tbuckley/cabot-search huggingface dataset:
IL-3 or IL-7 Increases ex Vivo Gene Transfer Efficiency in ADA-SCID BM CD34+ Cells while Maintaining in Vivo Lymphoid Potential
Authors: Francesca Ficara, Daniela B. Superchi, Raisa Jofra Hernández, Cristina Mocchetti, Nicole Carballido-Perrig, Grazia Andolfi, Sara Deola, Augusto Colombo, Claudio Bordignon, José M. Carballido, Maria Grazia Roncarolo, Alessandro Aiuti
Journal: Molecular Therapy (2004)

To improve maintenance and gene transfer of human lymphoid progenitors for clinical use in gene therapy of adenosine deaminase (ADA)-deficient SCID we investigated several gene transfer protocols using various stem cell-enriched sources.The lymphoid differentiation potential was measured by an in vitro clonal assay for B/NK cells and in the in vivo SCID-hu mouse model.Ex vivo culture with the cytokines TPO, FLT3-ligand, and SCF (T/F/S) plus IL-3 or IL-7 substantially increased the yield of transduced bone marrow (BM) CD34 + cells purified from ADA-SCID patients or healthy donors, compared to T/F/S alone.Moreover, the use of IL-3 or IL-7 significantly improved the maintenance of in vitro B cell progenitors from ADA-SCID BM cells and allowed the efficient transduction of B and NK cell progenitors.Under these optimized conditions transduced CD34 + cells were efficiently engrafted into SCID-hu mice and gave rise to B and T cell progeny, demonstrating the maintenance of in vivo lymphoid reconstitution capacity.The protocol based on the T/F/S + IL-3 combination was included in a gene therapy clinical trial for ADA-SCID, resulting in long-term engraftment of stem/progenitor cells.Remarkably, gene-corrected BM CD34 + cells obtained from one patient 4 and 11 months after gene therapy were capable of repopulating the lymphoid compartment of SCID-hu hosts.
Abstract 15400: Stress Provokes Insulin Resistance and Impairs Endothelial NO Production in Mice Probably Through Activation of Endoplasmic Reticulum Stress and Inflammation Pathways by Corticotropin-releasing Hormone
Authors: Ick-Mo Chung, Hee Young Kim, Sangeun Yeon, Iseul Kim, Youngmi Lee
Journal: Circulation (2014)

Introduction: Previous studies suggested that psychological stress may provoke insulin resistance, although its mechanism is obscure. Corticotropin-releasing hormone (CRH) plays as a key regulator of hypothalamus under stress, however its role in the vascular cells and insulin signaling is not known well. Hypothesis: Stress may provoke insulin resistance thus contributing to endothelial dysfunction probably by the role of CRH in insulin signaling pathway. Methods and Results: Male C57BL/6 mice (8wk-old) were subject to immobilization stress (IS: 2 hr/d) and electric stimuli (ES: 12 times of 2 mA for 0.5 sec/d) for 2-4 wk. Control group comprised of mice without stress (n≥7 for each). Glucose tolerance test (i.p.) showed that stress (IS+ES) for 2 wk induced impaired glucose tolerance compared with control group. Stress (IS+ES) for 4 wk induced greater HOMA-IR than control group (2.5±0.6 vs. 0.8±0.3 mmol/LxμIU/mL, p<0.05). Total released NO in the aorta responding to acetylcholine (10-5M), measured by elect...
Emphysema distribution determines distinct pulmonary function features
Authors: Helder Novais e Bastos, Inês Neves, Margarida Redondo, Rui Cunha, Adriana Magalhães, Gabriela Fernandes
Journal: European Respiratory Journal (2013)

Lung emphysema has distinct clinical features that can be independent of airflow obstruction severity. The aim of this study was to evaluate the impact of emphysema distribution on patients’ clinical and functional features.

Eigthy-six patients (mean age 65.2±12.2 years, 62.7±38.4 smoking pack-year) underwent clinical and lung CT scan evaluation. They were classified according to a lung CT 5-point visual scoring system for emphysema distribution. Groups were compared according to this stratification.

