tbuckley/cabot-search huggingface dataset:
Usefulness of 64-Slice Cardiac Computed Tomographic Angiography for Diagnosing Acute Coronary Syndromes and Predicting Clinical Outcome in Emergency Department Patients With Chest Pain of Uncertain Origin
Authors: Ronen Rubinshtein, David A. Halon, Tamar Gaspar, Ronen Jaffe, Basheer Karkabi, Moshe Y. Flugelman, Asia Kogan, Reuma Shapira, Nathan Peled, Basil S. Lewis
Journal: Circulation (2007)

Background— Multidetector computed tomography (MDCT) has high diagnostic value for detecting or excluding coronary artery stenosis. We examined performance characteristics of MDCT for diagnosing or excluding an acute coronary syndrome in patients presenting to the emergency department (ED) with possible ischemic chest pain and examined relation to clinical outcome during a 15-month follow-up period. Methods and Results— We prospectively studied 58 patients (56±10 years of age, 36% female) with chest pain possibly ischemic in origin and no new ECG changes or elevated biomarkers. The patients underwent 64-slice contrast-enhanced MDCT, which showed normal coronary vessels (no or trivial atheroma) in 15 patients, nonobstructive plaque in 20 (MDCT-negative patients), and obstructive coronary disease (≥50% luminal narrowing) in 23 (MDCT-positive group). By further investigation (new elevation of cardiac biomarkers, abnormal myocardial perfusion scintigraphy and/or invasive angiography), acute coronary syndrome was diagnosed in 20 of the 23 MDCT-positive patients (ED MDCT sensitivity 100% [20/20], specificity 92% [35/38], positive predictive value 87% [20/23], negative predictive value 100% [35/35]). During a 15-month follow-up period, no deaths or myocardial infarctions occurred in the 35 patients discharged from the ED after initial triage and MDCT findings. One patient underwent late percutaneous coronary intervention (late major adverse cardiovascular events rate, 2.8%). Overall, ED MDCT sensitivity for predicting major adverse cardiovascular events (death, myocardial infarction, or revascularization) during hospitalization and follow-up was 92% (12/13), specificity was 76% (34/45), positive predictive value was 52% (12/23), and negative predictive value was 97% (34/35). Conclusions— We found that 64-slice cardiac MDCT is a potentially valuable diagnostic tool in ED patients with chest pain of uncertain origin, providing early direct noninvasive visualization of coronary anatomy. ED MDCT had high positive predictive value for diagnosing acute coronary syndrome, whereas a negative MDCT study predicted a low rate of major adverse cardiovascular events and favorable outcome during follow-up.
Effect of sera from patients with rheumatoid arthritis on normal lymphocytes: a possible immunoregulatory role for immune complexes.
Authors: J Highton, G S Panayi, P Shepherd, P Wooley
Journal: Annals of the Rheumatic Diseases (1982)

The ability of rheumatoid sera to support concanavalin-A transformation of normal lymphocytes was inversely related to serum C1q binding activity. When C1q binding activity of the sera was removed by absorption with staphylococcal protein A, subsequent lymphocyte response increased to the level found in immune-complex negative sera. Gel filtration of a small number of sera suggested that the suppressive material had a molecular weight in the range 1.8-4.9 x 10(5) daltons. Aggregated human gammaglobulin suppressed con-A transformation of normal lymphocytes in a dose-dependent fashion. These results suggest that immune complexes present in rheumatoid sera can suppress lymphocyte responsiveness. The relevance of this observation to be clinical features of rheumatoid arthritis is discussed.
Modeling and therapy of human liver diseases using induced pluripotent stem cells: How far have we come?
Authors: Alejandro Soto-Gutierrez, Edgar Tafaleng, Victoria Kelly, Jayanta Roy-Chowdhury, Ira J. Fox
Journal: Hepatology (2011)

