tbuckley/cabot-search huggingface dataset:
Screening for impaired glucose tolerance. Results from a population-based study in 21,057 individuals.
Authors: B Lindahl, L Weinehall, K Asplund, G Hallmans
Journal: Diabetes Care (1999)

OBJECTIVE: To study the distribution of fasting plasma glucose and impaired glucose tolerance (IGT) in a large general population and explore their possible implications for large-scale screening. The study focuses especially on the relation to age, obesity, and heredity background of diabetes. RESEARCH DESIGN AND METHODS: A total of 21,057 men and women aged 30-60 years were used for this cross-sectional study. Individuals with known diabetes and individuals with a fasting plasma glucose &amp;gt; or = 7 mmol/l were excluded. A physical examination, including blood sampling and an oral glucose tolerance test, was conducted. RESULTS: The relative risk for IGT increased more than fourfold among obese subjects compared with normal-weight subjects, yet only 25% of IGT subjects were obese. Similarly, IGT subjects more frequently reported having first-degree relatives with diabetes than did subjects with normal glucose tolerance. Nonetheless, &amp;gt; 70% of IGT subjects reported no heredity background of diabetes. Subjects with IGT showed higher mean values of BMI, blood pressure, and triglycerides. Only 13% of the men and 19% of the women having impaired fasting glucose (IFG) fulfilled the criteria of IGT. CONCLUSIONS: The present study shows that a high-risk screening strategy for IGT targeted solely toward subjects with obesity and/or heredity background of diabetes will fail to detect the majority of subjects with IGT in the general population. The new concept of IFG may not replace the concept of IGT as a risk marker for worsening to diabetes.
Phase III study (MONET1) of motesanib plus carboplatin/paclitaxel in patients with advanced nonsquamous nonsmall-cell lung cancer (NSCLC): Asian subgroup analysis
Authors: K. Kubota, Y. Ichinose, G. Scagliotti, D. Spigel, J.H. Kim, T. Shinkai, K. Takeda, S.-W. Kim, T.-C. Hsia, R.K. Li, B.J. Tiangco, S. Yau, W.-T. Lim, B. Yao, Y.-J. Hei, K. Park
Journal: Annals of Oncology (2014)
Early Risk Factors for Violence in Colombian Adolescents
Authors: David W. Brook, Judith S. Brook, Zohn Rosen, Mario De la Rosa, Ivan D. Montoya, Martin Whiteman
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: Violence and homicide are more prevalent in Colombia, South America, than in the United States, but the role of psychosocial factors in the violent behavior of Colombian adolescents remains unclear. The objective of the study was to identify personality, familial, peer, and ecological variables associated with violence in Colombian adolescents. METHOD: A survey of adolescents was conducted in 1995–1996. A standard self-report measure was adapted to ensure linguistic and cultural relevance. A total of 2,837 adolescents ages 12–17 years from various self-reported ethnic groups were randomly selected from the community in three Colombian cities: Bogota, Medellin, and Barranquilla. Eighty percent of eligible adolescents agreed to participate. Data were collected concerning the adolescent's personality attributes, family characteristics, peer characteristics, and ecological/cultural factors, including the availability of illicit drugs and the prevalence of violence in the community. The dependent variable was the adolescent's self-reported frequency of violent behavior. RESULTS: Violence directed at the adolescent and the adolescent's own drug use were both more highly correlated with the adolescent's violent behavior than were other risk factors. Significant risk factors of less importance included tolerance of deviance, peer drug use, peer deviance, and exposure to violence on television. CONCLUSIONS: The results supported a model in which violent behavior was correlated independently with a number of risk factors from several domains. The findings point to the use of specific intervention procedures for adolescents to prevent their own subsequent acts of violent behavior.
Calcium acts as a first messenger through the calcium-sensing receptor in the cardiovascular system
Authors: S SMAJILOVIC, J TFELTHANSEN
Journal: Cardiovascular Research (2007)

