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71.
Summary [2 m+ and [2m°] yeast were transformed to stable leucine prototrophy with the hybrid yeast — E. coli plasmid, pJDB219. This plasmid contains the entire sequence of the endogenous 2 m yeast DNA plasmid in addition to the yeast nuclear LEU2
+ gene and the Co1E1 derivative, pMB9. In the [2 m+] transformants, a new wholly yeast LEU2
+ plasmid, pYX, was generated, probably by a recombination event between pJDB219 and 2 m DNA. The plamid, pYX, in the absence of 2 m DNA, was found to exist in equimolar amounts of two forms, A and B, which probably arise by intramolecular recombination across the inverted repeat sequences of the 2 m DNA portion of the plasmid. pJDB219 was found to require the presence of 2 m DNA to undergo this intramolecular recombination. The results suggest that 2, m DNA and pYX code for a gene product required in this recombination event which pJDB219 cannot produce. 相似文献
72.
Roy G Dumas C Sereno D Wu Y Singh AK Tremblay MJ Ouellette M Olivier M Papadopoulou B 《Molecular and biochemical parasitology》2000,110(2):637-206
We have expressed the reporter firefly luciferase gene (LUC) in Leishmania donovani and Leishmania major either as part of episomal vectors or integrated into the parasite genome under the control of their respective ribosomal promoter regions. An excellent linear correlation between parasite number and luciferase activity was observed with all the transfectants. LUC-expressing recombinant parasites were useful to monitor Leishmania spp. infections in macrophages or in animal models. For prolonged growth in absence of drug selection, such as within animal models, quantitation of parasites is more reliable when the reporter gene LUC is stably integrated in the parasite genome. These recombinant strains should be useful tools to monitor Leishmania growth under a number of conditions. 相似文献
73.
Partial trisomy 6p and partial monosomy 9p from a de novo translocation 46, XY, -9, + DER(9)T(6:9)(p211:p24) 总被引:1,自引:0,他引:1
Melanie S. Eden James W. Thelin Karen Michalski Joyce A. Mitchell 《Clinical genetics》1985,28(5):375-384
This report describes an adult male with a partial trisomy 6p(p211-pter) and a partial monosomy 9p(9p24-pter) resulting from a de novo unbalanced translocation. This patient does not show the classical featured of the 9p partial monosomy syndrome, thus disputing the claim of Hoo et al. (1982) that 9p24 is the critical segment for the monosomy syndrome. Partial trisomy for 6p has only been previously reported in children. In addition to the chromosomal anomalies, the patient has autosomal recessive spinal muscular atrophy with a different age of onset than two affected sibs. Finally, he shows unusual audiologic and ophthalmologic signs nor previously reported as part of the 9p monosomy or 6p trisomy syndromes. 相似文献
74.
Molecular profiling of giant cell tumor of bone and the osteoclastic localization of ligand for receptor activator of nuclear factor kappaB 总被引:1,自引:0,他引:1
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75.
Recombinant Leishmania major secreting biologically active granulocyte-macrophage colony-stimulating factor survives poorly in macrophages in vitro and delays disease development in mice 总被引:3,自引:0,他引:3
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Dumas C Muyombwe A Roy G Matte C Ouellette M Olivier M Papadopoulou B 《Infection and immunity》2003,71(11):6499-6509
Leishmania is an intracellular pathogen that replicates inside macrophages. Activated macrophages produce a specific subset of cytokines that play an important role in the control of Leishmania infections. As part of our interest in developing suicide parasites that produce abortive infections for the purposes of vaccination, we engineered recombinant Leishmania major strains producing biologically active granulocyte-macrophage colony-stimulating factor (GM-CSF). We showed that GM-CSF is being produced in the phagosomes of infected macrophages and that it can be detected in the culture supernatants of both infected macrophages and extracellular parasites. Our data support the notion that GM-CSF secreted by both developmental forms of recombinant L. major can activate macrophages to produce high levels of proinflammatory cytokines such as interleukin-1beta (IL-1beta), IL-6, and IL-18 and various chemokines including RANTES/CCL5, MIP-1alpha/CCL3, MIP-1beta/CCL4, MIP-2/CXCL2, and MCP-1/CCL2, which enhance parasite killing. Indeed, GM-CSF-expressing parasites survive poorly in macrophages in vitro and produce delayed lesion development in susceptible BALB/c mice in vivo. Selective killing of intracellular Leishmania expressing cytokine genes capable of activating cellular responses may constitute a promising strategy to control and/or prevent parasitic infections. 相似文献
76.
