Biomedical subjects

H G Kim

Publications and source records attributed to H G Kim.

At least 55 records · Page 3Linked to original sources

PubMed1999

A role for phospholipase C-gamma-mediated signaling in tumor cell invasion.

The invasive and metastatic transformation of cancers often results in death. However, the mechanisms that promote this transformation remain unclear. Two closely related receptors, the epidermal growth factor receptor (EGFR) and ErbB2, are overexpressed in a significant percentage of breast and prostate carcinomas, among others, with this up-regulated signaling correlating with tumor progression. Previous studies in our laboratory have demonstrated that an EGFR-phospholipase C (PLC)gamma-mediated motility-associated signaling pathway is rate-limiting for tumor cell invasion in vitro and in vivo in one model of prostate carcinoma. Therefore, we investigated whether this PLCgamma signaling pathway also was rate-limiting for invasion in other tumor cell lines and types and whether this EGFR activity is subsumed by the closely related ErbB2. We determined the effects of PLCgamma signal abrogation by pharmacological (U73122) and molecular (expression of the dominant-negative PLCz) means on the in vitro invasiveness of tumor cells. Inhibition of PLCgamma signaling concomitantly decreased invasiveness of de novo-occurring transgenic adenocarcinoma mouse prostate (TRAMP) lines and the human breast cancer cell lines MDA-468 and MDA-231; these lines present up-regulated EGFR signaling. Because the prostate and breast cancer lines usually present autocrine stimulatory loops involving EGFR, we also examined transgenic adenocarcinoma mouse prostate C1 and MDA-468 treated with the EGFR-specific kinase inhibitor PD153035 to determine whether invasiveness is dependent on EGFR signaling. PD153035 reduced invasiveness to levels similar to those seen with U73122, suggesting that the autocrine EGFR stimulatory loop is functioning to promote invasiveness. To determine whether this signaling pathway also promotes invasiveness of ErbB2-overexpressing tumors, we examined the human breast carcinoma line MDA-361; again, U73122 inhibition of PLCgamma decreased invasiveness. In all situations, the inhibition of PLCgamma signaling did not decrease mitogenic signaling. Thus, the motility-associated PLCgamma signaling pathway is a generalizable rate-limiting step for tumor cell progression.

Adenocarcinoma↗

PubMed1998

Molecular evidence for an African origin of the Hawaiian endemic Hesperomannia (Asteraceae).

Identification of the progenitors of plants endemic to oceanic islands often is complicated by extreme morphological divergence between island and continental taxa. This is especially true for the Hawaiian Islands, which are 3,900 km from any continental source. We examine the origin of Hesperomannia, a genus of three species endemic to Hawaii that always have been placed in the tribe Mutisieae of the sunflower family. Phylogenetic analyses of representatives from all tribes in this family using the chloroplast gene ndhF (where ndhF is the ND5 protein of chloroplast NADH dehydrogenase) indicate that Hesperomannia belongs to the tribe Vernonieae. Phylogenetic comparisons within the Vernonieae using sequences of both ndhF and the internal transcribed spacer regions of nuclear ribosomal DNA reveal that Hesperomannia is sister to African species of Vernonia. Long-distance dispersal northeastward from Africa to southeast Asia and across the many Pacific Ocean island chains is the most likely explanation for this unusual biogeographic connection. The 17- to 26-million-year divergence time between African Vernonia and Hesperomannia estimated by the DNA sequences predates the age of the eight existing Hawaiian Islands. These estimates are consistent with an hypothesis that the progenitor of Hesperomannia arrived at one of the low islands of the Hawaiian-Emperor chain between the late Oligocene and mid-Miocene when these islands were above sea level. Subsequent to its arrival the southeast Pacific island chains served as steppingstones for dispersal to the existing Hawaiian Islands.

Africa↗

PubMed1998

Functional knock-out of c-myb by an intracellular anti-c-Myb single-chain antibody.

