tbuckley/cabot-search huggingface dataset:
Use of a combined oxygen and carbon dioxide transcutaneous electrode in the estimation of gas exchange during exercise.
Authors: M K Sridhar, R Carter, F Moran, S W Banham
Journal: Thorax (1993)

Accurate and reliable measurement of gas exchange during exercise has traditionally involved arterial cannulation. Non-invasive devices to estimate arterial oxygen (O2) and carbon dioxide (CO2) tensions are now available. A method has been devised and evaluated for measuring gas exchange during exercise with a combined transcutaneous O2 and CO2 electrode.Symptom limited exercise tests were carried out in 24 patients reporting effort intolerance and breathlessness. Exercise testing was performed by bicycle ergometry with a specifically designed protocol involving gradual two minute workload increments. Arterial O2 and CO2 tensions were measured at rest and during exercise by direct blood sampling from an indwelling arterial cannula and a combined transcutaneous electrode heated to 45 degrees C. The transcutaneous system was calibrated against values obtained by direct arterial sampling before each test.In all tests the trend of gas exchange measured by the transcutaneous system was true to the trend measured from direct arterial sampling. In the 140 measurements the mean difference between the O2 tensions estimated by direct sampling and the transcutaneous method was 0.08 kPa (0.62 mm Hg, limits of agreement 4.42 and -3.38 mm Hg). The mean difference between the methods for CO2 was 0.02 kPa (0.22 mm Hg, limits of agreement 2.20 and -1.70 mm Hg). There was no morbidity associated with the use of the transcutaneous electrode heated to 45 degrees C.A combined transcutaneous O2 and CO2 electrode heated to 45 degrees C can be used to provide a reliable estimate of gas exchange during gradual incremental exercise in adults.
DOHaD and Allergic Diseases in Schoolchildren: Does IUGR Affect Risk of Allergic Diseases?
Authors: K. Mukaida, T. Kusunoki, T. Morimoto, M. Sakuma, N. Mito, T. Yasumi, T. Fujii, R. Nishikomori, T. Heike
Journal: Journal of Allergy and Clinical Immunology (2011)
Empirical Derivation to Improve the Definition of the Metabolic Syndrome in the Evaluation of Cardiovascular Disease Risk
Authors: Rachel P. Wildman, Aileen P. McGinn, Mimi Kim, Paul Muntner, Dan Wang, Hillel W. Cohen, Alexandra D. Ogorodnikova, Kristi Reynolds, Vivian Fonseca
Journal: Diabetes Care (2011)

To examine whether a quantitatively derived metabolic syndrome definition predicts incident cardiovascular disease (CVD) events better than do existing definitions.Data were pooled from the Atherosclerosis Risk in Communities, Cardiovascular Health, and Framingham Offspring studies (n = 20,581). Incident coronary heart disease and stroke events were ascertained over 9 years.The sensitivity for incident CVD events was higher and the specificity lower for the empirically derived versus the Adult Treatment Panel (ATP) III, International Diabetes Federation (IDF), or Harmonized metabolic syndrome definitions (sensitivity/specificity 0.65/0.53 vs. 0.53/0.63, 0.51/0.66, and 0.64/0.56, respectively), resulting in no overall improvement in discrimination. Multivariable-adjusted hazard ratios for incident CVD events were similar across definitions and were 1.7 (95% CI 1.6-1.9) for ATP III, 1.8 (1.6-2.0) for IDF, 1.9 (1.7-2.0) for Harmonized, and 1.7 (1.6-1.9) for the empirically derived definition.Empirical derivation of the metabolic syndrome definition did not improve CVD discrimination or risk prediction.
Genotype Arg/Arg, but not Trp/Arg, of the Trp64Arg Polymorphism of the β3-Adrenergic Receptor Is Associated With Type 2 Diabetes and Obesity in a Large Japanese Sample
Authors: Toshihide Oizumi, Makoto Daimon, Tamotsu Saitoh, Wataru Kameda, Hiroshi Yamaguchi, Hiroshi Ohnuma, Masahiko Igarashi, Hideyuki Eguchi, Hideo Manaka, Makoto Tominaga, Takeo Kato
Journal: Diabetes Care (2001)

