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Biomedical subjects

D Catovsky

Publications and source records attributed to D Catovsky.

At least 415 records · Page 23Linked to original sources

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↗

DNA rearrangements of immunoglobulin genes correlate with phenotypic markers in B-cell malignancies.

We have investigated the configuration of immunoglobulin (Ig) genes in leukaemic cells in 17 patients with B-cell leukaemias (11 chronic lymphocytic leukaemias (B-CLL); 4 prolymphocytic leukaemias (B-PLL), and two hairy cell leukaemias (HCL)). In addition we studied four patients with T chronic lymphocytic leukaemia (T-CLL); four patients with acute leukaemia (3 acute lymphoblastic leukaemias (ALL), and 1 mixed acute leukaemia (M.AL)); and six patients with chronic granulocytic leukaemias in blastic crisis (CGL.BC). The heavy chain genes (H) were analysed by using probes for the constant region of the mu chains (C mu) and for the joining region (JH). The light chain genes were analysed by using probes for the constant region of the kappa (C kappa) and lambda (C lambda) chains. We have found rearranged Ig genes in all cases of B-CLL, B-PLL and HCL, but in none of the patients with T-CLL. In one case of HCL, both mu genes were deleted, indicating that in this case the class switch has taken place. In four out of six cases with either ALL or lymphoid CGL.BC and in one case of M.AL, an Ig gene rearrangement was also found. No rearrangement was detected in two cases of myeloid CGL.BC. When the combination of rearrangement versus germ-line configuration was considered, a variety of patterns emerge, but in no case did we find a L chain gene rearranged without at least one H chain gene being rearranged as well. Whereas in the majority of cases of B-CLL only one H chain gene is rearranged, in nearly all cases of B-PLL both H chain genes are rearranged. By systematic analysis of restriction fragment sizes of rearranged genes, we have established that a large number of different variable regions for the H chain (VH) are involved in Ig gene rearrangement in B-cell malignancies. Our data confirm that testing for Ig gene rearrangement may be the most sensitive and specific test for identifying leukaemic cells of B lineage.

B-Lymphocytes↗

The classification of acute leukaemia (AL) and its clinical significance.

The combination of morphological, cytochemical and immunological methods has resulted in a reproducible and more objective classification of AL. Several of the AML-FAB subtypes (M2, M3 and M5) correlate with specific chromosome abnormalities and are associated with distinct clinical and laboratory features. The classification of ALL based on morphology (FAB types L1, L2 and L3) has been shown to have prognostic value. The heterogeneity of ALL is better recognised by membrane marker analysis, now improved by the use of monoclonal antibodies. The enzyme terminal transferase is the best marker for lymphoblasts and helps in the differential diagnosis between ALL and AML. Cases of undifferentiated AL and rare types of AML can be identified by ultrastructural cytochemistry. The clinical significance of the classification of AL is briefly discussed.

Acute Disease↗

Complete recovery of histiocytic medullary reticulosis-like syndrome in a child with acute lymphoblastic leukemia.

A 6-year-old boy with acute lymphoblastic leukemia (ALL) developed a haemophagocytic syndrome resembling histiocytic medullary reticulosis (HMR) but made a complete recovery on supportive treatment. This was subsequently found to have been associated with a parainfluenzal infection. It is suggested that HMR in immunocompromised hosts may represent a reactive process to an opportunistic viral infection and that the use of chemotherapy in these patients may be deleterious.

Child↗

Evidence for human T cell lymphoma-leukemia virus infection of family members of human T cell lymphoma-leukemia virus positive T cell leukemia-lymphoma patients.

Sera of family members of patients from the United States, the Caribbean, and Japan, with human T cell lymphoma-leukemia virus (HTLV) associated T cell malignancies, possess HTLV-specific antibodies directed against internal structural components of HTLV, p24 and p19. The prevalence of antibodies to HTLV is greater in family members than in random healthy donors, which supports the infectious nature of HTLV and its association with particular aggressive T cell malignancies. Expression of HTLV p24 and p19 has also been observed in cultured T cells of some healthy relatives, and intact virus particles have been released from cells of one possibly pre-leukemic family member.

Antibodies, Neoplasm↗

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↗

1,25-dihydroxyvitamin D3 inhibits proliferation of human promyelocytic leukaemia (HL60) cells and induces monocyte-macrophage differentiation in HL60 and normal human bone marrow cells.

1,25-dihydroxyvitamin D3 induces monocyte-macrophage differentiation and inhibits proliferation of cells from the human promyelocytic leukaemia cell line HL60. Similarly human bone marrow progenitor cells differentiate preferentially along the monocyte-macrophage pathway when incubated in the presence of 1,25-dihydroxyvitamin D3. We suggest that the inhibition of growth which occurs after addition of the vitamin to HL60 might be paralleled in vivo by inhibition of proliferation of leukaemic cells; also we speculate that the vitamin may be involved in the control of both monocyte-macrophage and osteoclast production in vivo.

Animals↗

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↗

Chromosome abnormalities in B-cell prolymphocytic leukemia: a study of nine cases.

Chromosome abnormalities were demonstrated in 50-100% of Giemsa-banded metaphases from nine cases of B-cell prolymphocytic leukemia (B-PLL). Mitoses were obtained with pokeweed mitogen following pretreatment of peripheral blood (PB) prolymphocytes with neuraminidase-galactose oxidase. Chromosome 14 was abnormal in eight of the nine cases: a marker 14q+, with breakpoint at band q32 in seven and trisomy 14 in one. In four cases the abnormal No. 14 was one of several primary abnormalities and in four others it was seen in secondary clones. The origin of the translocated material was unknown in three cases, in two it resulted from t(11;14), later becoming t(11;14;21) in one of them, t(1;14) in another, progressing later to t(1;14;17); in yet another patient, the 14q+ was the result of a complex rearrangement t(6;14;17). Abnormalities of chromosome 6 were seen in six cases: 6q- as the primary abnormality in three; trisomy 6 was part of secondary changes in one case. Structural abnormalities of chromosome 1 were seen in six cases: 1q- in four (in one as the only abnormality), 1q+ in one case, and 1p- in another, both in the main clone. Trisomy 12 was demonstrated in three cases but not as the primary change. Spleen cells in two patients showed a higher frequency of abnormalities than in the PB, supporting the concept of the spleen being the organ primarily involved in B-PLL. Evidence of karyotypic evolution was demonstrated in six patients, in some clearly associated with clinical progression of the disease. The type and frequency of the abnormalities observed in B-PLL resemble those seen in non-Hodgkin's lymphomas and suggest major differences from B-CLL, although a relationship with the latter can not be completely ruled out at present.

Aged↗