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Biomedical subjects

M Yano

Publications and source records attributed to M Yano.

At least 487 records · Page 27Linked to original sources

Autoantibodies to glutamic acid decarboxylase in patients with IDDM and autoimmune thyroid disease.

Autoantibodies to glutamic acid decarboxylase (GAD), previously reported to be the 64,000-M(r) (64K) islet cell protein, were measured by a radioimmunoassay using purified pig brain GAD in 29 insulin-dependent diabetes mellitus (IDDM) patients with autoimmune thyroid disease (AITD) and in 29 sex- and disease duration-matched IDDM patients without AITD. Islet cell antibodies (ICAs) and 64K antibodies were also determined. In IDDM patients with short-duration diabetes (< 1 year), the prevalence and levels of GAD antibodies were 100% (8 of 8) and 609 +/- 166 U (means +/- SE), respectively, in IDDM patients with AITD and 81.8% (9 of 11) and 90 +/- 51 U, respectively, in patients without AITD. In patients with long-standing IDDM (3-22 years), the prevalence and levels of GAD antibodies were 76.2% (16 of 21) and 193 +/- 66 U, respectively, in patients with AITD and 50.0% (9 of 18) and 36 +/- 14 U, respectively, in patients without AITD. For up to 6 years after the onset of IDDM, the levels of GAD antibodies in IDDM patients with AITD were significantly higher than in IDDM patients without AITD. A close and significant correlation was found between GAD antibodies and ICA or 64K antibodies in IDDM patients with AITD. Our results demonstrate that high levels of GAD antibodies were present in IDDM patients with AITD. The observed differences in GAD immunoreactivity between IDDM patients with and without AITD might help evaluate the role of GAD antibodies in IDDM.

Adult↗

[A case of nonseminomatous germ cell tumor: usefulness of alphafetoprotein subfraction].

Alfa-fetoprotein (AFP) is an indispensable examination in the management of non-seminomatous germ cell tumor. However, many liver diseases also frequently show the elevation of AFP. Therefore, it is essential to discriminate between yolk sac-derived component and liver-derived one. A 32-year-old male who had suffered from chronic hepatitis, visited our clinic in December, 1991. He complained of left scrotal atrophy and dull pain. Surgical specimen was histologically diagnosed as embryonal carcinoma with syncytiotrophoblastic giant cell. The levels of tumor markers, such as AFP, beta-human chorionic gonadotropin (beta-HCG), were estimated. Both of them were elevated, and radiographical studies demonstrated metastatic lesions of bilateral lung field and retroperitoneal lymph nodes (RPLN). After three courses of cisplatin based chemotherapy, lung and RPLN metastases diminished and serum beta-HCG had normalized. However, the serum AFP persisted to show an abnormally high concentration. The subfraction profile with lens culinaris hemagglutinin (LCA) was estimated. The one after the first course was compared with the one after third course. The latter one showed complete diminution of peak 2. This implied the diminishment of yolk sac element.

Adult↗

[The indication and the evaluation of IFN treatment of chronic hepatitis C].

The indication and the evaluation of IFN treatment for chronic hepatitis type C has been discussed. Good response to IFN depend on the level of HCV RNA just before the treatment. The patients who has low level of HCV RNA (less than 1 Meq/ml by DNA probe assay) could be able to estimate the response more than 80%. On the contrary, it is less than 10% for the patients with high level of HCV RNA. The evaluation of IFN treatment for chronic hepatitis were divided into 3 groups. Cure was defined as the continuous normalization of serum ALT and disappearance of HCV RNA during 12 month or more after the treatment. Partial response was defined as continuous normalization of ALT level but positive for HCV RNA. The others were defined as non responder. First and second group should be evaluated for the IFN treatment. Final purpose for IFN treatment should be prevent to develop liver cirrhosis or hepatocellular carcinoma.

Alanine Transaminase↗

[Long-term prognosis after interferon therapy in chronic hepatitis type C].

263 patients with chronic hepatitis C who received interferon therapy were followed up for an average 2.7 years after therapy. 36% of patients showed complete response, 16% of patients showed partial response, 48% of patients showed no response. 96 patients underwent liver biopsy after therapy and were observed long-term prognosis. 13 cases developed to liver cirrhosis. Histopathology before and after interferon, HCV-DNA probe before therapy were examined.

Adult↗

The status of fluoride mouthrinse programmes in Japan: a national survey.

