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Biomedical subjects

J Kim

Publications and source records attributed to J Kim.

At least 379 records · Page 21Linked to original sources

Seroprevalence of porcine respiratory coronavirus in selected Korean pigs.

A total of 446 serum samples from 88 herds in Korea were examined for antibody to porcine respiratory coronavirus (PRCV) using blocking enzyme-linked immunosorbent assay (ELISA). All serum samples were collected from 24- to 26-week-old finishing pigs between December 1998 and June 1999. By ELISA, 237 out of 446 sera tested (53.1%) and 54 out of 88 sampled herds (61.3%) were positive against PRCV. Of 446 sera from 88 herd tested, 185 (41.5%) serum samples from 22 (25%) herds were seronegative against PRCV and transmissible gastroenteritis virus infection. Our data suggested that seropositive herds for PRCV are distributed diffusely throughout South Korea.

Animals↗

Failure to induce inhibition of cyclin A and up-regulation of p21 expression in phorbol ester-resistant U937 cells by phorbol ester.

Differentiation resistant U937 cells were derived from parental U937 cells by selecting for continuously growing U937 cells in cell cultures continuously exposed to phorbol 12 myristate 13-acetate (PMA). Unlike in other known PMA resistant U937, the basal expression of protein kinase C (PKC) isozymes in these PMA resistant cells (R-U937) was significantly decreased. Subsequent analyses revealed differences between the wild type U937 and the R-U937 cells with respect to G1 phase arrest, which seemed to occur in U937 because of low levels of cdk2 kinase activity. This abolished cdk2 kinase activity is mainly due to inhibition of cdk2 phosphorylation, cyclin A down-regulation and cyclin dependent kinase inhibitor p21 up-regulation. Our data suggest that events down-stream of PKC activation may mediate cell cycle control. Thus, the R-U937 cells could be useful for further PKC mediated cell cycle control studies.

Blotting, Western↗

Serum-induced hypha formation in the dimorphic yeast Yarrowia lipolytica.

The dimorphic yeast Yarrowia lipolytica forms true hyphae in a medium containing N-acetylglucosamine. We made a new finding that serum is a very effective inducer of hypha formation of Y. lipolytica: serum induced its hyphal growth very quickly compared to N-acetylglucosamine (4 h vs. 10 h). Osmotic and oxidative stresses (0.2 M NaCl and 20 mM H2O2) inhibited the hypha formation induced by N-acetylglucosamine, but did not suppress the hypha formation triggered by serum. Serum-specific morphological mutants, which formed hyphae in the N-acetylglucosamine medium but not in serum medium, could be isolated. These results suggest that the signal triggered by serum may be transduced through a different pathway, at least in part, from that used for the N-acetylglucosamine signal in Y. lipolytica.

Acetylglucosamine↗

Transduction effect of antisense K-ras on malignant phenotypes in gastric cancer cells.

The antitumoral effects of antisense RNA to K-ras were investigated in gastric cancer cell lines by examining the level of K-ras expression and the tumorigenicity in vitro and in vivo. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP), DNA sequencing, and immunoblotting analysis revealed that YCC-1 gastric cancer cells overexpressed wild type K-ras, whereas YCC-2 cells had a homozygous mutation in codon 12 from GGT (glycine) to AGT (serine), while SNU-1 cells had a heterozygous mutation to GAT (asparagine) in the identical position. Both YCC-1 and YCC-2 cells were transduced by LNC-AS/K-ras containing the antisense 2.2 kb genomic K-ras DNA fragment covering exon 2 and exon 3 specific for K-ras. The application of antisense K-ras significantly downregulated the expression of K-ras and had no influence on the expression of either H-ras or N-ras. The antisense-transduced YCC-2 cells grew considerably slower than the control group transduced by LNCX, whereas the growth inhibition of antisense-transduced YCC-1 cells was less prominent than that of transduced YCC-2 cells. In addition, the tumorigenicity of YCC-2 cells transduced by LNC-AS/K-ras was totally lost. Therefore, our results imply that the specific inhibition of K-ras p21 protein can be accomplished by introducing the antisense covering the K-ras- specific region to gastric cancer cells with aberrant K-ras expression, resulting in a reduction of the growth rate and suppression of tumorigenicity.

Animals↗

A ribozyme derived from the catalytic subunit of RNase P from Escherichia coli is highly effective in inhibiting replication of herpes simplex virus 1.

