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I Doxiadis

Publications and source records attributed to I Doxiadis.

At least 37 records · Page 2Linked to original sources
PubMed1988

Heterogeneity in protein patterns of cells from terminal blast crisis in chronic granulocytic leukemia: discrimination between lymphatic and myeloid lineages.

Terminal blast crisis cells of chronic granulocytic leukemia are biochemically distinct. Triton-X-114 detergent phase lysates revealed that myeloid types express predominantly proteins of a 24 kd apparent molecular weight range, whereas lymphatic types do not express these molecules but a 55 kd protein band. These biochemical differences, observed in the poorly differentiated blast crisis cells, are also found in well differentiated hemopoietic malignancies such as chronic lymphatic leukemia, or in mature granulocytes isolated from healthy individuals. The results support the concept of the different lineages of blast crisis cells in chronic granulocytic leukemia but question the role of these proteins in cell differentiation. In addition, the presence or absence of these proteins provide a helpful tool for classifying blast crises of chronic granulocytic leukemia.

Antibodies, Monoclonal↗
PubMed1987

HLA-DR4 and Gm 1;21 haplotypes are associated with pseudolupus induced by venopyronum dragées.

The phenotypic frequencies of human major histocompatibility complex class I, II, and III antigens and immunoglobulin allotypes (Gm factors) were determined in 56 patients (55 women, 1 man) who had lupus-like disease induced by venopyronum dragées. The findings in these patients were compared with those of a control group. We found a significant increase of HLA-DR4 (57.1% versus 26.5%, relative risk [RR] 3.7) and a decrease of HLA-DR3 (3.6% versus 19.1%, RR 0.16) in the patient group. In addition, the haplotype Gm 1;21 (60.7% versus 32.9%, RR 3.2), and the phenotype Gm 1,3;5,21 (46.4% versus 25.8%, RR 2.5) were significantly increased. Both the haplotype Gm 1;21 and the phenotype Gm 1,3;5,21 are associated with HLA-DR4 in pseudolupus patients but not in controls. The coincidence of HLA-DR4 and Gm 1;21 markedly increases the risk of acquiring pseudolupus (RR 6.9). We conclude that the pathogenesis of pseudolupus is influenced by at least 2 independent genetic factors. A similar HLA association has been described in hydralazine-induced lupus, and this suggests a common pathogenic mechanism.

Adult↗
PubMed1987

Statement on the nomenclature of dog C4 allotypes.

As a collaborative work of three laboratories the polymorphism of the canine fourth complement component (C4) was studied in a total of 131 unrelated dogs from different breeds and mongrels. Using high voltage electrophoresis followed by an immunoblotting technique, we detected eight distinct variants. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of canine C4 showed an additional heterogeneity of the alpha and gamma chains which resulted in a total of 11 variants in the population studied. So that more precise information concerning the respective C4 allotypes will be available, a nomenclature is proposed designating not only the migration pattern of the C4 variants in agarose gels but also the heterogeneity of the C4 chains observed in SDS-PAGE.

Alleles↗
PubMed1987

Joint report of the Third International Workshop of Canine Immunogenetics. II. Analysis of the serological typing of cells.

Using a standardized microlymphocytotoxicity assay, seven international laboratories evaluated 144 anti-dog lymphocyte antigen (DLA) sera in 319 mixed breed and 152 Beagle dogs. The workshop confirmed the serological definitions for DLA-A2, A3, A9; DLA-B4, B5, B6, B13; DLA-C11(Cwl); and C12(Cw2). Two new specificities were assigned to the DLA-A locus (Aw14 and Aw15) in only the mixed breed dogs. A third specificity (Cw3), was assigned to the DLA-C locus. The antigen and gene frequencies of these alleles differed between the two groups of dogs, but the frequencies of the "blank" were similar in both groups. Future international collaborations will be necessary to definite more completely the polymorphisms of the major histocompatibility complex (MHC) of the dog. Those efforts will benefit from the standard serological test established in this workshop.

Alleles↗
PubMed1986

An analysis of class I antigens of man and other species by one-dimensional IEF and immunoblotting.

