Summary Verapamil, the prototype calcium channel blocker, reversibly inhibits cell proliferation in many normal and tumour cell lines (Schmidt et al., Cancer Res., 48, 3617, 1988). We The calcium channel blockers have generated much interest in cancer research since the demonstration that at low concentration (5-10Mm) they augment the cytotoxicity of many standard anti-cancer agents in a variety of tumour cell types (Tsuruo et al., 1983a,b;Yalowich & Ross, 1984Robinson et al., 1985;Ince et al., 1986;Merry et al., 1986). Verapamil, the prototype calcium channel blocker, enhances the cytotoxic effects of both vincristine and adriamycin in vitro as well as in vivo in cells previously resistant to these drugs (Tsuruo et al., 1981(Tsuruo et al., , 1983a. Although the precise mechanism of this increased cytotoxic effect is not completely understood, the calcium channel blockers are thought to act by blocking efflux of the chemotherapeutic agents from the cell (Tsuruo et al., 1982).At higher concentrations (10-100yM), verapamil by itself reversibly inhibits cell growth in several human cell lines (Schmidt et al., 1988). Protein synthesis, DNA synthesis and RNA synthesis are all inhibited within minutes of addition of OO M verapamil to the cells; removal of the drug by simple washing of the cells results in a rapid resumption of cell growth (Schmidt et al., 1988). These reversible antiproliferative effects of verapamil make it an ideal compound to study cell cycle related events.Cell growth is controlled by a cascade of events that ultimately leads to DNA synthesis. Briefly, cell proliferation begins when growth factors interact with the cell membrane, sending a signal via inositol phospholipids to increase cytoplasmic ionised calcium by one pathway and to increase cytoplasmic pH by another pathway (Berridge, 1984). However, stimulation of protein kinase C by phorbol esters (e.g. TPA) directly causes cytoplasmic alkalinisation and in at least some cells this stimulation can by-pass the calcium pathway (Rozengurt & Mendoza, 1985). Furthermore, the involvement of c-onc genes in cell proliferation has been extensively documented (Kahn & Graf, 1986).One of the first genes linked to cell growth was the protooncogene c-myc. C-myc gene expression is known to be linked tightly to cell proliferation, increasing [10][11][12][13][14][15][16][17][18][19][20] al., 1983). The cmyc gene, which is expressed in both malignant and normal cells, encodes a protein that is functionally involved in DNA synthesis (Studzinski et al., 1986). This protein is believed to directly regulate the rate at which cells divide (Cole, 1986 Fidler & Kripke (1977). After injection of 50,000 to 100,000 cells into the tail veins of C57BL/6 mice, the B16 FIO cells form many more pulmonary metastases than the B16 Fl cells within 2-3 weeks. All experiments were performed at least twice.Radioisotope incorporation Actively growing cells (in the exponential phase) were always used when assessing isotope incorporation, Methyl-3H-thymidine was added to cell cultu...
-Background: Docosahexaenoic acid (DHA) has been the dominant acyl component of the membrane phosphoglycerides in neural signaling systems since the origin of the eukaryotes. In this paper, we propose, this extreme conservation, is explained by its special electrical properties. Based on the Pauli Exclusion Principle we offer an explanation on how its six methylene interrupted double-bonds provide a special arrangement of π-electrons that offer an absolute control for the precision of the energy of the signal. Precision is not explained by standard concepts of ion movement or synaptic strengthening by enhanced protein synthesis. Yet precision is essential to visual acuity, truthful recall and the exercise of a dedicated neural pathway. Concept: Synaptic membranes have been shown to actively incorporate DHA with a high degree of selectivity. During a learning process, this biomagnification will increase the proportion of membrane DHA with two consequential neuronal and synaptic enhancements which build into a David Marr type model of the real world: DHA induced gene expression resulting in enhanced protein synthesis; increased density of π-electrons which could provide memory blocks and provide for the preferential flow of a current in neural pathways. Proposal: Both the above imply memory from synaptic strengthening. We propose memory is achieved by the activation of neuronal synaptic activation with synaptic turnover resulting in enhanced membrane DHA, which in turn induces gene expression, protein synthesis and π-electron density. Repetition amplifies the process activating synapses, which form a matrix representing the memory. The electro-chemical potentials then fire the electrons as electromagnetic waves via the six methylene interrupted double bonds. These allow transmission at a specific energy level based on their quantum mechanical properties providing the precision required for faithful recall. It is difficult to conceive of protein synthesis alone providing for precision. Using the principle of the dual properties of photons and electrons we develop the idea of complex wave patterns representing the visual or auditory fields. These are likely to be noncomputable. We suggest that harmonization of the electromagnetic waves can result in cohesion explaining recall and associations. The cohesion of electromagnetic flow leads to a surge above the resting level, which is recognized by the brain as, demonstrated in artificial, electrical stimulus during neurosurgery.Keywords: chaos theory / docosahexaenoic acid / π-electrons / signal precision / quantum mechanics / memory / cognition / perception Résumé -Une théorie sur le rôle des électrons π de l'acide docosahexaénoïque dans la fonction cérébrale. Les six doubles liaisons interrompues par un groupe méthylène et la précision de la signalisation neuronale. Introduction : Depuis l'origine des eucaryotes, l'acide docosahexaénoïque (DHA) est l'acide gras majoritaire des phosphoglycérides des membranes dans les systèmes neuronaux de signalisation. Dans ...
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