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R Kato

Publications and source records attributed to R Kato.

At least 199 records · Page 11Linked to original sources
PubMed1995

Up-regulation of nitric oxide synthase by estradiol in human aortic endothelial cells.

We have examined the effects of sex hormones on calcium-dependent NO production and protein levels of NO synthase in cultured human aortic endothelial cells, which were treated with various doses of 17 beta-estradiol and testosterone for 8-48 h. Treatment with 17 beta-estradiol enhanced calcium-dependent NO production, but testosterone had exerted no effect. Western blot using monoclonal anti-human endothelial NO synthase antibody clarified that increased NO production by 17 beta-estradiol treatment was accompanied by increased NO synthase protein. Our results provide evidence that human endothelial NO synthase can be regulated by estrogens.

Amino Acid Oxidoreductases↗
PubMed1995

Del(12)(p11.21p12.2) associated with an asphyxiating thoracic dystrophy or chondroectodermal dysplasia-like syndrome.

We describe a 5-year-old Japanese boy who has some radiographic findings characteristic of asphyxiating thoracic dystrophy (ATD)-chondroectodermal dysplasia with a de novo chromosome abnormality. He also has mild mental retardation, short stature, hypoplastic hair and skin, oligodontia, small thoracic cage, hypoplastic pelvis and cone-shaped epiphyses of hands. On cytogenetic studies he was found to have a de novo del(12)(p11.21p12.2). These results suggest that the locus of the gene associated with ATD-chondroectodermal dysplasia may be situated at 12p11.21p12.2.

Child, Preschool↗
PubMed1995

Regulation of differentiated phenotype of rat hepatic lipocytes by retinoids in primary culture.

Activation of hepatic lipocytes to myofibroblastlike cells observed in cell culture and during liver fibrogenesis is characterized by an increase in collagen formation and cell proliferation. These changes appear to be associated with the loss of intracellular retinoid in lipocytes, the principal storage site for vitamin A in the body. To evaluate whether retinoids have the capability to suppress lipocyte activation, we exposed cultured lipocytes in both native and myofibroblastlike states to retinoids and determined their effects on collagen production, intracellular retinoid level, and cell proliferation. Retinol (1 microM) and retinoic acid (1 microM) supplementation of primary rat lipocyte cultures inhibited the spontaneous increase in collagen synthesis associated with lipocyte activation; lower concentrations of retinol (10 or 100 nM) were also effective. Simultaneously, retinol addition prevented a precipitous decline in intracellular retinoid content in the absence of added retinoid. These retinoid effects were reversed by a change to unsupplemented control medium. When cells in the myofibroblastlike state were exposed to retinol (> or = 1 microM), a significant increase in intracellular retinoid levels and reduction in collagen synthesis occurred. Lipocytes in both native and myofibroblastlike states secreted four to five times higher amounts of type I collagen than type III collagen, but retinol and retinoic acid particularly inhibited production of type I collagen. Cell proliferation measured by [3H]thymidine incorporation was also inhibited by retinol. These results demonstrate that extracellular retinoids suppress lipocyte-activated collagen synthesis and cell proliferation and support the interpretation that retinoids themselves are regulatory factors in maintenance of the lipocyte in its native, differentiated state.

Adipocytes↗
PubMed1995

Experimental tracheal replacement using the esophagus and an expandable metallic stent.

An experimental study was conducted to investigate whether a segment of autogenous esophagus with its lumen supported by an expandable metallic stent (EMS) could be successfully used as a tracheal substitute. Seven rings of the cervical trachea were circumferentially removed and reconstructed by interposing a pedicled segment of the esophagus with an EMS in six mongrel dogs. The interposed esophagus was observed endoscopically at various stages after the operation. By 1 month, the EMS was found to be buried under the esophageal mucosa, and the lumen was patent. The dogs died 5, 17, 61, 92, 210, and 478 days after the operation, but the cause of death could not be determined by postmortem examination and no respiratory tract complications were detected. The results of this study indicated that a segment of the esophagus with its lumen supported by an EMS could work as a reliable tracheal substitute, though its practical use is not clinically feasible. Nevertheless, we conclude that some autogenous material other than the esophagus with its lumen supported by an EMS could provide a feasible method for tracheal replacement.

