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Biomedical subjects

K Nagata

Publications and source records attributed to K Nagata.

At least 559 records · Page 31Linked to original sources
PubMed1993

Age-related changes in left and right ventricular filling velocity profiles and their relationship in normal subjects.

To confirm age-related changes in left and right ventricular filling velocity profiles and to compare left and right ventricular filling parameters in normal subjects, we performed pulsed Doppler echocardiographic studies in 108 normal subjects (72 men and 36 women) aged 15 to 78 years. An age-related decrease in peak early velocity (E velocity), an increase in peak atrial velocity (A velocity), and augmented ratio of A velocity to E velocity (A/E) were observed in left ventricle (r = -0.71, 0.63, and 0.83, respectively). Similar age-related changes were found in right ventricle (r = -0.71, 0.54, and 0.78). Aging had a greater effect on the filling of the left ventricle than the right one (i.e., a steeper slope). The difference between left and right ventricular filling increased with advancing age. Left ventricular filling indexes exceeded those of the right ventricle. Significant correlations were observed between the right and left ventricular filling parameters (r = 0.58 to 0.90). A strong relation was noted in A/E (r = 0.90). There was no significant relation between age and left ventricular mass. The left ventricular mass appeared to have little effect on left and right ventricular filling in normal individuals. Thus in clinical studies the age-related decrease in early diastolic filling and the increased atrial filling in both left and right ventricles should be considered. The atrial contribution to ventricular filling may be more pronounced in the left ventricle than the right ventricle in older subjects.

Adult↗
PubMed1993

Effect of a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor on triglyceride kinetics in chronically streptozotocin-diabetic rats.

The effect of simvastatin (MK-733, Banyu, Tokyo, Japan), a new inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase on triglyceride kinetics, was studied in chronically streptozocin-diabetic rats. Diabetic rats, in whom diabetes was induced by a single intravenous injection of streptozotocin (40 mg/kg body weight) 2 months before the experiment, had significantly higher plasma glucose, triglyceride, and cholesterol levels compared with nondiabetic control rats, but triglyceride secretion rate was not increased. Both triglyceride secretion rate and plasma triglyceride level were significantly suppressed under nonfasting conditions in diabetic rats fed a (0.1%) simvastatin-containing diet for 10 days. After an overnight fast, their triglyceride secretion rate was not suppressed by this diet. However, their plasma triglyceride level was significantly (50%) suppressed, suggesting improved triglyceride removal from the circulation. In diabetic rats, the newly secreted triglyceride-rich lipoprotein particles were significantly cholesterol-enriched, but simvastatin had no effect on their lipid composition. These results suggest that the hypertriglyceridemia seen in chronically diabetic rats is mainly due to a triglyceride-removal defect, and that simvastatin reduces plasma triglyceride levels in these rats both by stimulating triglyceride removal and by reducing its entry into the circulation.

Animals↗
PubMed1993

Microglia-derived plasminogen enhances neurite outgrowth from explant cultures of rat brain.

Recently, we reported the production and secretion of plasminogen (Pg) in cultured rat brain microglia [Nakajima et al., (1992) Fedn. Eur. Biochem. Socs Lett. 308, 179-182]. To investigate the physiological significance of Pg, we determined the effect of Pg on neurite outgrowth of cultured neocortical explants of an embryonic rat brain in serum-free chemically defined medium. Pg markedly enhanced the neurite outgrowth. Although plasmin, which is derived from Pg by activation by urokinase (UK), had a similar effect in this explant culture system, UK itself did not show any effect. Furthermore, we studied the characteristics of Pg binding to cultured neocortical neurons dissociated from an embryonic 16-day-old rat brain by using 125I-Pg. Specific binding of Pg to neocortical neurons was detected and Scatchard plot analysis revealed high- and low-affinity binding sites on the neurons. The estimated dissociation constants of high- and low-affinity binding sites were approximately 16.1 and 124.2 nM, respectively. These results suggest that microglia-derived Pg plays certain roles in the regulation of neurite extension through binding to the surface of neocortical neurons.

Animals↗
PubMed1993

Effects of fasudil hydrochloride on cerebral blood flow in patients with chronic cerebral infarction.

