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Biomedical subjects

S K Han

Publications and source records attributed to S K Han.

At least 73 records · Page 4Linked to original sources
PubMed1999

Association of HLA class I antigens with diffuse panbronchiolitis in Korean patients.

Diffuse panbronchiolitis (DPB) is a chronic obstructive pulmonary disease of unknown etiology. Observations of significantly increased frequency of human leukocyte antigen (HLA)-B54 in Japanese patients and occurrence of familial cases suggest possible genetic predisposition to the disease susceptibility. To evaluate the possible association of HLA with the disease in Koreans, we have analyzed 30 patients for HLA class I (A, B, C) and class II (DR) antigens by the serologic and DNA typing methods, respectively. The most significant change in the patients compared to the control subjects was increased frequency of HLA-A11 (53.3% versus 17.5%, corrected p [pc] = 1.2 x 10(-)4, odds ratio [OR] = 5.4). In addition, B55 showed significant positive association (16.7% versus 3.5%, pc = 0.05, OR = 5.5), and B62 and Cw4 showed rather weak association with the disease. Certain A11-associated haplotypes showed much stronger positive association with the disease, compared to A11 antigen itself. Observations of a strong association of HLA-A11 in Koreans and B54 in Japanese with DPB suggest that the candidate gene(s) responsible for the disease susceptibility is located within the HLA class I region, most probably between HLA-A and HLA-B loci.

Adult↗
PubMed1999

The clinical characteristics of pulmonary alveolar proteinosis: experience at Seoul National University Hospital, and review of the literature.

Pulmonary alveolar proteinosis is such an extremely rare disease in Korea, that only a few cases have been reported. Meanwhile five cases were experienced at Seoul National University Hospital over ten years since 1987. We summarized the clinical characteristics and courses of them. Seven cases reported in the literature were included to add data about clinical characteristics and courses although only a few case reports mentioned patient's course. Middle aged male patients were mainly affected. No association with particular environmental or occupational exposure was identified. Dyspnea on exertion was the main symptom. Bilateral crackles were consistent, and bilateral parahilar hazy infiltrations on plain chest radiograph and ground glass opacity on high-resolution CT were characteristic. Superimposed infection was not identified in any patient at the time of diagnosis. Decreased diffusing capacity and hypoxia were present in almost every case. Whole lung lavage proved to be an effective therapeutic measure. The response to treatment was good. Long-term course of the disease, e.g. recurrence rate, is not yet known.

Adult↗
PubMed1999

The effects of transferring tumor suppressor gene p16INK4A to p16INK4A-deleted cancer cells.

OBJECTIVES: p16 is known to be an important tumor suppressor gene and is also called MTS1 (multiple tumor suppressive gene 1). Especially in the case of non-small cell lung cancer, it was not expressed in more than 70% of cell lines examined. To determine changes in cell-cycle related proteins and the tumorigenic effect, we, therefore, transfected p16INK4A gene into lung cancer cell lines. METHODS: We transfected p16INK4A gene into lung cancer cell lines which do not express p16 protein. We evaluated the effect by clonogenic assay and observed the changes of cell-cycle related proteins. RESULTS: The newly-expressed p16 formed a complex with cdk4, and phosphorylated pRB was decreased, although cyclin D1 and pRB:cyclin D1 complex were unchanged. Clonogenic assay after selection with G418 showed that, in the cell lines transfected with p16, tumorigenicity was significantly less than in the control. CONCLUSION: These results suggest that the p16INK4A gene can be a candidate for gene therapy in cases of NSCLC in which p16INK4A gene is inactivated.

Carcinoma, Non-Small-Cell Lung↗
PubMed1998

Action of human group IIa secreted phospholipase A2 on cell membranes. Vesicle but not heparinoid binding determines rate of fatty acid release by exogenously added enzyme.