Human induced pluripotent stem (iPS) cells hold great promise for advancements in developmental biology, cell-based therapy, and modeling of human disease. Here, we examined the use of human iPS cells for modeling inherited metabolic disorders of the liver. Dermal fibroblasts from patients with various inherited metabolic diseases of the liver were used to generate a library of patient-specific human iPS cell lines. Each line was differentiated into hepatocytes using what we believe to be a novel 3-step differentiation protocol in chemically defined conditions. The resulting cells exhibited properties of mature hepatocytes, such as albumin secretion and cytochrome P450 metabolism. Moreover, cells generated from patients with 3 of the inherited metabolic conditions studied in further detail (alpha1-antitrypsin deficiency, familial hypercholesterolemia, and glycogen storage disease type 1a) were found to recapitulate key pathological features of the diseases affecting the patients from which they were derived, such as aggregation of misfolded alpha1-antitrypsin in the endoplasmic reticulum, deficient LDL receptor-mediated cholesterol uptake, and elevated lipid and glycogen accumulation. Therefore, we report a simple and effective platform for hepatocyte generation from patient-specific human iPS cells. These patient-derived hepatocytes demonstrate that it is possible to model diseases whose phenotypes are caused by pathological dysregulation of key processes within adult cells.
A Retinoid-Related Molecule that Does Not Bind to Classical Retinoid Receptors Potently Induces Apoptosis in Human Prostate Cancer Cells through Rapid Caspase Activation
Authors: Richard G. Keedwell, Yi Zhao, Lisette A. Hammond, Suofu Qin, Kwok-Yin Tsang, Armin Reitmair, Yanira Molina, Yumiko Okawa, Larissa I. Atangan, Dixie-Lee Shurland, Kaisheng Wen, D. Michael A. Wallace, Roger Bird, Roshantha A. S Chandraratna, Geoffrey Brown
Journal: Cancer Research (2004)

Synthetic retinoid-related molecules, such as N-(4-hydroxyphenyl)retinamide (fenretinide) and 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437) induce apoptosis in a variety of malignant cells. The mechanism(s) of action of these compounds does not appear to involve retinoic acid receptors (RARs) and retinoid X receptors (RXRs), although some investigators disagree with this view. To clarify whether some retinoid-related molecules can induce apoptosis without involving RARs and/or RXRs, we used 4-[3-(1-heptyl-4,4-dimethyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)-3-oxo-E-propenyl] benzoic acid (AGN193198) that neither binds effectively to RARs and RXRs nor transactivates in RAR- and RXR-mediated reporter assays. AGN193198 potently induced apoptosis in prostate, breast, and gastrointestinal carcinoma cells and in leukemia cells. AGN193198 also abolished growth (by 50% at 130-332 nM) and induced apoptosis in primary cultures established from prostatic carcinoma (13 patients) and gastrointestinal carcinoma (1 patient). Apoptosis was induced rapidly, as indicated by mitochondrial depolarization and DNA fragmentation. Molecular events provoked by AGN193198 included activation of caspase-3, -8, -9, and -10 (by 4-6 h) and the production of BID/p15 (by 6 h). These findings show that caspase-mediated induction of apoptosis by AGN193198 is RAR/RXR-independent and suggest that this compound may be useful in the treatment of prostate cancer.
Incidence of injuries and other health problems in the Auckland Citibank marathon, 1993.
Authors: P Satterthwaite, P Larmer, J Gardiner, R Norton
Journal: British Journal of Sports Medicine (1996)

OBJECTIVE: To describe the incidence of injuries and other health problems sustained during participation in a marathon. METHODS: A cohort study was undertaken involving the 1993 Auckland Citibank marathon participants. Demographic data and information on injuries and other health problems sustained during, immediately after, and 7 d following the marathon were obtained from a pre-race questionnaire, the medical aid posts, and a post-race questionnaire. RESULTS: Of the 1219 starters, 916 (75.1%) completed both questionnaires. Seventy five individuals (6.2%) sought assistance at the medical aid posts. During or immediately after the marathon, 283 systemic health problems were reported by 218 respondents (23.8%) and 2671 specific health problems were reported by 846 respondents (92.4%). In the 7 d following the marathon, 1905 specific health problems were reported by 723 respondents (79.2%). The majority of the specific health problems were blisters, stiffness, and pain, predominantly involving the lower limbs. CONCLUSIONS: Although a high proportion of participants experienced health problem during the race, very few of these problems were serious. Many of the entrants were still experiencing problems 7 d after the marathon.
Short term impact of smoke-free legislation in England: retrospective analysis of hospital admissions for myocardial infarction
Authors: M. Sims, R. Maxwell, L. Bauld, A. Gilmore
Journal: BMJ (2010)