The purpose of this investigation was to determine the current status of fluoride mouthrinse programmes throughout Japan. Data collection and analysis took place in 1992. The focus of this study was on schools that were participating in the rinse programme at the time of the survey. Questionnaires were sent by mail to 49 dentist-members of the Association for the Promotion of Fluoride Use in Japan. These members gathered information from the schools and, when necessary, also from local government offices. Starting with a single prefecture in 1970, the rinse programme increased to 32 out of 47 prefectures by 1992. The total number of schools using fluoride mouthrinse was 1,183 (nursery schools and kindergartens 48 per cent, primary schools 46 per cent, and secondary schools 6 per cent). In nursery schools and kindergartens, 60 per cent of the participating schools adopted the daily method using 0.05 per cent NaF solution. In primary and secondary schools, 78 per cent adopted the weekly method using 0.2 per cent NaF solution. The costs for the rinse regimen were paid for by public funds of the prefectural and municipal governments in 71 per cent of the schools. Fifty-four per cent of the schools which first initiated the rinse programmes in their districts identified dentists and dental associations as the most influential in programme acceptance and implementation. Although the number of fluoride rinse programmes is increasing, it is still modest. These results suggest that cooperation between dental organisations, dental schools and prefectural governments can play very important roles in implementing school based rinse programmes.

Child↗

Endothelin ETB receptors couple to two distinct signaling pathways in porcine kidney epithelial LLC-PK1 cells.

We characterized the endothelin (ET) receptor subtypes responsible for signal transduction in cultured porcine kidney epithelial LLC-PK1 cells. Both ET-1 (IC50, 43 pM) and ET-3 (IC50, 46 pM) inhibited the binding of [125I]ET-1 to LLC-PK1 cells to a similar extent. The binding affinity of LLC-PK1 cells was about 10,000 times higher for the ETB antagonist BQ-788 [N-cis-2,6-dimethyl-piperidinocarbonyl-L-tau-metylleucyl-D-+ ++Nin- methoxycarbonyltryptophanyl-D-norleucine] (IC50, 1.3 nM) than for the ETA antagonist BQ-123 [cyclo-(D-Trp-D-Asp-Pro-D-Val-Leu)] (IC50, 14 microM). ET-1 enhanced cyclic GMP (cGMP) production, but reduced vasopressin- and forskolin-stimulated cyclic AMP (cAMP) production. Both effects of ET-1 were antagonized by BQ-788, but not by BQ-123. The cAMP decrease, but not the cGMP increase, in response to ET-1 was inhibited by pertussis toxin, suggesting that the former response is mediated by pertussis toxin-sensitive Gi, whereas the latter is mediated by a pertussis toxin-insensitive G-protein. Therefore, the ETB receptors in LLC-PK1 cells couple to the two types of signal transduction cascades to reduce cAMP production and stimulate cGMP production via distinct G-proteins. ET-1 and probably also ET-3 may play a role in the regulation of renal epithelial transport by decreasing cAMP and increasing cGMP.

Amino Acid Sequence↗

Improvement of serum aminotransferase levels after phlebotomy in patients with chronic active hepatitis C and excess hepatic iron.

OBJECTIVES: Iron metabolism may be altered in patients with chronic active hepatitis C. In an attempt to evaluate whether excess iron contributes to liver injury, we used phlebotomy for removal of iron from patients with chronic hepatitis C. METHODS: All 10 patients had histochemically detectable iron in the liver and underwent an initial period of weekly or monthly phlebotomy of 200 or 400 ml. A serum ferritin level of 10 ng/ml or less was chosen as the endpoint, and maintenance phlebotomy was performed if the level rebounded. RESULTS: The treatment reduced mean serum alanine aminotransferase activity from 152 +/- 49 to 55 +/- 32 IU/L; this level became normal in five of the 10 patients. Anti-HCV antibodies could be detected in all patients throughout the study. Histologic abnormalities of the liver were unchanged except for disappearance of iron deposits from seven of the patients studied. CONCLUSIONS: Our findings suggest that iron removal may be beneficial for patients with chronic active hepatitis C and histochemical iron in the liver.

Adult↗

Expression of VpreB gene in common variable immunodeficiency.

We analyzed the expression of the VpreB gene in 5 common variable immunodeficiency (CVI) patients. There was no deletion or large mutation as compared with control DNA by Southern blotting. In the peripheral blood mononuclear cells of CVI patients, expression of the VpreB gene was not detected by polymerase chain reaction. These results suggest that there were no immature B cells such as pro- or pre-B stages in the peripheral blood mononuclear cells of these CVI patients. In B lymphoblastoid cell line (LCL) cells, expression of VpreB gene was observed in patients and Manca cells. The results suggest that the stages of these LCL cells may be a traditional stage between pre-B and mature B cell. As for the Manca cell, our result is in accordance with a recent report that surface immunoglobulin-positive cell lines also express the pre-B-related genes.

