Prenatal diagnosis of severe combined immunodeficiency.
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Biomedical subjects
Publications and source records attributed to P Beverley.
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This paper describes the use of a panel of seven monoclonal antibodies (selected so as to include reagents reactive with both epithelial and lymphoid cells) for distinguishing between anaplastic carcinoma and high grade lymphoma. Details are given of the immunohistological reactions of these antibodies against a wide range of both normal and malignant tissues and of a number of practical instances in which use of the antibody panel enabled a diagnosis to be made when routine histological examination had been inconclusive.
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This is a communication on the introduction of the first monoclonal marker at Graz University Medical School. Human peripheral blood mononuclear cells were used for immunisation of BALB/c mice by injecting 4,5 X 10(6) cells s. c. Boosting consisted of i.p. injection of 5 X 10(6) cells 4 times in monthly intervals. Spleen cells were taken 4 days after the last boost, fused with NS-1 myeloma cells, using PEG as fusogenic agent. After growth in HAT selective medium, antibody secreting clones were identified by testing the supernatants. Cultures with activity against lymphocytes were closed on normal BALB/C peritoneal cell feeder layers. One of them secreted IgG 1 with strong activity against all lymphoid cells and was named HLy D 1. Further testing showed activity with band cells, polymorphs, eosinophils, macrophages but not with tissue sections from anaplastic undifferentiated cancers and erythroid leukaemias. Since he was named H Le D 1 and introduced for differentiating rare undifferentiated carcinomas from malignant tumors of the lymphoid system.
Pathologic samples from 34 cases of human solid malignancies were tested for reactivity with monoclonal anti-human leucocyte antibody, designated 2D1. This antibody detects a human leucocyte antigen (HLe-I) that is expressed strongly on B and T lymphoid cells and weakly on early hemopoietic cells, but is not found on normal mesenchymal and epithelial tissues. This study demonstrates the use of this reagent in cryostat sections of tumor samples using indirect immunofluorescence in combination with other lymphoid markers such as anti-T cell serum, anti-Ia-like serum (detecting p28, 33 "B cell associated" membrane antigen) and antisera to different immunoglobulin isotypes. Tumor cells from all 12 cases of epithelial malignancies and sarcomas were HLe-I- although adjacent (normal) lymphoid cells showed strong positive staining. In contrast, 20 cases of lymphoma (B- as well as T-cell types) were HLe-I+. Two other malignancies involving the lymphoid system were HLe-I- and failed to express any of the other lymphoid markers tested.
Combinations of antibodies to membrane antigens and to terminal deoxynucleotidyl transferase (TdT) were used to study human thymocyte and bone marrow subpopulations and leukemia cells. Cortical thymocytes were TdT+ and expressed T-cell antigens (HuTLA+), a thymocyte-specific antigen (HTA-1+), and a leukocyte antigen (HLe-l++) but lacked detectable HLA-A,B,C and la (HLA-D) antigens. In contrast, medullary thymocytes were TdT-, HuTLA+, HTA-1-, HLe-l++. A small subpopulation of larger, probably immature, thymocytes were strongly TdT+, HuTLA+, la-, HTA-1-, HLe-l +/-. Many blast cells from cases of thymic acute lymphoblastic leukemia (Thy-ALL) showed the phenotype of this small subset, and only a proportion of Thy-ALL blast cells exhibited HTA-1 and HLe-l antigens as strongly as was observed on normal cortical thymocytes. In contrast, TdT+ cells observed in normal juvenile bone marrow were HuTLA, HTA-1-, HLA+, la+. This phenotype corresponded to the phenotype of the common form of ALL (non-T, non-B) and indicated that further studies are necessary to analyze the differentiation of bone marrow precursors to thymic cells.
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