OBJECTIVE—Despite a large number of studies, no association of the Trp64Arg polymorphism of the β3-adrenergic receptor gene with obesity and type 2 diabetes has yet to be clearly elucidated. We examined the associations in a large population-based sample. RESEARCH DESIGN AND METHODS—A total of 1,685 subjects (935 women and 750 men, aged 58.7 ± 12.4 years) from a cohort population (n = 3,706) of the Funagata Diabetes Study were divided into three groups according to genotypes: Trp/Trp (n = 1,155), Trp/Arg (n = 486), and Arg/Arg (n = 44). Glucose tolerance was diagnosed according to the 1985 World Health Organization criteria. Subjects who had a BMI ≥30 kg/m2 were considered obese. Associations with the traits related to obesity, diabetes, hypertension, and dyslipidemia were also examined. The χ2 test and analysis of variance were used for the association studies and to assess the differences in the traits’ values, respectively. RESULTS—More subjects with genotype Arg/Arg were obese and had diabetes (13.6% for each) than those with genotype Trp/Trp (3.29%, P &amp;lt; 0.001; and 4.16%, P = 0.007, respectively) or genotype Trp/Arg (2.06%, P &amp;lt; 0.001; and 5.97%, P = 0.051, respectively). No significant differences in the frequencies of occurrence of these conditions were observed between genotypes Trp/Arg and Trp/Trp. Traits related to obesity, such as percent body fat (28.82 ± 7.95 vs. 25.93 ± 7.21, P = 0.038) and BMI (25.07 ± 3.84 vs. 23.63 ± 3.18, P = 0.018), were higher in the genotype Arg/Arg than in the genotype Trp/Trp groups. CONCLUSIONS—Genotype Arg/Arg, but not Trp/Arg, of the β3-adrenergic receptor was associated with both obesity and type 2 diabetes in a large Japanese sample.
Predicting the Restenosis Benefit of Drug-Eluting Versus Bare Metal Stents in Percutaneous Coronary Intervention
Authors: Robert W. Yeh, Sharon-Lise T. Normand, Robert E. Wolf, Philip G. Jones, Kalon K.L. Ho, David J. Cohen, Donald E. Cutlip, Laura Mauri, Aaron D. Kugelmass, Amit P. Amin, John A. Spertus
Journal: Circulation (2011)

Drug-eluting stents (DES) for percutaneous coronary intervention decrease the risk of restenosis compared with bare metal stents. However, they are costlier, require prolonged dual antiplatelet therapy, and provide the most benefit in patients at highest risk for restenosis. To assist physicians in targeting DES use in patients at the highest risk for target vessel revascularization (TVR), we developed and validated a model to predict TVR.Preprocedural clinical and angiographic data from 27 107 percutaneous coronary intervention hospitalizations between October 1, 2004, and September 30, 2007, in Massachusetts were used to develop prediction models for TVR at 1 year. Models were developed from a two-thirds random sample and validated in the remaining third. The overall rate of TVR was 7.6% (6.7% with DES, 11% with bare metal stents). Significant predictors of TVR included prior percutaneous coronary intervention, emergency or salvage percutaneous coronary intervention, prior coronary bypass surgery, peripheral vascular disease, diabetes mellitus, and angiographic characteristics. The model was superior to a 3-variable model of diabetes mellitus, stent diameter, and stent length (c statistic, 0.66 versus 0.60; P<0.001) and was well calibrated. The predicted number needed to treat with DES to prevent 1 TVR compared with bare metal stents ranged from 6 (95% confidence interval, 5.4-7.6) to 80 (95% confidence interval, 62.7-116.3), depending on patients' clinical and angiographic factors.A predictive model using commonly collected variables can identify patients who may derive the greatest benefit in TVR reduction from DES. Whether use of the model improves the safety and cost-effectiveness of DES use should be tested prospectively.
HIGH LEVELS OF GROWTH DIFFERENTIATION FACTOR 11 ARE ASSOCIATED WITH LOWER PREVALENCE OF LEFT VENTRICULAR HYPERTROPHY: DATA FROM THE HEART AND SOUL STUDY
Authors: Kristoff Olson, Alexis Beatty, Bettina Heidecker, Mathilda Regan, Mary Whooley, Peter Ganz
Journal: Journal of the American College of Cardiology (2014)
Statistical Validation of the EORTC Prognostic Model for Malignant Pleural Mesothelioma Based on Three Consecutive Phase II Trials
Authors: Dean A. Fennell, Amit Parmar, Jonathan Shamash, Marie T. Evans, Michael T. Sheaff, Richard Sylvester, Kevin Dhaliwal, Nicole Gower, Jeremy Steele, Robin Rudd
Journal: Journal of Clinical Oncology (2004)

