Inflammatory skin diseases such as atopic dermatitis (AD) and rosacea were complicated by barrier abrogation and deficiency in innate immunity. The first defender of epidermal innate immune response is the antimicrobial peptides (AMPs) that exhibit a broad-spectrum antimicrobial activity against multiple pathogens, including Gram-positive and Gram-negative bacteria, viruses, and fungi. The deficiency of these AMPs in the skin of AD fails to protect our body against virulent pathogen infections. In contrast to AD where there is a suppression of AMPs, rosacea is characterized by overexpression of cathelicidin antimicrobial peptide (CAMP), the products of which result in chronic epidermal inflammation. In this regard, AMP generation that is controlled by a key ceramide metabolite S1P-dependent mechanism could be considered as alternate therapeutic approaches to treat these skin disorders, i.e., Increased S1P levels strongly stimulated the CAMP expression which elevated the antimicrobial activity against multiple pathogens resulting the improved AD patient skin.
Dermatitis, Atopic* ; Endoplasmic Reticulum Stress ; Fungi ; Gram-Negative Bacteria ; Humans ; Immunity, Innate ; Inflammation ; Peptides* ; Rosacea ; Skin ; Skin Diseases ; Sphingolipids*

Programmed death-1 (PD-1) is a strong negative regulator of T lymphocytes in tumor-microenvironment. By engaging PD-1 ligand (PD-L1) on tumor cells, PD-1 on T cell surface inhibits anti-tumor reactivity of tumor-infiltrating T cells. Systemic blockade of PD-1 function using blocking antibodies has shown significant therapeutic efficacy in clinical trials. However, approximately 10 to 15% of treated patients exhibited serious autoimmune responses due to the activation of self-reactive lymphocytes. To achieve selective activation of tumor-specific T cells, we generated T cells expressing a dominant-negative deletion mutant of PD-1 (PD-1 decoy) via retroviral transduction. PD-1 decoy increased IFN-γ secretion of antigen-specific T cells in response to tumor cells expressing the cognate antigen. Adoptive transfer of PD-1 decoy-expressing T cells into tumor-bearing mice potentiated T cell-mediated tumor regression. Thus, T cell-specific blockade of PD-1 could be a useful strategy for enhancing both efficacy and safety of anti-tumor T cell therapy.
Adoptive Transfer ; Animals ; Antibodies, Blocking ; Autoimmunity ; Cell- and Tissue-Based Therapy ; Humans ; Lymphocytes ; Mice ; T-Lymphocytes ; T-Lymphocytes, Cytotoxic* ; Zidovudine

BACKGROUND: Recently, the molecular pathologic investigation for clonality in lymphomas has been introduced and has gained a role in the diagnosis of lymphomas. In fact, the clonality test using TCRGR phenomenon has been done by Southern blot analysis (SBA) and polymerase chain reaction (PCR) for molecular pathologic diagnosis of T cell lymphomas. However, it is difficult to perform SBA with paraffin embedded specimens or with samples of small skin biopsies. OBJECTIVE: We investigated the efficacy of PCR amplification of TCR gene in paraffin em-bedded cutaneous T cell lymphomas. METHODS: Iii this study, the clonality was assessed by polymerase chain reaction (PCR) analysis of T cell receptor gamma (TCR) gene from the DNA extracts obtained from paraffin em-bedded tissues (PET) of malignant T cells, B cell lymphomas, and benign cutaneous T cell proliferative disorders. Heteroduple-x-analyses were also performed to rule out the false positives. RESULTS: Among the total of 62 cases analyzed, monoclonality was observed in 4 out of 10 mycosis fungoides, 7 out of 9 cutaneous T cell lymphomas excluding mycosis fungoides, 1 out of 3 angiocentric lymphomas, 2 out of 2 lymphomatosis papulosis, 1 out of 7 large plaque parapsoriasis, and 1 out of 2 T cell lymphomas in other organs. No monoclonality was observed in 9 inflammatory cutaneous diseases, 5 small plaque parapsoriasis, 4 cutaneous B cell lymphomas, and 11 B cell lymphomas in lymph nodes. CONCLUSION: The results suggest that the PCR method and heteroduplex analysis used in this study were not only practical but also efficacious for the diagnosis of cutaneous T cell lymphomas using tissues embedded in paraffins.
Biopsy ; Blotting, Southern ; Diagnosis ; DNA ; Gene Rearrangement* ; Genes, T-Cell Receptor ; Heteroduplex Analysis* ; Lymph Nodes ; Lymphoma ; Lymphoma, B-Cell ; Lymphoma, T-Cell ; Lymphoma, T-Cell, Cutaneous ; Mycosis Fungoides ; Paraffin ; Parapsoriasis ; Polymerase Chain Reaction* ; Receptors, Antigen, T-Cell* ; Skin ; T-Lymphocytes

