Search PubMed⌕ Search

Biomedical subjects

G Janossy

Publications and source records attributed to G Janossy.

At least 271 records · Page 15Linked to original sources

Immunofluorescence analysis of normal and malignant lymphoid tissues with selected combination of antisera.

Tissue sections stained with combinations of antisera labeled with different fluorochromes (i.e., conventional antisera to human immunoglobulin classes, T lymphocyte antigens, and Ia-like p28,33 antigens used in various double combinations with each other or with different mouse monoclonal antibodies) allow the identification of the different areas of lymph nodes in serial sections and provide great flexibility as well as precision in the analysis of the distribution and relationship of normal and malignant cells. Lymphoid microenvironments in the thymus and the paracortical areas of lymph nodes are described. The close association of T lymphocytes and nonlymphoid cells expressing large amounts of Ia-like antigens (such as interdigitating reticular cells and endothelium) may be relevant for the understanding of immunoregulatory disorders such as dermatopathic and angioimmunoblastic lymphadenopathies and some malignancies (e.g., mycosis fungoides) were the expression of Ia-like antigens on non-T cells seems to be abnormally abundant. The analysis of immunoglobulin and membrane marker expression of normal and malignant B cells and their relation to T cells can also be related to the histology of the disease. These studies are clinically useful for the classification of childhood lymphomas, the differential diagnosis of anaplastic carcinomas and lymphomas, and in the study of the early stages of lymphomas.

Antigens↗

Large mononuclear (veiled) cells like 'Ia-like' membrane antigens in human afferent lympn.

Studies were done to see whether large mononuclear cells in human afferent lymph possess cytoplasmic veils or Ia-like antigens on their surface. Small numbers of veiled cells were seen in lymph from five subjects: one with post-phlebitis oedema, one with trophic ulcers of the legs, one with common variable immoglobulin deficiency, and two control subjects. They were not seen in afferent lymph from two other patients with oedema of the legs, and one control subject. Only occasional large mononuclear (veiled) cells formed rosettes with IgG-coated erythrocytes, and they did not attach to glass after overnight culture. They had a distinctive nuclear structure and fluorescent antisera showed that their membranes and veils possessed large amounts of 'Ia-like' antigens. They did not have surface immunoglobulin or a monocyte membrane antigen. It was concluded that the membrane and nuclear structure of human large mononuclear (veiled) cells is in keeping with the possibility that they are derived from Langerhans' cells in the skin, and that they can become interdigitating cells in lymphoid tissues. It is suggested that these cells have an important role in the transport of antigens from the skin and the stimulation of T lymphocytes in lymphoid tissues.

Adult↗

Identification of cells expressing T and p28,33 (Ia-like) antigens in sections of human lymphoid tissue.

A method has been developed for identifying human lymphocyte populations in tissue sections using hetero-antisera to T cells and to the B cell associated Ia-like, p28,33 polypeptide complex. The differential topographical localisation of T and B cells is revealed by simultaneous staining with antibodies tagged with different fluorochromes; this approach also identifies a small population of T cells bearing Ia-like antigens. Preliminary studies on lymphomatous tissue suggests this approach will be of value in the study of malignancy and cellular infiltration in disease.

Antigens, Surface↗

Subpopulations of normal and leukemic human thymocytes: an analysis with the use of monoclonal antibodies.

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.

Antibodies↗

Cellular phenotypes of normal and leukemic hemopoietic cells determined by analysis with selected antibody combinations.

Individual leukemic cells and the corresponding rare normal cell types in nonleukemic bone marrow were analyzed with various combinations of antisera (labeled with different fluorochromes: TRITC and FITC). Double staining for membrane Ia-like molecules (TRITC) and nuclear terminal transferase (FITC) was a very useful combination that distinguished common non-T, non-B ALL (Ia+,TdT+) and thymic ALL (Ia-,TdT+) from the rare cases of B ALL (Ia+,TdT-) and from AML (frequently Ia+, TdT-; in some cases Ia-, TdT-). Additional antisera (such as anti-ALL, anti-HuTLA, anti-immunoglobulin reagents, etc.) confirmed the diagnosis and further characterized the leukemic blasts. Ia+,TdT+ cells could be observed in low numbers in normal and nonleukemic regenerating marrow and were probably normal precursor cells; this reagent combinations was, therefore, not useful for monitoring residual non-T, non-B ALL blasts in treated patients. Other marker combinations detecting pre-B ALL blasts (double staining for cytoplasmic IgM and nuclear TdT) and Thy-ALL blasts (HuTLA+,TdT+) were, however, virtually leukemia specific in the bone marrow and could be used to effectively monitor residual leukemic cells throughout the disease. These combined single-cell assays are not only economical and informative but are also important for assessing the heterogeneity of leukemia and for standardizing new mouse or rat monoclonal antibodies for diagnosis.

