scholarly journals Further Comments on the Causation of Malignant Disease

1928 ◽  
Vol 28 (1) ◽  
pp. 9-32
Author(s):  
Arthur Eastwood

Invisible infective agents may be divided into: (1) true, ultramicroscopic, living viruses, which do not arise de novo and, so far as is known, are not ubiquitous; (2) transmissible infective agents which arise de novo and are propagated through living cells, but are not themselves living organisms; (3) stimulants to variation which arise de novo, are not transmissible, and are not living organisms.Class (1) is not represented in malignant disease. “Bacteriophage” is a representative of class (2); very probably the infective agent of fowl sarcoma comes under the same category, and possibly some important human diseases of doubtful aetiology. There is no satisfactory evidence that mammalian malignant disease is related to class (2); its causation, according to the “chronic irritation” theory, must be attributed to influences comprised within class (3).The stimulants to variation in class (3) depend for their effectiveness upon the unstable energy of living matter. The changes which they produce are “biological” in the sense that they are changes of chemical constitution which could not be obtained without the aid of vital processes.Regulation of normal growth in the animal body means regulation of the cell's facilities for obtaining energy. I think it is misleading to regard it as a forceful restraint (or stimulus) upon the cell's inherent capacity for unlimited growth.The assumption, borrowed from “natural immunity” towards bacteria, that there is in the animal body a natural principle which destroys frequently occurring foci of incipient malignancy is also unsubstantiated and misleading.During the latent period, certain cells, which subsequently grow into a neoplasm, lose their capacity to respond to inhibitory systemic influences. This change is brought about by local and not by systemic causes.As regards the special class of tumour derived from cells which have been displaced in foetal life, long residence in an abnormal situation does not appear to be equivalent to the ordinary latent period; but it may have had the effect of increasing their susceptibility, so that, if exposed to chronic irritation, the cells would more readily lapse into the latent period predisposing to malignancy.It is known that the various tissues of the animal body differ in their degree of susceptibility to the precancerous change. This is a cellular characteristic; so also is the difference in the susceptibility of one animal as compared with another. It is not a question of difference in a hypothetical humoral property of “systemic resistance.”On the termination of the latent period by a fresh stimulus to proliferation, certain cells commence active growth and are incapable of responding to systemic inhibitory influences. These conditions seem sufficient for the origin of an innocent neoplasm. But something more is required to explain malignancy, because the malignant cell is essentially different from the cells in a benign tumour.About the actual cause of the change to malignancy one can only offer conjectures. I have suggested a way in which the change may possibly be produced through the agency of the local endothelium and the autogenous formation of antibodies.On taking a broad view, the change into the malignant variant is not something unique; equally remarkable changes are to be found in the properties of bacteria. In both cases the facts have to be accepted, at present, without satisfactory explanation of the conditions which gave rise to them. One finds with bacteria that degradation or “roughness” may be a phase preparatory to the acquirement of new properties, just as the degradation of cells in the latent period seems to be a requisite preparation for acquiring the new property of malignancy. But the actual steps involved in the change from a bacterial saprophyte to an invasive parasite are as difficult to understand as are the processes involved in the conversion of a normal animal cell into its malignant variant.Throughout the study of cancer it is very desirable to maintain a clear distinction between cause and effect. For example, the enzymes peculiar to cancer are not the cause of cancer but the effect of the biological change which produced the cancerous cell.

2009 ◽  
Vol 20 (11) ◽  
pp. 2796-2808 ◽  
Author(s):  
Sara Moutinho-Pereira ◽  
Alain Debec ◽  
Helder Maiato

