Search PubMed⌕ Search

Biomedical subjects

W J Kim

Publications and source records attributed to W J Kim.

At least 55 records · Page 3Linked to original sources

Modulation of TNF-alpha-induced apoptosis in corneal fibroblasts by transcription factor NF-kappaB.

PURPOSE: Previous studies have suggested no role for tumor necrosis factor (TNF)-alpha in the modulation of apoptosis in corneal fibroblasts. However, recent investigations have demonstrated that nuclear factor (NF)-kappaB activation by TNF-alpha mediates negative apoptotic effects that must be blocked to unmask the apoptotic effects of TNF-alpha in vitro. The purpose of this study was to investigate the role of transcription factor NF-kappaB in the suppression of TNF-alpha-induced apoptosis of corneal fibroblasts. METHODS: mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR) and RNase protection assay. Proteins were detected by immunocytochemistry and immunoprecipitation with Western blot analysis. Cell death was evaluated by trypan blue exclusion assay in corneal fibroblasts treated with TNF-alpha in presence or absence of the specific inhibitor of NF-kappaB activation, SN50, actinomycin D, or actinomycin D with dexamethasone, ketorolac tromethamine, or diclofenac sodium. Apoptosis was monitored by trypan blue exclusion, colorimetric cell assay, CPP32 activation assay, DNA fragmentation assay, and transmission electron microscopy. NF-KB activation was monitored using electrophoretic gel shift assay. RESULTS: TNF-alpha, TNF receptor (R)I, and TNFRII mRNAs were detected in all three cultured corneal cell types and in ex vivo corneal epithelium using RT-PCR. TNF-alpha mRNA was also detected in ex vivo corneal epithelium, corneal epithelial cells, and stromal fibroblasts with the RNase protection assay. TNF-alpha, TNFRI, and TNFRII proteins were detected by immunocytochemistry in all three major corneal cell types in human corneal tissue. TNF-alpha protein was also detected in ex vivo corneal epithelium, primary corneal epithelial cells, and primary stromal fibroblasts using immunoprecipitation and Western blot analysis. TNF-alpha stimulated corneal fibroblast cell death when NF-kappaB activation was blocked with actinomycin D or SN50. Enhanced cell death was noted with dexamethasone, ketorolac tromethamine, or diclofenac sodium when used in the presence, but not in the absence, of actinomycin D. A gel shift assay revealed induction of NF-KB by TNF-alpha and suppression of induction in the presence of actinomycin D or SN50, but not by the control peptide SN50M. CONCLUSIONS: The TNF-alpha receptor system is expressed in the cornea, and NF-kappaB activation is an important regulator of TNF-alpha-mediated corneal fibroblast apoptosis. Nonsteroidal anti-inflammatory agents or corticosteroids may potentiate corneal fibroblast apoptosis in response to cytokine stimulation.

Antigens, CD↗

Polymorphisms of N-acetyltransferase 2, glutathione S-transferase mu and theta genes as risk factors of bladder cancer in relation to asthma and tuberculosis.

PURPOSE: We investigated whether the polymorphisms of N-acetyltransferase 2 (NAT2), glutathione S-transferase-mu (GSTM1) and glutathione S-transferase-theta (GSTT1) genes were risk factors of bladder cancer among Korean people in relation to other risk factors. MATERIALS AND METHODS: In this case-control investigation of 113 patients with primary bladder cancer and 221 control subjects, we compared the association of bladder cancer with genetic polymorphisms of NAT2, GSTM1 and GSTT1, demographic characteristics, smoking status, and medical histories in a molecular epidemiological way. RESULTS: The risk of bladder cancer was significantly increased in patients with a medical history of tuberculosis (OR 3.61, 95% CI 1.57 to 8.26) and bronchial asthma (OR 4.15, 95% CI 1.61 to 10.75), while smoking history turned out to be insignificant. GSTM1 null genotype was a significant risk factor of bladder cancer (OR 1.81, 95% CI 1.12 to 2.93). On the other hand, slow acetylator and GSTT1 genotypes were insignificant. Also, we could not find any association between GSTM1, GSTT1, slow acetylator genotypes and bladder cancer risk among smokers. The rapid acetylator, GSTM1 null and GSTT1 null genotypes with a medical history of asthma or tuberculosis combinations were significant risk factors in Korean subjects. CONCLUSIONS: Among Korean subjects, GSTM1 null genotype was a significant risk factor for bladder cancer. The reason why bronchial asthma and tuberculosis are risk factors in Korean subjects is yet unknown, but a variety of factors, including enzyme activities for detoxification, medication for these diseases and immunological background might be involved.

