tbuckley/cabot-search huggingface dataset:
Basic polyamino acids rich in arginine, lysine, or ornithine cause both enhancement of and refractoriness to formation of endothelium-derived nitric oxide in pulmonary artery and vein.
Authors: L J Ignarro, M E Gold, G M Buga, R E Byrns, K S Wood, G Chaudhuri, G Frank
Journal: Circulation Research (1989)

The objective of this study was to elucidate the mechanism by which polyamino acids containing L-arginine, L-lysine or L-ornithine cause endothelium-dependent relaxation of bovine intrapulmonary artery and vein. Basic but not acidic or neutral polypeptides ranging in average molecular weights from 17 to 225 kDa elicited time- and concentration-dependent relaxation and cyclic GMP accumulation in precontracted rings of artery and vein by endothelium-dependent mechanisms. Vascular responses were markedly inhibited by oxyhemoglobin, methylene blue, or potassium. The basic polyamino acids stimulated the formation and/or release of an endothelium-derived relaxing factor (EDRF) identified as nitric oxide (NO) in perfused segments of both artery and vein as assessed by bioassay. The polyamino acids and A23187 released a similar endothelium-derived NO (EDNO) from artery and vein, as assessed by the similar half-life (3-5 seconds), antagonism by superoxide anion or oxyhemoglobin, enhancement by superoxide dismutase, and lack of influence by indomethacin. The basic polyamino acids elicited potent relaxant responses with EC50 values ranging from 3 x 10(-9) to 2 x 10(-7) M, and a direct correlation was obtained between molecular weight and relaxation potency irrespective of the basic amino acid incorporated. Prolonged contact of arterial or venous rings with basic polyamino acids resulted in the rapid development of marked refractoriness to relaxation and cyclic GMP formation on addition of polyamino acid. Moreover, refractoriness developed to the vascular responses of other endothelium-dependent vasodilators but not to glyceryl trinitrate or isoproterenol. The mechanism of refractory responses was attributed to interference with EDNO formation and release as assessed by bioassay and chemical assay. The hypothesis is forwarded that the basic polyamino acids serve as partial substrates for the enzyme system that catalyzes the conversion of L-arginine to NO. Prolonged contact between substrate and enzyme results in enzyme desensitization and the development of refractoriness or a form of tolerance to vasodilators whose action is mediated by EDNO.
Dutch paediatrician launches clinic for children with alcohol problems
Authors: Tony Sheldon
Journal: BMJ (2006)

A specialist hospital clinic for children with problems related to alcohol misuse is to be launched in the Netherlands. This follows a marked increase in admissions to hospital of children younger than 16 years old because of alcohol poisoning.

The initiative, the first of its kind in the Netherlands, is a response in particular to paediatricians' concerns about long term brain damage. An alarming trend has emerged of younger, prepubescent girls being admitted with increasingly greater concentrations of alcohol in their blood.

The trend reinforces the findings of the 2004 European school survey project on alcohol and other drugs, …
SHORT DURATION VERSUS 1-YEAR DUAL ANTIPLATELET THERAPY AFTER DRUG-ELUTING STENTS IMPLANTATION: SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS
Authors: Pedro Villablanca Spinetto, David Briceno, Amell Fredrik, Felipe Albuquerque, Salvador Villablanca, Mark Menegus, Vankeepuram Srinivas, Mark Greenberg, Anna Bortnick, Ernest Monrad, Michael Johnson, Robert Pyo
Journal: Journal of the American College of Cardiology (2015)
Evolutionary dynamics of eukaryotic selenoproteomes: large selenoproteomes may associate with aquatic life and small with terrestrial life
Authors: Alexey V Lobanov, Dmitri E Fomenko, Yan Zhang, Aniruddha Sengupta, Dolph L Hatfield, Vadim N Gladyshev
Journal: Genome biology (2007)

