tbuckley/cabot-search huggingface dataset:
Cardiovascular biomarkers predict susceptibility to lung injury in World Trade Center dust-exposed firefighters
Authors: Michael D. Weiden, Bushra Naveed, Sophia Kwon, Soo Jung Cho, Ashley L. Comfort, David J. Prezant, William N. Rom, Anna Nolan
Journal: European Respiratory Journal (2012)

Pulmonary vascular loss is an early feature of chronic obstructive pulmonary disease. Biomarkers of inflammation and of metabolic syndrome predict loss of lung function in World Trade Center (WTC) lung injury (LI). We investigated if other cardiovascular disease (CVD) biomarkers also predicted WTC-LI. This nested case–cohort study used 801 never-smoker, WTC-exposed firefighters with normal pre-9/11 lung function presenting for subspecialty pulmonary evaluation (SPE) before March 2008. A representative subcohort of 124 out of 801 subjects with serum drawn within 6 months of 9/11 defined CVD biomarker distribution. Post-9/11 forced expiratory volume in 1 s (FEV 1 ) at defined cases were as follows: susceptible WTC-LI cases with FEV 1 ≤77% predicted (66 out of 801) and resistant WTC-LI cases with FEV 1 ≥107% predicted (68 out of 801). All models were adjusted for WTC exposure intensity, body mass index at SPE, age on 9/11 and pre-9/11 FEV 1 . Susceptible WTC-LI cases had higher levels of apolipoprotein-AII, C-reactive protein and macrophage inflammatory protein-4 with significant relative risks (RRs) of 3.85, 3.93 and 0.26, respectively, with an area under the curve (AUC) of 0.858. Resistant WTC-LI cases had significantly higher soluble vascular cell adhesion molecule and lower myeloperoxidase, with RRs of 2.24 and 2.89, respectively (AUC 0.830). Biomarkers of CVD in serum 6 months post-9/11 predicted either susceptibility or resistance to WTC-LI. These biomarkers may define pathways either producing or protecting subjects from pulmonary vascular disease and associated loss of lung function after an irritant exposure.
ISOLATION OF SWINE-INFLUENZA-LIKE A(H1N1) VIRUSES FROM MAN IN EUROPE, 1986
Authors: J.C. De Jong, J.M. de Ronde-Verloop, P.J. Bangma, E. Van Kregten, J. Kerckhaert, M.F. Paccaud, F. Wicki, W. Wunderli
Journal: The Lancet (1986)
Ito cell contraction in response to endothelin-1 and substance P
Authors: Masaharu Sakamoto, Takato Ueno, Motoaki Kin, Hiromasa Ohira, Takuji Torimura, Sadataka Inuzuka, Michio Sata, Kyuichi Tanikawa
Journal: Hepatology (1993)

The contractile response of cultured Ito cells to endothelin-1 and substance P was examined. Ito cells were obtained from rat liver by perfusion with collagenase, followed by separation through centrifugal elutriation, and were cultured for 24 hr. The area of the Ito cells was measured after treatment with endothelin-1 or substance P at various concentrations in the culture medium. The area of the cells decreased dose dependently after treatment with endothelin-1 or substance P. The area of Ito cells before addition of interleukin-1 or substance P was defined as 100%. The area of the cells after treatment with endothelin-1 or substance P medium was expressed as the percentage against the area before treatment with endothelin-1 or substance P. The percentage in area after treatment with 200 nmol/L endothelin-1 was as follows: 81% +/- 13% at 30 min, 77% +/- 15% at 60 min, 87% +/- 15% at 120 min and 99% +/- 18% at 180 min. The maximal decrease in area occurred at 60 min after treatment. The percentage values for 200 nmol/L substance P were as follows: 88% +/- 15% at 10 min, 95% +/- 17% at 30 min and 101% +/- 17% at 60 min. The maximal decrease in area was noted at 10 min. Thus Ito cells contracted in response to treatment with endothelin-1 or substance P. The mode of the extent and onset of the contraction was different for the two peptides. These findings suggest that Ito cells are involved in the regulation of the hepatic sinusoidal microcirculation.
NIMA-Related Protein Kinase 1 Is Involved Early in the Ionizing Radiation-Induced DNA Damage Response
Authors: Rosaria Polci, Aimin Peng, Phang-Lang Chen, Daniel J. Riley, Yumay Chen
Journal: Cancer Research (2004)

