| 1. |
- Kanter-Smoler, Gunilla, et al.
(author)
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Novel findings in Swedish patients with MYH-associated polyposis: mutation detection and clinical characterization
- 2006
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In: Clin Gastroenterol Hepatol. - : Elsevier BV. - 1542-3565. ; 4:4, s. 499-506
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Journal article (peer-reviewed)abstract
- BACKGROUND & AIMS: Biallelic mutations in the base-excision repair gene MYH have recently been associated with recessive inheritance of multiple colorectal adenomas. An investigation and characterization of MYH mutations in Swedish patients were therefore carried out. METHODS: A set of 15 unrelated adenomatous polyposis coli (APC)-mutation negative patients from the Swedish Polyposis Registry was screened for germline mutations in the MYH gene. The patients were clinically characterized and compared with 43 APC-mutation positive probands diagnosed during the same period. RESULTS: Disease-causing biallelic MYH mutations were identified in 6 patients (40%). The mean age at diagnosis was 47.8 years versus 34.1 years in APC-mutation positive patients (P = .015). Colorectal cancer at diagnosis of polyposis was present in 67% (4/6) of the patients, and all were right-sided, compared with only 19% versus 12.5% right-sided cancer in APC-mutation positive patients. Upper gastrointestinal manifestations were diagnosed in 1 of 5 compared with 23 of 27 in APC-mutation positive patients (odds ratio, 23; 95% confidence interval, 2-263; P = .0086). One family exhibited apparent dominant inheritance of colorectal adenomatous polyposis. Two new pathogenic mutations, MYH p.G175E and p.P391L, were identified. The mutations are argued to introduce profound changes in substrate-recognizing domains of the protein. CONCLUSIONS: Biallelic MYH mutations, including 2 novel mutations, were found in a substantial number of the patients with multiple colorectal adenomas who were negative for APC-mutation. The examined MYH-mutation positive patients were found to have higher risks of colorectal cancer at diagnosis, right-sided location of cancers, and a significantly lower incidence of upper gastrointestinal manifestations, compared with APC-mutation positive patients.
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| 2. |
- Adamovic, Svetlana, 1965, et al.
(author)
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Fine mapping study in Scandinavian families suggests association between coeliac disease and haplotypes in chromosome region 5q32.
- 2008
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In: Tissue Antigens. - : Wiley. - 1399-0039 .- 0001-2815. ; 71:1, s. 27-34
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Journal article (peer-reviewed)abstract
- The previous genome-wide scan in Scandinavian families supported earlier evidence for linkage of a region on chromosome 5 (5q31–33) to coeliac disease. This study deals with further genetic mapping of an 18 cM region, spanning from marker GAh18A (131.87 Mb) to D5S640 (149.96 Mb). Linkage and association analyses were performed in a two-step approach. First, seven microsatellites were added. Strong evidence for linkage was obtained with a Zlr score of 3.96, Pnc = 4 × 10−5 at marker D5S436. The strongest association was with a haplotype consisting of the markers D5S2033 and D5S2490 (Pnc < 0.001). In the second step, we added 17 microsatellites and 69 single nucleotide polymorphisms (SNPs) to the analysis. These markers were located close to or within candidate genes across the region of approximately 7 Mb beneath the linkage peak marked by D5S2017 and D5S812. A substantial increase of the linkage signal with a maximum Zlr score of 4.6 at marker rs1972644 (Pnc = 2 × 10−6) was obtained and several SNPs showed association. Seven SNPs that individually showed the strongest association were genotyped in a second independent family sample set (225 trios). In the trio family sample as well as in the multiplex family sample, the strongest association was found with SNPs within the region flanked by the associated microsatellites D5S2033 and D5S2490 at 5q32.
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| 3. |
- amundsen, silja, et al.
(author)
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A comprehensive screen for SNP associations on chromosome region 5q31-33 in Swedish/Norwegian celiac disease families.
