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91.
In Vivo Complementation of ureB Restores the Ability of Helicobacter pylori To Colonize 总被引:4,自引:0,他引:4
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Kathryn A. Eaton Joanne V. Gilbert Elizabeth A. Joyce Amy E. Wanken Tracy Thevenot Patrick Baker Andrew Plaut Andrew Wright 《Infection and immunity》2002,70(2):771-778
The objective of this study was to determine (i) if complementation of ureB-negative Helicobacter pylori restores colonization and (ii) if urease is a useful reporter for promoter activity in vivo. Strains used were M6, M6DeltaureB, and 10 recombinant derivatives of M6 or M6DeltaureB in which urease expression was under the control of different H. pylori promoters. Mice were orally inoculated with either the wild type or one of the mutant strains, and colonization, in vivo urease activity, and extent of gastritis were determined. Of eight M6DeltaureB recombinants tested, four colonized mice. Of those, three had the highest in vitro urease activity of any of the recombinants, significantly different from that of the noncolonizing mutants. The fourth colonizing recombinant, with ureB under control of the cag-15 promoter, had in vitro urease activity which did not differ significantly from the noncolonizing strains. In vivo, urease activities of the four colonizing transformants and the wild-type control were indistinguishable. There were no differences in gastritis or epithelial lesions between mice infected with M6 and those infected with the transformants. These results demonstrate that recovery of urease activity can restore colonizing ability to urease-negative H. pylori. They also suggest that cag-15 is upregulated in vivo, as was previously suggested by demonstrating that it is upregulated upon contact with epithelial cells. Finally, our results suggest that total urease activity and colonization density do not contribute to gastritis due to H. pylori. 相似文献
92.
Lai M Wang F Rohan JG Maeno-Hikichi Y Chen Y Zhou Y Gao G Sather WA Zhang JF 《Nature neuroscience》2005,8(4):435-442
Voltage-gated Ca(2+) channels (VGCCs) are important in regulating a variety of cellular functions in neurons. It remains poorly understood how VGCCs with different functions are sorted within neurons. Here we show that the t-complex testis-expressed 1 (tctex1) protein, a light-chain subunit of the dynein motor complex, interacts directly and selectively with N- and P/Q-type Ca(2+) channels, but not L-type Ca(2+) channels. The interaction is insensitive to Ca(2+). Overexpression in hippocampal neurons of a channel fragment containing the binding domain for tctex1 significantly decreases the surface expression of endogenous N- and P/Q-type Ca(2+) channels but not L-type Ca(2+) channels, as determined by immunostaining. Furthermore, disruption of the tctex1-Ca(2+) channel interaction significantly reduces the Ca(2+) current density in hippocampal neurons. These results underscore the importance of the specific tctex1-channel interaction in determining sorting and trafficking of neuronal Ca(2+) channels with different functionalities. 相似文献
93.
Richard D Neal Victoria L Allgar Nasreen Ali Brenda Leese Phil Heywood Gill Proctor Joyce Evans 《The British journal of general practice》2007,57(536):212-219
BACKGROUND: Very few studies have reported cancer outcomes of patients referred through different routes, despite the prominence of current UK cancer urgent referral guidance. AIM: This study aimed to compare outcomes of cancer patients referred through the urgent referral guidance with those who were not, with respect to stage at diagnosis, survival, and delays in diagnosis. Design of study: Analysis of hospital records. SETTING: One hospital trust in England. METHOD: The records of 889 patients diagnosed in 2000-2001 with one of four types of cancer were analysed: 409 with lung cancer; 239 with colorectal cancer; 146 with prostate cancer; and 95 with ovarian cancer. Outcome measures were diagnostic stage, survival, referral and secondary care delays. RESULTS: For lung cancer, urgent referrals had more advanced TNM (tumor, node, metastasis) stage than patients diagnosed through other routes (P = 0.035) and poorer survival (P = 0.020). There was no difference in stage or survival for the other cancers. For each cancer, a higher proportion of urgent referrals was seen within 2 weeks. Secondary care delays for lung and colorectal cancer were shorter for inter-specialty referrals. CONCLUSION: For patients with lung cancer, the guidance appears to be prioritising those in the more advanced stages of disease. This was not the case for the other three cancers. Referral delays were shorter for patients urgently referred, as is the intention of the guidance. The avoidance of delays in outpatient diagnostics probably accounts for shorter secondary care delays for inter-specialty referrals. 相似文献
94.