Anastomosis, Surgical↗
PubMed1995

Benefits of arterial reconstruction in claudication.

We conducted a midterm follow-up of 150 claudicants who underwent surgical reconstruction by assessing cumulative patency, survival, and palliation (graft patency in live patients) rates. Eighty-nine claudicants (group I) underwent direct (in situ) proximal revascularization, 33 (group II) had indirect (ex situ) proximal revascularization, while 28 (group III) had distal revascularization. The secondary patency rates at 3 years were 97.5% in group I, 97.0% in group II, and 75.0% in group III, respectively. Only one patient with limb graft thrombosis required below-knee amputation. There were 3 perioperative deaths (2 in group I and 1 in group II). The survival rates at 3 years were 86.0% in group I, 69.5% in group II, and 95.8% in group III, respectively. The palliation rates at 3 years were 84.8% in group I, 70.0% in group II, and 77.9% in group III, respectively. These findings indicate the midterm benefits of supra- and infrainguinal arterial reconstructions, and also suggest that the preoperative assessment of risks in individual patients, the selection of the appropriate operative procedure and graft material, and intensive postoperative follow-up and management of any associated disease are all important aspects in the treatment of claudicants.

Aged↗
PubMed1995

Role of interleukin-1 in stress responses. A putative neurotransmitter.

Recently, the central roles of interleukin-1 (IL-1) in physical stress responses have been attracting attention. Stress responses have been characterized as central neurohormonal changes, as well as behavioral and physiological changes. Administration of IL-1 has been shown to induce effects comparable to stress-induced changes. IL-1 acts on the brain, especially the hypothalamus, to enhance release of monoamines, such as norepinephrine, dopamine, and serotonin, as well as secretion of corticotropin-releasing hormone (CRH). IL-1-induced activation of the hypothalamo-pituitary-adrenal (HPA) axis in vivo depends on secretion of CRH, an intact pituitary, and the ventral noradrenergic bundle that innervates the CRH-containing neurons in the paraventricular nucleus of the hypothalamus. Recent studies have shown that IL-1 is present within neurons in the brain, suggesting that IL-1 functions in neuronal transmission. We showed that IL-1 in the brain is involved in the stress response, and that stress-induced activation of monoamine release and the HPA axis were inhibited by IL-1 receptor antagonist (IL-1Ra) administration directly into the rat hypothalamus. IL-1Ra has been known to exert a blocking effect on IL-1 by competitively inhibiting the binding of IL-1 to IL-1 receptors. In the latter part of this review, we will attempt to describe the relationship between central nervous system diseases, including psychological disorders, and the functions of IL-1 as a putative neurotransmitter.

Animals↗
PubMed1995

The presence of phorbol ester responsive and non-responsive forms of the zeta isozyme of protein kinase C in mouse epidermal cells.

The possible involvement of zeta isozyme of protein kinase C (PKC zeta) in phorbol ester-induced signal transduction was investigated in mouse epidermal cells. Western blot analysis of RESOURCE Q column chromatography eluates obtained from 105,000 g supernatants and particulate fractions of epidermal cells was performed using anti-PKC zeta specific antibody. Anti-PKC zeta antibody recognised proteins in low salt range corresponding to 25-125 mM NaCl (low salt-eluted PKC zeta; 1-PKC zeta) as well as high salt range corresponding to 175-300 mM NaCl (high salt-eluted PKC zeta; h-PKC zeta) in both subcellular fractions. 1-PKC zeta and h-PKC zeta were detected as a doublet protein of 79,000 and 85,000 M(r) in 105,000 g supernatants, but as a 79,000 M(r) protein in particulate fractions. Immunoprecipitated 1-PKC zeta and h-PKC zeta with anti-PKC zeta specific antibody possessed phosphatidylserine (PS)-dependent protein kinase activity, but neither 1-PKC zeta nor h-PKC zeta were further activated by 40 nM phorbol 12-myristate 13-acetate (PMA) in the presence of PS. Furthermore, 1-PKC zeta and h-PKC zeta can be autophosphorylated, indicating that both 1-PKC zeta and h-PKC zeta are PKC zeta. Treatment of intact epidermal cells with PMA or other PKC activators caused the apparent shift of 79,000 M(r) 1-PKC zeta to the 85,000 M(r) from in particulate fractions. Prolonged treatment of the cells with PMA induced the downregulation of both forms of 1-PKC zeta in particulate fractions. Under the same condition, 1-PKC zeta in 105,000 g supernatants and h-PKC zeta in both fractions did not respond to PMA. This apparent shift was reversible and the content ratio of 85,000 to 75,000 M(r) 1-PKC zeta was decreased by acid phosphatase treatment, indicating that the apparent shift results at least in part from phosphorylation of 79,000 M(r) 1-PKC zeta. Total activity of 1-PKC zeta was increased in association with the apparent shift from the 79,000 to 85,000 M(r) form in response to PMA treatment of intact epidermal cells. All of these results indicate that PKC zeta is present as multiple forms in mouse epidermal cells, and that especially 1-PKC zeta in particulate fractions play a significant role(s) in PMA-induced signal transduction in mouse epidermal cells.

