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61.
Diazepam (5 mg/kg, ip) and tracazolate (40 mg/kg, ip), a nonbenzodiazepine anxiolytic, blocked electrically-induced head-turning without producing sedation. Bicuculline and picrotoxin, GABA antagonists, at doses not affecting head-turning (2 mg/kg, ip) antagonized the effects of diazepam and tracazolate on head-turning. However, at the same dose, bicuculline was more effective as an antagonist of diazepam whereas picrotoxin was more effective as an antagonist of tracazolate. These results suggest that benzodiazepine as well as nonbenzodiazepine anxiolytics possess GABAmimetic activity. The difference in potency between bicuculline and picrotoxin as antagonists of diazepam and tracazolate may be related to their reported differences as GABA antagonists (e.g., site of receptor interaction). 相似文献
62.
Depletion of intracellular potassium arrests coated pit formation and receptor-mediated endocytosis in fibroblasts 总被引:54,自引:0,他引:54
Depletion of intracellular potassium (K+) caused a marked reduction in the rate of endocytosis of receptor-bound low density lipoprotein (LDL) and epidermal growth factor (EGF) in human fibroblasts. K+ could be depleted slowly by a 3-hr incubation of cells in isotonic K+-free buffer. Rapid K+ depletion was induced by incubation of cells for 5 min with hypotonic medium, followed by transfer to isotonic K+-free buffer. Within 30 min of this treatment, cellular K+ levels fell by more than 60%. When the K+ level fell below a threshold of 40% of normal, the number of coated pits declined by 80% and the rate of endocytosis of 125I-LDL decreased by 70 to 95% despite normal to increased receptor binding. Similar results were obtained with 125I-epidermal growth factor. Addition of KCl to the culture medium up to 2 hr after K+ depletion restored cellular K+ levels and returned endocytosis of 125I-LDL promptly to normal. RbCl was as effective as KCl, but CsCl, LiCl, and (CH3)4NCl had no effect. Restoration by KCl was blocked by ouabain, indicating that uptake via the Na+/K+ ATPase was required. These data demonstrate that depletion of intracellular K+ reversibly arrests coated pit formation and receptor-mediated endocytosis in human fibroblasts. 相似文献
63.
Irwin J. Goldstein 《Journal of biosciences》1983,5(1):65-71
The physical-chemical and carbohydrate binding specificity ofGriffonia simplicifolia I (GS I) isolectins, one of the 4 lectins isolated fromGriffonia simplicifolia seeds, are described.Association constants for the binding of methyl α- and β-D-galactopyranoside and methyl 2-acetamido-2-deoxy-α-D-galactopyranoside to the A4, A2 B2 and B4 isolectins are reported.Precipitation reactions of theGriffonia simplicifolia isolectins with guaran and type B blood group substance are described.The hypothesis that subunit B is a precursor of subunit A, a process involving proteolytic cleavage of the B subunit, was tested by conducting structural studies on the 2 subunits. The results indicated that the A and B subunits are probably products of 2 separate but closely related, possibly contiguous genes. 相似文献
64.
Isolation and characterization of a family of alpha-D-galactosyl-containing glycopeptides from Ehrlich ascites tumor cells 总被引:8,自引:0,他引:8
A family of glycopeptides that contain nonreducing terminal alpha-D-galactosyl residues has been isolated from Pronase digests of delipidated Ehrlich ascites tumor cells. The glycopeptides, which comprise 17.2% of the total plasma membrane hexose, have an average molecular weight of 7500 and are precipitated by Griffonia simplicifolia B4 isolectin, wheat germ agglutinin, and Ricinus communis lectin. Exo- and endoglycosidase digestion, periodate oxidation, permethylation analysis, and lectin reactivity provided evidence for a tentative carbohydrate structure for the glycopeptide mixture. The glycopeptides possess tetraantennary branched structures containing a trimannosyl core N-glycosidically linked via an N,N'-diacetylchitobiosyl unit to an asparagine residue. Each branch contained repeating leads to 3)-beta-D-Galp-(1 leads to 4)-beta-D-GlcNAcp-(1 leads to units resulting in a keratan-like structure, terminated with alpha-D-Galp-(1 leads to 3)-[alpha-D-Galp-(1 leads to 6)]-beta-D-Galp-units. The variation in the molecular weight observed for the glycopeptide mixture can be attributed to the variable amounts of leads to 3)-beta-D-Galp-(1 leads to 4)-beta-D-GlcNAcp-(1 leads to units found in the branch chains. 相似文献
65.
Cristina Rinaldi-Garaci Enrico Garaci Vera Del Gobbo Cartesio Favalli Teresa Jezzi Allan L. Goldstein 《Cellular immunology》1983,80(1):57-65
The effects of thymosin-α1 on the stimulation of specific release of prostaglandin E2 (PGE2) from splenic lymphocytes and thymocytes were studied. Experiments were also performed to study in parallel the absolute levels of thymosin-α1 in the blood and the induction of serum FTS activity and of azathioprine sensitivity of spleen cells from adult thymectomized (ATx) mice. A significant difference in the release of PGE2 between normal splenocytes and splenocytes from ATx mice was observed. Thymosin-α1 at certain concentrations was able to stimulate PGE2 release from lymphocytes of ATx mice while inhibiting release in lymphocytes of normal mice. Also, thymocytes were stimulated to release PGE2 after incubation with α1 in a manner similar to that seen in spleen cells of ATx mice. Approximately the same concentration of α1 was found to also correct the low azathioprine sensitivity of splenocytes from ATx mice. Determinations of FTS-like activity in the blood and the pharmacokinetics of α1 after administration of this synthetic molecule show a clear dissociation. A maximum peak of α1 activity was obtained after 1 hr, while maximal FTS-like activity was observed after 24 hr. The inhibition of the induction by α1 of FTS-like activity and of Thy 1.2 antigen by indomethacin suggests that the action of α1 requires prostaglandin biosynthesis. 相似文献
66.
