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91.
Cloning, expression, and mapping of the Staphylococcus aureus alpha-hemolysin determinant in Escherichia coli K-12. 总被引:7,自引:7,他引:7
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A fragment of Staphylococcus aureus DNA encoding the alpha-hemolysin determinant was cloned from strain Wood 46 by inserting Sau3A-generated genomic DNA fragments between the BamHI sites of the lambda replacement vector L47.1. Phages expressing alpha-hemolysin were detected by overlaying plaques formed from several thousand independent recombinant phage with erythrocytes and looking for zones of hemolysis. One phage expressing alpha-hemolysin was purified and named lambda w alpha 3. This was subsequently shown to contain a 10.2-kilobase pair insert of S. aureus DNA. A 7.6-kilobase pair HindIII fragment encoding the alpha-hemolysin was subcloned from lambda w alpha 3 into the plasmid vector pACYC184 to form the hybrid plasmid pDU1148. Escherichia coli K-12 cells harboring pDU1148 synthesized a low level of alpha-hemolysin which remained associated with the cells and was not secreted into culture supernatants. When the same strain was stabbed onto blood agar plates, no zones of hemolysis were detected after overnight growth at 37 degrees C but hemolysis developed if the plates were left at room temperature for 48 h. By introducing specific deletions or Tn5 insertions into plasmid pDU1148, the alpha-hemolysin gene was mapped to a region within a 3.3-kilobase pair EcoRI-HindIII fragment which was subcloned onto the vector plasmid pBR322. A specific enzyme-linked immunosorbent assay with peroxidase-labeled rabbit anti-alpha-hemolysin antibodies was used to measure the levels of alpha-hemolysin antigen expressed in E. coli K-12 cells harboring pDU1148 or a variety of pDU1148::Tn5 and pDU1148 deletion mutants. 相似文献
92.
While both in vivo and in vitro evidence has suggested that liver cells undergo apoptosis in response to dengue virus infection, little is known about the mechanism of induction. Given that the p53 tumour suppressor gene is a key mediator of apoptosis, we sought to define the role of this gene in response to dengue virus infection. After infection, a p53 wild type liver cell line (HepG2) showed changes consistent with apoptosis including alterations of cell morphology, cellular detachment and DNA laddering. However, p53 was neither up-regulated, nor showed any evidence of complexing with dengue virus proteins as determined by immunoprecipitation. Infection of a p53 null liver cell line (Hep3B) also produced changes consistent with the induction of apoptosis. While the profile of the cells undergoing apoptosis in each cell line was similar as determined by flow cytometry, the absolute levels were markedly different with up to 90% of Hep3B cells undergoing apoptosis compared to only 20% of HepG2 cells at day 5 post infection. By day 7, all Hep3B infected cells were dead. In contrast, it proved possible to culture dengue virus infected HepG2 cells for 3 months. Viral progeny released from the p53 null cell line were nine-fold higher per attached cell than from the p53 wild type cell line. These results suggest that, while induction of apoptosis in liver cells is mediated by a non-p53 regulated pathway, p53 may play a role in restricting the level of viral progeny to below a critical level at which apoptosis is triggered. 相似文献
93.
94.
Association of ambient air‐pollution levels with acute asthma exacerbation among children in Singapore 总被引:1,自引:0,他引:1
BACKGROUND: Air-pollution levels have been shown to be associated with increased morbidity of respiratory diseases. METHODS: Data for ambient air-pollutant levels, meteorologic factors, and hospitalization or emergency room (ER) visits for acute asthma in Singapore children over a 5-year period (1990-4) were obtained and analyzed for associations by time-series methods. RESULTS: Throughout this period, the annual mean and 24-h mean levels for sulfur dioxide (SO2), nitrogen dioxide (NO2), and total suspended particles (TSP) and maximum 1-h daily average for ozone were generally within the air-quality guidelines established by the World Health Organization (WHO). However, positive correlation between levels of each of these pollutants and daily ER visits for asthma was observed in children aged 3-12 years, but not among adolescents and young adults (13-21 years old). The association with SO2 and TSP persisted after standardization for meteorologic and temporal variables. An adjusted increase in 2.9 ER visits for every 20 microg/m3 increase in atmospheric SO2 levels, lagged by 1 day, was observed on days when levels were above 68 microg/m3. With TSP, an adjusted increase of 5.80 ER visits for every 20 microg/m3 increase in its daily atmospheric levels, lagged by 1 day, was observed on days with levels above 73 microg/m3. Similar results were also obtained after controlling for autocorrelation by time-series analysis. CONCLUSIONS: These associations were observed even though the overall levels of all pollutants were generally within the air-quality guidelines established by the WHO. These findings suggest that asthmatic children are susceptible to increased levels of air pollutants, particularly SO2 and TSP, although the ambient levels are generally within "acceptable" ranges. 相似文献
95.
RhoC is dispensable for embryogenesis and tumor initiation but essential for metastasis 总被引:14,自引:0,他引:14
Hakem A Sanchez-Sweatman O You-Ten A Duncan G Wakeham A Khokha R Mak TW 《Genes & development》2005,19(17):1974-1979
The Rho proteins are Ras-related guanosine triphosphatases (GTPases) that function in cytoskeletal reorganization, cell migration, and stress fiber and focal adhesion formation. Overexpression of RhoC enhances the ability of melanoma cells to exit the blood and colonize the lungs. However, in vivo confirmation of RhoC's role in metastasis has awaited a RhoC-deficient mouse model. Here we report the generation of RhoC-deficient mice and show that RhoC is dispensable for embryonic and post-natal development. We demonstrate that loss of RhoC does not affect tumor development but decreases tumor cell motility and metastatic cell survival leading to a drastic inhibition of metastasis. 相似文献
96.
