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Biomedical subjects

K Goto

Publications and source records attributed to K Goto.

At least 253 records · Page 14Linked to original sources

Endothelin-1 expression in hearts of transgenic hypertensive mice overexpressing angiotensin II.

Cardiac myocytes and vascular endothelial cells produce endothelin (ET)-1, which has potent hypertrophic effects on cardiac myocytes. Although in cultured cardiomyocytes, angiotensin II (Ang II) was reported to enhance ET-1 production in vitro, it is not known whether ET-1 production is enhanced by Ang II in vivo. We investigated the production and pathophysiologic roles of ET-1 in 20-week-old male transgenic hypertensive mice (THM), in which the renin-angiotensin system (RAS) was markedly activated because of the presence of both human renin and angiotensinogen genes. Systolic blood pressure and the ratio of left ventricular weight to body weight were significantly higher in the THM than in control mice, indicating that THM developed cardiac hypertrophy. ET-1 production was significantly increased in the heart of THM because both ET-1 mRNA expression and peptide levels were significantly higher than in controls. However, circulating plasma ET-1 levels did not differ between the groups, and blood pressure did not change after i.v. injection with a high dose (3 mg/kg) of the ETA/B-nonselective receptor antagonist SB209670. These findings suggest that increased cardiac ET-1 production may contribute to the progression of cardiac hypertrophy and that endogenous ET-1 may not be involved in the short-term modulation of blood pressure in THM of this age.

Angiotensin II↗

Endothelin-converting enzyme and angiotensin-converting enzyme in failing hearts of rats with myocardial infarction.

We have previously reported that production of endothelin (ET)-1 is markedly increased in failing hearts of rats with chronic heart failure (CHF). It was also reported that the production of angiotensin II (Ang II) is increased in the failing heart. In this study we investigated both converting enzymes of the ET-1 system and the angiotensin system. We used left coronary artery-ligated rats as a model of CHF. The peptide level of ET-1 in the left ventricle (LV) was markedly higher in CHF rats than in control rats. In the LV, expression of preproET-1 mRNA was also markedly higher in CHF rats than in controls. The expression of endothelin-converting enzyme (ECE)-1 mRNA in the rats with CHF was similar to that in controls. Therefore, we believed that the increase in ET-1 production in the failing heart originated from an increase in preproET-1 production rather than increase in ECE. The expression of angiotensin-converting enzyme (ACE) mRNA in failing hearts of CHF rats was significantly higher than that of the sham-operated rats. The expression of angiotensinogen mRNA in failing hearts of these CHF rats was slightly higher than that of the sham-operated rats. This study suggests that there is a difference in the role of peptide synthesis between the ECE system and the ACE system in rats with CHF.

Angiotensinogen↗

Description of Arthrobacter creatinolyticus sp. nov., isolated from human urine.

Three strains of creatinine-hydrolysing bacteria isolated from human urine were characterized taxonomically. They were aerobic, non-spore-forming, Gram-positive rods with the peptidoglycan of the cell wall containing lysine. MK-8 and MK-9 were found to be the major types of menaquinone. The G + C content of the DNA was 66-67 mol%. The 16S rRNA sequence of one strain (GIFU 12498) was determined and aligned with other high-G + C-content Gram-positive rods from different genera. Following phylogenetic analysis, this strain was placed in the genus Arthrobacter. Arthrobacter protophormiae was the most closely related species in the phylogenetic tree, and this species also showed the highest sequence homology value (97%) with GIFU 12498. However, DNA-DNA hybridization indicated that GIFU 12498 did not belong to A. protophormiae (33.8 +/- 3.5% chromosomal similarity). The three urine strains belonged to one species because they shared more than 95% DNA-DNA similarity. It is proposed that these strains are placed in the genus Arthrobacter as a new species, Arthrobacter creatinolyticus sp. nov. The type strain of A. creatinolyticus is GIFU 12498, which has been deposited in the Japan Collection of Microorganisms (JCM) with the accession number JCM 10102.

Amino Acids↗

Major histocompatibility complex class II alleles in an Uygur population in the Silk Route of Northwest China.

HLA class II (DRB1, DQA1, DQB1 and DPB1) genotyping was performed in 57 unrelated Uygur individuals inhabiting the northwestern China area by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Among 98 DRB1 alleles tested, 23 alleles were detected, and DRB1*0701 (16.7%) and DRB1*0301 (14.0%) were the most and the second most common alleles, respectively. In 8 DQA1 alleles detected, DQA1*05 (26.3%), DQA1*03 (21.9%) and DQA1*0201 (21.1%) were very frequent. Of 21 DQB1 alleles tested, 13 were observed. Among them, DQB1*02 was highly predominant with the gene frequency of 32.5%. Of 46 DPB1 alleles tested, 15 were detected, among which DPB1*0401 (31.6%) was the most frequent. Two haplotypes predominate clearly; DRB1*0701-DQA1*0201-DQB1*02 (15.5%) and DRB1*0301-DQA1*05-DQB1*02 (12.6%). The dendrogram constructed by the neighbour-joining (NJ) method based on the allele frequencies of the DRB1, DQA1, DQB1 and DPB1 genes of 13 representative populations all over the world suggested that Uygur belonged to the Asian group and lay at the closest genetic distance to a Kazak population inhabiting the same area.

