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Biomedical subjects

S Miyata

Publications and source records attributed to S Miyata.

At least 181 records · Page 10Linked to original sources

WF11605, an antagonist of leukotriene B4 produced by a fungus. I. Producing strain, fermentation, isolation and biological activity.

WF11605, a new antagonist of leukotriene B4 (LTB4) was isolated as a product of fungal strain F11605. The molecular formula of WF11605 was determined to be C38H60O11. WF11605 inhibited LTB4-induced chemotaxis of rabbit polymorphonuclear leukocytes (PMNLs) with an IC50 value of 1.7 x 10(-7) M and blocked 3H-LTB4 binding to PMNL membranes at 5.6 x 10(-6) M (IC50). WF11605 also inhibited LTB4-induced degranulation of rabbit PMNLs at 3.0 x 10(-6) M (IC50). However, WF11605 did not show any inhibitory effect on platelet activating factor (PAF)- and N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP)-induced degranulation at concentrations up to 10(-4) M. These results suggest that WF11605 is a specific antagonist of LTB4.

Animals↗

WS-7338, new endothelin receptor antagonists isolated from Streptomyces sp. No. 7338. I. Taxonomy, fermentation, isolation, physico-chemical properties and biological activities.

WS-7338 A, B, C and D, novel endothelin receptor antagonists, have been isolated from fermentation broth of Streptomyces sp. No. 7338. These antagonists were purified from the culture mycelium by extraction with acetone, followed by carbon column chromatography and HPLC. Among them, WS-7338 B showed good activity in an endothelin receptor binding assay with an IC50 of 2.7 x 10(-7) M.

Amino Acid Sequence↗

WS-7338, new endothelin receptor antagonists isolated from Streptomyces sp. No. 7338. II. Biological characterization and pharmacological characterization of WS-7338 B.

WS-7338, produced by Streptomyces sp. No. 7338, was found to be a competitive and specific antagonist against ET-1 receptors in in vitro studies and WS-7338 B is also active in vivo. Furthermore, WS-7338 B was a specific antagonist for vascular ET-1 receptors (ETA receptors) and significantly prevented the accumulation of intracellular inositol 1,4,5-triphosphate (IP3) in endothelin treated rat aorta tissues.

Animals↗

Simple hypothermic retrograde cerebral perfusion during aortic arch replacement. A preliminary report on two successful cases.

We recently found that hypothermic retrograde cerebral perfusion can be performed by simply elevating the central venous pressure in Trendelenburg's position while the aortic arch is open. In this technique, with an occlusion balloon in the descending aorta, deep hypothermic perfusion of the lower half of the body is performed as oxygen-rich venous blood supplies the brain. Two successful cases are reported: one of dissecting aortic aneurysm, DeBakey type II, with a true aortic arch aneurysm, in a 53-year-old woman, and one of acute aortic dissection, DeBakey type I, in a 53-year-old man. With the brain under retrograde perfusion at a rectal temperature of 15 degrees C and a central venous pressure of 15 mm Hg, replacement of the ascending to the descending aorta in the former case and to the proximal aortic arch in the latter case was successful. Cerebral circulatory arrest times were 81 and 65 minutes, respectively. No neurologic deficit was found postoperatively. It is suggested that this simple technique protected the brain for a long period of cerebral circulatory arrest during the aortic arch operation by supplying it with oxygen and simplifying the operative procedure.

Aorta, Thoracic↗

[Simple hypothermic retrograde cerebral perfusion for brain protection during aortic arch surgery].