Cytoskeleton microtubules undergo a reversible metamorphosis as cells enter and exit mitosis to build a transient mitotic spindle required for chromosome segregation. Centrosomes play a dominant but dispensable role in microtubule (MT) organization throughout the animal cell cycle, supporting the existence of concurrent mechanisms that remain unclear. Here we investigated MT organization at the entry and exit from mitosis, after perturbation of centriole function in Drosophila S2 cells. We found that several MTs originate from acentriolar microtubule-organizing centers (aMTOCs) that contain γ-tubulin and require Centrosomin (Cnn) for normal architecture and function. During spindle assembly, aMTOCs associated with peripheral MTs are recruited to acentriolar spindle poles by an Ncd/dynein-dependent clustering mechanism to form rudimentary aster-like structures. At anaphase onset, down-regulation of CDK1 triggers massive formation of cytoplasmic MTs de novo, many of which nucleated directly from aMTOCs. CDK1 down-regulation at anaphase coordinates the activity of Msps/XMAP215 and the kinesin-13 KLP10A to favor net MT growth and stability from aMTOCs. Finally, we show that microtubule nucleation from aMTOCs also occurs in cells containing centrosomes. Our data reveal a new form of cell cycle–regulated MTOCs that contribute for MT cytoskeleton remodeling during mitotic spindle assembly/disassembly in animal somatic cells, independently of centrioles.


1987 ◽  
Vol 252 (5) ◽  
pp. C468-C476 ◽  
Author(s):  
M. P. Paccolat ◽  
K. Geering ◽  
H. P. Gaeggeler ◽  
B. C. Rossier

The effects of aldosterone on transepithelial sodium transport (measured by the short-circuit current (SCC) and on Na+-K+-adenosine triphosphatase (ATPase) biogenesis have been studied in A6 kidney cells grown on collagen-coated filters in two different media. In medium A, base-line SCCA was close to zero but transmural electrical resistance (RA) was high. Aldosterone (100 nM, t24h) drastically increased SCCA and RA, but only after a 4-h latent period. In medium B, base-line SCCB and RB were significantly higher than in medium A. Aldosterone significantly enhanced SCCB and to a lesser extent RB after a much shorter latent period (approximately 45 min) than in medium A. In medium A, aldosterone elicited a fourfold increase in the relative rate of synthesis of alpha- and beta-subunits of Na+-K+-ATPase. A twofold increase was already observed within the observed latent period. This time course suggests that de novo synthesis of sodium pumps might be one of the critical factors underlying the increase in sodium transport in this growth medium. In medium B, aldosterone elicited a two- to fourfold increase in the relative rate of synthesis of the alpha- and beta-subunits of Na+-K+-ATPase that paralleled SCCB. Thus de novo synthesis of Na+-K+-ATPase is clearly not a prerequisite for the early mineralocorticoid response (t90 min - t180 min), but still could be part of the late mineralocorticoid response (t3 h - t24 h). In both media, the immunochemical cellular pool of Na+-K+-ATPase was apparently not modulated by aldosterone for up to 48 h of incubation.(ABSTRACT TRUNCATED AT 250 WORDS)


1990 ◽  
Vol 36 (1) ◽  
pp. 1-5 ◽  
Author(s):  
T. E. Cleveland ◽  
D. Bhatnagar

The accumulation of both activity and protein of a methyltransferase (MTase) from Aspergillus parasiticus, which catalyzes conversion of sterigmatocystin to O-methylsterigmatocystin in the aflatoxin pathway, was detected in fungal mycelia slightly before the onset of aflatoxin biosynthesis in the same cultures. MTase protein was identified in mycelial postmicrosomal (soluble protein) fractions by electrophoresis and subsequent immunoblotting using antiserum raised against purified MTase protein; MTase activity was determined by measuring the rate of conversion of sterigmatocystin to O-methylsterigmatocystin in the presence of soluble protein fractions. Using the above technique, it was determined that MTase protein as well as MTase activity increased sharply in mycelia 30 to 45 h after inoculation, shortly after which, mycelial growth rate began to decline. During the subsequent time interval (45 to 70 h after inoculation), a sharp increase in aflatoxin levels was detected in the culture medium. Results obtained from an experiment in which cycloheximide was added to cultures at various times to inhibit protein synthesis and from an experiment in which mycelial proteins were radiolabelled to identify newly synthesized proteins indicated that accumulation of MTase activity and protein in late growth phase mycelia is due to de novo protein synthesis. Key words: aflatoxin, methyltransferase, biosynthetic pathway.