To evaluate the effect of the novel intracellular calcium antagonist fasudil hydrochloride, cerebral blood flow (CBF) was measured quantitatively with positron emission tomography following the intravenous administration of fasudil in five patients with chronic cerebral infarction. The hemispheric mean CBF increased significantly on both hemispheres 30, 60, and 90 min after the administration of fasudil when the CBF values were corrected according to PaCO2 level, although there was no significant change in raw CBF data. A significant increase of CBF was seen in the cerebellar hemisphere and thalamus at 30 min and in the occipital cortex at 90 min. There was no significant fall in the systemic blood pressure after the administration of fasudil.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1993

Cytochrome P450 mediated metabolism of diazepam in human and rat: involvement of human CYP2C in N-demethylation in the substrate concentration-dependent manner.

Metabolism of diazepam (DZP) was studied in vitro to clarify the involvement of different forms of hepatic cytochrome P450 (CYP) in rats, and humans of Japanese and Caucasian origin. Microsomal 3-hydroxylation was the major pathway of DZP metabolism in rats and was inhibited by anti-CYP3A antibodies. Purified CYP3As and CYP2C11 catalysed 3-hydroxylation and N-demethylation, respectively, in the reconstituted systems. The rates of both reactions in human liver microsomes depended on the substrate concentration: the rate of 3-hydroxylation was 3-4 times higher than N-demethylation at 0.2 mM; the two activities were essentially the same at a lower substrate concentration (0.02 mM). Inhibitions of the N-demethylation by anti-CYP2C antibody and S-mephenytoin also depended on the substrate concentration and was detectable only at a low substrate concentration. Kinetic studies revealed the presence of two distinct catalytic activities for the N-demethylation; low Km and low Vmax, and high Km and high Vmax. The former activity seems to be mediated by a CYP2C P450 form. On the other hand, DZP 3-hydroxylation was rather selectively catalysed by a CYP3A P450 at the low and high substrate concentrations. These results were consistent with the observation in vivo that DZP N-demethylation and S-mephenytoin 4'-hydroxylation are closely correlated in humans. These results also suggest that the apparent discrepancy on the role of CYP forms in DZP metabolism in vitro and in vivo may reside in the difference in substrate concentration.

Adolescent↗
PubMed1993

Difference of the 28-item general health questionnaire scores between Japanese high school and university students.

The General Health Questionnaire (GHQ) with 28 items was tested in Nagasaki city on 138 senior students in a prefectural high school and 685 freshmen in a national university to evaluate the degree of students' mental stress due to the highly competitive entrance examination for university. The average GHQ score tested on high school students was 5.33 for males and 7.07 for females, and 3.99 for males and 4.42 for females on university students. It showed that high school students were under greater pressure than university students and female students were in a higher tension compared with male students. The factor analysis showed that the primary and secondary factor of high school students were "severe depression" and "anxiety and insomnia," while "somatic symptoms" were the primary factor causing stress in university students.

Adolescent↗
PubMed1993

Microglia-derived elastase produces a low-molecular-weight plasminogen that enhances neurite outgrowth in rat neocortical explant cultures.

In the course of analysis of plasminogen in microglial conditioned medium (Mic-CM), novel low-molecular-weight (LMW) zymogen with a molecular mass of approximately 36 kDa was detected by casein-urokinase zymography. Because this form was produced when rat native plasminogen was incubated with Mic-CM, a specific protease in the Mic-CM was thought to be responsible for the production of LMW plasminogen. The production of LMW plasminogen was strongly inhibited by elastase inhibitors. Furthermore, elastase (pancreatic or leukocyte) was also found to produce LMW zymogen from native plasminogen. These results indicate that LMW plasminogen is produced through limited proteolysis by an elastase-like protease in Mic-CM. To determine the biochemical characteristics of LMW plasminogen, rat native plasminogen was cleaved by pancreatic elastase, and the fragments (LMW plasminogen and nonzymogen fragments) were purified by several kinds of column chromatography. Amino acid sequence analysis revealed that LMW plasminogen is a carboxy-terminal region that contains the fifth kringle domain and a protease active site, and the amino acid sequence is identical to that of LMW plasminogen produced by Mic-CM. On the other hand, the nonzymogen fragment was the amino-terminal region containing four kringle domains. The effects of native plasminogen and the fragments on neurite outgrowth of rat brain explant were examined. LMW plasminogen promoted neurite outgrowth as well as did native plasminogen, whereas nonzymogen fragments did not. These results suggest that LMW plasminogen, which is produced from native plasminogen by elastase, may be a physiologically active molecule that mediates the intercellular interaction between microglia and neurons.

