The KOrean College of Rheumatology BIOlogics and targeted therapy (KOBIO) registry is a nationwide observational cohort that captures detailed data on exposure of patients to biologic and targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs). This registry was launched in December 2012 with an aim to prospectively investigate clinical manifestations and outcomes of patients with rheumatoid arthritis (RA), ankylosing spondylitis, and psoriatic arthritis who initiated a biologic or targeted synthetic DMARD or switched to another. Demographic data, disease activity, current treatment, adverse events, terms based on Medical Dictionary for Regulatory Activities, and so on are registered for patients who are then followed up annually in a web-based unified platform. The KOBIO registry also recruits and collects data of patients with RA on conventional DMARDs for comparison. As of today, more than 5,500 patients were enrolled from 47 academic and community Rheumatology centers across Korea. The KOBIO registry has evolved to become a powerful database for clinical research to improve clinical outcomes and quality of treatment.

The KOrean College of Rheumatology BIOlogics and targeted therapy (KOBIO) registry is a nationwide observational cohort that captures detailed data on exposure of patients to biologic and targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs). This registry was launched in December 2012 with an aim to prospectively investigate clinical manifestations and outcomes of patients with rheumatoid arthritis (RA), ankylosing spondylitis, and psoriatic arthritis who initiated a biologic or targeted synthetic DMARD or switched to another. Demographic data, disease activity, current treatment, adverse events, terms based on Medical Dictionary for Regulatory Activities, and so on are registered for patients who are then followed up annually in a web-based unified platform. The KOBIO registry also recruits and collects data of patients with RA on conventional DMARDs for comparison. As of today, more than 5,500 patients were enrolled from 47 academic and community Rheumatology centers across Korea. The KOBIO registry has evolved to become a powerful database for clinical research to improve clinical outcomes and quality of treatment.

PURPOSE: The aim of the current study is to assess the spectrum of genetic variation in the BRIP1 gene among Korean high-risk breast cancer patients who tested negative for the BRCA1/2 mutation. MATERIALS AND METHODS: Overall, 235 Korean patientswith BRCA1/2 mutation-negative high-risk breast cancerwere screened for BRIP1 mutations. The entire BRIP1 gene was analyzed using fluorescent-conformation sensitive gel electrophoresis. In silico analysis of BRIP1 variants was performed using PolyPhen-2 and SIFT. RESULTS: A total of 20 sequence alterations including 12 exonic and eight intronic variantswere found. Among the 12 exonic variants, 10 were missense and two were silent mutations. No protein-truncating mutation was found among the tested patients. Among the 10 missense variants, four (p.L263F, p.L340F, p.L474P, and p.R848H) were predicted to be pathogenic by both PolyPhen-2 and SIFT, and these variants were found in five patients. Of the four missense variants, p.L263F, p.L474P, and p.R848H localize to regions between the helicase motifs, while p.L340F resides in an iron-sulfur domain of BRIP1. CONCLUSION: No protein-truncating mutation in BRIP1 was found among the tested patients. The contribution of BRIP1 variants is thought to be minor in Korean non-BRCA1/2 high-risk breast cancer.
Breast Neoplasms* ; Breast* ; Computer Simulation ; Electrophoresis ; Exons ; Genetic Variation ; Hereditary Breast and Ovarian Cancer Syndrome ; Humans ; Introns ; Korea ; Silent Mutation

Altered expression of neurotrophic factors as well as neuroinflammation is commonly associated with Major depressive disorder (MDD) and Alzheimer's disease (AD). To investigate whether or not reserpine-induced MDD affects the expression of AD-related proteins, the expression of gamma-secretase components and substrate were measured in brains of ICR mice following reserpine treatment for 15 days. In active avoidance test, total response time and peak slightly increased in the 2 mg/kg reserpine (RSP2)-treated group compared to vehicle-treated group (P<0.05). Expression and phosphorylation of MKP-1, which is a key factor in MDD pathology, were both higher in the RSP2-treated group than the vehicle- and 1 mg/kg reserpine (RSP1)-treated groups (P<0.02). Furthermore, full-length expression of amyloid precursor protein (APP) was enhanced in the RSP1 and RSP2-treated groups compared to the vehicle-treated group, whereas expression of gamma-secretase components decreased (P<0.03). Among the three components of the gamma-secretase complex, nicastrin protein underwent the largest decrease in expression, as detected by Western blotting (P<0.03). Therefore, the data presented here provide additional evidence about the pathological correlation between MDD and AD.
Alzheimer Disease ; Amyloid ; Amyloid Precursor Protein Secretases ; Animals ; Blotting, Western ; Brain ; Depressive Disorder, Major ; Membrane Glycoproteins ; Mice ; Mice, Inbred ICR ; Models, Animal ; Nerve Growth Factors ; Phosphorylation ; Proteins ; Reaction Time ; Reserpine

