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Biomedical subjects

K W Kim

Publications and source records attributed to K W Kim.

At least 91 records · Page 5Linked to original sources
PubMed2001

Cerebrospinal fluid and plasma concentrations of leptin, NPY, and alpha-MSH in obese women and their relationship to negative energy balance.

Leptin and its principal mediators, NPY and alpha-MSH are postulated to play a pivotal role in energy balance. To determine the possibility of the disturbance in neuropeptides in human obesity and their consequent changes in response to negative energy balance, we evaluated plasma and cerebrospinal fluid (CSF) leptin, NPY, and alpha-MSH levels in obese women before and after weight loss in comparison with normal control women. Subjects included 16 obese women [mean body mass index (BMI), 35.6 kg/m(2)] before and after weight loss induced by a 2-wk very low caloric diet (800 kcal/d) and 14 normal weight women (mean BMI, 20.4 kg/m(2)). The CSF to plasma leptin ratio in normal weight subjects was 2.3-fold higher than that in obese subjects. After weight loss in obese subjects, plasma leptin levels decreased by 40% and CSF levels decreased by 51%. There was a positive linear correlation between CSF and plasma leptin levels at baseline in obese subjects (r = 0.74, P < 0.05) and a positive logarithmic correlation in normal weight subjects (r = 0.89, P < 0.05) and in obese subjects after weight loss (r = 0.64, P < 0.05). The BMI was negatively correlated with the CSF to plasma leptin ratio (r = -0.86, P < 0.05) in all subjects. Neither the baseline plasma levels nor the baseline CSF levels of NPY were different between normal weight subjects and obese subjects. After weight loss, the CSF NPY level decreased significantly compared with baseline values in obese subjects. The alpha-MSH levels in plasma and CSF did not differ significantly from controls in obese subjects at baseline or after weight loss. Baseline CSF leptin level correlated with neither the baseline CSF NPY level nor the baseline CSF alpha-MSH level. In conclusion, this study demonstrated that the efficiency of brain leptin delivery is reduced in human obesity and central nervous system leptin uptake involves a combination of a saturable and an unsaturable mechanism. CSF NPY and alpha-MSH did not differ from controls in human obesity, and the CSF NPY level decreased significantly whereas alpha-MSH did not differ after weight loss in obese subjects compared with baseline. There was no significant correlation between CSF leptin and CSF NPY or alpha-MSH. This could be the result of leptin resistance present in human obesity and/or the more complex mechanisms involved in modulating appetite and regulating energy balance in human obesity.

Adult↗
PubMed2001

The properties of carbachol-activated nonselective cation channels at the single channel level in guinea pig gastric myocytes.

We investigated the properties of carbachol (CCh)-activated nonselective cation channels (NSC(CCh)) at the single channel level in the gastric myocytes of guinea pigs using a magnified whole-cell mode or an outside-out mode. The channel activity (NPo) recorded in a magnified whole-cell mode increased with depolarization (from -120 to -20 mV) and had the half activation potential of -81 mV under the symmetrical 140 mM Cs+ condition. The single channel conductance depended upon the extracellular monovalent cations with the order of Cs+ (35 pS) > Na+ (25 pS) > Li+ (21 pS). The channel activities markedly diminished or disappeared when external Cs+ was replaced with Na+ or N-methyl-D-glucamate (NMDG+). With Cs+ and Na+ as external cations, the channel showed a monotonic increase in NPo with the increased mole fraction of Cs+ over Na+, and it had an intermediate conductance value in solution containing 67% Cs+ with 33% Na+. These data suggested that the extracellular monovalent cations regulate the whole-cell current of NSC(CCh) by modulating both the open state probability and the unitary conductance, and there is one binding site for the extracellular cations within the pore.

Animals↗
PubMed2001

Apoptotic activity of novel bile acid derivatives in human leukemic T cells through the activation of caspases.

