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Biomedical subjects

T Aoyagi

Publications and source records attributed to T Aoyagi.

At least 289 records · Page 16Linked to original sources
PubMed1988

Feedback analysis of the behavior of the renin-angiotensin system under inhibition of angiotensin-converting enzyme.

It was previously shown that autoregressive modeling can be used for feedback analysis in the body. We used this method to investigate the dynamic changes in and around the renin-angiotensin system in vivo induced by angiotensin-converting enzyme (ACE) inhibition. Long-term studies were performed on rabbits, which were given a daily injection of one of the following ACE inhibitors: captopril, foroxymithine, or histargin. For comparison, other rabbits received injections of saline or the renin inhibitor pepstatin. Autoregressive coefficients were computed from the raw data thus observed and were used to simulate the impulse-response function proper to each animal. The response of each animal estimated in this way exposed the effects of ACE inhibitors in vivo which were obscured by the feedback regulation of the renin-angiotensin system. Also, it was suggested that histargin has a peculiar action, blocking the negative feedback that would be elicited by the usual ACE inhibition. Feedback analysis seems to be essential to elucidate the in vivo effects of enzyme inhibitors.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1987

Analgesic effect of actinonin, a new potent inhibitor of multiple enkephalin degrading enzymes.

Actinonin, previously isolated as an antibiotic and shown to be an inhibitor of aminopeptidase M (EC 3.4.11.2), has now been shown to inhibit three enkephalin-degrading enzymes from guinea-pig striatum. The values of IC50 were 0.39 microM for striatal membrane aminopeptidase ("enkephalin-aminopeptidase") and 5.6 microM striatal membrane neutral endopeptidase ("enkephalinase A"). Furthermore, soluble dipeptidylaminopeptidase in a rat whole brain homogenate was also inhibited by actinonin with the IC50 value of 1.1 microM. Actinonin administered intracisternally (i.cist., 50 micrograms) or intraperitoneally (i.p., 100 mg/kg), potentiated the analgesic action of met-enkephalin (50 micrograms i.cist.). analgesia by a tail-flick test. The potentiating activity of actinonin i.p. to met-enkephalin analgesia was almost the same potency as that of thiorphan, whereas the inhibitory activity of actinonin against enkephalinase A was 1/1000 that of thiorphan. Actinonin alone, administered either i.cist. or i.p., showed an analgesic action as estimated by the tail-flick test.

Aminopeptidases↗
PubMed1987

Composite effects of actinonin when inhibiting enkephalin-degrading enzymes.

Actinonin which has been found to be an inhibitor of aminopeptidase M (EC 3.4.11.2) also inhibited enkephalinase A (EC 3.4.24.11) and enkephalin aminopeptidase which were partially purified from the corpus striatum membrane of guinea-pig brain. The IC50 values were 5.6 microM for enkephalinase A and 0.39 microM for enkephalin aminopeptidase. Actinonin also inhibited with an IC50 value of 1.1 microM dipeptidyl aminopeptidase tested on whole brain homogenate of rats in the presence of thiorphan and bestatin. Analgesia was assessed by measuring the tail-flick latency of mice. The analgesic effect of [Met5]enkephalin injected intracisternally (i.cist., 50 micrograms) was potentiated by an intraperitoneal (i.p., 100 and 300 mg/kg) as well as an i.cist. (25 micrograms) injection of actinonin. Actinonin was found to inhibit all three enzymes of enkephalin metabolism and, when given peripherally, to potentiate enkephalin analgesia.

Aminopeptidases↗
PubMed1987

Relative deficiency of serine proteinase activities in spleens of aged mice.

We examined the relation of hydrolytic enzymes in spleen to the aging process in mice over a period of 30 months. When the enzymatic activities were expressed as activities per milligrams protein, those of serine proteinases and dipeptidyl peptidase IV (Gly-Pro-AP) significantly decreased with age, whereas that of L-leucine aminopeptidase (Leu-AP) increased significantly. However, when expressed as total activities, the enzymatic activities in spleen generally tended to increase with age, except in the case of serine proteinases, because of the age-related increase in spleen weight. The results were taken to indicate that the activities of serine proteinases become relatively more deficient in the spleen as age increases. The results of a multivariate study maintained this peculiarity of serine proteinases in comparison with other enzymes. The relative deficiency of serine proteinases in spleen may be somehow related to immunodeficiency in aged animals, as judged from similar findings in animal models of systemic erythematodes.

Aging↗
PubMed1987

Multilocular cystic nephroma in an adult: immunohistochemical study.

