tbuckley/cabot-search huggingface dataset:
Television Viewing Is Associated With Prevalence of Metabolic Syndrome in Hispanic Elders
Authors: Xiang Gao, Miriam E. Nelson, Katherine L. Tucker
Journal: Diabetes Care (2007)

We examined associations between television viewing and prevalence of the metabolic syndrome among a representative sample of Caribbean-origin Hispanic elders living in Massachusetts.We conducted a cross-sectional analysis of 350 Puerto Rican and 105 Dominican elders (> or = 60 years). Information on television viewing hours was collected by a questionnaire. The metabolic syndrome was defined by using the definition from the National Cholesterol Education Program.Prevalences for the metabolic syndrome were 50.1 and 56.9% among Puerto Ricans and Dominicans, respectively. Of the subjects, 82.6% had high blood pressure and 61.4% had high fasting glucose. Prevalence of the syndrome was significantly associated with television viewing. Each additional hour of television viewing was associated with a 19% greater likelihood of having the metabolic syndrome (odds ratio [OR] 1.19, 95% CI 1.1-1.3, P for trend 0.002), after adjusting for age, sex, ethnicity, BMI, education, alcohol use, smoking, household arrangement, physical activity, intake of energy and fat, and activities-of-daily-living score. We did not observe significant interactions of television viewing with sex, smoking status, alcohol use, or BMI (P for interaction > 0.15 for all) in relation to presence of the metabolic syndrome.A high prevalence of the metabolic syndrome in a representative sample of Caribbean-origin Hispanic elders was associated with prolonged television viewing, independent of physical activity and energy intake. Longitudinal studies are needed to clarify the causality of this relationship.
Exercise and hypertension: facts and uncertainties
Authors: M A van Baak
Journal: British Journal of Sports Medicine (1998)

The radial alveolar count method of Emery and Mithal has been re-evaluated on 76 normal postnatal lungs. Results of reproducibility assessments suggest that each observer should establish normal control values when beginning with the method, and should subsequently use control cases to maintain strict reproducibility. The use of 10 fields per case was found to be inadequate to obtain satisfactory reproducibility, even for a single observer. Prior inflation of the lungs significantly increased the radial counts, and this factor may help to explain the large discrepancy between the results of this study and that of Emery and Mithal. The radial counts correlated well with the chronological age of the child (r = +0.76; p less than 0.001). Alveolarization of the acinus occurs primarily between birth and 2 years; significant but slower growth is seen up to 8 years, after which the results plateau, suggesting that alveolarization is complete. The radial count method appears to provide a relatively simple and reasonably satisfactory assessment of alveolar development, as originally proposed by Emery and Mithal.
Changes Over Time in Glycemic Control, Insulin Sensitivity, and β-Cell Function in Response to Low-Dose Metformin and Thiazolidinedione Combination Therapy in Patients With Impaired Glucose Tolerance
Authors: Ravi Retnakaran, Ying Qi, Stewart B. Harris, Anthony J. Hanley, Bernard Zinman
Journal: Diabetes Care (2011)

OBJECTIVE In the Canadian Normoglycemia Outcome Evaluation (CANOE) trial, low-dose rosiglitazone/metformin reduced the risk of diabetes in subjects with impaired glucose tolerance by 66% over a median of 3.9 years. We evaluate the temporal changes in glycemic control, insulin sensitivity, and β-cell function during this trial. RESEARCH DESIGN AND METHODS CANOE participants (n = 207) underwent annual oral glucose tolerance testing, enabling temporal comparison of glycemia, insulin sensitivity (Matsuda index), and β-cell function (insulin secretion-sensitivity index-2 [ISSI-2]) between the rosiglitazone/metformin and placebo arms. RESULTS Glycemic parameters and insulin sensitivity improved in the rosiglitazone/metformin arm in year 1, but deteriorated in the years thereafter as in the placebo arm. Generalized estimating equation analysis confirmed that both insulin sensitivity and β-cell function decreased over time (Matsuda: β = −0.0515, P &amp;lt; 0.0001; ISSI-2: β = −6.6507, P &amp;lt; 0.0001), with no significant time-by-treatment interaction (Matsuda: P = 0.57; ISSI-2: P = 0.22). CONCLUSIONS Despite preventing incident diabetes, low-dose rosiglitazone/metformin did not modify the natural history of worsening insulin resistance and β-cell dysfunction.
Association of CA repeat number and R497K with PFS to EGFR TKIs in NSCLC patients having sensitive mutation of EGFR.
Authors: J. Kang, E. K. Jeon, J. Shin, J. Kim, M. A. Lee, Y. K. Kim, K. Y. Lee, Y. P. Wang, E. K. Cho
Journal: Journal of Clinical Oncology (2011)

