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Biomedical subjects

C H Ryu

Publications and source records attributed to C H Ryu.

7 recordsLinked to original sources

A novel strategy for designing irreversible inhibitors of metalloproteases: acetals as latent electrophiles that interact with catalytic nucleophile at the active site.

A new strategy for design of irreversible inactivators for carboxypeptidase A (CPA), a prototypic zinc protease, has been developed by exploiting the property of acetals to generate an oxacarbenium ion intermediate in the conversion into the corresponding carbonyl compounds. The design strategy is exemplified by 2-benzyl-5-alkyl-3,5-dioxapentanoic acids (1a-c). Interestingly, (R)-1b is slightly more potent than an (S)-1b as an inactivator of CPA.

Alkanes↗

Angiopoietin-1 inhibits irradiation- and mannitol-induced apoptosis in endothelial cells.

BACKGROUND AND PURPOSE: Angiopoietin-1 (Ang1) is a vasculogenic factor that signals through the endothelial cell-specific Tie2 receptor tyrosine kinase. We recently reported that Ang1 prevented apoptosis induced by serum deprivation in endothelial cells. In this study, we examined whether Ang1 prevents apoptosis in endothelial cells treated with irradiation or clinical concentrations of mannitol. METHODS AND RESULTS: ++Ang1 prevented irradiation- and mannitol-induced apoptosis in human umbilical vein endothelial cells in a dose-dependent manner. Pretreatment with soluble Tie2 receptor, but not Tie1 receptor, blocked the antiapoptotic effect of Ang1. Two phosphatidylinositol 3'-kinase (PI3-kinase)-specific inhibitors, wortmannin and LY294002, blocked the Ang1-induced antiapoptotic effect. The antiapoptotic potency of Ang1 was similar to or greater than that of vascular endothelial growth factor, basic fibroblast growth factor, and endothelin-1. Ang1 also prevented apoptosis in cultured endothelial cells from porcine pulmonary and coronary arteries and in endothelial cells of explanted rat aorta. CONCLUSIONS: Ang1 promotes the survival of endothelial cells in irradiation- and mannitol-induced apoptosis through Tie2 receptor binding and PI3-kinase activation. Pretreatment with Ang1 could be beneficial in maintaining normal endothelial cell integrity during intracoronary irradiation or systemic mannitol therapy.

Angiopoietin-1↗

Comparison of tear secretion and tear film instability after photorefractive keratectomy and laser in situ keratomileusis.

PURPOSE: To evaluate and compare tear secretion and tear film instability following photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK). SETTING: Department of Ophthalmology, Yonsei University School of Medicine, Seoul, Korea. METHODS: In a prospective study, 36 eyes (21 patients) had PRK and 39 eyes (25 patients) had LASIK to correct myopia. Tear secretion and tear film instability were tested preoperatively and 3 and 6 months postoperatively using Schirmer test values, tear breakup time (BUT) scores, and tear osmolarity. RESULTS: Six months after surgery, the change in Schirmer test values from preoperative levels was -14.57% +/- 6.39% (SD) in the PRK eyes and -23.40% +/- 5.94% in the LASIK eyes and the change in BUT scores, -12.54% +/- 8.28% and -18.79% +/- 13.01%, respectively. The change in tear osmolarity was 14.95% +/- 6.46% and 35.63% +/- 8.51%, respectively. CONCLUSIONS: The decrease in tear secretion was greater after LASIK than after PRK at 6 months. Proper treatment of dry eye is required after LASIK and PRK, particularly in the LASIK postoperative period.

Adult↗

Cell cycle regulators during human atrial development.