Science ◽  
2018 ◽  
Vol 362 (6417) ◽  
pp. 949-952 ◽  
Author(s):  
G. Lebreton ◽  
C. Géminard ◽  
F. Lapraz ◽  
S. Pyrpassopoulos ◽  
D. Cerezo ◽  
...  

The emergence of asymmetry from an initially symmetrical state is a universal transition in nature. Living organisms show asymmetries at the molecular, cellular, tissular, and organismal level. However, whether and how multilevel asymmetries are related remains unclear. In this study, we show that Drosophila myosin 1D (Myo1D) and myosin 1C (Myo1C) are sufficient to generate de novo directional twisting of cells, single organs, or the whole body in opposite directions. Directionality lies in the myosins’ motor domain and is swappable between Myo1D and Myo1C. In addition, Myo1D drives gliding of actin filaments in circular, counterclockwise paths in vitro. Altogether, our results reveal the molecular motor Myo1D as a chiral determinant that is sufficient to break symmetry at all biological scales through chiral interaction with the actin cytoskeleton.


1924 ◽  
Vol 39 (2) ◽  
pp. 219-244 ◽  
Author(s):  
Oswald H. Robertson ◽  
Richard H. P. Sia

Somewhat discordant results which have been reported by others who have investigated the property of the whole blood of resistant animals to cause inhibition of growth or death of pneumococci have led us to investigate this matter and to develop a new technique in which the conditions as they are present in the animal body are more nearly imitated. The observations already made have rendered it probable that phagocytosis plays some rôle in any destructive power for pneumococcus which whole blood possesses. We have, therefore, employed mixtures of serum and leucocytes in our tests, since when blood is coagulated the conditions become highly artificial. Furthermore, in order to imitate more nearly the conditions in the circulating blood the mixtures have been constantly, though gently, agitated. For this purpose a specially devised apparatus has been employed. The mixtures of serum and leucocytes have been inoculated with varying numbers of pneumococci in the active growth phase and after varying intervals of time the tubes containing the mixtures of serum, leucocytes, and bacteria have been opened, examined microscopically, and cultures made. Employing this technique it has been found that the growth of pneumococci having low virulence for cats is markedly inhibited in mixtures of cat serum and cat leucocytes. It was impossible to recover pneumococci from the tubes showing no apparent growth, either when the contents were transplanted into various kinds of culture media, or when the contents were injected into mice of a variety highly susceptible to pneumococcus infection. 10,000 times the number of pneumococci sufficient ordinarily to kill a mouse failed to do so after a 24 hour sojourn in the cat serum-leucocyte mixture. Mixtures of dog serum and leucocytes exert a similar action. The serum and leucocytes of animals susceptible to pneumococcus infection (rabbits and guinea pigs,) on the other hand, failed to injure pneumococci even in extremely small quantities. These results indicate that the blood of resistant animals, at least of the dog and cat, possesses destructive properties for pneumococci, and that this destructive power is not possessed by the blood of certain susceptible animals. The experiments suggest that natural immunity depends chiefly, if not entirely, upon this property. The leucocytes play an active part in this process, but whether the destruction of the pneumococci occurs entirely within the leucocytes or not is not determined. That the serum also plays a part is shown by the fact that when the serum of resistant animals was inactivated before being used in the serum-leucocyte mixture, the growth of even very small numbers of pneumococci was not prevented. Further experiments with cat serum and leucocytes were carried out to determine the optimum rate and time of agitation, the amount of serum and leucocytes required, and also the period of incubation necessary for the inhibition of growth and death of the pneumococci to occur.


2020 ◽  
Vol 37 (8) ◽  
pp. 2279-2286
Author(s):  
Aleksandra V Bezmenova ◽  
Elena A Zvyagina ◽  
Anna V Fedotova ◽  
Artem S Kasianov ◽  
Tatiana V Neretina ◽  
...  

