Methylmercury induced alterations in the nerve growth factor level in the developing brain.

Pre- and early postnatal stages in the development of the central nervous system (CNS) are very sensitive to the toxic effects of methylmercury. The influence of methylmercury on the level of nerve growth factor (NGF) during the development of CNS was studied. Sprague-Dawley rats were exposed indirectly throughout the fetal and suckling periods until weaning on postnatal day 25 (P 25) via their dams given methylmercury in the diet (3.9 mg/kg diet). In addition, after weaning offsprings were exposed directly to methylmercury via the diet until postnatal day 50 (P 50). The level of NGF was analyzed in cortical areas and in the septum with a sensitive enzyme immunoassay. The pups exposed to MeHg exhibited a 50% elevation in the level of NGF in the hippocampus on P 25 and P 50 compared to control animals. Concomitantly, the level of NGF decreased by 30% in the septum on P 25 and P 50, suggesting that the retrograde transport of NGF from hippocampus to septum could be affected by the exposure of methylmercury. The exact mechanism by which the low level of mercury is affecting the NGF concentration in the developing brain is yet unknown. The increase of NGF in the hippocampus and the decrease of NGF measured in the septum could reflect altered conditions for neurotrophic support in these areas of the brain as a result of the exposure to heavy metal. Thus, this finding might indicate a connection between exposure of heavy metals and neurodegeneration, such as that found in the basal forebrain in Alzheimer's disease.     

Evidence that the serotonin agonist, DOI, increases renin secretion and blood pressure through both central and peripheral 5-HT2 receptors

DOI [(+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCI] is a serotonin (5-HT1C/5-HT2) agonist, with potent cardiovascular effects. The purpose of the present studies was to determine the identity and location of the 5-HT receptor subtype(s) mediating the renin and blood pressure responses to DOI. Injection (i.p.) of DOI to conscious male rats elevated plasma renin activity in a dose-dependent manner. The 5-HT1C/5-HT2 antagonist ritanserin completely blocked the DOI-induced increase in plasma renin activity. In order to distinguish the 5-HT2- from the 5-HT1C- mediated effect of DOI, spiperone was administered before DOI. Low doses of spiperone (0.01 and 0.1 mg/kg, s.c.) significantly reduced the renin response to DOI. Because spiperone has a higher affinity for 5-HT2 than 5-HT1C receptors, these data suggest that DOI stimulates renin secretion through 5-HT2 receptors. To separate central from peripheral 5-HT receptors, we injected DOI into rats pretreated with saline or xylamidine, a 5-HT2 antagonist which does not cross the blood-brain barrier. Xylamidine produced a shift to the right and suppression of the maximal effect of DOI on plasma renin activity, suggesting a role for peripheral 5-HT2 receptors in the effect of DOI. On the other hand, i.c.v. administration of DOI, using doses lower than the peripherally effective doses, caused a significant elevation of plasma renin activity at 200 micrograms/kg. These experiments suggest that DOI's elevation of plasma renin activity has both peripheral and central sites of action.(ABSTRACT TRUNCATED AT 250 WORDS)     

Curriculum for musculoskeletal radiology.

Although general suggestions have been made regarding a radiology residency curriculum, no specific list of entities has been offered. Over the past ten years, we have developed a resident-run morning conference in musculoskeletal radiology that is supervised by faculty and covers a specific curriculum. We offer our curriculum as an example that may assist other departments in developing their own curricula.     

Pediatric urology

Development of the genital and urinary systems is interwoven. Developmental abnormalities may cause problems in both systems, although the presenting problem may be ambiguous genitalia, hypospadias, undescended testis, or a urinary tract infection. The primary care physician must understand the underlying significance of pediatric urologic problems and seek appropriate consultation in a timely manner.     

Linkage mapping of a mouse gene, iv, that controls left-right asymmetry of the heart and viscera.

Inherited single gene defects have been identified in both humans and mice that lead to loss of developmental control over the left-right asymmetry of the heart and viscera. In mice the recessively inherited mutation iv leads to such apparent loss of control over situs: 50% of iv/iv mice exhibit situs inversus and 50% exhibit normal situs. The affected gene product has not been identified in these animals. To study the normal function of iv, we have taken an approach directed to the gene itself. As a first step, we have mapped iv genetically, by examining its segregation in backcrosses with respect to markers defined by restriction fragment length polymorphisms. The iv locus lies 3 centimorgans (cM) from the immunoglobulin heavy-chain constant-region gene complex (Igh-C) on chromosome 12. A multilocus map of the region suggests the gene order centromere-Aat (alpha 1-antitrypsin gene complex)-(11 cM)-iv-(3 cM)-Igh-C-(1 cM)-Igh-V (immunoglobulin heavy-chain variable-region gene complex).