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71.
Flushing of intestinal vascular access ports (VAPs) is commonly performed to prevent the problems of blockage and infection, and in this study four different flushing solutions were compared. The growth of bacteria from canine duodenal contents was compared in: 0.9% saline, 50% dextrose, 8.4% sodium bicarbonate (NaHCO3) and 0.01 M phosphate buffered saline (PBS). Duodenal contents from three laboratory beagles were serially diluted in these four solutions, spread plated onto agar at 24 h periods for 7 days and bacterial counts were performed. Immediately after the duodenal juices were added, no significant differences could be seen in bacterial counts with any of the solutions. Over the 7 day period, bacterial numbers greatly increased in saline and phosphate buffered saline, but greatly decreased in dextrose and sodium bicarbonate solutions. Dextrose and sodium bicarbonate appeared to be the most promising flushing solutions tested to minimize infections of associated intestinal VAPs.  相似文献   
72.
African sleeping sickness is a debilitating and often fatal disease caused by tsetse fly transmitted African trypanosomes. These extracellular protozoan parasites survive in the human bloodstream by virtue of a dense cell surface coat made of variant surface glycoprotein. The parasites have a repertoire of several hundred immunologically distinct variant surface glycoproteins and they evade the host immune response by antigenic variation. All variant surface glycoproteins are anchored to the plasma membrane via glycosylphosphatidylinositol membrane anchors and compounds that inhibit the assembly or transfer of these anchors could have trypanocidal potential. This article compares glycosylphosphatidylinositol biosynthesis in African trypanosomes and mammalian cells and identifies several steps that could be targets for the development of parasite-specific therapeutic agents.  相似文献   
73.
A method is introduced to measure chloride permeability in cultured epithelial cells using 6-methoxy-N-(3-sulfopropyl)quinolinium (SPQ) and 6-methoxy-N-ethylquinolinium iodide quinolinium (MEQ) as fluorescent chloride-sensitive probes. The method involves growing cells in multiwell plates, incubating cells with SPQ or MEQ, and then exchanging intracellular or extracellular halide ions with nitrate. The resulting time course of SPQ or MEQ fluorescence is followed by repetitive readings with a multiwell fluorescence plate reader. Exchange times are extracted by fitting the time course with a single exponential function of time. The method was validated by measuring the effect of chloride channel activators and blockers in A6 and MDCK cells. The baseline iodide/nitrate exchange time was 200-300 s. Isoproterenol (a modulator of cAMP-activated chloride channels) increased the exchange rate by a factor of 1.4+/-0.1; A23187 (a modulator of calcium-activated chloride channels) increased the rate by 3.4+/-0.4; bradykinin (also a modulator of calcium-activated chloride channels) increased the rate by 2.0+/-0.4; forskolin (a direct stimulator of adenylate cyclase) increased the rate by 2.7+/-0.3. Diphenylamine-2-carboxylate (a chloride channel blocker) decreased the rate by 0.12+/-0.03. These results indicate that our method is a valid indicator of halide-nitrate exchange in cultured epithelial cells.  相似文献   
74.
75.
Current wound-healing models do not fully duplicate the in vivo human environment. The feasibility of grafting human full-thickness foreskin onto nude rats, as a model of acute wound healing, was evaluated. Incisions were then created on the grafted skin, and wound healing was evaluated. Full-thickness human skin was obtained after elective circumcision and was grafted subcutaneously onto the dorsal thorax of nude rats. At 10 days after transplantation, graft beds were judged for graft viability, on the basis of gross appearance, texture, and adherence. Full-thickness wounds were then made in the foreskin. Graft wounds were left to close by secondary intention. The wounds were allowed to heal for 7 days. Wounds were excised and tested for breaking stress. Histological evaluations included proliferating cell nuclear antigen, factor VIII, hematoxylin and eosin, and trichrome staining. Twenty grafts were performed, with 100 percent viability. Upon incision, all grafts bled freely, indicating a rich vascular supply and tissue viability. Graft viability was confirmed by the presence of proliferating cells in the parabasal stratum of the epithelium. Furthermore, there was evidence of angiogenesis, as confirmed by staining for factor VIII. Breaking stress was evaluated by tensiometry, 7 days after wounding. Histological evaluations revealed viable grafts and active wound-healing events. Full-thickness human skin can be successfully transplanted onto nude rats, providing a larger, more physiological model of human wound healing. This model closely parallels the in vivo situation, providing a promising model for study of the complex biological processes of acute human wound healing, in a reproducible manner.  相似文献   
76.
