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Biomedical subjects

G M Taylor

Publications and source records attributed to G M Taylor.

At least 127 records · Page 7Linked to original sources

In vitro stimulation of cell-mediated cytotoxicity by acute leukaemias.

Acute leukaemias stimulated proliferative and cell-mediated cytotoxic (CMC) responses in vitro in normal (unprimed) lymphocytes. Proliferation was detected by increases in viable cell counts and [3H]dT incorporation in mixed lymphocyte-leukaemia-cell cultures. CMC detected on cultured cell-line targets (CCL) including K562 was generally much stronger than on fresh leukaemia cells, and correlated with stimulation of [3H]dT uptake in the responding lymphocytes. Leukaemias which were resistant as targets to CMC were able competitively to inhibit CMC on K562, though not as efficiently as blocking by K562 itself. With one leukaemia, blocking of CMC increased as the level of CMC on K562 was amplified by greater numbers of stimulating cells in the sensitization phase. This suggests that in certain cases blocking of effector cells by acute-leukaemia cells may depend upon the state of activation of the effector cells. Lymphocytes from a leukaemia patient in remission, treated with allogeneic leukaemia-cell immunotherapy and stimulated in vitro with immunizing leukaemia cells, developed strong anti-leukaemic CMC. A non-immunized patient's lymphocytes did not respond in this way, despite comparable levels of CMC on K562 in both patients. Dual stimulation of unprimed normal lymphocytes and remission lymphocytes with allogeneic or autologous leukaemias and various cell lines, amplified anti-leukaemic CMC, but did not markedly alter CMC or CCL. These data do not formally exclude the mediation of in vitro-stimulated anti-leukaemic CMC by NK-like cells, but suggest that such effector cells differ qualitatively from NK-like cells detected in the absence of anti-leukaemic CMC.

Cell Line↗

Fc receptors on myeloid leukaemic cells: comparison between assays of rosette-forming cells.

A comparison has been made between assays of Fc receptor bearing cells among blood leucocytes from normal individuals and from patients with myeloid leukaemia, using human anti-D coated erythrocytes (HEA) and sheep erythrocytes sensitised with a rabbit anti-sheep erythrocyte antibody (SEA). Differences were found between the assays in both groups, demonstrating the heterogeneity of Fc receptors with respect to affinity for marker, and for Fc bearing leucocytes. Monocytoid cells reacted more readily with both markers than myeloid cells. The HEA rosette assay may be useful selective diagnostic aid for Fc+ myeloid leukaemia since the SEA assay detects Fc receptors on mature granulocytes.

Animals↗

The effect of food and tablet formulation on plasma prednisolone levels following administration of enteric-coated tablets.

1 Plasma prednisolone levels have been compared following the administration of enteric-coated prednisolone to fasted and non-fasted subjects. The effect on plasma levels of altering the formulation of the enteric-coating has also been studied. 2 The presence of food in the stomach at the time of administration does not affect the absorption of enteric-coated prednisolone tablets. 3 There was considerable inter-subject variation in plasma prednisolone levels after administration of shellac based enteric-coated tablets. However, plasma levels were more consistent when a preparation whose formulation was based upon cellulose acetate phthalate (CAP) was given. 4 It is concluded that the pattern of absorption and plasma prednisolone levels depend on the formulation of the enteric coating. The bioavailability of the CAP based preparation is similar to that of plain prednisolone.

Adult↗

Plasma prednisolone levels and adrenocortical responsiveness after administration of prednisolone-21-phosphate as a retention enema.

Plasma prednisolone levels have been measured by radioimmunoassay after oral and rectal administration to healthy volunteers and to patients with idiopathic proctocolitis. The amount of prednisolone absorbed from a 20 mg retention enema given to patients with proctocolitis was about 44% of that absorbed from the same dose orally administered. Adrenocortical response to synthetic ACTH in patients receiving prolonged rectal therapy was either normal, or only slightly impaired, and this may be related to the pattern of steroid absorption rather than to the total amount absorbed.

Adolescent↗

Suppression of lymphoproliferative responses to alloantigens by autologous AML cells.

Autologous acute myeloid leukaemia (AML), cells caused the suppression of incorporation of 3H-thymidine (3H-Tdr) by remission lymphocytes stimulated with allogeneic cells. In five patients, autologous AML cells suppressed 3H-Tdr uptake by lymphocytes stimulated with up to three different allogeneic cells. Responses to allogeneic AML cells were more strongly suppressed than responses to pooled allogeneic lymphocytes. Suppression was abolished by ultrasonic disintegration of the autologous AML cells, suggesting that a soluble factor was not involved. Suppression was absent from autologous AML cells exposed to ultraviolet light, or when untreated autologous AML cells were present in ratios of less than 1:1 to lymphocytes, or when added 24 or more hours after stimulation of remission lymphocytes with allogeneic cells. It is suggested that suppression is a property of the differentiative level of AML cells, rather than of their malignant properties, although malignant-transformation may bring AML cells into contact with circulating T cells in vivo. Autologous AML cells seem to interfere with the recognition phase of T cell function.

