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Biomedical subjects

I H Choi

Publications and source records attributed to I H Choi.

At least 37 records · Page 2Linked to original sources
PubMed2000

Restoration of P-glycoprotein function is involved in the increase of natural killer activity with exogenous interleukin-15 in human immunodeficiency virus-infected individuals.

A depressed level of natural killer (NK) activity is one of the various immunologic abnormalities in human immunodeficiency virus (HIV) infection. Interleukin-15 (IL-15), an immunotherapeutic candidate in HIV infection, increases NK activity and induces the excretion of CC-chemokines from divergent immune cells, but the mechanisms of NK activity enhancement by IL-15 stimulation is not clearly established in HIV infection. This study examined whether CC-chemokines, which are known to increase NK activity, are secreted adequately in HIV-infected individuals, and also investigated whether P-glycoprotein is involved in NK activity enhancement after IL-15 administration. NK activity increased with IL-15 stimulation in NK cells of HIV-infected individuals, as it does in normal NK cells. IL-15 stimulates NK cells to secrete CC-chemokines, such as, macrophage inflammatory protein-1alpha (MIP-1alpha), macrophage chemotactic protein-1alpha (MCP-1alpha) and regulated upon activation, normal T cells expressed and secreted (RANTES) in both HIV-infected individuals and controls with no significant difference. P-glycoprotein expression and function is decreased in HIV-infected individuals and restored only in NK cells of HIV-infected individuals after IL-15 stimulation. P-glycoprotein may play a role in the mechanism of increased NK cell activity in HIV-infected individuals after IL-15 stimulation.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

Fas ligand and Fas are expressed constitutively in human astrocytes and the expression increases with IL-1, IL-6, TNF-alpha, or IFN-gamma.

Fas ligand (FasL) and Fas are mediators of apoptosis, which are implicated in the peripheral deletion of autoimmune cells, activation-induced T cell death, and cytotoxicity mediated by CD8+ T cells. Fas is also believed to be involved in several central nervous system diseases, but until now, the effector cells expressing FasL in the brain have not been identified. We investigated the expression levels of Fas and FasL with the stimulation of cytokines and the possible effector cells targeting Fas-bearing cells. Our data demonstrated that: 1) FasL is expressed constitutively on astrocytes taken from a fetus or an adult and that its expression increases when these cells are treated with IL-1, IL-6, or TNF-alpha in which the pretreatment of IFN-gamma triggers astrocytes to express more FasL; 2) astrocytes induce apoptosis in MOLT-4 cells through FasL; 3) Fas is also expressed constitutively and is up-regulated by IL-1, IL-6, or TNF-alpha in which the pretreatment of IFN-gamma triggers astrocytes to express more Fas; 4) apoptosis occurs when fetal astrocytes are treated with agonistic anti-Fas IgM Ab after culture with IFN-gamma and TNF-alpha; and 5) TNF-related apoptosis inducing ligand is up-regulated in fetal astrocytes with stimuli of IL-1 or TNF-alpha. These findings suggest a possible role of astrocytes in the induction of apoptosis in central nervous system diseases.

Adult↗
PubMed1999

Germline mutations in the EXT1 and EXT2 genes in Korean patients with hereditary multiple exostoses.

Hereditary multiple exostoses (EXT) is an autosomal dominantly inherited disease characterized by the formation of cartilage-capped prominences (exostoses) that develop from the juxtaepiphyseal regions of the long bones. Recently, EXT1 and EXT2 genes were cloned and germline mutations of EXT1 and EXT2 were identified in EXT families. In this study, we performed a mutational analysis of EXT1 and EXT2 genes in eight unrelated Korean EXT families by polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) analysis followed by direct DNA sequencing. As a result, we were able to identify one family (SNU-OC3) with the EXT1 mutation and another family (SNU-OC15) with the EXT2 mutation. The EXT1 mutation was a 10-bp deletion at the 3' end of exon 5 (CTAATTTAGg) including the splice site of this exon. The EXT2 mutation identified in the SNU-OC15 family was a missense mutation at codon 85 of exon 2 (TGC-->CGC), resulting in an amino acid change from cysteine to arginine. This missense mutation cosegregated with the disease phenotype in this family, suggesting that it is the disease-causing mutation. These two mutations identified in EXT1 and EXT2 are novel ones.

