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Biomedical subjects

K W Kim

Publications and source records attributed to K W Kim.

At least 55 records · Page 3Linked to original sources
PubMed2001

Facet tropism: a comparison between far lateral and posterolateral lumbar disc herniations.

STUDY DESIGN: An assessment of the difference in the degree of facet tropism and disc degeneration between far lateral and posterolateral lumbar disc herniations. OBJECTIVE: To investigate the effect of the difference in the degree of the facet tropism and disc degeneration with respect to the development of far lateral lumbar disc herniation and posterolateral lumbar disc herniation, and to compare the effect between the two types of herniations. SUMMARY OF BACKGROUND DATA: The effect of facet tropism on the development of posterolateral lumbar disc herniation has been investigated previously, but there has been no study on far lateral lumbar disc herniation. METHODS: Thirty-eight lumbar disc herniations (far lateral, n = 19; posterolateral, n = 19) were included this study. The degree of facet tropism and disc degeneration was measured at the herniated disc level by using magnetic resonance imaging. The results were compared to show any differences between the two types of lumbar disc herniations. RESULTS: There were significant differences in the degree of facet tropism (24.74 vs. 14.26, P = 0.004) and disc degeneration (23.92 vs. 15.08, P = 0.005) between the far lateral and posterolateral lumbar disc herniations. There was no significant correlation between the degree of facet tropism and the degree of disc degeneration in far lateral lumbar disc herniation (r = -0.369, P = 0.120). CONCLUSION: This results suggest that the differences in the degree of facet tropism and disc degeneration might be considered a key factor in distinguishing the development of far lateral lumbar disc herniation from that of posterolateral lumbar disc herniation.

Adult↗
PubMed2001

Ligand binding profiles of delta-opioid receptor in human cerebral cortex membranes: evidence of delta-opioid receptor heterogeneity.

In this study, receptor binding profiles of opioid ligands for subtypes of opioid delta-receptors were examined employing [3H]D-Pen2,D-Pen5-enkephalin ([3H]DPDPE) and [3H]Ile(5,6)-deltorphin II ([3H]Ile-Delt II) in human cerebral cortex membranes. [3H]DPDPE, a representative ligand for delta1 sites, labeled a single population of binding sites with apparent affinity constant (Kd) of 2.72 +/- 0.21 nM and maximal binding capacity (Bmax) value of 20.78 +/- 3.13 fmol/mg protein. Homologous competition curve of [3H]Ile-Delt II, a representative ligand for delta2 sites, was best fit by the one-site model (Kd = 0.82 +/- 0.07 nM). Bmax value (43.65 +/- 2.41 fmol/mg) for [3H]Ile-Delt II was significantly greater than that for [3H]DPDPE. DPDPE, [D-Ala2,D-Leu5]enkephalin (DADLE) and 7-benzylidenaltrexone (BNTX) were more potent in competing for the binding sites of [3H]DPDPE than for those of [3H]Ile-Delt II. On the other hand, deltorphin II (Delt II), [D-Ser2,Leu5,Thr6]enkephalin (DSLET), naltriben (NTB) and naltrindole (NTI) were found to be equipotent in competing for [3H]DPDPE and [3H]Ile-Delt II binding sites. These results indicate that both subtypes of opioid delta-receptors, delta1 and delta2, exist in human cerebral cortex with different ligand binding profiles.

Adult↗
PubMed2001

Association of alpha-2-macroglobulin deletion polymorphism with sporadic Alzheimer's disease in Koreans.

