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41.
Leflunomide is an immunomodulatory agent used for the treatment of rheumatoid arthritis. In this study, we investigated the effect of A77 1726 – the active metabolite of leflunomide – on the production of IL-1 receptor antagonist (IL-1Ra) by human synovial fibroblasts and articular chondrocytes. Cells were incubated with A77 1726 alone or in combination with proinflammatory cytokines. IL-1Ra production was determined by ELISA. A77 1726 alone had no effect, but in the presence of IL-1β or tumour necrosis factor-α it markedly enhanced the secretion of IL-1Ra in synovial fibroblasts and chondrocytes. The effect of A77 1726 was greatest at 100 μmol/l. In synovial fibroblasts and de-differentiated chondrocytes, A77 1726 also increased IL-1β-induced IL-1Ra production in cell lysates. Freshly isolated chondrocytes contained no significant amounts of intracellular IL-1Ra. A77 1726 is a known inhibitor of pyrimidine synthesis and cyclo-oxygenase (COX)-2 activity. Addition of exogenous uridine did not significantly modify the effect of A77 1726 on IL-1Ra production, suggesting that it was not mediated by inhibition of pyrimidine synthesis. Indomethacin increased IL-1β-induced IL-1Ra secretion in synovial fibroblasts and de-differentiated chondrocytes, suggesting that inhibition of COX-2 may indeed enhance IL-1β-induced IL-1Ra production. However, the stimulatory effect of indomethacin was consistently less effective than that of A77 1726. A77 1726 increases IL-1Ra production by synovial fibroblasts and chondrocytes in the presence of proinflammatory cytokines, and thus it may possess chondroprotective effects. The effect of A77 1726 may be partially mediated by inhibition of COX-2, but other mechanisms likely concur to stimulate IL-1Ra production.  相似文献   
42.
It is anticipated that future climatic warming following the currently enhanced greenhouse effect will change the distribution limits of many vascular plant species. Using annual accumulated respiration equivalents, calculated from January and July mean temperatures and total annual precipitation, simple presence–absence response surface plots are constructed for 1521 native vascular-plant species in 229 75×75-km grid squares within Fennoscandia. The contemporary occurrences in relation to present-day climate and to predicted changes in climate (and hence annual accumulated respiration equivalents) are used to predict possible future immigrations and extinctions within each grid square. The percentage of potential change in species richness for each grid square is estimated from these predictions. Results from this study suggest a mean increase in species richness per grid square of 26%. Increases in species richness are greatest in the southern parts of the alpine/boreal regions in Fennoscandia. There are ten species that potentially may become extinct in Fennoscandia as a result of predicted climatic warming. Possible conservation strategies to protect such endangered species are outlined.  相似文献   
43.
Corynebacterium melassecola, a glutamate producing bacteria, has been cultivated in a 4-l batch aerated fermentor with glucose and fructose mixtures of various proportions as carbon sources and mineral ammonium as nitrogen source. Experimental results are analysed in order to obtain the specific rates and the conversion yields. A data reconciliation technique is used to manage with the experiments performed in similar conditions. The redundant experimental informations are used to test the carbon, nitrogen, available electrons, phosphorus and protons balances. The measurement of dissolved oxygen tension and volumetric oxygen transfer coefficient indicates that oxygen was never a limiting substrate in the experimental device though the oxygen demand was up to 70 mmoles/l.h and the heterogeneity of the liquid phase. The highest specific growth rate (0.59 h?1) and the highest biomass production yield (0.48 gX/gS) are obtained with glucose as the sole carbon source. These two parameters progressively decrease with the increase of the proportion of fructose in the medium down to 0.43 h?1 and 0.38 gX/gS on fructose so that the specific carbon uptake rate remains constant and equal to 0.04 C-mole/gX h. From a metabolic point of view, this decrease of the carbon conversion efficiency into cellular material is correlated to a lower carbon flux through the pentose pathway as the fructose proportion is increased. This is correlated with an accumulation of fructose 1,6-biphosphate which further activates the lactate deshydrogenase resulting to lactate production though the metabolism remains strictly aerobic.  相似文献   
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Summary Serum specimens of three unrelated black males had an unusual alpha-1-antitrypsin phenotype, designated Pi Ecincinnati because of its electrophoretic mobility. Family studies indicated that the new phenotype was the expression of an alpha-1-antitrypsin allele, labeled Pi Ecincinnati  相似文献   
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The regional distribution of L-homocysteine (Hcy) was determined in brains from mouse, rat, guinea pig, and rabbit, using a sensitive radioenzymatic assay. Large interspecies variations in the Hcy content in various parts of the brain were observed, but cerebellum contained the highest amount in all species investigated. In the rat the amount of Hcy in cerebellum (6.4 nmol/g) was about sixfold higher than in most other parts of the brain, whereas in the mouse and guinea pig the amount in cerebellum (about 1 nmol/g) was only twofold higher than in the other brain regions. There was a remarkably high level of Hcy in all regions of the rabbit brain (4-10 nmol/g); the highest concentration was found in the cerebellar white matter. In this species the amount of Hcy in all brain regions examined exceeded that in the liver.  相似文献   
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Summary Rhizobium sp. NGR234 in a fast-growing Rhizobium strain with a broad host range. The location and role of chromosomal genes involved in cellular metabolism or in the legume symbioses is unknown. We isolated a series of auxotrophic and antibiotic resistant mutants of NGR234 and utilized a chromosome mobilization system based on Tn5-Mob and pJB3JI; Tn5-Mob donor strains behaved like Hfr strains, transferring the chromosome polarly at high frequency from a fixed point of insertion. The use of four different strains with Tn5-Mob located at different nutritional loci in crosses with double auxotrophic recipients, allowed us to build up a circular linkage map of NGR234 based on relative recombination frequencies. Also, symbiotically important genes identified by site-directed mutagenesis, such as hemA and ntrA, could be located and mapped on the chromosome.Abbreviations Tc tetracycline - Sp spectinomycin - Rif rifampicin - Km kanamycin  相似文献   
50.
Five peaks of cyclic AMP-binding activity could be resolved by DEAE-cellulose chromatography of bovine adrenal-cortex cytosol. Two of the binding peaks co-chromatographed with the catalytic activities of cyclic AMP-dependent protein kinases (ATP-protein phosphotransferase, EC 2.7.1.37) of type I or type II respectively. A third binding protein was eluted between the two kinases, and appeared to be the free regulatory moiety of protein kinase I. Two of the binding proteins for cyclic AMP, sedimenting at 9S in sucrose gradients, could also bind adenosine. They bound cyclic AMP with an apparent equilibrium dissociation constant (K(d)) of about 0.1mum, and showed an increased binding capacity for cyclic AMP after preincubation in the presence of K(+), Mg(2+) and ATP. The two binding proteins differed in their apparent affinities for adenosine. The isolated regulatory moiety of protein kinase I had a very high affinity for cyclic AMP (K(d)<0.1nm). At low ionic strength or in the presence of MgATP, the high-affinity binding of cyclic AMP to the regulatory subunit of protein kinase I was decreased by the catalytic subunit. At high ionic strength and in the absence of MgATP the high-affinity binding to the regulatory subunit was not affected by the presence of catalytic subunit. Under all experimental conditions tested, dissociation of protein kinase I was accompanied by an increased affinity for cyclic AMP. To gain some insight into the mechanism by which cyclic AMP activates protein kinase, the interaction between basic proteins, salt and the cyclic nucleotide in activating the kinase was studied.  相似文献   
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