tbuckley/cabot-search huggingface dataset:
Acute effect of cigarette smoke on human bronchial epithelial cell metabolome is reversible by UPF1
Authors: Argo Aug, Siiri Altraja, Kalle Kilk, Liisi Laaniste, Riina Mahlapuu, Ursel Soomets, Alan Altraja
Journal: European Respiratory Journal (2013)

We assessed protective capacity of glutathione analogue UPF1 (4-methoxy-L-tyrosinyl-γ-L-glutamyl-L-cysteinyl-glycine) against cigarette smoke condensate (CSC)-induced alterations in metabolic profile of human bronchial epithelial cells (HBEC).  HBEC were exposed to 10 μg/mL CSC for 1 h, followed by treatment with 0-10 μM UPF1 or 2 mM N-acetylcysteine (NAC) for 1-12 h. Cell lysates were analysed on a Q-Trap 3200 mass spectrometer to obtain spectra between m/z ratios of 50-1700 Da. The data were subjected to principal component analysis, ANOVA, Pearson correlation analysis and hierarchical clustering.  CSC affected the highest number of signals at 2 h (245 signals, 13.4%). Signals affected by CSC with/without UPF1 or NAC formed 3 major clusters of metabolites that followed similar changing pattern within each cluster over time. In cluster 1, CSC caused a significant decrease of signals within 4 h, which was initially inverted by UPF1, before the signals returned to baseline. In contrast to UPF1, NAC had no redeeming effect. Among metabolites in cluster 1 species of phosphatidylcholines were identified using public databases. Signals of cluster 2 were decreased by CSC before returning to baseline after 4 h, followed by prolonged up-regulation by both UPF1 and NAC. Glutamine and glutamic acid were among the metabolites identified in cluster 2. Signals in cluster 3 were elevated by CSC and inverted by UPF1 and NAC showing a negative correlation with cluster 1 (r=-0.5).  UPF1 effectively inverts the immediate effect of CSC on certain metabolites and may thus provide basis for designing drugs for protecting HBEC to slow down the development of COPD.  Supported by ESF grants 7856, 9043, 9103.
Cancer mortality and atenolol treatment.
Authors: A E Fletcher, D G Beevers, C J Bulpitt, E C Coles, C T Dollery, J G Ledingham, A J Palmer, J C Petrie, J Webster
Journal: BMJ (1993)

hypertensive patients.'In this study nifedipine plus diuretic lowered blood pressure more effectively than propranolol plus diuretic, which has previously been shown to be effective in black hypertensive patients.2Although comparisons of fixed doses of drugs have limitations, the doses of propranolol and nifedipine used were in the middle of their therapeutic ranges.Experience in Kenyan hypertension clinics confirms reports that black hypertensive patients have lower plasma renin activities than white patients.Perhaps because of this, we found nifedipine plus diuretic to be an excellent combination for treating hypertension among black Kenyan patients.This study was sponsored by the Wellcome Trust.We thank Dr M Hills for his advice regarding analyses.
Pancreatic β Cell–specific Expression of Thioredoxin, an Antioxidative and Antiapoptotic Protein, Prevents Autoimmune and Streptozotocin-induced Diabetes
Authors: Mizuo Hotta, Fumi Tashiro, Hiroshi Ikegami, Hitoshi Niwa, Toshio Ogihara, Junji Yodoi, Jun-ichi Miyazaki
Journal: The Journal of Experimental Medicine (1998)

