tbuckley/cabot-search huggingface dataset:
Smoking and treatments among asthma patients in South Korea
Authors: Hae-Sim Park, Ki-Suck Jung, Kian Fan Chung, Hyejin Myeong, Shamila Irim, Sharlette Everett, Eric Maiese, Felicia Allen-Ramey, David Price
Journal: European Respiratory Journal (2011)

Background:  The prevalence of smoking in South Korea is high, an estimated 23.3% for adults. Studies have shown that active smoking impacts asthma morbidity and treatment response. However, little is known about the asthma therapies used by asthma patients who smoke, particularly in Asia Pacific. This analysis explores smoking and asthma treatments among asthma patients in South Korea.   Methods:  A cross-sectional survey was conducted from Aug 2010–Jan 2011 at 16 urban hospitals in South Korea. Information on smoking status, asthma medications and exacerbations in the prior year was collected for consecutive asthma patients aged 18-60 yrs presenting for medical care.   Results:  A total of 1347 asthma patients were included. Mean age was 43 yrs, 46% were male, 63% never smoked (NS), 16% were former smokers (FS) and 21% were current smokers (CS). The proportion of patients with ≥1 exacerbation in the prior year was 42% for NS, 38% for FS and 40% for CS (chi-squared p=0.52). Most patients were using ICS+LABA (73%) with no differences in use between smoking categories (72% of NS, 75% of FS and 76% of CS; p=0.40). Use of leukotriene modifiers (52%) was also common, with no differences in use between smoking categories (52%, 54% and 49% for NS, FS and CS, respectively; p=0.56). Twelve percent of patients were reported as using an ICS and there were slight differences in use between smoking categories (14%, 10% and 6% for NS, FS and CS, respectively; p=0.001).   Conclusion:  The prevalence of smoking among this asthma patient population was similar to previously reported national rates in South Korea. Smoking status does not appear to affect the use of two common asthma medications; however, smoking status may influence the use of ICS.
The impact of using different symptom-based exacerbation algorithms in patients with COPD
Authors: J.C.A. Trappenburg, A.C. van Deventer, T. Troosters, T.J.M. Verheij, A.J.P. Schrijvers, J-W.J. Lammers, E.M. Monninkhof
Journal: European Respiratory Journal (2010)

Not all exacerbations are captured by reliance on healthcare contacts. Symptom-based exacerbation definitions have shown to provide more adequate measures of exacerbation rates, severity and duration. However, no consensus has been reached on what is the most useful method and algorithm to identify these events. This article provides an overview of the existing symptom-based definitions and tests the hypothesis that differences in exacerbation characteristics depend on the algorithms used. We systematically reviewed symptom-based methods and algorithms used in the literature, and quantified the impact of the four most referenced algorithms on exacerbation-related outcome using an existing chronic obstructive pulmonary disease (COPD) cohort (n = 137). We identified 51 studies meeting our criteria using 14 widely varying symptom algorithms to define onset, severity and recovery. The most (71%) frequently referenced algorithm (modified Anthonisen) identified an incidence rate of 1.7 episodes·patient-yr −1 (95% CI 1.4–2.1), while for requiring only one major or two major symptoms this was 1.9 episodes·patient-yr −1 (95% CI 1.6–2.3) and 1.5 episodes·patient-yr −1 (95% CI 0.6–1.0), respectively. Studies were generally lacking methods to enhance validity and accuracy of symptom recording. This review revealed large inconsistencies in definitions, methods and accuracy to define symptom-based COPD exacerbations. We demonstrated that minor changes in symptom criteria substantially affect incidence rates, clustering type and classification of exacerbations.
Factors associated with relapse after ambulatory treatment of acute exacerbations of chronic bronchitis
Authors: M. Miravitlles, C. Murio, T. Guerrero
Journal: European Respiratory Journal (2001)