Abstract Cellular functions of the NimA-related mammalian kinase Nek1 have not been demonstrated to date. Here we show that Nek1 is involved early in the DNA damage response induced by ionizing radiation (IR) and that Nek1 is important for cells to repair and recover from DNA damage. When primary or transformed cells are exposed to IR, Nek1 kinase activity is increased within 4 minutes, and Nek1 expression is up-regulated shortly thereafter and sustained for hours. At the same early time frame after IR that its kinase activity is highest, a portion of Nek1 redistributes in cells from cytoplasm to discrete nuclear foci at sites of DNA double-strand breaks. There it colocalizes with γ-H2AX and NFBD1/MDC1, two key proteins involved very early in the response to IR-induced DNA double-strand breaks. Finally, Nek1-deficient fibroblasts are much more sensitive to the effects of IR-induced DNA damage than otherwise identical fibroblasts expressing Nek1. These results suggest that Nek1 may function as a kinase early in the DNA damage response pathway.
Prevalence of Diabetes and Intermediate Hyperglycemia Among Adults From the First Multinational Study of Noncommunicable Diseases in Six Central American Countries
Authors: Alberto Barcelo, Edward W. Gregg, Robert B. Gerzoff, Roy Wong, Enrique Perez Flores, Manuel Ramirez-Zea, Elizabeth Cafiero, Lesbia Altamirano, Melanie Ascencio Rivera, Gerardo de Cosio, Martha Dinorah de Maza, Roberto del Aguila, Englebert Emanuel, Enrique Gil, Ethan Gough, Valerie Jenkins, Patrícia Orellana, Ruben Palma, Ruben Palomo, Martha Pastora, Rodolfo Peña, Elia Pineda, Bismark Rodriguez, Luis Tacsan, Loraine Thompson, Lucy Villagra
Journal: Diabetes Care (2012)

The increasing burdens of obesity and diabetes are two of the most prominent threats to the health of populations of developed and developing countries alike. The Central America Diabetes Initiative (CAMDI) is the first study to examine the prevalence of diabetes in Central America.The CAMDI survey was a cross-sectional survey based on a probabilistic sample of the noninstitutionalized population of five Central American populations conducted between 2003 and 2006. The total sample population was 10,822, of whom 7,234 (67%) underwent anthropometry measurement and a fasting blood glucose or 2-h oral glucose tolerance test.The total prevalence of diabetes was 8.5%, but was higher in Belize (12.9%) and lower in Honduras (5.4%). Of the screened population, 18.6% had impaired glucose tolerance/impaired fasting glucose.As this population ages, the prevalence of diabetes is likely to continue to rise in a dramatic and devastating manner. Preventive strategies must be quickly introduced.
Allogeneic Stem Cell–Derived “Repair Unit” Therapy and the Barriers to Clinical Deployment
Authors: Terry B Strom, Loren J Field, Manfred Ruediger
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. The development of cellular therapies has been seriously hampered by the paucity of cells available for grafting from living or cadaver donors. This sourcing problem can be resolved, at least in theory, by generating tissue-specific cells from autologous or allogeneic stem cells. Nonetheless, there are formidable barriers to the use of stem cells in the clinic. This review focuses on identifying and surmounting these barriers.
Beta-carotene inhibits atherosclerosis in hypercholesterolemic rabbits.
Authors: A Shaish, A Daugherty, F O'Sullivan, G Schonfeld, J W Heinecke
Journal: Journal of Clinical Investigation (1995)

