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Biomedical subjects

D Catovsky

Publications and source records attributed to D Catovsky.

At least 487 records · Page 27Linked to original sources

Heterogeneity of B-cell leukemias demonstrated by the monoclonal antibody FMC7.

A new monoclonal antibody, FMC7, was studied in 68 patients with chronic B-cell leukemia. All 17 cases of prolymphocytic leukemia (B-PLL) and 8 of 9 of hairy-cell leukemia were positive. In contrast, FMC7 was negative in 32 of 38 chronic lymphocytic leukemias (B-CLL; p less than 0.001) and 4 cases of B-cell lymphoma. Four of the 6 positive B-CLL cases were in "prolymphocytoid" transformation; two of them had bright membrane Ig (SmIg) staining and may represent an intermediate form between B-CLL and B-PLL. Although there was a tendency for the intensity of the immunofluorescence reaction with FMC7 and SmIg to change in parallel, FMC7 did not correlate with any Ig class. In addition, almost all FMC7-negative B-CLL had weak expression of SmIg. FMC7 is different from other monoclonal antibodies raised against B-lineage cells in that it recognizes only some subsets, presumably those at a late stage of maturation. This property confers diagnostic potential to this reagent and may contribute to the better characterization of the B-cell neoplasias.

Animals↗

Stimulation of chronic lymphatic leukaemia cells by pokeweed mitogen after treatment with neuraminidase-galactose oxidase.

CLL lymphocytes gave a low response upon stimulation with PHA or PWM in 3-day cultures. However, after treatment with neuraminidase-galactose oxidase (NGO), in the presence of PWM, CLL lymphocytes transformed into blasts and incorporated 3H-thymidine in 3-day cultures. This response of CLL lymphocytes was similar to that given by normal lymphocytes to PWM in 3-day cultures. The best stimulation of CLL lymphocytes was achieved when conditioned medium (CM) from normal T lymphocytes was present in PWM cultures. Purified B lymphocytes from CLL (T lymphocytes and monocytes removed) did not respond to PHA or PWM. However, after NGO treatment these cells were stimulated by PWM, but only in the presence of CM. PHA failed to stimulate NGO-treated CLL lymphocytes or purified B lymphocytes. This study shows that CLL lymphocytes, which usually fail to respond to mitogens, can be stimulated by PWM to proliferate after treatment with neuraminidase-galactose oxidase (NGO). This technique of B cell stimulation has been found useful in cytogenetic studies of B cell proliferative disorders.

B-Lymphocytes↗

Inhibitory effect of cyclosporin A on peripheral blood and bone marrow T lymphocyte colony formation.

The effect of cyclosporin A on the formation of T lymphocyte colonies from human peripheral blood and bone marrow was tested using a double-layer technique. A moderate inhibition (27%) was observed on peripheral blood lymphocytes with concentrations of 0.1 microgram/ml of the drug; this increased to 57% with 1 microgram/ml and to almost 70% with 10 microgram/ml. Bone marrow cells were less sensitive to cyclosporin A. This was more evident at the lowest concentration of the drug (0.1 microgram/ml), with which a 14% inhibition was found. Higher concentrations (1--10 microgram/ml) produced 37 and 56% inhibition respectively. Overnight incubation with the drug followed by repeated washing of the cells did not influence colony growth. E-rosette formation was also not affected by cyclosporin A. The apparent greater sensitivity to the drug of peripheral blood than bone marrow T lymphocytes, possibly related to a different distribution of T colony-forming cells or of T lymphocyte subsets, may have some bearing on the clinical application of cyclosporin A in the prevention and treatment of graft-versus-host disease in man.

Bone Marrow↗

Increased proportion of Fc gamma and Fc mu positive T-lymphocytes following treatment with neuraminidase.

Membrane receptors for IgG (Fc gamma) and IgM (Fc mu) were assessed on isolated peripheral blood T-lymphocytes by rosette formation with ox-RBC coated with rabbit IgG or IgM antibodies. The mean percentage of Fc gamma and Fc mu rosettes on freshly separated T-cells was 19% (+/- 6% SD) and 4% (+/- 1% SD), respectively. These values increased significantly to 40% (+/- 9%) for Fc gamma and 34% (+/- 8%) for Fc mu after preincubation of the lymphocytes with Neuraminidase. The proportion of Fc mu, but not of Fc gamma, rosettes increased to 44% (+/- 8 SD) after overnight incubation at 37 degrees C, and less markedly after incubation for 45m at 37 degrees C (29% +/- 7). Fc gamma and Fc mu rosette formation, with or without neuraminidase, was specifically inhibited by human IgG or IgM. These findings suggest (1) that hidden receptors can be demonstrated on T-lymphocytes after Neuraminidase treatment which, in the case of Fc gamma, cannot be revealed by other means, and (2) that the proportion of T gamma lymphocytes in the peripheral blood is higher than generally believed.