This study aimed to identify the risk factors for relapse after ambulatory treatment of acute exacerbations of chronic bronchitis (AECB) that can easily be used in a primary care setting. Data were prospectively collected on 2,414 ambulatory patients with AECB from 268 general practices located throughout Spain. A multivariate model to identify risk factors independently associated with failures was developed and validated from the information recorded at the inclusion visit and at 30-days follow-up visit. A total of 507 patients relapsed (21%); of these, 84 required admission (16.5%). The multivariate model for prediction of the risk of relapse included 2,414 cases: 1,689 for the developmental sample and 725 in the validation sample. The model obtained contained three readily-obtainable variables: ischaemic heart disease (odds ratio (OR)=1.63; 95% confidence interval (CI)=1.07–2.47), degree of dyspnoea (OR=1.31; 1.14–1.50) and number of visits to the general practitioner the previous year (OR=1.07; 1.04–1.10). The model calibrated well in developmental and validation samples (goodness-of-fit tests: p=0.295 and p=0.637, respectively). Severity of the exacerbation was not associated with increased risk of relapse in either univariate or multivariate analysis. The present results suggest that baseline characteristics of the patients such as degree of dyspnoea, coexisting ischaemic heart disease and number of previous visits to the general practitioner for respiratory problems are strongly associated with increased risk of relapse after ambulatory treatment of acute exacerbations of chronic bronchitis. In contrast, exacerbation severity was not associated with clinical failure. Guidelines for management of acute exacerbations of chronic bronchitis should consider such risk factors and advocate intensive broad spectrum treatment and closer follow-up of patients exhibiting them.
Changes in Hypertensinase and Hypertensinogen Following Nephrectomy
Authors: DEAN A. COLLINS, CONCETTA D. HARAKAL
Journal: Circulation Research (1954)

The hypertensinase content of dog's plasma is decreased 48 hours after nephrectomy. This decrease may contribute to the increased blood pressure response to renin shown by nephrectomized animals. When plasma is incubated with a relatively small concentration of renin, the yield of hypertensin increases after nephrectomy. This finding correlates with decreased hypertensinase and the increased pressor response to renin characteristic of the postnephrectomy state. Mean plasma hypertensinogen shows about a threefold increase, and its significance is discussed.
Angiotensin II Induces Circadian Gene Expression of Clock Genes in Cultured Vascular Smooth Muscle Cells
Authors: Hidemi Nonaka, Noriaki Emoto, Koji Ikeda, Hiroyuki Fukuya, Mohammad Saifur Rohman, Sunu Budhi Raharjo, Kazuhiro Yagita, Hitoshi Okamura, Mitsuhiro Yokoyama
Journal: Circulation (2001)

Daily rhythms of mammalian physiology and endocrinology are regulated by circadian pacemakers. The master circadian pacemaker resides in the suprachiasmatic nucleus, which is located in the hypothalamus of the brain, but circadian oscillators also exist in peripheral tissues. Because many studies have demonstrated apparent circadian variations in the frequency of cardiovascular disorders, it is of great interest to investigate a possible relation between circadian gene expression and cardiovascular function. We examined whether a circadian oscillation system exists in the aorta and/or in cultured vascular smooth muscle cells (VSMCs).The mRNA levels of clock genes were assayed by northern blot analysis. The mouse aorta showed a clear circadian oscillation in the expression of mPer2, dbp, and Bmal1. Brief treatment of VSMCs with angiotensin II induced a robust increase in mPer2 gene expression, followed by a marked reduction in mPer2 mRNA levels and subsequent synchronous cycling of mPer2, dbp, and Bmal1 mRNAs. The induction of mPer2 in VSMCs by angiotensin II was completely abolished by treatment with CV11947, a specific angiotensin II type1 receptor antagonist.The present results demonstrate that the aorta and VSMCs possess a circadian oscillation system which is comparable to that of the suprachiasmatic nucleus and that the circadian gene expression in VSMCs is induced by angiotensin II through the angiotensin II type1 receptor. Our in vitro system will provide a useful tool to further analyze the physiological significance of the peripheral clock in cardiovascular function.
Assessing clinical performance. Where do we stand and what might we expect?
Authors: W. D. Dauphinee
Journal: JAMA (1995)

During the past decade the field of clinical assessment has demonstrated a clear move away from dependence on pencil and paper tests and the multiple-choice format as measures of predicting clinical competence to assessing what physicians do in the real world of practice.<sup>1</sup>This change is reflected in the orientation of numerous conferences on newer approaches to clinical assessment.<sup>2-5</sup> See also p 735. Among the many reasons for this shift are the increasing feasibility of administering large-scale, multicenter performance tests and the documented improvement in the measurement qualities of performance-based tests. These tests include the Objective Structured Clinical Examination (OSCE), in which candidates proceed through multiple, timed, independent stations designed to assess predetermined clinical skills, and the use of standardized patients (SPs), that is, lay people who are trained to simulate a variety of medical problems in a consistent, reliable, and realistic manner. Another reason for the shift
Longitudinal Study of Depressive Symptoms in Patients With Metastatic Gastrointestinal and Lung Cancer
Authors: Christopher Lo, Camilla Zimmermann, Anne Rydall, Andrew Walsh, Jennifer M. Jones, Malcolm J. Moore, Frances A. Shepherd, Lucia Gagliese, Gary Rodin
Journal: Journal of Clinical Oncology (2010)

