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Biomedical subjects

M Madsen

Publications and source records attributed to M Madsen.

At least 217 records · Page 12Linked to original sources
PubMed1983

The impact of HLA-DR antigen matching on the survival of cadaveric renal allografts. A prospective one-center analysis.

The impact of HLA-DR antigen matching on the survival of cadaveric renal allografts was assessed in 158 consecutive transplants performed in our unit since early 1978. In 41 donor-recipient pairs with two shared HLA-DR antigens, the actuarial graft survival rate at 6 months was 73% as compared with 51% in 76 transplants with one HLA-DR antigen shared and 32% in 41 transplants with zero shared HLA-DR antigens. This finding is highly significant (P for heterogeneity [PH] = 0.0005 and P for trend, [PT] = 0.0001). Our data clearly indicate that HLA-DR antigen sharing is more beneficial than merely avoiding HLA-DR incompatibility. But, the frequent antigen HLA-DRw6 was not taken into account in this study due to difficulties in its identification. We found no evidence that the observed beneficial effect of HLA-DR matching could be explained by interaction of other prognostic factors, such as sex, age, previous transplantation, diabetes mellitus or pretransplant blood transfusion. Patients who did not receive blood transfusion prior to transplantation had a significantly lower graft survival rate than those who did (13% vs. 56% at 6 months). HLA-DR matching was found to have a powerful effect on graft survival even among pretransplant blood transfused recipients (PH = 0.002, PT = 0.0006). We conclude that selection of recipients for transplantation should attempt to achieve HLA-DR identical combinations.

Adolescent↗
PubMed1983

Immune marker expression in 53 lymphomas of high-grade malignancy.

Tissue from 53 non-Hodgkin's lymphomas of high-grade malignancy according to the Kiel classification were analysed for cellular immunological markers. In most cases studies were performed in parallel on cell suspensions and cryostat sections. Histologically, the lymphomas were classified as anaplastic centrocytic (four), centroblastic (seven), Burkitt type (three), convoluted-cell type (five) lymphoblastic-unclassified (10), immunoblastic (IBL) (19) and pleomorphic T-cell type (five). Immunological phenotyping resulted in 60% B lymphomas characterized by monotypic surface membrane Ig (SmIg) and/or cytoplasmic Ig (CIg), and 23% T lymphomas with detectable E receptors; 17% of cases were non-expressive (O-type). Unusual SmIg-types were noticed in some monoclonal proliferations. Gamma (gamma) and mu chains occurred simultaneously in four cases; delta chain was the only heavy-chain in one case and a heavy-chain was absent in one case. Cases of IBL were of T-cell type in two cases, and two other cases were non-expressive. The cases of B-IBL expressed CIg in 93%, but the B lymphomas other than B-IBL only in 38%. Receptors for Fc-IgG and C3 were expressed by all major immune phenotypes (B, T, O), but were infrequent in lymphoblastic lymphoma unclassified (O-type). Adoption of immunological techniques to include frozen tissue studies was necessary in order to reach a conclusion regarding the immune phenotype in several cases.

Adolescent↗
PubMed1983

Influence of HLA-D/DR antigen disparity in CTL generation in vitro.

This report describes the influence of HLA-D/DR antigen disparity upon the level of cytotoxicity in allogeneic in vitro cultures. Allogeneic cultures, between unrelated HLA-D/-DR full house donors, tested in CML gave three different levels of cytotoxicity, termed weak, intermediate and strong cytotoxicity. HLA-D/-DR compatibility predicts weak cytotoxicity and two HLA-B antigen incompatibility predicts strong cytotoxicity. On the contrary, HLA-A antigens have no major influence upon the strength of cytotoxicity. Accepting that the MLC/CML reaction is an in vitro parallel to the in vivo transplantation of allogeneic tissue, the observations are in accordance with the results of HLA-D/-DR matching for graft survival in human renal transplantation.

Cytotoxicity, Immunologic↗
PubMed1983

One-way positive cellular reactions between two HLA-A, B, C, D/DR genotypically identical brothers following active allogeneic immunization.

