Anti-apoptotic signaling by a colony-stimulating factor-1 receptor/insulin receptor chimera with a juxtamembrane deletion

The intracellular mechanisms used by insulin and insulin-like growth factors to block programmed cell death are unknown. To identify receptor structures and signaling pathways essential for anti-apoptotic effects on cells, we have created a chimeric receptor (colony-stimulating factor-1 receptor/insulin receptor chimera (CSF1R/IR)) connecting the extracellular, ligand-binding domain of the colony-stimulating factor-1 (CSF-1) receptor to the transmembrane and cytoplasmic domains of the insulin receptor. Upon activation with CSF-1, the CSF1R/IR phosphorylates itself and intracellular substrates in a manner characteristic of normal insulin receptors. CSF-1 treatment protected cells expressing the CSF1R/IR from staurosporine-induced apoptosis. A chimeric receptor (CSF1R/IRDelta960) with a deletion of 12 amino acids from its juxtamembrane domain was constructed and expressed. CSF-1-treated cells expressing the CSF1R/IRDelta960 are unable to phosphorylate IRS-1 and Shc (Chaika, O. V., Chaika, N., Volle, D. J., Wilden, P. A. , Pirrucello, S. J., and Lewis, R. E. (1997) J. Biol. Chem. 272, 11968-11974). CSF-1 stimulated glucose uptake, mitogen-activated protein kinases, and IRS-1-associated phosphatidylinositol 3' kinase in cells expressing the CSF1R/IR but not in cells expressing the CSF1R/IRDelta960. Surprisingly, the CSF1R/IRDelta960 was as effective as the CSF1R/IR in mediating CSF-1 protection of cells from staurosporine-induced apoptosis. These observations indicate that the anti-apoptotic effects of the insulin receptor cytoplasmic domain can be mediated by signaling pathways distinct from those requiring IRS-1 and Shc.     

Kindling-like state occurring on periodic increases in the extracellular K+ concentration in field CA1 in rat hippocampal slices

Transient periodic increases in the extracellular K+ concentration (20 mM, 30 sec, 3-6 episodes) led to the appearance of a kindling-like state in local neuronal networks of field CA1 of rat hippocampal slices. A criterion for the appearance of this state was a reduction in the threshold for the generation of multiple population discharges and an increase in the total number of population spikes within discharges (epileptiform activity). This state correlated with potentiation of excitatory postsynaptic potentials (EPSP) (long-term increases in pyramidal neuron excitability), but not with potentiation of glutamatergic synaptic transmission in field CA1 of hippocampal slices. The role of the various Ca2+ channels in inducing and maintaining the kindling-like state in rat hippocampal sections, evoked by periodic increases in the extracellular K+ concentration, is discussed.     

Epidemiology of chronic, precancerous and oncologic diseases in workers of asbestos and cement industry

Hygienic, clinical and epidemiologic screening was performed in staff of asbestos and cement goods production enterprise. Various dystrophic processes of pharynx and nasal cavity appeared to prevail among upper respiratory tract diseases. Average exposure to dust during 22 years at the stated production can lead to asbestosis 0-I stage, average exposure during 20.5 years can result in dust bronchitis and occupational allergic dermatosis can result from average exposure to dust during 21 years. Retrospective cohort study of mortality within 1949-1988 failed to find oncologic risk in workers engaged into asbestos and cement goods production higher than in general population.     

Phenomenon of life span instability in Drosophila melanogaster: I. Nonrandom origin of life span variations in successive generations

The dynamics of life span (LS) and fecundity in Drosophila melanogaster, strain D-32, were analyzed in a series of successive generations. Highly reliable variations in both fitness components were found. On initial inspection the variations would be characterized as random or irregular wherein mean values differed up to threefold. The variance in longevity is greater in females than in males. By use of mathematical procedures we have shown a scale regularity in LS distributions for all generations. Such regularity, in spite of considerable differences in absolute values (mean and maximum LS), suggested that the origin of LS instability is nonrandom.     

Domestication as a possible mode of biodiversity conservation (as exemplified by the river otter Lutra lutra L., 1758)

On an experimental basis in the Institute of Cytology and Genetics Siberian Division, Russian Academy of Sciences, a cage population of river otter (Lutra lutra) was formed. During the introduction period of captivity, as the selection for stress resistance in an anthropogenic environment is shown to be a crucial factor. Through the course of domesticating river otters, directional selection occurs due to the increase in the number of individual otters and to the absence of fear-induced response toward humans. In the initial generation caught in the wild, three types of animals were revealed: cowardly or showing a fear-induced response (80%), aggressive (10%), and quiet (10%). After three generations were reared in captivity, the relationship between these three phenotypes changed in favor of otters with a quiet response toward man; the percentage increased. After three generations, these quiet animals comprised 37%. The percentages of aggressive and cowardly animals accounted for 11 and 52%, respectively.     

Amizon in the treatment of nervous system involvement in herpes zoster

The authors submit results of treatment of patients having suffered from postherpetic pain syndrome (herpetic ganglionitis of the cervical, thoracic, lumbosacral localization, postherpetic intercostal neuralgia, ganglionitis of the trigeminal nerve). In viral diseases, amizone has marked analgetic, antiinflammatory, and immunomodulating effects. The drug is well tolerated by patients, is not associated with side effects under prescribed doses (0.25-0.75 as one dose on a three- or four-times daily schedule during the course of treatment lasting three or four weeks). The drug preparation in question is less effective in the treatment of chronic recurring post-therapeutic intercostal neuralgias, radiculalgia.     

The effect of inhibitors of DNA topoisomerase II on the radiosensitivity, repair and conformational changes in the chromatin in mammalian cells

1. The pharmacological properties of four synthetic analogues of the wasp neurotoxin, Vespulakinin 1, were studied using a cascade of mammalian smooth muscle preparations and the synaptic transmission from the cockroach cercal nerves to a giant interneuron. 2. All analogues have an extremely slow bradykinin-like effect on the smooth muscles. The carbohydrate-free and the two mono-glycosylated analogues are about equally active with bradykinin. 3. The double glycosylated derivative is about 5 times more potent than bradykinin. 4. All analogues have two different effects on synaptic transmission in the insect CNS--at first a direct and reversible block of excitatory nicotinic transmission with a concurrent activation of the inhibitory GABA-ergic system and, secondly, a delayed irreversible block of the transmission, comparable to the block described earlier for bradykinin and Thr6-bradykinin. 5. For the synaptic transmission in the insect CNS the double glycosylated kinin is about 5 times more potent than bradykinin.