Renal Function Outcomes and Risk Factors for Risk Factors for Stage 3B Chronic Kidney Disease after Urinary Diversion in Patients with Muscle Invasive Bladder Cancer

ObjectivesTo assess the effects of urinary diversion on renal function, we retrospectively investigated renal function over 5 years after urinary diversion using a propensity score matching strategy.MethodsBetween May 1996 and November 2013, 345 consecutive adult patients underwent radical cystectomy and urinary diversion in our hospital; one hundred and fifteen patients with more than a 5-year follow-up were enrolled. Propensity scores were calculated using logistic analysis, and the data used in the analyses included age, gender, Eastern Cooperative Oncology Group Performance Status (ECOG-PS), clinical tumor stage, presence of cardiovascular disease; hypertension; and type 2 diabetes and preoperative eGFR at the initial visit. Multivariate logistic regression analysis was used to assess the risk factors for stage 3B chronic kidney disease (CKD) after the different types of urinary diversion.ResultsContinent and incontinent diversion were performed in 68 and 47 patients, respectively. The mean preoperative eGFR was significantly lower in the incontinent than in the continent group (P < 0.001). In propensity score-matched patients (n = 34 each), no significant differences were observed in pre- and postoperative eGFR and 5-year eGFR decrease rates between the groups. In the incontinent group, the number of postoperative stage 3B CKD patients was significantly increased than the continent group. Using multivariate analysis, independent risk factors significantly associated with stage 3B CKD at 5 years after surgery were older age, eGFR before surgery, incontinent diversion (cutaneous ureterostomy), and postoperative hydronephrosis.ConclusionsThe types of urinary diversion had no significant impact on renal function decline, whereas older age, preexisting impaired renal function, postoperative hydronephrosis, and cutaneous ureterostomy were independent risk factors for stage 3B CKD at 5 years after radical cystectomy.     

Association between Smoking Status and Obesity in a Nationwide Survey of Japanese Adults

Objective

A positive association between the number of cigarettes smoked per day and obesity has been reported, whereas how other smoking-related indices, such as pack-years and duration of smoking, are related with obesity has been less investigated. We analyzed the age-adjusted cross-sectional association between smoking and obesity in a general Japanese population.

Methods

We used data from a nationwide epidemiological study of Japanese adults (N = 23,106). We compared the prevalence of obesity (defined as body mass index ≥ 25kg/m²) among groups classified by smoking behavior, pack-years, number of cigarettes per day, duration of smoking, and duration and time of smoking cessation.

Results

In men, current smokers had a lower odds ratio (OR) for obesity of 0.80 (95% confidence interval (CI): 0.72–0.88) compared to non-smokers, whereas past smokers had a higher OR of 1.23 (95% CI: 1.09–1.37) compared to current smokers. In women, there were no differences in obesity between the three groups classified by smoking behavior. However, in both sexes, the prevalence of obesity tended to increase with pack-years and the number of cigarettes per day, but not with duration of smoking in current and past smokers. Further, in male smokers, the risks for obesity were markedly higher in short-term heavy smokers compared with long-term light smokers, even with the same number of pack-years. Regarding the impact of smoking cessation, female past smokers who quit smoking at an age > 55-years had an elevated OR of 1.60 (95% CI:1.05–2.38) for obesity.

Conclusions

In a general Japanese population, obesity is progressively associated with pack-years and number of cigarettes per day, but not with the duration of smoking. When investigating the association between obesity and cigarette smoking, the daily smoking burden and the duration of smoking require to be independently considered.     

Angiotensin II,as well as 5-hydroxytriptamine,is a potent vasospasm inducer of saphenous vein graft for coronary artery bypass grafting in patients with diabetes mellitus

Diabetes mellitus (DM) is an important risk factor for adverse outcomes of coronary artery bypass grafting. The bypass grafts harvested from patients with DM tend to go into spasm after their implantation into the coronary circulation. To clarify the contribution of 5-hydroxytriptamine (5-HT) and angiotensin II (AngII) in the bypass graft spasm, we examined the contractile reactivity to 5-HT or AngII of isolated human endothelium-denuded saphenous vein (SV) harvested from DM and non-DM patients. The 5-HT-induced constriction of the SV was significantly augmented in the DM group than in the non-DM group, which is similar to our previous report. AngII-induced constriction of the SV was also significantly augmented in the DM group than the non-DM group. Especially in the non-DM group, the AngII-induced maximal vasoconstriction was markedly lower than the 5-HT-induced one. Meanwhile, the increasing rates of AngII-induced vasoconstriction in the DM group to the non-DM group were significantly greater than those of 5-HT-induced vasoconstriction. These results indicate that 5-HT is a potent inducer of SV graft spasm in both DM and non-DM patients, while AngII is a potent inducer of SV graft spasm only in patients with DM. Furthermore, the protein level of AngII AT₁ receptor (AT₁R), but not the protein level of 5-HT_2A receptor, in the membrane fraction of the SV smooth muscle cells of DM patients was significantly increased as compared with that of the non-DM patients. These results suggest that the mechanism for hyperreactivity to AngII in the SV from DM patients is due to, at least in part, the increase in the amount of AT₁R on membrane of the SV smooth muscle cells.     

