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K S Choi

Publications and source records attributed to K S Choi.

At least 55 records · Page 3Linked to original sources
PubMed1998

The role of annexin II tetramer in the activation of plasminogen.

Annexin II tetramer (AIIt) is a major Ca2+-binding protein of endothelial cells which has been shown to exist on both the intracellular and extracellular surfaces of the plasma membrane. In this report, we demonstrate that AIIt stimulates the activation of plasminogen by facilitating the tissue plasminogen activator (t-PA)-dependent conversion of plasminogen to plasmin. Fluid-phase AIIt stimulated the rate of activation of [Glu]plasminogen about 341-fold compared with an approximate 6-fold stimulation by annexin II. AIIt bound to [Glu]plasminogen(S741C-fluorescein) with a Kd of 1. 26 +/- 0.04 microM (mean +/- S.D., n = 3) and this interaction resulted in a large conformational change in [Glu]plasminogen. Kinetic analysis established that AIIt produces a large increase of about 190-fold in the kcat, app and a small increase in the Km,app which resulted in a 90-fold increase in the catalytic efficiency (kcat/Km) of t-PA for [Glu]plasminogen. AIIt also stimulated the t-PA-dependent activation of [Lys]plasminogen about 28-fold. Furthermore, other annexins such as annexin I, V, or VI did not produce comparable activation of t-PA-dependent conversion of [Glu]plasminogen to plasmin. The stimulation of the activation of [Glu]plasminogen by AIIt was Ca2+-independent and inhibited by epsilon-aminocaproic acid. AIIt bound to human 293 cells potentiated t-PA-dependent plasminogen activation. AIIt that was bound to phospholipid vesicles or heparin also stimulated the activation of [Glu]plasminogen 5- or 11-fold, respectively. Furthermore, immunofluorescence labeling of nonpermeabilized HUVEC revealed a punctated distribution of AIIt subunits on the cell surface. These results therefore identify AIIt as a potent in vitro activator of plasminogen.

Annexin A2↗
PubMed1998

Annexin II tetramer inhibits plasmin-dependent fibrinolysis.

In this paper, we have characterized the regulation of plasmin activity by annexin II tetramer (AIIt). Plasmin activity was measured by a fibrin lysis assay in which a fibrin polymer was produced from purified components and the extent of polymer lysis was determined by following changes in turbidity. Extrinsic lysis of the fibrin polymer, initiated by addition of tissue plasminogen activator (t-PA), was totally blocked if AIIt was present during fibrin polymer formation. Furthermore, fibrin polymer formed in the presence of AIIt was resistant to extrinsic lysis initiated by addition of plasmin. AIIt bound to fibrin polymer under conditions in which polymer lysis was inhibited. Plasmin-dependent extrinsic lysis of the fibrin polymer was also blocked if AIIt was present in the incubation medium, and under these conditions the amidolytic activity of plasmin, measured with an artificial substrate, was inhibited about 5-fold. In contrast, in the absence of fibrin, and at an AIIt/plasmin molar ratio of 526, the amidolytic activity of plasmin was inhibited by only 22.3% +/- 7.4% (mean +/- SD, n = 5) by AIIt. Plasmin-dependent fibrinolysis was only slightly inhibited if fibrin polymer was formed in the presence of annexins I, II, V, or VI. These results identify AIIt as an in vitro regulator of plasmin activity.

Amides↗
PubMed1998

ICE-like protease (caspase) is involved in transforming growth factor beta1-mediated apoptosis in FaO rat hepatoma cell line.