A procedure for the molecular identification of MHC class I products based on 1-D IEF and subsequent immunoblotting is described. Optimal conditions for 1-D IEF, the electrophoretic transfer of proteins out of denaturing, nonionic detergent-containing gels to nitrocellulose, and the requisite antibodies, both polyclonal and monoclonal, for the visualization of class I heavy chains have been established. Cross-reactivity of antibodies has enabled the biochemical analysis of class I heavy chains in the dog. The procedure reported here requires modest amounts of cells and allows a rapid molecular characterization of class I heavy chain polymorphisms in man and other species without the need for radiochemical methods.

Animals↗
PubMed1986

Joint report of the Third International Workshop on Canine Immunogenetics. I. Analysis of homozygous typing cells.

The Third International Workshop on Canine Immunogenetics involved 80 potentially DLA-D homozygous typing cells obtained from dogs of various breeds and submitted from five laboratories in Europe and the United States. Mutual reactivity of all cells was studied in mixed leukocyte cultures, and stabilized relative responses were used for analysis. Intralaboratory and interlaboratory comparisons of results suggest that a stabilized relative response of 30% represents an acceptable parameter for "typing responses" indicating phenotypic DLA-D identity of stimulator and responder cells. Using this criterion, 10 clusters of homozygous typing cells were defined and accepted on an international level, and they were assigned the specificities Dw1 to Dw10. At least six additional (provisional) specificities were recognized that were well characterized within individual laboratories but require additional testing before workshop specificities can be assigned. These data show that DLA-D typing is feasible and represents a useful tool in the genetic analysis of the canine major histocompatibility complex. Much work is needed to confirm the present results in family studies, to determine gene frequencies, and to analyze at a molecular level the antigens responsible for mixed leukocyte culture reactivity.

Animals↗
PubMed1986

Immune transfer studies in canine allogeneic marrow graft donor-recipient pairs.

Transfer of immunity occurring with bone marrow grafting was studied using the dog as a preclinical model. Allogeneic bone marrow transplantation (BMT) was performed between DLA-identical beagle litter-mates. The donors were immunized with tetanus toxoid (TT) or sheep red blood cells (SRBC), and their humoral response was monitored by hemagglutination. The recipients of bone marrow from TT-immunized donors showed a marked increase of antibody titer one week posttransplantation, while in the recipients of marrow from SRBC immunized donors the antibody titers were considerably lower. Within the following 60 days the antibody titers in both groups diminished gradually to pregrafting levels. Control experiments in which cell-free plasma from donors immunized with TT and SRBC respectively was transfused indicated that the initial rise of specific antibody titers after marrow grafting is likely to be due to a passive transfer of humoral immunity. A single challenge of these marrow graft recipients with the respective antigen 15-18 weeks posttransplantation led to a secondary type of humoral immune response. In addition, it could be demonstrated that transfer of memory against TT or SRBC was independent from the actual antibody titer and the time of vaccination of the donor. One dog was immunized with TT after serving as marrow donor. When the donor had shown an antibody response, a peripheral blood leukocytes (PBL) transfusion was given to his chimera. Subsequent challenge of the latter resulted in a secondary type of specific antibody response. This indicates that specific cellular-bound immunological memory can be transferred after BMT from the donor to his allogeneic bone marrow chimera by transfusion of peripheral blood leukocytes. The data presented may be of importance in clinical BMT to protect patients during the phase of reduced immune reactivity by transfer of memory cells from histocompatible immunized donors.

Animals↗
PubMed1985

Polymorphism of human C2 detected by immunoblotting.

To allotype human complement component C2, thin layer agarose gel isoelectric focusing of human serum and/or EDTA-plasma was performed followed by direct immunofixation or by immunoblotting with a specific anti-human-C2 antibody. Using reference samples for C2 BC phenotypes and local samples from an HLA, C4, and Bf genotyped family, a differentiation of the C2*B and C2*C variants segregating with the respective HLA haplotype was achieved. The C2 BC phenotype is characterized by a double banding pattern similar to that observed in the haemolytic overlay assay usually used for the detection of C2 polymorphism. An homozygous C2*Q0 reference sample determined by functional assays was shown to be biochemically deficient, as demonstrated by immunofixation and immunoblotting. The visual interpretation of C2 phenotypes was definitely easier after immunofixation and immunoblotting than after an haemolytic overlay assay. In addition, the method for C2 allotyping described here has several advantages, in particular it saves time and tolerates repeated thawing and freezing of the samples.

