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P Bettelheim

Publications and source records attributed to P Bettelheim.

124 records · Page 7Linked to original sources

Distinct lymphoblastic and myeloblastic populations in TdT positive acute myeloblastic leukemia: evidence by double-fluorescence staining.

Double-immunofluorescent staining for the enzyme terminal deoxynucleotidyl transferase (TdT) as a marker of primitive lymphoblasts, and for the VIM-D5 antigen as a differentiation antigen of the myeloid system gave direct evidence for distinct lymphoblastic and myeloblastic populations (mixed leukemic cell populations) in seven patients with acute leukemia. The percentage of malignant TdT positive cells contributing to a leukemic cell bulk with unequivocal signs of myeloid origin was between 10 and 80%. A defect at the level of a common progenitor cell giving rise to both the TdT and the VIM-D5 positive blast cell population is discussed.

Antibodies, Monoclonal↗

Phenotypes of human large granular lymphocytes as defined by monoclonal antibodies.

Four monoclonal antibodies VEP8, VEP9, VIM-D5, VIB-C5 against antigens expressed on human mature myeloid cells (polymorphonuclear leukocytes [PMNL] and/or monocytes) as well as on immature cells in the bone marrow were tested for reactivity with cell preparations highly enriched for large granular lymphocytes (LGL). These cells are known to be the main effector cells responsible for natural killer (NK) cell activity in human peripheral blood. Using indirect membrane immunofluorescence (IMF), none of these antibodies showed any reactivity at all. In addition, LGL-enriched cell preparations were tested with the anti-lymphocyte monoclonal antibodies OKT6, anti-Leu1, anti-Leu2a, anti-Leu3a, and anti-human Lyt3, and also with OKM1 antibody. Significant reactivity was found with anti-Leu2a (59 +/- 8%), anti-Lyt3 (55 +/- 4%) and OKM1 (81 +/- 11%) antibodies, whereas T6, Leu1, and Leu3a antigens were less pronounced or missing on LGL. As a further approach, another monoclonal antibody, VEP13, which reacts with LGL, granulocytes but not monocytes and is therefore different in its specificity from OKM1 and OKT10, was used for identification of LGL. The coexpression of antigens as defined by the above-mentioned antibodies and OKT10 on VEP13+ cells was studied. Again, phenotypes similar to those observed on LGL enriched by Percoll gradient centrifugation were found: of VEP13+ cells 84 +/- 6% reacted with OKM1, 82 +/- 5% with OKT10, 52 +/- 17% with anti-human Lyt3, and 48 +/- 14% with anti-Leu2a, whereas VEP8, VEP9, VIM-D5, VIB-C5, T6, Leu1, Leu3a antigens were not expressed on VEP13+ cells. Taken together as an overall evaluation of phenotypic characteristics, our data indicate that LGL cannot be integrated into one of the known lymphocytic or myelomonocytic lineages. LGL show an intermediate phenotype depending possibly on varying differentiation or activation stages of haemopoietic cells. However, the possibility also exists that LGL belong to a separate, yet undefined cell lineage.

Antibodies, Monoclonal↗

Surface antigens defined by monoclonal antibodies as tumor markers in human leukemia.

The detection of surface-linked antigenic determinants by heteroantisera has greatly contributed to a better understanding of the heterogeneity of benign and malignant hematopoietic cells. The difficulties encountered in rendering these heteroantisera specific for a unique cell surface component have been a major drawback to a more rapid development of immunologic cell typing. With the introduction of hybridoma technology, it became possible to obtain monoclonal antibodies and markedly improve immunologic cell typing. We have, therefore, used this new technology for the production of monoclonal antibodies against human leukocyte surface antigens. This paper describes four cell type-specific monoclonal antibodies, which turned out to be very useful reagents in leukemia diagnosis. One of these antibodies, VIM-D5, is directed against a myeloid cell surface antigen. VIL-A1 is specific for the common acute leukemia associated antigen. VIB-C5 recognizes B-cell differentiation antigen and VIE-G4 is specific for glycophorin A, and thus detects erythroid precursor cells.

Antibodies, Monoclonal↗

[Bone marrow transplantation for aplastic anemia--initial results in 8 patients].

8 young patients (aged 11 to 23 years) with severe aplastic anaemia received bone marrow grafts from their HLA-identical, MLC-non reactive siblings. All patients had received repeated transfusions previously and had been unsuccessfully treated with corticosteroids (7 out of the 8 patients) and/or anabolic drugs (4 out of the 8 patients). In order to prevent graft rejection 5 patients received donor buffy coat cells after the marrow infusion and 3 patients underwent total body irradiation with 400 rad prior to the marrow transplantation. 5 patients are alive, 3 patients died. Death occurred from Candida septicaemia (day 4 after transplantation), left ventricular failure (day 14) and graft versus host reaction of the gut (day 85). The 5 living patients are in a very good state of health 30 to 166 days after transplantation. 4 patients already have normal blood cell counts. 2 of the surviving patients developed a transient GVH-reaction of the liver. One patient had a mild GVH-reaction of the skin on day 130.

ABO Blood-Group System↗

[Diagnosis of leukemia with monoclonal antibodies].

