Biomedical subjects

Young-Ho Kim

Publications and source records attributed to Young-Ho Kim.

At least 91 records · Page 5Linked to original sources

PubMed2003

Sodium orthovanadate potentiates EGCG-induced apoptosis that is dependent on the ERK pathway.

Epigallocatechin-3-gallate (EGCG) is a potent chemopreventive agent in many test systems and has been shown to inhibit tumor promotion and induce apoptosis. In the present study, we determined the effect of vanadate, a potent inhibitor of tyrosine phosphatase, on EGCG-induced apoptosis. Investigation of the mechanism of EGCG or vanadate-induced apoptosis revealed induction of caspase 3 activity and cleavage of phospholipase-gamma1 (PLC-gamma1). Furthermore, vanadate potentiated EGCG-induced apoptosis by mitogen-activated protein kinase (MAPK) signaling pathway. Treatment with EGCG plus vanadate for 24h produced morphological features of apoptosis and DNA fragmentation in U937 cells. This was associated with cytochrome c release, caspase 3 activation, and PLC-gamma1 degradation. EGCG plus vanadate activates multiple signal transduction pathways involved in coordinating cellular responses to stress. We demonstrate a requirement for extracellular signal-regulated protein kinase (ERK), a member of the mitogen-activated protein kinase family in EGCG plus vanadate-induced apoptosis in U937 cells. Elevated ERK activity that contributed to apoptosis by EGCG plus vanadate was supported by PD98059 and U0126, chemical inhibitor of MEK/ERK signaling pathway, prevented apoptosis. Taken together, our finding suggests that ERK activation plays an active role in mediating EGCG plus vanadate-induced apoptosis of U937 cells and functions upstream of caspase activation to initiate the apoptotic signal.

Anticarcinogenic Agents↗

PubMed2003

Molecular mechanisms of curcumin-induced cytotoxicity: induction of apoptosis through generation of reactive oxygen species, down-regulation of Bcl-XL and IAP, the release of cytochrome c and inhibition of Akt.

Curcumin, a natural, biologically active compound extracted from rhizomes of Curcuma species, has been shown to possess potent anti-inflammatory, anti-tumor and anti-oxidative properties. The mechanism by which curcumin initiates apoptosis remains poorly understood. In the present report we investigated the effect of curcumin on the activation of the apoptotic pathway in human renal Caki cells. Treatment of Caki cells with 50 microM curcumin resulted in the activation of caspase 3, cleavage of phospholipase C-gamma1 and DNA fragmentation. Curcumin-induced apoptosis is mediated through the activation of caspase, which is specifically inhibited by the caspase inhibitor, benzyloxycarbony-Val-Ala-Asp-fluoromethyl ketone. Curcumin causes dose-dependent apoptosis and DNA fragmentation of Caki cells, which is preceded by the sequential dephosphorylation of Akt, down-regulation of the anti-apoptotic Bcl-2, Bcl-XL and IAP proteins, release of cytochrome c and activation of caspase 3. Cyclosporin A, as well as caspase inhibitor, specifically inhibit curcumin-induced apoptosis in Caki cells. Pre-treatment with N-acetyl-cysteine, markedly prevented dephosphorylation of Akt, and cytochrome c release, and cell death, suggesting a role for reactive oxygen species in this process. The data indicate that curcumin can cause cell damage by inactivating the Akt-related cell survival pathway and release of cytochrome c, providing a new mechanism for curcumin-induced cytotoxicity.

Antineoplastic Agents↗

PubMed2003

Curcumin inhibits protease-activated receptor-2 and -4-mediated mast cell activation.