The therapeutic efficacies of bile acids, such as ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA), have been widely demonstrated in various liver diseases, suggesting that they might protect hepatocytes against common mechanisms of liver damage. Although they have been shown to prevent apoptotic cell death in certain cell lines, we have previously reported that a novel derivative (HS-1030) of UDCA significantly inhibited cell growth and induced apoptosis in cancer cells. To develop more effective agents, we synthesized several derivatives, named HS-1183, HS-1199 and HS-1200, based on the structure of UDCA and CDCA, and investigated them for anti-proliferative activity in Jurkat cells, a human leukemic T cell line. Whereas UDCA and CDCA had no significant effects on the growth of Jurkat cells in the concentration range tested, both HS-1199 and HS-1200 completely inhibited the cell proliferation, and HS-1183 showed only a weak inhibitory activity. Furthermore, chromatin condensation, DNA ladder formation and proteolytic cleavage of poly(ADP-ribose) polymerase (PARP) were observed after treatment of novel bile acids, indicating the occurrence of apoptotic cell death, which was associated with down-regulation of caspase-3 and -8. The apoptotic manifestations such as PARP cleavage and DNA fragmentation were abolished in the presence of the tripeptide caspase inhibitor zVAD-fmk or the specific caspase-3 inhibitor DEVD-fmk. Our data thus demonstrate that novel bile acid derivatives-induced apoptosis of leukemic T cells is dependent on caspase activation.

Apoptosis↗
PubMed2001

Hypoglycemia-induced VEGF expression is mediated by intracellular Ca2+ and protein kinase C signaling pathway in HepG2 human hepatoblastoma cells.

Vascular endothelial growth factor (VEGF) is a potent angiogenic factor that plays a central role in angiogenesis. In this study, we investigated the mechanism of VEGF expression in HepG2 human hepatoblastoma cells under hypoglycemia. The shortage of glucose significantly enhanced VEGF mRNA expression in a time-dependent manner as well as increased DNA-binding activity of AP-1 that plays an important role in VEGF transcription. In addition, treatment of a potent PKC inhibitor, H-7 in glucose-deprived HepG2 cells suppressed hypoglycemia-elevated VEGF expression as well as the increased AP-1 DNA-binding activity. Moreover, we observed that Ca2+ levels remarkably increased under low glucose condition. Consistently, an intracellular Ca2+ chelator, BAPTA/AM significantly decreased hypoglycemia-induced VEGF expression and AP-1 DNA-binding activity. Therefore, these results indicate that increase of intracellular Ca2+ level induces the activation of PKC, which induce the activation of AP-1 leading to the increase of VEGF in glucose-deprived environment. Furthermore, it provides one link in regulation of VEGF with hypoglycemia as well as information to understand how hypoglycemia induces VEGF expression and subsequently leads to tumor angiogenesis.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed2000

Insulin-like growth factor II induces interleukin-6 expression via NFkappaB activation in psoriasis.

IGF-II is known to induce the growth of keratinocytes and the level was significantly elevated in the tissue fluid of psoriatic lesion. However, the role of IGF-II in psoriasis is not well defined. Because an inflammatory cytokine, interleukin-6 (IL-6) is overexpressed in psoriatic lesions, we explored whether IGF-II has some role in psoriasis through induction of IL-6. Therefore, the expression of IL-6 was analyzed after treatment of IGF-II in primary cultured psoriatic cells and human keratinocyte cell line, HaCaT. We found that IGF-II induced the IL-6 mRNA expression significantly. To investigate the inducing mechanism of IL-6 by IGF-II, we examined the promoter activity of IL-6 and the DNA binding activity of NFkappaB, a strong regulator of IL-6. Interestingly, IL-6 promoter activity and the binding activity of NFkappaB were remarkably increased by IGF-II. Western blot data that IkappaB was reduced by IGF-II significantly suggest that NFkappaB activation by IGF-II may be mediated through the downregulation of IkappaB. Therefore, these results suggest a novel role of IGF-II in psoriasis possibly by inducing IL-6 through the activation of NFkappaB mediated by downregulation of IkappaB.

Base Sequence↗
PubMed2000

Retro-dental reactive lesions related to development of myelopathy in patients with atlantoaxial instability secondary to Os odontoideum.

