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Biomedical subjects

K Higashi

Publications and source records attributed to K Higashi.

At least 91 records · Page 5Linked to original sources
PubMed1998

A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy (Wolfram syndrome).

Wolfram syndrome (WFS; OMIM 222300) is an autosomal recessive neurodegenerative disorder defined by young-onset non-immune insulin-dependent diabetes mellitus and progressive optic atrophy. Linkage to markers on chromosome 4p was confirmed in five families. On the basis of meiotic recombinants and disease-associated haplotypes, the WFS gene was localized to a BAC/P1 contig of less than 250 kb. Mutations in a novel gene (WFS1) encoding a putative transmembrane protein were found in all affected individuals in six WFS families, and these mutations were associated with the disease phenotype. WFS1 appears to function in survival of islet beta-cells and neurons.

Adult↗
PubMed1998

Patterns of expression of the genes for glutamine synthetase isoforms during somatic and zygotic embryogenesis in carrot.

Three cDNA clones encoding isoforms of carrot glutamine synthetase (GS) were isolated and used as probes for analysis of the patterns of expression of the genes for GS isoforms during somatic embryogenesis and seed development in carrot. Transcripts corresponding to two of the cDNAs, CGS102 and CGS201, accumulated in both somatic embryos and developing seeds in the same manner. Their levels were high at the early stage of embryogenesis but decreased at the late stage. This pattern of expression is similar to the pattern of changes in GS activity observed during somatic embryogenesis. In contrast, expression of the transcript for another GS isoform detected with CGS103 cDNA was observed at the late stage of seed development and in senesced leaves but not in somatic embryos or young leaves. We also analyzed the levels of the transcripts in somatic embryos that had been cultured in media with either ammonium ions or glutamine as the nitrogen source. The amounts of the CGS102 and CGS201 transcripts fell when glutamine was supplied in the medium. These results indicated that GS activity was regulated at the transcriptional level and that the pattern of expression of the genes for GS during somatic embryogenesis reflected that during zygotic embryogenesis. It is possible that somatic embryogenesis and zygotic embryogenesis have common regulatory systems with respect to nitrogen metabolism.

DNA, Complementary↗
PubMed1998

Hepatitis G virus infection in patients with alcoholic liver disease.

The recently discovered hepatitis G virus (HGV) is believed to be a single-stranded RNA virus belonging to the Flaviviridae family, similar to hepatitis C virus (HCV), but much remains to be learned about its characteristics and clinical manifestations. Although it has been suggested that alcohol intake might have an effect on liver pathology by promoting the proliferation of HCV, the association between HGV infection and alcohol intake is yet to be elucidated. In the present study, we investigated the prevalence of HGV-RNA and HCV-RNA in 63 patients with alcoholic liver disease, and studied the effects of alcohol on the progression of hepatic damage in HGV-RNA positive patients. Among these 63 patients, 9 (14%) were HGV-RNA-positive and 37 (59%) were HCV-RNA-positive. Seven (78%) of the nine HGV-RNA positive patients were also infected with HCV. The patients showed no significant differences of clinical features in relation to the presence or absence of HGV infection. There were also no differences of liver histology among HCV-RNA-positive patients with or without HGV-RNA. The two patients infected with HGV alone had alcoholic hepatitis and nonspecific reactive hepatitis, respectively. In this study, alcohol seemed to have little influence on the progression of the liver histology in HGV-RNA-positive patients.

Adult↗
PubMed1998

Different responses other than the formation of DNA-adducts between the livers of carcinogen-resistant rats (DRH) and carcinogen-sensitive rats (Donryu) to 3'-methyl-4-dimethylaminoazobenzene administration.

