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J Y Choi

Publications and source records attributed to J Y Choi.

At least 55 records · Page 3Linked to original sources
PubMed2001

Genetic changes of hOGG1 and the activity of oh8Gua glycosylase in colon cancer.

oh8Gua glycosylase repairs DNA by removing oh8Gua, a highly mutagenic oxidative DNA adduct. Recently, the gene for human oh8Gua glycosylase (hOGG1) was cloned and several mutational types have been reported. However, the implications of such mutations in human cancer have not been clearly demonstrated. To test the involvement of hOGG1 mutation in colon carcinogenesis, we analysed the genetic changes of hOGG1 and the activity of oh8Gua glycosylase in 15 paired normal and tumorous colon specimens. The activity of antioxidant enzymes (catalase and superoxide dismutase (SOD)) and extent of oxidative cellular damage (oh8Gua and malondialdehyde) were also assessed to compare the oxidative status of normal and tumour tissues. An Arg 154 to His mutation was detected in two tumour samples, but not in the corresponding normal tissues. A Ser 326 to Cys mutation (polymorphism) was found in both the normal and tumour tissues of 3 patients. However, neither the Arg 154 to His mutation nor the polymorphism at codon 326 significantly decreased the oh8Gua glycosylase activity. The mean activity of oh8Gua glycosylase was significantly higher in the tumours than in normal tissues (P=0.022). Antioxidant enzyme activities were decreased (catalase; P=0.004 and SOD; P=0.002), and the extent of oxidative damage correspondingly increased in the tumour tissues (oh8Gua; P=0.007 and malondialdehyde; P=0.046). Although the sample size was limited, these results suggest that the somatic mutation or the polymorphism of hOGG1 is less likely to be involved in colon carcinogenesis. Nevertheless, the greater oxidative DNA damage in the tumour tissues, as a possible result of impaired antioxidant activity, implies an important role for oxygen free-radicals in colon carcinogenesis.

Adult↗
PubMed2001

Synthesis and phosphodiesterase 5 inhibitory activity of novel phenyl ring modified sildenafil analogues.

New sildenafil analogues containing an ether ring fused into the phenyl moiety, 6a--d and 7a--d, were efficiently synthesized from the readily available starting materials, 1a--d and 2, in five steps. Ab initio calculations indicated that introduction of a cyclic ether to the phenyl group might enhance the co-planarity of the molecule. The torsional angles were calculated to be 2--3 degrees for the 5-membered cyclic ether derivatives, 6a, 6c, 7a, and 7c, and 12--16 degrees for the 6-membered ones, 6b, 6d, 7b, and 7d. On the other hand, sildenafil showed the least co-planarity with the torsional angle of 23 degrees compared with the target compounds, 6a--d and 7a--d. In the enzyme assay, however, the in vitro PDE 5 inhibitory activity was found out to be inversely related to the degree of co-planarity. In other words, the least planar sildenafil showed the highest activity, and the most planar 5-membered cyclic ether derivatives were least active by 100--200-fold compared with sildenafil. Our study clearly demonstrated that the open chain 2'-alkoxy group of the phenyl ring, although less effective for inducing the co-planarity, seemed to act as a much better lipophilic requirement than the cyclic alkoxy moiety.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2001

Synthesis and phosphodiesterase 5 inhibitory activity of new 5-phenyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one derivatives containing an N-acylamido group phenyl ring.

New sildenafil analogues with an N-acylamido group at the 5'-position of the phenyl ring, 6a--e, were prepared from the readily available starting compound 2 in four straightforward steps. Enzyme assays demonstrated that all the target compounds 6a-e showed higher PDE5 inhibitory activities than sildenafil. It was observed that the PDE5 inhibitory activity was enhanced as the chain length of R group increased, but introduction of the branched alkyl groups such as isopropyl (6d) and cyclohexyl (6e) resulted in the drop of potency compared with 6c. In particular the N-butyrylamido derivative 6c exhibited the highest PDE5 inhibitory activity, and was about 6-fold more potent than sildenafil. However, all the compounds exhibited somewhat weak selectivity (1--3-fold) over PDE6, indicating that the compounds 6a--e have intrinsically lower selectivity than sildenafil.