Patients had mild airflow limitation in 28.2%, moderate in 22.4%, severe in 29.4% and very severe in 20%. Upper lung (UL) predominant emphysema was present in 36% patients, 25.6% cases had moderately UL predominance, 22.1% had moderately lower lung (LL) predominance and 16.3% had homogeneous distribution.

Moderately LL predominant emphysema was associated to lower paO2/fiO2 ratio, FEV1, FVC, FEV1/FVC, DLCO and DLCO/VA (r= -0.456 to r= -0.603, p<0.0005). Patients with moderate LL predominancy are more probable to have FEV1<65% than patients with UL predominant emphysema (OR 4.55, 95%CI 1.23-16.88; p=0.023) and paO2/fiO2 ratio <285 (OR 30.38, 95%CI 3.33-277.31; p= 0.002).

Patients with homogeneous emphysema had lower 6-minute walk distance (F=5.007, p=0.003) and higher desaturation (H=11.860, p=0.008). They had also higher RV/TLC, although without achieving significance (p=0.064).

Moderately predominant emphysema in LL was related to more severe disease than UL predominance. Patients with homogeneous emphysema had greater hyperinflation and worse exercise performance. Distribution of emphysema has an important impact on functional parameters and should be considered in disease evaluation.
Pressures in outpatient clinics
Authors: D J Niblett
Journal: BMJ (1998)

EDITOR—The pressure on outpatient clinics that Sellu highlights in his Personal View is commonplace and affects other aspects of hospital work, such as the planning of operating theatre schedules.1 He is a victim of a system that exploits its employees while simultaneously making scapegoats of them in order to conceal inadequacies that the purchasers and the government are not honest enough to shoulder responsibility for. I fear that this self sacrifice by consultants who work for free on behalf of the trusts merely compounds the problem and compromises the quality of individual patient care.

Doctors have a duty of care to individual patients. It is not acceptable to covertly trim this care for the greater good. But when doctors accept an excessive caseload, albeit under …
Oxidative stress is a critical mediator of the angiotensin II signal in human neutrophils: involvement of mitogen-activated protein kinase, calcineurin, and the transcription factor NF-κB
Authors: Rajaa El Bekay, Moisés Álvarez, Javier Monteseirín, Gonzalo Álba, Pedro Chacón, Antonio Vega, José Martín-Nieto, Juan Jiménez, Elízabeth Pintado, Francisco J. Bedoya, Francisco Sobrino
Journal: Blood (2003)
Anesthetic Management for Laparoscopic Cholecystectomy
Authors: Somchai Amornyotin
Journal: Endoscopy (2013)

Laparoscopic surgery aims to minimize trauma of the interventional process but still ach‐ ieve a satisfactory therapeutic result. It is commonly performed because of various advan‐ tages such as reduced postoperative pain, faster recovery and more rapid return to normal activities, shorter hospital stay, and reduced postoperative pulmonary complications. The operative technique requires inflating gas into the abdominal cavity to provide a surgical procedure. An intra-abdominal pressure (IAP) of 10-15 mmHg is used. Carbon dioxide (CO2) is commonly used because it does not support combustion, is cleared more rapidly than other gases, and is highly soluble in blood. However, the disadvantage of CO2 is that the absorption of CO2 can cause hypercapnia and respiratory acidosis [1].
Histamine H4 receptors in normal conjunctiva and in vernal keratoconjunctivitis
Authors: A. Leonardi, A. Di Stefano, C. Vicari, L. Motterle, P. Brun
Journal: Allergy (2011)

