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Biomedical subjects

Y H Kim

Publications and source records attributed to Y H Kim.

At least 91 records · Page 5Linked to original sources
PubMed2001

Differential effects of forskolin and phobol 12-myristate-13-acetate on the c-fos and c-jun mRNA expression in rat C6 glioma cells.

The effects of forskolin (FSK) and phobol 12-myristate-13-acetate (PMA) on c-fos and c-jun mRNA expressions in rat C6 glioma cells were studied. Both FSK and PMA increased the c-fos mRNA level. The C-jun mRNA level was decreased by FSK, whereas it was increased by PMA. The elevated c-fos mRNA level, induced by FSK or PMA, was significantly inhibited by dexamethasone (DEX). In contrast, DEX did not affect the FSK- and PMA-induced response of the c-jun mRNA level. Cycloheximide (CHX) caused a superinduction of the FSK- or PMA-induced c-fos mRNA level. Furthermore, CHX also potentiated the PMA-induced c-jun mRNA level. However, CHX did not affect the FSK-induced down-regulation of the c-jun mRNA level. When C6 glioma cells were incubated with PMA and FSK, the PMA-induced c-jun mRNA level was inhibited by FSK, whereas FSK did not affect the PMA-induced c-fos mRNA level. Our results suggest that the activations of PKA and PKC pathways have different roles in the regulation of the c-jun mRNA expression in rat C6 glioma cells. PKA activation can inhibit induction of the c-jun mRNA expression by PMA. In addition, DEX appears to have a selective inhibitory action against c-fos, but not c-jun, -mRNA expression that is regulated by PKA and PKC. On-going protein synthesis inhibition is required for the superinduction of the c-fos expression that is induced by PMA, or FSK and the PMA-induced c-jun mRNA level.

Animals↗
PubMed2001

Calcitermin, a novel antimicrobial peptide isolated from human airway secretions.

The human airways are protected from pathogenic colonization by a blanket of fluid impregnated with innate antimicrobial effector molecules. Among several previously uncharacterized components, we isolated a peptide that had activity primarily targeting Gram-negative bacteria. We named the peptide 'calcitermin' since its amino acid sequence and mass were equivalent to the 15 C-terminal residues of the S100 protein, calgranulin C. The antimicrobial activity of calcitermin was enhanced in acidic buffers (pH 5.4) and in the presence of micromolar concentrations of ZnCl(2). Analysis revealed a putative zinc-binding consensus sequence as well as an alpha-helical conformation in structure-promoting solvents.

Amino Acid Sequence↗
PubMed2001

Characterization of a novel laccase produced by the wood-rotting fungus Phellinus ribis.

The white-rot fungus Phellinus ribis produced a single form of laccase, which was purified to apparent electrophoretic homogeneity from cultures induced with 2,5-xylidine. This protein was a dimer, consisting of two subunits of 76 kDa as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Carbohydrate analysis revealed that the enzyme contained about 28% carbohydrate content. The laccase appeared to be different from other known laccases by the UV-visible absorption spectrum analysis. One enzyme molecule contained one copper, one manganese, and two zinc atoms. The laccase showed optimal activity at pH 4.0-6.0, 5.0, and 6.0 with 2,6-dimethoxyphenol, ABTS [2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid)], and syringaldazine, respectively. The enzyme preferably oxidized dimethoxyphenol and aromatic amine compounds. The stability of the laccase was low at acidic pH, whereas it showed high stability at neutral pH and mild temperature. The N-terminal amino acid sequence revealed a very low homology with other microbial laccases. With some substrates, the addition of manganese and H2O2 resulted in a remarkable increase in the oxidation rate. Without an appropriate phenolic substrate, the enzyme could not oxidize Mn(II) in the presence of H2O2 or pyrophosphate.

Amino Acid Sequence↗
PubMed2001

Immune response induced by immunization with Hepatitis B virus core DNA isolated from chronic active hepatitis patients.

