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1.
In a variety of tumour systems, individuals carrying progressively growing neoplasms have lymphoid cells with a specific cytotoxic effect on cultured tumour cells from the same individual1–4. Since the sera of tumour-bearing individuals have been shown to prevent tumour cell destruction by immune lymphocytes in vitro2,5–8 and since this serum blocking activity appears early in primary and transplant tumour development5,7, it has been suggested that the appearance of this serum blocking activity might be responsible for the progressive growth of tumours in individuals having cytotoxic lymphocytes. Counteraction of this blocking activity would thus be of primary importance in facilitating the function of an already existing or bolstered cell-mediated immunity. The serum blocking activity might be inhibited in various ways, by preventing the formation of blocking antibody or by interfering with its action (“unblocking”), as demonstrated in Moloney sarcoma regressor sera9. This type of serum also has a therapeutic effect on Moloney sarcomas in vivo10,11, which has been tentatively attributed to its unblocking activity8,9 or, possibly, to a complement-dependent cytotoxicity10. Tumour growth in the Moloney sarcoma system, however, might be due in part to continuous recruitment of neoplastic cells by virus-induced transformation and so the therapeutic effect could be due to a virus-neutralizing serum activity9,10. 相似文献
2.
On the mechanism of ATP-induced shape changes in the human erythrocyte membranes: the role of ATP
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In the preceding paper (Sheetz, M. and S.J. Singer. 1977. J Cell Biol. 73:638-646) it was shown that erythrocyte ghosts undergo pronounced shape changes in the presence of mg-ATP. The biochemical effects of the action of ATP are herein examined. The biochemical effects of the action of ATP are herein examined. Phosphorylation by ATP of spectrin component 2 of the erythrocyte membrane is known to occur. We have shown that it is only membrane protein that is significantly phosphorylated under the conditions where the shape changes are produced. The extent of this phosphorylation rises with increasing ATP concentration, reaching nearly 1 mol phosphoryle group per mole of component 2 at 8mM ATP. Most of this phosphorylation appears to occur at a single site on the protein molecule, according to cyanogen bromide peptide cleavage experiments. The degree of phosphorylation of component 2 is apparently also regulated by a membrane-bound protein phosphatase. This activity can be demonstrated in erythrocyte ghosts prepared from intact cells prelabeled with [(32)P]phosphate. In addition to the phosphorylation of component 2, some phosphorylation of lipids, mainly of phosphatidylinositol, is also known to occur. The ghost shape changes are, however, shown to be correlated with the degree of phosphorylation of component 2. In such experiment, the incorporation of exogenous phosphatases into ghosts reversed the shape changes produced by ATP, or by the membrane-intercalating drug chlorpromazine. The results obtained in this and the preceding paper are consistent with the proposal that the erythrocyte membrane possesses kinase and phosphates activities which produce phosphorylation and dephosphorylation of a specific site on spectrin component 2 molecules; the steady-state level of this phosphorylation regulates the structural state of the spectrin complex on the cytoplasmic surface of the membrane, which in turn exerts an important control on the shape of the cell. 相似文献
3.
Gold salts and phenylbutazone selectively inhibit the synthesis of PGF2α and PGE2 respectively. Lowered production of one prostaglandin species is accompanied by an increased production of the other. Selective inhibition by these drugs was observed in the presence of adrenaline, reduced glutathione and copper sulphate under conditions when most anti-inflammatory compounds inhibited PGE2 and PGF2α syntheses equally. It is postulated that selective inhibitors may have a different mode of action
and beneficial effects may be related to the endogenous ratio of PGE to PGF required for normal function. 相似文献
4.
5.
Pasquier CM; Promponas VI; Varvayannis NJ; Hamodrakas SJ 《Bioinformatics (Oxford, England)》1998,14(8):749-750
Summary : FT is a tool written in C++, which implements the Fourier
analysis method to locate periodicities in aminoacid or DNA sequences. It
is provided for free public use on a WWW server with a Java interface.
Availability : The server address is http://o2.db. uoa.gr/FT Contact :
shamodr@atlas.uoa.gr
相似文献
6.
NA Burd B Pennings BB Groen AP Gijsen JM Senden LJ van Loon 《Journal of applied physiology (Bethesda, Md. : 1985)》2012,113(6):896-902
We aimed to assess the reliability of the single biopsy approach for calculating muscle protein synthesis rates compared with the well described sequential muscle biopsy approach following a primed continuous infusion of L-[ring-(2)H(5)]phenylalanine and GC-MS analysis in older men. Two separate experimental infusion protocols, with differing stable isotope amino acid incorporation times, were employed consisting of n = 27 (experiment 1) or n = 9 (experiment 2). Specifically, mixed muscle protein FSR were calculated from baseline plasma protein enrichments and muscle protein enrichments obtained at 90 min or 50 min (1BX SHORT), 210 min or 170 min (1BX LONG), and between the muscle protein enrichments obtained at 90 and 210 min or 50 min and 170 min (2BX) of the infusion for experiments 1 and 2, respectively. In experiment 2, we also assessed the error that is introduced to the single muscle biopsy approach when nontracer naive subjects are recruited for participation in a primed continuous infusion of isotope-labeled amino acids. In experiment 1, applying the individual plasma protein enrichment values to the single muscle biopsy approach resulted in no differences in muscle protein FSR between the 1BX SHORT (0.031 ± 0.003%·h(-1)), 1BX LONG (0.032 ± 0.002%·h(-1)), or the 2BX approach (0.034 ± 0.002%·h(-1)). A significant correlation in muscle protein FSR was observed only between the 1BX LONG and 2BX approach (r = 0.8; P < 0.001). Similar results were observed in experiment 2. In addition, using the single biopsy approach in nontracer na?ve state results in a muscle protein FSR that is negative for both the 1BX SHORT (-0.67 ± 0.051%·h(-1)) and 1BX LONG (-0.19 ± 0.051%·h(-1)) approaches. This is the first study to demonstrate that the single biopsy approach, coupled with the background enrichment of L-[ring-(2)H(5)]-phenylalanine of mixed plasma proteins, generates data that are similar to using the sequential muscle biopsy approach in the elderly population. 相似文献
7.
