ABSTRACT
Recently, single-nucleotide polymorphisms (SNPs) in G-protein-coupled receptors (GPCRs) have been suggested to contribute to physiopathology and therapeutic effects. Leukotriene B4 receptor 2 (BLT2), a member of the GPCR family, plays a critical role in the pathogenesis of several inflammatory diseases, including cancer and asthma. However, no studies on BLT2 SNP effects have been reported to date. In this study, we demonstrate that the BLT2 SNP (rs1950504, Asp196Gly), a Gly-196 variant of BLT2 (BLT2 D196G), causes enhanced cell motility under low-dose stimulation of its ligands. In addition, we demonstrated that Akt activation and subsequent production of reactive oxygen species (ROS), both of which act downstream of BLT2, are also increased by BLT2 D196G in response to low-dose ligand stimulation. Furthermore, we observed that the ligand binding affinity of BLT2 D196G was enhanced compared with that of BLT2. Through homology modeling analysis, it was predicted that BLT2 D196G loses ionic interaction with R197, potentially resulting in increased agonist-receptor interaction. To the best of our knowledge, this report is the first to describe a SNP study on BLT2 and shows that BLT2 D196G enhances ligand sensitivity, thereby increasing cell motility in response to low-dose ligand stimulation.
Subject(s)
Humans , Asthma , Cell Movement , Ligands , Reactive Oxygen Species , Receptors, G-Protein-Coupled , Receptors, Leukotriene B4 , Therapeutic UsesABSTRACT
BACKGROUND/AIMS: Conflicting data have been reported about the seasonal variation in flare-up of inflammatory bowel disease (IBD). The aim of this study was to assess the occurrence of seasonal variations in flare-up of IBD in the Korean population. METHODS: Patients with IBD, who underwent more than 1 year of follow-up and showed more than 1 episode of flare-up, were included. Flares of disease were refined as follows; receipt of a new prescription and increasing dose of corticosteroids, 5-ASA or immunosuppressant; hospitalized or operated due to development and worsening of symptoms; elevation of inflammatory marker due to worsening of Crohn's Disease Activity Index (CDAI) or Mayo score. In addition, for patients with more than two episodes of flare-up, they were investigated in a monthly and seasonal pattern. RESULTS: Of 573 patients with IBD, 46 patients with Crohn's disease and 61 patients with ulcerative colitis were enrolled. There was no association between month of the year and flare of Crohn's disease (P=0.06) or ulcerative colitis (P=0.58). Further, no association between season of the year and flare of Crohn's disease (P=0.06) or ulcerative colitis (P=0.68). However, in Crohn's disease who experience 2 or more flare-ups, symptoms occurred more frequently during winter, especially December (P=0.029). CONCLUSIONS: In the Korean population, there was no association of seasonal and monthly variation in flares of Crohn's disease and ulcerative colitis. However, in Crohn's disease, individuals with 2 flar-up or more, symptoms occurred more frequently during December.
Subject(s)
Humans , Adrenal Cortex Hormones , Colitis, Ulcerative , Crohn Disease , Follow-Up Studies , Inflammatory Bowel Diseases , Prescriptions , SeasonsABSTRACT
BACKGROUND/AIMS: The adenoma detection rate (ADR) has been proposed as a quality indicator of colonoscopy; however, ADR cannot be measured easily with commonly used endoscopy reporting systems because substantial time and effort is required to acquire data from histologic assessments. The purpose of this study was to determine if polyp detection rate (PDR) could be used as a valid proxy for ADR. METHODS: A total of 1,156 consecutive, asymptomatic, individuals of average risk between 50 and 75 years-of-age who underwent screening colonoscopies at four tertiary medical centers by 27 gastroenterologists were included in this study. Each individual endoscopist performed at least 10 colonoscopies during the study period. The ADR and PDR were calculated as the proportion of an endoscopist's cases with an adenoma or polyp divided by the total number of colonoscopies. Pearson's correlation coefficient and the intraclass correlation coefficient were used to determine the level of agreement between ADR and PDR. RESULTS: The mean PDR and ADR for endoscopists was 47.4% (range, 21.7-75.0) and 36.5% (range, 13.0-66.7), respectively. There was a strong correlation between PDR and ADR (Pearson's correlation coefficient 0.94, P<0.001) and there was also good agreement between performance quintiles defined by ADR and PDR (intraclass correlation coefficient 0.94, P<0.001). CONCLUSIONS: PDR is a valid proxy for ADR and may be useful for quality assurance at centers where ADR cannot be easily measured.
Subject(s)
Humans , Adenoma , Colonoscopy , Endoscopy , Mass Screening , Polyps , Proxy , Quality Indicators, Health CareABSTRACT
Subject(s)
Animals , Gallium , Rats, Sprague-Dawley , Scandium , Skin , Thigh , Wound Healing , YttriumABSTRACT
Subject(s)
Bicuspid , Biopsy , Carcinoma, Squamous Cell , Connective Tissue , Epithelial Cells , Epithelium , Granuloma , Inflammation , Keratins , Leukoplakia , Mandible , Molar , OsteomyelitisABSTRACT
Subject(s)
Animals , Humans , Mice , Angiogenesis Inducing Agents , Antibodies , Carcinoma, Adenoid Cystic , Endothelial Growth Factors , Fibroblast Growth Factor 2 , Interleukins , Mice, Nude , Neoplasm Metastasis , Receptors, Vascular Endothelial Growth Factor , Research Design , Salivary Glands , Treatment Failure , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factor Receptor-2 , Vascular Endothelial Growth Factor Receptor-3ABSTRACT
It has been known that transglutaminase C (TGase C, TGase II) is directly participated in the DNA organization of chromosome, and affects the cellular processes such as proliferation, differentiation, and apoptosis of cells, but still not known what mechanism is working on. In this study, the cytogenetic and the immunohistochemical methods were used to observe the TGase C expression in the nuclear chromosome of the proliferating cells, especially in mitotic stage. The human gastric adenocarcinoma (SNU-1) cell line was used for immunohistochemistry and antisense inhibition study in vitro. The present study was also aimed to disclose the efficiency of antisense inhibition by using antisense oligonucleotide DNA labeled with fluorescence, and found that anti-TGase C probe was diffusely infiltrated into the cytoplasm and the nucleus of the cell. By the antisense inhibition the nuclei of SNU-1 cells became rough nuclear shape, as they were greatly reduced in TGase C immunoreactivity both for the normal and apoptotic SNU-1 cells. However, it is clearly presumed that the TGase C directly interacts with the chromosome of SNU-1 cells and it may play an important role in the division and organization of the chromosome during the mitotic stage.
Subject(s)
Humans , Adenocarcinoma , Apoptosis , Cell Line , Cytogenetics , Cytoplasm , DNA , Fluorescence , Immunohistochemistry , Nuclear MatrixABSTRACT