tbuckley/cabot-search huggingface dataset:
Role of cellular superoxide dismutase against reactive oxygen metabolite–induced cell damage in cultured rat hepatocytes
Authors: Yasuaki Ito, Hideyuki Hiraishi, Mahnaz Razandi, Akira Terano, Takashi Harada, Kevin J. Ivey
Journal: Hepatology (1992)

Reactive oxygen metabolites have been reported to be important in the pathogenesis of ischemia/reperfusion–induced and alcohol–and druginduced liver injuries. We investigated the role of superoxide dismutase, cellular and extracellular, in preventing reactive oxygen metabolite-induced cytotoxicity in cultured rat hepatocytes. Cells were exposed to reactive oxygen metabolites enzymatically generated by hypoxanthine–xanthine oxidase. Cytotoxicity was quantified by measuring 51 Cr release from prelabeled cells and lactate dehydrogenase release. Reactive oxygen metabolites caused dose–dependent cytotoxicity. Good correlation was found between the values for 51 Cr and lactate dehydrogenase release. Reactive oxygen metabolite-induced cell damage was reduced by catalase but not by superoxide dismutase. Cellular superoxide dismutase and catalase activities were not increased after incubation with exogenous superoxide dismutase and catalase for up to 5 hr. Pretreatment with diethyldithiocarbamate inhibited cellular superoxide dismutase activity without inhibiting other antioxidants such as catalase, glutathione, glutathione reductase and glutathione peroxidase and sensitized cells to reactive oxygen metabolite-induced cytotoxicity. We conclude that hydrogen peroxide is an important mediator in hypoxanthine–xanthine oxidase-induced cell damage and that superoxide dismutase plays a critical role in cellular antioxidant defenses against hypoxanthine–xanthine oxidase-induced cytotoxicity in cultured rat hepatocytes in vitro . (Hepatology 1992;16:247-254.)
Cytokine adsorption/release on uniform magnetic nanoparticles for localized drug delivery
Authors: Raquel Mejías, Rocío Costo, Alejandro G. Roca, Cristina F. Arias, Sabino Veintemillas-Verdaguer, Teresita González-Carreño, María del Puerto Morales, Carlos J. Serna, Santos Mañes, Domingo F. Barber
Journal: Journal of Controlled Release (2008)
Evaluating a telemedicine system to assist in the management of dermatology referrals
Authors: P. Taylor, P. Goldsmith, K. Murray, D. Harris, A. Barkley
Journal: British Journal of Dermatology (2001)

Background Teledermatology systems fall into two categories: live video or store‐and‐forward. In the former, video‐conferencing equipment is used to connect a patient with a remote consultant. This method has been evaluated as an aid to dermatology, but it is expensive both in terms of capital and running costs. Video consultations are generally longer than conventional ones and harder to schedule. Some authors have considered store‐and‐forward as an alternative to live video: instead of a consultation, specialists could make a rapid inspection of a transmitted still image. Objectives A study was conducted to evaluate the role of telemedicine in the dermatology outpatients department of a district general hospital (Whittington Hospital NHS Trust, London, U.K.). Methods One hundred and ninety‐four patients were seen by one of two consultant dermatologists. A nurse used a video camera to store digital images of each patient's problem and compiled a history from the GP's referral letter. The images were reviewed 13 months later by both dermatologists; they recorded a provisional diagnosis and an assessment of how urgent an appointment would have been made given the information provided by the system. A third consultant graded the level of agreement between the telemedicine diagnoses and the face‐to‐face consultations. Results High levels of agreement were found between the diagnoses of the dermatologists using the system to inspect images and those of the dermatologist who saw the patients (77%). Consultants using the system recommended fewer urgent appointments (32% compared with 64%) and felt that in 31% of cases the patient did not need to be seen. In 15% of these cases (5% of the total), however, their diagnosis differed significantly from that of the consultant who saw the patient. Had the system been in use, 14% of patients conventionally assigned a non‐urgent appointment would have been seen urgently. Conclusions The images allowed a reasonably accurate diagnosis. The software was not reliable (six cases could not be viewed), or easy to use (it took approximately an hour to view 20 cases) but an improved version could be used in triaging outpatient appointments.
Low Protein Intake Is Associated with a Major Reduction in IGF-1, Cancer, and Overall Mortality in the 65 and Younger but Not Older Population
Authors: Morgan E. Levine, Jorge A. Suarez, Sebastian Brandhorst, Priya Balasubramanian, Chia-Wei Cheng, Federica Madia, Luigi Fontana, Mario G. Mirisola, Jaime Guevara-Aguirre, Junxiang Wan, Giuseppe Passarino, Brian K. Kennedy, Min Wei, Pinchas Cohen, Eileen M. Crimmins, Valter D. Longo
Journal: Cell Metabolism (2014)
A Surprising Prevention Success: Why Did the HIV Epidemic Decline in Zimbabwe?
Authors: Daniel T. Halperin, Owen Mugurungi, Timothy B. Hallett, Backson Muchini, Bruce Campbell, Tapuwa Magure, Clemens Benedikt, Simon Gregson
Journal: PLoS Medicine (2011)

