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Biomedical subjects

Y Kanazawa

Publications and source records attributed to Y Kanazawa.

At least 19 recordsLinked to original sources
PubMed1995

Histamine release from Weibel-Palade bodies of toad aortas induced by endothelin-1 and sarafotoxin-S6b.

BACKGROUND: Endothelin-1 (ET-1) and sarafotoxin-S6b (STX) induce a remarkable degranulation of Weibel-Palade (WP) bodies prior to the vasocontraction of toad aortas. As WP bodies play the role of a reservoir site of the histamine in the endothelial cells, there is the possibility that ET-1 and STX evoke the release of histamine from WP bodies of this vessel. METHODS: Histamine concentrations were assayed by high-performance liquid chromatography (HPLC) from the perfusate after being perfused with a solution containing ET-1 and STX. Each vessel was fixed and embedded for conventional electron microscopy and immunoelectron microscopy using antihistamine sera. RESULTS: The appreciable concentrations of histamine were assayed by HPLC from the perfusate after the toad aortas were perfused with a solution containing ET-1 and STX. The immunoelectron microscopy revealed that histamine immunoreactive gold particles in the WP bodies remarkably decreased in number in the treated samples when compared to the control ones. Our immunoelectron micrographs indicated that the release of histamine from the endothelial cells occurred in association with the degranulation and the exocytosis of the WP bodies after treatment with ET-1 and STX. CONCLUSIONS: The present study clearly shows that ET-1 and STX induce the histamine release from WP bodies of the toad aortas by means of HPLC and immunoelectron microscopy. Histamine discharged from the WP bodies may be involved in the vasocontraction evoked by ET-1 and STX.

Animals↗
PubMed1995

Hepatitis C viral complexity detected by single-strand conformation polymorphism and response to interferon therapy.

BACKGROUND/AIMS: Hepatitis C virus (HCV) genome heterogeneity by sequence analysis in association with interferon (IFN) inefficacy has been reported. This study was performed to establish a convenient method for detecting the HCV quasispecies complexity and to determine the correlation between the complexity and the responsiveness to IFN therapy in patients with chronic hepatitis C. METHODS: The quasispecies complexity of HCV hypervariable region 1 in patients treated with IFN-alpha was analyzed by polymerase chain reaction-mediated single-strand conformation polymorphism (SSCP). RESULTS: Seven of 25 patients (28%) with low complexity (SSCP band number of < or = 2) were HCV RNA negative after treatment, whereas in 24 patients with high complexity (SSCP band number of > or = 3), the response to IFN was almost insignificant because only 1 patient (4.5%) remained HCV RNA negative after treatment (P < 0.05). Among type 1b patients, IFN therapy was only effective for patients with low amounts of HCV RNA (< or = 10(7.5) copies/mL serum) and low complexity. In contrast, most type 2a patients tended to respond to the therapy with exceptions being those with high amounts of HCV RNA and high complexity. CONCLUSIONS: The complexity of the hypervariable region 1 quasispecies may be a factor for predicting IFN inefficacy in patients with chronic hepatitis C.

Amino Acid Sequence↗
PubMed1995

Radiosynthesis, rodent biodistribution, and metabolism of 1-deoxy-1-[18F]fluoro-D-fructose.

Fluorine-18 labeled analog of D-fructose, 1-deoxy-1-[18F]fluoro-D- fructose (1-[18F]FDFrc), was synthesized by nucleophilic substitution of [18F]fluoride ion and the effect of the fluorine substitution on its in vivo metabolism was investigated. The tissue distributions of 1-[18F]FDFrc in rats and tumor bearing mice showed initial high uptake and subsequent rapid washout of the radioactivity in the principal sites of D-fructose metabolism (kidneys, liver and small intestine). The uptakes in the brain and tumor (fibrosarcoma) were the lowest and moderate, respectively, but tended to increase with time. The in vivo metabolic studies of 1-[18F]FDFrc and nonradioactive 1-FDFrc in mouse brain and tumor showed that the fluorinated analog remained unmetabolized in these tissues, indicating that the substitution of fluorine at the C-1 position produces a nonmetabolizable analog of D-fructose. Thus, 1-[18F]FDFrc had no features of a metabolic trapping tracer without showing any appreciable organ or tumor specific localization.

Animals↗
PubMed1995

Hepatitis C viral quasispecies in hepatitis C virus carriers with normal liver enzymes and patients with type C chronic liver disease.