- 2007
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In: European Journal of Human genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 15:9, s. 980-987
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Journal article (peer-reviewed)abstract
- Celiac disease (CD) is a gluten-induced enteropathy, which results from the interplay between environmental and genetic factors. There is a strong human leukocyte antigen (HLA) association with the disease, and HLA-DQ alleles represent a major genetic risk factor. In addition to HLA-DQ, non-HLA genes appear to be crucial for CD development. Chromosomal region 5q31–33 has demonstrated linkage with CD in several genome-wide studies, including in our Swedish/Norwegian cohort. In a European meta-analysis 5q31–33 was the only region that reached a genome-wide level of significance except for the HLA region. To identify the genetic variant(s) responsible for this linkage signal, we performed a comprehensive single nucleotide polymorphism (SNP) association screen in 97 Swedish/Norwegian multiplex families who demonstrate linkage to the region. We selected tag SNPs from a 16 Mb region representing the 95% confidence interval of the linkage peak. A total of 1404 SNPs were used for the association analysis. We identified several regions with SNPs demonstrating moderate single- or multipoint associations. However, the isolated association signals appeared insufficient to account for the linkage signal seen in our cohort. Collective effects of multiple risk genes within the region, incomplete genetic coverage or effects related to copy number variation are possible explanations for our findings.
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| 4. |
- Bergman, Annika, et al.
(author)
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A high frequency of germline BRCA1/2 mutations in western Sweden detected with complementary screening techniques
- 2005
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In: Familial Cancer. - : Springer. - 1389-9600 .- 1573-7292. ; 4:2, s. 89-96
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Journal article (peer-reviewed)abstract
- Dominant inheritance is presumed in 6-10% of breast and ovarian cancers. Mutations in BRCA1 and BRCA2 genes are the most commonly identified causative genes in such families. The frequency of mutation carriers with breast/ovarian cancer depends on the population studied, and display considerable variation that coincides with ethnic and geographical diversity. Mutation analyses were performed in 143 families registered at the Cancer Genetic Counseling Clinic of western Sweden. In a thorough mutation screening procedure, the entire BRCA1 and BRCA2 genes were analyzed using a combination of complementary mutation detection techniques. Mutations in either BRCA1 or BRCA2 were detected in 36% (52 out of 143) of all screened families. All families were clinically evaluated regarding age at diagnosis, type of cancer and number of cancer cases in the family. Among high-risk families, the mutation detection rate was 39% (46 out of 117). The detection rate observed among families with cases of ovarian cancer (42 out of 62, 68%), was substantially higher than in families with only breast cancer (10 out of 81, 12%). Age at ovarian cancer did not seem to have an effect on the detection rate. The analyses revealed 11 frameshift mutations, 4 nonsense mutations and 2 large deletions. Notably, the BRCA1 c.3171ins5 mutation accounted for 34 of 52 (65%) identified mutations. Seven mutations are novel: BRCA1c.409_410del; c.1912T>G; c.2228_2229del; c.3029delA; c.3433delA, a large deletion covering exons 1-3 of BRCA1and one BRCA2 mutation; BRCA2c.6287_6290del. We have shown that the founder mutation BRCA1 c.3171ins5 has a great influence on western Swedish breast/ovarian cancer families along with a high number of mutations unique for the region. In order to achieve a high mutation detection rate we suggest a combination of several detection techniques.
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| 5. |
- Bergman, Annika, et al.
