Biomedical subjects

R Kato

Publications and source records attributed to R Kato.

At least 19 recordsLinked to original sources

PubMed1992

[Transjugular intrahepatic portosystemic stent shunt (TIPSS) with use of Rösch-Uchida transjugular liver access set--evaluation by CT and its clinical application].

Appropriateness of the Rösch-Uchida transjugular liver access set designed for TIPSS procedure was confirmed, especially about the catheter angle and effective length of the 20 G puncture needle, by CT analysis on three dimensional vascular anatomy of the liver. Clinically, TIPSS using the set was successfully made for two patients, connecting superior right hepatic vein with right portal vein in one patient and middle hepatic vein with left portal vein in another patient with hypoplastic right portal vein. Prior to TIPSS procedure, verification of vascular anatomy on CT images is the key to success of TIPSS in safe.

Evaluation Studies as Topic↗

PubMed1992

[Gianturco expandable metallic stents in the treatment of tumor thrombus in portal vein--preliminary clinical experience].

Two cases of hepatocellular carcinoma with protal vein invasion (Vp3) were successfully treated by Gianturco expandable metallic stents (GEMS). Each case was treated through the different approach, i.e. the percutaneous transhepatic or ileocolic venous route. GEMS was easily expanded within the protal vein and carcinoma thrombi were pushed against the walls, resulting in increase of portal blood flow. The GEMS might improve the impaired portal blood flow with hepatic failure and esophagogastric varices, in spite of the possibilities of dissemination and ingrowth of carcinoma thrombi.

Aged↗

PubMed1992

Hormonal regulation of rat renal cytochrome P450s by androgen and the pituitary.

The hormonal regulation of rat renal cytochrome P450s, P450 4A2 (K-5) and K-2, was investigated. The level of P450 4A2 in male rats was five times that in female rats and accounted for some 90% of total cytochrome P450, measured photometrically. Lauric acid omega- and (omega-1)-hydroxylation activities of renal microsomes of male rats were also higher than those of female rats. The sex differences in lauric acid hydroxylation activity seemed to arise from the differences in P450 4A2 concentrations, according to an immunochemical study. P450 K-2 was a female-dominant form in rat kidneys. The level of P450 K-2 in renal microsomes of male rats was one-tenth that of P450 4A2. Castration of male rats decreased the levels of P450 4A2 and treatment of castrated male rats with testosterone reversed the decrease. The castration of male rats decreased the lauric acid hydroxylation of the renal microsomes to the level of female rats. The administration of testosterone to castrated male rats reversed the decrease. Hypophysectomy of male rats decreased the level of P450 4A2 and the administration of growth hormone reversed the decrease when intermittent injections mimicking the male secretory pattern were given, although continuous administration mimicking the female secretory pattern did not. Castration of male rats did not affect the level of P450 K-2, but testosterone decreased its level. Hypophysectomy of male rats increased the level of P450 K-2 and growth hormone decreased its level in hypophysectomized rats. These results suggested that the expression of P450 4A2 was regulated by androgen or growth hormone and regulation of P450 4A2 was different from that of P450 K-2. To explore the regulation of renal cytochrome P450 further, testosterone was given to control (intact) or hypophysectomized adult female rats. P450 4A2 was induced in the kidneys of both control and hypophysectomized female rats to close to the level of male rats. Thus, P450 4A2 was directly regulated by testosterone as well as growth hormone, and the regulation of the male-dominant form in rat kidneys was different from that of the male-specific form in the rat liver, which is regulated mostly by growth hormone.

Animals↗

PubMed1992

Protein kinase C-dependent and -independent actions of a potent protein kinase C inhibitor, staurosporine.

