Search PubMed⌕ Search

Biomedical subjects

P Platz

Publications and source records attributed to P Platz.

At least 73 records · Page 4Linked to original sources
PubMed1982

HLA and diabetes.

HLA studies have conclusively demonstrated that IDDM and non-IDDM are separate disease entities. A considerable part of the genetic susceptibility to IDDM is due to one or more HLA genes. The HLA-DR3 and -DR4 factors showing the strongest association with IDDM belong to the so-called DR antigens, which are believed to be the immune response determinants of man. A dominant model for the HLA-controlled susceptibility to IDDM has been ruled out and a recessive model seems unlikely. A gene-dose model intermediate between dominance and recessivity is still possible, but there is also some evidence against this model, because DR3/4 heterozygotes seem to have a considerably higher risk of developing IDDM than has DR3/3 and DR4/4 homozygotes. It has been suggested that DR3 (or a DR3-associated factor) and DR4 (or a DR4-associated factor) confer susceptibility to IDDM each by a separate mechanism, and more recently that DR3/4 heterozygotes may carry combinatorial antigens which could contribute to the susceptibility to IDDM. Studies of HLA-associated clinical heterogeneity within IDDM are indicated to gain further insight in the genetics of IDDM.

Diabetes Mellitus↗
PubMed1981

HLA-D and -DR antigens in genetic analysis of insulin dependent diabetes mellitus.

Three groups of patients with insulin-dependent diabetes mellitus, ascertained by different procedures, were investigated for HLA-A, B, C and D antigens (n = 164), and a subset (n = 93) for HLA-DR. Both HLA-D/DR3 and D/DR4 were strongly positively associated and D/DR2 was negatively associated with insulin-dependent diabetes. HLA-DR+ was found to be a better marker for insulin-dependent diabetes than Dw4. The HLA-B associations (B8, B15 and B18) were clearly secondary to the increases of HLA-D/DR3 and D/DR 4. The HLA associations did not differ between familial and isolated cases indicating that these two groups may well have a common genetic background. Based on analysis of HLA-haplotype sharing in affected sibling pairs, a simple dominant model of inheritance could be ruled out, and a simple recessive model was found unlikely. The relative risks for the HLA-Dw3,4 and HLA-DR3,4 phenotype were 21.2 and 44.4 respectively and exceeded those of both the HLA-Dw3 and HLA-DR3 (5.6 and 4.3) as well as the HLA-Dw4 and DR4 (10.1 and 10.5) phenotypes. This argues against an intermediate genetic model but further studies are needed to clarify whether there is more than one susceptibility gene for insulin-dependent diabetes mellitus within the HLA-system.

Diabetes Mellitus↗
PubMed1981

Typing for human alloantigens with the primed lymphocyte typing (PLT) technique with notes on the interpretation of PLT data.

A typing system for HLA-D/DR-associated PLT-defined determinants, which have been called "DP" antigens, is reported. Some of the results concerning a data interpretation system, the reproducibility of PLT results, and the correlations between the results of HLA-D, -DR, and DP typing are presented. Also, a "new" human alloantigen, EP1, not belonging to the series of DP antigens, is defined with PLT.

Epitopes↗
PubMed1981

Technical aspects of the primed lymphocyte typing (PLT) technique.

The influence of different culture conditions in the primary and secondary cultures of the primed lymphocyte typing (PLT) technique was investigated with special reference to the discriminatory capacity of the PLT-cells generated. In the primary cultures, the maximal yield of PLT-cells was observed early (about day 7) and decreased thereafter, while the maximal specificity was obtained considerably later (about day 14). In the secondary cultures, the optimal culture time was in the interval 42 h - 72 h, and up to this culture length, gamma-irradiation (2,200-8,800 rad) of the secondary stimulators had no effect on the 14C-thymidine uptake of the cultures. In U-form microtiterplates, the number of PLT-cells per well should not be less than 2.5 X 10(4), and higher PLT-cell numbers (e.g. 5.0 X 10(4) per well) may confer further robustness upon the technique. The PLT-cell response and the discrimination was only slightly influenced by the number of secondary stimulator cells in the interval 5 X 10(4) to 2 X 10(5) cells per well. Freezing of the PLT-cells under controlled conditions resulted in a minor loss of viable eosin-excluding cells, while the specificity of the PLT-cells was unaffected. Even when the culture conditions are standardized, it is necessary to perform a normalization of the data in order to obtain reproducible results. The normalization procedure should include a compensation for the variation in (i) the general responding capacity of each PLT-cell and in (ii) the general stimulatory capacity of each secondary stimulator.