Cell Division↗

Active immunotherapy in acute myelogenous leukaemia and the induction of second and subsequent remissions.

One hundred and ninety-one adults with acute myelogenous leukaemia were treated with combination chemotherapy consisting of daunorubicin and cytosine arabinoside (Barts III). Sixty-three patients achieved remission and were admitted to one of 3 trials of active immunotherapy: immunotherapy alone, immunotherapy and maintenance chemotherapy or neither of these. All patients had weekly clinical and blood examination and monthly marrow examination. Reinduction chemotherapy was given as soon as relapse was diagnosed in the marrow. The most striking observation was that immunotherapy was associated with easy and repeated reinduction of remission and marked prolongation of survival after first relapse when compared with immunotherapy plus chemotherapy. The possible reasons for this and the value of immunotherapy are discussed in relation to the third trial still in progress which includes 2 maintenance arms, immunotherapy alone and surveillance only.

BCG Vaccine↗

Prediction of relapse in men alcoholics.

Cognitive impairment, as measured by the Patterned Cognitive Impairment Test, was the best predictor of relapse in a group of patients after treatment for alcoholism.

Alcoholics Anonymous↗

Receptors for human immunoglobulin on acute myeloid leukaemic leucocytes.

Immunoglobulin (Fc) receptors were detected on leucocytes from patients with acute myeloid leukaemia (AML) by rosette formation with human cDE/cDE erthyrocytes (HE) sensitized with Rhesus (Rh) antisera (HEA). Of 7 Rh antisera tested, erythrocytes sensitized with anti-d (Gm10) detected the highest numbers of rosette-forming cells (HEA-RFC) in normal and AML leucocyte preparations. Using this assay, HEA-RFC was studied in 22 untreated AML patients and ce assay detected 11-6% lymphocyte and 2-1% granulocyte HEA-RFC in normal peripheral blood. Leucocytes from 16 to 22 AML patients had a similar or lower percentage than normal lymphocyte HEA-RFC, which could be explained by the dilution of peripheral blood leucocytes by poorly or non-rosetting leukaemic blasts. Ten of these 16 patients were diagnosed as having acute myeloblasts leukaemia. Six of the 22 AML patients had high HEA-RFC values of which 5 were diagnosed as having myelomonocytic leukaemia. Cytocentrifuge preparations of HEA-RFC showed that the proportion able to form rosettes was lower in myeloblasts than in monoblasts. Enzyme treatment (pronase), inhibition or simultaneous labelling of surface Ig and Fc receptors showed that the characteristic surface Ig found to AML cells is, at least in part, bound to Fc receptors. The HEA-RFC test described in this paper could be useful in the immuno-diagnosis of myelomonocytic leukaemia.

Adult↗

Cell-mediated cytotoxicity as a result of immunotherapy in patients with acute myeloid leukaemia.

Leucocytes from normal individuals and from patients with acute myeloid leukaemia (AML) in remission receiving active immunotherapy with allogeneic AML blasts (AML-I) were cultured for 6 days with AML-I blasts, Burkitt's lymphoma cells (BL) or lymphoblastoid cells (LCL). The leucocytes were then tested for cell-mediated cytotoxicity (CMC) against 51Cr-labelled AML-I, BL or LCL target cells. There was no substantial difference in the CMC of leucocytes from patients and normals cultured without stimulation, and tested against AML-I, BL or LCL targets. Patient's leucocytes stimulated in vitro with AML-I had a greater frequency of positive CMC responses against AML-I, BL and LCL than normal individuals. The results suggest that co-cultivation of leucocytes with AML-I blasts reactivates memory cytotoxic leucocytes in AML patients receiving immunotherapy and that this test may be useful in measuring the effectiveness of immunotherapy.

Burkitt Lymphoma↗

Response of remission lymphocytes to autochthonous leukaemic myeloblasts.

Thymidine incorporation in vitro by remission lymphocytes from a total of 6 patients with acute myeloid leukaemia (AML) was measured following stimulation by autochthonous and allogeneic AML blasts and cell lines. The early peak response to autochthonous blasts in 2 of these patients (48-72 h) is consistent with the concept of a population of lymphocytes pre-immunized to antigens carried by the blasts. Although stimulation in one patient was increased in the presence of more stimulating (S) blasts than responding (R) lymphocytes, positive responses in other tests were obtained at an S : R ratio of 1 : 1-5. When different methods of treatment of the stimulating autochthonous blasts were compared with untreated cells, mitomycin C gave the highest stimulation indices 2 out of 3 tests. Tissue culture medium in which autochthonous blasts had been incubated for 3-5 days failed to stimulate either remission lymphocytes alone, or combined cultures of lymphocytes with autochthonous or allogeneic blasts, suggesting that mitogenic factors released from autochthonous blasts are not responsible for lymphocyte stimulation. Treatment of autochthonous or allogeneic AML blasts with glycine-HC1(pH 3-0) to remove putative "blocking" factors failed to increase the stimulatory capacity of the leukaemic blasts.

Antigens↗