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Biomedical subjects

S K Han

Publications and source records attributed to S K Han.

At least 55 records · Page 3Linked to original sources

Topical and systemic anticoagulation in the treatment of absent or compromised venous outflow in replanted fingertips.

Adequate venous repair is not always possible in fingertip replantation. We have used topical and systemic anticoagulation for fingertip replantation to overcome venous congestion in cases without venous repair or in cases in which there is obstruction of a repaired vein. Our technique consists of continuous external bleeding via a stab incision on the paraungal area and dripping heparinized saline solution at the incision site to maintain external bleeding. From July 1985 to December 1993, 157 fingers in 140 patients with complete amputation of the fingertip were replanted at Korea University Guro Hospital. Of these, 74 fingers in 68 patients were managed by topical and systemic anticoagulation due to the impossibility of repair or obstruction of a repaired vein. The overall survival rate of the fingertip replantations was 76%; that of the topical and systemic anticoagulation group was 64%.

Administration, Topical↗

Characterization of monoclonal antibodies specific for 14-kDa human group V secretory phospholipase A2 (hVPLA2).

Secretory phospholipase A2 (PLA2) consists of several 14-kDa isoforms with extensive homology, which makes it difficult to identify a specific isoform. In this study, we have developed and characterized monoclonal antibodies (MAbs) directed specifically against human group V sPLA2 (hVPLA2) derived from cultured hybridomas. These hybridomas were produced from the fusion of BALB/c-derived myeloma s/p20-Ag14 and splenocytes from mice immunized with purified recombinant hVPLA2. Three hybridomas secreting MAbs, MCL-3G1, MCL-2A5, and MCL-1B7, were selected and subcloned on the basis of their specificity to recognize hVPLA2 using solid-phase enzyme-linked immunoadsorbent assay (ELISA). The purified MAbs demonstrated a common pattern of immunoreactivity to hVPLA2, but not to human group IIa isoform (hIIaPLA2). Isotype analysis indicates that these hybridomas are of the IgG1 type. Under reducing conditions, MCL-3G1 sensitively detected hVPLA2 and demonstrated no cross-reactivity to either hIIaPLA2 or group IV cytosolic PLA2. Although specific for hVPLA2, a relatively modest signal was recognized with MCL-1B7 and MCL-2A5. These newly developed MAbs allow for determination of tissue distribution and cell-specific functions of hVPLA2.

Animals↗

In vitro development of reconstructed porcine oocytes after somatic cell nuclear transfer.

This study was designed to examine the developmental ability of porcine embryos after somatic cell nuclear transfer. Porcine fibroblasts were isolated from fetuses at Day 40 of gestation. In vitro-matured porcine oocytes were enucleated and electrically fused with somatic cells. The reconstructed eggs were activated using electrical stimulus and cultured in vitro for 6 days. Nuclear-transferred (NT) embryos activated at a field strength of 120 V/mm (11.6 +/- 1.6%) showed a higher developmental rate as compared to the 150-V/mm group (6.5 +/- 2.3%) (P: < 0.05), but the mean cell numbers of blastocysts were similar between the two groups. Rates of blastocyst development from NT embryos electrically pulsed at different times (2, 4, and 6 h) after electrofusion were 11.6 +/- 2.9, 6.6 +/- 2.3, and 8.1 +/- 3.3%, respectively. The mean cell numbers of blastocysts developed from NT embryos were gradually decreased (30.4 +/- 10.4 > 24.6 +/- 10.1 > 16.5 +/- 7.4 per blastocyst) as exposure time (2, 4, and 6 h) of nuclei to oocyte cytoplast before activation was prolonged. There was a significant difference in the cell number between the 2- and 6-h groups (P: < 0. 05). Nuclear-transferred embryos (9.4 +/- 0.9%) had a lower developmental rate than in vitro fertilization (IVF)-derived (21.4 +/- 1.9%) or parthenogenetic embryos (22.4 +/- 7.2%) (P: < 0.01). The mean cell number (28.9 +/- 11.4) of NT-derived blastocysts was smaller than that (38.6 +/- 10.4) of IVF-derived blastocysts (P: < 0. 05) and was similar to that (29.9 +/- 12.1) of parthenogenetic embryos. Our results suggest that porcine NT eggs using somatic cells after electrical activation have developmental potential to the blastocyst stage, although with smaller cell numbers compared to IVF embryos.