The cytotoxicity of reactive oxygen intermediates (ROIs) has been implicated in the destruction of pancreatic β cells in insulin-dependent diabetes mellitus (IDDM). Thioredoxin (TRX), a redox (reduction/oxidation)-active protein, has recently been shown to protect cells from oxidative stress and apoptosis. To elucidate the roles of oxidative stress in the development of autoimmune diabetes in vivo, we produced nonobese diabetic transgenic mice that overexpress TRX in their pancreatic β cells. In these transgenic mice, the incidence of diabetes was markedly reduced, whereas the development of insulitis was not prevented. Moreover, induction of diabetes by streptozotocin, an ROI-generating agent, was also attenuated by TRX overexpression in β cells. This is the first direct demonstration that an antioxidative and antiapoptotic protein protects β cells in vivo against both autoimmune and drug-induced diabetes. Our results strongly suggest that oxidative stress plays an essential role in the destruction of β cells by infiltrating inflammatory cells in IDDM.
Dietary cholesterol withdrawal reduces vascular inflammation and induces coronary plaque stabilization in miniature pigs
Authors: P Verhamme
Journal: Cardiovascular Research (2002)

Objective: To study the effect of dietary cholesterol withdrawal on size and composition of LDL-hypercholesterolemia-induced coronary plaques in miniature pigs. Methods: Pigs were on normal chow (control group), on a cholesterol-rich diet for 37 weeks (hypercholesterolemic group) or on a cholesterol-rich diet followed by normal chow for 26 weeks (cholesterol withdrawal group). Endothelial function was assessed with quantitative angiography after intracoronary infusion of acetylcholine, plaque load with intra-coronary ultrasound and plaque composition with image analysis of cross-sections. The effect of porcine serum on coronary smooth muscle cell (SMC) function was studied in vitro. Results: Cholesterol-rich diet caused LDL-hypercholesterolemia, increased plasma levels of oxidized LDL (ox-LDL) and C-reactive protein (CRP), and induced endothelial dysfunction and coronary atherosclerosis. Dietary cholesterol withdrawal lowered LDL, ox-LDL and CRP. It restored endothelial function, did not affect plaque size but decreased lipid, ox-LDL and macrophage content. Smooth muscle cells and collagen accumulated within the plaque. Increased smoothelin-to-α-smooth muscle actin ratio indicated a more differentiated SMC phenotype. Cholesterol lowering reduced proliferation and apoptosis. In vitro, hypercholesterolemic serum increased SMC apoptosis and decreased SMC migration compared to non-hypercholesterolemic serum. Conclusions: Cholesterol lowering induced coronary plaque stabilization as evidenced by a decrease in lipids, ox-LDL, macrophages, apoptosis and cell proliferation, and an increase in differentiated SMC and collagen. Increased migration and decreased apoptosis of SMC may contribute to the disappearance of the a-cellular core after lipid lowering.
Dendritic-cell therapy after non-myeloablative stem-cell transplantation for renal-cell carcinoma
Authors: Katsunori Tatsugami, Masatoshi Eto, Masahiko Haarano, Koji Nagafuji, Kazuya Omoto, Mitsuo Katano, Mine Harada, Seiji Naito
Journal: The Lancet Oncology (2004)
Sunitinib Versus Sorafenib in Advanced Hepatocellular Cancer: Results of a Randomized Phase III Trial
Authors: Ann-Lii Cheng, Yoon-Koo Kang, Deng-Yn Lin, Joong-Won Park, Masatoshi Kudo, Shukui Qin, Hyun-Cheol Chung, Xiangqun Song, Jianming Xu, Guido Poggi, Masao Omata, Susan Pitman Lowenthal, Silvana Lanzalone, Liqiang Yang, Maria Jose Lechuga, Eric Raymond
Journal: Journal of Clinical Oncology (2013)

