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Biomedical subjects

H K Kim

Publications and source records attributed to H K Kim.

At least 37 records · Page 2Linked to original sources

Naringin supplementation lowers plasma lipids and enhances erythrocyte antioxidant enzyme activities in hypercholesterolemic subjects.

BACKGROUND AND AIMS: Preliminary studies have shown that naringin has a potent lipid-lowering effect and antioxidant capacity in high-cholesterol diet fed animals. Accordingly, the present study was conducted to investigate the effect of naringin on hypercholesterolemic subjects. METHODS: A hypercholesterolemic group (n=30) and healthy control group (n=30) were established based on the plasma cholesterol levels in the subjects, then all subjects received naringin (400mg/capsule/day) with regular meals for a period of 8 weeks. RESULTS: In the hypercholesterolemic subjects, naringin supplementation was found to lower the plasma total cholesterol by 14% and low-density lipoprotein cholesterol concentrations by 17%, while the plasma triglyceride and high-density lipoprotein cholesterol concentrations remained unaffected. The apolipoprotein B levels in the hypercholesterolemic subjects were significantly lowered after naringin treatment, yet no change was observed in the apolipoprotein A-1 levels. The erythrocyte superoxide dismutase and catalase activities in the hypercholesterolemic group were significantly increased, whereas the glutathione peroxidase activity and plasma TBARS levels were not different from the baseline measurements. Meanwhile, naringin supplementation had no affect on plasma lipids, apolipoproteins, and TBARS levels or antioxidant enzyme activities in the control group. CONCLUSIONS: Therefore, these data suggest that naringin may play an important role in lowering plasma cholesterol and regulating the antioxidant capacity in hypercholesterolemic subjects.

Adult↗

Elevated levels of circulating platelet microparticles, VEGF, IL-6 and RANTES in patients with gastric cancer: possible role of a metastasis predictor.

The activation of coagulation, angiogenesis and inflammatory cytokines are considered to be related with tumour growth and metastasis. We investigated the plasma levels of platelet microparticles (PMP), vascular endothelial growth factor (VEGF), IL-6, and the chemokine RANTES in patients with gastric cancer (n=109) and in healthy controls (n=29). The plasma levels of PMP, IL-6 and RANTES were significantly higher in the patients than in the healthy controls, and plasma levels of PMP, VEGF, IL-6 and RANTES were significantly higher in patients with stage IV disease than those in patients with stage I or stage II/III. In terms of predicting distant metastasis, the sensitivities of PMP, VEGF, IL-6 and RANTES were 93.3%, 56.7%, 70.0% and 81.8%, respectively, and the corresponding specificities were 91.1%, 64.6%, 79.7% and 50.0%. Among these parameters, PMP had the highest diagnostic accuracy. Significant correlations were found between PMP, VEGF, IL-6 and RANTES. This study demonstrates that the plasma levels of PMP, VEGF, IL-6 and RANTES were markedly increased in patients with stage IV disease, and that these increased plasma levels of IL-6, RANTES, and especially PMP, might be useful for identifying metastatic gastric patients.

Aged↗

Mutational analysis of forkhead transcriptional factor 2 (FOXL2) in Korean patients with blepharophimosis-ptosis-epicanthus inversus syndrome.

We screened for mutations in the forkhead transcription factor gene, FOXL2, in Korean patients with sporadic or familial blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) by polymerase chain reaction-single-stranded conformation polymorphism (PCR-SSCP) and direct sequencing. Five of nine BPES families and three of seven sporadic cases were detected to have FOXL2 mutations. We identified four types of FOXL2 mutations, two of which are novel. A new 14 bp deletion (939-952del14) causing a frameshift from G235W and the extension of the predicted protein to 527 amino acids was detected in a BPES family patient. In addition, a novel 845C > A transversion, resulting in a nonsense mutation (S203X), was found in a sporadic case of BPES. The previously reported in-frame 30 bp duplication (909-938dup30) was the most common mutation and was found in eight patients of four BPES families and one sporadic case. A known 17 bp duplication (1080-1096dup17) was observed in a sporadic BPES case. We were unable to find a causal mutation in four BPES families and four sporadic cases. These results suggest that in a fraction of BPES patients, the genetic defect might be associated with a mutation in the non-coding region of the FOXL2 gene or in other genes.

Adolescent↗

[Development of gerontological nursing curriculum model].

