Essential role of Flk-1 (VEGF receptor 2) tyrosine residue 1173 in vasculogenesis in mice

Flk-1 (human counterpart, KDR) tyrosine kinase, which is one of the two VEGF receptors, is crucial for vascular development. Recently, we showed that, among tyrosine residues of KDR, tyrosine residues 1175 (Y1175, corresponding to Y1173 in murine Flk-1) and Y1214 (Y1212 in Flk-1) are autophosphorylated in response to VEGF, and that Y1175 is important for VEGF-dependent phospholipase Cgamma/PKC/mitogen-activated protein kinase activation leading to DNA synthesis in cultured endothelial cells. However, the importance of these tyrosine residues in Flk-1/KDR in vivo is not yet known. To examine the role of these Flk-1 tyrosine residues in vivo, we generated knock-in mice substituting Y1173 and Y1212 of the Flk-1 gene with phenylalanine, respectively. As a result, Flk-1(1173F) homozygous mice died between embryonic days 8.5 and 9.5 without any organized blood vessels or yolk sac blood islands, and hematopoietic progenitors were severely reduced, similar to the case of Flk-1 null mice. In contrast, Flk-1(1212F) homozygous mice were viable and fertile. These results suggest that the signaling via Y1173 of Flk-1 is essential for endothelial and hematopoietic development during embryogenesis.     

C-reactive protein and peripheral artery disease among Japanese elderly: the Tsurugaya Project.

We investigated the cross-sectional relationship between ankle brachial index and cardiovascular disease risk factors, including C-reactive protein (CRP), among Japanese elderly, a topic which has had little prior epidemiologic study. Our study population comprised 946 subjects aged at least 70 years in whom both CRP and ankle brachial index were measured. The participants were classified into a low (ankle brachial index<0.9) and normal ankle brachial index group. We found that current smoking, high-density lipoprotein cholesterol <40 mg/dl, a low body mass index (continuous variable), hypertension, diabetes and statin use were all significantly related to a lower ankle brachial index. Higher log-transformed CRP level was significantly related to a lower ankle brachial index after adjustment for the cardiovascular risk factors mentioned above (p <0.01). The odds ratios for low ankle brachial index compared to 0-1 risk factors were 5.79 (95% confidence interval [CI]: 2.99-11.20) for 2 risk factors and 17.45 (95% CI: 6.78-49.91) for 3 or more risk factors; independently of other risk factors, the odds ratio for CRP>1.0 mg/l was 2.10 (95% CI: 1.13-3.88) compared to lower CRP values. Thus, a high level of CRP is related to a low ankle brachial index among Japanese elderly as well as Western subjects. This is the first study to report the relationship between CRP and low ankle brachial index among Japanese elderly.     

Strength estimation of a moving 125Iodine source during implantation in brachytherapy: application to linked sources

This study sought to demonstrate the feasibility of estimating the source strength during implantation in brachytherapy. The requirement for measuring the strengths of the linked sources was investigated. The utilized sources were ¹²⁵I with air kerma strengths of 8.38–8.63 U (μGy m² h^–1). Measurements were performed with a plastic scintillator (80 mm × 50 mm × 20 mm in thickness). For a source-to-source distance of 10.5 mm and at source speeds of up to 200 mm s^–1, a counting time of 10 ms and a detector-to-needle distance of 5 mm were found to be the appropriate measurement conditions. The combined standard uncertainty (CSU) with the coverage factor of 1 (k = 1) was ∼15% when using a grid to decrease the interference by the neighboring sources. Without the grid, the CSU (k = 1) was ∼5%, and an 8% overestimation due to the neighboring sources was found to potentially cause additional uncertainty. In order to improve the accuracy in estimating source strength, it is recommended that the measurment conditions should be optimized by considering the tradeoff between the overestimation due to the neighboring sources and the intensity of the measured value, which influences the random error.