Animals↗

Relation of "lymphoid" phenotype and response to chemotherapy incorporating vincristine-prednisolone in the acute phase of Ph1 positive leukemia.

Forty-four patients with Ph positive leukemia (36 developing blast crisis after chronic phase and eight presenting in acute leukemia) were classified into subgroups on the basis of reactivity of blasts with an anti-serum made against non-T,non-B acute lymphoid leukemia (ALL+), levels of terminal transferase enzyme (TdT+) and morphology. Positivity with anti-ALL serum was the most sensitive and reliable marker, and TdT was an important aid. The presence of "lymphoid" blasts in blast crisis of CML was related to the response to chemotherapy incorporating Vincristine and Prednisolone (VP). Patients with ALL+ blasts frequently (14 of 15 cases) responded to therapy while 21 of 25 patients who had no ALL+ blasts failed to respond. The clinical course of the ALL+ patients was variable: eight patients remitted with return to the appearances of the chronic phase; four patients demonstrated elimination of the Ph1 positive clone with hypoplasia and this was followed by normal (Ph1 negative) marrow regeneration in two. Subsequent relapse was of either the ALL+ "lymphoid" or the ALL-myeloid type. A regimen incorporating VP should be the treatment of choice in "lymphoid" blast crisis of CML.

Antigens, Neoplasm↗

The Ph1 chromosome in childhood leukaemia.

Ph1 positive leukaemia was diagnosed in eight of 123 (6.5%) consecutive new cases of childhood leukaemia. Four patients presented as typical chronic granulocytic leukaemia (CGL) and four as acute leukaemia, two of the four children with CGL have since developed blast crisis. Morphological and immunological characterization of the blasts in these six acute cases was suggestive of a lymphoid crisis in three, a mixed crisis in two, and a myeloid crisis in one. Remission was achieved in five of the six patients but lasted more than a year in only two; in one of these two patients the blasts at the time of crisis lacked the Ph1 chromosome and in the other, who presented in myeloid crisis, remission ended in a lymphoid crisis. Cytogenetic studies showed unusual translocations in two of the eight children. Serial examination showed that three children the proportion of Ph1 positive cells in the marrow was reduced to less than 6% at the time of remission from acute leukaemia. We conclude that Ph1 positive leukaemia in childhood presents frequently as acute leukaemia and may even mimic 'good risk' acute lymphoblastic leukaemia. The response to treatment cannot be predicted by morphological or immunological characterization of blast cells. Storage of bone marrow for possible autologous transplantation should be considered in children who achieve remission.

Adolescent↗

Acute promyelocytic leukaemia: further evidence of the differentiation-linked expression of Ia-like (p28,33) antigens on leukaemic cells.

Patients with acute non-lymphoblastic leukaemia were studied to determine if the presence of Ia-like antigens on leukaemic cells was related to the maturity of a leukaemic cell line. Ia-like antigens were present in the majority of acute myeloblastic and myelomoblastic leukaemias. 4 patients with acute promyelocytic leukaemia were Ia-negative. This finding suggests that Ia-like antigens reflect normal differentiation linked events in haemopoiesis. The presence of Ia-like antigens on leukaemic cells did not alter the patient's response to chemotherapy.

Adolescent↗

Clonal identification in acute lymphoblastic leukemia.

In a case of acute lymphoblastic leukemia, two distinct types of leukemia blast cells could be identified throughout the course of the disease. The initially dominant type of blast cell was sensitive to chemotherapy; the other was drug-resistant, gradually becoming dominant as the disease progressed. The cell types could be clearly separated by their morphologic and surface membrane marker characteristics. The same chromosomal constitution was present in both types of blast cells, indicating a common clonal origin. Additional chromosomal abnormalities were present in the later stages of the disease, demonstrating that a distinct subclone had proliferated. This study illustrates that in some cases of acute leukemia, disease relapse is caused by growth of drug-resistant subclones that may be clearly identified by changes in morphology and surface membrane marker characteristics.

Adult↗

Terminal transferase-positive human bone marrow cells exhibit the antigenic phenotype of common acute lymphoblastic leukemia.

Combined immunologic assays for TdT enzyme and membrane markers show that TdT+ cells in nonleukemic human bone marrow carry ALL-associated and Ia-like antigens but no thymocyte markers or surface Ig. These cells could be precursors involved in acute lymphoblastic leukemia of the "common" or non-T, non-B type and in lymphoid blast crisis of Ph' positive chronic myeloid leukemia. A few TdT+, Ia+ cells express cytoplasmic IgM, indicating that some pre-B cells may be TdT positive.

Antigens↗