B-Lymphocyte Subsets↗

Role of intracellular proteases in differentiation of L6 myoblast cells.

The activities of cathepsins B, L, and H increased by 3.0, 2.3, and 1.9 fold in differentiation of L6 myoblasts. Separating from the intrinsic inhibitor, both mu- and m-calpain activities also increased by 4.9 and 1.7 fold during differentiation. Calpeptin (10(-5)M), cell penetrating calpain inhibitor, blocked fusion of myoblast by 55% and increment of creatine phosphokinase (CPK) activity by 20.3% with inhibiting the activities of cathepsin L and mu-calpain. E-64(10(-4)M) did not block fusion of myoblasts but increment of CPK activity by 25.0% with inhibiting the activities of cathepsin L and B. Calpain may be involved in the process of myoblast fusion.

Animals↗

[Hypervascular liver metastases of gastric cancer completely responding to transcatheter oily chemoembolization using epirubicin hydrochloride, mitomycin C and lipiodol].

A 68-year old woman underwent transarterial oily chemoembolization using Lipiodol with epirubicin hydrochloride and mitomycin C for treatment of multiple hypervascular hepatic metastases of gastric cancer. The tumors showed a good fixation of Lipiodol with a complete biologic response. The tumor has been well controlled for eight months by only one chemoembolization on follow-up study. Transcatheter oily chemoembolization may be an effective treatment not only for hepatocellular carcinoma, but also for hypervascular liver metastases from gastrointestinal malignancies.

Adenocarcinoma↗

Big endothelin-1 structure important for specific processing by endothelin-converting enzyme of bovine endothelial cells.

Phosphoramidon-sensitive endothelin-converting enzyme of bovine endothelial cells showed substrate selectivity for big endothelin-1 (ET-1) when compared to big ET-1(1-38), big ET-2(1-37), big ET-2(1-38) and big ET-3(1-41). To investigate the big ET-1 structure important for specific conversion by the endothelin-converting enzyme, we synthesized a series of truncated analogues of big ET-1, measured the hydrolysis of their Trp21-Val22 bonds, and found that a 16-residue peptide, big ET-1(19-34), is the minimal peptide sequence. This suggests that an unusually long carboxy-terminal sequence is required for big ET-1 conversion. Alanine substitution for individual amino acids in the carboxy-terminal region of big ET-1(19-34) demonstrated that His27, Val29, Pro30, Tyr31, Gly32, Leu33 and Gly34 are more important than Asn23, Thr24, Pro25, Glu26 and Val28 for eliciting efficient hydrolysis of the Trp21-Val22 bond, even though the former residues are located at more distant positions from the cleavage sites than are the latter. These results, together with the fact that big ET-2 and big ET-3 show heterogeneity in the big ET-1 residues His27, Val28, Val29 and Gly34, suggest that the His27-Val-Val-Pro-Tyr-Gly-Leu-Gly34 sequence in the carboxy-terminal region of big ET-1 plays the most important role in selective conversion by endothelin converting enzyme.

Amino Acid Sequence↗

A novel endothelin ETA receptor antagonist, BQ-485, and its preventive effect on experimental cerebral vasospasm in dogs.

Because endothelin-1 has a potent and long-lasting vasoconstrictive action, it has been proposed that it plays some important roles in the pathogenesis of delayed cerebral vasospasm following subarachnoid hemorrhage. We examined the preventive effect of a novel ETA receptor antagonist, BQ-485, on experimental vasospasm using canine two-hemorrhage model of subarachnoid hemorrhage. The IC50 value of BQ-485 on [125I]endothelin-1 binding was 3.4 x 10(-9) M for ETA receptor and 26 x 10(-6) M for ETB receptor. Systemic continuous administration of 120 mg/day of the agent inhibited the narrowing of canine basilar artery on day 7 following experimental subarachnoid hemorrhage (75.0% vs 59.9% (control), p < 0.01). The present results suggest that endothelin-1 and ETA receptor participate in the pathogenesis of delayed cerebral vasospasm.

Animals↗

Developmental change of facilitative glucose transporter expression in rat embryonal and fetal intestine.