Animals↗

Correlation of electrodiagnostic findings with subjective symptoms in carpal tunnel syndrome.

The records of 138 patients (222 hands) who had been evaluated by preoperative nerve conduction study (NCS) and consecutive self-administered questionnaires were analyzed to determine diagnostic relations in carpal tunnel syndrome. Hands were categorized into six grades (extreme, severe, moderate, mild, minimal, and negative) according to the three modalities: the NCS data of the median sensory nerve, Symptom Severity Scale score, and Functional Status Scale score. The authors evaluated the correlation, independence, homogeneity, and association among parameters, and found the following: (1) the NCS data correlated more significantly (p < 0.05) and was associated more linearly with Symptom Severity Scale score than the Functional Status Scale score; (2) the choice of modality exerted an influence on grading severities, thus grades varied according to the modalities; and (3) the distribution of patients was not homogenous; there were more extremes in NCS, and more severe scores on the Symptom Severity Scale. Patients rated as one homogeneous severity by NCS data may be interpreted into different severities (from negative to extreme) by self-administered questionnaires and vice versa.

Adult↗

Genetic susceptibility to chronic obstructive pulmonary disease in Koreans: combined analysis of polymorphic genotypes for microsomal epoxide hydrolase and glutathione S-transferase M1 and T1.

BACKGROUND: Although smoking is the major causal factor in the development of chronic obstructive pulmonary disease (COPD), only 10-20% of chronic heavy cigarette smokers develop symptomatic COPD which suggests the presence of genetic susceptibility. This genetic susceptibility to COPD might depend on variations in enzyme activities that detoxify cigarette smoke products such as microsomal epoxide hydrolase (mEPHX) and glutathione-S transferase (GST). As there is increasing evidence that several genes influence the development of COPD, multiple gene polymorphisms should be investigated to find out the genetic susceptibility to COPD. METHODS: The genotypes of 83 patients with COPD and 76 healthy smoking control subjects were determined by polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (PCR-RFLP) for the mEPHX gene, and multiplex PCR for GST M1 and GST T1 genes. The frequencies of polymorphic genotypes of mEPHX, GST M1, and GST T1 genes were compared both individually and in combination in patients with COPD and healthy smokers. RESULTS: No differences were observed in the frequency of polymorphic genotypes in exons 3 and 4 of mEPHX, GST M1, and GST T1 genes between patients with COPD and healthy smokers. The frequencies of any combination of these genotypes also showed no differences between the COPD group and the control group. CONCLUSIONS: Genetic polymorphisms in mEPHX, GST M1, and GST T1 genes are not associated with the development of COPD in Koreans.

Adult↗

Bronchial anthracofibrosis (inflammatory bronchial stenosis with anthracotic pigmentation): CT findings.

OBJECTIVE: The aim of this study was to describe CT findings of patients with bronchial anthracofibrosis. CONCLUSION: Atelectasis caused by smooth bronchial narrowing, surrounded by calcified or noncalcified lymph nodes, in elderly and nonsmoking women is a typical finding of anthracofibrosis. Calcified lymph nodes adjacent to the involved bronchi and multifocal involvement of bronchial narrowing may be helpful in differentiating this condition from lung cancer.

Adult↗

Differential interfacial and substrate binding modes of mammalian pancreatic phospholipases A2: a comparison among human, bovine, and porcine enzymes.