A sequence-specific ribozyme (M1GS RNA) derived from the catalytic RNA subunit of RNase P from Escherichia coli was used to target the mRNA encoding human herpes simplex virus 1 (HSV-1) major transcription activator, ICP4. A reduction of more than 80% in the expression level of ICP4 and a reduction of about 1000-fold in viral growth were observed in cells that stably expressed the ribozyme. In contrast, a reduction of less than 10 % in ICP4 expression and viral growth was observed in cells that either did not express the ribozyme or produced a catalytically inactive ribozyme mutant. Thus, M1GS ribozyme is highly effective in inhibiting HSV-1 growth and can be used as a general gene-targeting agent for anti-HSV applications.

Animals↗

A role for CD40-CD40 ligand interactions in the generation of type 1 cytokine responses in human leprosy.

The interaction of CD40 ligand (CD40L) expressed by activated T cells with CD40 on macrophages has been shown to be a potent stimulus for the production of IL-12, an obligate signal for generation of Th1 cytokine responses. The expression and interaction of CD40 and CD40L were investigated in human infectious disease using leprosy as a model. CD40 and CD40L mRNA and surface protein expression were predominant in skin lesions of resistant tuberculoid patients compared with the highly susceptible lepromatous group. IL-12 release from PBMC of tuberculoid patients stimulated with Mycobacterium leprae was partially inhibited by mAbs to CD40 or CD40L, correlating with Ag-induced up-regulation of CD40L on T cells. Cognate recognition of M. leprae Ag by a T cell clone derived from a tuberculoid lesion in the context of monocyte APC resulted in CD40L-CD40-dependent production of IL-12. In contrast, M. leprae-induced IL-12 production by PBMC from lepromatous patients was not dependent on CD40L-CD40 ligation, nor was CD40L up-regulated by M. leprae. Furthermore, IL-10, a cytokine predominant in lepromatous lesions, blocked the IFN-gamma up-regulation of CD40 on monocytes. These data suggest that T cell activation in situ by M. leprae in tuberculoid leprosy leads to local up-regulation of CD40L, which stimulates CD40-dependent induction of IL-12 in monocytes. The CD40-CD40L interaction, which is not evident in lepromatous leprosy, probably participates in the cell-mediated immune response to microbial pathogens.

CD40 Antigens↗

Therapeutic immunization of HIV-infected chimpanzees using HIV-1 plasmid antigens and interleukin-12 expressing plasmids.

OBJECTIVE: To assess HIV-1 DNA vaccination and co-immunization with interleukin (IL)-12 and IL-10 as immunotherapy in the HIV-1 infected chimpanzee model system. METHODS: Four chimpanzees that were infected with HIV-1-IIIB for longer than 4 years and remained symptom free were immunized with HIV-1 plasmid vaccines. Two chimpanzees were immunized with DNA plasmids that encoded env/rev, gag/pol along with a plasmid that encoded both chains of human IL-12. A third animal was immunized with HIV-1 DNA vaccine constructs and co-immunized with an IL-10 expressing plasmid. Finally a control animal received the HIV-1 DNA vaccine constructs alone. RESULTS: There was no evidence of systemic toxicity associated with the administration of the DNA vaccines or the cytokine-expressing plasmids. We observed that the IL-12/HIV-1 DNA vaccinated animals had enhanced proliferative responses to multiple HIV-1 antigens at multiple time points. The animal that was co-immunized with HIV-1 and IL-10 did not have any changes in the proliferative responses. Finally, the control chimpanzee demonstrated moderate increases in the proliferative responses to HIV-1 antigens. The animal that received HIV-1 vaccines alone and the animals co-immunized with IL-12 all had declines in viral load over the course of the study, however, the decrease in viral loads were transient in all animals. CONCLUSION: Immunization of HIV-1 infected chimpanzees with DNA based vaccines containing the env, gag and pol genes can transiently boost the env specific proliferative responses. Co-administration of IL-12 expressing plasmids further leads to transient boosting of the proliferative response to the core protein, p24 as well. However, at these doses the impact on viral load is minimal.

AIDS Vaccines↗

Regional frontal abnormalities in schizophrenia: a quantitative gray matter volume and cortical surface size study.

