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1.
The 2',3'-dideoxyriboside of 2,6-diaminopurine selectively inhibits human immunodeficiency virus (HIV) replication in vitro 总被引:1,自引:0,他引:1
J Balzarini R Pauwels M Baba M J Robins R M Zou P Herdewijn E De Clercq 《Biochemical and biophysical research communications》1987,145(1):269-276
The 2',3'-dideoxyriboside of 2,6-diaminopurine(ddDAPR) is, like 2',3'-dideoxyadenosine (ddAdo), a potent and selective inhibitor of human immunodeficiency virus (HIV) in vitro. The ddDAPR compound inhibits HIV antigen expression and HIV-induced cytopathogenicity in MT4 cells at a 50% effective dose (ED50) of 2.5-3.6 microM, as compared to 3.1-6.4 microM for ddAdo. Both compounds are endowed with a high selectivity index: 112 for ddDAPR and 139 for ddAdo. The 2',3'-unsaturated derivatives of ddDAPR and ddAdo, i.e. ddeDAPR and ddeAdo, are considerably more cytotoxic and less effective against HIV than the parental compounds. Like ddAdo, ddDAPR is only weakly inhibitory to the proliferation and DNA and RNA synthesis of a series of human B-lymphoblast, T-lymphoblast and T-lymphocyte cell lines. In contrast to ddAdo, which is rapidly deaminated by beef intestine adenosine deaminase at an initial velocity (Vi) of 145 mumol/mg protein/min, ddDAPR and ddeDAPR are poor substrates for the enzyme (Vi: 8 and 0.7 mumol/mg protein/min, respectively), which further contributes to the potential of ddDAPR as a chemotherapeutic agent against AIDS. 相似文献
2.
The human gastrin precursor. Characterization of phosphorylated forms and fragments. 总被引:5,自引:0,他引:5
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A Varro H Desmond S Pauwels H Gregory J Young G J Dockray 《The Biochemical journal》1988,256(3):951-957
There is a potential phosphorylation site in the C-terminal region of the precursor for the acid-stimulating hormone gastrin, which is immediately adjacent to an important cleavage point. In the present study we have sought to identify, separate, quantify and characterize phosphorylated and unphosphorylated forms of human progastrin and its fragments. Identification was made by two radioimmunoassays: (a) a novel assay employing an antibody raised to intact human progastrin; and (b) an assay using antibody reacting with the C-terminal tryptic fragment of human progastrin, as well as progastrin itself. Two forms of human progastrin isolated from a gastrinoma were separated by ion-exchange h.p.l.c., and had similar elution positions on reverse-phase h.p.l.c. and on gel filtration. The more acidic peptide contained close to equimolar amounts of phosphate. On trypsinization, peptides were released that co-eluted on ion-exchange h.p.l.c. with, and had the immunochemical properties of, naturally occurring C-terminal fragments of progastrin. One of the latter was isolated and shown by Edman degradation after derivatization with ethanethiol to have the sequence Ser (P)-Ala-Glu-Asp-Glu-Asn. Similar peptides occur in antral mucosa resected from ulcer patients. The unphosphorylated forms of progastrin predominated, whereas the phosphorylated forms of the C-terminal fragments were predominant. This distribution could be explained by preferential cleavage of phosphorylated progastrin. We conclude that in human progastrin, Ser-96 can occur in the phosphorylated form; this residue immediately follows a pair of basic residues (Arg-Arg) that are cleaved during synthesis of the biologically active product. 相似文献
3.
