Association of MICA polymorphism with HLA-B51 and disease severity in Korean patients with Behcet's disease

The HLA-B51 allele is known to be associated with Behcet's disease (BD) in many ethnic group. However, it has not yet been clarified whether the HLA-B51 gene itself is the pathogenic gene related to BD or whether it is some other gene in linkage disequlibrium with HLA-B51. Recently, the Triplet repeat (GCT/AGC) polymorphism in transmembrane region of the MHC class I chain-related A (MICA) gene was identified. To investigate the association of MICA with BD, we studied the MICA polymorphism in 108 Korean BD patients and 204 healthy controls in relation to the presence of HLA-B51 and clinical manifestations. The triplet repeat polymorphism was determined by polymerase chain reaction (PCR)-denaturing polyacrylamide gel electrophoresis (PAGE). The phenotype frequency of the MICA*A6 allele (relative risk, RR=2.15, p=0.002) and HLA-B51(RR=1.87, p=0.022) were significantly increased in the Korean patients with BD. A strong linkage disequilibrium was observed between the MICA*A6 and HLA-B51 in both the patients with BD and control subjects. Stratification analysis showed that MICA*A6 homozygosity was strongly associated with BD in the HLA-B51-negative population, and HLA-B51 was also associated with MICA*A6-negative population. In conclusion, MICA*A6 rather than HLA-B51 was strongly associated with Korean patients with BD, and the MICA*A6 allele is a useful susceptibility marker of BD, especially in the HLA-B5-negative     

Machine learning–based prediction of radiographic progression in patients with axial spondyloarthritis

Clinical Rheumatology - Machine learning is applied to characterize the risk and predict outcomes in multi-dimensional data. The prediction of radiographic progression in axial spondyloarthritis...     

Sulindac sulfide-induced apoptosis in sinonasal cancer cells

CONCLUSIONS: These results demonstrate that sulindac sulfide can induce cell death in maxillary cancer cells, and that sulindac sulfide-induced apoptosis is related to the extracellular signal-regulated kinase/p38 MAPK-caspase 3 signaling pathway. OBJECTIVE: Head and neck cancer is the sixth commonest cancer in the human body. Squamous cell carcinoma accounts for most sinonasal cancers. However, little is known regarding the biochemical mechanism(s) of cell death in sinonasal cancers. Recently, human epidemiological and clinical intervention studies have indicated that sulindac, a non-steroidal anti-inflammatory drug, exhibits chemopreventive activity in colorectal cancer. In this study, we aimed to investigate whether sulindac sulfide can induce apoptosis in sinonasal cancer cells and what type of molecular mechanisms induces the death of sinonasal cancer cells. MATERIAL AND METHODS: Sinonasal cancer cells (Asan Medical Center Head and Neck Cancer 5) were treated with various concentrations of sulindac sulfide. The degree of cell death was determined by means of a fluorescence-activated cell scan and the signal transduction pathway for cell death was examined. RESULTS: Human nasal cavity cancer cells treated with sulindac sulfide underwent cell death, and the induction of apoptosis occurred in a dose-dependent manner. Moreover, sulindac sulfide-induced apoptosis was abolished by treatment with the caspase inhibitor Z-VAD-fmk and the mitogen-activated protein kinase (MAPK) inhibitors PD98059 and SB203580.     

Expression and regulation of nonsteroidal anti-inflammatory drug-activated gene (NAG-1) in human and mouse tissue