Complement C2↗
PubMed1985

Polymorphism of the fourth complement component in the dog.

The polymorphism of the fourth complement component was studied in 118 unrelated dogs from different breeds and 73 unrelated beagles. In the mixed breed population, five different variants were observed with the following gene frequencies: C4*1 = 3.9%; C4*2 = 13.6%; C4*21 = 6.0%; C4*3 = 9.0% and C4*4 = 51.1%. In beagles, only four variants could be identified with gene frequencies of C4*2 = 24.2%; C4*21 = 1.4%; C4*3 = 20.6% and C4*4 = 46.3%. In both populations analyzed positive linkage disequilibria between certain DLA antigens and C4 variants were recognized. The biochemical analysis of the canine C4 revealed a double-banding pattern for the C4 alpha chain which gives preliminary evidence for two gene loci encoding for the fourth complement component in the dog.

Animals↗
PubMed1985

Treatment of hairy-cell leukemia with recombinant leukocyte A interferon.

A 29-year-old male patient with hairy-cell leukemia was referred for bone marrow transplantation. For tumor mass reduction a treatment with recombinant leucocyte A interferon was started. A complete remission could be achieved in the third month of treatment and no adverse side effects were observed. The patient refused bone marrow transplantation and a relapse was diagnosed 51 days after discontinuation of interferon therapy. Treatment of hairy-cell leukemia with recombinant leukocyte A interferon seems to be a promising approach.

Adult↗
PubMed1983

[Immunogenetics of myasthenia gravis. Significance of HLA-, complement and Cm gene systems for clinical and immunologic parameters].

In 82 non-related patients with myasthenia gravis the following immunogenetic marker systems were investigated: HLA-A, -B, -C, -DR antigens, complement polymorphisms for Bf, C3 and C4 as well as immunoglobulin allotypes G1m, G3m and Km. In 78 patients the level of circulating acetylcholin receptor autoantibody was measured. The HLA antigens showed no significant differences in frequency when compared with healthy controls. This was also true for the HLA-bound Bf and C4 polymorphism, the non-HLA-bound C3 polymorphism and the immunoglobulin allotypes. A significant (P less than 0.005) increase in heterozygote frequency of 39.7% in the Gm allotype combination G1m (1), (17); (3) when compared with an expected frequency as calculated from the gene frequency of 19.8% was found. HLA-B8 and/or HLA-DR3 positive myasthenia gravis patients showed a significantly (P less than 0.025 and less than 0.005) earlier average onset of the disease whereas in HLA-DR2 positive patients the average onset was later (P less than 0.05). The same HLA antigens correlated with quantitative differences in the acetylcholine receptor autoantibodies: HLA-B8 and/or -DR3 positive patients had on average higher antibody levels than HLA-B8 or -DR3-negative patients. The difference for HLA-DR3 was statistically significant (P less than 0.05). On the other hand patients with HLA-DR2 antigens had significantly lower antibody levels (P less than 0.025). Increased mean antibody levels were also seen in G1m(1), (17) allotype (P less than 0.005) and G3m(21) (P less than 0.05). As the HLA antigens and Gm allotype genes are situated on different chromosomes (C6 and C14) two distinct gene regions are identified in myasthenia gravis. These are associated with quantitative differences in acetylcholine receptor antibody titres.

Autoantibodies↗
PubMed1983

Correlation between immunogenetic markers and "in vivo" response to the german hepatitis B vaccine.