Oxidatively damaged LDL may be of central importance in atherogenesis. Epidemiological evidence suggests that high dietary intakes of beta-carotene and vitamin E decreases the risk for atherosclerotic vascular disease, raising the possibility that lipid-soluble antioxidants slow vascular disease by protecting LDL from oxidation. To test this hypothesis, we fed male New Zealand White rabbits a high-cholesterol diet or the same diet supplemented with either 1% probucol, 0.01% vitamin E, 0.01% all-trans beta-carotene, or 0.01% 9-cis beta-carotene; then we assessed both the susceptibility of LDL to oxidation ex vivo and the extent of aortic atherosclerosis. As in earlier studies, probucol protected LDL from oxidation and inhibited lesion formation. In contrast, vitamin E modestly inhibited LDL oxidation but did not prevent atherosclerosis. While beta-carotene had no effect on LDL oxidation ex vivo, the all-trans isomer inhibited lesion formation to the same degree as probucol. Moreover, all-trans beta-carotene was undetectable in LDL isolated from rabbits fed the compound, although tissue levels of retinyl palmitate were increased. The effect of all-trans beta-carotene on atherogenesis can thus be separated from the resistance of LDL to oxidation, indicating that other mechanisms may account for the ability of this compound to prevent vascular disease. Our results suggest that metabolites derived from all-trans beta-carotene inhibit atherosclerosis in hypercholesterolemic rabbits, possibly via stereospecific interactions with retinoic acid receptors in the artery wall.
Treatment of severe, recalcitrant, chronic plaque psoriasis with fumaric acid esters: a prospective study
Authors: E.M. Wain, M.I. Darling, R.D. Pleass, J.N.W.N. Barker, C.H. Smith
Journal: British Journal of Dermatology (2009)

Fumaric acid esters (FAE) are used in Germany as a first-line systemic treatment for chronic plaque psoriasis, with proven efficacy and low toxicity. Their use in the U.K. is variable, and they remain unlicensed. Consequently, efficacy and safety data from U.K. patients is limited and their place in the psoriasis treatment armamentarium is unclear.To examine the efficacy and safety of FAE in a prospective cohort of U.K. patients with severe, treatment-recalcitrant, chronic plaque psoriasis.A single-centre, open, nonrandomized, prospective study was performed in a regional referral centre for patients with severe psoriasis. Outcomes were measured by the Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI), blood investigations and adverse events monitoring.Eighty patients were recruited. Fifty-nine per cent were taking a concomitant oral antipsoriatic agent; 20% achieved a PASI-50, 8% a PASI-75 and 4% a PASI-90 on intention-to-treat analysis at 3 months with an overall, statistically significant, reduction in PASI from 13.9 + or - 9.0 to 11.3 + or - 9.2 (P < 0.0001). At 3 months, lymphopenia was seen in 33% of the cohort with significantly lower counts in patients responsive to FAE (P = 0.008). In addition, by 3 months, 36% of concomitant antipsoriatic medication had been stopped and 25% of doses had been reduced without loss of disease control. Side-effects (most commonly diarrhoea, abdominal pain and flushing) were reported by 74% of patients resulting in cessation of FAE in 36%.FAE is a useful alternative treatment option in patients with severe, treatment-resistant, chronic plaque psoriasis and can allow dose reduction, and subsequent cessation, of other, potentially more toxic agents.
Body Fat Distribution and Risk of Premenopausal Breast Cancer in the Nurses' Health Study II
Authors: H. R. Harris, W. C. Willett, K. L. Terry, K. B. Michels
Journal: JNCI Journal of the National Cancer Institute (2010)

