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21.
K Lauritsen T Havelund L S Laursen P Bytzer J Kjaergaard J Rask-Madsen 《BMJ (Clinical research ed.)》1987,294(6577):932-934
One hundred and forty two patients with duodenal ulcer who after a short term study had relief of pain and healed ulcers proved endoscopically were allocated at random to double blind maintenance treatment with enprostil (a synthetic dehydroprostaglandin E2) 35 micrograms or ranitidine 150 mg at bedtime for up to 12 months. Patients were monitored every third month and examined by endoscopy at three, six, and 12 months, or more often if warranted. The cumulative relapse rates in the enprostil group at three, six, and 12 months were 37% (25/67), 56% (37/66), and 62% (41/66), respectively. The corresponding rates in the ranitidine group were 8% (6/71), 19% (13/69), and 29% (20/69). These differences were highly significant and further enhanced by life table analysis adjusting for withdrawals and by an "intention to treat" analysis in which absence of proof of non-recurrence was counted as failure, more patients in the enprostil group having been withdrawn because of adverse events or recorded as non-compliant with the protocol. Enprostil 35 micrograms at bedtime cannot be recommended for preventing relapse of duodenal ulcer. Furthermore, the results challenge the clinical relevance of using so called "cytoprotection" for preventing recurrence. 相似文献
22.
Background
Host parasitism by Trichomonas vaginalis is complex. Adherence to vaginal epithelial cells (VECs) is mediated by surface proteins. We showed before that antisense down-regulation of expression of adhesin AP65 decreased amounts of protein, which lowered levels of T. vaginalis adherence to VECs. We now perform antisense down-regulation of expression of the ap33 gene to evaluate and confirm a role for AP33 in adherence by T. vaginalis. We also used an established transfection system for heterologous expression of AP33 in T. foetus as an additional confirmatory approach. 相似文献23.
Crystallographic and solution studies of N-lithocholyl insulin: a new generation of prolonged-acting human insulins 总被引:4,自引:0,他引:4
Whittingham JL Jonassen I Havelund S Roberts SM Dodson EJ Verma CS Wilkinson AJ Dodson GG 《Biochemistry》2004,43(20):5987-5995
The addition of specific bulky hydrophobic groups to the insulin molecule provides it with affinity for circulating serum albumin and enables it to form soluble macromolecular complexes at the site of subcutaneous injection, thereby securing slow absorption of the insulin analogue into the blood stream and prolonging its half-life once there. N-Lithocholic acid acylated insulin [Lys(B29)-lithocholyl des-(B30) human insulin] has been crystallized and the structure determined by X-ray crystallography at 1.6 A resolution to explore the molecular basis of its assembly. The unit cell in the crystal consists of an insulin hexamer containing two zinc ions, with two m-cresol molecules bound at each dimer-dimer interface stabilizing an R(6) conformation. Six covalently bound lithocholyl groups are arranged symmetrically around the outside of the hexamer. These form specific van der Waals and hydrogen-bonding interactions at the interfaces between neighboring hexamers, possibly representing the kinds of interactions which occur in the soluble aggregates at the site of injection. Comparison with an equivalent nonderivatized native insulin hexamer shows that the addition of the lithocholyl group disrupts neither the important conformational features of the insulin molecule nor its hexamer-forming ability. Indeed, binding studies show that the affinity of N-lithocholyl insulin for the human insulin receptor is not significantly diminished. 相似文献
24.
25.
The murid rodent subfamily Sigmodontinae contains 79 genera which are
distributed throughout the New World. The time of arrival of the first
sigmodontines in South America and the estimated divergence time(s) of the
different lineages of South American sigmodontines have been controversial
due to the lack of a good fossil record and the immense number of extant
species. The "early-arrival hypothesis" states that the sigmodontines must
have arrived in South America no later than the early Miocene, at least 20
MYA, in order to account for their vast present-day diversity, whereas the
"late-arrival hypothesis" includes the sigmodontines as part of the
Plio-Pleistocene Great American Interchange, which occurred approximately
3.5 MYA. The phylogenetic relationships among 33 of these genera were
reconstructed using mitochondrial DNA (mtDNA) sequence data from the ND3,
ND4L, arginine tRNA, and ND4 genes, which we show to be evolving at the
same rate. A molecular clock was calibrated for these genes using published
fossil dates, and the genetic distances were estimated from the DNA
sequences in this study. The molecular clock was used to estimate the dates
of the South American sigmodontine origin and the main sigmodontine
radiation in order to evaluate the "early-" and "late-arrival" scenarios.
We estimate the time of the sigmodontine invasion of South America as
between approximately 5 and 9 MYA, supporting neither of the scenarios but
suggesting two possible models in which the invading lineage was either (1)
ancestral to the oryzomyines, akodonts, and phyllotines or (2) ancestral to
the akodonts and phyllotines and accompanied by the oryzomyines. The
sigmodontine invasion of South America provides an example of the advantage
afforded to a lineage by the fortuitous invasion of a previously
unexploited habitat, in this case an entire continent.
相似文献
26.
Previously, treatment of Tamm-Horsfall glycoprotein (THp) from different
donors with endo-beta-galactosidase has been shown to liberate a tetra- and
a Sd(a)-active pentasaccharide, concluding the presence of N-linked
carbohydrate chains containing additional N - acetyllactosamine units.