Chronic granulomatous infection of the skin and soft tissue by nontuberculous mycobacteria in patients with normal immune system is rarely reported. This case was about a child patient, with normal immune system, whose lower leg was lacerated after a slip down in the Philippines and it was previously treated at a hospital in the Philippines. After a couple of surgical debridement of the wound, the cause of the soft tissue infection was found to be a combined infection of nontuberculous mycobacteria and mycobacterium tuberculosis. We present a case that has been rare in Korea, but common overseas.
Child ; Debridement ; Humans ; Immune System ; Korea ; Leg ; Mycobacterium tuberculosis ; Nontuberculous Mycobacteria ; Philippines ; Skin ; Soft Tissue Infections

The purpose of this study was to examine the ultrastructural characteristic of the normal pylorus mucosa, and their structural changes induced by the ligation of common bile duct of the male rabbits weighing about 1.5 kg each. Experiment animals were divided into normal, sham operation, and experimental groups. Common bile duct ligation was performed under ether anesthesia and anjmals were sacrificed on the 1st, 3rd, 5th, 7th and 14th day after operation. The mucosal specimen of the pylorus, were fixed and embedded with common method. The sections were cut on a LKB-V ultratome, and observed under a JEM 100CX II electron microscope. The results were as follow : 1. In the early stages (1st, 3rd, 5th day groups) following the ligation, surface mucous cells have the various electron densities and shape of the mucous granules. In the late stages (7th, 14th day groups) following the ligation, many surface mucose cells containing numerous electron dense mucous granules are seen. 2. In the early stage of the ligation of bile duct, secretory function of EC cells was depressed, but in the later stage, the cells showed recovered secretory activity. 3. Secretory function of D cells was depressed on the early groups after the ligation of common bile duct, but they showed recovered secretory activity from the late groups after the ligation of the common bile duct. 4. Secretory function of G cells was activated on the early groups after the ligation of common bile duct, but they showed depressed secretory activity from the late groups after the ligation of the common bile duct. Considering the above findings, common bile duct ligation probably causes the dysfunction of the pyloric surface mucous cells that results in delayed mucous formation and secretion, and recovered mucous secretory function on the late stages. EC cells and G cells, depressed the secretory activities on the early stages and recovered on the late stages of the ligation of common bile duct. But D cells in the pyloric mucosa was activated on the early groups after the ligation of common bile duct ligation, but they was depressed secretory activities on the late groups.
Anesthesia ; Animals ; Bile Ducts ; Common Bile Duct* ; Ether ; Gastrin-Secreting Cells ; Humans ; Ligation* ; Male ; Mucous Membrane* ; Pylorus ; Rabbits ; Somatostatin-Secreting Cells