We have recently found that retrograde cerebral perfusion can be performed by simply elevating central venous pressure to 15 mmHg in the Trendelenburg position when the aortic arch is open during aortic arch surgery. During deep hypothermic (15 degrees C) perfusion of the lower half of the body with the descending aorta occluded, and with single cannulation of the right atrium for drainage, oxygen-saturated venous blood perfuses the brain retrogradely, supplying it with oxygen. This method renders clamping of the aortic arch and the arch vessels unnecessary. Eleven cases of aortic arch aneurysm (9 males, 2 females; 5 true aneurysms, 5 dissecting aneurysms, one combined aneurysm; mean age, 63 years) were operated using this technique, whose clinical significance was then evaluated. Median sternotomy was performed in 4 cases, left thoracotomy in 7. Patch replacement was performed in 2 cases and graft replacement in 9 cases (the proximal arch in 2, the whole arch in 2, the distal arch in 5). In two cases coronary artery bypass surgery using the internal thoracic artery was performed simultaneously via lateral thoracotomy. Operation time was 517 +/- 139 min, pump time was 211 +/- 34 min, cardiac arrest time was 84 +/- 34 min and the lowest rectal temperature was 15.7 +/- 1.1 degrees C. In the venous return, PO2 was 188 +/- 136 mmHg, and SO2 97.5 +/- 2.9%, the respective values in the retrogradely perfused blood in the aortic arch being 46 +/- 12 mmHg and 68.8 +/- 18.8%.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Competitive binding radioassay for the determination of 5-fluorodeoxyuridine and 5-fluorodeoxyuridine-5'-monophosphate levels in plasma and tumor tissue.

A competitive binding radioassay was developed to measure 5-fluoro-2'-deoxyuridine (FUDR) as well as 5-fluoro-2'-deoxyuridine monophosphate (FdUMP), FdUMP has been measured by a competitive binding radioassay with thymidylate synthase as the binding enzyme (TS assay). FUDR was enzymatically converted to FdUMP by thymidine kinase, and then the converted FdUMP was measured by the competitive binding assay to determine the concentration of FUDR in plasma and tumor tissue. As little as 100 pg/ml of FUDR or 50 pg/ml of FdUMP can be detected quantitatively by this method. When TS assay and high-performance liquid chromatography were compared for the measurement of FUDR and FdUMP levels in plasma and tumor tissue of Ehrlich carcinoma (EC)-bearing mice following administration of FUDR, a close agreement was observed for FUDR levels, though low FdUMP levels were detectable only by the TS assay method. The examination of intracellular metabolism of FUDR in EC cells by this method showed that metabolic conversion of FUDR into FdUMP or 5-fluorouracil is rapid. Thus, we have established a highly sensitive method for measuring not only FdUMP but also FUDR with TS assay. This should be very useful for experimental and clinical studies on fluoropyrimidines.

Animals↗

Mechanisms of protection against damage mediated by the Maillard reaction in aging.

In order to prevent or escape the ongoing damage to proteins and DNA resulting from amino-carbonyl reactions, the organism has to have powerful defense mechanisms. If the Maillard reaction played a role in determining longevity among mammalian species, one would expect protective mechanisms to be more developed in long- versus short-lived species. This article summarizes current knowledge in this field, and discusses the concept of anti-Maillard mechanisms as a basis for the genetic regulation of molecular damage by reducing sugars in aging and diabetes.

Aging↗

Calcium dependence of ouabain-induced contraction in aortas from spontaneously hypertensive rats.

