Induction of radioresistance to accelerated carbon-ion beams in recipient cells by nitric oxide excreted from irradiated donor cells of human glioblastoma

PURPOSE: To investigate whether nitric oxide excreted from cells irradiated with accelerated carbon-ion beams modulates cellular radiosensitivity against irradiation in human glioblastoma A-172 and T98G cells. MATERIALS AND METHODS: Western-blot analysis of inducible nitric oxide synthase, hsp72 and p53, the concentration assay of nitrite in medium and cell survival assay after irradiation with accelerated carbon-ion beams were performed. RESULTS: The accumulation of inducible nitric oxide synthase was caused by accelerated carbon-ion beam irradiation of T98G cells but not of A-172 cells. The accumulation of hsp72 and p53 was observed in A-172 cells after exposure to the conditioned medium of the T98G cells irradiated with accelerated carbon-ion beams, and the accumulation was abolished by the addition of an inhibitor for inducible nitric oxide synthase to the medium. The radiosensitivity of A-172 cells was reduced in the conditioned medium of the T98G cells irradiated with accelerated carbon-ion beams compared with conventional fresh growth medium, and the reduction of radiosensitivity was abolished by the addition of an inducible nitric oxide synthase inhibitor to the conditioned medium. CONCLUSIONS: Nitric oxide excreted from the irradiated donor cells with accelerated carbon-ion beams could modulate the radiosensitivity of recipient cells. These findings indicate the importance of an intercellular signal transduction pathway initiated by nitric oxide in the cellular response to accelerated heavy ions.     

Intraoperative hemodilutional autotransfusion using a closed circuit for patients of Jehovah's Witness

We conducted hemodilutional autotransfusion using a closed circuit combined with a cell washing reinfusing system (Cell Saver) for two surgical patients of Jehovah's Witness. One was a 12 yr-old boy for extirpation of the teratoma in the anterior mediastinum and another was a 44 yr-old woman for left total hip replacement. The patients and their relatives had consented to the use of blood substitutes, hemodilutional autotransfusion using a closed circuit and Cell Saver. We devised a closed circuit system for hemodilutional autotransfusion combined with Cell Saver, in which two pumps for blood transfusion were used; one was for drawing blood from the femoral or the internal jugular vein and the other for returning blood to the peripheral vein. Blood volume in a bag interposed in the closed circuit was easily controlled by adjusting the speed of each pump. Blood collected from the surgical field by Cell Saver was also led to the bag. Acid citrate dextrose solution was infused into the closed circuit from the site close to the blood drawing. Both of our surgical patients were safely managed without homologus blood transfusion, although there remained some problems concerning the use of anticoagulants.     

Relationship of coffee consumption with a decline in kidney function among patients with type 2 diabetes: The Fukuoka Diabetes Registry

Aims/IntroductionThe evidence regarding the effects of coffee consumption on incident chronic kidney disease is inconclusive, and no studies have investigated the relationship in patients with diabetes. We aimed to prospectively investigate the relationship between coffee consumption and the decline in estimated glomerular function rate (eGFR) in patients with type 2 diabetes.Materials and MethodsA total of 3,805 patients (2,112 men, 1,693 women) with type 2 diabetes (mean age 64.2 years) and eGFR ≥60 mL/min/1.73 m² were followed (completion of follow up, 97.6%; median 5.3 years). Coffee consumption was assessed at baseline. The end‐point was a decline in eGFR to <60 mL/min/1.73 m² during the follow‐up period.ResultsDuring follow up, 840 participants experienced a decline in eGFR to <60 mL/min/1.73 m². Higher coffee consumption reduced the risk of decline in eGFR. Compared with no coffee consumption, the multivariate‐adjusted hazard ratios (95% confidence intervals) were 0.77 (0.63–0.93) for less than one cup per day, 0.77 (0.62–0.95) for one cup per day and 0.75 (0.62–0.91) for two or more cups per day (P for trend 0.01). This trend was unaffected by further adjustment for baseline eGFR and albuminuria. The mean eGFR change per year was −2.16 mL/min/1.73 m² with no coffee consumption, −1.89 mL/min/1.73 m² with less than one cup per day, −1.80 mL/min/1.73 m² with one cup per day and −1.78 mL/min/1.73 m² with two or more cups per day (P for trend 0.03).ConclusionsCoffee consumption is significantly associated with a lower risk of decline in eGFR in patients with type 2 diabetes.     

Hit-and-runs more common with pedestrians lying on the road: Analysis of a nationwide database in Japan

Purpose: To determine the trends with fatally or otherwise injured pedestrians lying on the road and the relationship to hit-and-run incidents in Japan. Methods: We extracted data for 2012e2016 from the records of the Institute for Traffic Accident Research and Data Analysis, Japan, a nationwide traffic accident database. All the injured and fatally injured pedestrians were selected. We examined the levels of pedestrian injury, vehicle speed immediately before the collision, whether or not the pedestrian was lying on the road, and hit-and-run incidents. Chi-square test was employed to make a statistical comparison between the two groups. Results: The database contained data on 286,383 pedestrian casualties and 7256 fatalities; 8.3% of fatalities (602 persons) and 0.6% of casualties (1827 persons) involved pedestrians lying on the road. The rates of fatalities and severe injuries were significantly higher for pedestrians who were lying on the road than for those who were not. Hit-and-run incidents were evident in 4.0% of casualties and 7.3% of fatalities. The rate of hit-and-run cases was also significantly higher among pedestrians who were lying on the road. Among fatally injured pedestrians not lying on the road, the rates with speeds of 30 km/h did not differ significantly between hit-and-run and other cases. However, when the pedestrians were lying on the road, the rate was significantly increased in hit-and-run cases. Conclusion: This is the first report to focus on pedestrians lying on the road and being involved in hitand-run incidents. In addition to preventing hit-and-run incidents, prevention of pedestrians lying on the road could also decrease fatalities.     

