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61.
AndrewJ. Stott Michel C. Maillard Vahri Beaumont David Allcock Omar Aziz Alexander H. Borchers Wesley Blackaby Perla Breccia Gillian Creighton-Gutteridge Alan F. Haughan Rebecca E. Jarvis Christopher A. Luckhurst Kim L. Matthews George McAllister Scott Pollack Elizabeth Saville-Stones Amanda J. Van de Poël Huw D. Vater Julie Vann Rachel Williams Dawn Yates Ignacio Muoz-Sanjun Celia Dominguez 《ACS medicinal chemistry letters》2021,12(3):380
Using an iterative structure–activity relationship driven approach, we identified a CNS-penetrant 5-(trifluoromethyl)-1,2,4-oxadiazole (TFMO, 12) with a pharmacokinetic profile suitable for probing class IIa histone deacetylase (HDAC) inhibition in vivo. Given the lack of understanding of endogenous class IIa HDAC substrates, we developed a surrogate readout to measure compound effects in vivo, by exploiting the >100-fold selectivity compound 12 exhibits over class I/IIb HDACs. We achieved adequate brain exposure with compound 12 in mice to estimate a class I/IIb deacetylation EC50, using class I substrate H4K12 acetylation and global acetylation levels as a pharmacodynamic readout. We observed excellent correlation between the compound 12 in vivo pharmacodynamic response and in vitro class I/IIb cellular activity. Applying the same relationship to class IIa HDAC inhibition, we estimated the compound 12 dose required to inhibit class IIa HDAC activity, for use in preclinical models of Huntington’s disease. 相似文献
62.
Pollack S 《Ostomy/wound management》2005,51(2):12-3; author reply 13
63.
Cardiac muscle models. An overextension of series elasticity? 总被引:1,自引:0,他引:1
64.
E. J. Wawszkiewicz H. A. Schneider B. Starcher J. Pollack J. B. Neilands 《Proceedings of the National Academy of Sciences of the United States of America》1971,68(11):2870-2873
Salmonellosis pacifarin activity is detected by an increased survivorship of mice, doubly infected with avirulent and virulent Salmonella typhimurium, when heretofore unknown agents, found in certain natural foodstuffs and in the supernatants of certain bacterial cultures, are fed to the infected animals as dietary supplements. We now announce the identity of one of these agents: it is enterobactin, a cyclic trimer of 2,3-dihydroxy-N-benzoyl-L-serine. Basal diets enriched with as little as 2 mg of crystalline trimer per kg of diet show pacifarin activity to a statistically significant degree. Diets supplemented with as much as 100 mg of the monomer per kg of diet show no such activity. 相似文献
65.
S Charlap B Kimmel J Berezow S Molinas J Strom J Wexler H Willens N Klein S Pollack W H Frishman 《Angiology》1985,36(4):240-252
The short-term (1 month) and long-term (6 months) safety of combination lidoflazine-propranolol therapy was investigated in an open trial of 15 patients with stable angina of effort. The possible advantages of adding lidoflazine (titrated to 360 mg daily) to patients having a therapeutic response to propranolol (80-400 mg daily) was also evaluated. Effects on non-invasive indexes of left ventricular function (echocardiography, systolic time intervals, radionuclide ventriculography) and exercise tolerance (treadmill exercise testing) were determined. There was no change in mean resting heart rate with the combination therapy, although one patient developed sinus bradycardia at a rate of 44 and had to have his propranolol dose reduced. Electrocardiographic analysis showed significant prolongation of the QTc intervals on lidoflazine-propranolol therapy compared to propranolol alone, with 3 patients having QTc interval prolongation to above .53 seconds, but there was no evidence of increased arrhythmogenesis with the combination therapy compared to propranolol alone. Left ventricular end-diastolic volume index tended to rise with combination therapy. However, lidoflazine-propranolol therapy did not produce any significant effects on resting ejection fraction determined by M-mode echocardiography or by radionuclide ventriculography. Radionuclide ventriculography determined peak exercise ejection fractions were also not significantly changed with combination therapy compared to propranolol alone. There were only small, insignificant improvements in exercise tolerance with the lidoflazine-propranolol combination treatment compared to propranolol alone. It is concluded that lidoflazine-propranolol combination therapy is generally safe but has the potential of causing serious adverse effects in certain patients, i.e. those with sick sinus disease, prolonged QTc intervals, and severe baseline left ventricular dysfunction, and that caution must be exercised in its use. Furthermore, it would appear that combination therapy provides only slight, if any, improvements in exercise tolerance in patients with chronic stable angina having a therapeutic response to oral propranolol. 相似文献
66.