<h3>Background/aims</h3> To report refractive outcomes from an National Health Service (NHS) cataract surgery service and assess if results meet suggested benchmark standard. <h3>Methods</h3> Details of all patients undergoing cataract surgery in the Southern General and New Victoria hospitals in Glasgow, UK, between November 2006 and December 2016 were prospectively entered into an electronic database. Patients were reviewed 4 weeks postoperatively in the eye clinic and underwent refraction at their local optometrist prior to this appointment. Surgically uncomplicated cases with in the bag' non-toric intraocular lens implantation were included. Patients with previous laser refractive procedures or failing to achieve 6/12 acuity or better postoperatively were excluded. Proximity to targeted postoperative refraction was documented. <h3>Results</h3> Over this 10-year period, 11 083 eyes underwent cataract surgery. Of these, 8943 eyes of 6936 patients (80.69%) met the inclusion criteria and had both target and postoperative outcome refraction recorded. The mean difference between the targeted and outcome refraction was −0.07&nbsp;D (SD 0.67). The mean absolute error was 0.50&nbsp;D. Postoperative refraction was within 1 D of target refraction for 7938 eyes (88.76%) and within 0.50 D for 5577 eyes (62.36%). <h3>Conclusion</h3> Refractive outcomes following routine cataract surgery reported here are well within the targets recommended by the Royal College of Ophthalmologists and European guidelines, but suggest that higher cataract refractive outcome benchmark standards may not yet be a realistic expectation for all NHS units with current biometry practice.
Regulation of Hepatic Glutathione Turnover in Rats In Vivo and Evidence for Kinetic Homogeneity of the Hepatic Glutathione Pool
Authors: Bernhard H. Lauterburg, Jerry R. Mitchell
Journal: Journal of Clinical Investigation (1981)

The intracellular distribution of glutathione into kinetically distinct pools and the determinants of glutathione turnover were examined in vivo. Glutathione turnover was measured in individual, restrained rats with a biliary fistula by administration of acetaminophen to trap the previously labeled hepatic glutathione as an excretable acetaminophen adduct. Fasting for 48 h resulted in a decrease of hepatic glutathione from 4.7+/-0.9 to 3.6+/-0.8 mumol/g liver and a marked increase in the fractional rate of glutathione turnover from 0.19+/-0.04 to 0.43+/-0.07/h. Within 6 h following refeeding, the rate of glutathione turnover and the hepatic glutathione concentration returned to normal. The simultaneously determined specific activities of free intrahepatic glutathione and the acetaminophen-glutathione adduct in bile were identical, indicating that the hepatic glutathione pool is kinetically homogeneous. The synthesis of glutathione could, therefore, be estimated from the rate constant and the intrahepatic glutathione concentration. During fasting hepatic synthesis of glutathione increased from 0.86+/-0.17 to 1.50+/-0.23 mumol/g per h. In fed animals the administration of dibutyryl cyclic adenosine monophosphate and theophylline stimulated the rate of hepatic glutathione turnover similar to fasting. In contrast, glucose given intraduodenally to fasted animals decreased the rate of glutathione turnover. These data are consistent with the view that the increased glutathione turnover that occurs during fasting results from two mechanisms. Because of a decrease in the intrahepatic free glutathione/mixed disulfide ratio, which is apparently mediated by cyclic adenosine monophosphate, the free glutathione pool contracts and turns over more rapidly in order to maintain glutathione synthesis. In addition, glutathione consumption via the gamma-glutamyl cycle apparently is increased, which may be related to the increased uptake of amino acids for gluconeogenesis during fasting.
Telomerase activation in a model of lung adenocarcinoma
Authors: F. Suau, V. Cottin, F. Archer, S. Croze, J. Chastang, G. Cordier, F. Thivolet-Béjui, J-F. Mornex, C. Leroux
Journal: European Respiratory Journal (2006)

Ovine pulmonary adenocarcinoma (OPA) is a lung cancer strikingly similar to the pneumonic-type mixed invasive adenocarcinoma with a predominant bronchioloalveolar component in humans. Telomerase activity in OPA and the potential involvement of the kinase Akt in telomerase activation and regulation of cell proliferation were investigated. Lung tissues were collected from sheep with a histopathological diagnosis of OPA or controls. Epithelial cell cultures were derived in vitro from lung tissues. Telomerase activity was evaluated using the telomeric repeat amplification protocol method. Phosphorylation of Akt was detected by Western blotting. Telomerase activity was significantly higher in OPA lung tissues compared to control lung tissues. A high telomerase activity was detected in eight out of 12 (67%) primary cell cultures derived from tumours. A high level of expression of phosphorylated Akt was found in 10 out of 27 (37%) tumours, with abolition of Akt activation in response to epidermal growth factor stimulation demonstrated in primary cell cultures derived from tumours. Telomerase activation takes place in ovine pulmonary adenocarcinoma tumour cells and may be partly attributable to Akt activation. Telomerase may inhibit cellular senescence and contribute to the accumulation of tumour cells in mixed adenocarcinoma with a bronchioloalveolar component. Further work is necessary to identify alternative signalling pathways of telomerase activation in tumours.
Human Kaposi's Sarcoma Cell-Mediated Tumorigenesis in Human Immunodeficiency Type 1 Tat-Expressing Transgenic Mice
Authors: O. Prakash
Journal: JNCI Journal of the National Cancer Institute (2000)

