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11.
Demonstration of the heterozygous state for I-cell disease and pseudo-Hurler polydystrophy by assay of N-acetylglucosaminylphosphotransferase in white blood cells and fibroblasts 总被引:5,自引:1,他引:4 下载免费PDF全文
A Varki M L Reitman A Vannier S Kornfeld J H Grubb W S Sly 《American journal of human genetics》1982,34(5):717-729
The biochemical abnormalities of I-cell disease (mucolipidosis II) and pseudo-Hurler polydystrophy (mucolipidosis III) can be explained by a deficiency of the enzyme UDP-N-acetylglucosamine:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase. We demonstrate here that obligate heterozygotes for these autosomal recessive diseases have intermediate levels of this enzymatic activity in homogenates of peripheral blood white cells and in extracts from cultured fibroblasts. This finding provides further evidence that the enzyme deficiency is the primary genetic defect in these diseases. In addition, the previous observation that obligate heterozygotes for mucolipidosis III have elevations of total serum beta-hexosaminidase outside the range of normal was confirmed. In studies of three pedigrees of patients with mucolipidosis III, these techniques were used to score individuals at risk for the carrier state. 相似文献
12.
Y Shechter P Reitman A Hizi 《Biochemical and biophysical research communications》1982,109(3):776-785
Previous studies using rat adipocytes have shown that the ability of insulin to antagonize lipolysis induced by physiological concentrations of catecholamines is diminished at high concentrations of these hormones. Since such high concentrations of catecholamines cause an accumulation of free fatty acids, a decrease in cellular ATP level and a ‘short lived’ increase in cAMP (that is many fold higher than required to activate lipolysis maximally), we studied which of these modulates the antilipolytic activity of insulin. We found that inhibition of adenylate cyclase by virazole (2 mM), which lowers the initial cyclic AMP burst by about 70%, enables insulin to antagonize lipolysis at high isoproterenol concentrations. In contrast, reduction of cellular ATP level by 40% and 70%, using cyanide ion, or increasing free fatty acids in the medium to a level that suppresses the effects of insulin on glucose metabolism, failed to compromise the antilipolytic activity of the hormone. These data indicate that the inability of insulin to antagonize lipolysis induced by high isoproterenol concentrations is the direct consequence of the initial, larger burst of cyclic AMP. 相似文献
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Differential response of cycling and noncycling cells to inducers of DNA synthesis and mitosis 总被引:1,自引:0,他引:1 下载免费PDF全文
The objective of this study was to determine whether cells in G(0) phase are functionally distinct from those in G(1) with regard to their ability to respond to the inducers of DNA synthesis and to retard the cell cycle traverse of the G(2) component after fusion. Synchronized populations of HeLa cells in G(1) and human diploid fibroblasts in G(1) and G(0) phases were separately fused using UV-inactivated Sendai virus with HeLa cells prelabeled with [(3)H]ThdR and synchronized in S or G(2) phases. The kinetics of initiation of DNA synthesis in the nuclei of G(0) and G(1) cells residing in G(0)/S and G(1)/S dikaryons, respectively, were studied as a function of time after fusion. In the G(0)/G(2) and G(1)/G(2) fusions, the rate of entry into mitosis of the heterophasic binucleate cells was monitored in the presence of Colcemid. The effects of protein synthesis inhibition in the G(1) cells, and the UV irradiation of G(0) cells before fusion, on the rate of entry of the G(2) component into mitosis were also studied. The results of this study indicate that DNA synthesis can be induced in G(0)nuclei after fusion between G(0)- and S-phase cells, but G(0) nuclei are much slower than G(1) nuclei in responding to the inducers of DNA synthesis because the chromatin of G(0) cells is more condensed than it is in G(1) cells. A more interesting observation resulting from this study is that G(0) cells is more condensed than it is in G(1) cells. A more interesting observation resulting from this study is that G(0) cells differ from G(1) cells with regard to their effects on the cell cycle progression of the G(2) nucleus into mitosis. This difference between G(0) and G(1) cells appears to depend on certain factors, probably nonhistone proteins, present in G(1) cells but absent in G(0) cells. These factors can be induced in G(0) cells by UV irradiation and inhibited in G(1) cells by cycloheximide treatment. 相似文献
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Function of the upstream hypersensitive sites of the chicken beta-globin gene cluster in mice. 下载免费PDF全文
We have shown previously that the chicken beta A-globin gene, with its 3' enhancer, is expressed in a copy number-dependent manner in transgenic mice. The expression level was low but increased approximately 6-fold upon inclusion of 11 kb of upstream DNA containing four DNase I hypersensitive sites. To study the effect of the individual upstream hypersensitive sites on transgene expression, we produced lines of mice in which the individual upstream sites were linked to the beta A gene and enhancer. RNA levels were measured in blood from adult animals. With each of these four constructs, the level of transgene RNA per DNA copy varied over a > 20-fold range. These data suggest that addition of a hypersensitive site to the beta A-globin/enhancer region abrogates its position independent expression. The average beta A-globin expression per copy in the lines carrying an upstream site was comparable with that in lines without an upstream site. Thus, no single upstream hypersensitive site accounts for the higher level of beta A-globin expression seen in mice containing the complete upstream region. We had shown previously that control of the chicken beta-globin cluster is distributed between at least two regions, the beta A/epsilon enhancer and the upstream region. Our current results suggest that the control mediated by the upstream DNA is itself distributed and is not due to a single hypersensitive site. 相似文献
17.
