Dong-Uk Kim

Sebum output as a factor contributing to the size of facial pores

Background  Many endogenous and exogenous factors are known to cause enlarged pilosebaceous pores. Such factors include sex, genetic predisposition, ageing, chronic ultraviolet light exposure, comedogenic xenobiotics, acne and seborrhoea. This study was an attempt to determine the factors related to enlarged pores.

Structure of an Atypical Orphan Response Regulator Protein Supports a New Phosphorylation-independent Regulatory Mechanism

Two-component signal transduction systems, commonly found in prokaryotes, typically regulate cellular functions in response to environmental conditions through a phosphorylation-dependent process. A new type of response regulator, hp1043 (HP-RR) from Helicobacter pylori, has been recently identified. HP-RR is essential for cell growth and does not require the well known phosphorelay scheme. Unphosphorylated HP-RR binds specifically to its own promoter (P1043) and autoregulates the promoter of the tlpB gene (PtlpB). We have determined the structure of HP-RR by NMR and x-ray crystallography, revealing a symmetrical dimer with two functional domains. The molecular topology resembles that of the OmpR/PhoB subfamily, however, the symmetrical dimer is stable even in the unphosphorylated state. The dimer interface, formed by three secondary structure elements (α4-β5-α5), resembles that of the active, phosphorylated forms of ArcA and PhoB. Several conserved residues of the HP-RR dimeric interface deviate from the OmpR/PhoB subfamily, although there are similar salt bridges and hydrophobic patches within the interface. Our findings reveal how a new type of response regulator protein could function as a cell growth-associated regulator in the absence of post-translational modification.

The effect of wet-wrap dressing on epidermal barrier in patients with atopic dermatitis

Background  Wet‐wrap dressing has been shown to be effective for atopic dermatitis; however, the therapeutic mechanism of wet‐wrap dressing is only the hypothesis based on the recovery of decreased epidermal barrier function.

Circulating interleukin 17 is increased in the acute stage of Kawasaki disease

Objectives: During the acute phase, patients with Kawasaki disease (KD), an acute systemic vasculitis, demonstrate a drastic increase in serum interleukin‐6 (IL‐6), which parallels the duration of the fever. Recently, IL‐17 has been reported to induce IL‐6 production. The aim of this study was to elucidate the involvement of IL‐17 in the pathogenesis of KD. Methods: Serum samples were obtained from patients with KD (n=30) and normal controls (n=20), and the concentrations of IL‐17 and IL‐6 measured using enzyme‐linked immunosorbent assay (ELISA). Results: Compared with the normal controls (2.08±2.14 pg/mL), serum IL‐17 was markedly elevated in patients with acute KD (25.47±5.05 pg/mL); levels gradually decreased in the subacute phase (5.94±2.83 pg/mL). In the acute phase, levels of IL‐6 were 83.52±19.12 pg/L, which correlated well with the serum levels of IL‐17. Conclusion: These results suggest that IL‐17 may be involved in the development of, or the effects of inflammation in KD.

Sp1-associated activation of macrophage inflammatory protein-2 promoter by CpG-oligodeoxynucleotide and lipopolysaccharide.

Abstract.Macrophage inflammatory protein-2 (MIP-2) is a C-X-C chemokine that is important in recruiting neutrophils to inflammatory sites. Our previous reports demonstrated that lipopolysaccharide (LPS) or CpG-oligode-oxynucleotide (CpG-ODN) rapidly induce MIP-2 gene expression in the macrophage cell line, RAW 264.7. Here, we show that the DNA sequence of the MIP-2 promoter between −114 and +14 is sufficient for strong promoter activity in LPS- or CpG-ODN-stimulated RAW 264.7 cells. Importantly, comprehensive mutant analysis reveals that an Sp1 element in the promoter region between −114 and −94 is essential for synergistic MIP-2 promoter activation by NF-κB and c-Jun regardless of the presence of an AP-1 site. By combining deletion or site-specific mutant analysis with immunocomplex assays, we also confirmed that Sp1 mediates the recruitment of transcription factors NF- κB and c-Jun in LPS- or CpG-ODN-treated RAW 264.7 cells. Several lines of experimental evidence imply that the Sp1-binding element is an important determinant of MIP-2 promoter activity, and that NF-κB, c-Jun and Sp1 can functionally cooperate to elicit maximal activation of the promoter.

Inhibition of angiogenesis and tumor progression by hydrodynamic cotransfection of angiostatin K1-3, endostatin, and saxatilin genes

In vivo expression of angiostatin and endostatin, two different types of endothelial cell growth inhibitor, have been reported to inhibit vascularization in tumor tissues, resulting in tumor growth inhibition. Recently, in vivo expression of saxatilin, a novel disintegrin purified from snake (Gloydius saxatilis) venom, was able to strongly inhibit endothelial cell proliferation and smooth muscle cell migration, resulting in tumor growth inhibition. However, the antitumor efficacy of the individual antiangiogenic molecules expressed in vivo was not sufficiently potent to induce tumor regression in animal models. Therefore, in this study, we have systemically examined how combinational transfer of angiostatin, endostatin, and saxatilin genes affects neovascularization in tumor tissues and tumor progression in a mouse model. In Matrigel-implanted mice, cotransfection with plasmids encoding angiostatin K1-3 (pFLAG-Angio K1/3), endostatin (pFLAG-Endo), and saxatilin (pFLAG-Sax) resulted in the most effective inhibition of angiogenesis. In addition, hydrodynamic cotransfection of the three genes induced more inhibition of B16BL6 melanoma growth and pulmonary metastasis than other combinations of transfected genes. Compared with the empty vector-treated control group, cotreatment with the three plasmids reduced B16BL6 tumor growth by 89% and pulmonary metastasis by 90%. These results provide additional evidence supporting the combined systemic expression of antiangiogenic factors, such as angiostatin K1-3, endostatin, and saxatilin, as an alternative procedure for antiangiogenic cancer therapy.