Potent and selective anti-HTLV-III/LAV activity of 2',3'-dideoxycytidinene, the 2',3'-unsaturated derivative of 2',3'-dideoxycytidine 总被引:9,自引:0,他引:9
J Balzarini R Pauwels P Herdewijn E De Clercq D A Cooney G J Kang M Dalal D G Johns S Broder 《Biochemical and biophysical research communications》1986,140(2):735-742
2',3'-Dideoxycytidinene (ddeCyd), the 2',3'-unsaturated derivative of 2',3'-dideoxycytidine (ddCyd) is, like ddCyd itself, a potent and selective inhibitor of HTLV-III/LAV in vitro. This conclusion is based on the relatively high ratio of effective antiviral dose (0.3 microM) versus cell growth inhibitory concentration (20-35 microM) and the lack of any appreciable inhibitory activity against a series of non-oncogenic RNA and DNA viruses. Both compounds were considerably more inhibitory to human lymphoid cell lines than human nonlymphoid or murine cell lines. They were highly dependent on prior activation by deoxycytidine kinase to exert their anti-HTLV-III/LAV and cytostatic effects. In contrast with ddCyd, ddeCyd lost part of its anti-retrovirus effect upon prolonged incubation (10 days) with the virus-infected cells in culture. 相似文献
4.
Attenuation of neurotoxicity following anoxia or glutamate receptor activation in EGF- and hippocampal extract-treated neuronal cultures 总被引:1,自引:0,他引:1
Neurotoxicity following anoxia or glutamate receptor activation was studied in primary neuronal cultures grown in serum-free, chemically defined CDM R12 medium. Exposure to 1 mM KCN, 0.5 mM kainic acid and 0.5 mM N-methyl-D-aspartate led to progressive neuronal degeneration. This damage was quantified by measuring lactate dehydrogenase released in the culture medium. The toxic effects were observed early during the development of the neuronal culture (from 4 days in vitro on) and seemed to be neuron-specific since astrocyte cultures were not affected. Chronic treatment of the neuronal cultures with epidermal growth factor at 10 ng/ml and hippocampal extract at dil. 1/833 (w/v) induced morphological alterations, increased beta-adrenergic receptor coupled adenylate cyclase activity, increased level of total lactate dehydrogenase activity in the case of epidermal growth factor-treated cultures, and attenuation of lactate dehydrogenase release following exposure to KCN or glutamate receptor agonists. The alterations observed are probably due to the proliferation and differentiation of glial cells in these treated cultures. This suggests that glial cells protect neurons in vitro from degeneration induced by anoxia or glutamate receptor activation. 相似文献
5.
R Peeters N Buys I Pauwels E R Kühn E Decuypere O Siau J Van Isterdael 《Reproduction, nutrition, development》1989,29(3):237-245
In order to define the patterns of TSH, T4, T3, rT3, GH and cortisol during the estrous cycle of sheep, pluriparous and primiparous ewes were synchronized with progestagen-impregnated pessaries (Veramix) at the start of the normal breeding season. After the pessaries were removed (day 0), daily blood sampling was carried out in cannulated ewes during the ovulatory cycle. Hormonal analyses of TSH, T4, T3, rT3, GH, cortisol, LH and progesterone (P) were performed by RIA. P and LH levels during the cycle were conform to the literature and were not different between the primiparous and pluriparous ewes of different breeds used in this study. Neither age nor breed influenced the hormone patterns. A significant negative correlation was found between TSH and P during the cycle, although the correlation between P and T4 was not significant; during the estrous period, low P levels were paralleled by high T4 levels, whereas the reverse was observed during the luteal phase. Higher T3 levels and T3/T4 ratios were observed during the luteal phase. No obvious pattern of rT3 and cortisol during the cycle was found. The GH concentration increased during the 17 days of the cycle. A positive correlation with P was calculated. During the estrous cycle obvious changes in thyroid hormones, GH and TSH occurred. However, this study shows no causal relationship between the thyroid and the gonadal axes. 相似文献
6.
