| 1. |
- Lagerberg, Tove B, et al.
(author)
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Swedish Test of Intelligibility for Children (STI-CH) - Validity and reliability of a computer-mediated single word intelligibility test for children
- 2015
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In: Clinical Linguistics & Phonetics. - : Informa UK Limited. - 0269-9206 .- 1464-5076. ; 29:3, s. 201-215
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Journal article (peer-reviewed)abstract
- The aim of this study was twofold: first, to describe a new Swedish intelligibility test (Swedish Test of Intelligibility for Children, STI-CH) and second to evaluate its validity and reliability. STI-CH is based on the repetition of single words. Ten children with a speech-sound disorder (4:6-8:3 years of age, mean = 6.0 years) and 10 children with typical speech and language development (4:8-7:4 years of age, mean = 5.9 years) were included. Twenty speech-language pathology students served as listeners. Intra-judge reliability was high (r > 0.92), as was the intra-class correlation of inter-judge reliability (0.97). In terms of validity, there was a significant difference in STI-CH scores between the two groups, and the scores correlated statistically significantly with the Percentage of Consonants Correct (r = 0.94) and with intelligibility in spontaneous speech (r = 0.85). To sum up, the results indicate that STI-CH could be an option for the assessment of intelligibility in Swedish-speaking children, and that the principles used in the development of the test could be of use in the design of intelligibility tests in languages other than Swedish.
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| 2. |
- Lagergård, Teresa, 1946, et al.
(author)
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Formaldehyde treatment increases the immunogenicity and decreases the toxicity of Haemophilus ducreyi cytolethal distending toxin.
- 2007
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In: Vaccine. - : Elsevier BV. - 0264-410X. ; 25:18, s. 3606-14
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Journal article (peer-reviewed)abstract
- Haemophilus ducreyi cytolethal distending toxin (HdCDT) is a tripartite AB toxin, which causes DNA damage in affected cells. We investigated the effects of formaldehyde on the chemical, biological, and immunological properties of the HdCDT complex, which was purified by immobilizing the glutathione S-transferase (GST)-CdtB fusion protein, followed by binding of the CdtA and CdtC recombinant proteins. The HdCDT was treated with increasing concentrations of formaldehyde in the presence of lysine. The treatment of HdCDT at 1 and 0.1 mg protein/ml with 320 and 80 mM of formaldehyde, respectively, resulted in the complete abrogation of cytotoxic activity, loss of DNase activity, and loss of binding capacity to HeLa cells. The toxoid showed protein bands of 75-150 kDa in SDS-PAGE, composed of the three cross-linked CDT components detected by immunoblotting. Three doses of 10 microg protein/mouse of the formaldehyde-treated HdCDT elicited toxin-neutralizing antibodies at titers about 200 times higher than those elicited by the native toxin. The described methodology may be applied to produce immunogenic toxoids from other CDTs, which might be used as candidate components in vaccines against CDT-producing bacteria, including H. ducreyi.
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| 3. |
- Lundqvist, Annika, 1969, et al.
(author)
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Detoxified Haemophilus ducreyi cytolethal distending toxin and induction of toxin specific antibodies in the genital tract.
- 2010
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In: Vaccine. - : Elsevier BV. - 1873-2518 .- 0264-410X. ; 28:36, s. 5768-73
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Journal article (peer-reviewed)abstract
- Haemophilus ducreyi causes genital ulceration (chancroid), a sexually transmitted infection and still an important factor which contributes to the spread of HIV in developing countries. The bacterium produces a cytolethal distending toxin (HdCDT) causing cell cycle arrest and apoptosis/necrosis of human cells and contributes to the aggravation of ulcers. The aim of the study was to induce toxin-neutralizing antibodies in the genital tract of mice. Repeated subcutaneous (sc) immunisations with 5-10microg active HdCDT induced low levels of serum anti-HdCDT IgG without neutralizing capacity. High levels of specific IgG1 antibodies in serum and genital tract were generated after sc immunisations with 10microg formaldehyde detoxified HdCDT toxoid alone and the addition of aluminium salts or RIBI (based on the lipid A moiety) as adjuvant further increased the level of serum antibodies. A high correlation was found between elevated levels of anti-HdCDT IgG in sera, the level of neutralizing activity and the antibody level in genital tract (r=0.8). Thus, induction of high antibody levels specific to HdCDT in the genital tissue can be achieved by parenteral immunisation with the toxoid. The HdCDT toxoid can be considered as a candidate component in vaccine against chancroid.
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| 4. |
- Lundqvist, Annika, 1969, et al.
(author)
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Immunogenic and adjuvant properties of Haemophilus ducreyi lipooligosaccharides.