Daniel Halperin and colleagues examine reasons for the remarkable decline in HIV in Zimbabwe, in the context of severe social, political, and economic disruption.
Bleeding complications of oral anticoagulant treatment: an inception-cohort, prospective collaborative study (ISCOAT)
Authors: Gualtiero Palareti, Nicoletta Leali, Sergio Coccheri, Mario Poggi, Cesare Manotti, Armando D'Angelo, Vittorio Pengo, Nicoletta Erba, Marco Moia, Nicola Ciavarella, Gianluigi Devoto, Mauro Berrettini, Serena Musolesi
Journal: The Lancet (1996)
Pre- and postnatal parental smoking and wheeze in infancy: cross cultural differences
Authors: A.J. Henderson, A. Sherriff, K. Northstone, L. Kukla, D. Hruba
Journal: European Respiratory Journal (2001)

In longitudinal cohort studies, the relationships between prenatal and postnatal tobacco smoke exposure and infant wheezing illnesses were compared in two geographically defined populations in Avon, UK and Brno and Znojmo in the South Moravian Region of the Czech Republic. Pregnant females living in defined regions and with expected dates of delivery between defined dates were recruited. Females completed self-report questionnaires during pregnancy and when their infant was 6 months old. For this analysis, responses to questions about smoking during pregnancy, environmental tobacco smoke (ETS) exposure and reported wheezing illnesses of infants at 6 months after birth were used. Odds ratios for wheeze in relation to the smoking variables were calculated with adjustment for potential confounding effects. The prevalence of smoking during pregnancy was higher in Avon (17.5%) than the Czech Republic (7.1%). Exposure of infants to ETS during the first 6 months after birth was also reported to be higher in Avon (35.5%) than the Czech Republic (9.7%). The prevalence of reported wheezing by 6 months of age was 21.4% in Avon and 10.3% in Brno and Znojmo. In Avon, there was a significant relationship between infant wheeze and maternal smoking during pregnancy (odds ratio (95% confidence interval) 1.30 (1.09–1.56), p=0.004) but not with environmental exposure after birth (1.11 (0.98–1.25)). In contrast, in Brno and Znojmo in the Czech Republic, there was a significant relationship between infant wheeze and ETS exposure (1.66 (1.17–2.36), p=0.04) but not with maternal smoking during pregnancy (0.99 (0.64–1.55)). This study demonstrated an apparent difference in the associations between prenatal and postnatal tobacco smoke exposure and infant wheezing illnesses in two populations with different smoking prevalence. The relationships were independent of a number of potential confounding variables that have been associated with infant wheezing. Possible explanations of these observations include dose-related effects of prenatal and postnatal tobacco smoke exposure of infants.
Thromboxane generation after thrombin. Protective effect of thromboxane synthetase inhibition on lung fluid balance.
Authors: R R Garcia-Szabo, M B Peterson, W D Watkins, R Bizios, D L Kong, A B Malik
Journal: Circulation Research (1983)