Body mass index is inversely associated with risk of premenopausal breast cancer, but the underlying mechanisms for this association are poorly understood. Abdominal adiposity is associated with metabolic and hormonal changes, many of which have been associated with the risk of premenopausal breast cancer. We investigated the association between body fat distribution, assessed in 1993 by self-reported waist circumference, hip circumference, and waist to hip ratio, and the incidence of premenopausal breast cancer in the Nurses' Health Study II. Cox proportional hazards regression models were used to calculate hazard ratios and 95% confidence intervals (CIs). Statistical tests were two-sided. During 426 164 person-years of follow-up from 1993 to 2005, 620 cases of breast cancer were diagnosed among 45 799 women. Hormone receptor status information was available for 84% of the breast cancers. The age-standardized incidence rates of breast cancer were 131 per 100 000 person-years among those in the lowest quintile of waist circumference and 136 per 100 000 person-years among those in the highest quintile. No statistically significant associations were found between waist circumference, hip circumference, or the waist to hip ratio and risk of breast cancer. However, each of the three body fat distribution measures was statistically significantly associated with greater incidence of estrogen receptor (ER)–negative breast cancer. The multivariable-adjusted hazard ratios of ER-negative breast cancer for the highest vs the lowest quintile of each body fat distribution measure were 2.75 (95% CI = 1.15 to 6.54; Ptrend = .05) for waist circumference, 2.40 (95% CI = 0.95 to 6.08; Ptrend = .26) for hip circumference, and 1.95 (95% CI = 1.10 to 3.46; Ptrend = .01) for waist to hip ratio. Our findings suggest that body fat distribution does not play an important role in the overall incidence of premenopausal breast cancer but is associated with an increased risk for ER-negative breast cancer.
Effects of an intensive behavioral weight loss intervention consisting of caloric restriction with or without physical activity on common carotid artery remodeling in severely obese adults
Authors: Jennifer N. Cooper, Mindy L. Columbus, Kelly J. Shields, Julius Asubonteng, Michelle L. Meyer, Kim Sutton-Tyrrell, Bret H. Goodpaster, James P. DeLany, John M. Jakicic, Emma Barinas-Mitchell
Journal: Metabolism (2012)
Effect of salmeterol on respiratory muscle activity during exercise in poorly reversible COPD
Authors: W D C Man
Journal: Thorax (2004)

<b>Background:</b> Some patients with irreversible chronic obstructive pulmonary disease (COPD) experience subjective benefit from long acting bronchodilators without change in forced expiratory volume in 1 second (FEV<sub>1</sub>). Dynamic hyperinflation is an important determinant of exercise induced dyspnoea in COPD. We hypothesised that long acting bronchodilators improve symptoms by reducing dynamic hyperinflation and work of breathing, as measured by respiratory muscle pressure-time products. <b>Methods:</b> Sixteen patients with "irreversible" COPD (&lt;10% improvement in FEV<sub>1</sub> following a bronchodilator challenge; mean FEV<sub>1</sub> 31.1% predicted) were recruited into a randomised, double blind, placebo controlled, crossover study of salmeterol (50 μg twice a day). Treatment periods were of 2 weeks duration with a 2 week washout period. Primary outcome measures were end exercise isotime transdiaphragmatic pressure-time product and dynamic hyperinflation as measured by inspiratory capacity. <b>Results:</b> Salmeterol significantly reduced the transdiaphragmatic pressure-time product (294.5 <i>v</i> 348.6 cm H<sub>2</sub>O/s/min; p = 0.03), dynamic hyperinflation (0.22 <i>v</i> 0.33 litres; p = 0.002), and Borg scores during endurance treadmill walk (3.78 <i>v</i> 4.62; p = 0.02). There was no significant change in exercise endurance time. Improvements in isotime Borg score were significantly correlated to changes in tidal volume/oesophageal pressure swings, end expiratory lung volume, and inspiratory capacity, but not pressure-time products. <b>Conclusions:</b> Despite apparent "non-reversibility" in spirometric parameters, long acting bronchodilators can cause both symptomatic and physiological improvement during exercise in severe COPD.
Early Loss of the Glucagon Response to Hypoglycemia in Adolescents With Type 1 Diabetes
Authors: Aris Siafarikas, Robert J. Johnston, Max K. Bulsara, Peter O’Leary, Timothy W. Jones, Elizabeth A. Davis
Journal: Diabetes Care (2012)

