Disorder of the microfolds and tonofibrils in cervical leukoplakia

The ultrastructure of superficial cells of the normal human cervical squamous epithelium and that in leukoplakia was examined by scanning and transmission electron microscopy. The characteristic appearance of normal cells is described. Changes in the concentration of tonofilaments and formation of keratohyalin granules were revealed in leukoplakia. Alterations in surface microridges were also observed. The latter phenomenon is closely related to a decrease in the number of tonofilaments at the cell periphery. It is possible that the altered microridges do not retain the cushioning protective mucin and maintain the stationary of progressive states of leukoplakia.     

Teratogenic and embryotoxic activity of several 2,4-diaminopyrimidine derivatives

The degree of teratogenic and embryotoxic effects is dependent not only on the period of gestation and the agent dosage but also on the chemical structure of its molecule. In the series of derivatives of 2,4-diamino-5-phenylpyrimidine with different length of the alkul radical in the 6 position the preparation with ethyl group has the greatest injuring effect. Thus, the structural distinctions in the molecules of pharmacological agents are responsible for the selective toxicity of drugs in relation to mammalian embryos.     

Evidence for sex transformation of germline cells in ovarian tumor mutants of Drosophila

Mutations at a few genetic loci in Drosophila cause ovarian tumors with hundreds of poorly differentiated germ cells. We examined several of these mutants to test the hypothesis that such ovarian tumors contain sex-transformed cells. By testing for expression of male germline traits, we determined that partial germline sex transformation occurs in otu, snf, Sxlfs, and bam ovarian tumors. Thus these genes are likely to be required for proper establishment of germline sexual identity.     

Chemistry, binding affinities, and behavioral properties of a new class of "antineophobic" mitochondrial DBI receptor complex (mDRC) ligands

The mitochondrial DBI receptor complex (mDRC; previously called the peripheral benzodiazepine receptors) is linked to the production of neurosteroids such as pregnenolone sulfate, dehydroepiandrosterone sulfate, and others. In order to gain further information as to the function of the mDRC in the brain, we have constructed and tested both in vitro and in vivo a novel series of ligands, 2-arylindole-3-acetamides. The SAR studies detailed herein delineate some of the structural features required for high affinity binding to the mDRCs. In most cases the new ligands were prepared by use of the Fischer indole synthesis. Variations in the length and number of the alkyl groups on the amide nitrogen were probed together with the effects of halogen substituents on one or both of the aryl rings. Some ligands were also synthesized for study which represent conformationally constrained versions of the parent structure. Broad screening studies revealed these indoleacetamides to be highly selective for the mDRC, since they failed to bind with any significant affinity to other receptor systems. Some of the ligands were found to exhibit Ki values in the low nanomolar range for the mDRC as measured by the displacement of [3H]4'-chlorodiazepam. A subset of these ligands was also shown to stimulate pregnenolone formation from the mitochondria of C6-2B glioma cells with an EC50 of about 3 nM. In animal experiments ligands selected for further study were found to exhibit antineophobic effects, in spite of the fact that they exhibit no direct action on GABAA receptors. Consequently, it is postulated that these ligands owe their action to an indirect modulation of GABAA receptor function, presumably by stimulation of neurosteroid production and release from glial cells, followed by neurosteroid modulation of GABA's action on the chloride ion channel conductance of GABAA receptors.