BACKGROUND: Previous structural studies of the frontal lobe in schizophrenia have had somewhat inconsistent results, but most of them have measured the frontal lobe as a single brain structure. To investigate more specific abnormalities in frontal subregions, we measured gray matter volume and cortical surface size in 10 subregions in drug-naive patients during the early stages of the illness. METHODS: Magnetic resonance imaging was used to measure frontal subregions in 34 healthy male volunteers, and 26 male, drug-naive schizophrenia patients at early stages of the illness. Frontal subregions were manually traced using our locally developed parcellation method. RESULTS: Patients with schizophrenia had a significant deficit in cortical surface size in the right straight gyrus and left orbitofrontal cortex. No differences were found in gray matter volumes. CONCLUSIONS: Frontal structural abnormalities found in drug-naive schizophrenic patients appear to be subtle and circumscribed to ventral portions. Anomalies in the cortical surface size suggest neurodevelopmental abnormalities might occur during the early stages of the gyrogenesis. Further investigations are needed to explore the implications of paralimbic ventral frontal regions (i.e., straight gyrus and orbitofrontal cortex) in the pathophysiology of schizophrenia.

Adult↗

Genetic ablation of parathyroid glands reveals another source of parathyroid hormone.

The parathyroid glands are the only known source of circulating parathyroid hormone (PTH), which initiates an endocrine cascade that regulates serum calcium concentration. Glial cells missing2 (Gcm2), a mouse homologue of Drosophila Gcm, is the only transcription factor whose expression is restricted to the parathyroid glands. Here we show that Gcm2-deficient mice lack parathyroid glands and exhibit a biological hypoparathyroidism, identifying Gcm2 as a master regulatory gene of parathyroid gland development. Unlike PTH receptor-deficient mice, however, Gcm2-deficient mice are viable and fertile, and have only a mildly abnormal bone phenotype. Despite their lack of parathyroid glands, Gcm2-deficient mice have PTH serum levels identical to those of wild-type mice, as do parathyroidectomized wild-type animals. Expression and ablation studies identified the thymus, where Gcm1, another Gcm homologue, is expressed, as the additional, downregulatable source of PTH. Thus, Gcm2 deletion uncovers an auxiliary mechanism for the regulation of calcium homeostasis in the absence of parathyroid glands. We propose that this backup mechanism may be a general feature of endocrine regulation.

Animals↗

A population-based study of the effectiveness of inferior vena cava filter use among patients with venous thromboembolism.

BACKGROUND: There are few population-based data regarding the effectiveness of inferior vena cava filter use in the prevention of symptomatic pulmonary embolism. OBJECTIVE: To determine the 1-year cumulative incidence of rehospitalization for venous thrombosis or pulmonary embolism among patients with thromboembolism treated with a vena cava filter compared with the incidence in a control population with thromboembolism. PATIENTS AND METHODS: Population-based retrospective analysis of linked hospital discharge abstracts in California. From January 1, 1991, through December 30, 1995, 3632 patients were treated with a filter and 64,333 controls were admitted with a principal diagnosis of venous thromboembolism. RESULTS: Filter-treated patients had significantly greater comorbidity, with a higher frequency of previous pulmonary embolism, recent major bleeding, malignant neoplasm, and stroke. Patients who initially manifested pulmonary embolism were significantly more likely to be rehospitalized for pulmonary embolism than patients with an initial diagnosis of venous thrombosis alone, among filter-treated patients (relative risk, 6.72; 95% confidence interval, 3.61-12.49) and controls (relative risk, 5.30; 95% confidence interval, 4.61-6.10). Risk-adjusted proportional hazards modeling showed no significant difference between filter-treated patients and controls in the relative hazard of rehospitalization for pulmonary embolism. However, filter placement was associated with a significantly higher relative hazard of rehospitalization for venous thrombosis among patients who initially manifested pulmonary embolism (relative hazard, 2.62; 95% confidence interval, 2.09-3.29), but not among those who presented with venous thrombosis (relative hazard, 1.14; 95% confidence interval, 0.92-1.43). CONCLUSIONS: Insertion of a vena cava filter was not associated with a significant reduction in the 1-year incidence of rehospitalization for pulmonary embolism. Use of a filter was associated with a higher incidence of rehospitalization for venous thrombosis, but only among patients who initially manifested pulmonary embolism. A prospective clinical study is needed to determine the efficacy of filter use among patients with pulmonary embolism who do not meet strict guidelines for insertion of a vena cava filter.

Adult↗

LFA-3 plasmid DNA enhances Ag-specific humoral- and cellular-mediated protective immunity against herpes simplex virus-2 in vivo: involvement of CD4+ T cells in protection.