12-O-Tetradecanoylphorbol 13-acetate (TPA), an activator of protein kinase C (PKC), induced ornithine decarboxylase (ODC) in primary cultured mouse epidermal cells. Staurosporine, a potent protein kinase C inhibitor, also induced ODC activity. Both TPA- and staurosporine-caused ODC inductions were markedly suppressed in the PKC-down-regulated cells. Another PKC inhibitor, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7), inhibited both TPA- and staurosporine-caused ODC inductions. H-7 by itself never induced ODC activity. Under our experimental conditions, staurosporine induced no detectable phosphorylation of endogenous proteins. TPA induced a translocation of PKC from cytosol to membrane whereas an optimal concentration of staurosporine to induce ODC did not induce an obvious translocation of PKC. Indomethacin, a cyclooxygenase inhibitor, inhibited staurosporine-caused ODC induction, but not TPA-caused ODC induction. Staurosporine induced specific morphological changes of epidermal cells both in normal and in PKC-down-regulated cells. These results indicate that staurosporine induces ODC activity in a PKC-dependent manner and morphological changes possibly through a PKC-independent mechanism. The mechanism of ODC induction caused by staurosporine may be in some way different from that caused by TPA.

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

PubMed1992

Endothelium-accelerated hyporesponsiveness of norepinephrine-elicited contraction of rat aorta in the presence of bacterial lipopolysaccharide.

The role of the endothelium in the hyporesponsiveness of alpha-adrenoceptor-mediated contractions of the rat aorta was investigated. The norepinephrine-induced maximal contraction was diminished after repeated addition of the agonist. The hyporesponsiveness of the maximal contraction was endothelium dependent, being prevented by NG-monomethyl-L-arginine (0.5 mM), L-argininosuccinic acid (0.5 mM), puromycin (IC50 = 100 microM), actinomycin D (IC50 = 80 nM) but not by indomethacin, which suggests that nitric oxide (NO) synthase is induced. The sensitivity of the rings to NO-induced relaxation remained unchanged. The above-mentioned hyporesponsiveness of norepinephrine-induced maximal contractions of aorta rings was also observed after a 5-h incubation without norepinephrine. The agonist-independent hyporesponsiveness was also prevented by NG-monomethyl-L-arginine, puromycin and actinomycin D, which suggests that NO synthase is induced. Moreover, the norepinephrine-independent hyporesponsiveness was prevented by polymyxin B (10 micrograms/ml), which suggests that bacterial lipopolysaccharide (LPS) might be involved. The concentration of contaminating LPS was 89 +/- 11 ng/ml. When the concentration of contaminating LPS was reduced to 40-70 pg/ml, the hyporesponsiveness of the maximal contraction did not occur after repeated addition of norepinephrine or alter a 5-h incubation without the agonist. An addition of 30 or 100 ng/ml of E. coli lipopolysaccharide to the organ bath reproduced the hyporesponsiveness of the maximal contraction. After a 5-h incubation of aortic rings with 30 ng/ml LPS, only the endothelium-intact ring showed a reduced contraction. However, a 24-h incubation reduced the contraction even in the absence of endothelium.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗

PubMed1992

[Transjugular intrahepatic portosystemic stent shunt (TIPSS)].

Our first clinical experience of TIPSS made for a 52-year-old patient with recurrent life threatening variceal bleeding is described. Although shunt-making between the right hepatic vein and the right portal vein and placement of Gianturco-Rösch Z stents were successfully made without significant complication related to the procedure, sufficient decompression of the portal vein pressure was not obtained because of compression on these stents at the tortuous portion of the shunting tract. Some technical problems of the procedure are also discussed, especially about choice of metallic stents and puncture technique.

Esophageal and Gastric Varices↗

PubMed1992

Neurotransmitter release from synaptotagmin-deficient clonal variants of PC12 cells.

Synaptotagmin (p65) is an abundant synaptic vesicle protein of neurons and contains regions similar to the regulatory domain of protein kinase C. These domains are thought to be involved in calcium-dependent interaction with membrane phospholipids during exocytosis. To assess the functional role of synaptotagmin, synaptotagmin-deficient clonal variants of PC12 cells were isolated. All of the variant cells released catecholamine and adenosine triphosphate in response to elevated intracellular concentrations of calcium, which suggests that synaptotagmin is not essential for secretion of catecholamine and adenosine triphosphate from PC12 cells.

Adenosine Triphosphate↗

PubMed1992

Transmural pressure inhibits nitric oxide release from human endothelial cells.

