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1.
LW Seymour H Soyez A De Marre MA Shoaibi EH Schacht 《Canadian Metallurgical Quarterly》1996,11(5):351-365
Prodrugs of mitomycin C (MMC) based on soluble poly-[N-(2-hydroxyethyl)-L-glutamine] (pHEG) polymers have been evaluated as tumour-targeted drugs. These materials are designed to exploit the enhanced permeability of tumour vasculature, combining a passive tumour tropism with decreased systemic liberation of free MMC. A tri- or tetrapeptide linkage (e.g. Gly-Phe-Ala-Leu) between pHEG and the aziridine nitrogen of MMC can combine good hydrolytic stability with rapid cleavage by lysosomal enzymes, releasing free MMC. The conjugates showed decreased systemic toxicity and could be administered to mice at a total MMC dose of 15 mg/kg i.v., compared with just 6 mg/kg for free MMC. Conjugates also showed better activity against animal models of established tumours, achieving up to 77% increased life span (ILS) against solid P388 leukaemia, compared with only 23% for free MMC, and up to 121% ILS against solid C26 colorectal carcinoma, compared with no activity for the free drug. Improving the therapeutic index of anticancer drugs by combining tumour tropism with decreased systemic toxicity is a versatile approach that should produce a new generation of improved anticancer agents. 相似文献
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JL Banyer S Goldwurm L Cullen B van der Griend A Zournazi DJ Smit LW Powell EC Jazwinska 《Canadian Metallurgical Quarterly》1998,9(3):235-239
We have examined acetaminophen (paracetamol) dosing for outpatient management of posttonsillectomy pain in children. Forty children, 5-15 years of age, undergoing tonsillectomy and their parents were randomly assigned to use a scheduled administration of acetaminophen in weight appropriate doses, 60 mg.kg-1.24h-1 orally, 90 mg.kg-1.24h-1 rectally, or to use acetaminophen 'as needed' according to present standards (control group). Postoperative pain was assessed by the child using the poker chip tool for the first three days after discharge. The prevalence of pain amongst all the children was high. The second day after discharge 22%-64% of the children in the study group and 36%-73% of the children in the control group rated severe pain. Recommended dose ranges of acetaminophen do not provide sufficient pain relief in children following tonsillectomy. Further studies are required to determine, whether higher doses of acetaminophen or analgesics with different analgesic properties will lead to improved analgesia in children following tonsillectomy. 相似文献
4.
Ultrastructure of sperm and eggs of the ocean pout (Macrozoarces americanus L.), an internally fertilizing marine teleost, was examined by scanning and transmission electron microscopy. The results showed that the sperm do not have an acrosome but have a very long mid-piece (one to two times the sperm head length) containing numerous well-developed elongated mitochondria. The sperm also have two tails (is biflagellate) each consisting of nine peripheral and one central pair (9 +/- 2) of microtubules. This long mid-piece and the biflagellate nature of the sperm appear to be associated with the long life-span of the sperm and with sperm dispersal in the ovary to fertilize the eggs internally. The ocean pout eggs are enveloped by a porous chorionic membrane similar to that found in other teleosts but have two micropyles, a condition likely related to a mechanism of egg fertilization which increases the egg fertility in the presence of low sperm numbers. Following insemination, some biochemically undefined excretions appeared on the surface of fertilized eggs and led to the acquisition of adherent capability of the eggs which formed a tightly associated egg mass in sea water. 相似文献
5.