Adhesion molecules are important for cell trafficking and delivery of secondary signals for stimulation of T cells and antigen-presenting cells (APCs) in a variety of immune and inflammatory responses. Adhesion molecules lymphocyte function-associated antigen (LFA)-1 and CD2 on T cells recognize intercellular adhesion molecule (ICAM)-1 and LFA-3 on APCs, respectively. Recent studies have suggested that these molecules might play a regulatory role in antigen-specific immune responses. To investigate specific roles of adhesion molecules in immune induction we coimmunized LFA-3 and ICAM-1 cDNAs with a gD plasmid vaccine and then analyzed immune modulatory effects and protection against lethal herpes simplex virus (HSV)-2 challenge. We observed that gD-specific IgG production was enhanced by LFA-3 coinjection. However, little change in IgG production was observed by ICAM-1 coinjection. Furthermore, both Th1 and Th2 IgG isotype production was driven by LFA-3. LFA-3 also enhanced Th cell proliferative responses and production of interleukin (IL)-2, interferon-gamma, IL-4, and IL-10 from splenocytes. In contrast, ICAM-1 showed slightly increasing effects on T-cell proliferation responses and cytokine production. beta-Chemokine production (RANTES, MIP-1alpha, and MCP-1) was also influenced by LFA-3 or ICAM-1. When animals were challenged with a lethal dose of HSV-2, LFA-3-coimmunized animals exhibited an enhanced survival rate, as compared to animals given ICAM-1 or gD DNA vaccine alone. This enhanced protection appears to be mediated by CD4+ T cells, as determined by in vitro and in vivo T-cell subset deletion. These studies demonstrate that adhesion molecule LFA-3 can play an important role in generating protective antigen-specific immunity in the HSV model system through increased induction of CD4+ Th1 T-cell subset.

Animals↗

Synthesis and structures of new ternary aluminum chalcogenides: LiAlSe2, alpha-LiAlTe2, and beta-LiAlTe2.

The synthesis and crystal structures of new ternary aluminum chalcogenides, LiAlSe2, alpha-LiAlTe2, and beta-LiAlTe2, are reported. These compounds are synthesized by solid-state reaction at 800 degrees C. The single-crystal X-ray structures of these compounds have been determined. LiAlSe2: a = 68228(9) A, b = 8266(1) A, c = 65236(7) A, Pna2(1) (No 33, Z = 4) alpha-LiAlTe2: a = 65317(4) A, c = 116904(9) A, I42d (No 122, Z = 4) beta-LiAlTe2: a = 44810(6) A, c = 7096(1) A, P3m1 (No 156, Z = 1). These ternary compounds are formed by fusion of AlQ4 (Q = Se, Te) tetrahedra. LiAlSe2 shows beta-NaFeO2 structure type, which can be viewed as a wurtzite superstructure. alpha-LiAlTe2 adopts chalcopyrite structure type. In LiAlSe2 and alpha-LiAlTe2, AlQ4 (Q = Se, Te) tetrahedra share four corners to build three-dimensional structures and Li atoms are located in the tetrahedral sites between the chalcogen layers. beta-LiAlTe2 has polar layers formed by three-corner shared AlTe4 tetrahedra, and Li cations are in the distorted antiprisms between the layers. 7Li MAS NMR studies show that chemical shifts of Li in these ternary chalcogenides are nearly identical regardless of different chemical environments.

Journal Article↗

Mutation and expression of the p27KIP1 and p57KIP2 genes in human gastric cancer.

Cyclin-dependent kinase inhibitors (CDKI) are negative regulators of cell cycle progression by binding the cyclin-CDK complex and inhibiting the CDK activity. Genetic alteration in the CDKI genes has been implicated for carcinogenesis. To test the genetic alteration in the p27 and p57 genes, KIP family CDKI genes, 30 gastric tumor-normal pairs and 8 gastric cancer cell lines were analyzed for mutations by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP). No mutation was detected in these genes although length polymorphisms in the proline-alanine repeat of the p57 gene were detected. When the p27 and p57 mRNAs were analyzed in gastric cancer cell lines by RT-PCR, the p27 mRNA was expressed considerably high in tumor cells but expression of the p57 mRNA was much low in gastric cancer cell lines compared to that of normal cells. The result suggests that inactivation of gene expression rather than mutations in the p57 gene accounts possibly for the involvement of this gene in tumorigenesis of gastric cancer. However, expression of the p27 gene seems to be essential for cell survival.

Cell Cycle Proteins↗

Protective effect of etomidate on kainic acid-induced neurotoxicity in rat hippocampus.

The goal of this study was to determine whether etomidate has protective effect against kainic acid (KA)-induced neurotoxicity. Administration of etomidate (20 mg/kg i.p.) was performed in sequence, first being just 1 h after KA (10 mg/kg i.p.) injection, then three times at 1-h intervals. Neuronal damages in hippocampus were evaluated by using the acid fuchsin stain to detect cell death and the heat shock protein-70 (HSP-70) induction as an index of cell injury at 24 h after the administration of KA. HSP-70 induction and acid fuchsin positive neurons were increased in CA1 and CA3 regions of hippocampus after KA injection but significantly decreased by etomidate-injection. These results suggest that the etomidate hold potential effect on the protection of neurons against KA-induced neurotoxicity.