We examined the effect of transmural pressure on histamine-stimulated nitric oxide release from cultured endothelial cells prepared from human umbilical cord veins. PO2 and pH were kept constant throughout the experiments. Various levels of transmural pressure and atmospheric pressure (40, 80, 120 and 160 mm Hg) were applied. Nitric oxide release was inhibited in a pressure-dependent manner. The inhibitory effects were reversible, and nitric oxide had no effect on the morphology of the cells. Our results suggest that transmural pressure-mediated inhibition of nitric oxide release contributes to pressure-induced vasoconstriction and reduced endothelium-dependent relaxation in patients with hypertension.

Atmospheric Pressure↗

PubMed1992

N-nitrosodialkylamine dealkylation in reconstituted systems containing cytochrome P-450 purified from phenobarbital- and beta-naphthoflavone-treated rats.

Five cytochrome P-450 forms were purified from livers of rats pretreated with phenobarbital (PB) or beta-naphthoflavone (BNF), and the oxidative dealkylation of N-nitrosodialkylamines by the reconstituted cytochrome P-450 systems was measured. PB-II (P450IIB1) showed very high N-nitrosomethybutylamine (NMBA) debutylase activity, high NMBA demethylase activity and high N-nitrosomethyl-benzylamine (NMBeA) debenzylase activity, suggesting that the increase following PB treatment in hepatic microsomal NMBA debutylation and NMBeA debenzylation was due to the induction of PB-II. BNF-H (P450IA2) showed very high NMBA debutylase and high NMBeA debenzylase activities, and BNF-L (P450IA1) showed NMBA debutylase and high NMBeA debenzylase activities. These results suggested that the increase by BNF pretreatment in hepatic microsomal NMBA debutylation was due mainly to the induction of BNF-H and in some part to that of BNF-L. PB-II also showed very high dealkylation activity of lipophilic N-nitrosodialkylamines with long alkyl moieties. On the other hand, BNF-H dealkylated N-nitrosodipropylamine (NDPA), N-nitrosomethylbutylamine (NMBA) and N-nitrosoethylbutylamine (NEBA) at higher rates than N-nitrosodibutylamine (NDBA). BNF-L dealkylated NEBA at higher rates than NMBeA and NDBA. These results reveal that substrate specificity of each cytochrome P-450 form in N-nitrosodialkylamine metabolism is different from each other and several forms of cytochrome P-450 support each N-nitrosamine dealkylase activity in mammalians.

Animals↗

PubMed1992

Sex-specific cytochrome P450 as a cause of sex- and species-related differences in drug toxicity.

Male rats are the most frequently used experimental animals in drug toxicity tests. However, there are clear sex-related differences in toxicity of various drugs and chemicals in rats. These differences, in most cases, are closely connected with the sex-related differences in hepatic drug metabolisms. Recent studies indicate the existence of sex-specific cytochrome P450, such as P450-male (2C11) and P450-female (2C12) and P450(6) beta (3A2) in rat livers, and also show that their expression levels are markedly different between male and female rats. The expressions of sex-specific P450s are regulated by growth hormone, thyroid hormone, sex hormones and other chemicals. On the other hand, there are no or few cytochrome P450s that show the sex-related differences in species other than rats and mice. Although there are orthologous cytochrome P450s in viewpoints of amino acid sequence and substrate specificity in experimental animal species and humans, their expressions are not regulated by hormonal factors in most of the species. These differences may cause clear species differences, if male animals are used, in the toxicity caused by various drugs and chemicals. Thus we can predict the sex-related difference in drug toxicity on the basis of difference in the expression levels of sex-specific cytochrome P450s.

Animals↗

PubMed1992

Characterization of endogenous substrates for novel-type protein kinase C as well as conventional-type protein kinase C in primary cultured mouse epidermal cells.

