Predictive Factors of Rectal Toxicity After Permanent iodine-125 Seed Implantation: Prospective Cohort Study in 2339 Patients

Purpose: To evaluate the incidence and the associated factors of rectal toxicity in patients with prostate cancer undergoing permanent seed implantation (PI) with or without external beam radiation therapy (EBRT) in a nationwide prospective cohort study in Japan (J-POPS) during the first 2 years. Methods and materials: A total of 2,339 subjects were available for the analyses. Rectal toxicity was evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. Results: The 3-year cumulative incidence for grade ≥2 rectal toxicity was 2.88%, 1.76%, and 6.53% in all subjects, PI group and EBRT combination therapy group, respectively. On multivariate analysis, among all subjects, grade ≥2 rectal toxicity was associated with rectal volumes receiving 100% of the prescribed dose (R100; p Conclusions: Rectal toxicity was relatively rare in this study compared with previous reports. For Japanese prostate cancer patients, R100 < 1 mL in both PI and EBRT combination therapy groups and interactive planning in EBRT combination therapy group may be effective in decreasing the incidence of rectal toxicity

Prevention of hypoglycemia by intermittent-scanning continuous glucose monitoring device combined with structured education in patients with type 1 diabetes mellitus : A randomized, crossover trial

Aims: We conducted a randomized, crossover trial to compare intermittent-scanning continuous glucose monitoring (isCGM) device with structured education (Intervention) to self-monitoring of blood glucose (SMBG) (Control) in the reduction of time below range. Methods: This crossover trial involved 104 adults with type 1 diabetes mellitus (T1DM) using multiple daily injections. Participants were randomly allocated to either sequence Intervention/Control or sequence Control/Intervention. During the Intervention period which lasted 84 days, participants used the first-generation FreeStyle Libre (Abbott Diabetes Care, Alameda, CA, USA) and received structured education on how to prevent hypoglycemia based on the trend arrow and by frequent sensor scanning (≥10 times a day). Confirmatory SMBG was conducted before dosing insulin. The Control period lasted 84 days. The primary endpoint was the decrease in the time below range (TBR; <70 mg/dL). Results: The time below range was significantly reduced in the Intervention arm compared to the Control arm (2.42 ± 1.68 h/day [10.1 %±7.0 %] vs 3.10 ± 2.28 h/day [12.9 %±9.5 %], P = 0.012). The ratio of high-risk participants with low blood glucose index >5 was significantly reduced (8.6 % vs 23.7 %, P < 0.001). Conclusions: The use of isCGM combined with structured education significantly reduced the time below range in patients with T1DM

Endocytic Recycling in Yeast Is Regulated by Putative Phospholipid Translocases and the Ypt31p/32p–Rcy1p Pathway

Phospholipid translocases (PLTs) have been implicated in the generation of phospholipid asymmetry in membrane bilayers. In budding yeast, putative PLTs are encoded by the DRS2 gene family of type 4 P-type ATPases. The homologous proteins Cdc50p, Lem3p, and Crf1p are potential noncatalytic subunits of Drs2p, Dnf1p and Dnf2p, and Dnf3p, respectively; these putative heteromeric PLTs share an essential function for cell growth. We constructed temperature-sensitive mutants of CDC50 in the lem3Δ crf1Δ background (cdc50-ts mutants). Screening for multicopy suppressors of cdc50-ts identified YPT31/32, two genes that encode Rab family small GTPases that are involved in both the exocytic and endocytic recycling pathways. The cdc50-ts mutants did not exhibit major defects in the exocytic pathways, but they did exhibit those in endocytic recycling; large membranous structures containing the vesicle-soluble N-ethylmaleimide-sensitive factor attachment protein receptor Snc1p intracellularly accumulated in these mutants. Genetic results suggested that the YPT31/32 effector RCY1 and CDC50 function in the same signaling pathway, and simultaneous overexpression of CDC50, DRS2, and GFP-SNC1 restored growth as well as the plasma membrane localization of GFP-Snc1p in the rcy1Δ mutant. In addition, Rcy1p coimmunoprecipitated with Cdc50p-Drs2p. We propose that the Ypt31p/32p–Rcy1p pathway regulates putative phospholipid translocases to promote formation of vesicles destined for the trans-Golgi network from early endosomes

Cdc50p, a Protein Required for Polarized Growth, Associates with the Drs2p P-Type ATPase Implicated in Phospholipid Translocation in Saccharomyces cerevisiae

Cdc50p, a transmembrane protein localized to the late endosome, is required for polarized cell growth in yeast. Genetic studies suggest that CDC50 performs a function similar to DRS2, which encodes a P-type ATPase of the aminophospholipid translocase (APT) subfamily. At low temperatures, drs2Δ mutant cells exhibited depolarization of cortical actin patches and mislocalization of polarity regulators, such as Bni1p and Gic1p, in a manner similar to the cdc50Δ mutant. Both Cdc50p and Drs2p were localized to the trans-Golgi network and late endosome. Cdc50p was coimmunoprecipitated with Drs2p from membrane protein extracts. In cdc50Δ mutant cells, Drs2p resided on the endoplasmic reticulum (ER), whereas Cdc50p was found on the ER membrane in drs2Δ cells, suggesting that the association on the ER membrane is required for transport of the Cdc50p-Drs2p complex to the trans-Golgi network. Lem3/Ros3p, a homolog of Cdc50p, was coimmunoprecipitated with another APT, Dnf1p; Lem3p was required for exit of Dnf1p out of the ER. Both Cdc50p-Drs2p and Lem3p-Dnf1p were confined to the plasma membrane upon blockade of endocytosis, suggesting that these proteins cycle between the exocytic and endocytic pathways, likely performing redundant functions. Thus, phospholipid asymmetry plays an important role in the establishment of cell polarity; the Cdc50p/Lem3p family likely constitute potential subunits specific to unique P-type ATPases of the APT subfamily

