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Biomedical subjects

N Hashimoto

Publications and source records attributed to N Hashimoto.

At least 127 records · Page 7Linked to original sources
PubMed1994

Regulation of insulin receptor, insulin receptor substrate-1 and phosphatidylinositol 3-kinase in 3T3-F442A adipocytes. Effects of differentiation, insulin, and dexamethasone.

Insulin rapidly stimulates tyrosine kinase activity of its receptor resulting in phosphorylation of its cytosolic substrate insulin receptor substrate 1 (IRS-1), which in turn associates with and activates the enzyme phosphatidylinositol 3-kinase (PI 3-kinase). In the present study we have examined these three initial steps in insulin action during the differentiation of 3T3-F442A adipocytes and after treatment with dexamethasone or insulin. The differentiation of 3T3-F442A cells was characterized by a 13-fold increase in insulin receptor protein, a 9-fold increase in IRS-1, and a 10- and 4.5-fold increase in their insulin-stimulated phosphorylation, respectively. The mRNA expression of these two proteins showed a similar 8-fold increase during differentiation. In addition there was a 3.5-fold increase in PI 3-kinase protein [85 kilodalton (kDa) subunit] and a 16-fold increase in IRS-1-associated PI 3-kinase activity between day 0 and day 8 of differentiation. Dexamethasone (1 microM) treatment of differentiated cells induced a further 48% (P < 0.05) increase in insulin receptor level, but the autophosphorylation of the receptor was decreased by 31 +/- 1% (P < 0.02). At the same time there was a decrease by 56 +/- 4% (P < 0.005) in IRS-1 protein and by 31 +/- 1% (P < 0.001) in IRS-1 phosphorylation. The expression of insulin receptor mRNA was unchanged, but the expression of IRS-1 mRNA was decreased by approximately 75% after dexamethasone. By contrast, dexamethasone induced a 69% increase in the level of PI 3-kinase as determined by immunoblotting. The combined effect of decreased IRS-1 phosphorylation and increased PI 3-kinase protein was a minimal change (15% decrease) in the association/activation between IRS-1 and PI 3-kinase. Chronic treatment with 100 nM insulin induced a time- and dose-dependent decrease in insulin receptor and IRS-1 protein levels reaching a nadir of 34 +/- 5% (P < 0.005) and 39 +/- 5% (P < 0.01) of control levels after 24 h, respectively. There was an even more marked decrease in the phosphorylation level of these proteins. Chronic insulin treatment also produced a 30% decrease in PI 3-kinase protein levels and a approximately 50% decrease in the association/activation between IRS-1/PI 3-kinase. The expression of insulin receptor and IRS-1 mRNA was unchanged during chronic insulin treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

3T3 Cells↗
PubMed1994

Epizootiological studies of hantavirus infection among urban rats in Hokkaido, Japan: evidences for the persistent infection from the sero-epizootiological surveys and antigenic characterizations of hantavirus isolates.

Epizootiological studies of hantavirus infection among urban rats were carried out through the surveys repeated 11 times at the same dumping ground area in 1983 to 1988. A total of 279 rats (Rattus norvegicus) were captured during the surveys. Sero-positive animals to hantavirus strain SR-11 were detected in all the surveys. Overall positive rate of rats 6 months old or more (94/128, 73.4%) was significantly higher than that of younger rats (23/151, 15.2%, x2 = 96.4, P < 0.001). Therefore, age dependent acquisition of hantavirus infection among rats was confirmed. Seven hantavirus strains, KI-83-262 (August, in 1983, designated as strain KI-262 in our previous report (2)), KI-85-1 and 85-2 (July in 1985), KI-88-4, 88-11, 88-15 and 88-24 (October, 1988) were isolated from lung tissues of adult rats which have high titers of neutralizing antibody. Although the serum specimens of virus carrier rats neutralized the infectivity of all the KI isolates, no apparent antigenic change in the isolates was detected by indirect immunofluorescent antibody (IFA) assay using polyclonal and monoclonal antibodies (MAbs) regardless of isolation years. However, neutralization test showed slight difference of antigenicity among KI strains. These results epizootiologically confirmed that hantavirus infected persistently among urban rats in a presence of neutralizing antibody.

