Nakajo-Nishimura syndrome (NNS) is a disorder that segregates in an autosomal recessive fashion. Symptoms include periodic fever, skin rash, partial lipomuscular atrophy, and joint contracture. Here, we report a mutation in the human proteasome subunit beta type 8 gene (PSMB8) that encodes the immunoproteasome subunit β5i in patients with NNS. This G201V mutation disrupts the β-sheet structure, protrudes from the loop that interfaces with the β4 subunit, and is in close proximity to the catalytic threonine residue. The β5i mutant is not efficiently incorporated during immunoproteasome biogenesis, resulting in reduced proteasome activity and accumulation of ubiquitinated and oxidized proteins within cells expressing immunoproteasomes. As a result, the level of interleukin (IL)-6 and IFN-γ inducible protein (IP)-10 in patient sera is markedly increased. Nuclear phosphorylated p38 and the secretion of IL-6 are increased in patient cells both in vitro and in vivo, which may account for the inflammatory response and periodic fever observed in these patients. These results show that a mutation within a proteasome subunit is the direct cause of a human disease and suggest that decreased proteasome activity can cause inflammation.
The presence of anti-MDA5 Ab identifies the characteristic skin, musculoskeletal, pulmonary and prognostic features in patients with DM. In addition, anti-MDA5 Ab seems to predict a group of patients with CADM-complicated fatal RPILD.
A blue protein with a molecule weight of 12,000 containing 1 atom of type I Cu2+ was purified and crystallized from a denitrifying bacterium, Alcaligenes faecalis strain S-6, as an inactivating factor for copper-containing nitrite reductase of the same organism. Inactivation of the enzyme occurred when the enzyme was incubated aerobically with a catalytic amount of the blue protein in the presence of reducing agents such as cysteine and ascorbate. The blue protein acts as a direct electron donor for the enzyme to catalyze the reduction of nitrite, but in the absence of nitrite, the enzyme-reduced blue protein system reacts with oxygen to produce H2O2. A suicide inactivation mechanism of the enzyme due to this H2O2 production is proposed.
Our data showed that tumour infiltrating inflammatory and immune cells may play a pivotal role in ECC progression and a high-risk signature predicted poor prognosis in ECC patients.
Objective. To evaluate whether magnetic resonance imaging (MRI) of the wrists and finger joints and an analysis of serologic autoantibodies are clinically meaningful for the subsequent development of rheumatoid arthritis (RA) in patients with undifferentiated arthritis (UA). Methods. A total of 129 patients with UA, a disease status formally confirmed by a rheumatologist over a period of at least 1 year, were included. Gadolinium-diethylenetriamine-enhanced MRI of both wrists and finger joints and serologic variables were examined upon admission to our Early Arthritis Clinic at Nagasaki University. After a prospective followup of 1 year, a predictive value for the development of RA was determined for each patient. Results. The subjects were evaluated for their positive or negative status with respect to 3 objective measures at study entry: anti-cyclic citrullinated peptide (anti-CCP) antibodies and/or IgM-rheumatoid factor, MRI-proven symmetric synovitis, and MRI-proven bone edema and/or bone erosion. The patients who were positive for at least 2 of these measures progressed to RA at 1 year with a 79.7% positive predictive value (PPV), 63.0% negative predictive value, 75.9% specificity, 68.0% sensitivity, and 71.3% accuracy. Furthermore, in 22 UA patients positive for both anti-CCP antibodies and MRI-proven bone edema who were considered to have progressed to RA at 1 year, the PPV was increased to 100%. A close correlation was found between the present rule and that established in the Leiden Early Arthritis Cohort. Conclusion. MRI-proven early joint damage in conjunction with serologic autoantibodies is efficient in predicting progression from UA to RA. This method can be used to identify patients who would benefit from early treatment with disease-modifying antirheumatic drugs.
INTRODUCTIONEarly undifferentiated arthritis (UA) is defined as early arthritis that does not fulfill the classification criteria for a more definitive diagnosis, according to the 1987 American College of Rheumatology (ACR; formerly the American Rheumatism Association) criteria for rheumatoid arthritis (RA) (1-3). The natural disease course of UA is variable; therefore, to minimize under-and overtreatment of patients with UA, a model was recently constructed by the Leiden Early Arthritis Cohort to estimate the likelihood of progression to RA in individual patients (2,3). Their prediction rule consists of 9 clinical variables: sex, age, localization of symptoms, morning stiffness, tender joint count, ISRCTN: 021008-1.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.