Carcinogen-resistant inbred DRH rats developed from the Donryu strain showed a remarkably low incidence of liver tumors when they were fed diets containing hepatocarcinogens such as 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB). In this work, we examined various characteristics of male DRH and Donryu rats during 3'-Me-DAB administration for 8 weeks. 32P-Postlabeling analysis showed that essentially similar levels of DNA-adducts were generated by the metabolites of 3'-Me-DAB in the livers of these two strains of rats at several time points. However, both GADD45 (growth arrest and DNA damage-inducible) and O6-methylguanine methyltransferase (putatively DNA damage-inducible) mRNA levels were increased significantly in Donryu rat livers, but were increased to a lesser extent in DRH rats. [3H]Thymidine incorporation into hepatic DNA began to increase around 10 to 20 days after the start of 3'-Me-DAB administration in Donryu rats probably due to DNA repair, while no significant change occurred in DRH rats under the same conditions. Furthermore, inductions of heme oxygenase (due to degradation of heme-proteins) and hepatocyte growth factor (HGF; cell death and regeneration of hepatocytes) mRNAs were greater in Donryu rat livers than those of DRH, suggesting that the former were more sensitive to cytotoxic effects of 3'-Me-DAB than the latter. Another remarkable difference observed between these two strains was the significant induction of cytochrome P-450 2E1 mRNA in Donryu rat livers; this may contribute to the generation of reactive oxygen intermediates. Finally, increases of glutathione S-transferase (P-form) and gamma-glutamyltranspeptidase mRNAs as marker enzymes of preneoplastic changes of hepatocytes were clearly seen only in Donryu rat livers at 6 to 8 weeks after the start of 3'-Me-DAB administration. These results indicate that the different susceptibility to hepatocarcinogenesis between these two strains of rats may arise from events other than the DNA adduct formation.

Animals↗
PubMed1998

Effects of soy protein isolate (SPI) and casein on the postprandial lipemia in normolipidemic men.

To elucidate the effects of soybean protein and casein on postprandial lipemia, oral fat load tests were performed before and 3 weeks after the administration of soy protein isolate (SPI) and casein supplement to normolipidemic men. Eleven normolipidemic male subjects on otherwise identical controlled diets were assigned to either a 20 g/d soy protein isolate (SPI) dietary supplement or a casein dietary supplement for three weeks in a crossover design. Fat load tests with 40 g/m2 of bovine milk fat were carried out before and after 3 weeks on the experimental dietary supplements. Fasting plasma concentrations of lipids and apolipoproteins were not significantly different from baseline levels before or after the administration of SPI or casein supplemented diets. Neither SPI nor casein supplement affected the fasting plasma concentrations of lipids and apolipoproteins. The areas under the incremental curve (AUIC) of triglyceride (TG) and remnant-like particles triglyceride (RLP-TG) after both experimental diets were not significantly different from those before the experimental diets. However, the AUIC of remnant-like particles cholesterol (RLP-C) showed a tendency (p = 0.07) to decrease after administration of the diet supplemented with SPI than before the diet. The AUIC of RLP-C was significantly (p < 0.05) lower after the diet supplemented with SPI than after administration of the diet supplemented with casein. These results suggest that 3 weeks of 20 g/d SPI dietary supplement favorably affects the postprandial remnant lipoprotein response as compared to the casein dietary supplement.

Adult↗
PubMed1998

Signal transduction inhibitors, hibarimicins, A, B, C, D and G produced by Microbispora. I. Taxonomy, fermentation, isolation and physico-chemical and biological properties.

Strain TP-AO121 which produces a complex of novel tyrosine kinase inhibitors designated hibarimicins A, B, C, D and G was considered to be a new subspecies of Microbispora rosea, and the name, Microbispora rosea subsp. hibaria, was proposed. Hibarimicins A, B, C and D specifically inhibited the src tyrosine kinase activity without affecting protein kinase A or protein kinase C. They also showed in vitro anti-Gram-positive bacterial and antitumor activities. The molecular formulae of hibarimicins A, B, C, D and G were assigned to be C85H112O37, C85H112O37, C83H110O36, C85H112O38, and C85H112O39 respectively.

