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61.
Morphology of cells and hemagglutinogens of Bordetella species: resolution of substructural units in fimbriae of Bordetella pertussis. 总被引:1,自引:7,他引:1 下载免费PDF全文
The morphology of cells and the hemagglutinogens isolated from cultures of Bordetella pertussis, Bordetella bronchiseptica, and Bordetella parapertussis were studied by electron microscopy with the negative-staining technique. Cells of all three species had long, thin (3 nm thick), peritrichously arranged fimbriae on the cell surface. Similar structures were found in purified hemagglutinogen preparations together with shorter fimbrial structures 3 nm thick and from 40 to 100 nm long. In one experiment, long, thin fimbriae isolated from B. pertussis were found to be arranged in a crystalline structure on the specimen grid after negative staining. Optical diffraction analysis with a filtering technique performed on micrographs of these structures revealed 12.5-nm-long substructures within individual fimbriae. Further analysis resolved each of these structures into three globules, a central globule 3.5 nm in diameter and two diametrically opposed globules 2.5 nm in diameter. Based on this substructural composition, it is suggested that subunits of the individual fimbriae are connected by fragile regions. The presence of such regions would explain the size heterogeneity of the filamentous structures observed in preparations of hemagglutinogens isolated from cultures of B. pertussis and B. bronchiseptica. The concept that the short filamentous structures present in purified preparations of hemagglutinogens originate from the surface fimbriae present on the cells is supported. 相似文献
62.
Application of mycobacterial proteomics to vaccine design: improved protection by Mycobacterium bovis BCG prime-Rv3407 DNA boost vaccination against tuberculosis 总被引:4,自引:0,他引:4 下载免费PDF全文
Mollenkopf HJ Grode L Mattow J Stein M Mann P Knapp B Ulmer J Kaufmann SH 《Infection and immunity》2004,72(11):6471-6479
Information from comparative proteome analysis of Mycobacterium tuberculosis and Mycobacterium bovis bacillus Calmette-Guerin (BCG) principally allows prediction of potential vaccine candidates. Thirty-six M. tuberculosis DNA vaccine candidates identified by comparative proteome analysis were evaluated in the mouse model for protection against low-dose aerosol M. tuberculosis infection. We identified the DNA vaccine candidate Rv3407 as a protective antigen and analyzed putative major histocompatibility complex class I epitopes by computational predictions and gamma interferon Elispot assays. Importantly, we discovered that the DNA vaccine Rv3407 improved the efficacy of BCG vaccination in a heterologous prime-boost vaccination protocol. Our data demonstrate the rationale of a combination of proteomics, epitope prediction, and broad screening of putative antigens for identification of novel DNA vaccine candidates. Furthermore, our experiments show that heterologous prime-boost vaccination with a defined antigen boost "on top" of a BCG primer provides superior protection against tuberculosis over vaccination with BCG alone. 相似文献
63.
Inhibition of CDK activity and PCNA-dependent DNA replication by p21 is blocked by interaction with the HPV-16 E7 oncoprotein 下载免费PDF全文
Jens Oliver Funk Shou Waga Jo Beth Harry Erik Espling Bruce Stillman Denise A. Galloway 《Genes & development》1997,11(16):2090-2100
p21 inhibits cyclin-dependent kinase (CDK) activity and proliferating cell nuclear antigen (PCNA)-dependent DNA replication by binding to CDK/cyclin complexes and to PCNA through distinct domains. The human papillomavirus (HPV)-16 E7 oncoprotein (16E7) abrogated a DNA damage-induced cell cycle arrest in vivo, despite high levels of p21. Using cell lysates and purified proteins we show that 16E7 prevented p21 both from inhibiting CDK2/cyclin E activity and PCNA-dependent DNA replication, whereas the nononcogenic HPV-6 E7 had reduced effects. Inactivation of both inhibitory functions of p21 was attained through binding between 16E7 and sequences in the carboxy-terminal end of p21 that overlap with the PCNA-binding site and the second p21 cyclin-binding motif. These data imply that the carboxyl terminus of p21 simultaneously modulates both CDK activity and PCNA-dependent DNA replication and that a single protein, 16E7, can override this modulation to disrupt normal cell cycle control. 相似文献
64.
Black GF Weir RE Chaguluka SD Warndorff D Crampin AC Mwaungulu L Sichali L Floyd S Bliss L Jarman E Donovan L Andersen P Britton W Hewinson G Huygen K Paulsen J Singh M Prestidge R Fine PE Dockrell HM 《Clinical and diagnostic laboratory immunology》2003,10(4):602-611
We have previously shown that young adults living in a rural area of northern Malawi showed greater gamma interferon (IFN-gamma) responses to purified protein derivatives (PPD) prepared from environmental mycobacteria than to PPD from Mycobacterium tuberculosis. In order to define the mycobacterial species to which individuals living in a rural African population have been exposed and sensitized, we tested T-cell recognition of recombinant and purified antigens from M. tuberculosis (38 kDa, MPT64, and ESAT-6), M. bovis (MPB70), M. bovis BCG (Ag85), and M. leprae (65 kDa, 35 kDa, and 18 kDa) in >600 non-M. bovis BCG-vaccinated young adults in the Karonga District of northern Malawi. IFN-gamma was measured by enzyme-linked immunosorbent assay (ELISA) in day 6 supernatants of diluted whole-blood cultures. The recombinant M. leprae 35-kDa and 18-kDa and purified native M. bovis BCG Ag85 antigens induced the highest percentages of responders, though both leprosy and bovine tuberculosis are now rare in this population. The M. tuberculosis antigens ESAT-6 and MPT64 and the M. bovis antigen MPB70 induced the lowest percentages of responders. One of the subjects subsequently developed extrapulmonary tuberculosis; this individual had a 15-mm-diameter reaction to the Mantoux test and responded to M. tuberculosis PPD, Ag85, MPT64, and ESAT-6 but not to any of the leprosy antigens. We conclude that in this rural African population, exposure to M. tuberculosis or M. bovis is much less frequent than exposure to environmental mycobacteria such as M. avium, which have antigens homologous to the M. leprae 35-kDa and 18-kDa antigens. M. tuberculosis ESAT-6 showed the strongest association with the size of the Mantoux skin test induration, suggesting that among the three M. tuberculosis antigens tested it provided the best indication of exposure to, or infection with, M. tuberculosis. 相似文献
65.
