| 1. |
- Akhiani, Aliasghar, 1957, et al.
(författare)
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Immunological cross reactivity between Schistosoma mansoni and cholera toxin
- 1997
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Ingår i: Parasite Immunol. ; 19:8, s. 355-61
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Tidskriftsartikel (refereegranskat)abstract
- Intranasal administration of schistosome antigens in combination with appropriate adjuvant may be an effective route for immunization against schistosomes, since the lungs represent an important site of elimination of schistosomulae. Our previous studies have shown that in mice intranasal administration of cholera toxin (CT) before infection with Schistosoma mansoni results in an enhancement of the worm burden in comparison to nontreated infected animals. In the present study, it was shown that mice treated intranasally with CT displayed high numbers of schistosome-reactive IgM-secreting cells in the spleen as well as high levels of schistosome-reactive serum IgM antibodies, whereas no significant immunological response against two other antigens, ovalbumin (OVA) or keyhole limpet haemocyanin (KLH) was noted. Sera from mice treated intranasally with CT recognized a 22 kDA antigen on SWAP blots. This band was not demonstrable after absorption of the sera with SWAP. These findings indicate a possible cross reactivity between cholera toxin and schistosome antigens. Further analysis by Western blot revealed that a 22 kDa antigen was detected on CT blots by sera from mice and humans infected with S. mansoni. This band was not demonstrable after absorption of the mouse or the human sera with CT. The 22 kDa cross reactive antigen was heat-stable. The antibodies against the 22 kDa antigen were only found within the IgM class but not within other Ig isotypes. Our findings also indicate that the 22 kDa antigen detected by anti-S. mansoni antibodies represents the A1 fragment of the cholera toxin.
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| 2. |
- Greiff, Lennart, et al.
(författare)
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Effects of topical platelet activating factor on the guinea-pig tracheobronchial mucosa in vivo
- 1997
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Ingår i: Acta Physiologica Scandinavica. - 0001-6772. ; 160:4, s. 387-391
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Tidskriftsartikel (refereegranskat)abstract
- Platelet activating factor (PAF) has been reported to produce a variety of airway effects including epithelial damage and increased airway-lung absorption of hydrophilic tracers. The present study examines effects of PAF on the guinea-pig tracheobronchial mucosa in vivo. Vehicle with and without PAF (4.0 and 8.0 nmol) was superfused onto the tracheobronchial mucosa. The levels of 125I-albumin, previously given intravenously, were determined in tracheobronchial lavage fluids as an index of mucosal exudation of plasma. The mucosa was also examined by scanning electron microscopy. In separate animals, 99mTc-DTPA (a low molecular weight, 492 Da, hydrophilic tracer) was superfused onto the mucosal surface through an oro-tracheal catheter, together with vehicle or PAF (8.0 nmol). A gamma camera determined the disappearance rate of 99mTc-DTPA from the airways as an index of mucosal absorption. PAF produced dose-dependent mucosal exudation of plasma up to 20-fold greater than control (P < 0.001). However, PAF did not damage the epithelium and the absorption ability of the airway mucosa was unaffected. The results, in contrast to previous reports, suggest that PAF may not readily damage the airway mucosa even at large exudative doses of the agent. The present finding support the view that the plasticity of the epithelial junctions allows the creation of valve-like paracellular pathways for unidirectional clearance of extravasated plasma into the airway lumen. We suggest that endogenous PAF may participate in first line respiratory defence reactions by causing lumenal entry of bulk plasma without harming the epithelium.
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| 3. |
- Strannegård, Inga-Lisa, 1937, et al.
(författare)
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Prevalence of allergy in children in relation to prior BCG vaccination and infection with atypical mycobacteria.