Child, Preschool↗
PubMed1999

Substance P augments nitric oxide production and gene expression in murine macrophages.

We investigated the effects of substance P (SP) on nitric oxide (NO) synthase activity in macrophages by measuring the production of nitrite and the expression of inducible NO synthase (iNOS) mRNA and protein. In LPS-activated macrophages, SP stimulated NO production in time and concentration dependent manners. These SP effects were blocked by a specific NK-1 receptor antagonist. Furthermore, SP stimulation increased the levels of both iNOS mRNA and iNOS protein. These results demonstrate that SP can increase LPS induced NO production in macrophages by augmenting the induction of iNOS expression. We also examined the role of SP on acute-cold stress induced altered production of NO by mouse peritoneal macrophages. SP enhanced the LPS-induced macrophages NO production from stressed mice relative to the non-stressed mice. These results suggest that SP may have an important modulatory role in production of NO by macrophages.

Animals↗
PubMed1999

The histological spectrum of subperiosteal fibrocartilaginous pseudotumor of long bone (focal fibrocartilaginous dysplasia).

Clinicopathological features in six cases of focal fibrocartilaginous dysplasia (FFCD) which involved either the tibia (n = 4) or the femur (n = 2) were reviewed. All cases presented clinical and radiological characteristic features, and histopathological findings were analyzed in five of the six cases. The subject group comprised three boys and three girls, ages ranged from 12 to 18 months. Histologically, the individual lesions showed regional variation in cellularity, amount of fibrous and cartilaginous components. Paucicellular areas were mainly composed of dense fibrous tissue while more cellular areas contained foci of fibrocartilaginous element. The chondrocytes and stellate cells around cartilaginous area were positive for S-100 protein. One case contained both hyaline and fibrocartilage, and architecturally mimicked normal tendinous insertion. One case, which involved proximal tibia, was purely composed of fibrous tissue without fibrocartilage. All cases formed undulating and irregular borders against underlying cortical bone. Histopathologically variable spectrum suggests a strong possibility of undergoing transition from initial cellular and cartilagnous to late paucicellular, fibrous phase. Although any evidence that can explain basic pathogenesis or prognostic histological parameter is lacking, we believe that the term FFCD is not relevant because the presence of fibrocartilage is not an essential feature, and it can cause confusion with other pathological processes. We propose the term 'subperiosteal fibrocartilaginous pseudotumor of long bone' for this unique clinicopathological entity with which heterologous cartilaginous element can be associated.

Female↗
PubMed1999

Monoclonal antibodies with various reactivity to p58 killer inhibitory receptors.

Human natural killer (NK) cells have receptors that bind to HLA class I molecules. Among these receptors, p58 and p50 bind to HLA-C. P58 belongs to the killer inhibitory receptor (KIR) and p50 belongs to the killer activatory receptor (KAR). Previously, we obtained three recombinant p58 KIR or p50 KAR proteins, KAR-K1 (KIR2DS4), KIR-K6 (KIR2DL1), and KIR-K7 (KIR2DL3). In this study, we produced and characterized seven monoclonal antibodies (MAbs) to the p58 KIR and p50 KAR proteins. The MAbs were classified in three groups according to their antigen-binding specificity: 5IB103 and 26ID707 were KAR-K1-specific; A809, 190IIC311, and 197IIC611 were KIR-K7-specific; while A210 and A803g bound to all three recombinant proteins. The MAbs reactive to KIR-K7 bound to the gamma3 domain among two immunoglobulin (Ig) domains of KIR-K7. Immunofluorescence staining and flow cytometric analysis with A803g showed reactivity to about 10% of peripheral blood mononuclear cells and 35% of purified natural killer cells. Double immunofluorescence staining with A803g and anti-CD56 Ab showed that CD56 and p58 or p50 were expressed on NK cells in a mutually exclusive way. We also investigated T-cell markers in A803g+ cells. A803g+ T cells were almost CD8+ cells. MAbs produced in this study can be utilized practically in the investigation of biological characteristics of p58 KIR and p50 KAR.

Animals↗
PubMed1999

Limited stress response in Streptococcus pneumoniae.

