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21.
Metabolism of native and of lactosylated human low density lipoprotein: evidence for two pathways for catabolism of exogenous proteins in rat hepatocytes. 总被引:4,自引:2,他引:4 下载免费PDF全文
A D Attie R C Pittman D Steinberg 《Proceedings of the National Academy of Sciences of the United States of America》1980,77(10):5923-5927
Human low density lipoprotein (LDL) covalently conjugated with 200-250 residues of lactose per LDL particle (Lac-LDL) was bound and rapidly taken up by the galactose-specific receptor of rat hepatocytes. Uptake of Lac-LDL was associated with inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase and stimulation of cholesterol esterification. Uptake of native human LDL had no significant effects on these enzyme activities even when the rates of LDL uptake equaled those of Lac-LDL. When injected into rats, Lac-LDL was selectively removed by the liver (98% of injected dose). The hepatic subcellular distribution of simultaneously injected native 125I-labeled LDL and 131I-labeled Lac-LDL differed significantly, Lac-LDL was associated with fractions enriched in lysosomal hydrolases whereas native LDL was found predominantly in the supernatant fraction enriched in lactate dehydrogenase. Chloroquine (0.1 mM) markedly suppressed uptake of Lac-LDL by cultured rat hepatocytes (> 80%) but had only a small effect on uptake of native LDL. Leupeptin (0.625 mM) inhibited degradation of Lac-LDL more than it did degradation of native LDL. Colchicine (0.25 microM) dramatically suppressed uptake of Lac-LDL (> 70%) but did not affect native LDL uptake even at concentrations as high as 10 microM. Uptake of human LDL by rat hepatocytes occurs largely by nonspecific mechanisms, including fluid endocytosis, whereas Lac-LDL, as shown here, is taken up by a specific receptor-mediated mechanism. The results show further that native human LDL, representing an example of a protein taken up nonspecifically, is processed intracellularly by a pathway qualitatively distinct from that for Lac-LDL, an example of a protein taken up by a specific mechanism. Lac-LDL may serve as a vehicle for specifically delivering drugs, hormones, or radioactive compounds to hepatocytes for therapeutic or diagnostic purposes. 相似文献
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Catherine R. Ayers Mary E. Dozier Charles T. Taylor Tina L. Mayes James O. E. Pittman Elizabeth W. Twamley 《Cognitive therapy and research》2018,42(3):315-327
While cognitive-behavioral therapy for hoarding disorder (HD) has resulted in significant reductions in symptoms, most individuals continue to have significant hoarding symptoms following treatment. This investigation sought to extend the literature on the behavioral treatments for hoarding by examining (1) group cognitive rehabilitation and exposure/sorting therapy (CREST) and (2) group exposure therapy (ET) for hoarding. Participants in both studies reported significant decreases in hoarding symptom severity from baseline to post-treatment on all primary outcome measures using mixed-effects linear regression models with the intent to treat sample. Participants who received group CREST reported statistically significant reductions in anxiety, depression, and overall severity at post-treatment, while participants who received group ET did not. Results provide preliminary evidence for both group CREST and group ET as effective treatments for hoarding disorder. 相似文献
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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
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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29.
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30.
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