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Biomedical subjects

E Matutes

Publications and source records attributed to E Matutes.

At least 271 records · Page 15Linked to original sources
PubMed1985

Phenotypic conversion of TdT+ adult AML to CALLA+ ALL.

A case of acute leukaemia is described in which the blast cells showed Sudan Black and terminal deoxynucleotidyl transferase (TdT) positivity at presentation and did not react with the monoclonal antibodies (McAb) My9 (anti-myeloid) and J5 (anti-CALL antigen). The myeloid lineage of these cells was confirmed by the myeloperoxidase (MPO) reaction at electron microscopic level. The patient entered complete remission but relapsed one year later with blasts showing negative Sudan Black and MPO reactions. These cells were still TdT+ but J5 was now positive. This case points to the existence of a clonogenic leukaemic cell with potential for evolution in both myeloid and lymphoid lineages. This is also suggested by the reactivity of both types of blast cells with the McAb 3C5 which recognises an antigen present both on early myeloid and lymphoid precursors. It is possible that patients with such leukaemias may benefit from combined therapy directed against cells of both myeloid and lymphoid lineages.

Adult↗
PubMed1984

Adult T-cell lymphoma/leukemia in a Caribbean patient: cytogenetic, immunologic, and ultrastructural findings.

Cytogenetic findings on immunologically and morphologically characterized leukemic cells from a Caribbean patient with adult T-cell lymphoma/leukemia (ATLL) (HTLV+) are reported. Marker studies on peripheral blood lymphoid cells showed a mature postthymic phenotype: TdT-, OKT3+, OKT4+, OKT6-, OKT8-, 3A1-, anti-HLA-DR-. Light and electron microscopic analysis revealed a great cellular pleomorphism with respect to nuclear features. Three main types of leukemic cell were observed: typical multilobed ATLL lymphocytes, Sézary's syndrome (SS) cells, and cells intermediate between those two. Chromosome studies on PHA-stimulated cultures revealed three clones. The predominant clone was hyperdiploid; significant abnormalities were 1q+, 14q+, and 6q- (breakpoint q21), which are known to occur in lymphoid malignancies, together with trisomy 7q and i(17q), which have been reported previously in Japanese ATLL and the small variant of SS, respectively. The 14q+ marker was t(11;14)(q13;q22-24). The incidence of 6q-, trisomy 7q, and i(17q) varied within the main clone, and it is speculated that these chromosome abnormalities might be related to the variation observed in the cell types of this patient. Two minor clones had 6q- (breakpoint q25) and 13q+ markers, respectively. It was not possible to unequivocally establish the relationship between these three clones. The chromosomal, morphologic, and immunologic findings in this case support a close relationship between ATLL in Japan and in the Caribbean basin, as well as between the proliferating cells of ATLL and SS.

Antigens, Surface↗
PubMed1984

Myeloid progenitor cells in the circulation of patients with myelofibrosis and other myeloproliferative disorders.

We have measured the numbers of myeloid progenitor cells in the circulation of patients with myelofibrosis (MF) and other myeloproliferative disorders. In general, progenitor cell numbers were increased in the circulation of patients with MF compared with controls. The mean increases were 9-fold for the multilineage progenitor cells (CFU-GEMM), 13-fold for the erythroid progenitor cells (BFU-E), 37-fold for the granulocyte-macrophage progenitor cells (CFU-GM) and 167-fold for the megakaryocyte progenitors (CFU-MK). Splenectomized patients generally had reduced numbers of circulating progenitor cells. In the CFU-MK assay, mature megakaryocytes cultured from patients with MF regularly showed large vacuoles in the nucleus and cytoplasm, unlike control cells. The increased colony formation in patients with MK, involving especially CFU-MK colonies, is consistent with the hypothesis that MF is a primary myeloproliferative disorder in which a megakaryocyte-derived factor predisposes to the formation of marrow fibrosis.

Adult↗
PubMed1984

Clinical, immunological, ultrastructural, and cytogenetic studies in black patients with adult T-cell leukemia/lymphoma.

