tbuckley/cabot-search huggingface dataset:
Prevalence and Factor Analysis of Metabolic Syndrome in an Urban Korean Population
Authors: Jee-Young Oh, Young Sun Hong, Yeon-Ah Sung, Elizabeth Barrett-Connor
Journal: Diabetes Care (2004)

OBJECTIVE—The aim of this study was to explore the prevalence and pattern of the metabolic syndrome and its association with hyperinsulinemia in an urban Korean population of 269 men and 505 women. RESEARCH DESIGN AND METHODS—The National Cholesterol Education Program Adult Treatment Panel (ATP) III guidelines were used to calculate the sex-specific prevalence of the metabolic syndrome. After excluding individuals taking medication for hypertension, diabetes, or dyslipidemia, we used factor analysis to examine the pattern of the metabolic syndrome in 206 men and 449 women. RESULTS—The prevalence of metabolic syndrome was 16.0% in men and 10.7% in women aged 30–80 years. However, ATP III criteria for central obesity are not optimal for an Asian-Pacific population; when waist circumference is reduced from 102 to 90 cm in men and 88 to 80 cm in women, the prevalence of the metabolic syndrome increased to 29.0 and 16.8%, respectively. Sex-specific factor analysis showed four factors in men (obesity, glucose intolerance, hypertension, and dyslipidemia) and three in women (obesity-hypertension, glucose intolerance, and obesity-dyslipidemia). Insulin resistance estimated from fasting insulin levels clustered with three of the four factors in men and two of the three factors in women. By ATP III or Asian-Pacific waist circumference criteria, the prevalence of the metabolic syndrome increased with increasing tertiles of insulin resistance, which was estimated by a homeostasis model assessment. CONCLUSIONS—The metabolic syndrome is common in an urban Korean population when using Asian-Pacific waist criteria. The prevalence of the metabolic syndrome increased with increasing tertiles of insulin resistance.
Accelerated Aging, Decreased White Matter Integrity, and Associated Neuropsychological Dysfunction 25 Years After Pediatric Lymphoid Malignancies
Authors: Ilse Schuitema, Sabine Deprez, Wim Van Hecke, Marita Daams, Anne Uyttebroeck, Stefan Sunaert, Frederik Barkhof, Eline van Dulmen-den Broeder, Helena J. van der Pal, Cor van den Bos, Anjo J.P. Veerman, Leo M.J. de Sonneville
Journal: Journal of Clinical Oncology (2013)

CNS-directed chemotherapy (CT) and cranial radiotherapy (CRT) for childhood acute lymphoblastic leukemia or lymphoma have various neurotoxic properties. This study aimed to assess their impact on the maturing brain 20 to 30 years after diagnosis, providing a much stronger perspective on long-term quality of life than previous studies.Ninety-three patients treated between 1978 and 1990 at various intensities, with and without CRT, and 49 healthy controls were assessed with magnetic resonance diffusion tensor imaging (DTI) and neuropsychological tests. Differences in fractional anisotropy (FA)-a DTI measure describing white matter (WM) microstructure-were analyzed by using whole brain voxel-based analysis.CRT-treated survivors demonstrated significantly decreased FA compared with controls in frontal, parietal, and temporal WM tracts. Trends for lower FA were seen in the CT-treated survivors. Decreases in FA correlated well with neuropsychological dysfunction. In contrast to the CT group and controls, the CRT group showed a steep decline of FA with age at assessment. Younger age at cranial irradiation and higher dosage were associated with worse outcome of WM integrity.CRT-treated survivors show decreased WM integrity reflected by significantly decreased FA and associated neuropsychological dysfunction 25 years after treatment, although effects of CT alone seem mild. Accelerated aging of the brain and increased risk of early onset dementia are suspected after CRT, but not after CT.
Endocytosis of fluorescent microspheres by human oesophageal epithelial cells: comparison between normal and inflamed tissue.
Authors: D Hopwood, E M Spiers, P E Ross, J T Anderson, J B McCullough, F E Murray
Journal: Gut (1995)