To cite this article: Leonardi A, Di Stefano A, Vicari C, Motterle L, Brun P. Histamine H4 receptors in normal conjunctiva and in vernal keratoconjunctivitis. Allergy 2011; 66: 1360–1366. Background: While it is known that histamine is the primary mediator of ocular allergy, the presence and distribution of histamine receptors are not well documented in the human eye. Our aim was to evaluate histamine receptor expression in normal and vernal keratoconjunctivitis conjunctiva. Methods: Mucosal biopsies were obtained from conjunctiva of healthy donors and from tarsal conjunctiva of vernal patients. Immunostaining and semi-quantitative reverse-transcriptase polymerase chain reaction for H1, H2, H3, and H4 receptors were performed. Histamine receptor expression was also evaluated in conjunctival cell cultures exposed to histamine, interleukin-4, interleukin-5, interferon-γ and tumor necrosis factor-α. Results: Immunostaining for H1 and H2 receptors was slightly positive in normal and over-expressed in vernal tissues. H3 receptors were rarely present in normal and inflamed conjunctiva. In striking contrast to control tissues, H4 receptors were highly expressed in all inflamed tissues, particularly by stromal inflammatory cells. Semi-quantitative reverse-transcriptase polymerase chain reaction demonstrated an over-expression of H1, H2, and H4 receptors in vernal vs control tissues. Notably, H4 receptors were five times more expressed in vernal vs control tissues. In cell cultures, H2 receptor expression was stimulated eight times the normal levels by interleukin-4 and three times by histamine, but the H4 receptor was only slightly affected by stimulation with these mediators. Conclusions: Increased expression of H1, and particularly of H2 and H4 receptors in vernal keratoconjunctival tissues indicate their important role in the pathogenesis of this disease. H4 receptors may be a target in the treatment of allergic inflammation.
Abstract P276: Metabolic Profiles of Biological Aging in American Indians: The Strong Heart Family Study
Authors: Yun Zhu, Jiang He, Jue Lin, Tet Matsuguchi, Elizabeth Blackburn, Elisa T Lee, Barbara V Howard, Jinying Zhao
Journal: Circulation (2014)

Background: Telomere length is an emerging biomarker for cellular senescence or biological aging. Short leukocyte telomere length (LTL) has been associated with a wide range of age-related metabolic disorders such as diabetes and cardiovascular disease. Telomere attrition induces profound metabolic dysfunction in animal models, but no study has examined the metabolic profiles of biological aging assessed by telomere length in human. Objective: To identify metabolic profiles of leukocyte telomere length in American Indians participating in the Strong Heart Family Study (SHFS, 2001-2003). Methods: This study included 432 SHFS participants free of cardiovascular disease and type 2 diabetes. LTL was measured by quantitative polymerase chain reaction (qPCR). Plasma metabolites were detected using an untargeted metabolomics approach by high-resolution liquid chromatography-mass spectrometry (LC/MS). The association of leukocyte telomere length with concentration of each metabolite was examined using generalized estimating equation (GEE), adjusting for age, sex, study center, body mass index, fasting glucose and fasting insulin. Multiple testing was corrected by Bonferroni correction (significance level 2.8х10-6). Results: After adjusting for covariates and multiple testing, three metabolites including cytosine, selenophosphate and pentyl propanoate, were significantly associated with LTL. Of these, cytosine was positively associated with LTL (β=0.0476, 95% CI, 0.0474 to 0.0478, P=1.90х10-7), and selenophosphate (β =-0.1522, 95% CI, -0.1525 to -0.1519, P=2.48х10-8) and pentyl propanoate (β =-0.0644, 95% CI, -0.0683 to -0.0606, P=1.08х10-8) were negatively associated with LTL. Multivariate analysis demonstrated that participants with longer (top telomere tertile) and shorter (bottom telomere tertile) LTL can be clearly separated by partial least square discriminant analysis (PLS-DA) using these three metabolites. Multiple unknown compounds were also independently associated with LTL. Conclusions: This study, for the first time, identifies metabolites and metabolic profiles associated with interindividual variability in leukocyte telomere length, independent of potential confounders. Our findings provide novel insights into understanding of telomere biology and metabolic mechanisms underlying age-related disorders.
Epstein-Barr virus-specific cytotoxic T cell responses in HIV-1 infection: different kinetics in patients progressing to opportunistic infection or non-Hodgkin's lymphoma.
Authors: M J Kersten, M R Klein, A M Holwerda, F Miedema, M H van Oers
Journal: Journal of Clinical Investigation (1997)