Sperm lengths of non‐marine cypridoidean ostracods (Crustacea)

Length measurements of sperms of 51 species of Cypridoidea ostracods were taken to supplement the paucity of ostracod sperm data in the published literature. The lengths of the posterior regions (carrying the mitochondria) and the thinner anterior regions were also measured when appropriate. Maximum lengths of sperms for individual species varied from 268 μm for Fabaeformiscandona velifera Smith and Janz, 2008 through to 11 787 μm for Australocypris robusta De Deckker, 1974; these lengths represent the shortest so far recorded for the superfamily and the longest ever recorded in ostracods, respectively. There appears to be only a loose relationship between taxonomy and sperm lengths. Species of the subfamily Candoninae generally have the shortest sperms compared with other subfamilies, but one Candoninae species, Candona altoides Petkovski, 1961, has sperms longer than some species of the families Cyprididae, Ilyocyprididae and Notodromadidae. The family Cyprididae showed the most variation, with sperms ranging from 1000 μm through to 11 787 μm in length. No hypothesis satisfactorily explains the origin of giant sperms in ostracods or the longevity of this trait through geological eras, and their existence remains enigmatic.     

Knockdown of gene expression by antisense morpholino oligos in preimplantation mouse embryos cultured in vitro

Knockdown of gene expression by antisense morpholino oligos (MOs) is a simple and effective method for analyzing the roles of genes in mammalian cells. Here, we demonstrate the efficient delivery of MOs by Endo-Porter (EP), a special transfection reagent for MOs, into preimplantation mouse embryos cultured in vitro. A fluorescein-labeled control MO was applied for monitoring the incorporation of MOs into developing 2-cell embryos in the presence of varying amounts of EP and bovine serum albumin. In optimized conditions, fluorescence was detected in 2-cell embryos within a 3-h incubation period. In order to analyze the validity of the optimized conditions, an antisense Oct4 MO was applied for knockdown of the synthesis of OCT4 protein in developing embryos from the 2-cell stage. In blastocysts, the antisense Oct4 MO induced a decrease in the amount in OCT4 protein to less than half. An almost complete absence of OCT4-positive cells and nearly complete disappearance of the inner cell mass in the outgrowths of blastocysts were also noted. These phenotypes corresponded with those of Oct4-deficient mouse embryos. Overall, we suggest that the delivery of MOs using EP is useful for the knockdown of gene expression in preimplantation mouse embryos cultured in vitro.     

Py-GC/MS analysis of sediments from Lake Biwa,Japan: characterization and sources of humic acids

Humic substances extracted and purified from bottom sediments of northern Lake Biwa, Japan, in November 2012 and 2013 were characterized using elemental analysis, Fourier-transform infrared spectroscopy, hydrogen-1 nuclear magnetic resonance (¹H NMR) analysis, and pyrolysis gas chromatography/mass spectrometry (Py-GC/MS). The infrared (IR) bands in the spectra of humic acids showed the presence of amide linkages and polysaccharides. Results of ¹H NMR analysis showed that the humic acids contained approximately twice the number of aliphatic protons as those in the Japanese soil standards used for comparison. Results of the Py-GC/MS analysis, which evaluates pyrolysis temperature dependency of the amount of pyrolysis products, showed that the generation of pyrolysis products in humic acids also differed from that in Japanese soil standards but was similar to that of phytoplankton in Lake Biwa. This analysis method is the first to provide extensive information about the chemical structure of humic substances; conventional Py-GC/MS provides limited information for a single temperature. Data suggest that humic acids in lake sediments are related to chemical characteristics of phytoplankton. Results shed new light on the origins of humic substances in deep-water-lake sediments and provide insights into material recycling in such sediments.     

Vitamin B12 deficiency-induced increase of osteoclastic bone resorption caused by abnormal renal resorption of inorganic phosphorus via Napi2a

Vitamin B₁₂ deficiency is a risk factor for bone disorders via mechanisms not fully understood. In this study, an increase in serum inorganic phosphorus (Pi) concentrations was associated with a vitamin B₁₂ deficiency. Napi2a, a renal cotransporter for Pi reabsorption, accumulated on plasma membranes in a vitamin B₁₂ deficiency suggests that vitamin B₁₂ plays an important role in Pi homeostasis.     

Identification of a highly immunogenic mouse breast cancer sub cell line, 4T1-S

Cancer vaccines serve as a promising clinical immunotherapeutic strategy that help to trigger an effective and specific antitumor immune response compared to conventional therapies. However, poor immunogenicity of tumor cells remains a major obstacle for clinical application, and developing new methods to modify the immunogenicity of tumor cells may help to improve the clinical outcome of cancer vaccines. 4T1 mouse breast cancer cell line has been known as poorly immunogenic and highly metastatic cell line. Using this model, we identified a sub cell line of 4T1—designated as 4T1-Sapporo (4T1-S)—which shows immunogenic properties when used as a vaccine against the same line. In 4T1-S-vaccinated mice, subcutaneous injection of 4T1-S resulted in an antitumor inflammatory response represented by significant enlargement of draining lymph nodes, accompanied with increased frequencies of activated CD8 T cells and a subpopulation of myeloid cells. Additionally, 4T1-S vaccine was ineffective to induce tumor rejection in nude mice, which importantly indicate that 4T1-S vaccine rely on T cell response to induce tumor rejection. Further analysis to identify mechanisms that control tumor immunogenicity in this model may help to develop new methods for improving the efficacies of clinical cancer vaccines.