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81.
Estrogen therapy increases plasma HDL levels, which may reduce cardiovascular risk in postmenopausal women. The mechanism of action of estrogen in influencing various steps in hepatic HDL and apolipoprotein (apo) A-I synthesis and secretion are not fully understood. In this study, we have used the human hepatoblastoma cell line (Hep G2) as an in vitro model system to delineate the effect of estradiol on multiple regulatory steps involved in hepatic HDL metabolism. Incubation of Hep G2 cells with estradiol resulted in the following statistically significant findings: (1) increased accumulation of apoA-I in the medium without affecting uptake/removal of radiolabeled HDL-protein; (2) accelerated incorporation of [3H]leucine into apoA-I; (3) selective increase in [3H]leucine incorporation into lipoprotein (LP) A-I but not LP A-I+A-II HDL particles (HDL particles without and with apoA-II, respectively); (4) increased ability of apoA-I-containing particles to efflux cholesterol from fibroblasts; (5) stimulated steady state apoA-I but not apoA-II mRNA expression; and (6) increased newly transcribed apoA-I mRNA message without effect on apoA-I mRNA half-life. The data indicate that estradiol stimulates newly transcribed hepatic apoA-I mRNA, resulting in a selective increase in LP A-I, a subfraction of HDL that is associated with decreased atherosclerotic cardiovascular disease, especially in premenopausal women.  相似文献   
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1. The pharmacological effects of 14-deoxyandrographolide on rat isolated thoracic aorta were examined. 2. 14-Deoxyandrographolide (2.5-120 mumol/L) inhibited contractions induced by phenylephrine (PE; 0.1 mumol/L) and high K+ (80 mmol/L) in a concentration-dependent manner in endothelium-intact aorta. The effect was attenuated in endothelium-denuded aorta without modifying the maximal response. Like verapamil, 14-deoxyandrographolide produced a much greater vasorelaxant effect in aorta precontracted by KCl than by PE. 14-Deoxyandrographolide (20-60 mumol/L) also inhibited responses of the rat aorta to PE. 3. In Ca(2+)-free medium (KCl 55 mmol/L), 14-deoxyandrographolide (20-80 mumol/L) antagonized Ca(2+)-induced vasocontraction in a concentration-dependent manner and transient contractions induced by both caffeine (10 mmol/L) and nor-adrenaline (1 mumol/L) were suppressed or almost abolished by 14-deoxyandrographolide. 4. The vasorelaxant effect of 14-deoxyandrographolide was partially antagonized by NG-nitro-L-arginine methyl ester (25 mumol/L), a specific and competitive nitric oxide synthase (NOS) inhibitor, and methylene blue (10 mumol/L), a soluble guanylate cyclase inhibitor, but was not affected by indomethacin (20 mumol/L), a cyclo-oxygenase inhibitor, or glibenclamide (10 mumol/L), an ATP-sensitive K(+)-channel blocker. 5. These results suggest that the vasorelaxant activity of 14-deoxyandrographolide may be mediated via the activation of NOS and guanylate cyclase, as well as the blockade of Ca2+ influx through both voltage- and receptor-operated Ca2+ channels.  相似文献   
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Rotavirus (RV) strains infecting newborns often have unique neutralization antigens (P serotypes) on their outer capsids that are distinct from those found on RV strains that cause diarrhea in older children. We examined the hypothesis that unusual RV strains preferentially infect newborns because the newborns lack maternal neutralizing antibodies to these strains. To test this hypothesis, sera and saliva samples collected from neonates infected with 116E-like (P[11]G9) strains in the maternity ward of the All India Institute of Medical Sciences (AIIMS) hospital in New Delhi were tested for neutralizing antibodies against common RV strains and those infecting newborns and these titers were compared with those of newborns who did not become infected (controls). The infected neonates had significantly lower levels of cord blood neutralizing antibodies to 116E than the controls, suggesting that immunity to neonatal RV infection is acquired transplacentally through maternal antibodies. Further, this study confirmed the immunogenicity of the AIIMS neonatal strain 116E, a vaccine candidate, in its ability to evoke a potent RV-specific immunoglobulin A and neutralizing antibody response in serum and saliva among the infected babies. Our findings have important implications for the development of an effective RV vaccine. In India, where G9 strains are common in the community, the use of 116E as a vaccine, together with the rhesus tetravalent vaccine, may provide a broader protection against all the circulating RV serotypes, including serotype G9, which is not represented in the current rhesus RV tetravalent vaccine (G1-G4).  相似文献   
86.
