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91.
Takakura Yoshinobu Morita Takahiro Fujikawa Makoto Hayashi Mitsuko Sezaki Hitoshi Hashida Mitsuru Borchardt Ronald T. 《Pharmaceutical research》1995,12(12):1968-1972
Purpose. The purpose of this study was to assess whether LLC-PK1 renal epithelial cells could serve as an in vitro model for studying the renal tubular reabsorption of protein drugs.
Methods. The association of 111In-labeled model protein drugs, bovine serum albumin (BSA), superoxide dismutase (SOD), soybean trypsin inhibitor (STI), and [Asu1,7]-eel calcitonin (Asu-ECT), with the monolayers of LLC-PK1 renal epithelial cells was characterized under various conditions.
Results. The cellular association of these proteins was temperature-dependent and varied according to the protein. Saturation kinetics were observed for STI association, with the apparent Km and Vmax values determined to be 66.3 µg/ml and 250 ng/mg protein/min, respectively. The association of STI decreased with increases in medium pH from 5.4 to 8.4 and was inhibited significantly by 2,4-dinitrophenol, sodium azide, cytochalasin B, and colchicine, suggesting that the cellular association involved endocytosis. Mutual inhibition was observed in competitive binding experiments with the four protein drugs, suggesting that they shared a common binding site on the luminal membrane of LLC-PK1 cells. Taken together, these findings show that a variety of protein drugs bind to LLC-PK1 cells in a non-specific manner and possibly undergo endocytosis, a phenomenon that is similar to in vivo proximal tubular reabsorption.
Conclusions. LLC-PK1 renal epithelial cells would be a suitable model system for the study of the renal proximal tubular reabsorption of protein drugs. 相似文献
92.
93.
Fujimoto Sakata S Fujino M Matsuda K Maeda M Ohira H Kawasaki K Tamaki N 《Journal of nutritional science and vitaminology》2007,53(6):489-495
Liver tyrosine aminotransferase (TAT) activity is known to increase with ethanol treatment; however, the mechanism of this increase is unclear. Upon investigation we found that TAT activity and mRNA levels started to increase 2 h after ethanol administration and continued to increase until 6 h after ethanol administration. The increase in ethanol-induced TAT activity could not be explained by calorie loading after fasting, since ethanol loading increased TAT expression, while glucose loading decreased TAT expression. In addition, liver TAT activity was not related to serum tyrosine levels. TAT activity increased when an adenosine A2 agonist, 5'-N-ethylcarboxamide adenosine, was given. Since TAT activity is increased by cAMP, and ethanol increases cAMP production via an adenosine receptor-dependent mechanism, this increase in ethanol-induced TAT activity may occur via an adenosine receptor-dependent mechanism. 相似文献
94.
Yoichi Ezura Mitsuko Kajita Ryota Ishida Shoko Yoshida Hideyo Yoshida Takao Suzuki Takayuki Hosoi Satoshi Inoue Masataka Shiraki Hajime Orimo Mitsuru Emi 《Journal of bone and mineral research》2004,19(8):1296-1301
Correlation between 13 genetic variations of the glutaminyl-peptide cyclotransferase gene and adjusted aBMD was tested among 384 adult women. Among 13 variations with strong linkage disequilibrium, R54W showed a prominent association (p = 0.0003), which was more striking when examined among 309 elder subjects (> or =50 years; p = 0.0001). Contribution for postmenopausal bone loss was suggested. INTRODUCTION: Alterations in homeostatic regulation of estrogen through the hypothalamus-pituitary-gonadal axis (HPG axis) importantly affect the pathogenesis of osteoporosis. Osteoporosis-susceptibility genes have been proposed in this hormonal axis, such as estrogen receptor genes and the gonadotropin-releasing hormone gene (GnRH). Here we report another example of genes: glutaminyl-peptide cyclotransferase gene (QPCT), an essential modifier of pituitary peptide hormones, including GnRH. MATERIALS AND METHODS: Analyses of association of 13 single nucleotide polymorphisms (SNPs) at the QPCT locus with adjusted areal BMD (adj-aBMD) were carried out among 384 adult women. Linkage disequilibrium (LD) was analyzed by haplotype estimation and calculation of D' and r2. Multiple regression analysis was applied for evaluating the combined effects of the variations. RESULTS AND CONCLUSIONS: LD analysis indicated strong linkage disequilibrium within the entire 30-kb region of the QPCT gene. Significant correlations were observed between the genotypes of the six SNPs and the radial adj-aBMD, among which R54W (nt + 160C>T) presented the most prominent association (p = 0.0003). Striking association was observed for these SNPs among the 309 subjects >50 years of age (R54W, p = 0.0001; -1095T>C, p = 0.0002; -1844C>T, p = 0.0002). Multiple regression analyses indicated that multiple SNPs in the gene might act in combination to determine the radial adj-aBMD. These results indicate that genetic variations in QPCT are the important factors affecting the BMD of adult women that contribute to susceptibility for osteoporosis. The data should provide new insight into the etiology of the disease and may suggest a new target to be considered during treatment. 相似文献
95.
