Contribution of hematopoietic stem cells in blood vessel formation

Vascular development consists of vasculogenesis and angiogenesis. The system of TIE2-Angiopoietin (Ang) is involved in angiogenesis. TIE2 regulates adhesion and dissociation between endothelial cells and mural cells, and survival, apoptosis, and chemotaxis of endothelial cells. Ang-2, which is produced by endothelial cells under tissue hypoxia, has been suggested to be a key regulator for the initiation of endothelial cell sprouting from pre-existing vessels. Although Ang-2 binds to TIE2, it does not promote activation of TIE2 on endothelial cells. Ang-2 produced from endothelial cells under hypoxia inhibits the binding of Ang-1 to TIE2. On the other hand, Ang-1 promotes activation of TIE2 and adhesion between endothelial cells and mural cells. Therefore, endothelial cells dissociated from mural cells by Ang-2 are free to move to avascular area where oxygen or nutrient is needed. We recently found that hematopoietic stem cells produce Ang-1 and promote chemotaxis and network formation of TIE2-positive endothelial cells. Moreover, hematopoietic stem cells change their fate into mural cell and stabilize the vessel structure. This novel function may be applied clinically to promote neovascularization by transplanting the hematopoietic stem cells at the desired site.Biomedical Reviews 2003; 14: 1-8

Inhibitors of a Na⁺-pumping NADH-ubiquinone oxidoreductase play multiple roles to block enzyme function

The Na⁺-pumping NADH-ubiquinone (UQ) oxidoreductase (Na⁺-NQR) is present in the respiratory chain of many pathogenic bacteria and is thought to be a promising antibiotic target. Whereas many details of Na⁺-NQR structure and function are known, the mechanisms of action of potent inhibitors is not well-understood; elucidating the mechanisms would not only advance drug design strategies but might also provide insights on a terminal electron transfer from riboflavin to UQ. To this end, we performed photoaffinity labeling experiments using photoreactive derivatives of two known inhibitors, aurachin and korormicin, on isolated Vibrio cholerae Na⁺-NQR. The inhibitors labeled the cytoplasmic surface domain of the NqrB subunit including a protruding N-terminal stretch, which may be critical to regulate the UQ reaction in the adjacent NqrA subunit. The labeling was blocked by short-chain UQs such as ubiquinone-2. The photolabile group (2-aryl-5-carboxytetrazole (ACT)) of these inhibitors reacts with nucleophilic amino acids, so we tested mutations of nucleophilic residues in the labeled region of NqrB, such as Asp49 and Asp52 (to Ala), and observed moderate decreases in labeling yields, suggesting that these residues are involved in the interaction with ACT. We conclude that the inhibitors interfere with the UQ reaction in two ways: the first is blocking structural rearrangements at the cytoplasmic interface between NqrA and NqrB, and the second is the direct obstruction of UQ binding at this interfacial area. Unusual competitive behavior between the photoreactive inhibitors and various competitors corroborates our previous proposition that there may be two inhibitor binding sites in Na⁺-NQR

Comparison of the Fixation Strengths of Screws between the Traditional Trajectory and the Single and Double Endplate Penetrating Screw Trajectories Using Osteoporotic Vertebral Body Models Based on the Finite Element Method

Study Design This is a finite element (FE) study. Purpose To compare the fixation strength of traditional trajectory (TT) and single and double endplate penetrating screw trajectories (SEPST/DEPST) to the osteoporotic vertebral body model based on the FE method. Overview of Literature SEPST/DEPST have been developed to enhance the fixation strength in patients with diffuse idiopathic hyperostosis (DISH). This technique was also applied to patients with osteoporosis. However, determining the superiority of SEPST/DEPST is difficult because of the heterogeneous patient backgrounds. Methods Twenty vertebrae (T12 and L1) from 10 patients with osteoporosis (two males and eight females; mean age, 74.7 years) were obtained to create the 10 FE models. First, a single screw was placed with TT and SEPST/DEPST, and the fixation strength was compared by axial pullout strength (POS) and multidirectional loading tests. Second, two screws were placed on the bilateral pedicles with TT and SEPST/DEPST, and the fixation force of the vertebrae in the constructs in flexion, extension, lateral flexion, and axial rotation was examined. Results SEPST and DEPST had 140% and 171% higher POS values than TT, respectively, and the DEPST result was statistically significant (p=0.007). The multidirectional fixation strength was significantly higher in DEPST and SEPST than in TT in the cranial, caudal, and medial directions (p<0.05) but not in the lateral direction (p=0.05). The vertebral fracture strength at the lower instrumented vertebra of the DEPST tended to be higher than that of TT. The vertebral motion angles in SEPST and DEPST were significantly smaller in lateral bending (p=0.02) and tended to be smaller in flexion and extension than in TT (p=0.13). Conclusions This study may provide useful information for spine surgeons in deciding whether to choose the SEPS or DEPS technique for augmenting fixation in osteoporotic vertebral fracture surgery

本学ヘリカルCT(ProSpeed F II)における距離計測の精度評価

In order to evaluate image precision of a computed tomography (CT), acrylic and glass cubes soaked in the water were scaned and length was measured on a constructed image. The following conclusions were obtained from the above-mentioned results: 1. Length is different from that of the actual size according to software used for measurement in some cases. 2. Length of glass cubes with a high CT number tends to be measured longer than the actual one in comparison with acrylic cubes. 3. An error is apt to occur in the peripheral part due to the partial volume effect. 4. Difference in precision in the Z axis direction caused by the scan method is not observed. 5. Increase of errors towards the Z axis direction accompanying movement of the table is within the allowable range but should be considered clinically

アポリポプロテイン E ケッソン マウス ニ オイテ ケッショウバン ユライ ゾウショク インシ アルファ ジュヨウタイ デワ ナク ベータ ジュヨウタイ ノ キノウテキ シャダン ガ ケッカン ヘイカツキン サイボウ ノ センイセイ コウハン リョウイキ エノ チクセキ オ ヨクセイ スル

京都大学0048新制・課程博士博士(医学)甲第9093号医博第2401号新制||医||778(附属図書館)UT51-2001-G813京都大学大学院医学研究科内科系専攻(主査)教授 内山 卓, 教授 中尾 一和, 教授 北 徹学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDA