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Biomedical subjects

J M Kim

Publications and source records attributed to J M Kim.

At least 109 records · Page 6Linked to original sources

Description of a drug hierarchy in a concept-based reference terminology.

A concept-based reference terminology that covers all aspects of healthcare is essential in developing the Electronic Health Record (EHR). SNOMED Clinical Terms (CT), scheduled for release in December 2001, integrates the relative strengths of SNOMED RT, and the United Kingdom s Clinical Terms Version 3, formerly known as the Read Codes Version 3. It promises to be the most comprehensive terminology available. Since a significant portion of the EHR can be drug-related information, we describe here some of the background information and rationale for the structure and scope of the merged drug hierarchy within SNOMED CT. A controlled drug terminology within a reference terminology has the potential to support a number of functions within healthcare practice. One of the functions proposed is to serve as the bridge between reference terminology and drug knowledge bases.

Clinical Medicine↗

Direct imaging of the pores and cages of three-dimensional mesoporous materials.

Mesostructured composite materials, with features ranging from 20 to 500 A in size, are obtained by the kinetically controlled competitive assembly of organic and inorganic species into nanostructured domains. Short-range order is limited, and long-range order is determined by weak forces such as van der Waals or hydrogen-bonding. Three-dimensional mesoporous materials obtained by removing the organic phase are of particular interest for applications such as catalysis and chemical sensing or separation, for which structural features such as cavity shape, connectivity and ordered bimodal porosity are critical. But atomic-scale structural characterization by the usual diffraction techniques is challenging for these partially ordered materials because of the difficulty in obtaining large (> 10 microm) single crystals, and because large repeat spacings cause diffraction intensities to fall off rapidly with scattering angle so that only limited small-angle data are available. Here we present a general approach for the direct determination of three-dimensional mesoporous structures by electron microscopy. The structure solutions are obtained uniquely without pre-assumed models or parametrization. We report high-resolution details of cage and pore structures of periodically ordered mesoporous materials, which reveal a highly ordered dual micro- and mesoscale pore structure.

Journal Article↗

Phosphatidylinositol 3-kinase stimulates muscle differentiation by activating p38 mitogen-activated protein kinase.

The activation of both phosphatidylinositol 3-kinase (PI3-kinase) and p38 mitogen-activated protein kinase (p38 MAPK) is required for muscle differentiation. However, it is not known whether the signals from these two kinases interact during this process. In this work, we have investigated this using H9c2 cardiac myoblasts. The p38 MAPK-specific inhibitor SB203580 blocked muscle differentiation and suppressed the expression of myogenin and myosin heavy chain in a concentration-dependent manner. Consistent with this, expression of a wild-type p38 MAPK (Ha-p38) or a constitutively active MAPK kinase 6 (MKK6(glu)) promoted the rate of differentiation into multinucleated myotubes. LY294002, a PI3-kinase inhibitor, suppressed in a dose-dependent manner not only muscle differentiation but also activation of p38 MAPK. In addition, expression of a constitutively active form of PI3-kinase (p110*) enhanced myotube formation and p38 MAPK activation, while expression of a dominant negative form of PI3-kinase (Deltap85) attenuated these responses. Furthermore, SB203580 suppressed differentiation of H9c2 cells expressing p110*. Interestingly, LY294002 also suppressed differentiation of H9c2 cells expressing Ha-p38 or MKK6(glu). However, SB203580 did not affect PI3-kinase activity, suggesting that PI3-kinase myogenic signaling to p38 MAPK is unidirectional. Taken together, we concluded that PI3-kinase activates p38 MAPK, which in turn stimulates muscle differentiation, but that p38 MAPK does not substitute for PI3-kinase in this process.

Animals↗

Proliferation-associated SNF2-like gene (PASG): a SNF2 family member altered in leukemia.

