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Biomedical subjects

D Catovsky

Publications and source records attributed to D Catovsky.

At least 433 records · Page 24Linked to original sources

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↗

Anaemia in myelofibrosis: its value in prognosis.

Forty-four patients with myelofibrosis were investigated in our hospital in the period 1971-81. Their clinical, laboratory and radioisotope parameters were analysed. The direct correlation between plasma volume and splenic red cell pool has highlighted the role of the spleen in the dilutional anaemia seen in myelofibrosis. 52Fe quantitation enabled us to show that the bone marrow contributes relatively more to effective erythropoiesis than the extramedullary sites. The prognostic value of changes in plasma volume and bone marrow 52Fe activity has been demonstrated. We have shown that the Hb: reticulocyte relationship at diagnosis can be used to recognize probable stages of the disease and provides a useful prognostic determinant.

Adult↗

T-cell functional abnormality in B-chronic lymphocytic leukaemia: evidence of a defect of the T-helper subset.

The helper and suppressor capacity of T, T mu (T non gamma) and T gamma cells was assessed in a group of patients with B-cell chronic lymphocytic leukaemia (B-CLL) in a pokeweed mitogen (PWM) stimulated system. The enriched T-cells (E-rosette positive) from all B-CLL cases showed a reduced capacity to induce the differentiation of normal B-lymphocytes compared with normal T-cells (P less than 0.005). After enrichment of the T mu cells, the helper/inducer capacity was still significantly depressed compared with the same fraction from normal controls (P less than 0.01). On the other hand, enriched T gamma cells from B-CLL were effective in suppressing the differentiation of normal B-lymphocytes to a similar degree as normal T gamma cells. These findings are indicative of a deficient T-cell helper function in B-CLL, which appears to be unrelated to the clinical stage of the disease. The fractionation experiments suggest that this functional impairment is not only due to the abnormal T-cell subset distribution seen in the majority of cases, but point to a possible intrinsic defect within the T mu cell population.

Aged↗

Massive retroperitoneal lymphadenopathy as a terminal event in hairy cell leukaemia.

A case of hairy cell leukaemia complicated as a terminal event by massive retroperitoneal lymphadenopathy is described. The patient had recently been treated with lithium carbonate and had previously been demonstrated to suffer from a systemic vasculitis, either or both of which may have contributed to the development of this rare complication.

Adult↗

The histopathology of adult T-cell lymphoma/leukaemia in blacks from the Caribbean.

The histopathological features of seven cases of adult T-cell lymphoma/leukaemia (ATLL), all occurring in black patients from the Caribbean, are described. Lymph node infiltrates are initially restricted to the paracortical zone, with preservation of the nodal shape and subcapsular sinus, and accompanied by a proliferation of post-capillary venules. Cytologically, a range of cell types is present, from smaller cells with irregularly shaped nuclei and clumped nuclear chromatin to larger cells with dispersed chromatin and more prominent nucleoli, apparently corresponding to the stages of peripheral T-lymphocyte transformation. The proportion of each cell type present varies from case to case, as do the numbers of admixed eosinophils, plasma cells and interdigitating reticulum cells. These histological appearances are very similar to those of the pleomorphic T-cell lymphoma described in Japan, which also shows many clinical similarities, including a high incidence of complicating hypercalcaemia. There is a strong association in both Japanese and Caribbean patients with a recently described human retrovirus, HTLV, which occurs endemically in those areas where the disease clusters. Morphological similarities exist between ATLL and other peripheral T-cell lymphomata and leukaemias. These are illustrated by one notable 'linking' case. However, while related to other disorders of mature T-lymphocytes, ATLL nevertheless represents an identifiably separate clinicopathological entity.

Adult↗

Normal helper T-cell function in hairy-cell leukaemia.

