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Biomedical subjects

H-S Kim

Publications and source records attributed to H-S Kim.

At least 19 recordsLinked to original sources
PubMed2006

Di-(2-ethylhexyl) phthalate suppresses tamoxifen-induced apoptosis in GH3 pituitary cells.

Tamoxifen, an estrogen receptor antagonist, has been clinically used as an antitumor drug and induces apoptosis in GH3 pituitary cells. Although di-(2-ethylhexyl) phthalate (DEHP) is a well-known environmental estrogen and the exposure to this chemical is well expected, reports are limited regarding effects of DEHP on tamoxifen-induced apoptosis in pituitary cells. In the cytotoxicity assay, the reduced cell viability in tamoxifen-treated GH3 cells was reversed by DEHP (250 microM) treatment for 4 days. To characterize cell death, cells were stained using Hoechst 33258. Apoptotic morphological change such as chromatin condensation induced by tamoxifen was suppressed by treatment with DEHP. Flow cytometric analysis revealed that the number of apoptotic cells induced by tamoxifen was significantly decreased by DEHP treatment. Enhanced poly (ADP-ribose) polymerase (PARP) cleavage by tamoxifen treatment was also inhibited by DEHP. These results suggest that DEHP suppresses tamoxifen-induced apoptosis in association with its estrogenic effect in GH3 cells and might counteract the therapeutic effect of tamoxifen.

Animals↗
PubMed2006

Intracellular domains of amyloid precursor-like protein 2 interact with CP2 transcription factor in the nucleus and induce glycogen synthase kinase-3beta expression.

Amyloid precursor protein (APP) is a member of a gene family that includes two APP-like proteins, APLP1 and 2. Recently, it has been reported that APLP1 and 2 undergo presenilin-dependent gamma-secretase cleavage, as does APP, resulting in the release of an approximately 6 kDa intracellular C-terminal domain (ICD), which can translocate into the nucleus. In this study, we demonstrate that the APLP2-ICDs interact with CP2/LSF/LBP1 (CP2) transcription factor in the nucleus and induce the expression of glycogen synthase kinase 3beta (GSK-3beta), which has broad-ranged substrates such as tau- and beta-catenin. The significance of this finding is substantiated by the in vivo evidence of the increase in the immunoreactivities for the nuclear C-terminal fragments of APLP2, and for GSK-3beta in the AD patients' brain. Taken together, these results suggest that APLP2-ICDs contribute to the AD pathogenesis, by inducing GSK-3beta expression through the interaction with CP2 transcription factor in the nucleus.

Active Transport, Cell Nucleus↗
PubMed2006

Transcriptional control of the HERV-H LTR element of the GSDML gene in human tissues and cancer cells.

Long terminal repeats (LTRs) of human endogenous retroviruses (HERVs) have been reported to serve as alternative promoters in functional genes. The GSDML (gasdermin-like protein) gene located on human chromosome 17q21 has been found to be an oncogenomic recombination hotspot. Here, we identified the LTR element of HERV-H with reverse orientation as an alternative promoter of the GSDML gene and analyzed its expression pattern in human tissues and cancer cells. A reporter gene assay of the promoter activity of the LTR on the GSDML gene in human cancer cell lines (HCT-116 and HeLa) and a kidney cell line (Cos7) of African green monkey indicated that the LTR promoter with reverse orientation had stronger promoter activity than forward one. The transcripts of this LTR-derived promoter were widely distributed in various human tissues and cancer cells, whereas the transcripts of the cellular promoter were found only in stomach tissues and some cancer cells (HCT116, MCF7, U937, C-33A, and PC3). These findings suggest that the LTR element on the GSDML gene was integrated into the hominoid lineage and acquired the role of transcriptional regulation of human tissues and cancer cells.

Animals↗
PubMed2006

Hypoxia regulates the expression of PHLDA2 in primary term human trophoblasts.