Alleles↗

Prevalence of GBV-C/HGV infection in pregnant Japanese women.

Recently, a novel viral agent, hepatitis G virus, was identified by independent researchers from the serum of patients with liver disease, and termed GBV-C or HGV. At present, GBV-C and HGV are considered to be separate isolates of the same virus; however, the role of this virus in acute and chronic liver disease remains uncertain. Although vertical transmission is known to be one of the routes of transmission, the prevalence of GBV-C/HGV viremia in pregnant Japanese women is unknown. Thus, we determined this prevalence using the reverse transcription polymerase chain reaction (RT-PCR).

Female↗

Factors affecting the development of spontaneous recurrence of methamphetamine psychosis.

The process triggering spontaneous recurrences of methamphetamine (MAP) psychosis (i.e. flashbacks) was studied in 41 flashbackers, along with 84 non-flashbackers with a history of MAP psychosis. Plasma monoamine metabolite levels were assayed in 25 of the 41 flashbackers, 16 of the 84 non-flashbackers, 9 subjects with persistent MAP psychosis and 28 control subjects. All flashbackers had experienced threatening events or frightening paranoid-hallucinatory states during previous MAP use. The dominant factor triggering flashbacks was a mild fear of other people. Plasma norepinephrine levels were elevated during flashbacks. The results suggest that a mild fear of other people may have elicited memories of MAP psychosis associated with threatening experiences through increased sensitivity to psychosocial stressors. As a result the flashbacks occurred, including an increase in peripheral noradrenergic activity.

Adult↗

Prolonged exercise causes an increase in endothelin-1 production in the heart in rats.

Cardiac myocytes produce endothelin-1 (ET-1). ET-1 has potent positive inotropic and chronotropic effects. We investigated whether production of ET-1 in the heart is altered by prolonged exercise in rats. Rats ran on a treadmill for 45 min. Immediately after this exercise the heart and lungs were quickly removed. Control rats remained at rest during this 45-min period. Expression of preproET-1 mRNA in the heart was markedly higher in the exercised than in the control rats. The peptide level of ET-1 in the heart was also markedly higher in the exercised rats. Expression of endothelin type A- and type B-receptor mRNA and endothelin-converting enzyme mRNA in the heart did not differ between the groups. The peptide level of ET-1 and the preproET-1 mRNA level in the lungs of the exercised rats did not differ from those in the control rats. The present results show that production of ET-1 is markedly increased tissue specifically in the heart by exercise without appreciable changes in endothelin-converting enzyme and endothelin receptor expression. The present study suggests that myocardial ET-1 may participate in modulation of cardiac function during exercise.

Animals↗

Exercise causes tissue-specific enhancement of endothelin-1 mRNA expression in internal organs.

Endothelin-1 (ET-1) is a potent vasoconstrictor peptide, which also potentiates contractions to norepinephrine in human internal mammary and coronary vessels. Exercise causes a redistribution of blood flow, i.e., the increase in working muscles that is partly attributable to a decrease in visceral blood flow. We hypothesized that exercise causes a tissue-specific increase in ET-1 expression in internal organs. We studied whether exercise affects expression of preproET-1 mRNA in the kidneys and lungs. The rats performed treadmill running (0% grade) for 45 min at a speed of 25 m/min. The plasma concentrations of ET-1, epinephrine, and norepinephrine were greater in the exercise rats than in the sedentary control rats. The expression of preproET-1 mRNA in the kidneys was markedly higher in the exercise rats than in the sedentary control rats, whereas that in the lungs did not differ between the two groups. Therefore, the present study provides a possibility that the exercise-induced increase in production of ET-1 in the kidneys causes vasoconstriction and hence decreases blood flow in the kidneys through its direct vasoconstrictive action and/or its indirect effect of enhancing vasoconstrictions to norepinephrine.

Animals↗

Epilepsy and mental retardation in a subset of early onset 4q35-facioscapulohumeral muscular dystrophy.

