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11.
Report of the committee on comparative mapping 总被引:3,自引:0,他引:3
12.
R W Katzberg P L DiMarco T W Morris P P Harnish R F Graves P A Merguerian J A Ventura H M Proskin 《Life sciences》1988,42(20):1963-1971
This investigation examines the role of Angiotensin II in renal hemodynamic functions during acute unilateral ureteral obstruction (UUO) in a dog model. An electro magnetic flow probe was utilized to assess renal blood flow while the arteriovenous extraction technique of technetium 99m DTPA was utilized for the assessment of changes in filtration fraction and glomerular filtration rate. The effects of Angiotensin II receptor blockade on renal hemodynamic functions during acute UUO was evaluated in six dogs and compared to acute ureteral obstruction without receptor blockade in seven dogs. Angiotensin II blockade with (Sar1, Thr8)-Angiotensin II during UUO led to a striking increase in renal blood flow that was significantly different in comparison to normalized values from UUO alone (+delta 63 +/- 17 vs. +delta 22 +/- 6% at 30 min; p less than 0.05). There were, however, no significant differences in the magnitude of the decrease in filtration fraction and glomerular filtration rate in comparison to UUO alone. This investigation demonstrates that Angiotensin II has an inhibitory effect on the initial increase in renal blood flow with acute UUO. The possibility of successful pharmacologic intervention in the setting of UUO can be examined using animal models similar to the one described here. Pharmacologic treatment in the setting of acute UUO in patients might permit better preservation of renal function. 相似文献
13.
A J Valente R Delgado J D Metter C Cho E A Sprague C J Schwartz D T Graves 《Journal of cellular physiology》1988,136(3):479-485
Proliferation of smooth muscle cells (SMC) in the arterial intima of man and experimental animals is important in the pathogenesis of atherosclerosis. Vascular SMC proliferation in vitro is stimulated by a number of agents, including the potent protein mitogen, platelet-derived growth factor (PDGF). Recent studies on rat arterial SMC indicate that these cells may, under certain circumstances, synthesize PDGF protein mitogens, suggesting that the regulation of SMC proliferation in vivo may have an autocrine or paracrine component. In this study we demonstrate that cultured nonhuman primate (baboon) aortic SMC transcribe both the PDGF-A and PDGF-B genes but do not secrete detectable mitogenic activity characteristic of native PDGF. The absence of this activity was not due to the presence in the cell conditioned medium of factors inhibitory for PDGF-mediated mitogenic activity. Metabolic labeling of the cells and immunoprecipitation with specific antibodies to human PDGF did not detect a dimeric (30 kDa) PDGF protein in either the intracellular or extracellular compartments, but instead identified PDGF-related proteins of molecular weight 12 kDa and 100 kDa. These data suggest the presence in vascular SMC of a mechanism regulating the translation of PDGF mRNA that may play an important role in the control of SMC proliferation in vivo. 相似文献
14.
Jennifer A. Marshall Graves 《Journal of genetics》1988,67(1):9-22
Somatic cell hybrids between cells of widely divergent mammalian species display a range of chromosomal and genetic anomalies which may be the equivalent of the “genomic shock” phenomena observed in many plant and animal interspecific hybrids. Mouse-kangaroo hybrids show extreme segregation and fragmentation of the kangaroo chromosomes. Here 1 show that, in addition to the chromosomal instability, some hybrids display unstable expression of three genes borne on the kangaroo active maternal X chromosome. These genes (HPRT, G6PD andPGK) may be co-ordinately inactivated at high frequency, then reactivated once more. I suggest that this reversible inactivation in interspecific hybrids may be the result of an unstable change at an X inactivation centre located in the kangaroo Xq. 相似文献
15.
Carcinogen-nucleic acid interactions: equilibrium binding studies of aflatoxins B1 and B2 with DNA and the oligodeoxynucleotide d(ATGCAT)2 总被引:3,自引:0,他引:3
M P Stone S Gopalakrishnan T M Harris D E Graves 《Journal of biomolecular structure & dynamics》1988,5(5):1025-1041
Equilibrium binding is believed to play an important role in directing the subsequent covalent attachment of many carcinogens to DNA. We have utilized UV spectroscopy to examine the non-covalent interactions of aflatoxin B1 and B2 with calf thymus DNA, poly(dAdT):poly(dAdT), and poly(dGdC):poly(dGdC), and have utilized NMR spectroscopy to examine non-covalent interactions of aflatoxin B2 with the oligodeoxynucleotide d(ATGCAT)2. UV-VIS binding isotherms suggest a greater binding affinity for calf thymus DNA and poly(dAdT):poly(dAdT) than for poly(dGdC):poly(dGdC). Scatchard analysis of aflatoxin B1 binding to calf thymus DNA in 0.1 M NaCl buffer indicates that binding of the carcinogen at levels of bound aflatoxin less than 1 carcinogen per 200 base pairs occurs with positive cooperativity. The cooperative binding effect is dependent on the ionic strength of the medium; when the NaCl concentration is reduced to 0.01 M, positive cooperativity is observed at carcinogen levels less than 1 carcinogen per 500 base pairs. The Scatchard data may be fit using a "two-site" binding model [L.S. Rosenberg, M.J. Carvlin, and T.R. Krugh, Biochemistry 25, 1002-1008 (1986)]. This model assumes two independent sets of binding sites on the DNA lattice, one a high affinity site which binds the carcinogen with positive cooperativity, the second consisting of lower affinity binding sites to which non-specific binding occurs. NMR analysis of aflatoxin B2 binding to d(ATGCAT)2 indicates that the aflatoxin B2/oligodeoxynucleotide complex is in fast exchange on the NMR time scale. Upfield chemical shifts of 0.1-0.5 ppm are observed for the aflatoxin B2 4-OCH3, H5, and H6a protons. Much smaller chemical shift changes (less than or equal to 0.06 ppm) are observed for the oligodeoxynucleotide protons. The greatest effect for the oligodeoxynucleotide protons is observed for the adenine H2 protons, located in the minor groove. Nonselective T1 experiments demonstrate a 15-25% decrease in the relaxation time for the adenine H2 protons when aflatoxin B2 is added to the solution. This result suggests that aflatoxin B2 protons in the bound state may be in close proximity to these protons, providing a source of dipolar relaxation. Further experiments are in progress to probe the nature of the aflatoxin B1 and B2 complexes with polymeric DNA and oligodeoxynucleotides, and to establish the relationship between the non-covalent DNA-carcinogen complexes observed in these experiments, and covalent aflatoxin B1-guanine N7 DNA adducts. 相似文献
16.
