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81.
Regulation of human T cell leukemia virus expression 总被引:15,自引:0,他引:15
Retroviruses of the type C morphology have been implicated in a wide variety of diseases in animals and humans. The human T cell leukemia viruses types I (HTLV-I) and II (HTLV-II), the prototypic human-type C retroviruses, have been identified as the causative agents of some forms of human leukemia and neurological disorders. The genetic structure and regulation of the HTLVs are more complex than their avian and murine leukemia virus counterparts. In addition to the gag, pol, and env genes that encode the characteristic virion proteins of all replication competent retroviruses, the genomes of HTLV encode the non-structural proteins, Tax and Rex, which are required for regulating viral gene expression. To understand what appears to be a complex mechanism of disease induction by HTLV, elucidating the regulation and function of the viral gene products and the interaction of these products with each other, as well as with cellular factors, will be critical. This review focuses primarily on regulation of HTLV gene expression in the infected human T lymphocyte, but also discusses analogous gene regulation by the human immunodeficiency virus (HIV). It concentrates specifically on the role these gene products play in virus replication and, ultimately, pathogenesis. 相似文献
82.
E Hu K Watkins S Groshen S C Chen B Malloy R Agah P Nichols J Parker A Martin M G Boosalis 《Molecular biotherapy》1990,2(2):96-103
A phase I trial of interleukin-2 and interferon gamma combination treatment in patients with advanced malignancies was performed based on preclinical in vitro and in vivo data which demonstrated synergistic antitumor effect. The toxicities, immune parameters, and tumor responses are described. The clinical and biologic maximal tolerated doses were extrapolated from these data. 相似文献
83.
84.
An altered pattern of cross-resistance in multidrug-resistant human cells results from spontaneous mutations in the mdr1 (P-glycoprotein) gene 总被引:27,自引:0,他引:27
Multidrug resistance in human cells results from increased expression of the mdr1 (P-glycoprotein) gene. Although the same gene is activated in cells selected with different drugs, multidrug-resistant cell lines can be preferentially resistant to their selecting agent. The mdr1 cDNA sequence from vinblastine-selected KB cells, which are uniformly resistant to different lipophilic drugs, was compared with the corresponding sequence from colchicine-selected KB cells preferentially resistant to colchicine. These sequences differ at three positions, resulting in a single amino acid change in P-glycoprotein. These differences result from mutations that occurred during colchicine selection. The appearance of these mutations coincides with the emergence of preferential resistance to colchicine. We have constructed biologically active mdr1 cDNA clones that express either wild-type or mutant P-glycoprotein. Multi-drug-resistant transfectants obtained with the mutant sequence were characterized by increased relative resistance to colchicine compared with transfectants obtained with wild-type sequence. mdr1 mutations are therefore responsible for preferential resistance to colchicine in multidrug-resistant KB cells. 相似文献
85.
Hancai Chen James X. Gray Murali Nayudu Michael A. Djordjevic Michael Batley John W. Redmond Barry G. Rolfe 《Molecular & general genetics : MGG》1988,212(2):310-316
Summary R-prime plasmids were constructed from a derivative of Rhizobium strain NGR234 (ANU280) and were shown to contain overlapping genomic DNA segments involved in biosynthesis of exopolysaccharides (EPS). The R-primes originally constructed carried the mutant allele from Tn5-induced EPS-deficient (Exo–) mutant ANU2811. This plasmid-located mutant allele was dominant to the corresponding wild-type allele as merodiploid strains were Exo–. Exo+ revertants occurred at a low rate (1×10-7) and these were shown to result from double reciprocal recombination events, which led to the isolation of R-prime plasmids carrying functional wild-type exo alleles. R-prime plasmids that carry overlapping segments of DNA from parental strain ANU280 complemented 28 of the 30 group 2 Exo– mutants of strain ANU280. Complementation of these Exo– mutants also restored their symbiotic abilities of effective nodulation. Subsequent in vivo recombination between the wild-type alleles located on the R-prime and the corresponding mutated allele on the genome, was used to generate a new family of R-primes, which carried mutations in the exo genes. The 30 group 2 Exo– mutants were classified into 7 distinct genetic groups based upon complementation and physical mapping data. Five of the seven exo loci were gentically linked and located on a 15-kb region of DNA. Mutations at two loci were dominant only when the mutations were R-prime plasmid-located while a mutation at a second locus was cis-dominant to two other exo loci. At least five genes involved in the synthesis of acidic exopolysaccharide synthesis have been identified. 相似文献
86.
The monocyte differentiation antigen, CD14, is anchored to the cell membrane by a phosphatidylinositol linkage 总被引:59,自引:0,他引:59
A Haziot S Chen E Ferrero M G Low R Silber S M Goyert 《Journal of immunology (Baltimore, Md. : 1950)》1988,141(2):547-552
CD14 is a myeloid differentiation Ag expressed primarily on peripheral blood monocytes and macrophages. Although its function is unknown, the CD14 gene maps to a region encoding several myeloid growth factors and receptors. Analysis of the CD14 protein sequence deduced from the cDNA shows that although the CD14 protein contains a characteristic leader peptide, it lacks a characteristic transmembrane region, suggesting that CD14 may be anchored to the membrane via glycosylphosphatidylinositol (PI). Treatment of monocytes as well as a CD14-expressing neuroglioma cell line with PI-phospholipase C removed CD14 from the cell surface. Furthermore, monocytes from a patient with paroxysmal nocturnal hemoglobinuria, a disease characterized by lack of expression of other PI-linked proteins, failed to express CD14. Interestingly, the CD14-expressing neuroglioma cell line, which had been transfected with a single CD14 cDNA, released a soluble form of CD14 into the supernatant. Soluble forms of CD14 have previously been observed in serum of normal individuals and in culture supernatants of CD14+ cells. Biosynthetic experiments reveal that this soluble form of CD14 (48 kDa), which is smaller than the form released from the membrane by PI-phospholipase C (53 kDa), does not contain ethanolamine, the first constitutent of the PI-anchoring system. These studies demonstrate that CD14 is a member of the family of PI-anchored proteins and suggest that soluble forms of CD14 represent molecules that completely lack the PI-anchoring system. 相似文献
87.