STUDY DESIGN: A retrospective analysis of 13 patients with atlantoaxial instability secondary to Os odontoideum who underwent posterior atlantoaxial fusion. OBJECTIVE: To assess the relationships between the development of myelopathy and plain radiographic parameters in patients with atlantoaxial instability secondary to Os odontoideum and to determine whether the pathologic structures, which compress the spinal cord, are visualized using magnetic resonance imaging. SUMMARY OF BACKGROUND DATA: The development of myelopathy, which is the most serious complication associated with Os odontoideum, was thought to be related to either the degree of instability or direction of instability, or a decrease in the space available for the cord. However, such indirect radiographic parameters measured using plain radiographs cannot provide direct information concerning the causes of myelopathy in patients with atlantoaxial instability secondary to Os odontoideum. METHODS: Thirteen patients who underwent posterior atlantoaxial fusion for clinical symptoms due to Os odontoideum were classified into two groups depending on whether they had (n = 9) or did not have (n = 4) myelopathy. Four radiographic parameters were measured using flexion and extension lateral radiographs; the degree of instability, the direction of instability, and the space available for the cord in flexion and extension. MRI was performed on all patients in the myelopathy group. The radiologic and clinical data were compared for the two groups. RESULTS: There were no significant statistical differences in the degree of instability (6.83 vs. 7.38, P = 0.816), space available for the cord in flexion (6.94 vs. 7.13, P = 0.938), and space available for cord in extension (7.56 vs. 5.75, P = 0.434) between the two groups. There was a poor agreement between the direction of instability and the development of myelopathy (kappa = 0.268, P = 0.308). Magnetic resonance imaging did demonstrate, however, cord compression caused by retro-dental reactive lesions in the myelopathy; cystic masses were present in two patients; and fibrocartilaginous masses were present in seven. CONCLUSION: The current study suggests that the value of plain radiographic parameters should be reevaluated as a means of evaluating myelopathy in patients with atlantoaxial instability secondary to Os odontoideum, and that retro-dental reactive lesions should be considered as the potential cause of myelopathy.

Adult↗
PubMed2000

Endostatin inhibits endothelial and tumor cellular invasion by blocking the activation and catalytic activity of matrix metalloproteinase.

Here we report the inhibition of cellular invasion by a recombinant mouse endostatin and the possible mechanism of the inhibition. Endostatin significantly reduced endothelial as well as tumor cellular invasion into the reconstituted basement membrane in vitro. Gelatin zymographic analysis revealed that the activation of promatrix metalloproteinase-2 (proMMP-2) that was secreted from endothelial cells was blocked upon endostatin treatment. Studies with recombinant MMPs confirmed that endostatin inhibited proMMP-2 activation, mediated by both membrane-type 1 MMP and 4-aminophenylmercuric acetate. Furthermore, enzymatic assays using a peptide substrate demonstrated that endostatin inhibited the catalytic activities of both MMP-2 and membrane-type 1 MMP. Finally, coimmunoprecipitation experiments revealed that endostatin formed a stable complex with proMMP-2. These novel findings would, at least in part, explain the mechanism of the potent antiangiogenic and antitumor activities of endostatin.

Angiogenesis Inhibitors↗
PubMed2000

Hypoxia-induced VEGF enhances tumor survivability via suppression of serum deprivation-induced apoptosis.