Transforming growth factor-beta1 (TGF-beta1) arrests growth and/or stimulates apoptosis of a variety of cells. The biochemical pathways involved in the apoptotic processes, however, remain poorly defined. TGF-beta1 induces DNA fragmentation together with morphological changes, which are characteristic of apoptosis in the FaO rat hepatoma cell line. Histones were remarkably enriched in lysates of these cells during TGF beta1-induced apoptosis. We identified U1-70 kd as a death substrate which is cleaved following TGF-beta1 treatment. The tetrapeptide caspase inhibitor carbobenzoxy-valyl-alanly-aspartyl-(beta-O-methyl)-fluoromethyl ketone (ZVAD-FMK) prevented TGF beta1-induced apoptotic DNA fragmentation and cleavage of the U1-70 kd protein, showing that caspase(s) are involved in TGF beta1-mediated apoptosis. To identify specific caspases involved in apoptosis induced by TGF-beta1 in FaO cells, proteolytic activation of several of these caspases and their substrates were studied as a function of time following TGF beta1-treatment. TGF beta1-treatment induced the progressive proteolytic processing of caspase-2 (ICH-1L/Nedd-2), whereas caspase-1 itself did not show any cleavage from the precursor. Pretreatment with ZVAD-FMK abrogated the maturation of caspase-2 and blocked the apoptotic progress. These results suggest that caspase-2, but not caspase-1, may play a crucial role in TGF beta1-induced apoptosis in these cells.

Amino Acid Chloromethyl Ketones↗
PubMed1998

Gliomatosis cerebri: clinical features, treatment, and prognosis.

To clarify clinical features and to elucidate prognostic factors and prognosis, the authors retrospectively analyzed 16 cases of gliomatosis cerebri treated at Seoul National University Hospital between January 1988 and December 1995. Age at diagnosis ranged from 19 to 62 (median 34) years and male to female ratio was 10:6. Most presented with headache or seizure, and the mean duration of symptoms was 12.8 months. A poorly defined diffuse high signal intensity lesion, extending in T2-weighted images for two lobes or more, was the characteristic magnetic resonance (MR) image finding. On postcontrast T1-weighted MR imaging, focal enhancement of the lesion was detected in five cases. All patients underwent histological confirmation by craniotomy (9 cases) or stereotactic biopsy (7 cases). Histologically, all patients had compatible findings of gliomatosis cerebri which are the widespread infiltration of neoplastic glial cells with minimal destruction of pre-existing structures. After histological diagnosis, external radiation therapy was begun except in one case, who declined this treatment. Fourteen patients completed the whole procedure and received the planned dose (mean 5780 cGy). Median survival time after diagnosis was 38.4 months. In univariate analysis, the Ki-67 labelling index (> 1) showed significant correlation with the length of survival (p = 0.006). It is suggested that 1) gliomatosis cerebri can be diagnosed by a combination of MR imaging findings and histological examination; 2) histological diagnosis and external radiation therapy might be a good treatment modality; 3) the Ki-67 labelling index correlates significantly with survival time.

Adult↗
PubMed1998

Determination of the solute removal index for urea by using a partial spent dialysate collection method.

In 22 hemodialysis patients, during a dialysis session, the solute removal index (SRI) for urea obtained from the use of a partial spent dialysate collection method was compared with that derived from the use of a total spent dialysate collection technique. The partial spent dialysate collection method was used to harvest a small representative sample of the total spent dialysate. The volumes of spent dialysate collected by the partial and the total spent dialysate collection methods were 1.7 +/- 0.4 L and 129.6 +/- 15.3 L, respectively. The total amount of urea nitrogen removed by dialysis as estimated by the partial spent dialysate collection method was similar to that determined by the total spent dialysate collection approach. As a result, the SRI value for urea obtained by the partial spent dialysate collection method (namely, 63% +/- 8%) correlated very well (r = 0.95, P < 0.001) with that derived by the total spent dialysate collection technique (namely, 62% +/- 8%). Our data suggest that it is feasible to use a simple partial spent dialysate collection method to obtain SRI results in patients treated with hemodialysis.

Female↗
PubMed1998

Inhibition of p53 transactivation function by the human T-cell lymphotropic virus type 1 Tax protein.

