Biomedical subjects

Chan-Hyung Kim

Publications and source records attributed to Chan-Hyung Kim.

17 recordsLinked to original sources

PubMed2006

Lack of association between polymorphisms of the dopamine receptor D4 and dopamine transporter genes and personality traits in a Korean population.

Human personality traits have a considerable genetic component. Cloninger et al. were the first to postulate that certain personality traits, such as novelty seeking, are related to the dopamine neurotransmitter system. In this study, we investigated the associations between dopamine receptor D4 (DRD4) exon III and dopamine transporter (DAT1) polymorphisms and personality traits. The DRD4 and DAT1 gene polymorphisms were genotyped in 214 healthy Korean subjects, whose personality traits were assessed with the Temperament and Character Inventory (TCI). There were no significant differences between scores of TCI temperament dimensions (novelty seeking, harm avoidance, reward dependence, and persistence) and DRD4 gene polymorphism. The DAT1 gene polymorphisms also showed no significant association with any of the temperament subscales of the TCI. These data suggest that DRD4 and DAT1 gene polymorphism may not associated with personality traits in a Korean population.

Adult↗

PubMed2006

The genetic studies of obsessive-compulsive disorder and its future directions.

Obsessive-compulsive disorder (OCD) is characterized by recurrent and persistent thoughts (obsessions), and repetitive behaviors or mental acts (compulsions). In Korea, an epidemiological study reported that the lifetime prevalence of OCD in the population was greater than two percent. The exact cause of OCD is still unknown. Evidence from familial, twin and segregation studies supports the role of a genetic component in the etiology of OCD. In addition, there is growing evidence that OCD has a specific neurochemical and neuroanatomical basis. According to this evidence, researchers have selected various candidate genes which have been implicated in the neurophysiology of OCD, and differences of allelic variants in OCD patients and controls have been analyzed. In this review we will introduce the results of previous genetic studies of OCD which have been performed in other populations, including twin studies, family studies, segregation analyses, linkage analyses, and association studies. In addition to these studies, we will present the results of our genetic studies of OCD performed in Korea.

Alleles↗

PubMed2006

Bilateral anterior cingulotomy for refractory obsessive-compulsive disorder: Long-term follow-up results.

OBJECTIVE: To investigate the long-term efficacy and adverse cognitive effects of stereotactic bilateral anterior cingulotomy as a treatment for refractory obsessive-compulsive disorder (OCD) patients. MATERIALS AND METHODS: Seventeen patients suffering from refractory OCD underwent stereotactic bilateral anterior cingulotomies and were followed for 24 months. The Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), the Clinical Global Impression and other neuropsychological tests were used to assess the efficacy and cognitive changes of cingulotomy. The tests were taken before and 12 and 24 months after surgery. RESULTS: The mean improvement rate of the Y-BOCS score achieved from the baseline was 48%. Eight patients out of 17 met the responder criteria. During the 24-month follow-up, there were no significant adverse effects observed after surgery. CONCLUSIONS: Bilateral anterior cingulotomy was effective for the treatment of refractory OCD, and no other significant adverse cognitive effects on long-term follow-up were found.

Adult↗

PubMed2006

An association study of catechol-O-methyltransferase and monoamine oxidase A polymorphisms and personality traits in Koreans.

Catechol-O-methyltransferase (COMT) and monoamine oxidase A (MAOA) are both involved in the degradation of various biogenic amines which have been hypothesized to have a relationship with personality traits. The present study investigated the possible relationships between the genotypes of COMT Val158Met and MAOA-uVNTR polymorphisms and personality traits measured by the Temperament and Character Inventory (TCI). We recruited 286 normal, unrelated Korean subjects (138 males and 148 females). There were no associations between the COMT Val158Met genotypes or the TCI subscales in the male subjects. However, a significant correlation was observed between the COMT genotype and harm avoidance (HA, F=6.0, p=0.003) in females. Post hoc analyses showed that the subjects with the Met/Met genotype had the lowest mean HA (HA=13.8+/-5.7, p=0.02), Val/Met group had an intermediate mean HA score (HA=16.3+/-7.0, p=0.02), and Val/Val group had the highest mean HA value (HA=19.6+/-7.0, p=0.02). There were no associations between the MAOA-uVNTR and the TCI subscales in either the male or female subjects. These results suggest that genetic variants of the COMT Val158Met gene may play a role in HA in Korean females but not in males.

