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Biomedical subjects

H Kim

Publications and source records attributed to H Kim.

At least 127 records · Page 7Linked to original sources
PubMed2001

Effects of genetic polymorphisms of CYP1A1, CYP2E1, GSTM1, and GSTT1 on the urinary levels of 1-hydroxypyrene and 2-naphthol in aircraft maintenance workers.

This study was undertaken to investigate the effects of genetic polymorphisms of the cytochrome P450 1A1 (CYP1A1) and 2E1 (CYP2E1), and glutathione S-transferases mu (GSTM1) and theta (GSTT1) on urinary 1-hydroxypyrene and 2-naphthol levels, and to estimate the level of exposure to polycyclic aromatic hydrocarbons (PAHs) in aircraft maintenance workers. In 218 Korean aircraft maintenance workers, the geometric means of urinary 1-hydroxypyrene and 2-naphthol were 0.32 and 3.25 micromol/mol creatinine, respectively. These urinary concentrations were approximately at the upper limit of the general population. Mean urinary 2-naphthol concentrations were significantly different between smokers and non-smokers. CYP1A1 and GSTM1 were statistically significant in analyses on both 1-hydroxypyrene and 2-naphthol levels among smokers. The results suggest that smoking has more profound effects on urinary PAH metabolites than does genetic polymorphisms in this population, and that CYP1A1 and GSTM1 activity might be related to the metabolism of 1-hydroxypyrene and 2-naphthol.

Adult↗
PubMed2001

Through induction of juxtaposition and tyrosine kinase activity of Jak1, X-gene product of hepatitis B virus stimulates Ras and the transcriptional activation through AP-1, NF-kappaB, and SRE enhancers.

Here, based on the recent finding of HBx (X-gene product of hepatitis B virus) as the inducer of Jak1, we investigated the mechanism for the HBx-mediated host cell regulation and found that (i) HBx associates specifically with Jak1 in vivo; (ii) HBx itself forms a dimer which leads to juxtaposition of associated Jak1 and subsequent activation of the tyrosine kinase activity of Jak1; (iii) HBx-mediated activation of the promoters containing AP-1-, NF-kappaB-, SRE-, and SIE-sites is dependent on the activation of Jak1; (iv) Jak1, once activated by HBx, induces Ras activity through recruitment of Grb2 and induces tyrosine phosphorylation of Raf1, but not shc. These findings show that previously reported functions of HBx, such as activation of multiple signaling pathways and transcriptional activation are attributable to HBx-mediated Jak1 activation.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Soy isoflavonoids and cancer -- metabolism at the target site.

Isoflavonoids are members of the broad class of plant polyphenols that have been shown in vivo to have benefit in the prevention of a wide variety of chronic diseases, including cancer. For genistein (5,7,4'-trihydroxyisoflavone) (GEN), the major isoflavone in soy, reported mechanisms for these biological activities are numerous and include regulation of estrogen-mediated events, inhibition of tyrosine kinase and DNA topoisomerase activities, synthesis and release of TGF beta, and modulation of apoptosis. However, the biochemical effects of GEN in cell culture occur at concentrations in the micromolar range, far above the circulating levels of the unconjugated GEN. This may point to the limitations of cell culture for the evaluation of the activity and mechanisms of potential anti-carcinogens. GEN is extensively metabolized in vivo, with only about 14-16% excreted in an unmodified form. Metabolism may also occur because of interaction between GEN (as well as other polyphenols) and oxidants produced by inflammatory cells (HOCl, HOBr and ONOO(-)). These react with GEN to form brominated, chlorinated and/or nitrated GEN. Emerging evidence indicates that these modifications may substantially increase the biological activities of the parent compound. Future investigations of GEN and other polyphenols must, therefore, take into account metabolism at the tissue site.

Anticarcinogenic Agents↗
PubMed2001

The rapid destabilization of p53 mRNA in immortal chicken embryo fibroblast cells.