Biologists view life as transient while theologians see it as eternal. An unbiased definition for life would respect both views until one or both were eliminated by evidence. This paper identifies pre-requisites for such a definition. First among these is that all assumptions be made explicit. Currently "life" is surrounded by implicit assumptions, e.g., that it is what organisms lose at death or that it is eternal, that its quality is inversely related to personal distress, that it originated some four billion years ago, and that animate matter can be distinguished from inanimate matter. None of these assumptions are supported by data. It is possible therefore that "life" is as meaningless as phlogiston. If life has meaning, i.e., if it is true, it must be as permanent as buoyancy, gravity, electricity, and the other truths of nature. Any definition for life that would permit such truth to be seen must be free of unwarranted assumptions. For the moment, at least, such a definition would need to be loosely structured and broadly focused. It would need to describe the long and convoluted process by which matter and energy form organisms which then evolve to form conscious organisms which then explore nature and eventually discover truth. Such a definition would include all the reactions and interactions of matter and energy and all the aspects of conscious discovery. It would suffer from superficiality, but, by being free from bias, provide a foundation for dialogue between biologists and theologians.  相似文献   
77.
Systemic hypoxia, produced by lowering inspired Po2, induces a rapid inflammation in several microcirculations, including cremaster muscle. Mast cell activation is a necessary element of this response. Selective reduction of cremaster microvascular Po2 (PmO2) with normal systemic arterial Po2 (PaO2; cremaster hypoxia/systemic normoxia), however, does not elicit increased leukocyte-endothelial adherence (LEA) in cremaster venules. This could be due to a short time of leukocyte exposure to the hypoxic cremaster environment. Conversely, LEA increases when PaO2 is lowered, while cremaster PmO2 remains high (cremaster normoxia/systemic hypoxia). An alternative explanation of these results is that a mediator released from a central site during systemic hypoxia initiates the inflammatory cascade. We hypothesized that if this is the case, cremaster mast cells would be activated during cremaster normoxia/systemic hypoxia, but not during cremaster hypoxia/systemic normoxia. The microcirculation of rat cremaster muscles was visualized by using intravital microscopy. Cremaster PmO2 was measured with a phosphorescence quenching method. Cremaster hypoxia/systemic normoxia (PmO2 7 +/- 1 Torr, PaO2 87 +/- 2 Torr) did not increase LEA; however, topical application of the mast cell activator compound 48/80 under these conditions did increase LEA. The effect of compound 48/80 on LEA was blocked by topical cromolyn, a mast cell stabilizer. LEA increased during cremaster normoxia/systemic hypoxia, (PmO2 64 +/- 5 Torr, PaO2 33 +/- 2 Torr); this increase was blocked by topical cromolyn. The results suggest that mast cell stimulation occurs only when PaO2 is reduced, independent of cremaster PmO2, and support the idea of a mediator that is released during systemic hypoxia and initiates the inflammatory cascade.  相似文献   
78.
Using the strictly neutral model as a null hypothesis, we tested for deviations from expected levels of nucleotide polymorphism at the alcohol dehydrogenase locus (Adh-1) within and among four species of pocket gophers (Geomys bursarius major, G. knoxjonesi, G. texensis llanensis, and G. attwateri). The complete protein-encoding region was examined, and 10 unique alleles, representing both electromorphic and cryptic alleles, were used to test hypotheses (e.g., the neutral model) concerning the maintenance of genetic variation. Nineteen variable sites were identified among the 10 alleles examined, including 9 segregating sites occurring in synonymous positions and 10 that were nonsynonymous. Several statistical methods, including those that test for within-species variation as well as those that examine variation within and among species, failed to reject the null hypothesis that variation (both within and between species of Geomys) at the Adh locus is consistent with the neutral theory. However, there was significant heterogeneity in the ratio of polymorphism to divergence across the gene, with polymorphisms clustered in the first half of the coding region and fixed differences clustered in the second half of the gene. Two alternative hypotheses are discussed as possible explanations for this heterogeneity: an old balanced polymorphism in the first half of the gene or a recent selective sweep in the second half of the gene.   相似文献   
79.