Estimation of biological profile for skeletal remains by forensic anthropological examination would be possible based on physical anthropological studies which were statistically analyzed. However, physical anthropological studies for Korean population are not enough to establish biological profile for Korean because there is lack of documented osteological specimens in Korea. Recent study suggested that physical anthropological examination could be possible on the three dimensional data which were reconstructed from computed tomography, instead of preparing skeletal specimen by defleshing bone. One of the aim of this study is to evaluate Digital Korean database which were composed of computed tomographic images of 100 cadavers. The other is to perform statistical analysis on morphometrics for segmented atlas whether the results could be helpful to estimate sex in Korean. We measured 100 segmentation atlases (male 51, female 49) from the Digital Korean database which were under the control of Catholic Institute for Applied Anatomy, The Catholic University of Korea. Measurements of segmented atlas were carried out by using Mimics software (Simulation module, Version 13.0, Materialise NV, Belgium), and values of measurement were performed statistical analysis by IBM(R) SPSS(R) (version 20.0, Armonk, New York). Among 19 measurements, the width of atlas showed most crucial element for estimating sex, which was consistent with the result using dried bones of atlas and hit ratio of discriminant functions was 88.0%. 76.7 was the cut-off score of discriminant functions. This results showed that morphometrics for segmented atlas could be helpful in estimating sex using the Digital Korean database. In the future, we expect that the other researchers could more actively use the Digital Korean database as a good specimen for physical and forensic anthropological study.
Cadaver ; Female ; Human Body* ; Humans ; Korea

Industrial glues contain many kinds of organic solvents and glue sniffing by young people has become a social problem in Korea. Glue vapor may induce chronic toxicities different from those induced by exposures to the solvent of single component. We studied the effects of the inhalation of glue vapor on the primary target organ, the pulmonary epithelium of the respiratory system. Vapor samples of glue were collected for analysis; the components were acetone, n-hexane, methyl cyclopentane, c-hexane, and toluene. For the inhalation of glue vapor, experimental mice were exposed in a whole body chamber for 20 min/d for 3, 5, 7, and 14 d. Control groups were exposed to room air. Animals were euthanized and lung tissues were fixed in 10% neutral formalin for light microscopy, and in 2.5% glutaraldehyde plus 1.5% paraformaldehyde for electron microscopy. The results are as follows. 1. Alcianophilic bands were not detected in the normal alveolar epithelium, but weak alcianophilic bands were detected in bronchioles. Alcian blue-PAS and PAS positive cells were found in the mucosae of mice exposed to glue vapor for 5 and 7 d. 2. Types I and II pneumocytes and capillary endothelial cells were found in the normal alveolar epithelium. The blood-air barrier consists of Type I pneumocytes, a common basal lamina, and the capillary endothelium. 3. The alveolar epithelium of vapor-exposed mice showed more type II pneumocytes. In the longerexposed group, Type I pneumocytes and endothelial cells contained many pinocytotic vesicles. 4. The vapor-exposed lungs showed macrophages in the alveolar space, mild interstitial swelling, and increased numbers of collagenous fibers. Clearly, ultrastructural changes in pulmonary epithelia can occur following glue sniffing.
Acetone ; Adhesives ; Animals ; Basement Membrane ; Blood-Air Barrier ; Bronchioles ; Collagen ; Cyclopentanes ; Endothelial Cells ; Endothelium, Vascular ; Epithelium ; Formaldehyde ; Glutaral ; Inhalant Abuse ; Inhalation* ; Korea ; Lung* ; Macrophages ; Mice* ; Microscopy ; Microscopy, Electron ; Mucous Membrane ; Pneumocytes ; Respiratory System ; Social Problems ; Solvents ; Toluene

