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Biomedical subjects

K C Jung

Publications and source records attributed to K C Jung.

At least 19 recordsLinked to original sources
PubMed2006

Fatty acids, inhibitors for the DNA binding of c-Myc/Max dimer, suppress proliferation and induce apoptosis of differentiated HL-60 human leukemia cell.

c-Myc is instrumental in the progression of Burkitt's lymphoma including HL-60 human leukemia cells. We tested fatty acids for their inhibitory effect on the DNA binding of c-Myc/Max dimeric proteins of human origin, prepared as recombinant proteins encompassing DNA binding (basic) and dimerization (HLHZip) domain, and found that those suppress proliferation and induce apoptosis of DMSO-differentiated HL-60 cells. The analyzed IC50 values of myristic acid, stearic acid, gamma-linolenic acid, linoleic acid, linolenic acid and arachidonic acid by EMSA were 97(+/-3), 2.2(+/-1.2), 55(+/-5), 32(+/-2), 62(+/-12), 22(+/-2)microM for DNA binding of recombinant c-Myc/Max, respectively. According to the results shown by XTT assay, their influence on proliferation was quite different from the rank order of IC50. Whereas the degree of influence of the unsaturated fatty acids on the proliferation of DMSO-differentiated HL-60 cells was similar, the influence of saturated fatty acids, stearic acid in particular, was very weak at same concentrations. In addition, we confirmed that these fatty acids have no influence on the expression of c-Myc in DMSO-differentiated HL-60 cells. Our experiments demonstrated that the inhibitors for the DNA binding of c-Myc/Max contribute to the downregulation of Myc-dependent proliferation and to the inducement of apoptosis, and serve as an exploration of potent new inhibitors.

Apoptosis↗
PubMed2005

Molecular cloning and characterization of bovine PRKAG3 gene: structure, expression and single nucleotide polymorphism detection.

The protein kinase adenosine monophosphate-activated gamma3-subunit (PRKAG3) gene encodes a muscle-specific isoform of the regulatory gamma-subunit of adenosine monophosphate-activated protein kinase, which plays a key role in regulating energy homeostasis in eucaryotes. It is well known that mutations in the PRKAG3 gene affect high glycogen content in the porcine skeletal muscle and, consequently, meat quality. The genomic structure and sequence of the bovine PRKAG3 were analysed from a Korean cattle BAC clone. The bovine PRKAG3 gene comprises 13 exons and spans approximately 6.8 kb on BTA2. From 5' and 3'-rapid amplification of cDNA ends experiments, the full-length cDNA of bovine PRKAG3 has been identified, encoding a deduced protein of 465 amino acids. Two splice isoforms, generated by the alternative splicing of exon 2, were also identified. Northern blot analysis demonstrated that, similar to other species, the bovine PRKAG3 transcript was only expressed in skeletal muscle. Seven single nucleotide polymorphisms, including two previously identified variants, were detected in four Bos taurus cattle breeds. The bovine PRKAG3 gene described in this study may be involved in muscle-related genetic diseases or meat quality traits in cattle.

Amino Acid Sequence↗
PubMed2004

Production and the characterization of monoclonal antibody against CD43, K06.

A monoclonal antibody against human CD43 has been developed and designated as K06. Its reactivity in the lymphoid organs was different from that of known anti-CD43 monoclonal antibodies suggesting that this may recognize a novel epitope of human CD43 molecule. The CD43 epitope detected by anti-K06 monoclonal antibody was highly expressed in cortical thymocytes, platelets, and myeloid cells of normal peripheral blood, and its reactivity was comparable to that of known anti-CD43 monoclonal antibodies. However, the density of this epitope was lower in the medullary thymocytes. Biochemical studies indicated that anti-K06 monoclonal antibody could recognize glycosylated moiety of CD43 antigen. The expression profile of anti-K06 monoclonal antibody in several cell lines was somewhat different from that of known anti-CD43 antibodies. In addition, CD43 ligation through the K06 epitope appeared to induce apoptosis in human leukemic cell line, Molt-4. We therefore assume that K06 epitope of human CD43 might have some role in T-cell development.