(author)
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Genome-wide linkage scan for breast cancer susceptibility loci in Swedish hereditary non-BRCA1/2 families : Suggestive linkage to 10q23.32-q25.3
- 2007
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In: Genes, Chromosomes and Cancer. - : John Wiley & Sons. - 1045-2257 .- 1098-2264. ; 46:3, s. 302-309
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Journal article (peer-reviewed)abstract
- The two breast cancer genes BRCA1 and BRCA2 were identified more than 10 years ago and, depending on population, mutations in these genes are responsible for a varying percentage of familial breast cancer. In more than half the families, the increased risk of breast cancer cannot be explained by mutations in these genes, and the goal of this study was to locate novel susceptibility genes. One of the main difficulties in identifying the cause of hereditary non-BRCA1/BRCA2 breast cancer is genetic heterogeneity, possibly due to multiple, incompletely penetrant susceptibility genes, along with ethnic and geographic differences. In this study, one large family and 13 small to medium-sized families with multiple cases of breast cancer were analyzed by genome-wide linkage analysis. The genome scan was performed by genotype analysis of 10,000 SNP markers on microarrays. The strongest evidence of linkage (HLOD 2.34) was obtained on chromosome region 10q23.32-q25.3. A further two regions were identified, with LOD scores above 2.10 on 12q14-q21 and 19p13.3-q12. In a subset of families of western Swedish origin, two regions generated LOD scores exceeding 1.8: 10q23.32-q25.3 and 19q13.12-q13.32. The large family in the study exceeded LOD 1.5 in three regions: 10q23.32-q25.3, 19q13.12-q13.32, and 17p13. Our results indicate that one or more of the suggested regions may harbor genes that are involved in the development of breast cancer.
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| 6. |
- Einbeigi, Zakaria, 1962, et al.
(author)
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Occurrence of both breast and ovarian cancer in a woman is a marker for the BRCA gene mutations: a population-based study from western Sweden.
- 2007
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In: Familial cancer. - : Springer Science and Business Media LLC. - 1389-9600 .- 1573-7292. ; 6:1, s. 35-41
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Journal article (peer-reviewed)abstract
- AIM: This study aimed to analyze whether the occurrence of both breast and ovarian cancer in a woman serves as a marker for BRCA gene mutations. MATERIAL AND METHODS: This population-based study included 256 women in western Sweden who developed both invasive breast and ovarian tumors between 1958 and 1999. Archival paraffin tissue blocks of their tumors were retrieved for DNA-extraction to analyze the founder mutation, BRCA1 c.3171_3175dup (c.3171ins5), which is most common in this geographic area and four other common Scandinavian BRCA1 gene mutations and one BRCA2 mutation. Together, account these mutations for approximately 75% of the BRCA1/2 gene mutations in the clinical unit. RESULTS: Ninteen percent (95% confidence interval (CI) 14-24%) of the women carried one of the analyzed BRCA1 gene mutations but none of the women were positive for the analyzed BRCA2 mutation. One-third of the women with both tumors before age 60 were mutation carriers. BRCA1 c.3171_3175dup (c.3171ins5) constituted 84% of all identified mutations. Although the majority of breast cancers were invasive ductal and atypical medullary types, a variety of other breast malignancies were seen among mutation carriers. Serous ovarian carcinomas predominated among ovarian tumors. A variety of other ovarian tumors, including three granulosa-theca cell tumors, were also observed among mutation carriers. CONCLUSIONS: The occurrence of both breast and ovarian cancer in a woman is associated with a high likelihood of a constitutional BRCA1 mutation. These women and their families might therefore be considered for mutation screening after appropriate genetic counselling.
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| 7. |
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| 8. |
- Friberg, Camilla, et al.
(author)
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Analysis of chromosome 5q31-32 and psoriasis: confirmation of a susceptibility locus but no association with SNPs within SLC22A4 and SLC22A5.
- 2006
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In: The Journal of investigative dermatology. - : Elsevier BV. - 0022-202X. ; 126:5, s. 998-1002
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Journal article (peer-reviewed)abstract
- We have previously reported a region on chromosome 5q as a possible susceptibility region for psoriasis. This cytokine cluster-rich region has also been suggested as a susceptibility locus in other autoimmune or inflammatory diseases including Crohn's disease (CD) and rheumatoid arthritis (RA). Three specific single-nucleotide polymorphisms (SNPs) have been reported to associate with RA and CD and to change the functional activity of two organic cation transporters, solute carrier family 22 member 4/5 (SLC22A4) and (SLC22A5). In this study, we have analyzed these SNPs for an association with psoriasis. We have also performed a denser linkage analysis of this region with an additional 31 microsatellite markers. We were not able to detect any association with any of the three SNPs analyzed. However, our linkage result supports the involvement of this region in the etiology of psoriasis. We obtained a peak non-parametric linkage value of 3.1 for marker D5S436 in a subgroup of patients with joint complaints. This result supports the findings in another study of psoriasis patients originating from Iceland in which the authors obtained a peak logarithm of the odds score of 2.6 for marker D5S2090, only 2 Mb from D5S436. This suggests a psoriasis susceptibility locus on chromosome 5q32 that is involved in the arthritic phenotype of the disease.