Analysis of a tissue-specific enhancer: ARF6 regulates adipogenic gene expression. 总被引:4,自引:0,他引:4
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The molecular basis of adipocyte-specific gene expression is not well understood. We have previously identified a 518-bp enhancer from the adipocyte P2 gene that stimulates adipose-specific gene expression in both cultured cells and transgenic mice. In this analysis of the enhancer, we have defined and characterized a 122-bp DNA fragment that directs differentiation-dependent gene expression in cultured preadipocytes and adipocytes. Several cis-acting elements have been identified and shown by mutational analysis to be important for full enhancer activity. One pair of sequences, ARE2 and ARE4, binds a nuclear factor (ARF2) present in extracts derived from many cell types. Multiple copies of these elements stimulate gene expression from a minimal promoter in preadipocytes, adipocytes, and several other cultured cell lines. A second pair of elements, ARE6 and ARE7, binds a separate factor (ARF6) that is detected only in nuclear extracts derived from adipocytes. The ability of multimers of ARE6 or ARE7 to stimulate promoter activity is strictly adipocyte specific. Mutations in the ARE6 sequence greatly reduce the activity of the 518-bp enhancer. These data demonstrate that several cis- and trans-acting components contribute to the activity of the adipocyte P2 enhancer and suggest that ARF6, a novel differentiation-dependent factor, may be a key regulator of adipogenic gene expression. 相似文献
17.
We have mapped five human chromosome 21 (HSA 21) markers in marsupials and a monotreme, two major groups of mammals that diverged from eutherians 130-150 and 150-170 million years before present (MYrBP), respectively. We have found that these genes map to two distinct autosomal sites, one containing SOD1/CBR/BCEI and the other containing ETS2/INFAR, in the marsupials Macropus eugenii and Sminthopsis macroura (which belong to orders that diverged 40-80 MYrBP), as well as in the monotreme Ornithorhynchus anatinus (the platypus). Since marsupials and monotremes diverged independently from eutherians, these data suggest that HSA 21 genes were originally located in two separate autosomal blocks. In another Sminthopsis species, SOD1 is linked to TRF (a marker on HSA 3q), suggesting that the ancestral SOD1/CBR/BCEI region also included HSA 3 markers. We suggest that these blocks became fused early in the eutherian evolution to form a HSA 3/21 chromosome, which has remained intact in artiodactyls, but has been independently disrupted in both the primate and rodent lineages. 相似文献
18.
There are many situations in which grain distributions resulting from in situ hybridization of radioactively labeled probes to unique genes should be subjected to a statistical analysis. However, the problems posed by analysis of in situ hybridization data are not straightforward, and no completely satisfying method is currently available. We have developed a procedure in which the major and any number of minor site(s) of hybridization may be specifically located and the significance of each tested. This Zmax procedure first tests the overall distribution for departure from randomness and then identifies significantly overlabeled whole chromosomes (or chromosome arms or other large segments), a process that may be repeated to pinpoint significantly overlabeled regions within these chromosomes. We describe in detail the derivation of the Zmax statistic, present tables of significant Zmax levels, and show with examples how Zmax is used in tests of significance of in situ hybridization data. 相似文献
19.
Mammalian sex chromosomes evolved (and are still evolving) from a homomorphic pair by the progressive loss of active genes from the Y chromosome. Among the changes that have accompanied this differentiation, it is difficult to determine causes, effects and correlates. Comparative studies suggest that the choice of a gene, and thus a chromosome pair, to control the sex-determining pathway may be quite arbitrary, and that sex chromosomes and sex-determining genes are more likely to be the products of random changes than the products of selection for function. 相似文献
20.
The characteristics of ADP-ribosyltransferase activity in skeletal muscle membranes have been studied. The membrane enzymes can ADP-ribosylate exogenous substrates such as guanylhydrazones, polyarginine, lysozyme, and histones. The properties of the enzyme are investigated by using diethylaminobenzylidineaminoguanidine as a model substrate. Incubation of the membranes with [32P]adenylate-labeled NAD results in the labeling of a number of cellular proteins. Magnesium ions, detergents, and diethylaminobenzylidineaminoguanidine stimulated the ADP-ribosylation of membrane proteins, whereas L-arginine methyl ester and arginine inhibited ADP-ribosylation. The labeling of specific proteins in the sarcoplasmic reticulum and glycogen pellet is influenced significantly by detergents, nucleotides, and thiols. The hydroxylamine sensitivity of the ADP-ribose linkage in the membrane proteins is similar to that reported for (ADP-ribose)-arginine linkage. Snake venom phosphodiesterase digestion of the ADP-ribosylated membranes produces 5'-AMP as the major acid-soluble digestion product. The results suggest that the primary mode of modification is mono(ADP-ribosyl)ation. The ADP-ribosyltransferase activity in the membrane preparations is not extracted under conditions used for solubilization of extrinsic proteins, suggesting that the activity is associated with some integral membrane protein. 相似文献