Selenocysteine (Sec) is a selenium-containing amino acid that is co-translationally inserted into nascent polypeptides by recoding UGA codons. Selenoproteins occur in both eukaryotes and prokaryotes, but the selenoprotein content of organisms (selenoproteome) is highly variable and some organisms do not utilize Sec at all. We analyzed the selenoproteomes of several model eukaryotes and detected 26 and 29 selenoprotein genes in the green algae Ostreococcus tauri and Ostreococcus lucimarinus, respectively, five in the social amoebae Dictyostelium discoideum, three in the fly Drosophila pseudoobscura, and 16 in the diatom Thalassiosira pseudonana, including several new selenoproteins. Distinct selenoprotein patterns were verified by metabolic labeling of O. tauri and D. discoideum with 75Se. More than half of the selenoprotein families were shared by unicellular eukaryotes and mammals, consistent with their ancient origin. Further analyses identified massive, independent selenoprotein losses in land plants, fungi, nematodes, insects and some protists. Comparative analyses of selenoprotein-rich and -deficient organisms revealed that aquatic organisms generally have large selenoproteomes, whereas several groups of terrestrial organisms reduced their selenoproteomes through loss of selenoprotein genes and replacement of Sec with cysteine. Our data suggest many selenoproteins originated at the base of the eukaryotic domain and show that the environment plays an important role in selenoproteome evolution. In particular, aquatic organisms apparently retained and sometimes expanded their selenoproteomes, whereas the selenoproteomes of some terrestrial organisms were reduced or completely lost. These findings suggest a hypothesis that, with the exception of vertebrates, aquatic life supports selenium utilization, whereas terrestrial habitats lead to reduced use of this trace element due to an unknown environmental factor.
RESIDUAL TRANSGENE EXPRESSION OF YAMANAKA FACTORS DETERMINE QUALITY AND DIFFERENTIATION EFFICIENCY OF CARDIOMYOCYTES DERIVED FROM MOUSE INDUCED PLURIPOTENT STEM CELL LINES
Authors: Yohei Ohno, Shinsuke Yuasa, Toru Egashira, Tomohisa Seki, Hisayuki Hashimoto, Shugo Tohyama, Masaki Kodaira, Dai Kusumoto, Fumiyuki Hattori, Kojiro Yae, Mitsushige Murata, Keiichi Fukuda
Journal: Journal of the American College of Cardiology (2012)
Human exposure to tetrachloroethylene: Inhalation and skin contact
Authors: Carl L. Hake, Richard D. Stewart
Journal: Environmental Health Perspectives (1977)

There is considerable potential for worker exposure to tetrachloroethylene, both by skin contact and by inhalation, during its use in dry cleaning and degreasing operations. This paper reviews accounts of both accidental overexposures of workers and controlled exposures of human subjects by these two routes of exposure. Several reported cases of accidental overexposure to anesthetic doses of the chemical reveal that recovery was generally complete but prolonged, and accompanied by many days of measurable levels of the chemical in the patient's alveolar breath. Chronic overexposures of workmen have lessened since the general acceptance by the Western world of the recommended TLV of 100 ppm for 8 hr of daily exposure. Controlled inhalation studies with volunteer subjects at this level of exposure revealed no effects upon health but did indicate a slight decrement in performance on a coordination test. Additional behavioral and neurological tests revealed no interactive effects when alcohol or diazepam, two depressant drugs, were added singly to tetrachloroethylene exposures. Individual susceptibility to the vapor of this chemical, as evidenced by subjective complaints, was noted in approximately one of ten subjects. The authors conclude that the TLV concentration of 100 ppm in the workplace has a negligible margin of safety regarding unimpaired performance during repeated exposures which could be especially hazardous if the worker is physically active or is in a situation where skin absorption presents an added burden.
Is sociopathy a type or not? Will the “real” sociopathy please stand up?
Authors: James Snyder
Journal: Behavioral and Brain Sciences (1995)

Abstract The validity of the classification of “primary sociopaths” as a qualitatively distinct group in the general population is questioned. Cenetic variation in the experience and expression of emotions may play a role in the development of antisocial behavior. However, research clearly documents that socialization environments powerfully modify the expression of genetic biases in a manner that increases or decreases the risk for “sociopathy.”
Abstract 102: Mathematical models for growth of metastatic tumors
Authors: Ardith W. El-Kareh, Timothy W. Secomb
Journal: Cancer Research (2010)

