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991.
DA Giussani SL Jenkins CA Mecenas JA Winter JG Pedro DM Farber RS Goland PW Nathanielsz 《Canadian Metallurgical Quarterly》1996,137(2):608-614
To assess the interaction among androgens, placenta, and the hypothalamo-pituitary-adrenal axis we studied effects of androstenedione administered intravascularly to the pregnant monkey on maternal plasma CRH, ACTH, dehydroepiandrosterone sulfate (DHEAS), cortisol, and estradiol concentrations. Ten monkeys (128 +/- 3 days gestation; mean +/- SEM) were instrumented under general halothane anesthesia with maternal femoral artery and venous catheters and uterine electromyogram electrodes. At 137-144 days gestation, baseline maternal femoral artery samples for CRH, ACTH, DHEAS, cortisol, and estradiol measurements were taken at 1.5-h intervals for 7 h starting 2 h before darkness. On the following day, a continuous iv androstenedione infusion (0.3 mg/kg.min at 0.25 ml/h) in 10% intralipid was started at 0930 h in four monkeys; the other six animals received vehicle alone at the same rate starting at the same time. Maternal blood sampling was repeated 1 and 3 days after androstenedione or vehicle administration. Maternal plasma CRH, ACTH, DHEAS, cortisol, and estradiol levels were unaffected by intralipid. In contrast, androstenedione infusion produced a sustained increase in maternal plasma estradiol and a sustained fall in maternal plasma ACTH, but did not affect maternal plasma CRH, DHEAS, or cortisol concentrations. These results provide evidence for negative feedback regulation by androgens at the hypothalamo-pituitary-adrenal axis in the pregnant monkey. Lack of inhibition of maternal plasma CRH after androstenedione administration supports differential regulation of hypothalamic and placental CRH by androgens. 相似文献
992.
993.
SL Hu P Polacino V Stallard J Klaniecki S Pennathur BM Travis L Misher H Kornas AJ Langlois WR Morton RE Benveniste 《Canadian Metallurgical Quarterly》1996,51(1-2):115-119
Using pathogenic simian immunodeficiency virus (SIV) infection of macaques as a model, we explored the limits of the protective immunity elicited by recombinant subunit vaccines and examined factors that affect their efficacy. Envelope gp 160 vaccines, when used in a live recombinant virus-priming and subunit-protein-boosting regimen, protected macaques against a low-dose, intravenous infection by a cloned homologous virus SIVmne E11S. The same regimen was also effective against intrarectal challenge by the same virus and against intravenous challenge by E11S grown on primary macaque peripheral blood mononuclear cells (PBMC). However, only limited protection was observed against uncloned SIVmne. Priming with live recombinant virus was more effective than immunization with subunit gp 160 alone, indicating a potential advantage of native antigen presentation and the possible role of cell-mediated immunity in protection. Whole gp 160 was more effective than the surface antigen (gp 130), even though both antigens elicited similar levels of neutralizing antibodies. Animals immunized with the core (gag-pol) antigens failed to generate any neutralizing antibody and were all infected following challenge. However, their proviral load was 10-100-fold lower than that of the control animals, indicating that immune mechanisms such as cytotoxic T lymphocytes (CTL) may play a role. Finally, animals immunized with both the core and the envelope antigens generated significant protective immunity, even with relatively low neutralizing antibodies. Taken together, these results indicate that multiple mechanisms may contribute to protection. It may therefore be advantageous to incorporate multiple antigens in the design of recombinant subunit vaccines against acquired immunodeficiency syndrome (AIDS). 相似文献
994.
995.
996.