We examined the role of thromboxane in mediating the alterations in pulmonary hemodynamics and in lung fluid and protein exchange after thrombin. Studies were made in control sheep and in sheep pretreated with the thromboxane synthetase inhibitor, Dazoxiben (injection of 10 mg/kg followed by infusion of 4 mg/kg per hr). Thrombin infusion caused an increase in mixed venous and aortic concentrations of thromboxane B2, a stable degradation product of thromboxane A2, whereas the concentrations of 6-keto-PGF1 alpha, a degradation product of prostacyclin, did not change significantly. In sheep pretreated with Dazoxiben, thromboxane B2 concentrations did not increase, indicating effectiveness of the thromboxane synthetase inhibitor. The blood concentrations of 6-keto-PGF1 alpha after thrombin increased in the thromboxane synthetase-inhibited group, indicating shunting towards prostacyclin synthesis. Thrombin in untreated sheep increased pulmonary lymph flow (Qlym) and the lymph protein clearance (Qlym X lymph-to-plasma protein concentration ratio). The increases in lymph parameters were due to an increase in pulmonary vascular permeability to proteins because raising left atrial pressure further increased Qlym but did not change lymph-to-plasma ratio. Dazoxiben prevented the thrombin-induced increase in pulmonary vascular permeability because the increase in left atrial pressure resulted in an increase in Qlym and a decrease in lymph-to-plasma ratio, as was the case after left atrial hypertension in normal animals. Therefore, thrombin results in selective release of thromboxane A2 which precedes the increase in pulmonary vascular permeability. Thromboxane A2 may contribute to the increased permeability after thrombin, since inhibition of thromboxane synthesis prevents the permeability change.
THE COMMONER COMPLICATIONS OF BACILLARY DYSENTERY IN MILITARY PRACTICE
Authors: P. Manson-Bahr
Journal: BMJ (1920)

COMPLICATIONS OF flCILLAIY DYSENTERY.B [M,B'a" -79T be on the look.outfor tlle protean signs and symptoms that are discernible very early.I have not time to deal witlh insufficiencies of the otlher ductless glands; nor lhave I time to mention some of these glands at all.You will find in my book, T'he Sex Complex, especially in tlle new edition about to be issued, a more complete picture.I slhall be amply satisfied if I have been lucid in this hasty sketch with wlhich I have sought to attract your attention to the triplication of effects-in the mind, in the soma, and in the reproductive organs- which forms such striking evidence of what I have called the Correlation of Function.
Thrombectomy for Iliofemoral Venous Thrombosis
Authors: Hendrick B. Barner
Journal: JAMA (1969)

Seventy patients with iliofemoral venous thrombosis underwent 73 thrombectomies. There were 12 deaths in the first postoperative month, one of which was due to pulmonary embolism. Eleven late deaths were unrelated to thromboembolic disease. Seven patients had phlebography one to three weeks after operation and ten were studied 16 to 102 months after thrombectomy. Despite a "good" or "fair" clinical result the early phlebograms frequently demonstrated extensive deep vein thrombosis or recanalized deep veins. Later phlebograms revealed thrombosed deep veins, recanalized deep veins, and collateral veins in patients with good and fair clinical results. Despite a favorable clinical course after thrombectomy, deep vein patency and valve function are infrequently restored. The proper indications for thrombectomy are as yet difficult to define.
Overexpression of the Protien Tyrosine Phosphatase PTP1B in Human Breast Cancer: Assocation With p185c-erbB-2 Protein Expression
Authors: J. R. Wiener, B.-J. M. Kerns, E. L. Harvey, M. R. Conaway, J. D. lglehart, A. Berchuck, R. C. Bast
Journal: JNCI Journal of the National Cancer Institute (1994)

