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71.
I J Goldberg J J Kandel C B Blum H N Ginsberg 《The Journal of clinical investigation》1986,78(6):1523-1528
Studies were designed to explore the association of lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) activities with lipoproteins in human postheparin plasma (PHP). The major peak of LPL activity after gel filtration of PHP eluted after the triglyceride-rich lipoproteins and just before the peak of low density lipoprotein (LDL) cholesterol. When PHP contained chylomicrons, an additional peak of LPL activity eluted in the void volume of the column. Most HTGL activity eluted after the LDL and preceded the elution of high density lipoprotein cholesterol. LPL activity in preheparin plasma eluted in the same position, relative to lipoproteins, as did LPL in PHP. Gel filtration of purified human milk LPL mixed with plasma or isolated LDL produced a peak of activity eluting before LDL. During gel filtration of PHP in high salt buffer (1 M NaCl) or after isolation of lipoproteins by ultracentrifugation in high salt density solutions, most of the lipase activity was not associated with lipoproteins. LPL activity was removed from PHP by elution through immunoaffinity columns containing antibodies to apolipoprotein (apo) B and apo E. Since lipoproteins in PHP have undergone prior in vivo lipolysis, LPL activity in PHP may be bound to remnants of chylomicrons and very low density lipoproteins. 相似文献
72.
Regression of established tumors and metastases by potent vascular endothelial growth factor blockade 总被引:11,自引:0,他引:11 下载免费PDF全文
Huang J Frischer JS Serur A Kadenhe A Yokoi A McCrudden KW New T O'Toole K Zabski S Rudge JS Holash J Yancopoulos GD Yamashiro DJ Kandel JJ 《Proceedings of the National Academy of Sciences of the United States of America》2003,100(13):7785-7790
Vascular endothelial growth factor (VEGF) is a critical promoter of blood vessel growth during embryonic development and tumorigenesis. To date, studies of VEGF antagonists have primarily focused on halting progression in models of minimal residual cancer. Consistent with this focus, recent clinical trials suggest that blockade of VEGF may impede cancer progression, presumably by preventing neoangiogenesis. However, VEGF is also a key mediator of endothelial-vascular mural cell interactions, a role that may contribute to the integrity of mature vessels in advanced tumors. Here, we report that high-affinity blockade of VEGF, using the recently described VEGF-Trap, abolishes mature, preexisting vasculature in established xenografts. Eradication of vasculature is followed by marked tumor regression, including regression of lung micrometastases. Thus, the contribution of relatively low levels of VEGF to vessel integrity may be critical to maintenance of even very small tumor masses. Potent blockade of VEGF may provide a new therapeutic option for patients with bulky, metastatic cancers. 相似文献
73.
74.
Mechanism of calcium current modulation underlying presynaptic facilitation and behavioral sensitization in Aplysia. 总被引:8,自引:23,他引:8 下载免费PDF全文
M Klein E R Kandel 《Proceedings of the National Academy of Sciences of the United States of America》1980,77(11):6912-6916
Behavioral sensitization of the gill-withdrawal reflex of Aplysia is caused by presynaptic facilitation at the synapses of the mechanoreceptor sensory neurons of the reflex onto the motor neurons and interneurons. The presynaptic facilitation has been shown to be simulated by serotonin (the putative presynaptic facilitatory transmitter) and by cyclic AMP and to be accompanied by an increase in the Ca2+ current of sensory neuron cell bodies exposed to tetraethylammonium. This increase in the Ca2+ current could result from either a direct action on the Ca2+ channel or an action on an opposing K+ current. Here we report voltage clamp experiments which indicate that the increase in Ca2+ current associated with presynaptic facilitation results from a decrease in a K+ current. Stimulation of the connective (the pathway that mediates sensitization) or application of serotonin causes a decrease in a voltage-sensitive, steady-state outward current measured under voltage clamp as well as an increase in the transient net inward and a decrease in the transient outward currents elicited by brief depolarizing command steps. The reversal potential of the steady-state synaptic current is sensitive to extracellular K+ concentration, and both the steady-state synaptic current and the changes in the transient currents are blocked by K+ current blocking agents and by washout of K+. These results suggest that serotonin and the natural transmitter released by connective stimulation act to decrease a voltage-sensitive K+ current. The decrease in K+ current prolongs the action potential, and this in turn increases the duration of the inward Ca2+ current and thereby enhances transmitter release. 相似文献
75.