Aberrant expression of the c-myb proto-oncogene is a key factor in the development of the neoplastic phenotype in a variety of contexts. On this basis, it has been proposed that ablation of c-myb function might be an effective approach for therapy. To this end, we have employed an intracellular single-chain antibody (sFv) approach to achieve the functional knock-out of the c-Myb onco-protein. We derived an anti-c-Myb sFv, which was configured into eukaryotic expression plasmids. We confirmed the expression of the cytoplasmic and nuclear forms of the sFvs in the correct subcellular compartments by immunofluorescent staining. Importantly, the anti-c-Myb sFvs strongly inhibited the transactivation activity of c-Myb. Furthermore, cytotoxic effect of the sFv was observed only in the c-Myb positive cell line K562. These results suggest that anti-c-Myb sFv is a valuable tool for understanding the molecular mechanisms of c-myb induced transformation. In addition, this approach may have potential utility in the gene therapy for c-myb-dependent malignant diseases.

Amino Acid Sequence↗

PubMed1998

Thioltransferase from Schizosaccharomyces pombe: purification to homogeneity and some properties.

Two types of thioltransferase were identified in the cytosolic extract of Schizosaccharomyces pombe, a fission yeast. In the present study, the major one of them was purified to homogeneity using chromatography processes such as ion-exchange chromatography and gel filtration. Purification was monitored by the transhydrogenase activity of thioltransferase with 2-hydroxyethyl disulfide as a substrate. Its molecular weight was estimated to be about 14,000 on SDS-polyacrylamide gel electrophoresis. The purified enzyme catalyzes the reduction of various disulfide compounds such as S-sulfocysteine, L-cystine, and insulin. It was also found to contain the reducing activity on non-disulfide substrates such as dehydroascorbic acid and alloxan. Its activity was greatly activated by high concentrations of reduced glutathione. It was found to be very heat-stable as like other thioltransferases. It was characterized on other aspects such as kinetic parameters and optimal reaction conditions.

Antidotes↗

PubMed1998

Inhibition of transcription of the human c-myc protooncogene by intermolecular triplex.

Triplex-forming oligonucleotides (TFOs) have been shown to inhibit both transcription in vitro and the expression of target genes in cell culture by binding to polypurine/polypyrimidine sequences in several human gene promoters. The c-myc protooncogene is overexpressed in a variety of human cancers and appears to play an important role in the proliferation of these cells. In an attempt to assay the ability of triplex-forming oligonucleotides to inhibit expression of a target gene in vivo, we have developed a cellular system involving transfection of a c-myc promoter-driven luciferase reporter plasmid with triplex-forming oligonucleotides targeted to the human c-myc protooncogene. To increase the stability of the TFO, we have used modified phosphorothioate oligonucleotides. Triplex formation with a modified phosphorothioate oligonucleotide occurs with approximately equal binding affinity as that seen using a phosphodiester oligonucleotide. Phosphorothioate-modified TFOs targeted to c-myc inhibit transcription of the c-myc promoter in HeLa cells as demonstrated by a decrease in luciferase expression from a luciferase reporter gene construct. These results suggests that triplex formation may represent a gene-specific means of inhibiting specific protooncogene expression.

Base Sequence↗

PubMed1998

A novel triplex-forming oligonucleotide targeted to human cyclin D1 (bcl-1, proto-oncogene) promoter inhibits transcription in HeLa cells.

The cyclin D1/bcl-1 proto-oncogene is one of a series of genes encoding proteins which regulate the cell cycle and are involved in the multistep process of tumorigenesis. Translocation of the cyclin D1 proto-oncogene is a common event in B cell lymphoma, and cyclin D1 amplification occurs in breast, esophageal, hepatocellular, and head/neck carcinomas. The human cyclin D1 proto-oncogene promoter contains an 18-base pair purine-pyrimidine rich motif with three C.G interruptions. This motif is a potential target for purine.purine. pyrimidine triplex formation. We have designed a G-rich antiparallel triplex forming oligonucleotide (TFO) targeted to this region. Electrophoretic mobility shift analysis (EMSA) shows that this purine-pyrimidine rich motif is a binding site for the transcription factor Sp1 and that triplex formation by the target sequence prevents the binding of recombinant Sp1. The exact location of triplex formation was confirmed by DNase I footprinting. In an attempt to increase stability, we have used modified phosphorothioate oligonucleotides for cell culture experiments. Triplex formation by the cyclin D1 targeted phosphorothioate oligonucleotide occurs with a binding affinity approximately equal to that of phosphodiester oligonucleotides. This phosphorothioate modified TFO targeted to cyclin D1 also inhibits transcription of the cyclin D1 promoter in HeLa cells, as demonstrated by a decrease in luciferase expression from a stably integrated human cyclin D1 promoter driven luciferase construct. This suggests that triplex formation may represent a gene specific means of inhibiting cyclin D1 expression.