Antibodies, Monoclonal↗
PubMed2003

Association of maspin expression with the high histological grade and lymphocyte-rich stroma in early-stage breast cancer.

AIMS: Maspin is a recently described member of the serpin family or protease inhibitors that is known to be a tumour suppressor gene product. Loss of maspin expression has been found in most breast cancer cases and is correlated with cell motility and tumour invasiveness. However, its precise role in human breast cancer remains to be discovered. We aimed to evaluate the role of maspin in early-stage breast cancer. METHODS AND RESULTS: We analysed the expression of maspin in 192 stage I and II primary breast cancers by immunohistochemistry. Of these cases, 34.4% showed maspin expression. Maspin expression was more frequently found in invasive ductal carcinoma (36.4%) than in invasive lobular carcinoma (7.1%). High maspin expression was demonstrated in breast cancers showing high histological grade or lymphocyte-rich stroma (P < 0.05). Maspin expression was not associated with overall and disease-free survival rate of breast cancer. CONCLUSIONS: The results indicate that different biological mechanisms may be responsible for maspin expression in histologically distinct types of breast cancer. Our survey suggests that maspin expression in breast cancer might have a compensatory role rather than prognostic one.

Adenocarcinoma↗
PubMed2001

CD99 expression is positively regulated by Sp1 and is negatively regulated by Epstein-Barr virus latent membrane protein 1 through nuclear factor-kappaB.

Epstein-Barr virus (EBV)-encoded latent membrane protein-1 (LMP1) is highly expressed in Hodgkin and Reed-Sternberg (H-RS) cells from patients with EBV-associated Hodgkin disease. It was previously demonstrated that CD99 can be negatively regulated by LMP1 at the transcriptional level, and the decreased expression of CD99 in a B lymphocyte cell line generates H-RS-like cells. In this study, detailed dissection of the CD99 promoter region was performed to search regulatory factor(s) involved in the expression of the gene. Using various mutant constructs containing deletions in the promoter region, it was revealed that the maximal promoter activity was retained on 5'-deletion to the position -137 from the transcriptional initiation site. Despite the presence of multiple putative Sp1-binding sites in the promoter region, the site located at -95 contributes heavily as a positive cis-acting element to its basal promoter activity. However, on examination of the involvement of the positive-acting Sp1-binding site of the promoter for the repressive activity of LMP1, it appeared to be dispensable. Instead, the repressive effect was mapped to the nuclear factor (NF)-kappaB activation domains in the cytoplasmic carboxyl terminus of LMP1 despite the absence of the NF-kappaB consensus sequences in the CD99 promoter region. Furthermore, the decreased CD99 promoter activity by LMP1 was markedly restored when NF-kappaB activity was inhibited. Taken together, these data suggest that Sp1 activates, whereas LMP1 represses, transcription from the CD99 promoter through the NF-kappaB signaling pathway, and they might aid in the understanding of the molecular mechanisms of viral pathogenesis in EBV-positive Hodgkin disease. (Blood. 2001;97:3596-3604)

12E7 Antigen↗
PubMed2001

CD99 regulates the transport of MHC class I molecules from the Golgi complex to the cell surface.

The down-regulation of surface expression of MHC class I molecules has recently been reported in the CD99-deficient lymphoblastoid B cell line displaying the characteristics of Hodgkin's and Reed-Sternberg phenotype. Here, we demonstrate that the reduction of MHC class I molecules on the cell surface is primarily due to a defect in the transport from the Golgi complex to the plasma membrane. Loss of CD99 did not affect the steady-state expression levels of mRNA and protein of MHC class I molecules. In addition, the assembly of MHC class I molecules and the transport from the endoplasmic reticulum to the cis-Golgi occurred normally in the CD99-deficient cells, and no difference was detected between the CD99-deficient and the control cells in the pattern and degree of endocytosis. Instead, the CD99-deficient cells displayed the delayed transport of newly synthesized MHC class I molecules to the plasma membrane, thus causing accumulation of the molecules within the cells. The accumulated MHC class I molecules in the CD99-deficient cells were colocalized with alpha-mannosidase II and gamma-adaptin in the Golgi compartment. These results suggest that CD99 may be associated with the post-Golgi trafficking machinery by regulating the transport to the plasma membrane rather than the endocytosis of surface MHC class I molecules, providing a novel mechanism of MHC class I down-regulation for immune escape.