BACKGROUND: Curcumin, a major yellow pigment and active component of turmeric powder extracted from Curcuma longa L. (Gingiberaceae), has been shown to possess anti-inflammatory and anti-cancer activities. Protease-activated receptors (PARs) play a role in inflammation, and human leukemic mast cells (HMC-1) co-express PAR2 and PAR4. In the present study, the effect of curcumin on PAR2- and PAR4-mediated HMC-1 activation was examined. METHODS: HMC-1 cells were stimulated with trypsin (100 nmol/l, PAR2 and PAR4 agonist), SLIGKV-NH(2) (100 microM, PAR2-activating peptide) or GYPGQV-NH(2) (100 micromol/l PAR4-activating peptide) in the presence or absence of curcumin (1, 10, and 100 micromol/l). TNF-alpha secretion was measured by enzyme-linked immunosorbent assay (ELISA). TNF-alpha and tryptase mRNA were measured by reverse-transcription PCR (RT-PCR). Mitogen-activated protein kinase (MAPK) activation was assessed by Western blot analysis. Trypsin activity was measured using the substrate Bz-DL-Arg-p-nitroanilide (BAPNA). RESULTS: Curcumin (10 and 100 micromol/l) inhibited TNF-alpha secretion from trypsin or activating peptide-stimulated HMC-1. Curcumin (10 and 100 micromol/l) also inhibited TNF-alpha and tryptase mRNA expression in trypsin-stimulated HMC-1. Furthermore, curcumin inhibited trypsin-induced extracellular signal-regulated kinase (ERK) phosphorylation. However, curcumin did not affect the trypsin activity even at 100 micromol/l. CONCLUSION: Curcumin inhibits PAR2- and PAR4-mediated human mast cell activation, not by inhibition of trypsin activity but by block of ERK pathway.

Cell Line, Tumor↗

PubMed2003

Anti-inflammatory effect of Lonicera japonica in proteinase-activated receptor 2-mediated paw edema.

BACKGROUND: Lonicera japonica (Caprifoliaceae) has long been used for treatment of infectious diseases. In the present study, the anti-inflammatory effects of L. japonica water extract (AELJ) were investigated in proteinase-activated receptor 2 (PAR2)-mediated mouse paw edema. METHODS: Paw edema was induced by injection of trypsin or trans-cinnamoyl-LIGRLO-NH(2) (tc-NH(2)) into hindpaw of mice. AELJ (10, 50, 100, and 200 mg/kg) was orally administered 1 h before induction of inflammation. RESULTS: At doses of 50, 100 and 200 mg/kg, the AELJ showed significant inhibition of both change in paw thickness and vascular permeability. The AELJ (100 mg/kg) also significantly inhibited PAR2 agonists-induced myeloperoxidase (MPO) activity and tumor necrosis factor (TNF)-alpha expression in paw tissue. CONCLUSION: The present study demonstrated that AELJ has an anti-inflammatory action for PAR2-mediated paw edema.

Administration, Oral↗

PubMed2003

Correlation of mental health problems with psychological constructs in adolescence: final results from a 2-year study.

In recent years, it has been widely witnessed that a surprising number of adolescents suffer emotional and mental health problems, and such turmoil is very often carried over into adulthood with serious implications for adjustment during the post-adolescent years. On this point, mental health problems in Korea are only now being considered crucial factors in the health status of adolescents and important public and social issues. It is also true that studies concerning the link between adolescents' mental health problems and their psychology are limited. The purposes of this study were to investigate mental health problems of Korean adolescents, to reveal factors affecting their negative mental health and to explore a possible relationship between mental health problems and psychological variables. 2052 Korean adolescents selected randomly from junior high and high schools in Seoul, Korea were surveyed. Korean Symptom Checklist, Health Locus of Control Scale, Self-efficacy Scale and Self-esteem Scale were used to identify mental health problems and psychological variables of adolescents. Results indicated that Korean adolescents showed high prevalence in interpersonal sensitivity, depression, anxiety and hostility. In addition, the findings revealed that there were significant differences in adolescents' mental health problems between gender and age. Furthermore, results revealed that the adolescents' mental health problems were statistically correlated with psychological variables. This study provides significant information for the relatively unstudied Korean adolescents and also has the potential to influence the development of better mental health programs for adolescents.

Adolescent↗

PubMed2003

p-Terphenyl curtisians protect cultured neuronal cells against glutamate neurotoxicity via iron chelation.