There are many mutations in the gene encoding Hepatitis B virus (HBV) core antigen of chronic active hepatitis patients, and such mutations are most likely to be related to the severity of disease. Here, we constructed plasmids containing wild-type and deletion type of HBV core gene (HBc) to develop an experimental DNA vaccine and to compare immunogenicity of two types of HBc vaccine. Twenty-nine wild-types and seven deletion types of HBc were detected in sera of 32 Korean patients with chronic active hepatitis. Four wild-types (W1, W2, W4, W6) and two deletion types (D3, D4) of HBc were cloned into the pcDNA3 vector. Intramuscular immunization with wild-type HBc efficiently increased serum anti-HBc antibody response in a dose-dependent manner. Anti-HBc antibody response in mice injected with W6 increased 14 days after immunization, and peaked after 30 days and was maintained at least up to 50 days. W6 immunization induced a specific cytotoxic T lymphocyte response to W6-transfected 3LL (3LL-W6), and reduced the sizes of tumor mass of mice challenged with 3LL-W6 or 3LL transfected with D4. However, intramuscular immunization with D3 and D4 did not show antibody response at all. D3 and D4 have 157 bp (from 331 to 491 bp) and 122 bp (from 327 to 448 bp) gene deletion, respectively, and these encode class II MHC-restricted T-cell epitope. Altogether, these results suggest that mutant virus that has deleted HBc gene may evade immune systems due to loss of T-cell epitope.

Animals↗
PubMed2001

Phase II trial of epirubicin, cisplatin, oral uracil and tegafur, and leucovorin in patients with advanced gastric carcinoma.

BACKGROUND: The results of chemotherapy for patients with gastric carcinoma generally have been modest, although regimens developed more recently have produced higher response rates. One such regimen is epirubicin, cisplatin, and protracted infusion of 5-fluorouracil (ECF). The advantage of a long-term oral administration of uracil and tegafur (UFT) is that this treatment may be used to mimic the protracted infusion of 5-fluorouracil (5-FU). In addition, UFT treatment combined with leucovorin had a favorable activity and tolerable toxicity in patients with advanced gastric carcinoma. Instead of the inconvenience of an infusion pump and intravenous catheter for the protracted infusion of 5-FU, the authors administered UFT plus leucovorin in an ECF regimen for the treatment of patients with advanced gastric carcinoma. METHODS: Fifty-two patients with advanced gastric carcinoma received epirubicin, cisplatin, and oral UFT plus leucovorin. Epirubicin 50 mg/m(2) and cisplatin 60 mg/m(2) were administered on Day 1 by intravenous injection. Tegafur and uracil 360 mg/m(2)/day orally was administered in conjunction with leucovorin administered at a fixed dose of 45 mg/day orally in divided daily doses for 21 days followed by a 7-day rest period. These courses were repeated every 4 weeks. The median age of the patients was 59 years with a median World Health Organization performance status of 1. Patients received a median of five courses of treatment (range, 1-10). RESULTS: Among the 47 patients evaluated, three patients achieved complete response, and 24 patients had partial responses, for an overall response rate of 57.5% (95% confidence interval, 71.5-43.3%). Stable disease was reported in 11 patients (23.4%), and another 9 patients (19.1%) showed disease progression. The median duration of survival was 15 months (range, 2-33+). The main toxicity was nausea/vomiting and neutropenia. Significant toxicity (modified National Cancer Institute common toxicity Grade 3 or 4) included neutropenia in 22 patients (42%), nausea in 14(27%), vomiting in 9 (18%), oral mucositis in 3 (6%), and diarrhea in 3 (6%) patients. CONCLUSIONS: The authors conclude that epirubicin, cisplatin, and oral UFT plus leucovorin, a convenient regimen, has a significant activity and tolerable toxicities in patients with gastric carcinoma.

Administration, Oral↗
PubMed2001

Cytotoxic activities of acetoxyscirpenediol and ergosterol peroxide from Paecilomyces tenuipes.