BACKGROUND & AIMS: Nonsteroidal anti-inflammatory drugs (NSAIDs) induce NSAID-activated gene 1 (NAG-1), which has proapoptotic and antitumorigenic activities. However, NAG-1 expression and its relationship with apoptosis in human and mouse intestinal tract have not been determined. METHODS: NAG-1 expression in human and mouse tissue was determined by immunohistochemistry, and apoptosis was estimated by in situ apoptosis detection. Apoptosis in NAG-1 overexpressing HCT-116 cells was examined with flow cytometry after cell sorting by green fluorescence protein. NAG-1 regulation in mouse cells was examined by Northern blot analysis, comparing sulindac-treated and nontreated mice. RESULTS: Apoptosis was higher in NAG-1 overexpressing cells compared with controls. Human NAG-1 protein was localized to the colonic surface epithelium where cells undergo apoptosis, and higher expression was observed in the normal surface epithelium than in most of the tumors. This localization and lower expression in tumors was similar to that in the Min mouse, in which NSAIDs were also shown to regulate the expression of NAG-1 in mouse cells. Sulindac treatment of mice increased the NAG-1 expression in the colon and liver. CONCLUSIONS: Based on these results, we propose that NAG-1 acts as a mediator of apoptosis in intestinal cells and may contribute to cancer chemoprevention by NSAIDs.     

Inhibitory effects of the fragrance inhalation of essential oil from Acorus gramineus on central nervous system

The present study was designed to evaluate central inhibitory effects of the essential oil from Acori graminei Rhizoma (AGR), the dry rhizomes of Acorus gramineus SOLANDER (Araceae) upon fragrance inhalation (aroma therapy). Preinhalation of the oil markedly delayed the appearance of pentylenetetrazole-induced convulsion. Furthermore, inhalation impressively inhibited the activity of gamma-aminobutyric acid (GABA) transaminase, a degrading enzyme for GABA as the inhalation period was lengthened. The GABA level was significantly increased and glutamate content was significantly decreased in mouse brain by preinhalation of the essential oil. The above results suggest that the anticonvulsive effect of this AGR oil is originated by the enhancement of GABA level in the mouse brain, because convulsion depends partially on GABA concentration which can be properly preserved by inhibiting GABA transaminase. Moreover, fragrance inhalation progressively prolonged the pentobarbital-induced sleeping time as inhalation time was lengthened. Ten hour inhalation corresponded almost to the effect (145% increase) of oral administration (60 mg/kg). This sedative effect after inhalation or oral administration of AGR essential oil suggests that this oil may act on the CNS via the GABAergic system. The inhibitory activity of preinhalation of the essential oil on lipid peroxidation, to which the anticonvulsive action is attributed, also supported the above results, confirming and amplifying our previous reports on the CNS inhibitory effects of AGR.     

Association of inflammatory bowel disease with ankylosing spondylitis and rheumatoid arthritis: A nationwide population-based study

Objectives: Tantalizing connections between autoimmune rheumatic diseases (ARDs) and inflammatory bowel disease (IBD) have become evident with regard to their genetic and immunologic background. However, the association between these two disease entities remains unclear. The aim of this study is to investigate the association between each ARD and IBD.

Methods: A nationwide population-based cross-sectional study was performed using the Korean National Health Insurance Claims database. The data of patients with IBD and age- and sex-matched controls between 2009 and 2013 were collected from the database. The prevalence of ARDs, including systemic lupus erythematosus (SLE), inflammatory myositis (polymyositis and dermatomyositis), systemic sclerosis (SSc), Sjögren’s syndrome (SjS), ankylosing spondylitis (AS), and rheumatoid arthritis (RA), was determined. The associations between each ARD and IBD were analyzed using multivariate logistic regression models.

Results: A total of 40,843 IBD patients (28,197 patients with ulcerative colitis and 12,646 with Crohn’s disease) and 122,529 controls were enrolled. The nonstratified analysis revealed that patients with IBD had significant risk of being concomitantly affected by AS (odds ratio [OR] 5.140, 95% confidence interval [95% CI] 4.069–6.492) and RA (OR: 3.474, 95% CI: 2.671–4.519) after adjusting for age and sex. No significant association was observed between IBD and other ARDs including SLE, inflammatory myositis, SSc, and SjS.

Conclusion: IBD is significantly associated with AS and RA in the large-scaled population-based study. This result suggests that etiopathogenesis of IBD might be shared with AS and RA.     

