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Biomedical subjects

E B Lee

Publications and source records attributed to E B Lee.

At least 19 recordsLinked to original sources

Immunoglobulin GM and KM genotypes in Korean patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by immune complex deposition. We genotyped immunoglobulin allotypes of G1M (f,z), G2M (n+,n-), G3M (b,g) and KM (1,3) in 142 Korean patients with SLE and 200 healthy controls to investigate the role of the allotypes in SLE. The allele frequency of G1M (z) was significantly higher in patients with SLE as compared to the healthy controls (94.6% vs. 84.3%, corrected P = 0.0004, OR 3.30, 95% CI 1.71-6.88). The frequency of G2M (n-) allele was also higher in patients with SLE (95.3% vs. 88.3%, corrected P = 0.008, OR = 2.71, 95% CI 1.38-5.72). Distribution of the tested allele frequencies for G3M and KM were not different between the patients and controls. In the respect of antibody production, there was increased genotype frequency of G1M (z/z) in anti-Sm(-) SLE (P = 0.023 vs. control, P = 0.042 vs. anti-Sm (+) SLE). In conclusion, particular genotypes at G1M (f,z) and G2M (n+,n-) loci are significantly associated with SLE. These immunoglobulin genes may contribute to the etiology of SLE and production of autoantibodies.

Adult↗

Dinucleotide repeat polymorphism in intron II of human Toll-like receptor 2 gene and susceptibility to rheumatoid arthritis.

Human Toll-like receptors (TLRs) participate in innate immune response and signal the activation of adaptive immunity. The presence of a functional intronic polymorphism consisting of guanine-thymine repeats in TLR2 gene was recently reported. Here, we investigated a dinucleotide repeat polymorphism in intron II of TLR2 in Korean patients with rheumatoid arthritis (RA). The numbers of guanine-thymine [(GT)(n)] repeats in intron II of the TLR 2 gene were counted in 183 patients with RA and in 148 healthy controls, using the gene scanning technique. We classified alleles into two subclasses for further analysis, 12-16 GT repeats (S allele) and 17-28 repeats (L allele). By subgroup analysis, we also examined whether the S allele is associated with the presence of shared epitope (SE), rheumatoid factor (RF), joint erosion and extra-articular complications. S-allele frequency was significantly increased in patients with RA than in healthy controls [30.3% vs. 23.0%, P = 0.03, or 1.46, 95% confidence interval (CI) 1.03-2.07], and genotypes containing S alleles were more frequent in patients with RA than in healthy controls (54.4% vs. 46.5%. P = 0.04, or 1.57, 95% CI 1.01-2.42). A skewed S-allele distribution was not found to be related to the presence of SE. Subgroup analysis showed no genotypic or allele frequency differences between patients with/without RF, joint erosion, or extra-articular complications. Genotype containing shorter GT repeats in intron II of the TLR2 gene may confer susceptibility to RA in Koreans.

Adolescent↗

Interstitial lung disease in patients with polymyositis, dermatomyositis and amyopathic dermatomyositis.

OBJECTIVE: To assess the prevalence, characteristics and prognostic factors of interstitial lung disease (ILD) in Korean patients with polymyositis (PM), dermatomyositis (DM) and amyopathic dermatomyositis (ADM). METHODS: We reviewed the medical records of 72 consecutive PM and DM patients, including six patients with ADM, who were seen at the Rheumatology Clinic of Seoul National University Hospital between 1984 and 2003. RESULTS: Twenty-nine PM/DM patients (40.3%) developed ILD. Anti-Jo-1 antibody and arthralgia were associated with the presence of ILD (P = 0.022 and P = 0.041, respectively), whereas dysphagia was more frequently found in patients without ILD (P = 0.041). Lung biopsies revealed diffuse alveolar damage (DAD) (n = 2), usual interstitial pneumonia (UIP) with DAD (n = 2), UIP (n = 1), and non-specific interstitial pneumonia (n = 2). Of the 29 patients, 11 (37.9%) died. The mean survival time in ILD patients was significantly shorter than in those without ILD (13.8+/-1.8 vs 19.2+/-0.9 yr, P = 0.017). Poor survival in ILD patients was associated with a Hamman-Rich-like presentation (P = 0.0000), ADM features (P = 0.0001) and an initial forced vital capacity (FVC) < or =60% (P = 0.024). CONCLUSIONS: ILD was observed in 40.3% of Korean PM/DM patients and was associated with poor survival. A Hamman-Rich-like presentation, ADM features and an initial FVC < or =60% were associated with poor survival in ILD.