Amino Acid Sequence↗
PubMed1995

Induction of anagen in telogen mouse skin by topical application of FK506, a potent immunosuppressant.

The effect of topical application of FK506 on the normal hair cycle of C57BL/6J mice was investigated. When telogen mice (7 weeks of age) were treated topically with 1 mumol FK506 on days 0 and 3, 50% of the tested mice entered anagen by day 9 and 100% by day 16. With 0.1 mumol of FK506, 50% of the tested mice entered anagen by day 13 and 80% by day 19, indicating that the effect of FK506 is dose dependent. In control mice, a spontaneous shift from telogen to anagen started on day 14, and 30% of the control animals were in anagen at day 19. Histologic studies revealed that FK506 markedly stimulated the skin and thickened it. The depth and size of hair follicles were also markedly increased in FK506-treated skin compared to control skin. The data on hair growth also support the contention that FK506 induces early onset of anagen and stimulates hair growth. The hair growth stimulated by FK506 looked normal and the hairs were of normal length. The hair growth was restricted to the site of application. These results clearly demonstrate that topical application of FK506 induces anagen hair growth in telogen mouse skin and indicate that the hair-growth-stimulating effect of FK506 is due at least in part to its promoting effect on the hair cycle.

Administration, Topical↗
PubMed1995

Formation of 2-amino-3-methylimidazo[4,5-f]quinoline- and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline-sulfamates by cDNA-expressed mammalian phenol sulfotransferases.

In rat liver cytosol systems, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) were converted into their sulfamates in the presence of 3'-phosphoadenosine 5'-phosphosulfate at rates of 51.2 and 50.7 pmol/min/mg cytosol in the male, and 23.7 and 22.5 pmol/min/mg cytosol in the female, respectively. IQ-sulfamate formation was low (0.24 pmol/min/mg cytosol) in human liver cytosols, and MeIQx-sulfamate was not detected (< 0.1 pmol/min/mg cytosol). These results suggest only a minor contribution of IQ- and MeIQx-sulfamate formation to the detoxification of both heterocyclic amines in humans. Using sulfotransferase cDNA-expression systems, a rat ST1A1 arylsulfotransferase has been shown to catalyze the formation of the sulfamates, suggesting a role of the ST1A type of sulfotransferase in the N-sulfation of heterocyclic amines.

Animals↗
PubMed1995

Effects of D-phenylalanine-derivative hypoglycemic agent A-4166 on pancreatic alpha- and beta-cells: comparative study with glibenclamide.

We have reported that N-[(trans-4-isopropyl-cyclohexyl)-carbonyl]-D-phenylalanine (A-4166) stimulates insulin secretion in animal studies. To further elucidate the mechanisms underlying the actions of this agent, we investigated the effects of A-4166 on insulin and glucagon secretion with or without diazoxide, an ATP-sensitive potassium channel opener, using isolated perfused rat pancreas preparations, and compared the results with those of glibenclamide. Both 30 mumol/l A-4166 and 3 mumol/l glibenclamide significantly stimulated insulin secretion and reduced glucagon secretion to similar levels at a glucose concentration of 5.6 mmol/l (p < 0.01 for both vs. basal levels). After infusion of A-4166 was stopped, insulin levels promptly returned to the basal values, while insulin levels increased further even after discontinuation of glibenclamide. Furthermore, 100 mumol/l diazoxide significantly inhibited the insulin-stimulatory effects of both 30 mumol/l A-4166 and 3 mumol/l glibenclamide (p < 0.05 and p < 0.01, respectively). However, the effects of diazoxide on glucagon secretion differed between the two groups; 30 mumol/l A-4166 produced a transient increase in glucagon secretion (p < 0.05 vs. basal levels) but 3 mumol/l glibenclamide suppressed glucagon secretion further (p < 0.01 vs. without diazoxide) with concomitant administration of 100 mumol/l diazoxide. These findings suggest that A-4166 directly stimulates insulin secretion, at least in part, through mechanisms resembling those of sulfonylurea, but exerts different effect on glucagon secretion in isolated perfused rat pancreas.

