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Biomedical subjects

G Janossy

Publications and source records attributed to G Janossy.

At least 253 records · Page 14Linked to original sources

Distribution of t lymphocyte subsets in the human bone marrow and thymus: an analysis with monoclonal antibodies.

A panel of reagents (OKT1, 3, 4, 6, 8, and 11) detects differentiation antigens expressed exclusively on HuTLA+ T lymphoid cells but absent on bone marrow precursors, such as terminal deoxynucleotidyl transferase- (TdT) positive cells, immature myeloblasts, and other myeloid/erythroid cell types. In the bone marrow no transitional forms could be detected between TdT+ and T cells. The BM T cells showed mostly the suppressor/cytotoxic phenotype (OKT8+) with only a few T cells of inducer type (OKT4+). Thymocyte heterogeneity was also analyzed directly in tissue sections and in double labeling assays in combination with TdT staining, a marker for cortical thymocytes. Many large thymic blasts (in fetal and infant thymus) showed reactivity with OKT11--a pan-T reagent, but had only weak or negligible activity with the other antibodies. Cortical thymocytes reacted strongly with OKT11, 6, 4, and 8, whereas medullary cells reacted with OKT11, 3, 4 (majority) and 8 (minority). Thus, the reactivity with these antibodies is generated in the thymus at various stages of differentiation. In contrast, OKT10 (an anti-"precursor cell" reagent) reacted not only with thymocytes but also with TdT+ BM precursors, myeloblasts, and BM B lymphocytes although it was unreactive with mature peripheral lymphoid and maturing myelo/erythroid cells.

Adolescent↗

A monoclonal antibody specific for immature human hemopoietic cells and T lineage cells.

An anti-human monoclonal antibody (RFB-1) has been produced that reacts with a group of hemopoietic precursor cells in human bone marrow. These include terminal deoxynucleotidyl transferase-positive (TdT+) cells and myeloid colony-forming unit cells, functionally identifiable progenitor cells of the granulocytic-monocytic series. The expression of RFB-1 antigen on myeloid cells decreases as the cells become more mature; myeloblasts are weakly RFB-1+ but most promyelocytes are RFB-1-. RFB-1 also reacts with TdT+ thymic blast cells and cortical thymocytes but is unreactive with TdT- medullary thymocytes, although the majority of peripheral T cells are weakly RFB-1+. RFB-1 is the first anti-precursor cell reagent that labels human TdT+ cells in both the thymus and bone marrow as well as hemopoietic precursor cells but is unreactive with pre-B blasts and B lymphocytes.

Animals↗

Immunologically defined subclasses of acute lymphoblastic leukaemia in children: their relationship to presentation features and prognosis.

Leukaemic cells from 542 patients under 21 years of age with a diagnosis of acute lymphoblastic leukaemia (ALL) were typed with immunological cell surface markers between June 1975 and December 1979; 379 of these patients entered into the trials up until December 1978 have been followed for more than 1 year. They were divided into four subgroups: common (c) ALL, T (thymic) ALL, 'null' (or 'unclassified') ALL and a rare lymphoma/leukaemia type B-ALL. A T-cell phenotype was found more frequently in boys and was usually but not invariably associated with a high white cell count at presentation. A mediastinal thymic mass was present in 53% of T-ALL patients but was not observed in any unequivocal not-T ALL. Clinical prognosis differed substantially between the three major phenotypic classes, remission induction rate and remission duration being lowest in T-ALL, better in 'null' ALL, and highest in cALL (P trend less than 0 . 0001; P = 0 . 0002 for comparison of cALL versus T-ALL). There was a much higher incidence of CNS involvement in the T-ALL group than in the cALL group or 'null' All group and although this was strongly correlated with WBC count it was also significantly associated with T-ALL independent of WBC count. Overall in this series and also within the major cALL subclass there is a strong correlation between high WBC count and poor clinical response (remission induction and duration). When the three major immunological subclasses are adjusted for WBC count the prognostic correlation of antigenic phenotype is reduced and statistically insignificant. It is suggested that immunological (and enzymatic) phenotype of ALL subclasses may not be an independent correlate of prognosis but nevertheless is linked to other cell differentiation features, especially growth rate and sites of clonal expansion (e.g. marrow versus thymus), which critically influence the size of the clonogenic leukaemic population and its associated evolutionary status with the respect to drug resistant mutants at the time of diagnosis and introduction of therapy.

Adolescent↗

The human thymic environment.

Selected combinations of antisera labelled with different fluorochromes were used to explore the cellular interactions in the human thymic cortex and the medulla. In the early fetal thymus the cortical epithelial cells and an apparently more mobile medullary interdigitating cell population expressed large amounts of Ia-like (HLA-DR) and moderate amounts of HLA-A,B,C antigens while the lymphoid cells in the cortex expressed human T lymphocyte and cortical thymocyte antigens but were Ia-, HLA-A,B,C-. This arrangement is maintained in the infant thymus. The terminal deoxynucleotidyl transferase enzyme is first generated in cortical thymocytes (around the 17th week of gestation) and appears in bone marrow precursor cells later. In the infant thymus the lymphoid populations could be classified, according to their reactivity pattern with the new monoclonal antibodies of the OKT series, into three cell types: putative prothymocytes, typical cortical thymocytes and medullary thymocytes. Among the medullary population the majority showed the phenotype of the "inducer" cell and a minority showed that of "suppressor-cytotoxic" cells. The thymic medulla (and interdigitating cells in peripheral lymphoid organs) may predominantly contribute to the generation of "inducer" T lymphocytes.