Antiadhesive effect of the mixed solution of sodium hyaluronate and sodium carboxymethylcellulose after endoscopic sinus surgery

BACKGROUND: We evaluated the clinical efficacy and safety of the mixed solution of sodium hyaluronate and sodium carboxymethylcellulose (HA-CMC) for prevention of adhesion after endoscopic sinus surgery. METHODS: Preoperative computed tomography (CT) scans were graded. At the completion of surgery, HA-CMC was applied to Merocel and repeatedly applied after the removal of Merocel. As a control, normal saline was applied. Endoscopic examination was performed postoperatively and grading was done. RESULTS: The rate of adhesion was the highest at 2 weeks postoperatively and was significantly lower in the HA-CMC-treated group than the control on all postoperative days. The grouping of cases by CT scores at 2 weeks postoperatively showed lower adhesion formation with the HA-CMC treatment than the control. The safety profile of the patients was normal at 4 weeks postoperatively. CONCLUSION: HA-CMC is an efficacious and safe material in decreasing the incidence of adhesion after endoscopic sinus surgery.     

CTLA4-Ig modifies dendritic cells from mice with collagen-induced arthritis to increase the CD4+CD25+Foxp3+ regulatory T cell population

Cytotoxic T lymphocyte antigen-4 (CTLA4) and IgG fusion protein, CTLA4-Ig, is a therapeutic agent used for rheumatoid arthritis. It binds B7 molecules on dendritic cells (DCs) and thereby blocks B7/CD28 costimulatory interaction and inhibits effective T cell proliferation. However, the effect of CTLA4-Ig on the regulatory T cell (Treg) is still not known. In this study, we investigated the influence of CTLA4-Ig on the CD4+CD25+Foxp3+ Treg population in collagen-induced arthritis (CIA) mouse model. CTLA4-Ig suppressed CIA and increased the CD4+CD25+Foxp3+ Treg population in joint and spleen. When CD11c + DCs and CD4+T cells from CIA mice were cultured with anti-CD3, CTLA4-Ig increased the CD4+CD25 + Foxp3+ Treg population in a TGF-β-dependent manner. When CD11c + DCs from CIA mice were treated with CTLA4-Ig and adoptively transferred into CIA-induced mice, arthritis did not develop in association with the increase in CD4+CD25+Foxp3+ Treg population. However, in CTLA4-Ig-untreated DC-transferred CIA mice, arthritis developed and then rapidly progressed. Our study demonstrated that CTLA4-Ig suppressed CIA by modifying DCs from CIA mice into tolerogenic DCs to increase the CD4+CD25+Foxp3+ Treg population and this seems to be the new immune regulatory mechanism of CTLA4-Ig.     

Safe Re-administration of Tumor Necrosis Factor-alpha (TNFα) Inhibitors in Patients with Rheumatoid Arthritis or Ankylosing Spondylitis Who Developed Active Tuberculosis on Previous Anti-TNFα Therapy

There is no consensus on whether it is safe to re-administer tumor necrosis factor-alpha (TNFα) inhibitors in patients with rheumatoid arthritis (RA) or ankylosing spondylitis (AS) flared after withdrawal of TNFα inhibitors due to active tuberculosis (TB). We evaluated the safety of restarting anti-TNFα therapy in patients with TNFα-associated TB. We used data of 1,012 patients with RA or AS treated with TNFα inhibitors at Seoul St. Mary''s Hospital between January 2003 and July 2013 to identify patients who developed active TB. Demographic and clinical data including the results of tuberculin skin tests (TST) and interferon-γ releasing assays (IGRA) were collected. Fifteen patients developed active TB. Five cases were occurred in RA and 10 cases in AS. Nine of 15 patients had a negative TST or IGRA and 6 TST-positive patients had received prophylaxis prior to initiating anti-TNFα therapy. All patients discontinued TNFα inhibitors with starting the treatment of TB. Eight patients were re-administered TNFα inhibitors due to disease flares and promptly improved without recurrence of TB. TNFα inhibitors could be safely resumed after starting anti-TB regimen in patients with RA or AS.