tbuckley/cabot-search huggingface dataset:
Obstructive Sleep Apnea and Diabetic Neuropathy
Authors: Abd A. Tahrani, Asad Ali, Neil T. Raymond, Safia Begum, Kiran Dubb, Shanaz Mughal, Biju Jose, Milan K. Piya, Anthony H. Barnett, Martin J. Stevens
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Rationale: Diabetic peripheral neuropathy is common and causes significant morbidity. Obstructive sleep apnea (OSA) is also common in patients with type 2 diabetes. Because OSA is associated with inflammation and oxidative stress, we hypothesized that OSA is associated with peripheral neuropathy in type 2 diabetes.Objectives: To assess the relationship between OSA and peripheral neuropathy in patients with type 2 diabetes.Methods: A cross-sectional study of adults with type 2 diabetes recruited randomly from the diabetes clinic of two UK hospitals.Measurements and Main Results: Peripheral neuropathy was diagnosed using the Michigan Neuropathy Screening Instrument. OSA (apnea-hypopnea index ≥ 5 events/h) was assessed using home-based, multichannel respiratory monitoring. Serum nitrotyrosine was measured by ELISA, lipid peroxide by spectrophotometer, and microvascular function by laser speckle contrast imaging. Two hundred thirty-four patients (mean [SD] age, 57 [12] yr) were analyzed. OSA prevalence was 65% (median apnea-hypopnea index, 7.2; range, 0–93), 40% of which were moderate to severe. Neuropathy prevalence was higher in patients with OSA than those without (60% vs. 27%, P < 0.001). After adjustment for possible confounders, OSA remained independently associated with diabetic neuropathy (odds ratio, 2.82; 95% confidence interval, 1.44–5.52; P = 0.0034). Nitrotyrosine and lipid peroxide levels (n = 102, 74 with OSA) were higher in OSA and correlated with hypoxemia severity. Cutaneous microvascular function (n = 71, 47 with OSA) was impaired in OSA.Conclusions: We describe a novel independent association between diabetic peripheral neuropathy and OSA. We identified increased nitrosative/oxidative stress and impaired microvascular regulation as potential mechanisms. Prospective and interventional studies are needed to assess the impact of OSA and its treatment on peripheral neuropathy development and progression in patients with type 2 diabetes.
Functional SYNTAX Score for Risk Assessment in Multivessel Coronary Artery Disease
Authors: Chang-Wook Nam, Fabio Mangiacapra, Robert Entjes, In-Sung Chung, Jan-Willem Sels, Pim A.L. Tonino, Bernard De Bruyne, Nico H.J. Pijls, William F. Fearon
Journal: Journal of the American College of Cardiology (2011)
Hydrogen peroxide in exhaled air of healthy children: reference values
Authors: Q Jöbsis, H C Raatgeep, S L Schellekens, W C Hop, P W Hermans, J C de Jongste
Journal: European Respiratory Journal (1998)

An increased content of hydrogen peroxide (H2O2), a marker of inflammation, has been described in the condensate of exhaled air from adults and children with inflammatory lung disorders, including asthma. However, the normal range of [H2O2] in the exhaled air condensate from healthy children has not been established. Therefore, the aim of this study was to determine the reference range of exhaled [H2O2] in healthy school-aged children. Ninety-three healthy nonsmoking children (48 female and 45 male, mean age 10 yrs, range 8-13 yrs), with a negative history for allergy, eczema or respiratory disease and with a normal lung function, participated. Exhaled air condensate was examined fluorimetrically for the presence of H2O2. In addition, the reproducibility of [H2O2] within subjects and between days and the stability of [H2O2] during storage at -20 degrees C were assessed. The median [H2O2] in the exhaled air condensate of all children was 0.13 microM, with a 2.5-97.5% reference range of &lt;0.01-0.48 microM. No significant difference existed between males and females. There was no correlation between exhaled [H2O2] and age or lung function. Repeated [H2O2] measurements on 2 consecutive days showed satisfactory within-subject reproducibility and [H2O2] in stored samples remained stable for at least 1 month at -20 degrees C. In conclusion, this study provides reference data for exhaled hydrogen peroxide in a large group of healthy children. The observed levels were lower than those reported previously for healthy adults and were independent of age, sex and lung function.
Nutritional status in patients with rheumatoid arthritis.
Authors: M Helliwell, E J Coombes, B J Moody, G F Batstone, J C Robertson
Journal: Annals of the Rheumatic Diseases (1984)