It is well known that calcium is an important second messenger in the cardiovascular system. However, recent studies suggest that, in addition to its many functions as an intracellular messenger, Ca(2+) may also be an extracellular first messenger through the calcium-sensing receptor (CaR). The CaR belongs to family C of the G-protein-coupled receptors, which are also known as seven transmembrane domain receptors. The CaR receptor is expressed in all major organs involved in Ca(2+) homeostasis. Furthermore, increasing evidence suggests that the CaR is also involved in regulating various cellular functions in tissues not involved in Ca(2+) homeostasis. Recently, expression of a functional CaR has also been reported in crucial components of the cardiovascular system. It has previously been shown that the CaR is functionally expressed in the atria and ventricle of the rat heart. In blood vessels, the CaR protein was first reported in perivascular nerves of rat mesenteric resistance arteries, and was proposed to modulate myogenic tone in the arteries. Since then, the CaR has been detected in homogenates of whole vessels from rat subcutaneous small arteries and in endothelial cells from rat mesenteric and porcine coronary arteries. Furthermore, a recent report demonstrated that the CaR is present in endothelial cells from human aorta and that it stimulates production of nitric oxide in these cells. Taken together, these results indicate that the CaR present in blood vessels may have a physiological role in modulation of arterial blood pressure. This review discusses CaR expression and function, with a focus on the role of the CaR in the cardiovascular system.
Multiple Recurrences of Major Depressive Disorder
Authors: David A. Solomon, Martin B. Keller, Andrew C. Leon, Timothy I. Mueller, Philip W. Lavori, M. Tracie Shea, William Coryell, Meredith Warshaw, Carolyn Turvey, Jack D. Maser, Jean Endicott
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: The authors of this study examined multiple recurrences of unipolar major depressive disorder. METHOD: A total of 318 subjects with unipolar major depressive disorder were prospectively followed for 10 years within a multicenter naturalistic study. Survival analytic techniques were used to examine the probability of recurrence after recovery from the index episode. RESULTS: The mean number of episodes of major depression per year of follow-up was 0.21, and nearly two-thirds of the subjects suffered at least one recurrence. The number of lifetime episodes of major depression was significantly associated with the probability of recurrence, such that the risk of recurrence increased by 16% with each successive recurrence. The risk of recurrence progressively decreased as the duration of recovery increased. Within subjects, there was very little consistency in the time to recurrence. CONCLUSIONS: Major depressive disorder is a highly recurrent illness. The risk of the recurrence of major depressive disorder progressively increases with each successive episode and decreases as the duration of recovery increases.
Antisense chemoradioimmunotherapy consisting of anti-casm scfv linked onto high energy radioisotopes, docetaxel, and 21 nucleotide double stranded sirna targeted to dnmt1 induce apoptosis/pcd type i in pancreatic and periampullary carcinoma
Authors: J. Giannios, S. Delis, V. Barbunis, E. Maragudakis
Journal: Gut (2011)