Low oxygen and nutrient depletion play critical roles in tumorigenesis, but little is known about how they interact to produce tumor survival and tumor malignancy. In the present study, we investigated the mechanism underlying hypoxia-modulated apoptosis of serum-deprived HepG2 cells. Our results showed that hypoxia blocked the apoptosis, which was accompanied with decreased Bax/Bcl-2 ratio, inhibited cytochrome c release, and reduced caspase-3 activity. More importantly, increased expressions of VEGF and its receptor-2 (KDR) under hypoxic/serum-deprived condition suggest that VEGF may act as a survival factor in a self-promoting manner. Data were further supported by results that recombinant human VEGF (rhVEGF) suppressed the serum deprivation-induced apoptosis, and anti-VEGF neutralizing antibody block anti-apoptotic activity of hypoxia. In addition, inhibitors of receptor tyrosine kinase blocked antiapoptosis of hypoxia. Our study further showed that rhVEGF or hypoxia induced ERK phosphorylation in serum-deprived cells, and that a specific inhibitor of MAPK/ERK, PD98059 eliminated the anti-apoptotic activity of rhVEGF or hypoxia by increasing Bax/Bcl-2 ratio and caspase-3 activity. Our data led us to conclude that induction of ERK phosphorylation and decrease of Bax/Bcl-2 ratio by rhVEGF implies that hypoxia-induced VEGF prevents apoptosis of serum-deprived cells by activating the MAPK/ERK pathway. Taken together, we propose that hypoxia enhances survival of nutrient-depleted tumor cells by reducing susceptibility to apoptosis, which consequently leads to tumor malignancy.

Apoptosis↗
PubMed2000

Apoptotic activity of ursolic acid may correlate with the inhibition of initiation of DNA replication.

Ursolic acid (UA), a pentacyclic triterpene acid, has been reported to exhibit anti-tumor activity. In this study, we investigated the pro-apoptotic effect of UA on HepG2 human hepatoblastoma cells. Treatment with UA decreased the viability of HepG2 cells in a concentration- and time-dependent manner. Furthermore, 30 microM of UA induced DNA fragmentation and subdiploid cells and enhanced the release of cytochrome c and the activation of caspase-3. These results suggest that UA induces cell death through apoptosis, which may be mediated by cytochrome c-dependent caspase-3 activation. In addition, cell-cycle analysis revealed that UA-treated cells were arrested predominantly in the G(0) and G(1) phases with a concomitant decrease in the cell population of S phase. Moreover, expression of p21(WAF1), a cell-cycle regulator, was increased by UA, indicating that p21(WAF1) might mediate UA-induced cell-cycle arrest. However, UA markedly inhibited SV40 DNA replication in the initiation stage in vitro and significantly reduced the DNA cleaving of topoisomerase I and the ssDNA binding activity of replication protein A. These results indicate that the inhibition of DNA replication by UA may result from blockade of the establishment of the replication fork during initiation stage, consequently contributing to UA-induced cell-cycle arrest. Taken together, we suggest that UA-induced cell-cycle arrest may be mediated by inhibition of DNA replication and the increase of p21(WAF1) expression, which induces the release of cytochrome c and the activation of caspase-3, leading to apoptosis of HepG2 cells.

Antineoplastic Agents, Phytogenic↗
PubMed2000

Anti-angiogenic activity of torilin, a sesquiterpene compound isolated from Torilis japonica.

Torilin is a sesquiterpene compound purified from fruits of Torilis japonica (Umbelliferae). In this study, we demonstrated the anti-angiogenic activity of torilin using in vivo and in vitro assay systems. Torilin decreased both neovascularization of chick embryos in the chorioallantoic membrane assay and basic fibroblast growth factor-induced vessel formation in the mouse Matrigel plug assay. Torilin also reduced the proliferation and tube formation of human umbilical vein endothelial cells. In addition, the concentrated conditioned media obtained from torilin-treated HepG2 human hepatoblastoma cells blocked the angiogenic activation of torilin-untreated concentrated conditioned media, indicating that torilin may have an inhibitory effect on tumor-induced angiogenesis. To determine what molecules were involved in the anti-angiogenic activity, we examined the expression of hypoxia-inducible angiogenic factors in torilin-treated HepG2 cells. Torilin significantly down-regulated the expression of hypoxia-inducible vascular endothelial growth factor and insulin-like growth factor-II. Taken together, our data suggest that torilin may be a strong angiogenic inhibitor with the ability to decrease tube formation of vascular endothelial cells and to reduce expression of angiogenic factors of tumor cells.

Angiogenesis Inhibitors↗
PubMed2000

Receptor selectivity of Met-enkephalin-Arg6-Phe7, an endogenous opioid peptide, in cerebral cortex of human and rat.