To identify genes involved in cell growth and/or apoptosis in leukemia, differential display was used to identify mRNAs that showed altered expression levels after cytokine withdrawal from the cytokine-dependent MO7e cell line. Sequence analysis of one transcript that showed a profound decrease in expression after cytokine withdrawal revealed it to be a member of the SNF2 family of chromatin remodeling ATPases. This cDNA had a 2514-nucleotide (838-amino acid) open reading frame and encoded an additional 230 amino acids at the NH2 terminus compared with the murine homologue, lsh, and the human counterpart, Hells. This gene locus has been designated SMARCA6 (SWI/SNF2-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 6). The highest levels of mRNA expression in humans are observed in proliferative tissues such as the thymus, testis, and bone marrow. Whereas cytokine withdrawal in MO7e cells leads to apoptosis and decreased mRNA expression, growth arrest without the induction of apoptosis of MO7e cells also leads to down-regulation of mRNA expression, suggesting an association with cell proliferation and not suppression of apoptosis. Nuclear localization of this SNF2-like putative helicase is dependent on a nuclear localization sequence located in the NH2-terminal region. Based on sequence homology to other SNF2-like helicases, the pattern of tissue expression, and the association of expression with cell proliferation, we refer to the protein product as proliferation-associated SNF2-like gene product [PASG (D. W. Lee et al., Blood, 94: 594a, 1999)]. Examination of acute myelogenous leukemia and acute lymphoblastic leukemia samples revealed a high frequency of a PASG transcript containing an in-frame 75-nucleotide deletion, which codes for a conserved motif known to be critical for the transactivation activity of a related yeast SWI/SNF polypeptide. These results extend our knowledge of this SNF2-like family member and suggest a role for PASG in leukemogenesis.

Alternative Splicing↗

Detection of cryptic Y chromosome mosaicism by coamplification PCR with archived cytogenetic slides of suspected Turner syndrome.

Turner syndrome is one of the most common cytogenetic abnormalities. It is known that the Y chromosome or Y derived material is present in 6-9% of TS patient and it may develop a high risk of gonadoblastoma in 15-25%. So it is crucial to carry out cyto genetic analysis and Y-specific probe studies for all persons with gonadal dysgenesis to rule out mosaicism with Y-bearing cell line; eg 45,X/46,XY. In this study, 26 archival slides previously analyzed cytogenetically as 45,X, 45,X/46,X,i(X), 45,X/46,X,r(X), and 45,X/46,XX were examined. Coamplification PCR, having the advantage of providing rapid result and confirming PCR failure, was performed with the slide samples in the regions of dystrophin gene in Xp21and DYZ3 in the Y centromeric region. All of archived slides were positive for X-specific gene and one slide of 45,X was found to have the cryptic Y chromosome material. Our result suggests that the archived cytogenetic slides could be applied for the detection of Y chromosome rapidly and efficiently in TS patients.

Biopsy↗

Artificial recruitment of Sp1 or TBP can replace the role of IE1 in the synergistic transactivation by IE1 and IE2.

The IE1 and IE2 proteins of human cytomegalovirus transactivate various viral and cellular promoters in a synergistic manner, but the mechanism of their action has not been well elucidated. Here we have examined the IE1-IE2 synergy by artificial recruitment of either Sp1 or TBP to the promoter. We found that in the presence of Sp1, the synergistic effect of IE1 on IE2-mediated transactivation dramatically decreased. Furthermore, a 117-amino acids glutamine-rich fragment of Sp1, which can interact with dTAF(II)110 and hTAF(II)130, was sufficient to replace the role of IE1 in IE1-IE2 synergism. It was also found that TBP recruitment to the promoter markedly decreased the synergistic effect of IE1 on IE2-mediated transactivation. These results suggested that in the context of the synergism between IE1 and IE2, the function of IE1 might overlap with that of Sp1, for example by recruiting the TFIID complex.

Animals↗

Physical and functional interaction between the HCMV IE2 protein and the Wilms' tumor suppressor WT1.

Human cytomegalovirus (HCMV) is a major renal pathogen in congenitally infected infants and renal allograft recipients. It has been shown that human kidney cells of glomerular, tubular, and vascular origin were all infected by HCMV in vitro. It has previously been demonstrated that the IE2 protein of HCMV directly associates with the zinc finger domain of Egr-1. The zinc finger region of WT1 is a sequence-specific DNA-binding domain which also recognizes the consensus DNA binding site (5'-CGCCCCCGC-3') of Egr-1, thus suggesting a possible interaction between WT1 and IE2. Here we demonstrate that HCMV IE2 binds to the C-terminal region of WT1 containing zinc finger domain in vivo as well as in vitro and that WT1 can inhibit IE2-driven transactivation of the responsive promoter. Our results suggest that WT1 may be able to regulate the functional activity of HCMV IE2. Furthermore, these data may provide new insights into the possible involvement of HCMV in WT1-related pathogeneses.

Animals↗

Virulence factors of Helicobacter pylori in Korean isolates do not influence proinflammatory cytokine gene expression and apoptosis in human gastric epithelial cells, nor do these factors influence the clinical outcome.

