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⋄ Background Although the effects of angiotensin type 1 receptor blocker (ARB) have been studied, little is known about ARBs in hypertensive patients undergoing dialysis. In the present study, we evaluated the effect of an ARB, olmesartan medoxomil (CS866), on the progression of peritoneal fibrosis in peritoneal dialysis by examining its effect in a model of peritoneal fibrosis in hypertensive rats. ⋄ Materials and Methods W e all ocated 40 male Wistar rats with 2-kidney, 1-clip renovascular hypertension (2K1C-RVH) to 4 groups (each n = 10) that were dialyzed using various solutions for 42 days as follows: • Group I—10 mL pH 3.5 dialysis solution containing 1.35% glucose • Group II—10 mL pH 3.5 dialysis solution, plus oral administration of CS866 5 mg/kg daily • Group III—10 mL pH 3.5 dialysis solution, plus oral administration of the calcium channel blocker (CCB) amlodipine 3 mg/kg daily • Group IV—10 mL pH 7.0 dialysis solution Dialysis solution was injected every day for 42 days. ⋄ Results Treatment with CS866 and amlodipine induced a significant reduction of blood pressure in 2K1C-RVH rats. In rats treated with pH 3.5 dialysis solution, necropsy findings revealed features identical to those of encapsulating peritoneal sclerosis (EPS). The typical appearance was multiple surfaces covered with granulation tissue or fibrosic tissue or both. Multiple adhesions were present. Microscopic findings revealed that acidic dialysis solution induced peritoneal fibrosis and loss of mesothelium. Treatment with CS866 prevented the progression of peritoneal fibrosis and adhesions. However amlodipine did not improve the progression of peritoneal fibrosis and peritoneal adhesions. In CS866-treated rats, no signs of EPS were present. ⋄ Conclusions Long-term intraperitoneal exposure to acidic dialysis solution produced features typical of EPS. Acidic dialysis solution induces activation of the peritoneal renin– angiotensin system and progression of peritoneal fibrosis. For the peritoneum undergoing peritoneal dialysis, ARB protects against progression of peritoneal fibrosis and peritoneal adhesions.

Bood POZ containing gene type 2 (BPOZ-2) is involved in the growth suppressive effect of the phosphatase and tensin homologue (PTEN). We showed that BPOZ-2 is a human counterpart of yeast Btb3p, which is a putative adaptor for Pcu3p-based ubiquitin ligase. BPOZ-2 bound to E3 ligase CUL3 in vitro and in vivo. BPOZ-2 itself was ubiquitinated through the CUL3-based E3 ligase mainly within the nucleus and degraded by the 26S proteasome. Although BPOZ-2 was mainly expressed within the cytoplasm, it accumulated within the nucleus in the presence of the specific 26S proteasome inhibitor MG132. BPOZ-2 may be recruited to the nucleus from the cytoplasm. Terminal deoxynucleotidyltransferase (TdT) was detected as a BPOZ-2-binding protein using a yeast two-hybrid system by screening a human thymus cDNA library. TdT, BPOZ-2, and CUL3 formed a ternary complex in vivo. TdT was ubiquitinated only within the nucleus and degraded by the 26S proteasome. The ubiqutination or degradation of TdT was markedly promoted by co-expression of BPOZ-2 and CUL3 or BPOZ-2 in 293T cells, respectively.

Background: The role of aldosterone has been less investigated compared to the renin-angiotensin-aldosterone system in renovascular hypertension. The purpose of the present study was to compare the effects of a selective aldosterone receptor blocker, eplerenone (EP), and an angiotensin II receptor type 1 antagonist (AT1RA), losartan (LO) on cardiac and renal damage produced by two-kidney, one-clip (2K-1C) renovascular hypertension in rats. Method: Wistar rats (n = 48) were placed on one of six groups. Group 1 received sham operation. From group 2 to 6, all rats were made as 2K-1C renovascular hypertension. Group 2 received vehicle. Group 3 orally received 100 mg/kg/day of EP from the initiation of the study. Group 4 received 100 mg/kg/day of LO, from the initiation of the study. Groups 5 and 6 received EP and LO from the 4th week after the clipping respectively. Systolic blood pressure (SBP) and urinary protein excretion (UPE) were measured before and every 2 weeks. The remnant kidney was obtained for histopathological analysis and for measurement of endothelial cell nitric oxide synthase (ecNOS) gene expression (GE). Results: SBP increased in the placebo group (132.1 ± 2.4 vs. 115.0 ± 0.6 mm Hg in sham group at week 10, p = 0.019). Treatment with LO or EP from the beginning of the study decreased SBP significantly as measured in the sham group at week 10. The placebo group developed significant UPE (21.7 ± 1.9 mg/day) compared with the sham group (13.4 ± 0.8 mg/day, p < 0.05). Treatment with both LO (12.5 ± 1.5 mg/day, p < 0.01 vs. placebo) and EP (14.8 ± 1.0 mg/ day, p < 0.05 vs. placebo) significantly decreased UPE. On the other hand, the late start of treatment with EP failed to decrease the increased UPE. UPEs were not significantly different between the LO- and EP-treated groups throughout the study. There was no significant pathological change in heart and kidney in all groups. In heart, ecNOS GE was significantly increased in the EP-treated (from the beginning of the study) rats compared with placebo group (0.47 ± 0.01 vs. 0.43 ± 0.01, p < 0.05). LO did not have an effect on ecNOS GE in heart. In aorta, ecNOS GE was significantly increased in the two EP-treated groups compared with the placebo group (0.22 ± 0.01, 0.22 ± 0.02 vs. 0.15 ± 0.01, p < 0.05, respectively). LO also did not have an effect on ecNOS GE in aorta. In kidney, ecNOS GE was significantly increased in the LO group (from the beginning of the study) and two EP-treated groups compared with placebo. Conclusion: This study demonstrated that EP treatment significantly reduced SBP and UPE compared with placebo in both development and established 2K-1C renovascular hypertension. EP was as effective as LO in lowering the blood pressure of this renin-dependent animal model.