This study was undertaken to examine the receptor selectivity of Met-enkephalin-Arg6-Phe7 (MERF) employing radioreceptor binding assays in human cerebral cortex membranes, and to elucidate the responsible receptors that mediate the regulatory action of MERF on high (20 mM) K+-stimulated release of [3H]norepinephrine ([3H]-NE) in rat cortex slices. Specific binding of [3H]MERF was inhibited by DAMGO, Tyr-D-Arg-Phe-Sar(TAPS), bremazocine and ethylketocyclazocine (EKC), but not by U69,593 (U69) and DPDPE. MERF showed high affinity for specific binding sites of [3H]DAMGO. However, MERF had little influence on the specific binding of [3H]DPDPE, [3H]U69 and [3H]diprenorphine ([3H]DIP) in the presence of 1 microM each of DAMGO, DPDPE and U69. In [3H]NE release experiments using rat cortex slices, DAMGO, MERF and EKC, in order of their potency, inhibited K+-stimulated release of [3H]NE. The inhibitory effects of MERF and DAMGO were more sensitive than that of EKC to antagonism by CTAP, nor-binaltorphimine (nor-BNI) and naloxone. These results suggested that MERF possesses high affinity for mu-receptors, but not for delta-, kappa1-, and very low affinity for kappa2-receptors in human cerebral cortex membranes. Also, the inhibitory effect of MERF on the K+-stimulated release of [3H]NE appears to be mediated by mu-receptors in rat cerebral cortex slices.

Adult↗
PubMed2000

A novel technique for the effective production of short peptide analogs from concatameric short peptide multimers.

We designed a basic unit of the modified chicken gonadotropin releasing hormone II (cGnRH-II) peptide containing a trypsin cleavable linker peptide at both ends of the original peptide. We made a synthetic DNA coding for the modified cGnRH-II peptide with asymmetric and complementary cohesive ends of linker nucleotides. A tandemly repeated DNA cassette for the expression of concatameric short peptide multimers was constructed by ligating the basic units. The expressed peptide multimers were purified and subject to amino-terminal sequence analysis, which displayed the amino acid sequences expected from the designed nucleotides of the expression cassette. The monomeric cGnRH-II peptide analogs were generated after trypsin digestion. The present results showed that the technique developed for the production of the concatameric peptide multimers with cleavable linker peptides can be generally applicable to the production of short peptide analogs.

Amino Acid Sequence↗
PubMed2000

No association between alpha-1-antichymotrypsin polymorphism and Alzheimer's disease in Koreans.

To examine the possible involvement of the alpha-1-antichymotrypsin gene (ACT) polymorphism in the manifestation of Alzheimer's disease (AD), we analyzed genotypes of the ACT and apolipoprotein E gene (APOE) among 110 Korean patients with probable AD and 209 nondemented controls. No significant difference was obtained in genotypic (chi(2)=1.98, df=2, P>0.1) and allelic frequencies (chi(2)=1.61, df=1, P>0.1) of ACT between the AD and control groups. No overexpression of the ACT A/A genotype and ACT A allele was found when we analyzed the late-onset AD patients and the early-onset AD patients, separately. Then we stratified the ACT genotypes based on the presence or absence of the APOE epsilon4 allele to evaluate the possible interaction between them. In the APOE epsilon4-negative subjects, although the ACT A allele tended to be overexpressed in the AD group, the differences in the frequencies of the ACT A allele (chi(2)=2.79, df=1, P>0.1) and ACT A/A genotype (chi(2)=0.16, df=1, P>0.1) were not statistically significant. No significant overrepresentations of the ACT A allele (chi(2)=0.02, df=1, P>0.1) and ACT A/A genotype (chi(2)=0.17, df=1, P>0.1) were found in the APOE epsilon4-positive subjects, either. In addition, the status of the ACT genotype did not influence the age-at-onset of AD (F=0.03, df=2, P>0.1). Therefore, the ACT polymorphism does not contribute to the development of AD independently or interactively with the APOE epsilon4 allele in Koreans.

Age of Onset↗
PubMed2000

Identification of a novel human member of the DEAD box protein family.