95.
Catt SL; Sakkas D; Bizzaro D; Bianchi PG; Maxwell WM; Evans G 《Molecular human reproduction》1997,3(9):821-825
Controlling the sex of offspring by the separation of X and Y
chromosome-bearing spermatozoa using flow cytometry has been reported as a
clinical technique aiding prevention of X-linked diseases. Although this
technique has resulted in several hundred normal births in animals and at
least one human birth, there is still concern over its genetic safety due
to the involvement of two potentially mutagenic agents: UV light and the
fluorochrome dye, Hoechst 33342 (H33342). Human spermatozoa, particularly
those considered abnormal, may be more likely to suffer DNA damage
following exposure to mutagenic agents, compared with other mammalian
species. The stability of normal fresh and decondensed human spermatozoa
were examined after exposure to a range of levels of UV and H33342
staining, using an assay that detects endogenous nicks in the DNA of
spermatozoa. The stability of abnormal and normal, fresh and frozen-thawed
human spermatozoa was examined following UV laser, H33342 staining and flow
cytometry treatments utilizing the same assay. There was an increase in the
presence of endogenous nicks when spermatozoa were decondensed compared
with fresh spermatozoa. There was no increase in the incidence of nicks in
any group of spermatozoa after UV and fluorochrome exposure compared with
controls without exposure.
相似文献
96.
Multicenter evaluation of a Candida albicans peptide nucleic acid fluorescent in situ hybridization probe for characterization of yeast isolates from blood cultures
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Wilson DA Joyce MJ Hall LS Reller LB Roberts GD Hall GS Alexander BD Procop GW 《Journal of clinical microbiology》2005,43(6):2909-2912
We evaluated aliquots from 244 clinical blood culture bottles that demonstrated yeasts on Gram stain using a Candida albicans peptide nucleic acid (PNA) fluorescent in situ hybridization (FISH) probe. The sensitivity, specificity, positive predictive value, and negative predictive value of the C. albicans PNA FISH test in this study were 99%, 100%, 100%, and 99.3%, respectively. 相似文献
97.
Winberg JO; Hammami-Hauasli N; Nilssen O; Anton-Lamprecht I; Naylor SL; Kerbacher K; Zimmermann M; Krajci P; Gedde-Dahl T Jr; Bruckner-Tuderman L 《Human molecular genetics》1997,6(7):1125-1135
Dystrophic epidermolysis bullosa (EBD) is a clinically heterogeneous skin
disorder, characterized by abnormal anchoring fibrils (AF) and loss of
dermal-epidermal adherence. EBD has been linked to the COL7A1 gene at
chromosome 3p21 which encodes collagen VII, the major component of the AF.
Here we investigated two unrelated EBD families with different clinical
phenotypes and novel combinations of recessive and dominant COL7A1
mutations. Both families shared the same recessive heterozygous 14 bp
deletion at the exon-intron 115 boundary of the COL7A1 gene. The deletion
caused in-frame skipping of exon 115 and the elimination of 29 amino acid
residues from the pro-alpha1(VII) polypeptide chain. As a result,
procollagen VII was not converted to collagen VII and the C-terminal NC-2
propeptide which is normally removed from the procollagen VII prior to
formation of the anchoring fibrils was retained in the skin. All affected
individuals also carried missense mutations in exon 73 of COL7A1 which lead
to different glycine- to-arginine substitutions in the triple-helical
domain of collagen VII. Combination of the deletion mutation with a G2009R
substitution resulted in a mild phenotype. In contrast, combination of the
deletion with a G2043R substitution led to a severe phenotype. The G2043R
substitution was a de novo mutation which alone caused a mild phenotype.
Thus, different combinations of dominant and recessive COL7A1 mutations can
modulate disease activity of EBD and alter the clinical presentation of the
patients.
相似文献
98.