Background
To identify patterns and correlates of developmental trajectories of DSM-IV nicotine dependence criteria from adolescence to early adulthood.Methods
The analytical sample of lifetime smokers (N = 877) is from a longitudinal cohort of 6th–10th graders drawn from an urban school system. Subjects were interviewed 5 times at 6-month intervals and once 4.5 years later. Growth mixture models were estimated to identify trajectories of DSM-IV nicotine dependence criteria over ages 12–23.Results
A four-class solution fitted the data best: No dependence criteria (Class 1, 32.0%); Early onset/Chronic course (Class 2, 26.1%); Early onset/Remission (Class 3, 15.4%); Late onset (Class 4, 26.5%). There appeared to be three critical periods. At ages 12–15, symptoms increased rapidly. As of age 16, the Early onset/Chronic class stabilized at high levels of symptoms, the Early onset/Remission class started its symptomatic decline, and the Late onset class experienced a sharp increase in symptoms. At age 20, there was a convergence in the prevalence of symptoms experienced at high (Classes 2 and 4) and low levels (Classes 1 and 3). Extensiveness of smoking and marijuana use were associated with higher baseline levels of nicotine dependence criteria. Anxiety disorders were associated with all three symptomatic trajectories. Parental smoking and nicotine dependence were associated specifically with the Early/Chronic class, while pleasant initial sensitivity and earlier onset ages of cigarette and marijuana use characterized the two early onset classes (2 and 3).Conclusions
Trajectories of dependence criteria constitute an advantageous phenotype for research and intervention over static summaries of smoking behaviors. 相似文献76.
Yoon-Jung Boo Mary Jo Haley Jessica J. Kandel Darrell J. Yamashiro 《Journal of pediatric surgery》2009,44(10):2031-2036
Clear cell sarcoma of the kidney (CCSK) is uncommon pediatric renal tumor and can present a significant therapeutic challenge in those patients whose tumors spread beyond the kidney. Thus, identifying potential novel targets for treatment may be clinically important. Clear cell sarcoma of the kidney is characterized by a unique vascular pattern, in which nests of tumor cells are separated by regularly-spaced, fine fibrovascular septa. This distinctive histopathology raises the possibility that understanding the factors which drive angiogenesis in CCSK tumors may suggest new therapeutic targets. Here, we describe a case of CCSK and present immunohistochemical studies of its vasculature. 相似文献
77.
Claudia J. Arana Eleftherios P. Diamandis Rita A. Kandel 《Arthritis \u0026amp; Rheumatology》2010,62(11):3395-3403
Objective
To investigate the effect of cartilage on nucleus pulposus (NP) tissue in an in vitro model.Methods
Cells were isolated from bovine NP or articular cartilage and allowed to form tissue in vitro. The NP tissue was grown either alone or in the presence of cartilage tissue (coculture) for up to 4 weeks and examined for histologic appearance, gene expression, and biochemical composition. For selected experiments, NP tissue was grown in coculture with fragments of cartilage end‐plate.Results
Coculture of in vitro–formed NP tissue with cartilage end‐plate tissue resulted in a significant increase in proteoglycan content in the NP tissue by 2 weeks, compared with NP tissue grown alone. Substituting in vitro–formed cartilage tissue for cartilage end‐plate also had a positive effect on the NP tissue, suggesting that it was an appropriate substitute for cartilage end‐plate. Coculture of NP with in vitro–formed cartilage for 2 weeks increased aggrecan and collagen gene expression compared with that in NP tissue grown alone, and also reduced expression of matrix metalloproteinase 3 (MMP‐3), MMP‐13, and ADAMTS‐5. NP cells from older and younger animals responded similarly to in vitro–formed cartilage. Expression of genes for tumor necrosis factor α (TNFα) and TACE in NP cells was higher when grown in the absence of cartilage. This corresponded with increased TNFα protein levels in the absence of cartilage.Conclusion
The data suggest that chondrocytes may secrete a factor(s) that positively enhances tissue growth, perhaps by inhibiting TNFα production. This could be a potential mechanism explaining how loss of the cartilage end‐plate may contribute to the development of NP degenerative changes.78.
Sang-Yong Jung Juhyun Kim Oh Bin Kwon Jung Hoon Jung Kyongman An A Young Jeong C. Justin Lee Yun-Beom Choi Craig H. Bailey Eric R. Kandel Joung-Hun Kim 《Proceedings of the National Academy of Sciences of the United States of America》2010,107(10):4710-4715
Despite considerable evidence for a critical role of neuroligin-1 in the specification of excitatory synapses, the cellular mechanisms and physiological roles of neuroligin-1 in mature neural circuits are poorly understood. In mutant mice deficient in neuroligin-1, or adult rats in which neuroligin-1 was depleted, we have found that neuroligin-1 stabilizes the NMDA receptors residing in the postsynaptic membrane of amygdala principal neurons, which allows for a normal range of NMDA receptor-mediated synaptic transmission. We observed marked decreases in NMDA receptor-mediated synaptic currents at afferent inputs to the amygdala of neuroligin-1 knockout mice. However, the knockout mice exhibited a significant impairment in spike-timing-dependent long-term potentiation (STD-LTP) at the thalamic but not the cortical inputs to the amygdala. Subsequent electrophysiological analyses indicated that STD-LTP in the cortical pathway is largely independent of activation of postsynaptic NMDA receptors. These findings suggest that neuroligin-1 can modulate, in a pathway-specific manner, synaptic plasticity in the amygdala circuits of adult animals, likely by regulating the abundance of postsynaptic NMDA receptors. 相似文献
79.
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