The olfactory placodes generate the primary sensory neurons of the olfactory sensory system. Additionally, the olfactory placodes have been proposed to generate a class of neuroendocrine cells containing gonadotropin-releasing hormone (GnRH). GnRH is a multifunctional decapeptide essential for the development of secondary sex characteristics in vertebrates as well as a neuromodulator within the central nervous system. Here, we show that endocrine and neuromodulatory GnRH cells arise from two separate, nonolfactory regions in the developing neural plate. Specifically, the neuromodulatory GnRH cells of the terminal nerve arise from the cranial neural crest, and the endocrine GnRH cells of the hypothalamus arise from the adenohypophyseal region of the developing anterior neural plate. Our findings are consistent with cell types generated by the adenohypophysis, a source of endocrine tissue in vertebrate animals, and by neural crest, a source of cells contributing to the cranial nerves. The adenohypophysis arises from a region of the anterior neural plate flanked by the olfactory placode fields at early stages of development, and premigratory cranial neural crest lies adjacent to the caudal edge of the olfactory placode domain [Development 127 (2000), 3645]. Thus, the GnRH cells arise from tissue closely associated with the developing olfactory placode, and their different developmental origins reflect their different functional roles in the adult animal.

No abstract

Anti-thymocyte globulin (ATG) is extensively used for both prophylaxis and treatment of rejection episodes in renal transplantation, but it is expensive and potentially hazardous. We report the utility of therapeutic monitoring by the readily available total lymphocyte count, compared with the more complex and expensive assay of CD3 counts by flow cytometry in eight renal transplant patients receiving ATG. Aiming for an absolute CD3 count of 0.2-0.5 x 10(9)/l, it was possible to reduce the mean daily dose of ATG from the recommended 2.5 mg/kg/d to a mean of 1.6 mg/kg/d. Analysis of simultaneously taken total lymphocyte counts showed that the same dose reductions could have been made if the target for therapeutic effect had been a total lymphocyte count of < 0.3 x 10(9)/l. Anti-rejection therapy was successful in all cases, with satisfactory graft function at 6-9 months post-therapy. Lower than recommended doses of ATG proved effective prophylaxis and treatment of renal allograft rejection, with considerable cost savings. A simple protocol may be followed titrating dose against total lymphocyte count, provided it remains below 0.3 x 10(9)/l. CD3 estimation can be reserved for those times when the total lymphocyte count rises to 0.3 x 10(9)/l or above.

No abstract