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71.
RE Sacco JS Haynes JA Harp WR Waters MJ Wannemuehler 《Canadian Metallurgical Quarterly》1998,153(6):1717-1722
Flora-bearing mice with targeted disruption of T cell receptor (TCR)-alpha or -beta genes spontaneously develop intestinal inflammation with features similar to ulcerative colitis in humans. TCR-alpha-deficient mice maintained germfree or colonized with a limited number of intestinal bacteria failed to develop inflammatory bowel disease (IBD)-like lesions. Evidently, inflammation in these mice does not develop spontaneously or result from a generalized antigenic stimulation, but rather requires induction by a heretofore unidentified specific stimulus. We describe the development of IBD-like lesions in germfree TCR-alpha-deficient mice monoassociated with the protozoan Cryptosporidium parvum. Lesions were seen in distal ileum, cecum, and colon and were most severe in the cecum. A prominent leukocytic infiltrate within the lamina propria was a common characteristic of the lesions observed in the C. parvum-infected germfree TCR-alpha-deficient mice. The leukocytic infiltrate was composed of aggregates of B220+ cells, the majority of which expressed surface IgD (ie, conventional B lymphocytes). It has been proposed that antigenic stimulation by a microorganism(s) is needed to initiate intestinal inflammation in TCR-alpha-deficient mice. Our results indicate that a single microbial species, C. parvum, is capable of triggering the development of IBD-like lesions in germfree TCR-alpha-deficient mice. 相似文献
72.
73.
The external region of a cell membrane, known as the glycocalyx, is dominated by glycosylated molecules, which direct specific interactions such as cell-cell recognition and contribute to the steric repulsion that prevents undesirable non-specific adhesion of other molecules and cells. Mimicking the non-adhesive properties of a glycocalyx provides a potential solution to the clinical problems, such as thrombosis, that are associated with implantable devices owing to non-specific adsorption of plasma proteins. Here we describe a biomimetic surface modification of graphite using oligosaccharide surfactant polymers, which, like a glycocalyx, provides a dense and confluent layer of oligosaccharides. The surfactant polymers consist of a flexible poly(vinyl amine) with dextran and alkanoyl side chains. We show that alkanoyl side chains assemble on graphite through hydrophobic interaction and epitaxial adsorption. This constrains the polymer backbone to lie parallel to the substrate, with solvated dextran side chains protruding into the aqueous phase, creating a glycocalyx-like coating. The resulting biomimetic surface is effective in suppressing protein adsorption from human plasma protein solution. 相似文献
74.
Isoniazid (INH), which acts by inhibiting mycolic acid biosynthesis, is very potent against the tuberculous mycobacteria. It is about 100-fold less effective against Mycobacterium avium. This difference has often been attributed to a decreased permeability of the cell wall. We measured the rate of conversion of radiolabelled INH to 4-pyridylmethanol by whole cells and cell-free extracts and estimated the permeability barrier imposed by the cell wall to INH influx in Mycobacterium tuberculosis and M. avium. There was no significant difference in the relative permeability to INH between these two species. However, the total conversion rate in M. tuberculosis was found to be four times greater. Examination of in vitro-generated mutants revealed that the major resistance mechanism for both species is loss of the catalase-peroxidase KatG. Analysis of lipid and protein biosynthetic profiles demonstrated that the molecular target of activated INH was identical for both species. M. avium, however, formed colonies at INH concentrations inhibitory for mycolic acid biosynthesis. These mycolate-deficient M. avium exhibited altered colony morphologies, modified cell wall ultrastructure and were 10-fold more sensitive to treatment with hydrophobic antibiotics, such as rifampin. These findings may significantly impact the design of new therapeutic regimens for the treatment of infections with atypical mycobacteria. 相似文献
75.
RA Alvarez AJ Ghalayini P Xu A Hardcastle S Bhattacharya PN Rao MJ Pettenati RE Anderson W Baehr 《Canadian Metallurgical Quarterly》1995,29(1):53-61
Defects in the Drosophila norpA (no receptor potential A) gene encoding a phosphoinositide-specific phospholipase C (PLC) block invertebrate phototransduction and lead to retinal degeneration. The mammalian homolog, PLCB4, is expressed in rat brain, bovine cerebellum, and the bovine retina in several splice variants. To determine a possible role of PLCB4 gene defects in human disease, we isolated several overlapping cDNA clones from a human retina library. The composite cDNA sequence predicts a human PLC beta 4 polypeptide of 1022 amino acid residues (MW 117,000). This PLC beta 4 variant lacks a 165-amino-acid N-terminal domain characteristic for the rat brain isoforms, but has a distinct putative exon 1 unique for human and bovine retina isoforms. A PLC beta 4 monospecific antibody detected a major (130 kDa) and a minor (160 kDa) isoform in retina homogenates. Somatic cell hybrids and deletion panels were used to localize the PCLB4 gene to the short arm of chromosome 20. The gene was further sublocalized to 20p12 by fluorescence in situ hybridization. 相似文献
76.
