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Biomedical subjects

G Janossy

Publications and source records attributed to G Janossy.

At least 235 records · Page 13Linked to original sources
PubMed1981

Rheumatoid arthritis: a disease of T-lymphocyte/macrophage immunoregulation.

In rheumatoid arthritis the synovial membrane has many of the characteristics of a hyperactive, immunologically-stimulated lymphoid organ. The basis of this hyperactivity is poorly understood. Highly specific antisera to human Ia-like (HLA-DR) antigens and monoclonal antibodies (OKT series) to various T-lymphocyte subsets were used to analyse both the normal and the rheumatoid synovium and to compare it with normal lymph nodes. In rheumatoid arthritis the synovium acquires an infiltrate with microanatomical similarities to the paracortical area of the lymph node. Large, very strongly HLA-DR-positive macrophage-like interdigitating cells form close contacts with the OKT4+ (inducer-type) T-cells, while the OKT8+ population (T-cells of suppressor-cytotoxic type) between the macrophage-OKT4+ cell clusters is scanty (T4/T8 ratio = 9:1). By contrast, in the lymph node there are more OKT8 T-cells interspersed between the HLA-DR+ interdigitating cells and OKT4+ cells (T4/T8 ratio = 2:1). The large interdigitating cells and the OKT4+ T-cell population may be mutually stimulatory. In the absence of efficient suppression this stimulation may lead to activation of B-lymphocytes and oligoclonal or polyclonal immunoglobulin synthesis, as is found in the synovial membrane in rheumatoid arthritis.

Antibodies, Monoclonal↗
PubMed1981

Diagnosis of meningeal involvement in patients with acute lymphoblastic leukemia: immunofluorescence for terminal transferase.

As indirect immunofluorescence technique (I) for detecting TdT enzyme was used to study leukocytes present in the cerebrospinal fluid (CSF) of patients with documented acute lymphoblastic leukemia, nonlymphoid leukemias, and unrelated nonmalignant disorders. TdT was found to be expressed in all cases of overt meningeal lymphoblastic leukemia studied but was absent from leukocytes in patients with nonlymphoid leukemia and lymphocytic meningitis. In addition, the IF test proved useful in identifying leukemic blasts in CSF where these were of atypical morphology or present in extremely low numbers. Immunofluorescence for TdT is a useful tumor marker in the CSF of patients with ALL.

Child, Preschool↗
PubMed1981

Long-term T-cell-mediated immunity to Epstein-Barr virus in renal-allograft recipients receiving cyclosporin A.

Peripheral-blood mononuclear cells from renal-allograft patients receiving cyclosporin A (CSA) were tested for their ability to produce T cells cytotoxic for EB-virus-infected B-cell targets in culture and compared with those from healthy seropositive subjects. Whereas in the control cultures the proliferating foci of EB-virus-transformed B cells regressed after 2 weeks, no such regression was seen in cultures from CSA-treated patients. These results indicate that patients receiving CSA cannot mount a cytotoxic response to EB-virus-infected B cells in vitro. It is suggested that suppression of memory-T-cell proliferation contributes to the high incidence of lymphomas in CSA-treated renal-allograft recipients.

Adolescent↗
PubMed1981

Studies on long-term T-cell-mediated immunity to Epstein-BArr virus in immunosuppressed renal allograft recipients.

Peripheral blood lymphocytes from normal seropositive donors and renal transplant recipients on various immunosuppressive regimens have been tested for their ability to mount a cytotoxic response when cultured with autologous EB virus-infected B cells and thereby to cause regression of proliferating b-cell foci. Cultures from 10 normal seropositive donors all showed the normal pattern of regression. Lymphocytes from patients receiving Cyclosporin A therapy with or without prednisolone completely failed to cause regression, thus allowing B-cell lines to proliferate unchecked. Cells from two of 17 patients treated with azathioprine and prednisone also failed to cause regression. The cells from the remaining 15 individuals showed regression response varying from minimal to normal. These results suggest a mechanism by which EB virus-related tumours may arise in immunosuppressed renal allograft recipients.

Azathioprine↗
PubMed1981

The analysis of lymphoid subpopulations in normal and malignant tissues by immunofluorescence techniques.

