Analysis of A-Type and B-Type Highly Polymeric Proanthocyanidins and Their Biological Activities as Nutraceuticals

Proanthocyanidins have a series of heteroflavan-3-ols, (+)-catechin/(−)-epicatechin units, which are linked through a single B-type linkage and a doubly linked A-type linkage. Recently, we have performed the structural characterization of seed shells of the Japanese horse chestnut and fruits of blueberry and cranberry. The molecular sizes of them were higher in the order of blueberry > cranberry > seed shells of the Japanese horse chestnut between the respective fractions. For the analysis of terminal and extension units in those proanthocyanidins, the isolated fractions were subjected to the thiolytic cleavage of the B-type linkages using 1-dodecanethiol, and the resulting degradation products were identified by ultraperformance liquid chromatography coupled with electrospray-ionization mass spectrometry. These analyses provided fast and good resolution of the degradation products and revealed higher proportions of A-type linkages compared with B-type linkages in both isolated fractions in the order of the seed shells > cranberry > blueberry. Moreover, the isolated fractions with higher molecular sizes and those more abundant in the proportions of A-type linkages were found to be more effective in the inhibition of pancreatic lipase activity. The results suggest that A-type highly polymeric proanthocyanidins are promising for the attenuation of lipid digestion as dietary supplements

Increased Intrathecal Chemokine Receptor CCR2 Expression in Multiple Sclerosis

Expression of CCR2, CXCR3 and CCR4 on CD4+ T or CD8+ T cells in blood and cerebrospinal fluid (CSF) for multiple sclerosis (MS) was measured by 3-color flow cytometry, and compared to blood from healthy controls and CSF from patients with other inflammatory neurological diseases (INDs). CD4+CXCR3+/CD4+CCR4+ ratio (representing Th1/Th2 balance) was higher in both CSF and blood of MS patients than those of IND patients or healthy controls. Percentage of CCR2-positive T cells was significantly higher in CSF from MS patients. Increased CCR2 expression on T cells in CSF and Th1/Th2 imbalance may reflect the pathological processes involved in MS

The Influence of Prior Abdominal Surgery on Robot-Assisted Partial Nephrectomy

[Background] We evaluated the influence of prior abdominal surgery on perioperative outcomes in patients who underwent robot-assisted partial nephrectomy in initial Japanese series. [Methods] We reviewed patients with small renal tumors who underwent robot-assisted partial nephrectomy from October 2011 to September 2020 at our institution. Patients with prior abdominal surgery were compared with those without prior surgery based on perioperative outcomes. The chi-square test and Mann–Whitney U test were used for statistical analyses of variables. [Results] Of 156 patients who underwent robot-assisted partial nephrectomy, 90 (58%) had no prior abdominal surgery, whereas 66 patients (42%) underwent prior abdominal surgery. No significant differences in perioperative outcomes were observed between with and without prior abdominal surgery groups. In transperitoneal approach robot-assisted partial nephrectomy, 31 patients (80.4%) had prior abdominal surgery. Trocar insertion time in the with prior abdominal surgery group took longer than the without prior abdominal surgery group (32 vs. 28.5 min, P = 0.031). No significant difference was observed in the conversion rate between the two groups (P = 0.556). [Conclusion] Robot-assisted partial nephrectomy appears to be a safe approach for patients with prior abdominal surgery. In transperitoneal approach robot-assisted partial nephrectomy with prior abdominal surgery, trocar insertion time was longer, but no significant differences were found in other outcomes. Transperitoneal approach robot-assisted partial nephrectomy is thus considered a safe procedure for patients with prior abdominal surgery

Health Related Quality of Life in Japanese Patients with Localized Prostate Cancer: Comparative Retrospective Study of Robot-Assisted Laparoscopic Radical Prostatectomy Versus Radiation Therapy

Background: Radical prostatectomy and radiotherapy are standard treatments for localized prostate cancer. When making decisions about treatment, it is important to not only consider medical information such as the patient’s age, performance status, and complications, but also the impact on quality of life (QOL) after treatment. Our purpose was to compare health related quality of life (HRQOL) after robot-assisted laparoscopic radical prostatectomy (RARP) versus radiation therapy in Japanese patients with localized prostate cancer retrospectively. Methods: Patients with localized prostate cancer receiving RARP or radiotherapy at Tottori University Hospital between October 2010 and December 2014 were enrolled in a retrospective observational study with follow-up for 24 months to December 2016. The Medical Outcome Study 8-Item Short-Form Health Survey was performed before treatment and 1, 3, 6, 12, and 24 months post-treatment. Results: Complete responses to the questionnaire were obtained from 154/227 patients receiving RARP, 41/67 patients receiving intensity-modulated radiation therapy, 35/82 patients receiving low dose rate brachytherapy, and 18/28 patients given low dose rate brachytherapy plus external beam radiation therapy. The median physical component summary score of the Medical Outcome Study 8-Item Short-Form Health Survey was significantly lower at 1 month after prostatectomy than radiotherapy, but was similar for both treatments at 3 months, and was significantly higher at 6, 12 and 24 months after prostatectomy. The median mental component summary score was also significantly lower in the prostatectomy group at 1 month, but not from 3 months onwards. Conclusion: Our study suggested that HRQOL was inferior at 1 month after RARP, however, recovered at 3 months after RARP and was better than after radiotherapy at 6, 12, and 24 months