Cells, Cultured↗
PubMed1981

Correlation between HLA-D/DR associated primed lymphocyte typing (PLT) defined DP-antigens, HLA-D and HLA-DR antigens.

A panel of 79 individuals were typed for HLA-D/DR associated Primed Lymphocyte Typing (PLT) defined "DP"-antigens, HLA-D and HLA-DR antigens. Typing for DP-antigens was carried out with local PLT-cells. HLA-D and -DR typing was performed with all homozygous typing cells and all DR-antisera included in the 8th International Histocompatibility Workshop. Assignments of DP-, HLA-D- and HLA-DR-antigens were done independently and the correlations between DP/D/DR1-8 were analyzed. The panel included random unrelated individuals, and individuals previously found to have one or no identifiable HLA-D antigen (B). In the random group, 80% of the individuals were assigned to possess the same antigen with the 3 techniques, while this was only the case in 46% of B-group individuals. The overall correlation coefficients, r, for the antigens HLA-Dw/-DR/DP1-8 were 0.95 (DP/D), 0.94 (DP/DR), and 0.89 (D/DR). There is a remarkably strong correlation between HLA-D and -DR typing results concerning D/DR1-8, in particular in random individuals. It is possible to select PLT-cells that give typing results which are almost identical to those of HLA-D and -DR typing. When discrepant results were seen, HLA-DR was in general "broader" than DP which in turn was broader than HLA-D, indicating that it may be possible to split HLA-DR/DP1-8 into more "narrow" specificities.

Blood Grouping and Crossmatching↗
PubMed1981

HLA-A, B, C, D, DR antigens and primed lymphocyte typing (PLT) defined DP-antigens in juvenile chronic arthritis.

A total of 48 patients with juvenile chronic arthritis (JCA) were typed for HLA-A, -B, -C, -D and -DR antigens and 36 patients were also typed for HLA-D/DR associated "DR"-antigens with the primed lymphocyte typing technique. In the total group of patients, we found increased frequencies of HLA-B27, HLA-Dw/DP5 and HLA-Dw/DP8, and decreased frequencies of HLA-Dw/-DR/DP2. The increased frequencies of HLA-Dw/DP8 and the decreased frequencies of HLA-Dw/-DR/DP2 were primarily found among patients with persistent pauciarticular arthritis. The frequencies of HLA-Dw/-DR/DP4 were increased in patients with polyarticular arthritis. The frequencies of HLA-B27 and -Dw/DP5 were increased in both pauciarticular and polyarticular arthritis. The results indicate (i) that genetic factors controlled by HLA confer susceptibility and/or resistance to JCA, and (ii) that the clinical subdivision of JCA into pauciarticular and polyarticular JCA can be supported by the presence of different genetic markers (HLA-antigens) in the two groups of JCA-patients. If these data can be confirmed HLA-D, -DR or DP typing may be of value in the prognostic evaluation of patients with pauciarticular onset JCA.

Antigens, Surface↗
PubMed1981

HLA-DR phenotype and HLA-B,DR haplotype frequencies in 704 unrelated Danes.

