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排序方式: 共有198条查询结果,搜索用时 718 毫秒
1.
Recently numerous attempts have been made to reduce the use of vertebrate animals in laboratory experiments to evaluate general and acute toxicity, mutagenesis and teratogenesis of new drugs or chemicals. One common approach is to use established, proliferating cell lines that preserve differentiated functions such as the competence to metabolize xenobiotics. To this end a continuous Chinese hamster epithelial liver cell line (CHEL cells) was established, cultured as used for mutagenesis studies. Structurally different promutagens, such as 7,12-dimethylbenz[a]anthracene (7,12-DMBA), benzo[a]pyrene (B(a)P), aflatoxin B1 (AB1) and cyclophosphamide (CP), were used in order to check and validate the test system. anti-Chrysene-1,2-diol 3,4-epoxide (CDE) and mitomycin C (MMC) were taken as representatives of direct mutagens. The genetic change induced by the mutagens was quantified by measuring mutation frequencies at the HGPRT locus. Several parameters, such as mutant expression time for each chemical, cell density for selection of mutants and enzymatic characterization for HGPRT phenotype, were examined to establish the optimal assay conditions. All promutagens analyzed significantly affected either the cloning efficiency and/or the mutant frequency of CHEL cells after 24 h of exposure. In addition, various enzyme activities involved in the metabolism of the promutagens were determined in CHEL cells, under the experimental conditions of chemical exposure used in the mutagenesis assay. The enzyme activities were compared with those found in uninduced Chinese hamster liver. 相似文献
2.
Arginyl residues in BamHI endonuclease were examined because of their alleged role in proteins that contain nucleotide- or phosphate-binding sites. Butanedione, an arginine-specific reagent, inhibited the endonuclease in the presence of sodium borate. The inhibition was decreased by preliminary incubation of the enzyme with DNA or competitive inhibitors which were the 5'-phosphoryl deoxydinucleotide subsets of the BamHI recognition sequence. The dinucleotide pdGpdG protected the enzyme most efficiently against the butanedione modification. Dinucleotides that were unrelated to the recognition sequence failed to protect the enzyme from inactivation. These studies indicate that arginine residues may reside in the enzyme's active site and might function in the sequence-specific recognition of the BamHI palindrome. 相似文献
3.
F De Marco G Palmieri G Capuano R Gentile G Nardone G Parrilli T Prantera G Budillon 《Bollettino della Società italiana di biologia sperimentale》1983,59(10):1576-1581
Typical changes in blood aminoacid concentrations have been described in patients with severe liver disease. In this study we measured the serum amino acid levels, by Beckman Aminoacid Analyzer, in 11 healthy subjects and 24 HBsAg-positive patients with biopsy-proven liver disease (4 CPH, 10 CAH, 10 cirrhosis). A significant decrease in total aminoacids was observed in CAH and cirrhosis groups (-24% and -22% respectively). The three branched chain aminoacids (BCAA = val + leu + isoleu) were reduced by 24% (P less than 0.002) and 37% (P less than 0.001) in the CAH and cirrhosis groups respectively. Tyrosine was the only of the aromatic aminoacids (AAA) to increase in cirrhotics (+ 34%, P less than 0.02). The molar ratio BCAA/AAA was 3.6 in controls, 3.8 in CPH, 3.1 in CAH (P less than 0.025) and 1.9 in cirrhosis (P less than 0.001). A linear correlation was found between molar ratio BCAA/AAA and serum albumin in all patients (P less than 0.001). These results document the presence of specific quantitative changes in serum aminoacids of HBsAg positive patients, which appear related to severity of liver disease and comparable to the alterations described in non viral chronic liver disease. 相似文献
4.