Alpha-2-macroglobulin (A2M) deletion polymorphism was recently reported to be associated with Alzheimer's disease (AD) in a way comparable to apolipoprotein E (APOE) polymorphism in a family-based study. However, the association of A2M deletion polymorphism with AD has not been consistently replicated in successive case-controlled studies. In order to evaluate whether this A2M polymorphism is associated with AD in Koreans, we examined the frequencies of the A2M deletion (D) allele and D-bearing genotypes in a group of Koreans composed of 100 sporadic AD patients and 203 control subjects. The frequency of the deletion (D) allele (P=0.046) was significantly different between the total group of AD patients and the controls, although the frequency of the D-bearing genotypes did not attain significance (P=0.078). When the subjects were stratified according to age at onset, there was significant difference in the frequencies of the D allele (P=0.044) and D-bearing genotypes (P=0.041) between late-onset AD patients (> or =65 years) and the controls. However, no significant difference was observed between early-onset AD patients (<65 years) and the control group. Additionally, when we divided the late-onset AD and control subjects by APOE epsilon4 status, the difference of the A2M D allelic frequency was significant only in the APOE epsilon4 negative subjects (P=0.015). In conclusion, our data suggests that the A2M D allele is a modest risk factor for late-onset sporadic AD in Koreans, and the AD risk conferred by the A2M D allele increases in APOE epsilon4 negative subjects.

Aged↗
PubMed2001

Novel bile acid derivatives induce apoptosis via a p53-independent pathway in human breast carcinoma cells.

We have compared the anti-proliferative effects of ursodeoxycholic acid (UDCA), chenodeoxycholic acid (CDCA) and their derivatives, HS-1183, HS-1199 and HS-1200, on MCF-7 (wild-type p53) and MDA-MB-231 (mutant p53) cells. While UDCA and CDCA exhibited no significant effect, their novel derivatives inhibited the proliferation of both cell lines in a concentration-dependent manner, concomitant with apoptotic nuclear changes and the increase of a sub-G1 population and DNA fragmentation. Furthermore, we also observed an increase in the ratio of pro-apoptotic protein Bax to anti-apoptotic protein Bcl-2 and cleavages of lamin B and poly(ADP-ribose) polymerase (PARP) in MCF-7 and MDA-MB-231 cells. Cell cycle related proteins, cyclin D1 and D3, as well as retinoblastoma protein (pRb) were down-regulated, while the level of cyclin-dependent kinase inhibitor p21(WAF1/CIP1) was increased in both cancer cells after treatment with novel bile acids. These findings suggest that these cytotoxic effects of novel bile acid derivatives on human breast carcinoma cells were mediated via apoptosis through a p53-independent pathway.

Apoptosis↗
PubMed2001

Pharmacological effects of naltriben as a ligand for opioid mu and kappa receptors in rat cerebral cortex.

Naltriben (NTB) has been used to differentiate the subtypes of delta opioid receptors, delta1 and delta2. However, there is considerable evidence suggesting that NTB may act on other types of opioid receptors too. We examined the effects of NTB on the specific binding of radiolabeled ligands for opioid mu and kappa2 receptors, and the effects on the release of [3H]norepinephrine ([3H]NE) in rat cerebral cortex slices. NTB displaced the specific binding of [3H]DAMGO with Ki value of 19.79 +/- 1.12 nM in rat cortex membranes. Specific binding of [3H]diprenorphine ([3H]DIP) was inhibited by NTB with Ki value of 82.75 +/- 6.32 nM in the presence of DAMGO and DPDPE. High K+ (15 mM)-stimulated release of [3H]NE was attenuated by DAMGO in rat cerebral cortex slices. NTB (30 nM) shifted the dose-response curve of DAMGO to the right and attenuated the maximal effect. In the meantime, NTB inhibited high K+-stimulated [3H]NE release at concentrations above 100 nM. The inhibitory effect of NTB was not attenuated by CTAP (10 nM) and naloxone (3 nM) but by higher concentration of naloxone (30 nM), nor-BNI (300 nM) and bremazocine (3 nM). These results indicate that NTB, depending on the dosage, could acts not only as an antagonist at delta but also as a noncompetitive antagonist for mu receptors, and as an agonist for kappa2 receptors in rat cerebral cortex.

Animals↗
PubMed2001

Extracellular signal-regulated kinase/90-KDA ribosomal S6 kinase/nuclear factor-kappa B pathway mediates phorbol 12-myristate 13-acetate-induced megakaryocytic differentiation of K562 cells.

