Biomedical subjects

Yong-Sik Kim

Publications and source records attributed to Yong-Sik Kim.

12 recordsLinked to original sources

PubMed2003

Tsp57: a novel gene induced during a specific stage of spermatogenesis.

Recently, we described the identification of a novel protein, nuclear receptor-associated protein 80 (RAP80), which is highly expressed in spermatocytes and appears to have a role in regulating gene expression. To identify proteins interacting with this protein, we performed yeast two-hybrid screening using full-length RAP80 as bait. This screen identified one in-frame clone encoding a novel testis-specific protein (Tsp), referred to as Tsp57. Tsp57 encodes a basic protein with a mass of 56.8 kDa. The amino acid sequence of Tsp57 is highly conserved (87%) between mouse and human. The mouse and human Tsp57 genes map to chromosomes 9A1 and 11q21, respectively. Northern blot analysis showed that the expression of Tsp57 mRNA was highly restricted to the testis and temporally regulated during testicular development. Tsp57 mRNA was greatly induced between Day 21 and Day 25 of postnatal testicular development. In situ hybridization analysis demonstrated that the hybridization signal for Tsp57 mRNA was strongest in sections of seminiferous tubules at stages VI-VIII of spermatogenesis, consistent with the conclusion that Tsp57 is most highly expressed in round spermatids. Study of Tsp57 expression in several purified subpopulations of spermatogenic cells confirmed maximum levels of expression in round spermatids. Consistently, Tsp57 expression was absent in testes from vitamin A-deficient mice, which do not have any round spermatids, and was reduced in RARalpha null mice, which have lowered numbers of round spermatids in their testes. These results indicate the possibility that Tsp57 protein plays a role in the postmeiotic phase of germ cell differentiation. Tsp57 contains two putative nuclear localization signals: NLS1 and NLS2. Examination of the cellular localization showed that the green fluorescent protein-Tsp57 fusion protein localized to both cytoplasm and nucleus. After deletion of NLS1 but not NLS2, Tsp57 localized solely to the cytoplasm, indicating a role for NLS1 in the nuclear localization of Tsp57. The localization suggests a nuclear function for Tsp57. Pull-down analysis demonstrated that Tsp57 and RAP80 form a complex in intact cells.

Amino Acid Sequence↗

PubMed2003

Acupuncture prevents 6-hydroxydopamine-induced neuronal death in the nigrostriatal dopaminergic system in the rat Parkinson's disease model.

Parkinson's disease (PD) is a chronic neurodegenerative disorder, and it has been suggested that treatments promoting survival and functional recovery of affected dopaminergic neurons could have a significant and long-term therapeutic value. In the present study, we investigated the neuroprotective effects of acupuncture on the nigrostriatal system in rat unilaterally lesioned with 6-hydroxydopamine (6-OHDA, 4 microg/microl, intrastriatal injection) using tyrosine hydroxylase (TH) and receptor for brain-derived neurotrophic factor, trkB, immunohistochemistries. Two weeks after the lesions were made, rats presented with asymmetry in rotational behavior (118.3 +/- 17.5 turns/h) following injection with apomorphine, a dopamine receptor agonist (0.5 mg/kg, sc). In contrast, acupunctural treatment at acupoints GB34 and LI3 was shown to significantly reduce this motor deficit (14.6 +/- 13.4 turns/h). Analysis via TH immunohistochemistry revealed a substantial loss of cell bodies in the substantia nigra (SN) (45.7% loss) and their terminals in the dorsolateral striatum ipsilateral to the 6-OHDA-induced lesion. However, acupunctural treatment resulted in the enhanced survival of dopaminergic neurons in the SN (21.4% loss) and their terminals in the dorsolateral striatum. Acupuncture also increased the expression of trkB significantly (35.6% increase) in the ipsilateral SN. In conclusion, we observed that only acupuncturing without the use of any drug has the neuroprotective effects against neuronal death in the rat PD model and these protective properties of acupuncture could be mediated by trkB.

Acupuncture Therapy↗

PubMed2003

Protective effect of methanol extract of Uncaria rhynchophylla against excitotoxicity induced by N-methyl-D-aspartate in rat hippocampus.