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| 9. |
- Gudjonsdottir, Audur, 1959, et al.
(author)
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Association Between Genotypes and Phenotypes in Coeliac Disease.
- 2009
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In: Journal of pediatric gastroenterology and nutrition. - 1536-4801 .- 0277-2116. ; 49:2, s. 165-169
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Journal article (peer-reviewed)abstract
- BACKGROUND:: Coeliac disease (CD) is a genetically driven immunological intolerance to dietary gluten with a wide range of clinical presentations. The aim of this study was to investigate the heritability of the phenotype in CD and the influence on the phenotype of different genes associated with the disease. PATIENTS AND METHODS:: One hundred and seven families with at least 2 siblings with CD were collected. The patients were grouped in symptom grades on the basis of the clinical presentation, the age at diagnosis, and sex. Stratification analyses of the human leucocyte antigen-DQA1 and human leucocyte antigen-DQB1 genotypes, the CTLA4 +49A/G polymorphism, the CTLA4 haplotype MH30*G:-1147*T:+49*A:CT60*G:CT61*A and the 5q31-33 loci were done. RESULTS:: The heritability of the phenotype was estimated to be 0.45. Significant association and linkage was found between the clinical presentation and the CTLA4 +49A/G polymorphism but not for the other genotypes. No correlation was found between genotypes and age at diagnosis or sex. CONCLUSIONS:: Our results indicate that the heritability is determiner of the phenotype in CD. The CTLA4 +49A/G polymorphism is correlated to the clinical presentation: the AA genotype is associated with clinically silent disease.
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| 10. |
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| 11. |
- Inerot, Annica, 1949, et al.
(author)
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Collecting a set of psoriasis family material through a patient organisation; clinical characterisation and presence of additional disorders.
- 2005
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In: BMC Dermatology. - : Springer Science and Business Media LLC. - 1471-5945. ; 5:10
-
Journal article (peer-reviewed)abstract
- The aim of the present study was to describe the clinical characteristics of a population of psoriatics sampled from a patient organisation and not from hospitals or out-patient clinics. Furthermore, we wanted to compare siblings with and without psoriasis regarding the occurrence of other diseases.At the end of 1991, we initiated a project which aimed to study genetic factors leading to psoriasis. Firstly, we sent questionnaires to all the members of the Swedish Psoriasis Association. We then examined 1,217 individuals (570 with psoriasis) from 310 families, in their homes in the southern part of Sweden. All the available family members were examined clinically and asked about the course of the skin disease and the occurrence of other diseases. The eight hundred members of the proband generation were divided into two groups, with or without psoriasis, and their clinical features were compared.Most individuals in this study population had a mild form of psoriasis. The siblings with psoriasis had joint complaints significantly more frequently than their siblings without the skin disease and those with joint complaints had more widespread skin disease. Among the other studied concomitant diseases (iritis, heart or hypertension disease, endocrine disease, inflammatory bowel disease and neurological disease), we were not able to find any difference. Seventy-seven of 570 persons were found to be in remission (13.5%). Females had a mean onset 2.5 years earlier than males. We were not able to find any correlation between the extent of the skin disease and age at onset. Twice as many persons with joint complaints were found among those with psoriasis than among those without, 28% versus 13%. Almost half (48%) the psoriatics who also had joint complaints had psoriasis lesions on their nails. Endocrine disorders were found in 9% of those without any allele for Cw6, but only in 1% of those who had Cw6. In fact, none of 183 Cw6 carriers had diabetes, as compared to the population prevalence of 3-5% in Sweden.With the exception of joint complaints, persons with psoriasis, collected from a patient organisation, did not have an increased frequency of (studied) co-existing diseases.