The hyperactivity of ionotropic glutamate receptors has been implicated in the development of the neuronal cell death seen in many neurodegenerative processes including ischemic stroke, traumatic brain injury, and epilepsy. Thus neuronal protection against glutamate-induced neurotoxicity is considered as an appropriate therapeutic strategy for preventing and treating neurodegenerative diseases. Whilst searching for blockers of glutamate-induced toxicity in mouse cortical cells, we isolated p-terphenyl curtisians A - D from the mushroom Paxillus curtisii. Curtisians protected cortical neurons from glutamate-induced toxicity in a dose-dependent manner. Among the glutamate receptor subtypes, curtisians were found to block NMDA receptor-mediated but not AMPA/kainate-mediated cell death. In addition, we found that curtisians exhibited potent antioxidative activity against iron-mediated oxidative damage which was generated by H2O2 neurotoxocity and lipid peroxidation, but no activity was detected in the superoxide, DPPH and ABTS radical scavenging systems, and in protection of N18-RE-105 cells subjected to glutamate-induced glutathione depletion. This effect was likely due to the iron chelating properties of curtisians. The iron chelation ability of curtisians was then further investigated on DNA single strand breakage (SSB) induced by the addition of iron and H2O2, and curtisians prevented DNA SSB like the iron chelator desferrioxamine. These results suggest that the neuroprotective action of curtisians is dependent on their ability to chelate iron as well as to block the NMDA receptor, and that in this context curtisians may be useful as neuroprotective agents against neurological disorders which result in neuronal cell death.

Animals↗

PubMed2003

Central facilitation of the glottic closure reflex in humans.

The sphincteric function of the larynx, essential to lower airway protection, is most efficiently achieved through strong reflex adduction by both vocal cords. We hypothesize that central facilitation is an essential component of a bilateral adductor reflex and that its disturbance could result in weakened sphincteric closure. Five patients during supraglottic laryngectomy underwent evoked response laryngeal electromyography under 0.5 and 1.0 minimal alveolar concentration (MAC) isoflurane anesthesia. The internal branch of the superior laryngeal nerve was stimulated through bipolar platinum-iridium electrodes, and recording electrodes were positioned in the ipsilateral and contralateral thyroarytenoid muscles. Consistent threshold responses were obtained ipsilaterally from 0.5 to 1.0 MAC anesthesia. However, the contralateral reflex responses approached 0% in successive trials as anesthetic levels approached 1.0 MAC. In human subjects, alteration of central facilitation by deepening anesthesia abolishes the crossed adductor reflex, predisposing to a weakened glottic closure response. A precise understanding of this effect may improve the prevention of aspiration in patients emerging from prolonged sedation or under heavy psychotropic control.

Aged↗

PubMed2003

Anti-complement activity of constituents from the stem-bark of Juglans mandshurica.

Four known flavonoids and two galloyl glucoses isolated from the stem-bark of Juglans mandshurica (Juglandaceae), namely taxifolin (1), afzelin (2), quercitrin (3), myricitrin (4), 1,2,6-trigalloylglucose (5), and 1,2,3,6-tetragalloylglucose (6), were evaluated for their anti-complement activity against complement system. Afzelin (2) and quercitrin (3) showed inhibitory activity against complement system with 50% inhibitory concentrations (IC(50)) values of 258 and 440 microM. 1,2,6-Trigalloylglucose (5) and 1,2,3,6-tetragalloylglucose (6) exhibited anti-complement activity with IC(50) values of 136 and 34 microM. In terms of the evaluation of the structure-activity relationship of 3,5,7-trihydroxyflavone, compounds 2, 3, and 4 were hydrolyzed with naringinase to give kaempferol (2a), quercetin (3a), and myricetin (4a) as their aglycones, and these were also tested for their anti-complement activity. Of the three aglycones, kaempferol (2a) exhibited weak anti-complement activity with an IC(50) value of 730 microM, while quercetin (3a) and myricetin (4a) were inactive in this assay system. Among the compounds tested, 1,2,3,6-tetragalloylglucose (6) showed the most potent anticomplement activity (IC(50), 34 microM).

Animals↗

PubMed2003

Radioprotective effect of chitosan in sub-lethally X-ray irradiated mice.