Adult↗

Osteopenia in men with mild and severe ankylosing spondylitis.

We investigated the frequency and distribution of osteopenia according to the clinical severity in ankylosing spondylitis (AS). Bone mass was measured in men with mild (n = 45) and severe AS (n = 31) with dual-energy X-ray absorptiometry (DEXA). Definition of clinical severity was based on the Schober's test. Osteopenia was commonly detected (48% in mild AS and 39% severe AS) and, in mild disease, more frequently observed at the lumbar spine than any of the proximal femur sites. In severe AS, however, the frequency of osteopenia at the femoral neck and Ward's triangle was as high as at the lumbar spine. Both bone mineral density and T-scores in severe disease were lower than in mild disease at the femur neck, Ward's triangle, and total proximal femur, but not in the lumbar spine. The progression of osteopenia may be reflected more reliably at proximal femur sites than at the lumbar spine.

Absorptiometry, Photon↗

Clinical features of adult-onset ankylosing spondylitis in Korean patients: patients with peripheral joint disease (PJD) have less severe spinal disease course than those without PJD.

OBJECTIVE: We investigated the clinical features of Korean patients with adult-onset ankylosing spondylitis (AAS) and examined the differences between AAS patients with and without peripheral joint disease (PJD). METHODS: We studied 67 consecutive patients with primary AAS who visited the rheumatology clinic of a tertiary referral hospital. All patients experienced joint symptoms after the age of 15 and fulfilled the modified New York criteria for ankylosing spondylitis. Hips and shoulders were not considered as peripheral joints. RESULTS: The male-to-female ratio was 8.6:1.0. Mean age at disease onset was 22.3 +/- 5.5 (mean +/- s.d.) yr and disease duration was 10.8 +/- 8.0 yr. Spinal symptoms were the first manifestations in 80.6% of patients. During the disease course, hip, shoulder and peripheral joint involvement were found in about 60% of patients. In patients with PJD, the most commonly affected joints were the knees and ankles. The pattern of PJD, in most cases, was asymmetrical and mono/oligoarticular. AAS patients with PJD had fewer spinal symptoms than those without PJD as a presenting feature (71.8 vs 92.9%, P = 0.035). The modified Schober test showed greater increments in patients with PJD (4.9 +/- 2.4 vs 3.0 +/- 2.4 cm, P = 0.002). Forced vital capacity was better in patients with PJD (79.0 +/- 11.4 vs 70.8 +/- 15.5% of predicted value, P = 0.016). Totally ankylosed sacroiliitis, spinal squaring and syndesmophytes on radiographs were less common in the patients with PJD than in those without PJD (33.3 vs 64.2%, P = 0.012; 20.5 vs 67.9%, P = 0.000; and 38.5 vs 71.4%, P = 0.008, respectively). CONCLUSION: Peripheral joints as well as shoulder and hip joints were more frequently involved during the disease course in Korean AAS patients compared with earlier reports in Caucasians. The general joint involvement pattern of PJD was similar to patterns reported previously. Our data suggest that, clinically and radiographically, AAS patients with PJD have a less severe spinal disease course than those without PJD.

Adolescent↗

Transforming growth factor-beta1 polymorphisms in Korean patients with systemic sclerosis.

Transforming growth factor-beta1 (TGF-beta1) plays an important role in the pathogenesis of systemic sclerosis (SSc). To investigate the role of TGF-beta1 gene polymorphisms in SSc, we genotyped six biallelic polymorphic positions (position -988, -800, and -509; and codons 10, 25, and 263) in 61 Korean SSc patients and in 148 healthy controls, using polymerase chain reaction-sequence-specific primers. Genetic polymorphisms were found at position -509 and codon 10 in Koreans. The allele frequencies of C/T at position -509 were 0.59/0.41 in patients and 0.56/0.44 in controls. The allele frequencies of C/T at codon 10 were 0.40/0.60 in patients and 0.50/0.50 in controls. In conclusion, no skewed distribution of TGF-beta1 gene polymorphisms was found in Korean patients with SSc.

