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Biomedical subjects

S T Kim

Publications and source records attributed to S T Kim.

At least 37 records · Page 2Linked to original sources
PubMed2001

ATM--a key determinant of multiple cellular responses to irradiation.

Ataxia-telangiectasia is a rare clinical disorder manifesting a variety of different abnormalities, including progressive neurodegeneration, increased cancer incidence, immune deficiency, sterility, and extreme radiosensitivity. Recent studies have demonstrated that the defective gene product in this disease, ATM, is a protein kinase. The identification of several different substrates for this kinase is beginning to explain the wide array of different physiologic abnormalities that occur when this gene product is dysfunctional. Since the ATM protein is a critical signaling molecule in the cellular response to ionizing irradiation, the identification of these substrates also results in elucidation of the steps involved in a number of different cellular signaling pathways initiated by irradiation. Such insights also result in the identification of potential new targets for enhancing the efficacy of radiation therapy.

Ataxia Telangiectasia↗
PubMed2001

Trimeresurus flavoviridis (habu snake) venom induces human erythrocyte lysis through enzymatic lipolysis, complement activation and decreased membrane expression of CD55 and CD59.

Trimeresurus flavoviridis (habu snake) bites can be fatal to man because of its virulent venom, which is clinicopathologically classified as haemorrhagic, necrotic, and haemolytic toxins. Trimeresurus flavoviridis venom causes lysis of human erythrocytes in conditions where plasma is present as well as in plasma-free conditions in a dose-dependent manner. The haemolytic process requires Ca2+ and Mg2+ ions in the solution. Additionally, the venom initiates activation of the human complement cascade as evidenced by C3a and C5a releases, complement consumption indicated by CH50 and formation of soluble membrane attack complex. The insertion of membrane attack complex into the erythrocyte membranes is morphologically identified by electronmicroscopy. Immunofluorescence analysis reveals that incubation of erythrocytes with the venom decreased cell-surface expression of CD55 (decay accelerating factor) and CD59 (protectin), which renders erythrocyte more vulnerable to adherent C3 and C5 convertases and to polymerization of C9 into membranes, and may enhance autologous complement-mediated haemolysis triggered by the venom. Our data demonstrate that Trimeresurus flavoviridis venom induces haemolysis in the presence of plasma by three distinct mechanisms, direct lipolysis through PLA2 activity, activation of the human complement system, and cleavages of CD55 and CD59 from erythrocyte membranes.

Animals↗
PubMed2001

Deficiency of D-erythroascorbic acid attenuates hyphal growth and virulence of Candida albicans.

In some lower eukaryotes, D-erythroascorbic acid, a five-carbon analog of L-ascorbic acid, is present instead of L-ascorbic acid. We have cloned ALO1, the gene encoding D-arabinono-1,4-lactone oxidase, which catalyzes the final step of D-erythroascorbic acid biosynthesis in Candida albicans. The ALO1 gene contained a continuous open reading frame of 1,671 bp that encodes a polypeptide consisting of 557 amino acids with a calculated molecular mass of 63,428 Da. To investigate the functional roles of D-erythroascorbic acid in C. albicans, we disrupted or overexpressed the ALO1 gene. In the alo1/alo1 null mutants, the activity of D-arabinono-1,4-lactone oxidase was completely lost and D-erythroascorbic acid could not be detected. When ALO1 on a multicopy plasmid was transformed in C. albicans, the enzyme activity and the intracellular D-erythroascorbic acid level were increased up to 3.4-fold and 4.0-fold, respectively. The alo1/alo1 null mutants of C. albicans showed increased sensitivity towards oxidative stress. Overexpression of ALO1 made the cells more resistant to the same stress. The alo1/alo1 mutants showed defective hyphal growth and attenuated virulence. Taken together, our results suggest that D-erythroascorbic acid functions as an important antioxidant and can be considered one of the virulence factors enhancing the pathogenicity of C. albicans.

Amino Acid Sequence↗
PubMed2001

Occlusive myocardial infarction: investigation of bis-gadolinium mesoporphyrins-enhanced T1-weighted MR imaging in a cat model.

