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O J Kwon

Publications and source records attributed to O J Kwon.

At least 37 records · Page 2Linked to original sources

Expression of brain/kidney protein in Müller cells of rat retina following transient ischemia.

We have investigated the expression and cellular localization of brain/kidney (B/K) protein in the rat retina following transient ischemia. In the normal retina, strong B/K immunoreactivity was localized to some ganglion cells. In addition, a few radial Muller cell processes showed B/K immunoreactivity. Following ischemia and reperfusion, most B/K-labeled ganglion cells were lost, whereas between 1 day and 2 weeks post-lesion B/K immunoreactivity appeared in many more Muller cell processes with increasing intensity. Quantitative evaluation by immunoblotting confirmed that B/K expression then decreased progressively, to 35% of control values at four weeks post-lesion. Our findings suggest that Muller cells are involved in the pathophysiology of retinal ischemia through the expression of B/K following transient ischemia.

Animals↗

The expression and cellular localization of brain/kidney protein in the rat retina.

Brain/kidney (B/K) protein is a new protein of 474 amino acids, which contains two C2 domains structurally homologous to those present in synaptotagmins. The expression of B/K protein was identified in the rat retina and B/K protein immunoreactivity was localized to a number of ganglion cells, a few amacrine cells and the radial processes of Müller cells. Thus, B/K protein appears to be important in the homeostasis in these cells of the rat retina.

Animals↗

Grain dust induces IL-8 production from bronchial epithelial cells: effect on neutrophil recruitment.

BACKGROUND: There have been several investigations suggesting an involvement of activated neutrophils in the development of grain dust (GD)-induced occupational asthma. Interleukin-8 in the sputa from GD-induced asthmatic patients increased significantly after the exposure to GD. OBJECTIVE: To confirm IL-8 production from bronchial epithelial cells when exposed to GD, and to evaluate the role of IL-8 on neutrophil recruitment. MATERIALS AND METHOD: We cultured Beas-2B, a bronchial epithelial cell line. To observe GD-induced responses, four different concentrations ranging from 1 to 200 microg/mL of GD were incubated for 24 hours and compared with those without incubation of GD. To evaluate the effect of pro-inflammatory cytokines on IL-8 production and neutrophil chemotaxis, epithelial cells were incubated with peripheral blood mononuclear cell (PBMC) culture supernatant derived from subjects with GD-induced asthma exposed to 10 microg/mL of GD, and then compared with those without addition of PBMC supernatant. The level of released IL-8 in the supernatant was measured by enzyme-linked immunosorbent assay. Neutrophil chemotactic activity of the culture supernatant was determined by modified Boyden chamber method. RESULTS: Interleukin-8 production and neutrophil chemotactic activity from bronchial epithelial cells significantly increased with additions of GD in a dose-dependent manner (P < .05, respectively), and were significantly augmented with additions of PBMC supernatant (P < .05, respectively) at each concentration. Close correlation was noted between neutrophil chemotactic activity and IL-8 level (r = 0.87, P < .05). Compared with the untreated sample, pre-treatment of anti-IL-8 antibody induced a significant suppression (up to 67.2%) of neutrophil chemotactic activity in a dose-dependent manner. CONCLUSION: These results suggest that IL-8 produced from bronchial epithelial cells may be a major cytokine, which induces neutrophil migration into the airways when exposed to GD.

Antibodies↗

Partial liquid ventilation shows dose-dependent increase in oxygenation with PEEP and decreases lung injury associated with mechanical ventilation.

