| 1. |
- Ehlers, Stephan, et al.
(författare)
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Mental Impairment and Attention Deficit Hyperactivity Disorder in a Family with FRAXF
- 1999
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Ingår i: Neurocase. - : Informa UK Limited. - 1355-4794 .- 1465-3656. ; 5:6, s. 533-536
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Tidskriftsartikel (refereegranskat)abstract
- A mother and her three children with fragile X syndrome (FRAXF fragile site), shown by cytogenetic and molecular genetic methods, were neuro psychiatrically and psychometrically evaluated. All individuals exhibited clear learning disability, as well as attention deficit hyperactivity disorder. The findings suggest that these clinical attributes, particularly mental impairment, may be a phenotypic expression of the FRAXF fragility.
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| 2. |
- Enerbäck, Charlotta, 1965, et al.
(författare)
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Cytogenetic analysis of 477 psoriatics revealed an increased frequency of aberrations involving chromosome region 11q
- 1999
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Ingår i: Eur J Hum Genet. ; 7:3, s. 339-44
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Tidskriftsartikel (refereegranskat)abstract
- Psoriasis is an inflammatory skin disorder affecting approximately 3% of the population. Genetic studies published so far have shown a complex genetic inheritance with heterogeneity and a putative major susceptibility locus in the HLA region on chromosome 6. We have collected a large amount of material consisting mostly of small nuclear families in order to perform a genome-wide scan for psoriasis-associated genes. In order to focus the scan properly on possible candidate regions, we performed a cytogenetic analysis of 477 unrelated psoriatics. We divided our findings into sporadic, affecting a minor fraction of the cells, and constitutional, i.e. they were present in all cells examined. We found three cases of balanced translocation, all of which involved chromosome 11q. Two of these had a breakpoint in q12-13, whilst one involved the telomeric part of chromosome 11q. In order to characterise further the breakpoint on 11q12-13, we used bacterial artificial chromosomes (BACs) analysed by fluorescent in situ hybridisation (FISH). We were able to show that the persons had a close, but not identical breakpoints; they were separated by at least 5 cM. The major atopy locus is located in this region, as well as a locus for insulin-dependent diabetes mellitus, both being conditions with a pathogenetic mechanism involving antigen presentation.
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| 3. |
- Enerbäck, Charlotta, 1965, et al.
(författare)
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Evidence that HLA-Cw6 determines early onset of psoriasis, obtained using sequence-specific primers (PCR-SSP)
- 1997
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Ingår i: Acta Derm Venereol. ; 77:4, s. 273-6
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Tidskriftsartikel (refereegranskat)abstract
- Psoriasis vulgaris has previously been shown to associate with certain HLA alleles. HLA-Cw6 is considered to be the primary association, based on calculations of relative risk after serological typing. This association is reportedly more pronounced in early- than in late-onset psoriasis. We performed a PCR-based typing with sequence-specific primers, which has been shown to give a more complete result than serology. Two hundred and one unrelated patients with psoriasis, with a mean age of 40 years, and 77 healthy controls were typed. Two thirds (67%) of the patients were positive for one or two copies of the allele, while the corresponding figure for the control group was 12%. A significant peak for age at onset of 21 or younger was seen for the Cw6 carriers. For patients older than 21 at onset, the frequency of Cw6 was significantly lower; e.g. for patients with an age at onset between 30 and 35 the frequency was comparable to the level of the control group. The high frequency of Cw6 among patients with an age at onset of 21 or younger is in agreement with data of other groups. In comparison with this age-at-onset group the frequency of Cw6 is sharply reduced among patients with an age at onset of 22 years or older, which contrasts with earlier studies. This may reflect differences between population groups but may also be due to the higher sensitivity of the PCR-based HLA-Cw6 typing method. In view of these findings, we suggest that psoriasis is a genetically determined disease, in which the additional presence of HLA-Cw6 is associated with the characteristic of early onset.
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| 4. |
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| 5. |
- Enlund, Fredrik, 1968, et al.
(författare)
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Analysis of three suggested psoriasis susceptibility loci in a large Swedish set of families: confirmation of linkage to chromosome 6p (HLA region), and to 17q, but not to 4q
- 1999
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Ingår i: Hum Hered. ; 49:1, s. 2-8
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Tidskriftsartikel (refereegranskat)abstract
- Psoriasis is known to be a heterogeneous disease with so far three reported major psoriasis susceptibility loci on chromosome 4q, 6p and 17q. In this study we investigated three reported gene locations by nonparametric and parametric linkage analysis in a large family set consisting of 104 families (153 sib pairs) from Sweden. We could confirm linkage to chromosome 6p. A maximum heterogeneous lod score of 2.78 was reached at locus D6S276 (alpha = 0.60). Allelic association studies within the HLA region indicated linkage disequilibrium at locus TNFbeta with a significant p value of 0.0009. Furthermore, we obtained weak evidence of linkage to the locus on chromosome 17q while no evidence of linkage could be found to the chromosome 4q region.
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| 6. |
- Enlund, Fredrik, 1968, et al.
