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991.
We review and present current evidence supporting independent regulation of nuclear Ca2+ ([Ca2+]n). The nucleus and nuclear envelope contain proteins to both regulate and respond to changes in [Ca2+]n. However, this does not prove that [Ca2+]n is independently regulated from cytosolic Ca2+ ([Ca2+]c). Studies using fluorescent dyes suggested that changes in [Ca2+]n differed in magnitude from changes in [Ca2+]c. These studies have been criticised as the nuclear environment alters the fluorescent characteristics of these dyes. We have evaluated this question with aequorin targeted to the nucleus and cytoplasm and shown that the characteristics of the indicators are not altered in their respective environments. We have demonstrated that different stimuli induce changes in [Ca2+]n and [Ca2+]c that vary both temporally and in magnitude. The nucleus appeared to be shielded from increases in [Ca2+]c, either through a mechanism involving the nuclear envelope or by cytosolic buffering of localised increases in Ca2+. In addition, agonist stimulation resulted in an increase in [Ca2+]n, consistent with release from the perinuclear Ca2+ store. There was a stimulus dependence of the relation between [Ca2+]n and [Ca2+]c suggesting differential regulation of [Ca2+]n. These results have important implications for the role of Ca2+ as a specific regulator of nuclear events through Ca2+ binding proteins. In addition, they highlight the advantages of using targeted aequorin in intact cells to monitor changes in organelle [Ca2+].  相似文献   
992.
993.
The precise mechanism whereby mitomycin C enhances IOP reduction in glaucoma filtering surgery still eludes us. Ten rabbits received full-thickness Nd:YAG laser sclerostomy ab interno and adjunctive intraoperative treatment with mitomycin C (MMC) applied topically over the intact conjunctiva (0.5 mg ml-1 for 5 min). A systematic ultrastructural analysis of the fistulas and surrounding tissue was then conducted in conjunction with clinical observations, over the ensuing 10 weeks. In order to investigate also the extent to which MMC impedes fistula occlusion in the absence of percolating aqueous humour, we created non-perforating ('half-thickness') sclerostomies ab interno in three additional rabbits, one with and two without MMC therapy. Transconjunctival MMC application resulted in no serious complications. Eight of the ten full-thickness fistulas remained patent throughout the study, maintaining significant IOP reduction; the other two sclerostomies were compromised by iris incarceration. The MMC-treated, half-thickness canal remained as a tissue-free cul de sac; the two non-treated ones became completely occluded within one week without having recourse to extraocular cell populations. MMC suppressed the migration and proliferation of fibroblasts, macrophages and clump cells from the episclera, sclera, ciliary body and iris root. Repolymerization of heat-damaged collagen was abortive; neosynthesis was not observed. Myofibroblasts were encountered in the vicinity of the sclerostomy canals, and, after the fifth week, these cells were also found to be deployed as a canal-lining layer, delimiting the lumen from the surrounding stroma along most of the fistula length. Towards the external ostium, this layer of myofibroblasts was incomplete or absent. Near the internal ostium, lining cells were derived from the corneal endothelium. The transconjunctival mode of applying MMC appears to be efficient. This antifibrotic drug exerts its inhibitory influence by suppressing not only cell migration and proliferation, but also phagocytic and synthetic activities. However, exposed tissues are not acellular, and amongst the populations present, myofibroblasts are found to dominate the scene. The canal-delimiting cellular lining may play a role in maintaining fistula patency in MMC-treated eyes.  相似文献   
994.
We investigated effects of the endopeptidase 24.11 inhibitor, SCH 39370, on uterotonic effects of endothelins (ETs) and sarafotoxin S6b. Responses of uteri from non-pregnant rats were inhibited by the ETA receptor antagonist, BQ123 (1 microM) but not the ETB receptor antagonist, BQ 788 (1 microM). ET-1, sarafotoxin S6b and ET-2 were more potent than ET-3 in tissues from non-pregnant and pregnant rats. SCH 39370 (10 microM) did not affect uterotonic responses to these peptides in either group, but inhibited those of big ET-1 in non-pregnant rat tissues, indicating inhibition of conversion of big ET-1 to ET-1. These data indicate that endopeptidase 24.11 does not inactivate the endothelin peptides in the rat uterus.  相似文献   
995.