The steady-state levels of p53 mRNA were dramatically lower in immortal chicken embryo fibroblast (CEF) cell lines compared to primary CEF cells. In the presence of cycloheximide (CHX), the steady-state levels of p53 mRNA markedly increased in immortal CEF cell lines, similar to levels found in primary cells. The de novo synthetic rates of p53 mRNA were relatively similar in primary and immortal cells grown in the presence or absence of CHX. Destabilization of p53 mRNA was observed in the nuclei of immortal, but not primary, CEF cells. The half-life of p53 mRNA in primary cells was found to be a relatively long 23 h compared to only 3 h in immortal cells. The expression of transfected p53 cDNA was inhibited in immortal cells, but restored upon CHX treatment. The 5'-region of the p53 mRNA was shown to be involved in the rapid p53 mRNA destabilization in immortal cells by expression analysis of 5'- and 3'-deleted p53 cDNAs as well as fusion mRNA constructs of N-terminal p53 and N-terminal deleted LacZ genes. Together, it is suggestive that the downregulation of p53 mRNA in immortal CEF cells occurs through a post-transcriptional destabilizing mechanism.

Animals↗
PubMed2001

Necrotic cell death by hydrogen peroxide in immortal DF-1 chicken embryo fibroblast cells expressing deregulated MnSOD and catalase.

The reactive oxygen species are known as endogenous toxic oxidant damaging factors in a variety of cell types, and in response, the antioxidant genes have been implicated in cell proliferation, senescence, immortalization, and tumorigenesis. The expression of manganese superoxide dismutase mRNA was shown to increase in most of the immortal chicken embryo fibroblast (CEF) cells tested, while expression of catalase mRNA appeared to be dramatically decreased in all immortal CEF cells compared to their primary counterparts. The expression of copper-zinc superoxide dismutase mRNA was shown to increase slightly in some immortal CEF cells. The glutathione peroxidase expressed relatively similar levels in both primary and immortal CEF cells. As primary and immortal DF-1 CEF cells were treated with 10-100 microM of hydrogen peroxide (concentrations known to be sublethal in human diploid fibroblasts), immortal DF-1 CEF cells were shown to be more sensitive to hydrogen peroxide, and total cell numbers were dramatically reduced when compared with primary cell counterparts. This increased sensitivity to hydrogen peroxide in immortal DF-1 cells occurred without evident changes in either antioxidant gene expression, mitochondrial membrane potential, cell cycle distribution or chromatin condensation. However, the total number of dead cells without chromatin condensation was dramatically elevated in immortal DF-1 CEFs treated with hydrogen peroxide, indicating that the inhibition of immortal DF-1 cell growth by low concentrations of hydrogen peroxide is due to increased necrotic cell death, but not apoptosis. Taken together, our observation suggests that the balanced antioxidant function might be important for cell proliferation in response to toxic oxidative damage by hydrogen peroxide.

Animals↗
PubMed2001

Observation of Cabibbo suppressed B --> D(*)K- decays at Belle.

We report observations of the Cabibbo suppressed decays B-->D((*))K- using a 10.4 fb(-1) data sample accumulated at the Upsilon(4S) resonance with the Belle detector at the KEKB e(+)e(-) storage ring. We find that the ratios of Cabibbo suppressed to Cabibbo favored branching fractions are B(B--->D0K-)/B(B--->D0pi(-)) = 0.079+/-0.009+/-0.006, B(B(0)-->D+K-)/B(B(0)-->D+pi(-)) = 0.068+/-0.015+/-0.007, B(B--->D(*0)K-)/B(B--->D(*0)pi(-)) = 0.078+/-0.019+/-0.009, and B(B(0)-->D(*+)K-)/B(B(0)-->D(*+)pi(-)) = 0.074+/-0.015+/-0.006. These are the first observations of the B-->D+K-, D(*0)K-, and D(*+)K- decay processes.

Journal Article↗
PubMed2001

The plant flavonoid wogonin suppresses death of activated C6 rat glial cells by inhibiting nitric oxide production.

