Increased urinary excretion of monocyte chemoattractant protein-1 in proteinuric renal diseases

Monocyte chemoattractant protein-1 (MCP-1) is a chemokine that is produced mainly by tubular epithelial cells in kidney and contributes to renal interstitial inflammation and fibrosis. More recently, we have demonstrated that urinary MCP-1 excretion is increased in proportion to the degree of albuminuria (proteinuria) and positively correlated with urinary N-acetylglucosaminidase (NAG) levels in type 2 diabetic patients. Based on these findings, we have suggested that heavy proteinuria, itself, probably aggravates renal tubular damage and accelerates the disease progression in diabetic nephropathy by increasing the MCP-1 expression in renal tubuli. In the present study, to evaluate whether urinary MCP-1 excretion is increased in the proteinuric states not only in diabetic nephropathy but also in other renal diseases, we examined urinary MCP-1 levels in IgA nephropathy patients with macroalbuminuria (IgAN group; n = 6), and compared the results with the data obtained from type 2 diabetic patients with overt diabetic nephropathy (DN group; n = 23) and those without diabetic nephropathy (non-DN group; n = 27). Urinary MCP-1 excretion levels in non-DN, DN, IgAN groups were 157.2 (52.8-378.5), 346.1 (147.0-1276.7), and 274.4 (162.2-994.5) ng/g creatinine, median (range), respectively. Expectedly, urinary MCP-1 and NAG excretion levels in DN and IgAN groups were significantly elevated as compared with non-DN group. Therefore, we suggest that MCP-1 expression in renal tubuli is enhanced in proteinuric states,irrespective of the types of renal disease, and that increased MCP-1 expression probably contributes to renal tubular damage in proteinuric states.     

The effect of repeated small doses of radiation on cell killing and repair capacity in plateau phase C3H 10T 1/2 cells

Using plateau phase C3H 10 T 1/2 cells, we studied the effect of multiple-dose irradiation on the repair capacity of cells after further irradiation. Cells were irradiated with repeated doses of 2.5 Gy delivered two fractions per day at 6 to 7 hours interval. The cell survival after exposure to 1 to 9 fractions was lower above fractions as compared to that predicted by calculating from single dose survival curve by assuming that cells retain their capacity to repair radiation damage after each fraction. Repair kinetics experiments showed that cells were less able to repair only slow type potentially lethal damage after test dose following multiple dose irradiations. Thus, it would appear that an enhancement of the lethal expression of potentially lethal damage of three types of damage may, at least in part, contribute to the difference between the cell survival curve after multiple fractions and that predicted by calculation.     

Consensus Paper: Neuroimmune Mechanisms of Cerebellar Ataxias

In the last few years, a lot of publications suggested that disabling cerebellar ataxias may develop through immune-mediated mechanisms. In this consensus paper, we discuss the clinical features of the main described immune-mediated cerebellar ataxias and address their presumed pathogenesis. Immune-mediated cerebellar ataxias include cerebellar ataxia associated with anti-GAD antibodies, the cerebellar type of Hashimoto’s encephalopathy, primary autoimmune cerebellar ataxia, gluten ataxia, Miller Fisher syndrome, ataxia associated with systemic lupus erythematosus, and paraneoplastic cerebellar degeneration. Humoral mechanisms, cell-mediated immunity, inflammation, and vascular injuries contribute to the cerebellar deficits in immune-mediated cerebellar ataxias.     

Comparison of dose accuracy between 2D array detectors for pre-treatment IMRT QA

The dosimetric properties between various 2D array detectors were compared and were evaluated with regard to the accuracy in absolute dose and dose distributions for clinical treatment fields. We used to check the dose accuracy: 2D array detectors; MapCHECK (Sun Nuclear), EPID (Varian Medical Systems), EPID-based dosimetry (EPIDose, Sun Nuclear), COMPASS (IBA) and conventional system; EDR2 film (Eastman Kodak), Exradin A-14SL ion chamber (0.016 cc, Standard Imaging). First, we compared the dose linearity, dose rate dependence, and output factor between the 2D array detectors. Next, the accuracy of the absolute dose and dose distributions were evaluated for clinical fields. All detector responses for the dose linear were in agreement within 1%, and the dose rate dependence and output factor agreed within a standard deviation of ±1.2%, except for EPID. This is because EPID is fluence distributions. In all the 2D array detectors, the point dose agreed within 5% with treatment planning system (TPS). Pass rates of each detector for TPS were more than 97% in the gamma analysis (3 mm/3%). EPIDose was in a good agreement with TPS. All 2D array detectors used in this study showed almost the same accuracy for clinical fields. EPIDose has better resolution than other 2D array detectors and thus this is expected for dose distributions with a small field.     

Cone-beam computed tomography-derived adaptive radiotherapy

The purpose of this study was to evaluate the reliability of cone-beam computed tomography (CBCT)-derived adaptive radiotherapy. We evaluate planning computed tomography (pCT) and CBCT in 50 patients who had undergone image guided radiotherapy (IGRT) with CBCT. Irradiated sites included head, neck, chest, abdomen, and pelvis; there were 10 patients in each group. Treatment plans including 153 beam data were recalculated based on CBCT. To compare between pCT and CBCT, we estimated CT values of normal tissues, body contour, effective depth, and monitor units (MU) calculation. The maximum difference in CT values was observed in lung estimation. The 5 mm or more differences in depth were observed in 2 beams of 2 pelvic cases, but CBCT also demonstrated a shift of abdominal wall due to intestinal motility. There were downward trends for the effective depth and MU based on CBCT, especially in lung cases. However, the differences in prescribed dose due to MU calculation were less than 5% because all patients were treated with a multifield irradiation plan. CBCT provides not only precise daily setup but also accurate anatomical information on body contour. In addition, CBCT may be considered as a useful tool for dose calculation.     

Effect of cimetidine on gastric mucus glycoprotein biosynthesis

The effects of cimetidine on gastric mucus glycoprotein biosynthesis in rat gastric mucosa were investigated using organ culture technique. 2 h following oral administration of cimetidine (40 mg/kg body weight), corpus tissue was placed in the organ culture. Mucus glycoprotein synthesis was accelerated to 137% of control (p less than 0.01). In order to investigate the direct effect of cimetidine on mucus glycoprotein biosynthesis, corpus tissue was cultured in the medium containing cimetidine. 100 microM cimetidine enhanced mucus glycoprotein biosynthesis to 174% (p less than 0.01). Cimetidine was found to stimulate gastric mucus glycoprotein biosynthesis both in vivo and in vitro.