Large, rapidly evolving intergenic spacers in the mitochondrial DNA of the salamander family Ambystomatidae (Amphibia: Caudata) 总被引:5,自引:2,他引:3
We report the presence, in the mitochondrial DNA (mtDNA) of all of the
sexual species of the salamander family Ambystomatidae, of a shared 240- bp
intergenic spacer between tRNAThr and tRNAPro. We place the intergenic
spacer in context by presenting the sequence of 1,746 bp of mtDNA from
Ambystoma tigrinum tigrinum, describe the nucleotide composition of the
intergenic spacer in all of the species of Ambystomatidae, and compare it
to other coding and noncoding regions of Ambystoma and several other
vertebrate mtDNAs. The nucleotide substitution rate of the intergenic
spacer is approximately three times faster than the substitution rate of
the control region, as shown by comparisons among six Ambystoma
macrodactylum sequences and eight members of the Ambystoma tigrinum
complex. We also found additional inserts within the intergenic spacers of
five species that varied from 87-444 bp in length. The presence of the
intergenic spacer in all sexual species of Ambystomatidae suggests that it
arose at least 20 MYA and has been a stable component of the ambystomatid
mtDNA ever since. As such, it represents one of the few examples of a large
and persistent intergenic spacer in the mtDNA of any vertebrate clade.
相似文献
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Shen M Reitman ZJ Zhao Y Moustafa I Wang Q Arnold JJ Pathak HB Cameron CE 《The Journal of biological chemistry》2008,283(2):875-888
Picornaviruses have a peptide termed VPg covalently linked to the 5'-end of the genome. Attachment of VPg to the genome occurs in at least two steps. First, Tyr-3 of VPg, or some precursor thereof, is used as a primer by the viral RNA-dependent RNA polymerase, 3Dpol, to produce VPg-pUpU. Second, VPg-pUpU is used as a primer to produce full-length genomic RNA. Production of VPg-pUpU is templated by a single adenylate residue located in the loop of an RNA stem-loop structure termed oriI by using a slide-back mechanism. Recruitment of 3Dpol to and its stability on oriI have been suggested to require an interaction between the back of the thumb subdomain of 3Dpol and an undefined region of the 3C domain of viral protein 3CD. We have performed surface acidic-to-alanine-scanning mutagenesis of 3C to identify the surface of 3C with which 3Dpol interacts. This analysis identified numerous viable poliovirus mutants with reduced growth kinetics that correlated to reduced kinetics of RNA synthesis that was attributable to a change in VPg-pUpU production. Importantly, these 3C derivatives were all capable of binding to oriI as well as wild-type 3C. Synthetic lethality was observed for these mutants when placed in the context of a poliovirus mutant containing 3Dpol-R455A, a residue on the back of the thumb required for VPg uridylylation. These data were used to guide molecular docking of the structures for a poliovirus 3C dimer and 3Dpol, leading to a structural model for the 3C(2)-3Dpol complex that extrapolates well to all picornaviruses. 相似文献
20.