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| 12. |
- Janosik, Tomasz, et al.
(author)
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Efficient sulfonation of 1-phenylsulfonyl-1H-pyrroles and 1-phenylsulfonyl-1H-indoles using chlorosulfonic acid in acetonitrile
- 2006
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In: Tetrahedron. - : Elsevier BV. - 0040-4020 .- 1464-5416. ; 62:8, s. 1699-1707
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Journal article (peer-reviewed)abstract
- The sulfonation of various 1-phenylsulfonyl-1H-pyrroles and 1-phenylsulfonyl-1H-indoles using chlorosulfonic acid in acetonitrile has been studied, leading to the development of a clean and operationally simple protocol allowing direct synthesis of the corresponding 1-phenylsulfonyl-1H-pyrrole-3-sulfonyl chlorides and 1-phenylsulfonyl-1H-indole-3-sulfonyl chlorides, respectively, both of which may be easily converted to various sulfonamide derivatives by treatment with nitrogen nucleophiles. Efficient and selective removal of the phenylsulfonyl- or tosyl groups in the sulfonamide series may be achieved under mild conditions.
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| 13. |
- Knoppers, B.M., et al.
(author)
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Ethic's issues in stem cell research
- 2006
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 312:5772, s. 366-367
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Journal article (other academic/artistic)abstract
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| 14. |
- Knoppers, Bartha Maria, et al.
(author)
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Oocyte donation for stem cell research
- 2007
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 316:5823, s. 368-
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Journal article (peer-reviewed)
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| 15. |
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| 16. |
- Low, W C, et al.
(author)
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Hereditary multi-infarct dementia of the Swedish type is a novel disorder different from NOTCH3 causing CADASIL
- 2007
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In: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 130:Part 2, s. 357-367
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Journal article (peer-reviewed)abstract
- Several hereditary small vessel diseases (SVDs) of the brain have been reported in recent years. In 1977, Sourander and Wålinder described hereditary multi-infarct dementia (MID) in a Swedish family. In the same year, Stevens and colleagues reported chronic familial vascular encephalopathy in an English family bearing a similar phenotype. These disorders have invariably been suggested to be cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) but their genetic identities remain unknown. We used molecular, radiological and neuropathological methods to characterize these disorders. Direct DNA sequencing unexpectedly confirmed that affected members of the English family carried the R141C mutation in the NOTCH3 gene diagnostic of CADASIL. However, we did not detect any pathogenic mutations in the entire 8091 bp reading frame of NOTCH3 or find clear evidence for NOTCH3 gene linkage in the Swedish DNA. This was consistent with the lack of hyperintense signals in the anterior temporal pole and external capsule in Swedish subjects upon magnetic resonance imaging. We further found no evidence for granular osmiophilic material in skin biopsy or post-mortem brain samples of affected members in the Swedish family. In addition, there was distinct lack of NOTCH3 N-terminal fragments in the cerebral microvasculature of the Swedish hereditary MID subjects compared to the intense accumulation in the English family afflicted with CADASIL. Several differences in arteriosclerotic changes in both the grey and white matter were also noted between the disorders. The sclerotic index values, density of collagen IV immunoreactivity in the microvasculature and number of perivascular macrophages were greater in the English CADASIL samples compared to those from the Swedish brains. Multiple approaches suggest that the Swedish family with hereditary MID suspected to be CADASIL has a different novel disorder with dissimilar pathological features and belongs to the growing number of genetically uncharacterized familial SVDs.