Flavonoids are a group of low molecular weight polyphenolic compounds derived from plants. 5,7-dihydroxy-8-methoxyflavone (Wogonin), a flavonoid originated from the root of Scutellaria baicalensis Georgi, has been shown to exert various anti-inflammatory effects such as inhibition of nitric oxide (NO) and prostaglandin E2 production in macrophages. Because glial cells have been previously shown to undergo NO-dependent apoptosis upon inflammatory activation and this auto-regulatory process may be negatively affected by exogenous factors possessing anti-inflammatory activities, we examined the effects of wogonin on NO production and activation-induced cell death of C6 rat glial cells. Activation of C6 glial cells with lipopolysaccharide (LPS), interferon-gamma, and tumor necrosis factor-alpha induced NO production followed by cell death. Pretreatment of C6 cells with wogonin before LPS and cytokine treatment dose-dependently inhibited NO production as well as death of activated C6 cells. Wogonin-mediated inhibition of NO production was accompanied by suppression of inducible nitric oxide synthase (iNOS) protein induction and nuclear factor kappa B (NF-kappaB) reporter activity. Wogonin, however, did not affect a NO donor-induced cytotoxicity. Taken together, our results indicate that wogonin inhibits activation-induced death of C6 glial cells by suppressing NO production, and these inhibitory effects of wogonin on NO production are exerted through inhibition of NF-kappaB-mediated iNOS induction.

Animals↗
PubMed2001

Self-assembled monolayer of a redox-active calix[4]arene: voltammetric recognition of the Ba2+ ion in aqueous media.

The Redox-active monolayer of a novel calix[4]arene recognizing redox-inactive ionic species by voltammetry is reported. Calix[4]arene-disulfide-diquinone, which is not only redox-active but is also a highly selective ionophore for the Ba2+ ion, spontaneously forms a stable and dense monolayer film on gold. The redox-active calixarene monolayer selectively recognizes Ba2+ ion in aqueous media, and the voltammetric signals are proportional to the ionic concentration. A new voltammetric peak can be detected by square-wave voltammetry upon adding a dilute solution containing Ba2+ ion having a concentration as low as 1.0 x 10(-6) M. The Langmuir plot (1/ip vs 1/[Ba2+]) shows a linear slope in the range from 1.0 x 10(-6) M to 1.0 x 10(-4) M. This modified electrode does not show any significant interference from alkali and alkaline earth metal ions except for Sr2+ and Ca2+. Only 100- and 500-fold concentrations of Sr2+ and Ca2+ ions, respectively, can lead to voltammetric responses comparable to that of Ba2+.

Journal Article↗
PubMed2001

Observation of large CP violation in the neutral B meson system.

We present a measurement of the standard model CP violation parameter sin2 phi(1) based on a 29.1 fb(-1) data sample collected at the Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric-energy e(+)e(-) collider. One neutral B meson is fully reconstructed as a J/psi K(S), psi(2S)K(S), chi(c1)K(S), eta(c)K(S), J/psi K(L), or J/psi K(*0) decay and the flavor of the accompanying B meson is identified from its decay products. From the asymmetry in the distribution of the time intervals between the two B meson decay points, we determine sin2 phi(1) = 0.99+/-0.14(stat)+/-0.06(syst). We conclude that we have observed CP violation in the neutral B meson system.

Journal Article↗
PubMed2001

CoMFA of artemisinin derivatives: effect of location and size of lattice.

A CoMFA study of artemisinin derivatives with changes of the location and the number of lattice points was performed. The location of probe atoms in a large lattice has practically no effect on the cross-validated r(2) value (r(2)(cv)). The selection of only 18 probe atoms around the peroxide bond, considering the action mechanism of artemisinin, provided a less time-demanding and more reliable CoMFA model, which forecasts better than the large lattice model despite the lower r(2)(cv) value. Only 1 A displacement of the small lattice caused a reduction of cross-validated r(2) value of more than 50%, which indicates the lattice location played an important role in this small lattice model.

Antimalarials↗
PubMed2001

NF-kappaB, inducible nitric oxide synthase and apoptosis by Helicobacter pylori infection.