Base Sequence↗

PubMed1998

Manganese: a transition metal protects nigrostriatal neurons from oxidative stress in the iron-induced animal model of parkinsonism.

It has been suggested that transition metals such as iron and manganese produce oxidative injury to the dopaminergic nigrostriatal system. which may play a critical role in the pathogenesis of Parkinson's disease. Intranigral infusion of ferrous citrate (0 to 8.4 nmol, i.n.) acutely increased lipid peroxidation in the substantia nigra and dopamine turnover in the caudate nucleus. Subsequently, it caused a severe depletion of dopamine levels in the rat caudate nucleus. In contrast to iron's pro-oxidant effect, manganese (up to 30 nmol, i.n.) causes neither lipid peroxidation nor nigral injury/dopamine depletion. Manganese (1.05 to 4.2 nmol, i.n.) dose-dependently protected nigral neurons from iron-induced oxidative injury and dopamine depletion. Manganese also suppressed acute increase in dopamine turnover and contralateral turning behaviour induced by iron. In brain homogenates manganese (0 to 10 microM) concentration-dependently inhibited propagation of lipid peroxidation caused by iron (0 to 5 microM). Without the contribution of manganese-superoxide dismutase manganese was still effective in sodium azide and/or heat-pretreated brain homogenates. Surprisingly, iron but not manganese, catalysed the Fenton reaction or the conversion of hydrogen peroxide to hydroxyl radicals. The results indicate that iron and manganese are two transition metals mediating opposite effects in the nigrostriatal system, as pro-oxidant and antioxidant, respectively. In conclusion, intranigral infusion of iron, but not manganese, provides an animal model for studying the pathophysiological role of oxidant and oxidative stress in nigrostriatal degeneration and Parkinsonism. The present results further suggest that the atypical antioxidative properties of manganese may protect substantia nigra compacta neurons from iron-induced oxidative stress.

Animals↗

PubMed1998

Primary malignant melanoma of the esophagus.

Primary malignant melanoma of the esophagus is exceedingly rare. The existence of primary malignant melanoma in the esophagus had been in doubt until the presence of benign melanocytes was demonstrated within the esophagus. Hematogenous and lymphatic metastases are common. The prognosis is poor even after a radical procedure due to early metastasis. We report here two cases of primary malignant melanoma of the esophagus. One is a melanotic melanoma and the other is an amelanotic melanoma.

Adult↗

PubMed1998

Mercury inhalation poisoning and acute lung injury.

Acute mercury inhalation poisoning is a rare cause of acute lung injury. It is usually fatal because of progressive pulmonary failure. We experienced a patient with acute respiratory distress syndrome (ARDS) after illicit use of mercury vapor for hemorrhoid treatment; he developed acute chemical pneumonitis following exposure to mercury vapor. Prompt treatment with corticosteroids and penicillamine for acute chemical pneumonitis was instituted; radiologic pulmonary infiltrates disappeared within a week, but late phase neurologic sequelae and pulmonary interstitial fibrosis progressed.

Adrenal Cortex Hormones↗

PubMed1997

The physical map of the chloroplast DNA from Korean ginseng (Panax ginseng C.A. Meyer).

To compare the gene order of the chloroplast genome among dicotyledonous plants, we constructed a physical map of chloroplast DNA (cpDNA) of Korean ginseng (Panax ginseng C.A. Meyer) with four restriction enzymes, BamHI, HindIII, EcoRI, and PstI. The restriction enzyme recognition sites of the physical map were also confirmed by Southern hybridization of total ginseng cpDNA with homologous and heterologous probes. The cpDNA of Korean ginseng was determined as a circular molecule with a total size of about 154 kb, which contain two inverted repeats of 23 kb each that disrupt the rest of the molecule into a large (90 kb) and a small single copy region (18 kb). The genome structure of Korean ginseng cpDNA was similar in size and gene order to that of tobacco cpDNA. The cpDNA of Korean and American ginseng (P. quinquefolius) showed very similar restriction patterns.