77.
JP Gagliardi RE Nettles DE McCarty LL Sanders GR Corey DJ Sexton 《Canadian Metallurgical Quarterly》1998,26(5):1165-1168
The effect of age on the presentation and outcome of infective endocarditis (IE) is unclear. Many of the available data are based on analyses of mixed populations of patients including intravenous drug users or those with prosthetic valve endocarditis or native valve IE. We used the Duke criteria to compare the characteristics of 44 episodes of definite native valve IE in elderly patients (> 64 years old) with the characteristics of 64 similarly defined episodes of native valve IE in younger, nonintravenous-drug-using adult patients (> 29 years and < 60 years old). Our data suggest that the clinical presentation, characteristics, and outcome of native valve IE are similar for elderly patients and younger adult patients, although elderly patients were hospitalized an average of 12 days longer. Although we found that the occurrence of renal failure and cerebral embolism during an episode of IE was associated with higher rates of death (odds ratios, 4.8 and 4.0, respectively), age was not a significant contributor to mortality. 相似文献
78.
Immunological mimicry between host and microbial proteins has been suggested as a potential mechanism in the development of uveitis in humans. In this study immunological crossreactivity between anti-streptococcal monoclonal antibodies (MAbs) and the human eye was investigated. In indirect immunofluorescence, we demonstrated novel immunological crossreactivity of two anti-streptococcal MAbs (27 and 112) with the rod outer (and inner) segments of the retina of the human eye. In further studies, retinal S-Ag, a uveitogenic protein in the rod outer (and inner) segments, was found to react with the anti-streptococcal MAbs. In addition, several uveitogenic peptides of S-Ag were recognized by the anti-streptococcal MAbs. In the ELISA and Western immunoblot, anti-S-Ag MAbs crossreacted with group A streptococci and the streptococcal M protein further demonstrating sites of antigenic similarity. Homology between the retinal S-Ag and streptococcal M protein was observed in amino acid sequences repeated in the B repeat region of the streptococcal M5 protein. These data show that retinal S-antigen has immunological similarities with streptococcal M protein, a major virulence determinant and strong bacterial cell surface antigen. 相似文献
79.
Bovine rotavirus strain B223 is the North American prototype for group A P8[11] serotype/genotype rotaviruses. Rotaviruses with this serotype/genotype are a prevalent cause of neonatal calf diarrhea and have also been isolated from asymptomatic human infants. On the basis of deduced amino acid sequence of the outer capsid viral protein 4 (VP4), strain B223 lacks a cysteine at position 318 that is conserved among all other rotavirus strains. It has been speculated that this may result in the loss of disulfide bond and a change in the structure of the VP4 that may affect the infectivity and antigenicity of the virus. This paper describes partial sequences of the VP4 gene (nucleotides 613 to 1016 coding for amino acid positions 202 to 335) of 16 bovine rotavirus field isolates with P8[11] that were obtained from calves in Nebraska and Indiana. All the isolates lack a cystein at position 203 and had a conserved valine residue at position 318, thus indicating that the prototype strain B223 is representative of group A rotaviruses with P8[11] serotype/genotype. 相似文献
80.
BE Schreuder RE Geertsma LJ van Keulen JA van Asten P Enthoven RC Oberthür AA de Koeijer AD Osterhaus 《Canadian Metallurgical Quarterly》1998,142(18):474-480
The efficacy of the procedures in use at the two rendering plants in the Netherlands was assessed on a laboratory-scale using procedures that simulated the pressure cooking part of the rendering process. A pool of bovine spongiform encephalopathy (BSE)-infected brainstem from the United Kingdom and a pool of scrapie-infected brainstem from Dutch sheep were used to spike the rendering materials. The mixtures were subjected to various time-temperature combinations of hyperbaric heat treatment related to the conditions used in Dutch rendering plants in the early 1990s, and to the combination of 20 minutes at 133 degrees C required by the EU Directive on rendering of 1996. The efficacy of the procedures in inactivating BSE or scrapie infectivity was measured by titrating the materials before and after heat treatment in inbred mice, by combined intracerebral and intraperitoneal inoculations at limiting dilutions. Two independent series of experiments were carried out. The design of the study allowed for minimum inactivations of up to 2.2 log (2.0 in the second series) to be measured in the diluted infective material and 3.1 log in the undiluted material. After 20 minutes at 133 degrees C there was a reduction of BSE infectivity of about 2.2 log in the first series (with some residual infectivity detected), and in the second series more than 2.0 log (with no residual infectivity detected). With undiluted brain material there was an inactivation of about 3.0 log (with some residual infectivity detected). With the same procedure, scrapie infectivity was reduced by more than 1.7 log in the first series and by more than 2.2 log in the second series. With undiluted brain material there was an inactivation of more than 3.1 log. In each case no residual scrapie infectivity was detected. The BSE agent consistently appeared to be more resistant to heat inactivation procedures than the scrapie agent, particularly at lower temperatures and shorter times. 相似文献