A nutritional assessment of 50 patients with rheumatoid arthritis (RA) showed evidence of malnutrition in 13 (26%), while all 50 control subjects had normal nutritional status. Of the anthropometric measurements the body-mass index and triceps skinfold thickness values in men and women were significantly reduced in RA patients compared with controls. Upper arm muscle circumference was significantly less in male but not female rheumatoid patients. In addition all six biochemical determinants of nutrition assayed-serum albumin, transferrin, retinol-binding protein, thyroxine-binding prealbumin, zinc, and folic acid-were significantly lower in the RA group of patients. Malnourished patients had more active disease than the remaining RA patients, with significantly higher ESR, C-reactive protein, and alpha 1 antichymotrypsin measurements. Significant inverse correlations were found between some biochemical measurements of nutrition and indices of disease activity. Our results suggest that in RA the severity of disease adversely affects the nutritional status.
Systematic quantification of gene interactions by phenotypic array analysis
Authors: John L Hartman, Nicholas P Tippery
Journal: Genome biology (2004)

A phenotypic array method, developed for quantifying cell growth, was applied to the haploid and homozygous diploid yeast deletion strain sets. A growth index was developed to screen for non-additive interacting effects between gene deletion and induced perturbations. From a genome screen for hydroxyurea (HU) chemical-genetic interactions, 298 haploid deletion strains were selected for further analysis. The strength of interactions was quantified using a wide range of HU concentrations affecting reference strain growth. The selectivity of interaction was determined by comparison with drugs targeting other cellular processes. Bio-modules were defined as gene clusters with shared strength and selectivity of interaction profiles. The functions and connectivity of modules involved in processes such as DNA repair, protein secretion and metabolic control were inferred from their respective gene composition. The work provides an example of, and a general experimental framework for, quantitative analysis of gene interaction networks that buffer cell growth.
Cardiac lipoprotein lipase: Metabolic basis for diabetic heart disease
Authors: T PULINILKUNNIL, B RODRIGUES
Journal: Cardiovascular Research (2005)

The heart has a limited potential to synthesize fatty acid (FA), and, therefore, FA is supplied from several sources: lipolysis of endogenous cardiac triglyceride (TG) stores or from exogenous sources in the blood. Lipoprotein lipase (LPL), synthesized in cardiomyocytes, catalyzes the breakdown of the TG component of lipoproteins to provide FA to the heart. It is the vascular endothelial-bound LPL that determines the rate of plasma TG clearance, and, hence, it is also called heparin-releasable (HR) "functional" LPL. Functional LPL is regulated by numerous dietary and hormonal factors and is sensitive to pathophysiological alterations like those observed during diabetes. In this condition, absolute or relative lack of insulin impairs cardiac glucose transport and oxidation, resulting in FA becoming the preferred means of energy supply. To make available this increased requirement of the heart for FA, the diabetic heart upregulates its luminal LPL activity by posttranslational mechanisms. Chronically elevated cardiac LPL can result in abnormal FA supply and utilization by the heart tissue that could potentially initiate and sustain cardiac dysfunction during diabetes. As effective blood glucose control is difficult during diabetes, it is conceivable that a parallel increase in functional cardiac LPL activity may predispose people with diabetes to premature death from cardiac disease. By gaining more insight into the initial metabolic processes in the diabetic heart, we can attempt to piece together a part of the cascade of events leading to diabetic heart disease.
Retroviral Gene Transduction of Adult Peripheral Blood or Marrow-Derived CD34+ Cells for Six Hours Without Growth Factors or on Autologous Stroma Does Not Improve Marking Efficiency Assessed In Vivo
Authors: R.V.B. Emmons, S. Doren, J. Zujewski, M. Cottler-Fox, C.S. Carter, K. Hines, J.A. O'Shaughnessy, S.F. Leitman, J.J. Greenblatt, K. Cowan, C.E. Dunbar
Journal: Blood (1997)
Reduced interferon-gamma release in patients recovered from Legionnaires' disease
Authors: K D Lettinga
Journal: Thorax (2003)

