Observation of B̅0→D(*)0pp̅

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Lanthanide tetrad effect of Naegi granite-pegmatite suite, central Japan : Convex tetrad effect by fractional loss of fluid from hydrous felsic melt

2007The Late Cretaceous (ca. 67 Ma) Naegi granite-pegmatite suite in Nakatsugawa City, Gifu Prefecture, central Japan, has been studied in view of the lanthanide tetrad effect in evolved felsic rocks. The pegmatite occurring sparsely in the granite body as small patches (<20 cm) and the matrix granite were sampled. REE including Y, major and some minor elements in the samples have been determined. The REE data for mineral separates (quartz, plagioclase, K-feldspar, biotite, and residual heavy minerals) from a granite sample have also been obtained. The chondrite-normalized REE patterns for pegmatite and granite commonly show convex tetrad effects and huge negative Eu anomalies of Eu/Eu^*=0.02-0.004 but no notable Y/Ho fractionation. The whole-rock sample of granite and its mineral separates show similar convex tetrad effects, suggesting the convex tetrad effect in the original magma before crystallization. The granite and pegmatite show no significant differences in major element chemistry and mineralogy except mineral size and texture, but the pegmatite is depleted in Eu, Sr, and Ba relative to the granite. In addition, the pegmatite exhibits a convex tetrad effect and a fairly large negative Eu anomaly, when normalized by the granite. The field occurrence of pegmatite suggests a heterogeneous distribution of aqueous fluid inside of the granitic magma, which is possibly related to the unmixing phenomenon of fluid and silicate melt. Here is proposed a simple model of fractional loss of fluid from hydrous felsic melt. Applying the model to the observed REE fractionation between pegmatite and host granite pairs, REE partition coefficients between aqueous fluid and melt, K_d(REE: fluid/melt), have been evaluated. The logK_d(REE: fluid/melt) values indeed exhibit small concave tetrad effects, positive Eu anomalies, and light REE enrichment trends. Fractional loss of fluid from a hydrous felsic melt system leaves residual silicates in which the small concave tetrad effect and positive Eu anomaly of logKd(REE: fluid/melt) can be exaggerated in reversed manners. As a result, the residual silicates acquire pronounced convex tetrad effects and huge negative Eu anomalies.国立情報学研究所で電子化したコンテンツを使用している。departmental bulletin pape

Structural and Kinetic Analyses of Macrophage Migration Inhibitory Factor Active Site Interactions

Macrophage migration inhibitory factor (MIF) is a secreted protein expressed in numerous cell types that counters the antiinflammatory effects of glucocorticoids and has been implicated in sepsis, cancer, and certain autoimmune diseases. Interestingly, the structure of MIF contains a catalytic site resembling the tautomerase/isomerase sites of microbial enzymes. While bona fide physiological substrates remain unknown, model substrates have been identified. Selected compounds that bind in the tautomerase active site also inhibit biological functions of MIF. It had previously been shown that the acetaminophen metabolite, N-acetyl-p-benzoquinone imine (NAPQI), covalently binds to the active site of MIF. In this study, kinetic data indicate that NAPQI inhibits MIF both covalently and noncovalently. The structure of MIF cocrystallized with NAPQI reveals that the NAPQI has undergone a chemical alteration forming an acetaminophen dimer (bi-APAP) and binds noncovalently to MIF at the mouth of the active site. We also find that the commonly used protease inhibitor, phenylmethylsulfonyl fluoride (PMSF), forms a covalent complex with MIF and inhibits the tautomerase activity. Crystallographic analysis reveals the formation of a stable, novel covalent bond for PMSF between the catalytic nitrogen of the N-terminal proline and the sulfur of PMSF with complete, well-defined electron density in all three active sites of the MIF homotrimer. Conclusions are drawn from the structures of these two MIF−inhibitor complexes regarding the design of novel compounds that may provide more potent reversible and irreversible inhibition of MIF

Validity of LupusQoL-China for the Assessment of Health Related Quality of Life in Chinese Patients with Systemic Lupus Erythematosus

<div><p>Objectives</p><p>To adapt and assess the validity and reliability of LupusQoL for use in Chinese patients with systemic lupus erythematosus (SLE).</p><p>Methods</p><p>Debriefing interviews of subjects with SLE guided the language modifications of the tool. The process of adaptation proceeded according to the guideline and pre-testing results of LupusQoL-China. 220 SLE patients completed LupusQoL-China and a generic preference-based measurement of health EuroQoL scale (EQ-5D), and 20 patients repeated them after 2 weeks. Internal consistency (ICR) and test-retest (TRT) reliability, convergent and discriminant validity were examined. Factor analysis and Rasch analysis were performed.</p><p>Results</p><p>The mean (SD) age of the 208 subjects with SLE was 33.93 (±9.19) years. ICR and TRT of the eight domains ranged from 0.811 to 0.965 and 0.836 to 0.974, respectively. The LupusQoL-China domains demonstrated substantial evidence of construct validity when compared with equivalent domains on the EQ-5D (physical health and usual activities r = −0.63, pain and pain/discomfort r = −0.778, emotional health and anxiety/depression r = −0.761, planning and usual activities r = −0.560). Most LupusQoL-China domains could discriminate patients with varied disease activities and end-organ damage (according to SELENA-SLEDAI and SLICC-DI). The principal component analysis revealed six factors, and confirmatory factor analysis result of which is similar to eight factors model.</p><p>Conclusions</p><p>These results provide evidence that the LupusQoL-China is valid as a disease-specific HRQoL assessment tool for Chinese patients with SLE.</p></div