Actinomycetales↗
PubMed1998

Signal transduction inhibitors, hibarimicins A, B, C, D and G produced by Microbispora. II. Structural studies.

The structure of hibarimicins A, B, C, D and G which are inhibitors for tyrosine specific protein kinase are determined using spectroscopic techniques. Hibarimicins described in this report consist of a common aglycon and six deoxyhexoses. The aglycon contains a highly oxidized naphtylnaphthoquinone as a chromophore. Among them, hibarimicin B was identical with angelmicin B.

Actinomycetales↗
PubMed1998

Comparison of fluorine-18-FDG PET and thallium-201 SPECT in evaluation of lung cancer.

UNLABELLED: We compared the diagnostic value of [18F]2-fluoro-2-deoxy-D-glucose (FDG) PET imaging and 201Tl SPECT imaging in the detection of primary lung cancer and mediastinal lymph node metastases. METHODS: Thirty-three patients with histologically-proven primary lung cancer were examined with both FDG PET and TI SPECT (early and delayed scans) within a week of each study. For semiquantitative analysis, the tumor-to-nontumor activity ratio (T-to-N ratio) was calculated. RESULTS: Although both techniques delineated focal lesions with an increase in tracer accumulation in 28 patients, PET identified three additional patients in whom Tl SPECT images did not visualize any lesions on both early and delayed scans. In the detection of lung cancer of less than 2 cm in size, FDG PET provided higher sensitivity (six of seven, 85.7%) than did Tl SPECT early scan (one of seven, 14.3%) and delayed scan (four of seven, 57.1%). Neither technique visualized any lesions in two patients who had bronchioloalveolar carcinoma. The T-to-N ratio was significantly higher with FDG PET (10.39 +/- 6.63) than it was with Tl SPECT (early scan, 2.37 +/- 0.86; delayed scan, 3.01 +/- 1.01) (p < 0.0001), whereas there was significant positive correlation between the FDG T-to-N ratio and the thallium T-to-N ratio (p < 0.01). Twenty-two patients had thoracotomies. Regarding the staging of mediastinal nodes, FDG PET detected mediastinal lymph node metastasis that was negative on Tl SPECT, whereas both techniques excluded tumor involvement in enlarged node at CT. CONCLUSION: Both techniques have clinical value for the noninvasive detection of primary lung cancer that is 2 cm or greater in diameter. However, if a PET camera is available, FDG PET is considered the method of choice for the evaluation of patients with suspected primary lung cancer that is less than 2 cm in diameter.

Adenocarcinoma↗
PubMed1998

Fluorine-18-FDG PET imaging is negative in bronchioloalveolar lung carcinoma.

UNLABELLED: The goals of our study were to establish PET accuracy with 18F-fluorodeoxyglucose (FDG) in finding localized formations of bronchioloalveolar lung carcinoma (BAC) and to investigate the correlation between FDG uptake and the degree of cell differentiation in adenocarcinoma of the lung. MATERIALS: Twenty-nine patients with 30 adenocarcinomas of the lung (7 bronchioloalveolar lung carcinomas, 9 well differentiated, 2 well-moderately differentiated, 11 moderately differentiated and 1 poorly differentiated) were studied. All patients underwent thoracotomies within 4 wk after the FDG PET study. For qualitative analysis, the degree of FDG activity in the tumors was visually scored using a five-point grading system: 0 = same to background activity, 1 = less than mediastinal blood-pool activity, 2 = same to mediastinal blood-pool activity, 3 = slightly greater than mediastinal blood-pool activity and 4 = substantially greater than mediastinal blood-pool activity. Foci of activity with Grades 2-4 were considered tumors. For semiquantitative analysis, standardized uptake values (SUV) were calculated. RESULTS: In 7 BACs, 4 lesions (57%) showed negative results on FDG PET, while in 23 non-BACs, only 1 lesion (4%), which was a well-differentiated adenocarcinoma showed a negative result. BACs' mean visual score (1.43 +/- 1.27) was significantly lower than that of non-BACs (3.17 +/- 1.03) (p = 0.001). The BACs' mean SUV (1.36 +/- 0.821) was significantly lower than that of well-differentiated adenocarcinomas (2.92 +/- 1.28) (p = 0.014); the mean SUV of well-differentiated adenocarcinomas was significantly lower than that of moderately differentiated adenocarcinomas (4.63 +/- 1.86) (p = 0.031). No significant differences were apparent in average size among these three histologic types. CONCLUSION: A correlation was observed between FDG uptake and the degree of cell differentiation in adenocarcinoma of the lung. FDG PET may show negative results for BAC.