In Streptococcus pneumoniae, heat shock induces the synthesis of 65-, 73-, and 84-kDa proteins, and ethanol shock induces a 104-kDa protein. In this study, the 65-, 84-, and 104-kDa proteins were identified as members of the GroEL, ClpL and alcohol dehydrogenase families, respectively, and the general properties of the stress response of S. pneumoniae to several other stresses were characterized. However, several stresses which are known to induce stress responses in Escherichia coli and Bacillus subtilis failed to induce any high molecular weight heat-shock proteins (HSPs) such as GroEL and DnaK homologues. A minor temperature shift from 30 to 37 C triggered induction of the homologues of DnaK and GroEL of E. coli. These features may provide a foundation for evaluating the role of heat-shock proteins relative to the physiology and pathogenesis of pneumococcus.

Amino Acid Sequence↗
PubMed1999

Correction of genu recurvatum by the Ilizarov method.

The Ilizarov apparatus was used to carry out opening-wedge callotasis of the proximal tibia in ten patients who had suffered premature asymmetrical closure of the proximal tibial physis and subsequent genu recurvatum. In four knees, the genu recurvatum was entirely due to osseous deformity, whereas in six it was associated with capsuloligamentous abnormality. Preoperatively, the angle of recurvatum averaged 19.6 degrees (15 to 26), the angle of tilt of the tibial plateau, 76.6 degrees (62 to 90), and the ipsilateral limb shortening, 2.7 cm (0.5 to 8.7). The average time for correction was 49 days (23 to 85). The average duration of external fixation was 150 days (88 to 210). Three patients suffered complications including patella infera, pin-track infection and transient peroneal nerve palsy. At a mean follow-up of 4.4 years, all patients, except one, had achieved an excellent or good radiological and functional outcome.

Adolescent↗
PubMed1999

Optimum ratio of distraction in double level tibial lengthening.

The authors reviewed 43 double level tibial lengthenings by Ilizarov technique in 34 consecutive patients (6-31 years old), and investigated the factors affecting regenerate bone healing to determine the optimum ratio of distraction rate or magnitude of lengthening at the proximal and distal osteotomy sites. Length gain averaged 6.1 cm (range, 2.5-12.3 cm), equivalent to a 28% increase of the segment. The variables investigated included age, gender, concomitant deformity correction, etiology, and the amount of length gain. The healing index averaged 1.8 months per centimeter proximally and 2.8 months per centimeter distally. Age and the amount of length gain affected the healing index at proximal and distal lengthening sites. However, the proximal to distal healing index ratio, which averaged 0.72, was not affected by any parameters investigated. This study suggests that to minimize external fixation treatment time, the distraction rate, or amount of length gain, of the distal osteotomy site should be approximately 3/4 that of the proximal site in the double level tibial lengthening.

Adolescent↗
PubMed1998

Immunoglobulin E-dependent active fatal anaphylaxis in mast cell-deficient mice.

Mast cells have long been believed to be the central effector cells in the development of immunoglobulin (Ig)E-dependent anaphylaxis. In this study, we investigated the role of mast cells in IgE-dependent hapten-induced active fatal anaphylaxis using mast cell-deficient WBB6F1- W/Wv (W/Wv) and congenic normal (+/+) mice. Although a 5-min delay in shock signs and death were observed in W/Wv mice, 100% fatal reactions to penicillin V (Pen V) occurred in both +/+ and W/Wv mice. Administration of monoclonal anti-IL-4 antibody completely prevented the fatal reactions, and the effect of anti-IL-4 was associated with its suppressive activity on Pen V-specific serum levels of IgE, but not IgG. The platelet-activating factor (PAF) antagonist, BN 50739, completely prevented the fatal reactions in both strains of mice. Our kinetic study revealed, in contrast to no elevation of plasma histamine level in W/Wv mice, high levels of PAF in the circulation after challenge in both +/+ and W/Wv mice, albeit to a lesser degree in the latter case. These data indicate that cells other than mast cells are sufficient to induce an IgE-dependent active fatal anaphylaxis by elaborating PAF, which is the critical mediator for fatal murine anaphylaxis.

Anaphylaxis↗
PubMed1998

Molecular cloning, expression, and characterization of dnaK in Streptococcus pneumoniae.