Paecilomyces tenuipes is one of the famous Chinese medicinal entomopathogenic fungi that parasites in the lavae of silkworm. Two cytotoxic components were isolated from methanolic extract of the carpophores of this fungus that was cultivated artificially. Spectral analyses of the cytotoxic components showed that they were known ergosterol peroxide (5alpha,8alpha-epidioxy-24(R)-methylcholesta-6,22-dien-3beta-ol) and acetoxyscirpenediol (4beta-acetoxyscirpene-3alpha,15-diol) that were isolated for the first time from this fungus. The 50% inhibitory concentrations (IC50) of ergosterol peroxide against human gastric tumor cell line (SNU-1), human hepatoma cell line (SNU-354), human colorectal tumor cell line (SNU-C4) and murine sarcoma-180 were 18.7, 158.2, 84.6 and 74.1 microM, respectively. The IC50 values of acetoxyscirpenediol against SNU-1, SNU-C4, SNU-354 and sarcoma-180 were 1.2,4.0, 2.2 and 1.9 microM, respectively. Cytotoxic activities of acetoxyscirpenediol were about 4.0-6.6 times stronger than those of cisplatin which is currently used clinically for cancer patients.

Animals↗
PubMed2001

Characterization and expression of calpain 10. A novel ubiquitous calpain with nuclear localization.

Calpains are calcium-dependent intracellular nonlysosomal proteases that are believed to hydrolyze specific substrates important in calcium-regulated signaling pathways. Recently, an atypical member of the calpain family, calpain 10, was described, and genetic variation in this gene was associated with an increased risk of type II diabetes mellitus in humans. In the present report, a polyclonal antibody directed against rat calpain 10 was developed. This antibody was used to monitor the expression of calpain 10 protein in tissues from rats, mice, and humans. Calpain 10 protein was found to be present in all tissues examined by Western blotting including the lens, retina, brain, heart, and skeletal muscle. Although some calpain 10 was detectable in the water-soluble protein fraction of these tissues, it was preferentially found in the water-insoluble fraction. In the lens, immunohistochemistry revealed that calpain 10 was predominately located in the cytoplasm of epithelial and newly differentiating lens fibers at the transition zone. However, calpain 10 was found to be associated with the plasma membrane of differentiated lens fiber cells and the sarcolemma of skeletal muscle. In the lens epithelium-derived cell line, alphaTN4-1, the calpain 10 protein was found in a punctate distribution in the cell nucleus as well as the cytoplasm. After the elevation of intracellular calcium levels with ionomycin, calpain 10 protein levels in the nucleus of alphaTN4-1 cells increased markedly, whereas those in the cytoplasm decreased. In the lens, the elevation of intracellular calcium levels after selenite administration resulted in increased levels of calpain 10 RNA within 1 day and a loss of calpain 10 protein from the lens nucleus coincident with the onset of selenite cataract. In conclusion, calpain 10 seems to be a ubiquitous calpain, the expression level and subcellular distribution of which are dynamically influenced by calcium.

Adult↗
PubMed2001

Pannier is a transcriptional target and partner of Tinman during Drosophila cardiogenesis.

During Drosophila embryogenesis, the homeobox gene tinman is expressed in the dorsal mesoderm where it functions in the specification of precursor cells of the heart, visceral, and dorsal body wall muscles. The GATA factor gene pannier is similarly expressed in the dorsal-most part of the mesoderm where it is required for the formation of the cardial cell lineage. Despite these overlapping expression and functional properties, potential genetic and molecular interactions between the two genes remain largely unexplored. Here, we show that pannier is a direct transcriptional target of Tinman in the heart-forming region. The resulting coexpression of the two factors allows them to function combinatorially in the regulation of cardiac gene expression, and a physical interaction of the proteins has been demonstrated in cultured cells. We also define functional domains of Tinman and Pannier that are required for their synergistic activation of the D-mef2 differentiation gene in vivo. Together, these results provide important insights into the genetic mechanisms controlling heart formation in the Drosophila model system.

Animals↗
PubMed2001

Possible roles of JNK pathway in the regulation of hippocampal proenkephalin and immediate early gene expression induced by kainic acid.