Animals↗
PubMed1994

Induction of lung tumors in C3H strain mice after single or fractionated irradiation with X-rays.

Murine model for lung tumor induction was studied in C3H/He male mice, a strain with low spontaneous incidence of lung tumors. Dose-response relationships in lung tumor induction were compared following irradiation with single doses and split doses of X-rays to the thorax either at night or in the daytime. The tumor incidence after a single 1.25 Gy dose at night during the period of nocturnal activity almost reached the maximum level after a 5 Gy dose in the daytime. Proliferative activity determined by observing the labeling index with tritiated thymidine in the normal lung was low as a whole, but tended to decrease in the daytime. When the proliferative response was induced by X-irradiation, significantly higher activity was observed at night. These circadian fluctuations were thought to affect radiosensitivity and lung tumor induction in mice. When split doses or fractionated doses of X-rays were applied to the thorax, lung tumor incidence definitely increased. The incidence after two 7.5 Gy doses with a 12 hr-interval was 41%, 3-fold higher than that after a single 15 Gy dose. Moreover, fractionated whole body irradiations (three times at 3 Gy with 3-month-interval) after a single 7.5 Gy thoracic irradiation was most effective in increasing not only the incidence (47%) but also the multiplicity of the lung tumor. More than 30% of tumor-bearing mice had two or more tumors following thoracic and whole body irradiations, while only 10% of tumor-bearers had multiple tumors after single or fractionated thoracic irradiation alone.

Animals↗
PubMed1994

Lymphocytic hypophysitis presenting with diabetes insipidus: case report and literature review.

Lymphocytic adenohypophysitis is an autoimmune disorder of the anterior pituitary gland which usually occurs in a women in the postpartum period. It has been considered that lymphocytic hypophysitis is confined to the adenohypophysis sparing the neurohypophysis, and that diabetes insipidus is not a clinical feature of the disorder. Here we report the case of a 50-year-old woman with lymphocytic hypophysitis which presented with diabetes insipidus. MRI indicated homogeneous swelling of the whole pituitary gland, loss of the normal high intensity of the posterior pituitary, and thickening of the pituitary stalk. A biopsied specimen of the pituitary revealed diffuse lymphocytic infiltration. The diabetes insipidus was controlled by the administration of DDAVP. The anterior pituitary function was not greatly damaged, and no hormonal replacement therapy was necessary. We suggest that this case represents a variant of lymphocytic adenohypophysitis and/or lymphocytic infundibuloneurohypophysitis, in which the chronic inflammatory process involves the infundibulum, adenohypophysis and neurohypophysis.

Autoimmune Diseases↗
PubMed1994

Follow-up study of patients with "unilateral" moyamoya disease.

Sixty-four patients with "unilateral" occlusive disease of the circle of Willis were studied to evaluate progression to bilateral disease. Seventeen patients developed bilateral lesions during a period of 1-7 years after the diagnosis of unilateral lesion. Most of these patients had ischemic attack as the initial episode and had repeated attacks before admission. Young children, mostly less than 10 years of age, tended to develop bilateral lesions within 1-2 years, but adults tended to have only a unilateral lesion. Children or young adults with unilateral occlusive lesion of the terminal portion of the internal carotid artery are likely to develop bilateral disease within 1-5 years.

Adolescent↗
PubMed1994

[Effect of combination therapy with disodium cromoglycate (DSCG) and Ozagrel on non-atopic asthmatics].