Adult↗

PubMed2005

Obsessive-compulsive disorder, factor-analyzed symptom dimensions and serotonin transporter polymorphism.

Recently, on the basis of the effects of serotonin (5-HT) reuptake inhibitors in obsessive-compulsive disorder (OCD) treatment, several candidate genes related to 5-HT regulation have been hypothesized to play an important role in the development of OCD. One of them is 5-HT transporter gene. Therefore, the aims of this study were to investigate the associations between 5-HT transporter polymorphism and OCD. One hundred and twenty-four OCD patients and 171 normal controls participated in this study. Genomic DNA was extracted from their blood. Comparison of the genotypes and allele frequencies of the SERTPR polymorphism between the OCD group and the control group was made. Using principal component analysis, we derived four factors from thirteen main contents of the Y-BOCS checklist and investigated the association between these four factors and the SERTPR polymorphism. In this case-control study, we could not find any associations between the SERTPR polymorphism and the development of OCD. In the OCD group, patients with the L genotype had higher scores for the religious/somatic factor than with the S genotype. In conclusion, the SERTPR polymorphism does not affect the development of OCD. But SERTPR polymorphisms affect certain factors of OC symptoms. Moreover, the factor analytic approach used in the present study has identified meaningful symptom dimensions to help guide future research.

Adult↗

PubMed2005

Serotonin transporter gene polymorphism and personality traits in a Korean population.

Recently, there has been growing enthusiasm for exploring biological approaches to personality, especially in the area of genetic research into the identification of those genes responsible for particular personality traits. The aim of this study was to investigate the association between the serotonin transporter-linked promoter region (5-HTTLPR) polymorphism and personality traits. We recruited 211 unrelated, normal subjects. The Korean version of the Temperament and Character Inventory (TCI) was used to assess certain personality traits. From blood samples taken from the subjects, DNA was isolated using standard techniques and the 5-HTTLPR polymorphism was genotyped by means of polymerase chain reaction and electrophoresis. We classified the subject into the s/s, s/l, and l/l groups according to their genotype. The differences in the temperament factors of the TCI between group S (s/s genotype) and group L (s/l + l/l genotype) were assessed, after the inclusion of gender and age as covariates in the analysis of variance. After controlling for gender and age, there were no associations between the harm avoidance, novelty seeking, and reward dependence scores and the genotypes. However, the persistence score of group S was significantly higher than that of group L. Our results suggest that the 5-HTTLPR polymorphism may be associated with the persistence score of the TCI in a normal Korean population.

Adult↗

PubMed2005

Serotonin transporter gene polymorphism and migraine in the Korean population.

OBJECTIVE: To evaluate the association between a serotonin (5-HT) transporter gene polymorphism and migraines in Koreans. BACKGROUND: The 5-HT metabolism is believed to play an important part in the pathophysiology of migraines, and a polymorphism of the serotonin transporter (5-HTT) promoter region might influence 5-HTT expression and serotonin uptake. METHODS: This study compared 52 patients with migraine and 170 healthy control subjects in order to determine the association between a polymorphism of the 5-HTT gene-linked polymorphic region (5-HTTLPR) and migraine. Using PCR techniques, the products of the 484-base pair (bp) fragments were denoted as being short alleles (s) and those of 528 bp as being long (l). RESULTS: The genotype distribution of the healthy controls was s/s (56.5%), s/l (38.2%), and l/l (5.3%) and that of the patients with migraine was 65.4%, 30.8%, and 3.8%, respectively. No significant differences were noted in the genotype and allele frequencies of 5-HTTLPR between the patients with migraine and the control subjects. CONCLUSIONS: A 5-HTTLPR polymorphism does not appear to be involved in the genetic predisposition to migraines.