Two signaling pathways, the extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK)-dependent pathway and the nuclear factor-kappaB (NF-kappaB)-dependent pathway, have been known to mediate megakaryocytic differentiation of K562 cells induced by phorbol 12-myristate 13-acetate (PMA). In this study, we examined whether 90-kDa ribosomal S6 kinase (RSK), known as a substrate of ERK/MAPK and a signal-inducible IkappaBalpha kinase, would link two pathways during the differentiation. RSK1 was activated in a time- and dose-dependent manner during the PMA-induced differentiation. Overexpression of wild-type or dominant inhibitory mutant (D205N) of RSK1 enhanced or suppressed PMA-stimulated NF-kappaB activation and megakaryocytic differentiation as shown by morphology, nonspecific esterase activity, and expression of the CD41 megakaryocytic marker, respectively. In addition, overexpression of the dominant inhibitory mutant (S32A/S36A) of IkappaBalpha inhibited PMA-stimulated and RSK1-enhanced megakaryocytic differentiation, indicating that NF-kappaB mediates a signal for megakaryocytic differentiation downstream of RSK1. PMA-stimulated activation of ERK/MAPK, RSK1, and NF-kappaB and the PMA-induced megakaryocytic differentiation were prevented by pretreatment with PD98059, a specific inhibitor of the mitogen-activated ERK kinase (MEK). Therefore, these results demonstrate that the sequential ERK/RSK1/NF-kappaB pathway mediates PMA-stimulated megakaryocytic differentiation of K562 cells.

Amino Acid Substitution↗
PubMed2001

Cloning and characterization of tissue inhibitor of metalloproteinase-3 (TIMP-3) from shark, Scyliorhinus torazame.

We cloned the full-length cDNA encoding TIMP-3 from the cartilage of cloudy dogfish, Scyliorhinus torazame. The entire open reading frame was composed of 645 nucleotides and 214 residues including 12 conserved cysteines and asparagine-184, a putative site for N-linked sugars. It showed about 72% identity to those of other species based on the deduced amino acid sequence. The mRNA of shark TIMP-3 were expressed abundantly in brain and cartilage tissues. To investigate the roles of shark TIMP-3, an expression vector was constructed and transfected into HT1080 human fibrosarcoma cells. Overexpression of shark TIMP-3 reduced the activity of MMP-2 in gelatin zymography. Through human Alu PCR based CAM assay, we also confirmed that shark TIMP-3 transfected HT1080 cells had less intravasation effects.

Amino Acid Sequence↗
PubMed2001

Inactivation of farnesyltransferase and geranylgeranyltransferase I by caspase-3: cleavage of the common alpha subunit during apoptosis.

Caspase plays an important role in apoptosis. We report here that farnesyltransferase/geranylgeranyltransferase (FTase/GGTase)-alpha, a common subunit of FTase (alpha/beta(FTase)) and GGTase I (alpha/beta(GGTase)), was cleaved by caspase-3 during apoptosis. FTase/GGTase-alpha (49 kDa) was cleaved to 35 kDa (p35) in the Rat-2/H-ras, W4 and Rat-1 cells treated with FTase inhibitor (LB42708), anti-Fas antibody and etoposide, respectively. This cleavage was inhibited by caspase-inhibitors (YVAD-cmk, DEVD-cho). Serial N-terminal deletions and site-directed mutagenesis showed that Asp59 of FTase/GGTase-alpha was cleaved by caspase-3. The common FTase/GGTase-alpha subunit, but not the beta subunits, of the FTase or GGTase I protein complexes purified from baculovirus-infected SF-9 cells was cleaved to be inactivated by purified caspase-3. In contrast, FTase mutant protein complex [(D(59)A)alpha/beta(FTase)] was resistant to caspase-3. Expression of either the cleavage product (60-379) or anti-sense of FTase/GGTase-alpha induced cell death in Rat-2/H-ras cells. Furthermore, expression of (D(59)A)FTase/GGTase-alpha mutant significantly desensitized cells to etoposide-induced death. Taken together, we suggest that cleavage of prenyltransferase by caspase contributes to the progression of apoptosis.

Alkyl and Aryl Transferases↗
PubMed2001

Expression of Fas receptor on disc cells in herniated lumbar disc tissue.