<b>Background: </b><i>Legionella pneumophila</i>, a Gram negative intracellular pathogen, causes Legionnaires9 disease (LD). Interferon (IFN)-γ is important for host defence against <i>L pneumophila</i> so reduced IFN-γ production capacity and/or responsiveness might render humans more susceptible to infection with <i>L pneumophila</i>. <b>Methods:</b> Seventy seven patients who suffered from LD after a point source outbreak one year earlier participated in the study. Whole blood was incubated with non-specific stimuli (lipopolysaccharide (LPS) or interleukin (IL)-12) or specific stimuli (viable or heat killed <i>L pneumophila</i>) to evaluate IFN-γ production, and with IFN-γ to evaluate IFN-γ responsiveness. Expression of complement receptor 3 on monocytes was determined by flow cytometry. Thirty seven companions who were also exposed but had not developed LD served as controls. <b>Results:</b> Patients released less IFN-γ than controls in response to stimulation with LPS (mean (SE) 393 (58) pg/ml <i>v</i> 914 (178) pg/ml; p=0.001) and IL-12 (96 (14) pg/ml <i>v</i> 177 (41) pg/ml; p=0.058). IFN-γ responsiveness, measured by release of IFN-γ inducible protein (IP)-10, tumour necrosis factor α, IL-12 production capacity, and monocyte expression of complement receptor 3, did not differ between patients and controls. IFN-γ release after stimulation with LPS and IP-10 release after stimulation with IFN-γ were weakly associated with severity of LD in the former patient group (ρ=–0.3, p=0.011 and ρ=–0.3, p=0.037, respectively). <b>Conclusion:</b> These results suggest that impaired IFN-γ production may contribute to susceptibility to <i>L pneumophila</i> infection.
Multiple Genetic Alterations Cause Frequent and Heterogeneous Human Histocompatibility Leukocyte Antigen Class I Loss in Cervical Cancer
Authors: Louise A. Koopman, Willem E. Corver, Arno R. van der Slik, Marius J. Giphart, Gert Jan Fleuren
Journal: The Journal of Experimental Medicine (2000)

The nature and frequency of human histocompatibility leukocyte antigen (HLA) class I loss mechanisms in primary cancers are largely unknown. We used flow cytometry and molecular analyses to concurrently assess allele-specific HLA phenotypes and genotypes in subpopulations from 30 freshly isolated cervical tumor cell suspensions. Tumor-associated HLA class I alterations were present in 90% of the lesions tested, comprising four altered pheno/genotype categories: (a) HLA-A or -B allelic loss (17%), mostly associated with gene mutations; (b) HLA haplotype loss, associated with loss of heterozygosity at 6p (50%). This category included cases with additional loss of a (third) HLA-A or -B allele due to mutation, as well as one case with an HLA class I–negative tumor cell subpopulation, caused by a β2-microglobulin gene mutation; (c) Total HLA class I antigen loss and retention of heterozygosity (ROH) at 6p (10%); and (d) B locus or HLA-A/B downregulation associated with ROH and/or allelic imbalance at 6p (10%). Normal HLA phenotypes and ROH at 6p were observed in 10% of the cases. One case could not be classified (3%). Altered HLA class I antigen expression occurs in most cervical cancers, is diverse, and is mainly caused by genetic changes. Combined with widespread tumor heterogeneity, these changes have profound implications for natural immunity and T cell–based immunotherapy in cervical cancer.
Editor's snapshot: an unexpected duodenal finding
Authors: Andrew David Nelson, Gillian H Bain, Ashley D Graham, Marianne C Nicolson, John S Leeds
Journal: Gut (2012)

A 32-year-old Caucasian man presented with a 2-month history of fatigue, 4 kg weight loss and vague dyspepsia. He described no vomiting and no lower gastrointestinal symptoms. He was previously healthy with no significant past medical history, did not smoke and consumed around 10 units of alcohol per week. Systemic examination was normal. Blood tests revealed a mild normocytic anaemia (haemoglobin 128 g/l) with normal haematinics. Urea and electrolytes, liver function tests, calcium and c reactive protein were all within normal limits.

Upper gastrointestinal endoscopy revealed an unusual raised lesion in the second …
Association of Secondhand Smoke Exposure with Pediatric Invasive Bacterial Disease and Bacterial Carriage: A Systematic Review and Meta-analysis
Authors: Chien-Chang Lee, Nicole A. Middaugh, Stephen R. C. Howie, Majid Ezzati
Journal: PLoS Medicine (2010)

Majid Ezzati and colleagues report the findings of a systematic review and meta-analysis that probes the association between environmental exposure to secondhand smoke and the epidemiology of pediatric invasive bacterial disease.
Changes in Weight During a 1-Year Trial of Fluoxetine
Authors: D Michelson, J D Amsterdam, F M Quitkin, F W Reimherr, J F Rosenbaum, J Zajecka, K L Sundell, Y Kim, C M Beasley
Journal: American Journal of Psychiatry (1999)