Malignant pleural mesothelioma (MPM) carries a poor prognosis due to chemoresistance. The European Organisation for Research and Treatment of Cancer (EORTC) prognostic model was reported to predict survival in MPM. Our retrospective analysis set out to test the validity of the model as a prognostic tool in patients treated in three phase II trials at St Bartholomew's Hospital (London, United Kingdom) between 1999 and 2003.A total of 145 patients were treated in three phase II trials; vinorelbine (VIN; 70 patients), vinorelbine/oxaliplatin (VO; 26 patients), and irinotecan/cisplatin/mitomycin C (IPM; 49 patients). Two subgroups, high-risk and low-risk, were defined by EORTC prognostic score (EPS). EPS was determined by a five-parameter model incorporating age, sex, histology, probability of diagnosis, and leukocyte count. An EPS cutoff of less than 1.27 (low risk) or more than 1.27 (high risk) was used to stratify Kaplan-Meier survival curves. Each of the EPS variables exhibited either trends or significant stratification of overall survival (OS).Multivariate analysis confirmed leukocyte count, Eastern Cooperative Oncology Group performance status, and sarcomatous histology as independent prognostic variables. EPS stratified OS in both individual and pooled trial datasets. No association between objective tumor response and EPS classification was identified by multinomial logistic regression. EPS stratified progression-free survival for the VO and IPM cohorts, but not for VIN.This study validates the EPS system as a robust tool for stratifying small trials into low- and high-risk subgroups. EPS should facilitate patient selection and analysis in randomized clinical trials.
Anoikis, Initiated by Mcl-1 Degradation and Bim Induction, Is Deregulated during Oncogenesis
Authors: Nicholas T. Woods, Hirohito Yamaguchi, Francis Y. Lee, Kapil N. Bhalla, Hong-Gang Wang
Journal: Cancer Research (2007)

Abstract Anoikis, a Bax-dependent apoptosis triggered by detachment from the extracellular matrix, is often dysfunctional in metastatic cancer cells. Using wild-type and c-Src–transformed NIH3T3 cells as a model, we identified Mcl-1 degradation and Bim up-regulation as a critical determinant of anoikis initiation. Detachment rapidly degraded Mcl-1 via a GSK-3β–dependent proteasomal pathway and transcriptionally up-regulated Bim expression. Mcl-1 degradation in the presence of Bim was sufficient to induce anoikis. By analyzing nonmetastatic Saos-2 and metastatic derivative LM7 cells, we confirmed that dysregulation of Mcl-1 degradation and Bim induction during detachment contributes to decreased anoikis sensitivity of metastatic cells. Furthermore, knockdown of Mcl-1 or pharmacologic inhibition of the phosphoinositide-3-kinase/Akt and mitogen-activated protein kinase pathways that suppress Mcl-1 degradation and Bim expression could markedly sensitize metastatic breast cancer cells to anoikis and prevent metastases in vivo. Therefore, Mcl-1 degradation primes the cell for Bax activation and anoikis, which can be blocked by oncogenic signaling in metastatic cells. [Cancer Res 2007;67(22):10744–52]
New Superfamilies of Eukaryotic DNA Transposons and Their Internal Divisions
Authors: W. Bao, M. G. Jurka, V. V. Kapitonov, J. Jurka
Journal: Molecular Biology and Evolution (2009)

