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71.
Purified natural cholecystokinin (CCK-33) was infused continuously for two days at a rate of 5.9 μg/hr in two rats trained to bar-press for food (Noyes pellet 45 mg) on a fixed ratio of five bar presses to obtain one pellet. The animals also received control surgery and were tested in the operant chamber for two days, one prior to and the other following the CCK-33 treatment. CCK-33 suppressed the number of meals, the total amount of food eaten, and the total duration of time spent eating. However, the size of each meal and the rate of intake were not affected. The CCK effect did not interact with the light-dark phases of diurnal cycle. It appears that a major effect of continuous systemic elevation of CCK-33 is to reduce food intake by prolonging the satiety period rather than by decreasing the individual meal size. 相似文献
72.
Hsiao G Teng CM Sheu JR Cheng YW Lam KK Lee YM Wu TS Yen MH 《Biochimica et biophysica acta》2001,1525(1-2):77-88
The antioxidant properties of cinnamophilin were evaluated by studying its ability to react with relevant reactive oxygen species, and its protective effect on cultured cells and biomacromolecules under oxidative stress. Cinnamophilin concentration-dependently suppressed non-enzymatic iron-induced lipid peroxidation in rat brain homogenates with an IC50 value of 8.0+/-0.7 microM and iron ion/ADP/ascorbate-initiated rat liver mitochondrial lipid peroxidation with an IC50 value of 17.7+/-0.2 microM. It also exerted an inhibitory activity on NADPH-dependent microsomal lipid peroxidation with an IC50 value of 3.4+/-0.1 microM without affecting microsomal electron transport of NADPH-cytochrome P-450 reductase. Both 1,1-diphenyl-2-picrylhydrazyl and 2,2'-azo-bis(2-amidinopropane) dihydrochloride-derived peroxyl radical tests demonstrated that cinnamophilin possessed marked free radical scavenging capacity. Cinnamophilin significantly protected cultured rat aortic smooth muscle cells (A7r5) against alloxan/iron ion/H2O2-induced damage resulting in cytoplasmic membranous disturbance and mitochondrial potential decay. By the way, cinnamophilin inhibited copper-catalyzed oxidation of human low-density lipoprotein, as measured by fluorescence intensity and thiobarbituric acid-reactive substance formation in a concentration-dependent manner. On the other hand, it was reactive toward superoxide anions generated by the xanthine/xanthine oxidase system and the aortic segment from aged spontaneously hypertensive rat. Furthermore, cinnamophilin exerted a divergent effect on the respiratory burst of human neutrophil by different stimulators. Our results show that cinnamophilin acts as a novel antioxidant and cytoprotectant against oxidative damage. 相似文献
73.
We have addressed the role of occipital and somatosensory cortex in a tactile discrimination task. Sight-ed and congenitally blind subjects rated the roughness and distance spacing for a series of raised dot patterns. When judging roughness, intermediate dot spacings were perceived as being the most rough, while distance judgments generated a linear relation. Low-frequency rTMS applied to somatosensory cortex disrupted roughness without affecting distance judgments, while rTMS to occipital cortex disrupted distance but not roughness judgments. We also tested an early blind patient with bilateral occipital cortex damage. Her performance on the roughness determination task was normal; however, she was greatly impaired with distance judgments. The findings suggest a double-dissociation effect in which roughness and distance are primarily processed in somatosensory and occipital cortex, respectively. The differential effect of rTMS on task performance and corroborative clinical evidence suggest that occipital cortex is engaged in tactile tasks requiring fine spatial discrimination. 相似文献
74.
Bradykinin-stimulated p42/p44 MAPK activation associated with cell proliferation in corneal keratocytes 总被引:1,自引:0,他引:1
Bradykinin (BK) is released into the tear-film in ocular allergic patients. BK has been shown to exert mitogenic effects on several cell types. However, the mechanisms underlying its action on corneal keratocytes (CKs) were largely unknown. This study was to investigate the mitogenic effect of BK on rabbit CKs linked to activation of p42/p44 mitogen-activated protein kinase (MAPK), assessed by [3H]thymidine incorporation and Western blotting analysis, respectively. BK stimulated [3H]thymidine incorporation and p42/p44 MAPK phosphorylation in a time- and concentration-dependent manner. Pretreatment with pertussis toxin attenuated the BK-induced responses. BK-stimulated responses were attenuated by inhibitors of selective B2 receptor (Hoe 140), phosphatidylinositol (PI)-PLC (U73122), an intracellular Ca2+chelator (BAPTA/AM), PKC (GF109203X), tyrosine kinase (genistein), and MEK1/2 (PD98059). BK also stimulated translocation of p42/p44 MAPK into nucleus and led to expression of c-fos and c-jun in CKs. These results demonstrate that in CKs, BK-stimulated phosphorylation of p42/p44 MAPK is mediated through the activation of BK B2 receptors and leads to cell proliferation. 相似文献
75.
