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Biomedical subjects

J A Beech

Publications and source records attributed to J A Beech.

14 recordsLinked to original sources
PubMed1994

Carcinogenesis and initiation of cell cycling by charge-induced membrane clusters may be due to mitogen receptors and Na+/H+ antiports.

The membrane cluster hypothesis of mitogenesis and carcinogenesis is extended by proposing that much of the Na+ ingress across a cell's plasma membrane at surface charge-induced (SCI) aggregates is due to mitogen-induced activation of Na+/H+ antiports. Intrinsic proteins (including mitogen receptors and antiports) are electrostatically attracted to and become part of the aggregate. In this location, close proximity facilitates antiport activation. Resulting Na+ ingress may cause sustained partial depolarization, cytoplasmic alkalinization, and initiation of cell cycling. Chronic phosphorylation-dephosphorylation at SCI aggregates too weak to induce cycling, may slowly form polyionic bonds between adjacent proteins at the inner lipid layer. These bonds convert the SCI aggregates to 'permanent' clusters that pass to a daughter cell with parental plasma membrane at mitosis, and are associated with malignancy. EGF and PDGF growth factors are used to develop the hypothesis, which is also applied to steroid and dioxin receptors and to oncogene products.

Animals↗
PubMed1993

The membrane cluster hypothesis of mitogenesis and carcinogenesis.

This paper modifies and extends an earlier one on the same subject. It explains why external (but not internal) surface molecules of plasma membrane clusters may be rapidly scattered by any external challenging bioelectrical field. Temporary clusters from challenges may induce mitosis in cells near wounds and in epithelial stem cells. Weak challenges of much longer duration may initiate carcinogenesis by permanent clusters. Basic intracellular ligand/receptors or oncogene products in sufficient concentration at the membrane inner lipid layer may form permanent clusters rapidly. Additive increase of inner surface clusters by initiating agents is equated to promotion; accelerated cluster growth to progression. As a malignant cell grows, its cluster population increases until its membrane becomes permeable enough to stimulate mitosis. A progression mechanism is suggested that is consistent with the known properties of ras p21 proteins. The effect of long term exposure to power transmission line fields on mitosis and carcinogenesis is discussed. An approach to anticancer therapy is suggested, using a hypothesis-based mechanism for the anti-cancer activity of retinoic acid.

Animals↗
PubMed1992

Cell proliferation and carcinogenesis may share a common basis of permeable plasma membrane clusters.

Wound potentials increase the surface potential of exposed areas of nearby cells. In these cells, soluble cytoplasmic bases are assumed gradually to move nearer the exposed area. Acidic molecules on the cell surface migrate to points opposite the bases. The image-charged species are mutually attracted to form transmembrane clusters. At clusters, membrane permeability increases and the cell is stimulated to cycle. When the wound heals, its clusters disperse, leaving a small 'permanent' residuum. Permanent clusters initiate cells to malignancy. They have (or develop) lipophilic molecules on both surfaces that help fix them in the membrane. Exposed cells contaminated with polycyclic aromatic hydrocarbon carcinogens (PAH) readily form permanent clusters. At mitosis, clusters on parental plasma membrane pass with that membrane to a daughter cell. Promotion results from many short-term or a single long-term exposure of initiated membranes to abnormal surface charge. Permanent clusters increase on the membrane after repeated wounding, proximity of charged foreign bodies like plastic film or asbestos, or oxidation of surface molecules. Progression requires acceleration of cluster growth so the daughter cell membranes become as leaky at maturity as was the parent membrane. One mechanism suggested involves reversible phosphorylation by membrane-bound kinases; another involves attraction of a basic protein (p36) to the membrane.

Animals↗
PubMed1991

Polycyclic aromatic hydrocarbons initiate carcinogenesis by forming permanent membrane lesions of increased permeability. Other non-viral carcinogens may also form similar lesions.

Complexes of carcinogenic polycyclic aromatic hydrocarbons (PAH) and cationic Ah receptors, may be attracted to the cell membrane if its surface is exposed to external negative charge. At the membrane they may be trapped by lipophilic bonding. When the negative charge dissipates, the bound complexes create a local transmembrane charge imbalance. Molecules with organic anions are attracted to the outer surface to restore equilibrium. The two charged species form permanent dipoles (lesions) across the membrane. The membrane at the dipoles is more permeable. Similar permanent lesions involving steroid/receptor complexes may form after the local abnormal surface charge has been long-lived.

Animals↗
PubMed1991

Mitosis stimulation near wounds by temporary membrane lesions of increased permeability.

Ah and other positively charged organic receptors in cytosol are attracted to the membrane inner lipid layer if surface potential on part of their cell membrane is increased by potential from a nearby wound. At the membrane they form temporary transmembrane dipoles (lesions) of increased permeability that stimulate cell mitosis. This may be a normal mechanism assisting wound healing.

Animals↗
PubMed1989

The membrane potential theory of carcinogenesis.

Inoculation of target cells with oncogenic viruses can cause production of tumors after an extremely short latent period, whereas other carcinogenic stimuli have a much longer latency. These differences are consistent with a new and novel theory of carcinogenesis.

Animals↗
PubMed1989

Two stage carcinogenesis by membrane potential changes.

The membrane potential theory is modified and extended. It is shown to be applicable to carcinogenesis by prolonged treatment of target tissues with an initiating external carcinogen or by a single sub-threshold exposure to the initiating external carcinogen followed by subsequent treatment with a phorbol ester internal promoter.

Animals↗
PubMed1987

A theory of carcinogenesis based on an analysis of the effects of carcinogens.

Carcinogenic stimuli appear to act on target cells (and their daughters) by one or more of three mechanisms. The first is by oxidation of membrane component molecules on the extracellular surfaces of their plasma membranes. The second is by chronic and continuous impingement of electrons on the extracellular surfaces of their plasma membranes and the third is by relocation of predominantly basic molecules to the cytoplasmic surfaces of their plasma membranes. This latter effect in turn causes electrostatic attraction of image charged acidic molecules to the extracellular surfaces to balance the transmembrane charge of the target cells. Each of the above mechanisms results in a condition of increased electronegativity of the extracellular surfaces of plasma membranes of the target cells and their daughters. A theory of transformation is advanced based on the above related modes of action and it is used to explain some previously unexplainable properties of tumors.

Animals↗
PubMed1980

Nitrates, chlorates and trihalomethanes in swimming pool water.

Water from swimming pools in the Miami area was analyzed for nitrates, chlorates and trihalomethanes. The average concentrations of nitrate and chlorate found in freshwater pools were 8.6 mg/liter and 16 mg/liter respectively, with the highest concentrations being 54.9 mg/liter and 124 mg/liter, respectively. The average concentration of total trihalomethanes found in freshwater pools was 125 micrograms/liter (mainly chloroform) and in saline pools was 657 micrograms/liter (mainly bromoform); the highest concentration was 430 micrograms/liter (freshwater) and 1287 micrograms/liter (saltwater). The possible public health significance of these results is briefly discussed.

Chlorates↗