LW Didenko IB Buchwalow W Schulze K Augsten M Susa E Unger 《Canadian Metallurgical Quarterly》1996,98(4):399-409
Heterotrimeric GTP-binding proteins (G-proteins) have been shown to play an important role in cellular signalling. However, G-protein involvement in the intracellular spreading of bacterial pathogens is still poorly understood. In this study, antibodies, that recognize G-protein alpha-subunits (anti-G alpha), were used to investigate the localization of G-proteins in the macrophage-like cell line P388D1 and E. coli, also in their L-forms, during phagocytosis. In E. coli, anti-G alpha-binding sites were detected preferably in the cell wall and septa of the whole bacterial forms as well as in the cytoplasm of L-forms. Western blotting of bacterial lysates demonstrated protein bands with positive immunoreaction to antibodies against Gs alpha, Gi alpha, and Gcommon alpha with a higher affinity to the antibody against Gs alpha. Immunoreaction with the anti-Gs alpha-antibody was markedly higher in pathogenic strains of E. coli. Because of the conserved structure in all GTP-binding proteins which seem to derive from a single primordial protein involved in signal transduction mechanisms, it is reasonable to assume that some anti-Ga-positive proteins in E. coli might be related to G-proteins of higher organisms. A putative candidate for bacterial G-proteins seems to be a 36 kDa protein. Enhancement in G-protein immunostaining in the cytoplasm of macrophages around the internalized bacteria testifies to the involvement of G-proteins in mediation of endocytosis responses of phagocytes. 相似文献
6.
A parameter-free geometric model for nuclear absorption is derived from microscopic theory. The expression for the absorption cross section in the eikonal approximation taken in integral form is separated into a geometric contribution, described by an energy-dependent effective radius, and two surface terms which are shown to cancel in an asymptotic series expansion. For collisions of light nuclei, an expression for the effective radius is derived using harmonic-oscillator nuclear density functions. A direct extension to heavy nuclei with Woods-Saxon densities is made by identifying the equivalent half density radius for the harmonic-oscillator functions. Coulomb corrections are incorporated and a simplified geometric form of the Bradt-Peters type obtained. Results spanning the energy range of 1 MeV/nucleon to 1 GeV/nucleon are presented. Good agreement with experimental results are obtained. 相似文献
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A. Goyal E. D. Specht Z. L. Wang D. M. Kroeger J. A. Sutliff J. E. Tkaczyk J. A. Deluca L. Masur G. N. Riley 《Journal of Electronic Materials》1994,23(11):1191-1197
Microstructural origins for reduced weak-link behavior in high-Jc melt-processed YBCO, spray pyrolyzed thick films of Tl-1223, metallic precursor Y-124 polycrystalline powder-in-tube (PIT)
wires and PIT Bi-2212/2223 are discussed. Since the materials studied are the highest Jc, polycrystalline, high-Tc superconductors fabricated worldwide, the results provide important guidelines for further improvements in superconducting
properties, thereby enabling practical applications of these materials. It is found that strongly linked current flow within
domains of melt-processed 123 occurs effectively through a single crystal path. In c-axis oriented, polycrystalline Tl-1223
thick films, local in-plane texture has been found to play a crucial role in the reduced weak-link behavior. Formation of
“colonies” of grains with a common c-axis and modest in-plane misorientation was observed. Furthermore, a colony boundary
in general has a varying misorientation along the boundary. Large regions comprised primarily of low angle boundaries were
observed. Percolative transport through a network of such small angle boundaries appears to provide the nonweak-linked current
path. Although powder-in-tube BSCCO 2212 and 2223 also appear to have a “colony” microstructure, there are some important
differences. Colonies in BSCCO consist of stacks of grains with similar c-axis orientation in contrast to colonies in Tl-1223
films where few grains are stacked on top of one another. Furthermore, most grains within a colony in BSCCO have the same
lateral dimensions as that of the colony, resulting largely largely in “twist” boundaries. Further microstructural characterization
of high-Jc PIT 2212 and 2223 is currently underway. In the case of Y-124 wires, weak macroscopic in-plane texture is found. Additional
measurements are underway to determine if a sharper, local in-plane texture also exists. It is found that in three of the
four types of superconductors studied, reduced weak-link behavior can be ascribed to some degree of biaxial alignment between
grains, either on a “local” or a “global” scale. 相似文献
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