The cytotoxin-associated gene (cagA) and vacuolating cytotoxin (Vac) production have been reported to be major virulence factors of Helicobacter pylori. However, there have been some disputes regarding the correlation between these virulence factors and clinical outcomes. We evaluated whether the cagA-positive genotype and Vac production might be correlated with various gastroduodenal diseases in Korea and whether this correlation could be due to differences in proinflammatory cytokine gene expression and apoptosis of gastric epithelial cells in vitro. The presence of the cagA gene was examined by the polymerase chain reaction (PCR), and Vac production was detected using the bacterial culture supernatant and HeLa cells after H. pylori was isolated from Korean patients. Gastric epithelial cells were infected with cagA+Vac+, cagA+Vac-, or cagA-Vac- strains, after which cytokine gene expression was evaluated, using quantitative reverse transcription (RT)-PCR. Apoptosis and caspase-3 activation were measured in H. pylori-infected gastric epithelial cells. There was no significant correlation between the presence of these virulence factors in H. pylori isolates and peptic ulcer or gastric cancer. Upregulation of cytokine gene expression, including that of interleukin (IL)-1alpha, IL-8, granulocyte macrophage colony-stimulating factor (GM-CSF), and monocyte chemotactic protein (MCP)-1, as well as apoptosis and caspase-3 activation, were similar in infections with cagA-positive and cagA-negative strains, but were not correlated with the production of Vac. These results suggest that the lack of correlation between virulence factors of isolated H. pylori strains and serious gastroduodenal disease entities in Korea may be due to the similar capacity for proinflammatory cytokine gene expression and apoptosis caused by infection with each of the H. pylori strains.

Antigens, Bacterial↗

Expression of tenascin-C in astrocytic tumors: its relevance to proliferation and angiogenesis.

BACKGROUND: The expression and distribution of the extracellular matrix protein tenascin-C (TN-C) may be enhanced in human astrocytomas. The purpose of this study is to evaluate the expression of TN-C according to histological malignancy of tumor cells and its relevance to neoplastic angiogenesis in human astrocytic tumors. METHODS: Between 1994 and 1998, 52 astrocytic tumor specimens including 4 pilocytic astrocytomas, 13 astrocytomas, 3 anaplastic astrocytomas, and 32 glioblastomas were used in this study. A retrospective analysis was performed to evaluate a statistical correlation between TN-C expression and proliferative indices. We characterized the expression of TN-C in neoplastic vessels, around individual tumor cells as a tumor network, and in tumor cells by immunohistochemistry using antibodies against human TN-C. The proliferative indices were also investigated by immunostaining with the MIB-1 antibody against the Ki-67 proliferation antigen. RESULTS: TN-C immunoreactivity was found to be enhanced in tumor vessels and tumor networks of high-grade astrocytic tumors. The vascular TN-C deposition was greater in high-grade than in low-grade astrocytic tumors (p < 0.05). Its expression was the most intense in glioblastomas. Proliferation indices increased with tumor grade and MIB-1 labeling index (LI) was highest in glioblastomas. Moreover, expression of TN-C in tumor vessels was correlated with proliferative indices. CONCLUSIONS: Our data show that TN-C in human astrocytic tumors may be identified as a factor contributing to malignant progression. And also, enhanced expression of TN-C in tumor vessels having a high proliferative index indicates that TN-C could be involved in neoplastic angiogenesis.

Adolescent↗

Steaming of ginseng at high temperature enhances biological activity.

The present study was performed to evaluate the effect of steaming ginseng at a temperature over 100 degrees C on its chemical constituents and biological activities. Raw ginseng was steamed at 100, 110, and 120 degrees C for 2 h using an autoclave. The ginseng steamed at 120 degrees C was more potent in its ability to induce endothelium-dependent relaxation. Steaming the raw ginseng at 120 degrees C also remarkably increased the radical-scavenging activity. Ginsenosides F(4), Rg(3), and Rg(5), which were not present in raw ginseng, were produced after steaming. Ginsenosides Rg(3) and Rg(5) were the most abundant ginsenosides in the ginseng steamed at 120 degrees C, accounting for 39% and 19% of all ginsenosides, respectively.

Chromatography, High Pressure Liquid↗

Helicobacter pylori water-soluble surface proteins activate human neutrophils and up-regulate expression of CXC chemokines.

