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1.
Plasminogen activator and collagenase production by cultured capillary endothelial cells 总被引:33,自引:17,他引:16
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Cultured bovine capillary endothelial (BCE) cells produce low levels of collagenolytic activity and significant amounts of the serine protease plasminogen activator (PA). When grown in the presence of nanomolar quantities of the tumor promoter 12-O-tetradecanoyl phorbol-13-acetate (TPA), BCE cells produced 5-15 times more collagenolytic activity and 2-10 times more PA than untreated cells. The enhanced production of these enzymes was dependent on the dose of TPA used, with maximal response at 10(-7) to 10(-8) M. Phorbol didecanoate (PDD), an analog of TPA which is an active tumor promoter, also increased protease production. 4-O-methyl-TPA and 4α-PDD, two analogs of TPA which are inactive as tumor promoters, had no effect on protease production. Increased PA and collagenase activities were detected within 7.5 and 19 h, respectively, after the addition of TPA. The TPA-stimulated BCE cells synthesized a urokinase-type PA and a typical vertebrate collagenase. BCE cells were compared with bovine aortic endothelial (BAE) cells and bovine embryonic skin (BES) fibroblasts with respect to their production of protease in response to TPA. Under normal growth conditions, low levels of collagenolyic activity were detected in the culture fluids from BCE, BAE, and BES cells. BCE cells produced 5-13 times the basal levels of collagenolytic activity in response to TPA, whereas BAE cells and BES fibroblasts showed a minimal response to TPA. Both BCE and BAE cells exhibited relatively high basal levels of PA, the production of which was stimulated approximately threefold by the addition of TPA. The observation that BCE cells and not BAE cells produced high levels of both PA and collagenase activities in response to TPA demonstrates a significant difference between these two types of endothelial cells and suggests that the enhanced detectable activities are a property unique to bovine capillary and microvessel and endothelial cells. 相似文献
2.
Ann C. Chandley T. B. Hargreave J. M. Fletcher M. Soos D. Axworthy W. H. Price 《Human genetics》1980,55(1):31-38
Summary Trisomy 8, in mosaic or non-mosaic form is an extremely rare chromosomal condition in man. Liveborn subjects usually present with mental retardation, bone and joint anomalies and a variety of other physical anomalies. The mental retardation associated with the condition is, however, usually moderate compared to that found in other viable human autosomal trisomic conditions. The present report describes a trisomy 8 mosaic male subject with normal IQ and near-normal phenotype, ascertained through infertility. Chromosome studies on peripheral blood lymphocytes reveal a pure trisomy 8 constitution; cultured skin fibroblasts show 46,XY/47,XY+8 mosaicism. At meiosis, the extra No. 8 chromosome is missing from the germ line. The testicular histology indicates a germ cell maturation arrest in many spermatocytes and the patient is severely oligospermic. Biochemical studies to assay levels of glutathione reductase, a red cell enzyme, the gene for which resides in chromosome 8, show increased levels in the trisomy 8 patient compared with controls. 相似文献
3.
A common polygenic basis for quinine and PROP avoidance in mice 总被引:3,自引:2,他引:1
Inbred strains of mice (Mus musculus) differ greatly in ability to taste
various bitter compounds. For some compounds, the differences result from
allelic variation at a single locus. However, segregation patterns
incompatible with monogenic inheritance have been found for quinine
avoidance. The Soa bitter sensitivity locus exerts some influence on this
phenotype, but an unknown number of other loci also contribute. Relative
avoidance patterns for quinine sulfate in panels of naive inbred strains
resembled avoidance patterns for 6-n-propyl-2- thiouracil (PROP),
suggesting a common genetic basis. In particular, C57BL/6J mice strongly
avoided both 0.1 mM quinine sulfate and 1 mM PROP in two-bottle preference
tests, whereas C3H/HeJ mice were indifferent to both. Therefore, 12 BXH/Ty
recombinant inbred strains, derived from these strains, were tested with
both solutions to begin identification of the unknown bitter loci. Naive
mice were tested for four consecutive days with each compound (order
counterbalanced). Some BXH/Ty strain means resembled those of the parent
strains, but others were intermediate. This indicated recombination among
loci affecting avoidance, and therefore polygenic inheritance. The strain
means were highly correlated across compounds (r = 0.98), suggesting that
the same polygenes controlled both phenotypes. The BXH/Ty means for both
compounds were then compared with the strain genotypes at 212 chromosome
position markers distributed throughout the genome. Eight markers on five
chromosomes (3, 6, 7, 8 and 9) yielded significant correlations. Six of the
markers were correlated with both phenotypes, again suggesting common
polygenic inheritance. The marker with the highest correlation was Prp,
tightly linked to Soa on chromosome 6. The correlated marker regions likely
contain quantitative trait loci affecting bitter avoidance. The phenotypic
similarity of PROP to quinine, rather than to phenylthiourea, apparently
stemming from a common polygenic basis, indicates a difference between mice
and humans in gustatory organization related to bitters.
