Nd-ion Substitution Effect on f-electron Multipole Order of PrRu4P12

We studied the effect of magnetic Nd-ion substitution on the metal-nonmetal transition at a transition temperature of 63 K of PrRu4P12, which is characterized by antiferro-type electric multipole ordering of Pr-ion 4f electrons. The transition temperature of Pr1-xNdxRu4P12 depends weakly on the Nd concentration x as compared to Laand Ce-substituted compounds. Inelastic neutron-scattering measurements revealed that the energies and widths of crystalline field excitation peaks of Pr 4f 2 in Pr0.85Nd0.15Ru4P12 are very similar to those of PrRu4P12. These experimental results indicate that the ordered state is robust against the substitution of magnetic Nd ions as compared to the La and Ce substitutions. Magnetic interactions between the Pr ions and the Nd ions in Pr1-xNdxRu4P12 help stabilize the magnetic triplet ground state of the Pr ions that appears in the antiferro-type multipole ordered phase. Therefore, the nonmagnetic multipole ordered phase of PrRu4P12 is compatible with the magnetic perturbation.Conference : 20th International Conference on Magnetism, ICM 2015Location : Barcelona, SPAINDate : JUL 05-10, 201

The Establishment of a Primary Culture System of Proximal Tubule Segments Using Specific Markers from Normal Mouse Kidneys

The proximal tubule contains the highest expression of angiotensinogen mRNA and protein within the kidney and plays a vital role in the renal renin-angiotensin system. To study the regulation of angiotensinogen expression in the kidney in more detail, the proximal tubule needs to be accurately isolated from the rest of the nephron and separated into its three segments. The purpose of this study was to design a novel protocol using specific markers for the separation of proximal tubule cells into the three proximal tubule segments and to determine angiotensinogen expression in each segment. Kidneys were removed from C57BL/6J mice. The proximal tubules were aspirated from region of a Percoll gradient solution of the appropriate density. The proximal tubule was then separated into its three segments using segment-specific membrane proteins, after which each segment was characterized by a different specific marker (sodium-glucose transporter 2 for Segment 1; carbonic anhydrase IV for Segment 2; ecto-adenosine triphosphatase for Segment 3). The isolation of proximal tubules into three segments was successful, and angiotensinogen mRNA in Segment 2 and 3 and angiotensinogen protein in all three segments were confirmed. This protocol will be helpful for future studies of the detailed mechanisms of the intrarenal renin-angiotensin system

Role of Organic Cation Transporter 1, OCT1 in the Pharmacokinetics and Toxicity of cis-Diammine(pyridine)chloroplatinum(II) and Oxaliplatin in Mice

PurposeThe goal of this study was to test the hypothesis that by controlling intracellular uptake, organic cation transporter 1, Oct1 is a key determinant of the disposition and toxicity of cis-diammine(pyridine)chloroplatinum(II)(CDPCP) and oxaliplatin.MethodsPharmacokinetics, tissue accumulation and toxicity of CDPCP and oxaliplatin were compared between Oct1-/- and wild-type mice.ResultsAfter intravenous administration, hepatic and intestinal accumulation of CDPCP was 2.7-fold and 3.9-fold greater in Oct1 wild-type mice (p < 0.001). Deletion of Oct1 resulted in a significantly decreased clearance (0.444 ± 0.0391 ml/min*kg versus 0.649 ± 0.0807 ml/min*kg in wild-type mice, p < 0.05) and volume distribution (1.90 ± 0.161 L/kg versus 3.37 ± 0.196 L/kg in wild-type mice, p < 0.001). Moreover, Oct1 deletion resulted in more severe off-target toxicities in CDPCP-treated mice. Histologic examination of the liver and measurements of liver function indicated that the level of hepatic toxicity was mild and reversible, but was more apparent in the wild-type mice. In contrast, the effect of Oct1 on the pharmacokinetics and toxicity of oxaliplatin in the mice was minimal.ConclusionsOur study suggests that Oct1 plays an important role in the pharmacokinetics, tissue distribution and toxicity of CDPCP, but not oxaliplatin

Presence of fructose transporter GLUT5 in the S3 proximal tubules in the rat kidney