Oxygen radicals are considered as an important regulator in the pathogenesis of Helicobacter pylori (H. pylori)-induced gastric ulceration and carcinogenesis. Inflammatory genes including inducible nitric oxide synthase (iNOS) may be regulated by oxidant-sensitive transcription factor, nuclear factor-kappaB (NF-kappaB). iNOS induction has been related to gastric apoptosis. We studied the role of NF-kappaB on iNOS expression and apoptosis in H. pylori-stimulated gastric epithelial AGS cells. AGS cells were treated with antisense oligonucleotide (AS ODN) for NF-kappaB subunit p50, an antioxidant enzyme catalase, an inhibitor of NF-kappaB activation pyrrolidine dithiocarbamate (PDTC), iNOS inhibitors N(G)-nitro-L-arginine-methyl ester (L-NAME) and 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine (AMT), a peroxynitrite donor SIN-1, and a nitric oxide donor NOC-18 in the presence or absence of H. pylori. H. pylori induced cytotocixity time- and dose-dependently, which occurred with induction in iNOS expression and nitrite production. SIN-1 and NOC-18 induced dose-dependent cytotoxicity in AGS cells. Catalase, PDTC, L-NAME, and AMT prevented H. pylori-induced cytotoxicity and apoptosis. It was related to their inhibition on iNOS expression and nitrite production. The cells treated with AS ODN had low levels of p50 and NF-kappaB and inhibited H. pylori-induced cytotoxicity, apoptosis, iNOS expression, and nitrite production. In conclusion, NF-kappaB plays a novel role in iNOS expression and apoptosis in H. pylori-infected gastric epithelial cells.

Antioxidants↗
PubMed2001

Caffeine inhibits exercise-induced increase in tryptophan hydroxylase expression in dorsal and median raphe of Sprague-Dawley rats.

Effect of caffeine on the expression of tryptophan hydroxylase (TPH), rate limiting enzyme of serotonin synthesis, in dorsal and median raphe was investigated via immunohistochemistry. In exercise groups, Sprague-Dawley rats were put on treadmill running for 30 min per day for 6 consecutive days. On the seventh day, animals of control-with-caffeine group were injected subcutaneously with 4 mg/kg caffeine, while control-without-caffeine group were injected with 0.9% NaCl, sacrificed 2 h later. Exercise-with-caffeine group and exercise-without-caffeine group were injected with caffeine and NaCl, respectively; all-out time was determined 1 h after injection, and then sacrificed. Caffeine increased all-out time in exercised rats, and inhibited the exercise-induced elevation in TPH expression. The suppressive effect of caffeine on TPH expression in exercised rats can be suggested as one possible ergogenic mechanism of caffeine.

Animals↗
PubMed2001

Structure of the Ba-induced Si(111)- (3 x 2) reconstruction.

The Ba/Si(111) surface, previously known as a 3 x 1 phase, is found to have a 3 x 2 periodicity and a semiconducting band gap. The substrate reconstructs into the honeycomb chain-channel (HCC) structure with Ba atoms in the channel, as in the alkali-metal-induced Si(111)-(3 x 1). However, the metal coverage is determined to be 1/6 monolayers, half the alkali-metal coverage. We propose that the structure and the metal coverage determined for the Ba adsorbate is universal for other alkaline-earth-metal adsorbates. With the alkali-metal-induced 3 x 1 case, our results lead to a rule that one donated electron per 3 x 1 surface unit is necessary to stabilize the HCC reconstruction of Si.

Journal Article↗
PubMed2001

IFN-gamma induces cell death in human hepatoma cells through a TRAIL/death receptor-mediated apoptotic pathway.

We demonstrated the induction of cell death in a hepatoma cell line by IFN-gamma and its possible mechanism. Among the 2 hepatitis B virus (HBV)-associated hepatoma cell lines, SNU-354 and SNU-368, IFN-gamma induced cell death and increased caspase-3 activity in SNU-368 but not in SNU-354. IFN-gamma induced several changes in the mRNA expression level of apoptosis-regulating genes, e.g., increased expression of Fas, caspase-1 and TNF-related apoptosis-inducing ligand (TRAIL). In particular, IFN-gamma potently increased the mRNA expression of TRAIL in both cell lines. However, it did not change the mRNA expression level of death-mediating TRAIL receptors, e.g., DR4 and DR5, which were constitutively expressed in both cell lines. In contrast, the decoy receptor DcR1 was expressed in SNU-354 but not in SNU-368, and its expression level in SNU-354 was increased by IFN-gamma. Another decoy receptor, DcR2, was constitutively expressed in both cell lines; however, its expression level in SNU-368 was decreased by IFN-gamma. In addition, exogenous recombinant TRAIL reduced viability in SNU-368, but not in SNU-354, cells. From these findings, we speculated that TRAIL up-regulation and the subsequent TRAIL-mediated apoptosis serve as a mechanism of IFN-gamma-induced cell death in SNU-368. To confirm this hypothesis, we demonstrated that soluble DR4-Fc fusion protein, a TRAIL pathway inhibitor, inhibited IFN-gamma-induced cell death in SNU-368. Our results demonstrated that IFN-gamma acts as an inducer of cell death through TRAIL-mediated apoptosis.