Mitogen-activated protein kinases (MAPKs) may play crucial roles in the kainic acid (KA)-evoked excitotoxic effect and the regulation of transcription factors (e.g. c-Fos and c-Jun) in hippocampus, but their exact role in the regulation of KA-induced opioid peptides expression has not been well characterized in vivo. Therefore, we examined possible involvement of the phosphorylated form of JNK, as well as CREB, in the regulation of KA-induced proenkephalin and immediate early genes (IEGs) expression in the rat hippocampus. KA increased proenkephalin mRNA expression in rat hippocampus, which was decreased by pre-administration with cycloheximide (CHX, a protein synthesis inhibitor). KA alone increased c-fos as well as c-jun mRNA levels. CHX further enhanced KA-induced c-fos and c-jun mRNA levels. Additionally, KA increased the phosphorylation of JNK, especially JNK1, which was attenuated by CHX. CHX decreased KA-induced c-Fos protein expression. Interestingly, CHX itself increased the phosphorylation of CREB, which was abolished by KA administration. Our results suggest that the phosphorylation of JNK is involved in the up-regulation of the proenkephalin gene expression via c-Fos and c-Jun that is induced by KA in rat hippocampus. However, the phosphorylation of CREB is not associated with the up-regulation of the proenkephalin mRNA level induced by KA in the rat hippocampus.

Animals↗
PubMed2001

IFNalpha sensitizes ME-180 human cervical cancer cells to TNFalpha-induced apoptosis by inhibiting cytoprotective NF-kappaB activation.

Tumor necrosis factor alpha (TNFalpha) induces apoptosis of a variety of tumor cell types. The anti-tumor effect of TNFalpha is often augmented by interferon (IFN) gamma. We hypothesized that IFNalpha, which shares many biological activities with IFNgamma, might also synergize with TNFalpha for the induction of tumor cell death. We tested our hypothesis using ME-180 human cervical cancer cells exposed to either IFNalpha or TNFalpha alone or both. We analyzed the death of ME-180 cells by biochemical and cytological means, and investigated the molecular mechanism underlying cytotoxic synergism between the two cytokines. We found that (i) IFNalpha/TNFalpha synergistically induced apoptosis of ME-180 cells, which was accompanied by activation of caspases-3 and -8; (ii) IFNalpha induced signal transducer and activator of transcription (STAT) 1 phosphorylation, and transfection of phosphorylation-defective STAT1 dominant-negative mutant inhibited IFNalpha/TNFalpha-induced apoptosis; (iii) inhibition of nuclear factor kappaB (NF-kappaB) by proteasome inhibitor MG-132 sensitized ME-180 cells to TNFalpha alone; (iv) IFNalpha treatment attenuated TNFalpha-induced NF-kappaB reporter activity, while it did not inhibit DNA binding of NF-kappaB. Taken collectively, our results indicate that IFNalpha sensitizes ME-180 cells to TNFalpha-induced apoptosis by inhibiting TNFalpha-mediated cytoprotective NF-kappaB activation, and this sensitizing effect of IFNalpha is mediated through a STAT1-dependent pathway.

Apoptosis↗
PubMed2001

Natural killer/natural killer-like T-cell lymphoma, CD56+, presenting in the skin: an increasingly recognized entity with an aggressive course.