STUDY DESIGN: The expression of Fas receptor, an apoptosis-related protein, on disc cells was examined in surgically obtained disc specimens. OBJECTIVE: To assess the fate of disc cells in herniated disc tissue and the difference in the degree of expression of the Fas receptor between contained and noncontained discs. SUMMARY OF BACKGROUND DATA: Little is known about the fate of disc cells after herniation. METHODS: Twenty-three herniated lumbar disc specimens were classified into contained discs (protrusion or subligamentous extrusion; n = 9) and noncontained discs (transligamentous extrusion or sequestration; n = 14). All specimens were stained using the avidin-biotin-peroxidase complex method. The percentage of disc cells positive for Fas receptor was calculated and compared with clinical and radiologic data. RESULTS: There was a significant difference in the percentage of Fas-positive disc cells between the contained and noncontained discs (8.44 vs.- 14.29;P = 0.044). The percentage of Fas-positive disc cells correlated significantly with the patient's age (r = 0.455, P = 0.029), but not with the degree of disc degeneration on magnetic resonance imaging (r = 0.252, P = 0.214). CONCLUSION: This is the first study to identify the expression of Fas receptor on disc cells in herniated disc tissue. The results show that the disc cells after herniation may undergo Fas-mediated apoptosis and that the degree of expression of Fas receptor differs depending on the type of herniation.

Adolescent↗
PubMed2001

Determination of hypoxic region by hypoxia marker in developing mouse embryos in vivo: a possible signal for vessel development.

Hypoxia is a well-known signal for angiogenesis, but the recent proposal that hypoxia exists in developing embryonic tissues and that it induces vascular development remains to be proven. In the present study, we demonstrate the presence of hypoxia in normal developing embryos by means of a hypoxia marker, pimonidazole, and its associated antibody. Our data clearly show that hypoxia marker immunoreactivity was highly detected in developing neural tubes, heart, and intersomitic mesenchyme at an early stage of organogenesis, suggesting that hypoxia may exist in the early stages of embryo development. We also found that hypoxia inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) were spatiotemporally co-localized with possible hypoxic regions in embryos. Investigation of platelet endothelial cell adhesion molecule (PECAM) expression provides evidence that endothelial cells proliferate and form the vessels in the hypoxic region in developing organs. Furthermore, we found that hypoxia induced both HIF-1alpha and VEGF in F9 embryonic stem and differentiated cells. Thus, we suggest that hypoxia may exist widely in developing embryonic tissues and that it may act as a signal for embryonic blood vessel formation in vivo.

Animals↗
PubMed2001

Correlation of hematopoietic progenitor cell count determined by the SE-automated hematology analyzer with CD34(+) cell count by flow cytometry in leukapheresis products.

The yield of stem cell collection after mobilization is crucial for autologous peripheral blood stem cell (PBSC) transplantation. Quantitative determinations of CD34(+) cells using flow cytometry or stem cell culture have been used, but these methods require much time, technical experience, and expensive reagents. The automated hematology analyzer (Sysmex SE-9000trade mark, TOA, Japan) equipped with the Immature Information (IMI) channel for immature myeloid cells can detect IMI(+) cells within 90 sec. Detection is made possible by the combination of a special reagent system and direct current/radiofrequency biosensors. We studied the relation of IMI(+) cells and variable cell counts with CD34(+) cell yield in autologous stem cell harvest. In a series of 32 patients (median age, 44 years; M:F = 11:21), 184 leukaphereses were performed after mobilization regimens with chemotherapy and G-CSF or G-CSF alone. Full blood cell counts were enumerated on peripheral blood (PB) samples taken prior to each leukapheresis. Mononuclear cell (MNC) and IMI(+) cell counts by automated hematology analyzer and flow cytometry based CD34(+) cell yield were measured on the harvested product. The relationship among PB white blood cells (WBC), PB monocytes, IMI(+) cells, MNC, and CD34(+) cell yield in a single leukapheresis was estimated by Pearson correlation analysis. PB WBC count showed no correlation with CD34(+) cell yield in a single leukapheresis (r = 0.02, P = 0.81). PB monocyte count showed a weak correlation (r = 0.21, P = 0.01) and MNC in harvest also showed a weak correlation (r = 0.36, P = 0.0001) with CD34(+) cell yield. In contrast, CD34(+) cell yield correlated well with IMI(+) cell count (r = 0.68, P = 0.0001), and data could be fitted by a linear regression equation, y = 0.330 + 0.974x. IMI(+) cell assay by the automated hematology analyzer correlated well with the CD34(+) cell yield in a mobilized autologous stem cell harvest. The IMI(+) cell count might be used as a simple and efficient indicator of blood stem cell mobilization and collection.