OBJECTIVES: The molecular mechanisms that regulate cardiomyocyte cell cycle and terminal differentiation in humans remain largely unknown. To determine which cyclins, cyclin dependent kinases (CDKs) and cyclin kinase inhibitors (CKIs) are important for cardiomyocyte proliferation, we have examined protein levels of cyclins, CDKs and CKIs during normal atrial development in humans. METHODS: Atrial tissues were obtained in the fetus from inevitable abortion and in the adult during surgery. Cyclin and CDK proteins were determined by Western blot analysis. CDK activities were determined by phosphorylation amount using specific substrate. RESULTS: Most cyclins and CDKs were high during the fetal period and their levels decreased at different rates during the adult period. While the protein levels of cyclin D1, cyclin D3, CDK4, CDK6 and CDK2 were still detectable in adult atria, the protein levels of cyclin E, cyclin A, cyclin B, cdc2 and PCNA were not detectable. Interestingly, p27KIP1 protein increased markedly in the adult period, while p21CIP1 protein in atria was detectable only in the fetal period. While the activities of CDK6, CDK2 and cdc2 decreased markedly, the activity of CDK4 did not change from the fetal period to the adult period. CONCLUSION: These findings indicate that marked reduction of protein levels and activities of cyclins and CDKs, and marked induction of p27KIP1 in atria, are associated with the withdrawal of cardiac cell cycle in adult humans.

Adult↗

Inhibition of papain with 2-benzyl-3,4-epoxybutanoic acid esters. Mechanistic and stereochemical probe for cysteine protease catalysis.

Papain, a prototypic cysteine protease was inactivated by methyl and benzyl esters of (2S,3S)-2-benzyl-3,4-epoxybutanoic acid. On the other hand, methyl ester of (2S,3R)-2-benzyl-3,4-epoxybutanoic acid was shown to be a competitive inhibitor for the enzyme. It was inferred from the inactivation stereochemistry that in the papain catalytic reaction the nucleophilic attack of the side chain thioalkoxide of Cys-25 on the scissile peptide bond of substrates occurs in the 're' fashion. The papain inactivating potency of (2S,3S)-2-benzyl-3,4-epoxybutanoic acid methyl ester was enhanced over three-fold in a pH 8.0 solution compared with in the neutral solution. This together with our previous observation with alpha-chymotrypsin and the recent theoretical treatment of the enzymic reaction of papain, suggest that in the inactivation of papain by oxirane containing inhibitors, the oxirane does not need to be activated by prior protonation as thought previously. The oxirane ring is sufficiently labile that the unprotonated oxirane moiety can undergo an electrophilic reaction with the Cys-25 thiolate.

Binding Sites↗

Transfer of conjugative plasmid pAM beta 1 from Lactococcus lactis to mouse intestinal bacteria.

Conjugal transfer of plasmid pAM beta 1 from Lactococcus lactis to intestinal bacteria of BALB/c mice was studied. Plasmid transfer was observed to Enterococcus faecalis in vitro by a filter mating method with transfer frequencies of 2.3 x 10-3 and with lower frequencies to other species. In vivo, using gastric intubation with the pAM beta 1-bearing Lactococcus lactis as donor and Ent. faecalis as recipient, a few transconjugants were detected from faecal Ent. faecalis. However, when these mice were given erythromycin through drinking water, a large number of conjugated Ent. faecalis were detected in faeces. Plasmid transfer to Ent. faecalis occurred at high frequency, 1.2 x 10-3, in mice whose anus was artificially closed after gastric intubation with pAM beta 1-bearing Lactococcus lactis. These results demonstrate clearly that pAM beta 1 transfer occurs between Gram-positive bacteria in the gut of mice harbouring many species of bacteria.

Animals↗

The incidence of Listeria species in retail foods in Japan.

Meat, fish and vegetable products obtained at retail shops in or around Tokyo were examined for Listeria contamination. Listeria spp. were isolated from 43 (56.6%) out of 76 samples of meat products. L. monocytogenes occurred in 26 (34%) of the samples, L. monocytogenes was isolated from 7 (6.1%) out of 114 samples of fish and fish products including 'ready-to-eat' foods. Listeria was not isolated from any of 21 samples of vegetable and vegetable product including 'ready-to-eat' foods investigated.

Fish Products↗