Abstract The basidiomycete Schizophyllum commune has the highest level of genetic polymorphism known among living organisms. In a previous study, it was also found to have a moderately high per-generation mutation rate of 2×10−8, likely contributing to its high polymorphism. However, this rate has been measured only in an experiment on Petri dishes, and it is unclear how it translates to natural populations. Here, we used an experimental design that measures the rate of accumulation of de novo mutations in a linearly growing mycelium. We show that S. commune accumulates mutations at a rate of 1.24×10−7 substitutions per nucleotide per meter of growth, or ∼2.04×10−11 per nucleotide per cell division. In contrast to what has been observed in a number of species with extensive vegetative growth, this rate does not decline in the course of propagation of a mycelium. As a result, even a moderate per-cell-division mutation rate in S. commune can translate into a very high per-generation mutation rate when the number of cell divisions between consecutive meiosis is large.


2015 ◽  
Vol 55 (4) ◽  
pp. 343-350 ◽  
Author(s):  
Navodit Goel ◽  
Prabir Kumar Paul

Abstract Tomato (Solanum lycopersicum L.) is attacked by Pseudomonas syringae pv. tomato causing heavy damage to the crops. The present study focused on the application of aqueous fruit extracts of neem (Azadirachta indica L.) on a single node of aseptically raised tomato plants. Observations were done, and the changes in the activity and isoenzyme profile of polyphenol oxidase (PPO) and lysozyme, both at the site of treatment as well as away from it, were noted. The results demonstrate that neem extract could significantly induce the activities of both the enzymes as well as upregulate the de novo expression of additional PPO isoenzymes. Induction of systemic acquired resistance (SAR) by natural plant extracts is a potent eco-friendly crop protection method.


2019 ◽  
Vol 49 (1) ◽  
Author(s):  
Sanja Brekalo Lazarević ◽  
Edina Handžić ◽  
Abdel Đozić ◽  
Ivana Lazarević ◽  
Zahida Ademović ◽  
...  

The development of industry, agriculture, transport and urbanization has resulted in excessive emissions of heavy metals into the environment, which due to their bioaccumulative properties express negative effects on the environment and living organisms as a whole. In this work the presence of heavy metals in the soil samples of the urban area of Lukavac and Kalesija municipality and their effect on the health of the population were studied. Soil samples were collected in October 2017 at five locations in the urban area of Lukavac municipality and two urban locations in Kalesija municipality. Concentrations of chromium (Cr) copper (Cu), cobalt (Co), nickel (Ni), cadmium (Cd), lead (Pb), manganese (Mn), iron (Fe) and zinc (Zn) in the soil samples were determined. The results indicated that in some locations the concentration of heavy metals exceeded the maximum permissible concentration (MPC). MPC value for chromium was exceeded at four locations in the urban area of Lukavac, whereas MPC value for nickel and cadmium was exceeded at all locations. In Kalesija, MPC value was exceeded for chromium and nickel at one location, while cadmium MPC was exceeded at both locations. The negative impact of heavy metals on the health of the population is the cause of many malignant diseases. Statistical analysis of the number of patients with malignant diseases in the area of the Lukavac and Kalesija revealed significantly higher prevalence of malignant diseases of the lungs, breast, skin and cervix in the Lukavac (p<0,05) in comparisson to Kalesija municipality.


2019 ◽  
Author(s):  
Mónica Arias ◽  
Marianne Elias ◽  
Christine Andraud ◽  
Serge Berthier ◽  
Doris Gomez

AbstractPredation is a ubiquitous and strong selective pressure on living organisms. Transparency is a predation defence widespread in water but rare on land. Some Lepidoptera display transparent patches combined with already cryptic opaque patches. While transparency has recently been shown to reduce detectability in conspicuous prey, we here test whether transparency decreases detectability in already cryptically-coloured terrestrial prey, by conducting field predation experiments with free avian predators and artificial moths. We monitored and compared survival of a fully opaque grey artificial form (cryptic), a form including transparent windows and a wingless artificial butterfly body. Survival of the transparent forms was similar to that of wingless bodies and higher than that of fully opaque forms, suggesting a reduction of detectability conferred by transparency. This is the first evidence that transparency decreases detectability in cryptic terrestrial prey. Future studies should explore the organisation of transparent and opaque patches on the animal body and their interplay on survival, as well as the costs and other potential benefits associated to transparency on land.


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