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Biomedical subjects

T Iwata

Publications and source records attributed to T Iwata.

At least 361 records · Page 20Linked to original sources
PubMed1984

Highly potent and specific inhibitors of human renin.

We designed aldehyde derivatives of small peptides representing the C-terminal portion of angiotensin I sequence as an inhibitor of human renin. Among compounds that we synthesized, benzyloxycarbonyl (Z)-Phe-His-Leucinal (compound V), Z-Pro-Phe-His-Leucinal (Compound IV) and Z-[3-(1'-naphthyl)Ala]-His-Leucinal (compound VII) markedly inhibited human renin (IC50, 7.5 X 10(-7), 3.2 X 10(-7) and 8.0 X 10(-8) mol/l, respectively). Compound VII was shown to be noncompetitive (Ki = 2.4 X 10(-7) mol/l). It did not inhibit either cathepsin D or pepsin. Compound V had slight or no inhibitory effect at the concentration of 10(-5) mol/l on six animal renins except for monkey and rabbit renins. Results obtained show that these aldehyde compounds are highly selective and species specific inhibitors for human and monkey renins.

Aldehydes↗
PubMed1984

Purification of human plasma alpha 1-proteinase inhibitor and its inactivation by Pseudomonas aeruginosa elastase.

Human alpha 1-proteinase inhibitor was purified according to a modification of the method of Kurecki et al. (Anal. Biochem. 99, 415 (1979) ), with Affi-Gel Blue treatment before Zn-affinity column chromatography. The inhibitor was inactivated in the presence of Pseudomonas aeruginosa elastase (1/2,000 molar ratio) for 2 h at pH 7.5 and 25 degrees C. The inactivated inhibitor was purified by column chromatography on Sephadex G-75 and DE-52. Little or no difference was observed between the native and inactive inhibitors in immunological response, amino acid composition or far-ultraviolet CD spectrum. On the other hand, a considerable difference was observed in the near-ultraviolet CD spectrum. Two amino-terminal sequences were found in the inactive inhibitor in almost the same ratio; one was the same as that of the intact inhibitor and the other was Met-Ser-Ile-Pro-. The two components were separated by high-performance liquid chromatography using 0.1% trifluoroacetic acid containing 30-70% CH3CN (gradient) as the eluent. Amino acid analysis and N- and C-terminal amino acid sequence analyses indicated that one fraction corresponded to the sequence of 1-357 of the alpha 1-proteinase inhibitor and the other to 358-394. We concluded that P. aeruginosa elastase can inactivate human alpha 1-proteinase inhibitor by splitting the peptide bond of Pro357-Met358, leading to local change near the active site but little change in the structure as a whole. The split carboxy-terminal fragment binds tightly to the rest of the inhibitor.

Amino Acids↗
PubMed1984

Malignant cystosarcoma phyllodes of prostate.

A case of malignant cystosarcoma phyllodes of the prostate is reported in a 45-year-old male. This tumor was composed of benign columnar or squamous cystic folds and sarcomatous stroma including rhabdomyomatous elements. The prostatic origin of the tumor was clearly proved by the unlabeled immunoperoxidase method.

Autoantibodies↗
PubMed1984

Intracerebellar hemorrhage due to rupture of angiomatous malformations in the cerebellum.

Two infants were reported with intracerebellar hemorrhage due to rupture of angiomatous malformations in the cerebellum. There have been only a few reports on intracerebellar hemorrhage under 6 years of age, which was due to angiomatous malformation in all cases. The results of operations for intracerebellar hemorrhage in infants were more favorable than those in adults, so even if the infant patient shows severe neurological symptoms preoperatively, an operation should be performed.

Cerebellar Diseases↗
PubMed1984

Changes of plasma renin activity by intracerebroventricular administration of biological active peptides in conscious rats.

We studied the effects of intracerebroventricular administration of angiotensin II (ANG II), bradykinin (BK), leucine-enkephalin (Leu-ENK) and neurotensin (NT) on plasma renin activity (PRA), blood pressure and heart rate in conscious and unrestrained rats. Five microliters of each peptide solution was injected into the lateral cerebral ventricle. These four peptides all produced pressor effects after intracerebroventricular injection. ANG II and NT significantly suppressed PRA, BK did not affect PRA, and Leu-ENK significantly increased PRA. The central peptidergic stimulation caused by these four peptides increased blood pressures in conscious rats but showed different effects on PRA.

Angiotensin II↗
PubMed1983

Mutagenicity of bis- and mono-(2,3-dibromopropyl)phosphate, and their salts used as flame retardants, in the Salmonella/microsome system.

