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91.
T Oya H Kumon H Kobayashi M Akiba T Hosokawa N Kakimoto K Nakamura Y Morimitsu T Osawa 《Canadian Metallurgical Quarterly》1998,246(1):267-271
Long-lived proteins can undergo non-enzymatic glycation to form highly crosslinked structures with characteristic fluorescence during aging and diabetes processes. In this paper, a typical fluorophore, named Maillard reaction product X (MRX), was isolated from the hydrolysate of glycated proteins. MRX could be formed by incubation of bovine serum albumin with glucose, followed by acid hydrolysis. The structure of MRX was determined to be 8-hydroxy-5-methyldihydrothiazolo[3,2-alpha] pyridinium-3-carboxylate. MRX was also found to be formed by the incubation of cysteine and arginine with glucose, followed by hydrolysis. We found the formation of MRX in the recently developed genetically diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats and compared them with that in the control Long-Evans Tokushima Otsuka (LETO) rats. Significantly higher levels of MRX were observed from the serum (p < 0.005) and urinary protein (p < 0.001) of OLETF rats in comparison with those of LETO rats. MRX must be a potential candidate as a biomarker for hyperglycemia. 相似文献
92.
T Fujioka S Teramoto S Tsujimi K Takemoto T Mori T Hosokawa T Sumida M Tominaga Y Yabuuchi 《Canadian Metallurgical Quarterly》1996,44(8):1596-1598
The enantiomers of 6-[3-(3,4-dimethoxybenzylamino)-2-hydroxypropoxy]-2(1H)-quinolinon e (OPC-18790), a novel cardiotonic agent, were synthesized and evaluated for positive inotropic activity. The key intermediates, 2,3-epoxypropoxy derivatives, were obtained by the alkylation of 6-hydroxy-2(1H)-quinolinone with optically active epichlorohydrin and subsequent ring closure. In an in vitro study, the (R)-(+)-isomer was about 10-fold more potent than the (S)-(-)-isomer. 相似文献
93.
K Kusano T Seko S Tanaka Y Shikata T Ando S Ida M Hosokawa T Satoh T Yuzuriha T Horie 《Canadian Metallurgical Quarterly》1996,24(11):1186-1191
We previously showed that a polymorphism for E6123 [(S)-(+)-6- (2-chlorophenyl)-3-cyclopropanecarbonyl-8,11-dimethyl-2,3,4,5- tetrahydro-8H-pyrido[4',3':4,5]thieno[3,2-f][1,2,4]triazolo[4,3-a] [1,4]diazepine] metabolism exists only in rhesus monkeys. In the present study, we purified, from rhesus monkey hepatic microsomes, three amido hydrolases that are involved in the metabolic polymorphism. Two forms of amido hydrolase from an extensive metabolizer and one from a poor metabolizer were purified by Q-Sepharose Fast Flow, Red A-agarose, octylamino-Sepharose 4B, and hydroxyapatite-Ultrogel chromatography, after solubilization with Lubrol. The three purified enzymes had the same molecular mass (47 kDa), and their amino-terminal amino acid sequences were identical. The enzymes were different from various known carboxylesterases in terms of substrate specificity, molecular mass, and amino-terminal amino acid sequence. They resembled arylacetamide deacetylase from human hepatic microsomes with respect to molecular mass and amino-terminal amino acid sequence. The KM values of the high and low affinity enzymes in the extensive metabolizer and the sole enzyme in the poor metabolizer were 37.6, 73.0, and 76.5 microM, respectively. The Vmax values were 3312.4, 504.8, and 427.9 pmol/min/mg of protein, respectively. The high affinity enzyme in extensive metabolizer appears to be quite distinct, whereas the low affinity enzyme in extensive metabolizer in similar or identical to the sole enzyme in poor metabolizer. Thus, the metabolic polymorphism in rhesus monkey may depend upon the existence of the high affinity enzyme in extensive metabolizer. 相似文献
94.