Although the high incidence of EBV-associated diffuse large cell lymphomas (DLCL) in HIV-1 infection is believed to be related to loss of immune control due to HIV-induced immune deficiency, it has been claimed that cytotoxic T lymphocyte (CTL) responses to EBV are longer lasting in HIV-1-infected persons than CTL directed against HIV-1 itself. We approached this apparent paradox by performing the first longitudinal study into the kinetics of EBV and HIV-specific CTL responses in HIV-infected patients progressing either to AIDS with non-Hodgkin's lymphoma (NHL) or AIDS with opportunistic infection (OI). Multiple samples were tested from HIV-1 seroconversion to AIDS-diagnosis. Four out of six patients that were either long-term asymptomatic or progressing to OI showed declining HIV-1 CTL precursor (CTLp) frequencies whereas EBV-CTLp remained stable, suggestive for HIV-1-specific immune exhaustion. In two patients rapidly progressing to AIDS-OI, a parallel decline of HIV-1- and EBV-CTL responses was seen, indicative for total collapse of cellular immunity. In all these six patients EBV-load remained low. However, in four out of five patients that progressed to DLCL, EBV-load was high and increasing several months preceding the NHL. In all five patients, EBV-CTLp decreased before the emergence of the NHL. Thus, our data show that in HIV-1 infection loss of HIV-1-specific T cell immunity is not necessarily paralleled by loss of EBV-specific T cell responses. The occurrence of AIDS-related DLCL is preceded by decreasing EBV-CTLp and increasing EBV load. Failing EBV-control might therefore be an important step in the pathogenesis of AIDS-related DLCL.
Adipokines in end-stage lung diseases: The crosstalk between bone and adipose tissue
Authors: Evgenia Kochetkova, Ludmila Ugay, Vera Nevzorova, Gilbert Massard, Yulia Maistrovskaia
Journal: European Respiratory Journal (2013)

Aim: investigate the role of the circulating adipokines in formation of osteoporosis in end-stage lung diseases.

Materials: Bone mineral density (BMD) at the lumbar spine (LS) and femur neck (FN), adipokines, osteopontine, osteoprotegerin (OPG) and receptor activator of nuclear factor-kB ligand (RANKL), bone biomarkers were determined in 78 patients with end-stage of lung diseases and 65 healthy controls.

Results: procollagen type 1 amino-terminal propeptide (P1NP) was higher in lung diseases and osteocalcin was similar between lung and control groups. Type 1 collagen C-telopeptide (CTx) was higher in lung patients and was related to FN (r=-0.62,p<0.01) and with P1NP (r=0.72,p<0.001). Adiponectin, resistin, visfatin, TNF-a, IL-6, osteopontine, RANKL were higher; leptin, OPG were low in lung group. Where were correlations between leptin (r=0.64,p<0.001; r=0.52,p<0.001), adiponectin (r=-0.54,p<0.01; r=-0.47,p<0.01), TNF-a (r=-0.43,p<005; r=-0.41, p<0.05) and BMD FN and LS. It was correlation between resistin (r=0.57, p<0.001) in LS. Omentin-1 were correlated with BMD FN (r=0.48,p<0.05), BMI (r=0.58, p<0.01), osteopontin (r=0.46,p<0.05), OPG (p<0.05), osteocalcin (r=0.53, p<0.05) and RANKL (r=-0.52,p<0.05) in lung patients. No correlations were found between visfatin, biochemical, and BMD measures in both groups. Total and active ghrelin (p<0.01) were higher in lung group and associated with BMI (total ghrelin: r=-0.57,p<0.01; active ghrelin: r=-0.48,p<0.05). Resistin had inverse correlations with FEV1%; FEV1/FVC% and positive with BMI. Visfatin was positive correlations with FEV% and TNF-a (p<0.05).