The radioprotective effect of chitosan was studied in mice following whole-body X-ray irradiation. C3H/He mice were exposed to 7 Gy, and their survival rates were examined. The survival rates of chitosan-diet mice were about 20% higher than those of mice on a standard diet, and the rates dropped sharply to a plateau at day 10 after X-ray irradiation. The chitosan-diet mice had an increased weight ratio of spleen to body within the experimental period. The leukocyte, thrombocyte, and erythrocyte counts as well as the hematocrit and hemoglobin levels were recovered significantly and more rapidly in the chitosan-diet mice than the standard-diet mice at day 14 after irradiation. The scavenging abilities of chitosan were evaluated by the ESR spin-trapping method. These observations suggested that chitosan led to hematopoetic activation and leukocytogenesis in mice after sub-lethal dose irradiation, and that the biological response might be caused by radical trapping or scavenging.

Animals↗

PubMed2003

Neuroprotective activity of p-terphenyl leucomentins from the mushroom Paxillus panuoides.

The neuroprotective mechanism of p-terphenyl leucomentins from the mushroom Paxillus panuoides was studied. Leucomentins showed potent inhibition of lipid peroxidation and H2O2 neurotoxicity, but free from any role as reactive oxygen species (ROS) scavengers. Iron-mediated oxidative damage has been implicated in these processes, as a provider of ROS via iron. Leucomentins can chelate iron when DNA is present with iron and H2O2, and so inhibiting DNA single strand breakage. These results suggest that the neuroprotective action of leucomentins is dependent on their ability to chelate iron.

Agaricales↗

PubMed2003

Epidemiologic survey of head and neck cancers in Korea.

Head and neck cancers have never been systematically studied for clinical purposes yet in Korea. This epidemiological survey on head and neck cancer patients was undertaken from January to December 2001 in 79 otorhinolaryngology resident-training hospitals nationwide. The number of head and neck cancer patients was 1,063 cases in the year. The largest proportion of cases arose in the larynx, as many as 488 cases, which accounted for 45.9%. It was followed by, in order of frequency, oral cavity (16.5%), oropharynx (10.0%), and hypopharynx (9.5%). The male:female ratio was 5:1, and the mean age was 60.3 yr. Surgery was the predominant treatment modality in head and neck cancers: 204 (21.5%) cases were treated with only surgery, 198 (20.8%) cases were treated with surgery and radiotherapy, 207 cases (21.8%) were treated with combined therapy of surgery, radiotherapy, and chemotherapy. Larynx and hypopharynx cancers had a stronger relationship with smoking and alcohol drinking than other primary site cancers. Of them, 21 cases were found to be metastasized at the time of diagnosis into the lung, gastrointestinal tract, bone, or brain. Coexisting second primary malignancies were found in 23 cases. At the time of diagnosis, a total of 354 cases had cervical lymph node metastasis accounting for 42.0%.

Adolescent↗

PubMed2003

[Clinical characteristics of colonic diverticulitis in Koreans].

BACKGROUND/AIMS: In western countries, symptomatic diverticulitis develops in about 20% of the population with colonic diverticula, and it is mainly located at the left-sided colon. The clinical characteristics of diverticulitis have rarely been investigated although its incidence is increasing in Asia including Korea. The aim of this study was to compare diverticulitis with asymptomatic diverticulosis and to compare the clinical characteristics of right-sided diverticulitis with those of left-sided diverticulitis. METHODS: We retrospectively investigated the medical records of the patients who had symptoms and signs of diverticulitis. Their diagnosis was confirmed with computed tomography, barium study, colonoscopy and/or operations at Samsung Medical Center from September 1998 to February 2002. The control cases of asymptomatic and incidental diverticulosis were randomly selected during routine health check-up after matching age and sex. RESULTS: Twenty-seven patients with diverticulitis (male : female = 14 : 13) were included. The mean age was 53 (27~86). The ratio of right and left diverticulitis was 20:7, which was similar to the ratio of diverticulosis. The complications, especially perforation, were more frequent in the patients with left-sided diverticulitis (p<0.05). CONCLUSIONS: Colonic diverticulitis is more prevalent at the right colon and left colonic diverticulitis has more complications than right colonic diverticulitis in Korea.

