Implications of the human genome initiative for the primary care physician

... Despite the need for physicians to be knowledgeable about and open to advances in genetic technology, little is known about the level of preparedness of primary care physicians to offer new genetic tests. Evidence suggests that several barriers exist to physicians adopting genetic tests. These include lack of knowledge, inability to interpret probabilistic information, low tolerance for uncertainty, negative attitudes about their responsibility for genetic counseling and testing, lack of confidence in their clinical skills, and unfamiliarity with ethical issues raised by testing. This paper will explore some of these barriers in further depth, discuss the ethical impact of physician unpreparedness on both patient care and the diffusion of genetic tests, and describe a study that is currently underway to investigate some of these issues.     

Fluoride inhibits agonist-induced formation of inositol phosphates in rat cortex

Sodium fluoride inhibited carbachol, 5-hydroxytryptamine and noradrenaline stimulated formation of inositol phosphates in rat cerebral cortex. For example, carbachol (1 mM) induced a 337% increase of inositol phosphates above basal in 30 min which was reduced to 69% in the presence of NaF (10 mM). The IC50 for NaF was approximately 1.5 mM and inhibition was mediated by a decrease in maxima of the carbachol dose response curve rather than a shift to the right. This inhibitory action was not mimicked by NaBr or NaI, or by agents which increase cAMP. Inhibition did not appear to result from a toxic action of NaF since it had no effect on the formation of inositol phosphates by high K+; moreover, in higher concentrations NaF stimulated phospholipase C activity. Since fluoride ions are known to activate G-proteins in the concentrations used in this study, these results may indicate the existence of a novel G-protein linked to receptor inhibition of phospholipase C.     

The Drosophila ets-2 gene: molecular structure, chromosomal localization, and developmental expression

The cellular homologs of the ets gene from the avian erythroblastosis retrovirus E26 have been studied in chickens, humans, mice, and cats. In this report a further evolutionary step is taken by isolating and characterizing a Drosophila ets-related genomic clone. Sequence analysis of this clone has shown it to contain the 3' end of the v-ets gene, called ets-2, corresponding to the last two exons of chicken ets. The predicted amino acid sequence was found to have over 90% homology when compared to that of v-ets. This is the highest level of conservation observed for any previously characterized Drosophila oncogene homolog. Expression of the ets-2 gene occurs throughout development, but is highest during the embryonic and pupal stages. By in situ hybridization, the ets-2 chromosomal position was determined to be 58A/B which corresponds to no known phenotypic mutant. As this is a highly conserved gene, the Drosophila model system should prove useful for the determination of the ets gene function.     

Generation of hydroxyeicosatetraenoic acids by human inflammatory cells: analysis by thermospray liquid chromatography-mass spectrometry

Arachidonic acid was converted to a series of hydroxyeicosatetraenoic acids (HETEs) by mixed human inflammatory cells following stimulation with the calcium ionophore A23187. HETEs were purified by a simple one-step extraction procedure followed by HPLC. The HPLC was coupled to a Finnigan quadrupole mass spectrometer using the now commercially available thermospray liquid chromatography-mass spectrometry interface. The HPLC eluant was monitored 'on line' by the mass spectrometer. Soft ionisation occurs, generating intense molecular ion species in the negative ion mode (M - H-:m/z 319) for each of the isomeric HETEs. The (M + H+ - H2O) ion at m/z 303 is the major species in the positive ion spectra of HETEs. Mass spectra were obtained on-line post-HPLC for HETEs formed by the human cells, and the HPLC-MS profile compared with that obtained from standards; species corresponding to the 11-, 9- and 5-HETEs were observed.     

In vitro translation of B-cell stimulatory factor-1 in Xenopus laevis oocytes

B-cell stimulatory factor-1 (BSF-1) can be translated in vitro in Xenopus laevis oocytes. This activity is blocked by an antibody to BSF-1. The RNA species coding for BSF-1 activity sediments of approximately 8-9S and is separable from RNA coding for interleukin-2 activity which sediments at approximately 11.5S. Finally, the fact that BSF-1 can be translated in vitro confirms that functions attributed to BSF-1 do not depend on contamination with other biologically active molecules such as phorbol myristate acetate.     

Biology of Subanguina picridis,a Potential Biological Control Agent of Russian Knapweed

The knapweed nematode, Subanguina picridis, forms galls on the leaves, stems, and root collar of Russian knapweed, Acroptilon repens. After being revived from a dormant, cryptobiotic state, second-stage juveniles required at least 1 month in a free-living state before becoming infective. Galls were induced on relatively slow-growing host plants that retained their apical meristems at or near the soil surface for 2-5 weeks. Galls developed extensive areas of nutritive tissue. The nematode was introduced from the Soviet Union and released in Canada for the biological control of Russian knapweed.