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31.
Autologous disc cell implantation, growth factors and gene therapy appear to be promising therapies for disc regeneration. Unfortunately, the replicative lifespan and growth kinetics of human nucleus pulposus (NP) cells related to host age are unclear. We investigated the potential relations among age, replicative lifespan and growth rate of NP cells, and determined the age range that is suitable for cell-based biological therapies for degenerative disc diseases. We used NP tissues classified by decade into five age groups: 30s, 40s, 50s, 60s and 70s. The mean cumulative population doubling level (PDL) and population doubling rate (PDR) of NP cells were assessed by decade. We also investigated correlations between cumulative PDL and age, and between PDR and age. The mean cumulative PDL and PDR decreased significantly in patients in their 60s. The mean cumulative PDL and PDR in the younger groups (30s, 40s and 50s) were significantly higher than those in the older groups (60s and 70s). There also were significant negative correlations between cumulative PDL and age, and between PDR and age. We found that the replicative lifespan and growth rate of human NP cells decreased with age. The replicative potential of NP cells decreased significantly in patients 60 years old and older. Young individuals less than 60 years old may be suitable candidates for NP cell-based biological therapies for treating degenerative disc diseases. 相似文献
32.
Background
Alternative exons encode different isoforms of the human insulin-like growth factor-I (IGF-I) precursor without altering mature IGF-I. We hypothesized that the various IGF-I precursors may traffic IGF-I differently. Chimeric IGF-I precursors were made with green fluorescent protein (GFP) cloned between the signal and mature IGF-I domains. 相似文献33.
Identification of three functions of the adenovirus e4orf6 protein that mediate p53 degradation by the E4orf6-E1B55K complex 下载免费PDF全文
Querido E Morrison MR Chu-Pham-Dang H Thirlwell SW Boivin D Branton PE Morisson MR 《Journal of virology》2001,75(2):699-709
Complexes containing adenovirus E4orf6 and E1B55K proteins play critical roles in productive infection. Both proteins interact directly with the cellular tumor suppressor p53, and in combination they promote its rapid degradation. To examine the mechanism of this process, degradation of exogenously expressed p53 was analyzed in p53-null human cells infected with adenovirus vectors encoding E4orf6 and/or E1B55K. Coexpression of E4orf6 and E1B55K greatly reduced both the level and the half-life of wild-type p53. No effect was observed with the p53-related p73 proteins, which did not appear to interact with E4orf6 or E1B55K. Mutant forms of p53 were not degraded if they could not efficiently bind E1B55K, suggesting that direct interaction between p53 and E1B55K may be required. Degradation of p53 was independent of both MDM2 and p19ARF, regulators of p53 stability in mammalian cells, but required an extended region of E4orf6 from residues 44 to 274, which appeared to possess three separate biological functions. First, residues 39 to 107 were necessary to interact with E1B55K. Second, an overlapping region from about residues 44 to 218 corresponded to the ability of E4orf6 to form complexes with cellular proteins of 19 and 14 kDa. Third, the nuclear retention signal/amphipathic arginine-rich alpha-helical region from residues 239 to 253 was required. Interestingly, neither the E4orf6 nuclear localization signal nor the nuclear export signal was essential. These results suggested that if nuclear-cytoplasmic shuttling is involved in this process, it must involve another export signal. Degradation was significantly blocked by the 26S proteasome inhibitor MG132, but unlike the HPV E6 protein, E4orf6 and E1B55K were unable to induce p53 degradation in vitro in reticulocyte lysates. Thus, this study implies that the E4orf6-E1B55K complex may direct p53 for degradation by a novel mechanism. 相似文献
34.
Ilke van Hazel Francesco Santini Johannes Müller Belinda SW Chang 《BMC evolutionary biology》2006,6(1):97-15
Background
Vertebrate SWS1 visual pigments mediate visual transduction in response to light at short wavelengths. Due to their importance in vision, SWS1 genes have been isolated from a surprisingly wide range of vertebrates, including lampreys, teleosts, amphibians, reptiles, birds, and mammals. The SWS1 genes exhibit many of the characteristics of genes typically targeted for phylogenetic analyses. This study investigates both the utility of SWS1 as a marker for inferring vertebrate phylogenetic relationships, and the characteristics of the gene that contribute to its phylogenetic utility. 相似文献35.
36.
Avise JC; Shapira JF; Daniel SW; Aquadro CF; Lansman RA 《Molecular biology and evolution》1983,1(1):38-56
We address the problem of the possible significance of biological
speciation to the magnitude and pattern of divergence of asexually
transmitted characters in bisexual species. The empirical data for this
report consist of restriction endonuclease site variability in maternally
transmitted mitochondrial DNA (mtDNA) isolated from 82 samples of
Peromyscus polionotus and P. leucopus collected from major portions of the
respective species' ranges. Data are analyzed together with previously
published information on P. maniculatus, a sibling species to polionotus.
Maps of restriction sites indicate that all of the variation observed can
be reasonably attributed to base substitutions leading to loss or gain of
particular recognition sites. Magnitude of mtDNA sequence divergence within
polionotus (maximum approximately equal to 2%) is roughly comparable to
that observed within any of five previously identified mtDNA assemblages in
maniculatus. Sequence divergence within leucopus (maximum approximately
equal to 4%) is somewhat greater than that within polionotus. Consideration
of probable evolutionary links among mtDNA restriction site maps allowed
estimation of matriarchal phylogenies within polionotus and leucopus.
Clustering algorithms and qualitative Wagner procedures were used to
generate phenograms and parsimony networks, respectively, for the
between-species comparisons. Three simple graphical models are presented to
illustrate some conceivable relationships of mtDNA differentiation to
speciation. In theoretical case I, each of two reproductively defined
species (A and B) is monophyletic in matriarchal genealogy; the common
female ancestor of either species can either predate or postdate the
speciation. In case II, neither species is monophyletic in matriarchal
genotype. In case III, species B is monophyletic but forms a subclade
within A which is thus paraphyletic with respect to B. The empirical
results for mtDNA in maniculatus and polionotus appear to conform closely
to case III. These theoretical and empirical considerations raise a number
of questions about the general relationship of the speciation process to
the evolution of uniparentally transmitted traits. Some of these
considerations are presented, and it is suggested that the distribution
patterns of mtDNA sequence variation within and among extant species should
be of considerable relevance to the particular demographies of speciation.
相似文献
37.
Valid measures of nausea are needed to evaluate the various treatments used to counter the nausea produced by chemotherapy. The overall nausea intensity (ONI) produced by 17 chemotherapy drugs was estimated by 17 physicians and 8 nurses, and 25 patients undergoing chemotherapy described the subjective qualities and ONI of their nausea on a modified form of the McGill Pain Questionnaire. The scores for the affective and miscellaneous categories of words in the questionnaire were found to correlate significantly with the physicians'' and nurses'' ONI estimates. The results formed the basis for the Nausea Questionnaire, which provided three indices of nausea: a nausea rating index (NRI), ONI and intensity of nausea according to a visual analogue scale (VAS). All three indices correlated significantly with the physicians'' and nurses'' ONI estimates and were significantly intercorrelated. All three also provided significant differences when the scores of patients who had received cisplatin or 5-fluorouracil were compared. The results indicate that the Nausea Questionnaire provides three valid indices of the subjective experience of nausea. 相似文献