Altered expression of p27Kip1‐interacting cell‐cycle regulators in the adult testicular germ cell tumors: potential role in tumor development and histological progression

We examined the potential role of cell‐cycle dysregulation in the development and histological progression of adult testicular germ cell tumors (TGCTs). Expressions of p27^Kip1‐interacting cell‐cycle regulators (down‐regulation of p27^Kip1 and overexpression of Skp2, Cks1, cyclin A, and cyclin E) and Ki‐67 labeling index (LI) were immunohistochemically examined in histological components of 50 intratubular germ cell neoplasms, unclassified (IGCNUs); 74 seminomas; and 25 embryonal carcinomas, identified from 88 patients. Altered expression of p27^Kip1, Skp2, Cks1, cyclin A, and cyclin E was observed in 20%, 12%, 16%, 10%, and 24% of IGCNUs; 26%, 36%, 27%, 89%, and 23% of seminomas; and 48%, 68%, 56%, 100%, and 60% of embryonal carcinomas, respectively. A significant difference in the frequency of Skp2 and cyclin A overexpression was observed between IGCNUs and seminomas. Significantly more frequent alterations of Skp2, Cks1, and cyclin E and p27^Kip1 were detected in embryonal carcinomas than in seminomas. Alterations of all cell‐cycle regulators were significantly more frequent in embryonal carcinomas than in IGCNUs. The mean Ki‐67 LI significantly increased from IGCNU (21.2%) through seminoma (34.7%) to embryonal carcinoma (54.2%). These results suggest that alterations of the p27^Kip1‐interacting cell‐cycle regulators are common in TGCTs and may be involved in their histological progression.     

The future of clinical laboratory database management system]

To assess the present status of the clinical laboratory database management system, the difference between the Clinical Laboratory Information System and Clinical Laboratory System was explained in this study. Although three kinds of database management systems (DBMS) were shown including the relational model, tree model and network model, the relational model was found to be the best DBMS for the clinical laboratory database based on our experience and developments of some clinical laboratory expert systems. As a future clinical laboratory database management system, the IC card system connected to an automatic chemical analyzer was proposed for personal health data management and a microscope/video system was proposed for dynamic data management of leukocytes or bacteria.     

Underestimation of urinary biomarker-to-creatinine ratio resulting from age-related gain in muscle mass in rats

Recent efforts have been made to identify useful urinary biomarkers of nephrotoxicity. Furthermore, the application of urine to the other toxicities as new biomarker source has been recently expanded. Meanwhile, correction of urinary biomarker concentrations according to fluctuations in urine flow rate is required for adequate interpretation of the alteration. The urinary biomarker-to-creatinine ratio (UBCR) is widely used because of the convenience, while the urinary biomarker-excretion rate is regarded as the gold standard corrective method. Because creatinine is a catabolite in energy production in muscles, we hypothesized that altered muscle mass could affect creatinine kinetics, ultimately affecting UBCR. However, no study has examined this hypothesis. In this study, we examined the influence of muscle mass gain on UBCR, using male Sprague-Dawley rats during the growth phase, 6–12-week old. Both plasma creatinine and excretion of urinary creatinine (Ucr excretion) showed increases with muscle mass gain in rats, in which the alterations of UBCR were lowered. The renal mRNA level of the organic cation transporter-2 (Oct2), a creatinine transporter, showed an age-related increase, whereas the mRNA level of multidrug and toxin extrusions-1 (Mate1) remained constant. Multiple regression analysis showed that the increase in creatinine clearance highly contributed to the age-related increase in Ucr excretion compared to the mRNA levels of Oct2 and Mate1. This suggested that the age-related increase in Ucr excretion may be attributable to the increased transglomerular passage of creatinine. In conclusion, the results suggest that muscle mass gain can affect creatinine kinetics, leading to underestimation of UBCR. Therefore, it is important to understand the characteristics of the corrective method when using urinary biomarker, the failure of which can result in an incorrect diagnosis.     

Waist circumference,but not body mass index,is a predictor of ventricular remodeling after anterior myocardial infarction

ObjectiveThe impact of obesity on ventricular remodeling after myocardial infarction (MI) is still poorly understood. Therefore, the aim of this study was to evaluate the role of waist circumference (WC) and body mass index as predictors of cardiac remodeling in patients after an anterior MI.MethodsEighty-three consecutive patients with anterior MI were prospectively evaluated. Clinical characteristics and echocardiographic data were analyzed at admission and at a 6-mo follow-up. Ventricular remodeling was defined as a 10% increase in left ventricular end-systolic or end-diastolic diameter at the 6-mo follow-up.ResultsIn our study, 83 consecutive patients were evaluated (72% men). Ventricular remodeling was present in 31% of the patients (77% men). Patients with remodeling had higher creatine phosphokinase and creatine phosphokinase-MB peak values, a higher resting heart rate, a larger left atrial diameter, and a larger interventricular septum diastolic thickness. In addition, patients with remodeling had lower peak velocity of early ventricular filling deceleration time and ejection fraction. Patients with remodeling presented higher WC values (with remodeling, 99.2 ± 10.4 cm; without remodeling, 93.9 ± 10.8 cm, P = 0.04), but there were no differences in the body mass index values. In the logistic regression analysis, WC, adjusted by age, gender, ejection fraction, and creatine phosphokinase levels, was an independent predictor of left ventricular remodeling (odds ratio 1.067, 95% confidence interval 1.001–1.129, P = 0.02).ConclusionWaist circumference, but not body mass index, is a predictor of ventricular remodeling after an anterior MI. Therefore, the WC of these patients should be measured in clinical practice.