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41.
SC Liang TR Schoeb JK Davis JW Simecka GH Cassell JR Lindsey 《Canadian Metallurgical Quarterly》1995,32(6):661-667
In several chronic diseases, lesions are more severe in LEW rats than in F344 rats. To determine whether or not acute viral diseases also are more severe in LEW rats than in F344 rats, we inoculated 6-7-week-old LEW and F344 rats with 10(7.2) cell culture infective units of sialodacryoadenitis virus or 10(4.7) infective units of Sendai virus. Twenty-four rats of each strain were given each virus. Lesions in nasal passages, tracheas, intrapulmonary airways, and pulmonary alveoli in 6 or 12 rats inoculated with each virus were assessed by scoring 5, 10, and 14 days after inoculation. Both viruses caused typical patchy necrotizing rhinitis, tracheitis, bronchitis, and bronchiolitis, with multifocal pneumonitis, in rats of both strains. Mean lesion indices for LEW rats given sialodacryoadenitis virus were significantly different from those for F344 rats for nasal passages on days 10 (0.999 vs. 0.680) and 14 (0.736 vs. 0.278), bronchi on day 5 (0.479 vs. 0.361), and alveoli on day 5 (0.677 vs. 0.275). Lesion indices for LEW rats given Sendai virus were significantly different from those for F344 rats for nasal passages on days 10 (1.000 vs. 0.611) and 14 (0.778 vs. 0.583); trachea on day 10 (0.625 vs. 0.028); bronchi on days 5 (0.476 vs. 0.331), 10 (0.123 vs. 0.013), and 14 (0.038 vs. 0); and alveoli on days 5 (0.413 vs. 0.114) and 10 (0.185 vs. 0.020). Thus, at the tested doses, both viruses caused more severe respiratory tract lesions in LEW rats than in F344 rats. 相似文献
42.
Replacement of Met31 by (N-Me)Nle in CCK8 or CCK4 has been shown to improve the affinity and selectivity for CCK-B receptors. In order to obtain molecules with enhanced bioavailability, two novel series of protected tetrapeptides of the general formula Boc-Trp30-X-Asp-Y33 have been developed. Introduction of (N-Me)Nle and the bulky, aromatic naphthylalaninamide (Nal-NH2) in positions X and Y, respectively, does not greatly modify the affinity for guinea pig brain CCK-B receptors. In contrast, incorporation of hindering N-methyl amino acids such as (N-Me)Phe, (N-Me)Phg, or (N-Me)Chg, but not their non-methylated counterparts, in position X induced a large decrease in affinity for the CCK-B binding sites. Among the various peptides synthesized, Boc-[(N-Me)Nle31,1Nal-NH2(33)]CCK4 (2) (KI = 2.8 nM), Boc-[Phg31,1Nal-NH2(33)]CCK4 (15) (KI = 14 nM), and Boc-[Phg31,1Nal-N(CH3)2(33)]CCK4 (17) (KI = 39 nM) displayed good affinities for brain CCK-B receptors and had good selectivity ratios. These pseudopeptides, in which the presence of unnatural and hydrophobic residues is expected to improve their penetration of the central nervous system, were shown to be very resistant to brain peptidases. Interestingly, whereas compounds 2 and 15 proved to be full agonists for rat hippocampal CCK-B receptors when measured in an electrophysiological assay, compound 17 behaved as a potent antagonist in the same test and displayed a good affinity in rat brain KI(CCK-B) = 51 nM as compared to the Merck antagonist L365,260,KI(CCK-B) = 12 nM. This illustrates a simple means to obtain CCK-B antagonists and suggests that the free, CONH2 group plays a critical role in the recognition of the agonist state of brain CCK-B receptors. 相似文献
43.
