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91.
The amyloid beta-protein (A beta) that is progressively deposited in Alzheimer's disease (AD) arises from proteolysis of the integral membrane protein, beta-amyloid precursor protein (beta APP). Although A beta formation appears to play a seminal role in AD, only a few studies have examined the chemical structure of A beta purified from brain, and there are discrepancies among the findings. We describe a new method for the rapid extraction and purification of A beta that minimizes artifactual proteolysis. A beta purified by two-dimensional reverse-phase HPLC was analyzed by combined amino acid sequencing and mass spectrometry after digestion with a lysylendopeptidase. The major A beta peptide in the cerebral cortex of all five AD brains examined was aspartic acid 1 to valine 40. A minor species beginning at glutamic acid 3 but blocked by conversion to pyroglutamate was also found in all cases. A species ending at threonine 43 was detected, varying from approximately 5 to 25% of total A beta COOH-terminal fragments. Peptides ending with valine 39, isoleucine 41, or alanine 42 were not detected, except for one brain with a minor peptide ending at valine 39. Our findings suggest that A beta 1-40 is the major species of beta-protein in AD cerebral cortex. A beta 1-40 and A beta 1-43 peptides could arise independently from beta APP, or A beta 1-43 could be the initial excised fragment, followed by digestion to yield A beta 1-40. These analyses of native A beta in AD brain recommend the use of synthetic A beta 1-40 peptide to model amyloid fibrillogenesis and toxicity in vitro. 相似文献
92.
S Yamada M Suzuki Y Kato R Kimura R Mori K Matsumoto M Maruyama K Kawabe 《Life sciences》1992,50(2):127-135
Binding properties of naftopidil and alpha 1-adrenoceptor antagonists to alpha-adrenoceptors in prostates from benign prostatic hypertrophy (BPH) were characterized by radioreceptor assays using [3H]prazosin and [3H]rauwolscine. Specific binding of [3H]prazosin and [3H]rauwolscine in human prostatic membranes was saturable and of high affinity, and it showed a pharmacological specificity which characterized alpha 1 and alpha 2-adrenoceptors, respectively. Naftopidil and several alpha 1 antagonists competed for prostatic [3H]prazosin binding in order: R-(-)-YM-12617 greater than prazosin greater than bunazosin greater than terazosin greater than naftopidil greater than urapidil, and the inhibitory effect (Ki = 11.6 nM) of naftopidil was 10 to 45 times less potent than quinazoline derivatives such as prazosin, bunazosin and terazosin. The potencies of these antagonists in competing for [3H]prazosin binding sites in human prostates correlated well with their pharmacological potencies (pA2). Scatchard analysis indicated that the decrease of prostatic [3H]prazosin binding by naftopidil was due to a marked increase in the Kd value without a change in the Bmax value. The inhibition of prostatic [3H]prazosin binding by naftopidil was reversible. Naftopidil also inhibited prostatic [3H]rauwolscine binding (Ki = 70.0 nM). Thus, it is suggested that naftopidil antagonizes alpha 1-adrenoceptors in human prostates in a competitive and reversible manner. 相似文献
93.
Inhibitory effects of danazol, an isoxazol derivative of synthetic steroid 17 alpha-ethinyl-testosterone, on the development of uterine adenomyosis, a pathological disorder of endometrial tissue defined as the presence of endometrial glands and stroma in the myometrium, were investigated in mice of SHN strain. Mice treated with 0.5 microgram danazol for 5 weeks during 4-9 weeks of age and killed at 21 weeks of age showed significantly lower incidence of the spontaneous development of adenomyosis than the age-matched intact control mice. The inhibitory effects of danazol were also evident in mice bearing pituitary isografts which were effective in inducing an early and a high incidence of adenomyosis. Furthermore, the treatment with danazol resulted in the decrease of serum levels of luteinizing hormone (LH) and prolactin (PRL) associated with hypofunction of ovaries and persistent diestrus. These results support the usefulness of danazol for the clinical treatment of gynecological disorders except for hypofunction of ovaries. 相似文献
94.
cDNA Cloning of Indole-3-Acetic Acid-Regulated Genes: Aux22 and SAUR from Mung Bean (Vigna radiata) Hypocotyl Tissue 总被引:3,自引:0,他引:3
Five cDNAs of auxin-regulated genes were isolated from mungbean (Vigna radiata) hypocotyl sections by differential hybridizationscreening. They were related to the soybean genes, Aux22 [Ainleyet al. (1988) J. Biol. Chem. 263: 10658] and SAUR [McClure etal. (1989) Plant Cell 1: 229]. Regulation of expression of thesegenes, examined by Northern blot analysis, appeared similarto that reported in soybean hypocotyls. (Received August 10, 1991; Accepted October 14, 1991) 相似文献
95.