Adolescent↗

PubMed2004

Dopamine transporter density of the basal ganglia assessed with [123I]IPT SPECT in drug-naive children with Tourette's disorder.

There is evidence that abnormalities in the dopaminergic system involving the dopamine transporter (DAT) are involved in the pathophysiology of Tourette's disorder (TD) from previous studies using [(123)I]2beta-carbomethoxy-3-(4-iodophenyl)tropane ([(123)I]beta-CIT) and single photon emission tomography (SPECT). However, because those studies were performed in medicated adult patients with TD, we decided to compare DAT densities in nine drug-naive children with TD and eight normal children. The children with TD did not suffer from associated psychiatric problems such as obsessive-compulsive symptoms, attention deficit hyperactivity disorder, anxiety, depression and developmental difficulties. We performed brain SPECT 2 h after the intravenous administration of I-123N-(3-iodopropen-2-yl)-2beta-carbomethoxy-3beta-(4-chlorophenyl)tropane ([(123)I]IPT) and carried out both quantitative and qualitative analyses using the obtained SPECT data, which were reconstructed for the assessment of the specific/non-specific DAT binding ratio in the basal ganglia. We then investigated the correlation between the severity of tics in children with TD assessed with the Yale Global Tic Severity Scale (YGTSS) and the specific/non-specific DAT binding ratio of the basal ganglia. Drug-naive children with TD showed a significantly increased specific/non-specific DAT binding ratio in the basal ganglia compared with normal children that did not correlate significantly with the severity of tics. Our results with drug-naive children with TD between the ages of 6 and 12 may help to clarify previous findings concerning DAT binding in adult patients with TD and suggest that DAT densities may be associated directly with the pathophysiology of TD, regardless of disease progress or drug effect.

Basal Ganglia↗

PubMed2004

Local delivery of green tea catechins inhibits neointimal formation in the rat carotid artery injury model.

It has been shown that green tea catechins (GTC) suppress proliferation of vascular smooth muscle cells (VSMCs) and that epigallocatechin-3-gallate (EGCG), which is a major constituent of GTC, selectively inhibits the platelet-derived growth factor-BB (PDGF-BB)-induced intracellular signaling transduction pathway. Vascular smooth muscle cell proliferation is one of major mechanisms of restenosis following percutaneous coronary intervention. This study tested whether GTC can inhibit VSMC proliferation and prevent neointimal formation in a rat carotid artery injury model. Vascular smooth muscle cell proliferation inhibition was analyzed with [3H]thymidine incorporation. Green tea catechins were applied to the endothelium-denuded carotid arteries of rats for 20 min. Angiography and morphometric analysis was performed after 2 weeks. Green tea catechins decreased [3H]thymidine incorporation stimulated with PDGF-BB dose dependently. In the absence of PDGF-BB, the decrement of [3H]thymidine incorporation was evident above a concentration of 10 micro g/ml of GTC. Carotid arteriographic evaluation showed that the minimum luminal diameter in the GTC-treated group (n=12) was 5.9 +/- 1.6 arbitrary units (a.u.) and was significantly larger than in the control group (4.3 +/- 1.4 a.u., n=10) ( P <0.05). The GTC-treated group also showed a significant reduction in neointimal formation compared with the control group (0.29 +/- 0.11 vs 0.42 +/- 0.10 mm2, P < 0.05). To identify the active ingredients, we performed a similar experiment using EGCG. The effects of EGCG were similar to those of GTC. Green tea catechins effectively inhibited VSMC proliferation. Neointimal formation was prevented in the rat carotid artery injury model by local delivery of GTC. As EGCG showed similar effects, it may be one of the major constituents of GTC having these effects.

Angiography↗

PubMed2003

Manganese superoxide dismutase expression correlates with chemosensitivity in human gastric cancer cell lines.