Human group IIa phospholipase A2 (hIIa-PLA2) is a highly basic protein that is secreted from a number of cells during inflammation and may play a role in arachidonate liberation and in destruction of invading bacteria. It has been proposed that rodent group IIa PLA2 is anchored to cell surfaces via attachment to heparan sulfate proteoglycan and that this interaction facilitates lipolysis. hIIa-PLA2 contains 13 lysines, 2 histidines, and 10 arginines that fall into 10 clusters. A panel of 26 hIIa-PLA2 mutants were prepared in which 1-4 basic residues in each cluster were changed to glutamate or aspartate (charge reversal). A detailed analysis of the affinities of these mutants for anionic vesicles and for heparin and heparan sulfate in vitro and of the specific activities of these proteins for hydrolysis of vesicles in vitro and of living cell membranes reveal the following trends: 1) the affinity of hIIa-PLA2 for heparin and heparan sulfate is modulated not by a highly localized site of basic residues but by diffuse sites that partially overlap with the interfacial binding site. In contrast, only those residues on the interfacial binding site of hIIa-PLA2 are involved in binding to membranes; 2) the relative ability of these mutants to hydrolyze cellular phospholipids when enzymes were added exogenously to CHO-K1, NIH-3T3, and RAW 264.7 cells correlates with their relative in vitro affinity for vesicles and not with their affinity for heparin and heparan sulfate. 3) The rates of exogenous hIIa-PLA2-catalyzed fatty acid release from wild type CHO-K1 cells and two mutant lines, one lacking glycosaminoglycan and one lacking heparan sulfate, were similar. Thus basic residues that modulate interfacial binding are important for plasma membrane fatty acid release by exogenously added hIIa-PLA2. Binding of hIIa-PLA2 to cell surface heparan sulfate does not modulate plasma membrane phospholipid hydrolysis by exogenously added hIIa-PLA2.

3T3 Cells↗
PubMed1998

Bacterial expression and characterization of human secretory class V phospholipase A2.

Mammalian secretory class V phospholipase A2 (PLA2) is a newly discovered PLA2 that is implicated in eicosanoid formation in inflammatory cells. As a first step towards understanding the structure, function and regulation of this PLA2, we constructed a bacterial expression vector for human secretory class V PLA2 (hV-PLA2), over-expressed and purified the protein, and determined its physical and kinetic properties. When compared with human class IIa enzyme (hIIa-PLA2), hV-PLA2 has several distinct properties. First, hV-PLA2 can catalyse the hydrolysis of phosphatidylcholine more effectively than hIIa-PLA2 by two orders of magnitude. Secondly, hV-PLA2 has much higher binding affinity and activity for compactly packed phosphatidylcholine bilayers than hIIa-PLA2. Finally, hV-PLA2 has much reduced thermal stability compared with hIIa-PLA2. These data suggest that hV-PLA2 is better suited than hIIa-PLA2 for acting on the outer cellular membrane and liberating arachidonic acid from membrane phospholipids. Also, the unusually low thermal stability of hV-PLA2 might contribute to tighter regulation of its activities in extracellular media.

Amino Acid Sequence↗
PubMed1998

Microvascular anastomosis with minimal suture and fibrin glue: experimental and clinical study.

A comparative study was undertaken to evaluate a new microvascular anastomosis technique utilizing only four sutures placed 90 degrees apart and sealed with fibrin glue, in contrast to the conventional method of eight sutures as a control. The two methods were compared in regard to patency rates, time needed for vascular anastomosis, and microscopic evaluation. Postoperative patency rates were 100% and 85% with the fibrin glue technique compared with 100% and 90% with the conventional technique immediately postoperative and 2 weeks postoperative, respectively. Less time was consumed with the fibrin glue technique, which took 16 minutes, compared with the conventional technique, which took 21 minutes. Microscopically, re-endothelization was complete, with a smooth and less injured inner lining and also with less inflammatory response in the fibrin glue technique compared with the conventional technique. We applied this new technique to clinical cases of 17 digit replantations and one free flap. All cases survived completely except for one toe replantation case, which was severely crushed at the time of injury.

Adult↗
PubMed1998

Synthesis and evaluation of 5-aminosalicyl-glycine as a potential colon-specific prodrug of 5-aminosalicylic acid.

As a new colon-specific prodrug of 5-aminosalicylic acid (5-ASA), 5-aminosalicyl-glycine (5-ASA-Gly) was prepared by a simple synthetic route in good yield. Apparent partition coefficients of 5-ASA-Gly were lower than those of 5-ASA, which determined in CHCl3/pH 6.8 buffer or n-octanol/pH 6.8 buffer system. Stability of 5-ASA-Gly by peptidases was investigated by incubation of 5-ASA-Gly with the homogenates of tissue and contents of stomach, proximal small intestine or distal small intestine of rats at 37 degrees C. 5-ASA was not detected, indicating that the prodrug was stable in the upper intestine. The amount of 5-ASA liberated from incubation of the prodrug in cecal or colonic contents of rats was about 65% or 27% in 8 hrs, respectively, which indicated that the prodrug activation took place more readily in the rat cecum whose bacterial counts are high like human colon. Results from in vitro experiments suggested 5-ASA-Gly as a promising candidate of a colon-specific prodrug of 5-ASA.

Aminosalicylic Acids↗
PubMed1998

Isolation and characterization of beta-galactoside specific lectin from Korean mistletoe (Viscum album var. coloratum) with lactose-BSA-sepharose 4B and changes of lectin conformation.