Although early intervention is increasingly advocated to prevent and relieve distress in patients with metastatic cancer, the risk factors for such symptoms and their trajectory are not well established. We therefore conducted a longitudinal study to determine the course and predictors of depressive symptoms.Patients (N = 365) with metastatic gastrointestinal or lung cancer completed measures of physical distress, self-esteem, attachment security, spiritual well-being, social support, hopelessness, and depression at baseline; physical distress, social support, hopelessness, and depression were subsequently assessed at 2-month intervals.Of the sample, 35% reported at least mild depressive symptoms, with 16% reporting moderate to severe depressive symptoms that persisted in at least one third of such individuals. Moderate to severe depressive symptoms were almost three times more common in the final 3 months of life than > or = 1 year before death. Predictors of depressive symptoms included younger age, antidepressant use at baseline, lower self-esteem and spiritual well-being, and greater attachment anxiety, hopelessness, physical burden of illness, and proximity to death. The combination of greater physical suffering and psychosocial vulnerability put individuals at greatest risk for depression.Depressive symptoms in advanced cancer patients are relatively common and may arise as a final common pathway of distress in response to psychosocial vulnerabilities, physical suffering, and proximity to death. These findings support the need for an integrated approach to address emotional and physical distress in this population and to determine whether early intervention may prevent depression at the end of life.
Dengue viruses and mononuclear phagocytes. I. Infection enhancement by non-neutralizing antibody
Authors: SB Halstead, EJ O'Rourke
Journal: The Journal of Experimental Medicine (1977)

Cultured mononuclear peripheral blood leukocytes (PBL) from nonimmune human beings and monkeys are nonpermissive to dengue 2 virus (D2V) infection at multiplicities of infection of 0.001-0.1, but become permissive when non-neutralizing dengue antibody is added to medium. D2V infection occurred in PBL prepared from anti-coagulated but not from defibrinated plasma. Infection enhancement was produced by multiple lots of heterotypic anti-dengue raised in several mammalian species. Homotypic anti-dengue neutralized D2V at high concentrations but enhanced at low concentrations; enhancement end point in one serum was 1:320,000. The infection-enhancing factor was a noncytophilic antibody of the IgG class. D2V infection occurred in the absence of heat-labile complement components but did not occur when complexes were prepared with anti- dengue F(ab)(2). Treatment of PBL with several proteases increased permissiveness to D2V infection by immune complexes but not by virus alone. Two rhesus monkey serums collected 14 days after D2V infection contained an IgG antibody with high-titered enhancing activity but with no hemagglutination-inhibition or neutralizing activity. Virus-antibody complexes are irreversibly attached to PBL within 15 min and completely internalized in 60 min. There was considerable variation in cellular infection in different experiments, however, maximum virus yields usually exceeded 1,000 plaque-forming units per 1 x 10(6) PBL occurring between 2 and 4 days in culture. In vitro antibody-dependent infection of PBL provides a possible model for study of pathogenetic mechanisms in infants with dengue shock syndrome who passively acquire maternal anti-dengue IgG.
The Dca Gene Involved in Cold Adaptation in Drosophila melanogaster Arose by Duplication of the Ancestral regucalcin Gene
Authors: C. E. Arboleda-Bustos, C. Segarra
Journal: Molecular Biology and Evolution (2011)