PURPOSE: The purpose is to investigate the potential correlation between antioxidant enzyme (AOE) levels and resistance to anticancer drugs in human gastric carcinoma cell lines. EXPERIMENTAL DESIGN: Protein contents of AOEs such as manganese superoxide dismutase (MnSOD), copper/zinc superoxide dismutase, catalase, glutathione S-transferase-pi, p-glycoprotein, and multidrug resistance-associated protein were observed by Western blot analysis, and MnSOD activity was measured in six Korean gastric cancer cell lines. The direct correlation between AOEs and the chemosensitivity to doxorubicin (DOX), mitomycin C, 5-fluorouracil, and vinblastine was analyzed by cytotoxicity test. MnSOD was overexpressed by transient transfection of human MnSOD cDNA. RESULTS: Expressions of AOEs in gastric cancer cell lines were variable. MnSOD expression was related with the resistance to DOX and mitomycin C but not with that to 5-fluorouracil and vinblastine. In comparison, expressions of other AOEs, p-glycoprotein and multidrug resistance-associated protein, were not correlated with tumor sensitivity to any of the drugs used. Cell lines with a high MnSOD protein content showed higher MnSOD activity than those with a low MnSOD protein content. In addition, MnSOD overexpression increased the resistance of gastric carcinoma cells to DOX. CONCLUSIONS: MnSOD is an important factor of drug response to reactive oxygen species-generating anticancer drugs in the gastric cancer cells. Thus, measurement of MnSOD levels in clinical samples may provide an indication of subsequent treatment response of gastric cancer patients.

Antineoplastic Agents↗

PubMed2003

Dopamine transporter density of basal ganglia assessed with [123I]IPT SPET in obsessive-compulsive disorder.

It has been suggested that dopamine, as well as serotonin, is associated with the pathophysiology of obsessive-compulsive disorder (OCD). Thus, many studies have been performed on brain regions associated with dopamine in patients with OCD. In the present study, we investigated the DAT density of the basal ganglia using iodine-123 labelled N-(3-iodopropen-2-yl)-2beta-carbomethoxy-3beta-(4-chlorophenyl) tropane ([123I]IPT) single-photon emission tomography (SPET) and evaluated the activity of the presynaptic dopamine function in patients with OCD. Fifteen patients with OCD and 19 normal control adults were included in the study. We performed brain SPET 2 h after the intravenous administration of [123I]IPT and carried out both quantitative and qualitative analyses using the obtained SPET data, which were reconstructed for the assessment of the specific/non-specific dopamine transporter (DAT) binding ratio in the basal ganglia. We then investigated the correlation between the severity scores of OCD symptoms assessed with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and the specific/non-specific DAT binding ratio of the basal ganglia. Compared with normal control adults, patients with OCD showed a significantly increased specific/non-specific DAT binding ratio in the right basal ganglia and a tendency towards an increased specific/non-specific DAT binding ratio in the left basal ganglia. No significant correlation was found between the total scores on the Y-BOCS and the specific/non-specific DAT binding ratio of the basal ganglia. These findings suggest that the dopaminergic neurotransmitter system of the basal ganglia in patients with OCD could be involved in the pathophysiology of OCD.

Adolescent↗

PubMed2003

Hopelessness, neurocognitive function, and insight in schizophrenia: relationship to suicidal behavior.

Insight and hopelessness have been reported to be associated with suicidality in schizophrenia. In addition, there is evidence that diminished insight is correlated with impairment in some domains of cognitive function in schizophrenia. The purpose of this study was to clarify the relative importance for suicidality in patients with schizophrenia of hopelessness, cognitive dysfunction, and insight. This study included 333 patients with chronic schizophrenia who were prospectively studied. Insight was rated by the insight items from the Schedule for Affective Disorders and Schizophrenia (SADS) and the Hamilton Depression Rating Scale (HDRS). Positive, negative, and anxiety-depression symptoms were measured with the Brief Psychiatric Rating Scale (BPRS). Cognition was assessed with a neurocognitive battery, which included measures of attention and psychomotor speed, verbal fluency, verbal memory, working memory, and executive function. Current and lifetime suicidality was prospectively assessed. Hopelessness, substance abuse, and greater insight were associated with attempted suicide and suicidal ideation. Those with a history of lifetime, but not current, suicidality had better function on tests of psychomotor speed and attention, verbal working memory, verbal fluency, verbal memory, and executive function. Neurocognitive measures were not significantly correlated with hopelessness and insight. Hopelessness was more severe in those with current and lifetime suicidality. A multiple regression analysis was used to predict current and lifetime suicidality from hopelessness, substance abuse, insight, and cognitive factor scores. The regression models predicting current and lifetime suicidality indicated that hopelessness was the most important predictor of both (beta=0.41, p=0.0001; and beta=0.35, p=0.01, respectively). These findings suggest that hopelessness, substance abuse, greater insight into illness, and higher cognitive function are associated with greater suicidality in chronic schizophrenia, but that among these, hopelessness may be the principal predictor of suicidality.