Hypoxia influences gene expression in placental trophoblasts. We sought to examine the effect of hypoxia on trophoblast expression of human PHLDA2 (also termed IPL, TSSC3 or BWR-1C), a product of an imprinted gene on human chromosome 11p15.5 whose murine ortholog plays a pivotal role in placental development. We initially confirmed that PHLDA2 was expressed in term placental villi, primarily in the trophoblast layer. Using quantitative PCR we found that the expression of PHLDA2 gradually declined during differentiation of primary term human trophoblasts. A similar expression pattern was seen for p57(Kip2) and IGF-II, both products of imprinted genes on chromosome 11p15.5. Exposure of trophoblasts to hypoxia in vitro (O(2)<or=2%) markedly reduced the expression of PHLDA2 mRNA and protein. This effect was not consistent among other chromosome 11p15.5 genes products, as the expression of p57(Kip2) decreased, but that of IGF-II increased in hypoxic trophoblasts. PHLDA2 expression in trophoblasts exposed to TGFbeta1, -beta2 or -beta3 was unchanged. We conclude that hypoxia down-regulates the expression of PHLDA2 in human term placental trophoblasts. As murine PHLDA2 limits placental growth, our results suggest that down-regulation of PHLDA2 attenuates the impact of hypoxia on placental growth.

Cells, Cultured↗
PubMed2006

Endogenous retrovirus HERV-I LTR family in primates: sequences, phylogeny, and evolution.

A human endogenous retrovirus (HERV-I; RTVL-I) has been located within the first intron of a haptoglobin-related gene. Two members of the HERV-I family were identified in proximal Yq11.2 and caused AZFa microdeletions as a result of intra-chromosomal recombination events in azoospermic patients. Using PCR25 and the sequencing approach with the genomic DNAs of primates, hominoids, Old and New World monkeys, and prosimians, the HERV-I LTR elements were identified and analysed. The LTR elements were detected only in the hominoids and the Old World monkeys, indicating that the HERV-I LTR elements were inserted into the primate genome after the split of the New World monkeys in the Oligocene era, about 33 million years ago. Nineteen members of the HERV-I LTR elements from the hominoids and the Old World monkeys showed multiple insertions or deletions. They showed a 78.6-97.4% sequence similarity to that of Hu-15 (accession no. AF290422; HERV-I LTR on human Yq11.2). The evolutionary relationships within the HERV-I LTR family among hominoids and Old World monkeys showed a random cluster, indicating that HERV-I LTR elements have evolved independently in primate evolution.

Animals↗
PubMed2006

Molecular evolution of the HERV-E family in primates.

More than 50 copies of HERV-E family elements have been estimated to exist in the human genome. Here we examined the recent evolutionary history of the HERV-E family by a PCR approach using genomic DNA from hominoid primates and a human monochromosomal panel. From the HERV-E family, 25 and 68 env fragments, were identified and analyzed from hominoid primates and human chromosomes 1, 2, 3, 4, 6, 7, 8, 10, 11, 12, 13, 14, 15, 16, 17, 19, X, and Y, respectively. They showed 76.7-99.6% sequence similarity to that of HERV-E (accession no. M10976). Phylogenetic analysis of HERV-E env family distinctively divided into two groups (groups I and II) that each contained three subgroups. Divergence times of the two groups were estimated as 10.7 MYr for group I and 41.3 MYr for group II using an average evolutionary rate of 0.3% per MYr. These data are consistent with that of PCR analysis, which showed a band of the HERV-E family in the genomes of the hominoids, Old World monkeys, and New World monkeys. Therefore, the HERV-E family may have integrated into the primate genome after prosimians and New World monkeys diverged. Then they proliferated extensively in the genome of humans and great apes during primate evolution.

Animals↗
PubMed2006

Liver-directed gene therapy of diabetic rats using an HVJ-E vector containing EBV plasmids expressing insulin and GLUT 2 transporter.