Adults of the human parasitic trematode Schistosoma mansoni, which causes hepatosplenic/intestinal complications in humans, synthesize glycoconjugates containing the Lewis x (Lex) Galbeta1-->4(Fucalpha1-- >3)GlcNAcbeta1-->R, but not sialyl Lewis x (sLex), antigen. We now report on our analyses of Lexand sLexexpression in S.haematobium and S.japonicum, which are two other major species of human schistosomes that cause disease, and the possible autoimmunity to these antigens in infected individuals. Antigen expression was evaluated by both ELISA and Western blot analyses of detergent extracts of parasites using monoclonal antibodies. Several high molecular weight glycoproteins in both S. haematobium and S. japonicum contain the Lexantigen, but no sialyl Lexantigen was detected. In addition, sera from humans and rodents infected with S.haematobium and S.japonicum contain antibodies reactive with Lex. These results led us to investigate whether Lexantigens are expressed in other helminths, including the parasitic trematode Fasciola hepatica , the parasitic nematode Dirofilaria immitis (dog heartworm), the ruminant nematode Haemonchus contortus , and the free-living nematode Caenorhabditis elegans . Neither Lexnor sialyl-Lexis detectable in these other helminths. Furthermore, none of the helminths, including schistosomes, express Lea, Leb, Ley, or the H- type 1 antigen. However, several glycoproteins from all helminths analyzed are bound by Lotus tetragonolobus agglutinin , which binds Fucalpha1-->3GlcNAc, and Wisteria floribunda agglutinin, which binds GalNAcbeta1-->4GlcNAc (lacdiNAc or LDN). Thus, schistosomes may be unique among helminths in expressing the Lexantigen, whereas many different helminths may express alpha1,3-fucosylated glycans and the LDN motif.   相似文献   
80.
The selectins interact in important normal and pathological situations with certain sialylated, fucosylated glycoconjugate ligands containing sialyl Lewisx(Neu5Acalpha2-3Galbeta1-4(Fucalpha1-3)GlcN Ac). Much effort has gone into the synthesis of sialylated and sulfated Lewisxanalogs as competitive ligands for the selectins. Since the natural selectin ligands GlyCAM-1 and PSGL-1 carry sialyl Lewisxas part of a branched Core 2 O-linked structure, we recently synthesized Galbeta1-4(Fucalpha1-3)GlcNAcbeta1-6(SE-3Galbeta1++ +-3)GalNAc1alphaOMe and found it to be a moderately superior ligand for L and P-selectin (Koenig et al. , Glycobiology 7, 79-93, 1997). Other studies have shown that sulfate esters can replace sialic acid in some selectin ligands (Yeun et al. , Biochemistry, 31, 9126-9131, 1992; Imai et al. , Nature, 361, 555, 1993). Based upon these observations, we hypothesized that Neu5Acalpha2-3Galbeta1-3GalNAc might have the capability of interacting with L- and P-selectin. To examine this hypothesis, we synthesized Galbeta1-4(Fucalpha1-3)GlcNAcbeta1-6(Neu5Acalpha2++ +-3Galbeta1-3)- GalNAc alpha1-OB, which was found to be 2- to 3-fold better than sialyl Lexfor P and L selectin, respectively. We also report the synthesis of an unusual structure GalNAcbeta1-4(Fucalpha1- 3)GlcNAcbeta1-OMe (GalNAc- Lewisx-O-methyl glycoside), which also proved to be a better inhibitor of L- and P-selectin than sialyl Lewisx-OMe. Combining this with our knowledge of Core 2 branched structures, we have synthesized a molecule that is 5- to 6-fold better at inhibiting L- and P-selectin than sialyl Lewisx-OMe, By contrast to unbranched structures, substitution of a sulfate ester group for a sialic acid residue in such a molecule resulted in a considerable loss of inhibition ability. Thus, the combination of a sialic acid residue on the primary (beta1-3) arm, and a modified Lexunit on the branched (beta1-6) arm on an O-linked Core 2 structure generated a monovalent synthetic oliogosaccharide inhibitor superior to SLexfor both L- and P-selectin.   相似文献   
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