To assess the glucagon response to hypoglycemia and identify influencing factors in patients with type 1 diabetes compared with nondiabetic control subjects.Hyperinsulinemic hypoglycemic clamp studies were performed in all participants. The glucagon response to both hypoglycemia and arginine was measured, as well as epinephrine, cortisol, and growth hormone responses to hypoglycemia. Residual β-cell function was assessed using fasting and stimulated C-peptide.Twenty-eight nonobese adolescents with type 1 diabetes (14 female, mean age 14.9 years [range 11.2-19.8]) and 12 healthy control subjects (6 female, 15.3 years [12.8-18.7]) participated in the study. Median duration of type 1 diabetes was 0.66 years (range 0.01-9.9). The glucagon peak to arginine stimulation was similar between groups (P = 0.27). In contrast, the glucagon peak to hypoglycemia was reduced in the group with diabetes (95% CI): 68 (62-74) vs. 96 (87-115) pg/mL (P < 0.001). This response was greater than 3 SDs from baseline for only 7% of subjects with type 1 diabetes in comparison with 83% of control subjects and was lost at a median duration of diabetes of 8 months and as early as 1 month after diagnosis (R = -0.41, P < 0.01). There was no correlation in response with height, weight, BMI, and HbA(1c). Epinephrine, cortisol, and growth hormone responses to hypoglycemia were present in both groups.The glucagon response to hypoglycemia in adolescents with type 1 diabetes is influenced by the duration of diabetes and can be lost early in the course of the disease.
Widespread cutaneous necrosis and antiphospholipid antibodies: Two episodes related to surgical manipulation and urinary tract infection
Authors: L.F. Del Castillo, C. Soria, C. Schoendorff, C.Garcia Garcia, N. Diez-Caballero, A.Rodriguez Alen, A.I. Saez, S. Urrutia, D.Garcia Almagro
Journal: Journal of the American Academy of Dermatology (1997)
Human CD1-restricted T cell recognition of lipids from pollens
Authors: Elisabetta Agea, Anna Russano, Onelia Bistoni, Roberta Mannucci, Ildo Nicoletti, Lanfranco Corazzi, Anthony D. Postle, Gennaro De Libero, Steven A. Porcelli, Fabrizio Spinozzi
Journal: The Journal of Experimental Medicine (2005)

Plant pollens are an important source of environmental antigens that stimulate allergic responses. In addition to acting as vehicles for foreign protein antigens, they contain lipids that incorporate saturated and unsaturated fatty acids, which are necessary in the reproduction of higher plants. The CD1 family of nonpolymorphic major histocompatibility complex-related molecules is highly conserved in mammals, and has been shown to present microbial and self lipids to T cells. Here, we provide evidence that pollen lipids may be recognized as antigens by human T cells through a CD1-dependent pathway. Among phospholipids extracted from cypress grains, phosphatidyl-choline and phosphatidyl-ethanolamine were able to stimulate the proliferation of T cells from cypress-sensitive subjects. Recognition of phospholipids involved multiple cell types, mostly CD4(+) T cell receptor for antigen (TCR)alphabeta(+), some CD4(-)CD8(-) TCRgammadelta(+), but rarely Valpha24i(+) natural killer-T cells, and required CD1a(+) and CD1d(+) antigen presenting cell. The responding T cells secreted both interleukin (IL)-4 and interferon-gamma, in some cases IL-10 and transforming growth factor-beta, and could provide help for immunoglobulin E (IgE) production. Responses to pollen phospholipids were maximally evident in blood samples obtained from allergic subjects during pollinating season, uniformly absent in Mycobacterium tuberculosis-exposed health care workers, but occasionally seen in nonallergic subjects. Finally, allergic, but not normal subjects, displayed circulating specific IgE and cutaneous weal and flare reactions to phospholipids.
Nerve growth factor enhances Clara cell proliferation after lung injury
Authors: S. S. Sonar, D. Schwinge, A. Kilic, A. O. Yildirim, M. L. Conrad, K. Seidler, B. Muller, H. Renz, W. A. Nockher
Journal: European Respiratory Journal (2010)

