Accuracy of measurement of radiochromic film density for high-energy X-rays

Radiochromic film (RC-film) is of great interest as a film-type dosimeter for radiation oncology applications. We present a two-dimensional image-based evaluation of the measurement accuracy of a commercial RC-film product (Gafchromic MD-55-2 film, ISP TECHNOLOGIES, Inc.) by using a commercial Laser Densitometer (Model 1710, Computerized Medical Systems, Inc.) as an optical density imaging system. The coefficient of variation of the density (pixel-value) in one sample was approximately 3% to 11% at 3 Gy or less, and 3% or less at 4 to 60 Gy. Although the coefficient of variation between three samples at the same dose was about 14% at 1 Gy, it decreased as the dose increased, reaching several percent. In 1 to 6 Gy samples, geometric imaging artifacts [interference (moire) patterns] were observed, and it was found that scan-sampling pitch influenced the accuracy of measurement of the density of the sample. To improve the accuracy of density measurement, sufficient knowledge about characteristic features of the density measuring system is essential.     

Pilot Phase I/II Study of New Salvage Therapy (CHASE) for Refractory or Relapsed Malignant Lymphoma

A pilot phase I/II study was conducted as a single-institute trial for evaluation of the feasibility and efficacy of a new salvage chemotherapy, CHASE, for patients with refractory or relapsed lymphoma . The CHASE regimen, consisting of cyclophosphamide, cytosine arabinoside, etoposide, and dexamethasone, was administered every 3 weeks in a maximum of 5 courses. A total of 16 patients were eligible and registered for this study. Myelosuppression was the major toxicity. Although grade 4 leukopenia and grade 3 thrombocytopenia were identified in 15 and 16 patients, respectively, duration of the nadir was brief (median, 3 days). Nonhematological grade 4 toxicity was not observed, and transient elevations of bilirubin and grade 3 aspartate aminotransferase/alanine aminotransferase (AST/ALT) were observed in 2 and 3 courses, respectively, in a total of 57 courses. Complete and partial response rates were 71.4% (10/14) and 7.1% (1/14), respectively. The median percentage of maximal CD34+ cells was 6.1% on day 15, and a median number of 1.88 x 10(6) CD34+ cells/kg per apheresis were obtained. Thirteen patients received high-dose chemoradiotherapy followed by autologous peripheral blood stem cell transplantation. With a median follow-up time of 36 months from the start of CHASE, the overall survival rate for the 16 patients was 66.6%. These results indicated that CHASE is a safe and effective salvage regimen for malignant lymphoma, has sufficient mobilizing effect on peripheral blood stem cells, and warrants further phase II study.     

Urinary albumin as an indicator of diabetic nephropathy lesions in Japanese type 2 diabetic patients

Caucasian type 2 diabetic patients with microalbuminuria (MA) or overt nephropathy (ON) show greater heterogeneity of renal lesions than type 1 diabetic patients. We examined whether a similar situation exists in 30 Japanese type 2 diabetic patients [21 male, age 48 +/- (SD) 8 years, known duration 11 +/- (SD) 8 years] without definable renal disease other than diabetic nephropathy. Six patients were normoalbuminuric (NA), 11 MA, and 13 had ON. Normal controls were 9 age-matched Japanese living-related renal transplant donors. Electron microscopic morphometry was performed on renal biopsy specimens and related to renal function. Glomerular basement membrane width and mesangial fractional volume [Vv(Mes/glom)] were increased in all type 2 diabetic patients groups (NA, MA, ON) as compared with normal controls. The Vv(Mes/glom) correlated directly with urinary albumin/creatinine. However, Vv(Mes/glom) as well as glomerular basement membrane width overlapped among the three functional categories (NA, MA, ON) and normal controls. In conclusion: (1) similar to Caucasian type 2 diabetic patients, Japanese type 2 diabetic patients have greater heterogeneity of renal structure than Caucasian type 1 diabetic patients, and (2) urinary albumin is not a reliable indicator of underlying renal structure in Japanese type 2 diabetic patients.     