Purpose Open-label, phase III trial evaluating whether sunitinib was superior or equivalent to sorafenib in hepatocellular cancer. Patients and Methods Patients were stratified and randomly assigned to receive sunitinib 37.5 mg once per day or sorafenib 400 mg twice per day. Primary end point was overall survival (OS). Results Early trial termination occurred for futility and safety reasons. A total of 1,074 patients were randomly assigned to the study (sunitinib arm, n = 530; sorafenib arm, n = 544). For sunitinib and sorafenib, respectively, median OS was 7.9 versus 10.2 months (hazard ratio [HR], 1.30; one-sided P = .9990; two-sided P = .0014); median progression-free survival (PFS; 3.6 v 3.0 months; HR, 1.13; one-sided P = .8785; two-sided P = .2286) and time to progression (TTP; 4.1 v 3.8 months; HR, 1.13; one-sided P = .8312; two-sided P = .3082) were comparable. Median OS was similar among Asian (7.7 v 8.8 months; HR, 1.21; one-sided P = .9829) and hepatitis B–infected patients (7.6 v 8.0 months; HR, 1.10; one-sided P = .8286), but was shorter with sunitinib in hepatitis C–infected patients (9.2 v 17.6 months; HR, 1.52; one-sided P = .9835). Sunitinib was associated with more frequent and severe adverse events (AEs) than sorafenib. Common grade 3/4 AEs were thrombocytopenia (29.7%) and neutropenia (25.7%) for sunitinib; hand-foot syndrome (21.2%) for sorafenib. Discontinuations owing to AEs were similar (sunitinib, 13.3%; sorafenib, 12.7%). Conclusion OS with sunitinib was not superior or equivalent but was significantly inferior to sorafenib. OS was comparable in Asian and hepatitis B–infected patients. OS was superior in hepatitis C–infected patients who received sorafenib. Sunitinib-treated patients reported more frequent and severe toxicity.
Structural analysis of human Ia antigens reveals the existence of a fourth molecular subset distinct from DP, DQ, and DR molecules.
Authors: G Carra, R S Accolla
Journal: The Journal of Experimental Medicine (1987)

Structural analysis by two-dimensional peptide maps (2D-PM) of the human Ia molecular pool expressed on the cell surface of two distinct lymphoblastoid cell line, LG-2 and Raji, revealed the existence of a novel MHC class II molecular heterodimer that differs at the level of both alpha and beta subunits from the previously described DP, DQ, and DR antigens. These differences were also seen at the level of two-dimensional electrophoresis (2D-PAGE) of biosynthetically labeled intact molecules, although to a lesser extent, due to the intrinsic limitations of this technique in resolving fine structural differences. We have designated this new class II antigen as the fourth Ia subset. The fourth Ia subset seems to represent a small proportion of the human Ia pool. Comparative analysis by 2D-PM of the two cell lines showed the presence of structural variations in the alpha chains of the fourth Ia subset, suggesting the existence of polymorphism for these subunits. Cell surface iodination did not show appreciable labeling of the fourth subset beta chain in LG-2 cells, and this prevented analysis of the structural polymorphism of this subunit. Furthermore, for the first time, we have shown that DP alpha chains display distinct peptide maps in LG-2 and Raji cells, thus suggesting the presence of structural polymorphism for these Ia subunits also. The DQ1 alpha and beta allelic products present in LG-2 cells (DQ homozygous) did not show appreciable structural variation when compared with the homologous allelic products present in Raji cells (DQ heterozygous). Finally, we have confirmed the absence of polymorphism for the DR alpha subunits. By 2D-PM, relatively low structural variation was instead found for the highly polymorphic DR beta subunits expressed in the two cell lines, suggesting that cell surface iodination preferentially labels constant domains of DR beta chains.
Brainstem Serotonergic Deficiency in Sudden Infant Death Syndrome
Authors: Jhodie R. Duncan
Journal: JAMA (2010)