To identify the residues essential for interfacial binding and substrate binding of human pancreatic phospholipase A2 (hpPLA2), several ionic residues in the putative interfacial binding surface (R6E, K7E, K10E, and K116E) and substrate binding site (D53K and K56E) were mutated. Interfacial affinity of these mutants was measured using anionic polymerized liposomes, and their enzymatic activity was measured using various substrates including phospholipid monomers, zwitterionic and anionic micelles, and anionic polymerized mixed liposomes. Similar mutations (R6E, K10E, K56E, and K116E) were made to porcine pancreatic phospholipase A2 (ppPLA2), and the properties of mutants were measured by the same methods. Results indicate that hpPLA2 and ppPLA2 have similar interfacial binding mechanisms in which cationic residues in the amino terminus and Lys-116 in the carboxy terminus are involved in binding to anionic lipid surfaces. Small but definite differences between the two enzymes were observed in overall interfacial affinity and activity and the effects of the mutations on interfacial enzyme activity. The interfacial binding of hpPLA2 and ppPLA2 is distinct from that of bovine pancreatic phospholipase A2 in that Lys-56 is involved in the interfacial binding of the latter enzyme. The unique phospholipid headgroup specificity of hpPLA2 derives from the presence of Asp-53 in the substrate binding site. This residue appears to participate in stabilizing electrostatic interactions with the cationic ethanolamine headgroup, hence the phosphatidylethanolamine preference of hpPLA2. Taken together, these studies reveal the similarities and the differences in the mechanisms by which mammalian pancreatic phospholipases A2 interact with lipid aggregates and perform interfacial catalysis.

Animals↗

Mechanisms by which elevated intracellular calcium induces S49 cell membranes to become susceptible to the action of secretory phospholipase A2.

Exposure of S49 lymphoma cells to exogenous group IIA or V secretory phospholipase A2 (sPLA2) caused an initial release of fatty acid followed by resistance to further hydrolysis by the enzyme. This refractoriness was overcome by exposing cells to palmitoyl lysolecithin. This effect was specific in terms of lysophospholipid structure. Induction of membrane susceptibility by lysolecithin involved an increase in cytosolic calcium and was duplicated by incubating the cells with calcium ionophores such as ionomycin. Lysolecithin also activated cytosolic phospholipase A2 (cPLA2). Inhibition of this enzyme attenuated the ability of lysolecithin (but not ionomycin) to induce susceptibility to sPLA2. Lysolecithin or ionomycin caused concurrent hydrolysis of both phosphatidylethanolamine and phosphatidylcholine implying that transbilayer movement of phosphatidylethanolamine occurred upon exposure to these agents but that susceptibility is not simply due to exposure of a preferred substrate (i.e. phosphatidylethanolamine) to the enzyme. Microvesicles were apparently released from the cells upon addition of lysolecithin or ionomycin. Both these vesicles and the remnant cell membranes were susceptible to sPLA2. Together these data suggest that lysolecithin induces susceptibility through both cPLA2-dependent and -independent pathways. Whereas elevated cytosolic calcium was required for both pathways, it was sufficient only for the cPLA2-independent pathway. This cPLA2-independent pathway involved changes in cell membrane structure associated with transbilayer phospholipid migration and microvesicle release.

Calcium↗

Roles of Trp31 in high membrane binding and proinflammatory activity of human group V phospholipase A2.

Group V phospholipase A2 is a recently discovered secretory phospholipase A2 (PLA2) that has been shown to be involved in eicosanoid formation in inflammatory cells, such as macrophages and mast cells. We have demonstrated that human group V PLA2 (hsPLA2-V) can bind phosphatidylcholine (PC) membranes and hydrolyze PC substrates much more efficiently than human group IIa PLA2, which makes it better suited for acting on the outer plasma membrane (Han, S.-K., Yoon, E. T., and Cho, W. (1998) Biochem. J. 331, 353-357). In this study, we demonstrate that exogenous hsPLA2-V has much greater activity than does group IIa PLA2 to release fatty acids from various mammalian cells and to elicit leukotriene B4 formation from human neutrophils. To understand the molecular basis of these activities, we mutated two surface tryptophans of hsPLA2-V to alanine (W31A and W79A) and measured the effects of these mutations on the kinetic activity toward various substrates, on the binding affinity for vesicles and phospholipid-coated beads, on the penetration into phospholipid monolayers, and on the activity to release fatty acids and elicit eicosanoid formation from various mammalian cells. These studies show that the relatively high ability of hsPLA2-V to induce cellular eicosanoid formation derives from its high affinity for PC membranes and that Trp31 on its putative interfacial binding surface plays an important role in its binding to PC vesicles and to the outer plasma membrane.