This paper examines the presence and characteristics of endocytosis by oesophageal epithelial cells. Biopsy specimens from normal and inflamed oesophagus were incubated in organ culture with fluorescent microspheres (0.1 and 0.01 microns diameter). These markers were taken into early endosomes and the lysosomes of both the smaller differentiating prickle cells and the larger mature squamous cells. Confocal and electron microscopy showed that markers passed to the early endosomes and the lysosomes by endocytosis. The process was energy dependent. Larger, 1 micron microspheres adhered to the epithelial cells but were not phagocytosed. Disaggregated cells were analysed by flow cytometry. Microspheres were endocytosed in proportion to the concentration in the culture medium in a dose dependent manner. Cells from inflamed oesophagus were significantly smaller (p = 0.013) and took up significantly more microspheres than cells from normal biopsy specimens (p = 0.015). In conclusion, endocytosis occurs in oesophageal epithelial cells and is increased in inflammation.
Histological improvement in HBeAg positive chronic hepatitis B patients treated with adefovir dipivoxil
Authors: Patrick Marcellin, Zack Goodman, Ting-Tsung Chang, Seng Gee Lim, Myron Tong, William Sievert, Mitchell Shiffman, Lennox Jeffers, Michael Wulfsohn, Richard Fallis, John Fry, Carol Brosgart
Journal: Journal of Hepatology (2002)
A Multidimensional Model of Obsessive-Compulsive Disorder
Authors: David Mataix-Cols, Maria Conceição do Rosario-Campos, James F. Leckman
Journal: American Journal of Psychiatry (2005)

Obsessive-compulsive disorder (OCD) is a clinically heterogeneous condition. This heterogeneity can reduce the power and obscure the findings from natural history studies to genome scans, neuroimaging, and clinical trials. The authors review the evidence supporting a multidimensional model of OCD.Computerized and manual literature searches were performed to identify factor-analytic studies of obsessive-compulsive symptoms before data from disciplines that bear on the potential usefulness of these dimensions were considered. Selection criteria included the novelty and importance of studies and their relevance to outcomes of interest to well-informed mental health professionals.Twelve factor-analytic studies involving more than 2,000 patients were identified that consistently extracted at least four symptom dimensions: symmetry/ordering, hoarding, contamination/cleaning, and obsessions/checking. These dimensions were associated with distinct patterns of comorbidity, genetic transmission, neural substrates, and treatment response. The evidence supporting the hoarding dimension is particularly robust.The complex clinical presentation of OCD can be summarized with a few consistent, temporally stable symptom dimensions. These can be understood as a spectrum of potentially overlapping syndromes that may 1) coexist in any patient, 2) be continuous with normal obsessive-compulsive phenomena, and 3) extend beyond the traditional nosological boundaries of OCD. Although the dimensional structure of obsessive-compulsive symptoms is imperfect, this quantitative approach to phenotypic traits has the potential to advance our understanding of OCD and may aid in the identification of more robust endophenotypes. The need for a dimensional rating scale and suggestions for future research aimed at reducing the burden of this disorder are discussed.
Appropriate Use Criteria for Coronary Revascularization and Trends in Utilization, Patient Selection, and Appropriateness of Percutaneous Coronary Intervention
Authors: Nihar R. Desai, Steven M. Bradley, Craig S. Parzynski, Brahmajee K. Nallamothu, Paul S. Chan, John A. Spertus, Manesh R. Patel, Jeremy Ader, Aaron Soufer, Harlan M. Krumholz, Jeptha P. Curtis
Journal: JAMA (2015)

Appropriate Use Criteria for Coronary Revascularization were developed to critically evaluate and improve patient selection for percutaneous coronary intervention (PCI). National trends in the appropriateness of PCI have not been examined.
Impact of the Pulmonary Artery Catheter in Critically Ill Patients
Authors: Monica R. Shah, Vic Hasselblad, Lynne W. Stevenson, Cynthia Binanay, Christopher M. O’Connor, George Sopko, Robert M. Califf
Journal: JAMA (2005)

