Biomedical subjects

C G Park

Publications and source records attributed to C G Park.

At least 37 records · Page 2Linked to original sources

PubMed1999

Reconstitution of killer cell inhibitory receptor-mediated signal transduction machinery in a cell-free model system.

Recognition of class I MHC molecules on target cells by killer cell inhibitory receptors (KIRs) blocks natural cytotoxicity and antibody-dependent cell cytotoxicity of NK cells and CD3/TCR dependent cytotoxicity of T cells. The inhibitory effect of KIR ligation requires phosphorylation of the cytoplasmic tail of KIR and subsequent recruitment of an SH2-containing protein tyrosine phosphatase, SHP-1. To better understand the molecular mechanism of the KIR-mediated inhibitory signal transduction, we developed an in vitro assay system using a purified His-tag fusion protein of KIR cytoplasmic tail (His-CytKIR) and Jurkat T cell lysates. We identified a target molecule of SHP-1 by comparing the phosphorylation of major cellular substrates following in vitro phosphorylation of Jurkat cell lysates in the presence and absence of the His-CytKIR in this cell-free model system. The His-CytKIR was tyrosine phosphorylated by Lck in vitro, and the phosphorylated His-CytKIR recruited SHP-1. Interestingly, we observed that among major substrates phosphorylated in vitro, PLC-gamma exhibited a dramatic decrease in phosphorylation when the His-CytKIR was mixed with Jurkat T cell lysates. However, PLC-gamma exhibited no decrease in phosphorylation when SHP-1 or Lck was depleted or deficient in this reaction mixture, suggesting that the SHP-1 recruited by the phosphorylated His-CytKIR directly mediate the dephosphorylation of PLC-gamma. The cell-free model system could be used to reveal the detailed molecular interactions in the KIR-mediated signal transduction.

Amino Acid Sequence↗

PubMed1999

The cytoplasmic tail of killer inhibitory receptor (KIR) associates with TCR zeta in a phosphorylation-dependent manner.

Killer inhibitory receptor (KIR) inhibits cytolytic function of killer cells by specific interaction with class I MHC molecules. The inhibitory effect mediated by KIR requires co-engagement of KIR with an activating receptor, such as TCR or FcR. This implies that KIR may function in the immediate vicinity of activating molecules, and previous studies have shown that p58 KIR is associated with TCR zeta- and FcR gamma-chain in NK cells. To better understand the molecular interaction between KIR and TCR zeta-chain, we generated a His-tag fusion protein of a p70 KIR cytoplasmic tail (His-CytKIR) and used this protein to coprecipitate TCR zeta-chain from Jurkat T cells. Western blots of the resolved coprecipitates showed that the cytoplasmic tail of KIR associates with TCR zeta in vitro. Interestingly, the association between the His-CytKIR and TCR zeta was dependent on the phosphorylation of the His-CytKIR. Unlike the unphosphorylated His-CytKIR, the phosphorylated form no longer associated with TCR zeta. However, the association was not affected by the tyrosine phosphorylation of TCR zeta. These results suggest that the cytoplasmic tail of KIR may couple to TCR zeta in a phosphorylation-dependent manner, so it could fine-tune the activation signals induced via the TCR.

Humans↗

PubMed1999

Antiviral effects of 28-deacetylsendanin on herpes simplex virus-1 replication.

The compound purified from the fruit of Melia azedarach exerted an antiviral effect on herpes simplex virus-1 (HSV-1) in Vero cells. It was identified as 28-deacetylsendanin (28-DAS). The 50% inhibitory concentration (IC50) of 28-DAS was 1.46 microg/ml without cytotoxicity at 400 microg/ml on Vero cells. Electron microscopy showed that low electron-dense cores of newly synthesized nucleocapsids remained in swollen nuclei and no extracellular virus particles were observed at 15 h p.i. Consistent with this result, it was confirmed by a plaque assay that few infectious progeny viruses were released from the 28-DAS-treated virus-infected cells at 24 h p.i. Intracellular viruses in 28-DAS-treated virus-infected cells were 23% of untreated and infected cells. The synthesis of thymidine kinase (TK) was reduced by 28-DAS at early stage. In conclusion, 28-DAS inhibited the replication of HSV-1, reduced the synthesis of HSV-1 TK, and led to the formation of defective nucleocapsids.