The mutagenicity of pure synthesized samples of bis(2,3-dibromopropyl)phosphate (bis-BP) and mono(2,3-dibromopropyl)phosphate (mono-BP) against Salmonella typhimurium TA100 was examined in relation to microsomal activation of tris(2,3-dibromopropyl)phosphate (tris-BP). Both mono- and bis-BPs were weak direct mutagens. Their mutagenicities increased with S9 mix, but the rates were much less than that of tris-BP. The magnesium and ammonium salts of mono- and bis-BPs were also prepared and their mutagenicities were examined with S9 mix in relation to 2 commercial flame retardants (our abbreviations: DB-1 and DB-2). In both mono- and bis-BP series, an apparent increase of mutagenicity was observed in the order: ammonium salt greater than magnesium salt greater than free acid. On the other hand, mono-BP and its salts are usually more active than the corresponding bis-BPs independently of the kind of cation. DB-1 (DB-2), however, is more potent than the magnesium (ammonium) salts of mono- and bis-BPs, the constituents in DB-1 (DB-2). No synergistic effect between mono-BP salts and bis-BP salts was observed. The different unknown mutagenic compounds in DB-1 and DB-2 are suggested.

Animals↗
PubMed1983

Circulating thymic hormone levels in severe combined immunodeficiency.

Twenty-three patients with severe combined immunodeficiency disease were studied for circulating thymic hormone levels (facteur thymique serique, FTS), 21 prior to treatment by transplantation of bone marrow, thymus or fetal liver. Thirteen showed undetectable FTS activity. Only two had normal levels of this hormone. In serial determinations of FTS activity prior to and after transplantation, patients given bone marrow transplants developed sustained increments of serum FTS activity early in the course of their immunological reconstitution. However, patients given transplants of fetal liver alone or fetal liver plus thymus from fetuses of less than 12 weeks gestation generally did not show an increment of FTS activity during the period of observation. Transplantation of irradiated thymus derived from fetuses of more than 14 weeks gestation produced sustained increases of thymic hormone activity. These observations suggest that a cell of haematopoietic origin provides a stimulus necessary for differentiation or maturation of thymic secretory activity and that this cell(s) is present in post-natal marrow, but is either undeveloped or immature in the early fetal liver or fails to migrate to the thymus of an allogeneic host.

Antibody Formation↗
PubMed1982

Amyloid deposits in heart valves.

Localized amyloid deposits were found in 44% of the surgically removed heart valves. They are recognized only in severely destructed valves and the manner of the deposition closely resembles that of aortic intimal amyloid. Although the amyloid fibril protein of the chronically diseased valves is still unknown, it may be neither protein AA nor AL, and another type of amyloid is suggested.

Adolescent↗
PubMed1982

Amyloidosis associated with juvenile rheumatoid arthritis.

Clinical and pathological findings are reported in a Japanese girl who died of secondary amyloidosis associated with juvenile rheumatoid arthritis two years after the onset of symptoms. The patient had intermittent high fever, rheumatoid rash, polyarthralgia, and hepatosplenomegaly. The joints showed the typical histologic changes of juvenile rheumatoid arthritis. Amyloid deposition was found in various tissues; however, remarkable deposition of amyloid was observed in the gastrointestinal tract, especially in the ileum. The amyloid protein in this patient was identified as protein AA using the methods of potassium permanganate treatment and the peroxidase-antiperoxidase unlabeled antibody technique.

Amyloidosis↗
PubMed1982

Biotransformation of coumarin derivatives (1). 7-alkoxycoumarin O-dealkylase in liver microsomes.

The in vitro metabolic fate of 7-alkoxycoumarin was studied using liver microsomes. Microsomal enzyme catalyzed dealkylation of 7-alkoxycoumarin to 7-hydroxycoumarin in the presence of NADPH and molecular oxygen as cofactors was found to be one of the metabolic pathways. The metabolite 7-hydroxycoumarin was further metabolized to unidentified metabolite(s) in the presence of NADPH and O2 at a very slow rate, while the formation of the conjugate of 7-hydroxycoumarin with glucuronic acid was observed in the presence of UDPGA. Microsomal 7-alkoxycoumarin O-dealkylase activity was altered by the substitution of the alkyl group of the substrate, and the substitutions to either an O-propyl or an O-butyl group resulted in a decrease of the enzyme activity. Species differences were observed in the substrate specificity of microsomal O-dealkylation. The O-dealkylase activities in rat liver microsomes were stimulated by pretreatment of the animals with phenobarbital, regardless of the O-alkyl substituent at the 7 position of the coumarin ring. On the other hand, pretreatment with 3-methylcholanthrene or beta-naphthoflavone resulted in marked increase of O-deethylation. O-depropylation and O-debutylation activities, but not of O-demethylation activity. Pretreatment of animals with beta-naphthoflavone also resulted in remarkable stimulation of 7-hydroxycoumarin-glucuronide formation by the microsomal enzyme, while the conversion of 7-hydroxycoumarin to unidentified metabolite(s) was activated by the pretreatment of rats with only phenobarbital. The O-dealkylation activities in liver microsomes from intact and phenobarbital pretreated rats were inhibited markedly by the addition of hexobarbital to the incubation mixture, but no inhibition was observed with alpha-naphthoflavone. On the other hand, the O-dealkylation activities in microsomes from beta-naphthoflavone-pretreated rats were inhibited remarkably by alpha-naphthoflavone. These results confirmed that several microsomal enzymes, including the cytochrome P-450's and UDP-glucuronyltransferase, participate in the biotransformation of 7-alkoxycoumarin, and these enzymes are regulated differently by inducers.

7-Alkoxycoumarin O-Dealkylase↗