OBJECTIVES: This study quantified the impairment of quality of life attributable to body fatness by using the standardized SF-36 Health Survey. METHODS: Tertiles of waist circumference and body mass index (BMI) in 1885 men and 2156 women aged 20 to 59 years in the Netherlands in 1995 were compared. RESULTS: The odds ratios and 95% confidence intervals of subjects with the largest waist circumferences, compared with those in the lowest tertile, were 1.8 (1.3, 2.4) in men and 2.2 (1.7, 2.9) in women with difficulties in bending, kneeling, or stooping; 2.2 (1.4, 3.7) in men and 1.7 (1.2, 2.6) in women with difficulties in walking 500 m; and 1.3 (1.0, 1.9) in men and 1.5 (1.1, 1.9) in women with difficulties in lifting or carrying groceries. Anthropometric measures were less strongly associated with social functioning, role limitations due to physical or emotional problems, mental health, vitality, pain, or health change in 1 year. The relationship between quality of life measures and BMI were similar to those between quality of life measures and waist circumference. CONCLUSIONS: Large waist circumferences and high BMIs are more likely to be associated with impaired quality of life and disability affecting basic activities of daily living.  相似文献   
996.
997.
A simple two-step thermal processing technique was devised to impart a microduplex structure in a high strength 250 grade commercial maraging steel. A martensite grain size of approximately 1 μm was obtained with interspersed islands of retained austenite whose volume fraction and mechanical stability could be controlled by varying the thermal processing conditions. The microstructure and mechanical properties of the microduplex structure were compared to those of the alloy in the maraged, martensitic condition. Due to the presence of the austenite phase, the microduplex structure showed a much smaller temperature and strain rate dependence of deformation than the martensitic structure. A remarkable increase in uniform elongation was observed below theM d temperature of retained austenite. The microduplex structure did not show any significant advantage in fracture toughness over the martensitic structure when compared at similar strength levels. By suitably adjusting austenitic stability a deformation-induced phase transformation (TRIP) of the retained austenite in the microduplex structure could be made to occur; however, the transformation did not lead to any evident increase in toughness. The micro-duplex structure exhibited a slight improvement in fracture toughness at high strain rate in contrast to the martensitic structure in which the rate effect significantly reduced the toughness.  相似文献   
998.
999.
Solders of Pb-rich compositions, such as 5Sn-95Pb, are commonly used in electronic packaging applications, and this demanding use necessitates that the microstructure-property-processing relationships of the solder be understood fully. In this study, the microstructure of 5Sn-95Pb solder was characterized using a variety of metallographic techniques. The effect of cooling rate on the precipitation of β-Sn from supersaturated α-Pb was determined. On slow cooling, β-Sn precipitates discontinuously with resultant β-Sn lamella alternating with the α-Pb. Upon rapid cooling, the β-Sn precipitates with a nominally homogeneous distribution. These discrete precipitates were found to have a platelike shape with a (111)Pb habit plane and an orientation relationship of (111)Pb‖(010)Sn and [011]Pb‖ [001]Sn. Regions of the β-Sn precipitates that curved away from this habit plane formed ledges. Upon heating, the precipitates were found to dissolvevia a ledge mechanism. Prolonged aging of both the fast and slow cooled 5Sn-95Pb resulted in a coarsening of the β-Sn precipitates with a resultant decrease in strength. Furthermore, the strength of the aged alloy was observed to be independent of cooling rate. D.R. FREAR, formerly Graduate Research Assistant, Lawrence Berkeley Laboratory  相似文献   
1000.
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