Background: The human immunodeficiency virus type 1 (HIV-1) transactivator (Tat) protein has been linked to the development and course of Kaposi's sarcoma (KS) associated with acquired immunodeficiency disease syndrome (AIDS–KS). Tat is an 86–101 amino-acid protein encoded by two exons. To evaluate the growth-promoting effects of Tat in AIDS–KS in vivo, we developed transgenic mice expressing the one-exon-encoded 72 amino-acid protein (Tat72) and the two-exon-encoded 86 amino-acid protein (Tat86). Methods: Human KS SLK cells were injected subcutaneously into CD4+ T-cell-depleted male mice, and the tumors that formed after 3–4 weeks were recovered and analyzed for the expression of Tat protein(s), different cytokine messenger RNAs (mRNAs), and matrix metalloproteinases (MMPs). All statistical tests were two-sided. Results: The average tumor weight was maximum in Tat86 mice (∼600 mg) compared with Tat72 (∼200 mg) and nontransgenic (∼100 mg) mice (P<.005). Histologic examination of tumors showed spindle-shaped SLK cells with prominent infiltrates of inflammatory cells. All of the tumors from Tat mice expressed abundant Tat mRNA, suggesting that the infiltrating mouse cells actively expressed Tat. A comparison of the growth-promoting cytokines in the tumors from Tat86-transgenic and nontransgenic mice showed that the expression of the following cytokines was substantially increased in the tumors of the Tat86 mice: tumor necrosis factor-α, interleukin 6, interleukin 8, granulocyte–macrophage colony-stimulating factor, and basic fibroblast growth factor. Furthermore, these tumors showed abundant expression of a 105-kd MMP activity associated with infiltrates of host leukocytes in the lesions. Conclusion: Our in vivo data clearly suggest that extracellular Tat can contribute to the growth and tumorigenesis of human KS cells.
The Mechanism of Chemokine Receptor 9 Internalization Triggered by Interleukin 2 and Interleukin 4
Authors: Xiaoling Tong, Lijun Zhang, Li Zhang, Meng Hu, Jun Leng, Beibei Yu, Beibei Zhou, Yi Hu, Qiuping Zhang
Journal: Cellular and Molecular Immunology (2009)
Efficacy of Functional Remediation in Bipolar Disorder: A Multicenter Randomized Controlled Study
Authors: Carla Torrent, Caterina del Mar Bonnin, Anabel Martínez-Arán, Jesús Valle, Benedikt L. Amann, Ana González-Pinto, José Manuel Crespo, Ángela Ibáñez, Mari Paz Garcia-Portilla, Rafael Tabarés-Seisdedos, Celso Arango, Francesc Colom, Brisa Solé, Isabella Pacchiarotti, Adriane R. Rosa, Jose Luis Ayuso-Mateos, Celia Anaya, Patricia Fernández, Ramon Landín-Romero, Silvia Alonso-Lana, Jordi Ortiz-Gil, Bàrbara Segura, Sara Barbeito, Patricia Vega, Miryam Fernández, Amaia Ugarte, Marta Subirà, Ester Cerrillo, Núria Custal, José Manuel Menchón, Jerónimo Saiz-Ruiz, Jose Maria Rodao, Sandra Isella, Analucía Alegría, Susana Al-Halabi, Julio Bobes, Gonzalo Galván, Pilar A. Saiz, Vicent Balanzá-Martínez, Gabriel Selva, Inmaculada Fuentes-Durá, Patricia Correa, María Mayoral, Guadalupe Chiclana, Jessica Merchan-Naranjo, Marta Rapado-Castro, Manel Salamero, Eduard Vieta
Journal: American Journal of Psychiatry (2013)