The Drosophila cold acclimation gene (Dca) is involved in the adaptive response to low temperatures. This gene is upregulated at the transcriptional level when D. melanogaster flies are exposed 1 day to 15 °C. Dca (or smp-30) is a member of the SMP-30/Gluconolactonase/LRE-like family. In the current study, we characterized the members of this gene family in the 12 Drosophila species with available complete genomes sequences. Two paralogous genes, Dca and regucalcin, were identified in all the Sophophora subgenus species (9 of the 12 species), and their presence was further confirmed in three other species of the subgenus (D. subobscura, D. madeirensis, and D. guanche). However, only regucalcin was present in the species of the Drosophila subgenus (D. grimshawi, D. virilis, and D. mojavensis). The phylogenetic analysis and the molecular organization of Dca that is a nested intronic gene support that Dca arose by a duplication event from the ancestral regucalcin gene after the split of the Sophophora and Drosophila subgenera but before the Sophophora radiation. After the duplication event, the nonsynonymous fixation rate increased in the branch leading to Dca (but not to regucalcin), suggesting the neofunctionalization of the former duplicate. Thus, regucalcin would have maintained the ancestral gene function, and Dca would have acquired a new function likely related to Ca2+ homeostasis and cold acclimation. Molecular evolution of Dca has been affected by its implication in the adaptive response to cold temperatures. Indeed, the gene has evolved under stronger purifying selection in the temperate than in the tropical Sophophora species, as reflected by the ratio of nonsynonymous to synonymous substitutions. This result is consistent with functional constraints acting on the DCA protein to keep species adaptation to temperate climates. Dca and regucalcin also differ in their expression patterns. The expression profile of regucalcin is similar to that of the anterior fat body protein gene (AFP) of Sarcophaga peregrina and Calliphora vicina, which is also a member of the SMP-30/Gluconolactonase/LRE-like gene family. Sequence similarity and expression profile suggest that AFP and regucalcin are indeed orthologous genes.
<i>TERT</i> Polymorphism rs2736100-C Is Associated with EGFR Mutation–Positive Non–Small Cell Lung Cancer
Authors: Rongrong Wei, Lan Cao, Hengying Pu, Hongwei Wang, Yonglan Zheng, Xiaomin Niu, Xiaoling Weng, Hong Zhang, Murray J. Favus, Lanjun Zhang, Weihua Jia, Yixin Zeng, Christopher I. Amos, Shun Lu, Hui-Yun Wang, Yun Liu, Wanqing Liu
Journal: Clinical Cancer Research (2015)

EGF receptor (EGFR) mutation-positive (EGFRmut(+)) non-small cell lung cancer (NSCLC) may be a unique orphan disease. Previous studies suggested that the telomerase reverse transcriptase (TERT) gene polymorphism is associated with demographic and clinical features strongly associated with EGFR mutations, for example, adenocarcinoma histology, never-smoking history, and female gender. We aim to test the association between TERT polymorphism and EGFRmut(+) NSCLC.We conducted a genetic association study in Chinese patients with NSCLC (n = 714) and healthy controls (n = 2,520), between the rs2736100 polymorphism and EGFRmut(+) NSCLC. We further tested the association between the EGFR mutation status and mean leukocyte telomere length (LTL). The potential function of rs2736100 in lung epithelial cells was also explored.The rs2736100-C allele was significantly associated with EGFRmut(+) NSCLC [OR, 1.52; 95% confidence interval (CI), 1.28-1.80; P = 1.6 × 10(-6)] but not EGFRmut(-) NSCLC (OR = 1.07, 95% CI, 0.92-1.24, P = 0.4). While patients with NSCLC as a whole have significantly longer LTL than healthy controls (P ≤ 10(-13)), the EGFRmut(+) patients have even longer LTL than EGFRmut(-) patients (P = 0.008). Meanwhile, rs2736100 was significantly associated with TERT mRNA expression in both normal and tumor lung tissues. All results remained significant after controlling for age, gender, smoking status, and histology (P < 0.05 for all tests). Moreover, the rs2736100 DNA sequence has an allele-specific affinity to nuclear proteins extracted from lung epithelial cells, which led to an altered enhancer activity of the sequence in vitro.Our study suggests that telomerase and telomere function may be essential for carcinogenesis of EGFRmut(+) NSCLC. Further investigation for the underlying mechanism is warranted.
Metabolic response to intravenous salbutamol therapy in acute asthma.
Authors: T R Tickner, D G Cramp, A Y Foo, A J Johnson, S M Bateman, J Pidgeon, S G Spiro, S W Clarke, M R Wills
Journal: Thorax (1977)