- 1998
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Ingår i: Allergy. - 0105-4538. ; 53:3, s. 249-54
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Tidskriftsartikel (refereegranskat)abstract
- By influence on the Th1/Th2 cell balance, infectious agents may affect the development of atopic allergy. In this study, we investigated whether previous BCG vaccination or infection with atypical mycobacteria might be related to the development of atopic disease. The study, which involved skin testing with mycobacteria and answers to a questionnaire for more than 6000 children in Sweden, revealed a low prevalence of allergy among BCG-vaccinated children who were immigrants or adopted from other countries. Vaccinated children born in Sweden, however, did not have significantly lower allergy prevalence than age-matched, unvaccinated children. Furthermore, the overall frequencies of skin-test reactivity to the atypical mycobacteria M. avium and M. scrofulaceum were higher rather than lower in allergic than in nonallergic children. By contrast, there was a tendency toward a lower frequency of more strongly positive skin reactions (> or = 10 mm) to mycobacteria in allergic than in nonallergic children. These findings do not support the hypothesis that early mycobacterial infections have a suppressive effect on the development of atopic disease. Earlier findings of an apparent association between atopy and lack of previous mycobacterial infection may possibly be explained by a relatively decreased ability of atopic patients to mount strong Th1 cell-mediated immune responses.
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| 4. |
- Leickt, Lisa, et al.
(författare)
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Affinity screening for weak monoclonal antibodies
- 1998
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Ingår i: Journal of Immunological Methods. - : Elsevier BV. - 0022-1759. ; 220:1-2, s. 19-24
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Tidskriftsartikel (refereegranskat)abstract
- When selecting for monoclonal antibodies of a desired affinity, affinity chromatography can be a feasible alternative. This is of particular interest when low affinity monoclonal antibodies (dissociation constant (Kd) > 10(-4) M) are screened, as they are not easily recognised by traditional immunoassay procedures. In this study we have evaluated this approach by monitoring low affinity monoclonal antibodies on high performance liquid affinity chromatography columns with oligosaccharides, dinitrophenol and digoxin as immobilised antigen. Crude monoclonal antibodies in ascites or cell culture supematants, directed against these antigens, were retarded or adsorbed according to affinity or avidity on the antigen columns. Based on antibody retention, we were able to select hybridomas with the desired low affinity characteristics.
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| 5. |
- Mattsby-Baltzer, Inger, 1949, et al.
(författare)
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IL-1beta, IL-6, TNFalpha, fetal fibronectin, and endotoxin in the lower genital tract of pregnant women with bacterial vaginosis.
- 1998
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Ingår i: Acta obstetricia et gynecologica Scandinavica. - : Wiley. - 0001-6349. ; 77:7, s. 701-6
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Tidskriftsartikel (refereegranskat)abstract
- In our studies on women with bacterial vaginosis (BV) in early pregnancy a strong association has been found between BV and the levels of endotoxin or interleukin-1alpha (IL-1alpha) in the lower genital tract. In the present study we investigated if an association could be found between BV and other cytokines (IL-1beta, IL-6, tumor necrosis factor alpha, TNF) or fetal fibronectin (FFN). The cytokine-inducing capacity of endotoxins present in the cervical mucus was explored in a monocytic cell assay.Cervical mucus or cervicovaginal fluid was collected from women with (BV) and without BV (nonBV) attending a family planning unit for first trimester abortion. The concentrations of IL-1beta, IL-6, TNF and FFN were determined by quantitative enzyme immunoassays. TNF was determined in 63 women (BV, n=25) out of whom 37 (BV, n=11) were analyzed for IL-1beta and the remaining 26 for IL-6 (BV, n=14). FFN was determined in another 36 women (BV, n= 19). The cytokine-inducing capacity of endotoxin-containing cervical mucus and purified endotoxin of Prevotella bivia were studied by an in vitro cell assay using a human monocytic cell line (THP-1).IL-lbeta and IL-6 were found in almost all women. The levels of IL-1beta, but not IL-6, TNF or FFN, were significantly increased in women with BV compared with the nonBV women (p<0.05). Purified endotoxin from P. bivia, and cervical mucus from BV women containing high levels of endotoxin were able to induce a cytokine response (IL-6) in monocytic cells in vitro.BV is associated with increased levels of IL-1beta in the lower genital tract of pregnant women in the first trimester. The ability of BV-associated endotoxins to induce cytokine production in monocytic cells may partly explain the increased IL-1beta levels.