Isolation and characterization of a large,neurite-associated glycoconjugate from neuroblastoma cells
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A high molecular weight glycoconjugate has been isolated from neurite-producing neuronal tumor cells in culture and has been designated as I(0) based on its elution characteristics in gel filtration chromatography. This molecule cannot be found in a variety of nonneuronal cells. I(0) is found in the substratum-attached material or cell fraction of neurite-producing neuroblastoma cells, depending upon culture conditions. It is found in the substratum-bound fraction of B104 rat neuroblastoma cells during serum starvation and in the EGTA-detached cell fraction of B104 cells grown in chemically defined N2 medium. It occurs only in the cell fraction of the human neuroblastoma line Platt. Examination of behavioral variants of the B104 rat line further strengthens the association of I(0) with neurite production; the constitutive neurite-producing E(R)B9 variant contains I(0) while the non-neurite-producing E(R)A11 variant does not. I(0) is large, eluting in the void volume of sepharose-CL2B columns. Radioiodination of intact cells with lactoperoxidase shows I(0) to be a cell surface component. Metabolic radiolabeling studies show that it contains a high proportion of polysaccharide to protein, does not contain mannose, and is unsulfated. Alkaline borohydride reduction release two size classes of large polysaccharide chain. The alkaline reduction results, along with the mannose incorporation studies, show the presence of O-glycosidic linkages and few, if any, N-linkages. Resistance to nitrous acid deamination, insensitivity to glycosaminoglycan lyases, and the absence of sulfation, indicate that I(0) does not contain the glycosaminoglycans hyaluronic acid, chondroitin-, dermatan-, or heparin- sulfates. Affinity column chromatography reveals high binding affinity of I(0) to polyornithine and no binding to gelatin (collagen) or the glycosaminoglycans hyaluronate and heparin. These studies describe a unique high molecular weight glycoconjugate on the surface of neurite-producing neuroblastoma cell lines from two species. 相似文献
5.
Relative apparent synapomorphy analysis (RASA). I: The statistical measurement of phylogenetic signal 总被引:10,自引:9,他引:1
We have developed a new approach to the measurement of phylogenetic signal
in character state matrices called relative apparent synapomorphy analysis
(RASA). RASA provides a deterministic, statistical measure of natural
cladistic hierarchy (phylogenetic signal) in character state matrices. The
method works by determining whether a measure of the rate of increase of
cladistic similarity among pairs of taxa as a function of phenetic
similarity is greater than a null equiprobable rate of increase. Our
investigation of the utility and limitations of RASA using simulated and
bacteriophage T7 data sets indicates that the method has numerous
advantages over existing measures of signal. A first advantage is
computational efficiency. A second advantage is that RASA employs known
methods of statistical inference, providing measurable sensitivity and
power. The performance of RASA is examined under various conditions of
branching evolution as the number of characters, character states per
character, and mutations per branch length are varied. RASA appears to
provide an unbiased and reliable measure of phylogenetic signal, and the
general approach promises to be useful in the development of new techniques
that should increase the rigor and reliability of phylogenetic estimates.
相似文献
6.
Maura Turriani Rossana Pesi Antonella Nardone Gino Turchi Francesco Sgarrella Pier Luigi Ipata Maria Grazia Tozzi 《Journal of biochemical and molecular toxicology》1994,9(1):51-57
Nucleoside phosphotransferase acting on inosine and deoxyinosine has been partially purified from cultured Chinese hamster lung fibroblasts (V79). The activity is associated with a cytosolic 5′-nucleotidase acting on IMP and deoxyIMP. The transfer of the phosphate group from IMP to inosine catalyzed by this enzyme was activated by ATP and 2,3-bisphosphoglycerate. Inosine, deoxyinosine, guanosine, deoxyguanosine, and the nucleoside analogs 2′,3′-dideoxyinosine and 8-azaguanosine are substrates, while adenosine and deoxyadenosine are not. IMP, deoxyIMP, GMP, and deoxyGMP are the best phosphate donors. The cytosolic 5′-nucleotidase/phosphotransferase substrate, 8-azaguanosine, was found to be very toxic for cultured fibroblasts (LD50 = 0.32 μM). Mutants resistant to either 8-azaguanosine and the correspondent base 8-azaguanine were isolated and characterized. Our results indicated that the 8-azaguanosine-resistant cells were lacking both cytosolic 5′-nucleotidase and hypoxanthine-guanine phosphoribosyltransferase, while 8-azaguanine resistant cells were lacking only the latter enzyme. Despite this observation, both mutants displayed 8-azaguanosine resistance, thus indicating that cytosolic 5′-nucleotidase is not essential for the activation of this nucleoside analog. 相似文献
7.