The three-dimensional ultrastructure of diabetic glomeruli revealed by the quick-freezing and deep-etching method

The three-dimensional ultrastructure of the glomerular basement membrane (GBM) and mesangial matrix (MM) in streptozotocin (STZ)-induced diabetic rats and in one case of a human diabetic nephropathy were examined using the quick-freezing and deep-etching method. In the diabetic rats, the GBM inner layer was diffusely enlarged, and the meshwork structures in the GBM middle layer and the MM were markedly irregular due to the rupturing of fine fibrils. These irregularities and enlargements of the mesh pores in the diabetic rats developed during the experimental period and were significantly different from those in the control rats. Insulin treatment after STZ injection significantly prevented ultrastructural changes in the GBM and MM. The human diabetic case was a 69-year-old male who had been suffering from non-insulin dependent diabetes mellitus for 29 years. He had a background diabetic retinopathy, microalbuminuria and a decrease in lower limb tendon reflexes. Conventional electron microscopy revealed electron-lucent areas in enlarged subendothelial spaces and mesangium. By the quick-freezing and deep-etching method, the GBM inner layer was diffusely enlarged, and the meshwork structure of the GBM middle layer and the MM showed marked irregularity due to the rupturing of fine fibrils. These findings suggest that the initial morphological changes in diabetic nephropathy include structural abnormalities of fine fibrils in the GBM and MM, which may correspond to the subendothelial and mesangial electron-lucent areas as observed in conventional ultrathin sections.     

The spread of human lung cancer cells on collagens and its inhibition by type III collagen

The cell spreading ability of human lung cancer cells on collagen substrata was examined in comparison with normal human tracheal epithelial cells. Plastic dishes or multiwells were coated with type I, III or IV collagen gel at a concentrate of 200 g/cm². Ninety per cent of the normal cells were round on all collagens. Adenocarcinoma RERF-LC-MS and VMRC-LCD cell lines and squamous cell carcinoma VMRC-LCP cell line, which metastasize weakly after intrasplenic transplantation in nude mice, spread relatively poorly. Adenocarcinoma, A549 and SK-LU-1 and squamous cell carcinoma Calu-1 cell lines, which were highly metastatic to liver, spread well. Adenocarcinoma ABC-1 cell line, which is moderately metastatic to liver in nude mice, spread moderately. On type III collagen, three adenocarcinoma cell lines (A549, ABC-1 and VMRC-LCD) gradually started to contract after initial spreading and became round at 24 h. These results suggest that there may be a correlation between the degree of malignancy of human lung cancer cells and their spreading ability on collagen substrata, and that the cell spreading ability may be regulated by type III collagen in some lung cancer cells.     

An association between serum testosterone level and HLA phenotype

The concentration of testosterone was determined in sera of 122 HLA-typed women. Subsequently the women were classified in the category below or above the mean serum testosterone concentration. When the frequencies of HLA antigens were compared in these two categories of women, it was found that HLA-B5 and HLA-B12 antigens were significantly increased in the category of women with serum testosterone level above the mean concentration (P < 0.01 and P < 0.05, respectively). The frequency of HLA-B8 antigen was significantly decreased in the same category of women (P < 0.05). The comparisons of the mean testosterone values of each HLA antigen and the variance analysis have also shown significant differences between the mean of HLA-B8 antigen and the means of other HLA antigens — HLA-A2, A3, A9, B5, B12 and Bw35. These results gave further conclusive evidence that gene(s) inside HLA region influence either the androgen hormone metabolism itself or cellular sensitivity to hormonal action as it has been presented for congenital adrenal hyperplasia.     

Alkaline earth atom doping-induced changes in the electronic and magnetic properties of graphene: a density functional theory study

Density functional theory was used to investigate the effects of doping alkaline earth metal atoms (beryllium, magnesium, calcium and strontium) on graphene. Electron transfer from the dopant atom to the graphene substrate was observed and was further probed by a combined electron localization function/non-covalent interaction (ELF/NCI) approach. This approach demonstrates that predominantly ionic bonding occurs between the alkaline earth dopants and the substrate, with beryllium doping having a variant characteristic as a consequence of electronegativity equalization attributed to its lower atomic number relative to carbon. The ionic bonding induces spin-polarized electronic structures and lower workfunctions for Mg-, Ca-, and Sr-doped graphene systems as compared to the pristine graphene. However, due to its variant bonding characteristic, Be-doped graphene exhibits non-spin-polarized p-type semiconductor behavior, which is consistent with previous works, and an increase in workfunction relative to pristine graphene. Dirac half-metal-like behavior was predicted for magnesium doped graphene while calcium doped and strontium doped graphene were predicted to have bipolar magnetic semiconductor behavior. These changes in the electronic and magnetic properties of alkaline earth doped graphene may be of importance for spintronic and other electronic device applications.