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| 6. |
- Greiff, Lennart, et al.
(författare)
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Effects of hydrogen peroxide on the guinea-pig tracheobronchial mucosa in vivo
- 1999
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Ingår i: Acta Physiologica Scandinavica. - : Wiley. - 0001-6772 .- 1365-201X. ; 165:4, s. 415-420
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Tidskriftsartikel (refereegranskat)abstract
- Lumenal entry of plasma (mucosal exudation) is a key feature of airway inflammation. In airways challenged with histamine-type mediators and allergen the mucosal exudation response occurs without causing epithelial derangement and without increased airway absorption. In contrast, reactive oxygen metabolites may cause mucosal damage. In this study, involving guinea-pig airways, we have examined effects of H2O2 on airway exudation and absorption in vivo. Vehicle or H2O2 (0.1 and 0.5 M) was superfused onto the tracheobronchial mucosal surface through an oro-tracheal catheter. 125I-albumin, given intravenously, was determined in tracheobronchial tissue and in lavage fluids 10 min after challenge as an index of mucosal exudation of plasma. The tracheobronchial mucosa was also examined by scanning electron microscopy. In separate animals, 99mTc-DTPA was superfused 20 min after vehicle or H2O2 (0.1 and 0.5 M) had been given. A gamma camera determined the disappearance rate of 99mTc-DTPA from the airways as an index of airway absorption. The high dose of H2O2 (0.5 M) produced epithelial damage, increased the absorption of 99mTc-DTPA (P < 0.001), and increased the exudation of plasma (P < 0.001). Notably, it appeared that all extravasated plasma had entered the airway lumen within 10 min. These data demonstrate that H2O2 differs from exudative autacoids such as histamine by causing both epithelial damage and plasma exudation responses. These data also agree with the view that the epithelial lining determines the rate of absorption and is responsible for the valve-like function that allows lumenal entry of extravasated bulk plasma without any increased inward perviousness.
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| 7. |
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| 8. |
- Aniansson, Gustaf
(författare)
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Breast-feeding, nasopharyngeal colonization and otitis media.
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis analyzed the relationship between breastfeeding, nasopharyngeal colonization and acute otitis media (AOM) in children. Nasopharyngeal cultures were collected from 400 children and milk samples from their mothers in connection with the scheduled visits to well baby clinics at 1-3, 4-7 and 8-12 months of age, and episodes of AOM and URI were documented. The nasopharyngeal flora was acquired more slowly by Swedish infants than in developing countries. The carriage increased with the number of siblings and day care center. (Aniansson et al. J Infect Dis. 1992;165:38-42). Breast-feeding was associated with a reduced frequency of AOM and URI, but the frequencies were higher in children with day-care contact and siblings. The nasopharyngeal bacterial carriage was higher in children with AOM. (Aniansson et al .Pediatr Infect Dis. J 1994;13:83-188). The pneumococcal anti-capsular antibody activity, in milk samples collected from the nursing mothers, was low or absent in >90% of the milk samples. In contrast anti-phosphorylcholine and anti-cell wall polysaccharide antibody activity was common. The frequency of AOM did not vary with the milk antibody activity (Andersson v Rosen et al. Pediatr Infect Dis J. 1996;15:498-507). The pneumococcal isolates were tested for adherence to human respiratory tract epithelial cells. Adhesive capacity was found in virtually all isolates. Anti-adhesive activity was found in 98.8% of the individual milk samples and it increased with age (Aniansson et al. Submitted). Children with a cleft palate were investigated between 6 and 10 years of age. Despite surgical repair and early treatment with a tympanic membrane tube, AOM and secretory otitis media were common, presumably due to Eustachian tube dysfunction and premature cessation of breast-feeding (Aniansson et al. Submitted).