Tissue sections of frozen biopsy specimens obtained from normal and hyperplastic human lymphoid tissues as well as 40 cases of non-Hodgkin's lymphomas were analysed in immunofluorescence tests (using red TRITC and green FITC double-labeling). A panel of antisera including well-characterized conventional reagents to immunoglobulin classes, T-lymphoid and Ia-like antigens and monoclonal antibodies, including the OKT range made by Ortho Laboratories, was used. 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. Furthermore, the monoclonal antibodies to well defined lymphocyte subsets can provide data which suggests (although does not prove) functional relationships between different types of cells in normal and malignant lymph nodes. Thus, the technology described fills the gap between conventional histology and cellular immunology.

Antibodies, Monoclonal↗
PubMed1981

Immunological characterization of hemopoietic cells in the common marmoset, rhesus monkey, and man. In search of a model for human marrow transplantation.

Bone marrow, lymphoid, and peripheral blood cells from the common marmoset and rhesus monkey have been tested with a panel of heterologous and monoclonal antibodies, and their reactivity pattern has been compared with that of blood and bone marrow cells from human donors. Conventional antibodies reveal extensive cross-reactivity within the B cell, T cell, and granulocytic systems in all three species, however, some important differences have been exposed. Only the monoclonal antibodies to HLA-A,B,C and Ia-like antigens react with marmoset cells, and we have exploited this finding to show that the vast majority of colony-forming units (CFU-c) in the marmoset bone marrow (as in man) are Ia positive. The use of the common marmoset as a suitable model for human bone marrow transplantation is discussed in the light of these findings.

Animals↗
PubMed1981

Heterogeneous blast cell crises in Philadelphia negative chronic granulocytic leukaemia.

A case of Philadelphia negative chronic granulocytic leukaemia (Ph1-CGL) is described showing features only previously demonstrated in Ph1+ disease. These features include: (1) lymphoid blast crisis, determined by morphology and immunological marker analysis; (2) dual blast cell populations that can be distinguished both morphologically and by immunological markers; (3) clonal evolution, as shown by the emergence of chromosome markers and in one of the cell lines a change in membrane phenotype. These changes were apparently associated with the emergence of a relatively drug resistant subclone of leukaemic cells. This study demonstrates that the lymphoid blast crisis of CGL, and its sequelae, can occur in Ph1- cases. It is similar in respect to morphology, enzyme, and membrane markers and responsiveness to vincristine and prednisolone therapy to the lymphoid blast crisis seen in Ph1+ CGL. This suggests that the Philadelphia chromosome is a clonal marker only, and its presence is not directly related to the subsequent clinical course of the disease.

Bone Marrow↗
PubMed1981

Immunofluorescent and biochemical studies of terminal deoxynucleotidyl transferase in treated acute leukaemia.

Indirect Immunofluorescence (IF) for terminal deoxynucleotidyl transferase (TdT) was used in conjunction with the biochemical assay of TdT enzymatic activity to study human leukaemias before and during therapy. In addition, non-leukaemic marrows were analysed to compare the enzyme expression on normal cells. An excellent correlation was observed between the IF and biochemical methods when specimens contained greater than 5% TdT+ cells (by IF); below this level the biochemical assay was less reliable, while the sensitive IF test could detect isolated TdT+ cells among greater than 10 000 TdT negative cells. The IF method also had the advantage of allowing further immunological characterization of TdT+ cells, by simultaneous labelling of membrane antigens with appropriate antisera. TdT+ cells expressing Ia-like antigens (but lacking other antigens associated with B- and T- lymphoid differentiation) were frequently found in low numbers in remission marrows from acute lymphoblastic leukaemia (ALL) patients. However, similar cells were also observed in remission acute myeloid leukaemia, as well as in non-leukaemic regenerating marrows, and marrow from normal donors. The presence of these normal TdT+ precursor cells therefore precluded the use of either IF or biochemical TdT tests for estimating the degree of residual disease or predicting early relapse in patients with non-T, non-B ALL. In contrast, the detection of TdT+ cells with T lymphoid antigens (HuTLA+) but lacking Ia antigens, in thymic (T-cell)-ALL, but not in normal marrow, allowed the use of this combination of markers to detect minimal residual disease in T-ALL.

Acute Disease↗
PubMed1981

Terminal deoxynucleotidyl transferase expression in acute non-lymphoid leukaemia: an analysis by immunofluorescence.