The gene for facioscapulohumeral muscular dystrophy (FSHD) has been mapped to chromosome 4q35. In most patients with FSHD, a deletion of 3.3 kb tandemly repeated units within the EcoRI fragment that can be detected by probe p13E-11 is associated with the disease. To elucidate the relation between the phenotype and the genotype in FSHD, we examined 91 Japanese unrelated families with a clinical diagnosis of FSHD (140 patients, 205 healthy individuals). Of these, 78 families (86%) had 4q35-FSHD (127 patients), in which 20 patients (20/127, 16%) were classified as early onset FSHD. We found that all nine patients with the smallest EcoRI fragments (10 to 11 kb) were classified among the early onset group (9/20, 45%), and these patients showed a high frequency of both epilepsy (4/9, 44%) and mental retardation (8/9, 89%). In contrast, none of the remaining patients with 4q35-FSHD had epilepsy or mental retardation. We conclude that FSHD patients with a large gene deletion in the FSHD gene region tend to have a higher chance of showing severe clinical phenotypes with CNS abnormalities. This finding may have practical implications for genetic counseling, although the molecular genetic background remains unclear.

Adolescent↗

Differential distribution of actin and cytokeratin in isolated full-length rabbit renal tubules.

The distribution of basal actin bundles and cytokeratin intermediate filaments in the rabbit kidney was examined along isolated renal tubules by confocal laser microscopy. Perfusion of collagenase and subsequent manipulation of kidney tissues yielded well preserved renal tubules free of connective tissue components often extending from glomeruli to collecting tubules. Such isolated renal tubules were fluorescently stained with phalloidin and with anti-cytokeratin antibody and then observed as whole-mount preparations by confocal laser microscopy. Epithelial cells of Bowman's capsules showed conspicuous actin bundles which were arranged parallel to each other in individual cells. In proximal ducts, thick actin bundles were seen running in the basal regions of epithelial cells perpendicular to the tubule axis. Basal actin bundles in proximal tubules appeared to be somewhat thinner and run more irregularly in more distal parts of the tubule. Thin limbs of Henle's loop showed bright but very short rod or dot-like stainings of actin, while in thick limbs, there were thick and short actin bundles. In distal tubules basal actin bundles were somewhat longer than those in thick limbs of Henle's loop. In the collecting ducts in the renal cortex, a few short actin bundles as well as dotty or patchy stainings were shown in the basal region. In both whole-mount preparations and cryostat sections, cytokeratin immunoreactivities were almost exclusively detected in epithelial cells of Henle's loops and collecting ducts but poorly in proximal and distal tubules. Epithelial cells of Henle's loops showed dense networks of cytokeratin immunoreactivities throughout the cytoplasm, whereas cell boundaries were immunostained in collecting ducts. The actin and cytokeratin distribution in such isolated renal tubules was confirmed by immunofluorescence of cryostat sections and by thin-section electron microscopy. The observations that actin and intermediate filaments varied in distribution in different segments of renal tubules are interesting in view of the segmental differentiation of renal tubule functions.

Actins↗

Effect of side chains including the N-methyl-tetrazole-thiol group of beta-lactam antibiotics on transport in cultured kidney epithelial cells LLC-PK1.

In this study, the transcellular transport characteristics of four beta-lactam antibiotics (cefotaxime, cefmenoxime, cefmetazole, and cefotiam) were investigated in a kidney epithelial cell line LLC-PK1, especially focusing on the effect of the N-methyl-tetrazole-thiol (NMTT) group attached to 7-amino-cephalosporanic acid. There were no directional differences between the apical-to-basolateral and basolateral-to-apical transport of cefotaxime, cefmenoxime, and cefmetazole, suggesting that the NMTT group does not influence the transcellular transport behaviors of beta-lactam antibiotics. In contrast, cefotiam transport across LLC-PK1 cell monolayers was 1.3-fold greater in the basolateral-to-apical direction than in the apical-to-basolateral direction. It is considered that the ionization of nitrogen in the N-dimethylaminoethyl group attached to NMTT is a factor in the secretory-oriented movement of cefotiam. The transcellular transport of cefotiam in both directions was significantly depressed at a low temperature (4 degrees C) and by 2,4-dinitrophenol. The basolateral-to-apical transport of cefotiam was also shown to be concentration-dependent. These results suggest that a specialized transport process might participate in the transcellular transport of cefotiam. The lipophilicities of these beta-lactam antibiotics were not correlated to the degree of transcellular transport, directly.

Animals↗

Effect of Gosha-jinki-gan, a Kampo medicine, on enhanced platelet aggregation in streptozotocin-induced diabetic rats.

We evaluated the effects of Gosha-jinki-gan on platelet aggregation in streptozotocin-induced diabetic rats. Enhanced ADP (2 microM)-induced aggregation of platelets obtained from diabetic rats was inhibited by a single treatment with Gosha-jinki-gan (0.3, 1.5 g/kg, p.o.). The anti-platelet aggregatory effect of Gosha-jinki-gan (1.5 g/kg, p.o.) was attenuated by simultaneous administration of atropine (1 mg/kg, i.p.) and was abolished by combination of atropine with Hoe 140 (250 microg/kg x 2, i.p.), a bradykinin B2 receptor antagonist or L-NAME (10 mg/kg, i.p.), an inhibitor of nitric oxide-synthase. These results suggested that Gosha-jinki-gan could improve platelet aggregation in diabetes through increased production of nitric oxide via bradykinin B2-receptors and muscarinic acetylcholine receptors.

