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Objectives. To evaluate the correlation between the efficacy of mizoribine (MZR) and the factors that might effect MZR concentration: renal function and dosage and administration of MZR in patients with rheumatoid arthritis (RA). Methods. The efficacy of MZR treatment was prospectively evaluated in 97 RA regardless of dosage, at the 14 participated institutions. The Disease Activity Score 28-CRP3 was used to assess RA activity. The renal function was evaluated based on the serum creatinine and serum cystatin-C (Cys-C). The patients were followed up for 24 weeks. Results. The patients with a mean age 66.2 years included 18 male. The renal function assessment showed increased creatinine in 16.4% of patients and increased Cys-C in 54.5%, suggesting the higher sensitivity of Cys-C to detect impaired renal function than creatinine. In patients with good or moderate response according to the European League against Rheumatism classification criteria, the Cys-C was significantly higher compared with those with no response. MZR treatment was significantly more effective in patients with an arithmetic product of the single MZR dose used and Cys-C of 179 or more. Conclusions. The efficacy of MZR may increase in proportion to its single dose, or increased Cys-C level in patients with impaired renal function. [ABSTRACT FROM AUTHOR]

Objective: Osteoprotegerin (OPG), a regulator of bone resorption, is involved in the pathogenesis of rheumatoid arthritis (RA) and atherosclerosis. OPG is elevated in patients with coronary artery disease, and high OPG levels are associated with cardiac disease severity and mortality in the general population. The purpose of this study was to investigate the relationship of serum OPG levels, traditional coronary risk factors, and RA-related factors to carotid atherosclerosis in RA patients. Methods: Ninety-one RA patients were studied (85 % women, age 60 ± 10 years). Serum OPG levels were measured by an enzyme-linked immunosorbent assay. The prevalence of carotid plaque was assessed by ultrasonographic imaging in all patients. The relationship between various clinical characteristics, OPG, and carotid plaque was examined. Results: Serum OPG levels were significantly higher in patients with carotid plaque than in those without plaque (median level 1,397 vs. 887 pg/mL, respectively; P = 0.006). There were no significant differences between RA patients with and without carotid plaque with respect to sex, duration of RA, blood pressure, body mass index, smoking, low-density lipoprotein cholesterol, Disease Activity Score-28, van der Heijde-modified Sharp score, and prednisolone dose. After adjusting for age, sex, and C-reactive protein, elevated levels of OPG were still associated with a higher prevalence of carotid plaque in patients with RA ( P = 0.038). Conclusion: RA patients suffer from accelerated atherosclerosis and also have increased levels of OPG. The serum OPG level is independently associated with carotid plaque. [ABSTRACT FROM AUTHOR]

We had a rheumatoid arthritis (RA) patient resistant to multiple drugs and who developed panniculitis due to etanercept treatment, then responded fairly well to rituximab. Intracellular staining of cytokines in the peripheral blood mononuclear cells before and after rituximab administration revealed that the cytokine production, representative of T-helper (Th)1-, Th2-, and Th17-type responses, decreased abruptly after the treatment. Interestingly, this timing coincided with that of the manifestation of the beneficial effect. This relationship may provide useful insight into the mechanism of action of the drug and hence about the pathogenesis of RA. [ABSTRACT FROM AUTHOR]

We report a patient with vasculo-Behçet’s disease treated successfully with a high dose of prednisolone. In 2002, the patient was diagnosed with vasculo-Behçet’s disease. He was admitted to our hospital because of sudden-onset right lower back pain in June 2006. Upon admission, abdominal angiography revealed aneurysmal dilatations of the celiac and superior mesenteric arteries. He was treated promptly with high-dose prednisolone, after which the aneurysms displayed no further enlargement. As we believe this case to be quite rare, we report this case with a literature review in support of this characterization. [ABSTRACT FROM AUTHOR]

The objective of this study is to evaluate the cellular mechanism underlying filtration leukocytapheresis (LCAP) therapy for the treatment of rheumatoid arthritis (RA). Thirteen patients with refractory RA each underwent three sessions of LCAP. Before (pre-) and after (post-) the completion of the first LCAP session, peripheral blood was sampled and analyzed for neutrophil surface markers using flow cytometry. The surface antigens of peripheral blood mononuclear cells (PBMCs) and neutrophils obtained at pre- and post-LCAP were then analyzed using a fluorescence-activated cell sorter. The American College of Rheumatology's criterion of a 20% improvement was achieved in six patients, but not in the other seven patients, after LCAP therapy. The post-LCAP number of blood band form neutrophils with a bone marrow phenotype (CD49ddim+, low density) was higher among the responders than among the nonresponders, suggesting an association between the clinical response and the recruitment of bone-marrow-derived neutrophils. After the nonspecific absorption of WBCs during a 1-h Cellsorba procedure, the number of PBMCs was consistently decreased, although the number of neutrophils that were affected by removal plus recruitment varied in a manner that was independent of efficacy. In contrast, the emergence of immature neutrophils in the peripheral blood was characteristic of the effective therapies. These cells were found after the 1st session of responders and also found following sessions of LCAPs. Immature neutrophils, which may be recruited from the bone marrow in the peripheral blood after the first session of LCAP, can predict the clinical efficacy of subsequent LCAP sessions. J. Clin. Apheresis, 2007. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

The article focuses on a study on the stimulating effects of APRIL, a ligand involved in tumor proliferation, and its specific effect on fibroblast-like synoviocytes (FLS) in the affected rheumatoid arthritis (RA) synovium. FLS is one of the main effector cells in the joint destruction of RA through their ability to degrade soft tissue and cartilage. The researchers found that APRIL induces RA FLS to express pathogenic phenomena observed in the RA synovium. APRIL was also found to stimulate RA FLS to produce APRIL itself.

The Wisconsin Card Sorting Test, which probes the ability to shift attention from one category of stimulus attributes to another (shifting cognitive sets), is the most common paradigm used to detect human frontal lobe pathology. However, the exact relationship of this card test to prefrontal function and the precise anatomical localization of the cognitive shifts involved are controversial. By isolating shift-related signals using the temporal resolution of functional magnetic resonance imaging, we reproducibly found transient activation of the posterior part of the bilateral inferior frontal sulci. This activation was larger as the number of dimensions (relevant stimulus attributes that had to be recognized) were increased. These results suggest that the inferior frontal areas play an essential role in the flexible shifting of cognitive sets. [ABSTRACT FROM AUTHOR]

We investigated the response inhibition function of the prefrontal cortex associated with the go/no-go task using functional magnetic resonance imaging in five human subjects. The go/no-go task consisted of go and no-go trials given randomly with roughly equal probability. In go trials a green square was presented and the subjects had to respond by promptly pushing a button using their right or left thumbs, but in no-go trials a red square was presented and subjects were instructed not to respond. When brain activity in no-go trials is dominant over that in go trials in areas in the prefrontal cortex, this no-go dominant brain activity would reflect the neural processes for inhibiting inherent response tendency. We used a new strategy of image data analysis by which transient brain activity in go or no-go trials can be analysed separately, and looked for the prefrontal areas in which the brain activity in no-go trials is dominant over that in go trials. We found the no-go dominant foci in the posterior part of the right inferior frontal sulcus reproducibly among the subjects. This was true whether the right or left hand was used. These results suggest that this region in the prefrontal cortex is related to the neural mechanisms underlying the response inhibition function. [ABSTRACT FROM AUTHOR]