PURPOSE: To test whether bis-gadolinium mesoporphyrins-enhanced magnetic resonance (MR) imaging can accurately depict irreversibly damaged myocardium in occlusive myocardial infarction. MATERIALS AND METHODS: Ten cats were subjected to 90 minutes of occlusion of the left anterior descending coronary artery. Bis-gadolinium mesoporphyrins-enhanced T1-weighted MR imaging was performed in the cats for 6 hours. Histopathologic examinations with 2'3'5-triphenyl tetrazolium chloride (TTC) staining and electron microscopy were performed on the resected specimens. The time course and pattern of signal intensity enhancement were evaluated. The size of the infarcted myocardium was estimated on the MR images by measuring the size of the signal intensity-enhanced area. RESULTS: In eight of 10 cats, it was impossible to distinguish infarcted myocardium from normal myocardium at visual inspection of T1-weighted MR images. The contrast ratio between infarcted and normal myocardium did not increase significantly over time. In one of the two remaining cats, a doughnut pattern of signal intensity enhancement was noted. The other cat showed intensely homogeneous enhancement of infarcted myocardium at MR imaging. The size of the area of signal intensity enhancement at MR imaging in these two cats was accurately mapped to that of the infarction on the TTC-stained specimens. CONCLUSION: Occlusive myocardial infarction cannot be accurately detected at bis-gadolinium mesoporphyrins-enhanced MR imaging.

Animals↗
PubMed2001

Epidemiologic and clinical survey of Behcet's disease in Korea: the first multicenter study.

The prevalence of Behcet's disease is the highest in the East Asian and the Mediterranean countries. Behcet's disease is also distributed in the Asian countries, but the nationwide survey has not been performed in Korea yet. The Korean Study Group for Behcet's Disease, founded in 1999, conducted a multicenter, retrospective survey on epidemiologic and clinical features of the patients with Behcet's disease from 20 hospitals around the nation from 1997 to 1999. Of 3,497 patients, 1,527 were classified into complete or incomplete type of Behcet's disease according to the revised Shimizu's classification. The sex ratio was 1:1.75 with the female predominance. Geographical distribution showed the highest frequency in Seoul (38.5%). Clinically, 98.8% had oral ulcers, 83.2% had genital ulcers, 84.3% had skin lesions and 50.9% had ocular lesions. As for the minor clinical manifestations, articular symptoms were the most frequent. The pathergy test showed positive in 15.4% of patients and revealed a higher positive rate in males (20.2%) than in females (12.7%). In conclusion, we performed the first multicenter study on Behcet's disease in Korea and revealed the female predominance, higher frequency of ocular lesions, and lower positivity of pathergy test in the patients.

Adolescent↗
PubMed2001

Characterization of Cre-loxP interaction in the major groove: hint for structural distortion of mutant Cre and possible strategy for HIV-1 therapy.

Although the crystal structure of Cre recombinase complexed with DNA, named loxA, was elucidated a couple of years ago, it has not yet been determined which amino acids of the protein are involved in the specific Cre-loxP interaction. Arg259 and Gln90 interact with DNA substrate in the major groove from which the specificity of protein-DNA interaction comes. In this study, we substituted these residues for other amino acids. Also, two mutated DNA substrates were constructed. In each mutant, one of the bases that interact with Arg259 or Gln90 was changed into another base. In vitro binding assays and recombination assays of variant lox sites with wild-type and mutant-type Cre revealed that Arg259 plays a key role in Cre-loxP binding but Gln90 does not. However, the recombination activity still remained intact, although the binding between Cre and DNA substrate was not ensured.

Base Sequence↗
PubMed2000

Role of two histidines in the (6-4) photolyase reaction.

The reaction mechanism of Xenopus (6-4) photolyase was investigated using several mutant enzymes. In the active site, which is homologous between the cis,syn-cyclobutane pyrimidine dimer and (6-4) photolyases, four amino acid residues that are specific to (6-4) photolyase, Gln(288), His(354), Leu(355), and His(358), and two conserved tryptophans, Trp(291) and Trp(398), were substituted with alanine. Only the L355A mutant had a lower affinity for the substrate, which suggested a hydrophobic interaction with the (6-4) photoproduct. Both the H354A and H358A mutations resulted in an almost complete loss of the repair activity, although the Trp(291) and Trp(398) mutants retained some activity. Taking the pH profile of the (6-4) photolyase reaction into consideration with this observation, we propose a mechanism in which these histidines catalyze the formation of the four-membered ring intermediate in the repair process of this enzyme. When deuterium oxide was used as a solvent, the repair activity was decreased. The proton transfer shown by this isotope effect supports the proposed mechanism. The substrate binding and the reaction mechanism are discussed in detail using a molecular model.

Alanine↗
PubMed2000

Cadaveric renal allograft at the time of implantation has the similar immunological features with the rejecting allograft.