Animals↗

PubMed1999

Induction of neutralizing antibody against human cytomegalovirus (HCMV) with DNA-mediated immunization of HCMV glycoprotein B in mice.

Immunization was accomplished by inoculating pcGB containing human cytomegalovirus (HCMV) glycoprotein B (gB) gene into BALB/c mice intramuscularly. IgM antibody was detected in all the immunized group. IgG antibody was also found in all the tested mice with a mean peak antibody titer of 1:262 in three-times immunized groups. IgG antibody appeared at 2 weeks postinoculation, raised peak levels at 7 weeks postinoculation and persisted over 6 months. Neutralizing antibody was developed, and the percent reduction of input infectivity in 1:100 diluted sera was 74.5 % in three-times immunized groups. This study suggested that DNA vaccine using the gene encoding HCMV gB is a candidate method for developing immunity to HCMV.

Animals↗

PubMed1998

Microvascular integrity as a predictor of left ventricular remodeling after acute anterior wall myocardial infarction.

The purpose of this study was to investigate the relation of microvascular integrity and ventricular remodeling after acute myocardial infarction. Twenty-six patients with first acute anterior myocardial infarction were studied before discharge with myocardial contrast echocardiography (MCE). Opacification index (OI) and wall motion index were calculated in the left anterior descending artery territory and left ventricular diastolic volume was measured at baseline and during a 9-month follow-up. In total 26 patients, the regional wall motion improved but the left ventricular volume and global function was not changed significantly at follow-up. When the patients were divided into 3 groups according to opacification index (> or = 0.75, 0.5 approximately 0.75, < or = 0.5) at baseline, functional recovery was not observed and significant left ventricular dilatation was developed in patients with < or = 0.5 OI. Among the baseline echo-parameters such as ejection fraction, wall motion score, left ventricular volume and opacification index, the best predictor for long term left ventricular dilatation was the opacification index by multivariate analysis. In patients with acute anterior wall infarction the assessment of microvascular integrity by MCE at acute stage provides useful information regarding recovery of dysfunctional regional wall motion and ventricular remodeling.

Coronary Vessels↗

PubMed1998

Protean effects of a natural peptide agonist of the G protein-coupled secretin receptor demonstrated by receptor mutagenesis.

G protein-coupled receptors initiate signaling cascades after associating with heterotrimeric G proteins. This is typically initiated by agonist binding, but can also occur spontaneously, particularly in receptors bearing distinct missense mutations. Two such mutations in the parathyroid hormone receptor are associated with constitutive activity, manifesting clinically as Jansen's metaphyseal chondroplasia. We introduce analogous mutations separately and together into the secretin receptor to explore their impact on another family member. Constructs were expressed transiently in COS cells, and had binding and signaling (cAMP generation) studied. Each construct was processed appropriately to lead to cell surface expression and signaling. Secretin bound to the wild-type receptor with two affinity states recognized, 1% of sites in the high affinity state (Ki = 0.5 +/- 0.1 nM) and 99% in the low affinity state (Ki = 23 +/- 3 nM). Mutant receptor binding best fit a single affinity state, having values for Ki of 5 +/- 1 nM (H156R), 8 +/- 1 nM (T322P) and 6 +/- 1 nM (H156R/T322P), with each of these demonstrating a shift to higher affinity than the predominent low affinity state of the wild-type receptor. Each mutant receptor expressed small to moderate constitutive activity, with basal levels of cAMP activity greater than control (P < .01): H156R, 1.4-fold; T322P, 4.5-fold and H156R/T322P, 6.8-fold. The level of basal activity of even the most active construct was only 15% of the maximal response of wild-type receptor. Although each of the single site mutants responded to secretin by increasing their cAMP levels in a concentration-dependent manner, the dual mutant decreased its cAMP in response to hormone (EC50 = 13 nM). Thus, a natural agonist had become an inverse agonist at this unique construct. Because this could reflect reduced normal coupling with Gs or increased aberrant coupling with Gi, the mechanism was further explored using pertussis toxin and a stable analogue of GTP. Although ligand-binding determinants were retained in the dual receptor mutant, the conformation of this receptor upon secretin binding effected a reduction in its basal coupling with Gs, thereby resulting in inverse agonism.

