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Platelet-activating factor (PAF) is a potent lipid mediator playing various inflammatory and physiological roles. PAF is biosynthesized through two independent pathways called the de novo and remodeling pathways. Lyso-PAF acetyltransferase (lyso-PAF AT) was believed to biosynthesize PAF under inflammatory conditions, through the remodeling pathway. The first isolated lyso-PAF AT (LysoPAFAT/LPCAT2) had consistent properties. However, we show in this study the finding of a second lyso-PAF AT working under noninflammatory conditions. We partially purified a Ca 2؉ -independent lyso-PAF AT from mouse lung. Immunoreactivity for lysophosphatidylcholine acyltransferase 1 (LPCAT1) was detected in the active fraction. Lpcat1-transfected Chinese hamster ovary cells exhibited both LPCAT and lyso-PAF AT activities. We confirmed that LPCAT1 transfers acetate from acetyl-CoA to lyso-PAF by the identification of an acetyl-CoA (and other acyl-CoAs) interacting site in LPCAT1. We further showed that LPCAT1 activity and expression are independent of inflammatory signals. Therefore, these results suggest the molecular diversity of lyso-PAF ATs is as follows: one (LysoPAFAT/LPCAT2) is inducible and activated by inflammatory stimulation, and the other (LPCAT1) is constitutively expressed. Each lyso-PAF AT biosynthesizes inflammatory and physiological amounts of PAF, depending on the cell type. These findings provide important knowledge for the understanding of the diverse pathological and physiological roles of PAF.

Background: The 2009 Asian multicenter study for derivation of reference intervals (RIs) featured: 1) centralized measurements to exclude reagent-dependent variations; 2) inclusion of non-standardized analytes (hormones, tumor makers, etc.) in the target; and 3) cross-check of test results between the central and local laboratories. Transferability of centrally derived RIs for non-standardized analytes based on the cross-check was examined. Methods: Forty non-standardized analytes were centrally measured in sera from 3541 reference individuals recruited by 63 laboratories. Forty-four laboratories collaborated in the cross-check study by locally measuring aliquots of sera from 9 to 73 volunteers (average 22.2). Linear relationships were obtained by the reduced major-axis regression. Error in converting RIs using the regression line was expressed by the coefficient of variation of slope b [CV(b)]. CV(b) < 10% was set as the cut-off value allowing the conversion. The significance of factors for partitioning RIs was determined similarly as in the first report. Results: Significant sex-, age-, and region-related changes in test results were observed in 17, 15, and 11 of the 40 analytes, respectively. In the cross-comparison study, test results were not harmonized in the majority of immunologically measured analytes, but their average CV(b)s were < 10% except for total protein, cystatin C, CA19-9, free thyroxine, and triiodothyronine. After conversion, 74% of centrally derived RIs were transferred to each local laboratory.

1 The aim of this study was to determine whether nifedipine could suppress an atherogenic process such as balloon-injured intimal thickening in vivo and the proliferation of vascular smooth muscle cells (VSMC) in vitro. 2 First, we examined the in vivo eect of nifedipine to determine whether it could suppress intimal thickening induced by balloon catheterization. Sprague-Dawley (SD) rats were divided into three groups (L, nifedipine 0.3 mg kg 71 day 71; H, nifedipine 3 mg kg 71 day 71; C, no nifedipine), and Alzet 1 osmotic pumps were implanted in their backs for continuous administration. The neointimal layers were completely occupied by proliferated VSMC, and the area ratios of neointima/media treated with nifedipine signi®cantly decreased dose-dependently compared to those of the control. Neither blood pressure nor lipid levels changed among the three groups. 3 We next evaluated the in vitro eect of nifedipine on the proliferation of cultured rat VSMC. Nifedipine decreased the values of [ 3 H]-thymidine incorporation and total cellular protein content as well as the levels of phosphorylated extracellular signal-regulated protein kinase (ERK) 1/2, mitogen-activated protein kinase kinase (MEK) 1/2, and even the phosphorylation of Pyk2, in dosedependent fashions. In addition, nifedipine suppressed the levels of proliferative cell nuclear antigen (PCNA) dose-dependently in both VSMC and balloon-injured thoracic aortae. 4 These results indicate that nifedipine has an inhibitory eect on intimal thickening by attenuating intimal VSMC proliferation, suggesting that nifedipine could be eective for preventing the progression of atherosclerotic plaque as in restenosis after angioplasty.

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The results of our study suggest that the serum levels of cystatin C are not always a reliable marker of the GFR in patients with a malignancy, probably in relation to its nature as a cysteine protease inhibitor.

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