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G Janossy

Publications and source records attributed to G Janossy.

At least 181 records · Page 10Linked to original sources
PubMed1985

An immunohistological approach to persistent lymphadenopathy and its relevance to AIDS.

Recent evidence has shown that not only AIDS but also the majority of 'unexplained' persistent, generalized lymphadenopathy (PGL) are related to HTLV-III/LAV infections. The early detection how these changes may proceed to AIDS then become a prime interest. Eleven patients with PGL (10 homosexual males and one heterosexual haemophiliac) have been studied by immunohistology using monoclonal antibodies to dendritic reticulum cells of the germinal centre, T and B lymphocyte subsets, plasma cells and factor VIII, as an endothelial marker. In six cases only follicular and paracortical hyperplasia was detected, while in five other cases destruction of the dendritic reticulum cell network was seen with this sensitive method. This early destruction may explain the release of activated B cells into the circulation and prove to be an ominous prognostic sign, as it appears to correlate with 'prodromal' symptoms. In four out of 11 cases the depletion of T4+ cells in the paracortex was not as severe as in the blood, indicating that T4+ cells may preferentially settle in tissues at the time of T4 lymphopenia. In addition, germinal centres contained an additional patchy infiltration of T8+ cells. A patient with Kaposi's sarcoma did not show germinal centre destruction but did reveal extensive plasma cell infiltrates. Immunohistology may contribute to the definition of prognosis and analysis of disease progression in patients with PGL.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Human macrophages and T-lymphocyte subsets infiltrating nodules of Onchocerca volvulus.

The nature of the lymphoid infiltrate in nodules of Onchocerca volvulus was assessed using monoclonal antibodies to lymphoid cell surface markers. Although B cells were generally absent, T cells were present, but in variable amounts. The ratio of T4+ (helper phenotype) to T8+ (suppressor-cytotoxic phenotype) was usually in the normal peripheral blood range of about 3, although ratios ranging from 1 to 10 were seen in selected areas of the onchocercoma. The possibility of immunosuppression through dominance of T4+, Leu-8+ cells (suppressor-inducer phenotype) within the T4+ population was also excluded. The T cells did not tend to concentrate in close proximity to the parasite, and there was no general bias in favour of the T suppressor cell phenotype (T8) within the infiltrate. Macrophages and dendritic cells were consistently observed and consisted of three defined cell types in approximately equal proportions: normal, unactivated macrophages (HLA-DR-, acid phosphatase positive), activated macrophages (HLA-DR+, acid phosphatase positive) and cells of dendritic morphology (HLA-DR+, acid phosphatase negative). These results are discussed in relation to immune suppression in filariasis.

Antibodies, Monoclonal↗
PubMed1985

Human B cell development. I. Phenotypic differences of B lymphocytes in the bone marrow and peripheral lymphoid tissue.

The phenotype of B lineage cells (TdT+, pre-B, IgM+, IgD-, and IgM+,IgD+) in infant and adult human bone marrow was compared with that of B cells seen in peripheral tissues such as tonsil and blood. The range of B cell-associated antibodies used included four reagents with greater than 90% reactivity on peripheral B cells: RFB4 and To15 (both p135, corresponding to CD22), RFB6 (p140 corresponding to CD21), and Y29/55, a unique B cell-specific antibody. In addition, AL-1, an antibody with virtually no reactivity against peripheral B cells was also used. The BM cell subpopulations were heterogeneous in respect of antibody reactivity. The TdT+, pre-B and IgM+, IgD- cells were AL-1+ but did not express membrane antigens recognized by the antibodies To15, RFB4 (CD22), and RFB6 (CD21). TdT+, pre-B cells, and 50% of IgM+, IgD- BM B cells were also unreactive with antibody Y29/55, the other 50% being Y29/55+. In contrast, the IgM+,IgD+ BM B cells, like peripheral B cells, were positive with antibodies To15, RFB4, RFB6, and Y29/55, but reacted only in small numbers with AL-1. The orderly differentiation-linked display of these antigens was also suggested by the findings that normal TdT+, pre-B, and IgM+,IgD- cells expressed the To15 and RFB4 (CD22) antigens in their cytoplasm (in the Golgi region). This observation was confirmed in malignant common acute lymphoblastic and pre-B blast cells, as well as in the corresponding permanent cell lines KM3 and NALM-6. In these lines the membrane expression of To15 and RFB4 could be induced by phorbol ester during a 48 to 72 hr culture period.