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| 17. |
- Palm, Lars, 1960-
(author)
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On Fixation of Hip Prostheses
- 2007
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Doctoral thesis (other academic/artistic)abstract
- This thesis, comprising 5 separate studies, is concerned with fixation of prosthetic components in total hip arthroplasty. The results and conclusions of the studies fol-low;The initial stability of femoral revision components, the long cementless PCA stem and the Exeter standard stem cemented in a bed of impacted bone graft, was com-pared in an experimental study. The PCA stem was more stable than the Exeter stem. However, for both stems initial stability may not be sufficient to allow bone ingrowth. Initial fixation is especially vulnerable to torsion.Identical femoral stems with or without HA-coating were compared in a prospec-tive randomized clinical trial. The long-term stable fixation of a cementless Link RS femoral component was improved by application of hydroxyapatite coating to the femoral stem.In a clinical study the method of extensive impaction of morsellized bone allograft and a hydroxyapatite-coated cementless Mallory-Head acetabular component was found to be advantageous for acetabular revision in the presence of contained or acetabular wall defects. The limited contact between the HA-coated implant and living host bone did not seem to compromise long-term stable fixation.Two different cup designs were compared in a prospective randomized RSA study. At 3 years after implantation the cemented low profile Lubinus FAL cup performed as well as the cemented Lubinus Standard cup in terms of migration and polyethyl-ene wear.In a study of the relationship between radiolucent lines and migration the Lubinus FAL cup displayed more radiolucent lines in the cement bone interface than the Lubinus Standard cup but no difference in migration was found. Early appearance of such radiolucent lines represents an unspecific finding without reliable correla-tion to 3-year migration of the acetabular component.
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| 18. |
- Sahlin, Nils-Eric, et al.
(author)
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Läkaren som riskanalytiker
- 2009
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In: Läkartidningen. - 0023-7205. ; 106:52, s. 3517-3519
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Journal article (other academic/artistic)
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| 19. |
- Swartling, Malin, et al.
(author)
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Sick-listing as a psychosocial work problem : a survey of 3997 Swedish physicians
- 2007
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In: Journal of occupational rehabilitation. - : Springer Science and Business Media LLC. - 1053-0487 .- 1573-3688. ; 17:3, s. 398-408
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Journal article (peer-reviewed)abstract
- OBJECTIVES: To quantify the extent of emotionally straining sick-listing problems among three categories of physicians and find associations with workplace characteristics. METHODS: A questionnaire was answered by 3997 physicians (response rate: 71%). RESULTS: A larger proportion of physicians at orthopaedic clinics and, in particular, at Primary Health Care Centres (PHCCs), experienced sick-listing problems, compared to physicians at other clinics. Ten percent of PHCC physicians felt threatened by patients, at least once per month, in relation to sickness certification or worried about getting reported to the disciplinary board. PHCC physicians found sick-listing more problematic compared to others (OR 4.9; 95% CI 4.1-6.0). Having a workplace policy on sick-listing was associated with a reduced risk of experiencing several problems (OR 0.5-0.6, P < 0.05). CONCLUSION: The extent and nature of sick-listing problems warrant further concerns, especially in PHCCs. The nature of perceived threats should be elucidated. Developing workplace policies on sick-listing should be encouraged.
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| 20. |
- Tajsharghi, Homa, et al.
(author)
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Mutations and sequence variation in the human myosin heavy chain IIa gene (MYH2)
- 2005
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In: European Journal of Human Genetics. - : Nature Publishing Group. - 1018-4813 .- 1476-5438. ; 13:5, s. 617-22
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Journal article (peer-reviewed)abstract
- We recently described a new autosomal dominant myopathy associated with a missense mutation in the myosin heavy chain (MyHC) IIa gene (MYH2). In this study, we performed mutation analysis of MYH2 in eight Swedish patients with familial myopathy of unknown cause. In two of the eight index cases, we identified novel heterozygous missense mutations in MYH2, one in each case: V970I and L1061V. The mutations were located in subfragment 2 of the MyHC and they changed highly conserved residues. Most family members carrying the mutations had signs and symptoms consisting mainly of mild muscle weakness and myalgia. In addition, we analyzed the extent and distribution of nucleotide variation in MYH2 in 50 blood donors, who served as controls, by the complete sequencing of all 38 exons comprising the coding region. We identified only six polymorphic sites, five of which were synonymous polymorphisms. One variant, which occurred at an allele frequency of 0.01, was identical to the L1061V that was also found in one of the families with myopathy. The results of the analysis of normal variation indicate that there is strong selective pressure against mutations in MYH2. On the basis of these results, we suggest that MyHC genes should be regarded as candidate genes in cases of hereditary myopathies of unknown etiology.