Phosphodiesterase Inhibitors↗
PubMed2001

Synthesis and phosphodiesterase inhibitory activity of new sildenafil analogues containing a carboxylic acid group in the 5'-sulfonamide moiety of a phenyl ring.

New sildenafil analogues possessing a carboxylic acid group in the 5'-sulfonamide of the phenyl ring, 9a-l, were prepared from the readily available starting compounds 6a-b and cyclic amines 3-5 in a three-step sequence. In the enzyme assays, it has been shown that all the target compounds 9a-l proved to be more potent in inhibiting phosphodiesterase type 5 (PDE5) than sildenafil by 4-38-fold. The effects on the IC(50) values were investigated by varying the alkoxy group (R) of the phenyl ring, the sulfonamide type (X), and the length of the methylene chain linking the carboxylic acid, and the results were discussed in detail. From this study, we have clearly demonstrated that introduction of a carboxylic acid group to the 5'-sulfonamide moiety of the phenyl ring greatly enhanced PDE5 inhibitory activity, probably by mimicking the phosphate group of cGMP. The piperidinyl propionic acid derivative 9i, which showed the highest PDE5 inhibitory activity and comparable to better selectivity over PDE isozymes in comparison with sildenafil, has been selected for more detailed biological investigations.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2001

Original sagittal split osteotomy revisited for mandibular distraction.

Introduction: A malformed mandible and an abnormally positioned mandibular foramen make it difficult to plan an ideal osteotomy line for mandibular distraction. In addition, there have been reports of such complications as nonunion, damage and stretch injury of the inferior alveolar nerve and tooth germ damage when conventional osteotomy or corticotomy are used for mandibular distraction. The authors utilized the original sagittal split ramus osteotomy for mandibular distraction. Patients and Methods: Five patients (three unilateral hemifacial microsomia, one bilateral hemifacial microsomia, and one mandibular retrusion) were included in this study of distraction osteogenesis using the sagittal split ramus osteotomy. Extraoral distraction devices were applied to the first four patients. An intraoral device with mono-cortical screw fixation was used for the fifth patient. Result: In all five cases, the results of the distraction were satisfactory. Complications (as listed) of conventional osteotomy when used for distraction were avoided. Satisfactory results were achieved and these were also well maintained postoperatively (mean follow up: 36 months). Conclusion: The authors believe that sagittal osteotomy for mandibular distraction osteogenesis makes it possible, to avoid injury to the inferior alveolar nerve during operation and stretching injury during distraction and to prevent tooth germ injury. It is also possible to diversify the osteotomy line for various force vectors to enlarge the bony contact surface area. Therefore, we suggest that sagittal split ramus osteotomy should be used as a preferred modification of osteotomy for mandibular distraction. Copyright 2001 European Association for Cranio-Maxillofacial Surgery.

Journal Article↗
PubMed2001

Odontogenic keratocyst: Review of 256 cases for recurrence and clinicopathologic parameters.

Odontogenic keratocyst (OKC) is of particular interest because of its high recurrence rate and aggressive behavior. Two hundred fifty-six cases of OKC were reviewed for the age of the patient at diagnosis, sex of the patient, OKC location, and radiographic findings, and 132 patients with OKC were observed to estimate recurrence, which was analyzed for age, sex, location, and several histopathologic findings. OKCs occurred more frequently in men (58.6%) than in women (41.4%), and they occurred in patients within a wide age range, most commonly in patients in the third decade of life (28.9%), followed by those in the second decade (25.0%); the mean age of patients with OKC was 30.8 years. One hundred ninety-six of the 256 cases (76.5%) occurred in the mandible, and the other 60 cases (23.5%) occurred in the maxilla. The mandibular molar and the premolar areas (51.2%) were the most common sites, and the most frequent clinical manifestations at first admission were swelling, pain, or both (82.4% of total cases). Radiographic impressions included dentigerous cyst (27.3%), OKC (25.4%), primordial cyst (14.8%), ameloblastoma (11.7%), residual cyst (9.8%), and radicular cyst (3.1%). The frequency of recurrence at the follow-up examination was 58.3%. There was no significant difference in the recurrence rate on the basis of the sex of the patient. However, OKCs had a significantly higher recurrence rate in patients in the fifth decade of life than in patients in the other age groups (P = .005).Recurrence rates were significantly dependent on the sites of involvement, and OKCs in the mandibular molar region had significantly higher recurrence rates than those in other sites (P = .001). The histopathologic presence of one or more daughter cysts was significantly related to recurrence (P = .03).

