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101.
LM Barone HH Mu CJ Shih KB Kashlan BP Wasserman 《Canadian Metallurgical Quarterly》1998,118(1):315-322
Plasma membrane vesicles from red beet (Beta vulgaris L.) storage tissue contain two prominent major intrinsic protein species of 31 and 27 kD (X. Qi, C.Y Tai, B.P. Wasserman [1995] Plant Physiol 108: 387-392). In this study affinity-purified antibodies were used to investigate their localization and biochemical properties. Both plasma membrane intrinsic protein (PMIP) subgroups partitioned identically in sucrose gradients; however, each exhibited distinct properties when probed for multimer formation, and by limited proteolysis. The tendency of each PMIP species to form disulfide-linked aggregates was studied by inclusion of various sulfhydryl agents during tissue homogenization and vesicle isolation. In the absence of dithiothreitol and sulfhydryl reagents, PMIP27 yielded a mixture of monomeric and aggregated species. In contrast, generation of a monomeric species of PMIP31 required the addition of dithiothreitol, iodoacetic acid, or N-ethylmaleimide. Mixed disulfide-linked heterodimers between the PMIP31 and PMIP27 subgroups were not detected. Based on vectorial proteolysis of right-side-out vesicles with trypsin and hydropathy analysis of the predicted amino acid sequence derived from the gene encoding PMIP27, a topological model for a PMIP27 was established. Two exposed tryptic cleavage sites were identified from proteolysis of PMIP27, and each was distinct from the single exposed site previously identified in surface loop C of a PMIP31. Although the PMIP31 and PMIP27 species both contain integral proteins that appear to occur within a single vesicle population, these results demonstrate that each PMIP subgroup responds differently to perturbations of the membrane. 相似文献
102.
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104.
CA Bernhart PM Perreaut BP Ferrari YA Muneaux JL Assens J Clément F Haudricourt CF Muneaux JE Taillades MA Vignal 《Canadian Metallurgical Quarterly》1993,36(22):3371-3380
Starting from the structure of the novel nonpeptide AT1 receptor antagonist DuP 753 (losartan), a new series of potent antagonists was designed. In these compounds the central imidazole nucleus was replaced by the dihydroimidazol-4-one structure. The most active compounds had a spirocyclopentane or a spirocyclohexane ring in position 5. Like the imidazole series, the best substituents were the linear butyl chain in position 1 and the [2'-(tetrazol-5-yl)biphenylyl]methyl group in position 3. Antagonistic activity was assessed by the ability of the compounds to competitively inhibit [125I]AII binding to the AT1 subtype receptor and to antagonize AII-induced contractions in rabbit aorta rings. The most active compounds had IC50 values in the nanomolar range. In conscious rats, compounds 4 and 21 antagonized the AII pressor response when administered orally. Compound 21 (SR 47436) was the most active; it was recently shown to also be active in cynomolgus monkeys both intravenously and orally. This molecule is now undergoing clinical trials for the treatment of hypertension. 相似文献
105.
M Sukumar M Bommaraju JE Fisher FC Morin MC Papo BP Fuhrman LJ Hernan CL Leach 《Canadian Metallurgical Quarterly》1998,84(1):327-334
Partial liquid ventilation using conventional ventilatory schemes improves lung function in animal models of respiratory failure. We examined the feasibility of high-frequency partial liquid ventilation in the preterm lamb with respiratory distress syndrome and evaluated its effect on pulmonary and systemic hemodynamics. Seventeen lambs were studied in three groups: high-frequency gas ventilation (Gas group), high-frequency partial liquid ventilation (Liquid group), and high-frequency partial liquid ventilation with hypoxia-hypercarbia (Liquid-Hypoxia group). High-frequency partial liquid ventilation increased oxygenation compared with high-frequency gas ventilation over 5 h (arterial oxygen tension 253 +/- 21.3 vs. 17 +/- 1.8 Torr; P < 0.001). Pulmonary vascular resistance decreased 78% (P < 0.001), pulmonary blood flow increased fivefold (P < 0.001), and aortic pressure was maintained (P < 0.01) in the Liquid group, in contrast to progressive hypoxemia, hypercarbia, and shock in the Gas group. Central venous pressure did not change. The Liquid-Hypoxia group was similar to the Gas group. We conclude that high-frequency partial liquid ventilation improves gas exchange and stabilizes pulmonary and systemic hemodynamics compared with high-frequency gas ventilation. The stabilization appears to be due in large part to improvement in gas exchange. 相似文献
106.
Mediators of septic shock: new approaches for interrupting the endogenous inflammatory cascade 总被引:1,自引:0,他引:1
BP Giroir 《Canadian Metallurgical Quarterly》1993,21(5):780-789
OBJECTIVES: To review the molecular pathogenesis of septic shock, with particular emphasis on the induction of cytokines by endotoxin. By understanding the mechanisms that result in the systemic inflammatory response, novel clinical interventions may be more effectively studied. DATA SOURCES: The English medical literature was reviewed, including human clinical trials, animal experiments, and in vitro studies elucidating cellular and molecular interactions. Expert testimony from the Roundtable Conference on Sepsis (Brussels, March 1992) was also used to synthesize emerging concepts and to ensure inclusion of ongoing investigations. STUDY SELECTION: Emphasis on controlled experimental studies which elucidated the molecular and cellular interactions during sepsis. DATA EXTRACTION: This study focused only on data that directly involved the induction and regulation of protein mediators of sepsis, especially tumor necrosis factor (TNF) and interleukin-1. Data concerning the role of TNF during health were extracted from the author's peer-reviewed data. DATA SYNTHESIS: Information concerning the many facets of the systemic inflammatory response was integrated into a chronological, clinically oriented model of cytokine induction during endotoxemia. CONCLUSIONS: The induction of inflammation during sepsis is a complex, but increasingly understood, biological cascade that is dependent on inter- and intracellular signaling. Novel biotherapies may improve patient outcome in sepsis by interrupting any or all points of signal transduction. 相似文献
107.