77.
Complex CGH alterations on chromosome arm 8p at candidate tumor suppressor gene loci in breast cancer cell lines 总被引:1,自引:0,他引:1
Venter DJ Ramus SJ Hammet FM de Silva M Hutchins AM Petrovic V Price G Armes JE 《Cancer Genetics and Cytogenetics》2005,160(2):134-140
Loss of genetic material from chromosome arm 8p occurs frequently in human breast carcinomas, consistent with this region of the genome harboring one or more tumor suppressor genes (TSGs). We used the complementary techniques of microsatellite-based LOH, high-density FISH, and conventional CGH on 6 breast cancer cell lines (MCF7, SKBR3, T47D, MDA MB453, BT549, and BT474) to investigate the molecular cytogenetic changes occurring on chromosome 8 during tumorigenesis, with particular emphasis on 6 potential TSGs on 8p. We identified multiple alterations of chromosome 8, including partial or complete deletion of 8p or 8q, duplication of 8q, and isochromosome 8q. The detailed FISH analysis showed several complex rearrangements of 8p with differing breakpoints of varying proximity to the genes of interest. High rates of LOH were observed at markers adjacent to or within PCM1, DUSP4/MKP2, NKX3A, and DLC1, supporting their status as candidate TSGs. Due to the complex ploidy status of these cell lines, relative loss of 8p material detected by CGH did not always correlate with microsatellite-based LOH results. These results extend our understanding of the mechanisms accompanying the dysregulation of candidate tumor suppressor loci on chromosome arm 8p, and identify appropriate cellular systems for further investigation of their biological properties. 相似文献
78.
Thierry J Perrier-Gros-Claude JD Clavier B Dumas M Aubert G Barbe G Bland S Boucaud-Maitre Y Boyer M Carricajo A Chomarat M Clergeau P Delubac F Fevre D Fuhrmann C Gravagnat B Lelievre H Letouzey MN Mandjee A Martelet P Meley R Reverdy ME Ros A Roure C Tixier A 《Pathologie-biologie》1999,47(10):1060-1064
Throughout 1996, 22 hospital-based laboratories in the Rh?ne-Alpes region of France collected pneumococcal strains and used a standardized protocol to record the following data; patient age and sex; type of specimen; and determination of susceptibility to at least the following antibiotics: oxacillin 1 microgram and 5 micrograms, erythromycin (Ery), tetracycline (Tet), chloramphenicol (Chl), rifampin (Rmp), and loracarbef. For penicillin-nonsusceptible strains (PNSSs), which were identified based on results with oxacillin, MICs for penicillin G, amoxicillin (Amx), and cefotaxime (Ctx) were determined using the E Test, at the study site and agar dilution at the coordinating center. Of the 1153 strains, 65.5% were from adults and 31.8% from children; patient age was unknown in 2.7% of cases. PNSPs (MIC > 0.06 mg/l) contributed 32.9% of strains (I: 23.3%; R: 9.6%) and were more common in children (41.1%) than in adults (28.1%). The frequency of PNSSs varied across specimen types: 27.9% in blood cultures (305 strains), 15.6% in cerebrospinal fluid (32), 38.7% in protected bronchopulmonary specimens (31), 31.5% in unprotected bronchopulmonary specimens (434), 50.8% in acute otitis media (118), and 34.4% in other specimens (221). Among PNSSs, nonsusceptibility (I + R) to other antibiotics was variable: Ery, 62.1%; Tet, 41.5%; Chl, 40.4%; Rmp, 1.1%. Corresponding figures for the overall strain population were Ery, 33.3%; Tet, 22.7%; Chl, 22.8%; Rmp, 0.9%. In addition, 56.5% of PNSSs exhibited multiple drug resistance. Resistance to amoxicillin (MIC > 2 mg/l) was demonstrated for only 5 strains. No strains were resistant to loracarbef or cefotaxime. Serotypes of the 379 PNSSs were as follows: 23F, 26.6%; 14 (25.6%); 9V (18.2%), 6 (8.7%), 15 (5%), 19 (4.5%). 相似文献
79.
