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91.
92.
Koen JP Verhees Nicholas AM Pansters Hoeke A Baarsma Alexander HV Remels Astrid Haegens Chiel C de Theije Annemie MWJ Schols Reinoud Gosens Ramon CJ Langen 《Respiratory research》2013,14(1):117
Background
Chronic obstructive pulmonary disease (COPD) is accompanied by pulmonary inflammation and associated with extra-pulmonary manifestations, including skeletal muscle atrophy. Glycogen synthase kinase-3 (GSK-3) has been implicated in the regulation of muscle protein- and myonuclear turnover; two crucial processes that determine muscle mass. In the present study we investigated the effect of the selective GSK-3 inhibitor SB216763 on muscle mass in a guinea pig model of lipopolysaccharide (LPS)-induced pulmonary inflammation-associated muscle atrophy.Methods
Guinea pigs were pretreated with either intranasally instilled SB216763 or corresponding vehicle prior to each LPS/saline challenge twice weekly. Pulmonary inflammation was confirmed and indices of muscle mass were determined after 12 weeks. Additionally, cultured skeletal muscle cells were incubated with tumor necrosis factor α (TNF-α) or glucocorticoids (GCs) to model the systemic effects of pulmonary inflammation on myogenesis, in the presence or absence of GSK-3 inhibitors.Results
Repeated LPS instillation induced muscle atrophy based on muscle weight and muscle fiber cross sectional area. Intriguingly, GSK-3 inhibition using SB216763 prevented the LPS-induced muscle mass decreases and myofiber atrophy. Indices of protein turnover signaling were unaltered in guinea pig muscle. Interestingly, inhibition of myogenesis of cultured muscle cells by TNF-α or synthetic GCs was prevented by GSK-3 inhibitors.Conclusions
In a guinea pig model of LPS-induced pulmonary inflammation, GSK-3 inhibition prevents skeletal muscle atrophy without affecting pulmonary inflammation. Resistance to inflammation- or GC-induced impairment of myogenic differentiation, imposed by GSK-3 inhibition, suggests that sustained myogenesis may contribute to muscle mass maintenance despite persistent pulmonary inflammation. Collectively, these results warrant further exploration of GSK-3 as a potential novel drug target to prevent or reverse muscle wasting in COPD. 相似文献93.
Y Novik LM Ryan DG Haller R Asbury JP Dutcher A Schutt 《Cancer immunology, immunotherapy : CII》1999,16(4):261-266
The study was a Phase II randomized study to evaluate the efficacy of new agents for the treatment of advanced gastric carcinoma.
Patients were randomized to receive single agent chemotherapy with mitoxantrone, etoposide, aclacinomycin-A or spirogermanium.
The patients were stratified by prior use of chemotherapy, prior doxorubicin use and ECOG performance status. Patients with
a history of cardiac disease or prior doxorubicin exceeding a dose of 400 mg/m2 were restrictively randomized to sopirogermanium or etoposide only. One hundred and fourteen patients were registered for
the study. Among 98 evaluable patients there were only two partial responses (both in the etoposide arm), and one complete
response in the mitoxantrone arm. The median survival on the study was 3.3 months. One hundred and six patients were analyzable
for toxicity. There were four treatment-related deaths and four life-threatening toxicities. Because of low response rates
and relatively high toxicities the studied compounds were not deemed worth further investigation for advanced gastric cancer. 相似文献
94.
95.
The robustness of two phylogenetic methods: four-taxon simulations reveal a slight superiority of maximum likelihood over neighbor joining 总被引:6,自引:3,他引:3
The robustness (sensitivity to violation of assumptions) of the maximum-
likelihood and neighbor-joining methods was examined using simulation.
Maximum likelihood and neighbor joining were implemented with Jukes-
Cantor, Kimura, and gamma models of DNA substitution. Simulations were
performed in which the assumptions of the methods were violated to varying
degrees on three model four-taxon trees. The performance of the methods was
evaluated with respect to ability to correctly estimate the unrooted
four-taxon tree. Maximum likelihood outperformed neighbor joining in 29 of
the 36 cases in which the assumptions of both methods were satisfied. In
133 of 180 of the simulations in which the assumptions of the
maximum-likelihood and neighbor-joining methods were violated, maximum
likelihood outperformed neighbor joining. These results are consistent with
a general superiority of maximum likelihood over neighbor joining under
comparable conditions. They extend and clarify an earlier study that found
an advantage for neighbor joining over maximum likelihood for
gamma-distributed mutation rates.
相似文献
96.
97.
Expression of N-linked sialyl Le(x) determinants and O-glycans in the carbohydrate moiety of human amniotic fluid transferrin during pregnancy 总被引:3,自引:0,他引:3
Transferrin, a glycoprotein involved in iron transport in body fluids, was
isolated from amniotic fluid of a hydramniospatient by sequential
anion-exchange chromatography and gel filtration. The N-glycans of human
amniotic fluid transferrin (hAFT) were enzymatically liberated by PNGase-F
digestion, isolated by gel filtration and fractionated by (high-pH)
anion-exchange chromatography. After alkaline borohydride treatment of
native hAFT, the released O-glycans were isolated by gel filtration and
fractionated by anion-exchange chroma-tography. Structure elucidation of 14
N- and 2 O-glycans was performed by 500 or 600 MHz1H-NMR spectroscopy.
Besides conventional N-glycans established earlier for human serum
transferrin (hST), new (alpha1-3)-fucosylated N- glycans were found,
representing sialyl Le(x) elements. Furthermore, as compared to hST, a
higher degree of (alpha1-6)-fucosylation and an increase in branching from
di- to triantennary compounds has been detected. The presence of O-glycans
is demonstrated for the first time in transferrin.
相似文献
98.
Gill Furze Alun Roebuck Peter Bull Robert JP Lewin David R Thompson 《BMC cardiovascular disorders》2002,2(1):4
Background
What people believe about their illness may affect how they cope with it. It has been suggested that such beliefs stem from those commonly held within society . This study compared the beliefs held by people with angina, regarding causation and coping in angina, with the beliefs of their friends who do not suffer from angina. 相似文献99.
Publication of the complete diploid genome sequence of the yeast Candida albicans will accelerate research into the pathogenesis of Candida infections. Comparative genomic analysis highlights genes that may contribute to C. albicans survival and its fitness as a human commensal and pathogen. 相似文献
100.