| 1. |
- Berggård, Karin, et al.
(author)
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Binding of human C4BP to the hypervariable region of M protein: a molecular mechanism of phagocytosis resistance in Streptococcus pyogenes
- 2001
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In: Molecular Microbiology. - : Wiley. - 1365-2958 .- 0950-382X. ; 42:2, s. 539-551
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Journal article (peer-reviewed)abstract
- The amino-terminal hypervariable region (HVR) of streptococcal M protein is required for the ability of this virulence factor to confer phagocytosis resistance. The function of the HVR has remained unknown, but the finding that many HVRs with extremely divergent sequences bind the human complement regulator C4b-binding protein (C4BP) has suggested that this ligand may play a role in phagocytosis resistance. We used the M22 system to study the function of bound C4BP and provide several lines of evidence that C4BP indeed contributes to phagocytosis resistance. First, the ability of anti-HVR antibodies to cause opsonization correlated with their ability to inhibit binding of C4BP. Secondly, a short deletion in the HVR eliminated C4BP binding and also reduced the ability of M22 to confer phagocytosis resistance. Thirdly, the addition of an excess of pure C4BP to a phagocytosis system almost completely blocked the effect of opsonizing anti-HVR antibodies. Together, our data indicate that binding of C4BP to the HVR of M22 plays an important role in phagocytosis resistance, but other properties of M22 also contribute. This study provides the first molecular insight into the mechanisms by which the HVR of an M protein confers phagocytosis resistance.
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| 2. |
- Buckley, Patrick G, et al.
(author)
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A full-coverage, high-resolution human chromosome 22 genomic microarrayfor clinical and research applications
- 2002
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In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 11:25, s. 3221-3229
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Journal article (peer-reviewed)abstract
- We have constructed the first comprehensive microarray representing a human chromosome for analysis of DNA copy number variation. This chromosome 22 array covers 34.7 Mb, representing 1.1% of the genome, with an average resolution of 75 kb. To demonstrate the utility of the array, we have applied it to profile acral melanoma, dermatofibrosarcoma, DiGeorge syndrome and neurofibromatosis 2. We accurately diagnosed homozygous/heterozygous deletions, amplifications/gains, IGLV/IGLC locus instability, and breakpoints of an imbalanced translocation. We further identified the 14-3-3 eta isoform as a candidate tumor suppressor in glioblastoma. Two significant methodological advances in array construction were also developed and validated. These include a strictly sequence defined, repeat-free, and non-redundant strategy for array preparation. This approach allows an increase in array resolution and analysis of any locus; disregarding common repeats, genomic clone availability and sequence redundancy. In addition, we report that the application of phi29 DNA polymerase is advantageous in microarray preparation. A broad spectrum of issues in medical research and diagnostics can be approached using the array. This well annotated and gene-rich autosome contains numerous uncharacterized disease genes. It is therefore crucial to associate these genes to specific 22q-related conditions and this array will be instrumental towards this goal. Furthermore, comprehensive epigenetic profiling of 22q-located genes and high-resolution analysis of replication timing across the entire chromosome can be studied using our array.
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| 3. |
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| 4. |
- Lopez, Rodrigo, et al.
(author)
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Time-resolved ellipticity gating of high-order harmonic emission
- 2004
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In: Physical Review A. ; 69, s. 1-053811
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Journal article (peer-reviewed)abstract
- We present time-resolved cross-correlation measurements of extreme ultraviolet (xuv) pulses generated as high-order harmonics of intense 35 fs pulses, using a short (12 fs) probe pulse. We modulate the ellipticity of the laser driving the generation process such that the polarization is linear for short times around the temporal peak of the pulse. Since harmonic generation is strongly suppressed for very small amounts of driving laser ellipticity, the emission of xuv radiation can therefore be confined to times much shorter than the laser pulse duration. In addition, our setup allows us to continuously confine the xuv emission as well as to determine its frequency sweep during the pulse.
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| 5. |
- Morfeldt, E, et al.
(author)
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Isolated hypervariable regions derived from streptococcal M proteins specifically bind human C4b-binding protein : implications for antigenic variation.
- 2001
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In: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 167:7, s. 3870-7
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Journal article (peer-reviewed)abstract
- Antigenic variation in microbial surface proteins represents an apparent paradox, because the variable region must retain an important function, while exhibiting extensive immunological variability. We studied this problem for a group of streptococcal M proteins in which the approximately 50-residue hypervariable regions (HVRs) show essentially no residue identity but nevertheless bind the same ligand, the human complement regulator C4b-binding protein (C4BP). Synthetic peptides derived from different HVRs were found to retain the ability to bind C4BP, implying that the HVR corresponds to a distinct ligand-binding domain that can be studied in isolated form. This finding allowed direct characterization of the ligand-binding properties of isolated HVRs and permitted comparisons between different HVRs in the absence of conserved parts of the M proteins. Affinity chromatography of human serum on immobilized peptides showed that they bound C4BP with high specificity and inhibition experiments indicated that different peptides bound to the same site in C4BP. Different C4BP-binding peptides did not exhibit any immunological cross-reactivity, but structural analysis suggested that they have similar folds. These data show that the HVR of streptococcal M protein can exhibit extreme variability in sequence and immunological properties while retaining a highly specific ligand-binding function.