Sudden infant death syndrome (SIDS) is postulated to result from abnormalities in brainstem control of autonomic function and breathing during a critical developmental period. Abnormalities of serotonin (5-hydroxytryptamine [5-HT]) receptor binding in regions of the medulla oblongata involved in this control have been reported in infants dying from SIDS.To test the hypothesis that 5-HT receptor abnormalities in infants dying from SIDS are associated with decreased tissue levels of 5-HT, its key biosynthetic enzyme (tryptophan hydroxylase [TPH2]), or both.Autopsy study conducted to analyze levels of 5-HT and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA); levels of TPH2; and 5-HT(1A) receptor binding. The data set was accrued between 2004 and 2008 and consisted of 41 infants dying from SIDS (cases), 7 infants with acute death from known causes (controls), and 5 hospitalized infants with chronic hypoxia-ischemia.Serotonin and metabolite tissue levels in the raphé obscurus and paragigantocellularis lateralis (PGCL); TPH2 levels in the raphé obscurus; and 5-HT(1A) binding density in 5 medullary nuclei that contain 5-HT neurons and 5 medullary nuclei that receive 5-HT projections.Serotonin levels were 26% lower in SIDS cases (n = 35) compared with age-adjusted controls (n = 5) in the raphé obscurus (55.4 [95% confidence interval {CI}, 47.2-63.6] vs 75.5 [95% CI, 54.2-96.8] pmol/mg protein, P = .05) and the PGCL (31.4 [95% CI, 23.7-39.0] vs 40.0 [95% CI, 20.1-60.0] pmol/mg protein, P = .04). There was no evidence of excessive 5-HT degradation assessed by 5-HIAA levels, 5-HIAA:5-HT ratio, or both. In the raphé obscurus, TPH2 levels were 22% lower in the SIDS cases (n = 34) compared with controls (n = 5) (151.2% of standard [95% CI, 137.5%-165.0%] vs 193.9% [95% CI, 158.6%-229.2%], P = .03). 5-HT(1A) receptor binding was 29% to 55% lower in 3 medullary nuclei that receive 5-HT projections. In 4 nuclei, 3 of which contain 5-HT neurons, there was a decrease with age in 5-HT(1A) receptor binding in the SIDS cases but no change in the controls (age x diagnosis interaction). The profile of 5-HT and TPH2 abnormalities differed significantly between the SIDS and hospitalized groups (5-HT in the raphé obscurus: 55.4 [95% CI, 47.2-63.6] vs 85.6 [95% CI, 61.8-109.4] pmol/mg protein, P = .02; 5-HT in the PGCL: 31.4 [95% CI, 23.7-39.0] vs 71.1 [95% CI, 49.0-93.2] pmol/mg protein, P = .002; TPH2 in the raphé obscurus: 151.2% [95% CI, 137.5%-165.0%] vs 102.6% [95% CI, 58.7%-146.4%], P = .04).Compared with controls, SIDS was associated with lower 5-HT and TPH2 levels, consistent with a disorder of medullary 5-HT deficiency.
Interleukin-1β gene polymorphisms associated with hepatocellular carcinoma in hepatitis C virus infection
Authors: Yue Wang, Naoya Kato, Yujin Hoshida, Hideo Yoshida, Hiroyoshi Taniguchi, Tadashi Goto, Masaru Moriyama, Motoyuki Otsuka, Shuichiro Shiina, Yasushi Shiratori, Yoichi Ito, Masao Omata
Journal: Hepatology (2003)

Hepatitis C virus (HCV) infection is a major risk factor for developing hepatocellular carcinoma (HCC), a life-threatening sequel. However, the factors that affect disease progression to HCC have not been thoroughly elucidated. Genetic polymorphisms in proinflammatory cytokines, the interleukin 1 (IL-1) family (IL-1β and IL-1ra) and tumor necrosis factor-α (TNF-α), were studied in 274 Japanese patients with chronic HCV infection and 55 healthy individuals using standard polymerase chain reaction-based genotyping techniques. The association between these polymorphisms and disease status was evaluated while controlling for confounding clinical variables. The proportion of patients with HCC in the IL-1β-31 T/T (55%, odds ratio to C/C was 2.63, P = .009) genotype was higher than in the T/C (44%, odds ratio to C/C was 1.64, P = .149) and C/C genotypes (35%). The IL-1β-31 and -511 loci were in near complete linkage disequilibrium, and the IL-1β-511/-31 haplotype C-T was significantly associated with the presence of HCC (odds ratio of 1.51, P = .02). Polymorphisms in the TNF-α gene were not associated with disease. A multivariate analysis revealed that the IL-1β-31 T/T genotype, α-fetoprotein &gt;20 μg/L, presence of cirrhosis, male sex, and age &gt;60 years were associated with the presence of HCC at odds ratios of 3.73 (T/T vs. C/C), 4.12, 4.03, 3.89, and 3.27, respectively. In conclusion, the IL-1β-31 genotype T/T or the IL-1β-511/-31 haplotype C-T is associated with the presence of HCC in Japanese patients with chronic HCV infection.
Polymerase chain reaction amplification applied to the direct detection of a 4 bp deletion in the promoter region of the <sup>A</sup>γ gene
Authors: Laura Manca, Elena Cocco, Bruno Masala, John G. Gilman
Journal: American Journal of Hematology (1990)