Adolescent↗
PubMed2001

Microvascular decompression for hemifacial spasm: a long-term follow-up of 1,169 consecutive cases.

We analyzed the records of 1,169 patients with hemifacial spasm (HFS) who underwent microvascular decompression (MVD) and were followed up for more than 6 months from January 1987. The mean follow-up duration was 23.8 months (6-145 months). Excellent surgical outcome was obtained in 90.5% and good in 4.5%, giving an overall success rate of 95.0%. There was statistically significant relationship between vertebral artery (VA) shift and side of symptom. Permanent facial weakness and hearing impairment were 1.4% and 2.3%, respectively. There were no anatomical differences at the root entry zone (REZ) and significant differences of surgical outcome in young HFS (34 patients). Factors such as type of offender, severity of compression on the facial nerve root, and the degree of decompression of the REZ on postoperative MRI did not correlate with surgical outcome.

Adult↗
PubMed2001

Gamma knife radiosurgery for metastatic brain tumors.

We reviewed our series of metastatic brain tumors treated by Gamma Knife Radiosurgery. From May 1992 to January 2001, 115 consecutive patients with 425 lesions were treated over 128 treatment sessions. Forty three patients were known to have died at the end of the recording period. The mean follow-up duration was 11.6 months and mean number of lesions was 3.5. The most common primary sites were lung and breast. Mean tumor volume was 4.2 cm(3) and mean margin dose was 16.2 Gy. 6-month, 1-year, and 18-month survival rates were 73.6, 58, and 46%, respectively. Multivariate analysis revealed that higher KPS scores, no evidence of extracranial metastasis, and controlled primary disease were significantly related to longer survival. Adjuvant whole brain irradiation did not significantly influence on the prolongation of survival time and local control of radiosurgically treated lesions.

Brain Neoplasms↗
PubMed2001

Differential regulation of the two principal Runx2/Cbfa1 n-terminal isoforms in response to bone morphogenetic protein-2 during development of the osteoblast phenotype.

Cbfa1/Runx2 is a transcription factor essential for bone formation and osteoblast differentiation. Two major N-terminal isoforms of Cbfa1, designated type I/p56 (PEBP2aA1, starting with the sequence MRIPV) and type II/p57 (til-1, starting with the sequence MASNS), each regulated by distinct promoters, are known. Here, we show that the type I transcript is constitutively expressed in nonosseous mesenchymal tissues and in osteoblast progenitor cells. Cbfa1 type I isoform expression does not change with the differentiation status of the cells. In contrast, the type II transcript is increased during differentiation of primary osteoblasts and is induced in osteoprogenitors and in premyoblast C2C12 cells in response to bone morphogenetic protein-2. The functional equivalence of the two isoforms in activation and repression of bone-specific genes indicates overlapping functional roles. The presence of the ubiquitous type I isoform in nonosseous cells and before bone morphogenetic protein-2 induced expression of the type II isoform suggests a regulatory role for Cbfa1 type I in early stages of mesenchymal cell development, whereas type II is necessary for osteogenesis and maintenance of the osteoblast phenotype. Our data indicate that Cbfa1 function is regulated by transcription, cellular protein levels, and DNA binding activity during osteoblast differentiation. Taken together, our studies suggest that developmental timing and cell type- specific expression of type I and type II Cbfa isoforms, and not necessarily molecular properties or sequences that reside in the N-terminus of Cbfa1, are the principal determinants of the osteogenic activity of Cbfa1.

