Search PubMed⌕ Search

Biomedical subjects

J W Kim

Publications and source records attributed to J W Kim.

At least 55 records · Page 3Linked to original sources
PubMed2004

Comparison of HPV DNA vaccines employing intracellular targeting strategies.

Intradermal vaccination via gene gun efficiently delivers DNA vaccines into dendritic cells (DCs) of the skin, resulting in the activation and priming of antigen-specific T cells in vivo. In the context of DNA vaccines, we previously used the gene gun approach to test several intracellular targeting strategies that are able to route a model antigen, such as the human papillomavirus type-16 (HPV-16) E7, to desired subcellular compartments in order to enhance antigen processing and presentation to T cells. These strategies include the use of the sorting signal of lysosome-associated membrane protein (LAMP-1), Mycobacterium tuberculosis heat-shock protein 70 (HSP70), calreticulin (CRT) and the translocation domain (dII) of Pseudomonas aeruginosa exotoxin A (ETA). Vaccination with DNA vaccines encoding E7 antigen linked to any of these molecules all led to a significant enhancement of E7-specific CD8(+) T-cell immune responses and strong antitumor effects against an E7-expressing tumor, TC-1. However, we were interested in identifying the most potent DNA vaccine for our future clinical trials. Thus, we performed a series of experiments to directly compare the potency of the various DNA vaccines. Among the DNA vaccines we tested, we found that vaccination with pcDNA3-CRT/E7 generated the highest number of E7-specific CD8(+) T cells and potent long-term protection and treatment effects against E7-expressing tumors in mice. Interestingly, we observed that pcDNA3-CRT/E7 is also capable of protecting against an E7-expressing tumor with downregulated MHC class I expression, a common feature associated with most HPV-associated cervical cancers. Our data suggest that the DNA vaccine linking CRT to E7 (CRT/E7) may be a suitable candidate for human trials for the control of HPV infections and HPV-associated lesions.

Animals↗
PubMed2004

Impact of IL-1 receptor antagonist gene polymorphism on schizophrenia and bipolar disorder.

OBJECTIVES: Variable levels of cytokines were observed in patients with schizophrenia and bipolar disorder, and an especially high level of interleukin-1 (IL-1) was detected in schizophrenia patients. It is known that IL-1 receptor antagonist (IL-1RA) binds to IL-1 receptors and inhibits the receptor binding of IL-1alpha and IL-1beta. METHODS: In this study, the association between the variable number of tandem repeats polymorphism of the IL-1RA gene and schizophrenia (n=269) and bipolar disorder (n=83) was investigated. RESULTS: The genotype distribution and allele frequency were significantly different between schizophrenic patients and the control group (P<0.05); however, there were no prominent differences between bipolar patients and the control group. The carriage rate for the IL1RN*2 allele was associated with higher risk of schizophrenia (odds ratio=2.24). CONCLUSIONS: This study indicates that IL-1RA could be a candidate gene for susceptibility to schizophrenia.

Adult↗
PubMed2004

Modeling the fate and transport of organic and nitrogen species in soil aquifer treatment process.

Soil aquifer treatment (SAT) is a promising technique for wastewater reclamation and reuse. This treatment strategy takes advantage of physicochemical and biological processes in the subsurface. The model employed in this study is based on MODFLOW-SURFACT (HydroGeoLogic, Inc.), a three-dimensional model for variably saturated flow and reactive mass transport. The model accounts for reactions including the nitrification of ammonium, the denitrification of nitrate, and the oxidation of organic carbon. Concentration of dissolved oxygen and biomasses involved in aerobic and anaerobic biological reactions forms the basis for estimates of nonlinear reaction rates formulated using a multiple-Monod expression. Illustrative simulations were conducted in a two-dimensional cross-sectional domain, with unsaturated and saturated zones. They examine the effects that site and operational conditions have on the performance of a SAT system. The parameters and conditions of concern included length of the wet/dry cycle, ground surface condition, and infiltration rate. From the simulations, we found that organic carbon was effectively removed in all cases. The availability of oxygen was a key factor in predicting the production and removal of nitrate. Overall, the model successfully described the fate and transport of the key constituents during the wet/dry operational periods in both unsaturated and saturated subsurface.

Conservation of Natural Resources↗
PubMed2003

Spontaneous N incorporation onto a Si(100) surface.

Initial nitridation of the Si(100) surface is investigated using photoemission, ion-scattering and ab initio calculations. After dissociation of NO or NH3, nitrogen atoms are found to spontaneously form a stable, highly coordinated N[triple bond]Si(3) species even at room temperature. The majority of the N species is incorporated into the subsurface Si layers occupying an interstitial site, whose atomic structure and unique bonding mechanism is clarified through ab initio calculations. This unusual adsorption behavior elucidates the atomistic mechanism of initial silicon nitride formation on the surface and has important implication on the N-rich layer formation at the SiO(x)N(y)/Si interface.

