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The multiple genetic hit model of cancer predicts that normal individuals should have stable populations of cancer-prone, but noncancerous, mutant cells awaiting further genetic hits. We report that whole-mount preparations of human skin contain clonal patches of p53-mutated keratinocytes, arising from the dermal-epidermal junction and from hair follicles. These clones, 60-3000 cells in size, are present at frequencies exceeding 40 cells per cm2 and together involve as much as 4% of the epidermis. In sun-exposed skin, clones are both more frequent and larger than in sun-shielded skin. We conclude that, in addition to being a tumorigenic mutagen, sunlight acts as a tumor promoter by favoring the clonal expansion of p53-mutated cells. These combined actions of sunlight result in normal individuals carrying a substantial burden of keratinocytes predisposed to cancer.  相似文献   
23.
The behavior of hydrogen in solids under the action of intense ionizing radiation is of importance in solving numerous problems of materials science for the nuclear and thermonuclear power industry, spacecraft engineering, hydrogen energetics, and microelectronics. Experimental results are presented that provide evidence of the radiation-induced yield of hydrogen from single crystal silicon bombarded with 710-MeV bismuth ions.  相似文献   
24.
Phospholamban (PLN) is an intrinsic membrane protein of 52 amino acids which regulates the Ca2+ pump of the sarcoplasmic reticulum of heart, slow-twitch and smooth muscle (SR): it is normally assumed to exist in the membrane as a homopentamer. A monomeric analogue of phospholamban PLN(C41F), in which Cys41 was replaced by a Phe, was synthesized and its conformation studied by 1H NMR spectroscopy in a 1:1 mixture of chloroform/methanol. Most of the resonances in the 1H NMR spectra were assigned. The work has shown that the C-terminal hydrophobic portion forms a very stable alpha-helix. The hydrophilic N-terminal part adopts an alpha-helix configuration which is much less stable except for the stretch containing the phosphorylation sites.  相似文献   
25.
The physical preconditions are considered for the temperature of a body to influence the force of gravity experienced by it. The results are given of experiments on weighing metal rods heated by ultrasound which confirm a dependence of the weight of the rods on their temperature.  相似文献   
26.
Twenty seven Aeromonas strains (5A. hydrophila, 8A. sobria and 14A. caviae) isolated from children with diarrhoea and 34 Aeromonas strains (9A. hydrophila, 7A. sobria an 18A. caviae) isolated from children without diarrhoea were tested from haemolysin production. The results obtained showed that haemolysin production using human, horse or sheep erythrocytes was significantly associated with A.hydrophila and A sobria but not with A.caviae, regardless of whether these strains were isolated from children with or without diarrhoea. Human or horse rather than sheep erythrocytes are recommended for use in the haemolysin assay.  相似文献   
27.
Southern blot analysis was performed with a panel of DNA probes to detect rearrangements of c-myc, bcl-1, bcl-2 and bcl-3 in 14 cases of B-cell non-Hodgkin's lymphoma (NHL) with a clonal cytogenetic rearrangement involving the chromosome 14q32 locus and no known donor chromosome [t(14;?)(q32;?)]. In our experience, 21% of all chromosomal abnormalities involving the 14q32 locus in B-cell NHL are of this type. We found oncogene rearrangements in five of the 14 cases: bcl-1 rearrangement on one mantle zone lymphoma, bcl-2 rearrangements in two follicular lymphomas, and c-myc rearrangements in two small noncleaved cell lymphomas. We conclude that a 14q32+ abnormality of unknown origin is a relatively frequent karyotypic finding in B-cell NHL. In one third of the cases, known oncogenes that have been previously described in reciprocal translocations involving the immunoglobulin heavy chain locus were shown to be involved in the 14q32+ abnormality. The translocations in the other cases are likely to have involved one of the above oncogenes with breakpoints not revealed by the probes employed, other known oncogenes, or oncogenes that have not yet been identified.  相似文献   
28.
An analogue of netropsin has been synthesized consisting of two N-propylpyrrolcarboxamide units linked covalently to a copper-chelating tripeptide Gly-Gly-L-His by means of two and three glycine residues. Binding to DNA and synthetic polynucleotides of netropsin analogue containing three glycine residues between Gly-Gly-L-His tripeptide and the N-end of netropsin analogue (His-Nt) has been studied. It is shown that this netropsin analogue chelates a copper ion with 1:1 stoichiometry, similar to a free Gly-Gly-L-His peptide. It is found that this netropsin analogue occupies 3 to 4 base pairs upon binding to poly(dA).poly(dT) and poly[d(AT)].poly[d(AT)] polymers, irrespective of whether it binds in Cu(2+)-ligated or unligated forms. Binding constants and binding site sizes have been calculated for netropsin analogue complexes with DNA, poly(dA).poly(dT) and poly[d(AT)].poly[d(AT)] polymers at the [Cu2+]/[His-Nt] ratio equal to 0 and 1.0. In the three-component system including His-Nt and Cu(2+)-His-Nt, cooperative effects are recognized which can be explained by heterodimer generation on interaction of His-Nt and Cu(2+)-His-Nt at adjacent binding sites.  相似文献   
29.
Investigation of the morphology of ganglion cells in the cat retina has shown that a remarkable reduction in the number of dendritic spines and branches occurs during development of the alpha and beta cell classes. To learn whether dendritic remodelling represents a generalized mechanism of mammalian retinal ganglion cell development, we have examined the morphology of ganglion cells in the retina of the developing rat. The present study has concentrated on type II cells, which retain a great number of dendritic spines and branches in the adult and comprise a large proportion of the population of rat retinal ganglion cells. To reveal fine dendritic and axonal processes, Lucifer yellow was injected intracellularly in living retinae maintained in vitro. Size and complexity of the dendritic trees were found to increase rapidly during an initial stage of development lasting from late fetal life until approximately postnatal day 12 (P12). Dendrites and axons of immature ganglion cells expressed several transient morphological features comprising an excessive number of dendritic branches and spine-like processes, and short, delicate axonal sidebranches. The following developmental stage was characterized by a remarkable decrease in the morphological complexity of retinal ganglion cells and a slowed growth of their dendritic fields. The number of dendritic branches and spines of types I and II retinal ganglion cells declined after P12 to reach a mature level by the end of the first postnatal month. Thus, even cells that retain a highly complex dendritic tree into the adult state undergo extensive remodelling. These results suggest that regressive modifications at the level of the dendritic field constitute a generalized mechanism of maturation in mammalian retinal ganglion cells.  相似文献   
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