Indirect immunofluorescence for terminal transferase enzyme (TdT) was used to study the blasts of 64 patients with acute non-lymphoid leukaemia (ANLL). In 32 patients no TdT positive cells were seen. In 19 cases a small subpopulation of cells expressing TdT was detected; these constituted up to 5% of total nucleated cells, and it was not clear whether these TdT positive cells were part of the leukaemic process or represented residual normal bone marrow lymphoid cells. The remaining 13 patients had TdT positive cells accounting for 7-90% of the total. In two of these cases TdT was expressed on blasts with myeloid features, representing an aberrant expression of TdT by myeloid cells; in contrast, in three cases mixed populations of TdT positive lymphoid blasts and TdT negative myeloid blasts were observed. In the remaining cases it was not possible to determine whether the TdT positive cells had definite lymphoid or myeloid features. Cytogenetic analysis showed no evidence of the Philadelphia chromosome. Response to treatment was assessed in 11 of the 13 patients. Only one patient remitted with the initial choice of therapy (DAT); four failed to respond to initial regimes of vincristine and prednisone (V & P) while the other five patients did not respond to myelotoxic combinations (DAT). Only one patient subsequently entered complete remission on second line therapy (V & P). This group of patients with TdT+ ANLL had a particularly bad prognosis, and appeared to differ from cases of TdT positive acute undifferentiated leukaemia, which often respond to V & P therapy.

Acute Disease↗
PubMed1981

Reactivity of monoclonal antibodies with human myeloid precursor cells.

Five monoclonal antibodies have been tested for their ability to bind to myeloid precursor cells in normal human bone marrow. Indirect immunofluorescence and the fluorescence activated cell sorter was used to separate cells according to their reactivity for trial culture in vitro in order to grow granulocyte-macrophage colony forming cells (CFUc). Two antibodies (OKT3 and OKT11) which react strongly with bone marrow T lymphocytes were found to be unreactive with CFUc. YD1/23 reacts very strongly with both T and B lymphocytes but is only weakly reactive with CFUc. In contrast, OKT10 and YE2/36 did react with CFUc. The consequences of these findings and the potential clinical use of these antibodies in bone marrow transplantation are discussed.

Adult↗
PubMed1981

Immunohistological characterisation of intraepithelial lymphocytes of the human gastrointestinal tract.

Intraepithelial lymphocytes (IEL) of the normal human stomach, small intestine, and large intestine have been characterised in tissue sections by a double marker immunofluorescent technique. A panel of reagents was used in combination, including antisera to T lymphocyte antigen (HuTLA), Ia-like (p28, 33) antigens and immunoglobulin subclasses, as well as a mouse monoclonal antibody to a human leucocyte antigen (HLe-1). In stomach and proximal small intestine over 95% of IEL were T lymphocytes (HLe-1+, HuTLA+). The proportion was slightly lower in the colon and rectum (85--95%). IEL rarely expressed Ia-like antigens. B lymphocytes were not seen within the epithelium of any of the tissues examined. The functions of IEL must be assessed in the light of the finding that they are predominantly T cells.

Digestive System↗
PubMed1981

Enzyme and membrane markers in leukaemia: recent developments.

Terminal deoxynucleotidyl transferase (TdT) assay has proved a valuable test for distinguishing lymphoblastic from myeloblastic leukaemias, particularly in adults whose blast cells are often negative for the c-ALL antigen. The immunofluorescence assay, particularly when used in combination with antisera to surface membrane antigens, has proved a sensitive technique for detecting small numbers of lymphoblasts in extramedullary sites, for example, testis or cerebrospinal fluid, or of residual Thy-ALL blasts in the marrow, which might otherwise be difficult to recognise. Differences in concentration of several enzymes concerned in purine metabolism have been detected between the blast cells in the various acute leukaemias. Adenosine deaminase (ADA) concentrations tend to be higher in Thy-ALL than in other forms of leukaemia, but the wide overlap reduces the diagnostic value of this assay. Thy-ALL blasts, however, appear to be selectively and exquisitely susceptible to inhibition of ADA by the drug deoxycoformycin, which has now been used sucessfully in a number of other wise resistant patients with Thy-ALL to obtain a complete remission. The recently introduced technique for the production of monoclonal antibodies has substantially widened the reagents available for analysing the membrane characteristics of bone marrow stem cells and of cell lineages derived from them. These have revealed previously unsuspected heterogeneity among different cases of acute lymphoblastic leukaemia, for example, among Thy-ALL blasts from different patients, and they have also delineated minor populations of immature thymocytes from which these leukaemic cells are derived. The potential use of these antibodies to prevent graft-versus-host disease by selective removal of T-lymphocytes from donor bone marrow before allogeneic bone marrow transplantation, or to prevent recurrence of Thy-ALL and other lymphoblastic leukaemias or lymphomas by selective removal of leukaemic or lymphoma malignant cells before autologous transplantation, is reviewed.