7592 Background: It has been well known that EGFR mutation on particular exons is a strong predictive biomarker to EGFR TKIs (tyrosine kinase inhibitors) in NSCLC pts. However, some pts having wild type EGFR do not infrequently show clinically favorable outcome to EGFR TKIs. Accordingly, we hypothesized that clinical outcome and skin toxicity to EGFR TKI might be related to specific single nucleotide polymorphisms (SNPs) regulating the expression of EGFR gene. Methods: In 165 advanced or metastatic NSCLC pts receiving gefitinib or erlotinib, we assayed mutation status of EGFR in paraffin embedded tumor tissue using direct sequencing and genotyped six different SNPs in genomic DNA extracted from peripheral blood; exon 191C>A, exon 216 G>T, CA repeat number, exon 13 R497K, exon 20 2607G>A, and exon 25 D994D. Results: Sex ratio was 80:85 and median age was 63.1 (35-82). Histological subtype was adenocarcinoma 131, squamous cell ca. 22, and BAC 3, etc. Objective response (CR+PR) was observed in 63pts (38.2%) and SD in 52 pts (31.5%). Median PFS was 4.3 months (95% CI 2.87-5.80). Analysis for EGFR mutation was done in 90 pts and 44 (48.9%) showed EGFR harboring sensitive mutation (mutEGFR). The pts having total number of CA repeat (38) was 100 (60.6%). In R497K, wild type (RR) was 36 (21.8%). Heterozygote (RK) and homozygote variants (KK) were 71 (43.0%) and 58 (35.2%), respectively. In D994D, wild type (GG) was 72 (43.6%) and heterozygote and homozygote variants (GA+AA) were 93 (56.4%). Statistically significant differences of PFS and OS were observed between wild and hetero-/homozygote variants of R497K (4.2 vs. 15.9 m, p=0.002 and 10.0 vs. 32.0 m, p=0.007, respectively). In the pts harboring mutEGFR, low (CA)N (and RK+KK variants of R497K demonstrated much longer PFS compared with high (CA)N and wild type (30.4 vs. 8.3 m, p=0.08 and 15.8 vs. 3.6 m, p=0.01, respectively). In the pts having wild type EGFR, GA+AA variants of D994D showed much longer PFS compared with wild type (12.6 vs. 3.8 m, p=0.09). Conclusions: Taken together, we suggest that (CA)N and R497K, germline genetic variations of EGFR gene, might be useful pharmacogenetic biomarker to predict longer PFS in NSCLC pts harboring mutEGFR.
Long-term effects of budesonide on airway responsiveness and clinical asthma severity in inhaled steroid-dependent asthmatics
Authors: EF Juniper, PA Kline, MA Vanzieleghem, EH Ramsdale, PM O'Byrne, FE Hargreave
Journal: European Respiratory Journal (1990)

Budesonide 400 micrograms daily, in nonsteroid-dependent asthma, can produce improvements in airway responsiveness and clinical asthma severity, with some patients returning to normal responsiveness and becoming asymptomatic. This study examined whether similar improvements occur when asthmatics, who are dependent upon inhaled steroids, take either a regular maintenance dose of inhaled steroid or twice that amount for a year. Thirty two asthmatics were each stabilized on the minimum amount of inhaled steroid that would keep symptoms non-troublesome. In a double-blind, randomized manner, half were assigned to remain on a maintenance dose (MD) and the rest received twice that dose (MDx2) for one year. Before and monthly throughout the study, airway responsiveness to methacholine was measured and clinical asthma severity assessed by questionnaire, inhaled bronchodilator use and number of asthma exacerbations. There was a significant improvement in airway responsiveness and clinical asthma severity in both treatment groups. Those on MDx2 showed the greatest improvement but the difference between the two groups did not reach significance. This study provides strong evidence that prolonged use of inhaled steroids is associated with improvement in airway responsiveness and clinical asthma severity in inhaled steroid-dependent asthma with a suggestion that the improvements are dose related.
Pig interleukin 1. Purification of two immunologically different leukocyte proteins that cause cartilage resorption, lymphocyte activation, and fever.
Authors: J Saklatvala, S J Sarsfield, Y Townsend
Journal: The Journal of Experimental Medicine (1985)