The diagnosis and classification of leukaemic diseases is still primarily based on morphological and cytochemical criteria. Interpretational difficulties occur quite frequently, especially in acute leukaemias. Subjective morphological cell-type characterization--which is acquired only after many years of experience--is rather unsatisfactory in the long run. Therefore in order to obtain uniform results in all haematological areas, new methods are needed. In principle, immunological cell-type characterization represents an alternative method. By applying requisite antibodies practically any cell component can be demonstrated and quantitated. Up to recently the major obstacle to a more rapid development of immunological cell typing was the lack of specific antisera, but with the introduction of hybridoma technology it became possible to obtain monoclonal antibodies and thus, markedly improve immunological cell typing virtually overnight. We have, therefore, used this new technology for the production of monoclonal antibodies to human leucocyte antigens. This paper describes six of the cell-type specific monoclonal antibodies obtained, their suitability for diagnostic purposes and the classification of human leukaemias. With the help of these antibodies the majority of human leukaemias can now be typed. Without claiming completeness and in full awareness of the fact that a number of problems remain to be solved, we nevertheless believe that the presented data point to the possibilities opened up by this technology for leukaemia diagnosis in the future.

Animals↗

VIL-A1, a monoclonal antibody reactive with common acute lymphatic leukemia cells.

The VIL-A1 monoclonal antibody raised against Reh cells reacts with common acute lymphatic leukemia (CALL) cells but not with normal or malignant B or T lymphocytes. It also shows no binding to normal or malignant myeloid, monocytic or erythroid cells, nor does it react with thrombocytes. The antibody is of IgM class and lyses CALL cells very efficiently in the presence of rabbit but not human complement. Immunoprecipitation experiments followed by SDS-polyacrylamide gel electrophoresis under reducing conditions revealed that VIL-A1 defines a 95,000 mol. wt membrane protein. Approximately 40% of it binds to lens culinaris lectin. Capping experiments showed that the membrane component defined by VIL-A1 co-caps with the one recognized by another recently described monoclonal antibody to CALL cells (J5).

Antibodies, Monoclonal↗

Expression of a myeloid marker on TdT-positive acute lymphocytic leukemic cells: evidence by double-fluorescence staining.

The expression of a myeloid-specific antigen was detected on TdT-positive blast cell populations in two cases of childhood acute lymphocytic leukemia. Double-fluorescence staining by using the monoclonal antibody, VIM-D5, which is specific for cells of myeloid origin, in combination with TdT antiserum revealed that a distinct portion of the blast cells carried both markers. The finding represents the first direct demonstration of this specific biphenotype in leukemic cells and was interpreted as the abnormal expression of a myeloid antigen on lymphoid blast cells.

Animals↗

Glycosylated hemoglobins (GHb): an index of red cell survival.

Levels of glycosylated hemoglobins (GHb) are significantly (p less than 0.0005) lower in patients with hemolytic anemia (n = 20; mean = 3.9% +/- 0.1% SD GHb of total Hb) compared to patients with nonhemolytic anemia (n = 20; mean = 7.0% +/- 0.7% GHb) and normal controls (n = 30; mean = 6.7% +/- 0.7% GHb). A curvilinear correlation between GHb and red cell survival is demonstrable (n = 20;r2 = 0.88; p less than 0.001). Determination of GHb may be useful as a screening test for hemolytic anemia and for the evaluation of the degree of hemolysis, provided that diabetes mellitus can be excluded.

Adolescent↗

[Oestrogen receptors and prognosis in breast cancer].

The determination of oestrogen receptors seems to be of prognostic value in the radically-operated breast cancer patient. Patients with negative receptor values exhibit early recurrence in a significantly higher percentage of cases than those with positive values. The prognostic implications of oestrogen receptor determination seem to be even higher than an assessment of axillary lymph node involvement. In metastatic breast carcinoma a correlation exists between response to hormonal therapy and receptor assay. The clinical implications for therapeutic management are discussed.

Adult↗

Post-transfusion thrombocytopenic purpura: immunological and clinical studies in two cases and review of the literature.

Two patients with post-transfusion thrombocytopenic purpura are described, the first cases recognized in Austria and Germany. Both patients were female, 51 and 60 years of age. The purpura was evoked by blood transfusions with a latent period of 2 and 7 days. The thrombocytopenic episode lasted for 22 and 60 days. In one case, thrombocytopenia was associated with agranulocytosis due to transient bone marrow failure. Both patients were negative for the platelet-specific antigen PlA1 (= ZWa). Their sera contained PlA1 as well as potent HLA antibodies. Detailed clinical and serological data are presented. The literature with a total of 25 cases so far reported is surveyed.

Agranulocytosis↗

[Prognostic value of estrogen receptors in breast cancer (author's transl)].

One hundred and ninety-one patients with operable breast cancer were followed for up to 34 months after operation and the early recurrence of disease was noted in relation to the presence or absence of estrogen receptor. Recurrence rates were significantly higher in patients whose tumors did not contain receptors than in those whose tumors did. The response to cytotoxic chemotherapy in patients with advanced breast carcinoma seems to be independent of the presence of E2R in cancer tissue.

Breast Neoplasms↗

[Prognostic factors in the drug therapy of metastasizing breast cancer].

175 patients with metastatic breast cancer, treated with chemotherapy, were analyzed retrospectively to identify the characteristics of prognostic importance in predicting response to chemotherapy and survival from onset of the chemotherapy. The most significant factors were the sites of metastatic disease and an estimate of the total extent of disease.

Antineoplastic Agents↗