Reversal of established lupus nephritis and prolonged survival of New Zealand black x New Zealand white mice treated with the topoisomerase I inhibitor irinotecan.

Systemic lupus erythematosus is a chronic autoimmune disorder that predominantly affects women of childbearing age. Lupus-associated glomerulonephritis is a major cause of mortality in these patients. Current treatment protocols for systemic lupus erythematosus include cyclophosphamide, prednisolone, azathioprine, and mycophenolate mofetil.

Colloidal aggregates of insoluble inclusions in human goiters.

To shed some light on the physicochemical properties of the thyroid follicular colloid, we have screened retrospectively the autoradiographs of 60 human nodular goiters labeled 17 h preoperatively with 100 microCi 125I for evidence of colloid compartmentalization. In 87% (52/60) of all goiters examined, sporadic or multiple colloidal inclusions ('colloid stones') not mixing with newly labeled Tg were detected. The detailed analysis of 17 goiters revealed a mean incidence of 0.

Expression of transforming growth factor beta1, beta2, and beta3 in multinodular goiters and differentiated thyroid carcinomas: a comparative study.

The various isoforms of transforming growth factor-beta (TGFbeta) are growth-inhibiting cytokines for cells of epithelial origin. In malignant thyroid tumors, several studies documented a high expression of TGFbeta in the majority of thyroid follicular cells suggesting a possible role as an inhibitor of cell proliferation. In contrast to this uniform pattern of TGFbeta expression in thyroid cancer, scarce and controversial data have been reported on the expression of TGFbeta in benign multinodular goiter.

Expression of functional stimulatory guanine nucleotide binding protein in nonfunctioning thyroid adenomas is not correlated to adenylate cyclase activity and growth of these tumors.

In thyroid cells, the alpha-subunit of the stimulatory guanine nucleotide binding protein (Gs alpha) acts as signal transducer between the TSH receptor and the adenylate cyclase (AC), and it regulates both growth and function. In order to analyze Gs alpha expression by both Western blot analysis and in situ, we generated an antibody raised against a recombinant human Gs alpha protein. With this antibody, a strong cytoplasmic Gs alpha-immunostaining was detectable in cultured human thyroid cells and in TSH-stimulated rat thyroids, in contrast to normal human thyroids and to T4-treated rat thyroids, which showed only weak immunoreactivity.

Morphological and functional polymorphism within clonal thyroid nodules.

Thirty-nine thyroid nodules, removed because of recent growth, were analyzed morphologically by serial histological sections for the classical histomorphological hallmarks of follicular cell replication and for immunohistochemically demonstrable overexpression of the growth-associated ras-gene product p21ras. Clonal analysis was performed using the highly informative probe M27 beta that detects polymorphisms on the locus DXS255 of the X-chromosome. Twenty-four nodules were of clonal and 15 nodules were of poly-clonal origin.

Histomorphological and immunohistochemical evidence that human nodular goiters grow by episodic replication of multiple clusters of thyroid follicular cells.

This study was aimed at dissecting the cellular mechanisms that underly the growth of actively expanding human goiter nodules. Thirty-two nodules from different patients, all removed because of steady recent growth, were serially sectioned and screened for 1) histomorphological signs of cell proliferation and 2) in situ expression of the immunohistochemically stained p21ras protooncogene product. Bovine, porcine, and rat thyroid glands (the latter from both T4- and perchlorate-treated animals) were used as controls.