T Mori K T Mills H A Bern 《Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.)》1992,199(4):466-469
Newborn female BALB/cCrgl mice receiving 5 micrograms of testosterone or 0.01 micrograms of diethylstilbestrol daily for the first 5 days of life were examined at various times after secondary exposure to testosterone and 17 beta-estradiol, respectively. Neonatal administration of testosterone induced squamous stratification associated with constant cornification of the vaginal epithelium in intact mice. Later exposure to testosterone suppressed cornification, resulting in superficial epithelial mucification in almost all mice by 4 months of age. However, at 6 months of age, the incidence of mucification dropped to 58%. Cervicovaginal lesions developed in the groups of mice given neonatal testosterone in combination with later testosterone and sacrificed at 4 and 6 months of age. Continuous vaginal stratification was found in 14% of ovariectomized, neonatally diethylstilbestrol-treated mice at 13 months of age. The incidence of this ovary-independent change increased to 40% at 24 months of age. Postnatal estrogen replacement significantly increased the incidence of squamous stratification in these mice. Neonatal diethylstilbestrol treatment alone induced cervicovaginal lesions in 4.5% of ovariectomized mice at 13 months of age; secondary 17 beta-estradiol exposure significantly enhanced the development of lesions to 44%. However, at 24 months of age, there was no difference in the incidence of lesions in ovariectomized, neonatally treated mice with or without the secondary 17 beta-estradiol treatment. These results suggest that the effects of neonatal exposure to a relatively low dose of estrogen, androgen, or related substance may become obvious later in life as a result of later exposure to hormones. 相似文献
96.
The effect of light exposure during collection and culture of hamster embryos on their subsequent development in vitro was examined. When embryos were collected under dark conditions (70 lux) within 10 minutes and then cultured in a HECM-1 medium in 5% CO(2) in air, the developmental rates of 1-cell embryos to the 4- and 8-cell stages were 88.6% (93 105 ) and 66.7% (70 105 ), respectively. These rates were significantly higher than those under light conditions (1600 lux): 51.9% (56 108 ) and 34.3% (37 108 ). Light irradiation during the culture of 1-cell embryos suppressed subsequent development. The degree of suppression correlated inversely with duration of light irradiation, and light irradiation of 30 minutes or more completely blocked development to the 2-cell stage. When 1-cell embryos were irradiated through a yellow filter, cutting the light wavelengths to less than 500 nm, embryonic development was still suppressed. However, the degree of the suppression varied and 45.7% (53 116 ), 6.0% (7 116 ), and 0.9% (1 116 ) of the embryos developed to the 2-, 4-, and 8-cell stages, respectively, under 30 minute light irradiation. Inhibitory effects of light irradiation on the development of 2- and 8-cell embryos were also observed, showing an inverse correlation with duration; the developmental rates of 2-cell embryos to the 8-cell stage under 0, 10, and 30 minutes of irradiation were 85.6% (107 125 ), 1.6% (2 122 ), and 0% (0 129 ), respectively, and those of 8-cell embryos to the blastocyst stage were 79.8% (91 114 ), 74.8% (86 115 ), and 0% (0 110 ), respectively. These findings indicate that early-stage embryos are sensitive to light exposure; however, severe light exposure adversely affects the development of embryos at any stage. Thus, the protection of embryos from light exposure at all stages of embryo manipulation, from collection to culture, is essential. 相似文献
97.
