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Biomedical subjects

I C Kim

Publications and source records attributed to I C Kim.

At least 37 records · Page 2Linked to original sources
PubMed1996

In-vitro and in-vivo antibacterial activity of LB10517, a novel catechol-substituted cephalosporin with a broad antibacterial spectrum.

LB10517 is a new injectable cephalosporin with a broad spectrum of antibacterial activity against Gram-positive and Gram-negative bacteria. LB10517 inhibited 90% of methicillin-susceptible Staphylococcus aureus (MSSA) at 0.25 mg/L (MIC90), and was 8-fold more active than cefpirome. LB10517 was two- or four-fold more active than cefpirome against methicillin-susceptible Staphylococcus epidermidis (MSSE), Streptococcus pyogenes and Enterococcus faecalis. Both methicillin-resistant S. aureus (MRSA) and methicillin-resistant S. epidermidis (MRSE) were highly resistant to all compounds. LB10517 activity against most Enterobacteriaceae was comparable to or greater than that of cefpirome, and it also showed high activity against Pseudomonas aeruginosa. In a mouse septicaemia model, LB10517 exhibited excellent protective effects. In a respiratory tract infection model, the protective effect of LB10517 was comparable to that of cefpirome and ceftazidime. It was highly stable to hydrolysis by beta-lactamases, showing better physiological efficiency for TEM-9 than the other test compounds. LB10517 had the most potent antibacterial activity against beta-lactamase producing resistant strains. LB10517 did not induce beta-lactamase production in Enterobacter cloacae 1194E.

Animals↗
PubMed1996

In vitro and in vivo evaluations of LB20304, a new fluoronaphthyridone.

In vitro activity of LB20304 against 1,231 clinical isolates was evaluated and compared with those of ciprofloxacin, sparfloxacin, lomefloxacin, and ofloxacin. LB20304 demonstrated the most potent activity against gram-positive bacteria. It was 32- to 64-fold more active than ciprofloxacin against methicillin-susceptible Staphylococcus aureus, methicillin-resistant S. aureus, methicillin-resistant Staphylococcus epidermidis, and Streptococcus pneumoniae (penicillin G resistant). LB20304 was also highly active against most members of the family Enterobacteriaceae. Its activity was more potent than those of sparfloxacin, ofloxacin, and lomefloxacin and comparable to that of ciprofloxacin. The protective activities of LB20304 against systemic infections caused by gram-positive bacteria in mice were superior to those of ciprofloxacin and sparfloxacin. Against infections by gram-negative bacteria, LB20304 was slightly less active than ciprofloxacin.

Animals↗
PubMed1996

In vitro and in vivo activities of LB10522, a new catecholic cephalosporin.

In vitro activity of LB10522 was compared with those of cefpirome, ceftazidime, ceftriaxone, and cefoperazone against clinical isolates. Against gram-positive bacteria, LB10522 was most active among the compounds tested. It was fourfold more active than cefpirome against methicillin-susceptible Staphylococcus aureus and Enterococcus faecalis. LB10522 was highly effective against most members of the family Enterobacteriaceae tested. Ninety percent of isolates of Escherichia coli, Klebsiella oxytoca, Proteus vulgaris, Proteus mirabilis, and Salmonella spp. were inhibited at a concentration of < or = 0.5 micrograms/ml. These activities were comparable to those of cefpirome. Against Pseudomonas aeruginosa, LB10522 with a MIC at which 90% of the isolates are inhibited of 2 micrograms/ml was 16- and 32-fold more active than ceftazidime and ceftazidime against systemic infections caused by Staphylococcus aureus giorgio, Streptococcus pneumoniae III, Pseudomonas aeruginosa 1912E, Escherichia coli 851E, Proteus mirabilis 1315E, Serratia marcescens 1826E, and Acinetobacter calcoaceticus Ac-54. LB10522 was very resistant to hydrolysis by various beta-lactamases such as TEM-3, TEM-7, SHV-1, FEC-1, and P-99. LB10522 did not induce beta-lactamase in Enterobacter cloacae 1194E, although most of the reference cephalosporins acted as inducers of beta-lactamase in this strain. Time-kill study showed that LB10522, at concentrations of two or four times the MIC, had a rapid bactericidal activity against Staphylococcus aureus 6538p, Escherichia coli 851E, and Pseudomonas aeruginosa 1912E.

