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111.
112.
Noriko Usui Kouji Matsushima Anne M. Pilaro Dan L. Longo Robert H. Wiltrout 《Biotherapy》1996,9(4):199-208
Recombinant human interleukin 1α (rh IL-1α) and etoposide (VP-16) synergize for direct growth inhibition of several human
tumor cell linesin vitro. Our previous studies demonstrated that VP-16 increased the number of membrane-associated IL-1 receptors (IL-1Rs) and also
enhanced the internalization of receptor-bound rh IL-1α. The purposes of this study were to test our hypothess that these
events were critical to the synergy between rhIL-1α and VP-16, to determine whether rhIL-1α and VP-16 synergize to increase
superoxide (SO) anion radical productionin vitro since SO anion has been implicated in the toxic effects of IL-1, and to investigate the antitumor efficacy of the combinaton
against tumors in vivo. A375/C6 melanoma cells and OVCAR-3 ovarian carcinoma cells were tested with IL-1 receptor antagonist
(IL-1ra) before exposure to rhIL-1α, VP-16 and rhIL-1α plus VP-16. The synergistic or antagonistic effects were assessed by
MTT assay. SO production was measured by reduction of cytochrome C. Athymic female mice bearing the A375/C6 melanoma were
treated by rhIL-1α, VP-16, and rhIL-1α+VP-16. The antitumor effects were evaluated by quantitating tumor growth and survival
time. Pretreatment with the IL-1ra abrogated the synergistic effects of rhIL-1α and VP-16. The production of SO radical by
A375/C6 cells was increased 2.5 fold by the combination of rhIL-1α and VP-16, and the addition of exogenous SOD blocked the
synergy between rhIL-1α and VP-16. However, when A375/S0D15 cells which over-expressed manganese superoxide dismutase (MnSOD)
after MnSOD cDNA transfecton were exposed to rhIL-1α and VP-16, in vitro antagonism was observed. In vivo studies demonstrated
that the combination of rhIL-1α and VP-16 delayed tumor growth better than either agent alone, although long-term survival
was not improved because of substantial toxicity. Our results suggest that the synergistic antitumor effects of IL-1α and
VP-16 may be due to IL-1R modulation and increased internalization of IL-1-IL-1R complex by VP-16 treatment, as well as to
a subsequent increase in SO anion radical production from the tumor cells exposed to both drugs. Thus, the combnation of IL-1α
and VP-16 might prove useful for the treatment of malignant diseasein vivo, if the increased toxicity can be reduced or managed.
The US Government’s right to retain a non-exclusive royalty-free license on and to any copyright is acknowledged. 相似文献
113.
Jiří Fajkus Aleš Kovařík Robert mKrálovics Milan Bezděk 《Molecular genetics and genomics : MGG》1995,247(5):633-638
We have examined the structure and chromatin organization of telomeres in Nicotiana tabacum. In tobacco the blocks of simple telomeric repeats (TTTAGGG)n are many times larger than in other plants, e.g., Arabidopsis thatiana or tomato. They are resolved as multiple fragments 60–160 kb in size (in most cases 90–130 kb) on pulsed-field gel electrophoresis (PFGE) of restriction endonuclease-digested DNA. The major subtelomeric repeat of the HRS60 family forms large homogeneous blocks of a basic 180 by motif having comparable lengths. Micrococcal nuclease (MNase) cleaves tobacco telomeric chromatin into subunits with a short repeat length of 157±5 bp; the subtelomeric heterochromatin characterized by tandemly repeated sequences of the HRS60 family is cut by MNase with a 180 by periodicity. The monomeric and dimeric particles of telomeric and subtelomeric chromatin differ in sensitivity to MNase treatment: the telomeric particles are readily digested, producing ladders with a periodicity of 7 bp, while the subtelomeric particles appear to be rather resistant to intranucleosomal cleavage. The results presented show apparent similarities in the organization of telomeric chromatin in higher plants and mammals. 相似文献
114.
以IL-8免疫的BALB/C小鼠脾细胞与Sp2/0或653小鼠骨髓瘤细胞融合构建了淋巴细胞杂交瘤克隆I8-S2和I8-63。ELISA叠加试验(ELISA Additivity Test)表明这两杂交瘤克隆分泌的单抗分别识别IL-8分子的不同表位。IL-8能激活人颗粒细胞,引起细胞内Ca~(2 )浓度([Ca~(2 )]_i)上升。通过流式细胞仪分析[Ca~(2 )]_i的变化,发现两个克隆单抗对IL8激活细胞的活力具有不同的中和作用。克隆I8-S2具有很强的中和作用,而克隆18-63则不然。上述结果提示IL-8的激活细胞活力局限于该分子的某表位。 相似文献
115.
116.
117.
