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31.
A large region (approximately equal to 95 kDa) of human factor VIII is dispensable for in vitro procoagulant activity. 总被引:13,自引:4,他引:13 下载免费PDF全文
J J Toole D D Pittman E C Orr P Murtha L C Wasley R J Kaufman 《Proceedings of the National Academy of Sciences of the United States of America》1986,83(16):5939-5942
Factor VIII (antihemophilic factor) is a high molecular weight plasma glycoprotein that participates in the blood clotting cascade. The recent cloning and sequence analysis of the cDNA encoding human factor VIII revealed an obvious domain structure for the protein, which can be represented as A1-A2-B-A3-C1-C2. We now report the DNA sequence analysis of porcine exons encoding the entire B domain and part of the A2 and A3 domains. We found an unusually high degree of porcine-human amino acid sequence divergence in the B region compared with the limited sequence available for other regions of the porcine factor VIII molecule. In addition to sequence divergence, there are numerous gaps in the porcine B domain totalling over 200 amino acids. Recombinant DNA techniques were used to effect the removal of large segments of DNA encoding the B domain from the full-length human factor VIII cDNA. These constructs directed the synthesis of biologically active factor VIII when introduced into mammalian cells despite the deletion of up to 38% of the factor VIII molecule. 相似文献
32.
A nomenclature for tests of thyroid hormones in serum: report of a committee of the American Thyroid Association 总被引:4,自引:0,他引:4
33.
Misty R. Gilbert Yinxing Liu Janna Neltner Hong Pu Andrew Morris Manjula Sunkara Thomas Pittman Natasha Kyprianou Craig Horbinski 《Acta neuropathologica》2014,127(2):221-233
IDH1 mutations in gliomas associate with longer survival. Prooxidant and antiproliferative effects of IDH1 mutations and its d-2-hydroxyglutarate (2-HG) product have been described in vitro, but inconsistently observed. It is also unclear whether overexpression of mutant IDH1 in wild-type cells accurately phenocopies the effects of endogenous IDH1-mutations on tumor apoptosis and autophagy. Herein we investigated the effects of 2-HG and mutant IDH1 overexpression on proliferation, apoptosis, oxidative stress, and autophagy in IDH1 wild-type glioma cells, and compared those results with patient-derived tumors. 2-HG reduced viability and proliferation of U87MG and LN18 cells, triggered apoptosis in LN18 cells, and autophagy in U87MG cells. In vitro studies and flank xenografts of U87MG cells overexpressing R132H IDH1 exhibited increased oxidative stress, including increases of both manganese superoxide dismutase (MnSOD) and p62. Patient-derived IDH1-mutant tumors showed no significant differences in apoptosis or autophagy, but showed p62 accumulation and actually trended toward reduced MnSOD expression. These data indicate that mutant IDH1 and 2-HG can induce oxidative stress, autophagy, and apoptosis, but these effects vary greatly according to cell type. 相似文献
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Robert F. Leeman Elizabeth Ralevski Diana Limoncelli Brian Pittman Stephanie S. O’Malley Ismene L. Petrakis 《Psychopharmacology》2014,231(14):2867-2876
Rationale
Impulsivity and individual differences in subjective response to alcohol are risk factors for alcohol problems and possibly endophenotypes for alcohol dependence. Few prior studies have addressed relationships between the two constructs.Objectives
To predict subjective responses to ethanol, we tested self-reported impulsiveness, ethanol dose condition (high dose, low dose, or placebo), and time (seven time points) along with interactions among these variables.Methods
The present study is a secondary analysis of data from a within-subject, placebo-controlled, dose-ranging ethanol administration study using IV infusion with a clamping technique to maintain steady-state breath alcohol concentration. The sample consisted of healthy, non-alcohol dependent social alcohol drinkers between the ages of 21 and 30 (N?=?105). Participants at varying levels of impulsivity were compared with regard to stimulant and subjective responses to three ethanol dose conditions over time.Results
Individuals with higher impulsivity reported elavated stimulant and dampened sedative response to alcohol, particularly at the higher dose. Higher impulsivity was associated with a steeper increase in stimulant effects during the first half of clamped ethanol infusion with the higher dose.Conclusions
These results suggest that impulsive individuals may experience enhanced reinforcing, stimulant effects, and relatively muted aversive sedative effects from alcohol. These subjective responses may relate to enhanced risk of alcohol problems among more impulsive individuals. 相似文献38.
