Fundamental studies of adrenal retinoid-X-receptor: Protein isoform, tissue expression, subcellular distribution, and ligand availability.

Adrenal gland reportedly expresses many nuclear receptors that are known to heterodimerize with retinoid-X-receptor (RXR) for functions, but the information regarding the glandular RXR is not adequate. Studies of rat adrenal homogenate by Western blotting revealed three RXR proteins: RXRα (55kDa), RXRß (47kDa) and RXR (56kDa). RXRγ was not detectable. After fractionation, RXRα was almost exclusively localized in the nuclear fraction. In comparison, substantial portions of RXRß and RXR were found in both nuclear and post-nuclear particle fractions, suggesting genomic and non-genomic functions. Cells immunostained for RXRα were primarily localized in zona fasciculata (ZF) and medulla, although some stained cells were found in zona glomerulosa (ZG) and zona reticularis (ZR). In contrast, cells immunostained for RXRß were concentrated principally in ZG, although some stained cells were seen in ZR, ZF, and medulla (in descending order, qualitatively). Analysis of adrenal lipid extracts by LC/MS did not detect 9-cis-retinoic acid (a potent RXR-ligand) but identified all-trans retinoic acid. Since C20 and C22 polyunsaturated fatty acids (PUFAs) can also activate RXR, subcellular availabilities of unesterified fatty acids were investigated by GC/MS. As results, arachidonic acid (C20:4), adrenic acid (C22:4), docosapentaenoic acid (C22:5), and cervonic acid (C22:6) were detected in the lipids extracted from each subcellular fraction. Thus, the RXR-agonizing PUFAs are available in all the main subcellular compartments considerably. The present findings not only shed light on the adrenal network of RXRs but also provide baseline information for further investigations of RXR heterodimers in the regulation of adrenal steroidogenesis.

Blastomycosis presenting as recurrent tender cutaneous nodules.

Blastomycosis is caused by inhalation of airborne spores from Blastomyces dermatitidis, a dimorphic fungus found in soil. It is endemic in the southeastern, Midwestern, and south central states of North America. The clinical spectrum of blastomycosis is varied, including asymptomatic infection, acute or chronic pneumonia, and disseminated disease. Definitive diagnosis is based on identification of the characteristic thick-walled, broad-based budding yeasts by direct examination of tissue or the isolation of Blastomyces in culture. Itraconazole is the treatment of choice for mild to moderate pulmonary disease. Amphotericin B is the first line agent in life-threatening disseminated disease, central nervous system involvement, acute respiratory distress syndrome, pregnancy, immunocompromised states, and in those who cannot tolerate or fail azole therapy. We report a case of blastomycosis presenting as a fever of unknown etiology and recurrent skin nodules.

Detection of thiopental in the steroid fraction of serum from neonates following maternal exposure.

To follow up an investigation which studied effects of antenatal dexamethasone therapy on neonatal respiratory performance in multifetal gestations, neonatal serum steroids were determined by HPLC. A major peak (X) whose retention time coincided with that of dexamethasone was observed in many, but not all, serum samples. However, there was no correlation between the neonates whose serum samples displayed this X-peak and the mothers who had actually received the steroid therapy, indicating that the X-substance was not dexamethasone. An alternate mobile phase was employed which separated the X-substance and dexamethasone validating the indication. Among ten clinical conditions of the neonate birth, the X-substance was found to correlate only with the mothers who had the cesarean operation for delivery, suggesting that the substance was not necessarily a steroid. Four anesthetic agents used for cesarean operations were studied; the X-substance was identified as thiopental using a LC/MS technique. This was based on the same retention times, the same negative ions at m/z 240.9 and the same daughter ions at m/z 100.8 between the two substances. Thus, caution must be exercised when HPLC is employed to study serum steroids of patients who have previously been exposed to thiopental. Moreover, recent reports have shown that thiopental affects certain metabolic reactions in the rat; the present findings also suggest a need for further investigations of thiopental effect on neonates.