Adolescent↗
PubMed1984

The demonstration of cell surface antigens on T cells, B cells and accessory cells in paraffin-embedded human tissues.

This paper describes a method for processing fresh tissue that allows immunohistological analysis on paraffin sections. The method is based on the use of periodate-lysine-paraformaldehyde fixation. The effects of variation in fixation time, concentration of paraformaldehyde, dehydration, clearing, wax embedding and enzyme treatment of cut sections were examined. An optimal processing procedure was established that retains good tissue morphology and allowed 21 out of 27 monoclonal antibodies tested to be used successfully on paraffin sections to identify all major cell subpopulations by their membrane antigenic characteristics. The value of this approach in studying the immunopathology of potentially dangerous infectious diseases and in leukaemia/lymphoma diagnosis is discussed.

Antibodies, Monoclonal↗
PubMed1984

Depletion of T lymphocytes in donor marrow prevents significant graft-versus-host disease in matched allogeneic leukaemic marrow transplant recipients.

For more than 15 years preclinical studies have suggested that acute graft-versus-host disease (aGvHD) might be prevented by the removal of immunocompetent T lymphocytes from the donor marrow inoculum. To test this observation in man 14 patients were given marrows virtually (greater than 99%) depleted of identifiable donor marrow T lymphocytes by the use of a "cocktail" of specific anti-T-cell monoclonal antibodies (MBG6 and RFT8) and rabbit complement. Patients were not given immunosuppressive prophylaxis after bone-marrow transplantation. Moderate to severe (grades II-IV) GvHD was totally prevented. 2 of 13 evaluable patients showed mild (grade I) skin GvHD only. Although peripheral blood recovery was slower than that obtained with other forms of GvHD prophylaxis, no fatal infections occurred. All patients survived the early post-transplant period.

Acute Disease↗
PubMed1984

The role of monoclonal antibodies in the prevention of graft versus host disease.

We have previously reported that the elimination of T-lymphocytes (greater than 99%) from the donor bone marrow prevents significant graft versus host disease (GvHD). This has been confirmed by other centres. Many of these groups have applied monoclonal antibodies with cytolytic rabbit complement. In some of these studies mostly patients with fully matched sibling donors have been studied and no further immunosuppression has been given during the regeneration period. The experience here shows that the haemopoietic regeneration (to recover a total leucocyte count of 1.0 X 10(9)/l) has only been minimally delayed (mean 25 days) when compared to patients receiving standard methotrexate (Mtx) GvHD prophylaxis (22 days). The incidence of cytomegalovirus (CMV) infections (14%; none fatal) was lower than that in our previous 54 patients (43% CMV infections, 13% fatal). Furthermore, no fatal pneumonitis was seen. The regeneration of T-cells in our patients has shown normal values of T8-positive cells in the circulation from 45 to 50 days onwards, as opposed to the previous groups of patients whose T8-positive cells regenerated to 3-4 times higher than normal values. These observations indicate that T-cell depletion with monoclonal antibodies is an effective method for preventing GvHD, but further studies are necessary to investigate the cause(s) of a new occasional complication, the rejection of the newly established bone marrow.

Adolescent↗
PubMed1984

Lineage relationship of chronic lymphocytic leukemia and hairy cell leukemia: studies with TPA.

The tumor promoting agent TPA (phorbol ester; 1.6 X 10(-8)M) was used to induce the differentiation in vitro of B-chronic lymphocytic leukemia (B-CLL) cells from 14 untreated patients. The uninduced phenotype was SIg+, Mrbc+, RFT-1+, RFA-4-, FMC7-. After 72 h incubation with TPA, B-CLL cells became RFA-4+, FMC7+ and lost the capability of Mrbc rosetting. Large proportions of the "induced" cells also showed morphological and ultrastructural changes, such as undulating membranes and bleblike protusions and became strongly positive for tartrate resistant acid phosphatase (TRAP+) and also contained cytoplasmic immunoglobulins. These features are very similar to the features of hairy cell leukemia (HCL). These observations confirm previous clinical findings that B-CLL and HCL are related disorders of the B lineage. The development of "hairy" features in induced B-CLL and in HCL seems to be a malignancy-associated feature because the Mrbc+ normal B cells (B-CLL-equivalent cells) isolated from tonsil also develop TRAP positivity but no membrane aberrations.

B-Lymphocytes↗
PubMed1984

Immunohistochemical analysis of thymoma. Evidence for medullary origin of epithelial cells.