These type of oligosaccharides were not found in a detailed structure
elucidation of the carbohydrate moiety of THp of one male donor, suggesting
a donor-specific feature for these type of structures. Therefore, THp was
isolated from four healthy male donors and each subjected to
endo-beta-galactosidase treatment in order to release these tetra- and
Sd(a)-active pentasaccharide. Differences were observed in the total amount
of released tetra- and Sda-active pentasaccharide of the used donors (42,
470, 478, 718 microg/100 mg THp), indicating that the presence of repeating
N-acetyllactosamine units incorporated into the N-glycan moiety of THp is
donor specific. Furthermore, a higher expression of the Sd(a) determinant
on antennae which display N-acetyllactosamine elongation was observed,
suggesting a better accessibility for the
beta-N-acetylgalactosaminyltransferase. In order to characterize the
N-glycans containing repeating N- acetyllactosamine units, carbohydrate
chains were enzymatically released from THp and isolated. The
tetraantennary fraction, which accounts for more than 33% of the total
carbohydrate moiety of THp, was used to isolate oligosaccharides containing
additional N - acetyllactosamine units. Five N-linked tetraantennary
oligosaccharides containing a repeating N-acetyllactosamine unit were
identified, varying from structures bearing four Sd(a) determinants to
structures containing no Sd(a) determinant (see below). One compound was
used in order to specify the branch location of the additional N-
acetyllactosamine unit, and it appeared that only the Gal-6' and Gal-8'
residues were occupied by a repeating N -acetyllactosamine unit.
相似文献
27.
Wingfield BD; Grant WS; Wolfaardt JF; Wingfield MJ 《Molecular biology and evolution》1994,11(3):376-383
The genus Ceratocystis sensu stricto includes important fungal pathogens of
woody and herbaceous plants. This genus is distinguished from species in
Ceratocystis sensu lato by the presence of Chalara anamorphs. Ascospore
shape has been used extensively in delineating Ceratocystis taxa, which
show a large variety of ascospore shapes. Sequence analysis of one region
of he 18S ribosomal RNA subunit and two regions of the 28S ribosomal RNA
subunit showed that there was a majority of multiple substitutions at
nucleotide sites and that there was a low transition/transversion ratio, T
= 0.72. Both of these results suggest that these are well established, old
species. Ascospore morphology, for the most part, was not congruent with
the molecular phylogeny, and the use of morphological characters may be
misleading in the taxonomy of these species.
相似文献
28.
Membrane compartmentalized ATP and its preferential use by the Na, K-ATPase of human red cell ghosts
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This paper describes work which begins to define the molecular organization in the region of the membrane that comprises the functional domain of the Na:K pump. The membrane-bound phosphoglycerate kinase (PGK) and Na, K-ATPase appear to be directly linked via a compartmentalized form of ATP. Evidence for the membrane pool of ATP is based on the labeling characteristics of the phosphoproteins by [γ-(32)P]ATP of ghosts incubated under various conditions. Preincubation of ghosts in the presence of ATP at 37 degrees C, but not at 0 degrees C, completely obscures the formation of the Na-phosphoprotein in ghosts washed and subsequently incubated in the presence of [gamma-(32)P]ATP. In contrast to the Na component, the Mg component of phosphorylation is only slightly altered by preincubation with ATP. ATPase activity measured as (32)P(i) liberated during the subsequent incubation at 0 degrees C, reflects completely the differential effects of preincubation with ATP on (32)P incorporation into phosphoprotein. ATP placed within the pool by preincubation can be removed by operating the Na, K-ATPase or the PGK reaction in the reverse direction by use of exogenous substrates. Alternatively, the membrane pool of ATP can be formed also from exogenous substrates by running the PGK reaction in the forward direction. These results, while providing direct support for a membrane compartment of ATP, also indicate the location of this compartment in relation to the PGK and the Na, K-ATPase. In addition, these results also imply that the Mg and Na components are different enzymatic entities since substrate ATP can be derived from separate sources. 相似文献
29.
The thermal stability of human insulin was studied by differential scanning microcalorimetry and near-UV circular dichroism as a function of zinc/protein ratio, to elucidate the dissociation and unfolding processes of insulin in different association states. Zinc-free insulin, which is primarily dimeric at room temperature, unfolded at approximately 70 degrees C. The two monomeric insulin mutants Asp(B28) and Asp(B9),Glu(B27) unfolded at higher temperatures, but with enthalpies of unfolding that were approximately 30% smaller. Small amounts of zinc caused a biphasic thermal denaturation pattern of insulin. The biphasic denaturation is caused by a redistribution of zinc ions during the heating process and results in two distinct transitions with T(m)'s of approximately 70 and approximately 87 degrees C corresponding to monomer/dimer and hexamer, respectively. At high zinc concentrations (>or=5 Zn(2+) ions/hexamer), only the hexamer transition is observed. The results of this study show that the thermal stability of insulin is closely linked to the association state and that the zinc hexamer remains stable at much higher temperatures than the monomer. This is in contrast to studies with chemical denaturants where it has been shown that monomer unfolding takes place at much higher denaturant concentrations than the dissociation of higher oligomers [Ahmad, A., et al. (2004) J. Biol. Chem. 279, 14999-15013]. 相似文献
30.
Niels Reinmuth Nadine Payer Thomas Muley Hans Hoffmann Felix JF Herth Matthias Villalobos Michael Thomas 《Respiratory research》2013,14(1):139