Amino Acid Sequence↗
PubMed1993

Early afterdepolarizations in a patient with idiopathic monomorphic right ventricular tachycardia.

To identify the role of afterdepolarizations in the induction of idiopathic monomorphic right ventricular tachycardia (VT), monophasic action potentials (MAPs) were recorded in a patient with this type of VT. The VT had a left bundle branch block configuration and inferior axis, and originated in the right ventricular outflow tract (RVOT). MAPs were recorded with a contact electrode at the origin of the VT, as well as other ventricular sites. The VT was induced by the intravenous administration of isoproterenol and/or rapid ventricular pacing and was preceded by short-long-short sequences of RR intervals. Early afterdepolarizations (EADs) in MAPs were recorded at the origin of VT (RVOT), but not recorded at other ventricular sites. These data suggest that catecholamine sensitive triggered activity seems to be the mechanism of idiopathic monomorphic right VT and EADs can be recorded in association with the occurrence of this type of VT.

Action Potentials↗
PubMed1993

Potent inhibitory action of the gastric proton pump inhibitor lansoprazole against urease activity of Helicobacter pylori: unique action selective for H. pylori cells.

The gastric proton pump inhibitor lansoprazole, its active analog AG-2000, and omeprazole dose dependently inhibited urease activity extracted with distilled water from Helicobacter pylori cells; the 50% inhibitory concentrations were between 3.6 and 9.5 microM, which were more potent than those of urease inhibitors, such as acetohydroxamic acid, hydroxyurea, and thiourea. These compounds also inhibited urease activity in intact cells of H. pylori and Helicobacter mustelae but did not inhibit ureases from other bacteria, such as Proteus vulgaris, Proteus mirabilis, and Providencia rettgeri. The mechanism of urease inhibition was considered to be blockage of the SH groups of H. pylori urease, since SH residues in the enzyme decreased after preincubation with lansoprazole and glutathione or dithiothreitol completely abolished the inhibitory action. The SH-blocking reagents N-ethylmaleimide and idoacetamide were also examined for their inhibition of the urease activity; their 50% inhibitory concentrations were 100- to 1,000-fold higher than those of lansoprazole. These results suggest that lansoprazole and omeprazole can potently and selectively inhibit H. pylori urease and that inhibition may be related to earlier findings indicating that these compounds have selective activity against HP growth.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1993

Purification of a factor which provides a costimulatory signal for gamma interferon production.

A protein factor which induces high levels of gamma interferon (IFN-gamma) in resting splenic nonadherent cells was isolated from the sera of mice with generalized inflammation caused by endotoxic shock. The factor was highly purified by ammonium sulfate precipitation followed by ion-exchange column chromatography on DEAE-Sepharose, molecular sieving on Ultrogel AcA 44, and hydrophobic column chromatography with phenyl-Sepharose. It was further purified to apparent homogeneity by polyacrylamide gel electrophoresis. It induced IFN-gamma production in a dose-dependent manner in the presence of interleukin-2, monoclonal anti-CD3 antibody (anti-CD3 MAb), or concanavalin A (ConA) in spleen cells deprived of plastic plate- and nylon wool-adherent cells. Anti-CD3 MAb induced the highest level of production of the three. The factor, interleukin-2, anti-CD3 MAb, or ConA alone induced a trace of or no detectable IFN-gamma in these cells. The factor also exhibited an accessory function during proliferation in these cells in the presence of a suboptimal dose of ConA. However, the factor failed to stimulate IFN-gamma production when staphylococcal enterotoxin A, a superantigenic T-cell mitogen, was employed. Treatment with pronase or heat abolished these activities. These studies confirm the existence of a soluble protein factor which is able to exhibit a novel accessory function in IFN-gamma production in resting T or natural killer cells. It will be of interest to compare this factor with the recently cloned human natural killer stimulatory factor (NKSF/IL-12).