Adenosine Deaminase↗
PubMed1981

Increased numbers of cells with suppressor T cell phenotype in the peripheral blood of patients with infectious mononucleosis.

Peripheral blood cells from six patients with acute infectious mononucleosis were studied by two-colour immunofluorescence using antibodies to human T cells, inducer and suppressor-cytotoxic T cell subsets and Ia-like antigens. The absolute number of T cells with the suppressor-cytotoxic phenotype was substantially increased in each case; many of these cells also expressed Ia-like antigens and had the morphology of the large atypical cells characteristic of infectious mononucleosis. These activated suppressor T cells of infectious mononucleosis may therefore represent a control mechanism to prevent viral-induced proliferation of B cells.

Cytotoxicity Tests, Immunologic↗
PubMed1981

T lymphocyte subsets in human intestinal mucosa: the distribution and relationship to MHC-derived antigens.

T lymphocytes in the normal human intestinal tract have been analysed in tissue sections by a double-marker immunofluorescence technique, combining antiserum to T lymphocyte antigen (HuTLA) with a monoclonal antibody detecting T cells of suppressor-cytotoxic phenotype (OKT8). The distribution of HLA-A -B, -C and Ia-like antigens in intestinal mucosa was also examined by a similar method. In small and large intestine 67 to 90% (mean 70%) of intraepithelial T lymphocytes were of suppressor-cytotoxic phenotype (OKT8+). In contrast, only 27 to 56% (mean 39%) of lamina propria T cells were OKT8+. Intestinal epithelial cells demonstrated strong membrane staining for HLA-A, -B, -C antigens. Ia-like antigens were detected on the epithelial cells of small intestinal villi, but not on colonic epithelial cells. Lamina propria macrophages expressed both HLA-A, -B, -C and Ia-like antigens, the latter having strong membrane and cytoplasmic fluorescence. The distribution of T cells with suppressor-cytotoxic or inducer phenotype in the intestinal epithelium and lamina propria may be related to the differential expression of Ia-like and HLA-A, -B, -C antigens in intestinal mucosa.

Antibodies, Monoclonal↗
PubMed1981

Delineation of human thymocyte differentiation pathways utilizing double-staining techniques with monoclonal antibodies.

Three new techniques have been introduced for the phenotypic analysis of human thymocytes and T cells. Monoclonal antibodies of different subclasses (i.e. IgG1 and IgG2) were used in various combinations and labelled with subclass-specific second layers conjugated to different fluorochromes. Tissue sections were studied with combinations of monoclonal and conventional reagents, and anti-mouse Ig-coated macrobead columns were used to separate antibody-tagged cells. With the help of these simple techniques, four stage of thymocyte differentiation (prothymocyte, cortical, intermediate and medullary cell types) can be described in detail and the microanatomical relation of T cell subsets with other cell types studied.

Antibodies, Monoclonal↗
PubMed1981

Recognition of a human T-lymphocyte differentiation antigen by an IgM monoclonal antibody.

A monoclonal antibody directed at a determinant on human T cells was produced and characterized. This IgM antibody, MBG6, bound to human peripheral blood T lymphocytes and to medullary thymocytes. It was unreactive with normal B cells, B-cell lines and granulocytes. Apart from T lymphocytes, bone marrow cells (including cells positive for the terminal transferase marker, myeloid colony-forming cells, myeloblasts, and differentiating myeloid and erythroid cells) were negative. Peripheral blood cells that were treated with MBG6 and rabbit complement were no longer capable of proliferating in response to phytohaemagglutinin or concanavalin A; MBG6 did not have any direct mitogenic action on T lymphocytes. Double immunofluorescence studies using IgM MBG6 and OKT3, and IgG2a monoclonal antibody that recognizes all peripheral T cells, showed that these two antibodies identified exactly the same cell populations. Competitive binding studies, however, indicated that MBG6 and OKT3 recognized different epitopes. The antibody may have clinical applications in bone marrow transplantation.

Animals↗