Adolescent↗

PubMed2003

Hypoxic activation of the atrial natriuretic peptide gene promoter through direct and indirect actions of hypoxia-inducible factor-1.

Atrial natriuretic peptide (ANP) is a cardiac peptide, the transcription of which is up-regulated in the ischaemic ventricle. However, the molecular mechanism of ANP induction is unclear. This study demonstrated that ANP mRNA expression in rat ventricular myocardium is induced in an early phase of ischaemia, preceded by hypoxia-inducible factor-1 (HIF-1) alpha expression. The ANP gene was also induced by hypoxia or HIF-1 inducers such as CoCl2 and desferrioxamine in H9c2 and neonatal cardiomyocytes. The 2307 bp 5'-flanking region of the rat ANP gene was cloned and fused to the luciferase gene. Evidence of the promoter activity was only apparent in the myocytes and was induced by hypoxia and HIF-1 inducers. The overexpression of HIF-1alpha markedly enhanced ANP promoter activity, and a dominant-negative isoform completely suppressed it. We demonstrated that the promoter regions are essential for hypoxic ANP induction. One promoter region, containing the HIF-1-binding sequence, is regulated directly by HIF-1. The other region is also activated by HIF-1 despite having no HIF-1-binding sequence. These results suggest that HIF-1 enhances the transactivation of the ANP gene in hypoxic myocytes, implying that stimulation of the ANP promoter by HIF-1 may in fact be responsible for the induction of the ANP gene in ischaemic ventricular myocardium.

Animals↗

PubMed2003

General pharmacology of indole [2',3':3,4]pyrido[2,1-b]quinazolinium- 5,7,8,13-tetrahydro-14-methyl-5-oxo-chloride, a new anti-dementia agent.

The general pharmacological properties of indolo[2',3':3,4]pyrido[2,1-b]quinazolinium-5,7,8,13-tetrahydro-14- methyl-5-oxo-chloride (dehydroevodiamine-HCl, DHED, CAS 67909-49-3), a new potential anti-dementia agent, were studied to investigate side effects using various experimental animals. Both oral and intraperitoneal administration of DHED had no effects on the central nervous system except that they showed an analgesic activity. DHED had no significant effect on heart rate, blood pressure and coronary flow in isolated rat hearts. DHED had negligible effects on the autonomic nervous system and smooth muscle in isolated rat ileum, rat vas deferens and rat aorta. DHED did not influence the gastrointestinal system except that it inhibited the intestinal travel of a charcoal meal in mice. Neither blood coagulation mechanism nor liver function was affected by DHED. Therefore, it is concluded from these general pharmacological studies that DHED does not induce any serious side effects at the dose levels showing anticholinesterase and memory enhancing activities in the experimental animals.