Two forms of interleukin 1 (IL-1) were purified to homogeneity from the culture supernatants of pig buffy coat leukocytes stimulated with concanavalin A. The two proteins had identical Mr of 21,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, but one, which had previously been purified as a cartilage-resorbing protein, had pI 5 (IL-1/5) and the other, pI 8.3 (IL-1/8). After initial gel filtration and separation by chromatofocusing IL-1/5 was purified by chromatography on hydroxyapatite and the ion exchangers, Mono S and Mono Q; IL-1/8 was purified by chromatography at pH 4.0 and pH 6.4 on Mono S. Purification was monitored by a cartilage proteoglycan release assay and both proteins had a final specific activity approximately 10(5) times that of the leukocyte culture medium. Medium conditioned by cells from 200 L of blood yielded approximately 15 micrograms of IL-1/5 and 50 micrograms IL-1/8. IL-1/8 augmented mouse thymocyte proliferation, stimulated synovial fibroblasts to produce prostaglandin E and latent collagenase, and was pyrogenic upon intracerebroventricular injection into rabbits. IL-1/5 has previously been shown to possess all these activities. An antiserum to each IL-1 was raised in rabbits. Each antiserum inhibited its respective IL-1 in a cartilage bioassay and stained it upon Western blotting. Neither antiserum inhibited or stained the other IL-1. We conclude that pig leukocytes make two immunologically distinct forms of IL-1 that have identical Mr, demonstrate the same range of biological activity, but differ in isoelectric point.
Cardiovascular disease risk factors in Welsh adolescents: where are we now?
Authors: N E Thomas, R Williams, D A Rowe, J S Baker
Journal: British Journal of Sports Medicine (2010)

The aim was to investigate secular trends in cardiovascular disease (CVD) risk factors in Welsh adolescents between 2002 and 2007. CVD risk factor data were examined from two school-based cross-sectional studies. The initial study (September to October, 2002) included 73 participants, aged 12.9±0.3 years. The final study of 90 participants, aged 12.9±0.4 years, was completed during September to October, 2007. Measurements included adiposity, physical activity (PA), physical fitness (PF), diet, total cholesterol, high-density-lipoprotein cholesterol, low-density-lipoprotein cholesterol, triglyceride, fibrinogen (Fg) and high-sensitivity C reactive protein (hs-CRP). On both occasions, testing was carried out in the same school, and by the same experienced researcher using identical procedure. PA and PF levels improved for boys and girls in 2007; however, 80% of girls still did not meet the recommended 1 h/day of moderate PA. For both sexes, dietary fat intake did not differ between 2002 and 2007 cohorts; Welsh adolescents continued to consume a diet that was too high in saturated fat. Although mean adiposity tended to decrease between 2002 and 2007 in boys, this was not significant (p≥0.05). Overall, there were improvements in mean lipid profile and inflammatory status (p&lt;0.05). More adolescents in the earlier cohort exceeded the recommended levels for lipids, Fg and hs-CRP. Despite our finding that overweight continues to be widespread in Welsh adolescents, levels had not risen in our later cohort. This concurs with recent international evidence which suggests a “levelling off” in childhood obesity. The authors identified an upward trend in PA and PF, but no changes in dietary habits. This suggests that increased PA/PF, without dietary modification, has little effect on adiposity. Generally, our findings present a positive trend in lipid profile, as well as inflammatory factors. These improvements may be linked to the enhanced PA and PF profiles of the 2007 cohort.
Neuropilin 1 is expressed on thymus-derived natural regulatory T cells, but not mucosa-generated induced Foxp3+ T reg cells
Authors: Jonathan M. Weiss, Angelina M. Bilate, Michael Gobert, Yi Ding, Maria A. Curotto de Lafaille, Christopher N. Parkhurst, Huizhong Xiong, Jayashree Dolpady, Alan B. Frey, Maria Grazia Ruocco, Yi Yang, Stefan Floess, Jochen Huehn, Soyoung Oh, Ming O. Li, Rachel E. Niec, Alexander Y. Rudensky, Michael L. Dustin, Dan R. Littman, Juan J. Lafaille
Journal: The Journal of Experimental Medicine (2012)

Foxp3 activity is essential for the normal function of the immune system. Two types of regulatory T (T reg) cells express Foxp3, thymus-generated natural T reg (nT reg) cells, and peripherally generated adaptive T reg (iT reg) cells. These cell types have complementary functions. Until now, it has not been possible to distinguish iT reg from nT reg cells in vivo based solely on surface markers. We report here that Neuropilin 1 (Nrp1) is expressed at high levels by most nT reg cells; in contrast, mucosa-generated iT reg and other noninflammatory iT reg cells express low levels of Nrp1. We found that Nrp1 expression is under the control of TGF-β. By tracing nT reg and iT reg cells, we could establish that some tumors have a very large proportion of infiltrating iT reg cells. iT reg cells obtained from highly inflammatory environments, such as the spinal cords of mice with spontaneous autoimmune encephalomyelitis (EAE) and the lungs of mice with chronic asthma, express Nrp1. In the same animals, iT reg cells in secondary lymphoid organs remain Nrp1(low). We also determined that, in spontaneous EAE, iT reg cells help to establish a chronic phase of the disease.
BCL6 positively regulates AID and germinal center gene expression via repression of miR-155
Authors: Katia Basso, Christof Schneider, Qiong Shen, Antony B. Holmes, Manu Setty, Christina Leslie, Riccardo Dalla-Favera
Journal: The Journal of Experimental Medicine (2012)