Uncaria rhynchophylla is a medicinal herb used for convulsive disorders in Oriental medicine. In this study, the effect of the methanol extract of Uncaria rhynchophylla against N-methyl-D-aspartate (NMDA)-induced excitotoxicity was investigated. Pretreatment with the extract of Uncaria rhynchopylla reduced the degree of neuronal damage induced by NMDA exposure in cultured hippocampal slices. In the patch clamp study, Uncaria rhynchophylla significantly inhibited NMDA receptor-activated ion current in acutely dissociated hippocampal CA1 neurons. These results indicate that Uncaria rhynchophylla offers protection against NMDA-induced neuronal injury and inhibitory action on NMDA receptor-mediated ion current may be a mechanism behind the neuroprotective effect of Uncaria rhynchophylla.

Animals↗

PubMed2002

The pattern of interleukin-12 and T-helper types 1 and 2 cytokine expression in herniated lumbar disc tissue.

STUDY DESIGN: A study was conducted to investigate the expression of cytokines related to the immune reaction in herniated lumbar disc tissues. OBJECTIVE: To investigate the immunologic status of lumbar disc tissue and the type of immune reaction that occurs in response to lumbar disc herniation. SUMMARY OF BACKGROUND DATA: It has been proposed that herniated lumbar disc tissue causes an immune reaction. Various inflammatory cells, proinflammatory cytokines, antibodies, and immunoglobulins have been identified in and around herniated lumbar disc tissue. Recently, it has been reported that lumbar disc tissue may be another potential immune-privileged site in the human body. METHODS: This study included 40 herniated lumbar disc tissues: 20 contained and 20 noncontained discs. The concentrations of interleukin-12, T-helper Type 1, interferon-gamma (IFN-gamma), and Th2 (IL-4) cytokines were determined by enzyme-linked immunosorbent assay, respectively. The results were compared between the two groups. RESULTS: The concentrations of interleukin-12 and interferon-gamma were higher in the noncontained discs than in the contained discs: 28.3 +/- 10.7 pg/mL vs 9.2 +/- 4.2 pg/mL (P = 0.001) and 4.7 +/- 5.0 pg/mL vs 2.3 +/- 3.8 pg/mL (P = 0.029), respectively. On the contrary, the concentration of IL-4 was higher in the contained discs than in the noncontained discs: 24.3 +/- 20.1 pg/mL vs 1.9 +/- 4.5 pg/mL; P= 0.001. The degrees of interleukin-12 and interferon-gamma expression were negatively correlated with that of IL-4 (n = 40): correlation coefficient, -0.671 (P = 0.001) and correlation coefficient, -0.344 (P = 0.03), respectively. CONCLUSIONS: The findings suggest that preferential expression of Th2 cytokines by disc cells, as shown in contained discs, is another factor contributing to the immune privileged status of lumbar disc tissue. The exposure of lumbar disc tissue to the epidural space may increase the concentration of interleukin-12 in herniated lumbar disc tissue, changing the pattern of T-helper Types 1 and 2 cytokine expression.

Adolescent↗

PubMed2002

Spatial working memory span, delayed response and executive function in schizophrenia.

This study investigated the spatial working memory span (SWMS) as well as the immediate memory span of schizophrenic patients, and examined the contribution of each span to the patients' executive function deficit in the visuospatial domain. SWMS measured the visuospatial working memory capacity that simultaneously processes and stores visuospatial information. Immediate memory span was measured with the spatial span (SS), a variant of Corsi's block-tapping test. A total of 16 patients diagnosed with schizophrenia and 16 normal control subjects participated in the study. SWMS, as well as the forward and backward SS, was significantly reduced in schizophrenia. The SWMS deficit observed in this study and previous findings of deficit in verbal working memory spans suggest that impairment in working memory capacity in schizophrenia is general, and not limited to the verbal domain. Executive function as assessed with the self-ordered pointing task (SOPT) was also impaired in the patients, which is consistent with clinical observations of self-monitoring impairment in schizophrenia. SWMS was able to account for the performance on the SOPT, but its contribution in the patients' impairment did not reach statistical significance. Backward span deficit explained this executive function impairment. SWMS was effective in explaining schizophrenic patients' impaired performance on the spatial delayed response, a prefrontal function task. Implications of the relations observed between the spans and the prefrontal function tasks are discussed.

Adult↗

PubMed2002

RAP80, a novel nuclear protein that interacts with the retinoid-related testis-associated receptor.