Conclusion: our results shows possibly role of adipokines in bone loss in end-stage lung disease.
Abstract 20784: Implantation of Differentiated Mesenchymal Stem Cell Through PKC Activation to Border Zone Restores Conduction and Suppresses Ventricular Arrhythmia
Authors: Hye Jin Hwang, Heesang Song, Il-Kwon Kim, Byeong-Wook Song, Min-Ji Cha, Eun Ju Choi, Onju Ham, Chungkeun Lee, Moon-Hyoung Lee, Sung Soon Kim, Yangsoo Jang, Ki-Chul Hwang
Journal: Circulation (2010)

Background: Focal application of MSCs of which differentiation has been observed in vivo at extremely low rates could create fixed tissue heterogeneity that may predispose to ventricular arrhythmia...
Abstract 13863: Stress Echocardiography in Asymptomatic Patients: Impact of Clinical Risk Profile on Test Results
Authors: Andrew D Calvin, Adelaide M Arruda-Olson, Patricia A Pellikka, Christopher G Scott, Robert B McCully
Journal: Circulation (2014)

Introduction: Stress echocardiography (SE) has an established role in the evaluation of symptomatic patients, but its utility in asymptomatic patients is unclear. Current guidelines discourage the use of SE in most asymptomatic patients, citing lack of data to support its use. We therefore sought to describe the yield of SE in a group of asymptomatic individuals according to risk profile. Hypothesis: We hypothesized that SE would rarely be abnormal in asymptomatic individuals. Methods: We conducted a retrospective cohort study of all asymptomatic individuals who underwent exercise or pharmacologic SE between 2003 and 2013. Reasons for SE included screening for CAD, preoperative evaluation, abnormal ECG, coronary calcification, and assessment of established CAD (defined as prior myocardial infarction or coronary revascularization). We grouped subjects using both the 10-year Framingham risk equation and ATP3-suggested categories of low-risk (&lt;10%), intermediate-risk (10-20%), and high-risk (&gt;20%) for non-diabetic subjects without known CAD and by ACC/AHA Pooled Cohort risk estimates for subjects with and without diabetes. Subjects with established CAD were considered separately. Abnormal echocardiograms were defined as having ischemic, fixed, or mixed defects. Results: The study population comprised 19,170 subjects; 63% men, mean±SD age was 64±13 years, and 52% underwent pharmacologic SE. The likelihood of abnormal SE results was proportional to risk, with the highest yield in those with established CAD (59%). Those with diabetes had a yield similar to those with a 10 year risk of 10-20% by both ATP3/FRS and ACC/AHA. Conclusions: SE abnormalities are commonly seen in asymptomatic individuals; the likelihood of abnormal SE results was proportional to patients’ estimated risk. The frequency of SE abnormalities in diabetic patients is similar to that of intermediate-risk, but not high-risk patients.
Ethnic differences in HSV1 and HSV2 seroprevalence in Amsterdam, the Netherlands
Authors: MA Kramer, DG Uitenbroek, JK Ujcic-Voortman, C Pfrommer, J Spaargaren, R  A Coutinho, NHTM Dukers-Muijrers
Journal: Eurosurveillance (2008)

Herpes simplex virus type 1 (HSV1) and 2 (HSV2) infection can lead to significant morbidity, and HSV2 is considered a risk factor for HIV transmission. The majority of HSV-infected people are asymptomatic and unaware of their infection. We aimed to determine the HSV1 and HSV2 prevalence among various ethnic groups in a large urban area in the Netherlands. In 2004, serum samples from a population-based serum repository of 1,325 people over 18 years living in Amsterdam were tested for HSV1 and HSV2 antibodies in order to determine high-risk groups. Prevalence ratios were estimated and all analyses were weighted by sex, age, and ethnicity. In the general population of Amsterdam, 67% had HSV1 antibodies, 22% had HSV2 antibodies, 15% had HSV1 and HSV2 antibodies, and 26% had no indication of HSV infection. In multivariate analyses, HSV1 seroprevalence increased with age, and was higher among people of Turkish and Moroccan origin, homosexual men, and individuals with low educational level. HSV2 seroprevalence was associated with increasing age, Surinamese/Antillean background, and having a history of sexually transmitted infections (STI). These differences between ethnic groups in Amsterdam regarding the distribution of HSV1 and HSV2 infection emphasise the importance of an ethnic-specific approach of serological testing as well as campaigns aimed at behavioural change and counselling to raise awareness of the risk of HSV transmission.
Abstract MP87: Association of Hemostasis Biomarkers with Intracerebral Hemorrhage: the REasons for Geographic and Racial Differences in Stroke Study (REGARDS)
Authors: Neil Zakai, Suzanne Judd, Nels Olson, Dawn Kleindorfer, Brett Kissela, George Howard, Mary Cushman
Journal: Circulation (2015)