Development of catecholaminergic phenotypic characters in the mouse locus coeruleus in vivo and in culture 总被引:1,自引:0,他引:1
While abundant studies have begun to elucidate ontogeny of the peripheral nervous system, molecular mechanisms underlying brain development remain obscure. To approach this problem, we initiated parallel in vivo and in vitro studies of the mouse locus coeruleus (l.c.), a brainstem noradrenergic nucleus. The catecholaminergic enzymes tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH) were used to monitor phenotype expression and development. TH catalytic activity and immunocytochemical reactivity were initially detectable on gestational Day 13 (E-13) in vivo, and adult levels of activity were approximately by the third postnatal week. Immunotitration studies indicated that the developmental increase was due to accumulation of enzyme molecules and not enzyme activation. The in vivo developmental profile of DBH approximated that of TH. To begin defining regulatory mechanisms, explants of embryonic brainstem were placed in culture. Explantation on E-12, prior to expression of TH or DBH, resulted in the de novo appearance of these phenotypic characters after 4 days. Explantation on E-18, after the enzymes are already expressed, was followed by a striking sixfold rise in TH activity. Immunotitration studies revealed that the increase in TH activity in E-18 cultures was attributable to increased molecule number, reproducing the in vivo results. Moreover, the E-18 explants, cultured for 3 weeks, attained higher plateau levels of TH activity than E-12 cultures, and this differences was due to increased molecule number. Morphometric analysis indicated that 3-week E-12 cultures actually had more l.c. cells than E-18 cultures, indicating that differences in TH were not due to increased cells in the E-18 l.c. Finally, systemic study revealed that the development of TH activity in culture increased progressively from E-11 to E-12 to E-13, suggesting that critical regulatory events occur at this time. Our studies suggest that the l.c. is an excellent model for the study of brain development in vivo and in vitro. Initial phenotypic expression and dramatic development occur in culture in the absence of normal targets, normal afferent innervation and, presumably, normal humoural milieu. 相似文献
67.
Thymosin and the immunopathology of aging 总被引:4,自引:0,他引:4
A L Goldstein J A Hooper R S Schulof G H Cohen G B Thurman M C McDaniel A White M Dardenne 《Federation proceedings》1974,33(9):2053-2056
68.
Nitrogen mustard (HN2)-sensitive Ehrlich ascites tumour cells, exposed to HN2 in vivo, showed an inhibition of DNA synthesis which increased with dosage. The effects of alkylation involved at least three distinct components: (1) interference with new 9S DNA chain formation, (2) slowing of the rate of chain growth and (3) loss of newly formed short chains. The dominant effect seemed to be abortive synthesis of new 9S chains; this effect could account for most of the inhibition of DNA synthesis if an initial rapid synthesis of 9S DNA were accompanied by an initial rapid rate of destruction of these chains. By relating the known frequencies of guaninyl alkylations to the postulated ‘replicon’ size observed in control experiments, it appears that only difunctional alkylation frequencies can be directly correlated with the inhibition of discontinuous DNA synthesis by HN2, Mechanistically, this could reflect interference of di-guaninyl alkylations with the integration of 9S chains into 30S, 44S and higher molecular weight species of DNA by ligases. The resulting obstructed short chains, ≦ 9S, might be exposed and so be vulnerable to destruction by the increased nuclease activities expected after alkylation. 相似文献
69.
Chemically modified nylons as supports for enzyme immobilization. Polyisonitrile-nylon 总被引:1,自引:0,他引:1 下载免费PDF全文
Four-component condensations between amine, carboxyl, isocyanide and aldehyde lead to the formation of N-substituted amides (Ugi, 1962). The present paper describes the use of such condensations for the introduction of chemically reactive groups on to the polyamide backbone of nylon. Polyisonitrile-nylon was synthesized by partial hydrolysis of nylon-6 powder, followed by resealing of the newly formed -CO(2)... NH(2) (-) pairs via a four-component condensation, by using acetaldehyde and 1,6-di-isocyanohexane. Polyisonitrile-nylon could also be converted into a diazotizable arylamino derivative, polyaminoaryl-nylon, by a four-component condensation by using a bifunctional amine, pp'-diaminodiphenylmethane, in the presence of an aldehyde and a carboxylate compound. The versatility of four-component condensations involving the isocyanide functional group of polyisonitrile-nylon allowed coupling of proteins, in an aqueous medium at neutral pH, through either their amino or carboxyl groups. Trypsin and papain were bound to polyisonitrile-nylon through their amino groups by a four-component condensation by using acetaldehyde and acetate; conversely, succinyl-(3-carboxypropionyl-)trypsin, pepsin and papain were coupled through their carboxyl groups in the presence of acetaldehyde and an amine (Tris). Diazotized polyaminoaryl-nylon could be utilized for the immobilization of papain, via the tyrosine residues of the enzyme. 相似文献
70.