PURPOSE: This study was conducted to develop gerontological curriculum model which reflects the need of Korean society. METHOD: Three round Delphi survey method was applied to find consensus of gerontological nursing competencies (knowledge, attitudes and skills) for graduates of nursing schools from the panel of gerontological nursing practice experts. Important concepts in gerontological nursing were delineated from literature review and discussions of gerontological nursing educators. Based on these results the gerontological nursing curriculum model was developed and course structure outlined by the researchers as a group. RESULT: As the result of delphi survey, 32 items of knowledge, 29 items of attitude, and 21 items of skill were identified. The curriculum model constructed around a cube with three plane- functional capacity levels, settings, and nursing practice. Specific knowledge, attitudes and skills for gerontological theory and practicum course were suggested. Competency items were assigned to theory and/or practice. CONCLUSION: A curriculum model for gerontological nursing has been developed by a group of gerontological nursing educators. The curriculum model should be further tested and developed with detailed theory and practicum course outline and textbooks.

English Abstract↗

Adhesion and growth of endothelial cell on amphiphilic PU/PS IPN surface: effect of amphiphilic balance and immobilized collagen.

Since natural blood vessels are lined with an endothelial cell (EC) monolayer, it is proposed that synthetic biomaterial surfaces be covered or seeded with endothelial cells for ideal nonthrombogenicity under normal conditions. The effects of the surface energy of hydrophilic-hydrophobic IPN on EC adhesion and growth were investigated. The human umbilical vein endothelial cells (HUVECs) were cultured on polyurethane (PU)/polystyrene (PS) IPN prepared by changing only the amphiphilic balance and controlling the microphase separated surface structure. The collagens were immobilized on the IPN surfaces for enhanced adhesion of HUVECs, and the morphology of the collagens immobilized highly depended on the surface energy of the IPNs. The stranded rope structure of the collagen molecules in the solution state was maintained only on the surface of the IPN with intermediate hydrophilicity. The adhesion and the proliferation of ECs on the nontreated IPN surfaces increased by increasing the hydrophobicity of the IPNs, and they were optimized on the collagen-treated IPN surface having an intermediate hydrophilicity. Finally, platelet adhesion was significantly reduced on the EC-hybridized surface of the IPNs.

Cell Adhesion↗

Hypoxia decreases Runx2/Cbfa1 expression in human osteoblast-like cells.

To elucidate the molecular mechanism in relation to vascular supply and osteoporosis, we investigated the effect of hypoxia on Runx2 expression in MG63 cells. Also investigated was expression of type I collagen and osteocalcin, which are regulated by Runx2, alkaline phosphatase (ALPase) to see if they are affected by hypoxia. Quiescent cultures of MG63 cells were exposed to hypoxia (2% O(2)) and normoxia (18% O(2)) for 24, 48, 72 and 96 h. In cells exposed to hypoxia, reverse transcription-polymerase chain reaction (RT-PCR) analysis showed that mRNA expression of Runx2, type I collagen, osteocalcin, and ALPase were decreased in a time dependent manner to 96 h. Activity of ALPase was also reduced in the same manner. Western blotting showed a marked decrease in Runx2 protein at 96 h in cells under hypoxia compared to normoxia. These data indicate that Runx2 expression in osteoblasts is reduced by hypoxia, and may be a mechanism of osteoporosis by decreased vascular supply.

Alkaline Phosphatase↗

Dopamine transporter density is decreased in parkinsonian patients with a history of manganese exposure: what does it mean?

Manganese (Mn) exposure can cause parkinsonism. Pathological changes occur mostly in the pallidum and striatum. Two patients with a long history of occupational Mn exposure presented with Mn-induced parkinsonism. In one patient, magnetic resonance imaging (MRI) showed findings consistent with Mn exposure, and Mn concentration was increased in the blood and urine. However, this patient's clinical features were typical of idiopathic Parkinson disease (PD). Previous pathological and positron emission tomography studies indicate that striatal dopamine transporter density is normal in Mn-induced parkinsonism, whereas it is decreased in PD. Therefore, we performed [(123)I]-(1r)-2 beta-carboxymethoxy-3beta-(4-iodophenyl)tropane ([(123)I]-beta-CIT) single-photon emission computed tomography. Severe reduction of striatal beta-CIT binding was indicated, which is consistent with PD. We propose three interpretations: (1) the patients have PD, and Mn exposure is incidental; (2) Mn induces selective degeneration of presynaptic dopaminergic nerve terminals, thereby causing parkinsonism; or (3) Mn exposure acts as a risk of PD in these patients. Our results and careful review of previous studies indicate that the axiom that Mn causes parkinsonism by pallidal lesion may be over-simplified; Mn exposure and parkinsonism may be more complex than previously thought. Further studies are required to elucidate the relationship between Mn and various forms of parkinsonism.

Causality↗

Genetic contribution to factor VII levels in families of patients undergoing coronary arteriography.