The HLA-D/Dr region in man encodes major determinants which stimulate T lymphocytes to proliferation. The genetic organization of this region is apparently complex and is at present largely unknown. One obstacle is the scarcity and quality of available typing reagents. In an attempt to obtain high quality anti-DR sera, a series of active immunizations was performed between highly selected, healthy unrelated donors and recipients. One recipient (AR8) was immunized using cells incompatible for HLA-A2, B40 (w60), Cw3 and D/DRw6 and readily developed anti-A2 and B40 antibodies but no anti-C, CR, or other antibodies. When tested against his HLA genotypically fully identical brother using te cellular MLC, PLT, or CML techniques before immunization, results were mutually negative as expected. Following immunization, however, AR8 was able to mount MLC, PLT, and possibly CML responses against lymphocytes from the brother while the reverse combinations remained negative. When tested in the family the trait(s) thus identified seems to be maternally inherited. These results suggest the existence of minor histocompatibility determinants encoded from regions not closely linked to HLA. The brother of AR8 and the immunizing donor thus seem to share one or more determinants not possessed by AR8.

Antibodies, Anti-Idiotypic↗
PubMed1982

Activation of human alloreactive cytotoxic precursor T lymphocytes.

The requirements for allogeneic T-cell activation have been studied in experiments with T and/or B cells as stimulator. Although target determinants (TDs, defined by CTL effectors in CML) are present on B and T cells used as target cells, this study indicates that TDs are functionally different when expressed on B and T cells used as stimulator cells, as only B cells can activate CTL precursors. Further, the study confirms that inducing TDs and strong lymphocyte-activating determinants (LADs, defined by proliferation in MLC) can be distinct structures found on two different stimulator B cells. The study suggests that binding of cytotoxic precursor T cells to TDs per se does not allow any detectable activation or start of proliferation and differentiation but requires another function of the stimulator cells in the non-T-cell compartment. The nature of this function is unknown, but it is the background for the first signal received by the TD-specific clones of CTL precursors, resulting in the expression of growth receptors for T-cell growth factor or interleukin 2 which is the second signal necessary for clonal expansion and differentiation.

B-Lymphocytes↗
PubMed1982

Planned immunization of human volunteers with HLA-DR incompatible lymphocytes I. Serological aspects.

Aiming at the production of anti HLA--DR test sera, eight healthy human volunteers were immunized by repeated intradermal injections of lymphocytes which were selected to be incompatible for one HLA--DR antigen, and matched as well as possible for HLA--A,--B,--C antigens. One out of 3 recipients immunized exclusively against HLA--DR produced lymphocytotoxic HLA-DR antibodies. The remaining 5 recipients were immunized against 1 or more HLA--A,--B,--C antigens in addition to one HLA--DR antigen. After 3 immunizations, 3 of these reacted with strong HLA--A or --B antibody production; however, only one showed a parallel anti HLA-DR antibody response detectable by complement dependent lymphocytotoxicity. Testing of the recipient sera in the antibody dependent cell-mediated cytotoxicity (ADCC) assay revealed that 6 of the 8 recipients did react early to the immunizations with HLA specific antibody production. However, in spite of repeated booster injections it was not possible to obtain more than the above-mentioned 2 sera with HLA--DR antibodies strong enough to react in the lymphocytotoxicity microtechnique.

Antibody Formation↗
PubMed1982

Human B-blast specific target determinants in CML: a family study.

Human B blast specific target determinants, selectively identified on PWM stimulated purified B lymphoblasts by in vitro generated CTLs, have previously been studied in the population and showed association to and inclusion of HLA-DR geneproducts. This report indicates that B blast target determinants are products of genes which in a codominant mendelain way segregate with the HLA haplotypes in 4 selected families. Furthermore tests of families with HLA-B/D, DR and HLA-D, DR/GLO recombinations show that human B blast specific target determinants are coded from loci (locus) in the HLA-D region, between HLA-B and GLO.

B-Lymphocytes↗
PubMed1982

Monoclonal mouse anti-I-Ak and anti-I-Ek antibodies cross-reacting with HLA-DR supertypic and subtypic determinants rather than classical DR allelic specificities.

