[Long-term follow up of intravenous mercury therapy]. / Radiologische Langzeitbeobachtung einer intravenösen Quecksilberapplikation.

In the case of an intravenous mercury injection, the mercury can be seen in the right heart, the lungs, the liver, and the kidney, but seldom in the spleen, the extremities, and the vertebral canal. In the subsequent period there is a distribution of the mercury and clinical symptoms will show the toxicity of the metal. We describe a patient with a follow-up time of 19 years, from the radiological point of view.

Glucocorticoid receptor concentration modulates glucocorticoid-regulated gene expression in rat pancreatic AR42J cells.

In this study we investigated the effects of altered intracellular glucocorticoid receptor (GR) concentrations on glucocorticoid-regulated gene expression in the rat pancreatic acinar cell line AR42J. Incubation of AR42J cells with dexamethasone results in a time-dependent transcriptional stimulation of amylase gene expression (about 5-fold) and a transcriptional inhibition of bombesin receptor (BR) gene expression. Decreasing the intracellular GR concentration to 50% by preincubation with RU 38486 results in a significant attenuation of dexamethasone-regulated amylase and BR gene expression. In contrast, increasing the intracellular GR concentration 2-fold by preincubation with the phosphodiesterase inhibitor IBMX significantly enhances the glucocorticoid inhibition of BR gene expression whereas amylase mRNA concentrations remain unaltered. These data demonstrate that intracellular GR concentrations determine the sensitivity of glucocorticoid-regulated gene expression in rat pancreatic AR42J cells.

Selective suppression of nuclear retinoic acid receptor beta gene expression in human pancreatic carcinomas.

Retinoids restore normal cell growth and differentiation in malignant cells and are considered as potential therapeutic agents. Before using retinoids for the treatment of pancreatic cancer it is important to determine the expression of nuclear retinoid receptors, which mediate most actions of retinoids on gene expression in normal and malignant tissues. Digoxigenin-labeled antisense riboprobes of retinoic acid receptors (RARs) alpha, beta, and gamma, and retinoid X receptor (RXR) alpha were used for in situ hybridization to histological sections of-specimens from 24 human pancreatic carcinomas, 20 of which also contained adjacent normal tissue. All four receptors were detected in adjacent normal pancreatic tissue specimens and RAR-alpha, RAR-gamma, and RXR-alpha were also detected in all pancreatic carcinoma specimens. In contrast, RAR-beta mRNA transcripts were detected in only 67% of the malignant tissues and when expressed, the level of expression was significantly lower than that of the corresponding adjacent normal tissues. Decreased RAR-beta gene expression was especially noted in moderately- and poorly-differentiated cancers. These findings suggest that selective decrease or lass of RAR-beta gene expression in certain pancreatic carcinomas in vivo might be associated with the development or progression of pancreatic cancer.

Retinoids: effects on growth, differentiation, and nuclear receptor expression in human pancreatic carcinoma cell lines.

BACKGROUND & AIMS: Advanced pancreatic carcinoma has a dismal prognosis despite extensive chemotherapeutic trials. The aim of this study was to evaluate the role of retinoids as an experimental therapeutic approach for pancreatic cancer. METHODS: Four ductal and one acinar pancreatic tumor cell lines were investigated. Growth was determined by cell number and a human tumor clonogenic assay. In vivo growth was assessed by xenografts transplanted into nude mice. Differentiation was characterized by immunofluorescence microscopy and carbonic anhydrase II gene expression. Retinoid receptors were characterized by Northern blotting and reverse-transcriptase polymerase chain reaction. RESULTS: Retinoid treatment results in a time- and dose-dependent growth inhibition in vitro and in vivo of ductal but not acinar pancreatic tumor cells. Retinoid treatment induces a more differentiated phenotype in ductal tumor cells as shown by morphological criteria and increased expression of carbonic anhydrase II. All pancreatic tumor cell lines expressed a broad panel of cellular retinoid binding proteins and nuclear retinoid receptors. Retinoic acid receptor gamma and cellular retinoic acid binding protein II were found in all retinoid-sensitive ductal tumor cell lines but not in the retinoid-resistant acinar cell lines. CONCLUSIONS: Detailed knowledge of nuclear retinoid receptor expression may provide rational strategies for retinoid treatment of pancreatic cancer.

Transcriptional regulation of carbonic anhydrase II by retinoic acid in the human pancreatic tumor cell line DANG.

Carbonic anhydrase II (CA II) generates bicarbonate in human pancreatic duct cells. We have developed the human pancreatic duct cell line DANG as a model to study the effects of all-trans-retinoic acid (ATRA) on CA II gene expression. ATRA treatment resulted in a time- and dose-dependent inhibition of CA II mRNA concentrations in DANG cells. These inhibitory effects were paralleled by a time-dependent decrease of CA II protein concentrations. Nuclear run on analysis revealed that the decrease of CA II mRNA concentrations was due to a decreased rate of CA II gene transcription. These data show that ATRA transcriptionally modulates CA II gene expression in human pancreatic carcinoma cells.

Glucocorticoid receptor gene expression in the exocrine and endocrine rat pancreas.

Although pleiotropic effects of glucocorticoids on the endocrine and exocrine pancreas are well documented, it remains controversial whether these effects are due to direct interactions of glucocorticoid hormones with their receptors in the respective target cells. We therefore examined gene expression of the glucocorticoid receptor (GR) in various functional compartments of the rat pancreas. Using in situ hybridization by generating a radioactive cRNA probe from a specific cDNA clone for the rat glucocorticoid receptor we found a gradient in the expression of receptor mRNA transcripts from endocrine > acinar > ductal cells. In contrast, no specific hybridization signal was observed in the endothelial cells of vascular structures. Using a monospecific polyclonal antibody against the rat glucocorticoid receptor in Western blot analyses we found significant expression of the 94 kD receptor protein in an enriched pancreatic acinar cell preparation. This data suggest that rat pancreatic exocrine cells might serve a direct target tissue for glucocorticoid action.