Lectins and its A- and B-chains from Korean mistletoe (Viscum album var. coloratum) were isolated by affinity chromatography on the Sepharose 4B modified by lactose-BSA conjugate synthesized by reductive amination of ligand (lactose) to epsilon-amino groups of lysine residues of spacer (BSA) after reduction by NaCNBH3. The lactose-BSA conjugate was coupled to Sepharose 4B activated by cyanogen bromide. The molecular weight determined by SDS-PAGE were a 31 kD of A-chain and a 35 kD of B-chain. Amino acid analysis and N-terminal sequencing were performed. The effects of pH, temperature and guanidine chloride on the conformation of the lectin were investigated by measuring its intrinsic fluorescence and compared with its hemagglutinating activities. Blue shift was detected on the acidic pH and there was a close relationship between activities and conformation of the lectin. Under denaturing conditions, the tryptophan emission profile of lectin showed typical denaturational red shift which also correspond to the conformations and activity of lectin.

Amino Acids↗
PubMed1998

Aerobic microbial degradation of aromatic sulfur-containing compounds and effect of chemical structures.

Batch data of aerobic microbial degradation rate constants Kb of phenylthio, phenylsulfinyl and phenylsulfonyl acetates have been determined, and the qualitative relationships between their Kb and chemical structures were analyzed. The phenylthio acetates were most subject to microbial transformation, followed by the phenylsulfonyl acetates. The compounds with a methoxy group were easier degraded than those with a isopropoxy group. The nitro-group and chloro-group on benzene were shown to lower the biodegradability, while the nitro-group at the para-position had stronger side effect on degradation than at the ortho-position.

Benzene Derivatives↗
PubMed1998

Telomerase activity in lung cancer cell lines and tissues.

Using TRAP assay, we studied the activity of the telomerase in the lung cancer cell lines, and lung cancer and normal tissues in which expression appears to be related to the immortality of cancer cells. All the human lung cancer cell lines and the majority of human lung cancer tissues (78%) expressed telomerase activity, but this was undetectable in normal human lung tissues. Positivity for telomerase activity in lung cancer cell lines was higher than in lung cancer tissues; this result implies the expression of telomerase activity may play a crucial role in the development or progression of lung cancer, and also suggests that improved method of detection may lead to the higher positivity for telomerase activity in primary lung cancer tissues. To determine whether there is a definite causal relationship between telomerase and cancer, and to develop new anti-cancer agents which inhibit telomerase, further study is needed.

Humans↗
PubMed1998

Genetic instability of microsatellite sequences in non-small cell lung cancers.

To evaluate the frequency and pattern of microsatellite instability in NSCLCs, we examined 36 cases of resected NSCLC. The mean age of the patients was 59.9+/-8.4 years. There were 19 cases of squamous cell carcinoma, 15 of adenocarcinoma and two of large cell carcinoma. We observed microsatellite instability at one or more loci in 13 (36%) of 36 tumors analyzed, and this instability ranged from six tumors showing instability in only a single microsatellite to three tumors that had alterations in three of four tested microsatellites. The microsatellite that showed instability most frequently in these tumors was D3S1340 (31%). Microsatellite instability was found in five (26%) of 19 squamous cell carcinomas, six (40%) of 15 adenocarcinomas, and in both large cell carcinomas tested. We found microsatellite instability in four (24%) of 17 cancers at stage I, in one (17%) of six at stage II, in eight (73%) of eleven at stage IIIa, and in neither at stage IIIb. In conclusion, microsatellite instability was noted in at least one third of non-small cell lung cancers, suggesting its possible role in cancer development.

Adenocarcinoma↗
PubMed1998

The reverse digital artery island flap: clinical experience in 120 fingers.

Fingertip injuries represent the most common type of injuries seen in the upper extremity. Their management is functionally and aesthetically important but at the same time very controversial. The aim of this study is to report usefulness and postoperative results of reverse digital artery island flaps for fingertip reconstruction. From July of 1984 to December of 1995, 120 fingers in 110 patients with defects of the distal phalanx were reconstructed by reverse digital artery island flaps at Korea University Guro Hospital. We reviewed the medical records of our cases and analyzed them in several aspects. In 21 cases, neurorrhaphy was performed to improve sensibility. In the majority of the cases, the defect was covered primarily, whereas in 27 cases it was covered secondarily after composite graft, replantation, and so on. All the flaps survived except for one. Long-term follow-up for more than 6 months was possible in 44 fingers in 41 patients. Light touch and temperature sensation could be detected in all the evaluated flaps. The mean values of the static two-point discrimination test in sensate and insensate flaps were 6.2 and 10.2 mm, respectively. The reverse digital artery island flap is a safe and reliable procedure with a high survival rate and therefore is an excellent choice for coverage of fingertip defects.

