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Biomedical subjects

V Malkovska

Publications and source records attributed to V Malkovska.

27 records · Page 2Linked to original sources
PubMed1989

Tumour immunotherapy.

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Bone Marrow Transplantation↗
PubMed1989

Impaired mitogen responses of the non-leukaemic B cells from patients with chronic lymphocytic leukaemia.

We investigated the immunological mechanism of the low level of circulating immunoglobulin and depressed primary and secondary responses of patients with chronic lymphocytic leukaemia (B-CLL) using purified non-leukaemic B cells in vitro. To assess the function of the non-leukaemic B cells we separated them from the much larger leukaemic population, which expresses the pan-T cell marker CD5, by immunoabsorption using anti-CD5 antibodies and Dynabeads. Immunoglobulin production was measured after the cells had been cultured with the B cell mitogens, pokeweed mitogen (PWM) and Staphylococcus aureus Cowan strain 1 (SAC). Autologous T cells that were found to function normally in our systems were added to cultures containing PWM. Non-leukaemic B cells from 15 B-CLL patients produced 539 ng/ml, immunoglobulin (mean value) with SAC and 162 ng/ml with PWM compared with 14,182 and 5513 ng/ml, respectively, from B cells from normal, age-matched control patients. Most of the immunoglobulin produced in the non-leukaemic B cell cultures carried the light chain associated with the leukaemic clone. We conclude that even at early stages in the disease (12 patients were Rai stage 0 patients) when the total serum immunoglobulin levels are still near normal, the B cells respond poorly to B cell mitogens.

B-Lymphocytes↗
PubMed1987

Direct effect of interleukin 2 on chronic lymphocytic leukaemia B cell functions and morphology.

The functional and morphological changes induced by recombinant interleukin 2 (IL-2) were studied in purified B cells from patients with untreated B chronic lymphocytic leukaemia (B-CLL). In eight of nine patients, purified B-CLL cells increased their DNA synthesis in response to IL-2 without preactivation in vitro. This response, studied in detail in three patients, was dose dependent and reached a maximum on day 5 or 6. IL-2 induced or increased IgM secretion in cultures from five of the nine patients studied. Two of this responsive group were particularly interesting as IL-2 not only stimulated IgM secretion but also induced the secretion of IgG. Immunoglobulin production was invariably monoclonal. B CLL cells incubated with IL-2 showed distinct morphological changes including an increase in the size of cytoplasm and enlargement of nuclei together with the appearance of nucleoli. These changes were present in all IL-2 treated cultures but were more pronounced in those containing immunoglobulin secreting cells. None of the IL-2 induced changes appeared to correlate with the clinical stage of the disease or the level of Tac antigen expression on the freshly isolated CLL B cells.

Aged↗
PubMed1987

Expression of functional interleukin 2 receptors on chronic lymphocytic leukaemia B lymphocytes is modulated by recombinant interleukin 2.

In 16 of 18 chronic lymphocytic leukaemia (CLL) patients examined, a significant proportion of B cells in the leukaemic clone bound monoclonal antibodies specific for the interleukin 2 (IL-2) receptor site (CD25). B lymphocytes from patients tested showed a direct response to recombinant interleukin (rIL-2) during culture in vitro as shown by: (a) a ligand-mediated upregulation in the level of IL-2 receptor (IL-2R) expression (12 of 12 patients), (b) an increase in cell size (eight of nine patients), (c) an increase in 3H-thymidine uptake (four of six patients). Taken together, this evidence suggests that the majority of leukaemic B cells from all the CLL patients examined expressed functional IL-2 receptors in vitro. Intriguingly, maximal receptor upregulation or increase in cell size was achieved at a lower concentration (50 u/ml) of rIL-2 than was required to achieve maximal 3H-thymidine incorporation.

B-Lymphocytes↗
PubMed1987

Generation of lymphokine-activated killer cells does not require DNA synthesis.

We studied the role of DNA synthesis in the induction of lymphokine-activated killer (LAK) cells by recombinant interleukin-2 (IL-2) and the dependence of this phenomenon on DNA synthesis. Doses of gamma-irradiation (1000-5000 rads) that profoundly reduced DNA synthesis in human peripheral blood mononuclear leucocytes (PBL) also effectively suppressed the development of cytotoxic activity in the absence of IL-2. However, the same doses of irradiation affected the induction of LAK activity by IL-2 to a much lesser extent. Blocking the formation of deoxyribonucleotides by hydroxyurea, which resulted in a complete inhibition of DNA synthesis in PBL or purified T lymphocytes, had virtually no effect on the generation of LAK cells. These results indicate that the expression of LAK activity is not dependent on DNA synthesis.

Cytotoxicity, Immunologic↗
PubMed1983

Acquired basophil and eosinophil deficiency in a patient with hypogammaglobulinaemia associated with thymoma.

A 55-year-old male with a history of recurrent bacterial and viral infection was found to have hypogammaglobulinaemia in association with a benign thymoma. The patient lacked eosinophils and was deficient in basophils in both the peripheral blood and bone marrow. The absence of eosinophils in a skin challenge known to recruit these cells, and below normal total peripheral blood leucocyte histamine content further suggests a deficiency of eosinophils and basophils respectively. Abnormal suppressor T cell function was documented both phenotypically, using OKT monoclonal antisera, and functionally in pokeweed mitogen stimulated cultures. This patient is the first reported with a deficiency of both eosinophils and basophils occurring in the presence of hypogammaglobulinaemia and thymoma; these abnormalities may be related to the abnormal suppressor T cell function that is present.

Agammaglobulinemia↗