We describe studies in 14 black patients with adult T-cell leukemia/lymphoma (ATLL) born in the Caribbean (13) and west Africa (1). Lymphadenopathy, hypercalcemia, and a leukemic blood picture were seen in the majority. The clinical course was short with a median survival of 5 months. Serum antibodies to human T-cell leukemia virus (HTLV) were detected in all the 10 cases investigated. Marker studies showed a mature (post-thymic) T4+ T-cell phenotype. Functional studies in 3 cases demonstrated that the cells did not provide help but rather suppressed B-cell differentiation. Cells from 2 cases of T4+ prolymphocytic leukemia (T-PLL) were shown to have helper function. Type C viral particles were identified by electron microscopy (EM) on cultured cells from 4 ATLL patients and these were shown to react with the monoclonal antibody (McAb) to the HTLV proteins p19 and p24. Such findings were not observed in HTLV negative T-cell leukemias except for cells of a T-PLL which showed evidence of budding and extracellular release of C-type particles after 5 days culture with phytohemagglutinin (PHA). A close association between the localization of the receptor for T-cell growth factor, demonstrated by McAb anti-Tac, and areas of the cell membrane showing release of HTLV viral particles was documented at EM level by the immunogold method. This technique also demonstrated the specific binding of anti-p19 to HTLV. Cytogenetic studies on PHA stimulated cultures from 2 ATLL revealed trisomy for 7q and this was also observed in 1 of 2 T-PLL and 2 of 4 Sezary syndrome cases. The clinical, morphological, immunological, and cytogenetic features of ATLL in black patients diagnosed in the U.K. are identical to those reported from Japan and the U.S.A. There is also strong evidence that the disease is caused by HTLV-I.

Adult↗
PubMed1984

Functional properties of neoplastic T cells in adult T cell lymphoma/leukemia patients from the Caribbean.

The neoplastic T cells from five patients with adult T cell lymphoma/leukemia (ATLL), born in the Caribbean, were studied with respect to immunoregulatory activity on pokeweed mitogen (PWM) driven immunoglobulin (Ig) synthesis as well as surface-marker phenotypes with monoclonal antibodies. The neoplastic T cells in all patients had an OKT1+4+8-11+M1-I1-3A1- phenotype, but differed in the reactivity with OKT3. None of the patients' cells exerted helper activity on PWM-induced Ig synthesis. The neoplastic cells of three patients had suppressor activity on PWM-induced Ig synthesis. All patients were positive for human T cell leukemia/lymphoma virus (HTLV) or had antibodies against HTLV antigens. It has previously been shown that the neoplastic cells in Japanese ATLL patients and in patients from the Caribbean are indistinguishable by morphology and marker phenotype. We now show them to be also similar with respect to their functional properties.

Adult↗
PubMed1983

Ultrastructural cytochemistry of chronic T-cell leukaemias. A study with four acid hydrolases.

The ultrastructural localization of four acid hydrolases (acid phosphatase, beta-glucuronidase, beta-glucosaminidase and alpha-naphthylacetate esterase) has been studied in lymphocytes from 16 patients with three types of chronic T-cell leukaemia, namely, T-prolymphocytic leukaemia (T-PLL), T-chronic lymphocytic leukaemia (T-CLL) and adult T-cell lymphoma leukaemia (ATLL). Different patterns of enzyme distribution were observed in the leukaemic T-cells from these disorders. In T-PLL, reactivity for the four acid hydrolases was confined to single or a few large granules. Gall bodies were reactive for beta-glucuronidase, b-glucosaminidase and alpha-naphthylacetate esterase but apparently unreactive for acid phosphatase. In T-CLL, scattered small- to medium-size cytoplasmic granules and many parallel tubular arrays were strongly reactive for acid phosphatase, beta-glucuronidase and beta-glucosidase but showed no reactivity for alpha-naphthylacetate esterase. Intermediate features were observed in ATLL. The observed differences in enzyme reactivity reflect a different content of lysosomal granules in the various types of leukaemic T-cells. They also suggest that similar differences may be found in normal T-lymphocyte subsets.

Acid Phosphatase↗
PubMed1983

Candidate counterparts of Sézary cells and adult T-cell lymphoma-leukaemia cells in normal peripheral blood: an ultrastructural study with the immunogold method and monoclonal antibodies.