PURPOSE: The purpose of this article is to evaluate the effect of positive end-expiratory pressure (PEEP) during partial liquid ventilation (PLV) and to investigate if lung damage associated with mechanical ventilation can be reduced by PLV. MATERIALS AND METHODS: Twenty-two New-Zealand white rabbits were ventilated in pressure-controlled mode maintaining constant tidal volume (10 mL/kg). Lung injury was induced by repeated saline lavage (PaO2 < 100 mm Hg). Two incremental PEEP steps maneuvers (IPSMs) from 2 to 10 cm H2O in 2 cm H2O steps were performed sequentially. The control group received the first IPSM in the supine position and were turned prone for the second IPSM. In the PLV group (n = 7), 12 mL/kg of perfluorodecalin was instilled after lung injury before the two IPSMs. The early prone group (n = 7) received both IPSMs in the prone position. Parameters of gas exchange, lung mechanics, and hemodynamics as well as pathology were examined. RESULTS: During the first IPSM, the PLV group showed a significant increase in PaO2 after instillation of perfluorodecalin (P < .05) and then showed a dose-dependent increase in PaO2 with PEER. The control and EP groups showed improvement in PaO2 only at higher PEEP, eventually showing no intergroup differences at PEEP of 10 cm H2O. During the second IPSM only the PLV group retained its ability to increase PaO2 to the level obtained during the first IPSM (P < .05 compared with control and EP groups). During the first IPSM all three groups showed increasing trend in static compliance (Cst) with PEEP peaking at PEEP of 8 cm H2O. During the second IPSM, only the PLV group showed increase in static compliance with PEEP (P < .05 compared with other groups). Lung histology revealed significantly less hyaline membrane formation in the PLV group (P < .05). CONCLUSION: PLV shows dose-dependent increase in oxygenation with PEEP and may reduce lung damage associated with mechanical ventilation.

Analysis of Variance↗

Extensive acute lung injury following limited thoracic irradiation: radiologic findings in three patients.

The aim of our study was to describe the radiologic findings of extensive acute lung injury associated with limited thoracic irradiation. Limited thoracic irradiation occasionally results in acute lung injury. In this condition, chest radiograph shows diffuse ground-glass appearance in both lungs and thin-section CT scans show diffuse bilateral ground-glass attenuation with traction bronchiectasis, interlobular septal thickening and intralobular smooth linear opacities.

Acute Disease↗

HLA class II susceptibility to multiple sclerosis among Ashkenazi and non-Ashkenazi Jews.

OBJECTIVE: To look for HLA class II alleles and haplotypes conferring susceptibility to multiple sclerosis (MS) in the Jewish population of Israel. DESIGN: Population-based cohort of clinically definite patients with MS tested prospectively over 7 years. SETTING: Referral center in a neurology clinic at a university hospital in the greater Jerusalem area in Israel. PATIENTS: A total of 162 consecutive patients with clinically definite MS from the 2 main ethnic Jewish groups in Israel: 104 Ashkenazi (80 with a relapsing remitting or secondary progressive and 24 with a primary chronic progressive course of the disease) and 58 non-Ashkenazi (36 with a relapsing remitting or secondary progressive course and 22 with a primary chronic progressive course of the disease), matched with 132 Ashkenazi and 120 non-Ashkenazi healthy controls. MAIN OUTCOME MEASURES: The relationship between the various HLA class II alleles and haplotypes and MS, as defined by the polymerase chain reaction and sequence-specific oligonucleotide probe hybridization, among the Ashkenazi and the non-Ashkenazi Jewish sections and with respect to the different clinical courses of the disease. RESULTS: The haplotype DRB1*1501, DQA1*0102, DQB1*0602 was found to be associated with MS among both Ashkenazi and non-Ashkenazi patients (P<.001 and P =.04, respectively). Among the non-Ashkenazi patients, a new association of haplotypes DRB1*1303, DQA1*05, and DQB1*030 with MS was detected (P = .03). The MS susceptibility alleles, DRB 1* 1501, DQA1*0102, and DQB1*0602 , were found in association with the Ashkenazi patients (P<.001, P=.02, and P=.01, respectively); DRB1*1501 and DRB1*1303 were more frequently observed among the non-Ashkenazi patients (P = .03, P = .04, respectively). On subdivision of the patients into clinical subgroups, associations of DRB1*0801, DQA1*0102, DQA1*0401, and DQB1*0602 with primary chronic progressive MS among the Ashkenazi patients were evident (P = .03, P = .04, P = .04 and P = .05, respectively), whereas DRB1* 1501, DRB1*03011, and DQB1*0602 were associated with relapsing remitting or secondary progressive among the non-Ashkenazi patients (P = .05, P = .05, and P = .03, respectively). CONCLUSIONS: This study, unlike previous ones, is the first to show a significant association between HLA class II alleles and MS in the Jewish population. The association with the HLA-DR2-related haplotype is similar to that among non-Jewish white patients with MS. Moreover, our data support the possibility that DRB1*1501 is the susceptibility allele responsible for the association between this haplotype and MS in the Jewish population. Our study also underscores differences in HLA profiles between Ashkenazi and non-Ashkenazi patients, and between the different clinical courses of the disease. The latter may indicate that the clinical courses of MS are influenced by the genetic background.

