Outline of the revision of ISO 15189 and accreditation of medical laboratory for specified health checkup

GOAL which accredited medical laboratory aims at is to continue "offering useful laboratory's service for patient medicine and treatment or the health of the nation". The medical laboratory, administers a quality management system, is competent technically and offers laboratory's service to satisfy the needs of all patients and clinicians taking responsibility for the medical testing and treatment. International standard ISO 15189 is a tool to embody thought of its basic quality and scientific grounds about the test result, and it was published in 2003. A revision for one part was considered to be it, and it was published afterwards for ISO 15189: 2,007 in this April. On the other hand, Ministry of Health, Labour and Welfare announced that all insurance members from 40 years old to 74 years old must have a checkup by the specified health checkup that paid its attention to visceral fat type obesity from April, 2008. And, in a standard health checkup program, it is shown that it strengthens the quality assurance management of laboratory carrying out medical testing. ISO 15189 which prescribed quality and competence of medical laboratory is an excellent standard, and it is hoped that it can offer high quality medical testing data with using quality management system. Here, I explain both outline of revised ISO 15189 and accreditation of the medical laboratory for specified health checkup using with this standard.     

Impairment of PI3-K/Akt pathway underlies attenuated endothelial function in aorta of type 2 diabetic mouse model

The phosphatidylinositol 3-kinase (PI3-K) pathway, which activates serine/threonine protein kinase Akt, enhances endothelial nitric oxide synthase (eNOS) phosphorylation and nitric oxide (NO) production. We investigated the involvement of the PI3-K/Akt pathway in the relaxation responses to acetylcholine (ACh) and clonidine in a new type 2 diabetic model (streptozotocin plus nicotinamide-induced diabetic mice). Plasma glucose and insulin levels were significantly elevated in our model, and intravenous glucose tolerance tests revealed clear abnormalities in glucose tolerance and insulin responsiveness. Although in our model the ACh-induced relaxation and NOx- (NO2-+NO3-)/cGMP production were unchanged, the clonidine-induced and insulin-induced relaxations and NOx-/cGMP production were all greatly attenuated. In control mice, the clonidine-induced and insulin-induced relaxations were each abolished by LY294002 and by Wortmannin (inhibitors of PI3-K), and also by Akt-inhibitor treatment. The ACh-induced relaxation was unaffected by such treatments in either group of mice. The expression level of total Akt protein was significantly decreased in the diabetic mice aorta, but those for the p85 and p110gamma subunits of PI3-K were not. The clonidine-induced Ser-473 phosphorylation of Akt through PI3-K was significantly decreased in our model; however, that induced by ACh was not. These results suggest that relaxation responses and NO production mediated via the PI3-K/Akt pathway are decreased in this type 2 diabetic model. This may be a major cause of endothelial dysfunction (and the resulting hypertension) in type 2 diabetes.     

Role of the suprachiasmatic nuclei of the hypothalamus on diurnal rhythm in cardiac arrhythmias

Summary Ambulatory EGG and EEG recordings were recorded under a 14/10-h light-dark illumination schedule using rats. The rats consisted of two groups: a suprachiasmatic (Sch) lesioned group (n=5) and a normal control group (n=5). Bilateral Sch nuclei were lesioned electrically (DC, 2.5 mA, 30 s for each) using a pair of platinum electrodes 0.3 mm in diameter. After recovery from surgery, recordings of ECGs (leads I, II, and III) and EEGs from the cortex and the left dorsal hippocampus were continued for 6 days. Diurnal periodicity in bradyarrhythmia (sinoatrial block, atrioventricular block) and heart rate was analyzed by the least square fit of 24-h cosines. Significant diurnal rhythm was observed in control rats, whereas Sch-lesioned rats showed no significant diurnal rhythm. The integrity of the Sch nuclei, therefore, is necessary for the generation and/or the expression of diurnal periodicity in bradyarrhythmia in rats.     

Relationship between the door-to-TIMI-3 flow time and the infarct size in patients suffering from acute myocardial infarction: analysis based on the fibrinolysis and subsequent transluminal (FAST-3) trial.