We studied the plasma pharmacokinetics of the lactone form and the carboxylate form of 7-ethyl-10-hydroxycamptothecin (SN-38), the active metabolite of irinotecan (CPT-11), after intravenous bolus administrations of each form of SN-38 and of CPT-11 to rats. After the SN-38 lactone injection, SN-38 lactone was predominant at first, and then the lactone to the carboxylate concentration ratio (LC ratio) was maintained from 30 to 90 min after the injection. The carboxylate was predominant throughout the period after the carboxylate dosing. Model-dependent analyses showed that the SN-38 lactone had greater plasma clearance and a greater distribution volume than the carboxylate. The CPT-11 administration resulted in a predominant plasma SN-38 lactone concentration. The contribution of the SN-38 lactone AUC to the total SN-38 AUC (57%) was independent of the dose of CPT-11. These results suggest that it is possible to estimate the SN-38 lactone concentration and AUC from the total SN-38 concentration without separate determination of the lactone and carboxylate. Our results showed that both SN-38 lactone and CPT-11 administration gave the predominant SN-38 lactone in plasma; however, only CPT-11 could sustain the lactone concentration at a high level, which is necessary for antitumor activity. 相似文献
95.
96.
T Kimoto R Hosokawa T Kubo M Maeda A Sano Y Akagawa 《Canadian Metallurgical Quarterly》1998,77(12):1965-1969
Some studies have shown that locally applied basic fibroblast growth factor (FGF-2) enhances bone regeneration at a fracture site, while others have not been in agreement. We developed a new continuous FGF-2 delivery system designed to accelerate cytokine-induced new bone formation. A subperiosteal pocket was surgically formed in 36 eight-week-old male Wistar rats. The rats were administered 0, 1, 10, or 100 ng of FGF-2 contained in a collagen minipellet, mixed with allogeneic demineralized bone matrix in a dome-shaped Millipore filter and then placed into the pocket. New bone formation in the dome was evaluated at 2, 4, and 8 wks after placement. Soft x-ray radiographs disclosed an apparently larger radiopaque region in the 1-ng group at 4 wks compared with those in the other groups. Morphometrical analysis revealed that the new bone area in the 1-g group was significantly larger than that in the 0-g group (p<0.01). In the 100-ng FGF-2 group, new bone formation seemed suppressed. We concluded that continuous slow administration of a small amount of FGF-2 accelerates bone-derived osteogenic cytokine-induced new bone formation. 相似文献
97.
O Hosokawa S Tsuda E Kidani K Watanabe Y Tanigawa S Shirasaki H Hayashi T Hinoshita 《Canadian Metallurgical Quarterly》1998,30(8):669-674
BACKGROUND AND STUDY AIMS: The degree of accuracy of gastroscopy for the detection of gastric cancer is poorly understood. The aim of this retrospective study was to determine the accuracy of gastroscopy by using cancer registry records. PATIENTS AND METHODS: Gastroscopic examinations (n = 37094) conducted between 1984 and 1989 were studied by linking them with hospital-based and population-based (Fukui Prefecture, Japan) cancer registry records between 1984 and 1992. False-negative gastroscopies that had been carried out within the three years preceding the diagnosis of gastric cancer were identified. RESULTS: The numbers of true-positive, false-positive, and false-negative examinations carried out were 659, six and 155, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value were 81.0%, 100.0%, 99.1%, and 99.6%, respectively. The overall diagnostic accuracy of gastroscopy was 99.6%. There was little difference in sensitivity results between the patient groups with regard to reason for referral, type of endoscope used, experience of endoscopist, or location of gastric cancer. The percentage of tumours representing early gastric cancer, identified after false-negative gastroscopy, was lower for those situated in the cardia or gastric body than for those in the angular notch or the antrum. CONCLUSIONS: The accuracy of gastroscopy in the detection of gastric cancer is satisfactory, but false-negative results are sometimes obtained. We emphasize the importance of repeated endoscopic examination for the detection of gastric cancer. 相似文献
98.
The contacting state of knife-edge seals was investigated and a new type of knife edge was developed. The contacting state of knife-edge seals was divided into three types according to the apex width of the knife edge: (a) penetration type, (b) indentation type, and (c) intermediate type. The developed knife edge had a contacting state of penetration type (a). Because of the narrow apex width of the knife edge, the values of Pc/l for the compressive forces per unit length required for sealing were lower than those of other types of knife-edge seals. The contact pressure required for sealing was nearly equal to the Meyer's hardness in the sealing surface layer, regardless of the surface roughness in turning. The optimum shape of the knife edge was of type (a) and had a ridge in a V-shaped cross-section with a plane inclined 30° off normal and the flat area of its apex finished by lapping was about 35 μm wide. The knife edge made of hard material with optimum shape could be utilized in the cases where the sealing materials were copper, carbon steel and stainless steel, and the values of Pc/l were approximately 15–40, 45–110 and 80–190 kN m−1, respectively. 相似文献
99.
