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Biomedical subjects

I Kim

Publications and source records attributed to I Kim.

At least 19 recordsLinked to original sources
PubMed2003

Fracture flow simulation using a finite-difference lattice Boltzmann method.

We present numerical computations for single phase flow through three-dimensional digitized rock fractures under varied simulated confining pressures appropriate to midcrustal depths. The computations are performed using a finite difference, lattice Boltzmann method and thus simulate Navier-Stokes flow. The digitized fracture data sets come from profiled elevations taken on tensile induced fractures in Harcourt granite. Numerical predictions of fracture permeability are compared with laboratory measurements performed on the same fractures. Use of the finite difference lattice Boltzmann method allows computation on nonuniform grid spacing, enabling accurate resolution across the aperture width without extensive refinement in the other two directions.

Journal Article↗
PubMed2003

Enhanced immunogenicity of human papillomavirus 16 L1 genetic vaccines fused to an ER-targeting secretory signal peptide and RANTES.

To increase the potency of human papillomavirus (HPV) DNA vaccines, we constructed a series of HPV16 L1 vaccines genetically fused with a secretion signal and/or immune cell-recruiting RANTES. The DNA vaccines encoding secretory HPV L1 were constructed by inserting HPV L1 gene into a vector with an ER-targeting secretory signal sequence. The expression plasmid encoding secretory HPV L1 (pER/L1) was fused with cDNA of RANTES, generating pER/L1/R. For comparison, HPV L1 genes were cloned into pVAX1 vector with no signal sequence (pL1), and further linked to the N-terminus (pL1/R) or C-terminus of RANTES (pR/L1). The secretion of L1 proteins was observed in the pER/L1, pER/L1/R, and pR/L1-transfected cells, except the pL1/R-transfected group. Cytoplasmic localization of L1 protein was observed in the cells transfected with pL1/R, but not with pER/L1/R at 48 h after transfection. In mice, RANTES-fused vaccines more effectively elicited the levels of HPV16 L1-specific IgG and IgG2a antibodies than pL1. Of RANTES-fused vaccines, pER/L1/R encoding the secreted fusion protein induced the highest humoral and CD8(+) T-cell-stimulating responses. These results suggest that the immunogenicity of HPV L1 DNA vaccines could be enhanced by genetic fusion to a chemokine and secretory signal peptide sequences.

Antibodies, Viral↗
PubMed2003

Major ketogenesis and the absence of an osmolar gap in an atypical case of alcoholic ketoacidosis.

A new case of alcoholic ketoacidosis (AKA) is presented because of unusual clinical and biochemical features. Although it shares some similarities with typical cases of AKA, it appears as unique because of predominantly neurological, rather than abdominal symptoms, major ketogenesis with normal ketone body ratio, the presence of large amounts of propanediol and the absence of an osmolar gap.

Acidosis↗
PubMed2002

Characterization of the kynurenine 3-monooxygenase gene corresponding to the white egg 1 mutant in the silkworm Bombyx mori.

Kynurenine 3-monooxygenase (KMO, EC 1.14.13.9), which catalyzes the oxidation of kynurenine to 3-hydroxykynurenine, is involved in the synthesis of ommochrome pigments in insects. A silkworm mutant, white egg 1 ( w-1), has been shown to be deficient in this enzyme activity. The mutant is characterized morphologically by its white eyes and the fact that the females lay white eggs. To analyze the relationship between the KMO gene and the mutation, we first determined the entire sequence of a full-length 2.0-kb cDNA and examined its expression pattern in the wild type. The cDNA sequence contains one ORF encoding a polypeptide of 456 amino acids, and transcripts were detected in the larval Malpighian tubules and the pupal ovaries, but not in other tissues. Southern analysis and nucleotide sequencing showed that the KMO gene is present in a single copy and consists of ten exons distributed over a 16-kb region. Comparison of the transcripts between the wild type and mutant silkworms showed that the wild type expressed a single transcript, whereas the mutant exhibited markedly reduced amounts of two transcripts with sizes of 2.0 kb and 1.8 kb. Nucleotide sequence analysis of these mutant transcripts indicated that sequences corresponding to the ninth and tenth exons were missing. Inverse PCR and Southern analysis of the mutant gene demonstrated that the corresponding genomic region was deleted in the w-1 mutant.

Amino Acid Sequence↗
PubMed2001

Molecular cloning and expression of a cDNA encoding the luciferase from the firefly, Pyrocoelia rufa.