Type 1 and type 2 tumor infiltrating effector cell subpopulations in progressive breast cancer 总被引:4,自引:0,他引:4
Effector T cells fall into two subpopulations based on cytokine-secretion. Type 1 cells secrete IFN-gamma, whereas type 2 cells secrete IL-4, IL-10, and GM-CSF. NKT cells represent a third subpopulation that secretes similar cytokines and have been associated with immunoregulation. Using the TS/A adenocarcinoma, we assessed the phenotype and kinetics of tumor-infiltrating lymphocytes (TIL) in mice challenged subcutaneously in the mammary region. Flow cytometric analysis shows that T cells do not infiltrate the primary tumor site until days 7-14 following tumor challenge. Both CD4 and CD8 TILs were predominantly CD44(High) and expressed CD25, CD69, and CD95 cell surface activation markers. Activated CD4/CD44(High) TIL numbers reached peak levels at day 21 that precipitously decreased by day 28 whereas corresponding CD8 cell numbers progressively increased, however, at lower levels and with later kinetics. Intracellular cytokine staining showed that greater numbers of IL-4-producing Th2 cells were elicited and with earlier kinetics than that of IFN-gamma-producing Th1 cells. T cells co-expressing DX5 (CD3(+)/DX5(+)) emerged (>21 days), suggesting a recruitment of NK-like T cells at later stages of tumor progression. Moreover, tumors selectively up-regulated TGF-beta, MIF, and IP-10 gene expression at times as early as day 4, with peak levels at day 7 in vivo. Such gene expression remained elevated and correlated with a continued progression in tumor growth suggesting that preferential effector cell recruitment and production of select factors during different stages of tumor maturation may aid in regulating effective endogenous antitumor responses in progressive breast cancer. 相似文献
99.
Aléssio AC Annichino-Bizzacchi JM Bydlowski SP Eberlin MN Vellasco AP Höehr NF 《American journal of medical genetics. Part A》2004,(3):256-260
Hyperhomocysteinemia is a risk factor for thrombosis, and methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) polymorphisms, folate, and B12 levels could contribute to plasma homocysteine (Hcy) variation. Although well established in adults, few studies have been performed in childhood. In this study, we investigated association of polymorphisms C677T and A1298C in the MTHFR gene and A66G in the MTRR gene with Hcy levels in children. These polymorphisms, as well as Hcy, folate, and vitamin B12 levels were investigated in 220 normal children with ages ranging from 1 to 8 years. Plasma Hcy, folate, and vitamin B12 levels were normal in all children. None of the polymorphisms could be considered an independent risk factor for hyperhomocysteinemia during childhood. The median Hcy levels in 37 children (17%) doubly heterozygous for C677T and A1298C mutations in the MTHFR gene were not different from the other genotypes. However, the association of the different genotypes with Hcy, folate, and vitamin B12 levels demonstrated significant P-values. The folate levels demonstrated a statistically significant decrease (P = 0.0477) from the C677T mutation in the MTHFR gene (TT genotype) when compared to the other groups. Folate was the only independent risk factor for hyperhomocysteinemia. Thus, monitoring the concentrations of folate would be more helpful for evaluating hyperhomocysteinemia and for preventing cardiovascular disease. 相似文献
100.
Tissue macrophages, which participate in chronic synovial inflammation, differentiate from haemopoietic precursors in bone marrow and subsequently in tissue. During this process, they acquire attributes which are essential for their function in inflammation. Modulation of this process may represent a means of regulating inflammatory competence of macrophages in inflammatory joint disease. The action of aurothiomalate (ATM), an anti-rheumatic gold compound, on the differentiation of a promonocytic cell line (U937) was, therefore, examined inin vitro systems. U937 cells exposed to retinoic acid (RA) for 4 days or to phorbol myristate acetate (PMA) for 2 days acquired characteristics of macrophages, including the capacity to produce superoxide (O
2
–
), responsiveness to formyl-methionyl-leucyl-phenylalanine (fMLP) and reduced proliferation. The activity of transglutaminase also increased in RA-exposed cultures. The effect of ATM exposure on acquisition of these characteristics was small and differed between RA- and PMA-stimulated cells. 相似文献