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| 21. |
- Torinsson Naluai, Åsa, 1968, et al.
(author)
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Searching for genes influencing a complex disease: the case of coeliac disease.
- 2008
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In: European journal of human genetics : EJHG. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 16:5, s. 542-53
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Journal article (peer-reviewed)abstract
- Recently, a few genes have been reported to be causative in inflammatory diseases. Still, we are waiting for the vast majority to be discovered. New tools for genotyping and statistical analysis have been developed and emphasis has been put on study design. Coeliac disease (CD) is a disorder, where prolamins in dietary wheat gluten and related proteins from rye or barley are not tolerated. It is one of the most common chronic diseases in humans exceeding a population prevalence of 1%. In this article, we will summarise what is currently known about the genetics influencing CD with the emphasis on the non-HLA genetic component. We will discuss some difficulties when searching for susceptibility genes in disorders with complex inheritance patterns.
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| 22. |
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| 23. |
- Wahlström, Jan, et al.
(author)
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Identification of HLA-DR-bound peptides presented by human bronchoalveolar lavage cells in sarcoidosis
- 2007
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In: Journal of Clinical Investigation. - 0021-9738 .- 1558-8238. ; 117:11, s. 3576-3582
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Journal article (peer-reviewed)abstract
- Sarcoidosis is an inflammatory disease of unknown etiology, most commonly affecting the lungs. Activated CD4(+) T cells accumulate in the lungs of individuals with sarcoidosis and are considered to be of central importance for inflammation. We have previously shown that Scandinavian sarcoidosis patients expressing the HLADR allele DRB1*0301 are characterized by large accumulations in the lungs of CD4(+) T cells expressing the TCR AV2S3 gene segment. This association afforded us a unique opportunity to identify a sarcoidosis-specific antigen recognized by AV2S3(+) T cells. To identify candidates for the postulated sarcoidosis-specific antigen, lung cells from 16 HLA-DRB1*0301(pos) patients were obtained by bronchoalveolar lavage. HLA-DR molecules were affinity purified and bound peptides acid eluted. Subsequently, peptides were separated by reversed-phase HPLC and analyzed by liquid chromatography-mass spectrometry. We identified 78 amino acid sequences from self proteins presented in the lungs of sarcoidosis patients, some of which were well-known autoantigens such as vimentin and ATP synthase. For the first time, to our knowledge, we have identified HLA-bound peptides presented in vivo during an inflammatory condition. This approach can be extended to characterize HLA-bound peptides in various autoimmune settings.
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| 24. |
- Wahlström, Niklas, et al.
(author)
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Synthetic Applications of Cyanoacetylated Bisindoles : Synthesis of Novel Cycloheptadiindoles, Indolocarbazoles, and Related Aza Analogues.
- 2007
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In: Journal of Organic Chemistry. - : American Chemical Society (ACS). - 0022-3263 .- 1520-6904. ; 72:15, s. 5886-5889
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Journal article (peer-reviewed)abstract
- (Chemical Equation Presented) Cyclization reactions involving cyanoacetylated bisindoles have been studied, providing access to various novel cyclohepta[2,1-b:3,4-b′]diindole derivatives as well as some related fused pentacyclic systems. Treatment of 3-cyanoacetyl-2,3′-diindolylmethane with methanesulfonic acid gave 6-(cyanomethyl)indolo[3,2-b]carbazole in a good yield.
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