Animals↗
PubMed1993

Cell-type-specific function of the C-type natriuretic peptide gene promoter in rat anterior pituitary-derived cultured cell lines.

The promoter function of the human C-type natriuretic peptide (CNP) gene in various cultured cells was examined by transient transfection assays. The CNP promoter functioned very effectively in GH3 cells, which originated from the growth hormone-producing tumor of the rat anterior pituitary and somatomammotroph phenotype, but functioned much less effectively in GH1 cells, another type of rat pituitary-derived cell with a somatotroph phenotype, and rat primary cardiocytes. The CNP promoter did not function at all in other cells, including AtT20 cells of murine pituitary corticotroph origin. Functional analyses of the deleted promoters with various 5' deletion breakpoints revealed the existence of at least two negative and one positive regulatory regions. Within the positive regulatory region (positions -54 to -19), which conferred 90% of the promoter activity in GH3 cells, two equipotent GC-rich cis elements (positions -49 to -45 and -40 to -35) were identified. Both sites shared half of the promoter activity and binding properties to the nuclear protein in GH3 cells. Rat anterior pituitary tissue contained the binding protein of the identified cis element, which was identical or similar to that of GH3 cells. With Southwestern (DNA-protein) analysis, a 70-kDa specific binding protein distinct from known factors such as SP-1, AP-2, and Pit-1 was identified in the nuclear extract of GH3 cells.

Animals↗
PubMed1993

Immunohistochemical studies on the distributions and age-related changes of types I and III collagen in the oral mucosa of mice.

The distribution of types I and III collagen in mouse oral mucosa and the age-related changes over 3 days to 2 years of age were examined by immuno-fluorescence and -electron microscopy, with use of affinity-purified polyclonal antibodies. Immunofluorescence microscopy revealed that types I and III collagen existed in all tissues and at all ages examined. The staining intensity for type I collagen was stronger and increased more markedly in the lamina propria of the hard palate (HPlp) and gingiva (G), compared with that in the submucosa of the hard palate (HPsm) and the buccal mucosa (BM). The staining intensity for type III collagen was strong and increased markedly with age in all connective tissues examined. Examination of immunogold-labeled tissues demonstrated that most of the collagen fibrils were labeled for both type I and type III collagen, which suggests that they were hybrid fibrils containing both types of collagen. The quantitative evaluation of the labeling densities of gold particles revealed that the labeling density of type III collagen in BM and HPsm was higher and increased more rapidly during growth than in HPlp and G, while the labeling density of type I collagen was higher in HPlp and G. The fibril diameters in HPlp were larger and increased more rapidly during growth than in BM and HPsm. These studies are the first to demonstrate the distribution of types I and III collagen and their age-related changes in mouse oral mucosa.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1993

Long-term results of catheter ablation for idiopathic ventricular tachycardia originated from the right ventricular outflow.

We performed catheter ablation in 10 consecutive patients with idiopathic monomorphic right ventricular tachycardia and studied the long-term outcome. All ventricular tachycardias had a left bundle branch block configuration with an inferior axis, and originated from right ventricular outflow. Antiarrhythmic drugs (3-6 drugs) had been ineffective in controlling ventricular tachycardia. The 2 patients who underwent direct-current ablation (2 shocks of 150 J) had no recurrence of ventricular tachycardia and did not require antiarrhythmic drugs during a follow-up of 56 and 51 months, respectively. Of the 8 patients who underwent radiofrequency ablation (30-40 watt, 20-40 sec, 2-15 application, using Inter Nova RA 50, 13.56 MHz), 1 patient had no recurrence of ventricular tachycardias and did not require antiarrhythmic drugs, 4 patients had no recurrence of ventricular tachycardias but did require anti-arrhythmic drugs, and 3 patients experienced recurrence of non-sustained ventricular tachycardia despite the use of antiarrhythmic drugs during a follow-up of 15-40 months. There were no complications except for cardiac perforation which occurred immediately after direct-current ablation in 1 patient. In conclusion, long-term success in preventing ventricular tachycardia was achievable with direct-current ablation, but this success was associated with serious risks, such as cardiac perforation. Radiofrequency ablation was safer than direct-current ablation, but had a lower long-term success rate.