Alleles↗

Molecular analysis of HLA class II polymorphisms among different ethnic groups in Israel.

The Jewish population in Israel comprises of inhabitants of heterogeneous ethnic backgrounds. Genetic studies classify the Israeli Jewish population into two major groups: Ashkenazi from Central and Eastern Europe and Sephardic or non Ashkenazi, from the Mediterranean and North Africa. The present study was aimed at elucidating the differential influx of HLA class II alleles in Ashkenazi, in various non-Ashkenazi subgroups and in Israeli Moslem Arabs. Using the PCR-SSOP technique, a large number of alleles were detected at each of the loci examined (DRB1, DQA1 and DQB1). In addition, gene frequencies, characteristic DR/DQ linkage disequilibria, population distance and their corresponding dendogram, were used to study the relationship between Israelis as a group, non Jewish Caucasians and Blacks. These populations could be grouped into three main clusters: the first consists of all the Israeli groups with the exception of the Ethiopian Jews; the second consists of non Jewish Caucasians, with a clear distinction seen between Israelis and non Jewish Europeans and U.S. Caucasians; the third, composed of Blacks, is distinctly different from the other populations. Ethiopian Jews were found to be closer to the Blacks than to any of the Israeli Jewish groups. We have shown that Jews share common features, a fact that points to a common ancestry. A certain degree of admixture with their pre-immigration neighbors exists despite the cultural and religious constraints against intermarriage.

Alleles↗

Grain dust induces IL-8 production from bronchial epithelial cells: the effect of dexamethasone on IL-8 production.

BACKGROUND: Recent publications have suggested an active participation of neutrophils to induce bronchoconstriction after inhalation of grain dust (GD). OBJECTIVE: To further understand the role of neutrophils in the pathogenesis of GD-induced asthma, this investigation was designed to determine whether human bronchial epithelial cells could produce IL-8 production and to observe the effect of dexamethasone on IL-8 production. MATERIALS AND METHODS: We cultured Beas-2B, a bronchial epithelial cell line. To observe GD-induced responses, four concentrations (1 to 200 microg/mL) of GD were incubated for 24 hours and compared with those without incubation of GD. To evaluate the effect of pro-inflammatory cytokines on IL-8 production, epithelial cells were incubated with peripheral blood mononuclear cell (PBMC) culture supernatant, which was derived from the culture of PBMC from a GD-induced asthmatic subject under the exposure to 10 microg/mL of GD, and compared with those cultured without addition of PBMC supernatant. The level of released IL-8 in the supernatant was measured by enzyme-linked immunosorbent assay. To evaluate the effect of dexamethasone on IL-8 production, four concentrations (5 to 5000 ng/mL) of dexamethasone were pre-incubated for 24 hours and the same experiments were repeated. RESULTS: There was significant production of IL-8 from bronchial epithelial cells with additions of GD in a dose-dependent manner (P < .05), which was significantly augmented with additions of PBMC supernatant (P < .05) at each concentration. Compared with the untreated sample, pretreatment of dexamethasone could induced a remarkable inhibitions (15% to 55%) of IL-8 production from bronchial epithelial cells in a dose-dependent manner. CONCLUSION: These results suggest that IL-8 production from bronchial epithelial cells may contribute to neutrophil recruitment occurring in GD-induced airway inflammation. The downregulation of IL-8 production by dexamethasone from bronchial epithelial cells may contribute to the efficacy of this compound in reducing cellular infiltration and ultimately to its anti-inflammatory property.