Adenosine Diphosphate↗

Thermostable beta-galactosidase from an extreme thermophile, Thermus sp. A4: enzyme purification and characterization, and gene cloning and sequencing.

We purified and characterized a thermophilic beta-galactosidase from Thermus sp. A4 isolated from the Atagawa hot spring (Shizuoka, Japan). The enzyme was monomeric, and its molecular mass was estimated to be 75 kDa by SDS-polyacrylamide gel electrophoresis. The enzyme was extremely thermostable and retained its full activity after incubation at 70 degrees C for 20 h. The Km observed were 5.9 mM for ortho-nitrophenyl beta-D-galactopyranoside and 19 mM for lactose. We cloned and analyzed the complete sequence of the gene encoding this enzyme. It was found to consist of 645 amino acid residues. We propose that this enzyme and seven other unclassified beta-galactosidases are new members of family 42 of the glycosyl hydrolases.

Amino Acid Sequence↗

Effects of gosha-jinki-gan, a kampo medicine, on peripheral tissue blood flow in streptozotocin-induced diabetic rats.

We examined the effects of Gosha-jinki-gan on peripheral tissue blood flow in streptozotocin-induced diabetic rats and its mechanism. The decrease in peroneal muscular blood flow in diabetic rats was dose-dependently improved by treatment with Gosha-jinki-gan (0.1-1 g/kg/day, p.o.) for 4 weeks. Investigation of the time course of blood flow in the hind paws revealed that single-dose of Gosha-jinki-gan (0.3, 1.5 g/kg, i.d.) increased peripheral blood flow. Peripheral blood flow-increasing effects of Gosha-jinki-gan (1.5 g/kg, i.d.) were reduced in combination with atropine (1 mg/kg, i.v.), and disappeared by pretreatment with NG-nitro-L-arginine methyl ester (10 mg/kg, i.v.). Levels of aortic guanosine 3',5'-cyclic monophosphate were dose-dependently increased by administration of Gosha-jinki-gan (0.3, 1.5 g/kg, p.o). These results suggest that Gosha-jinki-gan has vasodilating effects via increases in nitric oxide production. Gosha-jinki-gan may be useful for treating peripheral circulation disorders in the diabetic state.

Animals↗

Primary peripheral lung carcinoma smaller than 1 cm in diameter.

BACKGROUND: Several investigators have reported on the risk of limited resection in patients with small peripheral lung cancer. Primary peripheral lung carcinomas 1 cm or less in maximum dimension were reviewed to study the feasibility of limited surgery. METHODS: Among 1,051 lung cancer patients who underwent surgical resection of the lung in the National Cancer Center Hospital East, Kashiwa, Chiba, Japan, from January 1986 through March 1997, there were 13 patients who had untreated peripheral cN0M0 tumors 1 cm or less in maximum dimension on the resected specimens who underwent systematic mediastinal dissection. Their specimens were histopathologically reviewed. RESULTS: There were ten adenocarcinomas, one small cell carcinoma, one poorly differentiated squamous cell carcinoma, and one typical carcinoid tumor. One adenocarcinoma showed lymphatic vessel invasion, venous invasion, and a subcarinal node metastasis. The small cell carcinoma was accompanied by a lymph node metastasis in a segmental node. The small cell carcinoma and another adenocarcinoma showed lymphatic vessel invasion. Of the ten adenocarcinomas, six were Noguchi's type B and four were type C. CONCLUSION: Even among the pulmonary peripheral cancers smaller than 1 cm in diameter, more than one third showed an invasive nature. This fact must be considered in selecting limited resection in these patients. It is evident that tumor size alone cannot be an indicator for limited resection in lung cancer patients.

Adult↗

Peripheral blood stem cell transplantation for hepatoblastoma with microscopical residue: a therapeutic approach for incompletely resected tumor.

We report a nine-month-old boy with stage III B hepatoblastoma of caudate lobe origin. Surgical resection was attempted following six courses of chemotherapy, but viable tumor cells remained microscopically at resection margins. Subsequently, he received peripheral blood stem cell transplantation (PBSCT), whose preparative regimen being consisted of carboplatin, etoposide, tetrahydropyranyl adriamycin, and melphalan. Since then, the patient shows no relevance of local relapse or distant metastasis without any chemotherapy. PBSCT for patients with post-operative residue may improve the outcome of advanced hepatoblastoma and worth of a further clinical investigation.

Disease-Free Survival↗