Arylamine N-Acetyltransferase↗

Keratocyte apoptosis associated with keratoconus.

Keratoconus is an ectatic corneal dystrophy associated with stromal thinning and disruption of Bowman's layer. The purpose of this study was to explore a possible association between keratocyte apoptosis and keratoconus. Keratocyte apoptosis was evaluated in corneas of patients with keratoconus, corneas of patients with stromal dystrophies, and normal donor corneas using the transferase-mediated dUTP-digoxigenin nick and labeling (TUNEL) assay. Keratocyte apoptosis was also studied in keratoconus and normal corneas using transmission electron microscopy. TUNEL-stained keratocytes were detected in 60% of corneas with keratoconus, but only 35% of corneas with stromal dystrophies (P =0.03). The number of TUNEL-positive keratocytes detected in the keratoconus, stromal dystrophy, and normal corneas was 7+/-1 (mean+/-standard error, range 0-20), 2+/-0. 8 (range 0-9), and 0+/-0 (range 0-0) TUNEL-positive cells per section, respectively. The differences between the keratoconus and the stromal dystrophy (P =0.0097) or the normal cornea (P =0.01) groups were statistically significant. The difference between the stromal dystrophy and normal cornea groups was not statistically significant (P =0.45). The stromal dystrophy group was included to account for surgery-associated keratocyte apoptosis. No TUNEL-stained keratocytes were detected in normal corneas. Cell morphologic changes consistent with apoptosis were detected by transmission electron microscopy (TEM) in keratocytes of keratoconus corneas, but not in keratocytes in normal corneas. Chronic keratocyte apoptosis associated with ongoing epithelial injury may link risk factors associated with keratoconus such as chronic eye rubbing, contact lens wear, or atopic eye disease. Similarly, increases that have been detected in several different degradative enzymes in keratoconus corneas could be associated with chronic keratocyte apoptosis and less than perfect control of release of intracellular contents.

Apoptosis↗

Comparison of Korean-American adoptees and biological children of their adoptive parents: a pilot study.

This study compared a small group of Korean-American adoptees with their adoptive siblings who are biological children of the adoptive parents with respect to their psychosocial adjustment. Eighteen Korean-American adoptees were compared with nine biological children by a structured demographic, medical, clinical survey form and the Child Behavior Checklist-Parent Form (CBCL-P). The parents did not raise any more concerns about the adjustment of adopted children than their biological children. On the CBCL-P, the two groups did not differ significantly in competence T-scores, total behavioral problems, broad and T-scores and the total number of problem behaviors except for lower social competence in adopted children and a higher internalization score in biological children. In conclusion, the international adoptees, the Korean-American children have adjusted well during their early childhood after early adoption. Further studies employing a larger sample are warranted to better understand the international adoption practice.

Adolescent↗

The changing molecular epidemiology and establishment of endemicity of vancomycin resistance in enterococci at one hospital over a 6-year period.

The contributions of clonal spread, transfer of genetic elements, and introduction of new strains to the establishment of endemicity of vancomycin-resistant enterococci (VRE) were determined. The study took place at one hospital between 1990, when VRE were first detected, and 1996, when endemicity had become established. Isolates from 183 patients were categorized into 24 strain types by pulsed-field gel electrophoresis; the resistance genotype was determined by polymerase chain reaction. Between 1990 and 1993, 69% of patients were infected with the same vanB Enterococcus faecium strain. VanA resistance was not detected until 1993, but in 1996, the ratio of vanA to vanB was 2.2:1. Over time, 8 vanA strains were detected; a 35- or 40-kb conjugative vanA plasmid was found in 4 of the 8 strains. Clonal spread was a major factor in the establishment of endemicity. Transfer of genetic elements and introduction of new strain types were detected less often. However, these events may have been equally important evolutionarily.