Adolescent↗
PubMed1998

Bronchiolitis obliterans organizing pneumonia in Korea.

An analysis of the clinical features in 23 cases of bronchiolitis obliterans organizing pneumonia (BOOP) in Korea is presented. Six were men and 17 were female, with a male-to-female ratio of 1:2.4. Idiopathic BOOP was present in 18 of these patients, connective tissue disease-associated BOOP in five and all of them were females. The most frequent symptoms were dyspnoea and coughing in both groups; and crackles were the most prominent physical findings. Leukocytosis was observed in seven of the idiopathic BOOP group and all in the connective tissue disease-associated BOOP group. In most cases, FVC, FEV 1, diffusing capacity and arterial O2 pressure were reduced. In roentgenographic study, patchy air space consolidation was the major finding and subpleural predominance was observed in the majority of patients in both groups. Migration of lesions were identified in only two patients with idiopathic BOOP. Steroid treatment was effective in all of idiopathic BOOP. In contrast to previous reports, an analysis of the 23 Korean BOOP patients showed several interesting points. First, a female predominance was observed. Second, migration of lesion was rare. Third, it did not show any different prognosis in patients with reticular pattern on roentgenogram compared with patients with patchy air space consolidation on roentgenogram. Whether these differences were due to ethnic or environmental factors is to be determined.

Adult↗
PubMed1998

Deprenyl and desmethylselegiline protect mesencephalic neurons from toxicity induced by glutathione depletion.

Oxidative stress is thought to play an important role in the pathogenesis of Parkinson's disease (PD). Glutathione (GSH), a major cellular antioxidant, is decreased in the substantia nigra pars compacta of PD patients. The aim of the present study was to investigate whether deprenyl and its desmethyl metabolite, putative neuroprotective agents in the treatment of PD, could protect cultured rat mesencephalic neurons from cell death caused by GSH depletion due to treatment with L-buthionine-(S,R)-sulfoximine (BSO). BSO (10 microM) caused extensive cell death after 48 hr, as demonstrated by disruption of cellular integrity and release of lactate dehydrogenase into the culture medium. Both deprenyl and desmethylselegiline, at concentrations of 5 and 50 microM, significantly protected dopaminergic neurons from toxicity without preventing the BSO-induced loss in GSH. Protection was not associated with monoamine oxidase type B inhibition in that pargyline, a potent MAO inhibitor, was ineffective and pretreatment with pargyline did not prevent the protective effects of deprenyl. Protection was not associated with inhibition of dopamine uptake by deprenyl because the dopamine uptake inhibitor mazindol did not diminish BSO toxicity. The antioxidant ascorbic acid (200 microM) also protected against BSO-induced cell death, suggesting that oxidative events were involved. This study demonstrates that deprenyl and its desmethyl metabolite can diminish cell death associated with GSH depletion.

Amphetamines↗
PubMed1997

Mapping the interfacial binding surface of human secretory group IIa phospholipase A2.

Human secretory group IIa phospholipase A2 (hIIa-PLA2) contains a large number of prominent cationic patches on its molecular surface and has exceptionally high affinity for anionic surfaces, including anionic membranes. To identify the cationic amino acid residues that support binding of hIIa-PLA2 to anionic membranes, we have performed extensive site-directed mutagenesis of this protein and measured vesicle binding and interfacial kinetic properties of the mutants using polymerized liposomes and nonpolymerized anionic vesicles. Unlike other secretory PLA2s, which have a few cationic residues that support binding of enzyme to anionic membranes, interfacial binding of hIIa-PLA2 is driven in part by electrostatic interactions involving a number of cationic residues forming patches on the putative interfacial binding surface. Among these residues, the amino-terminal patch composed of Arg-7, Lys-10, and Lys-16 makes the most significant contribution to interfacial adsorption, and this is supplemented by contributions from other patches, most notably Lys-74/Lys-87/Arg-92 and Lys-124/Arg-127. For these mutants, complete vesicle binding occurs in the presence of high vesicle concentrations, and under these conditions the mutants display specific activities comparable to that of wild-type enzyme. These studies indicate that electrostatic interactions between surface lysine and arginine residues and the interface contribute to interfacial binding of hIIa-PLA2 to anionic vesicles and that cationic residues closest to the opening of the active-site slot make the most important interactions with the membrane. However, because the wild type binds extremely tightly to anionic vesicles, it was not possible to exactly determine what fraction of the total interfacial binding energy is due to electrostatics.

Arginine↗