DnaK is known to be highly conserved in all species and is a major immunogen in Streptococcus pneumoniae. To elucidate the role of dnaK in S. pneumoniae, dnaK was cloned in Escherichia coli using a homologous dnaK probe generated by PCR. The His-tagged DnaK was overexpressed in soluble form and purified from E. coli. Alignment of the deduced DnaK amino acid sequence from nucleotide sequences of the cloned dnaK revealed high homology with DnaK analogs in E. coli (53%) and Staphylococcus aureus (73%). However, anti-pneumococcal DnaK antiserum did not crossreact with DnaK analogs in E. coli, S. aureus and human cells suggesting that pneumococcal DnaK might be a good candidate as a vaccine.

Amino Acid Sequence↗
PubMed1998

Clonal expansion of T-cells in measles.

Some autoimmune complications such as postinfectious encephalomyelitis are associated with immunologic abnormalities induced by measles virus infection. To address the superantigenic stimulation in measles which might be related with autoimmune complications, T-cells bearing the TCRBV5S2 or TCRBV8 chains and the expression of activation markers were analyzed by monoclonal antibodies. To estimate clonal expansions, the CDR3 length profile in T-cells bearing the TCRBV5S2 or TCRBV8 chains was analyzed by two-stage PCR. Results showed that the expression of DR molecules in CD3+ cells was increased significantly in measles patients (19.6 +/- 20.7%) compared to healthy children (2.9 +/- 1.4%). The mean percentage (7.1 +/- 4.4%) of T-cells bearing the TCRBV8 chain was increased in measles patients compared to healthy children (5.6 +/- 3.1%). The percentage of T-cells bearing the TCRBV5S2 chain in measles patients (3.0 +/- 1.2%) was similar to that in healthy children (2.7 +/- 0.6%). By analysis of the CDR3 length we found that there was no evidence of clonal expansions in T-cells bearing the TCRBV8 chain and that there were clonal expansions in T-cells bearing the TCRBV5S2 chain. These data suggest a conventional antigenic stimulation with T-cells bearing the TCRBV5S2 chain and a superantigenic stimulation with T-cells bearing the TCRBV8 chain may occur in the acute stage of measles infection.

Antibodies, Monoclonal↗
PubMed1998

Generation of human Fab monoclonal antibodies against preS1 of hepatitis B virus using repertoire cloning.

Human monoclonal antibodies (MAbs) have considerable potential in the prevention and treatment of many viral diseases. A combinatorial antibody library of heavy (Fd)- and light-chain genes derived from peripheral blood lymphocytes of a volunteer with high antibody titer to preS1 of HBV was constructed and expressed on the surface of filamentous phages. The library contained 7 x 10(9) independent clones. A phage antibody population from the third panning against preS1 was converted to one expressing soluble Fabs by removal of the g3 sequences from the pComb3 phagemid vector and subsequent transformation into E. coli TG1 cells. Screening of the library led to the identification of two clones, 3DW and 8GW, showing high reactivity toward preS1. The authenticity of the Fabs was confirmed by immunoblot analysis which yielded approximately 60 and approximately 30 kDa bands under nonreducing and reducing conditions, respectively. The soluble Fabs of 3DW and 8GW exhibited relative affinities of 6 x 10(5) and 8 x 10(6) M(-1), respectively. The sequencing results demonstrate that all Fd sequences belong to subgroup II and all light chain sequences belong to subgroup I. There are differences in CDR length and composition, especially in the FW3 and CDR3 regions of the heavy- and light-chain genes. These human Fab MAbs specific to preS1, generated from a combinatorial library, represent prototypes of passive immunotherapy candidates for viral hepatitis B.

Amino Acid Sequence↗
PubMed1998

Enhanced expression of immunoglobulin kappa light chains with unusually long CDR3 regions in patients with rheumatoid arthritis.

OBJECTIVE: Our previous sequence analysis of immunoglobulin kappa light chains revealed that some patients with rheumatoid arthritis (RA) expressed repertoires enriched for transcripts containing unusually long CDR3 lengths of 11 amino acid codons. This was due, in part, to N region addition at the Vkappa-Jkappa joins. In this study, we analyzed a larger number of individuals to determine how often enrichment of kappa light chain repertoires for 11 amino acid CDR3 occurs in synovial lymphocytes and peripheral blood lymphocytes (PBL) of individuals with RA. METHODS: To measure length variability of kappa chain CDR3 regions, we performed a 2 stage polymerase chain reaction amplification and polyacrylamide gel electrophoresis. We sampled PBL and synovial lymphocytes of 9 patients with longstanding RA, and used PBL of 9 age and sex matched healthy individuals as controls. RESULTS: In PBL of healthy individuals, there was low level but consistent expression of kappa chains containing CDR3 with 11 amino acids. In patients, there was enhanced expression of kappa chains containing CDR3 with 11 amino acids compared to healthy individuals. This enhanced expression of kappa chains containing CDR3 of 11 amino acids was more pronounced in synovial lymphocytes compared to PBL of the same patients. CONCLUSION: These findings suggest that there is antigenic selection of B cells bearing antibodies with unusually long kappa light chain CDR3 in RA.