Despite their enormous diversity and abundance, all currently known eukaryotic DNA transposons belong to only 15 superfamilies. Here, we report two new superfamilies of DNA transposons, named Sola and Zator. Sola transposons encode DDD-transposases (transposase, TPase) and are flanked by 4-bp target site duplications (TSD). Elements from the Sola superfamily are distributed in a variety of species including bacteria, protists, plants, and metazoans. They can be divided into three distinct groups of elements named Sola1, Sola2, and Sola3. The elements from each group have extremely low sequence identity to each other, different termini, and different target site preferences. However, all three groups belong to a single superfamily based on significant PSI-Blast identities between their TPases. The DDD TPase sequences encoded by Sola transposons are not similar to any known TPases. The second superfamily named Zator is characterized by 3-bp TSD. The Zator superfamily is relatively rare in eukaryotic species, and it evolved from a bacterial transposon encoding a TPase belonging to the "transposase 36" family (Pfam07592). These transposons are named TP36 elements (abbreviated from transposase 36).
Prospects for Cervical Cancer Prevention by Human Papillomavirus Vaccination
Authors: John T. Schiller, Douglas R. Lowy
Journal: Cancer Research (2006)

Abstract Recent clinical trials in young women have shown that subunit vaccines based on human papillomavirus (HPV) 16 and HPV18 L1 virus-like particles are ∼100% effective in short-term prevention of persistent cervical infection and of cervical dysplasia by these major oncogenic types. These remarkable efficacy results, together with an excellent safety profile in thousands of vaccinated women, have led to the HPV prophylactic vaccine from one manufacturer having now been licensed for commercial use and the expectation that the vaccine from a second manufacturer will be approved in the near future. These vaccines seem to have great potential for reducing cervical cancer deaths and treatments to remove premalignant cervical lesions. However, before their public health effect can be fully estimated, several issues must be addressed. These include duration of protection, degree of cross-protection against nonvaccine types, efficacy in men, and vaccine availability to economically disadvantaged women. (Cancer Res 2006; 66(21): 10229-32)
Suspension Cell Culture and &lt;italic&gt;In Vivo&lt;/italic&gt; and &lt;italic&gt;In Vitro&lt;/italic&gt; Chromosome Constitution of Mouse Leukemia L1210&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: G. E. Moore, A. A. Sandberg, K. Ulrich
Journal: JNCI Journal of the National Cancer Institute (1966)

An in vitro culture of mouse leukemia L1210 was established, along with conditions for optimal growth in suspension culture . L1210 showed a high requirement for folic acid in comparison with other cell lines in vitro. As few as 10 viable cells cultured in vitro killed DBA/2 mice. Cells from ascites showed a sharp mode of 40 chromosomes, with a minute marker chromosome and an extra-small, T-type (telocentric) chromosome. Cells cultured in vitro showed a mode of 40 or 41 chromosomes and contained the minute marker but not the extra-small chromosome; in addition, an m-type (metacentric) marker chromosome was observed in the cultured cells. This in vitro system should lend itself to evaluation of karyogenesis in relation to carcinogenesis, drug effects, and cytogenetic dynamics, as well as to nutritional and metabolic studies.
Cxc Chemokine Receptor 5 Expression Defines Follicular Homing T Cells with B Cell Helper Function
Authors: Patrick Schaerli, Katharina Willimann, Alois B. Lang, Martin Lipp, Pius Loetscher, Bernhard Moser
Journal: The Journal of Experimental Medicine (2000)