PURPOSE: To describe and identify the clinical and pathologic features of prognostic significance for natural killer (NK) and NK-like T-cell (NK/T-cell) lymphoma presenting in the skin. PATIENTS AND METHODS: This study was a retrospective review of 30 patients with CD56+ lymphomas initially presenting with cutaneous lesions, with analysis of clinical and histopathologic parameters. RESULTS: The median survival for all patients was 15 months. Those with extracutaneous manifestations at presentation (11 patients) had a shorter median survival of 7.6 months as compared with those without extracutaneous involvement (17 patients), who had a more favorable median survival of 44.9 months (P =.0001). Age, gender, extent of cutaneous involvement, and initial response to therapy had no statistically significant effect on survival. Seven patients (24%) had detectable Epstein-Barr virus (EBV) within neoplastic cells. The patients with tumor cells that coexpress CD30 (seven patients) have not yet reached a median survival after 35 months of follow-up as compared with those with CD30- tumor cells (20 patients), who had a median survival of 9.6 months (P <.02). Routine histopathologic characteristics had no prognostic significance nor did the presence of CD3epsilon, EBV, or multidrug resistance. CONCLUSION: NK/T-cell lymphoma is an aggressive neoplasm; however, a subset with a more favorable outcome is identified in this study. The presence of extracutaneous disease at presentation is the most important clinical variable and portends a poor prognosis. The extent of initial skin involvement does not reliably predict outcome. Patients from the United States with NK/T-cell lymphoma presenting in the skin have a low incidence of demonstrable EBV in their tumor cells. Patients with coexpression of CD30 in CD56 lymphomas tend to have a more favorable outcome.

Adolescent↗
PubMed2001

IFN-gamma/TNF-alpha synergism as the final effector in autoimmune diabetes: a key role for STAT1/IFN regulatory factor-1 pathway in pancreatic beta cell death.

Fas ligand (FasL), perforin, TNF-alpha, IL-1, and NO have been considered as effector molecule(s) leading to beta cell death in autoimmune diabetes. However, the real culprit(s) in beta cell destruction have long been elusive, despite intense investigation. We and others have demonstrated that FasL is not a major effector molecule in autoimmune diabetes, and previous inability to transfer diabetes to Fas-deficient nonobese diabetic (NOD)-lpr mice was due to constitutive FasL expression on lymphocytes from these mice. Here, we identified IFN-gamma/TNF-alpha synergism as the final effector molecules in autoimmune diabetes of NOD mice. A combination of IFN-gamma and TNF-alpha, but neither cytokine alone, induced classical caspase-dependent apoptosis in insulinoma and pancreatic islet cells. IFN-gamma treatment conferred susceptibility to TNF-alpha-induced apoptosis on otherwise resistant insulinoma cells by STAT1 activation followed by IFN regulatory factor (IRF)-1 induction. IRF-1 played a central role in IFN-gamma/TNF-alpha-induced cytotoxicity because inhibition of IRF-1 induction by antisense oligonucleotides blocked IFN-gamma/TNF-alpha-induced cytotoxicity, and transfection of IRF-1 rendered insulinoma cells susceptible to TNF-alpha-induced cytotoxicity. STAT1 and IRF-1 were expressed in pancreatic islets of diabetic NOD mice and colocalized with apoptotic cells. Moreover, anti-TNF-alpha Ab inhibited the development of diabetes after adoptive transfer. Taken together, our results indicate that IFN-gamma/TNF-alpha synergism is responsible for autoimmune diabetes in vivo as well as beta cell apoptosis in vitro and suggest a novel signal transduction in IFN-gamma/TNF-alpha synergism that may have relevance in other autoimmune diseases and synergistic anti-tumor effects of the two cytokines.

Animals↗
PubMed2001

Arylamine N-methyltransferase and thiol methyltransferase activities in cholestatic rat liver induced by common bile duct ligation.

