| 4021. |
- Tay, GK, et al.
(författare)
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PERB11 (MIC) : a polymorphic MHC gene is expressed in skin and single nucleotide polymorphisms are associated with psoriasis.
- 2000
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Ingår i: Clinical and Experimental Immunology. - : John Wiley & Sons. - 0009-9104 .- 1365-2249. ; 119:3, s. 553-558
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Tidskriftsartikel (refereegranskat)abstract
- The susceptibility genes for psoriasis remain to be identified. At least one of these must be in the major histocompatibility complex (MHC) to explain associations with alleles at human leucocyte antigen (HLA)-A, -B, -C, -DR, -DQ and C4. In fact, most of these alleles are components of just two ancestral haplotypes (AHs) designated 13.1 and 57.1. Although relevant MHC gene(s) could be within a region of at least 4 Mb, most studies have favoured the area near HLA-B and -C. This region contains a large number of non-HLA genes, many of which are duplicated and polymorphic. Members of one such gene family, PERB11.1 and PERB11.2, are expressed in the skin and are encoded in the region between tumour necrosis factor and HLA-B. To investigate the relationship of PERB11.1 alleles to psoriasis, sequence based typing was performed on 97 patients classified according to age of onset and family history. The frequency of the PERB11.1*06 allele is 44% in type I psoriasis but only 7% in controls (Pc = 0.003 by Fisher's exact test, two-tailed). The major determinant of this association is a single nucleotide polymorphism (SNP) within intron 4. In normal and affected skin, expression of PERB11 is mainly in the basal layer of the epidermis including ducts and follicles. PERB11 is also present in the upper keratin layers but there is relative deficiency in the intermediate layers. These findings suggest a possible role for PERB11 and other MHC genes in the pathogenesis of psoriasis.
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| 4022. |
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| 4023. |
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| 4024. |
- Tegnell, Anders, et al.
(författare)
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[Smallpox : eradicated disease and a potential terrorist weapon]
- 2002
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Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 99:19, s. 2145-2149
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Smallpox is a disease that followed humanity for thousands of years up until thirty years ago. It was possible to eradicate, since an effective live vaccine from crossreacting vaccinia could be developed. Twenty years passed since vaccinations stopped and very few people are protected against the disease today. Variola today has become an object of discussion due to the possibility that it can be used as a bioweapon. Due to the number of complications that can be expected a general vaccination is probably not possible. Research is ongoing to develop new vaccines. Many countries are improving their capabilities to respond to a renewed threat of a smallpox epidemic.
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| 4025. |
- Telepnev, Max, et al.
(författare)
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Francisella tularensis inhibits Toll-like receptor-mediated activation of intracellular signaling and secretion of TNF-alpha and IL-1 in murine macrophages
- 2003
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Ingår i: Cellular Microbiology. - : Blackwell Publishing. - 1462-5814 .- 1462-5822. ; 5:1, s. 41-51
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Tidskriftsartikel (refereegranskat)abstract
- Microbial ligands, including lipopolysaccharide (LPS) and bacterial lipoproteins, activate Toll-like receptors (TLR) of mononuclear phagocytes, thereby inducing proinflammatory cytokines and antimicrobial activity. We show that Francisella tularensis, an intracellular pathogen, is capable of inhibiting this macrophage response. Infection with the live vaccine strain F. tularensis LVS rendered cells of the murine macrophage-like cell line J774A.1 incapable of secreting TNF-alpha or IL-1beta and mobilizing an antimicrobial activity in response to bacterial lipopeptide or Escherichia coli-derived LPS. Inhibition of TNF-alpha secretion occurred also when J774 cells were infected with F. tularensis LVS in the presence of chloramphenicol, but not when they were infected with a mutant of F. tularensis LVS defective in expression of a 23 kDa protein that is upregulated during intracellular infection. Purified F. tularensis LPS did not show an agonistic or antagonistic effect on the E. coli LPS-induced activation of the J774 cells. Francisella tularensis LVS suppressed the capability of the cells to respond to LPS or bacterial lipopeptide (BLP) with activation of nuclear factor kappa B (NF-kappaB), and degradation of the in-hibitor of NF-kappaB, IkappaB, was blocked during the infection. Also the LPS- or BLP-induced phosphorylation of the mitogen-activated protein kinase p38 and the transcription factor c-Jun was inhibited by F. tularensis LVS but not by the 23 kDa protein mutant. In conclusion, F. tularensis appears capable of abrogating the TNF-alpha and IL-1 responses of macrophages induced by E. coli LPS or BLP via a mechanism that involves suppression of several intracellular pathways and is dependent on expression of a bacterial 23 kDa protein.
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| 4026. |
- Tengel, Tobias, et al.