Animals↗

PubMed1998

A generalized estimating equations approach for testing ordered group effects with repeated measurements.

In repeated measures studies, we are often interested in comparing group effects in which groups are associated with a certain order relation. We propose testing procedures for ordered group effects using the generalized estimating equations (GEE) approach of Liang and Zeger (1986, Biometrika 73, 13-22). The order-constrained GEE estimators of group effects are approximated by the isotonic regression of the unconstrained GEE estimators. Based on these constrained estimators, we construct test statistics for detecting ordered group effects. The limiting distributions of the test statistics are mixtures of chi-square distributions. A Monte Carlo experiment shows improved performances of the proposed tests over the usual chi-square tests in detecting ordered group effects. The proposed test procedures are illustrated by familial polyposis supplementation trial data.

Adenomatous Polyposis Coli↗

PubMed1997

Co-expression of urokinase-type plasminogen activator and its receptor in human gastric-cancer cell lines correlates with their invasiveness and tumorigenicity.

The expression of urokinase-type plasminogen activator (u-PA), its receptor (u-PAR) and metalloproteases activity were analyzed in 4 human gastric-cancer cell lines (AGS, Hs746T, SNU-1, and SNU-5), in an attempt to relate these activities to their invasive potential and tumorigenicity on the modified chorioallantoic membranes (CAM) of chick embryos. Only 1 of the 4 cell lines tested, Hs746T, expressed both u-PA and u-PAR as well as MMP-2, but not MMP-9. This cell line was both tumorigenic and highly invasive (51.3 +/- 13.1%) on a modified CAM. Its invasive capacity was comparable with that of a highly malignant human epidermoid-carcinoma cell line (HEp3), which usually showed 40 to 50% invasiveness. The 3 other cell lines all produced MMP-2 and MMP-9, but only AGS showed moderate invasiveness (24.2 +/- 8.8%). While antibodies to u-PA were significantly effective in reducing CAM invasiveness of Hs746T cells by approximately 40%, the invasiveness of the t-PA-expressing AGS cell line was not affected by anti-t-PA antibodies. These results suggest that when one of the components of the u-PA/u-PAR system (the enzyme and/or the receptor) is not produced and u-PA/u-PAR-dependent cell-surface proteolytic activity is thereby diminished, the malignant phenotype that can be determined by tumorigenicity and invasion of connective tissue on a CAM is compromised. Production of both type-IV collagenases (MMP-2 and MMP-9) cannot offset this deficiency.

Animals↗

PubMed1997

Identifying the molecular control of T-cell death; on the hunt for killer genes.

Apoptosis, the series of morphological changes which result from a cell-suicide program, has fascinated biologists in recent years. Identifying apoptosis regulatory and effector genes to elucidate the molecular mechanisms of programmed cell death has been a challenging but successful endeavor. However, our knowledge of this process is far from complete. The discovery of 'death genes' has provided insight into the homeostatic mechanisms regulating the immune system including the clonal deletion of self-reactive and activated lymphocytes. Notably, apoptosis induced by T-cell receptor (TCR) stimulation is the critical event which drives negative selection of thymocytes and peripheral T cells. Differential display, differential screening and subtractive hybridization have provided the technical backbone for the isolation of genes whose expression is specific for apoptotic cells. However, the genes identified by these techniques only correlate with the apoptotic phenotype and their expression may be the result of non-apoptotic pathways also affected by the death-inducing agent. Here, we review what is known about the molecular mechanisms of TCR-triggered apoptosis and discuss techniques used to isolate and characterize death regulatory molecules. In addition, we present a novel approach utilizing somatic cell genetics to clone genes involved in TCR-triggered apoptosis.

Apoptosis↗

PubMed1997

Analysis of high-energy phosphometabolites in delayed experimental skin flaps using 31P nuclear magnetic resonance spectroscopy.