Adult↗

Intercellular adhesion molecule-1 polymorphisms in Korean patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is characterized by synovial proliferation and the accumulation of inflammatory cells in the affected joints. Intercellular adhesion molecule-1 (ICAM-1) is readily detected in RA synovial tissues and helps recruit inflammatory cells to the joint. ICAM-1 shows genetic polymorphisms at codons 241 (R241G) and 469 (K469E). In order to investigate the association between ICAM-1 gene polymorphisms and RA, we genotyped ICAM-1 R241G and ICAM-1 K469E polymorphisms in 143 Korean patients with RA, and in 138 healthy controls, by using the polymerase chain reaction-restriction fragment length polymorphism method. No polymorphism of R241G was found in Korean subjects. However, the frequency of the K469 allele was found to be significantly lower in RA patients than in healthy controls. Allele frequency of K469 was lower in RA patient group, compared to that in healthy controls, regardless of the shared epitope status. Distribution of K469E allele frequencies was not different whether the patient had rheumatoid factor, radiographic erosion or extra-articular complications. In conclusion, this study shows lower frequency of the ICAM-1 K469E allele in Korean patients with RA than that in healthy controls.

Alleles↗

188Re-tin-colloid as a new therapeutic agent for rheumatoid arthritis.

Radiation synovectomy is a useful treatment modality in patients with refractory synovitis. We have developed a 188Re-tin-colloid as a new radiopharmaceutical agent and investigated its efficacy and safety in patients with rheumatoid arthritis. Radiation synovectomy was performed using 188Re-tin-colloid in 22 knees from 21 rheumatoid arthritis patients refractory to intra-articular corticosteroid injection. The efficacy and safety of administration of 370-1110 MBq of 188Re-tin-colloid were evaluated after 1, 3, 6, 9 and 12 months. Pain intensity on a visual analogue scale decreased significantly 12 months after therapy (mean+/-SD: 68.0+/-26.1 mm vs. 25.1+/-23.4 mm; P=0.0001 by the paired t-test). Pain decreased in 19 cases (86.3%), joint tenderness improved in 14 cases (63.6%) and joint swelling was reduced in all cases (100%). 188Re-tin-colloid was safe. The residual activity of 188Re in the blood was 0.077%+/-0.25% of the injected dose. The radioactivity of 188Re in the urine was 0.14%+/-0.13% of the injected dose. Transient reactive synovitis was observed in 18 cases (81.8%). No clinical side-effects or abnormalities in leucocyte count, platelet count, liver function tests or urine analysis were observed in any patient. In conclusion, in this first study of radiation synovectomy using 188Re-tin-colloid for patients with rheumatoid arthritis, the treatment resulted in the improvement of arthritis and was well tolerated.

Arthritis, Rheumatoid↗

Anti-inflammatory, analgesic and antipyretic activities of loxoprofen sodium given intramuscularly in animals.

The evaluation of the anti-inflammatory, analgesic and antipyretic activities of loxoprofen sodium given in intramuscular route was investigated as compared to oral application in rats and mice. The intramuscular ED50 values of loxoprofen sodium in carrageenan edema and vascular permeability tests are 1.15 and 7.8 mg/kg, respectively, which represent more potent than in case of oral application. Its therapeutic effects in adjuvant arthritis were shown at 6 mg/kg i.m. and 3mg/kg p.o. Analgesic effect was shown to be more potent as given intramuscularly. Similar potency of antipyretic effects was shown in both administration routes. Considerably weak gastric damages were observed in intramuscular application.

Analgesics, Non-Narcotic↗

Tumor necrosis factor receptor 2 polymorphism in systemic lupus erythematosus: no association with disease.

Genetic factors and immune dysregulation play important roles in the development of systemic lupus erythematosus (SLE). Tumor necrosis factor receptor 2 (TNFR2) is suggested to be involved in the development of SLE because its genetic locus (1p36) encompasses one of the susceptible loci for SLE and its ligand (TNF) is associated with SLE. To investigate the role of TNFR2 in the pathogenesis of SLE, 139 Korean patients were genotyped with SLE, 137 healthy control subjects were genotyped for TNFR2 196 R/M polymorphism in exon 6 with PCR-SSCP, and the clinical characteristics of SLE were analyzed according to the genotypes. The genotype frequencies of 196 R/R, 196 R/M, and 196 M/M were 3.6%, 30.9%, and 65.5% in SLE patients and 4.4%, 26.3%, and 69.3% in healthy controls (p = 0.676). The allelic frequency of 196 R was 19.1% in SLE patients and 17.5% in healthy controls (p = 0.638, odds ratio = 1.109, and the 95% confidence interval = 0.720-1.708). The clinical characteristics were not different according to the genotypes. In conclusion, no skewed distribution of TNFR2 196 R/M polymorphism was found in Korean patients with SLE compared with healthy controls. Further studies in other populations will be needed to elucidate the role of the TNFR2 polymorphism in the development of SLE.