(författare)
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Psoriasis susceptibility locus in chromosome region 3q21 identified in patients from southwest Sweden
- 1999
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Ingår i: Eur J Hum Genet. ; 7:7, s. 783-90
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Tidskriftsartikel (refereegranskat)abstract
- We have performed a pair-wise linkage study in the search for psoriasis susceptibility regions. A preliminary scan was performed on 20 families. In this set we obtained indications of linkage on chromosome 3q21. This region was further investigated using material from a total of 104 families (set 1B) resulting in a non-parametric linkage (NPL) of 1.77. The material was stratified in families whose parental origin is in southwest Sweden (set 1C). A maximum NPL value of 2.77 was obtained in this group. A transmission disequilibrium test (TDT) was performed on the stratified material (set 1C) and a significant P value of 0.005 was obtained, at marker D3S1269. The locus was confirmed with TDT in replicate material consisting of 148 families in which a single member was affected (P value 0.0007) at marker D3S1551. Thus, we have observed a significant P value using TDT in the vicinity of markers D3S1269/D3S1551, suggesting a novel psoriasis susceptibility region.
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| 7. |
- Larsson, Jan, et al.
(författare)
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Effects of TRH and atropine on induction and duration of anesthesia with propofol in rats.
- 1996
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Ingår i: Peptides. - : Elsevier BV. - 0196-9781 .- 1873-5169. ; 17:2, s. 293-297
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Tidskriftsartikel (refereegranskat)abstract
- The effects of IV TRH pretreatment on induction of anesthesia with propofol or pentobarbital were investigated in rats. The effects of IV TRH, administered after induction, on duration of propofol anesthesia and the interaction with atropine were also studied. The doses of propofol or pentobarbital were not influenced by TRH. TRH reduced duration of anesthesia after propofol, with higher brain concentrations of propofol at recovery. Atropine did not block this effect, but given alone prolonged duration of anesthesia. It is concluded that TRH shortens the duration of propofol anesthesia, probably due to a pharmacodynamic effect and not to a pharmacokinetic interaction.
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| 8. |
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| 9. |
- Samuelsson, Lena, 1962, et al.
(författare)
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A genome-wide search for genes predisposing to familial psoriasis by using a stratification approach
- 1999
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Ingår i: Hum Genet. - 0340-6717 .- 0340-6717. ; 105:6, s. 523-9
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Tidskriftsartikel (refereegranskat)abstract
- We have performed a genome scan, using markers spaced by 10 cM, in the search for psoriasis-susceptibility loci. The family material of 134 affected sibling pairs was ascertained on the basis of a population genetic study in which 65% of the probands had two healthy parents. Genotyping results were analyzed for non-random excessive allele-sharing between sib pairs by using GENEHUNTER ver 1.1. A stratification approach was applied to increase the homogeneity of the material by means of an operational definition of joint complaints among affected individuals. Significant linkage to the human leukocyte antigen region on chromosome 6p in a cohort including 42 families without joint complaints (nonparametric linkage score of 2.83, P=0.002) strongly supported the validity of this operational definition as it replicated results from an earlier linkage report with similar stratification criteria. New candidate regions on chromosomes 3 and 15 were identified. The highest non-parametric linkage values in this study, 2.96 (P=0.0017) and 2.89 (P=0.0020), were reached on chromosome 15 in a subgroup with joint complaints and on chromosome 3 in a subgroup without joint complaints. In addition, confirmation of previously reported loci was established on chromosomes 4q, 6p, and 17q. This study indicates that distinct disease loci might be involved in psoriasis etiology for various phenotypes.
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| 10. |
- Swanbeck, Gunnar, 1934, et al.
(författare)
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Age at onset and different types of psoriasis
- 1995
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Ingår i: Br J Dermatol. ; 133:5, s. 768-73
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Tidskriftsartikel (refereegranskat)abstract
- The age at onset of psoriasis has been analysed for 11,366 psoriasis patients. The age at onset for siblings of probands has been analysed for 805 probands having one affected sibling and for 179 probands having two affected siblings. The age at onset curve for all probands shows a dominating maximum at about puberty but also indications for two more maxima at about 30 and 50 years of age, respectively. A more relevant picture of the risk of getting psoriasis at different ages is obtained if the onset for old people having psoriasis is investigated. The three maxima come out more clearly in this case, and the puberty maximum is not so dominating. For the families with one proband and two affected siblings there is a statistically significant correlation (P < 0.001) between the age at onset of the proband and of the siblings, and also between the siblings. The correlation coefficient is between 0.30 and 0.45. For the probands with one affected sibling, the ages at onset of the siblings mainly fall in the same range as those of the probands. These data indicate three groups of patients with respect to age at onset. However, the overlap between the different groups is considerable. The data presented are compatible with three, possibly genetically different, variants of psoriasis vulgaris. By studying the occurrence of psoriasis among parents of the probands, the gene frequency can be estimated assuming a recessive mode of inheritance. It then turns out that the gene frequency of the group with the earliest age at onset has a gene frequency of about 0.25, the next earliest, 0.18, and the latest, 0.14.