<h3>Introduction</h3> Failure of tumour cells to undergo PCD cause resistance to chemoradiological therapies due to overexpression of oncogenes and transcriptionally repressed apoptotic TSGs due to methylation. <h3>Methods</h3> We obtained surgically 19 pancreatic Ca specimens from 12 males and 7 females consisting of 9 ductal adeno Ca, 4 Ca of the papilla of Vateri, 1 acinus Ca, 1 neuroendocrine Ca, 1 intrapancreatic distal bile duct and 3 periampullary Ca. Genomic DNA of tumours was analysed for CpG island hypermethylation by using MS-PCR. All of the tumours showed hypermethylation of TSGs: DUSP6/MKP-3 88%, RASSF1A 80%, RARb2 70%, BRCA1 50%. IHC, WB, SB and RT-PCR exhibited overexpression of DNMT1, CaSm, mcl-1 and bcl-2. We treated the samples with the isolated tumour cells with anti-CaSm scFv attached onto high energy-radioisotopes, docetaxel and 21-nucleotide double-stranded siRNA segment generated against DNMT1 <h3>Results</h3> Post-treatment, we detected re-expression of DUSP6/MKP-3, RASSF1A, RARb2, BRCA1 after inhibition of DNMT1mRNA. There was downregulation of oncogene CaSm due to targeted scFv and inactivation of bcl-2 and mcl-1 due to phosphorylation by docetaxel. We detected upregulation of p21waf1, p27kip, Bid and Bak. The radioisotopes induced DNA double strand breaks in tumour cells arresting synergistically with docetaxel their growth at G2/M. We detected externalisation of PS, depolarisation of ΔΨΜ, activation of caspases 3, 7, 8, 9, bax, cleavage of PARP and DNA fragmentation. TEM exhibited apoptotic bodies which were phagocytosed by adjacent tumour cells leading to a bystander killing effect. <h3>Conclusion</h3> We have achieved to eradicate pancreatic Ca cells with combined chemoradioimmuno-therapy after circumvention of chemo- and radioresistant mechanisms such as hypermethylation of TSGs RASSF1A, RARb2, DUSP6/ MKP-3, BRCA1 and overexpression of oncogenes bcl-2, CaSm and mcl-1.
Effect of Testosterone Treatment on Glucose Metabolism in Men With Type 2 Diabetes: A Randomized Controlled Trial
Authors: Emily J. Gianatti, Philippe Dupuis, Rudolf Hoermann, Boyd J. Strauss, John M. Wentworth, Jeffrey D. Zajac, Mathis Grossmann
Journal: Diabetes Care (2014)

OBJECTIVE To determine whether testosterone therapy improves glucose metabolism in men with type 2 diabetes (T2D) and lowered testosterone. RESEARCH DESIGN AND METHODS We conducted a randomized, double-blind, parallel, placebo-controlled trial in 88 men with T2D, aged 35–70 years with an HbA1c ≤8.5% (69 mmol/mol), and a total testosterone level, measured by immunoassay, of ≤12.0 nmol/L (346 ng/dL). Participants were randomly assigned to 40 weeks of intramuscular testosterone undecanoate (n = 45) or matching placebo (n = 43). All study subjects were included in the primary analysis. Seven men assigned to testosterone and six men receiving placebo did not complete the study. Main outcome measures were insulin resistance by homeostatic model assessment (HOMA-IR, primary outcome) and glycemic control by HbA1c (secondary outcome). RESULTS Testosterone therapy did not improve insulin resistance (mean adjusted difference [MAD] for HOMA-IR compared with placebo −0.08 [95% CI −0.31 to 0.47; P = 0.23]) or glycemic control (MAD HbA1c 0.36% [0.0–0.7]; P = 0.05), despite a decrease in fat mass (MAD −2.38 kg [−3.10 to −1.66]; P &amp;lt; 0.001) and an increase in lean mass (MAD 2.08 kg [1.52–2.64]; P &amp;lt; 0.001). Testosterone therapy reduced subcutaneous (MAD −320 cm3 [−477 to −163]; P &amp;lt; 0.001) but not visceral abdominal adipose tissue (MAD 140 cm3 [−89 to 369]; P = 0.90). CONCLUSIONS Testosterone therapy does not improve glucose metabolism or visceral adiposity in obese men with moderately controlled T2D and modest reductions in circulating testosterone levels typical for men with T2D.
Coeliac disease: in vivo toxicity of the putative immunodominant epitope
Authors: J S Fraser
Journal: Gut (2003)

