Search PubMed⌕ Search

Biomedical subjects

F R Balkwill

Publications and source records attributed to F R Balkwill.

97 records · Page 6Linked to original sources

Growth inhibitory effects of interferon on normal and malignant human haemopoietic cells.

A study of the effects of human leukocyte and lymphoblastoid interferon preparation on the growth of normal, immune and malignant haemopoietic cells has been carried out. At a standard dose of 10,000 U/ml, incorporation of tritiated thymidine ([3H] TdR) was reduced by 7-92% of control values, and cell survival by 35-82% in acute myelogenous leukaemia cell cultures, whereas in normal bone-marrow cultures interferon showed a 58-62% reduction in [3H] TdR uptake but only up to 13% reduction in cell survival. [3H] TdR incorporation by MLC-stimulated lymphocytes was also significantly reduced by interferon but the blastogenic response to PHA was not. These effects of interferon were shown to be dose-dependent. The problems of using interferon in the treatment of AML in the light of these findings are discussed.

Cell Count↗

Neoplastic macrophages grown from human leukaemic monocytes.

Leucocyte suspensions from some cases of acute myelogenous leukaemia produced large numbers of macrophages when cultured in vitro. The macrophages increased steadily in number during the first 1-2 wk of culture. The increase was partly derived from division of the macrophages themselves, partly from augmentation from supernatant cells not adherent to the surface of the culture flask. This augmentation occurred mostly in the first 24 hr of culture. The leukaemic macrophages had many features of normal macrophages as regards light microscopy, surface receptors, phagocytic activity and cytochemistry. Under the electron microscope, however, they had many abnormal characteristics, all of which have been recorded previously as features of malignant transformation. Cultures containing the abnormal macrophages and their precursor cells caused local solid tumours when injected into immune-deprived mice. The tumours were composed of rather uniform cells many of which resembled neoplastic reticulum cells. It is concluded that human leukaemic monocytes or promonocytes can develop into macrophages with ultrastructural features of malignancy. This appears to be the first demonstration of the development of neoplastic macrophages. It is suggested that some lymph node tumours of man may be composed of similar neoplastic macrophages and their precursor cells.

Animals↗

Morphological characterisation of adult acute leukaemia in short-term liquid culture.

Peripheral blood leukocytes from 31 out of 48 patients with acute myelogenous leukemia grew in short-term liquid culture. Two distinct types of growth occurred. The first type was dimorphic with supernatant free-floating ("non-sticker") cells and, in addition, a plastic/glass adherent, trypsin resistant, phagocytic population ("stickers"). The second type which occurred less frequently than the first consisted almost entirely of free-floating "non-sticker" cells. Although patients with this second type of growth pattern almost invariably had AML, 44% of AML's produced monocytoid "sticker" cells in culture. Cells from the majority of patients with ALL did not grow in culture.

Adolescent↗

Diagnostic and prognostic significance of peripheral blood cultural characteristics in adult acute leukaemia.

A simple liquid culture technique has been used to study peripheral blood from patients with acute myelogenous leukaemia. Evidence is presented that cells from morphologically identical types of leukaemia have differing capacity for "differentiation" from free floating blast cells into plastic-adherent phagocytic, trypsin-resistant macrophage-like cells with Fc and C3 receptors. Preliminary analysis suggests that patients whose cells have the greatest capacity for "differentiation" have a better chance of achieving complete remission.

Adult↗

Multiple myeloma: an immunoclinical study of disease and response to treatment.

Plasma cytokines and immune markers were assessed during the clinical management of 42 patients with multiple myeloma, MM. Of the patients 22/42 (all with progressive disease) were studied from the time of diagnosis, through various treatment regimes, to remission, progression or death. 5/42 patients had monoclonal gammopathy of undetermined significance (MGUS), 8/42 others had either indolent MM or stable MM, and a further 7/42 with progressive disease were also studied. IL-6, TNF-alpha, IL-1 alpha, IL-1 beta, beta 2 microglobulin (beta 2M), and neopterin were estimated in bloods taken under optimal conditions for cytokine detection. The levels were compared with a panel of samples from healthy volunteers. Both immunoreactive and biologically active plasma IL-6 levels were measured. Pretreatment IL-6 levels (both immunoreactive and biologically active) were found to correlate with severity of disease. In 13/22 patients with progressive disease who had been followed from the time of diagnosis over a 12-month period or until death, pretreatment IL-6 levels were predictive of response to therapy. Elevated plasma levels of TNF-alpha, beta 2M and neopterin were found in patients with progressive multiple myeloma, and this correlated with renal impairment. The analytes measured during the course of chemotherapy did not show correlation with disease progression or response to therapy.

Adult↗