Journal Article↗
PubMed2003

Anterior cingulotomy for refractory obsessive-compulsive disorder.

OBJECTIVE: This study was designed to prospectively investigate the efficacy and cognitive adverse effects of stereotactic bilateral anterior cingulotomy as a treatment for refractory obsessive-compulsive (OCD) patients for 12 months. METHOD: Patients were eligible if they had severe OCD and rigorous treatments had been unsuccessful. Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), Clinical Global Impression (CGI) and neuropsychological tests were used to assess the efficacy and cognitive changes of cingulotomy before and 12 months after operation. RESULTS: The mean improvement rate of the Y-BOCS scores achieved from baseline was 36.0%. Out of 14 patients six met responder criteria; 35% or higher improvement rate on Y-BOCS and CGI improvement of very much or much better at 12-month follow-up. There was no significant cognitive dysfunction after cingulotomy. CONCLUSION: Anterior cingulotomy shows few cognitive adverse effects, with about half of the OCD patients demonstrating significant symptomatic improvement.

Adult↗
PubMed2003

Endothelial nitric oxide synthase gene polymorphisms in Behçet's disease and rheumatic diseases with vasculitis.

OBJECTIVE: To assess potential associations between Korean Behçet's disease (BD) or other rheumatic diseases with vasculitis and two polymorphisms of the endothelial nitric oxide synthase (eNOS) gene, which include the Glu298Asp polymorphism in exon 7 and a variable number of tandem repeats (VNTR) polymorphism in intron 4. METHODS: 65 patients with BD, 27 with rheumatic diseases with vasculitis, and 80 controls were studied. Analyses of the Glu298Asp polymorphism in exon 7 and VNTR polymorphism in intron 4 of the eNOS gene were made by the polymerase chain reaction (PCR)-restriction fragment length polymorphism technique and PCR genotyping, respectively. Additionally, HLA-B51 typing was performed in the BD group and controls by a two step PCR sequence-specific primers method. RESULTS: Significant differences in Glu298Asp genotype frequencies were found between the BD or vasculitis groups and the controls (BD group v controls: p(corr)=0.006; vasculitis group v controls: p<0.001). The Asp298 frequency was much higher in the BD and vasculitis groups than in the controls. Even after stratification of the BD group based on the results of HLA-B51 testing, a significant association of the Glu298Asp polymorphism was still found (p=0.002, Mantel-Haenszel weighted odds ratio 4.3, 95% confidence interval 1.7 to 10.9). Distribution of the genotype frequencies in two eNOS gene polymorphisms was similar in connective tissue diseases-associated vasculitis and primary vasculitic syndromes. In contrast, distribution of alleles and genotypes of VNTR polymorphism did not differ between BD or vasculitis groups and the controls. CONCLUSION: The Glu298Asp polymorphism in exon 7 of the eNOS gene seems to be a susceptibility gene for Korean BD and other rheumatic diseases.

Adult↗
PubMed2001

Mapping of the interaction sites between apoptosis linked gene ALG-2 and HEED.

The apoptosis linked gene (ALG-2) is a 22 kDa Ca2+-binding protein of the penta EF-hand motif family. ALG-2 was discovered in a "death trap" assay using T-cell receptor-mediated apoptosis. Depletion of ALG-2 using an anti-sense ALG-2 construct inhibits apoptosis that is induced by several stimuli, such as staurosporin, dexamethason, Fas, and glucocorticoid. The Ca2+-dependent function of ALG-2 is consistent with the observation that the cytoplasmic Ca2+ level is elevated in apoptotic cells. We found that ALG-2 interacted specifically with the carboxy-terminal region of HEED using a yeast two-hybrid assay system. The mutants of HEED were constructed by deleting five WD repeat motifs one by one from the C-terminus of the protein. These mutants of ALG-2 were made by combining the EF hand Ca2+ binding motifs in various ways. Mapping of the interaction sites, using each of the mutants, revealed that the interaction between HEED and a third EF-hand motif of ALG-2 was stronger than the other combination.

Apoptosis Regulatory Proteins↗
PubMed2001

Homodimers of mutant tryptophan synthase alpha-subunits in Escherichia coli.