Cell Membrane↗

Surgery increased the chance of cure in multi-drug resistant pulmonary tuberculosis.

BACKGROUND: Medical treatment of multiple drug resistant (MDR) pulmonary tuberculosis is generally quite unsuccessful. Recently, surgical management is increasing and shows promise. We analyzed our experience to identify the benefits and complications of pulmonary resection in MDR pulmonary tuberculosis. METHODS: A retrospective review was performed in 27 patients undergoing pulmonary resection for MDR pulmonary tuberculosis between January 1994 and March 1998. Their average ages were 40 years and were diagnosed a median of 15 months before surgery. All patients had resistance to an average of 4.4 drugs including isoniazid and rifampin, and had received second line drugs selected according to drug sensitivity test preoperatively. Most patients (92.6%) had cavitary lesions. Bilateral lesions were also identified in 19 patients (70.4%), but the main focus was recognized in one side of the lung. Most patients were indicated to operation for those who could not achieve negative sputum despite adequate medical treatment (n = 16, 59.3%); or for negative patients who had significant pulmonary parenchymal lesion (n = 11, 40.7%) which would have had a high probability of recurrence. Pneumonectomy was done in nine patients, lobectomy in 16 and segmentectomy in two. RESULTS: There was no operative mortality. Morbidity occurred in seven patients (25.9%); prolonged air leakage in three patients, reoperation due to bleeding in two, bronchopleural fistula in one, and reversible blindness in one. The median follow up period was 15 months (range 3-45). Sputum negative conversion was achieved in 22 patients (81.5%) initially. However, continued postoperative chemotherapy could convert to negative in another four patients (14.8%). Only one pneumonectomy patient (3.7%) failed because of considerable contralateral cavity. CONCLUSION: For patients with MDR pulmonary tuberculosis which is localized, and with adequate pulmonary reserve function, surgical pulmonary resection combined with appropriate pre and postoperative anti-tuberculosis chemotherapy can achieve high success rate with acceptable morbidity.

Adult↗

Pulmonary actinomycosis in Korea.

Pulmonary actinomycosis is a chronic pulmonary infection caused by Actinomyces, a Gram-positive, microaerophilic bacterium. Pulmonary involvement, other than cervicofacially or abdominopelvically, is uncommon and often leads to a misdiagnosis of pulmonary tuberculosis or lung cancer. In order to investigate the clinical, radiological, diagnostic and therapeutic characteristics of pulmonary actinomycosis, we reviewed a total of 25 cases reported in Korea. Thirteen were diagnosed at our hospital between 1985 and 1997 and 12 were reported in Korean publications. The condition occurred most frequently in middle-aged males, the most common symptom being haemoptysis, followed by cough and sputum. The main radiological features were peripherally located mass or nodule and consolidation, with central low attenuation. Complications such as empyema, sinus fistula or mediastinitis did not occur. Diagnosis was confirmed by percutaneous needle aspiration (n = 8), bronchoscopic biopsy (n = 3) or thoracotomy (n = 13). Eleven of 25 cases were treated medically and in nine others, surgical resection was followed by treatment with antibiotics. In conclusion, when a middle-aged male patient presents with haemoptysis and cough, together with radiologic findings of a peripheral mass or nodule with/without central low attenuation, pulmonary actinomycosis should be suspected.

Actinomycosis↗

Bronchoscopic findings of endobronchial vascular lesions in patients with haemoptysis.

Cases of endobronchial vascular lesions observed with bronchoscope are presented. These lesions tend to be diagnosed erroneously as true endobronchial tumours so that biopsies are tried frequently. Consequently, a catastrophic accident of massive bleeding can complicate the condition if endobronchial vascular lesions are injured during bronchoscopic biopsy or brushing. We present three types of endobronchial vascular lesion: tubular bulging type, mass-like type and haemangioma type. Because bronchoscopic findings of submucosal tubular structure and visible pulsation are highly suggestive of endobronchial vascular lesion, there must be extreme caution to prevent fatal bleeding.

