PubMed Health⌕ Search

Biomedical subjects

S H Hong

Publications and source records attributed to S H Hong.

At least 19 recordsLinked to original sources
PubMed1999

Relationship of arachidonic acid metabolizing enzyme expression in epithelial cancer cell lines to the growth effect of selective biochemical inhibitors.

Arachidonic acid (AA) metabolizing enzymes are emerging as significant mediators of growth stimulation for epithelial cells. The relative contribution of the various family members of AA metabolizing enzymes to epithelial cancer cell growth is not known. To study this question, we first analyzed a series of epithelial cancer cells to establish the relative frequency of expression for the various enzymes. We analyzed the expression of five AA metabolizing enzymes as well as 5-lipoxygenase activating protein (FLAP) in a panel of human epithelial cancer cell lines (n = 20) using reverse transcription-PCR. From this analysis, we found that cyclooxygenase-1 (COX-1), 5-lipoxygenase (5-LOX), and FLAP were universally expressed in all cancer cell lines tested. For the remaining enzymes, the expression of COX-2, 12-LOX, and 15-LOX varied among cell lines, 60, 35, and 90%, respectively. Although the pattern of expression varied among the different cell types, all of the enzymes were expressed in all major cancer histologies. Using a panel of selective biochemical AA metabolizing enzyme inhibitors, we then evaluated the effect of these agents on cell lines with known expression status for the AA metabolizing enzymes. For the enzymes that were not universally expressed, growth inhibition by selective biochemical inhibitors did not closely correlate with the expression status of specific enzymes (P > 0.05). For the universally expressed enzymes, the LOX inhibitors were more potent growth inhibitors than the COX inhibitors. The frequent expression of the AA metabolizing enzymes suggests that AA metabolism pathway may be modulated in response to xenobiotic exposure during carcinogenesis. Although establishing a priori AA metabolizing enzyme status was not consistently informative about what AA metabolizing enzyme inhibition would be most growth inhibitory, the frequent inhibition of many epithelial cancers by these biochemical inhibitors opens a new avenue for cancer therapy and intervention in carcinogenesis.

5-Lipoxygenase-Activating Proteins↗
PubMed1999

Isolation of developmentally regulated novel genes based on sequence identity and gene expression pattern.

Based on the surmise that a variety of genes might play important roles in embryonic development and tissue differentiation, and that some of them are likely to be expressed in undifferentiated ES cells, we attempted to identify new genes from the ES cell cDNA library. The modified method of expressed sequence tags (ESTs) and the examination of the expression patterns in adult tissues and in vitro differentiated ES cells were utilized in this study. We have isolated and identified several novel cDNA clones with interesting developmental expression pattern. Among the 83 clones randomly chosen, 23 clones (27.7%) have no homology to any sequences in public databases. The rest contain limited or complete sequence homology to the previously reported mammalian genes or ESTs, yet some clones have not been previously identified in the mouse. To examine the expression profile of clones during development and differentiation, sets of slot blots were hybridized with developmental stage specific or tissue specific probes. Out of 40 novel clones tested (21 totally unknown clones and 19 unidentified clones in mouse), most of them were up- or down-regulated as differentiation proceeded, and some clones showed differentiation-stage specific expression profiles. Surprisingly, a majority of genes were also expressed in adult tissues, and some clones even revealed tissue specific expression. These results demonstrate that not only was the strategy we employed in this study quite efficient for screening novel genes, but that the information gained by such studies would also be a useful guide for further analysis of these genes. It also suggests the feasibility of this approach to explore the genomewide network of gene expression during complicated biological processes, such as embryonic development and tissue differentiation.

Amino Acid Sequence↗
PubMed1999

Nonproteolytic neuroprotection by human recombinant tissue plasminogen activator.