CE Faggons C Mabedi CG Shores S Gopal 《Malawi medical journal : the journal of Medical Association of Malawi》2015,27(3):79-87
Aim
Review the literature from 1990 to 2013 to determine known anatomic sites, risk factors, treatments, and outcomes of head and neck squamous cell carcinoma (HNSCC) in sub-Saharan Africa.Methods
Using a systematic search strategy, literature pertaining to HNSCC in sub-Saharan Africa was reviewed and patient demographics, anatomic sites, histology, stage, treatment, and outcomes were abstracted. The contributions of human immunodeficiency virus (HIV), human papillomavirus (HPV) and behavioural risk factors to HNSCC in the region were assessed.Results
Of the 342 papers identified, 46 were utilized for review, including 8611 patients. In sub-Saharan Africa, the oropharyngeal/oral cavity was found to be the most common site, with 7750 cases (90% of all cases). Few papers distinguished oropharyngeal from oral cavity, making identification of possible HPV-associated oropharyngeal squamous cell carcinoma (SCC) difficult. SCC of the nasopharynx, nasal cavity, or paranasal sinuses was identified in 410 patients (4.8% of all cases). Laryngeal SCC was found in 385 patients (4.5% of all cases), and only 66 patients (0.8% of all cases) with hypopharyngeal SCC were identified. In 862 patients with data available, 43% used tobacco and 42% used alcohol, and reported use varied widely and was more common in laryngeal SCC than that of the oropharyngeal/oral cavity. Toombak and kola nut use was reported to be higher in patients with HNSCC. Several papers reported HIV-positive patients with HNSCC, but it was not possible to determine HNSCC prevalence in HIV-positive compared to negative patients. Reports of treatment and outcomes were rare.Conclusions
The oropharyngeal/oral cavity was by far the most commonly reported site of HNSCC reported in sub-Saharan Africa. The roles of risk factors in HNSCC incidence in sub-Saharan Africa were difficult to delineate from the available studies, but a majority of patients did not use tobacco and alcohol. 相似文献67.
68.
Megan L. Clayton Katherine Clegg Smith Roni A. Neff Keshia M. Pollack Margaret Ensminger 《International journal of occupational and environmental health》2015,21(4):314-327
Background
Foodborne disease is a significant problem worldwide. Research exploring sources of outbreaks indicates a pronounced role for food workers'' improper health and hygiene practice.Objective
To investigate food workers'' perceptions of factors that impact proper food safety practice.Method
Interviews with food service workers in Baltimore, MD, USA discussing food safety practices and factors that impact implementation in the workplace. A social ecological model organizes multiple levels of influence on health and hygiene behavior.Results
Issues raised by interviewees include factors across the five levels of the social ecological model, and confirm findings from previous work. Interviews also reveal many factors not highlighted in prior work, including issues with food service policies and procedures, working conditions (e.g., pay and benefits), community resources, and state and federal policies.Conclusion
Food safety interventions should adopt an ecological orientation that accounts for factors at multiple levels, including workers'' social and structural context, that impact food safety practice. 相似文献69.
NMR‐based approach to the analysis of radiopharmaceuticals: radiochemical purity,specific activity,and radioactive concentration values by proton and tritium NMR spectroscopy 下载免费PDF全文
David J. Schenk Peter G. Dormer David Hesk Scott R. Pollack Carolee Flader Lavey 《Journal of labelled compounds & radiopharmaceuticals》2015,58(7):291-298
Compounds containing tritium are widely used across the drug discovery and development landscape. These materials are widely utilized because they can be efficiently synthesized and produced at high specific activity. Results from internally calibrated 3H and 1H nuclear magnetic resonance (NMR) spectroscopy suggests that at least in some cases, this calibrated approach could supplement or potentially replace radio‐high‐performance liquid chromatography for radiochemical purity, dilution and scintillation counting for the measurement of radioactivity per volume, and liquid chromatography/mass spectrometry analysis for the determination of specific activity. In summary, the NMR‐derived values agreed with those from the standard approaches to within 1% to 9% for solution count and specific activity. Additionally, the NMR‐derived values for radiochemical purity deviated by less than 5%. A benefit of this method is that these values may be calculated at the same time that 3H NMR analysis provides the location and distribution of tritium atoms within the molecule. Presented and discussed here is the application of this method, advantages and disadvantages of the approach, and a rationale for utilizing internally calibrated 1H and 3H NMR spectroscopy for specific activity, radioactive concentration, and radiochemical purity whenever acquiring 3H NMR for tritium location. 相似文献
70.
Antibody against tuberlin: the specific visualization of cytoplasmic microtubules in tissue culture cells. 总被引:24,自引:11,他引:24 下载免费PDF全文
K Weber R Pollack T Bibring 《Proceedings of the National Academy of Sciences of the United States of America》1975,72(2):459-463
Cytoplasmic microtubules in tissue culture cells can be directly visualized by immunofluorescence microscopy. Antibody against tubulin from the outer doublets of sea urchin sperm flagella decorates a network of fine cytoplasmic fibers in a variety of cell lines of human, monkey, rat, mouse, and chicken origin. These fibers are separate and of uniform thickness and are seen throughout the cytoplasm. The fibers disappear either in a medium containing colchicine or after subjection of the cells to low temperature. The same treatments do not destroy the microfilamentous structures that are visualized by means of antibody against actin. When tryspin-treated enucleated cells are replated and then stained with antibody against tubulin, the fibers can be seen to traverse the entire enucleated cytoplasm. 相似文献