Biomedical subjects

D H Chung

Publications and source records attributed to D H Chung.

At least 37 records · Page 2Linked to original sources

PubMed2000

Three cases of pancreas allograft dysfunction.

We present dincopathologic features of three cases of biopsy-proven pancreas allograft dysfunction in Korea. All patients had advanced insulin-dependent diabetes mellitus (IDDM). Case 1 was a 30-year-old woman who underwent a simultaneous pancreas-kidney transplantation. Urinary infection developed 6 days after the operation, which remitted and reappeared, when urine amylase level was normal. Since the 55th day after the operation, intermittent hematuria has persisted. Cytomegalovirus inclusions were detected on the urinary bladder and grafted duodenal mucosa. The graft was removed due to perforation of the grafted duodenum and panperitonitis. Case 2 was a 27-year-old man undergoing pancreas transplantation alone (PTA). Ten days after the transplatation, the level of 24 urine amylase decreased and the graft was not delineated by 99mTc DTPA scintigraphy. Allograft needle biopsy revealed multiple acinar cell necrosis and mild lymphocytic infiltration which were compatible with mild acute rejection. Case 3 was a 25-year-old man undergoing cadevaric PTA. Three months after the transplantation, graft was removed due to gastric perforation associated with cytomegalovirus and angiodestructive fungal infection. Various causes of pancreas allograft dysfunction can be diagnosed by needle biopsy, thus appropriate biopsy specimen should be taken using improved biopsy technique.

Adult↗

PubMed2000

A novel point mutation of the splicing donor site in the intron 2 of the plasmin inhibitor gene.

Plasmin inhibitor (PI) is a major physiological inhibitor of plasmin-mediated fibrinolysis; hence, its deficiency results in a severe haemorrhagic diathesis. We analyzed the PI gene of a French boy apparently homozygous for PI deficiency and his heterozygous parents. Both alleles of the homozygous patient had a novel G to A transition at the consensus splicing donor site in the intron 2 of the PI gene. In an expression assay using the heterologous cells transfected with the mutant PI expression vector, 3 types of aberrant transcripts using a cryptic splicing donor site within the intron 2 were detected. All of these mRNAs had a stop codon upstream of the cryptic splicing site and encode only 25 amino acids, comprising the first 21 amino acids of the signal peptide (27 amino acids) plus 4 new amino acids. This mutant was designated as PI-Paris-Trousseau.

Animals↗

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

NK and CTL recognition of a single chain H-2Dd molecule: distinct sites of H-2Dd interact with NK and TCR.

We generated transgenic mice expressing a single-chain beta2-microglobulin (beta2m)-H-2Dd. The cell-surface beta2m-H-2Dd molecule was expressed on a beta2m-deficient background and reacted with appropriate mAbs. It was of the expected m.w. and directed the normal development of CD8+ T cells in the thymus of a broad TCR repertoire. It also presented both exogenously provided and endogenous peptide Ags to effector CD8+ T cells. In tests of NK cell education and function, it failed to reveal any interaction with NK cells, suggesting that the site of the interaction of NK receptors with H-2Dd was disrupted. Thus, the sites of TCR and NK receptor interaction with H-2Dd are distinct, an observation consistent with independent modes of TCR and NK receptor evolution and function.

Animals↗

PubMed1999

Inflammatory pseudotumor of carotid artery: a case report.

Inflammatory pseudotumor is an uncommon round and spindle cell proliferative lesion of unknown etiology that occurs most commonly in the lung. But it also occurs in diverse extrapulmonary locations such as the abdomen, retroperitoneum, pelvis, heart, head and neck, upper respiratory tract, trunk, bladder and extremities. The extrapulmonary inflammatory pseudotumor is often larger, less well circumscribed and multinodular. Proximity of the tumor to vital structures or involvement of vital organs compromises the opportunity for complete resection, thus higher recurrence rates are often reported even after surgical treatment. The authors report a case of inflammatory pseudotumor originating from the common carotid artery in a 42-year-old female patient with a rapidly growing neck mass, treated by en-bloc resection of inflammatory pseudotumor and a long segment of common carotid artery followed by PTFE graft interposition.

Adult↗

PubMed1999

Thrombomodulin with the Asp468Tyr mutation is expressed on the cell surface with normal cofactor activity for protein C activation.