T1c前立腺癌診断における予測因子としての前立腺体積およびvolume-adjusted prostate-specific antigenの検討

We examined the usefulness of the volume-adjusted prostate-specific antigen (PSA) parameters for prediction of T1c prostate cancer on 210 patients who had abnormal PSA levels but no abnormal findings in digital transrectal examination (DRE) or transrectal ultrasonography (TRUS). PSA, prostate volume (PV), transition zone volume (TZV), PSAD (PSA/PV) and PSATZD (PSA/TZV) were assessed with the receiver operating characteristic (ROC) curve and the area under the curve (AUC). Simple and stepwise logistic regression models were used to calculate the odds ratios of these parameters. Fifty-three (25.2%) of all 210 patients and 31 (19.9%) of 156 patients with intermediate PSA levels had biopsy-proved prostate cancer. The ROC curves of all patients revealed that PSA, PV, TZV, PSAD and PSATZD had significant predictive values, while AUCs of PV, PSAD and PSATZD had significant predictive values as compared to that of PSA. In the patients with intermediate PSA levels, the ROC curves revealed that PV, TZV, PSAD and PSATZD had significant predictive values, but there were no significant differences in AUCs among these parameters. The stepwise logistic regression analysis showed that PV and PSATZD were significant predictive parameters in all patients and that PSATZD was the only significant predictive parameter in the patients with intermediate PSA levels. In conclusion, not only PSAD and PSATZD but also PV and TZV had significant predictive values in discriminating prostate cancer. However, the multivariate analysis showed that PSATZD had the strongest predictive value in all patients and in those with intermediate PSA levels.T1c前立腺癌の診断におけるPSA density(PSAD)およびPSA transition zone density(PSATZD)の有用性について, 生検前にPSAのみに異常を認めた210例について検討した。210例中53例(25.2%), 生検前PSA値がグレーゾーン(4.1～10.0ng/ml)を示した156例中31例(19.9%)が癌と診断された。ROC曲線解析では, 全体210例では, PSA, PSAD, PSATZD, 前立腺体積(PV)および移行域体積(TZV)が癌診断の有効なパラメータであった。グレーゾーンを示した156例では, PSAD, PSATZD, PVおよびTZVが癌診断の有効なパラメータであった。多変量解析ではPSATZDが最も有効なパラメータであった。T1c前立腺癌を疑う症例において, PSATZDが最も有用性が高いことが示された。(著者抄録

Regulation of Renin Expression by &Beta;1-Integrin in As4.1 Juxtaglomerular Line Cells

(1) Background: Renal dysfunction and hypertension are mutually aggravating factors; however, the details of their interaction remain unclear. In a study using renal tissue from diabetic rats, we found that &beta;1-integrin, a cell-substrate adhesion molecule, is specifically phosphorylated in juxtaglomerular cells that secrete renin, a blood pressure regulator. (2) Methods: A mouse juxtaglomerular cell line (As4.1 cells) was used for the following experiments: drug-induced promotion of &beta;1-integrin phosphorylation/dephosphorylation; knockdown of &beta;1-integrin and the cell adhesion molecule connexin-40 (a candidate for the main body of baroreceptor); and pressurization to atmospheric pressure + 100 mmHg. culture in hypotonic liquid medium. The expression of renin under these conditions was measured by qRT-PCR. (3) Results: Phosphorylation of &beta;1-integrin suppressed the expression of renin, while dephosphorylation conversely promoted it. &beta;1-integrin and connexin-40 knockdown both promoted the expression of renin. Pneumatic pressurization and hypotonic medium culture both decreased the expression of renin, which was restored by the knockdown of &beta;1-integrin. (4) Conclusions: &beta;1-integrin plays an inhibitory role in the regulation of the expression of renin, which may be controlled by phosphorylation and dephosphorylation. It is hypothesized that &beta;1-integrin and other adhesion factors regulate the expression of renin by altering the sensitivity of baroreceptors on the plasma membrane

Regulation of Renin Expression by Β1-Integrin in As4.1 Juxtaglomerular Line Cells

(1) Background: Renal dysfunction and hypertension are mutually aggravating factors; however, the details of their interaction remain unclear. In a study using renal tissue from diabetic rats, we found that β1-integrin, a cell-substrate adhesion molecule, is specifically phosphorylated in juxtaglomerular cells that secrete renin, a blood pressure regulator. (2) Methods: A mouse juxtaglomerular cell line (As4.1 cells) was used for the following experiments: drug-induced promotion of β1-integrin phosphorylation/dephosphorylation; knockdown of β1-integrin and the cell adhesion molecule connexin-40 (a candidate for the main body of baroreceptor); and pressurization to atmospheric pressure + 100 mmHg. culture in hypotonic liquid medium. The expression of renin under these conditions was measured by qRT-PCR. (3) Results: Phosphorylation of β1-integrin suppressed the expression of renin, while dephosphorylation conversely promoted it. β1-integrin and connexin-40 knockdown both promoted the expression of renin. Pneumatic pressurization and hypotonic medium culture both decreased the expression of renin, which was restored by the knockdown of β1-integrin. (4) Conclusions: β1-integrin plays an inhibitory role in the regulation of the expression of renin, which may be controlled by phosphorylation and dephosphorylation. It is hypothesized that β1-integrin and other adhesion factors regulate the expression of renin by altering the sensitivity of baroreceptors on the plasma membrane