Human T-cell lymphotropic virus type 1 (HTLV-1) is the etiologic agent for adult T-cell leukemia. HTLV-1 transforms lymphocytes, and there is increasing evidence that the virus-encoded protein, Tax, plays a primary role in viral transformation. We have shown that wild-type p53 in HTLV-1-transformed cells is stabilized. This study was initiated to directly analyze whether the p53 in HTLV-1-transformed cell lines was transcriptionally active and to identify the viral gene product responsible for stabilization and inactivation. Transfection experiments using a p53-responsive reporter plasmid and gamma-irradiation studies demonstrate that the wild-type p53 in HTLV-1-transformed cell lines is not fully active. Further, we demonstrate that the HTLV-1-transforming protein, Tax, stabilizes and inactivates p53 function. Cotransfection of Tax with p53 results in a greater than 10-fold reduction in p53 transcription activity. Using Ga14-p53 fusion proteins, we demonstrate that Tax inhibition of p53 transactivation function is independent of sequence-specific DNA binding. Moreover, Tax inhibits p53 function by interfering with the activity of the N-terminal activation domain (amino acids 1 to 52). We conclude that Tax is involved in the inactivation of p53 function and stabilization of p53 in HTLV-1-infected cells. The functional interference of p53 function by Tax may be important for transformation and leukemogenesis.

Cell Line, Transformed↗
PubMed1998

Acute hemolytic crisis with fulminant hepatic failure as the first manifestation of Wilson's disease: a case report.

We report a 27-year-old woman who developed Coombs' negative hemolytic anemia and fulminant hepatic failure as the initial manifestation of Wilson's disease. Unmeasurably low level of serum alkaline phosphatase provided a clue to the diagnosis of Wilson's disease. The diagnosis was established with the presence of Kayser-Fleischer ring, decreased serum ceruloplasmin level, and elevated urine and serum copper levels. In spite of repeated plasmapheresis, she died of multiorgan failure on the fifth hospital day.

Acute Disease↗
PubMed1998

A case of chronic graft-versus-host-disease following allogeneic peripheral blood stem cell rescue for poor graft function after bone marrow transplantation.

To overcome poor graft function after allogeneic bone marrow transplantation (BMT), the use of peripheral blood stem cells (PBSC) instead of bone marrow is gaining more popularity because of its advantages. There may, however, be an increased risk of graft-versus-host-disease (GVHD) because of the large number of lymphocytes present in a leukapheresis product. An 18-year-old man with severe aplastic anemia underwent an allogeneic BMT using his HLA-identical sister. After initial excellent graft take for 8 months, his blood counts gradually decreased to 2.8 x 10(9)/L of white cells and 28 x 10(9)/L of platelets with marrow cellularity of < 10%. After allogeneic granulocyte-colony stimulating factor mobilized PBSC rescue, the patient's blood counts recovered satisfactorily. Around 1 year after the boost, he developed chronic GVHD that responded to prednisolone and cyclosporin A. He is now well on low-dose steroids at day +1055 after PBSC rescue. The present case is the first experience of a long-term follow-up who underwent allogeneic PBSC rescue in Korea.

Adolescent↗
PubMed1998

A case of Marfan syndrome with acute monoblastic leukemia.

We report on an 18-year-old man who had both acute monoblastic leukemia and Marfan syndrome. A diagnosis of Marfan syndrome was established by those characteristics of arachnodactyly, ectopia lentis, mitral valve prolapse, and mitral regurgitation. Findings on bone marrow examination of the patient showed that most of nucleated cells were monoblasts and immunophenotype of those cells showed CD13+, CD33+, CD56+, and HLA-DR+. To our knowledge, this is the second report of leukemia in Marfan syndrome in the world.

Adolescent↗
PubMed1997

Molecular cloning of a novel ubiquitin-specific protease, UBP41, with isopeptidase activity in chick skeletal muscle.

A cDNA encoding a new ubiquitin-specific protease, UBP41, in chick skeletal muscle was cloned using an Escherichia coli-based in vivo screening method. Nucleotide sequence analysis of the cDNA containing an open reading frame of 1,071 base pairs revealed that the protease consists of 357 residues with a calculated molecular mass of 40,847 Da, and is related to members of the UBP family containing highly conserved Cys and His domains. Chick UBP41 was expressed in E. coli and purified from the cells to apparent homogeneity, using 125I-labeled ubiquitin-alphaNH-MHISPPEPESEEEEEHYC as a substrate. The purified enzyme behaved as an approximately 43-kDa protein under both denaturing and nondenaturing conditions, suggesting that it consists of a single polypeptide chain. Like other deubiquitinating enzymes, it was sensitive to inhibition by ubiquitin-aldehyde and sulfhydryl blocking agents, such as N-ethylmaleimide. The UBP41 protease cleaved at the C terminus of the ubiquitin moiety in natural and engineered fusions irrespective of their sizes; thus, it is active against ubiquitin-beta-galactosidase as well as ubiquitin C-terminal extension protein of 80 amino acids. UBP41 also released free ubiquitin from poly-His-tagged di-ubiquitin. Moreover, it converted poly-ubiquitinated lysozyme conjugates to mono-ubiquitinated forms of about 24 kDa, although the latter molecules were not further degraded to free ubiquitin and lysozyme. These results suggest that UBP41 may play an important role in the recycling of ubiquitin by hydrolysis of branched poly-ubiquitin chains generated by the action of 26 S proteasome on poly-ubiquitinated protein substrates, as well as in the production of free ubiquitin from linear poly-ubiquitin chains and of certain ribosomal proteins from ubiquitin fusion proteins.

