Alterations in dopaminergic receptors in Huntington's disease.

To detect variations in dopaminergic receptors and cholinergic activity in regions of postmortem Huntington's diseased brains, ³H-spiroperidol binding assays and choline acetyltransferase (ChAc) activities were carried out. A significant reduction in ³H-spiroperidol binding in the caudate nucleus, putamen and frontal cortex of choreic brains was detected which appeared to be due to a decrease in the total number of binding sites rather than to a decrease in affinity of ³H-spiroperidol for the dopaminergic receptor. In choreic brains, there were also significant reductions in ChAc activity in the caudate nucleus and putamen. The decreases of both ³H-spiroperidol binding and ChAc activity in the neostriatum suggest that the dopaminergic receptors are localized postsynaptically on cholinergic interneurons. Dopaminergic receptor alterations in the basal ganglia may be one of the causes of the abnormal motor movements found in HD while alterations of these receptors in the frontal cortex may be associated with the neuronal degeneration found in that area of choreic brains.     

Evidence for dopaminergic modulation of pancreatic polypeptide secretion in man

This study examines the role of dopaminergic mechanisms in the regulation of human pancreatic polypeptide (hPP) secretion in 11 normal male volunteers. Administration of domperidone (20 mg iv), an extracerebral inhibitor of dopamine receptors, resulted in a hPP rise (p<0.05) within 10 min and a peak response (p<0.01) at 15 min after drug administration. Administration of the dopaminergic agonist, bromocriptine, 2.5 mg tid for 4 days eliminated hPP responses to isometric handgrip exercise in these 11 volunteers. These results suggest that dopaminergic mechanisms may exert a tonic inhibitory effect on hPP secretion in normal subjects.     

Differentiation of selected Enterobacteriaceae by pyrolysis-gas-liquid chromatography.

Pyrolysis-gas-liquid chromatography was used to differentiate selected species of Enterobacteriaceae. Individual cultures of Salmonella typhi, Hafnia alvei, and Proteus vulgaris, and 12 strains of Yersinia enterocolitica were grown in nutrient broth. After harvest and lyophilization, the bacterial samples were pyrolyzed at 900 degrees C, and their volatile fractions were separated on a 50-m capillary column coated with Carbowax 20M. The resulting pyrolysis elution patterns (pyrograms) of the four species were monitored on an integrating console, which was coupled with the chromatographic detector. The pyrograms were divided into 312 30-s time interval areas, and each interval area was normalized in relation to the area of the entire curve. The normalized areas were evaluated by stepwise linear discriminant analysis, and the discriminating component coordinates were used to generate a plot of the canonical variables. Distinct clustering patterns allowed discrimination among the four genera of Enterobacteriaceae studied. The tight clustering of the 12 Y. enterocolitica strains suggests the advantage of pyrolysis-gas-liquid chromatography over traditional approaches for species identification.     

Sexual Therapy of Patients with Cardiovascular Disease

Physical illness or disability inevitably has a damaging effect on sexual relationships. Physicians are usually unaware of the sexual consequences of illness on their patients, and lack experience in treating sexual dysfunctions.The report of treatment of a couple with serious cardiovascular disease illustrates the potential efficacy of brief sex therapy for improving the quality of a patient''s life. If a primary physician lacks the skills to conduct sex therapy, he may collaborate with nonphysician therapists. The physician''s knowledge of the physiological and psychological effects of a specific illness on his patient is essential to successful therapy. Often, simple education, encouragement or reassurance by the physician is enough to overcome the damaging effects of illness on a patient''s sex life.     

Experimental reversal of polarity in chick embryo epiblast sheets in vitro

The dorso-ventral polarity of cells within sheets of epiblast from early chick embryos can be experimentally reversed by applying low voltages across them in experimental chambers. The induced reversal is stable and affects the position of histochemically and ultrastructurally demonstrable markers.     

Spatial distribution of active genes implicated in the regulation of insulin-like growth factor stimulatory loops in human decidual and placental tissue of first-trimester pregnancy.

We have previously shown that the insulin-like growth factor-2 (IGF-2) gene is partially coexpressed with the IGF-1 and -2 receptor genes in proliferative cytotrophoblasts of the human extraembryonic tissue. Here we show that high levels of IGF-2 gene expression are not restricted to the embryonic tissue but can also be found in the decidua compacta. The IGF-2 gene is thus expressed at high levels in the mesenchymal stroma of the decidua to establish potentially short-range communication with primarily IGF-1 receptor-positive mesenchymal stroma cells. Conversely, the glandular and surface epithelia coexpress the IGF-1 receptor and IGF-1 genes, while the IGF-2 gene is not detected above background levels. The potential control mechanisms of these cell-cell signalling pathways were investigated by the analysis of the spatial distribution of active IGF binding proteins (IGFBP) genes. The IGFBP-3 gene is coexpressed with the IGF-2 gene in proliferative cytotrophoblasts of the embryonic placenta. While active IGFBP-1 and -2 genes in our hands cannot be detected in the embryonic placenta, all three IGFBP genes are expressed in complex and overlapping patterns in the decidua compacta. The results are discussed in terms of how the various IGFBP genes may operate in different cell types to restrict IGF local stimulatory pathways.     

Inhibition of protein tyrosine phosphatase activity by diamide is reversed by epidermal growth factor in fibroblasts.

Diamide (azodicarboxylic acid bis(dimethylamide] inhibits protein tyrosine phosphatase activity in fibroblasts without altering protein tyrosine kinase activity associated with the epidermal growth factor receptor. The loss of protein tyrosine phosphatase activity caused by diamide is reversed by 2-mercaptoethanol or epidermal growth factor.     

Parathyroid hormone (1-34) and Nleu8,18Tyr34-parathyroid hormone, (3-34) amide increase diacylglycerol in neonatal mouse calvaria.

Previously, we and others have presented evidence that a calcium second messenger system is involved in the action of parathyroid hormone (PTH) on bone. In the present report, the effects of PTH(1-34) and PTH(3-34)amide treatment on diacylglycerol (DG) in neonatal mouse calvaria are described. PTH(1-34) produced a rapid (within 5 minutes) increase in calvarial incorporation of 3H-arachidonic acid into DG. The effect was maximal at 0.1 nMPTH(1-34), the lowest concentration tested. The 3-34 amide analogue of PTH increased DG to the same extent as PTH(1-34). The effect was maximal at 10 nM PTH(3-34)amide, the lowest concentration tested. These concentrations were lower than those required to elicit maximal effects on bone resorption. In contrast to effects on cyclic AMP, where the 3-34 amide inhibited the increase elicited by PTH, combined treatment of calvaria with PTH(1-34) and PTH(3-34)amide did not inhibit effects on resorption or diacylglycerol.