Self-labeling of human polymorphonuclear leucocyte myeloperoxidase with125iodine

In order to obtain a radioimmunoassay (RIA) technique for the measurement of human plasma myeloperoxidase (MPO), we purified the enzyme from polymorphonuclear granulocytes (neutrophils), and compared three methods of labeling it with¹²⁵Iodine: chloramine T, lactoperoxidase, and an original technique of self labeling based on the ability of the enzyme to oxidize and bind¹²⁵I in the presence of H₂O₂. The chloramine T technique produced a degraded protein, as well shown by a high non-specific binding of tracer to antibody. The lactoperoxidase technique did not succeed in labeling MPO with an adequate specific activity. In contrast, the self-labeling method gave a stable tracer with a specific activity of 23 Ci/gmg MPO (85 MBq), a satisfactory level of immunoreactivity, and a low-specific binding (3%). After labeling, purification of tracer was achieved by gel filtration chromatography in phosphate buffer (0.05 M; pH7) to which 0.1% poly-L-lysine was added. The labeled molecule remained stable for 40 days and could be used for RIA with a polyclonal antibody raised in rabbits.     

Disruption of mitochondrial function as the basis of the trypanocidal effect of trifluoperazine onTrypanosoma cruzi

Summary The tricyclic anti-calmodulin drug trifluoperazine (TFP) inhibited growth and motility of epimastigotes ofTrypanosoma cruzi, at concentrations lower than 100 M, and motility and infectivity of the bloodstream trypomastigote form at 200 M. Electron microscopy of TFP-treated epimastigotes showed that the major effect was at the mitochondrial level, with gross swelling and disorganization. The oligomycin-sensitive, mitochondrial ATPase was completely inhibited by 20 M TFP, and the same drug concentration caused a 60% decrease in intracellular ATP content. The results suggest that the trypanocidal effect of TFP may be related more to mitochondrial damage than to the well-known anticalmodulin effect of the drug.     

Genetic factors in neurotoxicology and neuropharmacology: A critical evaluation of the use of genetics as a research tool

Animals have evolved a detoxication system to enable them to survive in a hostile chemical environment in which foods contain many non-nutrient chemicals. Detoxication depends on enzymes which are often genetically polymorphic. As a result, inter-individual variation is common, and in humans several Mendelian loci have been identified. However, most variation in response is probably due to the action of several genes. Genetic variation in response to the neurotoxin MPTP and to chemically and physically-induced seizures is reviewed. In the former case, differences between pigmented and white mouse strains have been noted which are consistent with the hypothesis that humans are more sensitive than mice or rats because of the presence of melanin in human brains. However, variation in sensitivity probably also depends on other genes. In the case of audiogenic seizures, a single locus has been identified and mapped, but its relationship with seizures induced by other agents is not clear. Genetic variation in response to alcohol is also discussed. The failure of most toxicologists to consider genetic variation as a potentially confounding variable, and as a powerful research tool, is discussed critically in relation to non-repeatability of research on the neurotoxic effects of lead, and in relation to the genetic variation in MPTP, seizures, and alcohol response already noted. It seems clear that genetic methods provide a powerful research tool which is largely being ignored by toxicologists.     

Morphological,biochemical and molecular changes during ectomycorrhiza development

Summary An ectomycorrhiza, a specialized root organ, is the result of a complex interaction leading to a finely-tuned symbiosis between a plant and a compatible ectomycorrhizal fungus. Ultrastructural observations combined with cytochemical and biochemical studies reveal that structural and metabolic changes in the symbiont cells lead to the final phenotype of the active ectomycorrhiza. In the present review these changes are interpreted as changes in gene expression and discussed within the context of ectomycorrhiza development. Recent genetic data indicate that the continued vegetative growth of the ectomycorrhizal hyphae and the root tissues, and their ability to switch to symbiotic organ formation, is basically controlled by developmentally critical genes. The activity of these symbiotic genes during the differentiation of ectomycorrhizas is associated with extensive changes in the concentration of particular polypeptides and protein biosynthesis. The present state of knowledge about the developmental biology of ectomycorrhizas allows only speculation about the events during their development.Puisant mes forces aux sources des galaxies En buvant la sève des arbres M. Jonasz     

