Infiltration of various types of leucocytes has been shown to play a crucial role in the pathogenesis of rheumatoid arthritis (RA). Macrophage inflammatory protein‐3α (MIP‐3α) is a recently identified chemokine which is a selective chemoattractant for leucocytes such as memory T cells, naïve B cells and immature dendritic cells. In this study, we investigated the expression of MIP‐3α and its specific receptor CCR6 in the inflamed joints of patients with RA. Increased amounts of MIP‐3α were found by ELISA in synovial fluids (SF) of patients with RA. MIP‐3α was apparently detected in all synovial tissue specimens of RA patients (n = 6), but it could not be detected in that of osteoarthritis (OA) patients (n = 4). Expression of MIP‐3α was detected especially in the sublining layer, and infiltrating mononuclear cells in RA synovial tissue. Gene expression of MIP‐3α was also found in six out of 11 RA‐synovial fluid cells by RT‐PCR. Cultured synovial fibroblasts derived from either RA or OA patients were capable of producing MIP‐3α in response to IL‐1β and TNFα in vitro. Furthermore, expression of CCR6 was found in infiltrating mononuclear cells in the cellular clusters and around the vessels of RA synovial tissue. These findings indicate that increased production of MIP‐3α may contribute to the selective recruitment of CCR6‐expressing cells in RA.

Background: Improvements in the biocompatibility of dialysis membranes have reduced biological responses elicited by blood-membrane interactions. In this article, recent technological developments in dialysis membranes with regard to biocompatibility and recent progress in the evaluation of the biocompatibility of dialysis membranes are reviewed. Summary: The focus of investigation into dialysis membranes in recent years has focused on not only membrane materials, but also their surface textures, which have been changed, for example, by coating with vitamin E or by changing the amount and type of hydrophilizing agents used. Research and development is directed at altering the chemical and physical properties of membrane surfaces to suppress biological responses that are particularly elicited as a result of platelet activation. To develop membranes with excellent biocompatibility, biocompatibility should be evaluated on a like-for-like basis under conditions that are similar to those in clinical settings. Evaluation using actual dialyzers can be performed using porcine blood, platelet-rich plasma isolated from porcine blood (and platelet-rich plasma with leukocytes), or suspension of neutrophils isolated from porcine blood or cultured human monocytes. Key Messages: Highly biocompatible dialysis membranes can be developed when the overall correlations among biological reactions are examined by integrating all data on biological responses elicited by blood-membrane interactions or mutual interactions among blood cells.

Tests were conducted to determine which horizontal reflection angles are most effective in stimulating subjective diffuseness for a listener in a room. Paired comparison tests were carried out where subjects were asked to judge in which of two sound fields they perceived more diffuseness. Results show that the most effective horizontal angle depends on the frequency of the one-third-octave-band noise, as is indicated by the interaural cross correlation. The remarkable finding in this investigation is that the scale value of subjective diffuseness may be formulated in terms of the 3/2 power of the magnitude of interaural cross correlation (IACC) and that the scale value does not vary with the frequency of the bandpass noise source.

SUMMARYTo evaluate the role of the prostaglandin E receptor (EP) subtypes in the development of inflammatory synovitis, we examined EP subtype mRNA distribution in the synovial tissue of rats with adjuvant arthritis and the effect of selective EP agonists on cytokine production by cultured rat synovial cells. We used reverse transcriptase-polymerase chain reaction (RT-PCR) and in situ hybridization to measure the level of EP subtype (EP1, EP2, EP3, and EP4) mRNA expression in synovial tissues and cultured synovial cells from the arthritic joints of rats. RT-PCR and ELISA were used to analyse the effects of two selective EP agonists on IL-6 production by cultured rat synovial cells. EP2 and EP4 mRNA expression in inflamed synovial tissues was up-regulated. EP2 and EP4 mRNA were co-expressed in synovial macrophages and fibroblasts in inflamed tissues. EP4 and EP2 agonists both inhibited IL-1-induced IL-6 production. Our results suggest that prostaglandin E 2 regulates the functions of synovial macrophages and fibroblasts through EP2 and EP4, which are induced by inflammatory stimuli in rats with adjuvant arthritis.

In atherosclerotic artery walls, mast cells, an inflammatory cell, are activated and secrete some proteases including chymase. Chymase, a chymotrypsin-like protease, cleaves the C-terminus of apolipoprotein A-I (apoA-I) at Phe225. This cleavage reduces the ability of apoA-I to promote the efflux of cellular cholesterol. The aim of this study is to detect C-terminally truncated apoA-I in normal human serum. For this purpose, we generated a monoclonal antibody that specifically recognizes C-terminally truncated apoA-I by immunizing mice with a peptide that corresponds to human apoA-I amino acid residues 216-225. The monoclonal antibody, termed 16-4 mAb, selectively reacted with recombinant C-terminally truncated apoA-I, but not recombinant full-length apoA-I. A two-dimensional electrophoresis analysis also indicated that only two out of six spots that contained apoA-I fragments and had a molecular mass of 26 kDa after chymase digestion reacted with the 16-4 mAb. We detected an extremely small amount of C-terminally truncated apoA-I in normal human serum by concentrating the serum through affinity chromatography using a 16-4 mAb-conjugated resin, and then performing Western blot analysis. The 16-4 mAb could be useful to examine whether C-terminally truncated apoA-I is associated with the progression of atherosclerosis.