Thrombomodulin (TM) is an endothelial cell glycoprotein that acts as an anticoagulant. Mutation in the TM gene is a potential risk factor for thrombosis. The first TM mutation identified was a heterozygous substitution of T for G at nucleotide position 1456, which predicted Asp468 with Tyr in a Ser/Thr-rich domain. To evaluate the reported TM gene mutation as a possible cause of thrombosis, we transiently tranfected a vector for TM gene carrying the mutation to mammalian COS7 cells. TM antigen levels in lysates of cells transfected with variant TM were comparable to those in preparations of normal TM. The TM cofactor activity for protein C (PC) activation on the variant TM-expressing cells was similar to that of the control. The Michaelis constant Km and Vmax. of variant TM for PC activation were shown to be similar compared to those of normal TM. The affinity of each TM for thrombin in PC activation was also similar. We obtained several stable cell lines expressing normal and variant TM. Lysate of the cell lines with normal and variant TM genes had a similar expression level of TM antigen. Pulse-chase analysis showed that normal and variant TM were glycosylated and resistant to endoglycosidase H, indicating that the variant TM was expressed on the cell surface in a mature form. Variant TM protein is apparently expressed on the cell surface with normal cofactor activity for PC activation. It is unlikely that the TM variant directly causes thrombosis by mechanism of reduced expression or impaired cofactor activity for PC activation, which comprises a major anticoagulant activity of TM.

Animals↗

PubMed1999

Clonal analysis of a solitary follicular nodule of the thyroid with the polymerase chain reaction method.

Solitary follicular nodules of the thyroid occasionally create a diagnostic problem, especially in the differential diagnosis between adenoma and nodular hyperplasia To obtain confident histologic parameters of clonal lesions, we analyzed DNA samples prepared from paraffin-embedded archival tissue from 20 solitary follicular nodules of the thyroid for clonality with the polymerase chain reaction (PCR) method. On the base of X chromosome inactivation mosaicism, we tested restriction fragment-length polymorphism of the phosphoglycerate kinase (PGK) gene and a highly polymorphic short tandem repeat of the human androgen receptor (HUMARA) gene. Of 18 informative cases, 10 were monoclonal, 7 were polyclonal, and 1 showed microsatellite instability. All of the five completely encapsulated nodules were monoclonal. Four of the five unencapsulated nodules showed polyclonality. Of the seven partially encapsulated nodules, four were monoclonal, and the others were polyclonal. The former showed 50% or more of encapsulation degree, whereas the latter showed less than 50%. The capsule tended to be thicker in monoclonal nodules (mean, 0.33 mm) than in polyclonal nodules (mean, 0.13 mm). Other histologic features of the nodules and surrounding parenchymal changes had no significance with respect to predicting clonality. This study suggests that the degree of encapsulation and capsular thickness are morphologically important for predicting the clonality of the thyroid nodule.

Adult↗

PubMed1998

Generation of cells with Hodgkin's and Reed-Sternberg phenotype through downregulation of CD99 (Mic2).

Despite the fact that Hodgkin's and Reed-Sternberg (H-RS) cells are morphological hallmarks of Hodgkin's disease (HD), the nature of H-RS cells still remains to be resolved. Here we report that downregulation of CD99 (Mic2) leads to the generation of cells with an H-RS phenotype. IM9 and BJAB B-cell lines that were transfected with an antisense CD99 expression construct showed the morphological and immunological characteristics of H-RS cells such as multinuclearity, expression of CD15, decreased expression of major histocompatibility complex (MHC) class I and CD45RB, and deregulated secretion of cytokines. The reduced expression of CD99 was also confirmed in H-RS cells of patient's lymph nodes and three HD-derived cell lines, L428, KM-H2, and HDLM-2. Moreover, features characteristic of H-RS cells were completely abolished by forced expression of CD99 and by a constitutively active form of Rac, which functions downstream of CD99. We suggest that CD99 molecules play a crucial role in regulating functions and morphology of cells through a Rac-Rho signaling pathway and that the loss of CD99 expression is a significant molecular event to generate H-RS cells.

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↗

PubMed1998

ILK (beta1-integrin-linked protein kinase): a novel immunohistochemical marker for Ewing's sarcoma and primitive neuroectodermal tumour.

