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1.
Jianxi Xiao Rayna M. Addabbo Janelle L. Lauer Gregg B. Fields Jean Baum 《The Journal of biological chemistry》2010,285(44):34181-34190
The mechanism by which enzymes recognize the “uniform” collagen triple helix is not well understood. Matrix metalloproteinases (MMPs) cleave collagen after the Gly residue of the triplet sequence Gly∼[Ile/Leu]-[Ala/Leu] at a single, unique, position along the peptide chain. Sequence analysis of types I-III collagen has revealed a 5-triplet sequence pattern in which the natural cleavage triplets are always flanked by a specific distribution of imino acids. NMR and MMP kinetic studies of a series of homotrimer peptides that model type III collagen have been performed to correlate conformation and dynamics at, and near, the cleavage site to collagenolytic activity. A peptide that models the natural cleavage site is significantly more active than a peptide that models a potential but non-cleavable site just 2-triplets away and NMR studies show clearly that the Ile in the leading chain of the cleavage peptide is more exposed to solvent and less locally stable than the Ile in the middle and lagging chains. We propose that the unique local instability of Ile at the cleavage site in part arises from the placement of the conserved Pro at the P3 subsite. NMR studies of peptides with Pro substitutions indicate that the local dynamics of the three chains are directly modulated by their proximity to Pro. Correlation of peptide activity to NMR data shows that a single locally unstable chain at the cleavage site, rather than two or three labile chains, is more favorable for cleavage by MMP-1 and may be the determining factor for collagen recognition. 相似文献
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肺癌在中国恶性肿瘤的发病率位居第一,随着低剂量薄层CT在肺癌筛查中的广泛应用,临床发现更多表现为非完全实性结节的肺腺癌,目前众多研究使CT影像学特征和肺腺癌病理的关系得到更进一步的认知,虽然CT能对部分非完全实性结节做出定性和定位诊断,但仍有部分非完全实性结节诊断困难,PET-CT结合了病灶的代谢信息和精确的定位信息,从而提高对肺部结节诊断的敏感性、特异性、准确性,综合多个文献PET-CT在非完全实性结节中的诊断分期价值较CT无明显提升,却在评估预后和制定合适手术方案上可以起到一定的作用,本文就PET-CT在SSN中的应用价值进行阐述。 相似文献
5.
An oxygen store based on the reversible combination of oxygen with hemoglobin or related hemoproteins could be of considerable value to organisms or tissues faced with intermittent hypoxia or anoxia. It would be of interest, therefore, to know the physical and chemical requirements and limitations of useful storage. A model is presented which predicts storage time from physical, chemical, and geometric properties of the store. Storage time is arbitrarily defined as the time for 50% of the stored O2 to diffuse from a fully-loaded store when the store is exposed to a zero O2 environment. Results are presented in the form of simple approximate equations and in graphical form and indicate that: (1) a wide range of storage times can be obtained with reasonable biological parameters; (2) storage times approaching 1,000 s can be achieved even with stores of microscopic dimension; (3) biological O2 storage is predominantly diffusion-limited, although reaction-limited behavior is not impossible; and (4) the major effect of co-operativity appears to be on the form of O2 release: hemoglobins without co-operativity release O2 at a constantly declining rate, whereas those with high co-operativity release O2 at a constant rate. The model is applicable not only to hemoglobin-based O2 storage, but also to any reaction-diffusion system in which one substance can be "stored" by reversible combination with some other substance which acts as the store. 相似文献
6.
M Fields C G Lewis T Beal D Scholfield K Patterson J C Smith S Reiser 《Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.)》1987,186(2):183-187
The present investigation was undertaken to establish whether the severity of copper deficiency in rats fed diets containing fructose is affected by the presence and type of endogenous sex hormones. Intact and castrated male rats and intact and ovariectomized females were fed from weaning a copper-deficient diet (0.6 ppm) containing 62% fructose for 8 weeks. Regardless of castration, male rats were anemic, exhibited heart hypertrophy, and died of the deficiency. However, castration ameliorated the anemia and delayed the mortality. In contrast, none of the females died of the deficiency. It is suggested that in addition to the sex of the animal, levels of testosterone in the male may also play a role in the severity of copper deficiency. 相似文献
7.