Ozagrel (OKY-046), a selective inhibitor of thromboxane biosynthesis has been reported to reduce airway hyperresponsiveness in asthmatics. DSCG has been widely used for atopic, but not for non-atopic asthmatics. We evaluated the additive effect of combination therapy with DSCG and Ozagrel on nonatopic asthmatics. Fourteen asthmatics were divided into two groups. The patients in the O-D group were initially treated with Ozagrel (400 mg/day) for 4 weeks, and then DSCG (8 mg/day) was added for another 4 weeks. The patients in D-O group were initially treated with DSCG (8 mg/day), and then Ozagrel (400 mg/day) was added for 4 more weeks. TXB2, PGF2 alpha, PGE2, 6-keto-PGF1 alpha in sputum and 11-dehydro TXB2 in urine were measured before and after 4th and 8th weeks of therapy. Ozagrel decreased the metabolites of thromboxane and PGF2 alpha in sputum and urine. PGE2 in sputum tended to be increased by Ozagrel. DSCG did not affect mediators in sputum. Combination therapy with Ozagrel and DSCG showed the additive effect to single use on attack score and PF in non-atopic asthmatics.

Adult↗
PubMed1994

HTLV-I associated uveitis and hyperthyroidism.

The records of 76 consecutive patients with etiology-undefined uveitis examined during the 3-year period between 1990 and 1992 were reviewed and 6 patients were found who had concomitant hyperthyroidism. These 6 patients had presented with uveitis symptoms and signs when hyperthyroidism was relieved with thiamazole therapy. The uveal disease was characterized by acute, granulomatous or nongranulomatous anterior uveal involvement and granular or membranous vitreous opacities with or without retinal vascular change. These manifestations resolved in a few weeks in response to topical and/or systemic corticosteroids. Three patients had recurrence of uveitis after remission for months to years. All of the patients had serum antibodies to HTLV-I. The uveal disease resembled HTLV-I associated uveitis that may develop in patients with HTLV-I associated myelopathy or HTLV-I carriers; 2 cases had chronic myelopathy or arthropathy that was considered associated with the retrovirus. The present observations suggest that the association between uveitis and hyperthyroidism is not accidental but shares a common underlying etiologic factor, HTLV-I, although the pathomechanism remains to be defined.

Adult↗
PubMed1994

[Type C insulin resistance].

Type C insulin resistance in insulin receptor mutations is characterized by normal insulin binding to cultured fibroblasts or EB virus transformed lymphocytes from the patients and decreased insulin receptor kinase activities. However, it is sometimes difficult to classify the state of insulin resistance clearly. The intracellular beta-subunit mutations of insulin receptor which showed decreased kinase activities is reviewed here. Moreover, two cases with typical type C insulin resistance reported previously are also described. One is a case with deletion of the tyrosine kinase domain of the insulin receptor and the other is a Glycine-1008 to Valine mutation. Our studies suggest that the insulin resistance associated with these mutated genes in the kinase domain of insulin receptor were inherited, as an autosomal dominant trait.

Adenosine Triphosphate↗
PubMed1994

[Clinical and autopsy studies on prognosis of sarcoidosis].

Prognosis of 435 sarcoidosis patients and epidemiologic features were studied in 320 autopsy cases. About 80-90% of Stage I or II patients showed spontaneous remission. The prognosis of Stage III patient was poor and corticosteroid therapy seemed to be rather ineffective. The proportion of sarcoidosis autopsy, relative to total autopsy cases, appears to be increasing. The number of female cases was about 2 times larger than that of males. Only 43.4% of the total autopsy cases had been diagnosed clinical sarcoidosis. Over 5 times more sarcoidosis patients than clinically diagnosed were estimated to exist. Approximately one half of the sarcoidosis autopsy cases were related to cardiac sarcoidosis.

Adolescent↗
PubMed1994

Humoral inhibitor of rat hepatocyte DNA synthesis from patients with fulminant liver failure.