Animals↗
PubMed1996

Synergistic inhibitory effect of angiotensin-converting enzyme inhibitor and heparin on intimal hyperplasia after rat aorta injury.

The respective efficacies of angiotensin-converting enzyme (ACE) inhibitor and standard heparin were investigated with respect to their inhibitory effects on intimal hyperplasia after balloon denudation of rat aorta. Local angiotensin II effects in the artery wall may participate in regulation of the vascular response to arterial injury, apparently independent of the plasma renin and angiotensin system. ACE inhibitors have been shown to block intimal hyperplasia after arterial injury in rats. Increasing evidence points toward an inhibitory effect of heparin on intimal hyperplasia independent of anticoagulation. Balloon catheter aortic denudation was performed in 25 rats pharmacologically treated from six days or one day before to fourteen days after surgery and split into four groups: group A (control group), normal feeding; group B (ramipril group), ramipril 10 mg/kg/day orally; group C (heparin group), heparin 1200 IU/kg/day subcutaneously; group D (combined group), both ramipril and heparin. Animals were killed and aortas were perfused and fixed at physiologic pressure fourteen days after denudation. Cross-sectional intima-to-media area ratios (I-M ratio) were calculated by an image analyze system.

Angioplasty, Balloon↗
PubMed1995

Chemical synthesis of 15-ketosterols and their inhibitions of cholesteryl ester transfer protein.

Described herein are the chemical syntheses of 3 beta-hydroxy-5 alpha-cholest-8(14)-en-15-one and 3 beta-hydroxy-5 alpha-cholest-8(14),16-dien-15-one from diosgenin and the examinations of their ability to inhibit the cholesteryl ester transfer protein (CETP). Clemmensen reduction of diosgenin gave cholest-5-ene-3 beta, 16 beta,26-triol. Tosylation of the latter compound gave cholest-5-ene-3 beta,16 beta,26-triol 26-tosylate which, upon reduction with LiAIH4, gave cholest-5-ene-3 beta,16 beta-diol. Hydrogenation-benzoylation of the latter to 5 alpha-cholest-3 beta,16 beta-diol 3 beta-benzoate followed by mesylation-elimination gave 5 alpha-cholest-16-ene-3 beta-ol 3 beta-benzoate. Controlled oxidation of the latter with CrO3-dimethylpyrazole gave 3 beta-hydroxy-5 alpha, 14 alpha-cholest-16-en-15-one 3 beta-benzoate. Oxidation of delta 16-15-one with SeO2 gave 3 beta-hydroxy-5 alpha-cholest-8(14),16-dien-15-one 3 beta-benzoate along with 3 beta-hydroxy-5 alpha, 14 beta-cholest-16-en-15-one 3 beta-benzoate. Selective hydrogenation of the delta 8(14),16-15-ketosteryl ester, followed by base hydrolysis gave 3 beta-hydroxy-5 alpha-cholest-8(14)-en-15-one. Hydrolysis of 3 beta-hydroxy-5 alpha-cholest-8(14),16-dien-15-one 3 beta-benzoate in basic media gave 3 beta-hydroxy-5 alpha-cholest-8(14),16-dien-15-one. The effects of the 15-ketosterols on the CETP activity were studied in vitro by incubating cholesteryl ester donor (HDL), cholesteryl ester acceptor (LDL) and human plasma as a CETP source at 37 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

Anticholesteremic Agents↗
PubMed1995

Characterization of the Bacillus stearothermophilus BR219 phenol hydroxylase gene.

The catabolic genes pheA and pheB, coding for the conversion of phenol to catechol and catechol to 2-hydroxymuconic semialdehyde, respectively, have been cloned from Bacillus stearothermophilus BR219 into Escherichia coli. Following its localization on the 11-kb B. stearothermophilus DNA insert by deletion and expression analysis, the phenol hydroxylase gene pheA was subcloned as a 2-kb HindIII fragment, whose transformant expressed the enzyme after phenol induction and even more strongly after o-, m-, and p-cresol induction. In vitro transcription-translation experiments indicated that the phenol hydroxylase and catechol 2,3-dioxygenase enzymes are constituted of single subunits with molecular weights of 44,000 and 33,000, respectively. Nucleotide sequencing of the pheA gene revealed a strong similarity to flavin hydroxylases from Rhodococcus and Streptomyces species. Hybridization experiments indicated that the fragment containing PheA and PheB is located on a 66-kb plasmid in the parental thermophile.