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77.
Hsu PI Li CN Tseng HH Lai KH Hsu PN Lo GH Lo CC Yeh JJ Ger LP Hsiao M Yamaoka Y Hwang IR Chen A 《Helicobacter》2004,9(6):605-613
BACKGROUND: The host genetic factors that determine the clinical outcomes for Helicobacter pylori-infected individuals remain unclear. AIMS: To elucidate the relations among interleukin-1 locus polymorphisms, and H. pylori infection in the development of duodenal ulcers. MATERIALS AND METHODS: In a case-control study involving 168 control subjects and 147 patients with duodenal ulcer, biallelic polymorphisms of two interleukin-1 loci, IL-1B(-511) and IL-1B(+3954), as well as the penta-allelic variable number of tandem repeats of interleukin-1 receptor antagonist IL-1RN, were genotyped, and the H. pylori states of controls and patients were examined. RESULTS: Helicobacter pylori infection, male gender and the carriage of IL-1RN*2 independently increased the risk of duodenal ulcer with odds ratios of 6.4 (95% confidence interval, 3.7-11.0), 1.9 (95% confidence interval, 1.1-3.4) and 2.7 (95% confidence interval, 1.1-6.8), respectively. Statistical analysis revealed an interaction between IL-1RN*2 and H. pylori infection with the duodenal ulcer risk conferred by the H. pylori infection substantially increased (odds ratios, 22.6; 95% confidence interval, 5.9-86.5) by the carriage of IL-1RN*2. In addition, a synergistic interaction between IL-1RN*2 and blood group O existed. The combined risk of H. pylori infection, the carriage of IL-1RN*2 and blood group O for duodenal ulcer was 27.5 (95% confidence interval, 3.1-243.6). CONCLUSIONS: This work is the first to verify IL-1RN*2 as an independent factor that governs the development of duodenal ulcers. Our data indicate that H. pylori infection and IL-1RN*2 synergistically determine susceptibility to duodenal ulcer. The blood group phenotype is possibly a crucial determinant for the outcome of the impact of an interleukin-1 locus polymorphism on H. pylori-infected individuals. 相似文献
78.
Plasticity of rat bone marrow-derived 5-hydroxytryptamine-sensitive neurons: dedifferentiation and redifferentiation 总被引:7,自引:0,他引:7
Li TY Shu C Wong CH Lo PS Zhu H Lau MC Chan MY Tsang LL Gou YL Chung YW Chan HC 《Cell biology international》2004,28(11):801-807
Inducing cellular dedifferentiation has been proposed as a potential method for enhancing endogenous regeneration in mammals. Here we demonstrate that phenotypic and functional neurons derived from adult rat bone marrow stromal stem cells (MSCs) can be induced to undergo dedifferentiation, then proliferation and redifferentiation. In addition to morphological changes and expression of neuronal markers, neuron-specific enolase and neurofilament H, functional differentiation was monitored by intracellular Ca2+ mobilization in response to a ubiquitous neurotransmitter, 5-hydroxytryptamine (5-HT) at different stages. The neurons derived from rMSCs were found to have increased 5-HT response. This 5-HT sensitivity could be reversed to basal level similar to that found in rMSCs when neurons, up to 3 days after neuronal induction, were induced to undergo dedifferentiation. Increase in 5-HT-induced Ca2+ mobilization was again observed when rMSCs derived from dedifferentiated neurons were induced to redifferentiate into neurons again. Variation in 5-HT1A receptor immunoreactivity was observed in stem cells, differentiated neurons, dedifferentiated neurons and redifferentiation neurons, consistent with their respective 5-HT sensitivity. These results suggest that adult bone marrow-derived 5-HT sensitive neurons are capable of dedifferentiation, then proliferation and redifferentiation, indicating their plasticity and potential use in treatment of neural degenerative diseases. 相似文献
79.