Deep soil heterogeneity and fine root distribution in forests and pastures of eastern Amazonia 总被引:2,自引:1,他引:1
Little is known about deep soil heterogeneity, or its relationship with fine root distribution. Beneath a mature, closed-canopy forest of eastern Amazonia, and the pastures and secondary forests that are derived from this forest, soil soft spots and hollow chambers occur to at least 9 meters depth. We measured the vertical distribution of these soil patches, and compared chemical characteristics, mycorrhizal infection, and root density of soil soft spots with the surrounding matrix of more homogeneous soil. Soil soft spots and chambers varied little with depth, but occupied the greatest soil volume (0.8 to 1.2%) from 4 to 6 m depth in the mature forest. Soft spots had lower pH, P availability and arbuscular mycorrhizal infection, and higher K availability than surrounding soil. Root length density was 2 to 15 times higher in soft spots than in surrounding soil. In the pastures, roots were found only in soil soft spots at depths of >3 m. Pastures and secondary forest had more soil chambers in the upper meter of soil than mature forest, but were otherwise indistinguishable in their patterns of deep soil heterogeneity. Soil soft spots may be vestiges of cutter ant nest chambers, while hollow chambers are cutter ant chambers and root channels. Chambers may act as conduits for root penetration and water penetration to deep soil.Abbreviations AM
arbuscular mycorrhizae
- RLD
root length density (root length per unit of soil volume) 相似文献
7.
Janaine Almeida Neto Daniel Amando Nery Katia Simoni Bezerra Lima Maria Eduarda Gomes da Cruz Silva Tarcísio Cícero de Lima Araújo Nathália Andrezza Carvalho de Souza Rodolfo Hideki Vicente Nishimura Camila de Souza Araújo Ana Paula de Oliveira Jackson Roberto Guedes da Silva Almeida Larissa Araújo Rolim 《化学与生物多样性》2023,20(3):e202201039
This article describes the phytochemical study of Cannabis sativa roots from northeastern Brazil. The dried plant material was pulverized and subjected to exhaustive maceration with ethanol at room temperature, obtaining the crude ethanolic extract (Cs-EEBR). The volatile compounds were analyzed by gas chromatography coupled with mass spectrometry (GC/MS), which allowed to identify 22 compounds by comparing the linear retention index (LRI), the similarity index (SI) and the fragmentation pattern of the constituents with the literature. By this technique the major compounds identified were: friedelan-3-one and β-sitosterol. In addition, two fractions were obtained from Cs-EEBR by classical column chromatography and preparative thin layer chromatography. These fractions were analyzed by NMR and IR and together with the mass spectrometry data allowed to identify the compounds: epifriedelanol, friedelan-3-one, β-sitosterol and stigmasterol. The study contributed to the phytochemical knowledge of Cannabis sativa, specifically the roots, as there are few reports on the chemical constituents of this part of the plant. 相似文献
8.
Nicoletta Zini Katia Scotlandi Nicola Baldini Giuseppe Nini Patrixia Sabatelli Nadir M Maraldi 《Biology of the cell / under the auspices of the European Cell Biology Organization》1995,84(3):195-204
Summary— Multidrug-resistant (MDR) variants of a human osteosarcoma cell line (U-2 OS) have been recently obtained by continuous exposure to doxorubicin (DX). The growth and phenotypic characteristics of these cell lines have been demonstrated to be related to the level of expression of P-glycoprotein. In this work, the morphological changes associated with MDR have been evaluated by quantitative image analysis and transmission electron microscopy. Resistant cells present morphological changes with respect to sensitive cells at both cytoplasmic and nuclear level. Some of these changes appear to be related to the degree of resistance but not to the direct presence of DX, since deprived cells maintain some modified characters, while others are partly lost. These findings suggest that DX exposure affects cell metabolism causing progressive changes of the cell morphotype. 相似文献
9.
10.
RNA viruses have high mutation rates, with the majority of mutations being deleterious. We examine patterns of deleterious mutation accumulation over multiple rounds of viral replication, with a focus on how cellular coinfection and heterogeneity in viral output affect these patterns. Specifically, using agent-based intercellular simulations we find, in agreement with previous studies, that coinfection of cells by viruses relaxes the strength of purifying selection and thereby increases the rate of deleterious mutation accumulation. We further find that cellular heterogeneity in viral output exacerbates the rate of deleterious mutation accumulation, regardless of whether this heterogeneity in viral output is stochastic or is due to variation in the cellular multiplicity of infection. These results highlight the need to consider the unique life histories of viruses and their population structure to better understand observed patterns of viral evolution. 相似文献