Interstitial pneumonitis induced by bicalutamide given for prostate cancer

We describe interstitial pneumonitis induced by bicalutamide prescribed to treat prostate cancer. A 78-year-old man with severe lower paralysis and a bladder/rectal disorder was referred to our hospital. Prostate-specific antigen was elevated to 1418 ng/mL at that time and magnetic resonance imaging revealed multiple bone metastases. A rectal examination revealed hard nodules in the bilateral lobes of the prostate. We diagnosed prostate cancer without a biopsy, and then maximally blockaded androgens by castration and bicalutamide administration. Eight months later, he was admitted to a local hospital with breathing difficulties, and a computed tomography scan revealed interstitial pneumonitis. A physician concluded that the cause of the interstitial pneumonitis was bicalutamide, which was immediately withdrawn and replaced with prednisolone. The patient recovered over a period of 3 months. Bicalutamide-induced interstitial pneumonitis is quite rare. However, adverse reactions to maximal androgen blockade therapy should be considered and appropriate treatment for interstitial pneumonitis should be promptly initiated, as this condition is reversible.     

Effects of thyroid hormone and actinomycin D on phosphate uptake of brush-border membrane vesicles from kidney of rachitic rats

It is generally accepted that 3,5,3'-triiodothyronine (T3) is responsible for most of the known physiological actions of thyroid hormone. Our new rachitogenic diets, deficient in both vitamin D and iodine and low in phosphorus (1.13% calcium and 0.14% phosphorus), induced typical rachitic changes in rats. To know the possible role of T3 on bone and phosphate (Pi) metabolism and its related biochemical and molecular mechanism, weanling male Wistar rats were fed this diet for 28 days, and then treated with 6 micrograms/100g BW of T3 and/or 60 micrograms/100g BW of actinomycin D intraperitoneally. After 2 hours of treatment, renal brush-border membrane vesicles (BBMV) were prepared according to the calcium precipitation method, and their Na(+)-dependent Pi uptake was analyzed by Lineweaver-Burk plots. Km value was not significantly altered by all these treatments. In contrast, Vmax value as a Pi uptake index was significantly increased in T3-treated rats compared with rachitic control. This increase was evident as less as 2 hr after T3 administration, so it was assumed that T3 stimulated the Pi uptake not by mediation of the de novo protein synthesis. However this increase was suppressed by administration of actinomycin D, and then this result suggests that the antirachitic effect of T3 is mediated by somehow de novo protein synthesis. After all, T3 acting as an antirachitic agent, the most likely possibility is that T3 provides favorable conditions for mineralization of bone by improving Pi transport in various types of cells, even under rachitogenic condition, at least of hypophosphatemic type, and correction of phosphate metabolism may be the most essential prerequisite for cure of this type of rickets.     

Bioavailability of phenytoin from oil suspension and emulsion in dogs

Phenytoin as a sesame oil suspension or emulsion was administered orally to beagle dogs to study improvement of its bioavailability. The absorption of phenytoin by the digestive tract was better when it was given as a sesame oil suspension or emulsion than as a powder. With the dose amount of sesame oil and water fixed, the absorption of phenytoin from the emulsion was greater than that from the oil suspension, although the difference was not significant. Therefore, the absorption of phenytoin was not affected significantly by emulsifying the sesame oil. Its absorption corresponded not to the amount of water given with the dose amount of sesame oil fixed, but to the dose amount of sesame oil with the dose amount of water fixed, reaching maximum when the ratio of sesame oil to water was 1:3. Study of the influence of the type of oil in the emulsion on the absorption by the digestive tract showed that absorption was best with cod-liver oil, followed by sesame oil, and then oleic acid.     