Amino Acid Sequence↗
PubMed1994

Endothelial F-actin changes in the alkali burned rabbit cornea.

The healing mechanism of corneal endothelium after alkali burn was not completely understood. Rabbit cornea was burned with 1N sodium hydxoside for 1 minute. Endothelial F-actin was stained with NBD-phallacidin in regular sequence to find out the details of endothelial healing after alkali burn. F-actin was completely destroyed leaving a sharp margin against the unaffected area 1 hour after the burn. In the 3, 5 and 7 day specimens, highly active F-actin reactions were noted at the wound margin. New multiple F-actin layers, arising from the intact endothelium near the wound margin, were noted in the 9 day specimen. In the 8 1/2 month specimen, the endothelial defected area was covered by large primitive cells, each of which showed F-actin fiber bundles in the cytoplasm with a large nuclear shadow. Nearly all of the large primitive cells showed F-actin fibers arranged in shapes of cell junctions. Twelve months after the burn, endothelial defects were not found. Nearly all of the endothelial cells were normal in size and shape except for some mushroom-like projections toward the anterior chamber in some areas. Nineteen months after the burn, the endothelial cells were normal. Endothelial wound healing process can be continued even 1 year after the alkali burn in rabbit cornea.

Actins↗
PubMed1993

Transforming growth factor beta modulates gonadotropin receptor expression in porcine and rat granulosa cells differently.

Almost without exception, the studies to date describing the effects of transforming growth factor beta (TGF beta) upon various ovarian cell types have utilized the subtype TGF beta 1. Since TGF beta 1 and TGF beta 2 have been demonstrated to influence major developmental processes differentially during hematopoiesis and embryogenesis, we investigated in two species (rat and pig) whether they might also differentially modulate principal regulatory processes of ovarian cellular differentiation, specifically FSH and/or LH receptor (FSHR, LHR) expression. TGF beta 1 plus FSH significantly stimulated LHR binding levels by cultured granulosa cells (GC) from prepubertal diethylstilbestrol-treated rats. TGF beta 2 produced the same effect. In porcine GC from 1-3-mm antral follicles, TGF beta 1 and TGF beta 2 again acted similarly, but the direction of the response was opposite to that in the rat GC system. This difference could not be ascribed to the fact that the GC utilized represented different stages of follicular development in vivo because TGF beta 1 also potentiated FSH-dependent LHR induction in GC from antral follicles of cycling rats at all stages of the estrous cycle. The major effect of TGF beta 1 on FSHR expression in the rat system was to increase binding by attenuating the down-regulatory action of cholera toxin (CTX) or FSH. In the porcine system, TGF beta reduced FSHR binding at FSH or CTX concentrations that enhanced expression, and it did not attenuate the down-regulatory effect of FSH or CTX at higher doses. In summary, TGF beta up- or down-regulated LHR and FSHR binding coordinately within species.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Analysis of antigenic characteristics of Rickettsia tsutsugamushi Boryong strain and antigenic heterogeneity of Rickettsia tsutsugamushi using monoclonal antibodies.

Twenty-four monoclonal antibodies were produced by immunizing BALB/c mice with Rickettsia tsutsugamushi Boryong strain and used for the analysis of antigenic characteristics of R.tsutsugamushi Boryong strain and antigenic heterogeneity of R.tsutsugamushi by indirect immunofluorescent(IF) test. R. tsutsugamushi Kato, Karp, Gilliam, TA686, TA716, TA763, TC586, TH1817, and Boryong were used for the analysis of antigenic heterogeneity of R.tsutsugamushi. Five monoclonal antibodies were reactive with 27-kDa protein, four monoclonal antibodies were reactive with 47-kDa protein, and eight monoclonal antibodies were reactive with 56-kDa protein of R.tsutsugamushi Boryong strain. The reactive protein of seven monoclonal antibodies could not be identified by immunoblotting method. All monoclonal antibodies to 27-kDa protein and three monoclonal antibodies to 47-kDa protein, and five monoclonal antibodies to 56-kDa protein were reactive with three to eight strains among nine strains of R. tsutsugamushi tested. One monoclonal antibody reactive to 47-kDa protein(KI18) and two monoclonal antibodies reactive to 56-kDa protein(KI36, and KI37) reacted with all the strains of R. tsutsugamushi tested. Strain-specific monoclonal antibody(KI58) could be found among antibodies which were reactive with 56-kDa protein. There was no strain which showed same reactivity pattern to these 24 monoclonal antibodies among nine strains. From this results, it could be concluded that Boryong strain is antigenically different from other strains of R.tsutsugamushi and antigenic heterogeneity of R.tsutsugamushi is due to the antigenic diversity of several proteins of R. tsutsugamushi including 56-kDa protein.