Mohini Ranganathan R. Andrew Sewell Michelle Carbuto Jacqueline Elander Ashley Schnakenberg Rajiv Radhakrishnan Brian Pittman Deepak Cyril D’Souza 《Psychopharmacology》2014,231(12):2385-2393
Background and aims
A family history (FH) of alcoholism accounts for approximately 50 % of the risk of developing alcohol problems. Several lines of preclinical evidence suggest that brain cannabinoid receptor (CB1R) function may mediate the effects of alcohol and risk for developing alcoholism including the observations that reduced CB1R function decreases alcohol-related behaviors and enhanced CB1R function increases them. In this first human study, we probed CB1R function in individuals vulnerable to alcoholism with the exogenous cannabinoid Δ9-tetrahydrocannabinol (Δ9-THC).Design, setting, and participants
Healthy volunteers (n?=?30) participated in a three test day study during which they received 0.018 and 0.036 mg/kg of Δ9-THC, or placebo intravenously in a randomized, counterbalanced order under double-blind conditions.Measurements
Primary outcome measures were subjective “high,” perceptual alterations, and memory impairment. Secondary outcome measures consisted of stimulatory and depressant subjective effects, attention, spatial memory, executive function, Δ9-THC and 11-hydroxy-THC blood levels, and other subjective effects. FH was calculated using the Family Pattern Density method and was used as a continuous variable.Findings
Greater FH was correlated with greater “high” and perceptual alterations induced by Δ9-THC. This enhanced sensitivity with increasing FH was specific to Δ9-THC’s rewarding effects and persisted even when FH was calculated using an alternate method.Conclusions
Enhanced sensitivity to the rewarding effects of Δ9-THC in high-FH volunteers suggests that alterations in CB1R function might contribute to alcohol misuse vulnerability. 相似文献39.
目的 分析延边地区建立肺结核归口转诊模式对肺结核病人的转诊到位率的影响,探讨提高转诊到位率的方法。方法 对全州8个县(市)医院、中医医院、中心卫生院、大型厂矿企事业单位职工医院的执法检查考核资料进行评价。结果 1.建立归口转诊模式前期转诊率为48.3%,转诊到位率为29.0%,后期转诊率为89.0%,转诊到位率为72.4%,有明显提高;2.前期年平均涂阳病人新登记率为13.36/10万,后期为17.86/10万,实施归口转诊模式前期与实施后期的指标有显著性差异(P<0.01)。结论 延边地区实施的肺结核病人归口转诊模式,对提高肺结核病的转诊到位率十分有效,应不断完善并深入推广。 相似文献
40.
Imran Syed Sami Khan Tahir Khan Sabeeh Syed Taha Khan Azhar Ali Katherine Harries Ermanno Capuano Alexia Farrugia Marcus Pittman Godwin Simon Tayyab Haider Fawad Ali Indrajit Gupta Qaiser Malik 《The British journal of radiology》2020,93(1116)
As the COVID-19 pandemic has spread across the globe, questions have arisen about the approach healthcare systems should adopt in order to optimally manage patient influx. With a focus on the impact of COVID-19 on the NHS, we describe the frontline experience of a severely affected hospital in close proximity to London. We highlight a protocol-driven approach, incorporating the use of CT in the rapid triage, assessment and cohorting of patients, in an environment where there was a lack of readily available, onsite RT-PCR testing facilities. Furthermore, the effects of the protocol on the effective streamlining of patient flow within the hospital are discussed, as are the resultant improvements in clinical management decisions within the acute care service. This model may help other healthcare systems in managing this pandemic whilst assessing their own needs and resources. 相似文献