Introduction:  Risk factors for intracerebral hemorrhage (ICH) are poorly characterized. Deficiencies of fibrinogen and factors VIII, IX, and XI cause bleeding disorders but whether these factors relate to ICH risk is unknown.   Methods:  REGARDS recruited 30,239 individuals ≥45 years from the contiguous US oversampling blacks (44%) and residents of the southeast (56%) from 2003-07. ICH were confirmed by medical record review. Biomarkers were measured in a case cohort study of ICH and a 1104 person cohort random sample. The hazard ratio (HR) and 95% confidence interval (CI) per standard deviation (SD) lower biomarker were estimated using Cox models adjusting for stroke risk factors (Table). Individuals on warfarin were excluded.   Results:  Over a median 5.8 years (Interquartile range 4.1, 7.0) 66 ICH occurred. Compared with participants without ICH, participants with ICH were older (67 vs 65 years), more likely male (62 vs 44%), had higher aspirin use (53 vs 44%), higher systolic blood pressure (135 vs 127mmHg), and a greater prevalence of cardiovascular disease (26 vs 16%), left ventricular hypertrophy (61 vs 51%), and a lower prevalence of atrial fibrillation (5 vs 7%); all p  112%), the lowest tertile (   Discussion:  Factor IX was associated with risk of ICH. As congenital factor IX deficiency is a bleeding disorder (hemophilia B), the observed gradation of risk, and the biologic plausibility, our results suggest a likely causal role for normal variation of factor IX levels and population ICH risk.
Variability of Organophosphorous Pesticide Metabolite Levels in Spot and 24-hr Urine Samples Collected from Young Children during 1 Week
Authors: Asa Bradman, Katherine Kogut, Ellen A. Eisen, Nicholas P. Jewell, Lesliam Quirós-Alcalá, Rosemary Castorina, Jonathan Chevrier, Nina T. Holland, Dana Boyd Barr, Geri Kavanagh-Baird, Brenda Eskenazi
Journal: Environmental Health Perspectives (2012)

Background: Dialkyl phosphate (DAP) metabolites in spot urine samples are frequently used to characterize children's exposures to organophosphorous (OP) pesticides. However, variable exposure and short biological half-lives of OP pesticides could result in highly variable measurements, leading to exposure misclassification.Objective: We examined within- and between-child variability in DAP metabolites in urine samples collected during 1 week.Methods: We collected spot urine samples over 7 consecutive days from 25 children (3–6 years of age). On two of the days, we collected 24-hr voids. We assessed the reproducibility of urinary DAP metabolite concentrations and evaluated the sensitivity and specificity of spot urine samples as predictors of high (top 20%) or elevated (top 40%) weekly average DAP metabolite concentrations.Results: Within-child variance exceeded between-child variance by a factor of two to eight, depending on metabolite grouping. Although total DAP concentrations in single spot urine samples were moderately to strongly associated with concentrations in same-day 24-hr samples (r ≈ 0.6–0.8, p < 0.01), concentrations in spot samples collected > 1 day apart and in 24-hr samples collected 3 days apart were weakly correlated (r ≈ –0.21 to 0.38). Single spot samples predicted high (top 20%) and elevated (top 40%) full-week average total DAP excretion with only moderate sensitivity (≈ 0.52 and ≈ 0.67, respectively) but relatively high specificity (≈ 0.88 and ≈ 0.78, respectively).Conclusions: The high variability we observed in children's DAP metabolite concentrations suggests that single-day urine samples provide only a brief snapshot of exposure. Sensitivity analyses suggest that classification of cumulative OP exposure based on spot samples is prone to type 2 classification errors.