OBJECTIVE: Fluoxetine has been associated with weight loss during acute treatment, but no controlled studies of weight change during long-term treatment with fluoxetine or other selective serotonin reuptake inhibitors have been reported. Weights were assessed for patients whose depressive symptoms had disappeared with acute fluoxetine treatment. Patients were then randomly assigned to continuation treatment with fluoxetine or placebo. METHOD: Patients whose illness had remitted after 12 weeks of treatment with fluoxetine, 20 mg/day, were randomly assigned to receive up to 38 weeks of treatment with fluoxetine or placebo. Weight was assessed at each visit. Change in weight was analyzed during the initial 12 weeks of acute treatment and after 14, 26, and 38 weeks. Relationships between weight change and body mass index and between weight change and appetite change were assessed. RESULTS: During the initial 4 weeks of therapy, a mean absolute weight decrease of 0.4 kg was observed for all patients. Among patients who completed 50 weeks of therapy, the mean absolute weight increase during continuation treatment was similar for both the placebo- and fluoxetine-treated groups. Weight increase was not related to initial body mass index but was related to both poor appetite at study entry and to improvement in appetite after recovery. No patients discontinued therapy because of weight gain. CONCLUSIONS: Acute therapy with fluoxetine is associated with modest weight loss. After remission of depressive symptoms, weight gain for patients taking fluoxetine for longer periods is not different from that for patients taking placebo and is most likely related to recovery from depression.
Amiodarone sensitizes human glioma cells but not astrocytes to TRAIL-induced apoptosis via CHOP-mediated DR5 upregulation
Authors: In Young Kim, You Jung Kang, Mi Jin Yoon, Eun Hee Kim, Seung U Kim, Taeg Kyu Kwon, In Ah Kim, Kyeong Sook Choi
Journal: Neuro-Oncology (2011)

Amiodarone is a widely used anti-arrhythmic drug that inhibits diverse ion channels, including the Na(+)/Ca(2+) exchanger (NCX), L-type Ca(2+) channels, and Na(+) channels. Here, we report that subtoxic doses of amiodarone and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) synergistically induced apoptosis of various glioma cells. Treatment of U251MG glioma cells with amiodarone increased intracellular Ca(2+) levels and enhanced the expression of the endoplasmic reticulum (ER) stress-inducible transcription factor C/EBP homologous protein (CHOP). This upregulation of CHOP was followed by marked upregulation of the TRAIL receptor, DR5. Suppression of DR5 expression by small interfering (si) RNAs almost completely blocked amiodarone/TRAIL-induced apoptosis in U251MG glioma cells, demonstrating that DR5 is critical to this cell death. siRNA-mediated CHOP suppression reduced amiodarone-induced DR5 upregulation and attenuated the cell death induced by amiodarone plus TRAIL. In addition, omitting Ca(2+) from the external medium using ethylene glycol tetraacetic acid markedly inhibited this cell death, reducing the protein levels of CHOP and DR5. These results suggest that amiodarone-induced influx of Ca(2+) plays an important role in sensitizing U251MG cells to TRAIL-mediated apoptosis through CHOP-mediated DR5 upregulation. Furthermore, subtoxic doses of bepridil and cibenzoline, two other anti-arrhythmic drugs with NCX-inhibitor activity, also sensitized glioma cells to TRAIL-mediated apoptosis, via the upregulation of both CHOP and DR5. Notably, amiodarone/TRAIL cotreatment did not induce cell death in astrocytes, nor did it affect the expression of CHOP or DR5 in these cells. These results collectively suggest that a combined regimen of amiodarone plus TRAIL may offer an effective therapeutic strategy for safely and selectively treating resistant gliomas.
Microfluidic Single-Cell Analysis of Transplanted Human Induced Pluripotent Stem Cell–Derived Cardiomyocytes After Acute Myocardial Infarction
Authors: Sang-Ging Ong, Bruno C. Huber, Won Hee Lee, Kazuki Kodo, Antje D. Ebert, Yu Ma, Patricia K. Nguyen, Sebastian Diecke, Wen-Yi Chen, Joseph C. Wu
Journal: Circulation (2015)