G B Fields H E Van Wart H Birkedal-Hansen 《The Journal of biological chemistry》1987,262(13):6221-6226
The sequence specificity of human skin fibroblast collagenase has been investigated by measuring the rate of hydrolysis of 16 synthetic octapeptides covering the P4 through P4' subsites of the substrate. The choice of peptides was patterned after potential collagenase cleavage sites (those containing either the Gly-Leu-Ala or Gly-Ile-Ala sequences) found in types I, II, and III collagens. The initial rate of hydrolysis of the P1-P1' bond of each peptide has been measured by quantitating the concentration of amino groups produced upon cleavage after reaction with fluorescamine. The reactions have been carried out under first-order conditions ([S] much less than KM) and kcat/KM values have been calculated from the initial rates. The amino acids in subsites P3 (Pro, Ala, Leu, or Asn), P2 (Gln, Leu, Hyp, Arg, Asp, or Val), P1' (Ile or Leu), and P4' (Gln, Thr, His, Ala, or Pro) all influence the hydrolysis rates. However, the differences in the relative rates observed for these octapeptides cannot in themselves explain why fibroblast collagenase hydrolyzes only the Gly-Leu and Gly-Ile bonds found at the cleavage site of native collagens. This supports the notion that the local structure of collagen is important in determining the location of the mammalian collagenase cleavage site. 相似文献
8.
J M Barbaree G W Gorman W T Martin B S Fields W E Morrill 《Applied microbiology》1987,53(7):1454-1458
A protocol for sampling environmental sites was developed and used to identify possible sources of Legionella species in support of epidemiologic investigations at two hospitals. In hospital A, legionellae were isolated from 43 of 106 (40%) different sites. Three separate Legionella pneumophila serotypes and a previously unrecognized species were present in different combinations in the positive samples. Two of five cooling towers contained the same L. pneumophila serogroup 1 monoclonal type (1,2,4,5) as was isolated from patients. The same monoclonal type was also isolated from make-up water for the two cooling towers, a hot water tank, water separators in four main air compressor systems for respiratory therapy, and cold and hot water faucets. In hospital B, 13 of 37 (38%) sample sites contained legionellae, all of which were L. pneumophila serogroup 1. The monoclonal type matching isolates from patients (1,2,4,5) was found at the highest concentration in a hot water tank, but it was also present at four other sample sites. Since legionellae not related to disease may be found in many of the sites sampled, an epidemiologic association with the probable source should be established before intervention methods, such as disinfection, are undertaken. 相似文献
9.
Active site of human liver aldehyde dehydrogenase 总被引:9,自引:0,他引:9
Bromoacetophenone (2-bromo-1-phenylethanone) functions as an affinity reagent for human aldehyde dehydrogenase (EC 1.2.1.3) and has been found specifically to label a unique tryptic peptide in the enzyme. Amino-terminal sequence analysis of the labeled peptide after purification by two different procedures revealed the following sequence: Val-Thr-Leu-Glu-Leu-Gly-Gly-Lys. Radioactivity was found to be associated with the glutamate residue, which was identified as Glu-268 by reference to the known amino acid sequence. This paper constitutes the first identification of an active site of aldehyde dehydrogenase. 相似文献
10.
Functional differences between small and large luteal cells of the late-pregnant vs. nonpregnant cow
D M Weber P A Fields L J Romrell S Tumwasorn B A Ball M Drost M J Fields 《Biology of reproduction》1987,37(3):685-697
This paper describes an in vitro model for the study of two types of steroidogenic luteal cells from cows in different physiological states. Two different populations of enzymatically dispersed bovine luteal cells were separated on the basis of size in a Cel-Sep Sedimentation Chamber. The separated small (12.5-23 micron in diameter) and large (greater than 23 micron in diameter) luteal cells of late-pregnant cows (Days 190-280) contained the distinct morphological characteristics previously defined for these two populations of cells. Cells were evaluated for progesterone (P4) production during a 3-h incubation with and without bovine luteinizing hormone (bLH, 10 ng/ml). Both small and large luteal cells from the late-pregnant cow were found to contain equal levels of P4 at Time 0 and increased but equal levels of P4 after a 3-h incubation. Neither cell type showed an increase in P4 production in response to the addition of bLH (p greater than 0.05). Since these results differed from earlier reports for luteal cells of the nonpregnant cow, small and large luteal cells of the mid-cycle (Day 14) were incubated, and the levels of P4 production were compared with P4 levels from the late pregnant cow. In agreement with previous reports for nonpregnant cows, progesterone content at Time 0 was 7-fold higher in large cells than in small cells (p less than 0.05), and after 3 h of incubation, 13-fold higher (p less than 0.05). Although the small cells responded to the presence of bLH in the incubation medium with a 4-fold increase in P4 production, this increase was not significant (p greater than 0.05). The large cell did not respond to bLH. However, the large cell type continued to contain and produce more P4 than did the small cells treated with bLH. This study indicates that both the small and large luteal cells of late-pregnancy are able to produce P4. However, the large luteal cell of the estrous cycle produces greater quantities of P4 than does the small luteal cell or the large luteal cell of late pregnancy. 相似文献