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Biomedical subjects

D Catovsky

Publications and source records attributed to D Catovsky.

At least 451 records · Page 25Linked to original sources
PubMed1982

Chronic T-cell leukaemias. III. T-colonies, PHA response and correlation with membrane phenotype.

The functional capacity of T lymphocytes from 28 cases of chronic T-cell leukaemia--T-CLL, T-PLL, T-LCL and Sézary syndrome--was evaluated in a T-colony forming system and in a PHA response assay. Reduced or absent T-colony growth was observed in 23 cases (82%) while in five the growth was normal. Although a good correlation was generally observed between colony formation and PHA transformation, in a few cases a low PHA response was accompanied by moderate colony growth and vice versa. Characterization of the leukaemic T lymphocytes using monoclonal antibodies (OKT series) indicates that cases with a helper/inducer phenotype (OKT4+) showed moderately reduced or near-normal T-colony numbers, whilst cases with a suppressor/cytotoxic phenotype (OKT8+)--confined to T-CLL in this study--had a very low or absent colony growth. The functional abnormalities reported here suggest that neoplastic T-cells with a helper/inducer phenotype show a low proliferative response in the assay systems used, although expressing mature T-cell characteristics. The low growth observed in T-CLL confirms that cells with a suppressor/cytotoxic phenotype form few T-cell colonies.

Cell Division↗
PubMed1982

Reduced T-colony forming capacity in B-chronic lymphocytic leukaemia.--II. Correlation with clinical stage and findings in B-prolymphocytic leukaemia.

The T-colony forming capacity of T-lymphocytes from 33 cases of B-chronic lymphocytic leukaemia (B-CLL) and five of B-prolymphocytic leukaemia (B-PLL) was studied. An absent or reduced (less than 50) colony growth was observed in 21 of the 33 B-CLL and in four of the five B-PLL studied. Seven of the nine stage 0 patients (77.7%) according to Rai's clinical staging) gave rise to more than 50 colonies, compared with five out of 24 (20.9%) in stages I-IV patients. Furthermore, the mean number of colonies was significantly (p less than 0.01) higher in stage 0 patients (57 +/- 33.6), compared with more advanced stages (22 +/- 29.9). Since in normal peripheral blood, T-colony formation appears to be a property of T mu lymphocytes, and T gamma cells are significantly increased in B-PLL and B-CLL, mainly in advanced disease, the T-colony growth was correlated with the percentage of T gamma cells. Despite a negative trend, a statistical correlation was not observed. Our findings are suggestive of a functional defect of the T-cell population in the majority of cases of B-CLL, with a partial sparing in stage 0 patients. This abnormality, apparently unrelated to the T mu: T gamma ratio, is probably due to an intrinsic defect of the T mu cell population.

B-Lymphocytes↗
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

Symposium: classification of leukemia. 1. The classification of acute leukemia.

Two main forms of acute leukemia have been recognized by the French-American-British (FAB) group: myeloid (AML) and lymphoblastic (ALL). Some types of AML can be diagnosed on well prepared bone marrow films stained with May-Grünwald-Giemsa. Poorly differentiated types, myeloblastic (M1) and monoblastic (M5PD), need confirmation by positive cytochemical reactions (Sudan Black B, myeloperoxidase and non-specific esterase). There are 2 sub-types of promyelocytic leukemia: M3 typical, hypergranular and M3 variant, microgranular. The M3 variant has a more acute course, higher WBC and may require cytochemistry to demonstrate promyelocytic differentiation. Electron microscopic cytochemistry can also help in the classification of difficult AML cases; the 'platelet-peroxidase' reaction, for example, is essential for the diagnosis of megakaryoblastic leukemia, a disorder often presenting as 'acute' myelosclerosis. Three morphological types are seen in ALL: L1, predominantly in children, L2, more frequently in adults, and the relatively rare L3 or Burkitt type. Immunological and enzyme markers (ALL and la antigens, terminal transferase, etc.) help define the cell phenotype: (1) non-B, non-T ALL with 3 forms (common, null and pre-B), (2) T-ALL, related to but distinct from T-lymphoblastic lymphoma, and (3) B-ALL, usually with L3 morphology, There is growing evidence that the FAB morphological types correlate with prognosis in ALL independently of other factors. The immunologically defined types also correlate with prognosis but not as an independent variable.