Adolescent↗

Anti-inflammatory activity of methanol extract of Kalopanax pictus bark and its fractions.

The methanol extract of Kalopanax pictus bark was evaluated on anti-inflammatory and anti-nociceptive activities in animal models. The extract produced a significant inhibition of vascular permeability at doses of 1 and 3 g/kg, p.o. in mice and of leucocyte emigration at doses of 0.15 and 0.3 g/rat, s.c., in CMC-pouch of rats. However, the extract (0.25 and 3 g/kg, p.o.) did not show anti-inflammatory activity in carrageenan induced edema of rats. The extract at a dose of 2.5 g/kg, p.o. inhibited writhing syndromes, whereas it did not exhibit anti-nociceptive in Randall-Selitto assay. The methanol extract was then partitioned with n-hexane, chloroform, ethyl acetate and butanol to give each soluble fraction and finally water soluble fraction. Among those fractions, the inhibitory effect on vascular permeability in mice was produced by ethyl acetate soluble fraction in this activity-guided fractionation. The methanol extract showed low acute toxicity in mice. These results suggest that the methanol extract of Kalopanax pictus bark has an anti-inflammatory activity which is distributed in the ethyl acetate fraction.

Analgesia↗

General pharmacological properties of YJA20379-8, a new H+/K(+)-ATPase inhibitor with anti-ulcer activities.

The general pharmacological properties of YJA20379-8 (3-butyryl-4-[(R)-1-methylbenzylamino]-8-ethoxy-1,7-naphthyridine, CAS 187654-40-6), a new H+/K(+)-ATPase inhibitor with anti-ulcer activities, were investigated in mice, rats and guinea pigs. YJA20379-8 at oral doses of 25, 50 and 100 mg/kg did not affect the locomotor activity, hexobarbital hypnosis and motor coordination in mice. The drug did not have analgesic action and anticonvulsant action at the doses of 100 mg/kg p.o. The respiration and blood pressure were not affected at 10 mg/kg i.v. in rats. YJA20379-8 at 2 x 10(-4) g/ml did neither produce any contraction nor relaxation of isolated organs, such as guinea pig ileum, rat fundus, rat uterus and guinea pig vas deferens, and the drug antagonized the contractile responses to several spasmogens, such as acetylcholine, histamine, serotonin, L-phenylephrine, oxytocin and BaCl2. The drug up to 100 mg/kg p.o. did not affect pupil size and the intestinal propulsion of mice. And it did not show an anticarrageenan action at 100 mg/kg. In this general pharmacology study, hypothermic effect in mice, retardation in gastric emptying in rats, decreases in urine excretion in rats at oral doses of 50 and 100 mg/kg of YJA20379-8 and the spasmolytic activity could be found. However, no other effects were exhibited at a high oral dose of 100 mg/kg in animals in this study.

Animals↗

Inhibition of prostaglandin E2 production by platycodin D isolated from the root of Platycodon grandiflorum.

Platycodin D, isolated from the root of Platycodon grandiflorum A. DC. (Campanulaceae) suppressed prostaglandin E2 production at 10 and 30 microM in rat peritoneal macrophages stimulated by the protein kinase C activator 12-O-tetradecanoylphorbol 13-acetate (TPA). Platycodin D3 and oleanolic acid showed no effect at these concentrations. Western blot analysis revealed that the induction of COX-2 protein by TPA was inhibited by platycodin D in parallel with the inhibition of prostaglandin E2 production. Platycodin D showed no direct effect on COX-1 and COX-2 activities. TPA-induced release of [3H]arachidonic acid from pre-labeled macrophages was also not inhibited by platycodin D.

Animals↗

Fibroblast culture on surface-modified poly(glycolide-co-epsilon-caprolactone) scaffold for soft tissue regeneration.

Novel porous matrices made of a copolymer of glycolide (G) and epsilon-caprolactone (CL) (51 : 49, Mw 103000) was prepared for tissue engineering using a solvent-casting particulate leaching method. Poly(glycolide-co-epsilon-caprolactone) (PGCL) copolymer showed a rubber-like elastic characteristic, in addition to an amorphous property and fast biodegradability. In order to investigate the effect on the fibroblast culture, PGCL scaffolds of varying porosity and pore size, in addition to surface-hydrolysis or collagen coating, were studied. The large pore-sized scaffold (pore size >150 microm) demonstrated a much greater cell adhesion and proliferation than the small pore-sized one. In addition, the higher porosity, the better the cell adhesion and proliferation. The surface-hydrolyzed PGCL scaffold showed enhanced cell adhesion and proliferation compared with the unmodified one. Type I collagen coating revealed a more pronounced contribution for increased cell interactions than the surface-hydrolyzed one. These results demonstrate that surface-modified PGCL scaffold can provide a suitable substrate for fibroblast culture, especially in the case of soft tissue regenerations.