Abstract The mathematical form best describing the growth of a single tumor mass has been found to be any of several models including the power law, logistic or Gompertzian, depending on the particular clinical or experimental tumor considered. All these models exhibit monotonically decreasing growth rate over time; some plateau at some finite volume. However, the kinetics of growth of the total mass of a metastatic tumor remains a separate question with relevance for understanding survival time, optimal treatment, and the development of symptoms that arise from total tumor burden. Here, exact analytical solutions for total tumor burden are derived under the assumption that both the primary tumor and each individual metastatic lesion grow with power law kinetics. Solutions are also derived for the case of metastatic growth after removal of the primary tumor. Two cases are considered: one where the rate of metastasis formation from an individual lesion grows with power law kinetics, and one where this rate is independent of size. Surprisingly, the latter assumption, which is consistent with only a small subpopulation of cells having metastatic potential, proves entirely adequate to describe data of Iwata et al on the cumulative distribution of metastases of a human hepatocellular carcinoma. For both cases, as time progresses, the growth ultimately becomes exponential, regardless of whether or not the primary tumor has been excised. However, it is shown that for the range of parameters describing observed tumors, this exponential limit is not reached before the tumor burden becomes lethal. The growth does not, however, show the trend of decreasing rate with increasing volume exhibited by single lesions, and appears in fact approximately exponential over the range of clinical detectability. This provides an explanation for experimental data showing near exponential growth of plasma tumor markers such as carcinoembryonic antigen in patients followed for metastatic colorectal or medullary thyroid carcinoma. Using the model, it can be seen that neither the growth rate of individual lesions, nor the rate of metastasis formation by itself causes tumor lethality; rather it is the ratio of these two rates that determines whether a large number of metastases form before the primary tumor reaches detectable size. The models derived here are expected to have application to mathematical modeling of optimal treatment and tumor-immune system interactions. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 102.
Individual responsiveness to exercise-induced fat loss is associated with change in resting substrate utilization
Authors: Nicholas D. Barwell, Dalia Malkova, Melanie Leggate, Jason M.R. Gill
Journal: Metabolism (2009)

Fat loss in response to exercise training varies between individuals, even when differences in compliance to the exercise program are accounted for. The purpose of this study was to investigate whether individual variation in change in fasting respiratory quotient (RQ) after exercise training contributes to this interindividual variability. Fifty-five premenopausal women participated in a 7-week endurance-type exercise training program; and fitness, body composition, and resting substrate utilization and metabolic rate in the fasted state were assessed at baseline and postintervention. Total net energy expenditure of the exercise intervention (exEE) was determined from heart rate obtained in all exercise sessions and individualized calibration of the heart rate vs oxygen uptake relationship. Dietary intake and physical activity (by constant heart rate monitoring) were assessed at baseline and during the final week of the intervention. Mean change in fat mass for the group was -0.97 kg (range, +2.1 to -5.3 kg). The strongest correlate of change in fat mass was exEE (r = 0.60, P < .0005). Change in fasting RQ correlated significantly (r = -0.26, P = .05) with the residual for change in fat mass after adjusting for the effects of both exEE and change in energy intake, explaining 7% of the variance. In multiple regression analysis, exEE (P < .0005) and change in fasting RQ (P = .02) were the only statistically significant independent predictors of change in fat mass, together explaining 40.2% of the variance. Thus, fat loss in response to exercise training depends not only on exercise energy expenditure but also on exercise training-induced changes in RQ at rest. This suggests that development of strategies to maximize the change in resting fat oxidation in response to an exercise training program may help individuals to maximize exercise-induced fat loss.
The Accelerated Internal Medicine Program at the University of Kentucky
Authors: John S. Thompson, Steven A. Haist, Philip A. DeSimone, Joseph Engelberg, Eugene C. Rich
Journal: Annals of Internal Medicine (1992)