K L Goldenthal K Hedman J W Chen J T August P Vihko I Pastan M C Willingham 《The journal of histochemistry and cytochemistry》1988,36(4):391-400
We have used electron microscopic immunocytochemistry to compare the distribution of LAMP-1, a marker for lysosomal membranes, with the intracellular localization of alpha 2-macroglobulin (alpha 2-M) and transferrin at various time points after their endocytosis into cultured NIH 3T3 cells. The purposes of this study were (a) to determine how soon endocytic ligands reach lysosomal organelles, (b) to examine whether the intermediate endocytic vesicles gained lysosomal markers gradually or in a precipitous, discrete event, and (c) to examine the relationship, if any, between the pathway of recycling ligands and lysosomes. At early time points (0-5 min) after initiation of endocytosis, most structures containing alpha 2-M labeled with colloidal gold (receptosomes) were not labeled by anti-LAMP-1 detected using ferritin bridge or peroxidase immunocytochemistry. At late time points (greater than or equal to 15 min), the structures containing alpha 2-M (lysosomes) were strongly labeled by anti-LAMP-1. In contrast, transferrin that was directly labeled with ferritin was mostly located in LAMP-1-negative structures at all time points studied. The proportion of alpha 2-M-gold containing vesicles strongly labeled for LAMP-1 roughly paralleled the proportion of alpha 2-M-gold-containing structures positive for cytochemically detectable acid phosphatase. Our data indicate that ligands such as transferrin that are internalized through coated pits and receptosomes, but not delivered to lysosomes, do not traverse a lysosomal organelle compartment as marked by LAMP-1 content. Ligands such as alpha 2-M that are destined for lysosomal delivery reach a LAMP-1-positive organelle compartment only after they traverse LAMP-1-negative, non-lysosomal vesicles previously described as receptosomes. 相似文献
88.
作者合成了阴离子型和阳离子型葡聚糖,以此为载体,用CNBr活化其剩余羟基,固定化了葡萄糖淀粉酶和葡萄糖异构酶。就离子型载体对固定化酶的蛋白载量、最适pH和热稳定性等的影响做了考察。发现固定化酶的蛋白载量不仅与载体的电性质有关,也与酶分子自身的电性质有关。当载体电性质与酶蛋白电性质相反时,固定化酶的蛋白载量增加,热稳定性提高、载体电性质与酶蛋白电性质相同时,固定化酶的蛋白载量不变或下降,其热稳定性不变。作者还发现当离子型载体孔度和体系缓冲液浓度一定时,酶分子能否进入多孔性载体内部,对其最适pH是否变化影响极大。若酶分子仅被连接在载体的外表层,其最适pH不发生变化,反之亦然。作者还观察到当多糖类载体引入氨基或羧基后,大大增强了其抵抗微生物侵蚀的能力。 相似文献
89.
Protein synthesis in the hippocampus associated with memory facilitation by corticotropin-releasing factor in rats. 总被引:2,自引:0,他引:2
The present study used pharmacological, biochemical, and behavioral methods to examine the role of protein synthesis in the hippocampus in memory processes of a passive avoidance learning in rats. Results indicated that corticotropin-releasing factor (CRF) significantly improved memory retention in rats. Both cycloheximide (CHX) and actinomycin-D (ACT-D) impaired memory at high doses. At doses of CHX and ACT-D that did not affect memory alone, they both antagonized the memory-enhancing effect of CRF. Biochemically, there were specific increases in the optical density of three protein bands in the cytosolic fraction of hippocampal cells in rats showing good memory. There were also marked increases in the optical density of two protein bands in the nucleus fraction of the same animals. Similar results were observed in animals injected with CRF. However, no significant protein alteration was observed in animals receiving stress. These results together suggest that there are new protein syntheses in the hippocampus that are specifically associated with passive avoidance learning in rats. 相似文献
90.
VCP, the mammalian homolog of cdc48, is tyrosine phosphorylated in response to T cell antigen receptor activation. 总被引:12,自引:2,他引:10 下载免费PDF全文
M Egerton O R Ashe D Chen B J Druker W H Burgess L E Samelson 《The EMBO journal》1992,11(10):3533-3540
Activation of T cells through the T cell antigen receptor (TCR) results in the rapid tyrosine phosphorylation of a number of cellular proteins, one of the earliest being a 100 kDa protein. We have sought to identify this 100 kDa substrate by partially purifying the protein by antiphosphotyrosine (APT) affinity purification, in order to obtain amino acid sequence data and, using this information, to isolate the cDNA clone encoding the molecule. We report here that the amino acid sequence data showed pp100 to be the murine equivalent of porcine valosin containing protein (VCP), a finding confirmed from the cloning and sequencing of the murine pp100 cDNA. Sequence analysis has shown VCP to be a member of a family of ATP binding, homo-oligomeric proteins, and the mammalian homolog of Saccharomyces cerevisiae cdc48p, a protein essential to the completion of mitosis in yeast. We also provide proof that both endogenous and expressed murine VCP are tyrosine phosphorylated in response to T cell activation. Thus we have identified a novel component of the TCR mediated tyrosine kinase activation pathway that may provide a link between TCR ligation and cell cycle control. 相似文献