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Biomedical subjects

H Kido

Publications and source records attributed to H Kido.

At least 199 records · Page 11Linked to original sources
PubMed1988

Kunitz-type protease inhibitor found in rat mast cells. Purification, properties, and amino acid sequence.

A low molecular weight serine protease inhibitor, named trypstatin, was purified from rat peritoneal mast cells. It is a single polypeptide with 61 amino acid residues and an Mr of 6610. Trypstatin markedly inhibits blood coagulation factor Xa (Ki = 1.2 x 10(-10) M) and tryptase (Ki = 3.6 x 10(-10) M) from rat mast cells, which have activities that convert prothrombin to thrombin. It also inhibits porcine pancreatic trypsin (Ki = 1.4 x 10(-8) M) and chymase (Ki = 2.4 x 10(-8) M) from rat mast cells, but not papain, alpha-thrombin, or porcine pancreatic elastase. Trypstatin forms a complex in a molar ratio of 1:1 with trypsin and one subunit of tryptase. The complete amino acid sequence of this inhibitor was determined and compared with those of Kunitz-type inhibitors. Trypstatin has a high degree of sequence homology with human and bovine inter-alpha-trypsin inhibitors, A4(751) Alzheimer's disease amyloid protein precursor, and basic pancreatic trypsin inhibitor. However, unlike other known Kunitz-type protease inhibitors, it inhibits factor Xa most strongly.

Amino Acid Sequence↗
PubMed1988

Biological functions of serine proteases in mast cells in allergic inflammation.

Serine proteases in mast cell granules, such as chymase, atypical chymase, and tryptase, which are major proteins in the granules, may play important roles in the process of immunoglobulin E (IgE)-mediated degranulation and in pathobiological alterations in tissues. Indeed, inhibitors of chymase, substrate analogs, and antichymase F(ab')2, but not inhibitors of tryptase, markedly inhibited histamine release induced by IgE-receptor bridging but not that induced by Ca ionophore. In contrast, inhibitors of metalloprotease inhibited histamine release induced not only by IgE-receptor bridging but also by Ca ionophore. These results suggest that chymase and metalloprotease are involved at different steps in the process of degranulation. The extents of inhibition of histamine release were closely correlated with the amounts of the inhibitors of chymase accumulated in the granules. After degranulation, the released proteases may in part contribute to pathobiological alterations in allergic disorders through generations of C3a anaphylatoxin and thrombin by human and rat tryptase, respectively, and those of angiotensin II and a chemotactic factor of neutrophils by human and rat chymase, respectively. Moreover, chymase and atypical chymase from rat were shown to destroy type IV collagen, and human tryptase was found to hydrolyze various plasma proteins, such as fibrinogen and high-molecular-weight kininogen. The biological activities of tryptase and chymase from rat may be regulated by their dissociation from and association with trypstatin, an endogenous inhibitor of these proteases.

Animals↗
PubMed1988

Studies on biomodulators of glucocorticoid action: amplifiers and suppressors of glucocorticoid action.

In this work we found that the induction of tyrosine aminotransferase by glucocorticoid in rat hepatocytes was suppressed concentration-dependently by TGF-beta and H-7, an inhibitor of protein kinase C, but not by other polypeptide growth factors tested or by H-8, an inhibitor of cyclic nucleotide dependent protein kinases. EGF, on the contrary, amplified the induction in the same way as activators of protein kinase C, such as 12-o-tetradecanoyl-phorbol 13-acetate (2,3) and 1,2-racemic dioctanoyl glycerol (1,3). These findings indicate that TGF-beta and H-7 act in the suppressive direction and EGF acts in the enhance direction on the action of glucocorticoid. H-7 inhibited the accumulation of glucocorticoid-receptor complexes in the nuclear fraction with associated accumulation of these complexes in the cytoplasmic fraction, but did not affect incorporation of glucocorticoid into hepatocytes. These results suggest that protein kinase C is essential in translocation of glucocorticoid-receptor complexes to the nuclei and that its inhibitors suppress glucocorticoid actions.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1988

Benign schwannoma of the gastrointestinal tract: a clinicopathologic and immunohistochemical study.

