Anti-F13A1 monoclonal antibody, clone 2F0

Objective: Although Asians have the highest birth prevalence of oral-facial clefts, the majority of gene mapping studies of cleft lip with or without cleft palate (CUP) have been in European or American Caucasians. Therefore, the objective of this study of Chinese families was to evaluate linkage and association between CUP and 10 genetic markers in five chromosomal regions that have shown positive results in Caucasians. Setting: Families were ascertained through nonsyndromic CUP surgical probands from hospitals throughout Shanghai, China. Participants: Study participants included 671 individuals from 60 families with two or more members affected with oral-facial clefts. Of the 671 total individuals, 145 were affected. Results: Ten markers from chromosomes 2, 4, 6, 17, and 19 were assessed (TGFA, MSX1, D4S194, D4S175, F13A1, GATA185H, D17S250, D17S579, D19S49, APOC2). LOD scores were calculated between each of the 10 markers and CUP as well as model-free statistics of linkage (SimIBD) and association (TDT). None of the markers showed significantly positive LOD scores with CUR A significantly positive result (p = .01) was seen using SimIBD for APOC2 on chromosome 19, and a positive TDT result (p = .004) was obtained for D19S49, near APOC2. Conclusions: This is the first gene mapping study of CUP in China. These results indicate that most of the genetic regions with positive results in Caucasian families may not be involved in CUP found in China, although there is some positive evidence for the candidate region on chromosome 19.

Background: Macrophages are crucial cells in the pathogenesis of atherosclerosis. Macrophages are plastic cells which can switch from a classical pro-inflammatory M1 to an alternative anti-inflammatory M2 macrophage phenotype, depending on the environmental stimuli. Because high-density lipoprotein (HDL) cholesterol levels are inversely correlated to cardiovascular disease and since HDL displays anti-inflammatory properties, we investigated whether HDL can affect alternative macrophage differentiation of primary human monocytes in the presence of interleukin (IL)-4, a M2 macrophage polarization driver, in vitro and ex vivo. Methods and results: M2 macrophages are highly responsive to HDL stimulation, since the expression of pentraxin 3 (PTX3), a well known HDL target gene, is induced by HDL more strongly in M2 macrophages than in control unpolarized resting macrophages (RM). As expected, the expression of M2 markers, such as Mannose Receptor (MR), CD200 Receptor (CD200R), Coagulation factor XIII A1 (F13A1), IL-1 receptor antagonist (IL-1RA) and IL10, was induced in IL-4 polarized M2 macrophages compared to RM. However, incubation with HDL added in vitro did not modulate the gene expression of M2 macrophage polarization markers. Moreover, monocytes isolated from subjects with genetically low HDL levels, carrying ABCA1 or LCAT mutations, differentiated ex vivo into M2 macrophages without any difference in the alternative macrophage marker expression profile. Conclusions: These in vitro and ex vivo results indicate that, contrary to mouse macrophages, HDL does not influence macrophage M2 polarization of human monocyte-derived macrophages. Thus, the anti-inflammatory properties of HDL in humans are probably not related to the enhancement of the M2 macrophage phenotype. (C) 2014 Elsevier Ireland Ltd. All rights reserved.