Multi-Dimensional Health Assessment Questionnaire in China: Reliability, Validity and Clinical Value in Patients with Rheumatoid Arthritis

<div><p>Objective</p><p>To evaluate the psychometric properties and clinical utility of Chinese Multidimensional Health Assessment Questionnaire (MDHAQ-C) in patients with rheumatoid arthritis (RA) in China.</p><p>Methods</p><p>162 RA patients were recruited in the evaluation process. The reliability of the questionnaire was tested by internal consistency and item analysis. Convergent validity was assessed by correlations of MDHAQ-C with Health Assessment Questionnaire (HAQ), the 36-item Short-Form Health Survey (SF-36) and the Hospital anxiety and depression scales (HAD). Discriminant validity was tested in groups of patients with varied disease activities and functional classes. To evaluate the clinical values, correlations were calculated between MDHAQ-C and indices of clinical relevance and disease activity. Agreement with the Disease Activity Score (DAS28) and Clinical Disease Activity Index (CDAI) was estimated.</p><p>Results</p><p>The Cronbach's alpha was 0.944 in the Function scale (FN) and 0.768 in the scale of psychological status (PS). The item analysis indicated all the items of FN and PS are correlated at an acceptable level. MDHAQ-C correlated with the questionnaires significantly in most scales and scores of scales differed significantly in groups of different disease activity and functional status. MDHAQ-C has moderate to high correlation with most clinical indices and high correlation with a spearman coefficient of 0.701 for DAS 28 and 0.843 for CDAI. The overall agreement of categories was satisfying.</p><p>Conclusion</p><p>MDHAQ-C is a reliable, valid instrument for functional measurement and a feasible, informative quantitative index for busy clinical settings in Chinese RA patients.</p></div

Discovery of Human Macrophage Migration Inhibitory Factor (MIF)-CD74 Antagonists via Virtual Screening

Macrophage migration inhibitory factor (MIF) is a cytokine that is involved in the regulation of inflammation as well as cell proliferation and differentiation. Deactivation of MIF by antibodies or inhibition of MIF binding to its receptor, CD74, attenuates tumor growth and angiogenesis. To discover small-molecule inhibitors of MIF’s biological activity, virtual screening was performed by docking 2.1 million compounds into the MIF tautomerase active site. After visual inspection of 1200 top-ranked MIF-ligand complexes, 26 possible inhibitors were selected and purchased and 23 of them were assayed. The in vitro binding assay for MIF with CD74 revealed that 11 of the compounds have inhibitory activity in the micromolar regime, including four compounds with IC50 values below 5 μM. Inhibition of MIF tautomerase activity was also established for many of the compounds with IC50 values as low as 0.5 μM; Michaelis−Menten analysis was performed for two cases and confirmed the competitive inhibition

The cross-tabulation of RAPID3 scores compared with DAS28 and CDAI in four categories.

<p>All percentages are row percentages, except total in rightmost column (column percentages).The kappa value was 0.467 for DAS28 and 0.491 for CDAI (p<0.001).H: high activity; M: moderate activity; L: low activity; R: remission.</p

Internal consistency and item analysis of FN and PS.

<p>Corrected Cronbach's alpha: the consistency coefficient of the remaining items when one item was deleted; Item-total: correlation between the item and the corresponding domains; Corrected item-total: correlation between the remaining items and the sales after one item was deleted. Statistics were significant at the level of p<0.001.</p

Scatter plots of correlation between RAPID3 and DAS28 in 156 patients with Rheumatoid Arthritis (spearman's method).

<p>Scatter plots of correlation between RAPID3 and DAS28 in 156 patients with Rheumatoid Arthritis (spearman's method).</p

Data_Sheet_1_MiRNA Regulation of MIF in SLE and Attenuation of Murine Lupus Nephritis With miR-654.PDF

Objective: Macrophage Migration Inhibitory Factor (MIF) is involved in the pathogenesis of systemic lupus erythematosus (SLE) and lupus nephritis (LN). MicroRNAs (miRNAs) play important roles in LN but whether specific miRNAs regulate the expression of MIF in LN is unknown. We explore specific miRNAs that can regulate MIF expression, and investigate miR-654 for the treatment of experimentally-induced murine lupus nephritis.Methods: Sera samples from 24 SLE patients and 24 controls were collected to measure the MIF concentration and its correlation with disease activity. A luciferase reporter assay was used to explore the target of miR-654. ELISA was used to detect the downstream cytokines regulated by miR-654 and MIF. Western blot was applied to measure the impact of miR-654 inhibition on downstream MIF signaling. The therapeutic efficacy of miR-654 was tested in the pristine-induced lupus mouse model. We further measured miR-654 expression and analyzed its relationship with MIF expression in SLE patients.Results: The serum MIF level was increased in SLE patients (p Conclusion: MiR-654 negatively correlated with MIF and disease activity in patients with SLE. MiR-654 inhibits MIF expression via binding to MIF 3'UTR, selectively suppresses the phosphorylation of ERK and AKT, and reduces downstream inflammatory cytokine production. In vivo miR-654 treatment decreases MIF and downstream cytokine production and ameliorates murine lupus nephritis.</p