Animals↗

Significance of splenomegaly in childhood acute lymphoblastic leukaemia in remission.

In 5 children with acute lymphoblastic leukaemia (ALL) splenomegaly occurred or persisted after induction of haematological remission. 3 patients underwent splenectomy but the spleen was free of leukaemia in each case; these patients relapsed and died 10 to 28 months after surgery. 2 patients who were not splenectomised are alive and free of leukaemia 2 and 6 years after splenomegaly was first noted; in 1 splenomegaly regressed after cessation of antileukaemic therapy. The isolated finding of splenomegaly in children with ALL in haematological remission does not necessarily indicate a relapse; instead, it is suggested that splenic enlargement may reflect an immunological process contributing to control the leukaemia and that removal of the spleen may be harmful.

Child↗

Priapism complicating chronic granulocytic leukemia.

Since 1952 we have seen nine patients with priapism leading to a diagnosis of chronic granulocytic leukemia (CGL) and a tenth patient who gave a history of priapism when CGL was diagnosed as a result of other symptoms. Seven patients had had one or more transient episodes of prolonged erection before the diagnosis of CGL was established. All ten had high blood leukocyte counts (mean 380 X 10(9)/liter, range 186-782) in comparison with other newly diagnosed patients. We estimate the incidence of this complication at 1%-2% of all male patients presenting with CGL. Treatment of patients in this series varied greatly. Five patients were treated mainly by local measures with r without cytotoxic drugs at conventional dosage, three were treated by sapheno-cavernous bypass operations and leukapheresis followed by cytotoxic drugs at high dosage, and two were treated initially by leukapheresis alone. In general, the prompt initiation of measures designed to reduce the leukocyte count seemed more valuable than the surgical procedures employed in these patients.

Adolescent↗

Prolymphocytic leukaemia: an ultrastructural study of 22 cases.

Twenty-two cases of prolymphocytic leukaemia (PLL) have been studied by transmission electron microscopy (TEM); 17 had B-cell surface markers (B-PLL) and five had T-cell characteristics (T-PLL). The predominant cell, the prolymphocyte, has distinct features which were common to all cases: it is a relatively large lymphoid cell with a prominent nucleolus, well condensed peripheral nuclear chromatin and a variable amount of heterochromatin in intranuclear clumps. Eight cases of PLL (seven B-PLL, one T-PLL) showed minor morphological deviations from typical PLL which may present diagnostic difficulties when studied only at light microscopy: the cells in four of these had some features in common with those of chronic lymphocytic leukaemia (CLL), namely round regular nuclei and heavy chromatin condensation, but the nucleoli were larger in the PLL cases. In four other cases nuclear clefting was a prominent feature at TEM. B-PLL can be distinguished by ultrastructural features from other B-cell malignancies, e.g. follicular lymphoma, B-CLL and B-acute lymphoblastic leukaemia.

B-Lymphocytes↗

Ultrastructural cytochemistry of leukaemic cells: characterization of the early small granules of monoblasts.

An ultrastructural study of blast cells showing either monocytic or granulocytic differentiation was carried out with the acid phosphatase (AP) and myeloperoxidase (MPO) reactions. Eight cases of acute myeloid leukaemia (AML) and three of chronic granulocytic leukaemia in blast crisis were studied. A hitherto unrecognized small lysosomal granule characterized by AP activity and lack of MPO was present in the majority of cells of all six monoblastic leukaemias. These granules ranged from 0.05 to 0.2 micron in size and were distributed throughout the cytoplasm, frequently at the periphery of the cells. A small proportion of monoblasts showed AP reactivity in the Golgi cisternae. Both AP and MPO were positive in the granules of promonocytes; however, MPO positive granules were predominant in late promonocytes. Larger granules (0.2--0.6 micron) with MPO reactivity were characteristic of myeloblasts. In only two out of four cases did these granules show AP positivity, suggesting that, in contrast to monoblasts, AP activity is a late feature of myeloblastic differentiation. This study shows that ultrastructural cytochemistry may be helpful in the recognition and classification of acute leukaemias by demonstrating the early differentiation features of monocytic and granulocytic precursors.

Acid Phosphatase↗

Cell volume studies in B-cell leukaemia.

