Association analysis of sphingomyelinase 2 polymorphisms for the extrinsic type of atopic dermatitis in Koreans.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to Jun-Mo Yang.
Explore the source record for details and available documents.
The monomeric state of creatine kinase (CK) was stably captured at the equilibrium state by employing cysteine residue modifications in the presence of a denaturant, and at a partially folded state. The partially folded monomeric CK (PF-CK) was aggregated with kinetic order, which was mainly caused by the hydrophobic surface interactions between the CK subunits. The artificial chaperone, described as a SDS-cyclodextrin, was applied to prevent aggregation as well as to refold the PF-CK: SDS treatment onto the monomeric CK can significantly block aggregation and can be successfully refolded in the solutions containing cyclodextrins and DTT. Three types of cyclodextrins such as alpha-, beta-, and gamma-cyclodextrins were applied to strip SDS from the enzyme molecule, and each kinetic course was measured. The intrinsic fluorescence changes showed that reactivation occurred and this accompanied the conformational changes. The size exclusion chromatography detected the variously trapped monomeric CKs such as the thiol residue modified PF-CK, the SDS-binding PF-CK, the cyclodextrin treated PF-CK, and the DTT treated SDS-binding PF-CK. Our study demonstrated monomer CK aggregation for the first time; we also demonstrated the complex reassociation of CK during refolding with the aid of the SDS-cyclodextrin, and these pathways followed first-order kinetics.
Explore the source record for details and available documents.
We conducted the proteomic studies to detect the dysregulated proteins in the atopic dermatitis (AD) proteome obtained from the patient-derived primary cultured fibroblasts. Acetaldehyde dehydrogenase 1 (ALDH1) was detected as being significantly down-regulated at the pH ranges of 6-9 and 4-7. The transcriptional levels of ALDH1, as detected by RT-PCR and real-time PCR, further confirmed the down-regulated phenomena for all the AD-fibroblasts (n = 20). The expression levels of ALDH1 in the whole skin tissue samples were further supported by the results of the primary cultured samples. These findings clearly demonstrate that ALDH1 can be a dermal biomarker for AD disease.
The International HapMap Project aims to generate detailed human genome variation maps by densely genotyping single-nucleotide polymorphisms (SNPs) in CEPH, Chinese, Japanese, and Yoruba samples. This will undoubtedly become an important facility for genetic studies of diseases and complex traits in the four populations. To address how the genetic information contained in such variation maps is transferable to other populations, the Korean government, industries, and academics have launched the Korean HapMap project to genotype high-density Encyclopedia of DNA Elements (ENCODE) regions in 90 Korean individuals. Here we show that the LD pattern, block structure, haplotype diversity, and recombination rate are highly concordant between Korean and the two HapMap Asian samples, particularly Japanese. The availability of information from both Chinese and Japanese samples helps to predict more accurately the possible performance of HapMap markers in Korean disease-gene studies. Tagging SNPs selected from the two HapMap Asian maps, especially the Japanese map, were shown to be very effective for Korean samples. These results demonstrate that the HapMap variation maps are robust in related populations and will serve as an important resource for the studies of the Korean population in particular.
BACKGROUND: During the past decade, several kinds of skin equivalents have been developed. However, the dermal equivalents have all contained exogenous materials, which can be difficult to obtain and a source of infections. OBJECTIVES: The aim of this study was to develop a new dermal equivalent by culturing dermal fibroblasts alone without exogenous materials and to evaluate its applicability in vitro and in vivo. METHODS: The postconfulent cultures of dermal fibroblasts in serum containing medium, that was supplemented with epidermal growth factor, insulin, hydrocortisone, transferrin and triiodothyronine for 3 weeks, produced a fibrous sheet that was visible macroscopically. To construct a skin equivalent, epidermal keratinocytes were cultured on the top of the fibrous sheet at the air-liquid interface. To evaluate its fate in vivo, the fibrous sheet was grafted into a nude mouse. RESULTS: Histologically, the fibrous sheet showed dermis-like tissue that consisted of an extracellular matrix around dermal fibroblasts, and revealed collagen fibers by Masson-trichrome staining. The components of dermal matrix such as type I collagen, type III collagen, elastin, fibrillin-1 and fibronectin were diffusely expressed. Some collagen fibrils were found by electron microscopy. In the skin equivalent, a multilayered epidermis with a horny layer was formed. Some differentiation markers (keratin 1 and 10, and involucrin) and the components of basement membrane (beta4 integrin chain, type IV and VII collagens) were expressed in a similar fashion to those in normal skin in vivo. Ultrastructurally, basement membrane zone such as hemidesmosomes, lamina lucida and lamina densa was found, although it was still incomplete. When the fibrous sheet was grafted in vivo, it revealed blood vessels that were derived from the nude mouse, and persisted for 4 weeks. CONCLUSION: These findings demonstrated that a new dermal equivalent, closely resembling a dermis in vivo, could be constructed by culturing dermal fibroblasts alone in a special culture medium. In addition, the dermal equivalent may be useful for experimental and clinical purposes, such as the reconstruction of a skin equivalent in vitro and grafting in vivo.