Adult↗

Acceleration of DNA strand exchange by polycation comb-type copolymer.

Polycation comb-type copolymers which are composed of poly(L-lysine) backbone and dextran graft chain (PLL-graft-Dex) accelerated DNA duplex and triplex formation and stabilized under physiologically relevant condition remarkably. In this study, we have examined the ability of polycation copolymer in promoting strand exchange between duplex DNA and its complementary single-stranded DNA. It was demonstrated that the strand exchange rate was considerably accelerated by the polycation comb-type copolymer.

DNA↗

The prognosis for control of seizures with medications in patients with MRI evidence for mesial temporal sclerosis.

PURPOSE: Mesial temporal sclerosis (MTS) is the most common and important pathology in temporal lobe epilepsy (TLE), and its presence in magnetic resonance imaging (MRI) scans is strongly correlated with a successful surgical outcome. Despite the general assumption that patients with MTS respond poorly to medication, the long-term prognosis for such patients has not yet been investigated. We studied the overall clinical prognosis of patients with MTS and analyzed the factors related to the degree of medical responsiveness. METHODS: Case patients were actively followed up at the Yonsei Epilepsy Clinic in Seoul, Korea, for >2 years. A structured interview and a thorough clinical evaluation were conducted. MRI scans, at the field strength of 1.0 or 1.5 Tesla, were performed with T1- and T2-weighted coronal and axial spin-echo images. All coronal slices were < or = 5-mm thick with no gap. Two neurologists and one radiologist determined the presence of MTS in MRIs by visual analysis. RESULTS: The MTS group consisted of 104 patients. Of these, 26 (25%) were completely controlled with adequate therapy, and 40 (38%) were intractable, despite aggressive anticonvulsant polytherapy. The remaining 37% had their seizure frequencies reduced by > or = 50%, but were not seizure free. The age of seizure onset was significantly younger in the intractable group than in the well-controlled group. Patients with a history of febrile convulsions or with epileptiform discharges in their electroencephalogram (EEG) had poorer seizure control (p < 0.05) than those who did not. Among the 16 patients who had no previous treatment, five (31%) became seizure free, and two were intractable. CONCLUSIONS: Not all patients with MTS are medically intractable; 25% of the patients in our study achieved complete control while receiving medication. Poor seizure control was related to an early age of seizure onset, a history of febrile convulsions, and epileptiform discharges on the EEG.

Adolescent↗

Pylephlebitis associated with appendicitis.

Pylephlebitis usually occurs secondary to infection in the region drained by the portal venous system. A most common antesecent focus of infection is diverticulitis and the most common blood isolate is E. coli (54%), followed by Proteus mirabilis (23%). Overall mortality is 32% and most of the patients who had died had severe sepsis prior to the initiation of antibiotic therapy. We describe a case of pylephlebitis which had appendicitis and consequent septic thrombosis of the portal vein and its branches, with dissemination of infection to the liver. The patient had recovered due to timely antibiotic treatment alone and resulted in complete resolution. Early diagnosis and treatment are basic to a favorable clinical course.

Adult↗

Effect of PDGF, IL-1alpha, and BMP2/4 on corneal fibroblast chemotaxis: expression of the platelet-derived growth factor system in the cornea.