HLA-ABC and DR antigens were studied in 704 unrelated Danes (84 cadaver kidney donors, 307 healthy individuals, and 313 uremic patients), HLA-DR1, 2, 3, 4, 7, w8, and w10 were investigated in all individuals, whereas DR5, "DRw6", and w9 were only studied in parts of the material. The frequencies of DR1, 2, 3, 4, 5, and w10 were similar in the three groups, while those of "DRw6", DR7 and w8 differed significantly. The deviation of the DR7 frequency was small and probably due to change; "DRw6" is considered difficult to define, and DRw8 may have been difficult to define in the early part of the material. DR-phenotype distributions showed perfect fits to Hardy-Weinberg expectations for the three groups separately and for the combined group. When our combined DR antigen frequencies were compared with those from another Danish sample (Madsen et al, 1981), significant differences were found for "DRw6", w8 and w10. However, in general, the same HLA-B,DR phenotype combinations showed significant positive associations in the two samples, and most of the corresponding haplotype frequencies and delta values were quite similar.

Denmark↗
PubMed1981

Effect of in vitro X-irradiation on lymphocyte and granulocyte function.

Granulocyte transfusions have been complicated by graft-versus-host disease (GVHD) in the recipients. This risk can be eliminated by irradiation of the cell product. The effect of in vitro irradiation on elements of lymphocyte and granulocyte function was therefore studied in order to determine the dose of irradiation which blocked lymphocyte function without affecting the function of granulocytes. Lymphocyte blast transformation after stimulation with mitogens was reduced by 90% after irradiation with 1500 rad and by 97% after 5 000 rad. The response to microbial agents and allogeneic cells was far more radio-sensitive, being completely abolished after irradiation with 1 000 and 500 rad, respectively. Mobility was the function of polymorphonuclear leucocytes (PMN) most affected by irradiation, being slightly but significantly reduced after irradiation with 10 000-20 000 rad. The bactericidal activity was reduced only after irradiation with 40 000 rad or more, while the hexose monophosphate shunt activity and the myeloperoxidase activity were largely unaffected by irradiation with doses of up to 120 000 rad. Hence the results indicate that the irradiation of leucocytes intended for transfusion with a dose of 2 000 rad is likely to prevent GVHD without causing any apparent damage to the PMN.

Chemotaxis, Leukocyte↗
PubMed1981

HLA-D antigen frequencies in Sjögren's syndrome. Differences between the primary and secondary form.

HLA-A, B, C and D typing was performed in 19 patients with primary Sjögren's syndrome (primary SS) and in 15 patients with rheumatoid arthritis (RA) and secondary Sjögren's syndrome (RA-SS). In the primary SS group, the frequency of HLA-Dw2 was increased (p less than 0.01; "corrected" p greater than 0.05) while the frequency of Dw3 was non-significantly increased. In the RA-SS patients, the frequency of HLA-Dw4 was increased to 84.6% (relative risk = 22.8; p less than 0.001) and the frequency of Dw2 was non-significantly decreased. An increased frequency of Dw2 in primary SS has not been reported before. To investigate if this observation was due to chance, a new series of 16 patients with primary SS were HLA typed. In this new group, the frequencies of both Dw2 and Dw3 were significantly increased, while the frequency of Dw4 was significantly decreased. In the whole group of primary SS patients, the frequencies of Dw2 were 56.3% (relative risk = 3.7; p less than 0.001). Dw3:50.0% (relative risk = 2.8; p less than 0.01) and Dw4: 6.3% (relative risk = 0.28; p less than 0.05). We conclude that genetic factors associated with the HLA-system are involved in the development of Sjögren's syndrome and that these genetic factors are different in primary and secondary Sjögren's syndrome. In primary Sjögren's syndrome, the association with both Dw2 and Dw3 might suggest a further heterogeneity of the syndrome.

Arthritis, Rheumatoid↗
PubMed1981

HLA-DR typing in cadaver kidney donors and recipients in Copenhagen.

Among 224 cadaver kidney transplantations performed since Spring 1977, successful DR typing of both donor and recipient could be done in 149 cases. Assessment of DR match grade and clinical data was done independently. The minimum observation time was 3 months and the time of follow up was 1 December, 1980. There was an effect of DR matching which became significant when only 1. transplants were considered and high risk recipients (i.e. diabetics) excluded. Transfusions were of minor importance on graft survival and the difference was only obvious in the first year after transplantation. Matching for HLA-A, B antigen had no obvious effect on graft survival in this material.