Thirty monoclonal alloantibodies (mAB) against mouse Iak antigens have been derived by fusion of mouse myeloma and spleen cells from A.TH (Ks Is Dd) mice immune to A.TL (Ks Ik Dd) lymphoid cells. Analysis of: (i) their reactivity (using 125I labelled protein A cell binding or cytotoxicity assays) on lymphoid cells from selected mouse strains with recombinant H-2 haplotypes; and (ii) the spatial arrangement of the specificities detected on the Iak molecules (studied by means of competitive inhibition of binding of radio-labelled monoclonal antibodies), permitted the identification of various epitopes present either on the I-Ak molecules (some of which were apparently identical to the conventional Ia.2, Ia.1 and Ia.19 specificities), or the I-Ek molecule (some being apparently analogous to the Ia.7 specificity) or on both I-Ak and I-Ek products. These mAB were tested in two different panels of human T and B lymphocytes. Panel (a) consisted of 28 Caucasian unrelated individuals, highly selected with regard to HLA-DR specificities, while panel (b) concerned 53 random HLA-A, B, C, DR typed individuals. The standard complement dependent lymphocytotoxicity microtechnique of histocompatibility workshop VIII was used throughout. All mAB were negative on resting T cells. Testing on B cells produced three patterns: 1) ten mAB did not react with any B cell tested; 2) four mAb reacted with all the panel cells; 3) sixteen mAb reacted with different sets of the panel indicating identification of polymorphic determinants. However, the strength of positivity obtained with a majority of single mAb varied considerably in the panel, suggesting identification of cross-reactive determinants. This necessitated the use of individual assignment criteria for each mAb. Following this procedure, 8 mAb were ascertained as reacting with HLA-DR supertypic determinants, 6 with associations to MT1, MT2, or both. Eight mAb reacted with HLA-DR subtypic determinants (more restricted than a classical DR allele). No mAb were ascertained, reacting exquisitely with acknowledged HLA-DR allelic specificities.

Alleles↗
PubMed1981

Clones of human cytotoxic T lymphocytes derived from an allosensitized individual: HLA specificity and cell surface markers.

By planned immunization of a volunteer, two stable (greater than or equal to 6 months), specific, alloreactive cytolytic T-cell clones have been established from his peripheral blood lymphocytes. One clone reacts with all serologically defined HLA-Cw3 cells from our panel, whereas the other defines a split within the serological HLA-B40 specificity. The two cytotoxic clones are SmIg-negative, E-rosette positive, EA and EAC rosette-negative, HLA-A, -B and -C- positive, and also HLA-DR- or 'Ia like'-positive. In addition, they present very similar patterns of iodinated cell surface molecules as analysed by sodium dodecylsulphate polyacrylamide gel electrophoresis (SDS-PAGE), contrasting with that of an EBV cell line derived from the same donor.

Adult↗
PubMed1981

Decreased expression of HLA-DR antigens on peripheral blood B lymphocytes during glucocorticoid treatment.

In 18 patients the expression of HLA-A, B, C and -DR antigens on peripheral blood T and B lymphocytes (PBTL and PBBL) was assessed using the lymphocytotoxic microtechnique before and during glucocorticoid administration. During steroid treatment we found a significant reduction in the reactivity of PBBL to allogeneic specific anti HLA-DR antisera as well as a xenogeneic multispecific anti HLA-DR antiserum, corresponding to approx. 1-2 dilution steps. In contrast, the reactivity of both PBBL and PBTL to allogeneic anti HLA-A, B, C antisera and anti beta 2-microglobulin was unaffected during the treatment. Membrane marker studies of the isolated PBBL and PBTL showed no differences in the relative distribution of mononuclear cell subpopulations before and during treatment, which seems to exclude extravascular redistribution of particular HLA-DR positive lymphocyte or monocyte subsets during steroid administration as an explanation for the finding. Incubation of isolated normal PBBL with dexamethasone under various conditions did not affect the reactivity of these cells to anti HLA-DR antisera. Furthermore, preliminary experiments gave no indication of decreased rate of HLA-DR antigen synthesis in the presence of dexamethasone in vitro. Thus, we conclude that glucocorticoid administration in vivo decreases the expression of HLA-DR antigens on PBBL, possibly in an indirect way, the mechanism of which is still unknown.

Antigen-Antibody Reactions↗
PubMed1981

Synergism and gene dose effect in HLA-DR serology.