An elevated plasma level of factor VII is a risk factor for coronary artery disease. We investigated environmental, familial, and genetic influences on factor VII activity in 508 family members of 87 probands who underwent elective coronary arteriography. Maximum likelihood methods were used to fit several genetic and non-genetic models of inheritance to these data to determine whether an unobserved Mendelian major gene could explain the familial distribution of factor VII. Factor VII activities were adjusted for age, gender, body mass index, smoking, alcohol consumption, menopause status, and triglycerides prior to this segregation analysis (this model accounted for 33.5% of the total variation). Adjusted factor VII activities showed strong familial aggregation with an estimated parent-offspring correlation of 0.34, sibling correlation of 0.36 and a smaller spouse correlation of 0.16. Regressive models were used to test genetic and non-genetic models in these 87 families. Mendelian single-locus models with either two or three underlying genotypic distributions of factor VII activities were best supported by these data. Essentially, these Mendelian models suggest most individuals come from a low distribution (mean, 116%), with a few individuals homozygous for a high allele drawn from a distribution with a mean of 166%. Future linkage studies may be worthwhile to further clarify the mechanisms controlling factor VII activity.

Adolescent↗

Optimized flow cytometric assay for the measurement of platelet microparticles in plasma: pre-analytic and analytic considerations.

Platelet microparticles (PMP) are submicroscopic membrane vesicles released by platelets during activation. Flow cytometry is the most widely used method for quantifying PMP, but the optimization of the technical method has not yet been fully evaluated. This study was designed to assess the pre-analytical variables including blood sampling conditions, and to evaluate the analytical variations including effect of the platelet-specific antibodies and quantitative beads, precision, linearity and accuracy in comparison with beta-thromboglobulin, which is one of the platelet activation markers. Numbers of PMP collected into citrate-theophylline-adenosine-dipyridamole (CTAD) tubes were increased with time, but to a lesser extent than when collected into sodium citrate tubes. The precision of the PMP assay was relatively high. Excellent linear correlation was observed for dilution linearity. Regarding the platelet-specific antibodies used, anti-CD41a-labeled samples resulted in higher PMP levels than those labeled with anti-CD61 and anti-CD42a. There was no significant difference of PMP counts according to the quantitative beads. The PMP assay is well correlated with beta-thromboglobulin levels. Our findings suggest that blood samples for the PMP assay should be collected in a CTAD tube and delayed measurement is not allowed to avoid artefactual platelet activation. The PMP assay can be used successfully as a useful marker of the detection of in vivo platelet activation, provided that pre-analytical and technical points are optimally taken into consideration.

Adenosine↗

Single-particle analysis of aerosols at Cheju Island, Korea, using low-Z electron probe X-ray microanalysis: a direct proof of nitrate formation from sea salts.

A recently developed electron probe X-ray microanalysis (EPMA), called low-Z EPMA, employing an ultrathin window energy-dispersive X-ray detector, was applied to characterize aerosol particles collected at two sampling sites, namely, Kosan and 1100 Hill of Cheju Island, Korea, on a summer day in 1999. Since low-Z EPMA can provide quantitative information on the chemical composition of aerosol particles, the collected aerosol particles were classified and analyzed based on their chemical species. Many different particle types were identified, such as marine-originated, carbonaceous, soil-derived, and anthropogenic particles. Marine-originated particles, such as NaNO3- and Na2SO4-containing particles, are very frequently encountered in the two samples. In this study, it was directly proven that the observed nitrate particles were from sea salts. In addition, two types of nitrate particles from sea salts were observed, with and without Mg. The sodium nitrate particles without Mg were believed to be collected as crystalline form, either with the sodium nitrate particles being fractionally recrystallized within evaporating seawater drops or with recrystallized sodium chloride particles having reacted with gaseous nitrogen species in the air to form the crystalline sodium nitrate particles. The other seemed to be collected as seawater drops, where the atmospheric reaction had occurred in the droplets, and thus sodium as well as magnesium nitrates were observed. Carbonaceous particles are the most abundant in the samples at both sites. From this study, it was found that about three-quarters of the carbonaceous particles in the samples were biogenic, which partially explains a previously reported observation of a large concentration of organic carbon particles as compared to elemental carbon. Various soil-derived particles were also observed. In addition to aluminosilicate- and iron oxide-containing particles, which are ubiquitous components in soil-derived particles, CaCO3-, Al2O3- and Cr-containing particles were also frequently encountered.

Aerosols↗

Microencapsulation of dissociable human growth hormone aggregates within poly(D,L-lactic-co-glycolic acid) microparticles for sustained release.