Animals↗
PubMed1992

Catalytic properties of the cloned amylase from Bacillus licheniformis.

A gene encoding a new amylolytic enzyme of Bacillus licheniformis (BLMA) has been cloned, and we characterized the enzyme expressed in Escherichia coli. The genomic DNA of B. licheniformis was double-digested with EcoRI and BamHI and ligated the pBR322. The transformed E. coli was selected by its amylolytic activity, which carries the recombinant plasmid pIJ322 containing a 3.5-kilobase fragment of B. licheniformis DNA. The purified enzyme encoded by pIJ322 was capable of hydrolyzing pullulan and cyclodextrin as well as starch. It was active over a pH range of 6-8 and its optimum temperature was 50 degrees C. The molecular weight of the enzyme was 64,000, and the isoelectric point was 5.4. It degraded soluble starch by cleaving maltose units preferentially but did not attack alpha-1,6-linkage. The enzyme also hydrolyzed pullulan to panose units exclusively. In the presence of glucose, however, it transferred the panosyl moiety to glucose with the formation of alpha-1,6-linkage. The specificity of transferring activity is evident from the result of the maltosyl-transferring reaction which produces isopanose from maltotriose and glucose. The molecular structure of the enzyme deduced from the nucleotide sequence of the clone maintains limited similarity in the conserved regions to the other amylolytic enzymes.

Amino Acid Sequence↗
PubMed1989

Magnetic circular dichroism studies of the active site structure of hemoprotein H-450: comparison to cytochrome P-450 and sensitivity to pH effects.

Ferric, ferrous and ferrous-CO hemoprotein H-450 from rat liver have been examined with magnetic circular dichroism spectroscopy under alkaline (pH 8.0) and acidic (pH 6.0) conditions. The spectral properties of these species require that one of the axial heme iron ligands in the alkaline ferric and ferrous states must be a thiolate sulfur, presumably from cysteine. The data are most consistent with the ligand trans to thiolate being either histidine or methionine. The reversible pH effects on the spectral properties of the ferrous protein, but not of the ferric protein, appear to involve protonation or displacement of the thiolate. As treatment of the ferrous protein with CO does not yield a thiolate-ligated ferrous-CO adduct, CO either displaces the thiolate or its addition is accompanied by protonation of the thiolate.

Animals↗
PubMed1989

Quantitation of testicular and somatic cytochromes c in testis and somatic tissues from developing rats.

By combining chromatographic and spectral procedures, simple and quantitative assays for somatic cytochrome c (cyt cs) and testicular cytochrome c (cyt ct) in crude animal tissue extracts were developed. Using this assay procedure, limited developmental studies of cyt ct and cs were performed with tissue extracts of 27-, 58-, and 85-day-old rats. Specific contents of cyt cs in somatic tissues (i.e., micrograms of cyt c/g of tissue) of these three age groups did not show significant variations. However, the amounts of both cyt ct and cs in testis were markedly increased as the rats approached maturity. Increasing cyt ct/cyt cs ratios as the rat developed to maturity suggest that expression of cyt ct is preferentially required for specific function of testis. Application of both molecular biological techniques and this assay (for holo-cyt ct) should be useful to study the overall regulation of the expression of cyt ct in testis.

Aging↗
PubMed1989

Isolation and identification of trophoblast lymphocyte cross-reactive (TLX) antigens from human lymphocytes.

It has been proposed that allotypic trophoblast lymphocyte cross-reactive (TLX) antigens are involved in the maintenance of normal human reproduction. Despite such a potentially important role for TLX antigens, isolation of human TLX proteins has not yet been reported. As an initial step toward elucidation of the structure and function of TLX antigens, we have isolated TLX proteins from Lubrol-solubilized lymphocytes (termed "wTLX") by anti-trophoblast membrane-Sepharose immunoaffinity chromatography. Using Ouchterlony immunodiffusion and immunoelectrophoresis, we have identified an immunoreactive wTLX antigen which forms a single immunoprecipitation line against absorbed anti-trophoblast membrane. From 17.5% sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblot analyses, a 35-kDa band was determined to be a major protein band in the immunoaffinity-isolated wTLX fraction, along with multiple minor wTLX bands. These results suggest the possible existence of antigenic polymorphism of TLX, with predominant expression of the 35-kDa wTLX antigen in lymphocytes. The strong staining of the TLX antigens with Coomassie Brilliant Blue and Amido Black indicates they are largely proteins. Co-isolation of beta 2-microglobulin in the immunoaffinity-isolated wTLX pool could imply that the wTLX antigens may be unique class I HLA-like antigens. This possibility has yet to be resolved.