Randomized clinical trials (RCTs) evaluating the pulmonary artery catheter (PAC) have been limited by small sample size. Some nonrandomized studies suggest that PAC use is associated with increased morbidity and mortality.To estimate the impact of the PAC device in critically ill patients.MEDLINE (1985-2005), the Cochrane Controlled Trials Registry (1988-2005), the National Institutes of Health ClinicalTrials.gov database, and the US Food and Drug Administration Web site for RCTs in which patients were randomly assigned to PAC or no PAC were searched. Results from the ESCAPE trial of patients with severe heart failure were also included. Search terms included pulmonary artery catheter, right heart catheter, catheter, and Swan-Ganz.Eligible studies included patients who were undergoing surgery, in the intensive care unit (ICU), admitted with advanced heart failure, or diagnosed with acute respiratory distress syndrome and/or sepsis; and studies that reported death and the number of days hospitalized or the number of days in the ICU as outcome measures.Information on eligibility criteria, baseline characteristics, interventions, outcomes, and methodological quality was extracted by 2 reviewers. Disagreements were resolved by consensus.In 13 RCTs, 5051 patients were randomized. Hemodynamic goals and treatment strategies varied among trials. A random-effects model was used to estimate the odds ratios (ORs) for death, number of days hospitalized, and use of inotropes and intravenous vasodilators. The combined OR for mortality was 1.04 (95% confidence interval [CI], 0.90-1.20; P = .59). The difference in the mean number of days hospitalized for PAC minus the mean for no PAC was 0.11 (95% CI, -0.51 to 0.74; P = .73). Use of the PAC was associated with a higher use of inotropes (OR, 1.58; 95% CI, 1.19-2.12; P = .002) and intravenous vasodilators (OR, 2.35; 95% CI, 1.75-3.15; P<.001).In critically ill patients, use of the PAC neither increased overall mortality or days in hospital nor conferred benefit. Despite almost 20 years of RCTs, a clear strategy leading to improved survival with the PAC has not been devised. The neutrality of the PAC for clinical outcomes may result from the absence of effective evidence-based treatments to use in combination with PAC information across the spectrum of critically ill patients.
Quality of life in patients with chronic obstructive pulmonary disease and severe hypoxaemia.
Authors: A. A. Okubadejo, P. W. Jones, J. A. Wedzicha
Journal: Thorax (1996)

BACKGROUND: Patients with severe chronic obstructive pulmonary disease (COPD) have impairment in most areas of quality of life, but a relationship between impairment of the partial pressure of oxygen in arterial blood (PaO2) and quality of life has not been established. Previous studies used general health measures such as the Sickness Impact Profile (SIP). In this study a disease-specific health measure, the St George9s Respiratory Questionnaire (SGRQ), was used to examine the relationship. METHODS: Forty one patients (20 men) of median age 71 years (range 47-85) with COPD were assessed. Forced expiratory volume in one second (FEV1), PaO2 and partial pressure of carbon dioxide in the arterial blood (PaCO2) were measured, and the patients completed the SGRQ, SIP, and the Hospital Anxiety and Depression Scale (HAD). RESULTS: The mean (SD) values were: FEV1, 0.83 (0.29) litres; PaO2, 7.49 (1.03) kPa; PaCO2, 6.30 (1.05) kPa; SGRQ total score, 55.3 (18.2); SIP total score 15.4 (9.2); anxiety score, 5.7 (4.3); depression score, 5.3 (3.4). PaO2 was significantly correlated with the SGRQ total scores but not with the SIP total score. The SGRQ total score also correlated with anxiety and depression. Multivariate analysis showed that depression score and PaO2 were both significant covariates of the SGRQ total score. CONCLUSIONS: These findings suggest that, in patients with severe COPD, quality of life is related to the severity of hypoxaemia, but this relationship is only detectable when using a disease-specific health measure.
Molecular and flow cytometric analysis of the Vβ repertoire for clonality assessment in mature TCRαβ T-cell proliferations
Authors: Anton W. Langerak, René van den Beemd, Ingrid L. M. Wolvers-Tettero, Patrick P. C. Boor, Ellen G. van Lochem, Herbert Hooijkaas, Jacques J. M. van Dongen
Journal: Blood (2001)
Genetic Variation in <i>KCNH2</i> Associated With Expression in the Brain of a Unique hERG Isoform Modulates Treatment Response in Patients With Schizophrenia
Authors: José A. Apud, Fengyu Zhang, Heather Decot, Kristin L. Bigos, Daniel R. Weinberger
Journal: American Journal of Psychiatry (2012)

Objective: Antidopaminergic drugs bind to hERG1 potassium channels encoded by the gene KCNH2, which accounts for the side effect of QT interval prolongation. KCNH2 has also been associated with schizophrenia risk, and risk alleles predict increased expression of a brain-selective isoform, KCNH2 3.1, that has unique physiological properties. The authors assessed whether genetic variation associated with KCNH2 3.1 expression influences the therapeutic effects of antipsychotic drugs. Method: The authors performed a pharmacogenetic analysis of antipsychotic treatment response in patients with schizophrenia using data from two independent studies: a National Institute of Mental Health (NIMH) double-blind, placebo-controlled inpatient crossover trial (N=54) and the multicenter outpatient Clinical Antipsychotic Trials in Intervention Effectiveness (CATIE) study (N=364). The KCNH2 genotype that was previously associated with increased expression of KCNH2 3.1 in the brain was treated as a predictor variable. Treatment-associated changes in symptoms were evaluated in both groups with the Positive and Negative Syndrome Scale. The authors also analyzed time to discontinuation in the olanzapine arm of the CATIE study. Results: In the NIMH study, individuals who were homozygous for the KCNH2 3.1 increased expression-associated T allele of rs1036145 showed significant improvement in positive symptoms, general psychopathology, and thought disturbance, while patients with other genotypes showed little change. In the CATIE study, analogous significant genotypic effects were observed. Moreover, individuals who were homozygous for the T allele at rs1036145 were one-fifth as likely to discontinue olanzapine. Conclusions: These consistent findings in two markedly different treatment studies support the hypothesis that hERG1-mediated effects of antipsychotics may not be limited to their potential cardiovascular side effects but may also involve therapeutic actions related to the brain-specific 3.1 isoform of KCNH2
Role of leukocytes in the activation of intravascular coagulation in patients with septicemia
Authors: Kenji Okajima, Wang‐Peng Yang, Hiroaki Okabe, Masayasu Inoue, Kiyoshi Takatsuki
Journal: American Journal of Hematology (1991)

