Critical Cell Number Research Articles

Some theoretical aspects of intercellular bridges as a potential mechanism of cancerous proliferation.

Abstract Recent experimental investigations have shown that formation of intercellular bridges accompanies malignant transformation of several cell types in vitro and that such bridges are capable of transmitting a mitotic stimulus from cell to cell. The present paper formulates on a generalized basis some of the more important theoretical properties of mitotically self-exciting syncytia of the type mentioned above, and establishes some conceptually useful criteria for determining the probability of formation and the relative malignancy of such systems. It is suggested that, in principle, syncytia formed of bridge-connected cells are mitotically unstable, and, provided they contain a critical minimum number of cells, whose value is defined by a ‘spontaneous mitotic index’, are highly malignant in nature.

Wechselwirkung von Riboflavin, Isoriboflavin und 2‐Thiouracil auf die Induktion zweidimensionalen Wachstums von Farnprothallien

Abstract Action of riboflavin, isoriboflavin and 2‐thiouracil in the induction of 2‐dimensional growth of fern prothallia.—The inhibition of cell division induced by 2‐thiouracil in prothallia of Dryopteris filix‐mas and Anemia phyllitidis is reversed by riboflavin as well as by its physiological inactive analogue isoriboflavin. This antagonism is not due to an in vivo interaction as stated by Yeoh and Raghavan, but is rather caused by an in vivo sensibilisation of photo destruction of the inhibitor during early phase of spore germination.Riboflavin as well as isoriboflavin strongly inhibit cell divisions in the prothallia of Anemia phyllitidis.In spite of a significantly reduced growth rate NO retardation of the onset of the 2‐diniensional differentiation, as related lo a critical cell number, can be slated in the Anemia prothallia.

The Induction of Biplanar Growth in Fern Gametophytes in the Presence of RNA Base Analogues

The RNA base analogues, 5-fluorouracil, 2-thiouracil, and 8-azaguanine, inhibit the growth of Dryopteris borreri, but do not prevent the transition from filamentous to biplanar growth. Transition, which occurs only when the filament has developed to 4 or 5 cells, may be considerably delayed, due to inhibition of filamentous growth, but it always occurs when the critical cell number of the filament is reached. Furthermore, the inhibitors show only a marginal differential effect on biplanar compared to filamentous growth when the growth rates are determined from kinetic studies. It is suggested that the selective effects previously reported may result from the experimental techniques used, coupled with the actual growth characteristics of the gametophyte.

Conditions for plaque formation with a phlebotomus (sandfly) fever virus.

Summary Naples virus, a member of the Phlebotomus fever group of arboviruses, is able to multiply in cells derived from hamster embryos. It produces no cyto- pathic effect in these cells in a fluid medium and no plaques upon infection of confluent monolayers overlaid with a medium containing agar or the sodium salt of carboxymethylcellulose. Plaques are produced only when these cells are infected in suspension and plated to form monolayers under an overlay containing carboxymethylcellulose. A critical number of cells is required and the presence of carboxymethylcellulose is essential. The survival or death of a hamster embryo cell infected with this virus appears to depend upon the stage of growth of the cells at the time of infection and the environmental conditions.

Corneal complications from cryoextraction of cataracts.

Routine use of cryosurgery in a series of 200 cataract extractions resulted in a marked increase in the incidence of irreversible corneal edema when compared with a series of 900 deliveries by conventional methods (increase from 0.66% to 4¼%). This is presumably due to inadvertent freezing and lysis of a critical number of endothelial cells. These clinical observations are consistent with laboratory findings of other workers who induced irreversible corneal edema in rabbits by surface freezing techniques. Further research appears indicated before cryosurgery can be routinely adopted as a safe method of cataract extraction. Until such time caution is urged.

Effect of inhibitors of DNA-, RNA-, and protein synthesis on growth and antheridium formation in Anemia phyllitidis

A number of inhibitors of DNA-, RNA-, and protein synthesis were applied to prothallia of Anemia phyllitidis, and their effects were investigated with regard to cell division and inhibition of antheridium formation (after induction by gibberellin A3). All compounds tested cause a significant inhibition of growth accompanied by teratologies typical for each inhibitor. Only 5-bromouracil proved to be inactive, even at a concentration of 8×10-4m. None of the inhibitors blocked the induction of the biplanar growth form in continuous light. With the exception of 5-bromodeoxyuridine and 5-iododeoxyuridine all the antimetabolites investigated cause a significant lag in antheridium formation. The result of an analysis of this inhibition on the basis of the “critical cell number” (Schraudolf, 1966a) demonstrates that this time lag is clearly a direct consequence of the retardation of cell division caused by the inhibitors. There is no inhibition of the induction process proper. So therefore it appears highly improbable that antheridium induction in Anemia by gibberellins is based on a specific gene activation in the sense of Jacob and Monod. The results presented in this paper demonstrate that the production of a time lag in the realisation of a process of differentiation or morphogenesis is not sufficient evidence to permit definite conclusions to be drawn about the basic mechanism of induction; the effect of inhibition of cell division caused by the inhibitors must be excluded or at least taken in to account. The possible function of gibberellins as “realisators” of already present but inactive m-RNA is discussed. 5-Bromo- and 5-iododeoxyuridine do not cause a time lag in antheridium formation; both inhibitors, however, cause a deformation of the cell pattern of the antheridia. The degree of this deformation depends on inhibitor concentration as well as on exposure time. Probably a competition exists between these halogensubstituted pyrimidines and thymidine for incorporation into DNA.

Estimation of the cellular lethal dose and the critical cell number for the C3H mouse mammary carcinoma from radiosensitivity studies in vivo.

IF it is assumed that irradiation of a tumour results in immediate or eventual sterilization of a given proportion of its constituent cells1, that the magnitude of this effect is an exponential function of dosage2,3, and that the ability of the residual viable cells to grow progressively depends upon whether their number exceeds that critical value below which their growth is effectively suppressed by host-resistance factors alone4,5, then the radiosensitivity, or mean lethal dose, of the individual cells, and the critical cell number for the C3H adenocarcinoma growing under various conditions, can be estimated indirectly from observed data on the radiosensitivity of the tumour in vivo.

THE CHEMICAL NATURE OF HEART FAILURE

Excerpt Heart failure in its commonest and simplest form represents an inadequacy in contraction of a critical number of individual heart muscle cells. Every clinician has witnessed the death of pa...