Using 31phosphorus magnetic resonance spectroscopy (31P-MRS) and surface coils, we noninvasively assessed the intracellular changes in delayed skin flaps of the high-energy phosphometabolites, ATP and phosphocreatine, which are basic energy sources of living cells. In 5 rats, a 3.5 x 7.5 cm bipedicled skin flap was elevated from the dorsum and its caudal base divided after a delay period of 2 weeks. MRS spectra were collected at four times: immediately, 1 week and 2 weeks after elevation of the bipedicled flap, and 18 hours after division of its caudal base. From the spectra, we calculated the intracellular pH and the following ratios: Pi/PCr, PCr/(PCr + Pi), ATP/(PCr + Pi) (PCr, phosphocreatine; Pi, inorganic phosphate; ATP, adenosine triphosphate). As an undelayed control group, cranially based skin flaps of the same size were elevated in another 5 rats, and MRS spectra were obtained 18 hours later. The length of the surviving area was longer in the delayed flaps than in the undelayed flaps. Intracellular pH and ATP/(PCr + Pi) showed no significant alteration in the delayed skin flaps, not only during the delay period but also after conversion of the flaps into cranially based flaps by division of their caudal base. In contrast, PCr/(PCr + Pi) decreased with each surgical procedure (bipedicled flap elevation and base division). Compared with the necrotic distal portion of the undelayed flaps, the surviving distal portion of the delayed flaps had higher levels of intracellular pH and ATP/(PCr + Pi) and lower levels of PCr/(PCr + Pi). Intracellular pH and ATP/(PCr + Pi) showed a strong correlation with the viability of the delayed and undelayed skin flaps, and they can be prognostic indices for predicting the fate of skin flaps. The reason the surviving distal portions of the delayed flaps maintained their level of ATP despite the low intracellular level of PCr may be that the accumulation of mitochondrial creatine kinase enhances the so-called 'energy transport' function of the creatine kinase/phosphocreatine system.

Adenosine Triphosphate↗

PubMed1997

Complications of pediatric craniofacial surgery in the Orient: analysis of a 10-year experience.

Numerous reports on the complications of craniofacial surgery have been published in the western world. However, relatively little such information concerning Oriental populations has been documented. We therefore set out to provide a retrospective analysis of all the complications of craniofacial surgery encountered during the 10-year period of 1986 to 1995 at Seoul National University Children's Hospital, the only children's hospital in Korea. Forty-nine children underwent 57 consecutive craniofacial procedures at our institution during 1986 to 1995. A retrospective chart analysis of the frequency and types of complications was performed. Mantel-Haenszel chi-square tests were then calculated for several factors, including age at surgery, duration of surgery, intraoperative losses of hemoglobin and hematocrit, total amount of blood transfusion, and the number of complications according to year, diagnosis, and operative procedure to find any significant correlation with the incidence of complications. Mortality was 1.8%. The major complication rate was 7.0% and included cases of visual loss and persistent cerebrospinal fluid leak. Analysis revealed the presence of several trends, including an increased incidence of complications with increased patient age at surgery, duration of surgery, and intraoperative loss of hematocrit. The number of complications was also noted to increase in cases with complex craniofacial synostosis syndromes (Crouzon's, Apert's Antley-Bixler, etc.) and tumors of the orbit and cranium. Finally, complications were noted to decrease in recent years, most likely due to the increased experience of our craniofacial team. Nevertheless, statistical analysis revealed that the incidence of complications correlated significantly only with increased duration of surgery (p < 0.05). The results of our study indicate that although craniofacial surgery in the Orient carries an inherent risk for significant complications, the risk can be minimized and the rate of mortality and major complications kept to an acceptable level by a careful and experienced craniofacial team. Groups at most risk for complications are those with a long duration of surgery.

Adolescent↗

PubMed1997

Masseter muscle atrophy after ostectomy of the mandibular angle in rabbits.

