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It is well known that deglycosylation of gonadotropins by enzymatic or chemical procedures or by deletion of sites for N-linked glycosylation produces antagonistic analogs which are able to interact strongly with the receptor and to inhibit binding of the wild-type hormone. In the present study, we analyzed the antagonistic properties of a naturally occurring basic follicle-stimulating hormone (FSH) charge isoform obtained after high-resolution chromatofocusing of human anterior pituitary glycoprotein extracts. Coincubation of increasing amounts of this isoform with a highly purified human pituitary FSH preparation or with recombinant human FSH at doses equivalent to their corresponding ED50 for estradiol and tissue-type plasminogen activator (tPA) production, inhibited FSH-induced estrogen production and tPA enzyme activity by cultured rat granulosa cells in a dose-dependent manner. These inhibitory effects were apparently exerted at steps following 3',5'-cyclic adenosine monophosphate (cAMP) formation and did not involve activation of the protein kinase C pathway since: (a) at low doses, this basic FSH isoform moderately increased FSH-induced cAMP production by cultured rat granulosa cells; (b) coincubation of the antagonist isoform with dibutyryl cAMP completely inhibited the effects of this cAMP analog on estrogen and tPA production; (c) the isoform was able to stimulate production of cAMP in a human fetal cell line expressing the recombinant human FSH receptor, and (d) the inhibitory effects of the isoform were not affected by staurosporine, a protein kinase C inhibitor. The effects of this isoform upon dibutyryl cAMP-induced estrogen and tPA production were blocked by the addition of a highly specific antibody directed against human FSH, further demonstrating that the antagonistic effects observed were due to FSH-like molecules. In contrast to the inhibitory effects exhibited by this basic FSH isoform, a more acidic FSH charge variant consistently acted as an agonist of pituitary and recombinant FSH on both estrogen production and induction of tPA enzyme activity. These results indicate that the anterior pituitary gland normally produces FSH isoforms which act as either agonists or antagonists of FSH at the target cell level. 相似文献
63.
HREM and FEG TEM were emphasized and extensively used to follow the most subtle changes in the structure and composition of ball-milled Cu, Fe-Cu, and thermally decomposed Fe60Cu40. Some significant results are obtained and summarized as follows: HREM shows that the deformation of ball-milled copper proceeds mainly by twinning and shear bands (SBs) formation. The nano-grains formed during ball milling (BM) contain a high density of dislocations. The grain boundaries (GBs) of nanocrystalline (NC) Cu prepared by BM are ordered, curved, and strained, but disordering, lattice distortion, and nanovoids in local regions were frequently observed. Nanoscale composition analysis on mechanically alloyed Fe16Cu84 shows that the average Fe content in both the interior of grains and the GBs is close to the designed composition, which proves that a supersaturated solid solution has really formed. However, the Fe content is rather inhomogeneous between the larger and smaller grains, which infers the inhomogeneous mixing of Fe and Cu during mechanical alloying (MA). NC structure and the mechanical force-enhanced fast diffusion are the reasons of the formation of supersaturated solid solutions in immiscible systems with positive enthalpy of mixing. HREM observations carried out with the thermally decomposed Fe60Cu40 solid solution show that the Nishiyama (N-W) or Kurdyumov-Sachs (K-S) orientation relationships exist between alpha-Fe and Cu. Energy dispersive X-ray spectra (EDXS) results show that the Cu content in these alpha-Fe grains reaches as high as 9.5 at.% even after heating to 1,400 degrees C, which is even higher than the maximum solubility of Cu in gamma-Fe at 1,094 degrees C. 相似文献
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Lysophosphatidylcholine (LPC) is formed by hydrolysis of PC in low density lipoprotein (LDL) and cell membranes by phospholipase A2 or by oxidation. Oxidized (ox) LDL activates endothelial cells, an effect mimicked by LPC. oxLDL also has the capacity to activate T and B cells, and antibody titers to oxLDL are related to the degree of atherosclerosis. The antigen in oxLDL responsible for its immune-stimulatory capacity is not well characterized, and we hypothesized that LPC was involved. We demonstrate herein the presence of antibodies against LPC, both of the IgG and IgM isotype, in 210 healthy individuals. This antibody reactivity was not specifically related to oxidation of the fatty acid moiety in LPC, since LPC containing only palmitic acid showed antibody titers equivalent to those of LPC containing unsaturated fatty acids. Antibody titers to PC were low compared with LPC, and hydrolysis of PC at the sn-2 position is thus essential for immune reactivity. There was a close correlation between anti-oxLDL and anti-LPC antibodies. Furthermore, LPC competitively inhibited anti-oxLDL reactivity, which indicates that LPC may explain a significant part of the immune-stimulatory properties of oxLDL. LPC, being a lipid, is not likely to be an antigen itself. Instead, LPC could form immunogenic complexes with peptides, which may induce and potentiate immune reactions in the vessel wall. This study adds to the evidence that LPC is an important component of oxLDL and emphasizes the potential role of phospholipase A2 in atherosclerosis. 相似文献
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Diagnosis and treatment of 17 patients who sustained 20 iatrogenic ureteral injuries were analyzed. Primary operations in which ureteral injury occurred are almost gynecologic procedures and general surgery. Injuries were managed by ureteroureterostomy in four, ureteral stent in one, removal suture ligation and ureteral double J-catheter in one, ureteroneocystostomy in ten, psoas-hitch technique and ureteroneocystostomy in one, nephrectomy in two. All patients with appropriate repair were followed-up periods of three to five years. Renal function of these patients had optimal results. When ureteral injury occurs, B-US, IVU, cystoscopy, retrograde ureterography or infusion of dye may be useful. An appropriate repair should be chosen according to length and position of ureteral injuries. Reoperation was optimal in two to three weeks. Immediate recognition of accidental ureteral injury provides optimal results. Patients with unrecognized injuries had suboptimal results. 相似文献
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新型高性能脉冲峰值保持电路 总被引:10,自引:7,他引:3
本文介绍了两种新型跨导型脉冲峰值保持器,分别用于多丝正比室(MWPC)和复合晶体闪烁探测器(Phoswich)输出脉冲信号的形状和幅度分析。电路的跨导放大级采用跨导型集成运算放大器,使电路结构简单化,且性能优良可靠,能响应输入脉冲最小上升时间分别为50ns(Phoswich)和500ns(MWPC)的信号,在40dB的动态范围内,两电路的积分非线性均好于0.1%,特别适用于空间γ射线观测。 相似文献