Amino Acid Sequence↗
PubMed1997

Protection of 5alpha-dihydrotestosterone against TGF-beta-induced apoptosis in FaO cells and induction of mitosis in HepG2 cells.

Administration of TGF-beta1 to both FaO and HepG2 cells significantly induced apoptosis, particularly in FaO cells. Degradation of genomic DNA in FaO cells was rapidly induced by treatment with TGF-beta1 (5 ng/ml) for only 4 hr. 5alpha-dihydrotestosterone (DHT, 25 nM) alone did not affect any significant changes in cell viability and in nuclei of FaO cells; however, pre-treatment with DHT protected genomic DNA degradation induced by TGF-beta1 for 14 hr. Simultaneous treatment with DHT plus TGF-beta1 (D + T) inhibited TGF-beta-induced apoptosis by approximately 50% in FaO cells. On the other hand, D + T treatment increased mitosis in actively growing HepG2 cells. Thus, it is reasonable to conclude that DHT gives growth advantage to hepatocellular-carcinoma cells by inhibiting TGF-beta-induced DNA fragmentation in FaO cells and by inducting mitosis in HepG2 cells.

Animals↗
PubMed1997

Central neurocytoma: the role of radiation therapy and long term outcome.

BACKGROUND: It has been suggested that the biologic behavior of central neurocytoma is indolent, although little is known regarding the role of radiation therapy and long term outcome. To clarify the role of radiation therapy and long term outcome, the authors retrospectively analyzed 15 cases of central neurocytoma. METHODS: Clinical records and radiologic findings of 15 cases of central neurocytoma diagnosed at Seoul National University Hospital between January 1982 and February 1995 were carefully reviewed. The duration of follow-up was from 18-168 months (mean, 52 months); follow-up images were reviewed and the patient's Karnofsky performance scale (KPS) was assessed up to the time of last follow-up. RESULTS: The age of the patients ranged from 15 to 60 years (mean, 25 years) and the male to female ratio was 11:4. Macroscopic total resection of the tumor was performed in seven patients, two of whom received fractionated radiation therapy. Subtotal removal of the tumor was performed in eight patients, five of whom received this same therapy. In 2 of the 5 patients who did not receive radiation therapy after macroscopic total resection, the tumors recurred 8 and 21 months after surgery, respectively; in contrast, recurrence was not detected in the 2 patients who received fractionated radiation therapy after macroscopic total resection. In all five patients who received fractionated radiation therapy after subtotal resection, the tumor shrank (n = 3) or disappeared (n = 2) during the postsurgical follow-up period ranging from 27-113 months; the tumor began to shrink from 6 months to 2 years after radiation. No change was found in the three patients who did not receive radiation therapy after subtotal resection. At the time of last follow-up, the KPS was greater than 90 in all patients except one who required assistance in his daily activities because of complications from radiation therapy. CONCLUSIONS: It is suggested that even if the biologic behavior of a central neurocytoma is benign, radiation therapy appears to have an effect on tumor control. However, it should be carefully decided whether to use radiation therapy for a residual tumor because radiation can cause delayed complications and the clinical course of subtotally resected patients who do not receive radiation therapy is extremely benign.

Activities of Daily Living↗
PubMed1997

Neuronal Cdc2-like kinase (Nclk) binds and phosphorylates the retinoblastoma protein.