Animals↗

Differential diagnosis of malignant lymphoma and nonlymphoid tumors using monoclonal anti-leucocyte antibody.

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.

Adolescent↗

Effects of cyclosporin A on suppressor and inducer T lymphocytes in primary biliary cirrhosis.

There is a significant decrease in the ratio of inducer (helper) to suppressor T lymphocytes in the peripheral blood of patients with primary biliary cirrhosis (PBC). These changes are not seen in other forms of cholestatic liver disease, but are similar to those described in chronic graft-versus-host disease. Cyclosporin A treatment increased the proportion of suppressor A lymphocytes and improved liver function in 6 patients with PBC. This indicates that cyclosporin A is an immunoregulatory drug. Unfortunately nephrotoxicity precluded long-term use.

Cyclosporins↗

Remission induction with adenosine-deaminase inhibitor 2'-deoxycoformycin in Thy-lymphoblastic leukaemia.

Two patients with relapsed acute lymphoblastic leukaemia of thymic phenotype (Thy-ALL) resistant to all conventional chemotherapy achieved complete remission when treated with 2'-deoxycoformycin, a selectively lymphocytotoxic compound that acts by inhibition of the enzyme adenosine deaminase. These observations show that malignant thymocytes are dependent on adenosine-deaminase activity and suggest that it may be possible to use deoxycoformycin in other patients with Thy-ALL to induce remission or to kill Thy-ALL blasts in bone marrow harvested before autologous bone-marrow transplantation, leaving normal haemopoietic stem cells intact.

Adenosine Deaminase↗

Immuno-histochemical characterisation of cells involved in dermatopathic lymphadenopathy.

Normal and pathological lymph nodes exhibiting the features of dermatopathic lymphadenopathy were analysed by immunochemical methods. Various antisera to human Ia-like antigens, to immunoglobulin, to T cells and myelo-monocytic cells were used. The paracortical enlargement typical of the condition was due to interdigitating cells containing Ia-like antigens on their membrane, and to adjacent T lymphocytes. The intensity of staining with anti-Ia-like serum on the interdigitating cells was comparable to the very strong staining of the fewer reticular cells present in the T dependent areas of normal nodes and normal spleen, and to the staining of Langerhans cells in the skin and appear to be higher than that seen on B lymphoid cells. These cells do not exhibit immunoglobulin and do not react with antisera made against circulating granulocytic and monocytic cells. Since sinus histiocytes of normal nodes and histiocytes in massive lymphadenopathy showed very weak staining with anti-Ia-like serum, strong Ia expression seems to be restricted to a subclass of mesenchymal cells which might be involved in the regulation of T cell function.

Atrophy↗

Immuno-histological diagnosis of lymphoproliferative diseases by selected combinations of antisera and monoclonal antibodies.

Tissue sections of frozen biopsy specimens obtained from normal and hyperplastic human lymphoid tissues, 33 cases of non-Hodgkin lymphomas as well as various forms of immunoregulatory disorders (angioimmunoblastic and dermatopathic lymphadenopathy) were analysed in immunofluorescence tests (using red TRITC and green FITC double-labelling). A panel of antisera including well-characterized conventional reagents to immunoglobulin classes, T lymphoid and Ia-like antigens, and monoclonal antibodies was used. In selected cases the results were compared with the observations of membrane-marker staining on viable cells in suspension. the findings show that the immunological methods can give a very accurate analysis of the normal and malignant lymphoid cells, and can provide complementary information to conventional histology. The investigator can choose the reagent combinations which give answers to various specific questions: e.g. antisera to light chains establish the monoclonality of lymphomas, whilst staining combinations for human T and Ia-like antigens are particularly useful in various immunoregulatory disorders. Monoclonal antibodies will be particularly useful in various immunoregulatory disorders. Monoclonal antibodies will be particularly useful reagents for analysing the tissue distribution of lymphoid subpopulations and ancillary cells in tissue biopsy specimens.

B-Lymphocytes↗

Terminal transferase enzyme assay and immunological membrane markers in the diagnosis of leukaemia: a multiparameter analysis of 300 cases.

Multiparameter analyses have been carried out with recently developed enzyme and membrane markers in 300 patients with various leukaemias including ALL, AML, but excluding Ph1 positive leukaemias. TdT enzyme levels were particularly valuable in the differential diagnosis of adult acute lymphoid and myeloid leukaemias. The levels were raised in 108 (94%) of the 115 patients who were considered to be non-T, non-B ALL on membrane marker and morphological analysis; all seven cases giving negative TdT results in this group were young children. Unexpectedly high levels were seen only in three (4.1%) of 73 cases of acute myeloid leukaemia verified by histochemistry and membrane markers. Anti-ALL serum was a most useful reagent in childhood leukaemias but blasts from 19 patients (10% of childhood ALL cases and 29% of adult ALL cases) failed to react with the serum in spite of TdT positivity. Strongly ALL+ blasts were seen only in non-T, non-B ALL and some undifferentiated leukaemias. Weakly ALL+ blasts were seen in seven of 32 cases of thymic ALL (Thy-ALL) but in other respects these blasts expressed Thy-ALL features, such as strong reactivity with anti-T cell (HuTLA) serum, negativity with anti-Ia-like serum and raised TdT. The combination of tests was particularly useful in 32 cases of undifferentiated leukaemia: in 10 of these cases TdT positivity indicated the probable 'lymphoblast', nature of blast cells: the remaining 22 cases remained unclassifiable with the markers used. The analysis revealed other interesting variant forms of leukaemias.

Acute Disease↗