Apoptosis↗
PubMed2001

Mutations of tumor necrosis factor-related apoptosis-inducing ligand receptor 1 (TRAIL-R1) and receptor 2 (TRAIL-R2) genes in metastatic breast cancers.

Several lines of evidence suggest that apoptosis dysregulation plays an important role in cancer metastasis. In this study, to explore the possibility that the mutations of death receptors are involved in the metastasis mechanism, we analyzed the death domains of Fas and tumor necrosis factor-related apoptosis-inducing ligand-receptor 1 and -2 (TRAIL-R1 and -R2) genes for the detection of somatic mutations in 57 breast cancers with (n = 34) or without (n = 23) metastasis to the regional lymph nodes. We found seven mutations (three TRAIL-R1 and four TRAIL-R2 mutations), and these mutations were detected only in the breast cancers with metastasis. Furthermore, we also analyzed the allelic losses of chromosome 8p21-22, where TRAIL-R1 and R2 reside in the same series of breast cancers, and found that the allelic losses were significantly higher in metastatic breast cancers. We expressed the tumor-derived TRAIL-R1 and TRAIL-R2 mutants in 293 cells and found that apoptosis was suppressed. These data suggest that TRAIL-R1 and R2 genes are relevant to the frequent loss of chromosome 8p21-22 in breast cancer and that the inactivating mutations of TRAIL-R1 and -R2 genes play a role in the metastasis of breast cancer.

Apoptosis↗
PubMed2001

Testis-specific expression of an intronless gene encoding a human poly(A) polymerase.

A mouse intronless gene, encoding a testis-specific poly(A) polymerase (mPAPT), was previously identified. mPAPT may play a role as a putative enzyme that is responsible for polyadenylation regulation during mouse spermatogenesis. In order to understand how PAPT genes are conserved in mammals, we isolated a human cDNA homolog encoding a human PAPT (hPAPT), which was specifically expressed in the testis. The structure of hPAPT was very similar to that of mPAPT. The about 100 residues at the C-terminal region of a nuclear poly(A) polymerase, PAP II, were missing in both PAPT proteins. An analysis of the genomic DNA showed that the hPAPT gene is an intronless gene that is similar to the mPAPT gene. Interestingly, the sequence homology between hPAPT and mPAPT was much lower than the homology between hPAP II and mPAP II. The phylogenetic analysis suggests that PAPTs arose through retrotransposition after the amphibian-amniote split during evolution.

Animals↗
PubMed2001

TUCAN, an antiapoptotic caspase-associated recruitment domain family protein overexpressed in cancer.

Caspase-associated recruitment domains (CARDs) are protein interaction domains that participate in activation or suppression of CARD-carrying members of the caspase family of apoptosis-inducing proteases. A novel CARD-containing protein was identified that is overexpressed in some types of cancer and that binds and suppresses activation of procaspase-9, which we term TUCAN (tumor-up-regulated CARD-containing antagonist of caspase nine). The CARD domain of TUCAN selectively binds itself and procaspase-9. TUCAN interferes with binding of Apaf1 to procaspase-9 and suppresses caspase activation induced by the Apaf1 activator, cytochrome c. Overexpression of TUCAN in cells by stable or transient transfection inhibits apoptosis and caspase activation induced by Apaf1/caspase-9-dependent stimuli, including Bax, VP16, and staurosporine, but not by Apaf1/caspase-9-independent stimuli, Fas and granzyme B. High levels of endogenous TUCAN protein were detected in several tumor cell lines and in colon cancer specimens, correlating with shorter patient survival. Thus, TUCAN represents a new member of the CARD family that selectively suppresses apoptosis induced via the mitochondrial pathway for caspase activation.

Adaptor Proteins, Signal Transducing↗