Explore the source record for details and available documents.
Recently, we reported altered protein expression in primary cultured fibroblasts from atopic dermatitis (AD) patients. As a sequential study, we conducted proteomic analysis of primary keratinocytes derived from AD patients to further identify AD-related proteins. Three pH ranges, 4-7, 6-9, and 7-11, were used to profile the altered protein expression in AD. We obtained 46 candidate spots from the 2-D gel image analysis: 18 proteins were up-regulated and 27 proteins were down-regulated. Among the several important candidate proteins, NCC27 showed the same profile of a defect in PTM in both AD-derived keratinocytes and fibroblasts. On the basis of current and previous reports, real-time PCR was performed on select candidate genes to compare RNA and protein expression levels in AD-derived keratinocytes and fibroblasts. Our results provide new clues to aid in understanding the mechanism of atopic alterations in keratinocytes and suggest new AD-associated proteins that are important in AD pathogenesis.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The inhibition of tyrosinase has attracted considerable attention for potential medicinal and cosmetic applications, as well as in agriculture. This study investigated the inhibition effects of thiol-associated Cu(2+) chelators and deduced a strategy for designing and/or selecting tyrosinase inhibitors. Among the several compounds tested, dithioglycerine (DTGC) was selected for further experiments on the inhibition kinetics on tyrosinase. Different types of tyrosinases derived from mushroom and from the transient overexpression in HEK293 cells were tested individually. The results showed that DTGC significantly inhibited human tyrosinase in a complex manner (slope-parabolic mixed-type inhibition), which was comparable to mushroom tyrosinase. The affinity of DTGC affinity to human tyrosinase was evaluated by setting up a K(i slope) equation. The results suggest that a Cu(2+) chelator modified with thiol groups has potential as a whitening agent. In addition, a strategy for designing and/or selecting tyrosinase inhibitors that target the active enzyme site was also suggested.
Childhood granulomatous periorificial dermatitis (CGPD) is a disease presenting most commonly in prepubertal children as yellow-brown papules limited to the perioral, perinasal and periocular regions. The condition is benign, self-limiting and is not associated with systemic involvement. We herein report a case of an 11-year-old Korean boy with multiple, asymptomatic, monomorphic, red-to-yellow-colored papular eruptions on the perioral areas of 7-month duration. Histopathological examination revealed upper dermal and perifollicular granulomatous infiltrate. After using oral erythromycin 500 mg daily for 1 year, the condition resolved completely without leaving a scar.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Research involving whitening agents requires several steps of experimentation, and the initial step is to test whitening agents with human melanocytes and those with human tyrosinase. Unfortunately, it takes a long time to gather human melanocytes, and these cells have some limitations when it comes to performing experiments, such as their passage difficulties and their cost. In this study, we suggest that the TXM13 human melanoma cells could be a useful cell candidate for studying human tyrosinase inhibition and depigmentation. We applied a tyrosinase inhibitor, such as dithioglycerine (DTGC), to validate the cell line's usefulness, and we tested the effect of DTGC on TXM13 melanogenesis. The results showed that human tyrosinase from TXM13 was appropriate, according to the inhibition kinetics, and that the conspicuous depigmentation of TXM13 occurred after DTGC treatment without downregulating the tyrosinase expression level. When taken together, our findings provide useful information regarding the use of the TXM13 melanoma cells for the development of whitening agents.
Tyrosinase requires two copper ions at the active site, in order to oxidize phenols to catechols. In this study, the inhibitory effect of the copper-chelating compound, ammonium tetrathiotungstate (ATTT), on the tyrosinase activity was investigated. ATTT was determined to inactivate the activity of mushroom tyrosinase, in a dose-dependent manner. The kinetic substrate reaction revealed that ATTT functions as a kinetically competitive inhibitor in vitro, and that the enzyme-ATTT complex subsequently undergoes a reversible conformational change, resulting in the inactivation of tyrosinase. In human melanin-producing cells, ATTT evidenced a more profound tyrosinase-inhibitory effect than has been seen in the previously identified tyrosinase inhibitors, including kojic acid and hydroquinone. Our results may provide useful information for the development of whitening agent.
Explore the source record for details and available documents.