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| 11. |
- Swanbeck, Gunnar, 1934, et al.
(författare)
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Genetic counselling in psoriasis: empirical data on psoriasis among first-degree relatives of 3095 psoriatic probands
- 1997
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Ingår i: Br J Dermatol. ; 137:6, s. 939-42
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Tidskriftsartikel (refereegranskat)abstract
- The risk of getting psoriasis dependent on the occurrence of psoriasis in the family has been determined empirically. Altogether 3717 families with one or both parents who had psoriasis have been analysed with regard to the number of children with or without psoriasis. The lifetime risk of getting psoriasis if no parent, one parent or both parents have psoriasis is 0.04, 0.28 and 0.65, respectively. If there is already one affected child in the family, the corresponding risks are 0.24, 0.51 and 0.83, respectively. The risk of getting psoriasis before the age of 32 years is dependent on the age-of-onset of psoriasis in one affected parent.
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| 12. |
- Vujic, Mihailo, 1945, et al.
(författare)
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Localization of a gene for autosomal dominant Larsen syndrome to chromosome region 3p21.1-14.1 in the proximity of, but distinct from, the COL7A1 locus.
- 1995
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Ingår i: American journal of human genetics. - 0002-9297. ; 57:5, s. 1104-13
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Tidskriftsartikel (refereegranskat)abstract
- Larsen syndrome (LS) is a skeletal dysplasia (osteochondrodysplasia) in which multiple dislocations of the large joints are the major feature. Nosology in this group of diseases, which constitutes 8% of Mendelian disorders in man, is primarily based on clinical and radiographic features. Hopes for more accurate classification grounds are currently being met by progress in elucidation of underlying genetic defects. We have performed linkage analysis in a large Swedish kindred with autosomal dominant LS and found the gene (LAR1) to be strongly linked to chromosome 3p markers (Zmax = 13.4 at (theta = .00). Recombination analysis indicates that the LAR1 locus is located in a region defined distally by D3S1581 and proximally by D3S1600, which cytogenetically maps to chromosome region 3p21.1-14.1. Linkage and recombination analysis of a COL7A1 PvuII intragenic polymorphism versus LS and chromosome 3 markers indicate that COL7A1 is located close to, but distinct from, the LAR1 locus.
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| 13. |
- Wahlström, Jan
(författare)
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T cell antigen receptor usage, phenotype and cytokine production in human diseases
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- T lymphocytes are of critical importance for initiating and controlling immune responses, as the T cell receptor (TCR) for antigen allows a highly specific antigen recognition. Determination of TCR usage and characterization of T cell subsets in different diseases helps us understand the underlying immunopathogenic mechanisms, and may also lead to the development of new therapeutic approaches. TCR usage was analyzed at the protein level by anti-TCR Va and V[beta] antibodies and flow cytometry. Vp-specific PCR amplification was followed by CDR3 fragment length analysis, cloning and sequencing or determination of J[beta] gene segment usage. Functional aspects were investigated via antibody staining for cell surface markers or intracellular cytokines. In allergic alveolitis most patients had lung-restricted CD8+ expansions of T cells using particular V[alpha] or V[beta] segments. These expansions, some of which were dramatic, normalized with clinical improvement. Similarly, patients with allergic asthma developed CD8+ T cell expansions in their lungs after allergen inhalation provocation. The correlation with antigen exposure implicates the expanded I cells in the pathogeneses of these diseases. In B-cell malignancies the immunoglobulin idiotype may serve as an autoantigen, being recognized by T cells that may have the capacity to control the myeloma tumour clone. Patients with multiple myeloma had more CD8+ T cell expansions, all of which were highly clonal, compared to age-matched controls. Interestingly, expansions were particularly common in patients with a low tumour burden. In Wegener's granulomatosis, a systemic vasculitis of unknown aetiology, very large T cell expansions were previously demonstrated in the CD4+ subset. We determined a high degree of clonality of all the expansions studied. Of utmost interest was the finding of a common, dominating TCR CDR3-motif that was found in CD4+ V[beta]8+ T cell expansions of several unrelated patients sharing the HLA DRB1*0401 allele, but not in age- and HLA-matched controls. This finding therefore suggests the existence of a specific vasculitis-associated antigen. A phenotypic analysis of T cell subsets in lung and blood of pulmonary sarcoidosis patients was undertaken, focusing on activation markers, adhesion molecules, and costimulatory molecules. There was substancial activation of CD4+ as well as of CD8+ lung T cells, and in the lung increased numbers of CD26+ CD28-CD57+ cells, indicating clonally expanded T helper 1 cells. Significantly more cells capable of producing IFN[gamma] and TNF[alpha], and fewer cells producing IL-4, were detected in both CD4+ and CD8+ lung T cell subsets compared to peripheral blood. Thus both subsets may contribute to the inflammatory process in the lung. The tendency to a relatively less pronounced Th1 response in HLA-DR17+ patients may be related to the very good prognosis of this patient group. These studies directs the attention to the potentially very important role for CD8+ T cells in several inflammatory pulmonary disorders.
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