Adult↗
PubMed1993

[Genetic polymorphism in human drug metabolism].

During the last decade, the influences of genetic factors on individual drug metabolizing capacity in humans have been characterized in fairly great detail at the molecular level. Debrisoquine/sparteine and mephenytoin polymorphisms are now known to be derived from defects in the human liver of specific forms of microsomal CYP (P450 or previously termed cytochrome P-450), CYP2D6 and CYP2C9 (2C18), respectively. In these polymorphisms, clear ethnic differences are observed in the incidence of poor metabolizers (PM). Although debrisoquine PM is detected in high incidence (5-10%) in Caucasians, little was found in Japanese. In contrast, mephenytoin PM is detected in higher percentages in Japanese (15-25%) than in Caucasians (3-7%). In this mini-review, current understanding of the molecular mechanisms of both types of polymorphism and structural relationships of CYP2D6 and CYP2C9 substrates are shown. Relationships between specific phenotypes and cancer risks or disease are also discussed.

Cytochrome P-450 Enzyme System↗
PubMed1993

Expression and functional characterization of a rat sulfotransferase (ST1A1) cDNA for sulfations of phenolic substrates in COS-1 cells.

A cDNA (PST-1) isolated from a rat liver cDNA library was expressed in COS-1 cells and found to encode a form of arylsulfotransferase (termed ST1A1), which sulfated p-nitrophenol, alpha-naphthol, minoxidil, beta-estradiol and dopamine, but not dehydroepiandrosterone and cortisol. ST1A1 showed a mobility identical with a major immunodetectable sulfotransferase contained in the livers of male and female rats in Western blots. In addition, ST1A1 mRNA was detected in the liver and extrahepatic tissues by Northern blots.

Animals↗
PubMed1993

Dexamethasone inhibits nitric oxide synthase mRNA induction by interleukin-1 alpha and tumor necrosis factor-alpha in vascular smooth muscle cells.

The effects of interleukin-1 alpha, tumor necrosis factor-alpha and dexamethasone on the induction of nitric oxide synthase mRNA in rat aortic smooth muscle cells were studied. Neither interleukin-1 alpha (up to 100 U/ml) nor tumor necrosis factor-alpha (up to 5000 U/ml) was capable of inducing nitrite/nitrate production and nitric oxide synthase mRNA in smooth muscle cells. In contrast, treatment for 12 hr or longer with a combination of the two synergistically induced nitrite/nitrate and cyclic GMP production in cell culture media and nitric oxide synthase mRNA, both of which were prevented by dexamethasone. Contamination with bacterial lipopolysaccharide, which may affect the induction of nitric oxide synthase, was below 30 pg/ml in all experiments. Our findings show that dexamethasone and these cytokines regulate the induction of nitric oxide synthase at the mRNA level in vascular smooth muscle cells.

Amino Acid Oxidoreductases↗
PubMed1993

Adenosine induces contractions in suncus ileum.

Purinoceptor-mediated responses were characterized in the ileum of Suncus murinus. Adenosine as well as adenosine 5'-triphosphate (ATP) contracted the ileum in a concentration-dependent manner. Contractile responses to transmural electrical stimulation were attenuated by adenosine only at high concentrations. Theophylline competitively blocked the adenosine-induced contraction. Atropine also inhibited the adenosine-induced contraction but in a non-competitive manner. The ATP-induced contraction was not affected by theophylline, atropine or alpha, beta-methylene ATP. Indomethacin shifted the concentration-response curves for adenosine and ATP to the right. These results suggest that adenosine elicited contractions via direct stimulation of postsynaptic P1-purinoceptors and postsynaptic potentiation of the acetylcholine response. Suncus ileum will be a unique model for the analyses of purinoceptor-mediated responses.

Adenosine↗