Bronchi↗

Genome-wide screen for systemic lupus erythematosus susceptibility genes in multiplex families.

Systemic lupus erythematosus (SLE) is the prototype of human autoimmune diseases. Its genetic component has been suggested by familial aggregation (lambdas = 20) and twin studies. We have screened the human genome to localize genetic intervals that may contain lupus susceptibility loci in a sample of 188 lupus patients belonging to 80 lupus families with two or more affected relatives per family using the ABI Prism linkage mapping set which includes 350 polymorphic markers with an average spacing of 12 cM. Non-parametric multipoint linkage analysis suggests evidence for predisposing loci on chromosomes 1 and 18. However, no single locus with overwhelming evidence for linkage was found, suggesting that there are no 'major' susceptibility genes segregating in families with SLE, and that the genetic etiology is more likely to result from the action of several genes of moderate effect. Furthermore, the support for a gene in the 1q44 region as well as in the 1p36 region is clearly found only in the Mexican American families with SLE but not in families of Caucasian ethnicity, suggesting that consideration of each ethnic group separately is crucial.

Chromosomes, Human, Pair 1↗

Nonspecific interstitial pneumonia with fibrosis: serial high-resolution CT findings with functional correlation.

OBJECTIVE: We assessed serial changes in high-resolution CT findings and pulmonary function in patients with nonspecific interstitial pneumonia with fibrosis. MATERIALS AND METHODS: Serial high-resolution CT findings in 13 patients with biopsy-proven nonspecific interstitial pneumonia with fibrosis (mean follow-up period, 11 months) and pulmonary function tests (mean follow-up period, 11 months) were retrospectively analyzed. On CT, the presence and extent of ground-glass opacity, irregular linear opacity, honeycombing, and consolidation were assessed. RESULTS: On initial CT, all patients had areas of ground-glass opacity (mean +/- SD, 21.6% +/-14.4) and irregular linear opacity (5.0% +/- 5.2). The areas of ground-glass opacity decreased significantly on follow-up CT (13.5% +/- 10.5, p = .003). The areas of irregular linear opacity decreased slightly (4.2% +/- 5.2, p > .05). Initial forced vital capacity (69.4% +/- 16.0) improved significantly on follow-up examination (83.9% +/- 16.5) (p = .003). The decrease in the extent of ground-glass opacity on CT correlated significantly with changes in forced vital capacity (r = -.702, p = .007) and diffusing capacity for carbon monoxide (r = - .597, p = .031). CONCLUSION: In patients with nonspecific interstitial pneumonia with fibrosis, areas of ground-glass opacity decrease on follow-up high-resolution CT, and the extent of decrease correlates significantly with that of functional improvement.

Adult↗

Partial liquid ventilation with perfluorocarbon improves gas exchange and decreases inflammatory response in oleic acid-induced lung injury in beagles.

The aim of this study was to determine the effect of partial liquid ventilation (PLV) using a perfluorocarbon (PFC) on gas exchange and lung inflammatory response in a canine acute lung injury model. After inducing severe lung injury by oleic acid infusion, beagle dogs were randomized to receive either gas ventilation only (control group, n = 6) or PLV (PLV group, n = 7) by sequential instillation of 10 mL/kg of perfluorodecalin (PFC) at 30 min intervals till functional residual capacity was attained. Measurements were made every 30 min till 210 min. Then the lungs were removed and bronchoalveolar lavage (BAL) (35 mL/kg) was performed on the right lung and the left lung was submitted for histologic analysis. There was significant improvement in PaO2 and PaCO2 in the PLV group compared to the control group (p < 0.05) which was associated with a significant decrease in shunt (p < 0.05). There was no significant difference in parameters of lung mechanics and hemodynamics. There was a significant decrease in cell count and neutrophil percentage in BAL fluid and significantly less inflammation and exudate scores in histology in the PLV group (p < 0.05). We conclude that PLV with perfluorodecalin improves gas exchange and decreases inflammatory response in the acutely-injured lung.