Analysis of Variance↗
PubMed1995

Stimulating activity of A-4166 on insulin release in in situ hamster pancreatic perfusion.

Using the in situ hamster pancreatic perfusion system, the stimulating action of A-4166 on insulin release was examined in comparison with that of glibenclamide. Both antidiabetic agents stimulated insulin release, but its onset by A-4166 was faster than that by glibenclamide. In the presence of a basal glucose concentration (3 mmol/l), insulin releases induced by A-4166 and glibenclamide were inhibited by preexisting diazoxide. At higher glucose concentrations (5-16.7 mmol/l), however, A-4166 was able to reverse the inhibitory effect of diazoxide on the first and second phases of insulin release, while glibenclamide did not reverse the first-phase release. On the other hand, in the presence of 16.7 mmol/l of glucose A-4166 completely reversed the inhibitory action of diazoxide added simultaneously, but glibenclamide reversed it only partially. In the presence of 8 mmol/l of glucose, the stimulating action of A-4166 and glibenclamide on insulin release was hardly affected by inhibitors of ATP production. These results indicate that the stimulating action of A-4166 on insulin release is different from glibenclamide in response to the inhibitory action of diazoxide. These results also suggest that A-4166 is an effective agent for release of insulin by acting on the KATP channel, especially under an impaired function of pancreatic B cells.

Animals↗
PubMed1995

Pressure enhances endothelin-1 release from cultured human endothelial cells.

The effect of pure pressure without shear stress or stretch on the release of endothelin-1 was investigated. Elevation of pressure significantly enhanced endothelin-1 release from cultured human umbilical vein endothelial cells. A calcium channel blocker, nifedipine, and a putative stretch-activated channel blocker, gadolinium, did not affect the pressure-induced endothelin-1 increase. On the other hand, a phospholipase C inhibitor, 2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate, and protein kinase C inhibitors, 1-5-(isoquinolinylsulfonyl)-2-methylpiperazine and chelerythrine, significantly inhibited the pressure-induced endothelin-1 increase. Moreover, pure pressure reduced basal nitric oxide release, while pretreatment with a nitric oxide synthase inhibitor, NG-monomethyl-L-arginine, had no effect on the pressure-induced endothelin-1 increase. In conclusion, our results show for the first time that pressure enhances endothelin-1 release partially through activation of phospholipase C and protein kinase.

Calcium Channels↗
PubMed1995

Cyclosporin A inhibits nitric oxide synthase induction in vascular smooth muscle cells.

The effect of cyclosporin A on induction of nitric oxide synthase in rat aortic smooth muscle cells was examined. A combination of interleukin-1 alpha (100 U/mL) and tumor necrosis factor--alpha (5000 U/mL) induced accumulation of nitrite/nitrate, the stable end products of nitric oxide, in culture media within 48 hours. Cyclosporin A inhibited this nitrite/nitrate accumulation in a concentration-dependent manner with an IC50 of 4 x 10(-7) mol/L when applied simultaneously with the cytokines. The expression of inducible nitric oxide synthase messenger RNA (mRNA) induced by the combination of interleukin-1 alpha and tumor necrosis factor-alpha was inhibited by the cyclosporin A cotreatment. Cyclosporin A did not decrease inducible nitric oxide synthase mRNA stability in the presence of transcription inhibitor actinomycin D (5 micrograms/mL). Induction of nitrite/nitrate production by the combination of tumor necrosis factor-alpha and bacterial lipopolysaccharide or that of interleukin-1 alpha and interferon gamma (100 U/mL) was also inhibited by cyclosporin A cotreatment. Another inhibitor of calcineurin, FK506 (up to 10(-6) mol/L), had no effect on the induction of nitrite/nitrate production, suggesting the possibility that the inhibitory effect of cyclosporin A may be exerted by means of a novel pathway other than inhibition of calcineurin. These results indicate that cyclosporin A inhibits inducible nitric oxide synthase induction at the mRNA level and that inducible nitric oxide synthase in vascular smooth muscle cells can be a target for cyclosporin A, providing a possible mechanism for the interference of the drug with the balance of vasoactive substances.