The p185 c-erbB-2 growth factor receptor protien tyrosine kinase (PTK) is overexpressed in one third of human breast cancer patients and indicates a poor prognosis in these patients. Protien tyrosine phosphatases (PTPs) may balance PTK activity as part of normal growth-regulation pathways. PTP1B is an intracelluar PTP that is involved in linkage between signal transduction pathways and may interface with inappropriate PTK activity in transformed cells. The aim of this study was to determine if PTP1B is overexpression in human mammary tumors and to determine if such overexpression is associated with the overexpression of the p185 c-erbB-2 receptor PTK. Our samples were frozen sections from 29 human mammary tumors (19 pure infiltrating, two pure intraductal, and eight combined intraductal and infiltrating) and nine sections from normal breast tissue. The sections were immunohisto-chemically stained for PTP1B and p185 c-erb-2 , and the results were analyzed statistically for association between overexpression of the two proteins. Northern blot analysis was used to assess if PTP1B overexpression was coincident with increased transcription of the PTP1B gene. Overxpression of the PTP1B protein was observed in 72.4% of the tumor sections compared with normal epithelium, with maximal expression occurring in 37.9% of the tumors. All of the tumor subtypes, including the pure intradutal lesions, overexpressed PTP1B. Statistical analyses demonstrated a significant association between PTP1B overexpression and breast cancer ( P <.038) and between the overexpression of PTP1B and the overexpression of PTP1D and the overexpression of p185 e-erbB-2 ( P <.006). PTP1B messenger RNA steady-state transcription was consistently increased in tumors versus normal tissues. PTP1B overexpression is a common phenotypic manifestation in human breast cancers and is associated with overexpression of p185 e-erbB-2 . Steadystate PTP1B transcription is in creased in tumor tissue. Further studies are needed to determine if PTP1B overexpression balances or augments PTK activity. PTP1B overexpression might also be evaluated as a clinical prognostic factor in human breast cancers. [J Natl Cancer Inst 86:372−378, 1994]
A Novel Anticancer Effect of Thalidomide: Inhibition of Intercellular Adhesion Molecule-1–Mediated Cell Invasion and Metastasis through Suppression of Nuclear Factor-κB
Authors: Yi-Chu Lin, Chia-Tung Shun, Ming-Shiang Wu, Ching-Chow Chen
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Thalidomide has been reported to have antiangiogenic and antimetastatic effects. Intercellular adhesion molecule-1 (ICAM-1) was shown to be involved in monocyte adherence to epithelial cells and cancer cell invasion. In this study, we further investigated the role of ICAM-1 in tumorigenesis, including tumor formation and metastasis. ICAM-1 as a molecular target for cancer and the anticancer effect of thalidomide were investigated. Experimental Design: Expression of ICAM-1 protein in human lung cancer specimens was assessed by immunohistochemistry. ICAM-1 overexpressing A549 cells (A549/ICAM-1) were established to investigate the direct effect of ICAM-1 on in vitro cell invasion and in vivo tumor metastasis. Transient transfection and luciferase assay, electrophoretic mobility shift assay, and chromatin immunoprecipitation were done to assess the activity and binding of nuclear factor-κB to the ICAM-1 promoter. A xenograft model in nude mice was conducted to evaluate the anticancer effect of thalidomide. Results: High expression of ICAM-1 in human lung cancer specimens was correlated with a greater risk of advanced cancers (stages III and IV). A549/ICAM-1 cells were shown to induce in vitro cell invasion and in vivo tumor metastasis. Anti-ICAM-1 antibody and thalidomide had inhibitory effect on these events. Thalidomide also suppressed tumor necrosis factor-α–induced ICAM-1 expression through inhibition of nuclear factor-κB binding to the ICAM-1 promoter. The in vivo xenograft model showed the effectiveness of thalidomide on tumor formation. Conclusion: These studies provide a framework for targeting ICAM-1 as a biologically based therapy for cancer, and thalidomide might be effective in human lung cancer.
Small-molecule screening using a human primary cell model of HIV latency identifies compounds that reverse latency without cellular activation
Authors: Hung-Chih Yang, Sifei Xing, Liang Shan, Karen O’Connell, Jason Dinoso, Anding Shen, Yan Zhou, Cynthia K. Shrum, Yefei Han, Jun O. Liu, Hao Zhang, Joseph B. Margolick, Robert F. Siliciano
Journal: Journal of Clinical Investigation (2009)

The development of highly active antiretroviral therapy (HAART) to treat individuals infected with HIV-1 has dramatically improved patient outcomes, but HAART still fails to cure the infection. The latent viral reservoir in resting CD4+ T cells is a major barrier to virus eradication. Elimination of this reservoir requires reactivation of the latent virus. However, strategies for reactivating HIV-1 through nonspecific T cell activation have clinically unacceptable toxicities. We describe here the development of what we believe to be a novel in vitro model of HIV-1 latency that we used to search for compounds that can reverse latency. Human primary CD4+ T cells were transduced with the prosurvival molecule Bcl-2, and the resulting cells were shown to recapitulate the quiescent state of resting CD4+ T cells in vivo. Using this model system, we screened small-molecule libraries and identified a compound that reactivated latent HIV-1 without inducing global T cell activation, 5-hydroxynaphthalene-1,4-dione (5HN). Unlike previously described latency-reversing agents, 5HN activated latent HIV-1 through ROS and NF-kappaB without affecting nuclear factor of activated T cells (NFAT) and PKC, demonstrating that TCR pathways can be dissected and utilized to purge latent virus. Our study expands the number of classes of latency-reversing therapeutics and demonstrates the utility of this in vitro model for finding strategies to eradicate HIV-1 infection.
The PREVASC study: the clinical effect of a multifaceted educational intervention to prevent childhood asthma
Authors: H. J. A. M. Schonberger
Journal: European Respiratory Journal (2005)