OBJECTIVE The authors sought to assess the efficacy of functional remediation, a novel intervention program, on functional improvement in a sample of euthymic patients with bipolar disorder. METHOD In a multicenter, randomized, rater-blind clinical trial involving 239 outpatients with DSM-IV bipolar disorder, functional remediation (N=77) was compared with psychoeducation (N=82) and treatment as usual (N=80) over 21 weeks. Pharmacological treatment was kept stable in all three groups. The primary outcome measure was improvement in global psychosocial functioning, measured blindly as the mean change in score on the Functioning Assessment Short Test from baseline to endpoint. RESULTS At the end of the study, 183 patients completed the treatment phase. Repeated-measures analysis revealed significant functional improvement from baseline to endpoint over the 21 weeks of treatment (last observation carried forward), suggesting an interaction between treatment assignment and time. Tukey's post hoc tests revealed that functional remediation differed significantly from treatment as usual, but not from psychoeducation. CONCLUSIONS Functional remediation, a novel group intervention, showed efficacy in improving the functional outcome of a sample of euthymic bipolar patients as compared with treatment as usual.
Uniformity of transmural perfusion in anesthetized dogs with maximally dilated coronary circulations.
Authors: H F Downey, F A Bashour, R B Boatwright, P E Parker, S J Kechejian
Journal: Circulation Research (1975)

In 14 beating hearts, coronary blood flow was measured electromagnetically in either the left circumflex or the left anterior descending coronary artery, and regional myocardial blood flow was computed from tissue uptake of 7-10^ radioactive microspheres.Metabolic dilation of the coronary circulation was induced by occluding the coronary artery for 10 or 90 seconds, and pharmacologic dilation was induced by infusing papaverine into the artery.In seven dogs, differently labeled microspheres were administered (1) before coronary artery occlusion, (2) at the peak reactive hyperemic response to a 10-second coronary artery occlusion, and (3) early in the rising phase of the hyperemic response following a 90-second coronary artery occlusion.Myocardial blood flow was distributed uniformly across the left ventricular free wall before occlusion and at peak hyperemia after the 10-second occlusion, but early in the hyperemic response to the 90-second occlusion coronary blood flow preferentially perfused subepicardial tissue.In another group of seven dogs, microspheres were administered (1) before coronary artery occlusion, (2) at the peak hyperemic flow after a 90-second occlusion, and (3) at the peak flow during local intracoronary infusion of papaverine.The left ventricular free wall was uniformly perfused under each condition.However, in 12 vented, fibrillating hearts with coronary circulations dilated maximally by perfusion with venous blood containing either papaverine or adenosine, left ventricular blood flow was preferentially directed to the subendocardium (endocardial-epicardial ratio averaged 1.37 ± 0.08 [SE]).We conclude that the coronary circulation of the normally functioning canine heart can dilate maximally without causing relative subendocardial ischemia because of a gradient of vascularity that favors the subendocardium and compensates for systolic flow limitation in that region.
Glucose absorption kinetics in Zambian African patients with and without systemic bacterial infections
Authors: G. C. Cook
Journal: Gut (1971)

Using a double-lumen tube perfusion system, solutions of glucose (10, 2.5, and 5.0 g lOOml -l) have been perfused into the upper jejunum of 22 Zambian African subjects in order tostudy their glucose absorption kinetics.None of them had clinical evidence of malnutrition or intestinal disease.In 10 there was no evidence of an infective disease ('normal' group); seven had tuberculosis; five had acute bacterial infections.The mean serum albumin concentration was significantly lower in those with infections; the mean total and y-globulin concentrations were significantly higher in the tuberculosis group.There was good reproducibility in triplicate assessments of glucose and water absorption rates in the individual subjects.Despite a wide scatter, the mean glucose kinetic curves were significantly flatter in those with infections than in the normal group (p <0.02).There was a significant association between glucose and water absorption rates in the individuals.D-xylose absorption was estimated in 11 subjects and there was a significant correlation between that and the glucose absorption rate.Jejunal morphology (n = 9) and disaccharidase concentrations (n = 6) were normal for African subjects and there were no significant associations between either of those and the absorption rates.Galactose absorption kinetics have been studied in an additional four relatively normal Zambian Africans.This study suggests that systemic bacterial infections can produce malabsorption.This may be relevant to the weight loss in patients with pulmonary tuberculosis and also to the aetiology of kwashiorkor.
Sponsored parachute jumps--can they cause prolonged pain?
Authors: N Straiton, J Sterland
Journal: British Journal of Sports Medicine (1986)

A survey of parachute injuries sustained in 1984 at a local parachute club was made using hospital notes and a questionnaire. The overall injury rate was 0.2%. The injury rate in first time jumpers was 1.1%. The injuries often resulted in a prolonged hospital stay, time off work and residual pain and disability. Injury rates may be reduced by more prolonged and intensive training preceding the first jumps. Those people not interested in parachuting as a regular sport and who jump once only in order to raise money for charity are at risk of serious injury and perhaps should consider less dangerous alternatives.