Porphyromonas gingivalis, a Gram-negative oral anaerobe, interacts with epithelium lining the gingival sulcus. Continuing our studies on the role of gingipain cysteine proteinases in P. gingivalis adherence to epithelial cells, we showed that antibody raised to the recombinant adhesin domain of arg-gingipain A blocked bacterial attachment, providing new additional evidence that P. gingivalis adherence to epithelial cells is mediated by gingipain adhesin peptides. 相似文献
97.
Richard Meehan Ulric Duncan Laureen Neale Gerald Taylor Harold Muchmore Nan Scott Keith Ramsey Eric Smith Paul Rock Randall Goldblum Charles Houston 《Journal of clinical immunology》1988,8(5):397-406
We investigated the effects on immune function after progressive hypobaric hypoxia simulating an ascent to 25,000 ft (7620 m) over 4 weeks. Multiple simultaneousin vitro andin vivo immunologic variables were obtained from subjects at sea level, 7500 ft (2286 m), and 25,000 ft during a decompression chamber exposure. Phytohemag-glutinin-stimulated thymidine uptake and protein synthesis in mononuclear cells were reduced at extreme altitudes. Mononuclear-cell subset analysis by flow cytometry disclosed an increase in monocytes without changes in B cells or T-cell subsets. Plasma IgM and IgA but not IgG levels were increased at altitudes, whereas pokeweed mitogen-stimulatedin vitro IgG, IgA, and IgM secretion was unchanged. During exposure to 25,000 ft,in vitro phytohemagglutinin-stimulated interferon production and natural killer-cell cytotoxicity did not change statistically, but larger intersubject differences occurred. IgA and lysozyme levels (nasal wash) and serum antibodies to nuclear antigens were not influenced by altitude exposure. These results suggest that T-cell activation is blunted during exposure to severe hypoxemia, whereas B-cell function and mucosal immunity are not. Although the mechanism of alteredin vitro immune responsiveness after exposure to various environmental stressors has not been elucidated in humans, hypoxia may induce alterations in immune regulation as suggested byin vitro immune assays of effector-cell function.Some of this study's results were presented as an abstract at the FASEB meeting in St. Louis, Missouri, 1986. 相似文献
98.
Porphyromonas gingivalis, the major etiologic agent of chronic periodontitis, produces a broad spectrum of virulence factors, including outer membrane vesicles. In this study, we investigated the capacity of P. gingivalis vesicles to promote the shedding or cleavage of the lipopolysaccharide (LPS) receptor CD14 from the surface of human U937 macrophage-like cells. SDS-PAGE/Western immunoblotting analysis of gingival crevicular fluid samples from patients affected by moderate or advanced periodontitis revealed the presence of soluble CD14 and CD14 fragments, thus supporting the hypothesis of an in vivo shedding and cleavage of CD14 receptors. Flow cytometry analysis of macrophage-like cells treated with a vesicle-containing culture supernatant of P. gingivalis showed a significant decrease in the binding of anti-human CD14 to the cell surface. However, no accumulation of soluble CD14 or immunoreactive CD14 fragments in the assay supernatant could be demonstrated by ELISA. Treatment of macrophage-like cells with various concentrations of P. gingivalis vesicles substantially suppressed TNF-alpha production triggered by Escherichia coli LPS. This suppressive effect was much less important using heat-treated vesicles or in the presence of leupeptin, a gingipain inhibitor, during the treatment. Recombinant human CD14 receptors were found to be susceptible to proteolytic degradation by P. gingivalis vesicles. A purified Arg-gingipain preparation produced much more degradation than a Lys-gingipain preparation. This study provides evidence that P. gingivalis outer membrane vesicles contribute to the loss of membrane-bound CD14 receptors and that gingipains degrade this LPS receptor. Such a phenomenon, which results in an hyporesponsiveness of macrophages to LPS stimulation, may contribute to an increased capacity of P. gingivalis, and other periodontopathogens, to evade the host immune system mechanisms. 相似文献
99.
IgA, IgM and IgG anti-M. leprae antibodies in babies of leprosy mothers during the first 2 years of life.
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IgA, IgM and IgG anti-M. leprae antibody activity was estimated by solid phase radioimmunoassay in repeated serum samples from cord sera to sera taken 2 years after birth from 29 babies of mothers with lepromatous leprosy (Group 1) and 16 babies of mothers with tuberculoid leprosy and non-leprosy control mothers (Group 2). IgA anti-M. leprae antibody activity could be detected in 30% and IgM anti-M. leprae antibody activity in 50% of cord sera from Group 1, but not in any of the cord sera from Group 2. After birth, there was a significantly higher increase of IgA and IgM anti-M. leprae antibody activity in sera taken 3-6 months after birth from babies of Group 1 compared to Group 2, but the IgA and IgM activity in sera taken after 6 months of age showed the same increase in the two groups. IgG anti-M. leprae antibody activity showed a marked decrease in sera from both Groups 1 and 2 taken 3-6 and 6-9 months after birth compared to the activity in the cord sera. No increase of the IgG activity could be demonstrated even in sera taken 15-24 months after birth in any of the two groups. These findings are discussed in relation to possible transfer of M. leprae bacilli across the placenta, the influence of M. leprae and other mycobacteria exposure on the antibody activity, the poor IgG anti-M. leprae antibody response and subclinical leprosy infection in babies exposed to leprosy below 2 years of age. 相似文献
100.