DD Donaldson MJ Whitters LJ Fitz TY Neben H Finnerty SL Henderson RM O'Hara DR Beier KJ Turner CR Wood M Collins 《Canadian Metallurgical Quarterly》1998,161(5):2317-2324
Two components of a receptor complex for IL-13, the IL-4R and a low affinity IL-13-binding chain, IL-13R alpha 1, have been cloned in mice and humans. An additional high affinity binding chain for IL-13, IL-13R alpha 2, has been described in humans. We isolated a cDNA from the thymus that encodes the murine orthologue of the human IL-13R alpha 2. The predicted protein sequence of murine IL-13R alpha 2 (mIL-13R alpha 2) has 59% overall identity to human IL-13R alpha 2 and is closely related to the murine low affinity IL-13-binding subunit, IL-13R alpha 1. The genes for both mIL-13-binding chains map to the X chromosome. A specific interaction between mIL-13R alpha 2.Fc protein and IL-13 was demonstrated by surface plasmon resonance using a BIACORE instrument. Ba/F3 cells that were transfected with mIL-13R alpha 2 expressed 5000 molecules per cell and bound IL-13 with a single Kd of 0.5 to 1.2 nM. However, these cells did not proliferate in response to IL-13, and the IL-4 dose response was unaffected by high concentrations of IL-13. In contrast, the expression of mIL-13R alpha 1 by Ba/F3 cells resulted in a sensitive proliferative response to IL-13. Consistent with its lower affinity for IL-13, IL-13R alpha 1.Fc was 100-fold less effective than IL-13R alpha 2.Fc in neutralizing IL-13 in vitro. These results show that mIL-13R alpha 2 and mIL-13R alpha 1 are not functionally equivalent and predict distinct roles for each polypeptide in IL-13R complex formation and in the modulation of IL-13 signal transduction. 相似文献
997.
CA Osborne SL Sanderson JP Lulich GR Johnston DJ Polzin 《Canadian Metallurgical Quarterly》1996,26(3):551-562
Surgical closure may not be necessary to successfully manage all patients with ruptured urinary bladders. If the margins of the walls of tears in the bladder wall are not devitalized, and if they remain in close apposition via maintenance of the bladder lumen in a nondistended state for an appropriate period, these conditions may simulate those created by use of surgical sutures. This is not advocating an all-or-none choice. Because the clinical status of patients with ruptured urinary bladders can range from that characterized by only hematuria and dysuria to life-threatening postrenal uremia, a range of surgical and medical options should be considered. 相似文献
998.
999.
GP Newnam RD Wegrzyn SL Lindquist YO Chernoff 《Canadian Metallurgical Quarterly》1999,19(2):1325-1333
The maintenance of [PSI], a prion-like form of the yeast release factor Sup35, requires a specific concentration of the chaperone protein Hsp104: either deletion or overexpression of Hsp104 will cure cells of [PSI]. A major puzzle of these studies was that overexpression of Hsp104 alone, from a heterologous promoter, cures cells of [PSI] very efficiently, yet the natural induction of Hsp104 with heat shock, stationary-phase growth, or sporulation does not. These observations pointed to a mechanism for protecting the genetic information carried by the [PSI] element from vicissitudes of the environment. Here, we show that simultaneous overexpression of Ssa1, a protein of the Hsp70 family, protects [PSI] from curing by overexpression of Hsp104. Ssa1 protein belongs to the Ssa subfamily, members of which are normally induced with Hsp104 during heat shock, stationary-phase growth, and sporulation. At the molecular level, excess Ssa1 prevents a shift of Sup35 protein from the insoluble (prion) to the soluble (cellular) state in the presence of excess Hsp104. Overexpression of Ssa1 also increases nonsense suppression by [PSI] when Hsp104 is expressed at its normal level. In contrast, hsp104 deletion strains lose [PSI] even in the presence of overproduced Ssa1. Overproduction of the unrelated chaperone protein Hsp82 (Hsp90) neither cured [PSI] nor antagonized the [PSI]-curing effect of overproduced Hsp104. Our results suggest it is the interplay between Hsp104 and Hsp70 that allows the maintenance of [PSI] under natural growth conditions. 相似文献
1000.
The effects of two potent sigma receptor agonists (+)-3-PPP ((R)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine) and DTG (N,N'-di-(o-tolyl)guanidine) on the insulin secretory responses in rat islets of Langerhans were investigated. Both sigma receptor ligands were able to potentiate the insulin secretory response of islets incubated at 6 mM glucose, in a dose-dependent manner and were also able to reverse the effects of diazoxide on insulin release. When islets were treated with efaroxan, a well-characterised imidazoline insulin secretagogue, and either (+)-3-PPP or DTG together, there was an unexpected and profound absence of stimulation of insulin release as compared to when islets were incubated with each compound alone. Experiments performed with islets where there was desensitization of DTG/sigma receptor or efaroxan/imidazoline binding site mediated responses suggest that at least two distinct receptor systems appear to be involved. The complex interactions of these two classes of drug require further investigation. 相似文献