Tryptophan synthase alpha-subunit from Escherichia coli functionally exists as a heterotetramer of alpha(2)beta(2) with beta-subunit. While wild-type and mutant (F139W, T24M/F139W, and T24L/F139W) alpha-subunits were expressed as a monomer from recombinant plasmids in Escherichia coli, T24A/F139W, T24S/F139W, and T24K/F139W mutant alpha-subunits were abnormally expressed as soluble homodimers in addition to monomers. Monomers of dimer-forming mutant alpha-subunits retain high affinity to beta-subunit, high activity in stimulating catalytic activities of beta-subunit, and nearly intact content of secondary structure, indicating that the global structures of these monomers are identical to that of F139W alpha-subunit. However, fluorescence spectra of Trp139 and ANS binding indicate that significant perturbations occur in the mutant proteins. Interestingly, these defective properties of monomers caused by residue replacement were partially repaired by the dimer formation. As a result, it is suggested that dimers may be formed by domain or loop swapping, and that residue 24 may play important role in maintaining on-pathway of alpha-subunit folding.

Anilino Naphthalenesulfonates↗
PubMed2001

Modulation of the multisubstrate specificity of Thermus maltogenic amylase by truncation of the N-terminal domain and by a salt-induced shift of the monomer/dimer equilibrium.

The relation between the quaternary structure and the substrate specificity of Thermus maltogenic amylase (ThMA) has been investigated. Sedimentation diffusion equilibrium ultracentrifugation and gel filtration analyses, in combination with the crystal structure determined recently, have demonstrated that ThMA existed in a monomer/dimer equilibrium. The truncation of ThMA by removing the N-terminal domain, which is composed of 124 amino acid residues, resulted in the complete monomerization of the enzyme (ThMADelta124) accompanied by a drastic decrease in the activity for beta-cyclodextrin (beta-CD) and a relatively smaller reduction of the activity for starch. Despite the overall low activity of ThMADelta124, the activity was higher toward starch than beta-CD, and the ratio of the specific activities toward these substrates was approximately 100 fold higher than that of wild-type ThMA. Furthermore, the addition of KCl to wild-type ThMA shifted the monomer/dimer equilibrium toward the monomer. In the presence of 1.0 M KCl, the relative activity of ThMA toward beta-CD decreased to 74%, while that for soluble starch increased to 194% compared to the activities in the absence of KCl. Thus, the ThMA monomer and dimer are both inferred to be enzymatically active but with a somewhat different substrate preference. Kinetic parameters of the wild-type and truncated enzymes also are in accordance with the changes in their specific activities. We thus provide evidence in support of a model, which shows that the relative multisubstrate specificity of ThMA is influenced by the monomer/dimer equilibrium of the enzyme.

Amino Acid Sequence↗
PubMed2001

Apoptosis-linked gene 2 binds to the death domain of Fas and dissociates from Fas during Fas-mediated apoptosis in Jurkat cells.

Apoptosis-linked gene 2 (ALG-2) is a member of the family of Ca(2+)-binding proteins with penta-EF-hand and is essential for the execution of apoptosis by various signals including Fas activation. We studied the regulation of ALG-2 during Fas-mediated apoptosis in Jurkat cells. The 22-kDa ALG-2 protein is cleaved and becomes a 19-kDa protein after Fas activation. The appearance of 19-kDa ALG-2 protein increases for 4 h after treatment with 200 ng/ml of anti-Fas Ab treatment and gradually degrades afterward. Confocal microscopic analysis showed that ALG-2 translocated from the plasma membrane to the cytosol during Fas-mediated apoptosis. Therefore, we examined if ALG-2 interacts with Fas. The protein-protein interaction of ALG-2 with Fas was demonstrated using yeast two-hybrid assays as well as in vitro GST pull-down assay. Endogenous ALG-2 was immunoprecipitated with anti-Fas Ab in Jurkat cells without Fas activation. However, the endogenous ALG-2 was no longer immunoprecipitated with anti-Fas Ab 2 h after anti-Fas Ab treatment. This study, for the first time, presents a direct molecular connection of ALG-2 to apoptosis by its direct interaction with Fas, and enlists ALG-2 as a new member of posttranslationally modified proteins during Fas-mediated apoptotic process.

Apoptosis↗
PubMed2001

Overexpression of the thymosin beta-10 gene in human ovarian cancer cells disrupts F-actin stress fiber and leads to apoptosis.

To understand the molecular changes during ovarian cancer development, we profiled differentially expressed genes in five paired normal and cancerous ovarian tissues. Among the genes that showed differential expression, thymosin beta-10 expression was decreased in four of five cancer tissues. The decreased level of expression was confirmed by Northern. To investigate the gene's functional role in ovarian cancers, we constructed an adenovirus vector expressing thymosin beta-10 and used it to infect ovarian cancer cell lines PA-I and SKOV3. The infected cells showed disrupted F-actin stress fibers, markedly decreased cell growth, and a high rate of apoptosis. Thus, because loss of thymosin beta-10 expression may contribute to the development of a subset of ovarian cancers, restoration of thymosin beta-10 expression may be a new strategy for ovarian cancer treatment.