Adenocarcinoma↗
PubMed1998

MR sialography in patients with Sjögren syndrome.

PURPOSE: The purpose of this study was to evaluate the effectiveness of MR sialography of the parotid gland ducts in the diagnosis and staging of Sjögren syndrome. METHODS: MR imaging was performed on a 1.5-T unit with a neck phased-array coil. MR sialographic source images were obtained using a heavily T2-weighted fast spin-echo sequence with spectral fat suppression. All images were analyzed on the basis of maximum intensity projection reconstruction. Five healthy control subjects and 51 patients with definite Sjögren syndrome (43 with primary disease and eight with secondary disease) were examined with MR sialography. A labial gland biopsy was performed in all patients and histopathologic grading was done by means of focal scores. The findings of MR sialography were compared with the results of labial gland biopsy to determine the effectiveness of the technique in the diagnosis and staging of Sjögren syndrome. RESULTS: In all five control subjects, the main duct and the primary branching ducts of the parotid glands were clearly visible on MR sialographic images. In patients with Sjögren syndrome, a punctate, globular, cavitary, or destructive appearance was well seen within the parotid glands. Findings obtained at MR sialography correlated well with the results of labial gland biopsy. CONCLUSION: MR sialography has the potential to produce diagnostic findings in the parotid gland ducts of patients with Sjögren syndrome. Our results suggest that this method will augment and possibly replace X-ray sialography.

Adolescent↗
PubMed1998

[A newly designed parallel connecting tube makes feasible high speed blood transfusion with a transfusion pump].

Use of a transfusion pump (BP 101, Terumo, Tokyo) makes it feasible to obtain a stable and almost constant ejection volume at a flow rate of 99 ml.min-1, with no untoward effects of the intravenously placed needle and the microfilter located in the circuit. An air sensor ensures that the pump will cease operation immediately and automatically if an air bubble occurrs in the circuit. When a blood bag is conventionally connected to a connecting tube, at the maximum flow rate, one must set up a new blood bag within a few minutes, and in emergency situations with a shortage of hands, this would be unduly troublesome. When 5-7 blood bags (400 ml) is connected to 5-7 parallel connecting tubes, the pump will continuously eject blood approximately to 2000 ml at 99 ml.min-1, without replacing the blood bags.

Blood Transfusion↗
PubMed1997

Studies on the microsomal cytochrome P450s in the livers of carcinogen-resistant and sensitive rats during long-term administration of 3'-methyl-4-dimethylaminoazobenzene.

Time-course studies on the microsomal cytochrome P450s in the livers of carcinogen-resistant (DRH) and sensitive (Donryu) rats were carried out during a long-term administration of 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB). Total contents of the microsomal cytochrome P450s were gradually reduced with time in the Donryu rat livers, while those in the DRH rats did not alter significantly under these conditions. The activities of several isoforms of cytochrome P450 (CYP1A1, CYP1A2, and CYP2E1) were determined separately during these experimental periods. However, we could not obtain satisfactory evidence which may explain the different susceptibility to chemical carcinogenic actions in the livers between DRH and Donryu rats. Lower total contents of cytochrome P450s in the Donryu rats during the later stage may be due to the hepatic injuries caused by long-term administration of 3'-Me-DAB.