Hepatitis C virus (HCV) has been reported to conform to a quasispecies nature, which is most evident in hypervariable regions of the putative envelope 2 domain. The aim of this study was to determine the relationship between the nucleotide complexity and diversity of hypervariable region 1 and various stages of the carrier states. The subjects studied were 20 HCV carriers with normal alanine aminotransferase (ALT) levels, 50 patients with chronic hepatitis who showed elevated ALT levels, 22 with cirrhosis, and 24 with hepatocellular carcinoma. The quasispecies complexity was analyzed by means of polymerase chain reaction-mediated single strand conformation polymorphism (PCR-SSCP). The value of nucleotide diversity was calculated by PCR cloning and sequencing. The number of SSCP bands ranged from 1 to 7, with no significant differences in the mean numbers among the stages of HCV infection. There was no correlation between the amounts of serum HCV RNA and the numbers of SSCP bands. No significant difference was found in the values of nucleotide diversity between carriers with normal ALT levels (mean, 6.6 x 10(-2) per site) and patients with chronic hepatitis (7.7 x 10(-2). These findings suggest that the quasispecies complexity of hypervariable region 1 is independent of the stage of chronic HCV infection.

Adolescent↗
PubMed1995

MR imaging of hepatocellular carcinoma. Correlation of metal content and signal intensity.

In order to clarify the factors contributing to the signal intensities (SIs) of HCC on T1-weighted images, the amount of water, lipid, copper (Cu), iron (Fe), and manganese (Mn) was determined in HCC and surrounding hepatic parenchyma of 13 patients. The relationships among these findings, the histopathologic findings, and the SIs of T1-weighted images were evaluated. Among the 13 HCC, 3 had a high SI, 5 were isointense, and 5 had a low SI on T1-weighted images compared to the surrounding hepatic parenchyma. The paramagnetic ions which contributed to the SI patterns were assumed to be Cu in HCC (38.0 +/- 62.4 micrograms/g ww), and Fe in the liver (61.1 +/- 42.4 micrograms/g ww) and HCC (40.0 +/- 34.3 micrograms/g ww). In 8 HCC with high- or isointensity, 2 were grades I, 5 were grade II, and one was grade III according to the Edmondson-Steiner's histopathologic classification. It is concluded that the SI patterns alone can not be a sign of low grade malignancy because of the existence of Fe in livers and HCC.

Aged↗
PubMed1994

Light and electron microscopy of hydroxyapatite depositions in the ligamentum flavum.

STUDY DESIGN: Ligamenta flava obtained from 24 patients who had undergone surgery for degenerative spinal diseases were investigated regarding the histopathology of hydroxyapatite crystal depositions. OBJECTIVES: Light and electron microscopy and energy dispersive x-ray microanalysis were done to clarify the cause and process of hydroxyapatite crystal depositions in the ligament. SUMMARY OF BACKGROUND DATA: No reports have been made regarding the cause of calcification in the ligamenta flava induced by hydroxyapatite crystal depositions. METHODS: Samples were fixed in 10% formalin and 2.5% glutaraldehyde for light and electron microscopy. Energy dispersive x-ray microanalysis was done to detect calcium and phosphate hydroxyapatite crystal deposition areas. RESULTS: Hydroxyapatite crystals, which occasionally formed clusters, existed in the connective tissue of the dural side around abundant profiles of growing capillaries. Hydroxyapatite crystals showed needle shaped figures, and the x-ray microanalysis revealed that the ratio of calcium to phosphate was about 1.66:1. A decrease or loss of collagenous and elastic fibers was prominent in these hydroxyapatite deposition areas. CONCLUSIONS: Hydroxyapatite crystal depositions occur around the growing capillaries in the dural side of the ligamenta flava.

Adult↗
PubMed1994

Association of polymorphism in the interferon gamma gene with IDDM.

Cytokines may play important roles in the pathogenesis of insulin-dependent diabetes mellitus (IDDM). We analysed a dinucleotide repeat polymorphism within the first intron of the interferon gamma (IFN-gamma) gene in Japanese diabetic patients (175 IDDM and 145 non-insulin-dependent diabetes mellitus) and 267 control subjects. A significant difference was observed in the global allele distribution of the polymorphism between the IDDM and control groups (p = 0.039). The difference from the control group was more evident in the patients whose insulin therapy started within 1 year from onset (p = 0.006) or in the young-onset (< 10 years) patients (p = 0.0006). The alleles "3" and "6" were increased in the IDDM patients, and a significant increase in the frequency of the "3/6" genotype was observed in the IDDM patient group (9.1%, RR 2.9, p = 0.010), in the patients with initial insulin therapy less than 1 year from onset (10.6%, RR 3.4, p = 0.004), or in the young-onset patients (16.7%, RR 5.7, p = 0.0003) in comparison to the control subjects (3.4%). There was a tendency towards frequent occurrence of clinical characteristics which reflect young or abrupt onset of diabetes or both, and depletion of insulin secretion capacity in the patients with "3/6" or "6/6" in comparison to the patients with other genotypes. These results suggest that the IFN-gamma gene region may contribute to the pathogenesis of IDDM and could be a genetic marker for IDDM.