E Buskens EW Steyerberg J Hess JW Wladimiroff DE Grobbee 《Canadian Metallurgical Quarterly》1997,87(6):962-967
OBJECTIVES: This study assessed the potential impact of fetal ultrasound screening on the number of newborns affected by cardiac anomalies. METHODS: A decision model was developed that included the prevalence and history of congenital heart disease, characteristics of ultrasound, risk of abortion, and attitude toward pregnancy termination. Probabilities were obtained with a literature survey; sensitivity analysis showed their influence on expected outcomes. RESULTS: Presently, screening programs may prevent the birth of approximately 1300 severely affected newborns per million second-trimester pregnancies. However, over 2000 terminations of pregnancy would be required, 750 of which would have ended in intrauterine death or spontaneous abortion. Further, 9900 false-positive screening results would occur, requiring referral. Only the sensitivity of routine screening and attitude toward termination of pregnancy appeared to influence the yield substantially. CONCLUSIONS: The impact of routine screening for congenital heart disease appeared relatively small. Further data may be required to fully assess the utility of prenatal screening. 相似文献
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F Petersen H Z?hner JW Metzger S Freund RP Hummel 《Canadian Metallurgical Quarterly》1993,46(7):1126-1138
During germination spores of Streptomyces viridochromogenes NRRL B-1551 excrete a compound, germicidin, which has an inhibitory effect on the germination of its own arthrospores at a concentration as low as 200 pM (40 pg/ml). At higher concentrations germicidin inhibits porcine Na+/K(+)-activated ATPase and retards the germination of the cress Lepidium sativum. Germicidin is the first known autoregulative inhibitor of spore germination in the genus Streptomyces and was isolated from the supernatant of germinated spores, but also from the supernatant of the submerged culture. Spectroscopic analysis and derivatization reactions revealed germicidin to be 6-(2-butyl)-3-ethyl-4-hydroxy-2-pyrone (C11H16O3). Crude isolates of germicidin from the supernatant of submerged culture, but not from the spores, contained a second, structurally very similar compound (C10H14O3), in which in contrast to germicidin a 2-propyl instead of the 2-butyl chain was bound to C-6 and which did not show any activity in the germination and ATPase assay. The germination assay was evaluated as a new screening model for specifically active compounds. 相似文献
47.
M Meyer B Keweloh K Güth JW Holmes B Pieske SE Lehnart H Just G Hasenfuss 《Canadian Metallurgical Quarterly》1998,30(8):1459-1470
Diastolic dysfunction at high heart rates may be associated with increased myocardial energy consumption. Frequency-dependent changes of isometric force and oxygen consumption (MVO2) were investigated in strip preparations from endstage failing human hearts exhibiting various degrees of diastolic dysfunction. MVO2 was determined by a new method which was validated. When stimulation rate was increased from 40 to 200 min-1 (n=7), developed force decreased from 16.5+/-4.3 to 7.9+/-2.9 mN/mm2 (P<0.01), diastolic force increased from 15.9+/-3.2 to 22.0+/-3.0 mN/mm2 (P<0.01), and total MVO2 increased from 2.6+/-0.6 to 4.7+/-0.9 ml/min/100 g (P<0.025). Resting MVO2 and resting force were 1.8+/-0.4 ml/min/100 g and 15.9+/-3.0 mN/mm2, respectively. After addition of 30 mm 2,3-butanedione monoxime (BDM) to inhibit crossbridges, resting MVO2 and resting force decreased by 46% (P<0.05) and 15% (P<0.01), respectively, indicating the presence of active force generation in unstimulated failing human myocardium. In each muscle preparation, there was a significant correlation between force-time integral (FTI) and total MVO2 (r=0.96+/-0.01). The strength of these correlations did not vary with the contribution of diastolic FTI to total FTI. The ratio of activity related MVO2 to developed FTI, an inverse index of the economy of contraction, increased depending on the rise of diastolic FTI at higher stimulation rates. In conclusion, in failing human myocardium, diastolic force development is occurring at the same energy expenditure as systolic force generation. Therefore, in muscle preparations with disturbed diastolic function economy of contraction decreases with higher stimulation rates, depending on the rise of diastolic force. 相似文献
48.
MN Janakiraman KD Watenpaugh PK Tomich KT Chong SR Turner RA Tommasi S Thaisrivongs JW Strohbach 《Canadian Metallurgical Quarterly》1998,8(10):1237-1242
Potent, non-peptidic, dihydropyrone sulfonamide HIV protease inhibitors have been previously described. Crystallographic analysis of dihydropyrone sulfonamide inhibitor/HIV protease complexes suggested incorporation of a second, C2 symmetry-related sulfonamide group. Selected bis-sulfonamide dihydropyrone analogues display high HIV protease inhibitory activity. 相似文献
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