Indoleamine 2,3-dioxygenase (IDO) is a key negative regulator of immune responses and has been implicated in tumor tolerance, autoimmune disease and asthma. IDO was detected in the joint synovial tissue in the inflammatory microenvironment of rheumatoid arthritis (RA), but IDO expression in joint synovial tissue is not sufficient to overcome the inflamed synovial environment. This study aimed to unravel the mechanisms involving the failure to activate tolerogenic IDO in the inflamed joint. We demonstrate that both poly (I:C) and lipopolysaccharide (LPS) induce expression of IDO in synovial fibroblasts. However, inflammatory cytokines such as IL-17, TNF-alpha, IL-12, IL-23 and IL-16 did not induce IDO expression. Poly (I:C) appeared to induce higher IDO expression than did LPS. Surprisingly, toll-like receptor (TLR)4-mediated IDO expression was upregulated after depletion of myeloid differentiation primary response protein 88 (MyD88) in synovial fibroblasts using small interfering RNA (siRNA). IDO, TLR3 and TLR4 were highly expressed in synovial tissue of RA patients compared with that of osteoarthritis patients. In addition, RA patients with severe disease activity had higher levels of expression of IDO, TLR3 and TLR4 in the synovium than patients with mild disease activity. These data suggest that upregulation of IDO expression in synovial fibroblasts involves TLR3 and TLR4 activation by microbial constituents. We showed that the mechanisms responsible for IDO regulation primarily involve MyD88 signaling in synovial fibroblasts, as demonstrated by siRNA-mediated knockdown of MyD88.
Adaptor Proteins, Vesicular Transport/genetics/metabolism ; Arthritis, Rheumatoid/*metabolism ; Blotting, Western ; Cells, Cultured ; Fibroblasts/drug effects/*metabolism ; Humans ; Immunohistochemistry ; Indoleamine-Pyrrole 2,3,-Dioxygenase/genetics/*metabolism ; Interleukin-12/pharmacology ; Interleukin-16/pharmacology ; Interleukin-17/pharmacology ; Interleukin-23/pharmacology ; Lipopolysaccharides/pharmacology ; Myeloid Differentiation Factor 88/genetics/*metabolism ; Poly I-C/pharmacology ; Polymerase Chain Reaction ; RNA, Small Interfering/genetics/physiology ; Synovial Membrane/*cytology ; Toll-Like Receptor 4/genetics/metabolism ; Tumor Necrosis Factor-alpha/pharmacology

In order to investigate the molecular basis of the aging process in brain, we have employed high-density oligonucleotide microarrays providing data on 10,108 gene clusters to define transcriptional patterns in three brain regions, cerebral cortex, cerebellum, and hippocampus. Comparison of the expression patterns between young (6-week-old) and aged (17-month-old) C57BL/6 male micerevealed that about ten percent (1098) of the genes showed a significant change in the expression level in at least one of the three tissues. Among them, 23 genes were upregulated and 62 genes were downregulated in all three tissues of the old mice. The number of genes upregulated exclusively in hippocampus (337) was much larger compared to other tissues. Gene ontology-based analysis showed the genes related with signal transduction or molecular transports are more likely to be upregulated than downregulated in the aging process of hippocampus. These data may provide some useful means for elucidating the molecular aspect of aging in hippocampus and other regions in brain.
Aging* ; Animals ; Brain* ; Cerebellum ; Cerebral Cortex ; DNA* ; Gene Expression* ; Hippocampus ; Humans ; Male ; Mice* ; Multigene Family ; Oligonucleotide Array Sequence Analysis* ; Signal Transduction ; Transcriptome*

Duodenal intramural hematoma is mostly caused by blunt abdominal trauma. It is also less commonly reported as a complication of anticoagulation therapy or as a blood dyscrasia, and as a complication of diagnostic/ therapeutic endoscopy. The presentation of these patients is abdominal pain, vomiting, fever and hematochezia, and this is rarely accompanied with intestinal obstruction, severe pancreatitis and acute peritonitis as its complications. The diagnosis is made clear by performing abdominal ultrasonography and abdominal computed tomography. We reported here on one case of intramural duodenal hematoma and hemoperitoneum after performing endoscopic hemostasis in a chronic renal failure patient who was on maintenance hemodialysis.
Abdominal Pain ; Diagnosis ; Duodenum ; Endoscopy* ; Fever ; Gastrointestinal Hemorrhage ; Hematoma* ; Hemoperitoneum* ; Hemostasis, Endoscopic ; Humans ; Intestinal Obstruction ; Kidney Failure, Chronic* ; Pancreatitis ; Peritonitis ; Renal Dialysis ; Ultrasonography ; Vomiting