The tumor suppressor retinoblastoma protein (RB) plays a central role in cellular growth regulation, differentiation, and apoptosis. Phosphorylation of RB results in a consequent loss of its ability to inhibit cell cycle progression. However, how RB phosphorylation might be regulated in apoptotic or postmitotic cells, such as neurons, remains unclear. Here we report that neuronal Cdc2-like kinase (Nclk), composed of Cdk5 and a neuronal Cdk5 activator (p25(nck5a)), can bind and phosphorylate RB. Since RB has been shown recently to associate with D-type G1 cyclins and viral oncoproteins through a common peptide sequence motif of LXCXE, Nclk binding may be mediated by a related sequence motif (LXCXXE) found in p25(nck5a). We demonstrate (i) in vitro binding of bacterially expressed p25(nck5a) to a GST-RB fusion protein, (ii) coprecipitation of GST-RB and reconstituted Cdk5.p25(nck5a), and (iii) phosphorylation of GST-RB by bacterially expressed Cdk5.p25(nck5a) kinase and by Cdk5.p25(nck5a) kinase purified from bovine brain. Finally, we show that immunoprecipitation of RB from embryonic mouse brain homogenate results in the coprecipitation of Cdk5 and that Cdk5 kinase activity is maximal during late embryonic development, a period when programmed cell death of developing neurons is greatest. Taken together, these results suggest that Nclk can bind to and phosphorylate RB in vitro and in vivo. We infer that Nclk may play an important role in regulating the activity of RB in the brain, including perhaps in apoptosing neurons.

Animals↗
PubMed1997

Interaction of human T-cell lymphotropic virus type I Tax, Ets1, and Sp1 in transactivation of the PTHrP P2 promoter.

We have previously shown that the parathyroid hormone-related protein (PTHrP) promoter contains binding sites for transcription factors Ets1 and Sp1 and that human T-cell lymphotropic virus type I (HTLV-I) Tax cooperates with Ets1 to transactivate the PTHrP P2 promoter. Using the yeast two-hybrid interaction system, we now provide evidence that Tax interacts with Ets1. Moreover, a double mutation (D22A,C23S) in the Tax protein that abrogated the Tax/Ets1 interaction also inhibited the Tax/Ets1 cooperative effect, suggesting that the interaction between Tax and Ets1 is important for transactivation of the PTHrP promoter. In coimmunoprecipitation assays, we find that Tax facilitates the interaction between Ets1 and Sp1, forming a ternary complex. When the Sp1 site in the PTHrP promoter was mutated, the Tax/Ets1 cooperative effect was dramatically decreased. This suggests that Sp1 plays an important role in the Ets1-dependent Tax transactivation of the PTHrP P2 promoter. Finally, we demonstrate that Gal4-Tax is a strong activator of the Gal PTHrP promoter, implying that Tax contributes directly to the transcriptional activation of the promoter. We propose a model in which the Tax/Ets1 cooperative effect on the PTHrP P2 promoter is based on the ability of Tax, Ets1, and Sp1 to form a ternary complex on the template DNA. Tax facilitates the interaction of Ets1/Sp1 and participates directly in the transcription initiation process.

Amino Acid Sequence↗
PubMed1997

Verruciform xanthoma of the oral mucosa: an immunohistochemical and ultrastructural study of two cases.

Verruciform xanthoma is an uncommon benign lesion of unknown aetiology and pathogenesis. Two cases of verruciform xanthoma are presented together with an immunohistochemical and ultrastructural study. One case co-occurred with an odontogenic keratocyst which, to our knowledge, has not been previously reported, and another case occurred on masticatory mucosa with an asymptomatic, granular, exophytic lesion causing a cleft-like gingival recession. In an immunohistochemical study using antibodies to macrophage (CD 68[KP1]), alpha-1-antitrypsin, vimentin, desmin, keratin, neuron-specific enolase (NSE) and S-100 protein, the characteristic foam cells of verruciform xanthoma showed strong positive staining for CD 68[KP1] and vimentin and weak positive staining for alpha-1-antitrypsin, while the other antibodies were negative. As in previous studies, S-100 protein positive dendritic cells were detected in lesional connective tissue. In addition, the ultrastructural findings revealed characteristics of macrophages containing varying sized lipid vacuoles and degenerating epithelial cells. These findings support the concepts that the foam cells in verruciform xanthoma are of monocyte-macrophage lineage and that the epithelial degeneration from uncertain causes may be related to the pathogenesis of the lesion.

