The initiation of a liver transplantation program in Stockholm.
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Biomedical subjects
Publications and source records attributed to E Möller.
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Glucose-induced insulin response and insulin sensitivity were studied in 32 HLA-identical, 38 haplo-identical and 24 non-identical, islet-cell-antibody-negative, healthy siblings of young Type 1 (insulin-dependent) diabetic patients (age range 10-28 years). No significant differences were obtained between HLA-identical, HLA-haplo-identical siblings and HLA-non-identical siblings in insulin response using an i.v. glucose infusion test even when the insulin sensitivity as estimated by the somatostatin-insulin-glucose infusion test was taken into account. A significant inverse correlation to age was found for both insulin response (r = -0.24, p = 0.02) and insulin sensitivity (r = -0.36, p less than 0.01) in the young siblings studied.
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Through the analysis of RFLP (restriction fragment length polymorphism) of the HLA-DR beta, -DQ alpha, and -DQ beta genes from 70 serologically well-characterized individuals, we have established unique HLA-DR-DQ RFLP haplotypes correlating to all of the DR1-w14 specificities. The RFLP of DR beta, DQ alpha, and DQ beta genes is very high using the restriction enzyme TaqI and 21 DR-DQ RFLP haplotypes were defined with this restriction enzyme. Our analysis confirms the strong linkage disequilibrium between alleles in the DR and DQ loci. DR beta RFLP indicates a common ancestor for the DR alleles within either of the supertypic DRw52 and DRw53 specificities. The DQ beta gene shows a high degree of RFLP, and the RFLP alleles partly reflect the serologic DQw1-w3 specificities. The results presented here also demonstrate the heterogeneity of DRw6 (DRw13 and DRw14) associated haplotypes, and the DRw13 related Dw18 and Dw19 specificities were found to have distinct DR-DQ haplotypes. The DQw1 positive haplotypes DR1, 2, w10, w13, and w14 are related with regard to DQ alpha and DQ beta RFLPs and the DRw52 positive haplotypes DR3, w11, and w12, as well as the DRw53 positive haplotypes DR4, 7, and w9, are related with regard to DR beta and DQ alpha RFLPs. These findings indicate that polymorphic sequences around the DQ alpha gene are associated with DR beta and DQ beta polymorphism, which suggests a location of the DQ alpha gene between DR beta and DQ beta.
One hundred children consecutively treated for simple febrile convulsions (FC) were investigated with respect to hereditary factors. Twenty-five of the children had parents or siblings with FC. HLA-typing was performed in all available members of ten families with one or two FC children and one FC parent, and in one family with two FC children but no FC parent. There was no clear association with a particular HLA haplotype in any of these families.
Eighteen MS patients were HLA-typed by RFLP-analysis using DR beta and DQ beta cDNA probes. A closer association to the DQ than to the DR locus was not found in this small material, not even within DR-specificities.
Thirty-five patients with psoriasis vulgaris were HLA-typed by RFLP-analysis using DR beta and DQ beta cDNA probes. A closer association to the DQ than to the DR locus was not found in this small material.
Of 25 patients with a longstanding diagnosis of narcolepsy 23 were HLA-DR2 positive. The 2 DR2 negative patients were misdiagnosed when retrospectively interviewed. HLA-DR2 determination is a valuable tool for ascertaining the narcolepsy diagnosis in uncertain cases.
The possible role of HLA phenotypes was investigated in the development of juvenile liver disease in persons with alpha 1-antitrypsin deficiency. Seventeen patients were investigated between the ages of 3-25 years. All of them had alpha 1-antitrypsin phenotype PiZ. After a longer follow-up a clinical diagnosis was established by the help of physical status, biochemical liver function tests and--in the cases of suspected liver disease--liver biopsy. The clinical course was correlated to the HLA phenotypes of the patients. In 2 cases all first degree relatives were investigated, as well. Our studies on the 17 unrelated patients indicated no correlation between HLA and juvenile liver disease in alpha 1-antitrypsin deficiency. The family studies confirmed these findings.
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Insulin-dependent diabetes is generally associated with the serologic HLA-DR specificities 3 and 4, in particular with DR-3,4 heterozygosity. The disease is negatively associated with DR-2. To investigate these associations further at the genomic level, DNA from 13 families with a proband having insulin-dependent diabetes, from 11 other individuals with the same disease, and from HLA-DR-matched control individuals was subjected to restriction fragment analysis. Three different enzymes (Bam HI, Eco RI, and Pvu II) and cDNA clones for three HLA-D region class II antigen alpha- and beta-chains (DR-beta, DQ-beta, and DQ-alpha) were used. In six families, a total of 11 siblings HLA-DR-identical to the proband were examined. There was no discrepancy between the hybridization patterns of the proband and those of the DR-identical siblings. Two different DQ-B fragment patterns were detected with each one of the serologic specificities DR-2 and DR-4. In both cases, only one of the patterns correlated significantly with diabetes. Thus, DQ-beta genomic hybridization may be used in conjunction with HLA-DR typing to identify individuals with higher relative risk to acquire insulin-dependent diabetes. These results may suggest that insulin-dependent diabetes is associated with the DQ rather than with the DR locus.
Cyclosporin A (CyA) is the immunosuppressive treatment of choice in preventing allograft rejection and graft-versus-host disease. However, clinical trials indicate that there may exist inter-individual variations in sensitivity to the drug. We have approached this issue by studying CyA-mediated inhibition of in vitro alloreactions, as measured by mixed lymphocyte reactions (MLR) and cell-mediated lympholysis (CML), using mouse and human normal spleen cells. The differences between individuals in the CyA concentration required for 50% inhibition of the human alloreactions were twentyfold for the MLR and fortyfold for the CML. Moreover, the CML appeared to be inhibited at lower doses of the drug. No correlation was found between inhibitory doses and variables such as the magnitude of the response, age, or human leukocyte antigen phenotype. When the same experiments were performed with mouse spleen cells, no differences were observed among eight inbred strains. The lack of demonstrable individual sensitivity of mice in relation to humans is discussed.