Human recombinant tissue plasminogen activator (tPA) may benefit ischemic stroke patients by dissolving clots. However, independent of thrombolysis, tPA may also have deleterious effects on neurons by promoting excitotoxicity. Zinc neurotoxicity has been shown to be an additional key mechanism in brain injuries. Hence, if tPA affects zinc neurotoxicity, this may provide additional insights into its effect on neuronal death. Independent of its proteolytic action, tPA markedly attenuated zinc-induced cell death in cortical culture, and, when injected into cerebrospinal fluid, also reduced kainate seizure-induced hippocampal neuronal death in adult rats.

Animals↗
PubMed1999

Characterization of a novel mouse cDNA, ES18, involved in apoptotic cell death of T-cells.

Using the modified screening approach in combination with expressed sequence tags, we have identified several novel cDNAs from mouse embryonic stem (ES) cells, whose expression is tissue-restricted and/or developmentally regulated. One of the cDNAs, ES18, is preferentially expressed in lymph node and thymus, and contains noteworthy features of transcriptional regulator. The expression of ES18 transcript was selectively regulated during the apoptosis of T-cell thymoma S49.1 induced by several stimuli. Interestingly, the ES18 transcript was differently regulated in the mutually antagonistic process, between dexamethasone- and A23187-induced cell death of T-cells. Moreover, the message level of ES18 was selectively enhanced by staurosporine, a broad protein kinase inhibitor, but not by other protein kinase inhibitors such as GF109203X and H89. In addition, ES18 transcript was induced by C2-ceramide, which is a mediator of both dexamethasone- and staurosporine-induced apoptotic signaling. We further showed that transient overexpression of ES18 in mouse T-cell lymphoma increased the apoptotic cell death. These data suggest that ES18 may be selectively involved in specific apoptotic processes in mouse T-cells.

Amino Acid Sequence↗
PubMed1999

Retinoid isomers differ in the ability to induce release of SMRT corepressor from retinoic acid receptor-alpha.

Nuclear hormone receptors are ligand-regulated transcription factors that modulate the expression of specific target genes in response to the binding of small, hydrophobic hormone ligands. Many nuclear hormone receptors, such as the retinoic acid receptors, can both repress and activate target gene expression; these bimodal transcription properties are mediated by the ability of these receptors to tether auxiliary factors, denoted corepressors and coactivators. Corepressors are typically bound by receptors in the absence of cognate hormone, whereas binding of an appropriate hormone agonist induces an allosteric alteration in the receptor resulting in release of the corepressor and recruitment of coactivator. Structural analysis indicates that there is a close induced fit between the hormone ligand and the receptor polypeptide chain. This observation suggests that different ligands, once bound, may confer distinct conformations on the receptor that may invoke, in turn, distinct functional consequences. We report here that different retinoids do differ in the ability to release corepressor once bound to retinoic acid receptor and suggest that these differences in corepressor release may manifest as differences in transcriptional regulation.

Alitretinoin↗
PubMed1999

Fibrinogen gene polymorphism in a non-Caucasian population.

OBJECTIVE: The purpose of this study was to investigate the two polymorphisms of fibrinogen gene (RsaI and MnlI RFLPs in the coding region of the fibrinogen gene) in Koreans, and their relation to plasma fibrinogen. METHODS: Using PCR-amplified DNAs, RsaI and MnlI RFLPs were analyzed in 112 patients with coronary artery disease (CAD) and 137 healthy subjects. To compare the mean of plasma fibrinogen and lipid levels among different genotypes, one-way analysis of variance (ANOVA) test was performed. RESULTS: Allele frequencies of fibrinogen gene polymorphism in Koreans were not significantly different between CAD and control groups; fibrinogen polymorphism in this population showed a lack of association with plasma fibrinogen levels, but significant association with BMI (p < 0.05). CONCLUSION: This evidence suggests that in Korean populations, fibrinogen gene polymorphism is not a factor in the expression of atherosclerosis. There might, however, be an association between fibrinogen gene and obesity in such population.

Aged↗
PubMed1999

Summary of results using the nucleus CI24M implant to record the electrically evoked compound action potential.

