Regulation of expression of murine transferrin receptor 2.

Complementary and genomic DNA for the murine transferrin receptor 2 (TfR2) were cloned and mapped to chromosome 5. Northern blot analysis showed that high levels of expression of murine TfR2 occurred in the liver, whereas expression of TfR1 in the liver was relatively low. During liver development, TfR2 was up-regulated and TfR1 was down-regulated. During erythrocytic differentiation of murine erythroleukemia (MEL) cells induced by dimethylsulfoxide, expression of TfR1 increased, whereas TfR2 decreased. In MEL cells, expression of TfR1 was induced by desferrioxamine, an iron chelator, and it was reduced by ferric nitrate. In contrast, levels of TfR2 were not affected by the cellular iron status. Reporter assay showed that GATA-1, an erythroid-specific transcription factor essential for erythrocytic differentiation at relatively early stages, enhanced TfR2 promoter activity. Interestingly, FOG-1, a cofactor of GATA-1 required for erythrocyte maturation, repressed the enhancement of the activity by GATA-1. Also, CCAAT-enhancer binding protein, which is abundant in liver, enhanced the promoter activity. Thus, tissue distribution of TfR2 was consistent with the reporter assays. Expression profiles of TfR2 were different from those of TfR1, suggesting unique functions for TfR2, which may be involved in iron metabolism, hepatocyte function, and erythrocytic differentiation.

Comparative study of superoxide dismutase in normal and hereditary cataract (UPL) rats.

In the present study, the levels of SOD activity and Cu, Zn-SOD mRNA in the brain, kidney, liver and eye of normal and Upjohn Pharmaceutics Limited (UPL) rats, a new hereditary cataract model derived from Sprague-Dawley rats, were measured. Although the levels of SOD activity in the eye and brain of UPL rats were significantly decreased compared with those of normal rats 3 and 5 weeks after birth, the levels of SOD activities in the kidney and liver were the same in both groups. The levels of Cu, Zn-SOD mRNA in kidney and liver of UPL rats were the same as those of normal controls. The level of Cu, Zn-SOD mRNA in the brain of normal rats 5 weeks after birth was about twofold greater than that of UPL, and that in the eye of UPL rats 3 weeks after birth was significantly decreased compared with that of normal controls. The sequences of cDNA encoding Cu, Zn-SOD and the sequences of the regulatory region of the Cu, Zn-SOD gene were confirmed to be the same in normal and UPL rats. These results indicated that the decreases in levels of SOD activity and Cu, Zn-SOD mRNA in the brain and eye of UPL rat were not due to mutation of the genomic Cu, Zn-SOD gene in UPL rats or differences in the sequence of the regulatory region of the Cu, Zn-SOD gene between normal and UPL rats.

Stevens-Johnson syndrome caused by a health drink (Eberu) containing ophiopogonis tuber.

Stevens-Johnson syndrome is considered to be a severe type of erythema exsudativum multiforme. It is characterized by erythema with bullous and eroded lesions of skin and mucous membranes. We report a case of Steven-Johnson syndrome following consumption of a health drink containing ophiopogonis tuber. A 66-year-old female took an O.T.C. health drink for fever. The next morning, she noted erythema and swelling of her face, neck, and chest. She started to develop bullous and eroded lesions on the skin of her entire body and the mucous membranes of her oral cavity, conjunctiva, and cornea, and she became feverish. She had high degrees of corneal erosion and liver dysfunction. Skin biopsy showed diffuse necrosis of the epidermis. After admission to the hospital, steroid pulse therapy (1000 mg/day of methylprednisolone sodium succinate) was continued for 5 days. The health drink induced a positive drug lymphocyte stimulation test (DLST) and patch test. A challenge test was done with a one hundredth dose, and it was positive. We did patch tests with all components of the drink and found that Mai-Meu-Dong-Tang (ophiopogonis) alone was positive at 72 hours. There is no previous report of Stevens-Johnson syndrome caused by a health drink or Mai-Meu-Dong-Tang. Even though it is a health drink, we should be aware of the possibility of a severe reaction.

Metamorphosis-associated and region-specific expression of calbindin gene in the posterior intestinal epithelium of Xenopus laevis larva.

The present study used a molecular approach toward understanding the mechanism of hormone- and region-dependent remodeling of the small intestine during metamorphosis of Xenopus laevis. A protein spot was noticed on a two-dimensional polyacrylamide gel as a protein whose expression was metamorphic stage- and region-dependent. The protein was identified as the Xenopus homolog (Xcalbindin) of chick calbindin D28k. Xcalbindin expression in the intestine was restricted to absorptive cells in the posterior part, being detectable at stages 49-61, not detectable at stages 62-63, detectable again at stages 64-66, and finally becoming undetectable in the adult. During spontaneous metamorphosis, the level of Xcalbindin mRNA was significantly increased between stages 57 and 58, dramatically reduced at stage 59, and the mRNA was undetectable from stages 60-63, after which it was weakly re-expressed until the end of metamorphosis. Such up- and down-regulation of Xcalbindin mRNA was induced precociously by exogenous thyroid hormone. These results indicated that Xcalbindin is a specific marker of the differentiated absorptive cells of the intestine. Immunohistochemistry with specific antibodies against Xcalbindin demonstrated that precursor cells of adult intestinal epithelial cells expressed Xcalbindin. Considering these results, the origin of adult intestinal epithelial cells was discussed.

Experience with calcium antagonists nitrendipine, diltiazem, and verapamil and beta 2-agonist salbutamol in salvaging ischemic skin flaps in rabbits.

This study investigated the efficacy of selected agents in the salvage of experimental skin flaps in rabbits after 21 hours of 25 degrees C ischemia. Calcium channel antagonists nitrendipine, diltiazem, and verapamil increased ischemic skin flap survival in rabbits from 33.3% for buffered saline infused controls to 71.4% (P less than 0.05), 71.4% (P less than 0.05), and 50.0% (not significant) respectively. The beta 2-adrenoceptor agonist salbutamol produced an increase in survival to 64.3%, which narrowly missed statistical significance. All four test agents invoked a vasodilatory response (greatest for nitrendipine, diltiazem, and salbutamol), a slight fall in blood pressure, and a small increase in heart rate. It is concluded that the vasodilatory response in the microcirculation of the ischemic flap helped to minimize the risk of occlusion due to thrombosis or cell sludging during reperfusion, thus leading to improved flap survival.

Inhibition of spontaneous and experimental tumor metastasis by the calcium antagonist verapamil.

Verapamil, a calcium antagonist, inhibited both experimental (IV inoculation of tumor cells) and spontaneous metastasis (SC inoculation) of the highly metastatic B16 melanoma and colon adenocarcinoma 26 cell lines. Verapamil treatment resulted in a maximum 80% inhibition of metastases, the degree of inhibition varying among the different metastatic systems. Verapamil inhibited platelet aggregation induced by these tumor cell lines, the patterns of inhibition being different for B16 melanoma and colon adenocarcinoma. The inhibition of platelet aggregation induced by tumor cells is proposed as a mechanism by which the calcium antagonist exerts its antimetastatic effect. These results, together with our previous findings that calcium antagonists can increase the cytotoxicity of drugs in tumor cells with induced or inherent drug resistance by inhibiting outward transport of the drug, indicate that calcium antagonists have potential as a new class of adjuvant agents in the field of cancer chemotherapy.