BACKGROUND: Compared to living donations, cadaveric transplants have a poorer outcome, and the immunologic status of renal tissues at the time of transplantation might influence the final outcome of the renal allograft. PATIENTS AND METHODS: We used quantitative RT-PCR to evaluate the differential expression of cytokine genes from 37 implantation tissues [18 cadaveric tissues (CI), 19 specimens from living donors (LI)]. We compared them with 17 acutely rejecting allograft (AR). RESULTS: Acute rejection within 6 months after transplantation occurred 8 times in patients with cadaveric allograft, but the living-donor recipients experienced 4 episodes (P<0.05). Proinflammatory cytokines were co-expressed more frequently in CI than in LI. The levels of IFN-gamma, TNF-alpha and IL-10 mRNA were also higher in CI. We compared the profiles of several cytokine expressions of CI with those of AR. The messages for IL-6 were more abundant in the CI, IFN-gamma was more expressed in AR, and the other cytokine expression levels were similar in both types. However, when comparing LI and AR, all the cytokine messages except IL-6 were up-regulated in AR than in LI. In CI, the levels of cytokine gene expressions were similar despite various cold ischemic time except IL-10 that were elevated for those cases where the operation was done within 4 hr of nephrectomy. CONCLUSIONS: The numbers and levels of gene transcription of inflammatory cytokines were higher in the tissues from a cadaver, and were not different from those of AR. This immunologic hostility at the time of implantation would contribute to the poorer outcome of cadaveric allograft.

Biopsy↗
PubMed2000

Asp41-His48 region of streptokinase is important in binding to a substrate plasminogen.

Streptokinase is a plasminogen activator protein produced by several strains of beta-hemolytic streptococci. Random mutagenesis of streptokinase was carried out for the determination of critical amino acid residues in plasminogen activation. We selected and sequenced 14 streptokinase mutants with no plasminogen activation activity on skim milk-plasminogen overlay plate. Specific activities of the selected streptokinase mutants were determined with chromogenic assay. Eight mutants (V19F, V35E, E85D, L292R, D325P, D341E, I345N, and M369L) resulted in greatly decreased amidolytic activities. However, unexpectedly, six mutants (D41C, S44K, S44P, R45P, H48T, and D220G) showed substantial amidolytic activities comparable to that of wild type. Moreover, five-point mutations were concentrated on the Asp41-His48 region. These data indicate that the Asp41-His48 region in a streptokinase-plasminogen binary complex plays an important role in binding to a substrate plasminogen.

Amidohydrolases↗
PubMed2000

Isolation of TC/AG repeat microsatellite sequences for fingerprinting rice blast fungus and their possible horizontal transfer to plant species.

Genome fingerprinting has been a major role in characterization of population structure and analysis of the variability in phytopathogenic fungi. In order to characterize Korean rice blast fungal isolates, the genomic DNAs were digested with AluI endonuclease and subsequent PCR amplifications using random decamer primers with combinations of microsatellite primers had been carried out. This Alu-Inter SSR technique revealed high polymorphism among the Korean blast fungal isolates. Then, fragments from the Alu-Inter SSR analysis were isolated to be used as probes in Southern hybridization, which also revealed high polymorphism between isolates to distinguish individuals. The sequences of the isolated fragments contained TC/AG tandem repeats interspersed with a 30 bp direct repeat. In gel blot analysis, the isolated TC/AG repeat microsatellite sequences were proved to be useful for characterizing the isolates in blast fungi in addition to the conventional MGR (Magnaporthe grisea repeat) probes. One interesting point was that the rice blast fungus derived TC/AG repeat microsatellite sequences were abundant in non-rice blast fungi and plant species, but not in other fungi and yeasts. A discussion on the possible horizontal gene transfer between phytopathogenic fungi and host plants is presented.

Base Sequence↗
PubMed2000

ATM phosphorylates p95/nbs1 in an S-phase checkpoint pathway.