As asthma is the most common chronic disease in childhood, much attention is directed towards primary prevention. Here, the clinical effectiveness of a multifaceted educational prevention was studied. A total of 476 high-risk children were recruited during the prenatal period by general practitioners and randomised to either: 1) a control group, receiving usual care; or 2) an intervention group in which families received instruction from nurses on how to reduce exposure of newborns to mite, pet and food allergens, and passive smoking. A total of 443 infants were followed-up for 2 yrs. At 2 yrs of age, the intervention group (n = 222) had less asthma-like symptoms, including wheezing, shortness of breath and night-time cough, than the control group (n = 221). No significant differences in total and specific immunoglobulin E were found between the groups. During the first 2 yrs of life, the incidence of asthma-like symptoms was similar in both groups; however, subanalysis revealed a significant reduction in the female, but not in the male, intervention group. In conclusion, the intervention used in this study was not effective in reducing asthma-like symptoms in high-risk children during the first 2 yrs of life, although it was modestly effective at 2 yrs. Follow-up is necessary to confirm whether the intervention can actually prevent the development of asthma.
Common <i>NOS1AP</i> Variants Are Associated With a Prolonged QTc Interval in the Rotterdam Study
Authors: Albert-Jan L.H.J. Aarnoudse, Christopher Newton-Cheh, Paul I.W. de Bakker, Sabine M.J.M. Straus, Jan A. Kors, Albert Hofman, André G. Uitterlinden, Jacqueline C.M. Witteman, Bruno H.C. Stricker
Journal: Circulation (2007)

QT prolongation is an important risk factor for sudden cardiac death. About 35% of QT-interval variation is heritable. In a recent genome-wide association study, a common variant (rs10494366) in the nitric oxide synthase 1 adaptor protein (NOS1AP) gene was found to be associated with QT-interval variation. We tested for association of 2 NOS1AP variants with QT duration and sudden cardiac death.The Rotterdam Study is a population-based, prospective cohort study of individuals > or = 55 years of age. The NOS1AP variants rs10494366 T>G and rs10918594 C>G were genotyped in 6571 individuals. Heart rate-corrected QT interval (QTc) was determined with ECG analysis software on up to 3 digital ECGs per individual (total, 11,108 ECGs from 5374 individuals). The association with QTc duration was estimated with repeated-measures analyses, and the association with sudden cardiac death was estimated by Cox proportional-hazards analyses. The rs10494366 G allele (36% frequency) was associated with a 3.8-ms (95% confidence interval, 3.0 to 4.6; P=7.8x10(-20)) increase in QTc interval duration for each additional allele copy, and the rs10918594 G allele (31% frequency) was associated with a 3.6-ms (95% confidence interval, 2.7 to 4.4; P=6.9x10(-17)) increase per additional allele copy. None of the inferred NOS1AP haplotypes showed a stronger effect than the individual single-nucleotide polymorphisms. There were 233 sudden cardiac deaths over 11.9 median years of follow-up. No significant association was observed with sudden cardiac death risk.Common variants in NOS1AP are strongly associated with QT-interval duration in an elderly population. Larger sample sizes are needed to confirm or exclude an effect on sudden cardiac death risk.
The Role of Acetaldehyde in Mediating the Deleterious Effect of Ethanol on Pyridoxal 5′-Phosphate Metabolism
Authors: Lawrence Lumeng
Journal: Journal of Clinical Investigation (1978)

Previous studies in vivo and with isolated perfused rat livers have suggested that the deleterious effect of ethanol on hepatic pyridoxal 5′-phosphate metabolism is mediated by acetaldehyde. Inasmuch as acetaldehyde has no effect on the synthesis of pyridoxal phosphate, it has also been postulated that acetaldehyde accelerates pyridoxal phosphate degradation by displacing this coenzyme from binding proteins, which protect it against hydrolysis. To test these hypotheses, studies have been performed with isolated rat hepatocytes, subcellular fractions of rat liver, and human erythrocytes. Ethanol oxidation lowered the pyridoxal phosphate content of isolated liver cells when acetaldehyde oxidation was inhibited by either disulfiram or prior treatment of rats with cyanamide. Additions of 7.5 mM acetaldehyde alone at 40-min intervals to cell suspensions decreased hepatic pyridoxal phosphate content only slightly because acetaldehyde was rapidly metabolized. However, when acetaldehyde oxidation and reduction were inhibited by cyanamide treatment and by 4-methyl-pyrazole and isobutyramide, respectively, a 40% decrease in hepatic pyridoxal phosphate content was observed in 80 min of incubation.