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21.
Haemophilus ducreyi is resistant to killing by normal serum antibody and complement. We discovered an H. ducreyi outer membrane protein required for expression of serum resistance and termed it DsrA (for "ducreyi serum resistance A"). The dsrA locus was cloned, sequenced, and mutagenized. An isogenic mutant (FX517) of parent strain 35000 was constructed and characterized, and it was found to no longer express dsrA. FX517 was at least 10-fold more serum susceptible than 35000. DsrA was expressed by all strains of H. ducreyi tested, except three naturally occurring, avirulent, serum-sensitive strains. FX517 and the three naturally occurring dsrA-nonexpressing strains were complemented in trans with a plasmid expressing dsrA. All four strains were converted to a serum-resistant phenotype, including two that contained truncated lipooligosaccharide (LOS). Therefore, serum resistance in H. ducreyi does not require expression of full-length LOS but does require expression of dsrA. The dsrA locus from eight additional H. ducreyi strains was sequenced, and the deduced amino acid sequences were more than 85% identical. The major difference between the DsrA proteins was due to the presence of one, two, or three copies of the heptameric amino acid repeat NTHNINK. These repeats account for the variability in apparent molecular mass of the monomeric form of DsrA (28 to 35 kDa) observed in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Since DsrA is present in virulent strains, is highly conserved, and is required for serum resistance, we speculate that it may be a virulence factor and a potential vaccine candidate. 相似文献
22.
We have identified Xenopus MADM-like (xMADML), a Xenopus laevis gene related to the murine MADM and the human NRBP genes. xMADML is expressed throughout early development and is expressed most strongly in the developing lens and more weakly in the retina and other anterior tissues. We demonstrate that disruption of xMADML translation by means of morpholino injection results in impaired retina and lens development. Reciprocal transplantation of the presumptive lens ectoderm between morpholino-injected embryos and those injected solely with a dextran lineage tracer demonstrates that xMADML is necessary in both the lens and the retina for correct development of these eye tissues. Analysis of gene expression after knockdown of xMADML revealed significant alterations in the expression of some genes, including Pax6, xSix3, Sox2, and Sox3, suggesting that xMADML plays a role in regulating gene expression during development of the eye. This investigation is the first in vivo study examining the developmental role of this novel gene and reveals an important role of xMADML in eye tissue development and differentiation. 相似文献
23.
Hill D Rose B Pajkos A Robinson M Bye P Bell S Elkins M Thompson B Macleod C Aaron SD Harbour C 《Journal of clinical microbiology》2005,43(10):5085-5090
Recent studies have determined that Pseudomonas aeruginosa can live in a biofilm mode within hypoxic mucus in the airways of patients with cystic fibrosis (CF). P. aeruginosa grown under anaerobic and biofilm conditions may better approximate in vivo growth conditions in the CF airways, and combination antibiotic susceptibility testing of anaerobically and biofilm-grown isolates may be more relevant than traditional susceptibility testing under planktonic aerobic conditions. We tested 16 multidrug-resistant isolates of P. aeruginosa derived from CF patients using multiple combination bactericidal testing to compare the efficacies of double and triple antibiotic combinations against the isolates grown under traditional aerobic planktonic conditions, in planktonic anaerobic conditions, and in biofilm mode. Both anaerobically grown and biofilm-grown bacteria were significantly less susceptible (P < 0.01) to single and combination antibiotics than corresponding aerobic planktonically grown isolates. Furthermore, the antibiotic combinations that were bactericidal under anaerobic conditions were often different from those that were bactericidal against the same organisms grown as biofilms. The most effective combinations under all conditions were colistin (tested at concentrations suitable for nebulization) either alone or in combination with tobramycin (10 microg ml(-1)), followed by meropenem combined with tobramycin or ciprofloxacin. The findings of this study illustrate that antibiotic sensitivities are dependent on culture conditions and highlight the complexities of choosing appropriate combination therapy for multidrug-resistant P. aeruginosa in the CF lung. 相似文献
24.