Insulin gene therapy in clinical medicine is currently hampered by the inability to regulate insulin secretion in a physiological manner, the inefficiency with which the gene is delivered, and the short duration of gene expression. To address these issues, we injected the liver of streptozotocin-induced diabetic rats with hemagglutinating virus of Japan-envelope (HVJ-E) vectors containing Epstein-Barr virus (EBV) plasmids encoding the genes for insulin and the GLUT 2 transporter. Efficient delivery of the genes was achieved with the HVJ-E vector, and the use of the EBV replicon vector led to prolonged hepatic gene expression. Blood glucose levels were normalized for at least 3 weeks as a result of the gene therapy. Cotransfection of GLUT 2 with insulin permitted the diabetic rats to regulate their blood glucose levels upon exogenous glucose loading in a physiologically appropriate manner and improved postprandial glucose levels. Moreover, cotransfection with insulin and GLUT 2 genes led to in vitro glucose-stimulated insulin secretion that involved the closure of K(ATP) channels. The present study represents a new way to efficiently deliver insulin gene in vivo that is regulated by ambient glucose level with prolonged gene expression. This may provide a basis to overcome limitations of insulin gene therapy in humans.

Animals↗
PubMed2006

A series of bed exercises to improve lymphocyte count in allogeneic bone marrow transplantation patients.

The purpose of this study was to investigate the effect of a series of bed exercises on lymphocyte and T-cell subsets in allogeneic bone marrow transplantation patients during hospitalization. Thirty-five patients were randomly assigned, with 18 assigned to an exercise group and 17 to a control group. The bed exercise intervention was applied by a nurse to the exercise group for 30 min every day for 6 weeks. Patients in the exercise group had a mean increase of 40.9 lymphocyte cells/microL and patients in the control group had a mean decrease of 640.7 lymphocyte cells/microL. There were no significant differences in the percentage of cluster of differentiation (CD)3+, CD4+ and CD8+, and CD4+/CD8+ ratio between the two groups. These findings indicate that bed exercise could be an effective nursing intervention with patients undergoing bone marrow transplantation by increasing the lymphocyte count during hospitalization.

Adult↗
PubMed2006

Growth inhibition of bloom-forming cyanobacterium Microcystis aeruginosa by rice straw extract.

AIMS: To inhibit the growth of the bloom-forming cyanobacterium Microcystis aeruginosa using a rice straw extract. METHODS AND RESULTS: The cell numbers of the algal strain M. aeruginosa UTEX 2388 significantly decreased after treatment with different concentrations (0.01, 0.1, 1 and 10 mg l(-1)) of a rice straw extract for an 8-day cultivation period. Among seven tested allelochemicals from rice straw, salicylic acid at 0.1 mg l(1) exhibited the highest allelopathic activity (26%) on day 8. A synergistic effect on algal growth inhibition was found when adding two or three phenolic compounds from the rice straw. CONCLUSIONS: The growth of M. aeruginosa was inhibited by rice straw extract concentrations ranging from 0.01 to 10 mg l(1). This activity was due to the synergistic effects of various phenolic compounds in the rice straw. SIGNIFICANCE AND IMPACT OF THE STUDY: The identification of rice straw as an effective material for the growth inhibition of M. aeruginosa implies it may have the potential to be used as an environment-friendly biomaterial for controlling the algal bloom of M. aeruginosa in eutrophic water.

Anti-Bacterial Agents↗
PubMed2006

Dual effect of nitric oxide in immortalized and malignant human oral keratinocytes: induction of apoptosis and differentiation.

BACKGROUND: Nitric oxide (NO) is known to act cytostatically on several tumor cell when functioning as an effector molecule of activated macrophages, but the differential effects of NO on immortalized and malignant oral keratinocytes have not been examined. METHODS: We investigated the influence of NO on the proliferation, cell cycle, apoptosis, and differentiation of immortalized human oral keratinocytes (IHOK) and primary oral cancer cells (HN4) using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, sulforhodamine B (SRB) assay, flow cytometry, nuclear DNA staining, and Western blotting. RESULTS: The MTT and SRB assays indicated inhibited growth of IHOK and HN4 cells that were treated with sodium nitroprusside (SNP) at concentrations higher than 1 mM but not at lower SNP concentrations. The higher concentrations of SNP up-regulated the apoptosis-related protein expression, which is consistent with the analyses of sub-G(1) phase arrest, annexin V-FITC (fluorescein isothiocynate) staining, nuclear staining, and DNA fragmentation. On the other hand, the lower concentrations of SNP enhanced the expression of keratinocyte differentiation markers in IHOK and HN4 cells. CONCLUSIONS: These data suggest that high concentrations of NO can inhibit the growth of IHOK and HN4 cells through the induction of apoptosis, while low concentrations of NO can induce cytodifferentiation. The dual effects of NO, namely, the induction of apoptosis or cytodifferentiation, have important implications for the possible anti-oral cancer treatment.

