Prolactin release induced by opiate agonists, effect of glucocorticoid pretreatment in intact and adrenalectomized rats

Cortisol administered at a dose of 25 mg/kg 24 h before measurements decreased the prolactin secretion induced by intraventricularly given opioids (dynorphin, beta-endorphin, Met-enkephalin or D-Met-Pro-enkephalinamide). The effect of cortisol was depressed by actinomycin D pretreatment. The cortisol-induced inhibition of the action of morphine was facilitated in adrenalectomized animals; measuring the effects of increasing doses of cortisol a maximal inhibition was obtained at a dose of 5 mg/kg. The opioid-induced corticosterone secretion was not affected 24 h after a single administration of cortisol. The present results show that the cortisol-induced inhibition of opioid-induced prolactin secretion is dependent on protein synthesis and independent of changes in drug metabolism, and of the type of opiate receptor preferentially affected by the opiate agonists employed.     

Gene conversion is a likely cause of mutation in PKD1

Approximately 70% of the gene responsible for the most common form of autosomal dominant polycystic kidney disease ( PKD1 ) is replicated in several highly homologous copies located more proximally on chromosome 16. We recently have described a novel technique for mutation detection in the duplicated region of PKD1 that circumvents the difficulties posed by these homologs. We have used this method to identify two patients with a nearly identical cluster of base pair substitutions in exon 23. Since pseudogenes are known to be reservoirs for mutation via gene conversion events for a number of other diseases, we decided to test whether these sequence differences in PKD1 could have arisen as a result of this mechanism. Using changes in restriction digest patterns, we were able to show that these sequence substitutions are also present in N23HA, a rodent-human somatic cell hybrid that contains only the PKD1 homologs. Moreover, these changes were also detected in total DNA from several affected and unaffected individuals that did not harbor this mutation in their PKD1 gene copy. This is the first example of gene conversion in PKD1 , and our findings highlight the importance of using gene-specific reagents in defining PKD1 mutations.      

Greater sensitivity of pigtailed macaques (Macaca nemestrina) than baboons to total body irradiation

Two juvenile pigtailed macaques (animals 1 and 2) received total body irradiation (TBI) followed by autologous stem cell transplantation, by a procedure known to be well tolerated by baboons. In this procedure, the TBI consisted of treatment on two consecutive days with 255cGy on one side, followed after 1-2 min by a similar dose on the other side. The two pigtailed macaques showed rapid haematopoietic engraftment, but succumbed either to systemic cytomegalovirus (CMV) infection and necrotising colitis or to haemorrhagic cystitis and tubulointerstitial nephritis. For four further pigtailed macaques (animals 3-6) the radiation procedure was changed to four equal doses of 255cGy, given 6-12 h apart. Animals 4-6 all showed engraftment and survived for long periods (>218 days), with no, or only minor treatable, complications. Animal 3 failed to show engraftment and succumbed to radiation-induced vascular lesions and severe multiorgan haemorrhages. The results suggest that pigtailed macaques have a lower tolerance threshold than baboons, rhesus macaques or human beings to TBI, the adverse effects of TBI being indistinguishable from those seen in human patients. The results also suggest that a hyperfractionated radiation procedure can prevent radiation-induced morbidity and mortality in pigtailed macaques.     

Dynamic and static phantoms for evaluation of digital subtraction angiographic systems

Two types of phantoms were developed with which to evaluate the overall performance of digital subtraction angiography (DSA) systems. A dynamic phantom, called a "fish bone" phantom, consists of polyethylene tubes that simulate blood vessels with various lesions, such as stenoses, ulcers, and aneurysms. With this phantom, washout curves were obtained representing the relationship between iodine content and time. It will be useful for qualitative assessment of DSA images, evaluation of different image-processing schemes, and studies of blood flow analysis. A static phantom, called a "C-D" phantom, can be used for measurement of quantitative contrast-detail (C-D) diagrams and for daily monitoring of DSA systems. This was constructed of tubes of seven different diameters (2.15-0.28 mm) and 14 different concentrations of contrast medium (100%-1.1% Renografin-76 [meglumine and sodium diatrizoate]). The C-D diagrams were determined from an observer performance study using C-D phantom images obtained at four different DSA settings.