Maintenance and induction of cytochrome P-450 in cultured rat hepatocytes.

Maintenance of microsomal cytochrome P-450 content by cultured rat hepatocytes has proven an elusive goal. It is reported here that exogenous heme maintains cytochrome P-450 content of cultured rat hepatocytes at high levels during the first 72 h of incubation. The maintenance studies have been expanded to demonstrate the in vitro induction of cytochrome P-450 by phenobarbital treatment. The induction of P-450 in vitro by phenobarbital required the trace element, selenium, in the presence of exogenous heme. The present findings suggest that selenium, and other trace elements, may have an essential role in the formation of holocytochrome P-450 in vitro.

Renal carcinoma and dialysis in end-stage renal disease.

We describe five patients receiving long-term hemodialysis (mean duration of 6.4 years) in whom eight renal carcinomas were found. In four patients, the carcinoma was confirmed by tissue pathology, while the fifth patient had multiple (four) areas of neovascularity on selective renal arteriography. Two patients died of metastases. In four patients the diagnosis was initially made with selective renal arteriography and in the remaining one, with sonography and computerized tomography. In three of the four arteriography showed diffuse cystic degeneration; pathologic findings revealed renal carcinoma and the changes of "end-stage" disease. Two patients had brief pharmacologic immunosuppression during unsuccessful renal transplantation six years earlier. These cases demonstrate an apparently increased risk of renal carcinomas in end-stage renal disease, a risk that appears to be independent of pharmacologic immunosuppression.

Focal intravascular coagulation in progressive ascending telangiectasia: ultrastructural studies of ketoconazole-induced involution of vessels.

We describe a unique form of telangiectasia that we have called progressive ascending telangiectasia. It is a noninflammatory process, characterized by the presence of greatly dilated venous capillaries in the upper dermis. By means of scanning electron microscopy, focal fibrin clots were observed in some of the dilated vessels in the skin of a patient with this disease. These were not apparent with either light microscopy or transmission electron microscopy. Immunofluorescent microscopy revealed deposition of complement and IgM in the vessel walls. The endothelial cells showed ultrastructural evidence of heightened metabolic activity (numerous pinocytotic vesicles, increased number and size of mitochondria, convoluted nuclei, and prominent rough endoplasmic reticulum). Around the dilated vessels there was a thick laminar wall of multiple basement membranes embedded in mucopolysaccharide. The electron microscopic appearance of the endothelial cells and their investments showed them to be dilated venous capillary channels. Ketoconazole therapy induced disappearance of many of the dilated vessels within 1 month. After 5 months of this treatment, skin biopsies of the cleared areas showed an absence of dilated vessels. The thick laminar walls and intravascular clots had disappeared. It is postulated that microbially induced focal intravascular coagulation plays a role in the pathogenesis of progressive ascending telangiectasia. Stasis factors would seem to account for the dependent, ascending nature of the loci of coagulation.

Malignant fibrous histiocytoma of the meninges. Histological, ultrastructural, and immunocytochemical studies.

A case of malignant fibrous histiocytoma arising from the meninges in a 12-year-old boy is reported. This tumor presented as an extracerebral hemorrhagic mass in the left frontal lobe without obvious invasion of the underlying brain. Histologically, a malignant tumor with the characteristic storiform pattern of malignant fibrous histiocytoma with focal areas of hemorrhage was observed. Ultrastructurally, fibroblastic cells, undifferentiated cells, histiocytic-type cells, multinucleated tumor giant cells, and xanthomatous cells were distinctly seen. The possible cell of origin of these meningeal tumors and their prognosis are discussed. The significance of considering this entity in the differential diagnosis of those tumors of the central nervous system with a spindle-cell or xanthomatous component is discussed, and the value of ultrastructural and immunocytochemical study with glial fibrillary acidic protein in the diagnosis is stressed.

Age-related changes in isolated rat hepatocytes. Comparison of size, morphology, binucleation, and protein content.

Hepatocytes isolated from 6-, 12-, 18-, and 30-month-old female Fischer F344 rats were examined by scanning electron microscopy. No significant change in cell size with age was observed. However, the surface morphology of the cells isolated from the older animals exhibited a significant increase in surface folds. This feature did not exceed 10% of the cell population until 12 months of age and continued to increase to 31% of the cells in 30-month-old rats. From 6 to 12 months of age, there was a significant increase in protein content of the hepatocytes. No further increase in protein content occurred during senescence. An increase in percentage of binuclear cells occurred after 24 months of age. Because ploidy and binucleation increase with increasing age, it appears that the nuclear/cytoplasmic ratio changes as a function of age.

Characteristics of a clone of endothelial cells derived from a line of normal adult rat lung cells.

A strain of endothelial cells derived from a single cell cloned from a line of normal adult rat lung parenchyma has been maintained in tissue culture for more than 3 years. These cells have been identified as endothelial cells based on the combination of their growth characteristics, cell morphology as observed with both light and electron microscopy, and their physiological properties. They have continued to produce granules, which stain specifically for glycosaminoglycans with Alcian blue, for over 2 1/2 years. During the same period of time, glycosaminoglycans were identified biochemically in both cells and medium. They have maintained the ability to degrade bradykinin over this period as well.

Ultrastructural studies of developing pulmonary alveolar septal elastin.

Eighteen fetal lambs have been studied at six different gestational ages ranging from 90 days to term. At 90 days gestation, only the microfibrillar component of elastin is present in pulmonary alveolar septal elastic fibers. The amorphous component appears at 110 days and gradually increases in amount, relative to microfibrils. At term (150 days), the composition of the pulmonary alveolar septal elastin resembles that of the adult ewe.