Apoptosis↗
PubMed2005

The effects of the overexpression of recombinant uncoupling protein 2 on proliferation, migration and plasminogen activator inhibitor 1 expression in human vascular smooth muscle cells.

AIMS/HYPOTHESIS: Increased oxidative stress in vascular smooth muscle cells (VSMCs) has been implicated in the pathogenesis of accelerated atherosclerosis in patients with diabetes mellitus. Uncoupling protein 2 (UCP-2) is an important regulator of intracellular reactive oxygen species (ROS) production. We hypothesised that UCP-2 functions as an inhibitor of the atherosclerotic process in VSMCs. METHODS: Overexpression of human UCP-2 was performed in primary cultured human VSMCs (HVSMCs) via adenovirus-mediated gene transfer. Its effects on ROS production, AP-1 activity, plasminogen activator inhibitor 1 (PAI-1) gene expression, and cellular proliferation and migration were measured in response to high glucose and angiotensin II (Ang II) concentrations, two major factors in the pathogenesis of atherosclerosis in patients with diabetes and hypertension. Mitochondrial membrane potential and NAD(P)H oxidase activity were also measured. RESULTS: High glucose and Ang II caused transient mitochondrial membrane hyperpolarisation. They also significantly stimulated ROS production, NAD(P)H oxidase activity, mitochondrial membrane potential, AP-1 activity, PAI-1 mRNA expression, and proliferation and migration of HVSMCs. Adenovirus-mediated transfer of the UCP-2 gene reversed all of these effects. CONCLUSIONS/INTERPRETATION: The present study demonstrates that UCP-2 can modify atherosclerotic processes in HVSMCs in response to high glucose and Ang II. Our data suggest that agents increasing UCP-2 expression in vascular cells may help prevent the development and progression of atherosclerosis in patients with diabetes and hypertension.

Aorta, Thoracic↗
PubMed2005

Molecular cloning and phylogeny of HERV-E family that is expressed in Japanese monkey (Macaca fuscata) tissues.

More than 50 copies of HERV-E family have been estimated to exist in the human genome. Here, we examined the expression pattern and their relationships of the HERV-E in Japanese monkey tissues by RT-PCR and sequence analysis. The env gene of HERV-E family was expressed in monkey tissues (testis, prostate, kidney, thymus, intestine and stomach) except for cerebellum, pancreas and ovary, exhibiting that they may have transcriptional potential. Phylogenetic analysis of the HERV-E env family from Japanese monkey tissues and our previous data could be divided into two distinctive groups (I and II). They were integrated into the genomes of anthropoids and have evolved at the rate of 0.3% nucleotide differences per MYr through evolutionary divergence in primate evolution. Divergence times of the two groups were estimated as 11.6 MYr for group I and 41.6 MYr for group II. Those HERV-E sequences were extensively proliferated in the genome of humans and great apes. These data will contribute to further studies on the transcriptional potential of the HERV-E family in the Japanese monkey genome and to biomedical knowledge related to human diseases.

Amino Acid Sequence↗
PubMed2005

Microarray-based identification of differentially expressed genes in hypoxic term human trophoblasts and in placental villi of pregnancies with growth restricted fetuses.

Hypoxia adversely influences the function of the human placenta. We sought to identify a set of hypoxia-regulated transcripts in both term human trophoblasts in vitro and in villous trophoblasts in vivo. Using high-density oligonucleotide microarrays we initially examined differences in gene expression between trophoblast cultured in standard conditions (20% oxygen) vs. hypoxic conditions (< or =1% oxygen), as well as in placental tissues from pregnancies complicated by intrauterine growth restriction vs. matched controls. We used a novel computation method to compile data from the two approaches and identify transcripts that exhibited a marked expression change. Using quantitative PCR we confirmed an up-regulation of transcripts for vascular endothelial growth factor, connective tissue growth factor, follistatin-related protein, N-Myc down-regulated gene 1 and adipophilin in hypoxic term trophoblasts. In contrast, the expression of human placental lactogen and Beckwith-Wiedemann region 1 C was reduced in hypoxic trophoblast. Using in situ hybridization we validated the expression of each transcript in cultured term villous trophoblasts, and determined transcript expression in placental samples derived from four sets of dichorionic twins complicated by growth restriction of one twin. The identification of hypoxic trophoblast signature transcripts may implicate new mediators in pathways underlying trophoblast hypoxic injury and adaptation.