OBJECTIVE: This study outlines a series of experiments using the neural response telemetry (NRT) system of the Nucleus CI24M cochlear implant to measure the electrically evoked compound action potential (EAP). The goal of this investigation was to develop a protocol that allows successful recording of the EAP in a majority of CI24M cochlear implant users. DESIGN: Twenty-six postlingually deafened adults participated in this study. A series of experiments were conducted that allowed us to examine how manipulation of stimulation and recording parameters may affect the morphology of the EAP recorded using the Nucleus NRT system. RESULTS: Results of this study show consistent responses on at least some electrodes from all subjects. Cross-subject and cross electrode variations in both the growth of the response and the temporal refractory properties of the response were observed. The range of stimulus and recording parameters that can be used to record the EAP with the Nucleus NRT system is described. CONCLUSIONS: Using the protocol outlined in this study, it is possible to reliably record EAP responses from most subjects and for most electrodes in Nucleus CI24M cochlear implant users. These responses are robust and recording these responses does not require that the subject sleep or remain still. Based on these results, a specific protocol is proposed for measurement of the EAP using the NRT system of the CI24M cochlear implant. Potential clinical implications of these results are discussed.

Adult↗
PubMed1998

Association between apolipoprotein(a) polymorphism and Lp(a) levels in Koreans.

In view of the clinical importance of lipoprotein(a) [(Lp(a)] in coronary artery disease (CAD), we investigated the apo(a) size polymorphism, sequence polymorphisms of five base repeats [(TTTTA)n] in the noncoding region, and of Met/Thr in the coding region of the apolipoprotein(a) [apo(a)] gene. The apo(a) polymorphisms were examined in 184 Korean patients with CAD and 121 healthy subjects. In size polymorphism, there was an inverse association between plasma Lp(a) levels and the apo(a) isoforms in the CAD group (p < 0.005). For (TTTTA)n sequence polymorphism, subjects with the 8/8 genotype were most frequently observed in the two groups. Plasma Lp(a) levels showed a significant difference between the 8/5 versus the 8/8 genotype in the CAD group. On the other hand, Lp(a) levels varied significantly among the genotypes of a Met/Thr polymorphism in normal controls (P < 0.01). The heterozygous genotype had an intermediate level of Lp(a) between the two homozygous genotypes, thereby showing gene dosage effect. Thus, it is possible that the apo(a) polymorphisms are responsible for variations in the Lp(a) levels.

Adult↗
PubMed1998

Histone deacetylase associated with mSin3A mediates repression by the acute promyelocytic leukemia-associated PLZF protein.

The PLZF gene was identified first by its fusion with the retinoic acid receptor alpha gene in the t(11;17) translocation associated with a retinoic acid resistant form of acute promyelocytic leukemia (APL). It encodes a krüppel-like zinc finger protein with a POZ domain shared with a subset of regulatory proteins including the BCL6 leukemogenic protein. PLZF, like BCL6, strongly represses transcription initiated from different promoters. Here we show that PLZF associates in vitro and in vivo with the Mad co-repressor mSin3A and the histone deacetylase HDAC1. Two domains in PLZF and the PAH1 structure of mSin3A mediate these interactions. Trichostatin A, a specific inhibitor of histone deacetylases, significantly reduces PLZF repression. These data strongly suggest that, like nuclear receptors and Mad, PLZF represses transcription by recruiting a histone deacetylase through the SMRT-mSin3-HDAC co-repressor complex. We also show that BCL6 associates with HDAC1 indicating that this type of regulation might be common to POZ/Zinc finger proteins involved in human leukemias. This work supports a role for deregulated histone deacetylation in the development of both lymphoid and myeloid neoplasia in human and suggests that targeted histone deacetylase inhibitors may be useful for treatment of certain types of malignancies.

Binding Sites↗
PubMed1998

Interaction of phospholipase C gamma 1 via its COOH-terminal SRC homology 2 domain with synaptojanin.