For the sustained release formulation of recombinant human growth hormone (rhGH), dissociable rhGH aggregates were microencapsulated within poly(D,L-lactic-co-glycolic acid) (PLGA) microparticles. rhGH aggregates were first produced by adding a small volume of aqueous rhGH solution into a partially water miscible organic solvent phase (ethyl acetate, EtAc) containing PLGA. These rhGH aggregates were then microencapsulated within PLGA polymer phase by extracting EtAc into an aqueous phase pre-saturated with EtAc. Release profiles of rhGH from these microparticles were greatly affected by changing the volume of incubation medium. The released rhGH species consisted of mostly monomeric form having a correct conformation. This study reveals that sustained rhGH release could be achieved by microencapsulating reversibly dissociable protein aggregates within biodegradable polymers.

Capsules↗

Crystallization and preliminary X-ray analysis of a thermoalkalophilic lipase from Bacillus stearothermophilus L1.

A thermoalkalophilic lipase from Bacillus stearothermophilus L1 (L1 lipase) was crystallized in two different crystal forms using a low concentration of the enzyme and a calcium-exchange process. The first, needle-like, crystal form, which diffracts to about 3.5 A, belongs to the orthorhombic space group P2(1)2(1)2(1), with unit-cell parameters a = 67.84, b = 72.96, c = 104.41 A. The second, monoclinic, crystal form, which behaves better than the first form for crystallographic analyses, belongs to the monoclinic space group C2 and has unit-cell parameters a = 119.62, b = 85.05, c = 98.36 A, beta = 99.73 degrees. From the monoclinic crystals, a native data set and a samarium-derivative data set were collected to 2.0 and 2.3 A resolution, respectively. The difference Patterson map between the two data sets shows strong heavy-atom peaks, indicating that the crystals are suitable for a high-resolution structure determination.

Crystallization↗

Calcium-dependent catalytic activity of a novel phytase from Bacillus amyloliquefaciens DS11.

The thermostable phytase from Bacillus amyloliquefaciens DS11 hydrolyzes phytate (myo-inositol hexakisphosphate, IP6) to less phosphorylated myo-inositol phosphates in the presence of Ca2+. In this report, we discuss the unique Ca2+-dependent catalytic properties of the phytase and its specific substrate requirement. Initial rate kinetic studies of the phytase indicate that the enzyme activity follows a rapid equilibrium ordered mechanism in which binding of Ca2+ to the active site is necessary for the essential activation of the enzyme. Ca2+ turned out to be also required for the substrate because the phytase is only able to hydrolyze the calcium-phytate complex. In fact, both an excess amount of free Ca2+ and an excess of free phytate, which is not complexed with each other, can act as competitive inhibitors. The Ca2+-dependent catalytic activity of the enzyme was further confirmed, and the critical amino acid residues for the binding of Ca2+ and substrate were identified by site-specific mutagenesis studies. Isothermal titration calorimetry (ITC) was used to understand if the decreased enzymatic activity was related to poor Ca2+ binding. The pH dependence of the Vmax and Vmax/Km consistently supported these observations by demonstrating that the enzyme activity is dependent on the ionization of amino acid residues that are important for the binding of Ca2+ and the substrate. The Ca2+-dependent activation of enzyme and substrate was found to be different from other histidine acid phytases that hydrolyze metal-free phytate.

6-Phytase↗

TFEC can function as a transcriptional activator of the nonmuscle myosin II heavy chain-A gene in transfected cells.

Transcription of the human nonmuscle myosin II heavy chain-A (NMHC-A) gene is regulated via multiple elements located in intron 1, including element F which contains an E-box. In this study we have identified and characterized the factors that are capable of binding to element F. Yeast one-hybrid screening using element F allowed isolation of cDNAs encoding transcriptional factors TFEC, TFE3, and USF2, each of which contains basic helix-loop-helix and leucine zipper motifs. Furthermore, cDNA cloning by polymerase chain reaction yielded cDNAs for two TFEC isoforms, designated TFEC-l and TFEC-s, which are generated by alternative pre-mRNA splicing. In addition to these four factors, USF1, which is known to share the same DNA binding elements with USF2, was isolated for comparison. Electrophoretic mobility shift assays and cotransfection studies of the expression constructs with reporter gene constructs revealed that the above five factors have different binding activities for element F with different transactivation potencies. USF1 and USF2 demonstrate the highest binding activity to element F, yet show the lowest element F-dependent transactivation. TFE3 has a high transactivation potency but the lowest binding activity. TFEC-l demonstrates a high binding activity with the highest transactivation potency, whereas TFEC-s has the same binding activity as TFEC-l with intermediate transactivation. We also demonstrate that an N-terminal activation domain exists only in TFEC-l, whereas a C-terminal activation domain is common to both the l and s isoforms. This study provides the first evidence of TFEC being an activator of transcription, with two separate activation domains.