A clinicopathologic and immunohistochemical review was made of 24 cases of distinctive nerve sheath tumors located in the gastrointestinal tract. The tumors were microscopically evident in the presence of peripheral lymphoid cuffing and benign nuclear atypia. The tumors arose in the muscularis propria of the stomach in 23 cases and in the ascending colon in 1 case. The patients included 9 men and 15 women whose ages ranged from 36 to 78 years (average, 58). No recurrence has developed in any patient who underwent resection. Although positive immunostaining for S-100 protein, Leu 7 antigen, and laminin might support the schwannian nature of these tumors, the positive immunoreactivity for glial fibrillary acidic protein (GFAP) indicated the possibility of a myenteric plexus origin. The pattern of S-100 protein immunostaining differed from that seen in cases of gastrointestinal stromal tumors associated with von Recklinghausen's neurofibromatosis or that noted in cases of conventional leiomyomas. We propose that these tumors be designated as benign schwannoma of the gastrointestinal tract.

Adult↗
PubMed1988

Peptide boronic acids, substrate analogs, inhibit chymase, and histamine release from rat mast cells.

Peptide boronic acids, such as methoxysuccinyl-Ala-Ala-Pro-(L)boro-Phe-OH, its pinacol ester, and t-butyloxycarbonyl-Phe-Pro-(L)boro-Phe-pinacol, inhibited the activity of chymase from connective tissue mast cells approximately 40- to 80-fold more than atypical chymase from mucosal mast cells, and did not inhibit trypsin. Only peptide boronic acids containing "L" forms of boronic acids were inhibitory. The Ki values of these peptide boronic acids for chymase were in the 60-170 nM concentration range, like those of the natural inhibitors tested, but all the natural inhibitors tested except Eglin C and chymostatin inhibited both chymase and trypsin. Thus these peptide boronic acids should be useful for selective inhibition of chymase with less inhibitory activity for atypical chymase and without inhibition of trypsin. These peptide boronic acids markedly inhibited histamine release induced by anti-rat immunoglobulin E, suggesting that chymase in connective tissue mast cells plays some role in the process of histamine release. These peptides are assumed to be therapeutically useful for treatment of allergic inflammations catalyzed by chymase.

Animals↗
PubMed1988

Episodic twilight state with severe autonomic symptoms in an epileptic patient.

A boy suffering from epileptic seizures experienced five episodes of a twilight state. His twilight states continued for at least two weeks, and were characterized by behavioral disorders and severe autonomic symptoms. Sometimes functional ileus was present. The electroencephalographic finding in the first episode was 6-per-second phantom spike and wave complex (PSW). For treatment, a combination of carbamazepine and sodium valproate was useful in preventing the reappearance of the episode of the twilight state and in suppressing PSW. From the clinical and electroencephalographic findings and therapeutic response to antiepileptics, the episodes were considered to have originated in localized epileptic discharges in the hippocampal, amygdaloidal and hypothalamic regions.

Amygdala↗
PubMed1988

A relationship between clomipramine brain concentration and its effect on serotonin metabolism.

The relationship between clomipramine (CMP) brain concentration and its inhibitory effect on serotonin (5HT) turnover was investigated in rats treated with a single dose and multiple doses of CMP. CMP reduced the 5-hydroxyindole acetic acid (5HIAA) brain levels in two groups of rats. Concerning the 5HT turnover measured by the probenecid (PBC) technique, there were significant correlations between the CMP brain level (x) and 5HIAA brain level (y) after PBC injections in both acute and chronic experiments. The regression lines for the respective groups were y = 764 - 117 log x (r = 0.84, P less than 0.001) and y = 770 - 97.7 log x (r = 0.68, P less than 0.001). The regression coefficient for the acute experiment was greater than that for the chronic one (p less than 0.001), indicating a less dose-response in the latter. From these findings, the acute dosing with CMP seemed to reduce the 5HT turnover without reference to the dose but a prolonged administration seemed to vary in its effect. This may be due to a compensatory mechanism in the 5HT system induced by chronic CMP-treatment.

Animals↗
PubMed1988

Antibodies and inhibitor of chymase are incorporated into mast cell granules and inhibit histamine release.

The release of histamine from rat mast cells induced by anti-immunoglobulin E (IgE) was markedly inhibited by Bowman-Birk soybean protease inhibitor (BBI) and anti-chymase F(ab')2 fragments which inhibit chymase activity [Kido, H., et al. (1985) Biochem. Int. 10, 863-871, and Fukusen, et al. (1987) Biochem. Med. Metab. Biol. 38, 165-169]. When radioiodinated anti-chymase F(ab')2 fragments or BBI were incubated with mast cells at 37 degrees C, they were subsequently recovered in the fractions of mast cell granules and of plasma membranes by Percoll density gradient centrifugation. However, when they were incubated with mast cells at 0 degrees C, they had no effect on histamine release and were subsequently recovered only in the plasma membrane fraction. Histamine release from mast cells was suppressed dose-dependently by the antibodies or BBI accumulated in mast cell granules at 37 degrees C. These results suggest that the antibodies and BBI are incorporated into mast cell granules and inhibit chymase activity, resulting in inhibition of histamine release.