To clone a cDNA encoding the luciferase of the firefly, Pyrocoelia rufa, we have constructed a cDNA library and isolated the luciferase gene using PCR with gene specific primers. Sequence analysis of the cDNA encoding the luciferase of P. rufa revealed that the 1647 bp cDNA has an open reading frame of 548 amino acid residues. The deduced amino acid sequences of the luciferase gene of P. rufa showed 98.9% homology to that of P. miyako. Phylogenetic analysis further confirmed the deduced amino acid sequences of the P. rufa luciferase gene belonged to the same subfamily, Lampyrinae. Southern blot analysis suggested possible presence of the P. rufa luciferase gene as a single copy and Northern blot analysis confirmed light organ-specific expression pattern at the transcriptional level. The cDNA encoding the luciferase of P. rufa was expressed as a 69 kDa band in baculovirus-infected insect cells and the recombinant baculovirus-infected cell extracts emitted luminescence in the luciferase activity assay.

Amino Acid Sequence↗
PubMed2001

Angiopoietin-1 reduces VEGF-stimulated leukocyte adhesion to endothelial cells by reducing ICAM-1, VCAM-1, and E-selectin expression.

Vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang1) are potent vasculogenic and angiogenic factors that hold promise as a means to produce therapeutic vascularization and angiogenesis. However, VEGF also acts as a proinflammatory cytokine by inducing adhesion molecules that bind leukocytes to endothelial cells, an initial and essential step toward inflammation. In the present study, we used human umbilical vascular endothelial cells (HUVECs) to examine the effect of Ang1 on VEGF-induced expression of three adhesion molecules: intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin. Interestingly, Ang1 suppressed VEGF-induced expression of these adhesion molecules. Furthermore, Ang1 reduced VEGF-induced leukocyte adhesion to HUVECs. These results demonstrate that Ang1 counteracts VEGF-induced inflammation by reducing VEGF-induced endothelial adhesiveness.

Angiopoietin-1↗
PubMed2001

Mechanism of synchronization in a random dynamical system.

The mechanism of synchronization in the random Zaslavsky map is investigated. From the error dynamics of two particles, the structure of phase space was analyzed, and a transcritical bifurcation between a saddle and a stable fixed point was found. We have verified the structure of on-off intermittency in terms of a biased random walk. Furthermore, for the generalized case of the ensemble of particles, a modified definition of the size of a snapshot attractor was exploited to establish the link with a random walk. As a result, the structure of on-off intermittency in the ensemble of particles was explicitly revealed near the transition.

Journal Article↗
PubMed2001

A novel fibroblast growth factor receptor-5 preferentially expressed in the pancreas(1).

Using the polymerase chain reaction on human embryonic cDNAs, we isolated a cDNA encoding a novel 504 amino acid protein, termed fibroblast growth factor receptor (FGFR)-5, which is highly homologous to known FGFRs. The NH(2)-terminal portion of FGFR5 contains a putative secretory signal sequence, three typical immunoglobulin-like domains, six cysteines, and an acidic box, but no HAV motif. The COOH-terminal portion of FGFR5 contains one transmembrane domain but no intracellular kinase domain. Recombinant FGFR5 expressed in COS-7 cells is not secreted, but recombinant truncated FGFR5 lacking the predicted transmembrane domain is secreted. Acidic fibroblast growth factor (aFGF) and basic fibroblast growth factor (bFGF) do not bind to FGFR5. Among 23 adult human tissues, FGFR5 mRNA is preferentially expressed in the pancreas. These results suggest that FGFR5 may provide a binding site for some other fibroblast growth factors and may regulate some pancreatic function.

Amino Acid Sequence↗
PubMed2001

Nonequilibrium roughening transition in a volume conserving system.

We introduce a simple volume conserving stochastic model undergoing a nonequilibrium roughening transition (NRT) in 1+1 dimensions. In our model, there is no deposition and evaporation of a particle breaking the volume conserving condition. The degree of roughness of the fluctuating interface in our model is determined by whether or not the hopping of a particle depends on the local slope of the interface. The hopping process of a particle is controlled by the probability 0 1/2, a particle tends to hop in the uphill direction, and so the interface cannot reach a saturated phase. When p=1/2, the hopping of a particle does not depend on the local slope of the interface. Then the interface can reach a saturated phase. The saturated interface at p=1/2 is in a rough phase with a nonzero roughness exponent. Our model, therefore, exhibits the NRT at the critical parameter p(c)=1/2.