The ultrastructural and immunologic features of normal convoluted T-lymphocytes were studied with a panel of monoclonal antibodies and the immunogold technique and these were compared with cells from patients with Sézary syndrome (SS) and adult T-cell lymphoma-leukaemia (ATLL). According to the characteristics of the nucleus, two distinct T-cell subtypes, representing 2-4% of normal peripheral blood lymphocytes were recognized: (i) a cerebriform lymphocyte ('Sézary-like') characterized by narrow and deep nuclear indentations, closely resembling the cells of SS, and (ii) a convoluted or polylobated lymphocyte ('ATLL-like'), with shorter and broader nuclear indentations than those seen in SS, that resemble the cells of ATLL. Both types of lymphocytes were positive with the monoclonal antibodies OKT3, OKT4, OKT17 and FMC3 and were negative with OKT8, OKM1 and FMC4 (anti-HLA-Dr) as SS and ATLL cells. A difference was observed with the expression of the anti-T monoclonal antibody 3Al: Sézary-like lymphocytes, like SS and ATLL cells, were 3Al negative whilst ATLL-like lymphocytes were 3Al positive. The close morphological and membrane phenotype similarities observed between these two types of lymphocytes and the cells from SS and ATLL suggest that they may well represent the normal counterparts of the malignant T cells in both conditions.

Antibodies, Monoclonal↗
PubMed1983

The ultrastructural morphology of T lymphocytes in B-chronic lymphocytic leukaemia: a study with monoclonal antibodies and the immunogold technique.

T-lymphocytes from five patients with B-cell chronic lymphocytic leukaemia (B-CLL) were analysed by light (LM) and electron microscopy (EM) by means of the immunogold technique with monoclonal antibodies combined with E rosettes. LM analysis confirmed the existence of a population of E+ lymphocytes unreactive with the OKT3 monoclonal antibody. The EM study showed that E+ lymphocytes from B-CLL can be distinguished morphologically from the leukaemic B-cells which were identified by their labelling with FMC4 (anti HLA-Dr). Within the E+ fraction two cell types were seen which differed both in reactivity with OKT3 and ultrastructural morphology. T3+ lymphocytes are similar to normal T3+, T4+ cells: they have high nucleocytoplasmic (N/C) ratio and few cytoplasmic organelles. Their reactivity with OKT3 is, however, considerably weaker than that of normal T3+ lymphocytes. T3- (E+) lymphocytes, on the other hand, are characterized by low N/C ratio, active Golgi, lysosomal granules and parallel tubular arrays. These cells resemble normal T gamma lymphocytes which comprise cells with the membrane phenotypes: T3+, T8+, M1- and T3-, T8-, M1+. These results provide further evidence for a T-cell imbalance in B-CLL and help define better the cellular basis for this abnormality.

Antibodies, Monoclonal↗
PubMed1982

Cytochemistry of acid hydrolases in chronic B- and T-cell leukemias.

Four acid hydrolases, acid phosphatase (AP), alpha-naphthyl acetate esterase (ANAE), beta-glucuronidase, and N-acetyl-beta-glucosaminidase, were determined cytochemically in peripheral blood lymphocytes from 50 patients with B and T chronic lymphocytic and prolymphocytic leukemias (CLL, PLL) and related disorders. Strong positive reactions were characteristic of the T-cell leukemias while the reactions were weak or negative in B-CLL and B-PLL. Differences in the cytochemical profile of T-CLL and T-PLL were noted. In both, beta-glucuronidase and N-acetyl-beta-glucosaminidase were positive; these enzymes are therefore good cytochemical markers of the chronic T-cell leukemias. AP and ANAE gave different results according to the disease process; AP was strong in T-CLL and variable in T-PLL, while ANAE was strongly positive in T-PLL, but weak or negative in T-CLL. The findings in T-CLL, a proliferation of T gamma lymphocytes, were similar to those of normal T gamma cells. In T-PLL, the findings did not relate to the membrane phenotype as defined by monoclonal antibodies.

Acetylglucosaminidase↗
PubMed1982

The membrane phenotype of T-prolymphocytic leukaemia.