Alkaline earth atom dopants on graphene induce work function tuning and spin polarized electronic properties by ionic bonding.     

Expression of the multidrug resistance-associated protein (MRP) gene in urothelial carcinomas

The intrinsic or acquired resistance of urothelial cancer to chemotherapy is one major obstacle to successful treatment. Generally, the expression level of P-glycoprotein in urothelial cancer is low, so we accordingly investigated the expression of multidrug resistance-associated protein (MRP). We examined the expression of MRP mRNA by means of slot-blotting samples of 11 renal pelvic and/or ureteral tumors, 33 bladder tumors, one lung metastasis from a ureter tumor, 7 non-cancerous urothelia from patients with transitional-cell carcinoma (TCC) and one urothelium from a patient with renal-cell carcinoma (RCC). We also estimated, by Southern blotting, whether or not the MRP gene was amplified in clinical specimens that overexpressed MRP mRNA. MRP was detected immunohistochemically using a polyclonal antibody against MRP. In all, 5 of 11 renal pelvic and/or ureter tumors (45.5%), 17 of 33 bladder tumors (51.5%) and 4 of 7 non-cancerous urothelia of TCC patients (57.1%) expressed more than 2-fold the MRP mRNA levels of drug-sensitive human KB cells. There was no significant difference in the MRP mRNA level between primary and recurrent tumors. Low-grade urothelial carcinomas (G1 and G2 TCCs) expressed significantly higher levels of MRP mRNA than the high-grade G3 TCC. The MRP gene was not amplified in urothelial carcinomas, irrespective of their expression levels of MRP mRNA. Immunohistochemically, MRP was located mainly on the plasma membrane, but also detected on the cytoplasm of cancer cells. MRP may be one mechanism responsible for intrinsic drug resistance in low-grade urothelial cancer. © 1996 Wiley-Liss, Inc.     

Cardiac involvement in Fukuyama muscular dystrophy is less severe than in Duchenne muscular dystrophy

Background

One of the main complications in patients with muscular dystrophies is cardiac dysfunction. The literature on cardiac involvement in patients with Fukuyama congenital muscular dystrophy (FCMD) is limited.

Methylenetetrahydrofolate reductase gene (MTHFR) polymorphisms and reduced risk of malignant lymphoma

Folate and methionine are important nutrients in the "one-carbon" metabolism that is closely associated with DNA synthesis and DNA methylation. Genetic variation in these pathways may change susceptibility to cancer development. We have previously reported associations between lymphoma risk and germline polymorphisms in genes of methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) and methionine synthase (MTR A2756G), finding the genotype other than the MTHFR 677CC/1298AA to confer a half-risk compared to the MTHFR 677CC/1298AA and a 3-fold higher risk with the MTR GG genotype than the AA/AG genotypes. To confirm the association and explore the histological difference, we extended the previous case series. A case-control study was conducted in Japan with a total of 372 lymphoma cases and 500 noncancer controls examined for genotypes. The relative risks were estimated by unconditional logistic regression analysis. In overall analyses, the age-sex adjusted odds ratio (OR) for the subjects harboring MTHFR 677T or 1298C alleles relative to 677CC/1298AA genotype was 0.58 (95% confidence interval: 0.41-0.83, P = 0.002). The MTR GG genotype showed an OR of 1.75 (0.87-3.52, P = 0.114). These findings were validated in separate analyses of the 273 new incident cases. Subgroup analyses according to histological subtype [diffuse large B-cell lymphoma (DLB), follicular lymphoma (FL), low-grade lymphoma of mucosa associated lymphoid tissue (MALT), and others] illustrated similar associations with certain exceptions for FL and MALT. Our data showed an association between the MTHFR polymorphisms and malignant lymphoma risk for all histological subtypes, although the extent of contribution of these polymorphisms may differ somewhat with histological subtype. Lack of association with MTR polymorphism was also confirmed.