Following invasion of human erythrocytes, the malaria parasite, Plasmodium falciparum, exports proteins beyond the confines of its own plasma membrane to modify the properties of the host red cell membrane. These modifications are critical to the pathogenesis of malaria. Analysis of the P. falciparum genome sequence has identified a large number of molecules with putative atypical signal sequences. The signals remain poorly characterized; however, a number of molecules with these motifs localize to the host erythrocyte. To examine the role of these atypical signal sequences in the export of parasite proteins, we have generated transfected parasites expressing a chimeric protein comprising the N-terminal region of the P. falciparum ring-infected erythrocyte surface antigen (RESA) appended to green fluorescent protein (GFP). This N-terminal region contains a hydrophobic stretch of amino acids that is presumed to act as a noncanonical secretory signal sequence. Modulation of the timing of transgene expression demonstrates that trafficking of malaria proteins into the host erythrocyte is dependent on both the presence of an appropriate transport signal and the timing of expression. Transgene expression under the control of a trophozoite-specific promoter mistargets the chimeric molecule to the parasitophorous vacuole surrounding the parasite. However, expression of RESA-GFP in schizont stages, under the control of the RESA promoter, enables correct trafficking of a population of the chimeric protein to the host erythrocyte. 相似文献
80.
Gastric helicobacter infection induces a Th2 phenotype but does not elevate serum cholesterol in mice lacking inducible nitric oxide synthase
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Persistent Helicobacter felis infection in (C57BL/6 x 129SvEv)F1 mice induces chronic gastritis. Expression of inducible nitric oxide synthase (iNOS) is upregulated in response to Helicobacter infection. In this study, 20 10-week-old iNOS-/- mice and 20 wild-type [(C57BL/6 x 129SvEv)F1] mice were infected with H. felis by oral gavage and were assessed histologically and serologically at 32 weeks postinfection. Equal numbers of uninfected controls were sham inoculated. The mice were scored for severity of gastric inflammation, hyperplasia, glandular atrophy, and mucous metaplasia in the corpus and for the level of helicobacter colonization. The immunoglobulin G1 (IgG1), IgG2a, and IgG2c antibody responses to H. felis were determined. As a secondary measure, serum cholesterol levels were assessed. iNOS-/- mice have a propensity for increased serum cholesterol, and although controversial, several human epidemiologic studies have demonstrated an association between Helicobacter infection and several risk factors for cardiovascular disease, including elevated serum cholesterol. Nevertheless, no differences in serum cholesterol levels were observed between the H. felis-infected and -uninfected iNOS-/- mice in this study. The uninfected animals had minimal to no gastric pathology. The gastric pathology scores for the infected animals were reduced significantly in the iNOS-deficient mice relative to those for the wild-type mice (all P <0.01). Helicobacter-infected iNOS-/- mice had chronic lymphoid infiltration and negligible to mild glandular atrophy and mucous metaplasia in the fundic mucosa, while H. felis-infected wild-type mice had severe atrophic and metaplastic mucosal changes. The atrophic gastritis in the infected wild-type mice, particularly the female mice, was also accompanied by greater granulocytic infiltration, antral hyperplasia, and diminished antral colonization, unlike that in the infected iNOS-/- mice. iNOS-/- mice developed significantly lower Th1-associated IgG2c antibody responses to H. felis (P <0.0003); the Th2-associated IgG1 responses were similar (P=0.09), suggesting a greater effect of the iNOS defect on Th1 responses. H. felis colonization was significantly greater in the iNOS-deficient mice. These findings are indicative of an impaired Th1 component of the H. felis-induced inflammatory response when the influence of iNOS is removed. 相似文献