12E7 Antigen↗
PubMed2001

Expression of leukemia-associated antigen, JL1, in bone marrow and thymus.

The identification of immunophenotypic markers with restricted expression has long been a critical issue in diagnostic and therapeutic advances for acute leukemias. We previously developed a monoclonal antibody against a new thymocyte surface antigen, JL1, and showed that JL1 is expressed in the majority of acute leukemia cases. In this study, using multiparameter flow cytometric analyses, we found that JL1 was uniquely expressed in subpopulations of normal bone marrow (BM) cells, implying the association of JL1 with the differentiation and maturation process. Although CD34(+) CD10(+) lymphoid precursors and some of maturing myeloid cells express JL1, neither CD34(+) CD38(-/lo) nor CD34(+) AC133(+) noncommitted pluripotent stem cells do. As for the myeloid precursors, CD34(+) CD33(+) cells do not express JL1. During lymphopoiesis, JL1 on the earliest lymphoid precursors disappear in the CD20(+) sIgM(+) stage of B-cell development or after CD1a down-regulation in thymocytes. Despite the highly restricted expression of JL1 in normal BM cells, most of the leukemias express JL1 irrespective of their immunophenotypes. These results indicate that JL1 is not only a novel differentiation antigen of hematopoietic cells, but also a leukemia-associated antigen. Therefore, we suggest that JL1 be a candidate molecule in acute leukemia for the diagnosis and immunotherapy that spares the normal BM stem cells.

Adult↗
PubMed2001

Methylation of the hMLH1 promoter in multiple gastric carcinomas with microsatellite instability.

Hypermethylation of the hMLH1 promoter is observed in the majority of sporadic gastric carcinomas with high frequency microsatellite instability (MSI), and it contributes to the genesis of MSI-positive gastric carcinoma. Multiple gastric carcinoma is known to have a higher frequency of MSI positivity than single gastric carcinoma. However, the molecular basis of MSI in these tumors remains obscure. We investigated the role of hMLH1 promoter hypermethylation in the genesis of multiple gastric carcinoma with MSI. We analyzed 33 tumors from 15 patients with multiple gastric carcinoma (12 double tumors and three triple tumors) for MSI, expression of hMLH1 and hMSH2, and hypermethylation of hMLH1 and hMSH2 promoters. High frequency MSI was found in seven out of 33 tumors (21%) in five out of 15 patients (33%). All of the tumors with high frequency MSI had a lack of hMLH1 expression, with the presence of hMSH2 expression, while all the tumors with no MSI or low frequency MSI were positive for both hMLH1 and hMSH2. All of the tumors with no expression of hMLH1 had hMLH1 hypermethylation, whereas hMLH1 hypermethylation was observed in two out of 26 (8%) tumors with no or low frequency MSI. None of the tumors showed hMSH2 hypermethylation. These results suggest that epigenetic changes in the hMLH1 promoter account for the genesis of multiple gastric carcinoma with high frequency MSI.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Costimulatory effect of Fas in mouse T lymphocytes.

To induce proper immune responses, T lymphocytes require two types of stimuli, antigen-specific and costimulatory signals. Among costimulatory molecules, CD28-engagement promotes the survival and proliferation of both naive and memory T cells. In addition, it is now believed that Fas may play a role in T cell activation in the human system. It is, however, controversial whether Fas can act as a costimulatory signal in the murine system. Thus, we investigated fundamental differences in the capacity to induce proliferation of T cells between Fas and CD28 in mice. Fas-mediated T cell proliferation was observed only with a full mitogenic dose of anti-CD3 antibodies, whereas CD28 engagement was able to enhance T cell proliferation in the presence of a suboptimal level of anti-CD3 antibody. Furthermore, Fas-engaged T cells showed faster response in the upregulation of CD25 and CD69 expression than CD28-engaged ones. Here, we report that Fas might play a role in mature T cell activation in the mouse system through a different mechanism from that in CD28 costimulation.