In this study, we describe the characterization of a novel nuclear protein, referred to as RAP80. The RAP80 cDNA was cloned from a human testis cDNA library and encodes a 719-amino acid protein containing two potential CX(2)CX(11)HX(3)C-type zinc finger motifs at its carboxyl-terminal region. Analysis of its genomic structure revealed that the RAP80 gene covers more than 90 kb and consists of 15 exons and 14 introns. Fluorescence in situ hybridization mapped the RAP80 gene to human chromosome 5q35. RAP80 mRNA is expressed in many human tissues, but its expression is particularly high in testis. In situ hybridization showed that RAP80 is highly expressed in germ cells of mouse testis but is not differentially regulated during spermatogenesis. Confocal microscopy showed that RAP80 is localized to the nucleus, where it is distributed in a speckled pattern. Deletion analysis showed that a bipartite nuclear localization signal at the amino terminus is important in mediating nuclear transport of RAP80. Monohybrid analysis showed that RAP80 might function as an active repressor of transcription. Mammalian two-hybrid analysis demonstrated that RAP80 was able to interact with the retinoid-related testis-associated receptor (RTR), an orphan receptor that has been implicated in the control of embryonic development and spermatogenesis. Pull-down analysis showed that RAP80 and RTR physically interact in vitro. Deletion and point mutation analyses revealed that part of the hinge domain of RTR is required for this interaction. RAP80 is able to inhibit the interaction of RTR with the co-repressor N-CoR likely by competing with N-CoR for RTR binding. Our results suggest that RAP80 may be functioning as a modulator of RTR signaling.

Alternative Splicing↗

PubMed2002

Identification of Glis1, a novel Gli-related, Kruppel-like zinc finger protein containing transactivation and repressor functions.

In this study, we describe the identification and characterization of a novel Krüppel-like protein named Gli-similar 1 (Glis1). The Glis1 gene encodes an 84.3-kDa proline-rich protein. Its five tandem zinc finger motifs exhibit highest homology with those of members of the Gli and Zic subfamilies of Krüppel-like proteins. Glis1 was mapped to mouse chromosome 4C6. Northern blot analysis showed that expression of the 3.3-kb Glis1 mRNA is most abundant in placenta and adult kidney and expressed at lower levels in testis. Whole mount in situ hybridization on mouse embryos demonstrated that Glis1 is expressed in a temporal and spatial manner during development; expression was most prominent in several defined structures of mesodermal lineage, including craniofacial regions, branchial arches, somites, vibrissal and hair follicles, limb buds, and myotomes. Confocal microscopic analysis showed that Glis1 is localized to the nucleus. The zinc finger region plays an important role in the nuclear localization of Glis1. Electrophoretic mobility shift assays demonstrated that Glis1 is able to bind oligonucleotides containing the Gli-binding site consensus sequence GACCACCCAC. Although monohybrid analysis showed that in several cell types Glis1 was unable to induce transcription of a reporter, deletion mutant analysis revealed the presence of a strong activation function at the carboxyl terminus of Glis1. The activation through this activation function was totally suppressed by a repressor domain at its amino terminus. Constitutively active Ca(2+)-dependent calmodulin kinase IV enhanced Glis1-mediated transcriptional activation about 4-fold and may be mediated by phosphorylation/activation of a co-activator. Our results suggest that Glis1 may play a critical role in the control of gene expression during specific stages of embryonic development.

Amino Acid Sequence↗

PubMed2002

Evidence for an N-glycosylation polymorphism of arylsulfatase a predisposing to alcoholism in Koreans.

This study investigated the possible effect of the pseudodeficient N-glycosylation polymorphism of the arylsulfatase A (ASA) gene on alcohol dependence among Koreans. Alcoholic patients (N=123) were more likely than control subjects to be heterozygous or homozygous for the ASA pseudodeficient N-glycosylation site (36% of alcoholics versus 20% of controls; P<0.01). Among these 123 alcoholic patients, 42 alcoholics were heterozygous and two were homozygous for the ASA pseudodeficient N-glycosylation polymorphism. This result provides evidence that the ASA pseudodeficient N-glycosylation site allele increases the risk of alcohol dependence within a Korean population.

Alcoholism↗

PubMed2002

Isolation and characterization of a Drosophila homologue of mitogen-activated protein kinase phosphatase-3 which has a high substrate specificity towards extracellular-signal-regulated kinase.