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4.
Mohsin H Jia F Bryan JN Sivaguru G Cutler CS Ketring AR Miller WH Simón J Frank RK Theodore LJ Axworthy DB Jurisson SS Lewis MR 《Bioconjugate chemistry》2011,22(12):2444-2452
The therapeutic efficacies of radiolabeled biotin, pretargeted by monoclonal antibody (mAb)-streptavidin fusion protein CC49 scFvSA, were compared to those of radiolabeled mAb CC49, using the three radiolanthanides in an animal model of human colon cancer. The purpose of the present study was to compare antibody pretargeting to conventional radioimmunotherapy using (149)Pm, (166)Ho, or (177)Lu. Nude mice bearing LS174T colon tumors were injected sequentially with CC49 scFvSA, the blood clearing agent biotin-GalNAc(16), and (149)Pm-, (166)Ho-, or (177)Lu-DOTA-biotin. Tumor-bearing mice were alternatively administered (149)Pm-, (166)Ho-, or (177)Lu-MeO-DOTA-CC49. Therapy with pretargeted (149)Pm-,(166)Ho-, and (177)Lu-DOTA-biotin increased the median time of progression to a 1 g tumor to 50, 41, and 50 days post-treatment, respectively. Therapy with (149)Pm-,(166)Ho-, and (177)Lu-MeO-DOTA-CC49 increased the median time to progression to 53, 24, and 67 days post-treatment, respectively. In contrast, saline controls showed a median time to progression of 13 days postinjection. Treatment with pretargeted (149)Pm-, (166)Ho-, and (177)Lu-biotin or (149)Pm-, (166)Ho-, and (177)Lu-CC49 increased tumor doubling time to 18-36 days, compared to 3 days for saline controls. Among treated mice, 23% survived >84 days post-therapy, and 11% survived 6 months, but controls survived <29 days. Long-term survivors showed tumor growth inhibition or partial regression, extensive necrosis in residual masses, and no evidence of nontarget tissue toxicity at necropsy. Both pretargeted and conventional RIT demonstrated considerable efficacy in an extremely aggressive animal model of cancer. Our results identified (177)Lu as an optimal radiolanthanide for future evaluation of these agents in toxicity and multiple-dose therapy studies. 相似文献
5.
Carla DB Fernandez Fernanda F Bellentani Glaura SA Fernandes Juliana E Perobelli Ana Paula A Favareto André F Nascimento Antonio C Cicogna Wilma DG Kempinas 《Reproductive biology and endocrinology : RB&E》2011,9(1):32
Background
Obesity is rapidly becoming a worldwide epidemic that affects children and adults. Some studies have shown a relationship between obesity and infertility, but until now it remains controversial. Thus, the aim of the present study was to investigate the effect of high-fat diet-induced obesity on male reproductive parameters. 相似文献6.
Jeremy B. Axworthy Joseph M. Smith Martina S. Wing Thomas P. Quinn 《Journal of fish biology》2019,95(6):1399-1406
We examined individual variation and the role of sex on the movements of the reef manta ray Mobula alfredi. Specifically, we analysed several movement metrics using 6 years of nightly observations (1 January 2009–31 December 2014) of 118 individually identifiable manta rays at two discrete but spatially proximate sites, locally known as Manta Heaven and Manta Village, 15 km apart on the west side of the island of Hawaii, USA. Males were slightly more often (33.5%, model fitted mean, P < 0.05) observed than females at Manta Heaven, but females were much more often (156.4%, model fitted mean, P < 0.05) observed at Manta Village. Movement patterns among individuals varied greatly, but the level of variation was similar between sexes. Some animals, mainly females, displayed more resident patterns, whereas other, more mobile, animals moved between sites more frequently and had longer gaps between sightings. We did not detect discrete behavioural groups; rather, individuals varied along a continuous spectrum from many observations and high affinity to few observations and low fidelity to survey locations. These complex and variable movement patterns observed at the individual level, between sexes and between two nearby sites, in Hawaii's manta rays highlight the need for finer scale considerations in conservation and management of highly mobile marine populations. 相似文献
7.
Whitehouse DB; Tomkins J; Lovegrove JU; Hopkinson DA; McMillan WO 《Molecular biology and evolution》1998,15(4):456-462
The expanding molecular database provides unparalleled opportunities for
characterizing genes and for studying groups of related genes. We use
sequences drawn from the database to construct an evolutionary framework
for examining the important glycolytic enzyme phosphoglucomutase (PGM).