Abstract We report here the identification of a 4 bp deletion in the A γ T globin gene promoter by means of Fnu4Hl digestion of DNA amplified by polymerase chain reaction (PCR). This deletion has been previously associated with haplotype II β‐thalassemia in Sardinia. This simple, non‐radioactive procedure should facilitate the screening of various populations of normal and β‐thalassemic subjects for this specific genetic alteration.
<i>EWSR1-CREB1</i> and <i>EWSR1-ATF1</i> Fusion Genes in Angiomatoid Fibrous Histiocytoma
Authors: Sabrina Rossi, Kàroly Szuhai, Marije Ijszenga, Hans J. Tanke, Lucia Zanatta, Raf Sciot, Christopher D.M. Fletcher, Angelo P. Dei Tos, Pancras C.W. Hogendoorn
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Angiomatoid fibrous histiocytoma (AFH) is a low-grade mesenchymal neoplasm which usually occurs in children and adolescents. Either FUS-ATF1 or EWSR1-ATF1 have been detected in the few cases published, pointing to the interchangeable role of FUS and EWSR1 in this entity. EWSR1-ATF1 also represents the most frequent genetic alteration in clear cell sarcoma, suggesting the existence of a molecular homology between these two histotypes. We investigated the presence of EWSR1-CREB1, recently found in gastrointestinal clear cell sarcoma, and FUS-CREB1, as well as the already reported FUS-ATF1 and EWSR1-ATF1 in a series of AFH. Experimental Design: Fourteen cases were analyzed by fluorescence in situ hybridization (FISH) on paraffin-embedded tissue sections, using a commercial EWSR1 probe and custom-designed probes for FUS, ATF1, and CREB1. In two cases, four-color FISH was also done. Reverse transcription-PCR for the four hypothetical fusion genes was done in one case, for which frozen material was available. Results: Thirteen cases showed rearrangements of both EWSR1 and CREB1, whereas one case showed the rearrangement of both EWSR1 and ATF1. Four-color FISH confirmed the results in two selected cases. Reverse transcription-PCR showed EWSR1-CREB1 transcript in the case analyzed. Conclusion: We identified the presence of either EWSR1-CREB1 or EWSR1-ATF1 in all the cases, strengthening the concept of chromosomal promiscuity between AFH and clear cell sarcoma. Either the occurrence of a second unknown tumor-specific molecular event or, perhaps more likely, divergent differentiation programs of the putatively distinct precursor cells of AFH and clear cell sarcoma might be invoked in order to explain the two different phenotypes.
The Relationship Between the Health Belief Model and Compliance of Persons with Diabetes Mellitus
Authors: Kathy A Bloom Cerkoney, Laura K Hart
Journal: Diabetes Care (1980)