<b>Background:</b> Peptides from α-gliadins have been used to characterise the immunodominant coeliac toxic epitope. A peptide corresponding to amino acid residues 57<b>–</b>73 of A-gliadin causes peripheral blood mononuclear cells from coeliac patients to secrete interferon γ (IFN-γ); gluten specific small intestinal T cell clones proliferate in response to peptides corresponding to residues 57<b>–</b>68 and 62<b>–</b>75 of α-gliadins. We wished to investigate whether a peptide corresponding to residues 56<b>–</b>75 of α-gliadins exacerbates coeliac disease in vivo. <b>Methods:</b> Four adults with coeliac disease, all of whom were on a gluten free diet, underwent three challenges. Peptic-tryptic gliadin (PTG 1 g) served as a positive control. The test peptide and a negative control peptide were studied on separate occasions. The peptides were instilled into the duodenum and biopsies were taken before the infusion, and two, four, and six hours after commencing the infusions, using a Quinton hydraulic multiple biopsy capsule. Biopsy specimens were assessed blindly for villus height to crypt depth ratio (VH:CD), enterocyte cell height (ECH), and intraepithelial lymphocyte (IEL) count. We used the Mann-Whitney U test, with 95% confidence intervals, for statistical analysis. <b>Results:</b> VH:CD and ECH fell, and IEL increased significantly 4–6 hours after commencing infusions with both PTG and the test peptide in all subjects. The negative control peptide caused no significant changes to villus morphology, enterocyte height, or IEL count in any patient. <b>Conclusion:</b> We have confirmed that the putative immunodominant epitope, a peptide corresponding to residues 56–75 of α-gliadins, exacerbates coeliac disease in vivo.
Smooth-muscle BMAL1 participates in blood pressure circadian rhythm regulation
Authors: Zhongwen Xie, Wen Su, Shu Liu, Guogang Zhao, Karyn Esser, Elizabeth A. Schroder, Mellani Lefta, Harald M. Stauss, Zhenheng Guo, Ming Cui Gong
Journal: Journal of Clinical Investigation (2014)

As the central pacemaker, the suprachiasmatic nucleus (SCN) has long been considered the primary regulator of blood pressure circadian rhythm; however, this dogma has been challenged by the discovery that each of the clock genes present in the SCN is also expressed and functions in peripheral tissues. The involvement and contribution of these peripheral clock genes in the circadian rhythm of blood pressure remains uncertain. Here, we demonstrate that selective deletion of the circadian clock transcriptional activator aryl hydrocarbon receptor nuclear translocator-like (Bmal1) from smooth muscle, but not from cardiomyocytes, compromised blood pressure circadian rhythm and decreased blood pressure without affecting SCN-controlled locomotor activity in murine models. In mesenteric arteries, BMAL1 bound to the promoter of and activated the transcription of Rho-kinase 2 (Rock2), and Bmal1 deletion abolished the time-of-day variations in response to agonist-induced vasoconstriction, myosin phosphorylation, and ROCK2 activation. Together, these data indicate that peripheral inputs contribute to the daily control of vasoconstriction and blood pressure and suggest that clock gene expression outside of the SCN should be further evaluated to elucidate pathogenic mechanisms of diseases involving blood pressure circadian rhythm disruption.
Risk of Myelodysplastic Syndromes in People Exposed to Ionizing Radiation: A Retrospective Cohort Study of Nagasaki Atomic Bomb Survivors
Authors: Masako Iwanaga, Wan-Ling Hsu, Midori Soda, Yumi Takasaki, Masayuki Tawara, Tatsuro Joh, Tatsuhiko Amenomori, Masaomi Yamamura, Yoshiharu Yoshida, Takashi Koba, Yasushi Miyazaki, Tatsuki Matsuo, Dale L. Preston, Akihiko Suyama, Kazunori Kodama, Masao Tomonaga
Journal: Journal of Clinical Oncology (2010)