PURPOSE: The purpose of this study was to examine expression of platelet-derived growth factor (PDGF) and PDGF receptors in the human cornea and to study the effects of the PDGF isotypes on proliferation and chemotaxis of human corneal fibroblasts. The effects of interleukin (IL)-1alpha, bone morphogenic protein (BMP)2, and BMP4 on chemotaxis of human corneal fibroblasts were also studied. METHODS: mRNA expression was monitored with reverse transcription-polymerase chain reaction (RT-PCR) in primary cultured cells. Protein expression in fresh-frozen human corneal sections was studied with immunocytology. Chemotaxis was measured using a modified Boyden chamber, and proliferation was quantitated by cell counting. RESULTS: PDGF A, PDGF B, PDGF receptor alpha, and PDGF receptor beta mRNAs were detected in corneal epithelial cells, fibroblasts, and endothelial cells in culture. The proteins were expressed in each major cell type in human corneal sections, with PDGF A and PDGF B detected at high levels in the epithelial basement membrane. PDGF, BMP2, and BMP4 had attractive chemotactic effects on corneal fibroblasts, with the PDGF BB dimer having a significantly greater positive chemotactic effect than the other PDGF isotypes. Interleukin-1alpha had a repulsive chemotactic effect on corneal fibroblasts. PDGF AA, AB, and BB stimulated proliferation of human corneal fibroblasts. CONCLUSIONS: The PDGF growth factor receptor system is expressed in the human cornea. PDGF, BMP2, BMP4, and IL-1alpha may modulate keratocyte chemotaxis and proliferation during homeostasis and wound healing.

Bone Morphogenetic Protein 2↗

Expression of transforming growth factor beta 1, 2, and 3 proteins in keloids.

Keloids represent a pathological response to cutaneous injury, creating disfiguring scars with no known satisfactory treatment. They are characterized by an excessive accumulation of extracellular matrix, especially collagen. Transforming growth factor beta (TGF-beta) has been implicated in the pathogenesis of keloids. The three TGF-beta isoforms identified in mammals (TGF-beta1, -beta2, and -beta3), are thought to have different biological activities in wound healing. TGF-beta1 and TGF-beta2 are believed to promote fibrosis and scar formation, whereas TGF-beta3 has been shown to be either scar inducing or reducing, depending on the study. The aim of this study was to characterize expression of TGF-beta isoforms in keloids at the protein level using Western blot analysis. The authors found that TGF-beta1 and -beta2 proteins were at higher levels in keloid fibroblast cultures compared with normal human dermal fibroblast cultures. In contrast, the expression of TGF-beta3 protein was comparable in both the normal (N = 3) and keloid (N = 3) cell lines. These findings, demonstrating increased TGF-beta1 and -beta2 protein expression in keloids relative to normal human dermal fibroblasts further support the roles of TGF-beta1 and -beta2 as fibrosis-inducing cytokines.

Adolescent↗

Lacrimal gland HGF, KGF, and EGF mRNA levels increase after corneal epithelial wounding.

PURPOSE: To evaluate the effect of corneal epithelial wounding on lacrimal gland expression of hepatocyte growth factor (HGF), keratinocyte growth factor (KGF), and epidermal growth factor (EGF) in the rabbit model. METHODS: Rabbits had corneal epithelial scrape injuries, and the lacrimal gland was removed at different times after wounding. HGF, KGF, and EGF mRNA expression was examined by quantitative RNase protection assay. HGF, KGF, and EGF proteins were detected in rabbit lacrimal tissue using immunoprecipitation and western blot analysis. RESULTS: HGF mRNA and EGF mRNA were significantly increased in rabbit lacrimal gland tissue within 8 hours after corneal epithelial injury. The increase in KGF mRNA expression was small and reached significance I clay after corneal injury. Lacrimal gland expression peaked at 3 days after wounding for each growth factor mRNA, the same day, on average, that the epithelial defect healed. After the peak increase in expression, there was a progressive decline in expression of each growth factor mRNA, but production was still increased compared with prewound levels. HGF protein, KGF protein, and EGF proteins were detected in rabbit lacrimal gland tissue. CONCLUSIONS: Levels of HGF, KGF, and EGF mRNAs increase in rabbit lacrimal gland tissue in response to corneal epithelial wounding. The results of this study are consistent with the existence of a cornea-nervous system-lacrimal gland regulatory loop modulating expression of these growth factor mRNAs. The lacrimal gland is a likely source of increased HGF and EGF proteins detected in tears in previous studies.