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| 6. |
- Zair, A, et al.
(author)
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Time-resolved measurements of high order harmonics confined by polarization gating
- 2004
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In: Applied Physics B. - : Springer Science and Business Media LLC. - 0946-2171 .- 1432-0649. ; 78:7-8, s. 869-872
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Journal article (peer-reviewed)abstract
- We investigate the temporal confinement of high order harmonic pulses generated by a femtosecond (fs) infrared (IR) pulse with a time varying polarization. We use a set of two birefringent quartz plates to modulate the IR polarization. It produces a short temporal gate of linear polarization where harmonics are efficiently generated during a small fraction of the IR pulse. By rotating one of the plates, the gate width can be continuously varied between 70 fs down to 7 fs. The XUV pulse duration is measured by cross-correlation with a probe IR pulse of 12 fs. When the gate width is decreased, a clear temporal confinement of the XUV emission is observed through the cross correlation signal. This experiment is the first direct experimental evidence in the temporal domain that the polarization gating technique can be used to significantly shorten the harmonic pulse duration.
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| 7. |
- Atroshi, I, et al.
(author)
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Quality of life after hip revision with impaction bone grafting on a par with that 4 years after primary cemented arthroplasty
- 2004
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In: Acta Orthopaedica Scandinavica. - : Medical Journals Sweden AB. - 0001-6470. ; 75:6, s. 677-683
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Journal article (peer-reviewed)abstract
- Background There have been few studies evaluating patient-reported quality of life outcomes after hip revision with impaction bone grafting. Patients and methods The inclusion criteria were aseptic loosening after primary arthroplasty performed for osteoarthrosis, and first-time revision with impacted morselized allograft bone and cemented Exeter stem. During a 4-year period, 35 patients were eligible and all were included. The Nottingham Health Profile (NHP) was completed by the patients and the Charnley hip scores recorded by the examining surgeon preoperatively, after 6 months and yearly up to 4 years (28 patients) postoperatively. For comparison, 35 osteoarthrotic patients completed the NHP 4 years after cemented Exeter primary arthroplasty. Results At 4 years, the NHP scores for the revision patients did not differ significantly from those recorded in the primary arthroplasty group. Among the revision patients, mixed model analysis showed improvement in NHP pain (p < 0.001) and physical mobility scores (p = 0.002). The effect size at 4 years was large for pain (1.2) and moderate for physical mobility (0.6). The major improvement was recorded at 6 months, with no further substantial change observed. The correlations between the NHP and Charnley scores were weak or moderate (r, -0.15 to -0.67). Interpretation Hip revision with impaction bone grafting leads to substantially improved quality of life, similar to that 4 years after primary arthroplasty.
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| 8. |
- Berglund, Mats, et al.
(author)
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Pharmacotherapy for alcohol dependence
- 2003
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In: Treatment of Alcohol and Drug Abuse. An Evidence-Based Review. - 9783527306824 - 352730682X ; , s. 4-4
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Book chapter (other academic/artistic)
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| 9. |
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| 10. |
- Borg, E, et al.
(author)
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Language development in hearing-impaired children - Establishment of a reference material for a 'Language test for hearing-impaired children', LATHIC
- 2002
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In: International Journal of Pediatric Otorhinolaryngology. - 1872-8464. ; 65:1, s. 15-26
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Journal article (peer-reviewed)abstract
- Objective: In Sweden, there has previously been no normalised test material for the evaluation of language development in individual hearing-impaired children, and for the assessment of various methods of auditory habilitation. The purpose of the present study was to compose, apply and evaluate a test for language development in hearing-impaired children, and to establish the first set of reference values related to age, sex, type and degree of hearing impairment. Methods: A test consisting of nine subtests was assembled and developed for, and subsequently applied to, hearing-impaired children in the age range 4-6 years. The inclusion criteria were a pure tone average of 80 dBHL or less and oral language (Swedish) as the first language. Two hundred and eleven hearing-impaired children and 87 normal hearing control children were tested. Results: The results show that: (1) children with hearing impairment-also unilateral-have a delayed language development; (2) the delay is greater in children with larger losses and tends to decrease with increasing age; (3) 6-year-olds with hearing loss greater than 60 dB have not reached the level of the control group; (4) no difference between right- or left sided deafness with respect to language development was observed; (5) a reference material, applicable during clinical assessment, was established for the most common types of hearing impairment. Conclusions: The test designed gave graded measures of important aspects of language development in hearing-impaired children. The results merit further application of the test material. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.
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