The histologic organization of lymphoid and nonlymphoid (epithelial and interdigitating) cells in a thymoma has been compared to that of the normal thymus. Enzyme and immunohistochemical methods were applied, using both conventional antisera (to cytokeratin) and monoclonal antibodies (to epithelial cells, HLA-DR and lymphoid subsets). Throughout the tumor, the epithelial cells shared phenotypical similarities with the epithelial cells of thymic medulla (RFD-4 positive, cytokeratin strongly positive, and HLA-DR essentially negative). On the other hand, the lymphoid cells were heterogeneous in phenotype and distribution, and "mimicked" the distribution seen in the normal infant thymus. Immature thymocytes of cortical type (TdT+, OKT6+, OKT3-) were predominant in the areas with moderate lymphocytic infiltration (ML). Mature T-lymphocytes (TdT-, OKT6-, OKT3+) were found mainly in areas with scanty lymphocytes (SL) together with an additional population of HLA-DR positive interdigitating and HLA-DR+, OKT6+ Langerhans'-type cells. These findings indicate that in thymoma tissue, the lymphoid elements of cortical type are apparently surrounded by an inappropriate (medullary) epithelium.

Antibodies, Monoclonal↗
PubMed1984

Intestinal lymphocyte subpopulations in inflammatory bowel disease: an analysis by immunohistological and cell isolation techniques.

Lymphocyte subpopulations in the intestinal mucosa of patients with ulcerative colitis or Crohn's disease have been studied using a double marker immunofluorescence technique. Analysis of tissue sections revealed that the majority of intraepithelial lymphocytes (IEL) were T cells (Hle-1+ HuTLA+ UCHT1+). Of these, over 80% were of suppressor-cytotoxic phenotype (OKT8+:83 +/- 10.2%) with a small population of helper type IEL (OKT4+). Only one third of OKT8+ IEL reacted with the T cell antibody, anti-Leu-1. IEL were also Tac-, C3b-receptor- (C3RT05-), and Ig-. Within the lamina propria, OKT4+ T cells predominated (ulcerative colitis 64 +/- 6.0%; Crohn's disease 63 +/- 6.0%). Less than half of the smaller OKT8+ population in the lamina propria was Leu-1+. These finding did not differ from those seen in histologically normal tissues from controls, and are similar to those reported in the small intestine. Mononuclear cells were also isolated from the intestinal lamina propria using an enzymatic technique. The majority of lymphocytes obtained were T cells (OKT3+), with populations of OKT4+ and OKT8+ cells. Comparison of the ratio of OKT4+ to OKT8+ lymphocytes determined by immunohistological analysis with that obtained in mucosal isolates, however, suggested that the isolation procedure may deplete OKT8+ cells. These findings indicate that an imbalance of mucosal immunoregulatory T cells, as defined by monoclonal antibodies, does not occur in inflammatory bowel disease. They also emphasize that functional studies of isolated intestinal mucosal cells should be combined with morphological studies of cell populations in situ.

Adolescent↗
PubMed1984

Monoclonal antibody (WT 1) directed against a T cell surface glycoprotein: characteristics and immunosuppressive activity.

WT 1, an IgG2a subclass monoclonal antibody, recognizes a human T lineage specific antigen (mol. wt 40,000). This antigen is strongly expressed on thymic T blasts, and on peripheral T cells activated by phytohaemagglutinin, whereas cortical thymocytes and peripheral T cells are moderately positive for WT 1. In contrast, B lymphocytes, myeloid and erythroid cells, including the progenitor cells of these lineages, and terminal deoxynucleotidyl transferase positive cells in the bone marrow, are all WT 1 negative. Binding of WT 1 to T cells is blocked by a previously described antibody (3A1) suggesting that both antibodies bind to the same antigen present on human T cells. WT 1, however, is also reactive with T lymphocytes from rhesus monkeys whereas 3A1 is not. Therefore, the biological effects of WT 1 could be studied in a monkey model. In a skin allograft model, WT 1 was immunosuppressive and induced a marked prolongation of graft survival.

Animals↗
PubMed1984

A combined immunohistological and histochemical analysis of lymphocyte and macrophage subpopulations in the rheumatoid nodule.