The lung epithelia facilitate wound closure by secretion of various cytokines and growth factors. Nerve growth factor (NGF) has been well described in airway inflammation; however, its likely role in lung repair has not been examined thus far. To investigate the repair function of NGF, experiments were performed <i>in vitro</i> using cultured alveolar epithelial cells and <i>in vivo</i> using a naphthalene-induced model of Clara epithelial cell injury. Both <i>in vitro</i> and <i>in vivo</i> experiments revealed airway epithelial cell proliferation following injury to be dependent on NGF and the expression of its receptor, tropomyosin-receptor-kinase A. Additionally, NGF also augmented <i>in vitro</i> migration of alveolar type II cells. <i>In vivo</i>, transgenic mice over-expressing NGF in Clara cells (NGFtg) did not reveal any proliferation or alteration in Clara cell phenotype. However, following Clara cell specific injury, proliferation was increased in NGFtg and impaired upon inhibition of NGF. Furthermore, NGF also promoted the expression of collagen I and fibronectin <i>in vitro</i> and <i>in vivo</i> during repair, where significantly higher levels were measured in re-epithelialising NGFtg mice. Our study demonstrates that NGF promotes the proliferation of lung epithelium <i>in vitro</i> and the renewal of Clara cells following lung injury <i>in vivo</i>.
Vaccination of risk groups in England using the 13 valent pneumococcal conjugate vaccine: economic analysis
Authors: M. H. Rozenbaum, A. J. van Hoek, D. Fleming, C. L. Trotter, E. Miller, W. J. Edmunds
Journal: BMJ (2012)

<b>Objective</b> To estimate the cost effectiveness of vaccinating people with high risk conditions against invasive pneumococcal disease using the 13 valent pneumococcal conjugate vaccine. <b>Design</b> Economic evaluation using a cohort model from the perspective of healthcare providers. <b>Setting</b> England. <b>Participants</b> People aged 2 years and older at increased risk of invasive pneumococcal disease due to chronic kidney disease; splenic dysfunction; HIV infection; a compromised immune system; chronic heart, liver, or respiratory disease; or diabetes. <b>Main outcome measures</b> Costs, gains in life years and quality adjusted life years (QALYs), and incremental cost effectiveness ratios. <b>Results</b> Increasing indirect protection resulting from the vaccination programme of infants using the 13 valent pneumococcal conjugate vaccine means that the burden of disease preventable by targeting high risk groups will diminish in time. Under base case assumptions—that is, no overall impact on non bacteraemic pneumonia in high risk groups and assuming the high risk vaccination programme would be launched two to three years after the infant programme—the incremental cost effectiveness ratio was estimated to be more than £30 000 (€37 216; $48 210) per QALY gained for most risk groups. If, however, the vaccine does not offer protection against non-bacteraemic pneumococcal pneumonia or the vaccine was introduced concomitantly with the infant 13 valent pneumococcal conjugate vaccination programme then vaccinating high risk people would (more) likely be cost effective. Sensitivity analyses showed that the cost effectiveness was particularly sensitive to assumed herd benefits and vaccine efficacy estimates. <b>Conclusion</b> Under base case assumptions it is unlikely that a pneumococcal vaccination programme aimed at risk groups could be considered cost effective. Uncertainty could be substantially reduced by establishing the effectiveness of the 13 valent pneumococcal conjugate vaccine against non-bacteraemic pneumococcal pneumonia, particularly in at risk groups.