The role of the phospholipase C gamma 1 (PLC gamma 1) in signal transduction was investigated by characterizing its interactions with proteins that may represent components of a novel signalling pathway. A 145-kDa protein that binds SH2 domain of PLC gamma 1 was purified from rat brain. The sequence of peptide derived from the purified binding protein now identify it as synaptojanin, a nerve terminal protein that has been implicated in the endocytosis of fused synaptic vesicles and shown to be a member of the inositol polyphosphate 5-phosphatase family. We demonstrate here stable association of PLC gamma 1 with synaptojanin, a protein that not only binds carboxyl terminal SH2 domain of PLC gamma 1, but also inhibits PLC gamma 1 activity.

Amino Acid Sequence↗
PubMed1998

Depletion of intracellular zinc induces protein synthesis-dependent neuronal apoptosis in mouse cortical culture.

The central nervous system (CNS) contains a large amount of zinc; a substantial fraction of it is located inside synaptic vesicles of glutamatergic terminals in chelatable forms and released in a calcium-dependent manner with intense neuronal activity. Recently, it has been shown that excessive zinc influx can kill neurons in rats subjected to transient forebrain ischemia. On the other hand, severe depletion of zinc has been also reported to induced cell death in certain nonneuronal cells. Since decreases in tissue zinc have been associated with Alzheimer's disease (AD) and senile macular degeneration, we examined whether depletion of intracellular zinc with a zinc chelator can directly induce neuronal death in mouse cortical cultures. Exposure of cortical cultures to a cell-permeant zinc-chelator, N,N,N',N'-tetrakis (2-pyridylmethyl) ethylenediamine (TPEN, 0.5-3.0 microM) induced gradually developing neuronal degeneration accompanied by various features of apoptosis: cell body shrinkage, nuclear condensation and fragmentation, and internucleosomal DNA breakage. At higher concentrations, TPEN induced additional glial cell death. TPEN-induced cell death was completely blocked by coaddition of zinc. Addition of a protein synthesis inhibitor cycloheximide as well as a caspase inhibitor carbobenzoxy-valyl-alanyl-aspartyl-fluoromethyl ketone (zVAD-fmk) markedly attenuated TPEN-induced neuronal death. On the other hand, brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), phorbol 12-myristate 13-acetate (PMA), high K+, or an antioxidant, trolox, did not show any protective effect. The present results demonstrated that depletion of intracellular zinc induces protein synthesis-dependent neuronal apoptosis in cortical culture. Combined with the findings that extracellular zinc may promote extracellular beta-amyloid (A beta) aggregation and that total tissue zinc is reduced in AD, present results suggest a possibility that redistribution of zinc from intracellular to extracellular space may synergistically contribute to neuronal apoptosis in AD.

Animals↗
PubMed1998

Isolation and characterization of hrp1+, a new member of the SNF2/SWI2 gene family from the fission yeast Schizosaccharomyces pombe.

The SNF2/SWI2 ATPase/helicase family comprises proteins from a variety of species, which serve a number of functions, such as transcriptional regulation, maintenance of chromosome stability during mitosis, and various types of DNA repair. Several proteins with unknown functions are also included in this family. The number of genes that belong to this family is rapidly expanding, which makes it easier to analyze the common biological functions of the family members. This study was designed to clone the SNF2/SWI2 helicase-related genes from the fission yeast Schizosaccharomyces pombe in the hope that this would help to elucidate the common functions of the proteins in this family. The hrp1+ (helicase-related gene from S. pombe) gene was initially cloned by PCR amplification using degenerate primers based on conserved SNF2 motifs within the ERCC6 gene, which encodes a protein involved in DNA excision repair. The hrp1+ ORF codes for an 1373-amino acid polypeptide with a molecular mass of 159 kDa. Like other SNF2/SWI2 family proteins, the deduced amino acid sequence of Hrp1 contains DNA-dependent ATPase/7 helicase domains, as well as a chromodomain and a DNA-binding domain. This configuration is similar to that of mCHD1 (mouse chromo-ATPase/helicase-DNA-binding protein 1), suggesting that Hrp1 is a S. pombe homolog of mCHD1, which is thought to function in altering the chromatin structure to facilitate gene expression. Northern blot analysis showed that the hrp1+ gene produces a 4.6-kb transcript, which reaches its maximal level just before the cells enter the exponential growth phase, and then decreases gradually. DNA-damaging agents, such as MMS, MNNG and UV, decrease the rate of transcription of hrp1+. Deletion of the hrp1+ gene resulted in accelerated cell growth. On the other hand, overexpression of Hrp1 caused a reduction in growth rate. These results indicate that hrp1+ may act as a negative regulator of cellular growth.