In order to get information about changes in the masseter muscle when operations are performed on the mandibular angle area, we classified 70 New Zealand White rabbits into group O (ostectomy) and group D (dissection). In group O we performed unilateral ostectomy of the mandibular angle, while in group D we performed unilateral dissection of the masseter muscle limited to the mandibular angle area. Then we compared morphologic, histologic, and histochemical changes in experimental masseter muscles with those in normal control masseter muscles. We examined 5 rabbits in each group at the following intervals: 1, 2, 4, 6, 8, 12, and 24 weeks. In group D (dissection), there were no remarkable changes at all examinations. In group O (ostectomy), there was a 30 percent decrease in experimental muscle mass compared with control muscle. On examination of muscle fiber types, a decrease in type I fibers and an increase in type IIA and IIB fibers were noticed (p < 0.05). Each experimental muscle fiber became more irregularly and angularly shaped, and mean fiber area also was reduced. Sarcomere lengths of experimental muscle fibers were significantly reduced to 80 percent of control values (p < 0.05) during the first 4 weeks, but after 6 weeks they were lengthened to control values. Collagen and fibrin did not show much difference between experimental and control muscles. All these findings imply that masseter muscle atrophy after ostectomy of the mandibular angle is not due to connective-tissue changes but to individual muscle fiber atrophy accompanied by functional adaptation of sarcomeres and changes in muscle fiber types.

Adaptation, Physiological↗

PubMed1997

Increased expression of urokinase type plasminogen activator(u-PA), plasminogen activator inhibitor-1(PAI-1), and collagenases in Caco-2 cells infected by Salmonella typhimurium.

Salmonella penetrates the basement membrane of intestinal epithelial cells into deeper tissues, in which process extracellular matrix proteases should be required. Hypothesizing that the proteases might be provided by host cells, we investigated the changes of expression of urokinase type plasminogen activator(u-PA), plasminogen activator inhibitor-1(PAI-1), and collagenases in epithelial cells(Caco-2) infected with Salmonella typhimurium. The change of mRNA levels, amount of the enzyme secretion and functional activity were analyzed by Northern blot, ELISA, and Zymography. The mRNA level of u-PA was elevated by Salmonella infection itself without any exogenous transcription regulators. u-PA was actively secreted into the medium and was enzymatically active. The synthesis and secretion of PAI-1 was increased over time from 2 hrs post infection(pi) to 8 hrs pi. Zymographic assay revealed that the secretion of collagenases (type IV, type V and interstitial collagenase) were also increased. Taken together, S. typhimurium infection might induce accumulation of pericellular proteolytic activity and consequently degrade the extracellular matrix surrounding the infected cells. These in turn might enable Salmonella to invade into deeper tissues.

Caco-2 Cells↗

PubMed1996

T cell receptor-dependent cell death of T cell hybridomas mediated by the CD30 cytoplasmic domain in association with tumor necrosis factor receptor-associated factors.

CD30 is a member of the tumor necrosis factor superfamily and a surface marker for Hodgkin's disease. Normal activated T cells and several virally transformed T or B cell lines also show CD30 expression. The interaction of CD30 with its ligand induces cell death or proliferation, depending on the cell type. In this report we characterize the signals mediated by the intracellular domain of CD30 and show that, in combination with signal(s) transduced by the T cell receptor, the multimerization of CD30 cytoplasmic domain induces Fas(CD95)-independent cell death in T cell hybridomas. Deletion analysis shows that the COOH-terminal 66 amino acids of CD30 are required to induce cell death. Using the yeast two-hybrid system, we have identified that the same region of CD30 interacts with tumor necrosis factor receptor-associated factor (TRAF)1 and TRAF2. These results indicate that TRAF1 and/or TRAF2 play an important role in cell death in addition to their previously identified roles in cell proliferation.

Base Sequence↗

PubMed1996

A novel gene product that couples TCR signaling to Fas(CD95) expression in activation-induced cell death.

Cross-linking the TCR in T cell hybridomas induces cell apoptosis following activation. This activation-induced apoptosis has been used as a model for clonal deletion of thymocytes or peripheral T cells. Anti-TCR-induced apoptosis of T cell hybridomas requires de novo macromolecular synthesis, including up-regulation of Fas and FasL. The Fas-FasL interaction then activates the apoptosis program. To study apoptosis-specific signaling processes, we generated a mutant T cell hybridoma line defective in induction of apoptosis, but competent to induce activation, upon TCR triggering. Subsequently, we cloned the gene TDAG51, which restored activation-induced apoptosis when transfected into the mutant cell line, and showed that TDAG51 expression was required for Fas expression. Thus, TDAG51 plays an essential role in induction of apoptosis by coupling TCR stimulation to Fas expression.