OBJECTIVE: Interleukin-15 (IL-15) recruits and activates synovial T cells, and IL-15 plays an important role in amplifying and perpetuating inflammation in the pathogenesis of rheumatoid arthritis (RA). Stromal cell-derived factor-1 (SDF-1) is a potent chemoattractant for memory T cells in the inflamed RA synovium. This study investigated the effect of IL-15 on SDF-1 production in RA fibroblast-like synoviocytes (FLS). METHODS: The expressions of IL-15 and SDF-1 were determined from the synovium of patients with RA and osteoarthritis (OA) by performing immunohistochemistry. The expressions of SDF-1 was measured from the RA FLS that were cultured with IL-15 and IL-17 by real-time RT-PCR and ELISA. The SDF-1 expression was also measured, via ELISA, from the RA FLS stimulated by IL-15 together with the inhibitors of such intracellular signal molecules as phosphatidylinositol 3-kinase (PI 3-kinase, LY294002), STAT3 (AG490), MAP Kinase (PD98059), NF-kappaB (parthenolide) and activator protein 1 (AP-1, curcumin). RESULTS: IL-15 and SDF-1 were mainly expressed in the RA synovium compared to that of the OA synovium. IL-15 increased the SDF-1 expressions and it, and had an additive effect with IL-17 on the SDF-1 expressions in the cultured RA FLS. The IL-15 induced increase of the SDF-1 expression in the cultured RA FLS was blocked by the inhibitors of PI 3-kinase, NF-kappaB and AP-1. CONCLUSION: The SDF-1 expression was increased in the RA synovium and it was up-regulated by IL-15 in the RA FLS through the PI 3-kinase, NF-kappaB, and AP-1 pathways. These results imply that the IL-15 induced increase of the SDF-1 expressions may be involved in the immunopathogenesis of RA.
Arthritis, Rheumatoid ; Enzyme-Linked Immunosorbent Assay ; Fibroblasts ; Humans ; Immunohistochemistry ; Inflammation ; Interleukin-15 ; Interleukin-17 ; Memory ; NF-kappa B ; Osteoarthritis ; Phosphatidylinositol 3-Kinase ; Phosphatidylinositol 3-Kinases ; Phosphotransferases ; Synovial Membrane ; T-Lymphocytes ; Transcription Factor AP-1

OBJECTIVE: Interleukin-15 (IL-15) recruits and activates synovial T cells, and IL-15 plays an important role in amplifying and perpetuating inflammation in the pathogenesis of rheumatoid arthritis (RA). Stromal cell-derived factor-1 (SDF-1) is a potent chemoattractant for memory T cells in the inflamed RA synovium. This study investigated the effect of IL-15 on SDF-1 production in RA fibroblast-like synoviocytes (FLS). METHODS: The expressions of IL-15 and SDF-1 were determined from the synovium of patients with RA and osteoarthritis (OA) by performing immunohistochemistry. The expressions of SDF-1 was measured from the RA FLS that were cultured with IL-15 and IL-17 by real-time RT-PCR and ELISA. The SDF-1 expression was also measured, via ELISA, from the RA FLS stimulated by IL-15 together with the inhibitors of such intracellular signal molecules as phosphatidylinositol 3-kinase (PI 3-kinase, LY294002), STAT3 (AG490), MAP Kinase (PD98059), NF-kappaB (parthenolide) and activator protein 1 (AP-1, curcumin). RESULTS: IL-15 and SDF-1 were mainly expressed in the RA synovium compared to that of the OA synovium. IL-15 increased the SDF-1 expressions and it, and had an additive effect with IL-17 on the SDF-1 expressions in the cultured RA FLS. The IL-15 induced increase of the SDF-1 expression in the cultured RA FLS was blocked by the inhibitors of PI 3-kinase, NF-kappaB and AP-1. CONCLUSION: The SDF-1 expression was increased in the RA synovium and it was up-regulated by IL-15 in the RA FLS through the PI 3-kinase, NF-kappaB, and AP-1 pathways. These results imply that the IL-15 induced increase of the SDF-1 expressions may be involved in the immunopathogenesis of RA.
Arthritis, Rheumatoid ; Enzyme-Linked Immunosorbent Assay ; Fibroblasts ; Humans ; Immunohistochemistry ; Inflammation ; Interleukin-15 ; Interleukin-17 ; Memory ; NF-kappa B ; Osteoarthritis ; Phosphatidylinositol 3-Kinase ; Phosphatidylinositol 3-Kinases ; Phosphotransferases ; Synovial Membrane ; T-Lymphocytes ; Transcription Factor AP-1