Adult↗

Acidosis potentiates oxidative neuronal death by multiple mechanisms.

Both acidosis and oxidative stress contribute to ischemic brain injury. The present study examines interactions between acidosis and oxidative stress in murine cortical cultures. Acidosis (pH 6.2) was found to potentiate markedly neuronal death induced by H2O2 exposure. To determine if this effect was mediated by decreased antioxidant capacity at low pH, the activities of several antioxidant enzymes were measured. Acidosis was found to reduce the activities of glutathione peroxidase and glutathione S-transferase by 50-60% (p < 0.001) and the activity of glutathione reductase by 20% (p < 0.01) in lysates of the cortical cultures. Like acidosis, direct inhibition of glutathione peroxidase with mercaptosuccinate also potentiated H2O2 toxicity. Because acidosis may accelerate hydroxyl radical production by the Fenton reaction, the effect of iron chelators was also examined. Both desferrioxamine and N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine, two structurally different iron chelators, significantly reduced H2O2-induced neuronal death under both pH 7.2 and pH 6.2 conditions. These results suggest that the increased cell death produced by severe acidosis during cerebral ischemia may result in part from exacerbation of oxidative injury. This exacerbation may result from both impaired antioxidant enzyme functions and increased intracellular free iron levels.

Acidosis↗

Solubilization of biphenyl dimethyl dicarboxylate by cosolvency.

Biphenyl dimethyl dicarboxylate (BDD) is a synthetic analogue of schizandrin C, one of the components isolated from Fructus schizandrae, and has been widely prescribed for improvement of liver functions and symptoms of patients with liver disease. However, its oral preparations have been known to have limited bioavailability due to its extremely low solubility in water, and its solubility problem also limits preparation of its parenteral dosage forms. In this research, we searched for solvent systems to solubilize BDD to overcome these problems. The ternary solvent systems of N,N'-dimethylacetamide (DMA)/alcohol/water and Cremophor EL/DMA/alcohol were studied intensively for this purpose. BDD was solubilized effectively in these cosolvents, and the results showed that the cosolvent systems were effective for solubilizing BDD up to the concentration that might be employed for preparation of parenteral dosage forms. Formulation of a BDD concentrate for intravenous infusion was proposed employing the cosolvent system of Cremophor EL/DMA/alcohol.

Cyclooctanes↗

Synchronization of diffusively coupled oscillators near the homoclinic bifurcation.

It has been known that a diffusive coupling between two limit cycle oscillations typically leads to the in-phase synchronization and also that it is the only stable state in the weak-coupling limit. Recently, however, it has been shown that the coupling of the same nature can result in the distinctive dephased synchronization when the limit cycles are close to the homoclinic bifurcation, which often occurs especially for the neuronal oscillators. In this paper we propose a simple physical model using the modified van der Pol equation, which unfolds the generic synchronization behaviors of the latter kind and in which one may readily observe changes in the sychronization behaviors between the distinctive regimes as well. The dephasing mechanism is analyzed both qualitatively and quantitatively in the weak-coupling limit. A general form of coupling is introduced and the synchronization behaviors over a wide range of the coupling parameters are explored to construct the phase diagram using the bifurcation analysis.

Journal Article↗

Gaegurin 4, a peptide antibiotic of frog skin, forms voltage-dependent channels in planar lipid bilayers.