Animals↗

Polymorphism of the CYP1A1 and glutathione-S-transferase gene in Korean lung cancer patients.

The levels of expressions and catalytic activities of cytochrome P450 (CYP1A1) and glutathione-S-transferase class mu (GSTM1) enzymes in lungs and their metabolic balance may be an important determinant host factor underlying lung cancer. Genetic differences in metabolism, MspI restriction sites, Ile-Val polymorphism of CYP1A1 gene, and the null genotype of GSTM1 have been reported to be associated with susceptibility to lung cancer. The present studies were undertaken to establish frequencies of the polymorphic genotypes of CYP1A1 and GSTM1 in Koreans, and to evaluate linkage disequilibrium of the genotypes associated with higher lung cancer risks among Koreans. GSTM1(-) genotype was found in 52% of control subjects, whereas it was found in 55% of lung cancer patients. The allelic variants in CYP1A1 were distributed differently in lung cancer patients and controls. The heterozygous genotype frequency of the MspI site in lung cancer patients (53%) was higher than in controls (49%). The frequency of Ile/Val genotype of CYP1A1 was low in lung cancer patients, which are mostly squamous cell carcinoma.

Adenocarcinoma↗

Thiol-dependent metal-catalyzed oxidation of copper, zinc superoxide dismutase.

Superoxide dismutase (SOD) is a key enzyme in the antioxidant system of the cells. When exposed to a metal-catalyzed oxidation (MCO) system composed of Fe3+, O2, and thiol as an electron donor copper, zinc SOD (CuZnSOD) was susceptible to oxidative modification and damage as indicated by the loss of activity, fragmentation and aggregation of peptide as well as by the formation of carbonyl groups. Oxidative damage to CuZnSOD was inhibited by diethylenetriaminepentaacetic acid as well as by free radical scavengers and spin-trapping agents. The results of the present study indicate that hydrogen peroxide may be generated from a thiol/Fe3+/O2 system and that hydroxyl free radicals, produced by metal-catalyzed Fenton reactions, may be the ultimate species mediating the SOD damage. Incubation with the MCO system resulted in the release of Cu ions from CuZnSOD. Incubation with the thiol-MCO did not significantly increase the formation of 2-oxohistidine in CuZnSOD. The lack of formation of 2-oxohistidine, as well as the pronounced preventive effect of spin-traps on the thiol-MCO-mediated damage to CuZnSOD, indicates that inactivation might actually be predominantly due to global oxidation rather than a site-specific oxidation. The thiol-MCO-mediated damage to SOD may result in the perturbation of cellular antioxidant defense mechanisms and subsequently lead to a pro-oxidant condition.

Chelating Agents↗

D-penicillamine-induced pancreatic islet autoantibody production is independent of the immunogenetic background: a lesson from patients with Wilson's disease.

D-penicillamine (d-PA) was reported to induce various immunological abnormalities including production of autoantibodies to insulin. These abnormalities were mainly described in patients with primary immunological disorders such as rheumatoid arthritis. In order to clarify whether d-PA-induced immune disorders are restricted to patients genetically prone to develop autoimmune diseases or to a direct drug effect, we tested for the presence of various autoantibodies and for molecular HLA typing in 17 patients with Wilson's disease treated with this drug. In 2/17 patients, low-titer (10 JDFU) circulating islet cell autoantibodies (ICA) were detected, while another patient was positive for the presence of insulin autoantibodies. None of the sera tested showed reactivity for glutamic acid decarboxylase or ICA512. Five of twelve patients were positive for anti-single-stranded DNA autoantibody. Molecular HLA typing of the autoantibody-positive subjects showed that they carry HLA haplotypes not associated with insulin-dependent diabetes. The insulin response to intravenous glucose tolerance test in two patients with autoantibodies was found to be normal. A second blood testing of the autoantibody-positive patients 5 months following initial evaluation revealed conversion to negativity in all three. Our results suggest that d-PA-induced autoantibodies in patients with Wilson's disease are independent of the immunogenetic background characteristics of diabetes.