Animals↗
PubMed1987

Epidermal growth factor as a new regulator of induction of tyrosine aminotransferase and tryptophan oxygenase by glucocorticoids.

Epidermal growth factor (EGF) dose-dependently enhanced the induction of tyrosine aminotransferase and tryptophan oxygenase by glucocorticoids in primary cultures of adult rat hepatocytes without itself having any effect on these enzymes in the absence of glucocorticoids. The amplifications were observed even with dexamethasone at high concentrations (10(-6) M-10(-5) M) that had a maximal effect. EGF had no effect on induction of tyrosine aminotransferase by glucagon or Bt2cAMP. The effect of EGF was also observed in adrenal-ectomized and submaxillary gland-ectomized rats. These results suggest that EGF is an endogenous amplifier of the action of glucocorticoids.

Adrenalectomy↗
PubMed1987

Tumor-promoting phorbol ester amplifies the inductions of tyrosine aminotransferase and ornithine decarboxylase by glucocorticoid.

In adrenalectomized rats, the tumor-promoting phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) markedly enhanced the inductions of tyrosine aminotransferase (TAT) and ornithine decarboxylase by glucocorticoids, even with sufficient concentration of glucocorticoids to have a maximal effect, whereas it had no effect on TAT activity and increased ornithine decarboxylase activity only slightly in the absence of glucocorticoids. Phorbol derivatives and components of TPA such as 4 beta-phorbol, phorbol 12-tetradecanoate, phorbol 13-acetate, and 4-O-methylphorbol 12-tetradecanoate 13-acetate, which have no tumor-promoting activity or ability to activate protein kinase C, did not have any effect on TAT induction by glucocorticoid. TPA enhanced the induction of TAT by various glucocorticoids but had no effect on induction of TAT by glucagon or insulin and did not enhance the induction of glucose-6-phosphate dehydrogenase by 17 beta-estradiol. These results suggest that TPA specifically enhances the induction of TAT and ornithine decarboxylase by glucocorticoids. Similar effects of TPA on TAT induction by glucocorticoid were observed in primary cultures of adult rat hepatocytes. Another activator of protein kinase C, rac-1,2-dioctanoylglycerol, was also found to have similar effects on the cells.

Adrenalectomy↗
PubMed1987

Inhibition by 1-(5-isoquinolinesulfonyl)-2-methylpiperazine, an inhibitor of protein kinase C, of enzyme induction by glucocorticoid and of nuclear translocation of glucocorticoid-receptor complexes.

Induction of tyrosine aminotransferase by glucocorticoid in rat hepatocytes was inhibited concentration-dependently by 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7), an inhibitor of protein kinase C, but not by N- [2-(methyl-amino)-ethyl]-5-isoquinolinesulfonamide dihydrochloride, an inhibitor of cyclic nucleotide dependent protein kinases. H-7 also inhibited the accumulation of glucocorticoid-receptor complexes in the nuclear fraction with associated accumulation of these complexes in the cytoplasmic fraction, but did not affect incorporation of glucocorticoid into hepatocytes. These results indicate that protein kinase C may be essential in translocation of glucocorticoid-receptor complexes to the nuclei.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1987

Studies on biomodulators of glucocorticoid actions; the nature and the modes of actions of glucocorticoid potency amplifiers.