Animals↗

Restoration of thoracic kyphosis in the hypokyphotic spine: a comparison between multiple-hook and segmental pedicle screw fixation in adolescent idiopathic scoliosis.

This study verified the efficacy of segmental pedicle screw fixation in restoring thoracic kyphosis in persons with hypokyphotic scoliosis. Fifty-one patients were divided into three groups by the degree of preoperative thoracic hypokyphosis and fixation method used: the hypokyphosis-hook (HH), hypokyphosis-screw (HS), and normal kyphosis-screw (NS) group. They were compared after a minimum follow-up period of 2 years. Preoperative thoracic kyphosis of 4.1 degrees +/- 8.6 degrees, 8.1 degrees +/- 5.6 degrees and 27.3 degrees +/- 9.8 degrees in the HH, HS, and NS groups were restored to 14.5 degrees +/- 10.2 degrees, 27.3 degrees +/- 11.3 degrees, and 28.3 degrees +/- 13.7 degrees, respectively. The difference between the HH and HS groups was significant (p = 0.000). The HS and the NS groups did not differ (p = 0.16). This indicates that segmental pedicle screw fixation was more effective than multiple hooks in restoring kyphosis in patients with hypokyphotic scoliosis and created kyphosis similar to that in patients without preoperative hypokyphosis.

Adolescent↗

Changes in corneal morphology associated with chronic epithelial injury.

PURPOSE: The purpose of this study was to evaluate the effect of chronic epithelial scrape injury on corneal morphology. METHODS: The corneal epithelia in one eye of 8-week-old New Zealand White rabbits were scraped at weekly intervals. Central corneal thickness was measured by ultrasonic pachymetry before epithelial scrape each week. Control never wounded (C), chronic wounded with scrape the last week (W), and chronic wounded without scrape the last week (WW) corneas were processed for histologic analysis and transmission electron microscopy (TEM). The time intervals for histologic analysis were 4 (4 C, 2 W, 2 WW), 8 (4 C, 2 W, 2 WW), and 16 (7 C, 2 W, 5 WW) weeks. Histologic findings were monitored using hematoxylin and eosin staining, the TdT-dUTP terminal nick-end labeling (TUNEL) assay, and TEM. RESULTS: Chronic wounded corneas developed marked epithelial hyperplasia and a subepithelial acellular zone. Keratocytes undergoing apoptosis were primarily detected adjacent to the acellular zone by TUNEL assay and TEM. Total central corneal thickness measured by ultrasonic pachymetry (n=7) was significantly thinner in chronically scraped eyes compared with control eyes after 8, 12, and 16 weeks (P < 0.05). Control corneas increased in total thickness over the 16 weeks of the study, but there was no significant change in total thickness of the corneas that had chronic epithelial scrape injury over this time interval. Two scraped corneas had marked decreases in total corneal thickness relative to the corneal thickness at the beginning of the study. Epithelial hyperplasia developed in all scraped corneas examined histologically after 4, 8, or 16 weeks of scraping. When central epithelial thickness measured on hematoxylin and eosin-stained sections was subtracted from the total pachymetric corneal thickness to give approximate stromal thickness, the stromal thickness was 23% lower in the chronic wounded (277+/-15 microm) compared with the unwounded (356+/-6 microm) corneas (P=0.0008) after 16 weeks of wounding. CONCLUSIONS: Chronic epithelial injury induces stromal thinning and epithelial hyperplasia. These changes in cornea structure associated with chronic epithelial injury may have relevance to the pathophysiology of keratoconus.

Animals↗

Signal transduction in wound pharmacology.

Growth factors such as TGF-beta, PDGF and FGF are thought to play important roles in wound healing. However, their biological activity and signal transduction during wound repair remain poorly understood. Growth factors are often ligands for receptor tyrosine kinase and receptor serine/threonine kinases. With recent advances in signal transduction by receptor kinases, we are beginning to understand the underlying mechanism of how growth factors may regulate cutaneous wound repair. In this paper, we will describe the pharmacological effects of growth factors on wound healing, and discuss the potential underlying signaling mechanisms. Thus, we hope to provide the basis for designing more specific therapeutics for wound healing in the near future.