The effect of a naturally occurring plant phenolic constituent (the acylphloroglucinol derivative, jensenone, derived from Eucalyptus jensenii) on the food intake of two folivorous marsupials, the common ringtail (Pseudocheirus peregrinus) and the common brushtail possum (Trichosurus vulpecula) was studied. When fed diets containing varying concentrations of jensenone, both species regulated their intake of jensenone so as not to exceed a ceiling intake. This ceiling was about twice as high for common ringtails as for common brushtails from northern Australia. Southern populations of common ringtails showed greatly reduced capacities to tolerate jensenone. When common brushtails were injected (0.5 mg.kg-0.75 body mass) with ondansetron (a selective antagonist of serotonin 5HT3 receptors), they ate significantly more jensenone than animals injected with physiological saline. The same pattern was observed when common ringtails were fed diets containing both jensenone and ondansetron (0.0035 mg.g-1 wet mass of diet). Ondansetron injection had no effect on food intake when the food did not contain jensenone while the addition of higher doses of ondansetron to diets of common ringtails very slightly reduced food intakes of a non-jensenone diet. When common brushtails were given 50 mg of jensenone by gastric lavage, their average subsequent intake of dietary jensenone matched the difference between the daily threshold and the dose given, although the response of individuals was highly variable. Lavage with water alone had no effect on subsequent jensenone intake compared with the pre-dose period. We interpret these results as evidence that the antifeedant effects of jensenone and related compounds are partly mediated by serotonin action on 5HT3 receptors most likely via "nausea" to condition a food aversion.  相似文献   
87.
Haemophilus influenzae is a bacterium of medical interest of which the entire genome has been sequenced. The proteome of the microorganism has been analyzed by two-dimensional gel electrophoresis, during which immobilized pH 3-10 gradient strips were used and approximately 300 proteins were identified. In order to detect additional, basic proteins, we analyzed the soluble protein fraction of H. influenzae and the proteins of fractions collected from affinity chromatography on heparin, by two-dimensional gel electrophoresis, using for the first-dimensional separation immobilized pH gradient strips comprising the pH region of 6-11. The protein spots were analyzed by matrix-assisted laser desorption ionization-mass spectrometry. One hundred and two proteins were identified, of which 58 were identified for the first time. A large percentage of the basic proteins represent nucleic acid binding and, in particular, ribosomal proteins. The locations of the identified basic proteins of H. influenzae are indicated in a two-dimensional map.  相似文献   
88.
PURPOSE: This study investigated the pathogenesis of tractional retinal detachment associated with proliferative vitreoretinopathy in an experimental model, using immunohistochemical staining. METHODS: To produce tractional retinal detachment in rabbit eyes, homologous cultured fibroblasts obtained from the gluteal muscle fascia were injected intravitreously. Right eyes of 20 rabbits in the study group, and 7 rabbits in the control group were followed for 26 days at weekly intervals with indirect ophthalmoscopy and fundus photographs. RESULTS: During the follow-up period grade III tractional retinal detachment developed in 11 eyes, grade II in six, and grade 1 in three eyes. The spindle-shaped cells contributed predominantly to the development of epiretinal membrane, and a smaller number of round small and large cells. In 10/17 grade II and III eyes, spindle-shaped cells had vimentin, 7/10 had actin, 5/17 had GFAP, 4/17 had S-100 protein immunoreactivity. Round small and large cells expressed S-100 protein, GFAP and actin in 5/17 eyes. Epiretinal membrane appeared to be formed by spindle-shaped fibroblast-like cells and small and large round glia-like cells. Actin positivity of spindle-shaped and round cells was taken as a marker of contractile elements of the cells and their locomotional features. CONCLUSIONS: These features are believed to be involved in contraction of the membrane and retinal detachment.  相似文献   
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We conducted a prospective randomized controlled study on the prophylactic effects of short-term intravesical instillation of pirarubicin (THP) against recurrence to determine the effective administration schedule. All patients gave their informed consent. The subjects included bladder cancer patients who had pTa or pT1, and G1 or G2 cancer, and became tumor-free after transurethral resection of the bladder tumor (TUR-BT). After dissolving 30 mg of THP into 5 ml of distilled water, physiological saline was added to adjust the total volume to 50 ml, which was then instilled into the bladder, and was retained for 5 minutes. The schedule of instillation was for daily for 7 consecutive days from the day of TUR-BT and subsequently once a week for 10 weeks, 17 times in total for Group I, and once every two weeks for 6 months (12 times) starting 2 weeks after TUR and subsequently once a month until one year had passed after surgery (6 times), 18 times in total for Group II. The total number of cases was 69 (36 in Group I, 33 in Group II). The tumor-free ratios determined by the Kaplan-Meier analysis were 93.9% in Group I and 72.7% in Group II for one year, and 86.8% in Group I and 59.5% in Group II for two years. There was a statistically significant difference in the tumor-free ratios between the two groups by the generalized Wilcoxon test and the Log rank test (p = 0.0145 and 0.0107, respectively). Multivariated analysis using Cox's comparison hazard model produced p-values of 0.0002, 0.0007, 0.0009 and 0.0040 in the order of therapeutic mode, initial onset/recurrence, stage and number of tumor. Adverse events that forced discontinuation of the therapy for a while occurred in 4.3%. These results demonstrated that short-term intensive intravesical instillation of THP immediately after TUR-BT was a safe and effective therapy.  相似文献   
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