Thirty insulin-treated diabetic individuals were interviewed in their homes 6–12 mo after having attended diabetic education classes at a community hospital. Self-report as well as direct observation were used to measure these patients' level of compliance with their insulin administration, urine testing, diet, hypoglycemia management, and foot care prescriptions. All patients were complying with at least 59% of the points measured. Over one-half of the group indicated compliance with at least 70% of the 61 points measured. However, only 7% complied with every one of the 45 points considered to be necessary for good control of their disease. The group was most compliant with regard to insulin administration and least compliant regarding urine testing. The level of these patients' beliefs regarding their disease (severity and susceptibility, treatment benefits, and barriers) and cues to action were also measured. A correlation of 0.5 occurred between these patients' overall compliance levels and a composit of their level of health belief motivation. The highest levels of correlations between the areas of compliance and the motivators occurred with cues to action.
A neutrophil elastase inhibitor reduces cigarette smoke-induced remodelling of lung vessels
Authors: J.L. Wright, S.G. Farmer, A. Churg
Journal: European Respiratory Journal (2003)

Cigarette smoking produces pulmonary hypertension (PHT) through unknown mechanisms. In animal models acute smoke exposure induces cell proliferation in the small arteries adjacent to the alveolar ducts, and chronic exposure results in muscularisation of these vessels, with changes related to the development of PHT. Studies indicate that serine-elastase inhibitors can prevent experimental monocrotaline-induced PHT. This study examined whether they could also prevent cigarette smoke-induced pulmonary vascular disease. Guinea-pigs were exposed to cigarette smoke or air for 6 months. Some animals also received ZD0892, an orally active, synthetic, selective, serine-elastase inhibitor. The percentage of muscularised, small, pulmonary arteries was determined by morphometric analysis of histological sections and vascular cell proliferation by proliferating cell nuclear antigen staining. Vascular cell proliferation was markedly increased in the smoke-exposed animals and the percentage of completely muscularised small vessels was increased four-fold. Cell proliferation indices correlated with muscularisation indices. In the animals treated with ZD0892, the number of completely muscularised vessels was reduced by 50% and cell proliferation was reduced by 61%. These data suggest that smoke-induced cell proliferation leads to pulmonary arterial muscularisation. Serine-elastase inhibitors appear to be able to reduce cell proliferation and vascular remodelling.
Impaired Glucose Tolerance and its Relationship to ECG-Indicated Coronary Heart Disease and Risk Factors Among Chinese: Da Qing IGT and diabetes study
Authors: Xiao-Ren Pan, Ying-Hua Hu, Gung-Wie Li, Ping-Am Liu, Peter H Bennett, Barbara V Howard
Journal: Diabetes Care (1993)

Objective— To determine the prevalence of IGT and diabetes and identify the occurrence of CVD and its risk factors. Research Design and Methods— This study was a population-based, cross-sectional study of 110,660 residents, 25–74 yr of age of DaQing, Hei Long Jiang Province, China. Results— Using 1985 WHO criteria, 577 (5.5/1000) subjects with IGT and 630 (6.0/1000) with newly diagnosed diabetes were identified. In addition, 190 (1.7/1000) with previously known diabetes were identified. Hypertension, obesity, and abnormal albumin excretion were twice as frequent in those with IGT as in 279 men and 240 women of similar age and sex distribution who had normal OGTTs. Plasma cholesterol and TGs were higher, and HDL cholesterol was lower in subjects with IGT than in nondiabetic subjects. Those with IGT had a prevalence of electrocardiographically recognized CHD 9.5-fold greater than the normoglycemic subjects. Subjects with IGT had higher plasma insulin concentrations, but the 1-h insulin-glucose ratio after the 75-g glucose load was lower. In a forward stepwise multiple logistic regression analysis, IGT itself remained an independent factor associated with CHD after adjustment for age, sex, cigarette smoking, plasma cholesterol, BP, and obesity. Conclusions— Therefore, in China, IGT may occur with almost as high a frequency as diabetes and is accompanied by an increased frequency of CVD and its risk factors. Estimates from this study indicate that &amp;gt;12.0% of all ECG-indicated CHD in the Da Qing population occurs in individuals with IGT and NIDDM. The IGT subjects identified in this survey form the cohort for a long-term follow-up and intervention study.