Paula A. Belinky Segula Masaphy Dan Levanon Yitzhak Hadar Carlos G. Dosoretz 《Applied microbiology and biotechnology》1994,40(5):629-633
The effect of nitrogen and fatty-acid-rich substrates on the production of 1-octen-3-ol by the edible fungus Pleurotus pulmonarius, during growth in both shaken flask and fermentor cultures, and in-vitro, in post-harvested mycelium, was studied. Addition of soybean flour and soybean oil to the growth medium enhanced 1-octen-3-ol production about sevenfold and doubled the fungal biomass, as compared to that obtained from P. pulmonarius cultured on a defined synthetic medium. A clear relationship between the production of 1-octen-3-ol and lipoxygenase activity was found during the growth of mushroom pellets. The highest in-vitro generation of 1-octen-3-ol was obtained upon addition of exogenous linoleic acid and pure O2 to pellets grown with soybean fluor and soybean oil. This generation was even higher than that of fruiting bodies exposed to the same conditions. These results suggest that lipoxygenase activity and, subsequently, 1-octen-3-ol biosynthesis in P. pulmonarius are enhanced by the presence of substrates containing fatty acids in the growth medium.
Correspondence to: D. Levanon 相似文献
118.
Analysis of HLA and Disease Susceptibility: Chromosome 6 Genes and Sex Influence Long-QT Phenotype 总被引:3,自引:1,他引:2
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Lowell R. Weitkamp Arthur J. Moss Raymond A. Lewis W. J. Hall Jean W. MacCluer Peter J. Schwartz Emanuela H. Locati Dan Tzivoni G. Michael Vincent Jennifer L. Robinson Sally A. Guttormsen 《American journal of human genetics》1994,55(6):1230-1241
The long-QT (LQT) syndrome is a genetically complex disorder that is characterized by syncope and fatal ventricular arrhythmias. LQT syndrome, as defined by a prolonged electrocardiographic QT interval, has a higher incidence in females than in males and does not exhibit Mendelian transmission patterns in all families. Among those families that are nearly consistent with Mendelian transmission, linkage between a locus for LQT syndrome and the H-ras-1 locus on the short arm of chromosome 11 has been reported in some families but not in others. Earlier analyses suggesting that LQT syndrome might be caused by a gene in the HLA region of chromosome 6 were not confirmed by standard linkage analyses. Here, we present an analysis of HLA haplotype sharing among affected pedigree members, showing an excess of haplotype sharing in a previously published Japanese pedigree and possibly also in 15 families of European descent. The haplotypes shared by affected individuals derive from both affected and unaffected parents. In an analysis of independent (unrelated) HLA haplotypes, we also found a nonrandom distribution of HLA-DR genes in LQT syndrome patients compared with controls, suggesting an association between the LQT phenotype and specific HLA-DR genes. Our data indicate that DR2 has a protective effect and, particularly in males, that DR7 may increase susceptibility to the LQT syndrome. Thus, LQT syndrome may be influenced by genes on chromosomes 11 and 6, possibly with a sex-specific effect. These results provide a model for an effect of HLA-region genes inherited from either parent on the expression of an illness that may be determined principally by alleles at loci not linked to HLA. 相似文献
119.
Dan W. Urry D. Channe Gowda Shaoqing Peng Timothy M. Parker Naijie Jing R. Dean Harris 《Biopolymers》1994,34(7):889-896
Commonly a key element enabling proteins to function is an amino acid residue or residues with functional side chains having shifted pKa values. This article reports the results on a set of protein-based polymers (model proteins) that exhibit hydrophobic folding and assembly transitions, and that have been designed for the purpose of achieving large hydrophobic-induced pKa shifts by selectively replacing Val residues by Phe residues. The high molecular weight polypentapeptides, actually poly (tricosapeptides) with six varied pentamers in fixed sequence, were designed and synthesized to have the same amino acid compositions but different proximities between a single aspartic acid residue and 5 Phe residues per 30 residues. With the 5 Phe residues distal from the Asp residue, the observed pKa shift was 2.9 when compared to the Val-containing reference. With the 5 Phe residues within 1 nm of the Asp residue, the pKa shift was 6.2. This represents a free energy of interaction of 8 kcal/moles. To our knowledge, this is the largest pKa shift documented for an Asp residue in a polypeptide– or protein–water system. Data are reviewed that do not support the usual electrostatic arguments for pKa shifts of charge–charge repulsion and/or unfavorable ion self-energies arising from displacement of water by hydrophobic moieties, but rather the data are interpreted to indicate the presence of an apolar–polar repulsive free energy of hydration, which results from a potentially highly cooperative competition between apolar and polar species for hydration. © 1994 John Wiley & Sons, Inc. 相似文献
120.
Serological data identify a single major histocompatibility complex (MHC) class I locus in cattle. Molecular data, however, demonstrate the presence of at least two cattle MHC (BoLA) class I loci. To investigate the number of transcribed BoLA class I genes, we amplified cattle cDNA by using a single MHC class I-specific primer that hybridized to a conserved region of exon 4 and a non-specific 3 primer. Six BoLA class I cDNAs have been cloned and sequenced from a Bos taurus bull heterozygous for BoLA class I serological antigens, demonstrating the presence of a minimum of three loci. Sequence comparisons suggested that one of these cDNAs may be an unexpressed allele or the product of a nonclassical locus.The nucleotide sequence data reported in this paper have been submitted to the GenBank nucleotide sequence database and have been assigned the accession numbers U01186 and U01187. 相似文献