BACKGROUND: The purpose of this study was to use the findings of a fibrinolysis and subsequent transluminal trial (FAST-3) to evaluate the association between the target time for obtaining a thrombolysis in myocardial infarction (TIMI)-3 flow after arrival at the emergency room with acute myocardial infarction (AMI) and the degree of myocardial salvage. METHODS AND RESULTS: The FAST-3 trial was administered to 100 patients suffering from AMI. Ranges in the door-to-TIMI-3 flow time (D-T3-time: TIMI-3 flow after arrival at the emergency room) according to quartile were as follows: 30-54 min (quartile 1), 55-77 min (quartile 2), 78-120 min (quartile 3) and 121-330 min (quartile 4). Peak creatine kinase (CK), peak CK-MB, and peak troponin-T values increased in a stepwise fashion across the increasing quartiles of D-T3-time. The left ventricular end diastolic volume index at 30 days after the start of treatment showed low values for quartile 1. In multiple logistic regression analyses for independent predictors of myocardial damage, the adjusted odds ratios for myocardial damage (peak CK>3,000 U/L) in quartiles 3 and 4 of the D-T3-time were 4.0 (95% CI: 1.0-16.1) and 7.0 (95% confidence interval (CI): 1.4-36.0), respectively. CONCLUSIONS: These findings suggest that physicians should monitor the D-T3-time for at least 55 min.     

Essential role of PDGFRalpha-p70S6K signaling in mesenchymal cells during therapeutic and tumor angiogenesis in vivo: role of PDGFRalpha during angiogenesis

Discovery of the common and ubiquitous molecular targets for the disruption of angiogenesis, that are independent of the characteristics of malignant tumors, is desired to develop the more effective antitumor drugs. In this study, we propose that the platelet-derived growth factor receptor-alpha (PDGFRalpha)-p70S6K signal transduction pathway in mesenchymal cells, which is required for functional angiogenesis induced by fibroblast growth factor-2, is the potent candidate. Using murine limb ischemia as a tumor-free assay system, we demonstrated that p70S6K inhibitor rapamycin (RAPA) targets mesenchymal cells to shut down the sustained expression of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF), via silencing of the PDGFRalpha-p70S6K pathway. Irrespective of the varied expression profiles of angiogenic factors in each tumor tested, RAPA constantly led the tumors to dormancy and severe ischemia in the time course, even associated with upregulated expression of VEGF from tumors. Because RAPA showed only a minimal effect to hypoxia-related expression of VEGF in culture, these results suggest that RAPA targets the host-vasculature rather than tumor itself in vivo. Thus, our current study indicates that the PDGFRalpha-p70S6K pathway is an essential regulator for FGF-2-mediated therapeutic neovascularization, as well as for the host-derived vasculature but not tumors during tumor angiogenesis, via controlling continuity of expression of multiple angiogenic growth factors.     

Underweight status at diagnosis is associated with poorer outcomes in adult patients with acute myeloid leukemia: a retrospective study of JALSG AML 201

Recent studies have described various impacts of obesity and being overweight on acute myeloid leukemia (AML) outcomes in adult patients, but little is known about the impact of being underweight. We compared the outcomes of underweight patients to those of normal weight and overweight patients. Adult patients with AML who registered in the JALSG AML201 study (n = 1057) were classified into three groups: underweight (body mass index [BMI] < 18.5, n = 92), normal weight (BMI 18.5–25, n = 746), and overweight (BMI ≥ 25, n = 219). With the exception of age and male/female ratio, patient characteristics were comparable among the three groups. Rates of complete remission following induction chemotherapy were similar among the three groups (p = 0.68). We observed a significant difference in overall survival (OS), disease-free survival (DFS), and non-relapse mortality (NRM) between underweight and normal weight patients (3-year OS 34.8 vs. 47.7%, p = 0.01; DFS 28.6 vs. 39.8%, p = 0.02; 1-year NRM 6.2 vs. 2.6%, p = 0.05), but not between underweight and overweight patients. In multivariate analysis, underweight was an independent adverse prognostic factor for OS (p < 0.01), DFS (p = 0.01), and NRM (p = 0.04). During the first induction chemotherapy, the incidences of documented infection (DI) and severe adverse events (AEs) were higher in underweight patients than those in normal weight patients (DI 16 vs. 8.1%, p = 0.04; AE 36 vs. 24%, p = 0.05). In conclusion, underweight was an independent adverse prognostic factor for survival in adult AML patients.