The Dominant Epitope of Borrelia garinii Outer Surface Protein C Recognized by Sera from Patients with Neuroborreliosis Has a Surface-Exposed Conserved Structural Motif 总被引:1,自引:0,他引:1 下载免费PDF全文
Marianne J. Mathiesen Arne Holm Michael Christiansen Jens Blom Klaus Hansen Sren
stergaard Michael Theisen 《Infection and immunity》1998,66(9):4073-4079
Epitope mapping of outer surface protein C (OspC) by using sera from patients with neuroborreliosis led to the identification of one single major immunodominant epitope within the C-terminal 10 amino acid residues. Peptide binding studies and alanine replacement scanning of the C-terminal decapeptide, PVVAESPKKP, revealed a critical role for the PKKP sequence and its terminal carboxyl group for the binding of immunoglobulin M (IgM) antibodies from patients with Lyme borreliosis. Electron microscopy of antibody-labeled spirochetes indicated that the C-terminal region is exposed on the surface of the spirochete. Based on homology to proteins of known function, this region most probably adopts a polyproline II-like helix, which is found in surface-exposed structures involved in protein-protein interactions. This structural motif is highly conserved in Borrelia species causing Lyme borreliosis and subjected to purifying selection. We suggest that the abundance of the C-terminal region of OspC on the surface of B. burgdorferi allows a multimeric high-avidity interaction between the spirochete and surface Igs on B cells. The resulting cross-linking of surface Igs on B cells may induce a T-cell-independent B-cell activation without IgM-to-IgG switching, thus explaining the lack of IgG antibodies to OspC in neuroborreliosis. 相似文献
66.
67.
Graupner J Göbels K Grobusch MP Lund A Richter J Häussinger D 《Parasitology research》2005,96(3):162-165
Falciparum Malaria is hyperendemic in southern Nigeria and chloroquine resistance is an increasing problem. Therefore, the parasitological and haematological response to treatment with amodiaquine was studied in children under 5 years during a 14-day follow-up. Of 105 children who accomplished the study (out of 114 who were enrolled), 95.3% were parasite-negative on thick blood film on day 7, which decreased to 89.5% on day 14. The haemoglobin levels increased on average by 1.3% on day 14 (±1.9) and more pronounced in children with anaemia < 10 g/dl on enrolment. The number of patients with adverse events (mainly pruritus and nausea) was few. This study shows that amodiaquine is effective, safe and affordable in an area with high resistance to chloroquine. 相似文献
68.
The objective was to investigate glucose-6-phosphate dehydrogenase (G6PD) activity in monolayer cultures of thyroid epithelial cells and to examine whether inhibition of nitric oxide synthase affects activity of G6PD or oxygen sensitivity of the assay. Primary cultures without TSH addition prior to experiments demonstrated a TSH-dependent increase in G6PD activity. G6PD activity was higher in F12 medium than in a serum-free physiological medium. Secondary cultures grown in F12 medium demonstrated a diminished activity of G6PD and a lack of response to TSH. In the serum-free physiological medium, G6PD activity was comparable to that found in primary cultures and a response to high concentrations of TSH was maintained. In primary cultures grown in F12 medium devoid of TSH, G6PD activity decreased dose-dependently when nitric oxide synthase activity was inhibited. The oxygen sensitivity of the assay was comparable to that reported previously in malignant cells and correlated with the activity of G6PD in primary cultures. We suggest that thyroid epithelial cells may be an appropriate system to investigate oxygen sensitivity of the G6PD assay as the cells demonstrate a reduced oxygen sensitivity which can be influenced by culture conditions. 相似文献
69.
Behavioural and hypothalamic-pituitary-adrenal (HPA) axis responses were investigated in farm mink (Mustela vison) selected for either confident or fearful behaviour for nine generations.Two groups of 2-year-old confident (n=12) and fearful (n=12) female mink were given the serotonin (5-HT) 1A receptor agonist buspirone (1.25 mg/kg/day), whereas two other groups of 2-year-old confident (n=12) and fearful (n=12) female mink were given saline, continuously for 5 weeks via osmotic minipumps. Behavioural reactions towards a novel object and towards humans were tested after 19-25 days, and HPA axis reactivity [adrenocorticotropic hormone (ACTH), cortisol] was measured after 28-31 days of treatment. Confident mink were more exploratory than fearful mink towards humans and a novel object. Confident mink spent more time in contact with the object than did fearful mink during saline-but not during buspirone-treatment. buspirone increased approach-withdrawal conflict behaviour towards a object in fearful mink only. The chronic dose of buspirone did not reduce fear towards humans and did not affect latencies to reaction, number of contacts, number and duration of manipulations, and stereotypic behaviour in a Novel Object test. Different HPA axis responses have emerged between confident and fearful mink, together with a different degree of fear-related behaviour. Fearful mink have a higher cortisol combined with a lower ACTH secretion than confident mink in response to capture and blood sampling. The central serotonergic system may be involved, and even though the precise underlying mechanisms are presently unknown, treatment with a 5-HT(1A) receptor agonist reduces the difference between confident and fearful mink in HPA axis reactivity. 相似文献
70.