The calcium sensitivity of ouabain-induced contractions of aortic strips from spontaneously hypertensive rat (SHR) was examined using several drugs which affect Na+ and Ca2+ movements across the cell membrane, and the results were compared with those obtained with age-matched Wistar-Kyoto rat (WKY). The Ca2+ concentration-response curves (10(-3) M ouabain-treated preparations) made with aortic strips from SHR lay to the left of those made with aortic strips from WKY (Ca EC50 values: SHR, 0.51 +/- 0.16 mM, n = 6; WKY, 1.23 +/- 0.41 mM, n = 7; P less than 0.05). Amiloride (a Na+ entry blocker) and nifedipine (a Ca2+ entry blocker) attenuated the sensitivity to Ca2+ of SHR and WKY aortic strips. With 2 x 10(-4) M amiloride, WKY vessels showed a 1.3-fold increase in the Ca EC50 value and SHR a 2.1-fold increase. With 10(-6) M nifedipine. WKY vessels showed a 1.1-fold increase in the Ca EC50 value and SHR a 1.5-fold increase. Addition of monensin (Na ionophore) produced a dose-dependent potentiation in ouabain-treated aorta from WKY, but not in ouabain-treated aorta from SHR. Addition of 1.5 x 10(-5) M A23187 (Ca ionophore) eliminated the difference between the Ca2(+)-induced contractions in aortas from SHR and WKY. These results suggest that enhancement of Ca2+ influx by Na(+)-Ca2+ exchange and/or voltage-dependent Ca2+ channels in vascular smooth muscle cell membranes may be an important factor in the difference between ouabain-induced contractions in aorta from SHR and WKY.

Animals↗

Effects of H-7 (protein kinase inhibitor) and phorbol ester on aortic strips from spontaneously hypertensive rats.

We investigated the vascular responsiveness to vasoactive agents and the inhibition by H-7 (1-(5-isoquinoline-sulfonyl)-2-methylpiperazine), which inhibits cyclic nucleotide-dependent protein kinases and protein kinase C(PKC) equally potently in helically cut strips of thoracic aortas from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). The susceptibility of norepinephrine (NE)- and angiotensin II (Ang II)-induced contractions to H-7 was significantly higher in the aortas from SHR than in those from WKY. H-7 decreased the contractile responses to KCl to a similar extent in both strains without affecting the high K(+)-stimulated Ca2+ influx. H-7 produced a shift to the right of the dose-response curve for the PKC activator, 12-o-tetradecanoylphorbol-13-acetate (TPA) in the case of SHR aortas, while no such shift was noted in tissues from WKY. Functional alterations in the PKC branch of the Ca2+ messenger system in vascular smooth muscle may play an important role in SHR during the sustained contraction.

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

Purification and characterization of a protease from Xenopus embryos.

A proteolytic enzyme was purified from Xenopus embryos. The purification procedure consisted of fractionation of an extract of embryos with acetone, gel filtration of Sephadex G-75 and chromatography on carboxymethyl-cellulose and hydroxylapatite. The preparation of enzyme appeared to be homogeneous as judged by electrophoresis in polyacrylamide gels. This protease had a molecular mass of 43-44 kDa and was composed of two subunits with molecular masses of 30 kDa and 13 kDa. The optimal pH of the reaction catalysed by the protease was approximately 4.0. This proteolytic activity was inhibited by antipain, leupeptin and iodoacetic acid; it was not affected by phenylmethylsulfonyl fluoride and pepstatin; and it was enhanced by dithiothreitol. In the presence of RNA, the optimal pH was shifted from pH 4.0 to pH 4.5. The protease was activated by addition of total RNA from Xenopus embryos, by poly(rU) or poly(rG). In contrast, after addition of tRNA or poly(rC), no activation of the protease was observed.

Animals↗

Aging of proteins: immunological detection of a glucose-derived pyrrole formed during maillard reaction in vivo.

Recent work from this laboratory revealed that glucose-derived pyrroles can form with model amines under physiological conditions (Niroge, F. G., Sayre, L. M., and Monnier, V. M. (1987) Carbohydr. Res. 167, 211-220). The major extractable product, 5-hydroxymethyl-1-alkylpyrrole-2-carbaldehyde (named by us pyrraline) was labile to acid hydrolysis. To allow its detection in proteins undergoing advanced glycosylation, an enzyme-linked immunosorbent assay was developed. An immunogen consisting of epsilon-caproyl pyrraline (hapten) was linked onto poly-L-lysine (114:1) and used to raise polyclonal antibodies in the rabbit. High antibody titers were obtained 16 weeks after immunization. The antibody cross-reacted with butyl pyrraline (88%), propyl pyrraline (8%), lysyl pyrraline (2%), and neopentyl pyrraline (1.3%). A time-related increase in pyrraline immunoreactivity was observed in bovine serum albumin incubated with glucose (1000 mM), glycated lysine (50 mM), and 3-deoxyglucosone (50 mM) which reached 25, 300, and 350 pmol/mg, respectively, after 30 days. Mean level of protein pyrraline immunoreactivity were 27.0 +/- 7.2 and 43.3 +/- 11.7 pmol/mg in serum albumin from control and diabetic subjects, respectively (p less than 0.001). The pathobiological relevance of pyrraline may relate to its reported antiproteolytic and mutagenic properties. In addition, glucose-derived pyrroles may play a role in diabetic neuropathy in analogy to pyrroles formed during hexane-induced neuropathy.

