Faculty Bibliography

Human hypercalcemia of malignancy (HHM) is generally due to the release into the circulation of parathyroid hormone-related peptide (PTHrP). PTHrP stimulates osteoclastic bone resorption and renal calcium reabsorption through the activation of a receptor similar to that of PTH (PTH-R). However, there is scarce information about the PTH-R regulation in the setting of the hypercalcemia. In the present study, we assessed the molecular basis of renal PTH-R regulation in Walker tumor-bearing rats either treated or not by a bisphosphonate, pamidronate. Twenty-seven 6-week-old rats were randomly divided into three experimental groups: WC- APD- (9 control rats), WC+ APD- (9 Walker tumor-bearing rats), and WC+ APD+ (9 Walker tumor-bearing rats receiving 15 mg/kg/day of sodium pamidronate every day for seven days). Pamidronate induced a significant decrease in the mean tumor weight (9.3+/-0.8 vs 6.3+/-0.6 g). Seven days after the subcutaneous implantation of the Walker cells, plasma total calcium was 10.8+/-0.4, 16.8+/-0.6, and 12.9+/-0.6 mg/dl in WC- APD-, WC+ APD-, and WC+ APD+, respectively. Plasma PTHrP concentration was undetectable, 15.9+/-2.6, and 7.2+/-1.4 pmol/l, respectively. Bone histomorphometric results showed high resorption in WC+ APD-, which returned below the basal level of the WC- APD- with pamidronate treatment. Densitometric analysis of Northern blots revealed that the renal PTH-R mRNA expression in WC+ WPD- rats was a quarter of the levels in the WC- APD- and WC+ APD+ groups. WC+ APD- also had a decreased PTH-stimulated cAMP production in renal membranes. The PTH-R was expressed in the Walker tumor and it was not modified by pamidronate treatment. In conclusion, the expression of PTH-R receptor mRNA is significantly reduced in the kidney of rats bearing Walker carcinoma tumor. Its regulation is tissue-specific: pamidronate, which partially corrected the hypercalcemia and elevated circulating PTHrP, normalized the PTH-R mRNA expression in the kidney but not in the tumor

Previous studies have shown that dexamethasone enhanced the expression of parathyroid-hormone/parathyroid-hormone-related peptide (PTH/ PTHrP) receptor mRNA in ROS 17/2.8 osteosarcoma cells. The aim of this study was to determine whether the induction of PTH/PTHrP receptor expression in such osteoblast-like cells is regulated at the gene level. Dexamethasone increased the steady-state levels of PTH/PTHrP receptor mRNA twofold at 6 h, and nearly threefold at 24 h. The half-life of the PTH/PTHrP receptor mRNA, in the presence of actinomycin D, was 6 h both in untreated and in dexamethasone-treated cells. When measured by nuclear run-on assay, the rate of PTH/PTHrP receptor gene transcription was increased twofold at 24 h. PTH/PTHrP receptor mRNA expression was blocked completely after 24 h of treatment with cycloheximide. The binding of PTH/PTHrP to their receptor required the synthesis of new protein and was shown to be specifically dependent on the interaction of dexamethasone with the glucocorticoid receptor. These data indicate that the enhancing effect of dexamethasone on PTH/PTHrP receptor expression is rapid, requires de novo protein synthesis, and increases the transcription rate of the PTH/PTHrP receptor gene

In two patients with hepatic cirrhosis and marked morphological distortion of the liver, the gallbladder was identified in a retrohepatic position on ultrasound and CT. The etiology of this anomalous position and the importance of the preoperative diagnosis of both congenital and acquired anomalous position of the gallbladder in patients with acute cholecystitis is discussed

Simultaneous intrauterine and ectopic pregnancies are extremely rare. The diagnosis is usually made by laparoscopy and/or laparotomy. Three cases are presented in which the diagnosis was made during sonographic examinations by simultaneous demonstration of fetal cardiac motion in both the intrauterine and extrauterine fetuses. Early diagnosis of this condition significantly reduces the morbidity and mortality of both the mother and the intrauterine gestation