In primary cultured mouse epidermal cells, phorbol 12-myristate 13-acetate (PMA), which activates protein kinase C (PKC), induced changes in the phosphorylation levels of 10 proteins, termed KP-1 to -10, in two-dimensional PAGE. Seven of these proteins were phosphorylated and three were dephosphorylated. Similar changes were induced by other PKC activators, but not by inactive phorbol ester. Among these substrate proteins, phosphorylation of three proteins, i.e. KP-1 (pI 4.7/23,000 M(r)), KP-2 (pI 4.7/20,700 M(r)) and KP-10 (pI 4.7/25,500 M(r)) was markedly enhanced by PMA and inhibited by a potent PKC inhibitor staurosporine. In vitro phosphorylation studies and phosphoamino acid analysis, using these proteins as substrate and PKC preparations obtained from epidermal cell lysate, revealed that KP-1 and -2 were directly phosphorylated by Ca(2+)-, phospholipid-dependent protein kinase (conventional-type PKC; cPKC), but not by Ca(2+)-independent, phospholipid-dependent protein kinase (novel-type PKC; nPKC). On the other hand, KP-10 was mainly phosphorylated by nPKC in intact epidermal cells. These results indicate that cPKC and nPKC in epidermal cells have different substrate specificity for endogenous proteins and may induce different signal transduction.

Alkaloids↗

PubMed1992

Increases in NO2-/NO3- excretion in the urine as an indicator of the release of endothelium-derived relaxing factor during elevation of blood pressure.

1. Under hormonally constant conditions, the effects of a sudden increase in blood pressure on the release of endothelium-derived relaxing factor were evaluated by measuring urinary excretion of NO2-/NO3- in rats with renal denervation. 2. Elevation of blood pressure from 136 +/- 2 to 153 +/- 3 mmHg by an aortic clamp below the renal arteries induced a significant increase in urinary excretion of NO2-/NO3- from 76.6 +/- 4.2 x 10(2) to 108.1 +/- 8.3 x 10(2) pmol min-1 g-1 kidney weight (P less than 0.05). 3. Infusion of NG-monomethyl-L-arginine (1 mg min-1 kg-1) without an aortic clamp raised mean blood pressure to a similar level; however, urinary excretion of NO2-/NO3- was decreased significantly. 4. During infusion of NG-monomethyl-L-arginine, aortic occlusion caused a significant increase in blood pressure without any changes in NO2-/NO3- excretion in the urine. 5. These results suggest that the formation of NO, an indicator of endothelium-derived relaxing factor release, was increased by mechanical pressure elevation without apparent changes in hormonal and neural factors.

Animals↗

PubMed1992

Can the chest tube draining the pleural cavity with persistent air leakage be removed?

The pleural drain with persistent air leak in six selected patients after pulmonary surgery was clamped or removed without causing pulmonary collapse. In all the patients, air leak through the chest tube was present when speaking or coughing but not seen when breathing normally at rest or taking deep breaths. The fact that the chest tube could be removed in selected patients is explained by supposing the air leakage through an alveolopleural fistula is dependent on pressure difference between the alveoli and the pleural cavity, and this was confirmed in a rethoracotomy case for persistent air leak. Removal of the chest tube following the above-mentioned rationale would reduce the number of rethoracotomy cases for air leak and facilitate early removal of the chest tube in some patients.

Aged↗

PubMed1992

Differential sensitivities of transplacentally initiated newborn mouse epidermal cells to different tumor promoters.

Epidermal cells isolated from newborn mice and cultured in low Ca2+ (0.02 mM) medium showed typical basal cell morphology and proliferated as monolayer. An increase in the medium Ca2+ concentration to normal level (1.8 mM) induced terminal differentiation of epidermal cells. Epidermal cells obtained from newborn mice transplacentally initiated with 7,12-dimethylbenz[a]anthracene (DMBA) produced a small number of rapidly growing cellular foci with epidermal morphology when the medium Ca2+ concentration was raised to normal level. The number of these Ca(2+)-induced differentiation-resistant colonies increased with increasing doses of DMBA, indicating that the differentiation-resistant colonies are the cells initiated by DMBA. Three differentiation-resistant colonies were cloned and designated as WY-1, WY-18 and WY-20 cells. All of these cell lines grew rapidly in the normal Ca2+ medium but not in the low Ca2+ medium. A potent skin tumor promoter, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), and other TPA-type second-stage tumor promoters such as mezerein and 12-O-retinoylphorbol-13-acetate, stimulated the growth of WY-18 and WY-20 cells in the low Ca2+ medium, but did not stimulate the growth of WY-1 cells. TPA stimulated DNA synthesis and ornithine decarboxylase induction in WY-18 and WY-20 cells but not in WY-1 cells. A non-TPA-type tumor promoter, okadaic acid, failed to stimulate the growth of these three cell lines. Another non-TPA-type tumor-promoting agent, 7-bromo-methylbenz[a]anthracene, also failed to stimulate the growth of WY-1 and WY-20 cells but stimulated the growth of WY-18 cells. WY-18 and WY-20 cells formed colonies in soft agar but WY-1 cells did not form colonies. When these cell lines were injected s.c. into nude mice, WY-1 cells produced fast-growing tumors, whereas WY-18 and WY-20 cells produced relatively slow-growing tumors. Our present results indicate that each initiated cell has different sensitivities for different types of tumor promoters, and each type of promoter acts on corresponding types of initiated cells.