Basic Helix-Loop-Helix Leucine Zipper Transcriptio↗

Purification and properties of Aquifex aeolicus DNA polymerase expressed in Escherichia coli.

The gene encoding Aquifex aeolicus (Aae) DNA polymerase was expressed under the control of the trp promoter on a high-copy plasmid, pTRPNS, in Escherichia coli. The expressed enzyme was purified 11-fold with a 13.8% yield and a specific activity of 2268.3 U mg(-1). The optimum pH of the enzyme was 6.8-7.2. The optimal concentrations of KCl and Mg(2+) were 20-30 mM and 4-5 mM, respectively. Aae DNA polymerase contained a double-strand-dependent 3'-->5' proofreading exonuclease activity but lacked any detectable 5'-->3' exonuclease activity.

Cations, Divalent↗

Homozygous VN (677C to T) and d/D (2756G to A) variants in the methylenetetrahydrofolate and methionine synthase genes in a case of hyperhomocysteinemia with stroke at young age.

Hyperhomocysteinemia is known to be associated with an increased risk of myocardial infarction, stroke, peripheral arterial disease, and venous thrombosis. Gene polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MS) may account for reduced enzyme activity and hyperhomocysteinemia. A recent study has documented evidence of polygenic regulation of plasma homocyteine. We report here on a case of occlusive stroke at young age and hyperhomocysteinemia with homozygous VN (677C to T) variant in the MTHFR gene as well as homozygous D/D (2756G to A) variant in the MS gene.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗

Altered expression of the fragile histidine triad gene in primary gastric adenocarcinomas.

Genomic alterations and abnormal expression of the fragile histidine triad (FHIT) gene in gastric carcinomas were examined to determine whether the FHIT gene is actually a frequent target for alteration during gastric carcinogenesis. To correlate DNA and RNA lesions of the FHIT gene with the effect on FHIT protein expression, we have investigated the FHIT gene for loss of heterozygosity (LOH), aberrant transcripts, point mutations, and protein expression in 35 gastric adenocarcinomas. Allelic loss at D3S1300 was detected in 7 of 33 (21%) informative cases. Aberrant transcripts, with deletions and/or insertions, were observed in 20 of 35 (57.1%) cases and resulted from alternative splicing through exon skipping and/or insertion of the FHIT intron 5 sequence or activation of the cryptic splice site. Point mutations were not found in the FHIT coding region but detected in noncoding exon 2, 3, 4, or 5 of eight aberrant transcripts. Significant reduction of FHIT protein expression was observed in 22 of 35 (62.9%) cases. Aberrant FHIT transcription was shown to be associated with loss of FHIT protein expression. However, aberrant FHIT transcripts themselves were not associated with any clinicopathological parameters, such as age, sex, tumor site, or clinical stage. Moreover, there was no association between the presence of LOH at D3S1300 and the expression of aberrant FHIT transcripts. Nevertheless, high frequency of aberrant FHIT transcripts, significant rate of LOH at D3S1300, and altered expression of the FHIT protein indicate that alterations of the FHIT gene can play an important role in gastric carcinogenesis.

Acid Anhydride Hydrolases↗

Inhibitory effect of ursolic acid purified from Origanum majorana L on the acetylcholinesterase.

We screened 139 herbal spices in search of the acetylcholinesterase (AChE) inhibitor from natural resources. AChE inhibitors, which enhance cholinergic transmission by reducing the enzymatic degradation of acetylcholine, are the only source of compound currently approved for the treatment of Alzheimer's Disease (AD). Among these herbs, edible plants and spices, the ethanol extract from Origanum majorana L. showed the highest inhibitory effect on AChE in vitro. By sequential fractionation of Origanum majorana L. the active component was finally identified as ursolic acid (3 beta-Hydroxyurs-12-en-28-oic acid). The ursolic acid of Origanum majorana L. inhibited AChE activity in a dose-dependent and competitive/non-competitive type. The Ki value (representing the affinity of the enzyme and inhibitor) of Origanum majorana L. ursolic acid was 6 pM, and that of tacrine was 0.4 nM. The concentration required for 50% enzyme inhibition of the active component (IC50 value) was 7.5 nM, and that of tacrine was 1 nM. This study demonstrated that the ursolic acid of Origanum majorana L. appeared to be a potent AChE inhibitor in Alzheimer's Disease.

Acetylcholinesterase↗