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| 9. |
- Håkansson, Anders
(författare)
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Apoptosis induced by a human milk protein complex. Cellular and structural studies in tumour cells and bacteria.
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Human milk contains a vast array of bioactive molecules, with nutritional and protective functions. This thesis describes the effects of a human milk protein complex, MAL, on tumour cells and bacteria. During our studies on the anti-adhesive properties of human milk we observed that a milk fraction killed tumour cells. The morphology of the cells indicated apoptotic cell death and this was verified by DNA fragmentation analysis (Proc Natl Acad Sci U.S.A 1995; 92: 8064-8068). The effect of MAL was selective for tumour cells and immature embryonic cells while mature differentiated cells were resistant. MAL bound to the surface of both sensitive and resistant cells but was internalised only in sensitive cells. MAL was shown to co-localise with mitochondria and this interaction caused a disruption of the mitochondrial membrane potential, which caused release of cytochrome c and caspase activation (Exp Cell Res 1999; 249: 260-268). The caspase activation was functional as shown by the cleavage of intracellular substrates. In parallel MAL was also transported via active nuclear transport to the nuclei of sensitive cells. MAL exerted a direct effect on isolated nuclei causing the induction of apoptotic DNA fragmentation without involvement of mitochondrial activation pathways (Exp Cell Res 1999; 2246: 451-460). MAL was purified from the casein fraction of human milk and was shown by N-terminal amino acid sequencing to contain alpha-lactalbumin. Native alpha-lactalbumin had no bactericidal or tumouricidal activity, suggesting that the alpha-lactalbumin of the active fraction had different structural properties. By spectroscopic techniques MAL was shown to have a more flexible tertiary structure with exposure of hydrophobic surfaces like the molten globule form of alpha-lactalbumin (J Biol Chem 1999; 274: 6388-6396). Native alpha-lactalbumin was inactive, but could be converted to the active form by a folding change combined with a fatty acid to stabilise this fold. These studies verified that alpha-lactalbumin was the active component and that the conformational change was required for the apoptosis-inducing activity. MAL was also shown to be bactericidal against S. pneumoniae, but had little effect against gram-negative and other gram-positive bacteria. In S. pneumoniae MAL was shown to induce identical DNA fragmentation as seen in tumour cells, suggesting apoptosis-like features of bacterial death. The bacterial death did not involve cytochrome c and caspase-activation but the bacteria had sequence homologies in three open reading frames of the pneumococcal genome with a caspase-independent effector molecule in eukaryotic cells, apoptosis inducing factor (AIF). These sequences are currently investigated.
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| 10. |
- Karlsson, Anna, 1967, et al.
(författare)
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Escherichia coli-induced activation of neutrophil NADPH-oxidase: lipopolysaccharide and formylated peptides act synergistically to induce release of reactive oxygen metabolites.
- 1995
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Ingår i: Infection and immunity. - 0019-9567. ; 63:12, s. 4606-12
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Tidskriftsartikel (refereegranskat)abstract
- The prevailing view of neutrophil NADPH-oxidase activation during interaction with bacteria is that the production of toxic oxygen metabolites should be directed into the phagosome containing the engulfed prey. However, in this report we show that a common Escherichia coli strain, HB101, may induce a release of neutrophil oxygen metabolites to the extracellular milieu. This phenomenon is dependent on three factors: (i) the mobilization (upregulation) of neutrophil secretory vesicles prior to interaction with the bacteria, (ii) soluble bacterial factors binding to the formylmethionyl-leucyl-phenylalanine receptor and tentatively identified as formylated peptides, and (iii) a bacterium-associated priming factor identified as lipopolysaccharide.
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