Endoscopic Ablation of Upper Tract Urothelial Carcinoma: A Report of Two Cases with Long Disease Recurrence-Free Periods

Upper tract urothelial carcinoma (UTUC) is a relatively rare disease that accounts for 5% to 10% of all urothelial carcinomas (UCs). Radical nephroureterectomy (RNU) with a bladder cuff is the current gold standard for the management of UTUC; however, endoscopic ablation is also an option for low-risk UTUC to preserve kidney function. Herein, we present two cases of solitary kidney with a right lower ureteral tumor. Both patients underwent left RNU in the past. An 82-year-old man with a right ureteral tumor whose histopathological examination revealed low-grade UC. Laser ablation was performed with ureteroscopy, and there was no recurrence for 7 years after treatment. A 67-year-old woman with a right lower ureteral tumor whose histopathological examination also revealed low-grade UC. Laser ablation was performed, and there was no recurrence for 5 years after the treatment. We closely followed-up our two patients after RNU. This allowed for early detection of tumor recurrence, after which we could perform laser ablation therapy

Optimal Number of Systematic Biopsy Cores Used in Magnetic Resonance Imaging/Transrectal Ultrasound Fusion Targeted Prostate Biopsy

[Background] In recent years, the effectiveness of magnetic resonance imaging (MRI)-ultrasound fusion targeted biopsy (MRF-TB) has been widely reported. In this study, we assessed the effect of reduction of the number of systematic biopsy (SB) cores on the cancer detection rate (CDR). [Methods] Patients with a high prostate-specific antigen (PSA) level underwent prostate MRI. The Prostate Imaging-Reporting and Data System version 2 (PI-RADS) was then used to rate the lesions. The inclusion criteria were as follows: (1) PSA level between 4.0 and 30.0 ng/mL and (2) patients with one or more lesions on MRI and a PI-RADS score of 3 or more. All enrolled patients were SB naïve or had a history of one or more prior negative SBs. A total of 104 Japanese met this selection criterion. We have traditionally performed 14-core SB following the MRF-TB. In this study, the CDRs of 10-core SB methods, excluding biopsy results at the center of the base and mid-level on both sides, were compared with those of the conventional biopsy method. [Results] We compared CDRs of the 14-core and 10-core SBs used in combination. The overall CDR was 55.8% for the former and 55.8% for the latter, thereby indicating that there was no significant difference (P = 1.00) between the two. In addition, the CDRs of csPCa were 51.9% for the former and 51.1% for the latter, which indicated that there was no significant difference (P = 0.317). [Conclusion] There was no significant difference in the CDR when the number of SB cores to be used in combination was 14 and 10

Identification of a novel therapeutic target that produces irreversible diabeticg lucotoxicky

科学研究費補助金研究成果報告書研究種目: 基盤研究(B)研究期間: 2006～2007課題番号: 18390100研究代表者: 小島 秀人（滋賀医科大学・医学部・准教授）研究分担者: 木村 博（滋賀医科大学・医学部・教授）研究分担者: 藤宮 峯子（滋賀医科大学・医学部・准教授

Construction of an All-in-one Double-conditional shRNA Expression Vector

Gene silencing by RNA interference （RNAi） is widely used for assessing gene function. An important advance in the RNAi field was the discovery that plasmid-based RNAi can substitute for synthetic small interfering RNA in vitro and in vivo. However, constitutive and ubiquitous knockdown of gene expression by RNAi in mice can limit the scope of experiments because this process can lead to embryonic lethality, or result in compensatory overexpression of other genes such that no phenotypic abnormalities occur. Either way, analyses of the physiological roles of the gene of interest in adult mice are not possible. To overcome these limitations, we previously constructed a double-conditional short-hairpin RNA （shRNA） expression vector that can regulate shRNA expression in a spatio-temporal manner with a tetracycline-inducible floxed stuffer sequence selectively excised by application of Cre recombinase. In this study, we aimed to modify this vector to create an all-in-one vector that produces double-conditional transgenic mice through a single round of gene transfer to fertilized eggs. We added a coding region for nuclear localizing Cre （NCre） recombinase with a multi-cloning site for a cell-specific promoter into the double-conditional short-hairpin RNA （shRNA） expression vector that we previously constructed. Using Escherichia coli, we confirmed successful construction of the vector. First, we confirmed isopropyl-β-D-thiogalactopyranoside-induced expression of NCre recombinase through the lac operon as a specific promoter by western blotting. Second, we confirmed functional recombination of the floxed sequence of loxP-like TATA-lox by analysing restriction enzyme-digested fragments. This all-in-one double-conditional shRNA expression vector will be useful for reversible in vitro and in vivo knockdown of target gene expression, in target cells via promoter-specific expression of NCre, and at specific times by tetracycline application