Autoantigens↗
PubMed1989

Identification of trophoblast membrane-originated proteins in human placental blood.

The human placenta secretes various fetoplacental proteins, including a trophoblast membrane (TM)-bound alkaline phosphatase. Five TM-originated proteins (TOPs), molecular weights 100, 39, 37, 35, and 26 kilodaltons (kDa), were isolated from placental blood by using an anti-TM Sepharose immunoaffinity column. Apparently, these five TOPs are secreted from TM into the maternal circulation during pregnancy. One of these five TOP bands (26 kDa) was identified by Western blot analysis to be human placental lactogen. The other four bands are newly identified as trophoblast-specific proteins and, therefore, could have potential diagnostic applications as serum markers for monitoring tumor development.

Alkaline Phosphatase↗
PubMed1989

The production of transforming growth factor-beta activity by rat granulosa cell cultures.

We have examined whether granulosa cells (GC) secrete transforming growth factor-beta (TGF beta)-like activity using cell cultures prepared from diethylstilbestrol-primed female rats. Our results indicate that a significant level of active as well as latent TGF beta activity is found in defined GC culture medium as assessed by 1) potentiation of FSH-induced differentiation of rat GC, 2) neutralization of its activity by anti-TGF beta immunoglobulin, 3) inhibition of DNA synthesis in mink lung epithelial cells (CCl 64), and 4) activation of latent TGF beta activity by either acid or heat treatment. TGF beta production was more pronounced when the cells were seeded on fibronectin-coated plates. There was no difference in the level of TGF beta secretion by GC preparations derived from either diethylstilbestrol-primed immature or normal immature rats or adult rats. Furthermore, rat GC-conditioned medium contained much more TGF beta activity than medium from normal rat kidney cells (NRK 49-F), human prostatic adenocarcinoma cells (PC-3), or porcine GC. Rat thecal/interstitial cell culture medium contained activity comparable to that of GC medium. We conclude that rat GC preparations secrete a high level of TGF beta activity in vitro. Taken together with previous results, this indicates the possibility that TGF beta may be an autocrine regulator as well as a paracrine one within the ovarian follicle. Moreover, because of the high level of TGF beta activity produced, the rat GC culture system appears to be a useful experimental model for further exploring relationships between TGF beta production and its action.

Animals↗
PubMed1988

Human platelet-derived growth factor preparations contain a separate activity which potentiates follicle-stimulating hormone-mediated induction of luteinizing hormone receptor in cultured rat granulosa cells: evidence for transforming growth factor-beta.

The ability of platelet-derived growth factor (PDGF) preparations to potentiate FSH-mediated LH receptor induction in rat granulosa cell cultures was shown to be due to a component distinct from PDGF. Purification of heat-treated platelet lysate by carboxymethyl-Sephadex C-50 and Cibacron blue-Sepharose chromatography, followed by Bio-Gel P-60 chromatography, resulted in the separation of two activities: 1) a growth-promoting activity, P60-PDGF, defined on the basis of increased DNA synthesis in BALB/c-3T3 cells, and 2) a differentiation-promoting activity which enhanced FSH-dependent LH receptor induction in granulosa cells. On the basis of electrophoretic mobility on sodium dodecyl sulfate-polyacrylamide gels, inhibition of tritiated thymidine uptake by epithelial cells, and attenuation of LH/hCG receptor expression in the presence of antitransforming growth factor-beta (anti-TGF beta) immunoglobulin G, the differentiation-promoting component of the preparations appears to be TGF beta. The Bio-Gel fractions that contained TGF beta did not stimulate LH receptor induction of cAMP production in the absence of FSH. PDGF prepared free of TGF beta did not potentiate receptor induction. We conclude, therefore, that the differentiative effects of PDGF previously described in this system are due to TGF beta.

Animals↗