Adult↗
PubMed1994

Predicting interferon therapy efficacy from hepatitis C virus genotype and RNA titer.

We classified 53 Japanese patients with chronic hepatitis C who were treated with natural interferon-alpha into genotypes and also tested the amounts of hepatitis C virus (HCV) RNA. The rate of the long-term complete response group, whose alanine aminotransferase levels remained within the normal range during the six months after therapy, was significantly higher (P < 0.01) in the type-III patients (4/5, 80.0%) than in type-II patients (4/43, 9.3%). For these long-term complete responders, the amounts of HCV RNA was less than 10(7) copies/ml serum in type-II patients, whereas two type-III patients with relatively high amounts of HCV RNA responded completely. These results confirm that the genotype of HCV is an important factor for predicting the response to interferon therapy. The amounts of HCV RNA can also predict its efficacy in type-II patients.

Adult↗
PubMed1994

Biliary lipid composition in heterozygous familial hypercholesterolemia and influence of treatment with probucol.

The lipid composition of fasting duodenal bile was determined in 11 healthy subjects with normolipidemia and 15 patients with heterozygous familial hypercholesterolemia (FH) (12 with type IIa, three with type IIb). The age distribution among the groups of subjects was similar. In the patients with heterozygous FH type IIa, the mean value for molar percentage of cholesterol and lithogenic index (LI) of bile were significantly higher than those of controls (8.4 +/- 1.0%, 1.47 +/- 0.18 calculated by Hegard, Dam, and Holzbach vs 4.3 +/- 0.4%, 0.81 +/- 0.07, respectively). The value of LI in the patients with FH type IIb was also found to be significantly higher than that of the controls. In the patients with heterozygous FH type IIa, we observed both a significant decrease in the molar percentages of glycochenodeoxycholic acid, glycoursodeoxycholic acid, and glycolithocholic acid, and a significant increase of taurochenodeoxycholic acid compared to the corresponding values in the controls. Bile analysis of six patients was reexamined during probucol treatment after 16 weeks. Probucol significantly lowered serum cholesterol levels. However, biliary lipid composition and individual bile acid proportions was not altered by the treatment. The results suggest that most of the patients with heterozygous FH have supersaturated bile and are predisposed to cholesterol gallstone formation. In addition, the mechanism by which probucol lowers serum cholesterol appears to be independent of any change in the metabolism of biliary lipid.

Adult↗
PubMed1994

Lack of association of the insulin gene region with type 1 (insulin-dependent) diabetes mellitus in Japanese subjects.

Although the insulin gene region is implicated in susceptibility to Type 1 (insulin-dependent) diabetes mellitus in Caucasians, significance of this region to Type 1 diabetes in Japanese remains unclear because the class 1 alleles (shorter insertion) of the variable number of tandem repeat in the 5' region of the insulin gene are predominant in both diabetic and non-diabetic subjects. The 5' insulin gene polymorphism was analysed in 75 Japanese patients and 69 control subjects with a precise method using PvuII and a polymorphism specific probe, which enabled us to divide class 1 alleles into four subclasses. Allelic frequencies were not significantly different between Type 1 diabetic patients and control subjects. The polymorphism in the 3' untranslated region of the insulin gene (1127/PstI) was also analysed and found to be tightly linked to the 5' insulin gene polymorphism, and thus was not associated with diabetes. Interaction between HLA-DR and the insulin gene region, which was reported in the French study, was not observed in Japanese. These results suggest that the insulin gene region is not a valuable genetic risk factor for Type 1 diabetes in Japanese.

Age of Onset↗
PubMed1994

Genetic markers for insulin-dependent diabetes mellitus in Japanese.

Although the HLA class II genes are clearly associated with insulin-dependent diabetes mellitus (IDDM) in all ethnic groups, considerable variation in the associated haplotypes is observed among the ethnic groups. In Japanese, DRB1*0405-DQA1*0301-DQB1*0401, DRB1*0901-DQA1*0301-DQB1*0303 and DRB1*0802-DQA1*0301-DQB1*0302 are the major susceptibility haplotypes to IDDM, while DRB1*1501-DQA1*0102-DQB1*0602 and DRB1*1502-DQA1*0103-DQB1*0601 are the major resistance haplotypes. The hypothesis that alleles encoding amino acids other than aspartic acid at the DQB1 position 57 contribute to IDDM susceptibility is not applicable to the Japanese, mainly because the first and second susceptibility haplotypes listed above have aspartic acid at DQB1 position 57. In the 5' insulin gene polymorphism, the shorter insertion (class 1 allele) is predominant, and is not associated with diabetes in Japanese. Subdivision of the class 1 alleles also failed to show an association with IDDM in Japanese. The insulin gene region appeared to be of less value as a genetic marker for IDDM in Japanese. Little is known about other genetic markers.