Sera and ultrafiltrates (relative molecular mass < 10,000 Da) from patients with fulminant liver failure inhibit hepatocyte DNA synthesis in vivo. In this study the effects of ultrafiltrates from pooled sera from fulminant liver failure patients in the United Kingdom and plasma ultrafiltrates from fulminant liver failure patients in Japan have been investigated in primary cultured rat hepatocytes, with incubation for up to 72 hr. Both types of ultrafiltrate inhibited the incorporation of [3H]thymidine into acid-precipitable material and reduced the cell labeling index as determined on autoradiography in hepatocytes stimulated by epidermal growth factor and insulin compared with normal sera/plasma ultrafiltrates. The inhibitory effects observed were dose dependent, reversible when the fulminant liver failure ultrafiltrate was removed and were not associated with increased release of lactate dehydrogenase or suppression of protein synthesis as assessed on the basis of the incorporation of [3H]leucine. The effects appeared to be specific for hepatocytes; in preliminary experiments DNA synthesis was not inhibited in cultured fibroblasts (NIH 3T3 cells). These experiments are further evidence of the presence of an inhibitory factor of relative molecular mass less than 10,000 Da in the blood of patients with fulminant liver failure.

Adolescent↗
PubMed1993

Differential contribution of M(r) 120 kDa rasGTPase-activating protein and neurofibromatosis type 1 gene product during the transition from growth phase to arrested state in human fibroblasts accompanied by a unique rasGTPase-activating activity.

Using octyl glucoside-solubilized cell extracts from human fibroblasts during growth phase to G0/G1 arrest state, we found that while the number of M(r) 120 kDa rasGTPase-activating protein (p120GAP) molecules per cell decreases to half its original levels, the amount of neurofibromatosis type 1 gene product (NF1, a neurofibromin) remains constant during the transition. The contribution of p120GAP to the total rasGTPase-activating (rasGA) activity in growing cells was found to be larger than that observed in arrested cells (84% vs 53%). On the other hand, NF1 contributes less than 15% of the total rasGA activity in either extract. These results indicate that the qualitative changes occur in the contributors to rasGA activity during transition. They also suggest that a unique rasGA activity exists in the arrested cells, which was obtained separately from both p120GAP and NF1 by heparin-Sepharose column chromatography.

Animals↗
PubMed1993

Common sequence elements are important for transcription and replication of the extrachromosomal rRNA-encoding genes of Tetrahymena.

Three types of conserved sequence elements have previously been identified in the generally non-conserved, 5' non-transcribed spacer region of the rRNA-encoding gene (rDNA) of Tetrahymena species. In vivo and in vitro experiments have identified the start point (tsp) for rDNA transcription. Comparative sequence analysis suggested that the type-I sequence element was likely to function as the promoter for rDNA transcription. We have used in vitro transcription assays to demonstrate that sequences in the 3' half of the type-I repeat located proximal to the tsp are essential for the accurate initiation of rRNA synthesis. These sequences define the 5' boundary of the core or minimal promoter element and include the sequences which function in rDNA replication and maintenance in the homologous regions in two upstream type-I sequence elements. These sequences may bind factors important for both the transcription and replication of rDNA.

Animals↗
PubMed1993

[Usefulness of enhanced MR angiography by nitroglycerin].

We tried to use nitroglycerin to enhance MR angiography (MRA). Nitroglycerin has an effect to dilate vessels. We made a direct comparison between pre and post enhanced MRA (3 D-TOF technique). MRA after administration of nitroglycerin could depict more details of cortical branches without enhancement of background. So we recommend this method to be used in any examination of MR angiography.

Adult↗
PubMed1993

Improved sensitivity in the antibody-forming cell assay for Japanese encephalitis virus in mice by optimal fixation of cells and avidin-biotin complex (ABC) immunocytochemistry.

A sensitive modified method for the detection in vitro of antibody-forming cells (AFCs) in Japanese encephalitis (JE) virus infected mice is described. The procedure involves the selection of the most appropriate incubation period, after the infection of monolayer cells, for expression of viral antigens to be recognized by AFCs. Adequate preservation of the expressed antigens was achieved after fixation with paraformaldehyde-lysine-periodate buffer (PLP). The development of spots which corresponded to AFCs was successfully obtained with the use of the avidin-biotin complex (ABC) amplification reaction. The number of the spots developing after completion of the assay was greater after PLP fixation compared with other fixation solutions such as methanol, formalin and acetone-water. Optimum antigen expression on the infected cells for recognition by lymphoid cells was reached after 24 h of infection. However, it was possible to detect viral antigens on the infected cells 8 h after infection. The ABC reaction was shown to be the best procedure for developing spots compared with other immunocytochemical methods. A linear increment was observed in the number of spots that developed at different spleen cell densities. This assay is simple to perform and could detect virus-specific Ig producing cells from the spleens of mice infected with JE virus. It also makes it possible to enumerate accurately the kinetics of the AFC response in different lymphoid organs during infection or after vaccination.