3T3 Cells↗

Association of HLA class II genes with systemic sclerosis in Koreans.

OBJECTIVE: To investigate HLA class II associations with systemic sclerosis (SSc) in Koreans according to anti-topoisomerase I (anti-topo I), anti-centromere antibody (ACA), and anti-U1 ribonucleoprotein (RNP) status. METHODS: HLA class II alleles (DRB1, DRB5, DQB1) were determined by DNA typing in 200 healthy control subjects and 74 patients with SSc: 35 anti-topo I positive, 3 ACA positive, and 19 anti-U1 RNP positive; among them were 34 diffuse and 40 limited subtypes, and 16 overlap syndrome. RESULTS: Anti-topo I positive SSc was strongly associated with DRB1*1502 compared with both controls (23% vs 5%; Pcorr = 0.003) and anti-topo I negative patients (23% vs 3%; p = 0.009); our study confirms observations in Japanese. HLA-DR 67FLEDR71, especially 38V-67FLEDR71 sequence (carried on DRB5*0102 in linkage disequilibrium with DRB1*1502, DRB1*0802, DRBI*1101), showed the strongest association with anti-topo I response (46% vs 16% in controls; Pcorr = 0.001), and 38L-67FLEDR71 group alleles were not associated with anti-topo I response. Anti-topo I response was not significantly associated with HLA-DQB1 alleles in Koreans. There were only 3 ACA positive patients, and all patients had DRB1*1501 and DQB1*0602 as heterozygotes. Anti-U1 RNP occurred at a high frequency (63%) among patients with overlap syndrome, and was not associated with HLA-DR or DQ genes. Among anti-topo I negative patients, diffuse and limited subtypes of SSc were significantly associated with DRB1*0803 (47% vs 15% in controls; Pcorr < 0.05) and DRB1*1501 (50% vs 17% in controls; Pcorr < 0.01), respectively. These HLA associations have not been reported in other ethnic groups and possible associations with certain autoantibody subsets remain to be confirmed. CONCLUSION: HLA-DR gene has a primary association with anti-topo I response, and HLA-DR 38V-67FLEDR71 group alleles including DRB5*0102 (in linkage disequilibrium with DRB1*1502) show the strongest association with anti-topo I response in Korean patients with SSc.

Adult↗

Rapid increase in immunoreactivity to GFAP in astrocytes in vitro induced by acidic pH is mediated by calcium influx and calpain I.

In higher vertebrates, reactive gliosis resulting from injury to the central nervous system (CNS) is characterized by a rapid increase in immunoreactivity (IR) to glial fibrillary acidic protein (GFAP). Little is known about the extracellular signals that initiate the increase in GFAP-IR following CNS injury. We demonstrated recently [T.H. Oh, G.J. Markelonis, J.R. Von Visger, B. Baik, M.T. Shipley, Acidic pH rapidly increases immunoreactivity of glial fibrillary acidic protein in cultured astrocytes, Glia 13 (1995) 319-322] that a rapid increase in GFAP-IR can be evoked in mature astrocyte cultures by exposing the cells to an acidic medium. We investigated the intracellular pathway(s) involved in initiating increased GFAP-IR, a hallmark of reactive astrocytes. The increase in GFAP-IR produced by exposure to acidic medium was blocked by pretreatment with nickel ions, by such blockers of L-type calcium channels as nifedipine, verapamil and diltiazem, by calpain inhibitor I, or by the intracellular calcium chelator, BAPTA-AM. At physiological pH, treatment with the calcium ionophore, A23187, resulted in increased GFAP-IR which could be blocked by pretreatment with calpain inhibitor I. Astrocytes exposed to low pH exhibited a marked increase in a GFAP fragment with a molecular weight of 48 kDa. In astrocytes exposed to acidic medium, alpha-fodrin, a selective endogenous substrate of calpain, was also found to be hydrolyzed producing fragments with molecular weights of 120-150 kDa. As anticipated, pretreatment with calpain inhibitor I prevented the proteolytic degradation of both GFAP and alpha-fodrin in these samples. These results suggest that the initial increase in GFAP-IR after CNS injury appears to be linked to Ca(++) influx, and is mediated further by a proteolytic process that seemingly involves the activation of the calcium-dependent protease, calpain I.

Acids↗