Alkaloids↗

PubMed2002

Dopamine transporter density in the basal ganglia assessed with [123I]IPT SPET in children with attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) is a psychiatric disorder in childhood that is known to be associated with dopamine dysregulation. In this study, we investigated dopamine transporter (DAT) density in children with ADHD using iodine-123 labelled N-(3-iodopropen-2-yl)-2beta-carbomethoxy-3beta-(4-chlorophenyl) tropane ([(123)I]IPT) single-photon emission tomography (SPET) and postulated that an alteration in DAT density in the basal ganglia is responsible for dopaminergic dysfunction in children with ADHD. Nine drug-naive children with ADHD and six normal children were included in the study. We performed brain SPET 2 h after the intravenous administration of [(123)I]IPT and carried out both quantitative and qualitative analyses using the obtained SPET data, which were reconstructed for the assessment of the specific/non-specific DAT binding ratio in the basal ganglia. We then investigated the correlation between the severity scores of ADHD symptoms in children with ADHD assessed with ADHD rating scale-IV and the specific/non-specific DAT binding ratio in the basal ganglia. Drug-naive children with ADHD showed a significantly increased specific/non-specific DAT binding ratio in the basal ganglia compared with normal children. However, no significant correlation was found between the severity scores of ADHD symptoms in children with ADHD and the specific/non-specific DAT binding ratio in the basal ganglia. Our findings support the complex dysregulation of the dopaminergic neurotransmitter system in children with ADHD.

Attention Deficit Disorder with Hyperactivity↗

PubMed2002

Early expression of myocardial HIF-1alpha in response to mechanical stresses: regulation by stretch-activated channels and the phosphatidylinositol 3-kinase signaling pathway.

Vascular endothelial growth factor (VEGF) expression is upregulated by hypoxia-inducible factor-1 (HIF-1) in ischemic tissues and growing tumors. Normally, HIF-1 activity depends on the amount of HIF-1alpha subunit, which is tightly regulated by the oxygen tension. In the myocardium, VEGF expression has been shown to be induced under nonhypoxic conditions by mechanical stresses. However, the cellular mechanism of stress-mediated VEGF induction remains unclear. Therefore, we examined the possible involvement of HIF-1 in stress-mediated VEGF induction in rat hearts. In this study, we increased the left ventricular wall tension using 3 different methods, namely by inducing regional ischemia, by expanding an intraventricular balloon, and by producing hemodynamic overload using an aortocaval shunt. In all cases, HIF-1alpha accumulated in the nuclei of cardiac myocytes in the early phase, and this was followed by VEGF induction. Phosphatidylinositol 3-kinase (PI3K)-dependent Akt phosphorylation was found to be activated by mechanical stress and completely blocked by wortmannin (a PI3K inhibitor). Moreover, the stress-mediated induction of HIF-1alpha and VEGF was suppressed by gadolinium (a stretch-activated channel inhibitor), wortmannin, and rapamycin (a FRAP inhibitor). Our results suggest that HIF-1alpha plays an important role in the induction of VEGF in nonischemic and mechanically stressed myocardium, and that this is regulated by stretch-activated channels and the PI3K/Akt/FRAP pathway. Moreover, this signaling pathway, which induces HIF-1alpha, seems to play an important role in the adaptation of the myocardium to stresses. The full text of this article is available at http://www.circresaha.org.

Androstadienes↗

PubMed2002

Involvement of adrenergic pathways in activation of catalase by myocardial ischemia-reperfusion.

In situ rabbit hearts were subjected to 15 min of regional myocardial ischemia, and at various time points of reperfusion, antioxidant enzyme activity and mRNA expression were measured in ischemic and nonischemic myocardium. Catalase activity increased significantly in both ischemic and nonischemic myocardium, peaking at 1 h after reperfusion and then gradually returning to the control level. Northern blot analysis showed enhanced expression of catalase mRNA in both areas. There were no changes in redox status, because glutathione levels were not altered by ischemia-reperfusion (I/R). We also tested whether catalase activation in the heart results from signaling pathways that might influence not only the heart but also other organs. We found that catalase activity in the brain was increased after myocardial I/R and ischemic stress to the intestine was equipotent to myocardial I/R in catalase activation. We next sought to elucidate the possible involvement of the adrenergic system in catalase stimulation induced by ischemic stimuli. After pretreatment with the alpha-adrenergic receptor antagonist prazosin, I/R failed to increase catalase activity in the heart and brain. Intravenous norepinephrine increased catalase activity in the heart, brain, and liver. This study shows that brief I/R activates a signaling mechanism to induce catalase activation in multiple organs and the alpha-adrenergic system is involved as an intermediate pathway in this signal transmission.

Adrenergic Fibers↗