The function of peripheral blood T-lymphocytes was tested in a series of untreated patients with hairy-cell leukaemia (HCL). The in vitro T-colony forming capacity fell within the normal range in 20 of the 22 cases studied. No difference in colony growth was found between splenectomized and non splenectomized patients. The ability to induce differentiation of normal B-lymphocytes into antibody producing plasma cells, in a pokeweed mitogen (PWM) stimulated system, was similar to that of normal T-cells in all 6 cases studied. Both the T-colony growth and the helper capacity were unrelated to the distribution of T-lymphocyte subsets defined by monoclonal antibodies, despite an increase in OKT8+ cells (suppressor/cytotoxic phenotype) and a decrease in OKT4+ cells (helper/inducer phenotype) in 44% of the patients. The significance of these findings is discussed in relation to T-cell abnormalities previously described in other B-cell leukaemias, chiefly chronic lymphocytic leukaemia (B-CLL). The preserved T-cell function in HCL correlates well with the normal humoral immunity found in this disease.

Antibodies, Monoclonal↗

Cytochemistry of normal lymphocyte subsets defined by monoclonal antibodies and immunocolloidal gold.

The cytochemical reactivities of 3 acid hydrolases, alpha-naphthyl acetate esterase (ANAE), acid phosphatase and beta-glucuronidase were investigated in normal peripheral blood lymphocyte subsets defined by monoclonal antibodies OKT3, 4, 8 and FMC4 (anti-Ia). A combined monoclonal antibody-immunocolloidal gold/cytochemical staining procedure was used to determine enzyme activities and distributions of reaction product in each subset. Cytochemical profiles for each lymphocyte subset were defined. The majority (greater than 85%) of T cells (OKT3+) were positive for all 3 enzymes whereas a minority (less than 40%) of B cells (FMC4+) displayed reactivity. The cytochemical profiles of T helper/inducer (OKT4+) and T suppressor/cytotoxic (OKT8+) cells were not significantly different and corresponded to that observed for OKT3+ cells; thus none of these enzymes can be used to distinguish normal lymphocyte subsets cytochemically. ANAE reactions were further analysed, in the respective subsets, on the basis of dot-like or scattered/diffuse reactivity. The ratios of cells displaying dot-like: scattered/diffuse reactivity, in the respective subsets, were OKT3+, 5.4:1; OKT4+, 8.1:1; OKT8+, 2.4:1; FMC4+, 0.4:1. The cytochemical profiles and ANAE reactivities of T cell subsets identified by monoclonal antibodies differ from those displayed by T cell subsets defined by Fc receptors and confirms that there is little correlation between subsets defined by these two methods.

Acid Phosphatase↗

Lymphoma-like presentation of acute monocytic leukaemia.

Four patients in whom a diagnosis of acute monocytic leukaemia (M5) was subsequently made presented with extramedullary disease clinically resembling lymphoma. In all patients histological sections were initially misinterpreted as showing malignant lymphoma or anaplastic carcinoma. The diagnosis of M5 leukaemia was subsequently made on the basis of morphological and cytochemical studies of peripheral blood and bone marrow. The histological diagnosis of the soft tissue lesions of M5 leukaemia (monocytic sarcoma) is difficult, although features such as abundant cytoplasm and the presence of some reniform nuclei are helpful. If there is no peripheral blood or bone marrow involvement and only fixed paraffin-embedded tissues are available, demonstration of lysozyme by an immunoperoxidase technique may confirm the diagnosis but results are not invariably positive. An early diagnosis of M5 leukaemia has therapeutic implications since the disease evolves through a progressive leukaemia phase and systemic therapy is essential.

Adolescent↗

Fractionation of whole body irradiation before bone marrow transplantation for patients with leukaemia.