Mitsuko Yamada Yoshio Yamamoto Akio Tanegashima Masateru Kane Yuzuru Ikehara Tatsushige Fukunaga Katsuji Nishi 《International journal of legal medicine》1994,106(6):285-287
Summary The gene encoding the specific glycosyltransferases which catalyze the conversion of the H antigen to A or B antigens shows a slight but distinct variation in its allelic nucleotide sequence and can be divided into 6 genotypes when digested with specific restriction enzymes. We extracted DNA from formalin-fixed, paraffin-embedded tissues using SDS/proteinase K treatment followed by phenol/chloroform extraction. The sequence of nucleotides for the A, B and O genes was amplified by the polymerase chain reaction (PCR). DNA fragments of 128 by and 200 by could be amplified in the second round of PCR, using an aliquot of the first round PCR product as template. Degraded DNA from paraffin blocks stored for up to 10.7 years could be successfully typed. The ABO genotype was deduced from the digestion patterns with an appropriate combination of restriction enzymes and was compatible with the phenotype obtained from the blood sample. 相似文献
96.
Chronic Localized Encephalitis (Rasmussen's Syndrome) Preceded by Ipsilateral Uveitis: A Case Report 总被引:1,自引:1,他引:0
Tokiko Fukuda Hirokazu Oguni Shigeru Yanagaki Yukio Fukuyama Mitsuko Kogure Hiroyuki Shimizu† Masaya Oda‡ 《Epilepsia》1994,35(6):1328-1331
Summary: Chronic localized encephalitis (Rasmussen's syndrome) developed in an 11-year-old girl 1 month after operation for residual cataract due to chronic uveitis that had appeared at age 9 years ipsilateral to the affected cerebral hemisphere. Although the pathogenesis of Rasmussen's syndrome remains unknown, our case provides additional evidence indicating that a viral ocular infection is a possible cause or part of the disorder. 相似文献
97.
98.
Ohtsuki Y Terao N Kuwahara M Ochi K Iguchi M Kurabayashi A Matsumoto M Takeuchi T Furihata M 《Medical molecular morphology》2007,40(1):29-33
Posttransurethral resection (TUR) status in the prostate and urinary bladder has been infrequently documented. Furthermore,
sequential changes in eosinophil count in peripheral blood (PB) after TUR have not been investigated in detail. In the present
study, eosinophil counts and changes in eosinophils in PB were examined before to after TUR of the prostate (P) in 20 patients
with benign prostatic hyperplasia. Among them, 14 patients exhibited increased numbers of eosinophils, the greatest increase
being 17%. After TUR to treat bladder tumor (BT), massive infiltration of eosinophils into the resected areas, peaking 1 month
later, was also detected in 8 of 15 cases of post-TUR cystitis. The PB eosinophil counts increased by more than 5% in two
of five cases of post-TUR cystitis in which eosinophil counts were obtained before and after surgery. Most infiltrating eosinophils
reacted positively to antibodies to eosinophil cationic proteins. These results indicated that, in patients with post-TUR
prostatitis, the number of eosinophils in PB increased, and peaked 1 month later, with infiltration by eosinophils observed.
Pathologists and urologists should be aware of the potential for increase in eosinophils not only in regions of TUR but also
in PB. 相似文献
99.
Hayashi T Hatanaka M Nagao K Nakaseko Y Kanoh J Kokubu A Ebe M Yanagida M 《Genes to cells : devoted to molecular & cellular mechanisms》2007,12(12):1357-1370
Nutrients are essential for cell growth and division. Screening of Schizosaccharomyces pombe temperature-sensitive strains led to the isolation of a nutrient-insensitive mutant, tor2-287. This mutant produces a nitrogen starvation-induced arrest phenotype in rich media, fails to recover from the arrest, and is hypersensitive to rapamycin. The L2048S substitution mutation in the catalytic domain in close proximity to the adenine base of ATP is unique as it is the sole known genetic cause of rapamycin hypersensitivity. Localization of Tor2 was speckled in the vegetative cytoplasm, and both speckled and membranous in the arrested cell cytoplasm. Using mass spectroscopic analysis, we identified six subunits (Tco89, Bit61, Toc1, Tel2, Tti1 and Cka1) that, in addition to the six previously identified subunits (Tor1, Tor2, Mip1/Raptor, Ste20/Rictor, Sin1/Avo1 and Wat1/Lst8), comprise the TOR complexes (TORCs). All of the subunits so far examined are multiply phosphorylated. Tel2 bound to Tti1 interacts with various phosphatidyl inositol kinase (PIK)-related kinases including Tra1, Tra2 and Rad3, as well as Tor1 and Tor2. Schizosaccharomyces pombe TORCs should thus be functionally redundant and might be broadly regulated through different subunits that are either common or specific to the two TORCs, or even common to various PIK-related kinases. Functional redundancy of the TORCs may explain the rapamycin hypersensitivity of tor2-287. 相似文献
100.