The BCL6 proto-oncogene encodes a transcriptional repressor that is required for germinal center (GC) formation and whose de-regulation is involved in lymphomagenesis. Although substantial evidence indicates that BCL6 exerts its function by repressing the transcription of hundreds of protein-coding genes, its potential role in regulating gene expression via microRNAs (miRNAs) is not known. We have identified a core of 15 miRNAs that show binding of BCL6 in their genomic loci and are down-regulated in GC B cells. Among BCL6 validated targets, miR-155 and miR-361 directly modulate AID expression, indicating that via repression of these miRNAs, BCL6 up-regulates AID. Similarly, the expression of additional genes relevant for the GC phenotype, including SPI1, IRF8, and MYB, appears to be sustained via BCL6-mediated repression of miR-155. These findings identify a novel mechanism by which BCL6, in addition to repressing protein coding genes, promotes the expression of important GC functions by repressing specific miRNAs.
Patterns of Cyclin E, Retinoblastoma Protein, and p21Cip1/WAF1 Immunostaining in the Oncogenesis of Papillary Thyroid Carcinoma
Authors: Jan Brzeziński, Adam Migodziński, Aleksandra Toczek, Józef Tazbir, Marek Dedecjus
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Uncontrolled cell proliferation, a hallmark of cancer, may result from an increased expression of cell cycle up-regulators, and/or from a reduced expression of cell cycle down-regulators. In the present study, we analyzed, by immunohistochemistry, the expression of a panel of three proteins: cyclin E and two cell cycle inhibitors, p21Cip1/WAF1 and retinoblastoma protein (pRb) product, in different stages of papillary thyroid carcinomas (PTC). Experimental Design: We investigated immunostaining patterns of the proteins in question in 51 resected PTC in pathologic stages, ranging from pT1a to pT4, taking into consideration their relation to clinicohistopathologic factors. Results: We observed a significant, progressive loss of expression of p21Cip1/WAF1 with advancing tumor grade. The differences reached values of significance between pT1a [papillary thyroid microcarcinomas (PMC)] and pT2 and between PMC and pT4 stages of PTC. pRb presented a similar immunostaining pattern to that of p21Cip1/WAF1 and the differences reached values of significance between pT1a and pT2, and between PMC and pT4 stages of PTC. The results of cyclin E immunostaining corresponded to our recently published result, and a negative correlation was observed between the immunostaining index of cyclin E and pRb. Conclusions: The results of the present study suggest that cyclin E expression and suppression of pRb and p21Cip1/WAF1 may be characteristic patterns of immunostaining for PTC with a tendency to early metastasizing. If our results are confirmed in a larger study, the diagnostic panel, constructed of the antibodies against these proteins, may become a valuable tool in predicting the metastatic potential in PTC.
The insulin-like growth factor system as a therapeutic target in colorectal cancer
Authors: A.B. Hassan, V.M. Macaulay
Journal: Annals of Oncology (2002)

The purpose of this review is to examine recent evidence that investigates the role of the insulin-like growth factor (IGF) system in colorectal cancer. We concentrate on the evidence that makes the case for the investigation of strategies that might be used to disrupt the IGF system in prevention and treatment. Even though the weight of evidence suggests that components of the IGF system may be appropriate targets, there are a lack of studies that make a systematic characterisation of all the system components in human colorectal cancer. It is anticipated that this information, and the new therapeutic molecules which follow, will impact on the prevention and treatment of patients with this disease.
M266 Development Of An Idiopathic Pulmonary Fibrosis (ipf) Patient Reported Outcome Measure (prom): An Iterative Approach To Item Generation
Authors: A. Russell, T. Sanderson, S. Fleming, A. Wells, T. Maher, T. Cullinan
Journal: Thorax (2014)