Leukocyte traffic through secondary lymphoid tissues is finely tuned by chemokines. We have studied the functional properties of a human T cell subset marked by the expression of CXC chemokine receptor 5 (CXCR5). Memory but not naive T cells from tonsils are CXCR5+ and migrate in response to the B cell–attracting chemokine 1 (BCA-1), which is selectively expressed by reticular cells and blood vessels within B cell follicles. Tonsillar CXCR5+ T cells do not respond to other chemokines present in secondary lymphoid tissues, including secondary lymphoid tissue chemokine (SLC), EBV-induced molecule 1 ligand chemokine (ELC), and stromal cell–derived factor 1 (SDF-1). The involvement of tonsillar CXCR5+ T cells in humoral immune responses is suggested by their localization in the mantle and light zone germinal centers of B cell follicles and by the concomitant expression of activation and costimulatory markers, including CD69, HLA-DR, and inducible costimulator (ICOS). Peripheral blood CXCR5+ T cells also belong to the CD4+ memory T cell subset but, in contrast to tonsillar cells, are in a resting state and migrate weakly to chemokines. CXCR5+ T cells are very inefficient in the production of cytokines but potently induce antibody production during coculture with B cells. These properties portray CXCR5+ T cells as a distinct memory T cell subset with B cell helper function, designated here as follicular B helper T cells (TFH).
Maternal smoking increases risk of allergic sensitization and wheezing only in children with allergic predisposition: longitudinal analysis from birth to 10 years
Authors: T. Keil, S. Lau, S. Roll, C. Grüber, R. Nickel, B. Niggemann, U. Wahn, S. N. Willich, M. Kulig
Journal: Allergy (2009)

Background: The role of passive smoking for allergies and asthma in children above the age of 3 years remains unclear and possible interactive effects with parental allergies have not been formally evaluated in long‐term studies. To examine the interaction of passive smoking and an allergic predisposition regarding allergic sensitization, allergic airway symptoms and respiratory infections during the first 10 years of life. Methods: In a prospective multicenter birth cohort study with 1314 recruited children in Germany, we assessed serum immunoglobulin E against common allergens at seven time points, and parental smoking and respiratory symptoms annually by using questionnaires. Longitudinal analyses were performed using generalized estimating equation models (stratified by parental allergy status). Results: During the first 10 years, 18% of the children were exposed to regular maternal smoking since pregnancy, 43% to irregular maternal or only paternal smoking. Among children with two allergic parents, a mother who smoked regularly significantly increased the odds for allergic sensitization (adjusted OR 4.8, 95% CI 1.3–18.2) and wheezing (adjusted OR 5.7, 95% CI 1.7–19.0) in her child compared with children who were never exposed. For those with only one allergic parent, the odds were doubled and also statistically significant, whereas in children without allergic parents maternal smoking had no effects. There was no association of maternal smoking with allergic rhinitis or respiratory infections. Conclusions: Our results suggest that regular maternal smoking is a strong risk factor for allergic sensitization and asthma symptoms during the first 10 years of life, but only in children with allergic parents.
Is Slower Early Growth Beneficial for Long-Term Cardiovascular Health?
Authors: Atul Singhal, Tim J. Cole, Mary Fewtrell, John Deanfield, Alan Lucas
Journal: Circulation (2004)