Amino Acid Sequence↗

PubMed1995

Proteolytic processing is required for viral superantigen activity.

The mouse mammary tumor virus-7 superantigen (vSAG7) is proteolytically processed in B cells at as many as three positions. Proteolytic processing appears to be important for superantigen activity because a processed form of vSAG7 was predominant among those forms that were found to bind to major histocompatibility complex class II molecules. To determine the functional significance of proteolytic processing, a mutation was introduced in vSAG7 at one of the sites where proteolytic cleavage is thought to take place in B cells. Elimination of the putative processing site at position 171 abrogated detectable vSAG7 surface expression in B cells, indicating that proteolytic processing is required for vSAG7 function. Coexpression in insect cells of vSAG7 and furin, a proprotein-processing enzyme, also demonstrated that furin could process vSAG7 at position 171.

Amino Acid Sequence↗

PubMed1995

The importance of accurate repair of the orbicularis oris muscle in the correction of unilateral cleft lip.

Most of the attempts and efforts in cleft lip repair have been directed toward the skin incision. The importance of the orbicularis oris muscle repair has been emphasized in recent years. The well-designed skin incision with simple repair of the orbicularis oris muscle has produced a considerable improvement in the appearance of the upper lip; however, the repaired upper lip seems to change its shape abnormally in motion and has a tendency to be distorted with age if the orbicularis oris muscle is not repaired precisely and accurately. Following the dissection of the normal upper lip and unilateral cleft lip in cadavers, we could find two different components in the orbicularis oris muscle, a superficial and a deep component. One is a retractor and the other is a constrictor of the lip. They have antagonistic actions to each other during lip movement. We also can identify these two different components of the muscle in the cleft lip patient during operation. We thought inaccurate and mixed connection between these two different functional components could make the repaired lip distorted and unbalanced, which would get worse during growth. By identification and separate repair of the two different muscular components of the orbicularis oris muscle (i.e., repair of the superficial and deep components on the lateral side with the corresponding components on the medial side), better results in the dynamic and three-dimensional configuration of the upper lip can be achieved, and unfavorable distortion can be avoided as the patients grow.(ABSTRACT TRUNCATED AT 250 WORDS)

Cleft Lip↗

PubMed1994

Surgical treatment of mandibular prognathism in collaboration with orthodontic treatment in Korea.

Mandibular prognathism is defined by John Hunter as follows: "The lower jaw projecting too far forward so that the foreteeth pass before those of the upper jaw, therefore disfigurement and malocclusion are two of the main facial characteristics." Other distinguishing features are the coexistence of class III malocclusion, incomplete closure of lip, deviation of the midline, and decrease of labiomental fold. Generally, the functional occlusal relationship and balanced facial harmony cannot be obtained by surgical or orthodontic treatment alone. Its success depends on careful conjoint, supplementary diagnostic, and treatment planning. As a cardinal principle the authors made the following combined surgical and orthodontic treatment plans: (1) Orthodontic treatment relocates and decompensates the malpositioned teeth (remove the masking effect of teeth) and, therefore, skeletal deformity is exposed maximally. (2) Surgical treatment eliminates the maximally exposed skeletal defect. Therefore, dramatic facial balance and functional occlusal relationship are obtained. Treatment planning includes the pre- and postoperative orthodontic treatment, lateral cephalometric prediction tracing (LCPT), and model surgery with dental cast. The authors made it easy with the use of an acrylic dental wafer to coordinate exact occlusal relationship after surgery. We treated mandibular prognathism by using Dautrey's modification of the sagittal split ramus osteotomy (SSRO) (10 cases) and intraoral vertical ramus osteotomy (IVRO) (5 cases) and sometimes additional genioplasty (2 cases). IVRO was used in those cases where (1) the amount of setback was more than 10 mm and (2) where there was a flat gonial angle.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