On the application of the theory of emergence and of the law of maximum entropy production to social processes

As there would be appear to be no limit to the process of successive emergence, the emergence of suprahuman autopoietic systems seems possible, if not yet necessary. Maybe there really are constraints on human behavior which would not permit such entities to emerge, or maybe the emergence of such entities entails the dissipation of more free energy than available at present. But unless such conditions are present, then, it appears to me, the emergence of suprahuman autopoietic systems is not just probable, it is inevitable.In any event, whether or not they share my concern about suprahuman autopoietic systems, all concerned with metaphor manufacture should attend to this important insight from Swenson (1989a, b, c, d) and should not be deterred by my so inadequate reflection of a new and important view of how the organizational world works.     

Increase in the survival time of mice exposed to ionizing radiation by a new class of free radical scavengers

Summary N-acyl dehydroalanines react with and scavenge mainly superoxide radical and hydroxyl radical (HO^.). The ortho-methoxyphenylacetyl dehydroalanine derivative, indexed as AD-20, protects mice against damage resulting from total body X-irradiation, as measured by the increase in their survival time. AD-20 increases the LD₅₀ at 30 days from 6.1 to 7.3 Gy in animals exposed to a wide range of X-rays (6 to 10 Gy). The dose reduction factor (D R F) of AD-20 is 1.20. We postulate that such radioprotective effect may result from its free radical scavenging activity.     

Effects of a new cholecystokinin antagonist (GE 410) on the smooth muscle of the guinea pig ileum

Summary Suc-Tyr-(SE)-Met-Gly-Trp-Met-Asp--phenethylamide (GE 410) competitively antagonized the contractions of smooth muscle strips from guinea pig ileum (pA₂=7.6, n=0.95) induced by cholecystokinin-octapeptide (CCK8). GE 410 inhibited the electrically-induced cholinergically mediated contractile responses and the [³H]ACh release in the ileum, as well as the CCK-stimulated electrical contractile responses and the [³H]ACh release in the cholinergic nerve terminals. The results suggest the existence of CCK-receptors not only in the smooth muscles but also on the neurons.     

Saccadic oscillations facilitate ocular perfusion from the avian pecten

THE evolution of the eye is constrained by two conflicting requirements--good vascular perfusion of the retina, and an optical path through the retina that is unobstructed by blood vessels. Birds are interesting in that they have higher metabolic rates and thicker retinas than mammals, but have no retinal blood vessels. Nutrients and oxygen must thus reach the neurons of the inner retina either from the choroid through 300 micron of metabolically very active retina, or from the pecten, a pleated vascular structure protruding from the head of the optic nerve into the vitreous chamber, and more than a centimetre away from some retinal neurons. Despite the diffusional distance involved, several lines of evidence indicate that the pecten is the primary source of nutrients for the inner retina: the presence of an oxygen gradient from pecten to retina, the large surface area produced by macroscopic folds and by microscopic infoldings of the luminal and external surfaces of the capillary endothelium, extrusion of circulating fluorescein, high content of carbonic anhydrase and alkaline phosphatase, and retinal impairments after pecten ablation. Another peculiarity of birds, their saccadic oscillations, occur with a large cyclotor-sional component during every saccadic eye movement. In different species, saccades, which occur at intervals of 0.5-40 s, have up to 13 oscillations with frequencies of 15-30 Hz and ampliá-tudes of about 10 degrees. Therefore, as much as 12% of some birds' total viewing time may be subject to the image instability caused by the oscillations. Using fluorescein angiography, we show here that during every saccade, the pecten acts as an agitator which propels perfusate towards the central retina much more effectively than is observed during intersaccadic intervals.