Journal Article↗
PubMed2001

Fine-needle aspiration cytology of pleuropulmonary blastoma: a case report with unusual features.

Pleuropulmonary blastoma (PPB) is a rare and aggressive intrathoracic neoplasm of childhood, typically presenting as a pulmonary and/or pleural-based mass with cystic, solid, or combined features. Histologically, the tumor is well characterized with a mixture of primitive mesenchymal and variably differentiated sarcomatous components, and the cytologic features described in the three previous reports are also compatible to the histologic ones. Now, we present another case of PPB showing unusual features. A 3-yr-old boy presented with a pleural- or chest wall-based tumor. The fine-needle aspiration cytologic smears were highly cellular with poorly differentiated cells showing variable size and shape rather than those of typical blastemal cells. The histologic findings were also distinctive, exhibiting diffuse sheets of poorly differentiated cells without typical blastemal cell component. Diagnosis was confirmed by the support of immunohistochemical and ultrastructural features. The patient underwent a typical aggressive clinical course to death within 8 mo after diagnosis.

Biomarkers, Tumor↗
PubMed2001

Reduction in cyclin D1/Cdk4/retinoblastoma protein signaling by CRE-decoy oligonucleotide.

We have previously demonstrated that the activation of p53 signaling may contribute to tumor growth inhibition by the CRE-decoy oligonucleotide containing CRE sequence (5'-TGACGTCA-3') (Lee et al., Biochemistry 39, 4863-4868, 2000). However, growth inhibition by CRE-decoy treatment was also observed in tumor cells containing a mutant p53 (Park et al., J. Biol. Chem. 274, 1573-1580, 1999). To understand additional mechanisms of the decoy oligonucleotide, we investigated the effect on cyclin D1 expression and a cyclin D1/Cdk4/retinoblastoma protein (pRB) signaling pathway. Here we show that in MCF7 breast cancer cells the CRE-decoy competed with cyclin D1-CRE (5'-TAACGTCA-3') for binding transcription factors and reduced cyclin D1 gene expression (in reporter gene assay, Northern blotting and Western blotting) to modulate cyclin D1/Cdk4/pRB signaling and G1-S progression in a steady state and/or under estrogen stimulation. Decrease of cyclin D1 protein level by CRE-decoy treatment was also observed in p53-mutated cancer cells. Cyclin D1 expression was also diminished in MCF7 cells stably expressing dominant negative mutant CREB indicating that the nonspecific effect of oligonucleotide or its degradation products could be excluded. These data suggest that inhibition of cyclin D1 expression contributes to the growth inhibition induced by the decoy oligonucleotide in MCF7 cells through a cyclin D1/Cdk4/pRB signaling pathway. Downregulation of cyclin D1 expression also provides a mechanism of CRE-decoy-induced growth inhibition in tumor cells having p53 mutation.

Breast Neoplasms↗
PubMed2001

Immunobead RT-PCR versus regular RT-PCR amplification of CEA mRNA in peripheral blood.

PURPOSE: The reverse transcription polymerase chain reaction (RT-PCR) amplification of tumor-specific mRNA has been used for the detection of cancer cells in peripheral blood. More recently, an immunomagnetic isolation and reverse transcription polymerase chain reaction (immunobead RT-PCR) was developed which has reportedly significant advantages over the previous RT-PCR analysis. In our study, we compared these two methods using a model set of peripheral blood containing tumor cells under standardized conditions. MATERIAL AND METHODS: In order to compare the false positive rate, normal peripheral blood samples from five volunteers were analyzed by both methods. A model set of peripheral blood containing tumor cells was established by adding SNUC4 human colon cancer cells to peripheral blood collected from normal volunteers not showing any nonspecific bands upon electrophoresis of the PCR products. RT-PCR amplification of carcinoembryonic antigen (CEA) mRNA was done with total RNA and mRNA prepared from this model sample. In immunobead RT-PCR analysis, mRNA was prepared from the cells isolated with anti-CEA antibody-coated magnetic beads or anti-Ber-EP4 antibody-coated magnetic beads before the RT-PCR analysis. RESULT: The immunobead RT-PCR yielded no non-specific band, while the regular RT-PCR using total RNA did show non-specific band formation in all five samples. When mRNA rather than total RNA was used, nonspecific bands were formed in three of the five samples. Immunobead RT-PCR allowed the detection of 10(1) tumor cells in 1 ml of peripheral blood. The regular RT-PCR analysis had a detection limit of 10(2) tumor cells in 1 ml of peripheral blood. CONCLUSION: The immunobead RT-PCR proved to be more sensitive and specific than the regular RT-PCR at least in our model system.