Accelerated neonatal growth increases the later propensity to cardiovascular disease (CVD) in animals, whereas slower growth is thought to have a beneficial effect. To test this hypothesis in humans, we measured flow-mediated endothelium-dependent dilation (FMD) in a population subject to slower early growth and in healthy controls.High-resolution vascular ultrasound was used to measure the change in brachial artery diameter in response to reactive hyperemia in adolescents age 13 to 16 years who were either part of a cohort born preterm and followed up prospectively (n=216) or controls born at term (n=61). Greater weight gain or linear growth in the first 2 weeks postnatally was associated with lower FMD at adolescence (regression coefficient, -0.026-mm change in mean arterial diameter per 100-g increase in weight; 95% CI, -0.040 to -0.012 mm; P=0.0003) independent of birthweight and potential confounding factors. Mean FMD in the half of the preterm population with the lowest rates of early growth was higher than in both the half with the greatest growth (P=0.001) and subjects born at term (P=0.03).FMD was 4% lower in adolescents with the highest compared with the lowest rate of weight gain in the first 2 weeks after birth, a substantial negative effect similar to that for insulin-dependent diabetes mellitus or smoking in adults. Our findings are consistent with the adverse effects of accelerated neonatal growth on long-term cardiovascular health and suggest that postnatal growth patterns could explain the previously reported association between birthweight and later CVD.
Pediatric Phase I Trial and Pharmacokinetic Study of MLN8237, an Investigational Oral Selective Small-Molecule Inhibitor of Aurora Kinase A: A Children's Oncology Group Phase I Consortium Study
Authors: Yael P. Mossé, Emily Lipsitz, Elizabeth Fox, David T. Teachey, John M. Maris, Brenda Weigel, Peter C. Adamson, Mark A. Ingle, Charlotte H. Ahern, Susan M. Blaney
Journal: Clinical Cancer Research (2012)

MLN8237, a selective small-molecule inhibitor of Aurora kinase A, has activity in a broad range of preclinical pediatric cancer models. We conducted a phase I trial in children with refractory/recurrent solid tumors to define the maximum-tolerated dose, toxicities, and pharmacokinetic properties of MLN8237.MLN8237 was administered orally either once daily or divided twice daily for seven days, every 21 days. Using a rolling-six design, four dose levels (45, 60, 80, and 100 mg/m(2)/day) were evaluated on the once-daily schedule, and two dose levels (60 and 80 mg/m(2)/d) on the twice-daily schedule. Pharmacokinetic studies were conducted with the initial dose and trough drug concentrations also measured at the steady state.Thirty-seven patients were enrolled. On the once-daily dosing schedule, myelosuppression was dose limiting in three of four patients at 100 mg/m(2), and one of six patients had dose-limiting mood alteration at 80 mg/m(2). At 45 mg/m(2), one of six patients experienced dose-limiting mucositis. Mucositis and myelosuppression were dose limiting at 80 mg/m(2) on the twice-daily schedule, and one of five patients at 60 mg/m(2) on the twice-daily schedule experienced a dose-limiting alkaline phosphatase. Five of 11 patients experienced hand-foot-skin syndrome with twice-daily dosing versus one of 21 after once-daily dosing. There was one partial response and six with prolonged stable disease among 33 evaluable subjects.The twice-daily dose regimen is well tolerated in adults; however, children experienced a greater frequency of myelosuppression and hand-foot-skin syndrome on this schedule. Children tolerated a higher dose and the recommended pediatric phase II dose is 80 mg/m(2)/d once daily for seven days.
First Identification of Flatbush Diabetes in Patients of Indian Origin
Authors: Sujeet Jha, Swati Waghdhare, Samreen Siddiqui, Kunal Srivastava, Amit Bhargava
Journal: Diabetes Care (2015)

Ketosis-prone diabetes is an emerging heterogeneous syndrome that encompasses the biochemical, clinical, genetic, and pathophysiological features of diabetes. This allows for a more comprehensive stratification of the disease vis-a-vis the traditional type 1 diabetes and type 2 diabetes subdivision (1). Flatbush diabetes, a subset of ketosis-prone diabetes, was first described in African Americans. Following this, it has been characterized in Hispanic, Chinese, and Japanese cohorts (2,3). A thorough literature search using MEDLINE/PubMed and the Cochrane Library databases (MeSH terms: Indian, ketogenic diabetes, ketosis prone diabetes, and Flatbush diabetes mellitus) determined that Flatbush diabetes has never been described in patients of Indian origin.

We identified a 39-year-old man who was admitted with mild diabetic ketoacidosis (based on his ketone status, serum …