Chromosome Mapping↗

PubMed1997

Adding posterior lumbar interbody fusion to pedicle screw fixation and posterolateral fusion after decompression in spondylolytic spondylolisthesis.

STUDY DESIGN: This is a retrospective study analyzing 76 patients treated by decompression, pedicle screw instrumentation, and fusion for spondylolytic spondyiolisthesis with symptomatic spinal stenosis. OBJECTIVES: To verify the advantages of adding posterior lumbar interbody fusion to the usual posterolateral fusion with pedicle screw instrumentation. SUMMARY OF BACKGROUND DATA: Stabilization after decompression of spondylolytic spondylolisthesis is difficult because of a lack of fusional bone bases, gap between the transverse process bases, and incompetent anterior disc support. Posterior lumbar interbody fusion offers anterior support, reduction, and a broad fusion base. METHODS: Forty patients were treated with posterolateral fusion, and 36 were treated with additional posterior lumbar interbody fusion. They were compared for union, reduction of the deformity, and clinical results. RESULTS: The patients were followed up for more than 2 years. Nonunion was observed in three patients who underwent posterolateral fusion (7.5%), and no cases of nonunion was found in patients who underwent posterior lumbar interbody fusion. Reduction of slippage was 28.3% in those who underwent posterolateral fusion and 41.6% in those who had posterior lumbar interbody fusion (P = 0.05). In the posterolateral fusion group, eight patients (20%) had recurrence of deformity, with loss of reduction more than 50%. Hardware failures occurred in two patients who had posterolateral fusion. There was no major neurologic complications in both groups. Both groups had satisfactory results in more than 90% of patients, with marked improvement of claudication. However, subjective improvement of back pain by Kirkaldy-Willis criteria revealed differences in the excellent results. An excellent result was reported by 45% in the posterolateral fusion group and by 75% in posterior lumbar interbody fusion group. CONCLUSIONS: The addition of posterior lumbar interbody fusion to posterolateral fusion after a complete decompression and pedicle screw fixation is a recommended procedure for the treatment of spondylolytic spondylolishesis with spinal stenosis.

Adult↗

PubMed1997

Comparative studies on omega-hydroxylation of 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha-triol in the mitochondrial and microsomal fraction of the liver from several vertebrates.

The activity and the stereospecificity of omega-hydroxylation, a hydroxylation at one of the two terminal methyl groups of 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha-triol, which is thought to be the first step in side-chain degradation resulting in the formation of cholic acid, was elucidated in mitochondria and microsomes of the liver from several evolutionarily primitive vertebrates, fish, frogs, turtles, and chickens in addition to such mammals as rats. hamsters, and rabbits. The detection of omega-hydroxylation products (25R)- and (25S)-5 beta-cholestane-3 alpha, 7 alpha, 12 alpha, 26-tetrols as well as the separation of their two isomers was facilitated using high-performance liquid chromatography after conversion to 9-anthroyl derivatives. All the mammals examined, except for the rat, exhibited predominant activity in the mitochondrial fraction. Although the hydroxylation activity was somewhat lower in the primitive vertebrates, it was present in the mitochondria more than in the microsomes. Furthermore, the stereospecific formation of a 25R-isomer was detected in the mitochondrial fraction of most animals estimated. However, activity in the carp liver was seven times higher in the microsomes than in the mitochondria, and the hydroxylation product was almost always a 25R-isomer. Omega-Hydroxylation activity could not be detected in rainbow trout, suggesting the existence of another biosynthetic pathway, not via 26-hydroxylation, as in the 25-hydroxylation pathway, for the production of bile acid.

Animals↗

PubMed1997

Relationship between nutritional intake and dental caries experience of junior high students.