ILK (beta1-integrin-linked protein kinase) is a recently identified 59-kDa serine/threonine protein kinase that interacts with the cytoplasmic domain of the beta1-integrin containing four ankyrin-like repeats. We have developed a polyclonal antibody against ILK and explored the ILK immunoreactivity in normal human cells and tissues. ILK was mainly expressed in cardiac muscle and skeletal muscles. Surprisingly, ILK expression was observed in Ewing's sarcoma (ES; 100%), primitive neuroectodermal tumour (PNET; 100%), medulloblastoma (100%), and neuroblastoma (33.3%), whereas other small round cell sarcomas were not stained by the anti-ILK antibody. These results suggest that ILK could be a novel marker for tumours with primitive neural differentiation. Our findings support the notion that ES is a tumour that is closely related to PNET and that both originate from the neuroectoderm. ILK may be a sensitive and specific immunohistochemical marker and useful for the positive identification of ES and PNET in formalin-fixed, paraffin-embedded tissue sections.

Adolescent↗

PubMed1998

Engagement of CD99 induces apoptosis through a calcineurin-independent pathway in Ewing's sarcoma cells.

Programmed cell death (PCD) is a prominent feature of the development of the immune and nervous systems. In both systems, widespread PCD occurs in primitive progenitor cells during development. In this study, we demonstrated that Ewing's sarcoma (ES) cells, undifferentiated neural precursors, underwent apoptosis upon engagement of CD99 with anti-CD99 monoclonal antibody. Apoptosis via CD99 occurred only in the undifferentiated state of ES cells, but not in differentiated ES cells. CD99-induced apoptosis in ES cells appeared to require de novo synthesis of RNA and protein as well as caspase activation. Cyclosporin A, known to be a potent inhibitor of both calcineurin activation and mitochondrial permeability transition pore opening, inhibited CD99-mediated apoptosis, whereas FK-506, a specific calcineurin inhibitor, did not, indicating the induction of CD99-mediated apoptosis through a calcineurin-independent pathway. Furthermore, the dying cells displayed the reduction of mitochondrial transmembrane potential (delta psi m). These results suggest that CD99 engagement induce CsA-inhibitable mitochondrial permeability transition pore opening, followed by a reduction of delta psi m and caspase activation, thereby leading to apoptosis. Based on these results, we suggest the possible involvement of CD99 in the apoptotic processes that occur during nervous system development and also its application in immunotherapeutic trials for ES cases.

12E7 Antigen↗

PubMed1998

Central venous catheter access.

Central venous access for the purpose of supplying parenteral nutrition to the pediatric age group requires a careful definition of the patient's caloric need, estimated duration of therapy, and an assessment of available sites. Peripheral vein parenteral nutrition is limited by caloric density of the nutrient fluids, while peripherally inserted central catheters (PICC) offers a new technology for accessing central veins while obviating the risk of central vein access. Routes of central vein access are several and there are also a variety of catheters available for placement. Tunneled percutaneous placement of silicone rubber cuffed catheters via the subclavian vein approach is that technique we use most commonly. The risks of such access catheters include mechanical risks of placement, venous thrombosis of the access sites, and most importantly catheter related infections, either at the exit site, the subcutaneous tunnel or pouch, or even generalized sepsis. With a full knowledge of the spectrum of access techniques, access materials, and risks, safe total parenteral nutrition can be safely delivered to the children in need.

Catheterization, Central Venous↗

PubMed1998

Fundoplication and gastrostomy.

Fundoplication and gastrostomy are among the most frequently performed procedures in infants and children. A laparoscopic approach with decreased morbidity has made fundoplication (with or without gastrostomy) more acceptable for patients who have significant gastroesophageal reflux disorders. Diagnostic evaluations to determine the presence of pathological gastroesophageal reflux have remained the same for patients being considered for open or laparoscopic procedures. Gastrostomy alone also is performed for patients who have swallowing difficulties or failure to thrive, after excluding the presence of gastroesophageal reflux. The authors review the indications and techniques of laparoscopic fundoplication and gastrostomy, as well as their experience with 390 patients.

Child↗

PubMed1998

A cell surface molecule, JL1; a specific target for diagnosis and treatment of leukemias.

We previously reported a novel differentiation antigen, which is specifically expressed in stage II double positive (CD4+CD8+) human cortical thymocytes (Park et al, J Exp Med 1993; 178: 1447-1451). This study was designed to investigate the expression pattern of JL1 in various types of leukemic cells from patients and normal hematopoietic cells to evaluate the possibility as a tool for diagnosis and treatment of leukemia. The expression of JL1 antigen was observed in 75.6% of leukemic cases (117 out of 154 leukemic patients tested) on flow cytometric analysis. The percentage of JL1-positive cases of T lineage acute lymphoblastic leukemia (T-ALL) (92.6%) was higher than that of other types of leukemias (75%). The presence of JL1 antigen was also confirmed by immunoblotting and immunoprecipitation. Since the JL1 antigen is selectively expressed on the surface of human leukemic cells but not on the mature human peripheral blood cells, normal bone marrow cells and various types of normal tissues, JL1 could be an excellent candidate for an immunodiagnostic and immunotherapeutic tool for hematopoietic malignancies such as leukemia.