Concern is growing about the ability of categorical medicine residency programs, structured within academic health centers, to provide balanced, progressive, postgraduate internal medicine education. Detrimental factors, including over-representation of critically ill patients, shortened length of hospitalization, stress, discontinuity between undergraduate and graduate training, rotational assignments driven by hospital service imperatives, and total costs, may all negatively affect internal medicine residency education. Therefore, an experimental accelerated internal medicine (AIM) curriculum combining 3 years of undergraduate with 3 years of graduate internal medicine education has been initiated by the Department of Medicine and the College of Medicine at the University of Kentucky. After completion of the third year and during the first 13 months of the AIM curriculum, selected students are rotated through an integrated series of educational experiences that incorporate all of the requirements for graduation from medical school and progressively advance the students' skills, knowledge, and responsibilities to that of a second-year resident. Thereafter, the curriculum is similar to that of the categorical residents, except that more ambulatory care and off-site rotations are interspersed to better provide the educational experiences representative of the practice of internal medicine. Evaluations of the first groups of AIM residents indicate that their performance has equaled that of the control residents who graduated after 4 years from the College of Medicine. Furthermore, the AIM residents report general acceptance by their fellow residents and attending physicians and report no undue stress in making the transition.
A Multiple-Dose Phase I Trial of Recombinant Leukocyte A Interferon in Cancer Patients
Authors: S. A. Sherwin, J. A. Knost, S. Fein, P. G. Abrams, K. A. Foon, J. J. Ochs, C. Schoenberger, A. E. Maluish, R. K. Oldham
Journal: JAMA (1982)

Eighty-one patients with a variety of refractory disseminated malignant neoplasms have been treated in the first multiple fixed-dose phase I trial of recombinant leukocyte A interferon (IFL-rA). Each patient received IFL-rA by intramuscular injection, three times weekly for 28 days. Dosages were escalated in different patients from 1 to 136 x 10(6) units per injection. The toxic reactions seen with IFL-rA resembled those of nonrecombinant leukocyte interferon and included fever, chills, fatigue, anorexia, myalgia, headache, occasional nausea and vomiting, and dose-dependent reversible leukopenia and hepatic transaminase elevations. The pharmacokinetics of IFL-rA were also comparable with nonrecombinant leukocyte interferon. Objective evidence of antitumor activity was seen in non-Hodgkin's lymphoma, chronic lymphocytic leukemia, Hodgkin's disease, breast cancer, and melanoma, indicating that IFL-rA, the first genetically engineered biological response modifier available for testing in cancer patients, is biologically active in vivo.
LAVAGE FOR INTESTINAL OBSTRUCTION IN CYSTIC FIBROSIS
Authors: N.K. Harrison, A.C. Davidson, D.M. Geddes, R. Nelson, I. Sharkey, J.R. Beesley, P.R. Durie, G.J. Cleghorn, G.G. Forstner, D.A. Stringer
Journal: The Lancet (1986)
RELATIONSHIP BETWEEN URINE MICROALBUMIN AND RED CELL DISTRIBUTION WIDTH: AN ANALYSIS OF THE NATIONAL HEALTH AND NUTRITION EXAMINATION SURVEY 1999 TO 2006
Authors: Sidakpal S. Panaich, Naga VA Kommuri, Sandip K. Zalawadiya, Vikas Veeranna, Ashutosh Niraj, Sony Jacob, Luis Afonso
Journal: Journal of the American College of Cardiology (2011)
Abstract 4906: Tamoxifen-mediated apoptosis relationship with ERα36 in gastric cancer cell BGC823
Authors: Yan Li, Hao Deng, Jun Fan, Diwei Zhou, Ying Chen, Chengxin Wang
Journal: Cancer Research (2012)