Animals↗
PubMed2001

A specific targeting signal directs Runx2/Cbfa1 to subnuclear domains and contributes to transactivation of the osteocalcin gene.

Key components of DNA replication and the basal transcriptional machinery as well as several tissue-specific transcription factors are compartmentalized in specialized nuclear domains. In the present study, we show that determinants of subnuclear targeting of the bone-related Runx2/Cbfa1 protein reside in the C-terminus. With a panel of C-terminal mutations, we further demonstrate that targeting of Runx2 to discrete subnuclear foci is mediated by a 38 amino acid sequence (aa 397-434). This nuclear matrix-targeting signal (NMTS) directs the heterologous Gal4 protein to nuclear-matrix-associated Runx2 foci and enhances transactivation of a luciferase gene controlled by Gal4 binding sites. Importantly, we show that targeting of Runx2 to the NM-associated foci contributes to transactivation of the osteoblast-specific osteocalcin gene in osseous cells. Taken together, these findings identify a critical component of the mechanisms mediating Runx2 targeting to subnuclear foci and provide functional linkage between subnuclear organization of Runx2 and bone-specific transcriptional control.

Amino Acid Sequence↗
PubMed2001

Differential expression patterns of Runx2 isoforms in cranial suture morphogenesis.

Runx2 (previously known as Cbfal/Pebp2alphaA/AML3), a key transcription factor in osteoblast differentiation, has at least two different isoforms using alternative promoters, which suggests that the isoforms might be expressed differentially. Haploinsufficiency of the Runx2 gene is associated with cleidocranial dysplasia (CCD), the main phenotype of which is inadequate development of calvaria. In spite of the biological relevance, Runx2 gene expression patterns in developing calvaria has not been explored previously, and toward this aim we developed three probes: pRunx2, which comprises the common coding sequence of Runx2 and hybridizes with all isoforms; pPebp2alphaA, which specifically hybridizes with the isoform transcribed with the proximal promoter; and pOsf2, which hybridizes with the isoform transcribed with the distal promoter. These probes were hybridized with tissue sections of mouse calvaria taken at various time points in development. Runx2 expression was localized to the critical area of cranial suture closure, being found in parietal bones, osteogenic fronts, and sutural mesenchyme. Pebp2alphaA and Osf2 showed tissue-specific expression patterns. The sites of Pebp2alphaA expression were almost identical to that of pRunx2 hybridization but expression was most intense in the sutural mesenchyme, where undifferentiated mesenchymal cells reside. The Osf2 isoform was strongly expressed in the osteogenic fronts, as well as in developing parietal bones, where osteopontin (OP) and osteocalcin (OC) also were expressed. However, in contrast to Pebp2alphaA, Osf2 expression did not occur in sutural mesenchyme. Pebp2alphaA also was expressed prominently in primordial cartilage that is found under the sutural mesenchyme and is not destined to be mineralized. Thus, Osf2 isoforms contribute to events later in osteoblast differentiation whereas the Pebp2alphaA isoform participates in a wide variety of cellular activities ranging from early stages of osteoblast differentiation to the final differentiation of osteoblasts.

Animals↗
PubMed2001

Two-stage reconstruction of bilateral alveolar cleft using Y-shaped anterior-based tongue flap and iliac bone graft.

