Morphologic and biologic studies were undertaken to clarify the biologic significance of basic fibroblast growth factor (bFGF) in human thyroid neoplasms. A total of 71 malignant tumors (50 papillary carcinomas, 14 follicular carcinomas, 7 anaplastic carcinomas), 11 follicular adenomas, 6 adenomatous goiters, and 6 Graves' disease tissues were examined employing immunohistochemical methods (avidin-biotin-peroxidase complex technique). An affinity-purified polyclonal rabbit antiserum to human bFGF was used as a primary antibody. The eluate of malignant thyroid tumor tissues from the heparin-Sepharose column was examined by Western blot analysis to elucidate the molecular weight form. With immunohistochemical staining, bFGF was frequently detected in the cytoplasm of malignant thyroid tumors compared to tissues of the benign diseases and normal controls. With anaplastic carcinoma, immunoreactivity of the tumor cells was particularly strong. In the correlative analyses between UICC TNM classification and bFGF staining in papillary carcinoma, there were significant differences when relating positive staining to the grade of nodal metastases. By Western blot analysis, the bFGF immunoreactivity was specifically detected in the two forms, with molecular weights of 18 and 33 kDa. The high-molecular-weight form was detected in only anaplastic carcinoma. The present investigations demonstrated a close correlation between the expression of bFGF and the degree of malignancy. bFGF might play an important role in promoting lymph node metastases. Moreover, the high-molecular-weight form of bFGF might have an intense influence on tumor growth.

Adenocarcinoma, Follicular↗

PubMedDate not supplied

Pharmacokinetics and metabolism of fosmidomycin, a new phosphonic acid, in rats and dogs.

The absorption, distribution, metabolism, and excretion of 3-(N-formylhydroxylamino) propylphosphonic acid monosodium salt (fosmidomycin), a new antibiotic, were investigated in rats and dogs after i.v. and oral dosing. After i.v. administration of 10 mg/kg of body weight, [14C]-fosmidomycin was excreted mainly in the urine (about 90% of dose within 72 h); and only a little was excreted in the expired air (14CO2) and bile of rats (less than 1% of dose), which suggested the absence of enterohepatic circulation. After oral administration of 10 mg/kg of body weight to rats, 34% and 61% of dose were excreted in the urine and faeces, respectively, suggesting about 30% gastro-intestinal absorption. No metabolites were found by autoradiography of the urine after thin layer chromatography. Radioactivity levels in the serum essentially agreed with the unchanged fosmidomycin levels determined by reverse isotope dilution method. [14C]-fosmidomycin was rapidly distributed in the tissues of rats, and was maintained in high concentration in the liver, kidneys, and bone. The serum level data after i.v. administration closely fitted a 3-compartment open model with first order kinetics after nonlinear least squares regression by NONLIN. The half-lives of the serum level curves for the early, midway, and terminal phases were: 0.13, 0.51, and 17.3 h, respectively in rats; and 0.44, 0.75, and 2.0 h, respectively in dogs.

Animals↗

PubMedDate not supplied

The effects of cadmium on a clonal osteogenetic cell, MC3T3-E1: inhibition of calcification and induction of metallothionein-like protein by cadmium.

To clarify the effects of cadmium (Cd) on bone formation, a clonal osteogenetic cell, MC3T3-E1, was used in the present study. After 24 h of culture, Cd at 1 ppm and above decreased DNA synthesis and alkaline phosphatase activity, but Cd at 1.5 ppm caused no significant decrease in collagen content. The cells treated with Cd (0.03-1.0 ppm) for 24 h showed the dose-dependent effects on metallothionein-like protein synthesis. The marked increase of Cd content unbound to metallothionein (MT)-like protein with cadmium at 1 ppm may be responsible for the toxic effects of cadmium. After 10 days of culture, the accumulation of 45Ca to the cell layer decreased with increasing level of cadmium at 0.03 and 0.1 ppm. The cadmium-treated cell layer showed a weaker reaction to histochemical staining for mineral compared with control culture. This result suggests that Cd inhibits an initial process of calcification.

Alkaline Phosphatase↗

PubMedDate not supplied

Mutagenicity and DNA-damaging activity of decomposed products of food colours under UV irradiation.

Five synthetic food colours Food Red Nos 3, 40 and 102 and Food Blue Nos 1 and 2, and their UV irradiated products were tested for mutagenic activity by means of the Ames test using Salmonella typhimurium strains TA98 and TA100. Food colours were irradiated with UV light for 14 days. Food Red Nos 3, 40 and 102 and Food Blue No. 1 were non-mutagenic before and after irradiation. UV irradiated products of Food Blue No. 2 were mutagenic in TA98 with or without S-9 mix. The mutagenic activity increased with increasing irradiation period, reached maximum potency on day 6, and then decreased. Moreover, Food Blue No. 2 showed DNA-damaging activity after 14 days of irradiation in rec-assay using Bacillus subtilis strains H17 and M45. The capillary electrophoresis was applied for the analysis of UV irradiated products of Food Blue No. 2. The original peak of Food Blue No. 2 was decomposed into seven peaks after UV irradiation.

Bacillus subtilis↗