Molecular evolution of voltage-sensitive ion channel genes: on the origins of electrical excitability 总被引:14,自引:0,他引:14
We have analyzed nucleic acid and amino acid sequence alignments of a
variety of voltage-sensitive ion channels, using several methods for
phylogenetic tree reconstruction. Ancient duplications within this family
gave rise to three distantly related groups, one consisting of the Na+ and
Ca++ channels, another the K+ channels, and a third including the cyclic
nucleotide-binding channels. A series of gene duplications produced at
least seven mammalian homologues of the Drosophila Shaker K+ channel;
clones of only three of these genes are available from all three mammalian
species examined (mouse, rat, and human), pointing to specific genes that
have yet to be recovered in one or another of these species. The
Shaw-related K+ channels and the Na+ channel family have also undergone
considerable expansion in mammals, relative to flies. These expansions
presumably reflect the needs of the high degree of physiological and
neuronal complexity of mammals. Analysis of the separate domains of the
four-domain channels (Ca++ and Na+) supports their having evolved by two
sequential gene duplications and implies the historical existence of a
functional two-domain channel.
相似文献
8.
mtDNA diversity in rhesus monkeys reveals overestimates of divergence time and paraphyly with neighboring species 总被引:4,自引:0,他引:4
Reconstructions of the human-African great ape phylogeny by using
mitochondrial DNA (mtDNA) have been subject to considerable debate. One
confounding factor may be the lack of data on intraspecific variation. To
test this hypothesis, we examined the effect of intraspecific mtDNA
diversity on the phylogenetic reconstruction of another Plio- Pleistocene
radiation of higher primates, the fascicularis group of macaque (Macaca)
monkey species. Fifteen endonucleases were used to identify 10 haplotypes
of 40-47 restriction sites in M. mulatta, which were compared with similar
data for the other members of this species group. Interpopulational,
intraspecific mtDNA diversity was large (0.5%- 4.5%), and estimates of
divergence time and branching order incorporating this variation were
substantially different from those based on single representatives of each
species. We conclude that intraspecific mtDNA diversity is substantial in
at least some primate species. Consequently, without prior information on
the extent of genetic diversity within a particular species, intraspecific
variation must be assessed and accounted for when reconstructing primate
phylogenies. Further, we question the reliability of hominoid mtDNA
phylogenies, based as they are on one or a few representatives of each
species, in an already depauperate superfamily of primates.
相似文献
9.
D. A. Nardone J. B. Reuler D. E. Girard 《The Yale journal of biology and medicine》1980,53(3):233-250
Knowledge in history-taking has increased rapidly over the last twenty years. Currently the principles to be taught include "conduct," "content," and "diagnostic reasoning." However, inattentiveness of medical schools, reluctance of busy faculty to be involved, and increasing enrollments have resulted in difficulties in teaching these skills. Studies have shown a beneficial short-term effect of teaching these materials on interview performance but it is unknown whether this effect is long-lasting. The methods for instruction include the bedside and videotape models utilizing the concept of the fifteen-minute interview technique, programmed instruction, patient instructors, and direct student feedback. Future research should focus on identifying strategies in diagnostic reasoning, developing graduated competency criteria for trainees at different levels of their education, refining methods to evaluate large numbers of students, measuring outcomes of effective training such as compliance, and comparing costs and effectiveness of various methods. In addition, there remains the need to establish an association of course directors. 相似文献
10.