The antibody response to the German HB-vaccine in 100 volunteers was investigated with respect to the individual immunogenetic markers. After 3 doses of vaccine at days 0, 28 and 140, 7 serum samples were collected at days 0, 28, 56, 98, 140, 154, 168 and anti-HBs concentrations determined. Seroconversion was 96% after the 3rd injection with a mean antibody concentration of 947 mIU/ml. On the basis of antibody values on day 154 four groups of responders could be observed. Nonresponders, late and low responders, early and high responders and mixed type high responders with an early peak (IgM) between days 28 and 42. Assigning immunogenetic markers of the HLA-system and immunoglobulin G-allotype system to the different groups yielded evidence that HLA-DR3 is associated with higher antibody production towards HBsAg.

Adolescent↗
PubMed1983

Antilymphocytic antibodies and marrow transplantation. VI. Absence of immunosuppression in vivo after injection of monoclonal antibodies blocking graft-versus-host reactions and humoral antibody formation in vitro.

The in vivo and in vitro effectiveness of several monoclonal antimouse T and B cell antibodies, of anti-Th-1 and of Iak serum, as well as of ATG were compared. The parameters were prolongation of skin graft survival, prevention of graft-versus-host disease (GVHD), antibody and primary and secondary plaque formation against sheep redblood cells (RBCs), and T cell depletion of lymphoid tissues. In general, in vitro effectiveness of the monoclonal antibodies exceeded their in vivo effectiveness. Skin graft survival was prolonged by ATG, but not by monoclonal anti-T, or anti-T plus anti-B antibody. GVHD was prevented by in vitro incubation of donor bone marrow with monoclonal anti-Th-1, but in vivo treatment of marrow donors was ineffective. Treatment with ATG was successful. Anti Iak antibody blocked plaque formation by spleen cells incubated with sheep RBCs, but had no effect on secondary plaque formation when given in vivo. Neither was there any in vivo effect of anti-Iak or anti-Th-1 on antisheep RBC agglutinin formation. ATG was effective in both of these assays, although its cytotoxic and complement-fixing titer did not exceed that of anti-Th-1 or anti-Iak. Although anti-Th-1 was cleared more rapidly from the serum of mice expressing the corresponding Th-1 alloantigen, than from mice with the noncorresponding alloantigen and although anti-Th-1 was shown to bind to the T cell areas of the lymphoid tissue, it did not--unlike ATG--deplete these areas of T cells. Possible reasons for the difference in effectiveness of in vitro and in vivo application of these monoclonal antibodies are discussed.

Animals↗
PubMed1982

Monoclonal antibodies against T-cell antigens studied by immunohistochemistry.

Fifteen monoclonal antibodies against different T-cell antigens were studied by immunohistochemistry in thymus, fetal thymus, fetal liver, palatine tonsils, and a few T-cell lymphomas. OKT 9 was identified as reacting with hemopoietic stem or precursor cells in fetal liver as well as with early B-determined lymphocytes in tonsillar germinal centres. OKT 10 labelled lymphocytes in thymus and surprisingly also the cytoplasm of some tonsillar cells with plasma-cell like appearance. OKT 6 and MAS 036 b reacted only with thymic cells. OKT 4, OKT 5, OKT 8,8-11, labelled thymic cells- and portions of interfollicular cells in tonsils. OKT 3, NEI 016, NEI 015, and T 28 stained a majority of thymic cells and of tonsillar interfollicular lymphocytes. IFH-M 203, NEI 012 and 4-11 were positive with the majority of T-lymphocytes in tonsils but labelled only a few thymic cells.

Animals↗
PubMed1981

Tritium radiolabeling of antibodies to high specific activity with N-succinimidyl [2,3-3H] propionate: use in detecting monoclonal antibodies.

A simple method has been established for tritium labeling immunoglobulins. This label avoids certain disadvantages of 125iodine such as high radiation hazard and requirement for frequent labeling owing to the short half-life of this isotope. High specific activities (range 1.8-9.0 cpm/mu g protein) were obtained with no loss of functional activity as demonstrated by passive hemagglutination. The labeled conjugate is especially suitable for detection of activity in hybridoma supernatants by indirect binding assay. Adapted to microtiter plates, the method is suitable for large numbers of samples, e.g. up to 800 supernatants may be examined daily. The utility and advantages of the binding assay with respect to reproducibility, sensitivity, binding kinetics, easy and rapid performance are described.

Animals↗