Adenosine Triphosphatases↗
PubMed1998

Effect of Syzygium aromaticum extract on immediate hypersensitivity in rats.

We investigated the effect of aqueous extract of Syzygium aromaticum (L.) Merr. et Perry (Myrtaceae) flower bud (SAFB) on immediate hypersensitivity. SAFB inhibited compound 48/80-induced systemic anaphylaxis in rats (IC50 = 31.25 mg/kg, i.p.). SAFB also inhibited local immunoglobulin E (IgE)-mediated passive cutaneous anaphylactic reaction (IC50 = 17.78 mg/kg, i.v.; IC50 = 19.81 mg/kg, p.o.). When SAFB was pretreated at concentrations ranging from 25 to 1000 mg/kg, the serum histamine levels were reduced in a dose-dependent manner. Moreover, SAFB dose-dependently inhibited histamine release from rat peritoneal mast cells (RPMC) by compound 48/80 or anti-dinitrophenyl IgE. When SAFB was added, the level of cAMP in RPMC transiently and significantly increased about 47-fold at 10 s compared with that of basal cells. These results indicate that SAFB inhibits immediate hypersensitivity by inhibition of histamine release from mast cells in vivo and in vitro.

Animals↗
PubMed1998

Photomorphogenic development of the Arabidopsis shy2-1D mutation and its interaction with phytochromes in darkness.

We previously reported a photomorphogenic mutation of Arabidopsis thaliana, shy2-1D, as a dominant suppressor of a hy2 mutation. Here, we report that shy2-1D confers various photo-responsive phenotypes in darkness and the dark phenotypes of the mutant are affected by phytochrome deficiency. Dark-grown seedlings of the mutant developed several photomorphogenic characteristics such as short hypocotyls, cotyledon expansion and opening, and partial differentiation of plastids. When grown further in darkness, the mutant plant underwent most of the developmental stages of a light-grown wild-type plant, including development of foliar leaves, an inflorescence stem with cauline leaves, and floral organs. In addition, two light-inducible genes, the nuclear-encoded CAB and the plastid-encoded PSBA genes, were highly expressed in the dark-grown mutant seedlings. Furthermore, reduced gravitropism, a phytochrome-modulated response, was observed in the mutant hypocotyl in darkness. Thus, shy2-1D is one of the most pleiotropic photomorphogenic mutations identified so far. The results indicate that SHY2 may be a key component regulating photomorphogenesis in Arabidopsis. Surprisingly, double mutants of the shy2-1D mutant with the phytochrome-deficient mutants hy2, hy3(phyB-1) and fre1-1(phyA-201) showed reduced photomorphogenic response in darkness with a longer hypocotyl, a longer inflorescence stem, and a lower level expression of the CAB gene than the shy2-1D single mutant. These results showed that phytochromes function in darkness in the shy2-1D mutant background. The implications of these results are discussed.

Arabidopsis↗
PubMed1998

Genetic identification of FIN2, a far red light-specific signaling component of Arabidopsis thaliana.