Amino Acid Oxidoreductases↗
PubMed1995

Natriuretic peptide-augmented induction of nitric oxide synthase through cyclic guanosine 3',5'-monophosphate elevation in vascular smooth muscle cells.

To elucidate the role of natriuretic peptides in vascular remodeling, the effects of atrial natriuretic peptide, brain natriuretic peptide, and C-type natriuretic peptide (CNP) on the induction of inducible nitric oxide (NO) synthase (iNOS) in rat aortic smooth muscle cells were examined. Although none of the peptides when applied alone induced the production of nitrite, a stable end product of NO, each peptide dramatically enhanced nitrite production induced by a cytokine combination of interleukin-1 alpha and tumor necrosis factor-alpha. Each natriuretic peptide stimulated intracellular cGMP accumulation in a dose-dependent manner. Time-dependent nitrite production by the cytokines was increased by CNP cotreatment and inhibited by NG-methyl-L-arginine, indicating involvement of the L-arginine-NO pathway. Northern blot analysis showed that the augmented nitrite production was accompanied by an increase in iNOS messenger RNA. A cGMP analog, 8-bromo-cGMP, completely mimicked all of the effects of CNP described above. A cGMP-dependent protein kinase inhibitor, KT5823, paradoxically increased nitrite production and iNOS messenger RNA levels induced by the combination of 8-bromo-cGMP and both cytokines or by the two cytokines only. These data demonstrate the stimulatory effect of cGMP on cytokine-induced iNOS and imply that natriuretic peptides may play a regulatory role in vascular remodeling via the production of large amounts of NO.

Amino Acid Oxidoreductases↗
PubMed1995

Effects of dicarboxylic acids on fatty acid-metabolizing enzymes in cultured rat hepatocytes.

A clear chain-length dependent effect was observed for peroxisomal fatty acid beta-oxidation and carnitine acetyltransferase and also for mitochondrial carnitine palmitoyltransferase in primary cultures of rat hepatocytes. The extent of modulation of peroxisomal beta-oxidation was higher with even-carbon numbered dicarboxylic acids than with odd-carbon numbered ones, although such a tendency was not detected in the mitochondrial reactions. These results indicate difference in the effect of fatty acid-derived dicarboxylates on peroxisomal and mitochondrial functions.

Animals↗
PubMed1995

[Molecular pharmacological and toxicological studies of drug-metabolizing enzymes].

Studies on drug metabolism have opened new fields in the evaluation of drug efficacy and drug safety in experimental animals and humans, especially in the development of new drugs. The author described the history of discoveries of induction and inhibition of drug-metabolizing enzymes as a key point in the development of drug interaction studies. Studies on the sex-related differences in drug-metabolism have been important fields for understanding the sex-related toxicity and efficacy of drugs and their species differences under normal and pathological conditions. Rats are unique animals among experimental animals and humans. The activities of hepatic drug-metabolizing enzymes, especially cytochrome P450 and sulfotransferase, are regulated through the sex-related secretion pattern of growth hormone. The drug-metabolizing enzymes convert drugs into not only inactive metabolites, but produce toxic intermediates which cause mutagenesis, carcinogenesis and drug-caused allergic reactions. The author carried out extensive studies on the metabolic activation of mutagenic-carcinogenic arylamines and demonstrated important roles of O-acetylation and O-sulfation to cause DNA damages by N-hydroxyarylamines. Pharmacogenetic studies on hamster acetyltransferase were described to understand the individual differences in polymorphic acetylation of arylamines and N-hydroxyarylamines in relation to DNA damages. Finally, the author emphasizes important roles of drug metabolism studies for the development of new drugs by showing a prototype, which has multiple metabolic pathways by multiple enzymes and this shows reduced-extents of individual differences, for increasing efficacy and safety in a future clinical drug therapy.

Animals↗