The histochemical demonstration of acid phosphatase (ACP) and adenosine triphosphatase (ATP) has been combined with standard immunofluorescence techniques, using a panel of monoclonal and conventional antibodies, to examine lymphocyte and macrophage subsets and their microanatomical relationships within the subcutaneous rheumatoid nodule (RN). This analysis reveals that the RN is composed largely of strongly HLA-DR+, ATP- macrophages which contain lysosomal enzymes (ACP) in large amounts. The lymphocytic infiltrate which is sparse and poorly organized is comprised almost entirely of thymus derived lymphocytes (T cells) with a normal proportion of helper/inducer (OKT4+) and suppressor/cytotoxic (OKT8+) cells. These observations are in contrast to the findings in the rheumatoid synovial membrane of a prevalence of interdigitating type, HLA-DR+ cells and the predominance of helper (OKT4+) type T cells.

Antibodies, Monoclonal↗
PubMed1984

Immunohistological analysis of bone marrow involvement in lymphoproliferative disorders. The use of cryostat sections from trephine biopsies.

Cryostat sections from frozen samples of human bone marrow trephine biopsies were used for immunohistochemical analysis. Immunoperoxidase and immunofluorescence techniques as well as enzyme histochemistry were applied to these sections in order to characterize bone marrow infiltrates in lymphoproliferative diseases. Various conventional antisera and monoclonal antibodies and several enzymes were able to identify different normal and malignant cell populations. This technology provides a new tool to be used in combination with classical morphology for studying bone marrow involvement during lymphoid malignancies.

Biopsy↗
PubMed1984

Distribution and heterogeneity of cells detected by HNK-1 monoclonal antibody in blood and tissues in normal, reactive and neoplastic conditions.

When studied with double staining techniques HNK-1+ cells include subsets not expressing T cell antigens (A), expressing T8 antigens (B) and expressing T4 antigens (C). Cells with phenotype A are observed as the dominant HNK-1+ population (greater than 50% of all HNK-1+ cells) in the blood from controls and from patients with solid tumours, infectious mononucleosis and sarcoidosis. Cells with phenotype B are always a substantial subset (35% of HNK-1+ cells) in the peripheral blood but in patients with B chronic lymphocytic leukaemia and angioimmunoblastic lymphadenopathy these cells are present in an even higher percentage (greater than 50% of all HNK-1+ cells). This cell subset is the only HNK-1+ population found in the few tumour samples where HNK-1+ cells are identifiable. Apart from these few cases of malignancies, the type A and B subsets are rare in the tissues. In these samples Leu 11+ cells seem to be absent. In contrast, cells with phenotype C are a minor population in the blood but represent most HNK-1+ cells in the germinal centres of lymph nodes and their malignant counterparts in follicular centre cell lymphoma. These HNK-1+, T4+ cells are Leu 11-. These phenotypic characteristics indicate that the most efficient NK cells may represent a circulating and not a tissue seeking population.

Adult↗
PubMed1983

The production of terminal deoxynucleotidyl transferase (TdT) positive cells in cultures of human pluripotent hemopoietic progenitor cells.

A transient increase in terminal deoxynucleotidyl transferase positive (TdT+) cells was observed during the early phase of (less than or equal to day 5) cultures supporting the growth of pluripotent myeloid progenitor cells (CFU-mix). T-cell growth-promoting medium and erythropoietin were not required. The rapidity with which TdT+ cells appeared in cultures and the results of cultures where TdT+ cells were high initially (greater than 800 cells/culture) were not consistent with their having been produced by proliferation of pre-existing TdT+ cells from the bone marrow inoculum. The results suggest production of TdT+ cells from a TdT-negative precursor either by altered enzyme expression or by production of TdT+ progeny.

Cell Division↗
PubMed1983

Routine immunofluorescent and histochemical analysis of bone marrow involvement of lymphoma/leukaemia: the use of cryostat sections.

Enzyme histochemical and immunohistological (immuno-fluorescence and -peroxidase) techniques have been routinely used for investigating over 70 normal and pathological bone marrow samples. This recently standardized diagnostic procedure is very quick and can be performed in a few hours. In 6 cases the clinical diagnosis of leukaemia/lymphoma has become apparent only after the immunohistological analysis of the bone marrow. In 6 other cases the information about the staging of B cell malignancies was superior in the frozen biopsies to the paraffin embedded preparations. Amongst many other features the monoclonality of B CLL/lymphomas, the special features of B CLL infiltrates (RFA-1+, Leu-1+, HLA-DR+, SmIg+), follicular lymphoma deposits (containing follicular dendritic cells) and non-T, non-B acute lymphoblastic leukaemic blasts (terminal transferase+, HLA-DR+) as well as the sometimes conspicuous presence of infiltrating normal T cells could be clearly and reproducibly demonstrated.

Adolescent↗