(författare)
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Use of 19F NMR spectroscopy to screen chemical libraries for ligands that bind to proteins
- 2004
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Ingår i: Organic and biomolecular chemistry. - : Royal Society of Chemistry (RSC). - 1477-0520 .- 1477-0539. ; 2:5, s. 725-731
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Tidskriftsartikel (refereegranskat)abstract
- Identification of compounds from chemical libraries that bind to macromolecules by use of NMR spectroscopy has gained increasing importance during recent years. A simple methodology based on F-19 NMR spectroscopy for the screening of ligands that bind to proteins, which also provides qualitative information about relative binding strengths and the presence of multiple binding sites, is presented here. A library of fluorinated compounds was assembled and investigated for binding to the two bacterial chaperones PapD and FimC, and also to human serum albumin (HSA). It was found that library members which are bound to a target protein could be identified directly from line broadening and/or induced chemical shifts in a single, one-dimensional F-19 NMR spectrum. The results obtained for binding to PapD using F-19 NMR spectroscopy agreed well with independent studies based on surface plasmon resonance, providing support for the versatility and accuracy of the technique. When the library was titrated to a solution of PapD chemical shift and linewidth changes were observed with increasing ligand concentration, which indicated the presence of several binding sites on PapD and enabled the assessment of relative binding strengths for the different ligands. Screening by F-19 NMR spectroscopy should thus be a valuable addition to existing NMR techniques for evaluation of chemical libraries in bioorganic and medicinal chemistry.
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| 4027. |
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| 4028. |
- Tengvald, Karin, et al.
(författare)
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Implementering the Addiction Severity Index (ASI) in Swedish human services sectors : Experiences, problems and prospects
- 2004
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Ingår i: Journal of Substance Use. - : Taylor and Francis. - 1465-9891 .- 1475-9942. ; 9:3-4, s. 163-171
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Tidskriftsartikel (refereegranskat)abstract
- In Sweden, agencies within both the health services and the social services sectors are responsible for treatment, rehabilitation and care of persons with substance‐abuse problems. Also in the prison and probation system such problems are common among clients. The article describes how a Swedish version of the Addiction Severity Index (ASI) was developed and introduced in these three systems in the late 1990s and the extent of its implementation in regular practice. The ASI is now used for treatment‐planning and outcome‐evaluation purposes and not only for research purposes in Swedish substance‐abuse treatment agencies. A comparison of the implementation of the ASI in the three human services sectors indicates that the top‐down implementation strategies used in the prison and probation system have some important benefits, when compared with bottom‐up strategies, although such strategies are more conducive to dissemination in more decentralized human services systems. But several implementation barriers are common in all three services sectors—for example, high levels of staff turnover and competition with other structured assessment instruments. It is concluded that the prospects for a more widespread use of the ASI in the future depends—in all three human services sectors—both on the external demands for effectiveness and transparency and on internal, particularly managerial, commitment to effective services and evidence‐based practice.
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| 4029. |
- Terao, Yasuo, et al.
(författare)
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Engagement of gaze in capturing targets for future sequential manual actions.
- 2002
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Ingår i: Journal of Neurophysiology. - 0022-3077 .- 1522-1598. ; 88:4, s. 1716-25
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Tidskriftsartikel (refereegranskat)abstract
- We investigated the role of saccadic gaze fixations in encoding target locations for planning a future manual task consisting of a sequence of discrete target-oriented actions. We hypothesized that fixations of the individual targets are necessary for accurate encoding of target locations and that there is a transfer of sequence information from visual encoding to manual recall. Subjects viewed four targets presented at random positions on a screen. After various delays following target extinction, the subjects marked the remembered target locations on the screen with the tip of a hand-held stick. When the targets were presented simultaneously among distracting elements, the overall accuracy of marking increased with presentation time and total number of targets fixated because the subjects had to serially fixate the individual targets to locate them. Without distractors, the marking accuracy was similarly high regardless of duration of target presentation (0.25-8 s) and number of targets fixated; it was comparable to that with distractors when all four targets had been fixated. This indicates parallel encoding of target locations largely based on peripheral vision. Location memory was stable in these tasks over the delay periods investigated (0.5-8 s). With parallel encoding there was a "shrinkage" in the visuomotor transformation, i.e., the distances between the markings were systematically smaller than the corresponding inter-target distances. When the targets were presented sequentially without distractors, marking accuracy improved with the total number of targets fixated and shrinkage in the visuomotor transformation occurred only with parallel encoding, i.e., when subjects did not fixate the targets. In all experimental conditions for trials in which targets were fixated during encoding, there was little correspondence between the marking sequence and the sequence in which the targets were fixated. We conclude that subjects benefit from fixating targets for subsequent target-oriented manual actions when the targets are presented among distractors and when presented sequentially; when distinct targets are presented simultaneously against a blank background, they are efficiently encoded in parallel largely by peripheral vision.
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| 4030. |
- Teterukovskiy, Alex, et al.
(författare)
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Contextual reclassification of multispectral images : a Markov Random Field approach
- 2002
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Ingår i: Information Processes. - 1819-5822. ; 2:1, s. 12-21
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Tidskriftsartikel (refereegranskat)abstract
- This work presents methods for multispectral image classification using the contextual classifiersbased on Markov Random Field (MRF) models. Performance of some conventional classification methods is evaluated, through a Monte Carlo study, with or without using the contextual reclassification. Spatial autocorrelation is present in the computer-generated data on a true scene. The total misclassification rates for varying strengths of autocorrelation and for different methods are compared. The results indicate that the combination of the spectral-contextual classifiers can improve to a great extent the accuracyof conventional non-contextual classification methods. It is also shown how the most complicated cases can be handled by the Gibbs sampler.
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