JD Luketich KE Sommers BP Griffith A Boujoukos RJ Landreneau PF Ferson RJ Keenan 《Canadian Metallurgical Quarterly》1996,62(6):1852-1854
Aortoesophageal fistula is a rare complication after thoracic aortic aneurysm repair. Six previously reported cases of aortoesophageal fistula management have been uniformly fatal. We present our successful management and review the literature of this topic. 相似文献
108.
R Goyal ZA Syed PS Mukhopadhyay J Souza A Zivin BP Knight KC Man SA Strickberger F Morady 《Canadian Metallurgical Quarterly》1998,9(3):269-280
1. (5R)-3-[2-((1S)-3-cyano-1-hydroxypropyl)benzothiazol-6-yl]-5-metho xymethyl-2-oxazolidinone (E2011) has two chiral centers in its structure. In vivo optical inversion of the hydroxy group at one of the chiral centers converts E2011 to a diastereoisomer (ER-20593). Pharmacokinetic parameters of E2011 and ER-20593 were determined after administration of E2011 to rat at 10 mg/kg, and the plasma concentration ratios of E2011 to ER-20593 were almost constant after Tmax of the plasma concentrations. 2. E2011 and ER-20593 were separately administered orally to six species in addition to rat, and the species differences in both directions of epimerization (i.e. from E2011 to ER-20593 and from ER-20593 to E2011) were studied by measuring the plasma concentrations of both compounds. In mouse, guinea pig, dog, and squirrel monkey, the epimerization of E2011 to ER-20593 did not occur, but the epimerization of ER-20593 to E2011 did. In rat, pig and rhesus monkey, the inversion of E2011 to ER-20593 occurred, but the ratios of this inversion were smaller than those for the inversion in the opposite direction. E2011 underwent about 15% inversion to ER-20593 in rat, which was the largest inversion in the seven species examined. 3. To study the mechanism of the epimerization, deuterium-labelled E2011 and ER-20593 (created by substituting the proton at the chiral center of the parent compounds for deuterium) were orally administered (separately) to rat and dog, and the concentration ratios and molecular weights of E2011 and ER-20593 in the plasma were determined by hplc and FAB(+)-mass spectrometry respectively. The results indicated that the major mechanism of the epimerization was oxidation to the carbonyl form followed by reduction to the original epimer and/or the other epimer. 4. The carbonyl form of E2011 (CO-E2011) was reduced to E2011 and ER-20593 (alcohol forms) by liver cytosol and microsomes from rat and dog in vitro with NADH or NADPH. The resultant epimeric ratios (E2011:ER-20593) were consistent with the in vivo results in rat and dog. 5. In conclusion, species differences in the epimerization of E2011 would result from product stereoselectivity of the reductase activity with the carbonyl intermediate. 相似文献
109.
I Hioki I Yada M Nishikawa Y Shomura BP Cruz K Onoda K Tani T Shimono H Shinpo 《Canadian Metallurgical Quarterly》1998,44(5):M397-M400
Contact between blood and artificial materials has various effects on blood. Impairment of platelet function is an especially important and well known effect, but its precise mechanism is not clearly understood. The authors constructed a circulation model to investigate the effect of extracorporeal circulation on platelet membrane glycoproteins (GPs), especially GP Ib, and to compare the changes in GP Ib in heparin coated (group C) and nonheparin coated (group N) circuits. As determined by flow cytometry, GP Ib in both groups decreased on initiating circulation, but the decrease in group N was significantly larger than that in group C. There was no observed change in GP IIb/IIIa levels in either group. The extent of shear stress induced platelet aggregation significantly decreased during circulation in both groups. Decreases in the extent of shear stress induced platelet aggregation were significantly less with the use of heparin coated circuits. In addition, the amount of GP Ib in the high speed pellet decreased progressively during circulation in both groups. In contrast, the amount of GP Ib in the Triton insoluble (low speed) pellet increased dramatically during circulation. However, expression of GP Ib in the Triton soluble platelet fraction was low in both groups. From the results, it was concluded that the cause of the decrease in platelet function during extracorporeal circulation is attributable to the internalization of GP Ib from the platelet surface inside the platelet. It also can be said that a heparin coated circuit is one effective means of controlling this change. 相似文献
110.
H Ruchatz BP Leung XQ Wei IB McInnes FY Liew 《Canadian Metallurgical Quarterly》1998,160(11):5654-5660
IL-15 has recently been detected in the synovium of patients with rheumatoid arthritis. IL-15-activated T cells induce significant TNF-alpha synthesis by macrophages via a cell contact-dependent mechanism, suggesting a key regulatory role for IL-15. Here, we report that the administration of a soluble fragment of IL-15Ralpha into DBA/1 mice, profoundly suppressed the development of collagen-induced arthritis. This was accompanied in vitro by marked reductions in Ag-specific proliferation and IFN-gamma synthesis by spleen cells from treated mice compared with control mice and in vivo by a significant reduction in serum anti-collagen Ab levels. These data directly demonstrate a pivotal role for IL-15 in the development of inflammatory arthritis and also suggest that antagonists to IL-15 may have therapeutic potential in rheumatic diseases. 相似文献