Antibodies, Monoclonal↗

PubMed1998

Effect of implant number on transverse bending moments during simulated unilateral loading of mandibular fixed-detachable prostheses.

High bending moments acting on osseointegrated implants due to transverse forces are believed to be potential contributors to mechanical implant failure. Theoretically, the rigidity of a system comprised of five implants would seem to counter these moments more effectively than one with only three implants. To study this, we built an experimental model comprised of five Brånemark implants embedded in an acrylic mandibular edentulous arch and connected by a metal framework. This lower prosthesis was mounted with an opposing maxillary complete denture in nonbalanced lingualized occlusion on a semiadjustable articulator. Eccentric static bites were simulated by fixing the dentures at 1.5 mm left and right working side (WS) and balancing side (BS) positions, respectively, and loading the upper member of the articulator with 50 N. The distal right implant abutment was transformed into a loadcell by bonding four strain gauges at 90 degrees intervals across its surface. Three 10-second static load ramps were carried out for each of 4 experiments: (1) WS loadcell with five implants, (2) BS loadcell with five implants, (3) WS loadcell with three implants, and (4) BS loadcell with three implants. Transverse bending moments were found to be significantly higher on the WS for the three-implant prosthesis as compared to the five-implant design (1.469 Ncm for five implants vs 2.151 Ncm for three implants; p = 0.001, Student's t-test). This difference was insignificant on the BS (0.532 Ncm for five implants vs 0.521 Ncm for three implants; p = 0.34). These results suggest that a higher number of mandibular implants may decrease the bending moments affecting mandibular fixed-detachable prostheses during unilateral biting tasks.

Dental Abutments↗

PubMed1998

Butyrate attenuates BCLX(L) expression in human fibroblasts and acts in synergy with ionizing radiation to induce apoptosis.

Ionizing radiation is a poor inducer of apoptosis in many cell types. In this study we investigated what effect the differentiation agent butyrate had on the cellular levels of the apoptosis regulators BCL2, BCLX(L) and BAX and on radiation-induced apoptosis. It was found that butyrate significantly lowered the level of the apoptosis antagonist BCLX(L) in a time- and dose-dependent manner in diploid human fibroblasts. The reduction of the level of BCLX(L) protein by butyrate correlated with an increased induction of apoptosis in cells irradiated with ionizing radiation. Butyrate also acted in synergy with ultraviolet (UV) light and cisplatin to induce apoptosis in human fibroblasts. Radiosensitization was obtained when butyrate was added before and/or after irradiation, although the combination of treatment both before and after irradiation was the most effective. Our results suggest that butyrate acts in synergy with ionizing radiation, UV light and cisplatin to induce apoptosis, perhaps by lowering the level of the apoptosis antagonist BCLX(L) in cells.

Apoptosis↗

PubMed1997

CD99 (MIC2) regulates the LFA-1/ICAM-1-mediated adhesion of lymphocytes, and its gene encodes both positive and negative regulators of cellular adhesion.

Despite the fact that integrin-mediated lymphocyte adhesion is a crucial event for an appropriate immune response, little is known about the mechanisms that control the adhesion and deadhesion processes generated by the engagement of CD99 between various types of immune cells. Here we report that the CD99 gene encodes two distinct proteins with opposite functions in the LFA-1/intercellular adhesion molecule 1 (ICAM-1)-mediated cell adhesion process. The two forms of the CD99 protein are produced by alternative splicing of the CD99 gene transcript. The major form induced homotypic adhesion of the human B lymphoblastoid cell line IM-9, whereas the minor, truncated form inhibited the adhesion process. Activation of the major form of CD99 with anti-CD99 monoclonal antibodies induced rapid aggregation of IM-9 cells, which was blocked by the addition of mAbs to LFA-1 or intracellular adhesion molecule 1. Overexpression of the minor truncated form of CD99 markedly down-regulated the expression of LFA-1. The two forms of CD99 are differentially expressed in most human cells tested and are highly conserved in monkey. Taken together, these observations suggest that the two forms of CD99 function in vivo in both positive and negative regulation of LFA-1-mediated adhesion of lymphocytes during an immune response.

12E7 Antigen↗

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↗