Animals↗
PubMed1993

A novel murine zinc finger gene mapped within the tw18 deletion region expresses in germ cells and embryonic nervous system.

A novel zinc finger gene, designated NT fin12, belonging to the C2H2-Krüppel-type gene family was isolated from a newborn mouse testis cDNA library by using zinc finger consensus motif probes. Northern blot analyses showed that NT fin12 mRNA was expressed during the meiotic prophase of spermatogenesis and in embryogenesis. Transcripts were localized by in situ hybridization in spermatogonia and in early spermatocytes, and in testis cords in the genital ridge as well as in oocytes and follicle cells in the ovary. In midgestational embryos at 8.5-13.5 days postcoitum, transcripts were present in the neuroectoderm, and they were progressively restricted to peripheral ganglia derived from neural crest cells and neural placodes and to the motor nerve cells in the central nervous system. Taken together these results indicate that NT fin12 functions during germ cell development and also plays a role in the specification of a subpopulation of neuroectodermal cells. Genetic linkage analyses revealed that the NT fin12 locus mapped to the deletion region of the tw18 haplotype on mouse chromosome 17.

Amino Acid Sequence↗
PubMed1993

A comparison of the metabolic changes after the distal splenocaval and portacaval shunts.

The distal splenorenal shunt (DSRS) is the recommended procedure for selective variceal decompression, but its use may be limited in patients who have undergone left nephrectomy, those with an anatomically aberrant relationship between the splenic and left renal veins, and those whose preoperative angiographic findings suggest a risk of developing postoperative renal vein hypertension. For these clinical situations, the selective distal splenocaval shunt (DSCS) is a useful alternative to the DSRS. However, the metabolic consequences of the DSCS have not yet been studied in detail and therefore, using a canine model, the metabolic changes following the DSCS and the portacaval shunt (Eck) were compared. The metabolic changes observed following the Eck were hyperammonia and amino acid imbalance, while those following the DSCS were similar to those of the control dogs. In terms of the hepatic adenosine triphosphate level, which reflects hepatic mitochondrial function, the DSCS dogs were also similar to the control dogs. These data suggest that there was no metabolic disadvantage of the DSCS compared to the control.

Adenosine Triphosphate↗
PubMed1993

Type 2 (non-insulin-dependent) diabetes mellitus associated with a mutation of the glucokinase gene in a Japanese family.

Mutations were screened for in the glucokinase gene of 25 Japanese patients with Type 2 (non-insulin-dependent) diabetes mellitus. Each exon was scanned by electrophoresis of enzymatically amplified DNA segments under non-denaturing conditions and variants were sequenced. A variant pattern was detected in exon 5 of one patient. Direct sequencing of this exon revealed a single nucleotide substitution in codon 188 (GCT-->ACT) of one of two alleles resulting in the mutation of Ala188-->Thr, an invariant residue in the sequence of all mammalian glucokinases and hexokinases. This mutation was not found in 40 normal control subjects. The proband had been diagnosed with Type 2 diabetes at the age of 62 years. Four other members of her family have the same mutation and all have Type 2 diabetes or impaired glucose tolerance. The youngest age at diagnosis of Type 2 diabetes in these other members was 13 years, suggesting that her pedigree was maturity-onset diabetes of the young (MODY). All subjects with the Thr188 mutation show a decreased insulin secretory response during oral glucose tolerance testing. Mutations in the glucokinase gene associated with Type 2 diabetes have been previously identified in Caucasian (French and British) subjects. This study indicates that mutations in this gene are also implicated in the development of Type 2 diabetes in Asians. Further studies are required to determine the frequency of mutations in glucokinase among Japanese patients with Type 2 diabetes.

Adolescent↗