Abstract To elucidate the role of leukocytes in intravascular coagulation in patients with septicemia, plasma levels of thrombin‐antithrombin III complex (TAT), soluble fibrin monomer complex (SFMC) and fibrinogen (Fbg) were determined in 33 patients with septicemia. Twenty of 33 patients revealed marked leukopenia caused by suppression of hematopoie‐sis by the administration of chemotherapeutic agents for the treatment of hematological malignancies; the total leukocyte count of these patients was &lt; 1,000/μl. Thirteen of 33 patients showed normal or increased leukocyte counts. Plasma levels of TAT and SFMC in septicemic patients without leukopenia were significantly higher than in patients with leukopenia. Although plasma TAT and SFMC levels correlated well with the number of leukocytes, a more significant positive correlation was found between the number of monocytes and the levels of TAT and SFMC. Plasma levels of Fbg were significantly lower in patients without leukopenia than in patients with leukopenia. No significant correlation was found between the number of leukocytes and the levels of Fbg. However, a significant negative correlation was found between the number of monocytes and the levels of Fbg. TAT levels did not correlate with the number of platelets. The fibrinolytic system was activated only in septicemic patients without leukopenia, which may be explained by secondary fibrinolysis following leukocyte‐activated coagulation. These findings suggest that leukocytes, in particular monocytes, may play a critical role in the pathogenesis of intravascular coagulation in septicemia.
Cognitive aspects of performance.
Authors: J. E. Kane
Journal: British Journal of Sports Medicine (1978)

The study of cognitive structures and processes in the control of skilled performance is considered and reviewed with special reference to a proposed hierarchical system incorporating levels of motor integration. Cognitive styles and dispositions of general behaviour are suggested as factors which may determine performance levels. The relative importance of these personal factors and stronger personality traits in accounting for variance in performance is considered in the light of a critique of the current interactional controversy.
Dissection of the APCCdh1-Skp2 Cascade in Breast Cancer
Authors: Takeo Fujita, Weijun Liu, Hiroyoshi Doihara, Hiroshi Date, Yong Wan
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Skp2 is a subunit of the SCF ubiquitin protein ligase, which plays a vital role in the control of tumorigenesis via its regulation of G1-S transition. Deregulation of Skp2 in various types of cancers correlates with aggressive clinical behavior and poor prognosis. Recent studies suggest that cell cycle–dependent fluctuation of Skp2 is governed by APCCdh1, another important E3 ligase, thereby preventing premature entry into S phase. To assess the potential role of APCCdh1 in tumorigenesis through proteolysis of Skp2, we have dissected the APCCdh1-Skp2 cascade. Experimental Design: We manipulated the APCCdh1-Skp2 cascade and examined its cellular behavior using both breast cancer and normal breast epithelial cells. Furthermore, applying immunohistochemistry, we analyzed the clinicopathologic significance of these molecules in patients with breast cancer. Results: Analysis of tissue arrays indicated that the percentage of samples positive for Cdh1 in breast cancer was significantly lower compared with normal breast tissues (P = 0.004). Conversely, the percentage of samples scored as positive for Skp2 in cancer was significantly higher than in normal tissues (P &amp;lt; 0.001). Moreover, prognostic studies revealed that relatively high levels of Cdh1 are associated with survivability in patients with breast cancer. In addition, depletion of Cdh1 by small interfering RNA in normal breast cells resulted in increased cellular proliferation, whereas knockdown of Skp2 significantly suppressed growth in breast cancer cells. Conclusions: This study shows a correlation between Skp2 and APCCdh1 in breast cancer. Thus, Cdh1 may act as an important component in tumor suppression and could be considered as a novel biomarker in breast cancer.
Induction of Apoptosis in Human Cancer Cells by Candidaspongiolide, a Novel Sponge Polyketide
Authors: Daniela Trisciuoglio, Badarch Uranchimeg, John H. Cardellina, Tamara L. Meragelman, Shigeki Matsunaga, Nobuhiru Fusetani, Donatella Del Bufalo, Robert H. Shoemaker, Giovanni Melillo
Journal: JNCI Journal of the National Cancer Institute (2008)