Adult↗

PubMed2002

The Ring-H2 finger motif of CKBBP1/SAG is necessary for interaction with protein kinase CKII and optimal cell proliferation.

Protein kinase CKII (CKII) is required for progression through the cell division cycle. We recently reported that the beta subunit of protein kinase CKII (CKIIbeta) associates with CKBBP1 that contains the Ring-H2 finger motif in the yeast two-hybrid system. We demonstrate here that the Ring-H2 finger-disrupted mutant of CKBBP1 does not interact with purified CKIIbeta in vitro, which shows that the Ring-H2 finger motif is critical for direct interaction with CKIIbeta. The CKII holoenzyme is efficiently co-precipitated with the wild-type CKBBP1, but not with the Ring-H2 finger-disrupted CKBBP1, from whole cell extracts when epitope-tagged CKBBP1 is transiently expressed in HeLa cells. Disruption of the Ring-H2 finger motif does not affect the cellular localization of CKBBP1 in HeLa cells. The increased expression of either the wild-type CKBBP1 or Ring-H2 finger-disrupted CKBBP1 does not modulate the protein or the activity levels of CKII in HeLa cells. However, the stable expression of Ring-H2 finger-disrupted CKBBP1 in HeLa cells suppresses cell proliferation and causes the accumulation of the G1/G0 peak of the cell cycle. The Ring-H2 finger motif is required for maximal CKBBP1 phosphorylation by CKII, suggesting that the stable binding of CKBBP1 to CKII is necessary for its efficient phosphorylation. Taken together, these results suggest that the complex formation of CKIIbeta with CKBBP1 and/or CKII-mediated CKBBP1 phosphorylation is important for the G1/S phase transition of the cell cycle.

Amino Acid Motifs↗

PubMed2002

Characterization of cytokines present in pediatric otitis media with effusion: comparison of allergy positive and negative.

To investigate the possible relationship between allergy and otitis media with effusion (OME), we investigated the cytokine level in the middle ear effusion (MEE)s of children with persistent OME. Interleukin (IL)-2, IL-4, IL-6 and tumor necrosis factor (TNF)-alpha in the MEEs were measured by devised sensitive sandwich enzyme-linked immunosorbent assay (ELISA) and compared allergy positive group with allergy negative group. The mean levels of IL-4, IL-6 and TNF-alpha in MEE were significantly higher in allergy positive group than allergy negative group (P<0.05). Elevation of Th-2-driven cytokines (IL-4, IL-6) and TNF-alpha in MEEs may be a contributing factor in the persistence of OME with allergy.

Adolescent↗

PubMed2002

Failure to activate caspase 3 in phorbol ester-resistant leukemia cells is associated with resistance to apoptotic cell death.

The protein kinase C (PKC)-specific inhibitor, Ro-31-8220, has been shown to induce anti-proliferation and apoptosis of human cancer cell lines. In the present study, we determined the molecular pathways that lead to apoptosis after treatment of cells with the PKC-specific inhibitor RO-31-8220. For this, we used the U937 human leukemia cell line and a phorbolmyristate acetate (PMA)-resistant derivative cell line, R-U937. Ro-31-8220 treatment of U937 cells leads to apoptosis, which is accompanied by activation of caspase 3 (as measured by decreased levels of the 32kDa inactive form and increased proteolytic cleavage of phospholipase C (PLC)-gamma1). The broad-range caspase inhibitor z-VAD-fmk inhibits this induction of apoptosis, supporting a direct link between caspase activation and Ro-31-8220 induction of apoptosis. This activation of apoptosis is also accompanied by release of cytochrome c, but not by altered expression of Bcl-2 family protein or IAP family proteins. In R-U937 cells, Ro-31-8220 fails to cause release of cytochrome c, activation of caspase 3, or apoptosis. Activation of Akt occurs to a greater extent in the R-U937 cells than the U937 cells and thus might be related to protection from Ro-31-8220-induced apoptosis.

Apoptosis↗

PubMed2002

Role of nitric oxide synthase inhibitors and NMDA receptor antagonist in nicotine-induced behavioral sensitization in the rat.