OBJECTIVE: When an alveolar cleft is too large to close with adjacent mucobuccal flaps or large secondary fistula following a primary bilateral palatoplasty exists, a one-stage procedure for bone grafting becomes challenging. In such a case, we have used the tongue flap to repair the fistula and cleft alveolus followed by bone grafting to the cleft defect performed several months later. The purpose of this article is to report on our experiences with the use of an anteriorly based Y-shaped tongue flap to fit the palatal and labial alveolar defects and on the ultimate result of the bone graft. PATIENTS: A series of 14 patients were treated with this approach from January 1994 to December 1998. The average age of the patients was 15.8 years (range 5 to 28 years). The mean period of follow-up following the second stage bone graft operation was 45.9 months (range 9 to 68 months). In 9 of the 14 patients, the long-fork type of a Y-shaped tongue flap was used for extended coverage of the labial-side alveolar defects with the palatal fistula; in the remaining patients, the short-forked design was used. RESULTS: All patients demonstrated a good clinical result after the initial repair of cleft alveolus and palatal fistula. There was no fistula recurrence, although partial necrosis of distal margin in long-forked tongue flap occurred in one patient. Furthermore, the bone graft, which was performed an average of 8 months after the tongue flap repair, was always successful. Occasionally, transferred tongue tissue bulging interfered with the hygienic care of nearby teeth; however, these problems could be solved with proper contour-plasty performed afterward. No donor site complications such as sensory disturbance, change in taste, limitations in tongue movement, normal speech impairments, or tongue disfigurement were encountered. CONCLUSION: This two-stage reconstruction of a bilateral cleft alveolus using a Y-shaped tongue flap and iliac bone graft was very successful. It may be indicated for a bilateral cleft alveolus patient in which the direct closure of the cleft defect with adjacent tissue or the buccal flap is not easy because of scarred fibrotic mucosa and accompanied residual palatal fistula.

Adolescent↗
PubMed2001

Effects of insulin and antioxidant on plasma 8-hydroxyguanine and tissue 8-hydroxydeoxyguanosine in streptozotocin-induced diabetic rats.

Cumulating evidence suggests that enhanced oxidative stress may contribute to diabetic angiopathy. The levels of 8-hydroxydeoxyguanosine (8-OHdG) and 8-hydroxyguanine (8-OHG), indicators of oxidative DNA damage, in tissue or body fluid are increased in diabetic patients. However, it is unclear whether plasma 8-OHG correlates with tissue 8-OHdG and whether insulin or antioxidant treatment reduces plasma 8-OHG in diabetic state. In this study, we measured the 8-OHG levels in plasma as well as the 8-OHdG levels in liver and kidney in streptozotocin-induced diabetic rats (DR) treated with insulin (DR+I), insulin and probucol (DR+I/P), or insulin and vitamin E (DR+I/E). There was a correlation between plasma 8-OHG levels and tissue 8-OHdG levels (plasma 8-OHG vs. liver 8-OHdG: r = 0.64, P < 0.001; plasma 8-OHG vs. kidney 8-OHdG: r = 0.38, P = 0.06). DR had levels of plasma 8-OHG that were three times higher than control rats (CR), whereas they had levels of tissue 8-OHdG that were approximately 1.5-2 times higher. Plasma 8-OHG levels in DR were almost normalized by insulin treatment, although insulin partially corrected hyperglycemia (plasma 8-OHG: CR 3.3 +/- 2.7 pmol/ml; DR 10.4 +/- 2.3 pmol/ml, P < 0.05 vs. CR; DR with insulin 3.6 +/- 1.0 pmol/ml, P < 0.05 vs. DR). However, tissue 8-OHdG levels in DR were significantly decreased by combined treatment with insulin and antioxidant (probucol or vitamin E), but not by insulin treatment alone. This data suggests that plasma 8-OHG could be a useful biomarker of oxidative DNA damage in diabetic subjects. The mechanism of differential response of plasma 8-OHG and tissue 8-OHdG to insulin and antioxidant treatment remains to be elucidated.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2001

Sustained ventricular tachycardia in children after repair of congenital heart disease.

To investigate an association between surface electrocardiographic (ECG) parameters and sustained ventricular tachycardia (VT) in children after repair of congenital heart disease (CHD), data were obtained and analyzed in three groups (group I, 7 postoperative patients with episode of sustained VT (4 tetralogy of Fallot (TOF), 2 double outlet right ventricle (DORV), 1 truncus arteriosus); group II, 14 children with postoperative TOF not associated with VT; group III, 14 normal children). Mean age at the onset of sustained VT was 129+/-77 months (range 60-232); mean age at corrective surgery, 44+/-33 months (range 10-102); mean follow-up period after surgery, 84+/-74 months (range 20-185); the duration from repair to the onset of sustained VT, range 1-185 months. Compared to group II and III, group I showed longer QRS duration (group I, 137+/-10 msec; group II, 114+/-22 msec; group III, 65+/-12 msec) and shorter corrected J to Tmax interval (group I, 209+/-24 msec; group II, 272+/-44 msec; group III, 249+/-18 msec). QT and corrected QT, J to Tmax interval, and their dispersions in group I and II are significantly different from those of group III. In conclusion, QRS duration and corrected J to Tmax interval could be helpful to predict ventricular tachycardia in postoperative CHD.