Peroxiredoxin I (Prx I) is a member of the peroxiredoxins (Prxs) family, which are antioxidant enzymes that regulate various cellular process via intracellular oxidative signal pathways. In order to investigate the correlation between Prx I and the gamma-secretase complex, which causes Alzheimer's disease (AD), the expression level of Prx I was firstly evaluated in an animal model for AD. NSE/hPen-2 transgenic (Tg) mice, which were used as animal model in this study, showed a high level of Pen-2 expression and accumulation of Abeta-42 peptides in the hippocampus of brain. The expression level of Prx I was significantly higher on the mRNA and protein level in the brain of this model, while not change in Prx VI expression was observed. Furthermore, to verify the effect of Prx I on the gamma-secretase components in vitro, the expression level of these components was analyzed in the Prx I transfectants. Of the components of the gamma-secretase complex, the expression of PS-2 and Pen-2 was lower in the transfectants overexpressing Prx I compared to the vector transfectants. However, the expression of APP, NCT and APH-1 did not change in Prx I transfectants. Therefore, these results suggested that the expression of Prx I may be induced by the accumulation of Abeta-42 peptides and the overexpression of Prx I in neuroblastoma cells may regulate the expression of gamma-secretase components.
Alzheimer Disease ; Amyloid Precursor Protein Secretases ; Animals ; Brain ; Hippocampus ; Humans ; Mice ; Models, Animal ; Neuroblastoma ; Peptides ; Peroxiredoxins ; RNA, Messenger ; Signal Transduction

Guided bone regeneration (GBR) is a technique that a barrier membrane is placed over the bone defect to prevent the cell growth from the connective tissue and epithelium. In this study, in order to determine whether GBR technique could induce stress in rats, the standardized bone defect in rat calvaria was covered with apatitte membrane. Bone and brain tissues were collected from rats at 3 days, 2, 4, and 16 weeks post-operation, and then alteration of the new bone formation at the defects and stress-related factors were detected with histological examination and Western blot, respectively. From 4 to 16 weeks after the operation, the apatitte membrane was attached to the region of regenerated bone and encapsulated with a thick fibrous layer. Furthermore, the concentration of cortisol, a good indicator of stress, significantly increased 3 days post-operation. However, the increase at 3 days was returned to the basal level in 2 weeks. In Western blot analysis, the highest phosphorylation level of extracellular signal-regulated kinase (ERK) was observed 3 day post-operation, while those of the c-jun N-terminal kinase (JNK) and p38 were detected 4 weeks post-operation. Taken together, the results suggest that GBR technique may induce the serious stress on the brain tissue via the induction of ERK phosphorylation during 2 weeks, and that the stress responses restored in 4 week via JNK and p38 signaling pathway.
Animals ; Blotting, Western ; Bone Regeneration ; Brain ; Connective Tissue ; Epithelium ; Hydrocortisone ; JNK Mitogen-Activated Protein Kinases ; Membranes ; Osteogenesis ; Phosphorylation ; Phosphotransferases ; Rats ; Skull ; Transplants

Ultraviolet (UV) irradiation is an environmental factor that causes skin aging, and is also a major factor leading to cumulative alterations of skin structure, function and appearance. To investigate the effects of Selenium (Sel) on UV-induced skin aging, hairless mice were treated for 4 weeks with UV irradiation and topical application of Sel. Then, the effects of Sel were measured in the skin of these mice via histological analysis and Western blotting. According to the results of wrinkle formation analysis, the topical application of Sel induced a reduction in wrinkling formation in the damaged skin of the UV-irradiated mice. Additionally, our histological analysis demonstrated that the skin thickness in the Sel-treated group was less than in the UV-irradiated group. Furthermore, in an effort to investigate the mechanisms underlying the effects of Sel, the expression levels of matrix-metalloproteinase (MMP) and MAPK protein were assessed in both groups. The application of Sel induced a reduction in MMP-1 expression levels to the levels observed in the non-irradiated group. However, the expression level of MMP-9 was increased slightly in the Sel application group as compared with the vehicle application group. Additionally, the levels of ERK phosphorylation were increased by the application of Sel, but the levels of JNK and p38 were not altered by Sel treatment. These results suggest the possibility that Sel should be considered as a skin aging-protective and therapeutic drug candidate, which functions via the regulation of MMP expression levels.
Animals ; Blotting, Western ; Mice ; Mice, Hairless ; Phosphorylation ; Selenium ; Skin ; Skin Aging