Acute Disease↗
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↗
PubMed1982

T-chronic lymphocytic leukaemia presenting as primary hypogammaglobulinaemia--evidence of a proliferation of T-suppressor cells.

A 63 year old man with late onset hypogammaglobulinaemia is described. Splenectomy, carried out because of marked splenomegaly and pancytopenia, demonstrated marked T lymphocytic infiltration in the splenic red pulp with prominent germinal centres. A persistent peripheral blood and bone marrow lymphocytosis ensued (10 X 10(9)/l and 40% respectively) and this was consistent with T-chronic lymphocytic leukaemia (T-CLL). Over 88% of his blood lymphocytes were E+, OKT3+, OKT8+ and OKT11+; 54% of the T lymphocytes had receptors for IgG (T gamma cells). Functional studies showed that the T lymphocytes of this patient lacked killer and natural killer cell function but they effectively suppressed the differentiation of normal B cells in a PWM stimulated system. It is suggested that the T-CLL in this patient resulted from the proliferation of the T suppressor subset which was responsible for his hypogammaglobulinaemia.

Agammaglobulinemia↗
PubMed1982

Prolymphocytic leukaemia.

A review of the main features of prolymphocytic leukaemia, based on 80 cases studied by the author since 1974, is presented. Prolymphocytes have a B-cell membrane phenotype with strong expression of surface Ig in 81% of cases (B-PLL) whilst the rest have T-cell markers (T-PLL). Both forms of the disease have distinct laboratory and clinical findings. T-PLL has a more aggressive course with a median survival of 7 months (24 months in B-PLL). Ultrastructural analysis demonstrates larger lysosomal granules in T-PLL cells which results in a higher content of acid hydrolases. The intriguing relationship of B-PLL with B-CLL is discussed in the light of new data with immunological markers.

Aged↗
PubMed1982

Proposals for the classification of the myelodysplastic syndromes.

New diagnostic criteria for the diagnosis of the various myelodysplastic syndromes (MDS) are proposed, and a detailed description is given of the features that may help define MDS. Five MDS are described: (1) refractory anaemia (RA), (2) RA with ring sideroblasts, (3) RA with excess of blasts (RAEB), (4) chronic myelomonocytic leukaemia (CMML), and (5) RAEB 'in transformation'. One of the main distinguishing features of these conditions is the proportion of blast cells in the peripheral blood (PB) and/or bone marrow (BM). The morphological features of the blast cells that are of diagnostic importance have been redefined. In RA, with or without ringed sideroblasts, there are fewer than 1% of blasts in the PB and fewer than 5% in the BM; RAEB is defined as having between 5% and 20% of blasts in the BM and fewer than 5% in the PB; RAEB in transformation (a newly defined category) will be considered when any of the following features is present: (i) more than 5% of blasts in the PB, (ii) 20-30% in the BM, and (iii) the presence of Auer rods in granulocyte precursors in BM or PB. In accordance with these newly defined criteria, it is now proposed that over 30% of bone marrow blasts will suffice for the diagnosis of acute myeloid leukaemia (AML) in any of its forms (M1-M6). The proposed descriptions of the MDS should facilitate the interpretation of data emerging from cytogenetic and bone marrow culture studies and the search for features of possible prognostic significance. Recognition of the new category, RAEB in transformation, may throw light on the pathogenesis of AML.

Anemia, Aplastic↗
PubMed1981

Buffy coat autografts for patients with chronic granulocytic leukaemia in transformation.

We have treated 20 patients with chronic granulocytic leukaemia (CGL) in transformation with cytotoxic drugs or with cytotoxic drugs and whole-body irradiation followed by transfusion of autologous blood cells collected at diagnosis and stored in liquid nitrogen. The mean number of nucleated cells autografted was 25.1 X 10(8)/kg (range: 12.5-40.1). Full myeloid engraftment occurred in 18 patients; it was partial in one patient and unassessable in another. The median survival for the 20 patients post-graft was 14 weeks. Two patients are alive, one now in recurrent transformation, and one in second chronic phase that has lasted 52 weeks. For the 18 patients who died the mean survival was 24 weeks (range: 2-125). Two patients with predominantly myelosclerotic transformation showed evidence of engraftment. One patient successfully autografted developed features consistent with graft-versus-host disease which proved fatal. We conclude that autografting may offer substantial palliation for some but not all patients with CGL in transformation.

Blood Cells↗