- 2009
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In: Microbes and infection / Institut Pasteur. - : Elsevier BV. - 1769-714X. ; 11:3, s. 352-60
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Journal article (peer-reviewed)abstract
- Haemophilus ducreyi, the chancroid-causing bacterium, produces lipooligosaccharides (HdLOS) that comprise 5-11 partially sialylated monosaccharides. Subcutaneous immunisation of mice with 5 microg of HdLOS purified from H. ducreyi strains 4438 and 7470 induced high levels of anti-HdLOS IgG. The antibody responses displayed T-cell-independent features, and were dependent upon Toll-like receptor 4/MyD88 signalling pathways as demonstrated using knockout mice. The immunogenicity of HdLOS was found to require the intact lipid A moiety. The specificity studies of the anti-HdLOS antibodies, as revealed by absorption studies, antibody detection in ELISA, and immune thin-layer chromatography, indicated that the majority of the anti-LOS antibodies were specific for the inner core of the HdLOS. Antibodies to HdLOS failed to inhibit LOS induction of TNF-alpha release from human mononuclear cells. The adjuvanticity of HdLOS7470 was assessed in BALB/c mice that were immunised with bovine serum albumin (BSA) with or without the addition of HdLOS. The addition of 5 microg HdLOS resulted in a 10-fold increase in the total anti-BSA IgG antibody level as estimated by ELISA. The highest increase was noted for IgG2b, which contrasted with the predominantly IgG1 subclass response to immunisation with BSA alone, indicating an immunomodulatory activity of the HdLOS.
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| 5. |
- Wising, Catharina, 1973, et al.
(author)
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Induction of apoptosis/necrosis in various human cell lineages by Haemophilus ducreyi cytolethal distending toxin.
- 2005
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In: Toxicon : official journal of the International Society on Toxinology. - : Elsevier BV. - 0041-0101. ; 45:6, s. 767-76
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Journal article (peer-reviewed)abstract
- We investigated the impact of highly purified Haemophilus ducreyi cytolethal distending toxin (HdCDT) on the apoptosis and necrosis of various human cells; including myeloid cells, epithelial cells, keratinocytes, and primary fibroblasts. The levels of apoptosis and necrosis induced in these cells were compared to those induced by HdCDT in human T cells and in the Jurkat T cell line. Levels of caspase-3 activity were measured, and membrane changes like phosphatidylserine (PS) translocation was evaluated after double-staining with the fluorescein isothiocyanate (FITC)-labeled annexin V and propidium iodide (PI) using flow cytometry. HdCDT induced various degrees of apoptosis and necrosis in dose- and time-dependent manners in cells of various lineages. Early and late apoptosis (annexin V-stained cells) were induced in more than 90% of T cells and monocytes after treatment with 100 ng/ml HdCDT for 24 and 48 h, respectively. The corresponding numbers for epithelial cells, keratinocytes, and fibroblasts were 26-32% after treatment with 100 ng/ml HdCDT for 48 h. HdCDT appears to eliminate effectively by inducing apoptosis those cells that are involved in immune responses. Epithelial cells, keratinocytes and fibroblasts, which are important for the healing of chancroid ulcers, are eliminated by apoptosis or necrosis after contact with HdCDT, albeit slower and to a lesser extent than T cells.
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| 6. |
- Wising, Catharina, 1973, et al.
(author)
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The cytolethal distending toxin of Haemophilus ducreyi aggravates dermal lesions in a rabbit model of chancroid
- 2005
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In: Microbes Infect. - : Elsevier BV. - 1286-4579. ; 7:5-6, s. 867-74
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Journal article (peer-reviewed)abstract
- Haemophilus ducreyi, the etiologic agent of the sexually transmitted disease chancroid, produces a cytolethal distending toxin (HdCDT) that inhibits cultured cell proliferation, leading to cell death. A rabbit model of dermal infection was used to investigate the roles of H. ducreyi bacteria and HdCDT in the development, clinical appearance, and persistence of infection. A non-toxin producing H. ducreyi strain, and for comparison purposes a non-capsulated Haemophilus influenzae strain, were inoculated intradermally, with and without co-administration of purified HdCDT. Co-administration of HdCDT resulted in significant aggravation of H. ducreyi-induced inflammatory lesions, and development of ulcers in rabbit skin. Less pronounced inflammatory lesions and lack of epithelial eruption were observed after inoculation with H. influenzae. Histopathological sections of the H. ducreyi-induced lesions, in both the presence and absence of HdCDT, showed dense infiltrates of the same type inflammatory cells, with the exception of a prominent endothelial cell proliferation noted in sections from lesions caused by H. ducreyi and toxin. Signs of chronic inflammation with involvement of T cells, macrophages, eosinophils, and granuloma formation were observed after H. ducreyi inoculation both with and without toxin. In conclusion, H. ducreyi causes a pronounced, chronic inflammation with involvement of T cells and macrophages, and in combination with HdCDT production of ulcers in the rabbit model. These pathogenic mechanisms may promote the development and persistence of chancroid ulcers.
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| 7. |
- Wising, Catharina, 1973, et al.
(author)
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Toxic activity of the CdtB component of Haemophilus ducreyi cytolethal distending toxin expressed from an adenovirus 5 vector
- 2010
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In: APMIS. - : Wiley. - 1600-0463 .- 0903-4641. ; 118:2, s. 143-149
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Journal article (peer-reviewed)abstract
- The Haemophilus ducreyi cytolethal distending toxin (HdCDT) catalytic subunit CdtB has DNase-like activity and mediates DNA damage after its delivery into target cells. We constructed a replication-deficient adenovirus type 5 (Ad5) vector expressing CdtB and investigated the toxic properties of this vector on HeLa cells. Ad5CdtB caused loss of cell viability, morphologic changes, and cell cycle arrest, findings similar to HdCDT intoxication. This confirmed that CdtB is responsible for the toxicity of the holotoxin when expressed in cells following transduction by an adenoviral vector, and indicated a possible potential of this novel strategy in studies of activity of intracellular products and in gene therapy of cancer.
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