The rare diseases ataxia-telangiectasia (AT), caused by mutations in the ATM gene, and Nijmegen breakage syndrome (NBS), with mutations in the p95/nbs1 gene, share a variety of phenotypic abnormalities such as chromosomal instability, radiation sensitivity and defects in cell-cycle checkpoints in response to ionizing radiation. The ATM gene encodes a protein kinase that is activated by ionizing radiation or radiomimetic drugs, whereas p95/nbs1 is part of a protein complex that is involved in responses to DNA double-strand breaks. Here, because of the similarities between AT and NBS, we evaluated the functional interactions between ATM and p95/nbs1. Activation of the ATM kinase by ionizing radiation and induction of ATM-dependent responses in NBS cells indicated that p95/nbs1 may not be required for signalling to ATM after ionizing radiation. However, p95/nbs1 was phosphorylated on serine 343 in an ATM-dependent manner in vitro and in vivo after ionizing radiation. A p95/nbs1 construct mutated at the ATM phosphorylation site abrogated an S-phase checkpoint induced by ionizing radiation in normal cells and failed to compensate for this functional deficiency in NBS cells. These observations link ATM and p95/nbs1 in a common signalling pathway and provide an explanation for phenotypic similarities in these two diseases.

Ataxia Telangiectasia↗
PubMed2000

A novel transcription factor, T-bet, directs Th1 lineage commitment.

Naive T helper cells differentiate into two subsets, Th1 and Th2, each with distinct functions and cytokine profiles. Here, we report the isolation of T-bet, a Th1-specific T box transcription factor that controls the expression of the hallmark Th1 cytokine, IFNgamma. T-bet expression correlates with IFNgamma expression in Th1 and NK cells. Ectopic expression of T-bet both transactivates the IFNgamma gene and induces endogenous IFNgamma production. Remarkably, retroviral gene transduction of T-bet into polarized Th2 and Tc2 primary T cells redirects them into Th1 and Tc1 cells, respectively, as evidenced by the simultaneous induction of IFNgamma and repression of IL-4 and IL-5. Thus, T-bet initiates Th1 lineage development from naive Thp cells both by activating Th1 genetic programs and by repressing the opposing Th2 programs.

Amino Acid Sequence↗
PubMed2000

Respective roles of cyclobutane pyrimidine dimers, (6-4)photoproducts, and minor photoproducts in ultraviolet mutagenesis of repair-deficient xeroderma pigmentosum A cells.

The role of UV light-induced photoproducts in initiating base substitution mutation in human cells was examined by determining the frequency and spectrum of mutation in a supF tRNA gene in a shuttle vector plasmid transfected into DNA repair deficient cells (xeroderma pigmentosum complementation group A). To compare the role of two major UV-induced photoproducts, cis-syn cyclobutane-type pyrimidine dimers (CPDs) and pyrimidine (6-4) pyrimidone photoproducts (6-4PPs), each photoproduct was removed from UV-irradiated plasmid by photoreactivation before transfection. Removal of either CPDs or 6-4PPs by in vitro photoreactivation reduced the mutation frequency while keeping the mutation distribution and the predominance of G:C-A:T transitions as UV-irradiated plasmid without photoreactivation, indicating that both cytosine-containing CPDs and 6-4PPs were premutagenic lesions for G:C-A:T transitions. On the other hand, A:T-G:C transitions were not recovered from plasmids after the removal of 6-4PPs, whereas this type of mutation occurred at a significant level (11%) after the removal of CPDs. Thus, the premutagenic lesions for the A:T-G:C transition are 6-4PPs. Removal of both CPDs and 6-4PPs resulted in the disappearance of mutational hot spots and random distribution of mutation as observed in unirradiated control plasmids. However, the mutational spectrum of photoreactivated plasmids differed significantly from that of unirradiated plasmids. A characteristic feature is a high portion of A:T-T:A transversions (11%) in the photoreactivated plasmid. This mutation is due to nondipyrimidinic "minor" photoproducts, and the mutation spectrum suggests that TA*, the major photoproduct of thymidylyl-(3'-5')-deoxyadenosine, is the premutagenic lesion for this mutation. This is the first report revealing the distinct mutagenic roles of the major UV photoproducts and "minor" photoproducts by the use of (6-4)photolyase.

Base Sequence↗
PubMed2000

Application of breath-hold T2-weighted, first-pass perfusion and gadolinium-enhanced T1-weighted MR imaging for assessment of myocardial viability in a pig model.

