Development and Significance of Cysteamine and Propionitrile Models of Duodenal Ulcer

Cysteamine is widely used in rodents to induce duodenal ulcer. Herein, the pathogenesis of duodenal ulceration in its earliest stages was reviewed using findings from cysteamine-and propionitrile-induced duodenal ulcer in rodent models, especially taking into account changes in the secretion of gastric acid, duodenal and pancreatic bicarbonate as well asgastroduodenal motility. The effect of cysteamine-HCl in inducing ulcers in rats is circadian rhythm-dependent. The effect is greatest from just before the end of diurnal rest to just after the start of nocturnal activity. The chronobiologic effect may be in part due to the circadian rhythm-dependent increased gastric acid production from cysteamine. Titratable acidity was found to be twice as great in the gastric juice of rodents when cysteamine was given by injection at 2000 (just after the start of nocturnal activity) in comparison to when given at 0800 or 1200 (at the beginning or middle span of daily rest). Further studies have shown that adrenalectomy of rats 7 days before cysteamine administration obliterated the observed circadian susceptibility to ulcer formation. Duodenal ulceration, at least in the cysteamine model, appears to be under chronobiologic neuroendocrine control or influence, seemingly mediated by the adrenal glands.     

Cell-by-cell flow cytometric analysis of chromosomes

The authors discuss various aspects of a recently developed method permitting a detailed flow cytometric analysis of the individual cell karyotypes such as instrumentation, histochemistry, data proceeding algorithms. Possible drawbacks of the method and the ways of their overcoming are considered. Results of analysis of the Chinese hamster cells are presented that illustrate the possibilities of the method, including the metaphase chromosome distribution according to their fluorescence intensity, the analysed cell distribution according to their chromosomes number, the table in which the individual cell karyotypes are distributed according to their fluorescence. The results obtained show that the developed method may be successfully used for investigating chromosomal iNstability and heterogeneity of the mammalian cells.     

Paramagnetic form of ribonucleotide reductase in human tissues

The paramagnetic form of ribonucleotide reductase was detected by ESR method in human cervix tissues, especially in tumor ones. The magnetic relaxation rate was proved to be slower for this form than for that in normal animal tissues having a high level of proliferative activity or in Ehrlich tumor cells studied before.     

Informosomes and translation activity of mRNA in eukaryotic cells

In this review we summarize recent results which are obtained in the field of structure and functions of cytoplasmic mRNP, or informosomes. These data lead to conclusion, that the informosomal structure of mRNA in eukaryotic cells makes possible the establishment of translational control by masking-demasking of messages.     

Mechanism of the radioprotective effect of cysteamine

The radioprotective effect of cysteamine combined with the modification of the chromatin state by sodium butyrate has been studied using V-79 and CHEL lines of Chinese hamster cells and HeLa cells. Sodium butyrate enhances the chromatin sensitivity to nucleases and removes the radioprotective effect of cysteamine as measured by the yield of cells with chromosome aberrations. As is indicated by changes in the intensity of fluorescence of the DNA-ethidium bromide complex, measured by laser flow cytometry, the protective agent decreases the binding of the dye with both irradiated and nonirradiated DNA whereas ionizing radiation and sodium butyrate increase thereof. It is concluded that the radioprotective effect of cysteamine depends in its ability to reduce the susceptibility of DNA to nucleases.     

Evidence for chromosome instability in vivo in bloom syndrome: Increased numbers of micronuclei in exfoliated cells

Summary The incidence of exfoliated epithelial cells containing micronuclei was determined in two small human populations, one homozygous and the other heterozygous for the Bloom syndrome gene (bl). The objectives of the study were two: (1) to learn whether the chromosome instability featured so prominently by Bloom syndrome (BS) cells proliferating in vitro also occurs in vivo, and (2) as part of a broad survey of various cancer-prone populations, to determine whether estimating micronucleus frequencies in exfoliated cell samples might be useful for identifying individuals with genetically determined chromosome instability. Eight individuals homozygous (bl/bl) for the BS gene, i.e., persons with the clinical syndrome, were examined, along with 11 obligate heterozygotes (bl/+), parents of affected persons. Exfoliated cells were obtained from two sites, the oral cavity and the urinary tract. Striking and statistically highly significant elevations in the frequencies of cells with micronuclei were observed in cells from both sites in bl/bl individuals compared to that in bl/+ (P<0.001) and in a control population, indicating that chromosome instability occurs in vivo in BS. In contrast, micronucleus frequencies at either site did not differ significantly between bl/+ individuals and the control population. This survey, in combination with similar earlier ones of populations predisposed to cancer not on a genetic basis but because of exposure to some environmental carcinogen, suggests that the exfoliated cell micronucleus test identifies individuals whose somatic genetic material has, for either genetic or environmental reasons, been damaged in a way that produces chromosome breakage and rearrangement.     

Bloom's syndrome

Summary The biochemical defect in Bloom's syndrome (BS) remains unknown, but two characteristic features of BS cells point to a disturbance of DNA replication, namely, an excessive number of sister-chromatid exchanges (SCEs) in bromodeoxyuridine (BrdU)-substibuted cells and an abnormally slow rate of replicon elongation. The hypothesis of an abnormal DNA polymerase as the explanation for these observations was tested using an in situ assay system for DNA polymerase activity and to estimate molecular weights in cellular extracts of cultured BS cells. DNA polymerase subunits in cellular extracts from the BS cells when separated electrophoretically on polyacrylamide gels showed the same mobilities (i.e., molecular weights) as the controls and were equally effective at promoting the incorporation of isotopically labeled nucleosides. It is concluded that the genetic defect in BS has no direct effect on either DNA-polymerase activity or the amounts and molecular weights of the different forms of the enzyme.     

Bloom's syndrome. III. Analysis of the chromosome aberration characteristic of this disorder

The following hypothesis is put forward: X chromatin in man condenses around a center which is situated on Xq at a short distance from the centromere. The hypothesis is based on, and explains, two classes of observations. (1) Abnormal X chromosomes that have the assumed center in duplicate form bipartite Barr bodies in part of the cells. The frequency of bipartite bodies and the distance between the two parts seem to be determined by the distance between the postulated centers. (2) A large number of variously abnormal X chromosomes have been described. Almost all of them possess the postulated center and it seems possible that the very few apparent exceptions represent misidentifications of chromosome Xq — as isochromosome i(Xp). According to the hypothesis, chromosomes lacking the center would form no Barr body and therefore presumably would not be inactivated, thus leaving the cell severely unbalanced. Furthermore, absence of the center might interfere with the viability of the chromosome itself.