Antibodies, Monoclonal↗
PubMed2001

The angiopoietin-tie2 system in coronary artery endothelium prevents oxidized low-density lipoprotein-induced apoptosis.

OBJECTIVES: A healthy, intact coronary artery endothelium is important because most common coronary artery diseases result from loss of endothelial integrity. In this study, we explored the biological significance of the angiopoietin-Tie2 system in porcine coronary artery. METHODS: Cultured porcine coronary artery endothelial cells and explanted coronary arteries were used. RESULTS: Immunohistochemical analyses indicated that Ang1 is selectively expressed in vascular muscular cells, whereas angiopoietin-2 (Ang2) and Tie2 are selectively expressed in endothelial cells. Accordingly, Ang1 mRNA is mainly expressed in cultured porcine coronary artery vascular smooth muscle cells, whereas Ang2 and Tie2 mRNAs are mainly expressed in cultured porcine coronary artery endothelial cells (PCAECs). Ang1 (200 ng/ml) induced Tie2 phosphorylation, while Ang2 (200 ng/ml) did not produce Tie2 phosphorylation. Ang1 increased the survival of cultured PCAECs during apoptosis induced by oxidized low-density lipoprotein (OxLDL). This survival effect was does-dependent and PI. Furthermore, Ang1 also protected endothelial cells of explanted coronary artery against OxLDL-induced apoptosis artery. CONCLUSION: These results suggest that adult coronary artery contains Ang1-Tie2 components that enhance endothelial cell survival to help maintain the normal integrity of the coronary artery endothelium.

Analysis of Variance↗
PubMed2001

Effect of hesperetin, a citrus flavonoid, on the liver triacylglycerol content and phosphatidate phosphohydrolase activity in orotic acid-fed rats.

The effect of dietary hesperetin on the hepatic lipid content and the enzyme activities involved in triacylglycerol (TG) synthesis in rats fed diets with or without 1% orotic acid (OA) was studied. Hepatic TG content was raised by approximately 5-fold after administration of OA for 10 days. The OA-feeding significantly increased the activity of hepatic microsomal phosphatidate phosphohydrolase (PAP), which is the rate-limiting enzyme for TG synthesis. Hepatic glucose-6-phosphate dehydrogenase (G6PDH) and malic enzyme activities were also increased. An addition of 1% hesperetin to the OA-supplemented diet resulted in the decrease of the hepatic TG content by 44% and of microsomal PAP activity. Dietary hesperetin alone neither affected liver TG content nor PAP activity significantly. OA-feeding caused an increased liver cholesterol level, whereas simultaneous addition of hesperetin and OA reduced its content to the control level. A slight reduction of hepatic cholesterol by hesperetin was also observed in the OA-free dietary group. The present study demonstrated that dietary hesperetin can reduce the hepatic TG accumulation induced by OA, and this was associated with the reduced activity of TG synthetic enzyme, PAP.

Animals↗
PubMed2001

Allogeneic bone marrow transplantation for chronic myeloid leukemia: a retrospective study of busulfan-cytoxan versus total body irradiation-cytoxan as preparative regimen in Koreans.

From January 1990 to December 1997, 53 Korean patients with chronic myeloid leukemia (CML) receiving bone marrow transplantation (BMT) from human leucocyte antigen (HLA)-identical sibling donors conditioned with either busulfan and cyclophosphamide (BU/CY regimen) or total body irradiation and cyclophosphamide (TBI/CY regimen) were compared retrospectively. Transplantation-related mortality was 19% in BU/CY and 12% in TBI/CY, and early death (<100 d) occurred in 3 patients conditioned with BU/CY. Grade II-IV acute graft-versus-host disease (GVHD) was 9% of BU/CY and 52% of TBI/CY patients. Overall incidence of chronic GVHD was 50% of BU/CY and 52% of TBI/CY patients. In patients with chronic phase, 5-yr overall survival was 73% in the BU/CY group compared with 87% in the TBI/CY group (p=NS), and overall disease-free survival was 75% in the BU/CY group and 59% in the TBI/CY group (p=NS). So far, with a median follow-up of 45 months, 11 patients have relapsed; three relapses occurred after BU/CY and 8 after TBI/CY. The actuarial 5-yr relapse rate was 15% after BU/CY, 34% after TBI/CY (p=0.46). For patients transplanted in chronic phase within 1 yr after diagnosis, there was a clear trend for a lower relapse rate in the BU/CY group (5-yr relapse rate 0%) compared with the TBI/CY group (5-yr relapse rate 30%). The BU/CY group had similar BMT-related toxicity and similar overall survival and showed a clear trend of low relapse compared with the TBI/CY group. Therefore, BU/CY is an acceptable alternative for patients with CML during HLA-identical sibling allogeneic BMT.