The purpose of this study was to correlate the abnormal signal area on various magnetic resonance (MR) images to the infarct area on pathologic examination and to assess the myocardial viability on the basis of MR images. T2-weighted, first-pass perfusion, and delayed gadolinium-enhanced T1-weighted images were used as "one-stop examinations" in a pig model of reperfused myocardial infarction. The results of each MR image were compared with those of 2,3, 5-triphenyltetrazolium chloride (TTC) staining. The abnormal signal areas on T2-weighted and Gd-enhanced T1-weighted images were larger than the infarct areas on TTC staining (34.7% and 32.3% vs. 28.3%; P< 0.05), whereas the nonperfused areas on perfusion images were correlated (25.6% vs, 28.3%; P = 0.139). Electron microscopic examination showed severely distorted ultrastructures in the infarct areas and mildly damaged ultrastructures in the peri-infarct areas. Perfusion images probably reflected the infarct areas, whereas T2-weighted and Gd-enhanced T1-weighted images seemed to include peri-infarct as well as infarct areas.

Animals↗
PubMed2000

Pityriasis lichenoides-like mycosis fungoides in children.

We report three children with clinical features of pityriasis lichenoides (scaly red to brown papules and macules) in whom there were histopathological findings of mycosis fungoides (disproportionate epidermotropism, Pautrier's microabscesses, and wiry and coarse collagen bundles). Immunohistochemical staining revealed a prevalence of T lymphocytes in the infiltrate. T-cell receptor gene rearrangement analysis in lesional skin demonstrated rearrangement of the gamma chain in all cases. Human T-cell lymphotropic virus type 1 serology was negative in the two patients in whom this test was performed. Thus, lesions resembling pityriasis lichenoides can be an unusual and potentially misleading presentation of mycosis fungoides.

Child↗
PubMed2000

The effects of Ledermix paste on discolouration of immature teeth.

AIM: The aims of this study were to: (i) investigate the effects of Ledermix paste as an intracanal medicament on discolouration of immature teeth, (ii) examine whether the discolouring effects were related to the method of application, (iii) examine the effects of sunlight upon discolouration of immature teeth and (iv) compare the degree of discolouration between mature and immature teeth. METHODOLOGY: The root canals of 45 immature extracted human teeth were prepared and filled with either Ledermix paste, calcium hydroxide [Ca(OH)2], or saline. In group 1, Ledermix paste was only placed apical to the cemento-enamel junction (CEJ) whilst in groups 2 and 3, the paste filled the entire pulp chamber and the root canals. In group 4, Ca(OH)2 paste and in group 5, saline (control) were allowed to fill the pulp chamber and the root canals. Group 3 teeth were kept in the dark and the other groups were exposed to daylight for 12 weeks. RESULTS: After 12 weeks, sunlight exposure had caused dark grey-brown staining in the Ledermix groups but this did not occur when the teeth were kept in the dark. More severe staining was noted when Ledermix paste filled the pulp chamber than when the paste was restricted to below the CEJ and when teeth were exposed to sunlight. When compared to the results of a similar study using mature teeth, the results were similar but the immature teeth were more severely stained than the mature teeth. The Ca(OH)2 paste caused an increase in lightness and yellowness in immature teeth. CONCLUSION: It was concluded that Ledermix paste may cause discolouration of immature teeth. Such effects can be minimized if placement of the paste is restricted to below the gingival margin. Clinicians should ensure that Ledermix paste is not left on the walls of access cavities, especially in immature teeth.

Analysis of Variance↗
PubMed2000

The effects of Ledermix paste on discolouration of mature teeth.

AIM: The aims of this study were to: (i) investigate the effects of Ledermix paste as an intracanal medicament on discolouration of mature teeth, (ii) examine whether the discolouring effects were related to the method of application, and (iii) examine the effects of sunlight upon discolouration of mature teeth. METHODOLOGY: The root canals of 45 mature extracted human teeth were prepared and filled with either Ledermix paste, calcium hydroxide [Ca(OH)2], or saline. In group 1, Ledermix paste was placed apical to the cemento-enamel junction (CEJ), whilst in groups 2 and 3 the paste filled the entire pulp chamber and root canals. In group 4, a Ca(OH)2 and methyl cellulose paste and, in group 5, saline (control) were allowed to fill the pulp chamber and the root canals. Group 3 teeth were kept in the dark and the other groups were exposed to indirect sunlight for 12 weeks. RESULTS: After 12 weeks, sunlight exposure had caused dark grey-brown staining of the teeth in the Ledermix groups, but this did not occur when the teeth were kept in the dark. More severe staining was noted when Ledermix paste filled the pulp chamber than when the paste was restricted to below the CEJ. CONCLUSIONS: It was concluded that Ledermix paste may cause discolouration of teeth. Such effects can be minimized if placement of the paste is restricted to below the gingival margin. Clinicians should ensure that Ledermix paste is not left on the walls of access cavities.

Analysis of Variance↗