Aging↗

[CALLA-positive leukemic multiple myeloma of IgA-kappa type].

A 73-year-old man was admitted into the hospital because of lumbago in October, 1986. Laboratory examination on admission showed anemia, an IgA-kappa Bence Jones proteinemia. The bone marrow picture disclosed a marked involvement by the neoplastic cells, followed by leukemic conversion 2 weeks later. The leukemic cells displayed a lymphoblastoid appearance on light microscopy, but rather compatible with plasma cells on electron microscopy, showing some strands of rough endoplasmic reticulum and a prominent Golgi apparatus in the cytoplasm. The cells expressed a wide spectrum of surface markers, including those of plasma cell (PCA-1, OKT10), B cell (B1, sIg) and CALLA. Reverse hemolytic plaque assay disclosed the immunoglobulin production of monoclonal kappa chain, but a heavy chain production was recognized only in a small proportion of the cells. Under the diagnosis of multiple myeloma, he was treated with vincristine, cyclophosphamide, and prednisolone. But he died of renal failure complicating hypercalcemia after only three months of the admission in accordance with previous reports that CALLA-positive myeloma was associated with poor prognosis. This case may also represent the clinical, morphological and phenotypic diversity in multiple myeloma.

Aged↗

[Properties of factor VIII/von Willebrand factor in two highly-purified factor VIII concentrates, Hemofil M and Monoclate, using monoclonal antibodies].

Properties of F. VIII/vWF in highly-purified factor VIII concentrates were examined using monoclonal antibodies. The F. VIII: C levels obtained with the chromogenic assay agreed with those obtained with the one-stage clotting method. The ratio between F. VIII: Ag and F. VII: C in Hemofil M and Monoclate was 1.09 and 1.34, respectively. The F. VIII: Ag levels assayed by monoclonal ELISAs were the same as those assayed by polyclonal ELISA, except that those assayed by C 5-ELISA tended to be higher. The ratio between F. VIII: Ag and vWF: Ag in Hemofil M and Monoclate was 105 and 45, respectively. Both concentrates lacked the large multimers of vWF and showed the intensification of the satellite bands. SDS-PAGE patterns showed almost no contamination. Immunoblot analysis revealed that F. VIII in both concentrates could react with 6 kinds of monoclonal antibodies to F. VIII. These results suggest that the fundamental structure of F. VIII molecule for coagulant activity in both concentrates are preserved.

Antibodies, Monoclonal↗

[Imaging diagnosis of hepatocellular carcinomas].

With the rapid progress of various imaging methods, including ultrasonography (US), computed tomography. (CT), digital subtraction angiography (DSA) and magnetic resonance imaging (MRI), it has become possible to detect small liver cancer less than 2 cm in diameter, and the prognosis of hepatocellular carcinomas is now improving rapidly. However, the accurate detection of smaller lesions about 1 cm in diameter and their differential diagnosis are difficult by conventional imaging methods such as US, CT and arteriography. For this purpose, we stressed the effectiveness of the combined use of CT and arteriography (the so-called CT arteriography), CT during arterial portography or Lipiodol CT. The promising future of MRI in this field is also discussed.

Appointments and Schedules↗