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1.
K. Yokochi E. Sideris F. Hamilton F. Coceani P.M. Olley 《Prostaglandins & other lipid mediators》1984,27(4):535-542
Previous work (Lock
, J. Pharm. Exp. Ther.
:156, 1980) has shown that conventional screening procedures for vasoactive PGI2 analogs have little value in predicting pulmonary vasodilator activity in the newborn lamb. To gain a better insight into the structural requirements for pulmonary vasoactivity and possibly identify useful compounds for the management of neonatal pulmonary hypertensive disorders, we have tested the following PGI2 analogs in normoxic and hypoxic newborn lambs: 15(S)-9-deoxy-15-methyl1–9α, 6-nitrilo-PGF1 (analog I); 9-deoxy-9α, 5-nitrilo-PGF1 (analog II); (6S, 15S)-15-methyl-PG11 (analog III); and (6R, 15S)-15-methyl-PGI1 (analog IV). A prostaglandin analog mimicking PGI2 (compound BW245C; (±)-5-(6-carboxyhexyl)-1-(3-cyclohexyl-3-hydroxypropyl)hydantoin) was tested as well. Compounds were injected into a branch pulmonary artery and any local pulmonary effect could be assessed from the change in the ratio of blood flow to the injected lung over total flow. None of the analogs tested proved to be a selective pulmonary dilator. BW245C was a potent peripheral vasodilator (threshold around 0.5 μg/kg) and indirectly lowered pulmonary vascular resistance through its systemic effects. Analog I also dilated the systemic circulation, but only at the highest dose tested (100 μg/kg). The latter finding is surprising because it was previously shown that the parent, non-methylated compound is a fairly potent and selective pulmonary vasodilator. Analog II and IV were inactive at a dose up to, respectively, 30 and 20 μg/kg. Analog III, on the other hand, weakly constricted the systemic circulation at a dose of 10 μg/kg. These findings suggest that the neonatal pulmonary vasculature is endowed with specific receptor sites which can discriminative between closely related PGI2 analogs. 相似文献
2.
The curricula vitae of four candidates for a professorial appointment at Athens University were examined to estimate the actual contribution of each candidate to the papers of which he was a coauthor. A total of 879 research papers by the four candidates were analysed in terms of the number of authors, the sequence of names, and the year of publication. The four authors presented 364, 349, 96, and 70 papers. If an equal contribution of all coauthors is assumed, the actual number of papers (all papers divided by the number of authors), is about 106, 83, 28, and 26, respectively, so that the rank of the four candidates did not change. On the assumption that the contribution was related to the candidate''s position in the order of the coauthors'' names, the numbers of papers were corrected to 84, 95, 26, 33 using one statistical method and to 88, 94, 28, 31 using another. These assumptions may not be valid, however, especially as the last author may be more important than the intermediate ones. It is suggested that the journals require authors to state their specific contribution to a paper, such as original idea, planning, collecting data, writing up, etc. 相似文献
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A study of bacterial surface oligosaccharides were investigated among
different strains of Neisseria gonorrhoeae to correlate structural features
essential for binding to the MAb 2C7. This epitope is widely expressed and
conserved in gonococcal isolates, characteristics essential to an effective
candidate vaccine antigen. Sample lipooligosaccharides (LOS), was prepared
by a modification of the hot phenol-water method from which de-O-acetylated
LOS and oligosaccharide (OS) components were analyzed by ES-MS-CID-MS and
ES-MSnin a triple quadrupole and an ion trap mass spectrometer,
respectively. Previously documented natural heterogeneity was apparent from
both LOS and OS preparations which was admixed with fragments induced by
hydrazine and mild acid treatment. Natural heterogeneity was limited to
phosphorylation and antenni extensions to the alpha-chain. Mild acid
hydrolysis to release OS also hydrolyzed the beta(1-->6) glycosidic
linkage of lipid A. OS structures were determined by collisional and
resonance excitation combined with MS and multistep MSn which provided
sequence information from both neutral loss, and nonreducing terminal
fragments. A comparison of OS structures, with earlier knowledge of MAb
binding, enzyme treatment, and partial acid hydrolysis indicates a generic
overlapping domain for 2C7 binding. Reoccurring structural features include
a Hepalpha(1-->3)Hepbeta(1-->5)KDO trisaccharide core branched on the
nonreducing terminus (Hep-2) with an alpha(1-->2) linked GlcNAc
(gamma-chain), and an alpha-linked lactose (beta-chain) residue. From the
central heptose (Hep-1), a beta(1-->4) linked lactose (alpha-chain),
moiety is required although extensions to this residue appear unnecessary.
相似文献
6.
Neutron and gamma irradiation of buffered solutions of calf thymus DNA resulted in changes in the dynamics of the macromolecule. In the low-dose region (0.8-10 cGy of 239Pu-Be neutrons and 0.34-3 Gy of 60Co gamma rays), the flexibility of DNA decreased as indicated by slower rotation of the molecules. Neutrons appeared to be approximately 35 times more effective than 60Co gamma rays. The rotational correlation time, tau C, was measured using the perturbed angular correlation (PAC) method. Its variation appears to follow a linear-exponential behavior. An attempt is made to formulate this behavior as a function of the energy deposited on the macromolecule (radiation dose), the average threshold energy (dose) required to form new lesions, and the available population of intact DNA sites. 相似文献
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8.
Georgakilas AG Haveles KS Sophianopoulou V Sakelliou L Zarris G Sideris EG 《Radiation research》2000,153(3):258-262
The effect of alpha-particle radiation on the thermal stability and size of calf thymus DNA molecules in deoxygenated aqueous solutions was investigated by thermal transition spectrophotometry, pulsed-field gel electrophoresis, and standard agarose gel electrophoresis. The thermal transition of DNA from helix to coil was studied through analysis of the UV A(260) absorbance. The results obtained for alpha particles of mean LET of 128 keV microm(-1) reveal a dual dose response: a tendency for thermal stability of the DNA helix at "low" doses, followed by an increasing instability at higher doses. The same phenomenon was observed for the mean molecular weight of DNA molecules exposed to alpha particles. The results reported here for alpha particles in the low-dose region of 0-16 Gy are consistent with our previous hypothesis of inter- and intramolecular interactions of a covalent character in gamma-irradiated DNA molecules in the dose region of 0-4 Gy. 相似文献
9.
Intrinsic protein fluorescence may interfere with the visualization of proteins after SDS-polyacrylamide electrophoresis. In an attempt to analyze tear glycoproteins in gels, we ran tear samples and stained the proteins with a glycoprotein-specific fluorescent dye. The fluorescence detected was not limited to glycoproteins. There was strong intrinsic fluorescence of proteins normally found in tears after soaking the gels in 40% methanol plus 1-10% acetic acid and, to a lesser extent, in methanol or acetic acid alone. Nanograms of proteins gave visible native fluorescence and interfere with extrinsic fluorescent dye detection. Poly-L-lysine, which does not contain intrinsically fluorescent amino acids, did not fluoresce. 相似文献
10.