Adult↗
PubMed1996

Primary central nervous system lymphoma: variety of clinical manifestations and survival.

A retrospective analysis of 23 non-immune compromised patients with primary central nervous system lymphoma (PCNSL) is reported. The patients consist of 14 males and 9 females and the median age is 50 years. Most patients presented with focal neurological deficits or symptoms of increased intracranial pressure (ICP) due to mass effects around the periventricular area. However, there were four cases of diffuse type, one case of intramedullary tumour, and four cases with rapid disease progression. All the patients underwent histological confirmation by craniotomy (16 cases) or stereotactic biopsy (7 cases). The radiation therapy started after histological diagnosis in all and 6 cases received additional chemotherapy. The median survival after diagnosis of overall patients was 23 months. Six patients are in disease free status at a mean of 35 months follow-up. The uni- and multi-variative risk analysis revealed five favourable factors on survival: (1) age less than 60 years (0.05 < p < 0.1); (2)pre-operative Karnofsky performance scale (KPS) > or = 70 (p < 0.05); (3) symptom duration over four weeks (p < 0.05); (4) radiation dosage > or = 5500 cGy (p < 0.05); (5)absence of malignant cells in cerebrospinal fluid (CSF) (p < 0.05). The most frequent site of recurrence was the local area as shown in seven cases out of 11 recurrent cases. But six patients had diffuse recurrence (4 cases), systemic recurrence (2 cases), and drop metastasis (1 case). Although the recurred PCNSL had rapid progression and a grave prognosis, aggressive treatment prolonged the postrecurrence survival time significantly. Our experience suggests that 1) there are various clinical and radiological presentations and progressions of the disease; 2) treatment method should be decided along with the clinical presentation, progression of disease, and prognostic factors; 3) early diagnosis and early detection of recurrence enable the start of definitive treatment when the medical condition is still satisfactory.

Adult↗
PubMed1996

The IE2 regulatory protein of human cytomegalovirus induces expression of the human transforming growth factor beta1 gene through an Egr-1 binding site.

Increases in transforming growth factor beta1 (TGF-beta1) mRNA and biological activity in the early phase of human cytomegalovirus (CMV) infection in fibroblasts are paralleled by increased TGF-beta1-chloramphenicol acetyltransferase (CAT) reporter gene activity. To determine how CMV infection transactivates the TGF-beta1 promoter, we examined the effects of the cotransfected IE2 regulatory protein of human CMV on 5'-deleted TGF-beta1 promoter-CAT reporter genes in transient DNA transfection assays. Two upstream TGF-beta1 promoter regions each containing an Egr-1 consensus site were shown to be important for IE2-induced transactivation in a cell type that displayed greatly reduced nonspecific activity. Furthermore, transfer of an Egr-l site from between positions -125 and -98, but not point mutant versions of this site, to a heterologous promoter also conveyed IE2 responsiveness. Addition of an IE2 expression vector or use of the U373 A45 astrocytoma cell line expressing IE2 also produced synergistic stimulation of GAL4-Egr-l-mediated activation of a target promoter containing GAL4 binding sites. The 80-kDa IE2 protein present in A45 cells proved to selectively bind to glutathione S-transferase (GST)-Egr-1 beads. The results of in vitro protein binding assays also revealed that an intact in vitro-translated IE2 protein bound directly to the GST-Egr-1 fusion protein through the zinc finger domain of the Egr-1 protein and that this binding activity was abolished by deletion of parts of the zinc finger DNA-binding domain. Similarly, the Egr-1 protein was found to associate preferentially with a small region within the C-terminal half of the IE2 protein adjacent to the DNA-binding and dimerization domains that are important for both transactivation and downregulation. We conclude from these observations that IE2 may regulate transcription of the TGF-beta1 gene as well as other potential cellular targets by virtue of its ability to interact with the Egr-1 DNA-binding protein.

Astrocytoma↗