Gaegurin 4 (GGN4) is a cationic peptide of 37 amino acids (MW 3748) isolated from the skin of Rana rugosa. It has shown a broad spectrum antimicrobial activity in vitro against Gram-negative and -positive bacteria, fungi and protozoa. To understand its mechanism of antimicrobial action, we examined the effect of GGN4 on the membrane conductance and the electrical properties of GGN4-induced pores in planar lipid bilayers under voltage clamp. Natural and synthetic GGN4 (0.01-1 microg/mL) increased the membrane conductance in a concentration-dependent manner, but GGN4 (1-23), an N-terminal fragment of the peptide with little antimicrobial activity, failed to increase the conductance. At symmetrical 100 mM KCI, unitary conductances of about 120 pS were frequently observed. Their current-voltage relations were linear and open state probabilities were close to 1, but longer closing events were seen more frequently at negative voltages. In addition, GGN4-induced pores were selective for cation over anion, the permeability ratio of K+ to Cl- being 6: 1 in neutral and 7: 1 in acidic lipid bilayers. In conclusion, our results indicate that GGN4 forms voltage-dependent and cation-selective pores in planar lipid bilayers. The ionophoric property of GGN4 is likely to contribute to its antimicrobial activity.

Amino Acid Sequence↗

Effect of diode laser trans-scleral cyclophotocoagulation in the management of glaucoma after intravitreal silicone oil injection for complicated retinal detachments.

AIMS: To evaluate the effect of trans scleral cyclophotocoagulation (TSCPC) on intraocular pressure (IOP) in the eyes retaining intravitreal silicone oil with medically uncontrolled secondary glaucoma following intravitreal silicone oil injection. METHODS: Medical records of 11 eyes of 11 patients who underwent TSCPC for medically uncontrolled glaucoma without pupillary block following intravitreal silicone oil injection for complicated retinal detachment were reviewed retrospectively. In all cases, intravitreal silicone oil was not removed for fear of retinal redetachment. Diode laser contact TSCPC was performed at a power of 1.5-2.5 W, for a duration of 2 seconds, and with 20-27 applications. IOP, number of glaucoma medications, and success rate were evaluated. RESULTS: After a mean follow up period of 52.5 (SD 8.2) (range 42-68) weeks, the mean pretreatment level of IOP, 43.0 (14.4) (26-67) mmHg, had fallen to 14.5 (4.3) (7-20) mm Hg (p=0.003). The number of glaucoma medications was reduced from 2.6 (0.8) to 0.6 (1.0) (p= 0.005). Qualified success was achieved in nine eyes (81.8%) and complete success in six (54.5%). After TSCPC, patients' retinal status had not changed. CONCLUSION: Patients with medically uncontrolled glaucoma secondary to intravitreal silicone oil injection can be treated with TSCPC in spite of the retained intravitreal silicone oil.

Adult↗

Pulmonary lymphangioleiomyomatosis in Korea.

BACKGROUND: Pulmonary lymphangioleiomyomatosis (LAM) is a rare disease occurring in women of reproductive age and leading to progressive respiratory failure in spite of treatment. In Korea the first case was reported in 1984 and by 1997 a total of 23 cases had been reported. The clinical findings of these Korean cases are reviewed. METHODS: The details of 10 cases of LAM on file at Seoul National University Hospital were reviewed together with those of 13 cases previously reported from other Korean institutes. Two, including the only one to be reported in a man, were excluded after reviewing the clinical, radiological, and pathological findings, leaving a total of 21 cases in the present study. RESULTS: All 21 patients were women and in all cases the disease was proven pathologically. The mean (SD) age at onset of symptoms was 32 (8.6) years. The most common symptoms were dyspnoea and pneumothorax which were seen in 19 (90%) and 13 (76%) patients, respectively. Pulmonary function tests showed decreased transfer factor (TLCO) (100%) and airflow limitation (67%). All the cases had characteristic cysts on high resolution computed tomographic (HRCT) scanning. The overall severity score based on HRCT scans correlated with the percentage predicted TLCO/VA (p = 0.03) and FEV1/FVC (p = 0.02). The patients were all treated with medroxyprogesterone and/or tamoxifen. Follow up was possible in 10 cases. Two of these patients appeared to stabilise with no appreciable change clinically or in lung function on medroxyprogesterone and/or tamoxifen, but the remaining patients all deteriorated with two dying of respiratory insufficiency and one of infection following lung transplantation. CONCLUSIONS: As in other countries, in Korea LAM occurs exclusively in women and progresses despite hormonal treatment.

Adult↗