We have found many compounds that amplify the action of glucocorticoid without themselves having any glucocorticoid-like action and have proposed the concept of 'Glucocorticoid Action Biomodulators'. These biomodulators consist of 'Glucorticoid Sensitivity Amplifiers', which greatly amplify the action of glucocorticoid at doses of glucocorticoid that alone have minimal effects, and 'Glucocorticoid Potency Amplifiers', which markedly enhance the effect of glucocorticoid at doses that have maximal effects. Potent activators of protein kinase C, such as 1,2-racemic dioctanoylglycerol, 12-o-tetradecanoyl-phorbol-13-acetate, and epidermal growth factor (EGF), markedly enhanced the induction of tyrosine aminotransferase and ornithine decarboxylase by dexamethasone in adrenalectomized rats in vivo and in primary cultures of adult rat hepatocytes in vitro. They amplified enzyme induction by even a large amount of dexamethasone that had a maximal effect, but had no effect in the absence of glucocorticoid. These modes of amplification show that these compounds are 'Glucocorticoid Potency Amplifiers'. They amplified not only enzyme induction in liver but also growth inhibition by glucocorticoid of solid tumor L5178Y lymphoblasts. They specifically amplified the actions of glucocorticoids and did not amplify the actions of other steroids, such as 17-beta estradiol, glucagon and insulin. The induction of tyrosine aminotransferase by glucocorticoid and its amplification by EGF were both inhibited by 1-(5-iso-quinoline-sulfonyl)-2-methylpiperazine, an inhibitor of protein kinase C, and not by N-[2-(methylamino)-ethyl]-5-isoquinoline-sulfonamide, an inhibitor of cyclic nucleotide dependent protein kinases, suggesting that the induction and the amplification are mediated by protein kinase C.

Animals↗
PubMed1987

Kinetic studies on the inhibitions of mast cell chymase by natural serine protease inhibitors: indications for potential biological functions of these inhibitors.

We have found that degranulation from mast cells is specifically inhibited by the inhibitors of chymase (10). Among the natural serine protease inhibitors tested, Bowman-Birk soybean protease inhibitor, Eglin C, and human alpha 1-antichymotrypsin inhibited chymase more strongly than did chymostatin, Kunitz soybean protease inhibitor, and phosphatidylserine. Of the inhibitors tested, Bowman-Birk soybean protease inhibitor was the strongest inhibitor of chymase, its Ki value being 13.2 X 10(-9) M. Kinetic studies showed that these inhibitors were all noncompetitive inhibitors of chymase. Bowman-Birk and Kunitz soybean protease inhibitors inhibited both chymotrypsin-type and trypsin-type serine proteases but Eglin C specifically inhibited chymotrypsin-type proteases.

Animals↗
PubMed1987

Serum levels of maprotiline and its adverse effects on depressed patients.

The relationships between the side effects of maprotiline (MPT) and the serum concentration of MPT and desmethylmaprotiline (DMPT) were investigated with 27 blood samplings in 15 depressed inpatients. There were significant correlations between the side effects and serum levels of MPT and DMPT. Mild side effects frequently occurred at levels of more than 130 ng/ml of MPT and 70 ng/ml of DMPT. At more than 220 ng/ml of the MPT levels and 110 ng/ml of DMPT levels, severe side effects occurred. Nearly sigmoidal serum level/side effect response curves occurred with both compounds.

Adult↗
PubMed1987

A comparison of maprotiline and its desmethylated metabolite serum concentrations in outpatients and inpatients.

An investigation was conducted on drug defaulting in 26 depressed patients (11 outpatients and 15 inpatients) treated with maprotiline (MPT), using the interrogation methods and measurements of drug serum levels. All the outpatients visited the clinic regularly and complied with taking the prescripted drugs as directed. The results were as follows: (1) The relationships between the MPT and desmethylmaprotiline (DMPT) serum levels and the daily MPT doses showed highly linear regressions in all the patients, and in the inpatients and outpatients separately. There were significant differences between the regression coefficients obtained in the outpatients and inpatients with respect to MPT (P less than 0.01) and DMPT (P less than 0.001). There was a discrepancy between the results from the patients' reports and measurements of the drug serum levels. This finding indicated noncompliance by the outpatients. (2) Comparing various factors of the outpatients to those of the inpatients, the DMPT/MPT ratio of the former was higher than that of the latter (P less than 0.05). This was also due to the patients' noncompliance, and this ratio, therefore, was considered to be a sensitive marker for checking the compliance of the patients treated with MPT.

Adult↗
PubMed1987

A simultaneous analytical method for catecholamines, indoleamines, and related compounds in 11 rat brain regions.

A simple high-performance liquid chromatographic method that allows the determination of 10 biogenic amines and related compounds for crude brain extracts has been developed. The compounds that can be quantified comprise norepinephrine, epinephrine, 3,4-dihydroxyphenylacetic acid, 3-methoxy-4-hydroxyphenylglycol, dopamine, 5-hydroxyindole-3-acetic acid, homovanillic acid, 3-methoxytyramine, 5-hydroxytryptamine and tryptophan. The detection system involves a three electrode-coulometric determination followed by fluorometric determination. This method is highly selective and sensitive, and in the present study, the usefulness of this methodology was confirmed by applying it to the determination of the levels of these various substances in 11 rat brain regions.

Animals↗