Skin is the first line of defense for protecting our bodies against external perturbations, including ultraviolet (UV) irradiation, mechanical/chemical stress, and bacterial infection. Nutrition is one of many factors required for the maintenance of overall skin health. An impaired nutritional status alters the structural integrity and biological function of skin, resulting in an abnormal skin barrier. In particular, the importance of micronutrients (such as certain vitamins and minerals) for skin health has been highlighted in cell culture, animal, and clinical studies. These micronutrients are employed not only as active compounds in therapeutic agents for treating certain skin diseases, but also as ingredients in cosmetic products. Here, the author describes the barrier function of the skin and the general nutritional requirements for skin health. The goal of this review is to discuss the potential roles and current knowledge of selected micronutrients in skin health and function.
Animals ; Bacterial Infections ; Cell Culture Techniques ; Micronutrients* ; Nutritional Requirements ; Nutritional Status ; Skin Diseases ; Skin* ; Vitamins

PURPOSE: We aimed to investigate the gene expression of human gingival fibroblasts on microgroove surface using DNA microarray. MATERIALS AND METHODS: Microgrooves were applied on grade II titanium discs to have 0/0 µm (NE0, control group), 60/10 µm (E60/10, experimental group) of respective width/depth by photolithography. The entire surface of the microgrooved Ti substrata was further acid etched and used as the two experimental groups in this study. Human gingival fibroblasts were cultured in the experimental group and the control group, and total RNA was extracted. The oligonucleotide microarray was performed to confirm the changes of various gene expression levels between experimental group and control group. Changes of gene expression level were determined at the pathway level by mapping the expression results of DNA chips, using the KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis. RESULTS: Gene expression levels on E60/10 and NE0 were analyzed, there were 123 genes showing significant differences in expression more than 1.5 times on E60/10 microgrooved surface compared to NE0 surface, and 19 genes showing significant differences in expression more than 2 times. The KEGG pathway analysis confirmed the changes in gene expression levels under experimental conditions. Cell signaling, proliferation, and activity among the various gene expression results were identified. CONCLUSION: Microgrooved surfaces induce gene expression changes and related cell signaling. According to the results of this study, microgrooves can be used as the surface of various biomaterials which need to improve cell activity through gene expression changes and activation of cell signaling.
Biocompatible Materials ; DNA* ; Fibroblasts* ; Gene Expression* ; Humans* ; Oligonucleotide Array Sequence Analysis* ; RNA ; Titanium

BACKGROUND: Emergence agitation after sevoflurane anesthesia in children can be prevented by midazolam. Alternative splicing of the GABAA receptor changes with age. Therefore, we hypothesized that alternative splicing of the gamma2 subunit affects the GABA current when applying sevoflurane and midazolam. METHODS: We performed the whole-cell patch clamp technique on human embryonic kidney 293 cells that were transfected with alpha1beta2gamma2L or alpha1beta2gamma2S. The concentration-response relations were recorded for midazolam and sevoflurane, and the co-application responses were measured at concentrations of 1.5 nM, 15 nM and 300 nM of midazolam and 0.5%, 2.0% and 4.0% of sevoflurane. Each GABA current was compared with that produced by 5 microM of GABA. RESULTS: The concentration-response relationships for midazolam and sevoflurane were dose-dependent without any differences between the alpha1beta2gamma2L and alpha1beta2gamma2S subtypes. 1.5 nM and 15 nM of midazolam did not significantly enhance the current after treatment with 0.5% sevoflurane for both subtypes. The current after treatment with 2.0% sevoflurane was enhanced by 1.5 nM midazolam for the alpha1beta2gamma2S subtype, but not for the alpha1beta2gamma2L subtype. In the case of 2.0% sevoflurane with 15 nM of midazolam, and 4.0% sevoflurane with 300 nM of midazolam, the GABA currents were significantly enhanced for both subtypes. CONCLUSIONS: These results show that the difference in the gamma2 subunit cannot explain the emergence agitation after sevoflurane anesthesia in children in vitro. This suggests that co-application of sevoflurane and midazolam enhances the GABA current according to the alternative splicing of the gamma2 subunit and the concentration of both drugs.
Alternative Splicing ; Anesthesia ; Child ; Dihydroergotamine ; gamma-Aminobutyric Acid ; Humans ; Kidney ; Methyl Ethers ; Midazolam