Adolescent↗
PubMed2001

Human rad21 gene, hHR21(SP), is downregulated by hypoxia in human tumor cells.

To identify genes differentially expressed under normoxic (21% O(2)) or hypoxic (1% O(2)) conditions, we used the technique of mRNA differential display using total RNA extracted from Chang human liver cells. Among downregulated genes by hypoxia, we focused on hHR21(SP) (human homologue of rad21 S. pombe) that is involved in DNA double-strand break repair. Northern blot analysis revealed that mRNA expression of hHR21(SP) was inhibited by hypoxia in various tumor cell lines, such as HepG2, SKHep1, MCF7, and HT1080 cells. We also found that hypoglycemia and heat shock significantly decreased the hHR21(SP) level, indicating that a DNA double-strand break repair gene, hHR21(SP) might be regulated by environmental stresses. In addition, wortmannin, a DNA-dependent protein kinase (DNA-PK) inhibitor, decreased the level of hHR21(SP) mRNA, indicating that DNA-PK might be involved in the regulation of hHR21(SP). These results propose a new understanding of hHR21(SP) regulations in human tumor cells.

Androstadienes↗
PubMed2001

4-Hydroxy-6-oxo-6,7-dihydro-thieno[2,3-b] pyrimidine derivatives: synthesis and their biological evaluation for the glycine site acting on the N-methyl-D-aspartate (NMDA) receptor.

Bioisostere approach has been shown to be useful to augment potency or to modify certain physiological properties of a lead compound. Based upon well documented bioisosterism, an isosteric replacement of benzene ring of 4-hydroxy-2-quinolone compound (L-695902) with a thiophene moiety was carried out to prepare the title compounds, 4-hydroxy-6-oxo-6,7-dihydro-thieno[2,3-b] pyrimidines 15. The resulting bioisosteric compounds 15 were evaluated for their antagonistic activity (binding assay) for NMDA receptor glycine site.

Animals↗
PubMed2001

Characterization of antidepressant-like effects of p-synephrine stereoisomers.

We previously reported that p-synephrine has antidepressant-like activity in the murine models of forced swimming and tail suspension. In the present study, we characterized antidepressant-like effects of p-synephrine stereoisomers in both in vivo and in vitro systems. In the tail suspension test, S-(+)-p-synephrine (3 mg/kg, p.o.) reduced the duration of immobility, while R-(-)-p-synephrine (0.3-3 mg/kg, p.o.) had no effect. S-(+)-p-synephrine (0.3, 1 and 3 mg/kg, p.o.) and R-(-)-p-synephrine (1 mg/ kg and 3 mg/kg, p.o.) significantly reversed the reserpine (2.5 mg/kg, i.p.)-induced hypothermia. S-(+)-p-synephrine was more effective than R-(-)-p-synephrine in inhibition of both [3H]noradrenaline uptake in rat cerebral cortical slices (maximal inhibition 85.7 +/- 7.8% vs. 59.8 +/- 4.3%; EC50 5.8 +/- 0.7 microM vs. 13.5 +/- 1.2 microM) and [3H]nisoxetine binding (Ki 4.5 +/- 0.5 microM vs. 8.2 +/- 0.7 microM). In contrast, R-(-)-p-synephrine was more effective than S-(+)-p-synephrine in stimulation of [3H]noradrenaline release from rat cerebral cortical slices (maximal stimulation 23.9 +/- 1.8% vs. 20.1 +/- 1.7%; EC50 8.2 +/- 0.6 microM vs. EC50 12.3 +/- 0.9 microM). The stimulatory effect of R-(-)-p-synephrine on [3H]noradrenaline release was inhibited by nisoxetine (100 nM), but tetrodotoxin (1 microM) and elimination of extracellular calcium had no effect. It is suggested that S-(+)-p-synephrine has more effective antidepressant-like activity than R-(-)-p-synephrine.