Ultrastructure of the endolymphatic sac in the mouse. 总被引:1,自引:0,他引:1
The ultrastructure of the endolymphatic sac (ES) in the mouse was examined by light and electron microscopy. This organ was divided into three parts: proximal, intermediate and distal. In the proximal portion of the ES, the epithelium consisted of thin squamous cells. The epithelial cells had acquired basolateral processes, numerous small vesicles and well-developed Golgi apparatus. In the intermediate portion, the epithelium consisted of columnar or cuboidal cells. The epithelial cells could be classified into two types: type I and type II. The type I cells had abundant microvilli, pinocytotic vesicles, vacuoles, multivesicular bodies, lysosomes and mitochondria. The type II cells had fewer numbers of these organelles. A few free-floating cells could be observed in the lumen of this intermediate portion, most of which were macrophages. In the distal portion, the epithelium consisted of squamous or cuboidal cells. The epithelial cells had a few cytoplasmic organelles. In the ultrastructural study, each portion of the mouse ES was found to have a very distinct morphological feature. It was suggested that each of these three portions has a different function. 相似文献
98.
Neutralization of microcystin shock in mice by tumor necrosis factor alpha antiserum. 总被引:1,自引:1,他引:0 下载免费PDF全文
Microcystis aeruginosa is a common cyanobacterium in water blooms that appear widely in nutrient-rich, fresh, and brackish waters, and its toxic blooms cause the death of domestic animals. The administration of a crude toxic cell extract of M. aeruginosa K-139 to mice can produce tumor necrosis factor (TNF) and prompt severe physiological disturbances, especially liver damage, which can lead to death. The in vitro production of TNF-alpha by peritoneal macrophages was observed after stimulation with the cell extract or the purified toxin from K-139 cells. The expression of a TNF-alpha mRNA was also detected in spleen cells and peritoneal macrophages after stimulation with the cell extract. However, a previous injection of rabbit anti-murine TNF-alpha serum could prevent the liver damage to some extent and protect the mice from death. These findings indicate the involvement of TNF in microcystin shock. 相似文献
99.
H Shimano C Fukazawa Y Shibasaki N Mori T Gotoda K Harada M Shimada N Yamada Y Yazaki F Takaku 《Biochimica et biophysica acta》1991,1086(3):245-254
To investigate the role of apolipoprotein E (apo E) secreted by peripheral tissues in local lipoprotein metabolism, we developed a cell strain that constitutively produced and secreted apo E. A fusion plasmid containing rat apo E genomic DNA under control of mouse metallothionein promotor was constructed and transfected into Chinese hamster ovary cells. A stable transformant designated CHO-MAEII constitutively secreted rat apo E mainly in the form of sialylated free protein. The secretion was further enhanced by metal induction up to 1 micrograms apo E/ml per 12 h. When incubated with 125I-labeled very low density lipoprotein (125I-VLDL) at 37 degrees C, CHO-MAEII took up and degraded 125I-VLDL with higher affinity than control cells. Furthermore, considerable amount of methylated 125I-VLDL was degraded by CHO-MAEII, while no methylated 125I-VLDL was degraded by control cells. No significant differences were found in the uptake of 125I-LDL. The data indicated that apo E molecules secreted by CHO-MAEII were transferred to 125-VLDL particles, which caused a higher affinity of these particles for LDL receptors on the cells. It is suggested that apo E secreted from peripheral tissues enhances the uptake of lipoproteins by themselves or by surrounding cells in the local environment which demand cholesterol and express LDL receptors. CHO-MAEII was a good model for these 'auto- or paracrine-like functions' of apo E. 相似文献
100.
Expression of the pS2 gene in human gastric cancer cells derived from poorly differentiated adenocarcinoma 总被引:2,自引:0,他引:2
NH2-terminal amino acid sequence of the pS2 protein produced and secreted by human gastric cancer cells, MKN-45, was determined to be identical to that of MCF-7 cells. A clone encoding pS2 protein was isolated from the cDNA library constructed from MKN-45 cells. The nucleotide sequence was identical to that of pS2 cDNA previously isolated from human breast cancer cells, MCF-7, except for one nucleotide in the 3' untranslated region. Thus, in this cell line, the pS2 gene product is translated and secreted as in MCF-7 cells. RNA blot hybridization analysis revealed that pS2 gene was expressed well in two (MKN-45 and KATO-III; derived from poorly differentiated adenocarcinoma) but not in three cell lines (MKN-1, MKN-28 and MKN-74; from well differentiated adenocarcinoma), suggesting that expression of the pS2 gene depends on the state of cell differentiation. These results suggest that pS2 is expressed in human gastric cancer cells in an estrogen-independent manner and is possibly associated with the malignant state of cells. 相似文献