Alleles↗
PubMed1994

Hyperproinsulinemia in Japan.

Four families with hyperproinsulinemia found in Japan were described. The details of the first case, who was investigated by Kanazawa et al., were reported and the similarity of the first case to the following cases was shown. Arginine 65 of the proinsulin molecule might be a hot spot of the insulin gene. A possible abnormality of insulin release in affected individuals was disclosed by investigation of the family members of the first case.

Arginine↗
PubMed1994

Hepatitis C virus genotype and RNA titer in the progression of type C chronic liver disease.

Hepatitis C virus genotype and the amounts of circulating HCV RNA are the most important factors in determining the efficacy of interferon therapy for chronic hepatitis C. To clarify the correlation of these two factors to the progression of liver disease, we classified 148 Japanese patients with type C chronic liver disease into genotypes and also measured their HCV RNA titers (logarithmic transformed copy number/ml serum) by competitive reverse transcription-polymerase chain reaction. We found type II in 23 (76.7%) of 30 patients with chronic persistent hepatitis, 34 (79.1%) of 43 with chronic active hepatitis, 29 (72.5%) of 40 with cirrhosis and 30 (85.7%) of 35 with hepatocellular carcinoma. Thus, there was no significant difference in the prevalence of type II among the various stages of chronic liver disease. We also found the RNA titer to be significantly higher in patients with chronic active hepatitis (8.0 +/- 0.8) than in those with chronic persistent hepatitis (7.0 +/- 1.0, p < 0.001), and also those with cirrhosis (7.6 +/- 0.8, p < 0.05) or hepatocellular carcinoma (7.7 +/- 0.8, p < 0.05). When the titers were compared among genotypes, there was no significant difference between type II and III at any stage (type II vs. type III: chronic persistent hepatitis, 7.2 +/- 1.0 vs. 6.7 +/- 0.8; chronic active hepatitis, 8.1 +/- 0.7 vs. 7.8 +/- 1.0; cirrhosis, 7.7 +/- 0.8 vs. 7.8 +/- 0.7; hepatocellular carcinoma, 7.7 +/- 0.8 vs. 7.8 +/- 0.5). In conclusion, although genotype affects interferon therapy efficacy, it seems to have little influence on serum RNA levels and the progression of type C chronic liver disease.

Adult↗
PubMed1994

In vivo 19F NMR comparative study of 5-fluorouracil, 1-(2-tetrahydrofuryl)-5-fluorouracil (FT) and an FT-uracil coadministration system in mouse tumors.

The suppression of alpha-fluoro-beta-alanine (FBAL) formation from 5-fluorouracil (FU) is an important subject in relation to tumor chemotherapy. This is the first comparative study of FU, 1-(2-tetrahydrofuryl)-5-fluorouracil (FT, a prodrug of FU) and of FT+uracil as a coadministration system (UFT) under an oral dose using the in vivo 19F NMR method. The slow release of FU from FT and the suppression of the catabolism of FU to FBAL in mouse livers and tumors by the coadministration of uracil with FT were demonstrated using consecutive NMR measurements. The applicability of the in vivo 19F NMR method to the drug evaluation in tumors and livers of small animals was successfully tested.

Animals↗
PubMed1994

[The reference value of plasma glucose in individuals over 65 years].

The characteristics of plasma glucose in individuals aged over 65 years was investigated by analysis of age dependent changes of fasting and post glucose (75 g) load values in population based studies and some follow-up studies. Institutional differences were surveyed in central laboratory of institutions which joined this study and found that differences were the range of +3.0-3.5% from the mean glucose levels between 100-400 mg/dl. Therefore plasma glucose values around cutoff level should be confirmed by repeated determinations for reaching final diagnosis. The reference interval of plasma glucose does not differ in an age-dependent manner. We may use the reference interval proposed by the Committee of Diagnostic Criteria of Diabetes Mellitus of Japan Diabetes Society for adult individuals. Cases of diabetes diagnosed before 65 years old should be judged by the adult criteria. However, those who were not diabetic before age 65 and were found to be hyperglycemic after that age can be diagnosed classifying as follows: (1) Diabetes should be diagnosed in individuals with a fasting plasma glucose of 140 mg/dl or more and 2 hours after glucose (75 g) of 240 mg/dl or more. Those with some symptoms suggesting diabetes and either 140 mg/dl more or fasting or 240 mg/dl or more 2 hours post 75 g glucose load can also be diagnosed as diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