Blood Transfusion↗
PubMed1981

A review of HLA antigens in longstanding IDDM with and without severe retinopathy.

The hitherto published studies of HLA antigens in diabetic retinopathy are reviewed. The existence of HLA associated genes conferring susceptibility (or resistance) to the development of diabetic retinopathy has neither been proved nor ruled out. Possible explanations of the lack of unanimous conclusions are discussed. Further studies in caucasians and other ethnic groups are warranted: future studies should be internationally accepted, well-defined diagnostic criteria and classifications of diabetes and diabetic retinopathy, and study and control groups should be carefully matched for other genetic and nongenetic risk factors. Future studies should include HLA D/DR typing.

Diabetes Mellitus↗
PubMed1980

Typing for HLA-D/DR associated DP-antigens with the primed lymphocyte typing (PLT) technique.

A total of 74 healthy unrelated random individuals and 36 patients with juvenile rheumatoid arthritis (JRA) were typed for HLA-D antigens with the homozygous typing cell technique and typed for HLA-D/DR associated DP-antigens with the primed lymphocyte typing (PLT) technique. All patients and some of the controls were also HLA-DR typed with a limited battery of anti-DR sera. Selected PLT-cells, specific for the HLA-D/DR antigens D/DRw1-8 and the local specificity D"H" were used. The results of the PLT-experiments were evaluated with the Normalized Median Response (NMR) method and the further procedure of DP-antigen assignment was analyzed. The DP-antigen assignments could be done solely according the NMR-values in approximately two thirds of the individuals. In the remaining individuals, further interpretation of the experimental data had to be done for the assignment of DP-antigens. The correlation coefficients were estimated between the HLA-D assignments and (i) the individual PLT-cell NMR-values with a fixed cut-off for positive reactions and (ii) the DP-antigen assignments. These coefficients were 0.79 and 0.92, respectively. The correlations between HLA-D, -DR and DP-antigen assignments of the specificities HLA-D, -DR and DP1, 2, 3, 4, 7 and 8 were analyzed in 42 controls and 36 JRA patients. The total correlation coefficients were: (i) HLA-D/DR: r = 0.78; HLA-DR/DP: 0.77; and HLA-D/DP: 0.96. The DP-antigen assignments correlated significantly better with HLA-D than with the HLA-DR antigen assignments, which does not agree with other studies. The DP-antigen frequencies among the controls were calculated and the estimated sum of gene frequency corresponding to definable DP-antigens was 0.94 indicating that about 12% of random individuals possess as yet undefined DP-antigens.

Antibody Specificity↗
PubMed1980

A "new" primed lymphocyte typing (PLT) defined DP-antigen associated with a private HLA--DR antigen.

We have recently described a "new" private HLA-DR antigen, DR"LTM", which has a frequency of approximately 0.6% in Danes. Primed Lymphocyte Typing (PLT) cells directed towards DR"LTM"-associated determinants were generated in vitro by haplotype primings in two unrelated families with DR"LTM" positive individuals. Both PLT-cells reacted in parallel and gave positive reactions with (i) two unrelated and (ii) eight related individuals, all of whom were DR"LTM"-positive. Both PLT-cells gave negative reactions with (i) 38 unrelated and (ii) 15 related DR"LTM"-negative individuals. Thus, there was total agreement between the results obtained by HLA-DR typing with the antiserum "LTM" and by PLT-typing with these two haplotype primed PLT-cells. None of the DP"LTM"-positive individuals carried more than one of the antigens HLA-Dw/-DRw/DP1-8 and the local specificity D/DP"H". Accordingly, this "new" PLT-defined antigen, DP"LTM", most probably belongs to the series of HLA-D/DR-associated DP-antigens previously described.

Arthritis, Juvenile↗