<h3>Introduction</h3> Patients diagnosed with IPF experience debilitating symptoms which impact upon quality of life. To date there is no curative treatment and the tolerability andefficacy of existing andemergent therapies require further evaluation. We are developing a new concise IPF-PRoM (according to FDA criteria¹) for use as a primary endpoint in studies exploring treatments of symptoms associated with IPF andas a secondary endpoint in clinical/therapeutic trials. Robust item generation is fundamental to the development of the IPF-PRoM reflecting what is important to patients and ensuring saturation is reached. <h3>Methodology</h3> Domains and items were identified in existing symptom and quality of life measures used in IPF studies reported in the literature 5 focus groups were held at one of 3 UK centres. 28 patients (18 male) stratified for disease severity according to Composite Physiological Index (CPI) participated. Transcripts underwent inductive analysis and data was coded using NVIVO 10 ©QSR software Expert Opinion was sought from 10 ILD physicians utilising the Nominal Group technique. The importance of each descriptor identified in the literature was rated and then ranked according to overall importance. The top 5 were noted anddiscussed. Descriptors defined by focus group participants (n = 9) were added and the process repeated A multidisciplinary Research Support Group including patient and carer representatives contribute to the analysis at each stage and have the authority to mandate for the inclusion of ‘grey’ items. <h3>Interim results</h3> A validation list applied to existing measures identified 208 items for inclusion. Systematic coding and recoding within NViVo reduced 28 categories initially identified to 10. Fatigue is identified as a dominant theme in patients with CPI ≥ 45 andmedication availability/impacts has emerged as a significant category in all groups. ILD experts place importance upon breathlessness and emotional and mental well-being (Table 1). <h3>Discussion</h3> This methodological approach to item generation will enhance the content validity of the IPF-PROM instrument. Items generated to date will be modified further by 80 patients from 4 UK centres and 20 ILD physicians participating in 3 rounds of a Qualtrics Delphi survey. This study is ongoing. 1 http://www.fda.gov/downloads/Drugs/Guidances/UCM193282.pdf
Successful Radiotherapy of Tumor in Pretargeted Mice by 188Re-Radiolabeled Phosphorodiamidate Morpholino Oligomer, a Synthetic DNA Analogue
Authors: Guozheng Liu, Shuping Dou, George Mardirossian, Jiang He, Surong Zhang, Xinrong Liu, Mary Rusckowski, Donald J. Hnatowich
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Pretargeting has been attracting increasing attention as a drug delivery approach. We recently proposed Watson-Crick pairing of phosphorodiamidate morpholino oligomers (MORF) for the recognition system in tumor pretargeting. MORF pretargeting involves the initial i.v. injection of a MORF-conjugated antitumor antibody and the subsequent i.v. injection of the radiolabeled complement. Our laboratory has reported on MORF pretargeting for diagnosis using 99mTc as radiolabel. We now report on the use of MORF pretargeting for radiotherapy in a mouse tumor model using 188Re as the therapeutic radiolabel. Experimental Design: An initial tracer study was done to estimate radiation dose, and was followed by the radiotherapy study at 400 μCi per mouse with three control groups (untreated, MORF antibody alone, and 188Re complementary MORF alone). Results: Tracer study indicated rapid tumor localization of 188Re and rapid clearance from normal tissues with a tumor area under the curve (AUC) about four times that of kidney and blood (the normal organs with highest radioactivity). Tumor growth in the study group ceased 1 day after radioactivity injection, whereas tumors continued to grow at the same rate among the three control groups. At sacrifice on day 5, the average net tumor weight in the study group was significantly lower at 0.68 ± 0.29 g compared with the three control groups (1.24 ± 0.31 g, 1.25 ± 0.39 g, and 1.35 ± 0.41 g; Ps &amp;lt; 0.05), confirming the therapeutic benefit observed by tumor size measurement. Conclusions: MORF pretargeting has now been shown to be a promising approach for tumor radiotherapy as well as diagnosis.
The IRF Family Transcription Factors in Immunity and Oncogenesis
Authors: Tomohiko Tamura, Hideyuki Yanai, David Savitsky, Tadatsugu Taniguchi
Journal: Annual Review of Immunology (2008)

The interferon regulatory factor (IRF) family, consisting of nine members in mammals, was identified in the late 1980s in the context of research into the type I interferon system. Subsequent studies over the past two decades have revealed the versatile and critical functions performed by this transcription factor family. Indeed, many IRF members play central roles in the cellular differentiation of hematopoietic cells and in the regulation of gene expression in response to pathogen-derived danger signals. In particular, the advances made in understanding the immunobiology of Toll-like and other pattern-recognition receptors have recently generated new momentum for the study of IRFs. Moreover, the role of several IRF family members in the regulation of the cell cycle and apoptosis has important implications for understanding susceptibility to and progression of several cancers.