Adult↗
PubMed1997

Cloning and characterization of cDNAs encoding VH and VL of a monoclonal anti-CEA antibody (CEA 79) cross-reactive with NCA-95 and generation of a single-chain Fv molecule (scFv).

We cloned complementary DNA (cDNA) encoding the variable regions of heavy chain (VH) and of light chain (VL) of a monoclonal anti-carcinoembryonic antigen (CEA) antibody cross-reactive with nonspecific cross-reacting antigen-95 (NCA-95), which had been previously prepared and designated as CEA 79 (gamma 2a, kappa). From these cDNAs, a phagemid expression vector for the CEA79 single chain variable fragment (scFv) was generated. Enzyme-linked immunosorbent assay (ELISA), competitive ELISAs, and Western blotting confirmed that the scFv displayed on the surface of the bacteriophage had retained affinity for CEA and NCA-95. We then determined the nucleotide sequences of the cloned cDNAs for VH and VL. The sequence analysis revealed that VH and VL of the CEA 79 antibody represent new members of the mouse heavy chain subgroup "miscellaneous" and the kappa light chain subgroup "V", respectively.

Amino Acid Sequence↗
PubMed1997

Molecular basis of HLA-C recognition by p58 natural killer cell inhibitory receptors.

NK cells express several inhibitory receptors that recognize class I MHC molecules expressed on target cells. The NK cell inhibitory receptors (KIRs) provide a key regulatory function for NK cells via specific interaction with MHC/peptide complexes, but the molecular details for recognition of class I MHC molecules by KIRs still remain unclear. Here we report cDNA cloning and expression of p58 KIRs and a p50 killer cell activatory receptor (KAR) from a Korean blood donor and demonstrate direct binding between recombinant soluble p58 KIRs and recombinant soluble HLA-C molecules. We identified three p58/p50 killer cell receptors (KAR-K1, KIR-K6, and KIR-K7), which are homologous to p50 cl-39, p58 47.11, and p58 cl-6, respectively. Native gel shift assay revealed that p58 KIR-K6 and KIR-K7 bind both HLA-Cw3 and HLA-Cw6 molecules, but p50 KAR-K1 binds neither of the HLA-C molecules. However, binding of HLA-C molecule by p58 KIR is affected by the antigenic peptide bound on the MHC molecule, suggesting that the p58 KIR binding to the HLA-C molecule may be dependent on the peptide. In addition, the binding interaction requires the presence of both p58 Ig domains, suggesting that the binding mode of HLA-C and p58 KIR may have some similarity to that of the neonatal Fc receptor and the Fc fragment of Ab and may be distinct from that of TCR and MHC.

Amino Acid Sequence↗
PubMed1997

Clonal expansion of CD8+ T cells in Kawasaki disease.

Kawasaki disease (KD) is the major cause of acquired heart disease in children. KD is suspected of being an infectious disease, but the etiology has not yet been clarified. Immunologically, the disease is associated with the activation of T cells, monocytes, and macrophages resulting in highly elevated levels of several cytokines. Recently, expansions of T cells expressing TCRBV2 and TCRBV8 chains have been reported, and this suggests the involvement of a superantigen in the pathogenesis of KD. To address the role of a superantigen in KD, we investigated clonal expansion of T cells by estimating the complementarity-determining region 3 size profile among T cells expressing TCRBV1, TCRBV2, TCRBV4, TCRBV5, TCRBV8, TCRBV14, TCRBV16, TCRBV17, TCRBV18, and TCRBV20 chains during acute KD, during subacute KD, and during the long term follow-up period. During the acute phase of KD, several clonal expansions were found mainly in the CD8+ T cells that disappeared during the long term follow-up period. Our data suggest that the conventional Ags rather than a superantigen were involved in the pathogenesis of acute KD.

Amino Acid Sequence↗