Estrada-Cuzcano A Neveling K Kohl S Banin E Rotenstreich Y Sharon D Falik-Zaccai TC Hipp S Roepman R Wissinger B Letteboer SJ Mans DA Blokland EA Kwint MP Gijsen SJ van Huet RA Collin RW Scheffer H Veltman JA Zrenner E;European Retinal Disease Consortium den Hollander AI Klevering BJ Cremers FP 《American journal of human genetics》2012,90(1):102-109
Cone-rod dystrophy (CRD) and retinitis pigmentosa (RP) are clinically and genetically overlapping heterogeneous retinal dystrophies. By using homozygosity mapping in an individual with autosomal-recessive (ar) RP from a consanguineous family, we identified three sizeable homozygous regions, together encompassing 46 Mb. Next-generation sequencing of all exons, flanking intron sequences, microRNAs, and other highly conserved genomic elements in these three regions revealed a homozygous nonsense mutation (c.497T>A [p.Leu166∗]) in C8orf37, located on chromosome 8q22.1. This mutation was not present in 150 ethnically matched control individuals, single-nucleotide polymorphism databases, or the 1000 Genomes database. Immunohistochemical studies revealed C8orf37 localization at the base of the primary cilium of human retinal pigment epithelium cells and at the base of connecting cilia of mouse photoreceptors. C8orf37 sequence analysis of individuals who had retinal dystrophy and carried conspicuously large homozygous regions encompassing C8orf37 revealed a homozygous splice-site mutation (c.156−2A>G) in two siblings of a consanguineous family and homozygous missense mutations (c.529C>T [p.Arg177Trp]; c.545A>G [p.Gln182Arg]) in siblings of two other consanguineous families. The missense mutations affect highly conserved amino acids, and in silico analyses predicted that both variants are probably pathogenic. Clinical assessment revealed CRD in four individuals and RP with early macular involvement in two individuals. The two CRD siblings with the c.156−2A>G mutation also showed unilateral postaxial polydactyly. These results underline the importance of disrupted ciliary processes in the pathogenesis of retinal dystrophies. 相似文献
8.
Gijsen HJ Berthelot D De Cleyn MA Geuens I Brône B Mercken M 《Bioorganic & medicinal chemistry letters》2012,22(2):797-800
The transient receptor potential A1 (TRPA1) channel has been implicated in a number of inflammatory and nociceptive processes, and antagonists of the TRPA1 receptor could offer a potential treatment for conditions such as inflammatory or neuropathic pain, airway disorders, and itch. In a high throughput screen aimed at the identification of TRPA1 antagonists, 4-phenyl-2-thioxo-1,2,3,4-tetrahydro-indeno[1,2-d]pyrimidin-5-one (1) was identified as a potent TRPA1 receptor antagonist. A series of analogous tricyclic 3,4-dihydropyrimidine-2-thiones has been prepared via the multi-component Biginelli reaction and subsequent derivatization. This has led to TRPA1 antagonists with potencies around 10nM for both rat and human derived TRPA1 receptors. The activity was shown to reside exclusively in the 4R-enantiomers. 相似文献
9.
Amiloride does not alter NaCl avoidance in Fischer-344 rats 总被引:2,自引:2,他引:0
Fischer-344 (F-344) rats differ from other common rat strains in that they
fail to show any preference for NaCl at any concentration in two- bottle
preference tests. Because 100 microM amiloride partially blocks the
NaCl-evoked chorda tympani (CT) response in electrophysiological studies,
we tested NaCl preference (0.068-0.273 M) in F-344 rats with and without
100 microM amiloride solution as the solvent. A third group was tested with
unadulterated NaCl solutions following CT transection. Amiloride had no
significant effect on the NaCl preference-aversion function, whereas CT
transection significantly reduced NaCl avoidance. These results suggest
that the amiloride-sensitive component of the NaCl response is not
necessary for F-344 rats to display avoidance of NaCl, but the entire CT
input is.
相似文献
10.
A numerical and experimental investigation of unsteady entry flow in a 90 degrees curved tube is presented to study the impact of the non-Newtonian properties of blood on the velocity distribution. The time-dependent flow rate for the Newtonian and the non-Newtonian blood analog fluid were identical. For the numerical computation, a Carreau-Yasuda model was employed to accommodate the shear thinning behavior of the Xanthan gum solution. The viscoelastic properties were not taken into account. The experimental results indicate that significant differences between the Newtonian and non-Newtonian fluid are present. The numerical results for both the Newtonian and the non-Newtonian fluid agree well with the experimental results. Since viscoelasticity was not included in the numerical code, shear thinning behavior of the blood analog fluid seems to be the dominant non-Newtonian property, even under unsteady flow conditions. Finally, a comparison between the non-Newtonian fluid model and a Newtonian fluid at a rescaled Reynolds number is presented. The rescaled Reynolds number, based on a characteristic rather than the high-shear rate viscosity of the Xanthan gum solution, was about three times as low as the original Reynolds number. Comparison reveals that the character of flow of the non-Newtonian fluid is simulated quite well by using the appropriate Reynolds number. 相似文献