Adult↗
PubMed2001

Gene therapy for gastric ulcers with single local injection of naked DNA encoding VEGF and angiopoietin-1.

BACKGROUND & AIMS: Angiogenesis, formation of new capillary blood vessels, is crucial for gastroduodenal ulcer healing because it enables delivery of oxygen and nutrients to the healing site. Because angiogenesis is stimulated by vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang1), we studied whether local gene therapy with nonviral DNA encoding VEGF and/or Ang1 into the ulcer base could accelerate ulcer healing through enhanced angiogenesis. METHODS: Gastric ulcers were induced in rats by acetic acid applied to the serosal surface of the stomach, and the site around the ulcer was injected with nonviral plasmid-encoding full-length complementary DNA (cDNA) of human recombinant (rh) VEGF165, rhAng1, or their combination. For some studies, neutralizing anti-VEGF antibody was administered. RESULTS: Single local injection of plasmids encoding VEGF165 and Ang1 significantly increased neovascularization and accelerated ulcer healing. A neutralizing anti-VEGF antibody significantly reduced the acceleration of ulcer healing resulting from the treatment. Coinjection of both plasmids encoding rhVEGF165 and rhAng1 resulted in formation of more mature vessels and to more complete restoration of gastric glandular structures within the ulcer scar. However, this did not result in further reduction of ulcer size. CONCLUSIONS: VEGF and Ang1 gene therapy, with limited duration of target gene expression, significantly accelerates gastric ulcer healing. Coinjection of both plasmids leads to more complete structural restoration. Inhibition of accelerated healing by a neutralizing anti-VEGF antibody indicates an essential role for VEGF and enhanced angiogenesis in ulcer healing.

Angiopoietin-1↗
PubMed2001

Multiple-dose pharmacokinetics and tolerability of gemifloxacin administered orally to healthy volunteers.

Gemifloxacin mesylate (SB-265805-S, LB-20304a) is a potent, novel fluoroquinolone agent with a broad spectrum of antibacterial activity. The pharmacokinetics and tolerability of oral gemifloxacin were characterized in two parallel group studies in healthy male volunteers after doses of 160, 320, 480, and 640 mg once daily for 7 days. Multiple serum or plasma and urine samples were collected on days 1 and 7 and were analyzed for gemifloxacin by high-performance liquid chromatography (HPLC)-fluorescence (study 1) or HPLC-mass spectrometry (study 2). Safety assessments included vital signs, 12-lead electrocardiogram (ECG) readings, hematology, clinical chemistry, urinalysis, and adverse experience monitoring. Gemifloxacin was rapidly absorbed, with a time to maximum concentration of approximately 1 h after dosing followed by a biexponential decline in concentration. Generally, maximum concentration and area under the concentration-time curve (AUC) increased linearly with dose after either single or repeat doses. Mean +/- standard deviation values of AUC(0-tau) on day 7 were 4.92 +/- 1.08, 9.06 +/- 2.20, 12.2 +/- 3.69, and 20.1 +/- 3.67 microg x h/ml following 160-, 320-, 480-, and 640-mg doses, respectively. The terminal-phase half-life was approximately 7 to 8 h, independent of dose, and was similar following single and repeated administrations. There was minimal accumulation of gemifloxacin after multiple dosing. Approximately 20 to 30% of the administered dose was excreted unchanged in the urine. The renal clearance was 160 ml/min on average after single and multiple doses, which was slightly greater than the accepted glomerular filtration rate (approximately 120 ml/min). These data show that the pharmacokinetics of gemifloxacin are linear and independent of dose. Gemifloxacin was generally well tolerated, although one subject was withdrawn from the study after 6 days at 640 mg for mild, transient elevations of alanine aminotransferase and aspartate aminotransferase not associated with any clinical signs or symptoms. There were no other significant changes in clinical chemistry, hematology or urinalysis parameters, vital signs, or ECG readings. In conclusion, the results of these studies, combined with the antibacterial spectrum and potency, support the further investigation of once-daily administration of gemifloxacin for indications such as respiratory tract and urinary tract infections.

Adult↗