Actins↗
PubMed2001

Failure of hormone therapy in prostate cancer involves systematic restoration of androgen responsive genes and activation of rapamycin sensitive signaling.

Androgen deprivation therapy for advanced prostate cancer is often effective, but not curative. Molecular pathways mediating the therapeutic response and those contributing to the subsequent hormone-refractory cell growth remain poorly understood. Here, cDNA microarray analysis of human CWR22 prostate cancer xenografts during the course of androgen deprivation therapy revealed distinct global gene expression profiles in primary, regressing and recurrent tumors. Elucidation of the genes involved in the transition between these states implicated specific molecular mechanisms in therapy failure and tumor progression. First, we identified a set of androgen-responsive genes whose expression decreased during the therapy response, but was then systematically restored in the recurrent tumors. In addition, altered expression of genes that encode known targets of rapamycin or that converge on the PI3K/AKT/FRAP pathway was observed in the recurrent tumors. Further suggestion for the involvement of these genes in hormone-refractory prostate cancer came from the observation that cells established from the recurrent xenografts were strongly inhibited in vitro by rapamycin. The results of this functional genomic analysis suggest that the combined effect of re-expression of androgen-responsive genes as well as the activation of rapamycin-sensitive signaling may drive prostate cancer progression, and contribute to the failure of androgen-deprivation therapy.

Algorithms↗
PubMed2001

Alterations of HLA class I and II antigen expression in preinvasive, invasive and metastatic cervical cancers.

HLA expression is altered in a large variety of human cancers. We performed immunohistochemical staining on tissues from normal, preinvasive, invasive and metastatic cervical cancer tissues using anti-HLA class I or class II antibody. In tissues from normal squamous epithelium, carcinoma in situ (CIS) and microinvasive carcinoma (MIC), the expressions of HLA-B, C heavy chains and class II heavy chain were significantly decreased as disease progressed. When the expression patterns were compared between primary and metastatic squamous cell carcinoma (SCC) lesions, statistically significant down-regulation of HLA class I and class II antigen in metastatic lesions was observed. The rates of HLA-B, C heavy chains and class II heavy chain expressions were all significantly down-regulated compared to the down-regulation rate of class I beta2-microglobulin (beta2m) in invasive squamous lesions, and the expressions of class II heavy chain in metastatic lesions was decreased further than that in primary lesions. Unlike SCC, the degree of HLA class I and class II loss was not evident as disease progressed in early stage of adenocarcinoma. In invasive adenocarcinoma lesions, only the expression of HLA-B, C heavy chains was decreased and no differences were seen in HLA-B, C heavy chain expression patterns between primary and metastatic lesions. These results suggest that alterations of HLA class I and II expressions seem to occur at a particular step in cervical cancer development and depend on tissue types: when the tumor becomes invasive and starts to metastasize.

Antibodies, Monoclonal↗
PubMed2001

Protein kinase C modulates telomerase activity in human cervical cancer cells.

Telomerase, a ribonucleoprotein reverse transcriptase that extends telomeres of eukaryotic chromosomes is repressed in normal somatic cells but is activated during development and neoplasia. The regulation mechanism of telomerase activity in cancer cells is not clearly known. In this report, a possible affect of PKC on telomerase activity was examined using HeLa and CUMC-6 cervical cancer cell lines. Exposure of cells to PKC inhibitor, bisindolylmaleimide I and Gö6976, and high levels of PKC activator, 12-O-tetradecanoyl phorbol 13-acetate (TPA) resulted in the inhibition of PKC activity in both cells. Telomerase activities were also inhibited by bisindolyl-maleimide I and Gö6976, respectively, in a time-dependent manner. As PKC activity changes in TPA-treated cervical cancer cells, telomerase activities were increased at low dose of TPA and decreased at high dose. The expression levels of human telomerase subunits, human telomerase RNA (hTR) were not influenced by PKC modulating drugs. In contrast, the expression of full-length human telomerase reverse transcriptase (hTERT) was decreased after exposure to bisindolylmaleimide I and Gö6976 in a time-dependent manner. hTERT expression was not affected by low dose of TPA. In contrast, high dose of TPA inhibited hTERT expression level. But the expression patterns of beta-deletion transcript of hTERT after 72 h of treatment with PKC inhibitors or high dose of TPA exposure were not discernable as compared with those of full-length hTERT transcripts to PKC modulating drugs. These results suggest that PKC-modulating drugs altered telomerase activities by affecting full-length hTERT expression profile in human cervical cancers.

Alternative Splicing↗