Thirty patients in various stages of acute leukaemia or chronic granulocytic leukaemia (CGL) were treated with cytotoxic drugs followed by whole body irradiation (TBI) administered in 200 cGy fractions twice daily to a total of 1000 or 1200 cGy. The immediate toxicity of fractionated TBI administered in this way was negligible and patients required only minor premedication and little treatment subsequently for complications attributable to TBI. Fourteen (47%) patients have died, ten of the 12 transplanted with active disease, and four of the 18 subjected to transplantation in remission of acute leukaemia or in chronic phase of CGL. Though the duration of follow-up is still short, no patient in the latter group (follow-up of survivors ranging from six to 146 weeks) has yet relapsed with any evidence of recurrent leukaemia. We conclude that this method of fractionating TBI reduced toxicity for the patient without necessarily reducing its antileukaemic effect.

Acute Disease↗

Hairy cell leukemia: a five-year update on seventy-one patients.

An updated analysis was done of 71 patients with hairy cell leukemia originally reported in 1978; 36 patients (51%) had died, 28 (39%) were still alive, and 7 (10%) were lost to follow-up. The median actuarial survival time for the entire group from the onset of symptoms was 70 months. Of the 28 known living patients, 8 had been followed for 12 years or more; the longest survivor has remained alive 289 months after the onset of symptoms. Eleven of the original 71 patients required no therapy; 5 remained alive 5 years or more. Causes of death included progressive disease in 4 patients, infections in 20, hemorrhage in 1, unknown causes in 4, and nonhematologic causes in 7.

Chlorambucil↗

Association of the human type C retrovirus with a subset of adult T-cell cancers.

To determine whether the human T-cell lymphoma-leukemia virus (HTLV) is associated with particular cancers, patient sera were surveyed for HTLV-specific antibodies. An association was seen with aggressive cancers of mature T-cells, specifically Japanese adult T-cell leukemia (ATL) and T-cell lymphosarcoma cell leukemia (TLCL), a similar cancer of Caribbean blacks. Ninety to 100% of these patients possessed HTLV-specific antibody. Forty-seven and 20% of relatives of ATL and TLCL patients, respectively, and 12 and 4% of healthy donors from ATL and TLCL endemic areas were also antibody positive. Visceral organ involvement, hypercalcemia, and skin manifestation, features of ATL and TLCL, were often seen in other antibody-positive patients. Childhood cancers, most cutaneous T-cell and all non-T-cell leukemias and lymphomas, myeloid leukemias, Hodgkin's disease, and solid tumors were not associated with HTLV. Healthy United States donors and European patients with non-malignant diseases were antibody negative. HTLV is thus associated with a subtype of adult T-cell leukemia-lymphoma, clustered in viral endemic areas, with apparent racial and geographic predilection.

Adult↗

Marrow transplantation for patients in the chronic phase of chronic granulocytic leukaemia.

In 1979 two patients with Philadelphia (Ph1)-chromosome-positive chronic granulocytic leukaemia (CGL) were treated with chemoradiotherapy and transplantation of bone marrow from their respective identical twins. Subsequently twelve patients with Ph1-positive CGL in chronic phase were treated with chemoradiotherapy followed by transplantation of bone marrow from their HLA-identical sibs. Two of the fourteen patients have died of complications of the transplant procedure; twelve patients are alive and well. All the survivors have normal or nearly normal blood counts; there is no evidence of recurrent leukaemia or Ph1-positive cells in any patient after follow-up periods ranging from 97 to 1112 days. Bone-marrow transplantation should be considered in the management of any young patient with CGL who has a suitable marrow donor.

Adolescent↗

The human type-C retrovirus, HTLV, in Blacks from the Caribbean region, and relationship to adult T-cell leukemia/lymphoma.