Erythroblasts derived in vitro from embryonic stem cells in the presence of erythropoietin do not express the TER-119 antigen

OBJECTIVE: In this study, we analyzed murine primitive erythropoiesis by coculturing Flk-1+ ES-derived cells with OP9 to find efficient culture conditions for erythroid cell induction. We utilized a nonserum culture system and EPO (erythropoietin) and found that this cytokine had unique properties. MATERIALS AND METHODS: ES cells (E14.1) were first differentiated to Flk-1+ cells and then cocultured with OP9 stromal cells. BIT9500 was used as a serum replacement. The erythroid morphology, hemoglobin types, and TER-119 expression levels were analyzed. RESULTS: Primitive erythroid cells with embryonic hemoglobin were generated very efficiently when the serum-containing culture was converted to the nonserum system. In this serum-free culture, TER-119+ erythroblasts appeared first on day 2 and maturation proceeded until day 7. When EPO was added to this coculture, the number of induced floating cells increased twofold to threefold. Unexpectedly, the erythroid-specific antigen TER-119 expression of these cells was drastically reduced. Since reduced TER-119 expression is usually interpreted as maturation arrest, we examined the phenotypic features of the EPO-treated cells. We found, however, no evidence of maturation arrest in the aspects of morphology and hemoglobin content. EPO did not suppress TER-119 expression of erythroblasts derived from fetal liver or adult bone marrow. CONCLUSIONS: Our results showed that EPO had the unusual property of inducing TER-119- erythroblasts in ES-derived primitive erythropoiesis. It is likely that this effect is unique to primitive erythropoiesis.     

Abnormal expression of BRCA1 and BRCA1-interactive DNA-repair proteins in breast carcinomas

Breast cancer is one of the most common malignancies among women. The molecular mechanisms involved in breast carcinogenesis, however, remain to be elucidated. Although somatic mutation of BRCA1 is rare, BRCA1 protein expression is reduced in about 30% of sporadic breast carcinomas (Yoshikawa et al., Clin. Cancer Res., 5:1249-1261, 1999), indicating its possible involvement even in sporadic breast carcinogenesis. Among the BRCA1-interactive proteins are hRAD51 (a human homologue of Escherichia coli rec A protein), BARD1 (BRCA1-associated RING domain 1) and p53, all of which are involved in DNA repair. We have analyzed the expression patterns of the hRAD51, BARD1 and p53 proteins in five breast cancer cell lines, including a BRCA1-deficient cell line, and in 179 breast cancer tissue samples from Japanese women, including 113 sporadic, 47 hereditary (i.e., BRCA1 status unknown), and 19 BRCA1-associated cases. Of the 179 breast carcinomas, fifty-four (30%) exhibited reduced hRAD51 expression, and sixty-two (35%) exhibited p53 overexpression. On the other hand, reduced expression level of BARD1, and of hMSH2 and hMLH1, which are components of DNA mismatch-repair pathway and are involved in colorectal carcinogenesis, was observed respectively in only 10 (6%), 8 (5%) and 3 (2%) cases. The overall frequency of sporadic breast carcinomas with abnormal expression of either BRCA1 or the BRCA1-interactive proteins was 67% (76/113). These results indicate that there may be an important role for the BRCA1-associated DNA-repair pathway, not only in BRCA1-associated breast carcinomas, but also in sporadic breast carcinomas.     

Fatigue Properties of Hot-Dip Galvanized AISI 1020 Normalized Steel in Tension–Compression and Tension–Tension Loading

Since hot-dip galvanizing causes a heat effect on cold-worked steel substrate and produces a coating layer comprised of distinct phases with varying mechanical properties, the fatigue mechanism of hot-dip galvanized steel is very complex and hard to clarify. In this study, AISI 1020 steel that has been normalized to minimize susceptibility to the heat effect was used to clarify the effect of the galvanizing layer on the tensile and fatigue properties. The galvanizing layer causes a reduction in the yield point, tensile strength, and fatigue strength. The reduction in the fatigue strength was more significant in the high cycle fatigue at R = 0.5 and 0.01 and in the low cycle fatigue at R = 0.5. The galvanizing layer seems to have very little effect on the fatigue strength at R = −1.0 in the low and high cycle fatigue. Since the fatigue strengths at R = 0.01 and −1.0 in the low cycle fatigue were strongly related to the tensile strength of the substrate, the cracking of galvanized steel was different than that of non-galvanized steel. The fatigue strength of galvanized steel at R = 0.5 dropped remarkably in the low cycle fatigue in comparison to the non-galvanized steel, and many cracks clearly occurred in the galvanizing layer. The galvanizing layer reduced the fatigue strength only under tension–tension loading. We believe that the findings in this study will be useful in the fatigue design of hot-dip galvanized steel.