Elevated anti-α-enolase antibody levels in Kawasaki disease

Objective: By functioning as a heat‐shock protein (HSP), α‐enolase has an important role in the pathophysiology of multivariant vasculitis. Kawasaki disease (KD) is a type of vasculitis occurring primarily in children. The role of α‐enolase in KD was assessed by measuring anti‐α‐enolase antibody (Ab) titres in patients with KD and the usefulness of anti‐α‐enolase Ab as a diagnostic tool in atypical KD patients was evaluated. Methods: Anti‐α‐enolase Ab titres were measured by using an enzyme‐linked immunosorbent assay (ELISA) in seven normal control patients, nine febrile control patients and 14 KD patients (10 typical KD, four atypical KD). A standard deviation (SD) of 3 above the mean of the normal control group was considered to be positive reactivity. Western blotting using recombinant human α‐enolase was performed in four KD patients and three normal controls. Results: With the positive reactivity limited to +3 SD over the mean (>0.6), 10 out of 14 patients (71%) were positive at the acute onset and 12 out of 14 patients (85.7%) were positive before discharge. In total, 12 out of 14 patients (85.7%) were positive either at acute onset or before discharge. All four atypical KD patients showed positive reactivity. Specific positive bands against recombinant human α‐enolase were detected by western blotting in all four KD patients, but no reactivity was seen in three patients with normal controls. Conclusion: This is the first study to demonstrate that autoantibodies against the α‐enolase are present in the sera of KD patients. We suggest that anti‐α‐enolase Ab should be a good candidate for a diagnostic tool in atypical KD.

Prevalence and patterns of anti‐nuclear antibodies in Korean children with juvenile idiopathic arthritis according to ILAR criteria

Objectives: To investigate the prevalence and patterns of anti‐nuclear antibodies (ANA) in different subtypes of juvenile idiopathic arthritis (JIA) according to the International League of Associations for Rheumatology (ILAR) criteria. Methods: One hundred and fifty‐three Korean patients (M:F 83:70) with JIA were followed between 1990 and 2006 and were tested for ANA by an indirect immunofluorescence method using HEp‐2 cells as the substrate. ANA tests were repeated in 37 patients during the course of the disease. The median age at onset was 7.5 years (range 0.8–15.9 years). Results: ANA were positive in 50 (33%) of the 153 patients at a dilution of 1:40 or higher (>1:40 in 70%, >1:80 in 2%, >1:160 in 16%, >1:320 in 2%, and >1:640 in 10%). The patterns of immunofluorescence staining were homogeneous in 50%, speckled in 38%, nucleolar in 8%, and centromere in 4%. ANA titres were decreased in 25 (68%) of the 37 patients, and the nuclear fluorescence patterns changed in 14 (38%) during follow‐up. ANA seropositivity was associated with female sex (p<0.0001), negative HLA‐B27 (p = 0.01), and a persistently elevated erythrocyte sedimentation rate (ESR) at follow‐up (p = 0.014). Furthermore, a high ANA titre (>1:160) was associated with a poor clinical outcome (active patients at follow‐up) (p = 0.005). Conclusions: ANA may be an important marker of disease activity in patients with JIA. ANA titres tend to decrease during disease remission but the fluorescence patterns do not appear to be related to disease activity or clinical outcome.

Crystallization and preliminary X-ray crystallographic analysis of EstE1, a new and thermostable esterase cloned from a metagenomic library

EstE1, a new thermostable esterase, was isolated by functional screening of a metagenomic DNA library from thermal environment samples. This enzyme showed activity towards short-chain acyl derivatives of length C4-C6 at a temperature of 303-363 K and displayed a high thermostability above 353 K. EstE1 has 64 and 57% amino-acid sequence similarity to est(pc)-encoded carboxylesterase from Pyrobaculum calidifontis and AFEST from Archaeoglobus fulgidus, respectively. The recombinant protein with a histidine tag at the C-terminus was overexpressed in Escherichia coli strain BL21(DE3) and then purified by affinity chromatography. The protein was crystallized at 290 K by the hanging-drop vapour-diffusion method. X-ray diffraction data were collected to 2.3 A resolution from an EstE1 crystal; the crystal belongs to space group P4(1)2(1)2, with unit-cell parameters a = b = 73.71, c = 234.23 A. Assuming the presence of four molecules in the asymmetric unit, the Matthews coefficient VM is calculated to be 2.2 A3 Da(-1) and the solvent content is 44.1%.

Pterygium unguis formation in porokeratosis of Mibelli

and has caused acute hepatitis after ingestion, and parts of the cashew and fig can produce oils that cause severe irritant reactions. The manufacturers on their website claim to have over 25 years of research and development experience that has proven that ‘Wart & Mole Vanish’, through extensive clinical studies, is the number one choice for removing warts and moles. However, when contacted they said, ‘We have used this product in clinics all over South East Asia since 1997 and have treated and removed millions of warts/moles and skin tags. If you are looking for scientific documents like you would produce in a U.S. type study, they are not available.’ The use of these creams for mole removal has not previously been reported in medical literature; however, use of a ‘black and yellow salve’ for the self-treatment of a basal cell carcinoma has been published. We need to deter patients from using such creams, as there would be no histological diagnosis for these lesions. The exact mechanism of action of the cream is not known and nor are the potential side-effects. As a result of the decline in the number of benign moles being removed (due to increased restrictions on cosmetic procedures) it may be that these creams are being more widely used than we previously believed.