Animals↗
PubMed1997

P110delta, a novel phosphoinositide 3-kinase in leukocytes.

Phosphoinositide 3-kinases (PI3Ks) are a family of lipid kinases that have been implicated in signal transduction through tyrosine kinase- and heterotrimeric G-protein-linked receptors. We report herein the cloning and characterization of p110delta, a novel class I PI3K. Like p110alpha and p110beta, other class I PI3Ks, p110delta displays a broad phosphoinositide lipid substrate specificity and interacts with SH2/SH3 domain-containing p85 adaptor proteins and with GTP-bound Ras. In contrast to the widely distributed p110alpha and beta, p110delta is exclusively found in leukocytes. In these cells, p110alpha and delta both associate with the p85alpha and beta adaptor subunits and are similarly recruited to activated signaling complexes after treatment with the cytokines interleukin 3 and 4 and stem cell factor. Thus, these class I PI3Ks appear not to be distinguishable at the level of p85 adaptor selection or recruitment to activated receptor complexes. However, distinct biochemical and structural features of p110delta suggest divergent functional/regulatory capacities for this PI3K. Unlike p110alpha, p110delta does not phosphorylate p85 but instead harbors an intrinsic autophosphorylation capacity. In addition, the p110delta catalytic domain contains unique potential protein-protein interaction modules such as a Pro-rich region and a basic-region leucine-zipper (bZIP)-like domain. Possible selective functions of p110delta in white blood cells are discussed.

Amino Acid Sequence↗
PubMed1997

Selective expression of HSP70-1 gene in the adrenal cortex but not in the medulla of thermally stressed rats.

The heat shock protein 70 (HSP70) gene expression in rat adrenal glands was investigated. In situ hybridization and Northern blotting revealed a marked increase of inducible HSP70 (HSP70-1) gene expression in the adrenal cortex, but not in the medulla, after whole body hyperthermia. In vivo footprinting assay of HSP70-1 promoter region suggested a possible involvement of other factor(s) in addition to the heat shock factor (HSF). We also detected significant increases of both ACTH and corticosterone in the plasma of the hyperthermic rats. These results suggested some physiological factors other than HSF may also participate in the tissue-specific induction of HSP70-1 gene in vivo.

Adrenal Cortex↗
PubMed1997

Role of tyrosine phosphorylation of HS1 in B cell antigen receptor-mediated apoptosis.

The 75-kD HS1 protein is highly tyrosine-phosphorylated during B cell antigen receptor (BCR)-mediated signaling. Owing to low expression of HS1, WEHI-231-derived M1 cells, unlike the parental cells, are insensitive to BCR-mediated apoptosis. Here, we show that BCR-associated tyrosine kinases Lyn and Syk synergistically phosphorylate HS1, and that Tyr-378 and Tyr-397 of HS1 are the critical residues for its BCR-induced phosphorylation. In addition, unlike wild-type HS1, a mutant HS1 carrying the mutations Phe-378 and Phe-397 was unable to render M1 cells sensitive to apoptosis. Wild-type HS1, but not the mutant, localized to the nucleus under the synergy of Lyn and Syk. Thus, tyrosine phosphorylation of HS1 is required for BCR-induced apoptosis and nuclear translocation of HS1 may be a prerequisite for B cell apoptosis.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Association of a genetic variation in the beta 3-adrenergic receptor gene with coronary heart disease among Japanese.

Mutation frequencies in the beta 3-adrenergic receptor gene were measured in 83 CAD patients and 107 controls (all Japanese nationals) and the mutation incidence in the two groups was compared. The relationship between characteristics of lipid and glucose metabolism and presence or absence of the mutation was examined in CAD patients. The frequency of this mutant allele in CAD patients was significantly higher than that of controls. The presence of this mutation was significantly associated with higher body mass index, but not with other plasma lipid and glucose levels in CAD patients. This mutation was associated with coronary heart disease and obesity but was not with glucose and lipid metabolism disorders in Japanese nationals.

Aged↗