To elucidate the mechanisms of the persistent neutrophil recruitment in H. pylori-infected gastric mucosa, we evaluated the activation of human neutrophils and CXC chemokine expression in neutrophils by H. pylori water-soluble surface proteins. H. pylori water extract (HPWE) was prepared from a supernatant of the H. pylori suspension in distilled water. After neutrophils were stimulated with HPWE, the mobilization of intracellular free calcium, the expression of lymphocyte function-associated antigen-1beta, and the secretion of myeloperoxidase (MPO) were enhanced in the neutrophils. In H. pylori-infected gastric mucosa, transendothelial and transepithelial migration of neutrophils were observed by electron microscopy and mucosal MPO levels were elevated. Up-regulation of the expression of interleukin-8 (IL-8) and growth-related oncogenes (GROs; GROalpha, GRObeta and GROgamma) mRNA and protein in neutrophils by HPWE was demonstrated by quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. In conclusion, H. pylori-induced neutrophil recruitment may be mediated by CXC chemokines which are expressed by neutrophils activated by H. pylori water-soluble surface proteins.

Chemokines, CXC↗

Upregulated cyclooxygenase-2 inhibits apoptosis of human gastric epithelial cells infected with Helicobacter pylori.

Helicobacter pylori induces apoptosis and alters the proliferation of gastric mucosal epithelial cells. Cyclooxygenase-2 (COX-2), the inducible form of prostaglandin (PG) synthesis, is known to cause alteration in epithelial cell growth. The goal of this study was to determine whether COX-2 gene expression by H. pylori infection could influence gastric epithelial cell apoptosis. Expression of COX-2 mRNA and proteins was up-regulated in Hs746T gastric epithelial cell lines infected with H. pylori, when assessed by quantitative RT-PCR and western blot. Inhibition of COX-2 expression using NS-398, a specific COX-2 inhibitor, showed a significant increase of gastric epithelial cell apoptosis and caspase-3 activation in Hs746T cells infected with H. pylori. Moreover, the effect of NS-398 on H. pylori-induced apoptosis was reversed by the addition of PGE2. These results suggest that up-regulated COX-2 expression by H. pylori infection can inhibit apoptosis of gastric epithelial cells.

Apoptosis↗

High efficiency retroviral vectors that contain no viral coding sequences.

Almost all currently available retroviral vectors based on murine leukemia virus (MLV) contain one or more viral coding sequences. Because these sequences are also present in the packaging genome, it has been suggested that homologous recombination may occur between the same nucleotide sequence in the packaging genome and the vector, resulting in the production of replication competent retrovirus (RCR). Up until now, it has been difficult to completely remove viral coding sequences since some were thought to be involved in the optimum function of the retroviral vector. For example, the gag coding sequence present in almost all available retroviral vectors has been believed to be necessary for efficient viral packaging, while the pol coding sequence present in the highly efficient vector MFG has been thought to be involved in achieving the high levels of gene expression. However, we have now developed a series of retroviral vectors that are absent of any retroviral coding sequences but produce even higher levels of gene expression without compromising viral titer. In these vectors, the intron and exon sequences from heterologous cellular or viral genes are present. When compared with the well-known MLV-based vectors, some of these newly developed vectors have been shown to produce significantly higher levels of gene expression for a longer period. In an experimental system that can maximize the production of RCR, our newly constructed vectors produced an absence of RCR. These vectors should prove to be safer than other currently available retroviral vectors containing one or more viral coding sequences.

3T3 Cells↗

Lumbar epidural blocks: a case report of a life-threatening complication.

A case of life-threatening complication resulting from a lumbar epidural block is presented. A 70-year-old woman with spinal stenosis developed cardiac and respiratory arrest 5 minutes after receiving a lumbar epidural block containing 80 mg of triamcinolone acetonide and 6mL of 1.5% lidocaine. The patient received cardiopulmonary resuscitation and recovered without any sequelae. It is suggested that this complication was caused by subdural or intravascular injection of local anesthetics. It might be preventable by injecting a test dose of local anesthetics before injecting a full dose of local anesthetics and by using fluoroscopy.

Aged↗

Multicenter surveillance study for nosocomial infections in major hospitals in Korea. Nosocomial Infection Surveillance Committee of the Korean Society for Nosocomial Infection Control.