Leucocyte volume histograms were obtained in 12 cases of B-chronic lymphocytic leukaemia (B-CLL), two cases of B-prolymphocytic leukaemia (B-PLL) and two cases of hairy-cell leukaemia (HCL) by means of a Coulter model ZBl linked to a channelyser. Visual examination of the histograms showed differences between the cases which were confirmed by measurement of the modal volume (MV) and the sigma value (SD of log-volume). The MV of the cells in B-CLL ranged from 153.8 to 244.2 fl (mean 198.24 fl) and was lower than the MV in the cases of HCL (427.5 and 465.6 fl). One case of B-PLL had cells with an MV within the B-CLL range while in the other the MV was greater (317.9 fl). The histogram in one of two cases of B-CLL in 'prolymphocytoid' transformation showed a relatively high sigma value, thus suggesting heterogeneity in cell size. The volume histogram is a simple method of sizing the predominant cell in the peripheral blood in lympho-proliferative disorders and permits an objective comparison between cell sizes in different diseases.

B-Lymphocytes↗

Haematological reconstitution after autografting for chronic granulocytic leukaemia in transformation: the influence of previous splenectomy.

Peripheral blood values and bone marrow appearances were monitored in eight patients treated for chronic granulocytic leukaemia in transformation by cytotoxic drugs with or without total body irradiation followed by autografting with cryopreserved-thawed peripheral blood nucleated cells. One of the patients was 'autografted' on two occasions. Five patients had been splenectomized early in the first chronic phase and the other three patients had their spleens intact. Recovery of peripheral blood values was more rapid in the splenectomized than in the non-splenectomized patients. CFUc were present in the circulation immediately after autografting in each case but subsequently the pattern of CFUc changes differed between patients. The bone marrow was hypocellular at the time of autografting but the rate at which it returned to a typical chronic phase picture varied. Peripheral blood nucleated cells collected at the time of diagnosis include stem cells with the capacity to repopulate the marrow after 'ablative' therapy for transformation. Elective splenectomy in the chronic phase may promote more rapid recovery of peripheral blood values but its long-term importance is unknown.

Blood Transfusion, Autologous↗

The association of eosinophilia with lymphoblastic leukaemia or lymphoma: a study of seven patients.

Seven patients with hypereosinophilia in association with a lymphoblastic malignancy are described. The eosinophilia preceded or was present at diagnosis in all patients. Eosinophil counts fell during complete remission but rose significantly before or during relapses in five patients. Hypogranular and sometimes Pelger-eosinophils were seen in five cases. Surface and enzyme markers defined the malignancy in six cases as common-ALL (three), T-ALL (two) and T-lymphoblastic lymphoma (one). Although a diagnosis of eosinophilic leukaemia or acute myeloid leukaemia with eosinophil differentiation was considered in three patients, cytochemical and ultrastructural studies failed to show any evidence of myeloid differentiation in the blast cells. The bone marrow karyotype was normal in the four patients studied. All seven patients had one or more relapses and six died 6-62 months from diagnosis. Severe complications of the hypereosinophilic syndrome developed in one patient. As T-lymphocytes have been shown to be involved in the induction of eosinophilia in rodents, it is suggested that the hypereosinophilia in these patients was induced by eosinopoietic stimuli produced by lymphoblasts.

Adolescent↗

Cell surface and enzyme markers of cord blood lymphocytes.

Human cord blood (CB) lymphocytes were studied with several markers for T- and B-cells and the results compared with those of adult peripheral blood (PB) samples. The proportion of E-rosettes was significantly lower in CB (mean 24.7+/-13.5 SD) than in PB (67.5+/-7.3 SD). Treatment with neuramidase produced a marked increase in the proportion of E-rosettes in CB (mean 47 +/-13.9 SD), still below the PB values. The proportion of CB lymphocytes showing block positivity with alpha-naphthyl-acetate-esterase correlated closely with the percentage of E-rosettes in neuraminidase treated cells. The percentage of H-rosettes (human RBC) was significantly higher in CB (7.2+/-6.0) than in PB (3.2+/-1.6 SD). Re-rosetting experiments showed that in CB about 30% of the E-positive cells formed H-rosettes, in contrast to 5% in PB. These findings indicate that in CB the real number of T-lymphocytes is higher than shown by conventional E-rosette formation. The proportion of B-lymphocytes, tested by surface immunoglobulins and by rosette formation with mouse RBC (M-rosettes), was similar in CB and in adult PB. A slight increase in cells with IgM on the surface was found in CB. The overall proportion of lymphocytes with negative B and T markers in CB is three times greater than in adult PB. Levels of the enzyme terminal deoxynucleotidyl transferase were marginally increased in CG; in two out of 41 samples the levels were above those found in normal bone marrow. CB may be a suitable model for the study of lymphocyte subsets with negative B and T markers in man.

Adult↗