Methylation catalyzed by methyltransferases is a major metabolic pathway for an inactivation of some catecholamines, niacinamide as well as aliphatic sulfhydryl drugs and toxic hydrogen sulfides. To investigate the effects of obstructive jaundice in an animal model, common bile duct ligation (CBDL) was performed in the rat and enzyme activities of S-adenosyl-L-methionine-dependent arylamine N-methyltransferase and thiol methyltransferase were examined in liver cell fractions and serum for a period of 42 d after CBDL. Both mitochondrial and microsomal arylamine N-methyltransferase showed significant increases in their activities between the 1st through the 7th day (P < or = 0.05 to 0.001), and between the 1st through the 28th day (P < or = 0.01 to 0.001) post-ligation, although the cytosolic arylamine N-methyltransferase activity did not show a significant change compared to the activities from the sham-operated control. The mitochondrial as well as microsomal thiol methyltransferase showed significant increases in their activities between the 1st through the 28th day (P < or = 0.05 to 0.01 and P < or = 0.01 to 0.001, respectively) post-ligation, although the cytosolic thiol methyltransferase activity did not show a significant change compared to the activities from the sham-operated control. Arylamine N-methyltransferase and thiol methyltransferase in the serum from cholestatic rats also showed significant increases in their activities between the 1st through 28th day (P < or = 0.01 to 0.001), and between the 0.5th through the 42nd day (P < or = 0.05 to 0.001) post-ligation compared to the sham-operated control, respectively. Enzyme kinetic parameters (Km and Vmax) of hepatic membrane-bound arylamine N-methyltransferase and thiol methyltransferase were analyzed with the preparation from the 7th day post-ligation, using tryptamine or 4-chlorothiophenol as substrates and S-Adenosyl-L-[methyl-3H]methionine as co-substrate. The results indicate that although the Km values were about the same as the sham-operated control, the Vmax values of both enzymes increased significantly (P < or = 0.01 and 0.001, respectively). These results suggest that the biosynthesis of arylamine N-methyltransferase and thiol methyltransferase have been induced in response to obstructive jaundice.

Animals↗
PubMed2001

Synthesis and antiviral activity of novel D- and L-2'-azido-2',3'-dideoxyribofuranosyl-4'-thiopyrimidines and purines.

Novel D- and L-2'-azido-2',3'-dideoxyribofuranosyl-4'-thiopyrimidines and purines have been synthesized starting from L-xylose and D-xylose, respectively. Among synthesized compounds tested against several viruses such as HIV-1, HSV-1, HSV-2, and HCMV, D-beta-N6-methyladenine (ent-22a) and D-alpha-N6-methyladenine (ent-22b) analogues were found to exhibit significant anti-HCMV activity.

Antiviral Agents↗
PubMed2001

Quantum teleportation of a polarization state with a complete bell state measurement.

We report a quantum teleportation experiment in which nonlinear interactions are used for the Bell state measurements. The experimental results demonstrate the working principle of irreversibly teleporting an unknown arbitrary polarization state from one system to another distant system by disassembling into and then later reconstructing from purely classical information and nonclassical EPR correlations. The distinct feature of this experiment is that all four Bell states can be distinguished in the Bell state measurement. Teleportation of a polarization state can thus occur with certainty in principle.

Journal Article↗
PubMed2001

Clinical characteristics and outcome of patients with extracutaneous mycosis fungoides.

PURPOSE: To identify prognostic factors predictive of outcome in patients with extracutaneous (stage IV) mycosis fungoides (MF) and to evaluate the risk of progression to extracutaneous disease by initial extent of skin involvement. PATIENTS AND METHODS: One hundred twelve patients with extracutaneous disease at presentation or with progression and 434 patients with initial cutaneous-only disease were identified. Actuarial survival curves were plotted according to the Kaplan-Meier technique. RESULTS: The median survival of all stage IV patients was 13 months from the date of first treatment for stage IV disease. Sex, race, age, extent of skin involvement, and peripheral blood Sezary cell involvement were not significant to survival outcome. Eleven patients (10%) had a complete response to therapy resulting in a significantly improved median survival compared with patients with a partial or no response (1.70 v 0.91 years, P =.047 and 1.70 v 0.57 years, P =.011, respectively). At 20 years from diagnosis, the risk for progression to extracutaneous disease by initial extent of skin involvement was 0% for limited patch/plaque, 10% for generalized patch/plaque, 35.5% for tumorous disease, and 41% for erythrodermic involvement. CONCLUSION: This was a larger scale study over a longer time period than had been completed previously on extracutaneous MF. Prognostic factors important in the cutaneous stages of disease are no longer significant once extracutaneous disease develops. Patients who had a more favorable response to therapy may have had a biologically less aggressive disease than their less fortunate counterparts. The risk of developing stage IV MF is highest in patients presenting with tumorous or erythrodermic skin disease and is lowest in patients with limited skin involvement.

Adult↗