The risk of myelodysplastic syndromes (MDS) has not been fully investigated among people exposed to ionizing radiation. We investigate MDS risk and radiation dose-response in Japanese atomic bomb survivors.We conducted a retrospective cohort study by using two databases of Nagasaki atomic bomb survivors: 64,026 people with known exposure distance in the database of Nagasaki University Atomic-Bomb Disease Institute (ABDI) and 22,245 people with estimated radiation dose in the Radiation Effects Research Foundation Life Span Study (LSS). Patients with MDS diagnosed from 1985 to 2004 were identified by record linkage between the cohorts and the Nagasaki Prefecture Cancer Registry. Cox and Poisson regression models were used to estimate relationships between exposure distance or dose and MDS risk.There were 151 patients with MDS in the ABDI cohort and 47 patients with MDS in the LSS cohort. MDS rate increased inversely with exposure distance, with an excess relative risk (ERR) decay per km of 1.2 (95% CI, 0.4 to 3.0; P < .001) for ABDI. MDS risk also showed a significant linear response to exposure dose level (P < .001) with an ERR per Gy of 4.3 (95% CI, 1.6 to 9.5; P < .001). After adjustment for sex, attained age, and birth year, the MDS risk was significantly greater in those exposed when young.A significant linear radiation dose-response for MDS exists in atomic bomb survivors 40 to 60 years after radiation exposure. Clinicians should perform careful long-term follow-up of irradiated people to detect MDS as early as possible.
LEUKEMOGENIC EFFECT OF RADIOACTIVE PHOSPHORUS IN ADULT AND FETALLY EXPOSED BALB MICE
Authors: E. A. D. Holmberg, C. Dosne de Pasqualini, E. Arini, A. Pavlovsky, S. L. Rabasa
Journal: Cancer Research (1964)

Summary  The leukemogenic effect of radioactive phosphorus has been studied in adult females and fetally exposed males and females of the BALB strain of mice.  The results obtained in this series of experiments indicate that fetally exposed females are more sensitive to the effect of the agent than males (46.5 and 10.8 per cent, respectively).  It has been observed that the incidence of leukemia in fetally exposed females is negatively correlated with the dose. In males, on the other hand, there is no such correlation and the over-all incidence is not increased (10.8 per cent).  Adult and fetally exposed females submitted to sterilizing doses of P 32  show the same incidence of leukemias (42 and 36.3 per cent, respectively).  The experiments herein reported demonstrate that P 32  is definitely leukemogenic.
Anti-CD20 monoclonal antibody with enhanced affinity for CD16 activates NK cells at lower concentrations and more effectively than rituximab
Authors: Julie A. Bowles, Siao-Yi Wang, Brian K. Link, Barrett Allan, Gregory Beuerlein, Mary-Ann Campbell, David Marquis, Brian Ondek, James E. Wooldridge, Brian J. Smith, James B. Breitmeyer, George J. Weiner
Journal: Blood (2006)

Growing evidence indicates that the affinity of monoclonal antibodies (mAbs) for CD16 (FcgammaRIII) plays a central role in the ability of the mAb to mediate antitumor activity. We evaluated how CD16 polymorphisms, and mAb with modified affinity for target antigen and CD16, affect natural killer (NK) cell phenotype when CD20(+) malignant B cells were also present. The mAb consisted of rituximab (R), anti-CD20 with enhanced affinity for CD20 (AME-B), and anti-CD20 with enhanced affinity for both CD20 and CD16 (AME-D). Higher concentrations of mAb were needed to induce CD16 modulation, CD54 up-regulation, and antibody-dependent cellular cytotoxicity (ADCC) on NK cells from subjects with the lower affinity CD16 polymorphism. The dose of mAb needed to induce NK activation was lower with AME-D irrespective of CD16 polymorphism. At saturating mAb concentrations, peak NK activation was greater for AME-D. Similar results were found with measurement of CD16 modulation, CD54 up-regulation, and ADCC. These data demonstrate that cells coated with mAb with enhanced affinity for CD16 are more effective at activating NK cells at both low and saturating mAb concentrations irrespective of CD16 polymorphism, and they provide further evidence for the clinical development of such mAbs with the goal of improving clinical response to mAb.
Gender determines the acute actions of genistein on intracellular calcium regulation in the guinea-pig heart
Authors: R Liew
Journal: Cardiovascular Research (2003)