This study was designed to investigate the relationship between nutritional intake and caries experience of junior high school students. The sample consisted of 295 boys and 356 girls in Kangwha county. Dependent variables were total caries experience, occlusal surface caries experience, smooth surface caries experience and DMFS score (Decayed, Missing, Filling Tooth Surface score). Independent variables such as pit and fissure retentiveness of first molars, oral hygiene status, intraoral acidogenicity were also measured by dentists. Other independent variables such as toothbrushing habits, socioeconomic conditions, between-meal eating habits, and daily nutritional intake were determined during an interview. Univariate and multivariate analysis was performed to evaluate how nutritional intake influences caries experience. The results were as follows: 1. The most influential factor on dental caries experience was pit and fissure retentiveness. 2. Dietary fiber and potassium were the significant nutritional factors on total caries experience and occlusal caries experience, and niacin was the significant nutritional factor on smooth surface caries. 3. DMFS score was positively associated with the daily amount of carbohydrate and niacin intake, and negatively associated with total energy intake. The above results suggested that pit and fissure retentiveness was the most influential factor on caries experience. However, in this study, the intake of potassium and niacin was identified to influence the caries experience in addition to confirming the well-known relationship between fiber and carbohydrate intake.

Adolescent↗

PubMed1997

Acute alpha 2 blockade by idazoxan increases insulin and lowers plasma glucose during positron emission tomography.

The sympathetic nervous system can modulate glucose levels through a variety of mechanisms, including inhibition of insulin release by alpha2-adrenergic receptors. Such effects could potentially confound measurements of brain glucose metabolism during studies of the central actions of sympathomimetic drugs. Plasma glucose, insulin, and sympathetic responses to alpha2 blockade were measured following infusion of idazoxan, a selective alpha2 antagonist, or placebo, in 33 healthy volunteers (idazoxan: n = 23, placebo: n = 10). These measures were compared with estimates of global brain metabolism obtained from positron emission tomography (PET) scans before and after the infusion. Glucose levels fell and fractional levels of insulin rose after idazoxan, compared with placebo. Relative increases in insulin correlated with increases in epinephrine after active drug. The increases in insulin are consistent with the hypothesized role of alpha2-adrenoceptors in regulating insulin release. Estimates of global brain glucose metabolism did not appear to be influenced by the modest changes in plasma glucose.

Adrenergic alpha-2 Receptor Antagonists↗

PubMed1997

Progressive dysregulation of proliferation during cervical carcinogenesis as measured by MPM-2 antibody staining.

To better characterize the amount and location of loss of proliferation control during cervical carcinogenesis, 44 cervical cone biopsy specimens containing various grades of premalignant and malignant lesions and 12 normal cervix specimens were immunohistochemically examined using MPM-2. This antibody recognizes a phosphorylated epitope on a group of proteins that are preferentially phosphorylated at mitosis. The spatial organization of mitotic figures was determined using a computer-assisted image analysis system. The mitotic figure frequencies/unit of epithelial area were found to increase as the histological type progressed; the numbers of mitoses/square millimeter was 1.7 +/- 0.5 (mean +/- SE) for control normal epithelium (n = 12), 3.1 +/- 1.7 for normal epithelium adjacent to cervical intraepithelial neoplasia (CIN) and cancer (n = 28), 7.9 +/- 1.3 for CIN1 (n = 24), 75.8 +/- 16.3 for CIN2 (n = 11), 127.2 +/- 9.7 for CIN3 (n = 22), 196.9 +/- 33.2 for carcinoma in situ (n = 9), and 156.2 +/- 31.0 for cervical carcinoma (n = 8). The MPM-2 index was higher in high-risk premalignant lesions (i.e., those adjacent to areas of high-grade CIN and carcinoma) than it was in lower risk premalignant lesions (i.e., those with no adjacent higher grade CIN or cervical cancer), even if they exhibited the same histological grade. Moreover, the mean relative distance of the mitotic cells from the basement membrane (i.e., the distance from the basal layer to the surface) also increased as the histological grade progressed. These results suggest that proliferation becomes sequentially dysregulated both quantitatively and spatially during cervical carcinogenesis and that the MPM-2 antibody might be useful as a proliferation biomarker.

Antibodies, Monoclonal↗

PubMed1996

Laminar origins of inhibitory synaptic inputs to pyramidal neurons of the rat neocortex.