Adrenergic Uptake Inhibitors↗
PubMed2001

Complex bronchopulmonary foregut malformation: extralobar pulmonary sequestration associated with a duplication cyst of mixed bronchogenic and oesophageal type.

We report a 13-year-old girl with an unusual, complex bronchopulmonary foregut malformation. The malformation included extralobar pulmonary sequestration and a duplication cyst of mixed bronchogenic and oesophageal type. Preoperative CT and MRI demonstrated the cystic and solid portions of the mass and indicated an aberrant vascular supply, suggesting the possibility of bronchopulmonary foregut malformation and several other differential diagnoses. A direct communication between the cyst and the bronchus of the sequestrated lung was found on pathological examination. This unusual combination of an extralobar pulmonary sequestration and a foregut cyst points to a common embryological pathogenesis.

Adolescent↗
PubMed2001

Protein kinase C suppresses spontaneous, transient, outwards K+ currents through modulation of the Na/Ca exchanger in guinea-pig gastric myocytes.

The effect of protein kinase C (PKC) on the Ca2+-activated K+ current (IK,Ca) in guinea-pig gastric myocytes was studied using the whole-cell voltage-clamp technique. At a holding potential of 0 mV, IK,Ca, recorded as spontaneous, transient, outwards currents (STOCs), was markedly inhibited, both in mean amplitude (54 +/- 5%) and frequency (60 +/- 8%) by 1 microM phorbol 12, 13 dibutyrate (PDBu, n = 6). These effects were antagonized by pretreatment with 10 nM bisindolylmaleimide I (n = 5), a selective inhibitor of PKC. The possibility that the inhibition of STOCs was due to direct channel inhibition by PKC was addressed using inside-out or open-cell-attached patch-clamp techniques, the latter established using beta-escin. PDBu did not alter the conductance or open probability of the KCa channel in any mode, suggesting that PKC does not inhibit the KCa channel directly. To study the involvement of the Na/Ca exchanger in the inhibition of STOCs by PDBu, its operation was prevented by replacing Na+ in the internal solution by tris(hydroxymethyl)aminomethane (TRIS) and external Na+ by equimolar K+ and Ca2+-activated inwards K+ currents recorded at a holding potential of 0 mV. Neither the mean amplitude (96 +/- 8%) nor the frequency of these currents was inhibited significantly by 1 microM PDBu (n = 5). Like PDBu, 5 microM 2-(2-[4-(4-nitrobenzyloxy)phenyl]ethyl) isothiourea methanesulphonate (KB-R7943), a selective inhibitor of the reverse mode Na/Ca exchanger, also inhibited the mean amplitude (45 +/- 6%) and frequency (26 +/- 2%) of STOCs at the holding potential of 0 mV (n=6). The results suggest that the suppression of STOCs by PKC is mediated by inhibition of the Na/Ca exchanger.

Animals↗
PubMed2001

Neither the butyrylcholinesterase K variant nor transferrin C2 variant confers a risk for Alzheimer's disease in Koreans.

To investigate the possible involvement of the butyrylcholinesterase (BCHE) K variant and transferrin (TF) C2 variant in the manifestation of Alzheimer's disease (AD), we analyzed the BCHE, TF and apolipoprotein E (APOE) genotypes of 164 sporadic AD patients and 239 normal elderly controls. The frequencies of the BCHE K and TF C2 did not differ between the AD patients and controls (P > 0.1). The occurrence of the APOE epsilon4 did not influence the distribution of the BCHE K and TF C2 variants (P > 0.1). No linkage disequilibrium between the BCHE K and TF C2 was observed either in both the AD patients and controls (P > 0.1). In conclusion, neither the BCHE K nor the TF C2 confers a risk for AD.

Aged↗