Objectives: The soy-isoflavone, genistein, appears to be cardioprotective partly through direct actions on the heart, although the relative benefits between men and women are not fully known. The purpose of the present study was to determine whether gender influences the acute electrophysiological actions of genistein at the level of isolated cardiac myocytes and to elucidate the mechanisms involved. Methods: Left ventricular myocytes, isolated from weight-matched male and female guinea-pigs and rats, were field stimulated at a rate of 1 Hz in a superfusion chamber (37 °C). The effects of acute application of genistein on cell shortening and the Ca2+ transients were measured. Electrophysiological recordings were performed using single electrode voltage-clamp. Results: Genistein increased cell contraction and the Ca2+ transients in a concentration-dependent manner in myocytes from male guinea-pigs [by 54±11% and 22±4%, respectively (mean±S.E.M., p<0.001, n = 18) at 40 μM], while having no significant corresponding effect in those from females. In contrast, genistein increased both parameters in myocytes obtained from male and female rats. The changes in guinea-pigs occurred despite inhibition of the L-type Ca2+ current in both sexes (n>23, p<0.001). In order to explain these observations, we measured sarcoplasmic reticulum (SR) Ca2+ contents by integrating the Na+/Ca2+ exchanger currents (INCX) following rapid caffeine application. Genistein increased INCX integrals by 27% in males (n = 12, p<0.01) and 20% in females (n = 14, p<0.01). The increased SR Ca2+ load in males, but not females, could be related to an impaired ability of the Na+/Ca2+ exchanger to extrude Ca2+. Conclusions: We have demonstrated novel, gender-related differences in the acute cardiac actions of genistein, which can be attributed to actions at distinct points of the intracellular Ca2+ cycle. Our results suggest that genistein may afford greater cardioprotection in females than in males.
Production of numerous autoantibodies in paraneoplastic pemphigus
Authors: T. Hashimoto
Journal: British Journal of Dermatology (2015)

Journal Article Production of numerous autoantibodies in paraneoplastic pemphigus Get access T. Hashimoto T. Hashimoto Kurume University Institute of Cutaneous Cell Biology 67 Asahimachi Kurume Fukuoka 830‐0011 Japan Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 172, Issue 4, 1 April 2015, Pages 849–850, https://doi.org/10.1111/bjd.13648 Published: 01 April 2015
Influence of Age at Virologic Control on Peripheral Blood Human Immunodeficiency Virus Reservoir Size and Serostatus in Perinatally Infected Adolescents
Authors: Deborah Persaud, Kunjal Patel, Brad Karalius, Kaitlin Rainwater-Lovett, Carrie Ziemniak, Angela Ellis, Ya Hui Chen, Douglas Richman, George K. Siberry, Russell B. Van Dyke, Sandra Burchett, George R. Seage, Katherine Luzuriaga
Journal: JAMA Pediatrics (2014)

Combination antiretroviral therapy initiated within several weeks of human immunodeficiency virus (HIV) infection in adults limits proviral reservoirs that preclude HIV cure. Biomarkers of restricted proviral reservoirs may aid in the monitoring of HIV remission or cure.
Electrochemotherapy as a new approach on pancreatic cancer and on liver metastases
Authors: Salvatore Tafuto, Claudia von Arx, Chiara De Divitiis, Claire Tracey Maura, Raffaele Palaia, Vittorio Albino, Roberta Fusco, Massimo Membrini, Antonella Petrillo, Vincenza Granata, Francesco Izzo
Journal: International Journal of Surgery (2015)
The Bronchoscopy-Guided Re-Biopsy of Non-Small Cell Lung Cancer in Patients Who Relapse After Gefitinib Therapy
Authors: N. Okamoto, H. Suzuki, T. Shiroyama, M. Tamiya, M. Kitani, K. Kurata, T. Otsuka, T. Yamadori, K. Kawahara, T. Hirashima
Journal: Annals of Oncology (2013)