Animals↗
PubMed2000

5' CpG island methylation of p16 is associated with absence of p16 expression in glioblastomas.

Recent evidence shows that transcriptional silencing as a consequence of hypermethylation of CpG islands is an important mechanism in the inactivation of p16INK4 tumor suppressor gene. This study is designed to clarify the significance of p16INK4 hypermethylation in 23 cases of glioblastomas (GBMs) by methylation-specific polymerase chain reaction (PCR) and p16 immunostaining. Fourteen cases (60.9%) out of 23 GBMs revealed hypermethylation on p16. p16 immunostaining revealed that 13 (93%) of these 14 hypermethylation cases showed complete loss of immunoreactivity and only one (7%) case retained immunoreactivity. Among 9 methylation-negative cases, 4 were immunonegative, which might be related to mutations or deletions other than hypermethylation. The most significant finding was that of 17 cases with immunonegativity, 13 cases (76.5%) showed hypermethylation. We reconfirmed that p16 hypermethylation may be one of the major mechanisms of tumorigenesis of GBMs and the results between the methylation specific-PCR study and p16 immunostaining had a good correlation.

5' Untranslated Regions↗
PubMed1999

Development of new adherent mutant from human myeloma-derived cell line: in vitro model of anaplastic transformation of myeloma.

Anaplastic myeloma is a rare but distinct, biologically aggressive variant of myeloma which usually results from dedifferentiation or anaplastic transformation of the myeloma cells. The molecular mechanisms that determine the biologic behavior of anaplastic myeloma and effective treatment modalities have not been well known due to lack of in vitro models. In the present study, we have developed an anaplastically transformed mutant from a human myeloma-derived cell line. In the process of long-term culture of the myeloma-derived IM-9 cell line in low serum and nutrient conditions, an adherent mutant line was developed and named IM-9/AD. This mutant cell line displayed several characteristics resembling anaplastic myeloma such as: 1, large cells with large vesicular nucleus and prominent nucleolus, multinuclearity and high mitotic figures; 2, loss of leukocyte-associated antigens; and 3, higher tumorigenecity in scid mice than its parental cell line. This newly developed mutant cell line may serve as a readily available in vitro model to investigate the biology of anaplastic myeloma.

Animals↗
PubMed1999

LFA-1- and ICAM-1-dependent homotypic aggregation of human thymocytes induced by JL1 engagement.

Cell-cell adhesion is essential for the appropriate immune response, differentiation, and migration of lymphocytes. This important physiological event is reflected in vitro by homotypic cell aggregation. We have previously reported that a 120 kDa cell surface glycoprotein, JL1, is a unique protein specifically expressed by immature double positive (DP) human thymocytes which are in the process of positive and negative selections through the interaction between thymocyte and antigen-presenting cells (APCs). The function of the JL1 molecule, however, is yet to be identified. We show here that anti-JL1 monoclonal antibody (mAb) induced the homotypic aggregation of human thymocytes in a temperature- and Mg2+-dependent manner. It required an intact cytoskeleton and the interaction between leucocyte function associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) since it was blocked by cytochalasin B and D, and mAb against LFA-1 and ICAM-1 which are known to be involved in the aggregation of thymocytes. Translocation of phosphatidylserine (PtdSer) through the cell membrane was not detected, implying that the molecular mechanism of JL-1-induced homotypic aggregation is different from that of CD99-induced homotypic aggregation. In summary, JL1 is a cell surface molecule that induces homotypic adhesion mediated by the LFA-1 and ICAM-1 interaction and cytoskeletal reorganization. These findings suggest that JL1 may be an important regulator of thymocyte development and thymocyte-APC interaction.

Antibodies, Monoclonal↗
PubMed1999

Reduced expression of CD99 and functional disturbance in anencephalic cortical thymocytes.