The cDNA library of human pancreatic islets was screened with sera from patients with insulin-dependent diabetes mellitus (IDDM). From the library screening, we isolated a novel cDNA, RNA helicase-like protein (RHELP), which exhibited strong sequence homology to p68 RNA helicase, a prototypic member of the DEAD (Asp-Glu-Ala-Asp) box protein family. Sequence analysis of the cDNA revealed that RHELP contained DEAD sequence motif and other conserved motifs of the DEAD box protein family, indicating that RHELP is a new member of this family. DEAD box-containing proteins are involved in the RNA processing, ribosome assembly, spermatogenesis, embryogenesis, and cell growth and division. RHELP showed 42% and 44% amino acid sequence identity to human p68 RNA helicase and yeast DBP2 RNA helicase, respectively, among the DEAD box protein family. Northern blot analysis revealed that RHELP is expressed in most tissues including the liver, lung, tonsil, thymus, and muscle in addition to the pancreatic islets. In vivo or in vitro functions of RHELP as a putative RNA helicase and its potential role as a diabetic autoantigen need to be further investigated.

Amino Acid Sequence↗
PubMed2000

Intraosseous calcifying pseudotumor of the axis: a case report.

STUDY DESIGN: A case report and review of the literature. OBJECTIVE: To present the first case of intraosseous calcifying pseudotumor arising from the axis. SUMMARY OF BACKGROUND DATA: Calcifying pseudotumor is a very rare disease. Only 24 cases have been previously reported. METHODS: A case of calcifying pseudotumor involving the body, dens, and laminae of the axis in a 60-year-old male patient was managed with total laminectomy of the axis and instrumented occipitocervical fusion, followed by the curettage of the body and dens of the axis and autogenous iliac bone graft. Medical records, imaging studies, microscopic findings, and related literature are reviewed. RESULTS: Microscopic examination showed amorphous, basophilic, and chondroid calcifying masses surrounded with palisading histiocytes and foreign body-type giant cells. The findings were consistent with those of calcifying pseudotumors previously reported in other sites of the body. At 24 months after operation, a significant reduction of neck pain was achieved. But there was evidence of local recurrence of the lesion in the body and dens of the axis with a local progression of the preexisting lesion in the facet joints. CONCLUSION: This is the first report of intraosseous calcifying pseudotumor arising from the axis.

Axis, Cervical Vertebra↗
PubMed2000

Downregulation of JNK/SAPK activity is associated with the cross-resistance to P-glycoprotein-unrelated drugs in multidrug-resistant FM3A/M cells overexpressing P-glycoprotein.

In the present study, cross-drug resistance in multidrug-resistant (MDR) cells, which overexpress P-glycoprotein (Pgp), a mdr1 gene product, against Pgp-unrelated drugs, and its relevance to c-Jun N-terminal kinase (JNK)/stress-activated protein kinase (SAPK) activity were examined. The multidrug-resistant FM3A/M cells overexpressing Pgp were resistant to apoptotic cell death induced either by Pgp-related drugs including vincristine and vinblastine, which are pumped out by Pgp, or by the Pgp-unrelated drugs including 5'-fluorouracil (5-FU) and bleomycin, which are not targets for Pgp, compared with the parental FM3A cells. Verapamil reversed the resistance of FM3A/M cells to apoptosis induced by the Pgp-related drugs but not that induced by the Pgp-unrelated drugs. Interestingly, FM3A/M cells have shown significantly lower basal and drug-stimulated JNK/SAPK activities than FM3A cells. After transfection with pEBG-SEK or pEBG-SAPK constructs, FM3A/M cells recovered the basal and Pgp-unrelated drug-stimulated activities of JNK/SAPK and the susceptibility to Pgp-unrelated drug-induced apoptotic cell death comparable to those of FM3A cells. Furthermore, FM3A cells became resistant to apoptotic cell death induced by vincristine and 5-FU after transfection with pEBG-SEK(K --> R), a dominant negative inhibitory mutant of SEK. These results suggest that downregulation of JNK/SAPK activity appears to confer on Pgp-associated FM3A/M cells a cross-resistance to Pgp-unrelated drugs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