Adolescent↗
PubMed2001

The relationship of histologic activity to serum ALT, HCV genotype and HCV RNA titers in chronic hepatitis C.

It is unclear whether serum ALT levels or virological characteristics of hepatitis C virus(HCV) including HCV genotypes and HCV RNA titers, can reflect the degree of histological injury in chronic hepatitis C. The aim of this study was to investigate the relationships between the levels of histological damage and serum ALT levels, HCV genotypes or circulating HCV RNA titers in chronic hepatitis C. A total of 56 patients underwent liver biopsy and the histological activity index (HAI) was evaluated by Knodell's scoring system. HCV genotype by RT-nested PCR and HCV RNA quantitation by competitive RT-PCR were performed. Thirty-four patients were infected with HCV genotype 1b, 20 patients with genotype 2a, and 2 patients with undetermined type. Serum ALT levels were not positively correlated with total HAI score or HCV RNA titers, but showed a linear correlation with scores of piecemeal necrosis (r=0.32, p<0.05) and portal inflammation (r=0.27, p<0.05). HCV genotype had no significant correlation with RNA titers, HAI score or with serum ALT levels. Also, no statistical relationship was seen between HCV RNA titer and HAI score. These results suggest that liver histology is essential to evaluate the severity of chronic hepatitis C precisely.

Adolescent↗
PubMed2001

Sweet's syndrome during the treatment of acute promyelocytic leukemia with all-trans retinoic acid.

All-trans retinoic acid (ATRA) is the standard induction treatment for acute promyelocytic leukemia (APL). Quite many ATRA-related side effects, including retinoic acid syndrome, were reported. So far, it has rarely been reported that Sweet's syndrome, characterized by fever, neutrophilia, painful erythematous cutaneous plaques, dense dermal infiltrates of mature neutrophils and rapid response to steroid therapy, is associated with ATRA. In the case that Sweet's syndrome associated with ATRA is found, physicians will have to face a great challenge over the possibility of infectious conditions. We present here a case of Sweet's syndrome associated with ATRA. A 35-year-old female with APL developed fever, painful erythematous cutaneous plaques on both cheeks, right wrist and both shins during induction chemotherapy with ATRA. A skin biopsy revealed a dense dermal infiltrate, consisting of mature neutrophils without vasculitis or cutaneous immunoglobulin deposits, which is compatible with Sweet's syndrome. Oral prednisone was administered and the lesions started to improve within 48 hours.

Adult↗
PubMed2001

Coordination of pancreatic HCO3- secretion by protein-protein interaction between membrane transporters.

Increasing evidence suggests that protein-protein interaction is essential in many biological processes including epithelial transport. In this report, we discuss the significance of protein interactions to HCO(3)(-) secretion in pancreatic duct cells. In pancreatic ducts HCO(3)(-) secretion is mediated by cystic fibrosis transmembrane conductance regulator (CFTR) activated luminal Cl(-)/HCO(3)(-) exchange activity and HCO(3)(-) absorption is achieved by Na(+)-dependent mechanisms including Na(+)/H(+) exchanger 3 (NHE3). We found biochemical and functional association between CFTR and NHE3. In addition, protein binding through PDZ modules is needed for this regulatory interaction. CFTR affected NHE3 activities in two ways. Acutely, CFTR augmented the cAMP-dependent inhibition of NHE3. In a chronic mechanism, CFTR increases the luminal expression of Na(+)/H(+) exchange in pancreatic duct cells. These findings reveal that protein complexes in the plasma membrane of pancreatic duct cells are highly organized for efficient HCO(3)(-) secretion.

Animals↗