Facial palsy following tooth extraction is rare and its mechanism is unclear. Possible mechanisms are direct anesthesia of facial nerve, compression and ischemia of facial nerve during edema, neurotoxicity of local anesthetic solution, viral reactivation and ascending infection. Viral reactivation and ascending infection are most likely mechanisms among them. Therefore, it is important to use an antiviral agent combined with steroid for treatment of dental origin facial palsy. We report our recent experience with one case of facial palsy that followed tooth extraction.
Anesthesia ; Edema ; Facial Nerve ; Facial Paralysis ; Ischemia ; Tooth ; Tooth Extraction

BACKGROUND: Although a laparoscopic cholecystectomy results in less pain than an open cholecystectomy, it is not a pain-free procedure. Therefore, this study was conducted to determine whether perioperative intravenous lidocaine would reduce postoperative pain after a laparoscopic cholecystectomy. METHODS: Fifty patients undergoing laparoscopic cholecystectomy were divided into two groups; a lidocaine group, in which patients were injected with a lidocaine bolus (1.5 mg/kg) and infusion (1.5 mg/kg/h); and a control group, in which patients were injected with the same volume of saline bolus and infusion. Intravenous lidocaine was initiated before anesthesia was administered and continued for 1 hour postoperatively. The intensity of abdominal and shoulder pain was then assessed 1, 6, 12 and 24 hours after surgery and recorded using a visual analog pain score (VAS) and verbal rating score (VRS). RESULTS: The abdominal pain score (VAS and VRS) was significantly lower in the lidocaine group than in the control group at all times evaluated during the first 24 hours after surgery (P < 0.05). In addition, the shoulder pain score and incidence were significantly lower in the lidocaine group than the control group at 12 hours and 24 hours after surgery (P < 0.05). In the lidocaine group, the incidences of epigastric, right flank, and back pain were lower than that of the control group, but these differences were not statistically significant. CONCLUSIONS: Perioperative intravenous lidocaine reduces shoulder and abdominal pain for 24 hours after laparoscopic cholecystectomy.
Abdominal Pain ; Anesthesia ; Back Pain ; Cholecystectomy ; Cholecystectomy, Laparoscopic ; Humans ; Incidence ; Lidocaine ; Oxalates ; Pain, Postoperative ; Shoulder ; Shoulder Pain

BACKGROUND: This study was performed to compare the clinical outcomes of intestinal Behcet's disease with a simple ulcer. METHODS: We analyzed the medical records of 52 patients that were suspected as having intestinal Behcet's disease. Of these patients, 27 patients (Group 1) met both the criteria of the International Study Group for Behcet's Disease and the Behcet's Disease Research Committee of Japan. Thirteen patients (Group 2) met only the latter criteria and the other patients (Group 3) did not meet any criteria. The efficacy of medical treatment was assessed by the presence of gastrointestinal symptoms and follow-up colonoscopic findings. RESULTS: The mean age for patients with a diagnosis of an intestinal lesion was 38.6+/-12.2 years. The sex ratio was 1.08:1 (M:F) and the mean follow-up duration was 35.2+/-39.5 months. A single, smaller than 5 mm, round and shallow ulcer with an erythematous margin that was located at the leocecal area showed most typical colonoscopic features for intestinal Behcet's disease. No significant differences were found in the clinical manifestations and colonoscopic findings among the three groups of patients. Nineteen (44%) patients achieved complere remission from a sumptomatic point of view and 10 (39%) patients were proved to be complete remission according to follow up colonoscopy after medical treatment. Eleven patients (21.2%) underwent surgery. The overall cumulative rates of a first surgery and re-surgery were 40.5% and 71.9% at 10 years. No statistical relationship was found in the response of medical treatment and the cumulative rate of surgery among the groups. CONCLUSIONS: The clinical course and outcomes of an intestinal simple ulcer are not different from that for intestinal Behcet's disease.
Colonoscopy ; Diagnosis ; Follow-Up Studies ; Humans ; Japan ; Medical Records ; Sex Ratio ; Ulcer*