Animals↗

Modulation of EWS/WT1 activity by the v-Src protein tyrosine kinase.

Desmoplastic small round cell tumor (DSRCT) is a malignant human cancer that is associated with a specific t(11;22) chromosome translocation, where 265 amino acids from the EWS amino-terminus are fused to the DNA binding domain of the WT1 tumor suppressor gene. We have noticed the presence of several SH3 interacting domains within the amino-terminus of EWS and have assessed the potential of EWS/WT1 to interact with such motifs. We find that EWS/WT1 can associate with the SH3 domain of several proteins, including v-Src. Ectopic expression of v-Src phosphorylates EWS/WT1 in vivo, as well as enhances the transactivation ability of the EWS amino-terminal domain. Structural alteration of the v-Src SH2 or SH3 domains produced mutants that could not interact with EWS/WT1 nor augment the transcriptional properties of EWS. Taken together, our results suggest the possibility that some transcriptional properties of EWS/WT1 may be regulated by a cytoplasmic signaling pathway.

Amino Acid Motifs↗

An observation on the mercury contents of scalp hair in the urban residents of South Korea.

The average value of total mercury (THg) in scalp hair of male residents in Seoul city was 1.7+/-0.18 ppm (mean+/-S.E.) and that of methylmercury (MeHg), 1.0+/-0.12 ppm (58.8% THg). In female, level of THg was 1.1+/-0.15 ppm and MeHg was 0.5+/-0.14 ppm (45.5%). Mercury was found more in the scalp hair of male than female (P<0.01). THg/MeHg increased with age of subjects in male (P<0.01), but not female. Coefficients of correlation (r) between THg and MeHg contents in scalp hair of male was +0.877 (P<0.01) and that of female was +0.508 (P<0.01), respectively.

Journal Article↗

Effective inhibition of human cytomegalovirus gene expression and replication by a ribozyme derived from the catalytic RNA subunit of RNase P from Escherichia coli.

A sequence-specific ribozyme (M1GS RNA) derived from the catalytic RNA subunit of RNase P from Escherichia coli was used to target the overlapping exon 3 region of the mRNAs encoding the major transcription regulatory proteins IE1 and IE2 of human cytomegalovirus. A reduction of more than 80% in the expression levels of IE1 and IE2 and a reduction of about 150-fold in viral growth were observed in human cells that stably expressed the ribozyme. In contrast, a reduction of less than 10% in the IE1/IE2 expression and viral growth was observed in cells that either did not express the ribozyme or produced a "disabled" ribozyme that carried mutations that abolished its catalytic activity. Examination of the expression of several other viral early and late genes in the cells that expressed the M1GS ribozyme further revealed an overall reduction of at least 80% in their expression. These results are consistent with the notion that the antiviral effects in these cells are due to the fact that the ribozyme specifically inhibits the expression of IE1 and IE2 and, consequently, abolishes the expression of viral early and late genes as well as viral growth. Our study is the first, to our knowledge, to use M1GS ribozyme for inhibiting human cytomegalovirus replication and demonstrates the utility of this ribozyme for antiviral applications.

Antiviral Agents↗

Fringe forms a complex with Notch.

The Fringe protein of Drosophila and its vertebrate homologues function in boundary determination during pattern formation. Fringe has been proposed to inhibit Serrate-Notch signalling but to potentiate Delta-Notch signalling. Here we show that Fringe and Notch form a complex through both the Lin-Notch repeats and the epidermal growth factor repeats 22-36 (EGF22-36) of Notch when they are co-expressed. The Abruptex59b (Ax59b) and AxM1 mutations, which are caused by missense mutations in EGF repeats 24 and 25, respectively, abolish the Fringe-Notch interaction through EGF22-36, whereas the l(1)N(B) mutation in the third Lin-Notch repeat of Notch abolishes the interaction through Lin-Notch repeats. Ax mutations also greatly affect the Notch response to ectopic Fringe in vivo. Results from in vitro protein mixing experiments and subcellular colocalization experiments indicate that the Fringe-Notch complex may form before their secretion. These findings explain how Fringe acts cell-autonomously to modulate the ligand preference of Notch and why the Fringe-Notch relationship is conserved between phyla and in the development of very diverse structures.

Animals↗