The developmental expression and localization of facilitative glucose transporter protein (GLUT-1, GLUT-2 and GLUT-5) in rat embryonal and fetal intestine were examined using immunohistochemical methods. The intestines were collected from embryo and fetus (term days, 10 to 20 of gestation), newborn and adult rats (16 weeks after birth). GLUT-1 was expressed abundantly in the gut tube on day 10 of gestation. From day 10 to birth, GLUT-1 was expressed continuously but its expression decreased gradually. In the adult, no GLUT-1 was detected. GLUT-2 was not expressed from day 10 to 14, but began to be expressed in the lumen of the gut tube on day 16, before the intestinal villi were evident. On day 18, when the intestinal villi were developing, GLUT-2 was localized to the basolateral membranes of the enterocytes. A similar pattern of GLUT-2 localization was also observed in newborn and adult rat intestines. The expression kinetics of GLUT-5 were almost the same as those of GLUT-2. GLUT-5 began to be expressed in the lumen of the gut tube on day 16. In contrast to GLUT-2, GLUT-5 was localized to the brush border membranes of intestinal villi after day 18. These results indicate that the expression and localization of each member of the glucose transporter family in the embryonal and fetal intestine vary with the gestational phase. GLUT-1 may be required for glucose metabolism early in gestation, and GLUT-2 and GLUT-5 may be required in both late gestational and perinatal stages.

Animals↗

The in vivo antiaggregatory action of endothelin-1 is not mediated through the endothelin ETA receptor.

Intravenous bolus injection of endothelin-1 (0.1 and 0.25 nmol/kg) resulted in a dose-dependent inhibition of in vivo platelet aggregation in anesthetized Beagle dogs. Pretreatment of the animals with the selective ETA receptor antagonist, BQ-123 (1 mg/kg), completely abolished the pressor response to endothelin-1 without affecting the magnitude of the depressor response. BQ-123 neither modified the antiaggregatory action of endothelin-1 nor affected the increase in plasma 6-keto prostaglandin F1 alpha level elicited by endothelin-1. These findings indicate that the in vivo antiaggregatory and prostacyclin releasing actions of endothelin-1 are not mediated by activation of the ETA receptor.

6-Ketoprostaglandin F1 alpha↗

A novel ligand, [125I]BQ-3020, reveals the localization of endothelin ETB receptors.

The precise localization of an endothelin (ET) receptor subtype, the ETB receptor, in porcine lung was elucidated by in vitro microautoradiography using a novel ETB-selective radioligand, [125I]BQ-3020 ([125I-Tyr]-N-acetyl-Leu-Met-Asp-Lys-Glu-Ala-Val-Tyr-Phe-Ala-His-Leu-Asp -Ile-Ile-Trp). Of the labeled native ET isopeptides, [125I]ET-3 is selective for ETB receptors. However, [125I]ET-3 was not suitable for autoradiography due to its high degree of non-specific binding. On the other hand, [125I]BQ-3020 showed extremely low non-specific binding on autoradiography. The distribution of [125I]BQ-3020 binding in porcine lung was clearly different from that of [125I]ET-1, which showed more widespread binding than [125I]BQ-3020 due to a high affinity to both ETA and ETB receptors. [125I]BQ-3020 was found to bind to parenchyma, parasympathetic ganglia, pulmonary and submucosal plexuses, but bound only slightly to circular smooth muscle layers and the epithelium of airway tracts. Although [125I]ET-1 bound to the smooth muscle layer of all blood vessels, the binding of [125I]BQ-3020 differed among blood vessels. [125I]BQ-3020 binding in blood vessels paralleled acetylcholinesterase activity, suggesting that ETB receptors in blood vessels are located on parasympathetic nerves. Thus, the radioligand [125I]BQ-3020 is very useful for studying the precise localization of ETB receptors.

Acetylcholinesterase↗

Role of endothelin ETB receptors in bronchoconstrictor and vasoconstrictor responses in guinea-pigs.

In anesthetized and ventilated guinea-pigs, intravenous injections of endothelin (ET)-1 (0.5 nmol/kg), ET-3 (0.5 nmol/kg), and [Ala1,3,11,15]ET-1 (20 nmol/kg), an ETB-selective receptor agonist, induced bronchoconstrictor and transient vasoconstrictor responses. Only the ET-1-induced transient vasoconstriction was followed by a secondary sustained pressor response. The ETA-selective receptor antagonist, BQ-123 (1 mg/kg i.v.), attenuated only the sustained pressor response. These results indicate that the bronchoconstrictor and transient vasoconstrictor responses to endothelins in guinea-pigs are mediated by ETB receptors, whilst the sustained pressor response is mediated by ETA receptors. The thromboxane A2 receptor antagonist, L-670,596 (0.5 mg/kg, i.v.) and a high dose of BQ-123 (30 mg/kg i.v.) abolished the bronchoconstriction only without affecting the transient pressor response to endothelin isopeptides. These results suggest that the ETB-mediated bronchoconstriction depends on thromboxane A2 formation. The different sensitivity of these ETB-mediated transient responses to BQ-123 suggests the possible existence of distinct ETB receptor subtypes.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