Phosphoglucomutase plays a pivotal role in the synthesis and utilization of
glycogen and is present in all organisms. In humans, there are three
well-described isozymes, PGMI, PGM2, and PGM3. PGM1 was cloned 5 years ago;
however, repeated attempts using both immunological approaches and
molecular probes designed from PGM1 have failed to isolate either PGM2 or
PGM3. Using a phylogenetic strategy, we first identified 47 highly
divergent prokaryotic and eukaryotic PGM-like sequences from the database.
Although overall amino acid identity often fell below 20%, the relative
order, position, and sequence of three structural motifs, the active site
and the magnesium-- and sugar-binding sites, were conserved in all 47
sequences. The phylogenetic history of these sequences was complex and
marked by duplications and translocations; two instances of transkingdom
horizontal gene transfer were identified. Nonetheless, the sequences fell
within six well-defined evolutionary lineages, three of which contained
only prokaryotes. Of the two prokaryotic/eukaryotic lineages, one contained
bacterial, yeast, slimemold, invertebrate, and vertebrate homologs to human
PGM1 and the second contained likely homologs to human PGM2. Indeed, an
amino acid sequence, derived from a partial human cDNA, that fell within
the second cross-kingdom lineage bears several characteristics expected for
PGM2. A third lineage may contain homologs to human PGM3. On a general
level, our phylogenetic-based approach shows promise for the further
utilization of the extensive molecular database.
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8.
Incorporation of axonally transported glycoproteins into axolemma during nerve regeneration 总被引:14,自引:4,他引:10
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The insertion of axonally transported fucosyl glycoproteins into the axolemma of regenerating nerve sprouts was examined in rat sciatic motor axons at intervals after nerve crush. [(3)H]Fucose was injected into the lumbar ventral horns and the nerves were removed at intervals between 1 and 14 d after labeling. To follow the fate of the “pulse- labeled” glycoproteins, we examined the nerves by correlative radiometric and EM radioautographic approaches. The results showed, first, that rapidly transported [(3)H]fucosyl glycoproteins were inserted into the axolemma of regenerating sprouts as well as parent axons. At 1 d after delivery, in addition to the substantial mobile fraction of radioactivity still undergoing bidirectional transport within the axon, a fraction of label was already associated with the axolemma. Insertion of labeled glycoproteins into the sprout axolemma appeared to occur all along the length of the regenerating sprouts, not just in sprout terminals. Once inserted, labeled glycoproteins did not undergo extensive redistribution, nor did they appear in sprout regions that formed (as a result of continued outgrowth) after their insertion. The amount of radioactivity in the regenerating nerves decreased with time, in part as a result of removal of transported label by retrograde transport. By 7-14 d after labeling, radioautography showed that almost all the remaining radioactivity was associated with axolemma. The regenerating sprouts retained increased amounts of labeled glycoproteins; 7 or 14 d after labeling, the regenerating sprouts had over twice as much of radioactivity as comparable lengths of control nerves or parent axons. One role of fast axonal transport in nerve regeneration is the contribution to the regenerating sprout of glycoproteins inserted into the axolemma; these membrane elements are added both during longitudinal outgrowth and during lateral growth and maturation of the sprout. 相似文献
9.
10.
Goldstein DB; Zhivotovsky LA; Nayar K; Linares AR; Cavalli-Sforza LL; Feldman MW 《Molecular biology and evolution》1996,13(9):1213-1218
It has recently been suggested that observed levels of variation at
microsatellite loci can be used to infer patterns of selection in genomes
and to assess demographic history. In order to evaluate the feasibility of
these suggestions it is necessary to know something about how levels of
variation at microsatellite loci are expected to fluctuate due simply to
stochasticity in the processes of mutation and inheritance (genetic
sampling). Here we use recently derived properties of the stepwise mutation
model to place confidence intervals around the variance in repeat score
that is expected at mutation-drift equilibrium and outline a statistical
test for whether an observed value differs significantly from expectation.
We also develop confidence intervals for the time course of the buildup of
variation following a complete elimination of variation, such as might be
caused by a selective sweep or an extreme population bottleneck. We apply
these methods to the variation observed at human Y-specific
microsatellites. Although a number of authors have suggested the
possibility of a very recent sweep, our analyses suggest that a sweep or
extreme bottleneck is unlikely to have occurred anytime during the last
approximately 74,000 years. To generate this result we use a recently
estimated mutation rate for microsatellite loci of 5.6 x 10(-4) along with
the variation observed at autosomal microsatellite loci to estimate the
human effective population size. This estimate is 18,000, implying an
effective number of 4,500 Y chromosomes. One important general conclusion
to emerge from this study is that in order to reject mutation-drift
equilibrium at a set of linked microsatellite loci it is necessary to have
an unreasonably large number of loci unless the observed variance is far
below that expected at mutation-drift equilibrium.
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