Phytochrome A (PhyA) mediates most, if not all, various plant responses to far-red (FR) light. Here, we report a novel genetic mutation that impairs a variety of responses in the PhyA-signaling pathway of Arabidopsis thaliana. The mutation was isolated by screening seedlings that show reduced sensitivity to continuous far-red (FRc) light irradiation, but not to continuous red (Rc) light irradiation. The mutation named fin2-1 is not allelic to a PHYA mutation. Furthermore, immunoblot analysis indicated that the amount of the phytochrome A apoprotein in the fin2-1 mutant was comparable to that in wild type. Seedling of the fin2-1 mutant showed defects in hypocotyl growth inhibition and apical hook and cotyledon opening in FRc light but not in Rc light. The results showed that the mutation occurred in a downstream signaling component potentially specific to PhyA. Other PhyA-mediated responses such as FR-preconditioned blocking of greening, anthocyanin accumulation, reduction of gravitropic response, and expression of the CAB and CHS genes were impaired by the fin2-1 mutation: the degree of the mutant effect on the responses was variable. However, FR light-mediated seed germination and photoperiodic flowering responses were not affected significantly in the mutant. These results showed that FIN2 defines an upstream branch point in the PhyA signaling pathway.

Alleles↗
PubMed1998

Multiple pigmented basal cell carcinomas.

Basal cell carcinoma is the most common of all skin cancers and the most prevalent one among Caucasians. Rarely, these tumors are seen in other races. We report a 77-year-old Korean woman who presented with multiple darkly pigmented enlarging nodules on her scalp, face, trunk, and extremities. The patient had first noted a 6-mm pigmented lesion on her left eyebrow 10 years previously. Since then, other lesions had appeared in many locations on her body. She had been otherwise healthy and without a history of exposure to arsenic or radiation. There was no family history of skin cancer, xeroderma pigmentosum, or basal cell nevus syndrome. On physical examination, multiple darkly pigmented dome-shaped papules and nodules were present on her scalp, face, right forearm, lower abdomen, and inguinal areas. They ranged in size from 0.5 mm to 2 cm. The larger ones showed central ulceration. Multiple biopsy specimens from different sites showed pigmented basal cell carcinomas. Clinically, there was no evidence of nevus sebaceus, xeroderma pigmentosum, basal cell nevus syndrome, or immunodeficiency. Clinical workup including chest radiography, abdominal ultrasound, bone scan, and brain computerized axial tomography scan did not demonstrate primary or secondary tumors. The results of serologic and hematologic tests were also within normal limits. This is an unusual case report of multiple pigmented basal cell carcinomas in an Asian woman without any predisposing risk factors.

Aged↗
PubMed1998

Signaling by tyrosine kinases negatively regulates the interaction between transcription factors and SMRT (silencing mediator of retinoic acid and thyroid hormone receptor) corepressor.

Nuclear hormone receptors are hormone-regulated transcription factors that bind to specific sites on DNA and modulate the expression of adjacent target genes. Many nuclear hormone receptors display bimodal transcriptional properties; thyroid hormone receptors, for example, typically repress target gene expression in the absence of hormone, but activate target gene expression in the presence of hormone. The ability to repress is closely linked to the ability of the apo-receptor to physically bind to auxiliary corepressor proteins denoted SMRT (silencing mediator of retinoic acid and thyroid hormone receptor) and N-CoR (nuclear receptor corepressor), which, in turn, help mediate the actual molecular events involved in transcriptional silencing. We report here that repression by thyroid hormone receptors can be regulated not only by cognate hormone, but also by certain tyrosine kinase signal transduction pathways, such as that represented by the epidermal growth factor-receptor. Activation of tyrosine kinase signaling leads to inhibition of T3R-mediated repression with relatively little effect on activation. These effects appear to be mediated by a kinase-initiated disruption of the ability of T3R to interact with SMRT corepressor. Intriguingly, tyrosine kinase signaling similarly disrupted the interactions of SMRT with v-Erb A, with retinoic acid receptors, and with PLZF, a nonreceptor transcriptional repressor. We conclude that tyrosine kinase signaling exerts potentially important regulatory effects on transcriptional silencing mediated by a variety of transcription factors that operate through the SMRT corepressor complex.

Animals↗