Cells from 13 cases of T-prolymphocytic leukaemia (T-PLL) were studied with a battery of immunological techniques in order to define their membrane phenotype. All cases were E-rosette positive and were negative with OKT6, anti-HLA-DR, anti-Ig and M-rosettes; in 3, 20-30% of the cells had receptors for C3b. 7 cases had predominantly a 'helper/inducer' T-subset phenotype, (OKT4+, OKT8-) and 4 had a 'suppressor/cytotoxic' phenotype (OKT8+, OKT4-). Cells in 2 cases coexpressed OKT4 and OKT8 in 48% and 95% of prolymphocytes and in another, both OKT4 and OKT8 were negative. Terminal transferase (TdT) was negative by IF in all the cases, but a low positive level was detected biochemically in one. Although T-PLL appears to be heterogenous in respect of membrane phenotype, the observation of unexpected features in 8 of the cases raises the possibility that it may originate in a cell of intermediate maturation between late thymocytes and mature T-lymphocytes. These features plus the clinical manifestation of the disease - typical morphology, splenomegaly, lymphadenopathy, skin lesions, high WBC and aggressive clinical course - help define T-PLL as a distinct clinicopathological entity.

Aged↗
PubMed1982

The fine structure of normal lymphocyte subpopulations--a study with monoclonal antibodies and the immunogold technique.

The ultrastructural characteristics of normal lymphocyte subpopulations, identified by monoclonal antibodies and visualized by a colloidal gold labelled anti-mouse IgG were analysed. Our study demonstrates: (1) the major T lymphocyte subsets (OKT4+ and OKT8+) have distinct ultrastructural morphology. The majority of OKT4+ cells have a high nuclear/cytoplasmic ratio (N/C) and few cytoplasmic organelles whilst most OKT8+ cells have a low N/C ratio and numerous organelles, namely a well developed Golgi apparatus, lysosomal granules and parallel tubular arrays (PTA); (2) a unique subtype with irregular nuclear outline that resembles Sézary cells was seen in 5-10% of OKT4+ lymphocytes; (3) OKM1, a reagent that reacts with monocytes and granulocytes, is positive in a small lymphocyte subset which appears to be negative with the OKT reagents and is morphologically identical to OKT8+ cells; (4) 'hand-mirror' cells were only seen labelled with OKT8 and OKM1; (5) B lymphocytes labelled with FMC4 (anti-IA) could be distinguished from OKT3+ lymphocytes by having numerous profiles of endoplasmic reticulum (ER) and ribosomes; these were particularly prominent in lymphoplasmacytoid cells. Morphological similarities between normal T lymphocyte subsets and T neoplasias of the same membrane phenotype suggest that these disorders arise from specific T cell types present in normal peripheral blood or from common precursors.

Antibodies, Anti-Idiotypic↗
PubMed1981

Increase in T gamma lymphocytes in B-cell chronic lymphocytic leukaemia. II. Correlation with clinical stage and findings in B-prolymphocytic leukaemia.

The proportion of T gamma and T mu lymphocytes was studied in 40 cases of B-chronic lymphocytic leukaemia (B-CLL) and six of B-prolymphocytic leukaemia (B-PLL). The significant increase in T gamma cells, previously reported in two small B-CLL series, was confirmed and shown to be directly correlated with the clinical stages of the disease (P less than 0.01 to less than 0.001). The normal T mu:T gamma ratio (2.3:1) was reversed in B-CLL (1:1.4) and B-PLL (1:1.9). The proportion of T mu cells was decreased but was not related to stage. Our findings suggest that the increase in T gamma cells may be responsible for the hypogammaglobulinaemia of B-CLL. This is supported by two sets of observations. First, serum Ig levels were more often normal in cases in Stages 0 and I than in Stages II-IV (P less than 0.05), while the levels of two or three Ig classes were below normal in Stages II-IV twice as frequently. Secondly, splenic irradiation in one case was followed by a fall in the absolute number of T gamma lymphocytes, a reversion to normal of the T mu: T gamma ratio and an improvement in serum Ig levels. Thus, the imbalance in ;the regulatory T-cell subsets may provide an important clue to understand the pathogenic mechanism of the immunodeficiency in the chronic B-cell leukaemias.

B-Lymphocytes↗