Animals↗

The morphology of the polyhedra of a host range-expanded recombinant baculovirus and its parents.

The host range-expanded recombinant baculovirus, RecB-8 was isolated from BmN-4 cells coinfected with Autographa californica and Bombyx mori nuclear polyhedrosis viruses. Its genome was compared with those of its parents by restriction endonuclease digestion and their polyhedra compared in an electron microscope. Interestingly, the polyhedra of RecB-8 were tetrahedral although the polyhedrin gene was the same as that of the BmNPV parent which has icosahedral polyhedra. Thus the morphology of the RecB-8 polyhedra resulted from host cell factors and/or another viral genome in the host cells.

Animals↗

Clinical courses of pure sleep epilepsies.

This study aims to understand seizure control outcomes and the risk of developing new wake seizures (WS) related to the different types of pure sleep epilepsies (SE), which is important in making rational management plans. A retrospective review of the Yonsei Epilepsy Clinic Registry identified 63 patients with pure SE not belonging to any specific epileptic syndromes. They were divided into the group of generalized tonic-clonic seizures during sleep (S-GTCS : n = 21) and the group of partial epilepsies during sleep (S-PE: n = 42) on the basis of seizure phenomenology, EEG, and neuroimaging data. These patients were followed for 2 years and their clinical variables were analysed for seizure control outcomes and development of new WS. Of 21 patients with S-GTCS, 17 achieved a seizure-free outcome and only one patient developed a new WS, which was consistent with a partial-onset secondary GTCS in phenomenology. Of 42 patients with S-PE only 15 patients achieved a seizure-free outcome and 11 patients developed WS during the 2-year follow-up period. Higher baseline seizure frequency and longer duration of epilepsy were associated with a higher incidence of new WS. The results suggest that the patients with S-GTCS carry a favorable clinical course, thus driving privileges or freedom of daily activities can be conferred without delay once their seizures are well controlled. However, the seizure control outcome was poor and the development of WS was frequent in patients with recurrent S-PE.

Adolescent↗

Bacterial resistance to antimicrobial agents: an overview from Korea.

Antimicrobial resistance of bacteria has become a worldwide problem. Available data suggest that the resistance problem is comparatively more serious in Korea. In large hospitals, the proportion of methicillin-resistant Staphylococcus aureus (MRSA) has been reported at over 70%, and of penicillin-nonsusceptible Streptococcus pneumoniae at around 70%. Infection or colonization of vancomycin-resistant enterococci has started to increase. Extended-spectrum beta-lactamase producing Escherichia coli and Klebsiella pneumoniae has become widespread and even carbapenem-resistant Pseudomonas aeruginosa has been increasing. Community-acquired pathogens such as Salmonella, Shigella and Neisseria gonorrhoeae are often resistant to various antimicrobial agents. The prevalence of resistant bacteria can lead to erroneous empirical selection of either noneffective or expensive drugs, prolonging hospitalization and higher mortality. The emergence and spread of resistant bacteria are unavoidable unless antimicrobial agents are not used at all. The high prevalence of resistant bacteria in Korea seems to be related to antibiotic usage: 1) easy availability without prescription at drug stores, 2) injudicious use in hospitals, and 3) uncontrolled use in agriculture, animal husbandry, and fisheries. Nosocomial infection is an important factor in the spread of resistant bacteria. Antimicrobial resistance problems should be regarded as the major public health concern in Korea. It is urgently required to ban the sale of antibiotics without prescription, to use antibiotics more judiciously in hospitals by intensive teaching of the principles of the use of antibiotics, and to establish better control measures of nosocomial infections. Regulation of antimicrobials for other than human use should also be required. These issues are not easy to address and require the collective action of governments, the pharmaceutical industry, health care providers, and consumers.

Bacterial Infections↗