Base Sequence↗
PubMed2005

AhR and PPARalpha: antagonistic effects on CYP2B and CYP3A, and additive inhibitory effects on CYP2C11.

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates a spectrum of toxic and biological effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds. The peroxisome proliferator-activated receptor alpha (PPARalpha) is a member of the nuclear receptor super-family of ligand-activated transcription factors and it functions as an obligate heterodimer with retinoid X-receptor alpha RXRalpha. The aim was to investigate whether the negative cross-talk recently proposed by the present authors between AhR and PPARalpha on CYP4A and CYP1A has any impact on other cytochrome P450 enzymes. Treatment of male Wistar rats with a PPARalpha ligand clofibric acid (CA) induced CYP2B1/2 and CYP3A proteins, activities, and the mRNA expression of CYP2B1, CYP2B2, CYP3A1 and CYP3A2, and suppressed CYP2C11 protein, activities and mRNA expression. AhR ligand Sudan III (S.III) treatment decreased basal and CA-induced CYP2B, CYP3A and CYP2C11 protein, activities and mRNA expression. To the best of the authors' knowledge, this is the first study showing the presence of mutual effects of AhR and PPARalpha on CYP2B and CYP3A and an additive inhibitory effect on CYP2C11 in the livers of male rats.

Administration, Oral↗
PubMed2005

Delayed emergence process does not result in a lower incidence of emergence agitation after sevoflurane anesthesia in children.

BACKGROUND: Emergence agitation (EA) is more frequent after sevoflurane anesthesia than other inhalational agents but the etiology remains unclear. We investigated whether the EA after sevoflurane anesthesia is related to rapid emergence. METHODS: Eighty-five patients, aged 1-7 years, undergoing elective urology surgery were studied. After induction, anesthesia was maintained with 2.0-2.5% sevoflurane and 50% N(2)O. BIS was monitored continuously throughout surgery and emergence. At the end of surgery, the children were randomly assigned to one of two groups: group I, immediate cessation of sevoflurane; or group G, gradual decrease of sevoflurane with the rate of 0.1%.min(-1). Emergence agitation score was recorded during recovery. RESULTS: Times from immediate cessation or start of decrease of sevoflurane to BIS 70, 80, 90 and extubation were significantly longer in group G. The incidence of severe agitation (score > or =3) was not significantly different between group I and group G: which were 35.7% and 32.6%, respectively. CONCLUSION: Prolonged recovery did not reduce the incidence of EA following sevoflurane anesthesia in children.

Anesthesia Recovery Period↗
PubMed2005

Chimpanzee chromosomes: retrotransposable compound repeat DNA organization (RCRO) and its influence on meiotic prophase and crossing-over.

The terminal C-bands that are a specific feature of chimpanzee chromosomes were dissected using a molecular cytogenetic technique, PRINS, with primers for telomeric sequences, subterminal satellite, and retrotransposable elements (HERV-K and -W). These DNA elements jointly formed a large block of retrotransposable compound repeat DNA organization (RCRO) at the terminal C-band regions of 30 chromosomes, and are also located at the centromeric regions of some chromosomes. Additionally, a block consisting of all members of the RCRO has transposed to the middle (q31.1) of the long arm of chromosome 6, and three members, the subterminal satellite and the two HERVs, have integrated into the proximal region (q14.4) of the long arm of chromosome 14. Terminal RCROs seem to induce and prolong the bouquet stage in meiotic prophase, and to affect chiasma formation, together with interstitial RCROs. It is also postulated that RCROs may cause a position effect to gene expression, resulting in gene silencing and/or late replication.

Animals↗