With the assumption that a portion that comprises some 10 percent of the genomes in higher organisms cannot be without a raison d'être, an extensive review led us to conclude that a certain amount of constitutive heterochromatin is essential in multicellular organisms at two levels of organization, chromosomal and nuclear. At the chromosomal level, constitutive heterochromatin is present around vital areas within the chromosomes. Around the centromeres, for example, heterochromatin is believed to confer protection and strength to the centromeric chromatin. Around secondary constrictions, heterochromatic blocks may ensure against evolutionary change of ribosomal cistrons by decreasing the frequency of crossing-over in these cistrons in meiosis and absorbing the effects of mutagenic agents. During meiosis heterochromatin may aid in the initial alignment of chromosomes prior to synapsis and may facilitate speciation by allowing chromosomal rearrangement and providing, through the species specificity of its DNA, barriers against cross-fertilization. At the nuclear level of organization, constitutive heterochromatin may help maintain the proper spatial relationships necessary for the efficient operation of the cell through the stages of mitosis and meiosis. In the unicellular procaryotes, the presence of a small amount of genetic information in one chromosome obviates the need for constitutive heterochromatin and a nuclear membrane. At higher levels of organization, with an increase in the size of the genome and with evolution of cellular and sexual differentiation, the need for compartmentalization and structural components in the nucleus became imminent. The portion of the genome that was concerned with synthesis of ribosomal RNA was enlarged and localized in specific chromosomes, and the centromere became part of each chromosome when the mitotic spindle was developed in evolution. Concomitant with these changes in the genome, repetitive sequences in the form of constitutive heterochromatin appeared, probably as a result of large-scale duplication. The repetitive DNA's were kept through natural selection because of their importance in preserving these vital regions and in maintaining the structural and functional integrity of the nucleus. The association of satellite (or highly repetitive) DNA with constitutive heterochromatin is understandable, since it stresses the importance of the structural rather than transcriptional roles of these entities. Nuclear satellite DNA's have one property in common despite their species specificity, namely heterochromatization. In this sense the apparent species specificity of satellite DNA may be the result of natural selection for duplicated short polynucleotide segments that are nontranscriptional and can be utilized in specific structural roles.
Tuberculous peritonitis, although common in Third World countries, remains an uncommon cause of ascites in the United States. Ascitic fluid adenosine deaminase (ADA) activity has been proposed as a useful diagnostic test. The aim of this retrospective study was to determine the clinical utility of ascitic fluid ADA activity in diagnosing tuberculous peritonitis in a U.S. patient population. A total of 368 ascitic fluid specimens from a well-characterized ascitic fluid bank, including tuberculous peritonitis (n = 7), tuberculous peritonitis in the setting of cirrhosis (n = 10), and consecutive specimens of widely varied etiologies (n = 351) were analyzed for ADA activity by ultraviolet spectrophotometry at 265 nm. The overall sensitivity of the ADA determination in diagnosing tuberculous peritonitis was only 58.8%, and the specificity was 95.4%. The accuracy of ADA determination (93.8%) compared favorably with that of the common ascitic fluid tests of white blood cell (WBC) count (>500/mm3), total protein (>2.5 g/dL), and combined WBC count and total protein (45.8%, 74.4%, and 81.3%, respectively). However, ADA was only 30% sensitive in detecting tuberculous peritonitis in the setting of cirrhosis, and cirrhosis was present in 59% of the tuberculous peritonitis patients in our population. In addition, malignancy-related ascites (13%) and bacterial peritonitis specimens (5.8%) occasionally yielded false-positive results. In conclusion, our results indicate that the ascitic fluid ADA activity has good accuracy but poor sensitivity and imperfect specificity in a U.S. patient population in which the prevalence of tuberculosis is low and underlying cirrhosis is common.
Total DNA and DNA from the heterochromatin and euchromatin fractions of male guinea pig liver nuclei were analyzed by cesium sulfate-silver density-gradient centrifugation. Total DNA is composed of three components: a heavy satellite DNA, a main DNA of intermediate density, and a light satellite DNA. Heterochromatin DNA shows a fourfold enrichment in the satellite components while euchromatin DNA is relatively devoid of them. The strands of both satellite DNA's are separable by centrifugation in alkaline cesium chloride. Base analyses on the separate strands demonstrate that the two satellite DNA's represent different species.
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