BACKGROUND: The goals of a surveillance for nosocomial infections (NIs) are to observe the magnitude and characteristics of NIs and to plan and evaluate policies and guidelines of infection control. This study was designed to determine the rate and distribution of NIs and their causative pathogens in Korean hospitals. METHODS: Prospective surveillance was performed at 15 acute care hospitals with more than 500 beds during a 3-month period from June to August 1996. The case-finding methods were laboratory-based surveillance for patients in the general wards and a direct review of medical charts done regularly for all the patients in the intensive care units. RESULTS: A total of 3162 NIs were found among 85,547 discharged patients, with an overall nosocomial infection rate of 3.70 per 100 patients discharged. Urinary tract infections constituted 30.3% of all NIs. Other infections were pneumonias, 17.2%, surgical site infections, 15.5%, and primary bloodstream infections, 14.5%. The infection rate was the highest in neurosurgery (14.21), followed by neurology (8. 62) and ontology services (6.70). The infection rate in intensive care units was higher than it was in the general wards (10.74 vs 2. 57, P =.001). The commonly isolated organisms were Staphylococcus aureus (17.2%), Pseudomonas aeruginosa (13.8%), and Escherichia coli (12.3%). CONCLUSIONS: This first multicenter surveillance study provided extensive information on the current status and trends of NIs in major hospitals in Korea. The results may contribute to the evaluation of infection control programs and the development of effective strategies in these hospitals.

Contact Tracing↗

Apoptosis of human gastric epithelial cells via caspase-3 activation in response to Helicobacter pylori infection: possible involvement of neutrophils through tumor necrosis factor alpha and soluble Fas ligands.

BACKGROUND: Infection with Helicobacter pylori activates a proinflammatory gene program in human gastric epithelial cells and neutrophils and is associated with significant epithelial cell damage, including an increased level of apoptosis. We evaluated whether immune mediators produced by neutrophils could modulate gastric epithelial cell apoptosis in response to H. pylori infection. METHODS: After gastric epithelial cells were infected with H. pylori in the presence of immune mediators, including tumor necrosis factor alpha (TNF-alpha) and Fas ligand (FasL), apoptosis and caspase-3 activity were assessed. The neutrophils were obtained from healthy volunteers, and Western blot for FasL and quantitative reverse transcription polymerase chain reaction for TNF-alpha transcripts were performed. Fas expression in gastric epithelial cells was explored by flow cytometric analysis. RESULTS: Activation of caspase-3 was first apparent 12 h after bacterial infection, and the phenotypic expression of apoptosis was first apparent 18 h after bacterial infection. The extent of apoptosis was similar in cases of cagA+ cytotoxin+, cagA+ cytotoxin-, cagA- cytotoxin- H. pylori-infected gastric epithelial cells. Approximately 20% of the Hs746T cells expressed Fas within 24 h of H. pylori infection. The soluble FasL was upregulated in neutrophils after treatment with H. pylori-soluble proteins for 24 and 48 h. The addition of TNF-alpha and the soluble form of FasL, produced by neutrophils, significantly increased H. pylori-infected cell apoptosis and caspase-3 activation. However, the combination of these two immune mediators showed only an additive increase. CONCLUSION: These results suggest that H. pylori-induced gastric epithelial cell apoptosis and caspase-3 activation can be modulated by the immune response of neutrophils.

Apoptosis↗

Synergy of Bacteroides fragilis and Escherichia coli in the induction of KC gene expression in mouse peritoneal tissues.

B. fragilis induces cytokine expression, which can serve as a host signal leading to inflammatory reaction and abscess formation in the peritoneal cavity. We assessed the hypothesis that enteric bacteria may alter the B. fragilis-induced expression of KC genes in mouse peritoneal tissues (MPT). After C57BL/6 mice were inoculated with abscess-forming mixture containing B. fragilis in the presence or absence of E. coli, RNA was extracted from MPT. Expression of KC mRNA was quantified using reverse-transcription polymerase chain reaction and standard RNA. KC and TNFalpha proteins were measured by enzyme-linked immunosorbent assay. KC mRNA in MPT was upregulated following inoculation of B. fragilis and this was paralleled by increased KC protein secretion. When the mice were co-infected with E. coli and B. fragilis intraperitoneally, there was a synergistic increase in the expression of KC of MPT. Co-infection with L. acidophilus and B. fragilis downregulated KC mRNA expression, but co-infection with E. faecalis and B. fragilis synergistically increased KC expression in the infected MPT. Inhibition of TNFalpha production could downregulate KC expression in mixed infected MPT. These results suggest that enteric bacteria may significantly affect the KC signal produced by the host peritoneal cavity in response to B. fragilis infection.

Abscess↗