBB while minimizing systemic toxicity. CED of nanoliposomal irinotecan (MM-398) has been optimized in animal models and shows superior anti-tumor activity. An advance in the use of CED is the development of real time CED (RCD), which utilizes MRI to visualize the CED process with the aid of co-convected contrast agents and thus monitor delivery into the brain and to take corrective action. METHODS: With support from an R21 we're conducting a phase I study of CED of liposomal-irinotecan using real-time imaging in patients with recurrent HGG. This is a 3 + 3 dose escalation trial; dose levels are 20 mg, 40 mg, 60 mg, and 80 mg liposomal-irinotecan, given via up to 3 catheters surgically placed in an intra-tumoral location. Concentration of gadoteridol will be 2 mM for all groups; both agents will be co-infused via the same catheters. Subjects in the two lowest dose groups will have tumor volumes of 1-4 cm3, the third dose group will be 2-5 cm3 and the highest dose group 2-6 cm3. Maximum total volume infused will be 1.0 ml for two lowest dose groups, 1.5 ml for the third dose group, and 2.0 ml for the highest dose group. RESULTS: Interim safety, efficacy, and imaging response results will be presented. Utilizing imaging software, we'll present the correlation of pre-infusion modeling of the drug distribution with post-infusion imaging and determination of the total volume of distribution (Vd) and the Vd to volume infused (Vi) ratio for each infusion. CONCLUSIONS: Image-guided distribution allows for real-time placement and adjustment of cannula for real time CED of MM-398 into the brains of patients with recurrent HGG.
Reducing the Glycemic Index or Carbohydrate Content of Mixed Meals Reduces Postprandial Glycemia and Insulinemia Over the Entire Day but Does Not Affect Satiety
Authors: Ann G. Liu, Marlene M. Most, Meghan M. Brashear, William D. Johnson, William T. Cefalu, Frank L. Greenway
Journal: Diabetes Care (2012)

We evaluated the effects of mixed meals differing in glycemic index (GI) and carbohydrate content on postprandial serum glucose and insulin response, hunger, and satiety over the course of a 12-h day.In this randomized crossover trial, 26 overweight or obese adults received four diets in random order (high GI, high carbohydrate [HGI-HC]; high GI, low carbohydrate [HGI-LC]; low GI, high carbohydrate [LGI-HC]; and low GI, low carbohydrate [LGI-LC]). All meals were prepared by a metabolic kitchen. Participants received breakfast, lunch, and dinner over the course of a 12-h day. Primary outcomes were postprandial serum glucose and insulin quantified as area under the curve. Hunger, fullness, and satiety were assessed by visual analog scale.The HGI-LC, LGI-HC, and LGI-LC diets significantly reduced glucose and insulin area under the curve compared with the HGI-HC diet (P < 0.001 for all comparisons). There were no significant differences in ratings of hunger, fullness, or satiety between the different dietary treatments.Reducing the GI or carbohydrate content of mixed meals reduces postprandial glycemia and insulinemia, and these changes can be sustained over the course of an entire day. However, there were no differences in subjective hunger and satiety ratings between the diets. These results demonstrate that maintaining a low GI or glycemic load diet is an effective method of controlling serum glucose and insulin levels.
Clinical Correlates of Circulating Visfatin Levels in a Community-Based Sample
Authors: Erik Ingelsson, Martin G. Larson, Caroline S. Fox, Xiaoyan Yin, Thomas J. Wang, Izabella Lipinska, Karla M. Pou, Udo Hoffmann, Emelia J. Benjamin, John F. Keaney, Ramachandran S. Vasan
Journal: Diabetes Care (2007)

Visfatin, a novel adipokine with insulin-mimetic characteristics, is highly expressed in visceral fat (1). Associations of circulating visfatin concentrations with diabetes and obesity have not been rigorously established, most likely due to small sample sizes of prior studies. Furthermore, relations of visfatin to other cardiovascular risk factors in the general population have not been examined systematically. Accordingly, we tested the hypothesis that plasma visfatin would be positively related to obesity, diabetes, and visceral adiposity in a community-based sample.

The design and selection criteria of the Framingham Third Generation Cohort are detailed elsewhere (2). Briefly, 4,095 adults (53% women; mean age 40 years) having at least one parent in the Framingham Offspring Study cohort were recruited in 2001–2005. At their first examination, participants underwent anthropometry, medical history and physical examination, laboratory assessment of cardiovascular risk factors, and, in a subsample, imaging for coronary calcification and adiposity using multidetector computer tomography (MDCT).

The present study was performed in a subsample of 374 participants (9% eligible; 53% women) in whom plasma visfatin was assayed. We randomly selected these participants using a weighted sampling scheme with oversampling of the lowest and highest sex-specific quintiles of BMI (ratio of 1.5:2:1.5 for the lowest, middle three, and upper quintiles, respectively) using the participants undergoing MDCT imaging as the sampling frame. We chose this sampling strategy for cost efficiency and optimizing the use of nonrenewable serological resources (given …
Molecular Pathways: Inflammation-Associated Nitric-Oxide Production as a Cancer-Supporting Redox Mechanism and a Potential Therapeutic Target
Authors: Elizabeth A. Grimm, Andrew G. Sikora, Suhendan Ekmekcioglu
Journal: Clinical Cancer Research (2013)

It is widely accepted that many cancers express features of inflammation, driven by both microenvironmental cells and factors, and the intrinsic production of inflammation-associated mediators from malignant cells themselves. Inflammation results in intracellular oxidative stress with the ultimate biochemical oxidants composed of reactive nitrogens and oxygens. Although the role of inflammation in carcinogensis is well accepted, we now present data showing that inflammatory processes are also active in the maintenance phase of many aggressive forms of cancer. The oxidative stress of inflammation is proposed to drive a continuous process of DNA adducts and crosslinks, as well as posttranslational modifications to lipids and proteins that we argue support growth and survival. In this perspective, we introduce data on the emerging science of inflammation-driven posttranslational modifications on proteins responsible for driving growth, angiogenesis, immunosuppression, and inhibition of apoptosis. Examples include data from human melanoma, breast, head and neck, lung, and colon cancers. Fortunately, numerous antioxidant agents are clinically available, and we further propose that the pharmacologic attenuation of these inflammatory processes, particularly the reactive nitrogen species, will restore the cancer cells to an apoptosis-permissive and growth-inhibitory state. Our mouse model data using an arginine antagonist that prevents enzymatic production of nitric oxide directly supports this view. We contend that selected antioxidants be considered as part of the cancer treatment approach, as they are likely to provide a novel and mechanistically justified addition for therapeutic benefit.