PURPOSE: This study evaluated the influence of abutment materials on the stability of the implant-abutment joint in internal conical connection type implant systems. MATERIALS AND METHODS: Internal conical connection type implants, cement-retained abutments, and tungsten carbide-coated abutment screws were used. The abutments were fabricated with commercially pure grade 3 titanium (group T3), commercially pure grade 4 titanium (group T4), or Ti-6Al-4V (group TA) (n=5, each). In order to assess the amount of settlement after abutment fixation, a 30-Ncm tightening torque was applied, then the change in length before and after tightening the abutment screw was measured, and the preload exerted was recorded. The compressive bending strength was measured under the ISO14801 conditions. In order to determine whether there were significant changes in settlement, preload, and compressive bending strength before and after abutment fixation depending on abutment materials, one-way ANOVA and Tukey's HSD post-hoc test was performed. RESULTS: Group TA exhibited the smallest mean change in the combined length of the implant and abutment before and after fixation, and no difference was observed between groups T3 and T4 (P>.05). Group TA exhibited the highest preload and compressive bending strength values, followed by T4, then T3 (P<.001). CONCLUSION: The abutment material can influence the stability of the interface in internal conical connection type implant systems. The strength of the abutment material was inversely correlated with settlement, and positively correlated with compressive bending strength. Preload was inversely proportional to the frictional coefficient of the abutment material.
Friction ; Joints* ; Titanium ; Torque ; Tungsten

Mycoplasma pneumoniae (M. pneumoniae) infection causes a wide variety of clinical manifestations in children and young adults, the main one being pneumonia. M. pneumoniae is transmitted from person to person by infected respiratory droplets. Symptoms caused by M. pneumoniae infection can be divided into those involving the respiratory tract, and those caused by extrapulmonary disease. M. pneumoniae infections may cause central nervous system (CNS) complications-with encephalitis being the most frequent-and stroke being a rare complication. The pathogenesis of the CNS disease is unclear; possibilities include direct infection and an immune-mediated reaction. We present two cases of CNS complications subsequent to infection with M. pneumoniae; both cases had convincing evidence of preceding M. pneumoniae respiratory disease with no evidence of viable M. pneumoniae in the cerebrospinal fluid. We report cases of encephalitis and stroke following a recent M. pneumoniae infection.
Central Nervous System ; Central Nervous System Diseases ; Child ; Encephalitis ; Humans ; Mycoplasma ; Mycoplasma pneumoniae ; Pneumonia ; Pneumonia, Mycoplasma ; Respiratory System ; Stroke ; Young Adult

Mucopolysaccharidosis is characterized by the progressive accumulation of glycosaminoglycans in multiple organs. Valve and coronary involvement, upper airway obstructive disease, joint stiffness, and mental retardation are associated perioperative anesthetic risks. Nineteen patients and 23 anesthetic cases were presented for elective surgery. The mean patient age was 10.8 years. General anesthesia was administered in 21 cases and intubation was failed in two. Mask ventilation without intubation was performed in two cases in day surgery unit. In one case, spinal anesthesia was performed. Otolaryngologic procedures, i.e., tonsillectomy and adenoidectomy, and ventilation tube insertion were most common. Percutaneous endoscopic gastrostomy and herniorrhaphy were also frequent. Dexamethasone was given to all intubated cases and all patients were extubated in the postanesthesia care unit or in the intensive care unit. There was no perioperative mortality. Cautious airway management until intubation is recommended and mask ventilation with short-acting inhalation or intravenous anesthetics is enough to manage relatively short procedures. For herniorrhaphy, a spinal block could be used.
Adenoidectomy ; Airway Management ; Ambulatory Surgical Procedures ; Anesthesia, General ; Anesthesia, Spinal ; Anesthetics, Intravenous ; Dexamethasone ; Gastrostomy ; Glycosaminoglycans ; Herniorrhaphy ; Humans ; Inhalation ; Intellectual Disability ; Intensive Care Units ; Intubation ; Joint Diseases ; Masks ; Mortality ; Mucopolysaccharidoses* ; Mucopolysaccharidosis I ; Tonsillectomy ; Ventilation