We report a case of multilocular cystic nephroma (cysts of the kidney). The tumor was enucleated surgically. It was well encapsulated, and composed of numerous cysts and cellular stroma. Microscopically, the stromal cells resembled blastematous cells seen in Wilms tumor. Immunohistochemical studies disclosed that the stromal cells resembled leiomyocytes, since vimentin and desmin were positive, and myoglobin was negative. An ultrastructural study supported these findings. The characteristics of these cells were compatible with those of congenital mesoblastic nephroma, which also is considered a metanephric tumor.

Adult↗
PubMed1987

Human skeletal muscle contains two major aminopeptidases: an anion-activated aminopeptidase B and an aminopeptidase M-like enzyme.

Two major aminopeptidases, an aminopeptidase B and an aminopeptidase M-like enzyme, were purified from human skeletal muscle by DEAE-cellulose, HPLC gel filtration, and hydroxyapatite column chromatographies. The purified aminopeptidase B exhibits a molecular weight of 76,000 under both native and denaturing conditions. The activity of the aminopeptidase B is regulated by C1 ions and other anions in vitro. On the other hand, the aminopeptidase M-like enzyme is a monomeric protein having a molecular weight of 96,000. It is capable of significantly cleaving Phe-, Leu-, Arg-, and Ala-aminoacyl bonds in the presence of 2-mercaptoethanol. The pH optima for both enzymes are around 7.0, and bestatin is an effective inhibitor of both enzymes.

Amino Acids↗
PubMed1987

A novel synthetic vitamin A-like compound (a polyprenoic acid derivative, E-5166) inhibits the release of arachidonic acid stimulated by epidermal growth factor.

Little is known about the mechanisms of anti-inflammatory activity of retinoids. A new synthetic vitamin A-like compound (polyprenoic acid derivative, E-5166) has a strong in vitro binding affinity to intracellular binding proteins for acidic retinoids. In order to elucidate the anti-inflammatory activity of E-5166, we studied the effect of E-5166 on the epidermal growth factor (EGF)-stimulated arachidonic acid (AA) release of pig epidermis. E-5166 significantly inhibited the EGF-stimulated AA release and this inhibitory effect of E-5166 required a longer incubation than hydrocortisone did. Furthermore, E-5166 inhibited the EGF-stimulated phosphatidylinositol (PI) turnover of pig epidermis. These results indicate that E-5166 inhibited the EGF-stimulated AA release through the inhibition of the EGF-stimulated PI turnover.

Animals↗
PubMed1987

Synthesis of p-hydroxyubenimex.

p-Hydroxyubenimex, (2S,3R)-3-amino-2-hydroxy-4-p-hydroxyphenylbutyryl-L-leucine, was synthesized starting from D-tyrosine. The structure and stereochemistry of the synthesized product were confirmed by comparison with p-hydroxyubenimex that was chemically transformed from ubenimex, an aminopeptidase inhibitor of microbial origin. Compared to ubenimex, p-hydroxyubenimex is more active against aminopeptidase B but less active against leucine aminopeptidase. By using the synthetic p-hydroxyubenimex as a reference sample, one of the metabolites of ubenimex was identified as p-hydroxyubenimex. The (2R,3R)-stereoisomer of p-hydroxyubenimex was also prepared. However, its activity against aminopeptidases was much weaker.

Aminopeptidases↗
PubMed1987

Dissociation between serine proteinases and proline related enzymes in spleen of MRL mouse as a model of systemic lupus erythematodes.

We investigated the changes in the activities of proteases and other hydrolytic enzymes in spleens of MRL mice as a model of systemic lupus erythematodes (SLE). Although there are various abnormalities in the activities of proteases in the spleens of such animals, a multivariate study helped to extract two important components. The first component, representing the activities of serine proteinases, tended to decrease with advancing age in MRL mice but not in control animals. The second component, representing Pro-IP and prolyl endopeptidase, tended to decrease with advancing age in control animals, but not in the MRL mice. The discrepancy between these two components may be related to the immunopathologic disturbances in this model.

Animals↗
PubMed1987

Decreased activities of serine proteinases in spleen of various murine models of systemic lupus erythematodes.

Previous studies indicated a relationship between immune deficiencies and abnormalities in the activities of various hydrolytic enzymes, including proteinases, in tissues. In the present study, we compared such activities in spleen among the three types of murine models of systemic lupus erythematodes (SLE) (i.e., New Zealand black/white mouse, MRL mouse, and BXSB mouse) and their controls. According to the results of multivariate analysis, it was shown that the most important enzymatic changes differentiating the pathologic animals from their controls were decreases in the activities of serine proteinases. Judging from the behavior of these enzymes in various immunological disturbances, it is likely that they play some important roles in pathophysiology of SLE.