In a significant proportion of cases, anencephaly is associated with thymic enlargement, suggesting a possibility that anencephalic fetuses have a functional disturbance in thymocyte differentiation and development. In this report, we demonstrated that CD99 expression was consistently reduced in cortical thymocytes of all anencephalic fetuses. In addition, the CD99-dependent aggregation of immature cortical thymocytes was almost completely impaired and apoptosis of thymocytes was markedly reduced in several cases. These results are in agreement with previous findings that CD99 regulates the aggregation and apoptosis of various types of cells. These data strongly suggest that functional disturbance of thymocytes and thymic hyperplasia are related to the reduced expression of CD99 molecule in anencephalic fetuses.

12E7 Antigen↗
PubMed1998

Engagement of CD99 induces up-regulation of TCR and MHC class I and II molecules on the surface of human thymocytes.

CD99 is a cell surface molecule involved in the aggregation of lymphocytes and apoptosis of immature cortical thymocytes. Despite its high level expression on immature cortical thymocytes, the functional roles of this molecule during thymic selection are only now being elucidated. Examination of the effects of CD99 engagement on the expression kinetics of the TCR and MHC class I and II molecules, which are involved primarily in thymic positive selection, revealed a marked up-regulation of these proteins on the surface of immature thymocytes. This increase was the result of accelerated mobilization of molecules stored in cytosolic compartments to the plasma membrane, rather than increased RNA and protein synthesis. Confocal microscopic analysis revealed the changes in subcellular distribution of these molecules. When CD99 was engaged, TCR and MHC class I and II molecules were concentrated at the plasma membrane, particularly at cell-cell contact sites. The TCRlow subpopulation of immature double positive thymocytes was much more responsive to CD99-mediated up-regulation than was the TCRhigh population. These findings suggest that CD99-dependent up-regulation may have possible implication in positive selection during thymocyte ontogeny.

12E7 Antigen↗
PubMed1998

Development of a new anti-CD4 monoclonal antibody (YG23) which inhibits the formation of colonies of human bone marrow progenitor cells.

We have previously reported CD4 expression in CD34+ hematopoietic progenitor cells and suggested a role of CD4 in normal hematopoiesis and its possible relationship with the pathogenesis of acquired immunodeficiency syndrome (AIDS). To investigate whether CD4 expression in bone marrow progenitor cells can explain bone marrow suppression in AIDS, monoclonal antibodies (mAbs) against human CD4 were developed by immunizing Balb/c mice with human thymocytes. Three mAbs completely blocked the binding of Leu3a antibody, a well-known anti-CD4 mAb, to thymocytes, which indicates overlap between the epitopes recognized by these and Leu3a antibodies. Interestingly, one of these mAbs, YG23, significantly inhibited colony formation of human bone marrow progenitor cells treated with GM-CSF. This is the first demonstration that ligation of CD4 by an anti-CD4 mAb suppresses GM-CSF mediated proliferation and differentiation of human hematopoietic progenitor cells by modifying the intracellular signaling pathway through CD4 molecules. Based on these findings, we propose that alteration of CD4 signaling by either cross-linked gp120 or antibodies directed against a certain epitope shared with the YG23 binding site of the CD4 molecule may play a role in bone marrow dysfunction in AIDS patients.

Animals↗
PubMed1997

Thymocytes positively select thymocytes in human system.

We previously demonstrated the expression of MHC class II molecules in a significant percentage of human fetal and postnatal thymocytes. These results, at that time, raised the question as to whether the MHC class II molecules on immature thymocytes could actively be involved in the selection of immature T cells. We have developed a human reaggregate culture system to address this issue. Surprisingly, despite the fact that thymic epithelial cells (TECs) have been shown to be a major selecting cell type of positive selection, we were clearly able to see the involvement of MHC class II+ thymocytes during selection process through T-T interaction. In addition, maturation to single positive (SP) cells occurred only in the presence of MHC class II molecules and immature thymocytes were found to be arrested at the double positive (DP) stage of differentiation by blocking of TCR recognition of MHC class II molecules. All these results strongly suggest that human MHC class II+ thymocytes actively participate in the selection of the TCR repertoire, for which TCR recognition of peptide/MHC class II may be an initial determining step.

Cell Aggregation↗