OxLDL induces mitogen-activated protein kinase activation mediated via PI3-kinase/Akt in vascular smooth muscle cells 总被引:14,自引:0,他引:14
Oxidized low-density lipoprotein (OxLDL) is a risk factor in atherosclerosis and stimulates multiple signaling pathways, including activation of phosphatidylinositol 3-kinase (PI3-K)/Akt and p42/p44 mitogen-activated protein kinase (MAPK), which are involved in mitogenesis of vascular smooth muscle cells (VSMCs). We therefore investigated the relationship between PI3-K/Akt and p42/p44 MAPK activation and cell proliferation induced by OxLDL. OxLDL stimulated Akt phosphorylation in a time- and concentration-dependent manner, as determined by Western blot analysis. Phosphorylation of Akt stimulated by OxLDL and epidermal growth factor (EGF) was attenuated by inhibitors of PI3-K (wortmannin and LY294002) and intracellular Ca2+ chelator (BAPTA/AM) plus EDTA. Pretreatment of VSMCs with pertussis toxin, cholera toxin, and forskolin for 24 h also attenuated the OxLDL-stimulated Akt phosphorylation. In addition, pretreatment of VSMCs with wortmannin or LY294002 inhibited OxLDL-stimulated p42/p44 MAPK phosphorylation and [3H]thymidine incorporation. Furthermore, treatment with U0126, an inhibitor of MAPK kinase (MEK)1/2, attenuated the p42/p44 MAPK phosphorylation, but had no effect on Akt activation in response to OxLDL and EGF. Overexpression of p85-DN or Akt-DN mutants attenuated MEK1/2 and p42/p44 MAPK phosphorylation stimulated by OxLDL and EGF. These results suggest that the mitogenic effect of OxLDL is, at least in part, mediated through activation of PI3-K/Akt/MEK/MAPK pathway in VSMCs. 相似文献
80.
Hsu YM Chiu CT Wang CC Chien CS Luo SF Hsiao LD Liang KY Yang CM 《Cellular signalling》2001,13(9):633-643
Inhalation of tumour necrosis factor-alpha (TNF-alpha) induced a bronchial hyperreactivity to contractile agonists. However, the mechanisms of TNF-alpha involved in the pathogenesis of bronchial hyperreactivity were not completely understood. Therefore, we investigated the effect of TNF-alpha on bradykinin (BK)-induced inositol phosphate (IP) accumulation and Ca(2+) mobilization, and up-regulation of BK receptor density in canine cultured tracheal smooth muscle cells (TSMCs). Pretreatment of TSMCs with TNF-alpha potentiated BK-induced IP accumulation and Ca(2+) mobilization. However, there was no effect on the IP response induced by endothelin-1 (ET-1), 5-hydroxytryptamine (5-HT), and carbachol. Pretreatment with PDGF B-chain homodimer (PDGF-BB) also enhanced BK-induced IP response. These enhancements induced by TNF-alpha and PDGF-BB might be due to an increase in BK B(2) receptor density (B(max)), since [3H]BK binding to TSMCs was inhibited by the B(2) selective agonist and antagonist, BK and Hoe 140, but not by the B(1) selective reagents. The enhancing effects of TNF-alpha and PDGF-BB were attenuated by PD98059 (an inhibitor of activation of MAPK kinase, MEK) and cycloheximide (an inhibitor of protein synthesis), suggesting that TNF-alpha may share a common signalling pathway with PDGF-BB via protein(s) synthesis in TSMCs. Furthermore, overexpression of dominant negative mutants, H-Ras-15A and Raf-N4, significantly suppressed p42/p44 mitogen-activated protein kinase (MAPK) activation induced by TNF-alpha and PDGF-BB and attenuated the effect of TNF-alpha on BK-induced IP response, indicating that Ras and Raf may be required for activation of these kinases. These results suggest that the augmentation of BK-induced responses produced by TNF-alpha might be, at least in part, mediated through activation of Ras/Raf/MEK/MAPK pathway in TSMCs. 相似文献