1. Inhibitory neuron-pyramidal cell interactions were investigated in slices of rat somatosensory cortex in which excitatory synaptic transmission was blocked with bath-applied glutamate receptor antagonists. Local inhibitory neurons were excited by focal pressure ejections of small (approximately 40 pl) volumes of 1-10 mM acetylcholine. 2. The frequency of inhibitory postsynaptic potentials (IPSPs) ("responses per trial' or R/T) declined as the stimulation distance was increased. Inhibitory inputs were most prevalent in layer II/III regular spiking (RS) pyramidal neurons (30 cells) where median R/T was 0.020. In layer V, the median R/T was 0.024 for RS neurons (25 cells), but significantly lower for burst-firing (IB) neurons (17 cells), where median R/T was 0.007 (P = 0.039). 3. IPSPs in individual layer V pyramidal cells were recorded with CsCl electrodes. In eight neurons, spontaneous picrotoxin-sensitive IPSPs were recorded and found to display a wide range of 10-90% rise times (1-34 ms), not correlated with amplitude (0.2-18 mV). For a further ten pyramidal neurons, extracellular stimulating electrodes were placed simultaneously in layers II/III and V/VI in order to evoke pairs of IPSPs whose waveforms were averaged and compared. In seven cells, IPSPs evoked from layer II/III (distal location) had longer 10-90% rise times than IPSPs evoked from layer V/VI stimulating electrodes (proximal location). In addition, "proximal' IPSPs could always be reversed by membrane depolarization whereas "distal' ones could not (n = 4/4). 4. This study showed that pyramid cell-inhibitory neuron interconnections are extensive but their spatial organization varies with cell class and with cortical layer. In addition, pyramidal neurons can receive inhibitory inputs from locations on their apical dendrites.

Acetylcholine↗

PubMed1996

Influence of GC and AT specific DNA minor groove binding drugs on intermolecular triplex formation in the human c-Ki-ras promoter.

We have used DNase I footprinting and gel shift assays to characterize the interaction of DNA binding drugs mithramycin, distamycin, and berenil with an intermolecular triplex formed by the human c-Ki-ras promoter. A purine-rich triplex-forming oligonucleotide (ODN) forms a stable intermolecular triple helix (triplex) with a homopurine (PR):homopyrimidine (PY) motif in the human c-Ki-ras promoter which contains a 22bp PR:PY region (-328 to -307). This triplex structure is comprised of 15 G.G:C triplets interspersed with 7 T.A:T triplets. Mithramycin binding sites in the human c-Ki-ras promoter encompass most of the triplex target site and three G-C-rich sequences downstream of this triplex-forming region. Mithramycin binding within the c-Ki-ras promoter completely abrogates triplex formation. Furthermore, the addition of mithramycin to pre-formed triplex by c-Ki-ras promoter displaces the major groove bound ODN. Five prominent distamycin binding sites are noted within the c-Ki-ras promoter including the triplex-forming site as well as A-T-rich regions upstream and downstream of the triplex site. Berenil does not bind within the triplex target sequence, and only one berenil binding sequence downstream of the triplex motif was present within the c-Ki-ras promoter fragment. Neither distamycin nor berenil prevents triplex formation, and, furthermore, the addition of either distamycin or berenil to the pre-formed triplex structure did not displace the major-groove-bound third strand. This study demonstrates that GC-specific and AT-specific minor groove ligands differentially affect the intermolecular pur.pur:pyr triplex. A possible biological significance of mithramycin interaction with intramolecular triplex is discussed.

Base Sequence↗

PubMed1996

A case of flutamide-induced acute cholestatic hepatitis--a case report.

Flutamide, an oral nonsteroidal, antiandrogenic, anilid compound which inhibits the uptake and binding of androgens to nuclear receptors in the prostate, is used with or without LH-RH analogues for treatment of patients with metastatic carcinoma of the prostate. Clinically significant hepatotoxicities such as toxic hepatitis, cholestatic hepatitis, hepatic failure, and even death have rarely been reported in the English literature, but no case has been reported in Korea. A 75-year-old man with metastatic carcinoma of the prostate had taken flutamide (750 mg/day) for 7 months and suddenly developed jaundice and general weakness. The findings of blood chemistries were compatible with cholestatic hepatitis, but ultrasonography, viral marker and auto-antibody studies did not reveal any attributable causes. Histologic examination of a sono-guided liver biopsy only disclosed centrilobular cholestasis, nuclear glycogenosis and mild sinusoidal lymphocytic infiltration. Discontinuation of flutamide resulted in an almost full recovery of the patient's liver function in 2 months. We, herein, report a case of flutamide-induced acute choestatic hepatitis with a brief review of the literature.

Acute Disease↗