Background— Human induced pluripotent stem cells (iPSCs) are attractive candidates for therapeutic use, with the potential to replace deficient cells and to improve functional recovery in injury or disease settings. Here, we test the hypothesis that human iPSC-derived cardiomyocytes (iPSC-CMs) can secrete cytokines as a molecular basis to attenuate adverse cardiac remodeling after myocardial infarction. Methods and Results— Human iPSCs were generated from skin fibroblasts and differentiated in vitro with a small molecule–based protocol. Troponin + iPSC-CMs were confirmed by immunohistochemistry, quantitative polymerase chain reaction, fluorescence-activated cell sorting, and electrophysiological measurements. Afterward, 2×10 6 iPSC-CMs derived from a cell line transduced with a vector expressing firefly luciferase and green fluorescent protein were transplanted into adult NOD/SCID mice with acute left anterior descending artery ligation. Control animals received PBS injection. Bioluminescence imaging showed limited engraftment on transplantation into ischemic myocardium. However, magnetic resonance imaging of animals transplanted with iPSC-CMs showed significant functional improvement and attenuated cardiac remodeling compared with PBS-treated control animals. To understand the underlying molecular mechanism, microfluidic single-cell profiling of harvested iPSC-CMs, laser capture microdissection of host myocardium, and in vitro ischemia stimulation were used to demonstrate that the iPSC-CMs could release significant levels of proangiogenic and antiapoptotic factors in the ischemic microenvironment. Conclusions— Transplantation of human iPSC-CMs into an acute mouse myocardial infarction model can improve left ventricular function and attenuate cardiac remodeling. Because of limited engraftment, most of the effects are possibly explained by paracrine activity of these cells.
“High–dose” calcitriol for control of renal osteodystrophy in children on CAPD
Authors: Isidro B. Salusky, Richard N. Fine, Hooshang Kangarloo, Richard Gold, Luc Paunier, William G. Goodman, Judith E. Brill, Giulio Gilli, Eduardo Slatopolsky, Jack W. Coburn
Journal: Kidney International (1987)
High Incidence of Posttransplant Lymphoproliferative Disease in Pediatric Patients with Cystic Fibrosis
Authors: ALAN H. COHEN, STUART C. SWEET, ERIC MENDELOFF, GEORGE B. MALLORY, CHARLES B. HUDDLESTON, MADELEINE KRAUS, MICHAEL KELLY, ROBERT HAYASHI, MICHAEL R. DeBAUN
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

A major cause of morbidity and mortality following lung transplantation is posttransplant lymphoproliferative disease (PTLD). In a retrospective cohort analysis of pediatric patients, we evaluated the risk factors associated with PTLD in 128 first-time lung transplant recipients from 1990 to 1997. The greatest risk factor for PTLD was a diagnosis of cystic fibrosis (CF). Of the 16 patients in our analysis who had PTLD, 13 had a diagnosis of CF (odds ratio [OR]: 5.8; confidence interval 95% [CI]: 1.6 to 21.4). Because of the high frequency of PTLD in patients with CF (13 of 61; 23%), we performed a retrospective cohort analysis in which patients with CF and PTLD were designated as cases and patients with CF and without PTLD served as controls. In patients with CF, the only risk factor associated with PTLD was two or more episodes of acute rejection within 3 mo after transplantation (OR: 11.0; 95% CI: 2.7 to 55.7). Age, recipient Epstein-Barr virus or cytomegalovirus status, induction with antilymphocyte globulin or antithymocyte globulin (ATG), or use of ATG or OKT3 for acute rejection episodes were not risk factors for PTLD. The high frequency of PTLD in the subgroup of patients with two or more episodes of graft rejection within 2 mo after lung transplantation was unexpected, and warrants further investigation in prospective clinical studies and basic laboratories.
Left Ventricular Apex Ablation Decreases the Upper Limit of Vulnerability
Authors: Nipon Chattipakorn, Parwis C. Fotuhi, Xiangsheng Zheng, Raymond E. Ideker
Journal: Circulation (2000)

Background —After shocks with an ≈50% probability of success for the upper limit of vulnerability (ULV 50 ) of strength, the first few activations appear focally on the epicardium at almost the same site at the left ventricular (LV) apex in both successful and failed induction of ventricular fibrillation (VF). We tested the hypothesis that subendocardial ablation at this early site would decrease the shock strength required for the ULV 50 . Methods and Results —Ten S1 stimuli were delivered from the right ventricular apex at a 300-ms coupling interval in 5 pigs. Biphasic shocks were delivered from right ventricular–superior vena cava electrodes after the last S1 stimulus. The ULV 50 was determined using an up/down protocol with T-wave scanning. Radiofrequency ablation was performed endocardially at the apical LV. The ULV 50 was determined again 30 minutes after ablation. To determine the importance of the ablation region, this protocol was repeated in another 5 pigs with ablation at the LV base. Delivered voltage (401±60 versus 323±50 V) and energy (11±3 versus 7±2 J) for the ULV 50 were significantly decreased after LV apex ablation by 19% and 34%, respectively. However, no difference existed in ULV 50 before and after LV base ablation. Lesions at both the LV apex and base were subendocardial and ranged from 0.8 to 1.1 cm in diameter. Conclusions —Subendocardial ablation at the apical LV markedly decreases ULV 50 , which suggests that the activation originating from this postshock early site is responsible for VF initiation and that interventions to electrically silence this site can influence the outcome of VF induction by ULV shocks.