K Hosokawa A Dantes C Schere-Levy A Barash Y Yoshida F Kotsuji I Vlodavsky A Amsterdam 《Canadian Metallurgical Quarterly》1998,139(11):4679-4687
We have established immortalized human granulosa cells by triple transfection of primary cells obtained from in vitro fertilization patients with SV40 DNA, Ha-ras oncogene, and a temperature sensitive (ts) mutant of the tumor suppressor gene p53 (p53val135). Forty-one clones were isolated, and their steroidogenic responses were analyzed. While all the cell lines proliferate rapidly and show only traces of progesterone production, upon stimulation with 50 microM of forskolin (FK), which elevates intracellular cAMP, they become steroidogenic as evidenced by progesterone production. The steroidogenic response of the cell lines was stable even after 20 generations and several cycles of freezing and thawing. A highly responsive cell line (HO-23) was further examined for characteristics of the steroidogenic response. Cells stimulated with FK and 8-Br-cAMP produced high levels of pregnenolone, progesterone, and 20alpha-hydroxy-4-pregnen-3-one (20alpha-OH-progesterone) comparable with amounts produced by highly differentiated primary human granulosa-luteal cells. Hydrocortisone and dexamethasone highly augment the cAMP-stimulated progesterone production, whereas testosterone and PRL enhanced cAMP-induced progesterone synthesis only moderately. Estradiol, insulin-like growth factor I, and insulin showed no significant effect on cAMP-induced steroidogenesis. The phorbol ester TPA, and basic fibroblast growth factor, dramatically suppress cAMP-induced production of progesterone, whereas bovine corneal endothelial cell ECM (BCE/ECM) enhanced cAMP-induced progesterone and antagonized basic fibroblast growth factor suppression of cAMP-induced steroidogenesis. Steroidogenic factor 1 (Ad4BP/SF-1) was expressed in control cells, and its expression was augmented by FK, whereas the steroidogenic acute regulatory protein showed low expression in the nonstimulated cells but was clearly elevated upon cAMP stimulation and was slightly decreased by TPA in cAMP-stimulated cells. Expression of the electron carrier adrenodoxin (ADX), which is a part of the cytochrome P450scc enzyme system, was very low in nonstimulated cells but was dramatically elevated in FK- and 8-Br-cAMP-stimulated cells, whereas no reduction of ADX was evident in cells costimulated with FK and TPA. Immunocytochemical studies revealed a weak staining of ADX in mitochondria of nonstimulated cells and intensive staining in highly clustered mitochondria of FK- or 8-Br-cAMP-stimulated cells. Only moderate reduction in ADX staining was evident in cells costimulated with FK and TPA. These unique cell lines can provide a useful model for the investigation of induced steroidogenesis in human granulosa cells. 相似文献
100.
E Nagura A Igata H Fujita T Inoue K Kanno T Matsuura H Tokuda T Hosokawa 《Canadian Metallurgical Quarterly》1997,34(7):589-595
We compared bedridden elderly people living at home to others who were hospital inpatients. Questionnaires regarding medical status and care were returned by 85 of 116 people caring for a bedridden elderly person at home in Obu city, Aichi prefecture and by 62 of 64 nurses and family members caring for bedridden inpatients at Chubu National hospital. All subjects were at least 65 years old. The median age in both groups was 81 years, neither age distribution nor female sex predominance differed between both groups. The percentage of subjects with only one underlying disease was 62.5% among those living at home and 64.4% among inpatients. In both groups the most common disease was cerebrovascular disease (42.5% among those at home and 39.0% among inpatients), followed by dementia (31.3%), infirmity of old age (17.5%) and bone fracture (13.8%) among those at home, and by bone fracture (27.1%), dementia (20.3%) and infirmity of old age (16.9%) among inpatients. The median durations of bedridden status were 2 years and 3 months among those at home and 3 months among inpatients. The proportion of subjects bedridden for less than 6 months was greater among inpatients (p < 0.0001). The percentage who needed medical treatment was 60.0% among those at home and 67.7% among inpatients. The most common conditions for which drugs were taken were hypertension, dementia, chronic cerebrovascular dysfunction, and osteoporosis. Among inpatients, 54.8% were ambulatory before admission, 24.2% were almost completely bedridden, and 17.7% were completely bedridden. The most common cause rending the patients bedridden was infection (usually pneumonia). The degree of disability did not differ between groups. Decubitus ulcers were present in 25.9% of those at home and 17.7% of inpatients. 相似文献