Animals↗

PubMed1992

Staurosporine, a potent protein kinase C inhibitor, augments phorbol ester-caused ornithine decarboxylase induction in mouse epidermis.

A single topical application of 12-O-tetradecanoylphorbol-13-acetate (TPA) to mouse skin caused an induction of epidermal ornithine decarboxylase (ODC) activity. When mice were topically pretreated with staurosporine, a most potent protein kinase C inhibitor, 6-84 h prior to TPA treatment, TPA-caused ODC induction was markedly enhanced. The enhancement of TPA-caused ODC induction by staurosporine was most pronounced when the time interval between staurosporine and TPA treatment was 36 h. Staurosporine elicited this enhancing effect in a dose-related manner. Staurosporine by itself also induced epidermal ODC activity. But the activity induced was very slight and would not directly contribute to the enhancing effect of this compound. Although staurosporine markedly augmented TPA-caused ODC induction, staurosporine-caused ODC induction was not augmented by this compound. Other protein kinase C inhibitors, such as 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine, sphingosine and palmitoylcarnitine did not mimic the enhancing effect of staurosporine. These results indicate that the enhancement of ODC induction by staurosporine is specific for the induction caused by TPA and that this enhancing effect is not related to the protein kinase C inhibitory action of staurosporine. TPA-caused epidermal ODC induction was inhibited by indomethacin, and this inhibition was reversed by prostaglandin E2 (PGE2). Staurosporine-caused ODC induction was also inhibited by indomethacin but the inhibition was not reversed by PGE2, indicating that the mechanism of staurosporine-caused ODC induction is different from that of TPA.

Administration, Topical↗

PubMed1992

Involvement of prostaglandin E2 in ornithine decarboxylase induction by a tumor-promoting agent, 7-bromomethylbenz[a]anthracene, in mouse epidermis.

A single topical application of 7-bromomethyl-benz[a]anthracene (BrMBA; 200 nmol) to mouse skin induced epidermal ornithine decarboxylase (ODC) activity. A topical application of indomethacin (1.2 mumol), a cyclooxygenase inhibitor, 10 min before BrMBA application markedly inhibited BrMBA-caused ODC induction. Concurrent application of prostaglandin E2 (PGE2; 0.1-1.5 mumol) reversed the inhibitory effect of indomethacin. Without indomethacin, PGE2 suppressed BrMBA-caused ODC induction. The results indicate that PGE2 has dual actions on the BrMBA-caused ODC induction, i.e. PGE2 plays an essential role in ODC induction caused by BrMBA, whereas exogenous PGE2 rather suppressed BrMBA-caused ODC induction.

Animals↗

PubMed1992

Phenotypic expression of carcinogen-initiated epidermal cells to tumor cells by 12-O-tetradecanoylphorbol-13-acetate in a manner dependent on 3T3 fibroblast-derived humoral factor(s).