A partial C-terminal cDNA sequence of a novel Drosophila mitogen-activated protein kinase phosphatase (MKP), designated DMKP-3, was identified from an epitope expressed sequence tag database, and the missing N-terminal cDNA fragment was cloned from a Drosophila cDNA library. DMKP-3 is a protein of 411 amino acids, with a calculated molecular mass of 45.8 kDa; the deduced amino acid sequence is most similar to that of mammalian MKP-3. Recombinant DMKP-3 produced in Escherichia coli retained intrinsic tyrosine phosphatase activity. In addition, DMKP-3 specifically inhibited extracellular-signal-regulated kinase (ERK) activity, but was without a significant affect on c-Jun N-terminal kinase (JNK) and p38 activities, when it was overexpressed in Schneider cells. DMKP-3 interacted specifically with Drosophila ERK (DERK) via its N-terminal domain. In addition, DMKP-3 specifically inhibited Elk-1-dependent trans-reporter gene expression in mammalian CV1 cells, and dephosphorylated activated mammalian ERK in vitro. DMKP-3 is uniquely localized in the cytoplasm within Schneider cells, and gene expression is tightly regulated during development. Thus DMKP-3 is a Drosophila homologue of mammalian MKP-3, and may play important roles in the regulation of various developmental processes.

Amino Acid Sequence↗

PubMed2002

Transvaginal evisceration after radical abdominal hysterectomy.

BACKGROUND: Intestinal evisceration through the vagina is rare and transvaginal evisceration after transabdominal surgery is far more rare. CASE: We present an unusual case of a postmenopausal woman who presented with transvaginal evisceration of the small bowel after radical abdominal hysterectomy and pelvic lymphadenectomy. CONCLUSION: This was a rare case of terminal ileal evisceration through a ruptured vaginal cuff after radical hysterectomy and bilateral pelvic lymphadenectomy. We performed a delayed closure of the vaginal defect through the vagina after manual reduction of the eviscerated small bowel, and the outcome was satisfactory.

Female↗

PubMed2002

A retrospective study of clozapine and electroencephalographic abnormalities in schizophrenic patients.

This study investigated the incidence and nature of clozapine-associated electroencephalographic (EEG) abnormalities and the relationship between EEG abnormality and clozapine dosage in Korean schizophrenic patients. Fifty schizophrenic patients with normal baseline EEG and with additional EEG record examined during clozapine treatment more than once were included. Thirty-one patients (62%) showed abnormal EEGs after clozapine treatment, and two of them had seizures. The majority of EEG abnormalities presented as nonspecific slow waves (SW). Spikes (or spike and wave complexes; SP) and frontal intermittent rhythmic delta activity (FIRDA) were relatively rarely observed. The probability of EEG abnormality was linearly dependent on the daily dose of clozapine and patient's age. Our results can be summarized as follows: (1) a substantial proportion of Korean patients treated with clozapine develops EEG abnormalities, and its incidence is comparable to the published results in Caucasian patients; (2) EEG abnormalities occurred in a dose-dependent manner; and (3) the occurrence of EEG abnormalities did not necessarily lead to future seizure development, except in a small number of cases.

Adult↗

PubMed2001

Characterization of Glis2, a novel gene encoding a Gli-related, Krüppel-like transcription factor with transactivation and repressor functions. Roles in kidney development and neurogenesis.

In this study, we describe the characterization of a gene encoding a novel Krüppel-like protein, named Glis2. Glis2 encodes a relatively proline-rich, basic 55.8-kDa protein. Its five tandem Cys(2)-His(2) zinc finger motifs exhibit the highest homology to those of members of the Gli and Zic subfamilies of Krüppel-like proteins. Confocal microscopic analysis demonstrated that Glis2 localizes to the nucleus. Analysis of the genomic structure of the Glis2 gene showed that it is composed of 6 exons separated by 5 introns spanning a genomic region of more than 7.5 kb. Fluorescence in situ hybridization mapped the mouse Glis2 gene to chromosome 16A3-B1. Northern blot analysis showed that the Glis2 gene encodes a 3.8-kb transcript that is most abundant in adult mouse kidney. By in situ hybridization, expression was localized to somites and neural tube, and during metanephric development predominantly to the ureteric bud, precursor of the collecting duct, and inductor of nephronic tubule formation. One-hybrid analysis using Glis2 deletion mutants identified a novel activation function (AF) at the N terminus. The activation of transcription through this AF domain was totally suppressed by two repressor functions just downstream from the AF. One of the repressor functions is contained within the first zinc finger motif. The level of transcriptional activation and repression varied with the cell line tested, which might be due to differences in cell type-specific expression of co-activators and co-repressors. Our results suggest that Glis2 behaves as a bifunctional transcriptional regulator. Both the activation and repressor functions may play an important role in the regulation of gene expression during embryonic development.

Amino Acid Motifs↗