Latent class models for medical diagnostic tests in multicenter trials

Medical diagnostic tests must enjoy appropriate validity and high reliability in order to qualify as adequate assessment tools. Without a gold standard test, available medical diagnostic tests are not perfect; hence, the reliability of such tests must be evaluated precisely. Kappa coefficient statistics are often utilized to assess reliability of tests when there are two or more medical diagnostic tests. However, the statistics are imprecise for a typical case when the prevalence rate of a target disease is unknown. Although latent class models could be used to assess reliability, the models cannot estimate reliability in the case of two tests, due to unidentifiability or the lack of degrees of freedom. An alternative approach to assess reliability for the case of two tests is stratifying a two‐by‐two contingency table under the assumption that sensitivities and specificities between the two tests be equal over all strata and that prevalence rates in the strata be different from each other. Because stratification is basically a multi‐sample analysis, it should not be applied to the situation where subsamples (i.e., centers) are randomly selected from a larger population. In this article, a type of mixed‐effect model is proposed to evaluate the reliability of two tests for trials in randomly selected multiple centers. Several types of distributions for prevalence rates over subpopulations are considered. Simulation studies show that our proposed method performs nicely. Analysis of real data is also reported. Copyright © 2013 John Wiley & Sons, Ltd.     

Heterogeneity of Glycosylation of Circulating Active and Inactive Renin

ABSTRACT

Concanavalin A chromatography was used to examine rat plasma and the incubation medium of rat renal cortical slices, the objective being to assess the heterogeneity of glycosylation of active and inactive renin. Inactive renin was measured by activation with trypsin. Concanavalin A chromatography could separate both active and inactive renin in the plasma into three forms, including the unbound form, the loosely-bound form and the tightly-bound form, thereby suggesting the presence of differently glycosylated forms of active and inactive renin in the plasma. Rat renal cortical slices secreted all these three forms of active and inactive renin, hence these forms are mainly of renal origin. These results suggest that differently glycosylated forms of active and inactive renin are released from the kidney into the blood circulation.     

Mechanistic Study of the Oxidative Degradation of the Triazole Antifungal Agent CS-758 in an Amorphous Form

In this study, the degradates generated from a pharmaceutical solid were characterized, and a mechanistic pathway underlying their formation was proposed. The chemical stability of a novel triazole antifungal drug, CS‐758, deteriorated significantly when the crystal was disordered, and characteristic degradates were generated. A total of eight degradates in solution and nine degradates in a solid state were isolated by preparative liquid chromatography. Degradates were characterized using high‐performance liquid chromatography–photodiode array, mass spectrometry, and nuclear magnetic resonance. Radical‐mediated oxidation is proposed as the main degradation pathway in the solid state. The initiation step of this pathway is hydrogen atom abstraction from a methine carbon that is adjacent to a dien moiety and the formation of a delocalized vinylic radical intermediate. Molecular oxygen is then added to the radical position to form hydroperoxides. There are three potential oxidation routes based on the proposed autoxidation pathway that lead to the generation of the dioxane ring‐opening hydroxyl form, the 9,10‐epoxide form, or the 11,12‐epoxide form, depending on the substituted position of the added molecular oxygen. The epimer compound generated via the vinylic radical intermediate and sulfoxides was characterized. This degradation mechanism provides the scientific foundation for an oxidative stressing system currently under investigation.     

MR imaging of adrenal masses smaller than 5 cm. Characterization with T2 relaxation time at 1.5 T]

The T2 relaxation times of 28 adrenal masses smaller than 5 cm obtained using a 1.5 Tesla MR imaging system were analysed to evaluate the ability of this parameter to characterize the tissue masses. The adrenal masses included 13 nonhyperfunctioning adenomas, five hyperfunctioning adenomas, five metastatic tumors, two pheochromocytomas, one nodular hyperplasia, one ganglioneuroma, and one cyst. The mean T2 value of nonhyperfunctioning adenomas was almost the same as that of hyperfunctioning adenomas. A significant difference was found in T2 (p less than 0.01) between nonhyperfunctioning adenoma (50 msec +/- 7 msec; mean +/- S.D.) and metastatic tumor (63 msec +/- 11 msec), whereas there was no significant difference in mass size between them. The two pheochromocytomas and the ganglioneuroma, which were derived from adrenal medulla, had relatively long T2 of over 70 msec. The T2 values of nodular hyperplasia and adrenal cyst were 58 msec and 123 msec, respectively. Although the T2 values of metastatic tumors tended to be longer than those of nonhyperfunctioning adenomas, differentiation between them with a T2 of 60 msec was not necessarily possible, especially in smaller masses. The T2 values of two metastatic tumors of less than 2 cm indicated 50 msec levels. There seemed to be a correlation between mass size and T2 in metastatic tumors. In adenomas, however, no significant correlation was demonstrated. We conclude that the characterization of small adrenal masses by T2 at 1.5 Tesla is unsatisfactory in differentiating metastatic tumors from nonhyperfunctioning adenomas.