Animals↗
PubMed1987

[A case of bilateral synchronous renal cell carcinoma managed with radical nephrectomy and ex-vivo tumor enucleation].

A 61-year-old female presented with gross hematuria and left flank pain. The arteriogram and CT scan revealed a large left renal tumor and multiple small right renal metastatic tumors. A chest X-ray and Ga scintigram showed no other metastatic lesions. A left radical nephrectomy and a right renal bench surgery were performed at the same time. The right multiple tumors were enucleated and the right kidney was autotransplanted into the right iliac fossa. The postoperative course was uneventful and the patient was free of tumor with good renal function. Renal preservation surgery was considered more beneficial for this patient than bilateral nephrectomy followed by hemodialysis.

Carcinoma, Renal Cell↗
PubMed1987

A multivariate study on enzymatic changes in limb muscles and heart muscle of dystrophic mice.

The present study was undertaken to elucidate further the enzymatic changes in dystrophic muscle using multivariate analysis. The activities of 14 kinds of enzymes, including 6 exopeptidases, 4 endopeptidases, beta-N-acetyl-D-glucosaminidase, phosphatase, esterase, and ribonuclease, were examined in forelimb and hindlimb muscles as well as in cardiac muscle of dystrophic mice and their controls. Two principal components identified from the enzymatic spectrum proved to be related especially to aminopeptidases and to serine proteinases, respectively. The enzymatic changes in forelimb muscle were very similar to those in hindlimb muscle when both were compared to those in cardiac muscle. The changes in aminopeptidases were unique to the limb muscles, whereas those of serine proteinases were unique to cardiac muscle of dystrophic mice. In the future, more attention should be focused on the role of exopeptidases in pathogenetic mechanisms of muscular dystrophy, because of the possibility that they play a major role in the initial stage of muscular dystrophy.

Animals↗
PubMed1986

Hydrophilic-hydrophobic microdomain surfaces having an ability to suppress platelet aggregation and their in vitro antithrombogenicity.

Block copolymers were synthesized by a coupling reaction of hydrophilic chains of poly(2-hydroxyethyl methacrylate) (PHEMA) with hydrophobic chains of polystyrene (PSt), or poly(dimethyl siloxane) (PDMS). Microstructures of films of the block copolymers exhibited a hydrophilic-hydrophobic microphase separated structure. For evaluation of in vivo antithrombogenicity, small diameter tubes (1.5 mm I.D. and 20 cm length) coated by the copolymers on their internal surfaces were implanted in rabbits as arteriovenous shunts. Occlusion times of the tubes, measured by formation of thrombus, were three days for PHEMA, two days for PSt, and three days for PDMS. The block copolymers showed excellent antithrombogenic properties: occlusion times were 20 days for HEMA-St block copolymer and 12 days for HEMA-DMS block copolymers. In vitro examination of polymer-platelet interaction in terms of platelet adhesion and aggregation, which are important initial processes of blood coagulation, demonstrated suppressed adhesion and aggregation on microdomain surfaces constructed of hydrophilic and hydrophobic block copolymers. From both in vivo and in vitro examination, it was concluded that HEMA-St and HEMA-DMS block copolymers showed promising antithrombogenic activities by suppressing activation and aggregation of platelets.

Animals↗
PubMed1986

Effects of 12-o-tetradecanoylphorbol-13-acetate and polyprenoic acid derivative on calcium-activated phospholipid-dependent protein kinase of pig skin.

12-o-Tetradecanoylphorbol-13-acetate (TPA) activates calcium-activated, phospholipid-dependent protein kinase (protein kinase C) partially purified in an ion exchange column from pig epidermis. Protein kinase C was activated by TPA in a concentration-dependent manner with simultaneous addition of Ca2+ and phospholipid. Polyprenoic acid derivative (E5166) which is a newly synthesized retinoic acid derivative, inhibited the TPA activation of protein kinase C. This inhibition may explain the mechanisms by which retinoids inhibit TPA-induced tumor promotion.

Animals↗
PubMed1986

Phosphorylation of soluble pig epidermal proteins by endogenous calcium-activated, phospholipid-dependent protein kinase.

Endogenous calcium-activated, phospholipid-dependent protein kinase phosphorylates pig epidermal protein. Pig epidermis was homogenized and centrifuged at 30,000 X g for 30 min. The supernatant was incubated with or without calcium and phospholipid. A 97 kD soluble protein from pig epidermis was phosphorylated in the presence of calcium and phosphatidylserine. The phosphorylation reaction occurred immediately. With the use of two-dimensional polyacrylamide gel electrophoresis, it was shown that the 97 kD fragment was a basic protein, and that several small proteins were also phosphorylated. The characterization of these proteins is yet to be undertaken.

Animals↗