Primary cultured newborn mouse epidermal cells cultured in the low Ca2+ (0.02 mM) medium showed typical basal cell morphology and proliferated as a monolayer. A stepwise increase in medium Ca2+ concentration induced terminal differentiation of epidermal cells. In the case of epidermal cells obtained from newborn mice transplacentally initiated with 7,12-dimethylbenz[a]anthracene (DMBA) or epidermal cells initiated in vitro by DMBA, a small number of rapidly growing cellular foci with epidermal morphology appeared and proliferated when the medium Ca2+ concentration was raised. Without increasing Ca2+ concentration, such foci never appeared. However, the Ca2+ concentration of the extracellular milieu of basal epidermal cells is known to be very low in in vivo epidermis. Under the low Ca2+ conditions, 12-O-tetradecanoylphorbol-13-acetate (TPA), a most potent skin tumor promoter, never induced rapidly growing cellular foci. When the initiated epidermal cells were co-cultured with 3T3 fibroblasts but without direct cell-to-cell contact, TPA induced rapidly growing cellular foci even under the low Ca2+ condition. Without initiation, such cellular foci hardly appeared. 3T3 fibroblasts induced only a very small number of cellular foci in the absence of TPA. Co-culture with mouse peritoneal macrophages was not effective in inducing such cellular foci, indicating that the effect is 3T3 fibroblast specific. The conditioned medium of 3T3 fibroblasts was also capable of inducing such cellular foci. Three of these rapidly growing cellular foci were cloned and designated as WYF-30, WYF-31 and WYF-32 respectively. All of these three cell lines grew rapidly in the normal (1.8 mM) Ca2+ medium, indicating that these cell lines were resistant to Ca(2+)-induced differentiation. In the low Ca2+ medium, the growth of these three cell lines was stimulated by TPA. All three cell lines formed colonies in soft agar. The number of colonies formed under the normal Ca2+ condition was larger than that formed under the low Ca2+ condition. Under the low Ca2+ condition, the colony formation of each cell line was augmented by TPA. All the cell lines formed tumors in nude mice. These results indicate that TPA induces phenotypic expression of dormant initiated cells to tumor cells in a manner dependent on 3T3 fibroblast-derived humoral factor(s).

3T3 Cells↗

PubMed1992

Sulfotransferase-mediated DNA binding of N-hydroxyarylamines(amide) in liver cytosols from human and experimental animals.

Characteristics of cytosolic sulfotransferase-mediated binding of carcinogenic N-hydroxyarylamines(amide) have been investigated and compared among experimental animal species and humans in vitro. Human cytosols exhibited significant sulfating activities towards 2-hydroxyamino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (N-hydroxy-Glu-P-1), N-hydroxy-2-aminofluorene (N-hydroxy-AAF) and N-hydroxy-2-acetylaminofluorene (N-hydroxy-AAF), but had no detectable activity toward 2-hydroxyamino-3-methyl-imidazo[4,5-f]quinoline (N-hydroxy-IQ). Although the extent of the covalent binding of these N-hydroxyarylamines(amide) differed significantly among individuals, clear correlations were observed among the sulfation of N-hydroxyarylamines (amide) and also with p-nitrophenol sulfation. Hepatic cytosols from mouse, rat, guinea-pig, hamster, rabbit, dog and monkey also mediated the binding of N-hydroxy-Glu-P-1, N-hydroxy-AF and N-hydroxy-AAF, while only rat cytosols showed detectable DNA binding of N-hydroxy-IQ. Among the species examined, rat showed the highest capability for activating these N-hydroxyarylamines(amides). Significant sex-related differences were detected in rat, dog and monkey for all substrates examined, except N-hydroxy-IQ. Clear correlations were observed in the animal species between N-hydroxyarylamines(amide), but not with p-nitrophenol. Using an ion-exchange chromatographic system, sulfating activity of p-nitrophenol in human livers was separated into two fractions and the PAPS-dependent DNA binding of N-hydroxy-AF was supported mainly by the later fraction. On Western blots, an immunoreactive protein was detected in these fractions using an antibody raised against rat hepatic N-hydroxy-AAF sulfotransferase. The band was also detected in human hepatic cytosols with considerable individual variation in their amounts. These results indicate the involvement of a closely related form(s) of sulfotransferase in the PAPS-mediated activation of N-hydroxyarylamines(amide) in human as well as in the experimental animal species.

Animals↗