Repeated injections of nicotine are well known to produce progressively larger increases in locomotor activity, an effect defined as behavioral sensitization. This study was carried out to investigate the role of nitric oxide (NO) and N-methyl-D-aspartate (NMDA) receptors in nicotine-induced behavioral sensitization. Rats were given repeated injections of nicotine (0.4 mg/kg, s.c., twice daily for 7 days) followed by one challenge injection on the fourth day after the last daily injection. Systemic challenge with nicotine produced a much larger increase in locomotor activity in nicotine-pretreated rats. Rats were pretreated with the nonselective nitric oxide synthase (NOS) inhibitor, N(G)-nitro-arginine-methyl-ester (L-NAME; 75 mg/kg, i.p.), the selective constitutive NOS inhibitor, N-nitro-L-arginine (L-NNA; 15 mg/kg, i.p.), the prototypical selective inducible NOS inhibitor, aminoguanidine (100 mg/kg, i.p.) or NMDA receptor antagonist, MK-801 ((5R,10S)-(+)-5-Methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine; 0.3 mg/kg, i.p.), 30 min before injections of nicotine during a 7-day development or a 3-day withdrawal phase after which challenged with nicotine on day 11. Pretreatment with L-NAME, L-NNA and MK-801, but not aminoguanidine, blocked the development of nicotine-induced sensitization to subsequent nicotine challenge. Injections of MK-801 twice daily during 3-day withdrawal periods after a 7-day induction period of nicotine attenuated nicotine-induced behavioral sensitization, whereas injections of L-NAME, L-NNA or aminoguanidine had no effects on the expression of sensitization produced by repeated nicotine. This study demonstrates that NMDA receptors can play a major role in the expression as well as development of nicotine-induced behavioral sensitization, and that NO is also involved in the development, but not critically involved in the expression of behavioral sensitization to nicotine.

Animals↗

PubMed2002

Apoptosis and its correlation with proliferative activity in rectal cancer.

BACKGROUND AND OBJECTIVES: Alterations in the normal control of apoptosis and cell proliferation are important factors in multistep colorectal carcinogenesis. The aim of this study was to determine the frequency of apoptosis and cell proliferation in rectal cancers and to examine their relationship to clinicopathological variables and expression of bcl-2 and p53. METHODS: Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) staining and immunohistochemical staining for Ki-67, bcl-2, and p53 were performed on paraffin-embedded tissue samples of 57 rectal cancers. RESULTS: There was a positive linear correlation between apoptotic index (AI) and proliferative index (PI) (gamma = 0.276, P = 0.038). Both apoptosis and cell proliferation were more frequently found in rectal cancers with lymph node metastasis (P = 0.045 and 0.010, respectively). However, the ratio of AI and PI was not different by nodal status. There was no association between Dukes stage and AI or PI. The frequency of apoptosis was inversely related to the expression of bcl-2, but was not related to the p53 status of rectal cancer. There were no association between cell proliferation and the expression of bcl-2 or p53. CONCLUSIONS: Our results suggest that the susceptibility to apoptosis in rectal cancer is clearly related to the proliferative activity and high turnover rate of tumor cells may contribute to lymph node metastasis.

Adult↗

PubMed2002

Gymnasterkoreaynes A-F, cytotoxic polyacetylenes from Gymnaster koraiensis.

Six new polyacetylenes, gymnasterkoreaynes A-F (1-6), were isolated from the roots of Gymnaster koraiensis, together with 2,9,16-heptadecatrien-4,6-diyn-8-ol (7) and 1,9,16-heptadecatriene-4,6-diyn-3,8-diol (8), by bioassay-guided fractionation using the L1210 tumor cell line as a model for cytotoxicity. The structures of compounds 1-6 were established spectroscopically, which included 2D NMR experiments. Gymnasterkoreaynes A-F (1-6) are linear diacetylenes and are structurally related to falcarinol, panaxynol, panaxydiol, and panaxytriol. Of the compounds isolated, gymnasterkoreaynes B (2), C (3), F (6), and 1,9,16-heptadecatrien-4,6-diyn-3,8-diol (8) exhibited significant cytotoxicity against L1210 tumor cells with ED(50) values of 0.12-3.3 microg/mL.

Acetylene↗