By mixing HLA-DR antisera of different specificities and testing them against B lymphocytes carrying the corresponding antigens, a synergistic action of HLA-DR antibodies was revealed. Furthermore, it was demonstrated that HLA-DR and HLA-ABC antibodies may act synergistically against appropriate B cells. HLA-DR homozygous B lymphocytes were found to react more strongly with HLA-DR specific antisera than heterozygous cells, thus revealing a gene dose effect in HLA-DR serology. ABO antibodies were found not to react against B lymphocytes, either alone nor in concert with HLA-DR antisera. The practical implications of synergism and gene dose effect in HLA-DR serology are discussed.

ABO Blood-Group System↗
PubMed1981

HLA-DR genes and antigens in the Danish population. A study of 500 unrelated Danes.

Five hundred unrelated Danes, including 202 healthy individuals, 35 cadaveric kidney donors, and 263 patients in terminal uraemia were typed for the HLA-DR antigens DR1-w8. The HLA-DR gene frequencies of healthy Danes are in good agreement with frequencies estimated during The Eighth International Histocompatibility Workshop of the Scandinavian population, but differ to some extent from other groups of European Caucasians. This indicates geographical variation in the distribution of DR genes within Europe. Very close associations were found between the HLA-DR antigens and their corresponding HLA-D specificities, except for Dw4 and Dw6, which were included in DR4 and DRw6, respectively. Linkage disequilibrium was calculated between alleles of two loci (HLA-A, -DR; -B, -DR and -C, -DR alleles was assessed for multiple loci by using haplotype data from 32 HLA-A, -B, -C, -D, -DR, and Bf typed Danish families. The haplotype data showed that HLA-DR4 is strongly associated with HLA-B15 only in haplotypes together with HLA-Dw4. This indicates genetic heterogeneity of HLA-DR4 which, however, does not appear serologically in this study.

Denmark↗
PubMed1981

Large-cell T-lymphoma with hypersegmented nuclei.

Clinical, morphological, cytochemical and immunological features in a case of T-lymphoma in a 67-year-old man are presented. Clinically, a predilection for lymph nodes was observed with a subsequent tumour-like spread to the liver, lungs and, to a minor extent, to the bone marrow. The skin, the spleen and the thymus were spared. Morphologically, the neoplastic lymphoid cells were characterized by their large size and particularly by their hypersegmented nuclei with a relatively coarse chromatin and large nucleoli. Cytochemically, a T-cell-like staining pattern in the acid phosphatase and in the acid alpha-naphthyl acetate esterase stains was absent. The neoplastic lymphocytes demonstrated a strong binding with sheep erythrocytes in suspension and in cryostat tissue sections. The morphological features of this lymphoma appear distinct from other non-Hodgkin's lymphomas. The similarities and the differences of our case in relation to some recently described cases of peripheral T-lymphomas comprising large cells with hyperlobated nuclei, are discussed.

Aged↗
PubMed1980

Epstein-Barr-virus-induced lymphoproliferative disorder converting to fatal Burkitt-like lymphoma in a boy with interferon-inducible chromosomal defect.

A 6-year-old boy presenting with swelling of cervical and axillary lymph-nodes was diagnosed as having an Epstein-Barr virus infection because of EBV-nuclear-antigen-positive B-lymphocytes in blood and lymph nodes and high antibody titres to EBV antigens. The natural killer activity of blood-lymphocytes was low, and so was the percentage of T-lymphocytes with Fc receptors for IgG (T-gamma cells). Chromosomal studies revealed a defect in the long arms of one of the chromosomes in pair no. 16 (16q22). The defect only appeared after addition of interferon to the lymphocyte cultures and preferentially in T-gamma lymphocytes. The disease progressed despite attempts to restore the patient's immune reactivity by interferon, transfer factor, and blood transfusions. Necropsy showed that the severe hyperplasia of lymph nodes found during life had become a Burkitt-like lymphoma. The possible connection between an interferon-induced chromosomal defect (break at 16q22) and reduced level of natural killer activity, reduced T-gamma lymphocytes, and proliferation of EBV-positive B-lymphocytes is discussed.

Burkitt Lymphoma↗