Adolescent↗

HLA class II immunogenetics of IDDM in Yemenite Jews.

The association between HLA-DR and DQ and insulin dependent diabetes mellitus (IDDM) was analyzed in 47 patients and 76 controls of Yemenite Jewish origin. The IDDM susceptibility alleles DRB1*03011, DQA1*0501, DQB1*02 and DRB1*0402, DQA1*0301, DQB1*0302 found in Caucasians had a very strong predisposing effect also in the Yemenite IDDM group. The DRB1*07, DQA1*0201 and DQB1*02 alleles were found to have a strong negative association with IDDM. None of the patients carried DRB1*07 and DQA1*0201 compared with healthy controls (43.7%). Our analysis revealed that the DRB1*03011 DQA1*0501 DQB1*02/DRB1*04 DQA1*03 DQB1*0302 heterozygous genotype confers the highest susceptibility (59.6% in patients vs. 0% in controls). The homozygous DRB1*03 and DRB1*04 genotypes were also found to be positively associated with the disease. 81% of the patients compared to 1.3% of controls carried the susceptibility alleles on both haplotypes. In conclusion, the development of IDDM in Yemenite Jews is strongly dependent on the presence of the susceptibility HLA alleles and on the absence of the DRB1*07 haplotype. The Yemenite Jewish group is uniquely homogenous with regard to genetic susceptibility factors involved in the process of IDDM, and may thus be an ideal model for further genetic studies.

Alleles↗

Neuropeptides and asthma.

Although asthma is considered to be an inflammatory disease of the airways, neural mechanisms remain very important. Neural control of airways is far more complex than has been previously recognized. In addition to the classic neural pathways, the nonadrenergic, noncholinergic pathway has been described in the airways of animals and humans. Neuropeptides are present in sensory, parasympathetic, and sympathetic neurons in airways, and have been shown to have proinflammatory effects, such as increased mucus production, microvascular leakage, and smooth muscle contraction. Neuropeptides released from sensory nerves (eg, neurokinin A and substance P) mediate excitatory nonadrenergic, noncholinergic transmission, which causes bronchoconstriction and, possibly, bronchial hyperresponsiveness. Better understanding of neural mechanisms might provide a useful therapeutic approach in the future.

Animals↗

Nitric oxide expression in airway epithelial cells in response to tubercle bacilli stimulation.

In order to investigate the role of airway epithelial cells in pulmonary tuberculosis, inducible nitric oxide synthetase (iNOS) expression and nitric oxide (NO) production were studied in A549 cells. Peripheral blood mononuclear cells (PBMC) from normal volunteers were separated and cultured for 24 h with LPS or tubercle bacilli (H37Rv, H37Ra). Thereafter, A549 cells were stimulated for another 24 h with culture supernatant fluids of PBMC. iNOS messenger RNA (mRNA) expression was measured with Northern blot analysis and NO production was measured with the Griess reaction, which can measure nitrite concentration. iNOS mRNA expression and NO production were minimal in the control cells. iNOS mRNA expression and NO production were significantly increased with LPS (P < 0.05) or tubercle bacilli (P < 0.01) stimulation. However, there was no difference in iNOS mRNA expression and NO production between H37Rv and H37Ra stimulations. Interestingly, iNOS mRNA expression and NO production were greater in A549 cells stimulated with tubercle bacilli-conditioned media than in the cells stimulated with LPS-conditioned media. IL-1beta, tumour necrosis factor-alpha and interferon gamma concentrations were increased in culture supernatant fluids of PBMC stimulated with tubercle bacilli. These findings suggest that airway epithelial cells may play a certain role in the pathogenesis of pulmonary tuberculosis by producing NO. However, the role of airway epithelial cells, regarding the virulence of tubercle bacilli, was not clear in this study.

Cells, Cultured↗