BACKGROUND/AIMS: This study was undertaken to identify the intracellular signaling pathway involved in induction of macrophage migration inhibitory factor (MIF) in human rheumatoid arthritis (RA) synovial fibroblasts. METHODS: Human RA synovial fibroblasts were treated with concanavalin A (ConA), various cytokines, and inhibitors of signal transduction molecules. The production of MIF by synovial fibroblasts was measured in culture supernatants by ELISA. The expression of MIF mRNA was determined using reverse transcriptase polymerase chain reaction (RT-PCR) and real-time PCR. Phosphorylation of p38 mitogen-activated protein (MAP) kinase in synovial fibroblasts was confirmed using Western blotting. The expression of MIF and p38 MAP kinase in RA synovium was determined using dual immunohistochemistry. RESULTS: The production of MIF by RA synovial fibroblasts increased in a dose-dependent manner after ConA stimulation. MIF was also induced by interferon-gamma, CD40 ligand, interleukin-15, interleukin-1beta, tumor necrosis factor-alpha, and transforming growth factor-beta. The production of MIF by RA synovial fibroblasts was significantly reduced after inhibition of p38 MAP kinase. The expression of MIF and p38 MAP kinase was upregulated in the RA synovium compared with the osteoarthritis synovium. CONCLUSIONS: These results suggest that MIF production was induced through a p38 MAP-kinase-dependent pathway in RA synovial fibroblasts.
Arthritis, Rheumatoid/genetics/*metabolism ; Base Sequence ; Cells, Cultured ; Concanavalin A/pharmacology ; Cytokines/pharmacology ; DNA Primers/genetics ; Fibroblasts/drug effects/metabolism ; Humans ; Macrophage Migration-Inhibitory Factors/*biosynthesis/genetics ; RNA, Messenger/genetics/metabolism ; Signal Transduction/drug effects ; Synovial Membrane/drug effects/metabolism ; p38 Mitogen-Activated Protein Kinases/metabolism

OBJECTIVES: Previous studies have shown relatively low correlations between self-reported and accelerometer-assessed physical activity (PA). However, this association differs by socio-demographic factors, and this relationship has not been fully investigated in the general population. Thus, we investigated the correlation between self-reported and accelerometer-assessed PA and whether it differed by demographic and socioeconomic factors among the Korean general population.METHODS: This cross-sectional study included 623 participants (203 men and 420 women) aged 30 to 64 years, who completed a PA questionnaire and wore a wrist-worn accelerometer on the non-dominant wrist for 7 days. We examined the agreement for metabolic equivalent task minutes per week (MET-min/wk) between the 2 measures and calculated Spearman correlation coefficients according to demographic and socioeconomic factors.RESULTS: The kappa coefficient between tertiles of self-reported and accelerometer-assessed total MET-min/wk was 0.16 in the total population, suggesting overall poor agreement. The correlation coefficient between the 2 measurements was 0.26 (p < 0.001) in the total population, and the correlation tended to decrease with increasing age (p for trend < 0.001) and depression scores (p for trend < 0.001).CONCLUSION: We found a low correlation between self-reported and accelerometer-assessed PA among healthy Korean adults, and the correlation decreased with age and depression score. When studying PA using accelerometers and/or questionnaires, age and depression need to be considered, as should differences between self-reported and accelerometer-assessed PA.
Adult ; Cross-Sectional Studies ; Depression ; Humans ; Korea ; Male ; Metabolic Equivalent ; Motor Activity ; Socioeconomic Factors ; Wrist