Cloning, overexpression, purification, and immunobiology of an 85-kilodalton outer membrane protein from Haemophilus ducreyi 总被引:5,自引:0,他引:5
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Thomas KL Leduc I Olsen B Thomas CE Cameron DW Elkins C 《Infection and immunity》2001,69(7):4438-4446
We have identified an 85-kDa outer membrane protein that is expressed by all tested strains of Haemophilus ducreyi. Studies of related proteins from other pathogenic bacteria, including Haemophilus influenzae, Pasteurella multocida, Neisseria gonorrhoeae, Neisseria meningitidis, and Shigella dysenteriae, suggested a role for these proteins in pathogenesis and immunity. In keeping with the first such described protein from Haemophilus influenzae type B, we termed the H. ducreyi protein D15. The gene encoding the H. ducreyi D15 protein was cloned and sequenced, and the deduced amino acid sequence was found to be most similar to sequences of the D15-related proteins from other Pasteurella spp. The arrangement of the flanking genes was similar to that of H. influenzae Rd and suggested that D15 was part of a multigene operon. Attempts to make a null mutation of the D15 gene were unsuccessful, paralleling results in other D15 gene studies. Overexpression of H. ducreyi D15 in Escherichia coli resulted in a source of recombinant D15 (rD15) from which it was readily purified. rD15 was immunogenic, and it was found that immunization of rabbits with an rD15 vaccine preparation conferred partial protection against a virulent challenge infection. Antisera to an N-terminal peptide recognized all tested strains of H. ducreyi. 相似文献
25.
Acute porphyria is rare in orientals. We describe a Chinese woman with recurrent generalised tonic-clonic seizures and abdominal pain. Genomic DNA studies identified a heterozygous base substitution from guanine to adenine at nucleotide position 503, resulting in substitution of arginine by histidine at position 168 of the protein (R168H). This genetic abnormality is similar to the mutation reported in Caucasians with variegate porphyria. To the best of our knowledge, this is the first report in the English literature a Chinese patient with variegate porphyria with an identifiable mutation. A brief review of porphyria is presented. 相似文献
26.
27.
Whipple's disease is a systemic illness that can affect the heart, causing pericarditis, myocarditis, and valvular endocarditis. We describe a 43-year-old man without gastrointestinal symptoms who underwent mitral and aortic valve replacement for endocarditis, in whom a diagnosis of Whipple's disease was made at operation. 相似文献
28.
This article explores the ethical issues confronted when the process of childbirth is threatened by premature labor and delivery. In this article, obstetric ethics are distinguished within the larger study of "ethics," frameworks for decision making are critiqued, and factors that frequently influence the formation of ethical judgments are commented on. 相似文献
29.
M elikta N Okur KS Aikimbaev F Binokay M Sert E Akgül 《Journal of Medical Imaging and Radiation Oncology》2004,48(3):398-400
Pheochromocytomas of the bladder are rare neoplasms, constituting <0.06% of all vesical tumours. Common presenting features of this tumour include episodes of sweating, hypertension, haematuria and postmicturition syncope. We describe a case of bladder pheochromocytoma in a 66‐year‐old man whose only symptom of macroscopic haematuria was initially assessed with ultrasonography. Clinical presentation highlights the need for a high index of suspicion during sonographic evaluation of bladder neoplasms because such tumours might present without symptoms of adrenergic excess. 相似文献
30.
Hydrogen peroxide inhibits gap junctional intercellular communication in glutathione sufficient but not glutathione deficient cells 总被引:7,自引:5,他引:7
Cell to cell communication via gap junctions is essential in the
maintenance of the homeostatic balance of multicellular organisms. Aberrant
intercellular gap junctional communication (GJIC) has been implicated in
tumor promotion, neuropathy and teratogenesis. Oxidative stress has also
been implicated in similar pathologies such as cancer. We report a
potential link between oxidative stress and GJIC. Hydrogen peroxide, a
known tumor promoter, inhibited GJIC in WB-F344 rat liver epithelial cells
with an I50 value of 200 microM. Inhibition of GJIC by H2O2 was reversible
as indicated by the complete recovery of GJIC with the removal of H2O2 via
a change of fresh media. Free radical scavengers, such as t-butyl alcohol,
propylgallate, and Trolox, did not prevent the inhibition of GJIC by H2O2,
which indicated that the effects of H2O2 on GJIC was probably not a
consequence of aqueous free radical damage. The depletion of intracellular
GSH reversed the inhibitory effect of H2O2 on GJIC. The treatment of
glutathione- sufficient cells with H2O2 resulted in the
hyperphosphorylation of connexin43, which is the basic subunit of the
hexameric gap junction protein, as determined by Western blot analysis.
TPA, a well-known tumor promoter, also inhibits GJIC via
hyperphosphorylation of GJIC, which is a result of protein kinase-C
activation. However, H2O2 also induced hyperphosphorylation in
GSH-deficient cells that had normal rates of GJIC. Therefore, the mechanism
of GJIC inhibition must be different from the TPA-pathway and involves GSH.
相似文献