Palliative sedation at the end of life has become an important last-resort treatment strategy for managing refractory symptoms as well as a topic of controversy within palliative care. Furthermore, palliative sedation is prominent in the public debate about the possible legalisation of voluntary assisted dying (physician-assisted suicide and euthanasia). This article attempts to demonstrate that palliative sedation is fundamentally different from euthanasia when it comes to intention, procedure, outcome and the status of the person. Nonetheless, palliative sedation in its most radical form of terminal deep sedation parallels euthanasia in one respect: both end the experience of suffering. However, only the latter intentionally ends life and also has this as its goal. There is the danger that deep sedation could bring death forward in time due to particular side effects of the treatment. Still that would, if it happens, not be intended, and accordingly is defensible in view of the doctrine of double effect.
Expression and Intracellular Localization of the Human N-acetylmuramyl-L-alanine Amidase, a Bacterial Cell Wall–Degrading Enzyme
Authors: M.A. Hoijer, M.J. Melief, J. Calafat, D. Roos, R.W.M. van den Beemd, J.J.M. van Dongen, M.P. Hazenberg
Journal: Blood (1997)
Orlistat Augments Postprandial Increases in Glucagon-like Peptide 1 in Obese Type 2 Diabetic Patients
Authors: Taner Damci, Serap Yalin, Huriye Balci, Zeynep Osar, Ustun Korugan, Mucahit Ozyazar, Hasan Ilkova
Journal: Diabetes Care (2004)

OBJECTIVE—Orlistat leads to improved glycemic control in obese type 2 diabetic patients, which is attributed to decreased insulin resistance associated with weight loss. Glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are gut hormones that are secreted in response to food intake, and they both stimulate insulin secretion. Orlistat decreases fat absorption and increases intestinal fat content, which may lead to increased secretion of these peptides. In this pilot study, we tested the hypothesis that increased levels of these intestinal hormones may be involved in the improvement of postprandial hyperglycemia observed previously with orlistat in type 2 diabetic patients. RESEARCH DESIGN AND METHODS—A total of 29 type 2 diabetic patients, who were not taking insulin or α-glucosidase inhibitors, were enrolled in the study. On a crossover and single-blind design, after an overnight fasting, the patients received 120-mg orlistat or placebo capsules, followed by a standard 600-kcal mixed meal that contained 38% fat. At baseline and 60 min after the meal, blood samples were obtained for the measurement of GLP-1, GIP, insulin, C-peptide, triglycerides, free fatty acids, and glucose. RESULTS—All measured parameters increased significantly in response to the mixed meal compared with baseline, both with orlistat or placebo. When compared with the placebo, the orlistat administration resulted in a significantly enhanced postprandial increase in GLP-1 and C-peptide levels and attenuated the postprandial rise in glucose and triglycerides. CONCLUSIONS—The results of this study suggest that apart from decreasing insulin resistance as a result of weight loss, orlistat may increase postprandial GLP-1 levels, thereby enhancing the insulin secretory response to the meal and blunting the postprandial rise in glucose in type 2 diabetic patients. Increased GLP-1 levels, which lead to decreased food intake, may also contribute to the weight loss that is associated with the use of this drug.
Essential Role for Smad3 in Regulating MCP-1 Expression and Vascular Inflammation
Authors: Mark W. Feinberg, Koichi Shimizu, Maria Lebedeva, Richard Haspel, Kiyoshi Takayama, Zhiping Chen, Joshua P. Frederick, Xiao-Fan Wang, Daniel I. Simon, Peter Libby, Richard N. Mitchell, Mukesh K. Jain
Journal: Circulation Research (2004)

Transforming growth factor (TGF)-β 1 is a pleiotropic growth factor with known inhibitory effects on immune cell activation. However, the specific mechanism(s) and in vivo significance of the effectors of TGF-β 1 modulation in the context of vascular inflammation are not well characterized. The chemokine monocyte chemoattractant protein (MCP)-1 is critical for the recruitment of macrophages in inflammatory disease states. In this study, we provide definitive evidence that the ability of TGF-β 1 to inhibit MCP-1 expression is mediated via its effector Smad3. Adenoviral overexpression of Smad3 potently repressed inducible expression of endogenous MCP-1. Conversely, TGF-β 1 inhibition of cytokine-mediated induction of MCP-1 expression was completely blocked in Smad3-deficient macrophages. Consistent with this impaired response, cardiac allografts in Smad3-deficient mice developed accelerated intimal hyperplasia with increased infiltration of adventitial macrophages expressing MCP-1. Previous studies show that MCP-1 inducibility is regulated by an AP-1 complex composed of c-Jun/c-Fos heterodimers. We demonstrate that the inhibitory effect of Smad3 occurs via a novel antagonistic effect of Smad3 on AP-1 DNA-protein binding and activity. Thus, Smad3 plays an essential role in modulating vascular inflammation characteristic of transplant-associated arteriopathy, is important in regulating MCP-1 expression, and plays a critical role in the ability of TGF-β 1 to repress stimuli from a major inflammatory signaling pathway.