Type-C RNA tumor viruses have been implicated in the etiology of naturally occurring leukemias and lymphomas of animals. Human T-cell leukemia/lymphoma virus (HTLV) is the first human virus of this class consistently identified in association with a specific type of human leukemia/lymphoma. The isolation of HTLV was made possible by the ability to grow mature T-cells in tissue culture usually with T-cell growth factor (TCGF). We now report a cluster of adult T-cell leukemia/lymphoma among Blacks from the Caribbean in which all eight cases are positive for HTLV virus and/or antibody. These patients have disease that appears indistinguishable from Japanese adult T-cell leukemia/lymphoma which, as we have also reported, is associated with HTLV in over 90% of cases. The finding of HTLV antibodies in some of the normal population in the Caribbean and Japan, and the clustering of a specific form of T-cell leukemia/lymphoma in these virus-endemic areas, suggest that HTLV infection may be associated with the occurrence of a distinctive clinico-pathologic entity.

Adolescent↗

Adult T-cell lymphoma-leukaemia in Blacks from the West Indies.

Six Black patients (five born in the West Indies and one in Guyana), aged 21-55 years, had adult T-cell lymphoma-leukaemia diagnosed in the U.K. This disorder is rare in Europe and the U.S.A., but is more common in Japan. Five patients had severe hypercalcaemia which correlated with disease activity, although osteolytic lesions were found in only one. Other clinical features were lymphadenopathy and a high white blood-cell count (range 27-67 X 10(9)/l) with a predominance of pleomorphic lymphoid cells with pronounced nuclear irregularities prominent at ultrastructural level. The cells in all cases formed rosettes with sheep red blood-cells and lacked terminal transferase. Analysis with OKT monoclonal antibodies in four cases confirmed a mature T-cell phenotype defined as helper/inducer (T4+, T6-, T8-) in three. Combination chemotherapy resulted in short-lived remissions; four patients died and two have survived 3-6 months. The disease in these patients is indistinguishable on clinical and pathological grounds from adult T-cell leukaemia/lymphoma in Japan. Geographical clustering among certain racial groups suggests common aetiological factors in the pathogenesis of this disease. The finding of high titre antibody against the structural core protein (p24) of a new human C-type leukaemia virus (human T-cell leukaemia/lymphoma virus) in all tested cases from this series and data from all but one case from Japan suggest that one such factor may be viral.

Adult↗

Co-trimoxazole alone for prevention of bacterial infection in patients with acute leukaemia.

43 patients undergoing treatment for acute leukaemia were randomised to receive either co-trimoxazole alone or co-trimoxazole with framycetin and colistin as antibacterial prophylaxis during periods of neutropenia. There were no significant differences between the two treatment groups in the time before the onset of the first fever, the number of episodes of fever or of septicaemia per patient, the number of neutropenic days during which patients remained afebrile or did not require systemic antibiotics, or the number of resistant organisms acquired. Co-trimoxazole alone is cheaper and easier to take than co-trimoxazole with framycetin and colistin, and it is therefore preferable to the three-drug combination for the prophylaxis of bacterial infection.

Acute Disease↗

Chronic T-cell leukemias. II. Cytogenetic studies.

Chromosome abnormalities were documented in the PHA-stimulated lymphoid cells from 10 patients with chronic T-cell leukemias (6 T-PLL, 3 T-CLL and 1 T-LCL). One or more marker chromosomes were present in most metaphases in every case of T-PLL but they were different in each case. Structural abnormalities were also observed in T-CLL and T-LCL but less consistently. Chromosomes involved in marker formation in two or more cases were: Nos. 2, 7, 8, 9, 11 and 16. The karyotype was hypodiploid in five cases and hyperdiploid in two. Chromosomes Nos. 2 and 8 were the most frequently involved in structural and numerical abnormalities: Nos. 8 in 2 T-CLL and the 6 T-PLL and No. 2 in 1 T-CLL, 1 T-LCL and 5 T-PLL. Abnormalities of chromosome No. 2 are rare in human neoplastic disease but may be common in T-lymphoproliferative disorders. The differences between T-PLL and T-CLL reported here may have some bearing on the clinical features. T-PLL, characterised in all cases by clonal abnormalities, has an aggressive clinical course. In contrast, T-CLL with less consistent karyotypic changes has a protracted and benign clinical evolution.

Adult↗