Abstract Aim: The growth, apoptosis and estrogen receptor α36 (ERα36) expression and location changes in gastric cancer cell line BGC823 were observed, when dealt with different concentrations Tamoxifen (TAM), to characterize the role of TAM in gastric cancer growth and apoptosis and the mechanism of it. Materials and Methods: BGC823 cell was dealt with 10-6M and 10-5M TAM for 24h and 48h. Cell growth was assessed by WST1 assay. The mRNA and protein expressions of ERα36 were examined by RT-PCR and Western blot methods. Average optical densities were detected and processed using Student's t test analysis. Immunofluorescence assay was used to examine ER-α36 location in BGC823 cell. Hoechest33258 assay was used to examine apoptosis. Results: TAM could promote apoptosis and inhibit growth of BGC823 cell, and this effect had concentration dependant (P&amp;lt;0.05). TAM could promote ERα36 mRNA expression, and the increase level of ERα36 mRNA expression had concentration dependent of E2β(P&amp;lt;0.05). TAM could promote ERα36 protein expression, and the increase level of ERα36 protein expression had concentration dependent of E2β(P&amp;lt;0.05). The location of ERα36 had no change, when BGC823 cell dealt with TAM.Conclusions: TAM could promote apoptosis and inhibit growth of BGC823 cell, and the effect had concentration dependant. TAM could promote ERα36 expression in BGC823 cell, and the effect had concentration dependant. ERα36 may participate apoptosis mediated by Tamoxifen in Gastric Cancer Cell Line BGC823 Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4906. doi:1538-7445.AM2012-4906
FRI0168 Drug discontinuation in 6,657 patients with ra starting their first tnf inhibitor: Comparison of adalimumab, etanercept &amp; infliximab
Authors: M. Neovius, E. Arkema, H. Olsson, J. Eriksson, J. Simard, J. Askling
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Biologics are likely to perform differently in different patient segments and between-drug differences may exist. Changing patient populations, practice and treatment alternatives may have led to calendar period differences in drug survival within and between TNF inhibitors. <h3>Objectives</h3> To compare drug discontinuation rates on adalimumab, etanercept, and infliximab in patients with RA overall and by calendar period. <h3>Methods</h3> Using the Swedish Biologics Register (ARTIS), adult patients with RA (n=6,657; 76% women; mean/median age 55/57y, HAQ 1.2/1.1, DAS28 5.2/5.3) initiating TNF inhibitor therapy between 2003 and 2009 were identified. Data on drug initiation and discontinuation of first anti-TNF prescription were collected through Dec 31, 2010. Drug discontinuation rates over a maximum of 5 years of follow-up for adalimumab, etanercept, and infliximab were compared overall and by calendar period (2003-2005/2006-2009; n=3,019/3,638). Adjustment was made for age, sex, education level, period, baseline HAQ, concomitant treatment (DMARD and steroids), and general frailty (using outpatient visits and hospital days in the previous two years as proxies). <h3>Results</h3> Over 13,808 person-years [pyrs; mean/median 2.1/1.6y] of follow-up, 3,141 patients discontinued their first line biologic (23/100pyrs; 43% due to inefficacy and 32% to adverse events). In adjusted analyses for the full period, infliximab (hazard ratio [HR] 1.7, 95%CI 1.5-1.8) and adalimumab (1.4, 95%CI 1.2-1.5) had higher discontinuation rates than etanercept, while infliximab had higher discontinuation rate than adalimumab (1.2, 95%CI 1.1-1.4; Figure). These findings were consistent across periods, but varied with HAQ and follow-up time (difference between etanercept and adalimumab present only during the first year of follow-up). The overall discontinuation rate was lower for starters in the 2003-2005 than the 2006-2009 period (crude rate 20 vs 27/100pyrs; adjusted HR 0.8, 95%CI 0.8-0.9). This held true also for each individual drug. The composition of 1y discontinuations also changed: discontinuations due to adverse events decreased from 40% to 32%, while inefficacy increased from 38% to 47% (both p&lt;0.001). <h3>Conclusions</h3> We found greater drug discontinuation rates in infliximab vs both adalimumab and etanercept, and adalimumab vs etanercept. The differences existed in both periods investigated, but varied with follow-up time and subgroup. <h3>Disclosure of Interest</h3> M. Neovius Grant/Research support from: This research received funding from Astra Zeneca through the Swedish public-private-partnership program on chronic inflammation (COMBINE), E. Arkema: None Declared, H. Olsson: None Declared, J. Eriksson: None Declared, J. Simard: None Declared, J. Askling: None Declared