Candidaspongiolide (CAN), a novel polyketide from a marine sponge, is the active component of a mixture that was found to be potently cytotoxic in the National Cancer Institute's 60-cell-line screen. Effects of CAN on U251 glioma and HCT116 colorectal cancer cells and on normal fibroblasts were assessed using radiolabeling studies to measure protein synthesis, clonogenic assays to measure cell survival, flow cytometry of annexin V– and propidium iodide–stained cells to measure apoptosis, and western blots in the presence or absence of specific inhibitors to assess accumulation and phosphorylation of potential downstream target proteins. CAN inhibited protein synthesis and potently induced apoptosis in both U251 and HCT116 cells, the latter in part by a caspase 12–dependent pathway. For example, 25%–30% of U251 or HCT116 cells became apoptotic after 24 hours of treatment with 100 nM CAN. CAN also rapidly induced sustained phosphorylation of eukaryotic translation initiation factor-2 (eIF2)-α at Ser51 and of the translation elongation factor eEF2 at Thr56, which could contribute to its dose-dependent inhibition of protein synthesis. Stable expression of dominant-negative eIF2α was sufficient to prevent CAN-induced eIF2α phosphorylation and induction of apoptosis but insufficient to prevent inhibition of protein synthesis. CAN induction of eIF2α phosphorylation did not occur by a classic endoplasmic reticulum stress pathway. However, an inhibitor of and small-interfering RNAs to the double-stranded RNA–dependent protein kinase PKR prevented CAN-mediated eIF2α phosphorylation and apoptosis, respectively. Although CAN inhibited protein synthesis in both cancer cells and normal human fibroblasts, it induced eIF2α phosphorylation and apoptosis only in cancer cells. CAN triggers PKR/eIF2α/caspase 12–dependent apoptosis and inhibits protein synthesis in cancer cells but only inhibits protein synthesis in normal cells.
Exercise-Induced Pulmonary Arterial Hypertension
Authors: James J. Tolle, Aaron B. Waxman, Teresa L. Van Horn, Paul P. Pappagianopoulos, David M. Systrom
Journal: Circulation (2008)

The clinical relevance of exercise-induced pulmonary arterial hypertension (PAH) is uncertain, and its existence has never been well studied by direct measurements of central hemodynamics. Using invasive cardiopulmonary exercise testing, we hypothesized that exercise-induced PAH represents a symptomatic stage of PAH, physiologically intermediate between resting pulmonary arterial hypertension and normal.A total of 406 consecutive clinically indicated cardiopulmonary exercise tests with radial and pulmonary arterial catheters and radionuclide ventriculographic scanning were analyzed. The invasive hemodynamic phenotype of exercise-induced PAH (n=78) was compared with resting PAH (n=15) and normals (n=16). Log-log plots of mean pulmonary artery pressure versus oxygen uptake (V(.)o(2)) were obtained, and a "join-point" for a least residual sum of squares for 2 straight-line segments (slopes m1, m2) was determined; m2<m1="plateau," and m2>m1="takeoff" pattern. At maximum exercise, V(.)o(2) (55.8+/-20.3% versus 66.5+/-16.3% versus 91.7+/-13.7% predicted) was lowest in resting PAH, intermediate in exercise-induced PAH, and highest in normals, whereas mean pulmonary artery pressure (48.4+/-11.1 versus 36.6+/-5.7 versus 27.4+3.7 mm Hg) and pulmonary vascular resistance (294+/-158 versus 161+/-60 versus 62+/-20 dyne x s x cm(-5), respectively; P<0.05) followed an opposite pattern. An exercise-induced PAH plateau (n=32) was associated with lower o(2)max (60.6+/-15.1% versus 72.0+/-16.1% predicted) and maximum cardiac output (78.2+/-17.1% versus 87.8+/-18.3% predicted) and a higher resting pulmonary vascular resistance (247+/-101 versus 199+/-56 dyne x s x cm(-5); P<0.05) than takeoff (n=40). The plateau pattern was most common in resting PAH, and the takeoff pattern was present in nearly all normals.Exercise-induced PAH is an early, mild, and clinically relevant phase of the PAH spectrum.