Triple-helical structures of (Pro-Hyp-Gly)n (n = 10, 11) at 100 K and room temperature (RT) were analyzed at 1.26 A resolution by using synchrotron radiation data. Totals of 49 and 42 water molecules per seven triplets in an asymmetric unit were found for the structures at 100 K and RT, respectively. These water molecules were classified into two groups, those in the first and second hydration shells. Although there was no significant difference between water molecules in the first shell at 100 K and those at RT, a significant difference between those in the second shell was observed. That is, the number of water molecules at RT decreased to one half and the average distance from peptide chains at RT became longer by about 0.3 A. On the other hand, of seven triplets in an asymmetric unit, three proline residues at the X position at 100 K clearly showed an up-puckering conformation, as opposed to the recent propensity-based hypothesis for the stabilization and destabilization of triple-helical structures by proline hydroxylation. This puckering was attributed to the interaction between proline rings and the surrounding water molecules at 100 K, which is much weaker at RT, as shown by longer average distance from peptide chains.

This paper addresses the development and the experimental results of an aerial ski robot, which can perform a somersault coupled with twist motion in the air. The robot is composed of three rigid links and two rotational joints driven by DC motors and contains control devices so that complicated motion can be performed in the air. To plan the motion of the robot, Fourier Basis Algorithm (FBA) is applied, which approximates the optimal joint trajectories by the finite terms of the Fourier basis. The joint trajectories to perform a twisting somersault from FBA were inputted to the robot, and the flight experiment was carried out. As the result, the robot achieved one backward somersault with half twist. From this, the validity of the analytical model and the motion planning method was shown.

Terminal deoxynucleotidyltransferase (TdT), which template-independently synthesizes DNA during V(D)J recombination in lymphoid cells, is ubiquitylated by a BPOZ-2/Cul3 complex, as the ubiquitin ligase, and then degraded by the 26 S proteasome. We show here that TdT is ubiquitylated by the Cul3-based ubiquitylation system in vitro. Because TdT could also be ubiquitylated in the absence of Cul/BPOZ-2, we determined that it could also be directly ubiquitylated by the E2 proteins UbcH5a/b/c and UbcH6, E3-independently. Furthermore, the ubiquitylated TdT inhibited its nucleotidyltransferase activity.

Triple-helical structures of (Pro-Hyp-Gly)n (n = 10, 11) at 100 K and room temperature (RT) were analyzed at 1.26 A resolution by using synchrotron radiation data. Totals of 49 and 42 water molecules per seven triplets in an asymmetric unit were found for the structures at 100 K and RT, respectively. These water molecules were classified into two groups, those in the first and second hydration shells. Although there was no significant difference between water molecules in the first shell at 100 K and those at RT, a significant difference between those in the second shell was observed. That is, the number of water molecules at RT decreased to one half and the average distance from peptide chains at RT became longer by about 0.3 A. On the other hand, of seven triplets in an asymmetric unit, three proline residues at the X position at 100 K clearly showed an up-puckering conformation, as opposed to the recent propensity-based hypothesis for the stabilization and destabilization of triple-helical structures by proline hydroxylation. This puckering was attributed to the interaction between proline rings and the surrounding water molecules at 100 K, which is much weaker at RT, as shown by longer average distance from peptide chains.

To investigate the role of adhesion molecules [intracellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and integrin alpha 5 beta 1] in the progression of encapsulating peritoneal sclerosis (EPS) under peritoneal dialysis, we examined changes in the expression of those adhesion molecules in Wistar-Kyoto (WKY) rats treated with acidic dialysis solution with or without angiotensin II type 1a receptor blocker (ARB). We divided 48 WKY rats into 4 groups and dialyzed them with various solutions as follows: (1) pH 7 1.5% glucose dialysis solution (control group, n = 12); (2) pH 3.5 1.5% glucose dialysis solution (EPS group, n = 12); (3) pH 3.5 1.5% glucose dialysis solution, plus oral administration of CS866 5 mg/kg daily (ARB group, n = 12); and (4) pH 3.5 1.5% glucose dialysis solution, plus oral administration of amlodipine (CA group, n = 12). We injected the dialysis solutions into the abdominal cavity and administered the ARB and CA daily for 42 days. On days 3, 7, 14, and 42, three rats in each group were humanely killed by decapitation, and we studied the expression of adhesion molecules in peritoneum by the immunofluorescence method. In the EPS rats, expression of adhesion molecules was observed in peritoneum on day 3 after start of acidic solution treatment, in conjunction with an increment of interleukin 6 (IL-6) in the dialysate. The peritoneum of EPS rats showed peritoneal fibrosis with interstitial cell infiltration. Treatment with ARB significantly suppressed expression of adhesion molecules in the peritoneum and suppressed peritoneal fibrosis. Treatment with a neutral solution induced no peritoneal fibrosis nor expression of adhesion molecules in the peritoneum. Our results suggest that adhesion molecules play an important role in the progression of peritoneal fibrosis and resultant EPS. Treatment with ARB prevents the progression of peritoneal fibrosis and suppresses expression of adhesion molecules in the peritoneum.

The original article to which this Erratum refers was published in Biopolymers (Peptide Science) (2004) 76(5) 367–377