Presence of fructose transporter GLUT5 in the S3 proximal tubules in the rat kidney.BackgroundFructose is a nutrient as well as a potent agent for the formation of advanced glycation end product in diabetes. GLUT5 is a facilitated-diffusion fructose transporter expressed in the small intestine and kidney. Previous reports on the localization of GLUT5 by in situ hybridization and immunohistochemistry were controversial.MethodsThe expression of GLUT5 was checked by reverse transcription-polymerase chain reaction and Southern blotting and immunoblotting analyses. Localization of GLUT5 was visualized by high-resolution immunofluorescence and immunogold electron microscopy.ResultsWe were able to confirm the expression of GLUT5 in the kidney. GLUT5 was predominantly present in the outer stripe of the outer medulla, where it was localized in the S3 proximal tubule cells. Double labeling with phalloidin showed that GLUT5 was localized in the brush border of the S3 proximal tubule cells. Ultrastructural examination revealed that GLUT5 was present along the plasma membrane of the apical microvilli.ConclusionGLUT5 is present at the apical plasma membrane of S3 proximal tubule cells and may serve as the transporter of fructose

Elderly patients aged over 75 years with glioblastoma: Preoperative status and surgical strategies

Background: Standards of care for the elderly with glioblastoma are still unknown, because most studies exclude elderly patients. The effects of preoperative status and surgical strategies on the prognosis for elderly glioblastoma patients were studied. Methods: We defined “elderly” as 75 years or older and retrospectively reviewed 137 patients with glioblastoma, including 31 (22.6%) elderly patients. Relationships between age and clinicopathological variables were investigated. Results: The median overall survival (OS) was 15.8 months in the nonelderly group and 10.8 months in the elderly group (p = 0.02). The median progression-free survival (PFS) was 9.1 months in the nonelderly group and 6.6 months in the elderly group (p = 0.02). Median OS and median PFS had no relationship between low (<70) and high (≥70) Karnofsky performance status (KPS) in the nonelderly group. However, the median OS was significantly longer in the elderly group with high KPS (8.4 months in low KPS, 12.4 months in high KPS; p = 0.003). The median PFS was also significantly longer in the elderly group with high KPS (4.3 months in low KPS, 9.1 months in high KPS; p = 0.04). OS and PFS were significantly longer in the nonelderly group with resection than with biopsy (OS, p = 0.016; PFS, p = 0.039). However, neither OS nor PFS showed any difference with surgical method in the elderly group (OS, p = 0.241; PFS, p = 0.131). Conclusions: Less invasive treatment can be considered as a treatment option in addition to radical resection in glioblastoma patients aged 75 years and older with KPS on admission of less than 70, depending on the general condition

Clinical value of fluorine-18α-methyltyrosine PET in patients with gliomas: comparison with fluorine-18 fluorodeoxyglucose PET

Abstract Background We investigated the relationship between metabolic activity and histological features of gliomas using fluorine-18α-methyltyrosine (18F-FAMT) positron emission tomography (PET) compared with fluorine-18 fluorodeoxyglucose (18F-FDG) PET in 38 consecutive glioma patients. The tumor to normal brain ratios (T/N ratios) were calculated, and the relationships between T/N ratio and World Health Organization tumor grade or MIB-1 labeling index were evaluated. The diagnostic values of T/N ratios were assessed using receiver operating characteristic (ROC) curve analyses to differentiate between high-grade gliomas (HGGs) and low-grade gliomas (LGGs). Results Median T/N ratio of 18F-FAMT PET was 2.85, 4.65, and 4.09 for grade II, III, and IV gliomas, respectively, with significant differences between HGGs and LGGs (p = 0.006). Both T/N ratio (p = 0.016) and maximum standardized uptake value (p = 0.033) of 18F-FDG PET showed significant differences between HGGs and LGGs. ROC analysis yielded an optimal cut-off of 3.37 for the T/N ratio of 18F-FAMT PET to differentiate between HGGs and LGGs (sensitivity 81%, specificity 67%, accuracy 76%, area under the ROC curve 0.776). Positive predictive value was 84%, and negative predictive value was 62%. T/N ratio of 18F-FAMT PET was not correlated with MIB-1 labeling index in all gliomas, whereas T/N ratio of 18F-FDG PET was positively correlated (r s  = 0.400, p = 0.013). Significant positive correlation was observed between T/N ratios of 18F-FDG and 18F-FAMT (r s  = 0.454, p = 0.004), but median T/N ratio of 18F-FAMT PET was significantly higher than that of 18F-FDG PET in all grades of glioma. Conclusions The T/N ratio of 18F-FAMT uptake has high positive predictive value for detection of HGGs. 18F-FAMT PET had higher T/N ratio, with better tumor-normal brain contrast, compared to 18F-FDG PET in both LGGs and HGGs. Therefore, 18F-FAMT is a useful radiotracer for the preoperative visualization of gliomas