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Biomedical subjects

R Powles

Publications and source records attributed to R Powles.

At least 181 records · Page 10Linked to original sources
PubMed1981

Maturation of human peripheral blood leukemic cells in short-term culture.

This work is a continuation of earlier studies in this laboratory (Palú et al. 1979) in which two populations of cryopreserved acute myelogenous leukaemia (AML) cells were shown to undergo progressive maturation in vitro. Twelve other populations of AML cells have since been studied and three distinct patterns of in vitro behaviour have been observed: 1. Cells which did not mature. 2. Cells which matured to the polymorph series and 3. Cells which matured to the macrophage series. Six populations of AML cells were studied both before and after cryopreservation to demonstrate that exposure to the cryopreservative agent dimethylsulphoxide (DMSO) does not influence the patterns of maturation observed. The effect of thioproline and prostaglandins A1 and A2 on maturation was also studied. It is too early to say whether any correlation between the prognosis of the AML patients and the maturation pattern of their AML cells can be established.

Cell Count↗
PubMed1979

Patterns of maturation in short-term culture of human acute myeloid leukaemic cells.

Leukaemic cells taken from the blood of patients with acute myelogenous leukaemia (AML) frequently proliferate in suspension culture without the addition of growth factors for a limited period only. After a 6--10-fold increase in total cells, cell numbers remain constant for a time and finally decline. The main cause for this limited growth in vitro is not, initially at least, cell death leading to a steady state, but maturation associated in its final stages with cessation of DNA synthesis. Two populations of AML cells from Patients St and Wi respectively were studied, and progressive maturation towards mature leucocytes was demonstrated by the gradual acquisition in culture by the growing blast cells of intracellular enzymes (lysozyme, arginase, acid phosphatase and esterase being measured), surface markers (Fc and C3 receptors), of lactoferrin by Wi cells and of colony-stimulating activity by St cells, as well as changes in Ia antigens, phagocytic properties, morphology and adhesiveness to plastic. With St cells, which carried a characteristic chromosome marker, maturation terminated in cells with the characteristic properties of macrophages. At an intermediate stage, non-adherent and still-dividing St cells acquired Fc and C3 receptors and enzymes characteristic of monocytes. Wi cells progressively became neutrophil-like, and again there was an intermediate population of dividing cells which had Fc and C3 receptors and proteins such as lactoferrin and esterases. characteristic of neutrophils.

Cell Adhesion↗
PubMed1979

Spontaneous regression of human acute myeloid leukaemia xenografts and phenotypic evidence for maturation.

A population of human AML cells which have a characteristic karyotypic marker was cryopreserved and then grown in short-term liquid culture for 2 weeks, during which time the cells increased about 7-fold in number and progressively acquired characteristics of macrophages. 10(7) cells obtained after 1 day in culture, when they were almost devoid of Fc receptors (Fc-), on inoculation into immune-deprived mice gave rise to tumours in more than 90% of the animals. However, after 13 days of culture, when almost all the cells had Fc receptors (Fc+), a similar inoculum did not grow as tumours. After 7 days in culture the cells were heterogeneous, and divided about equally into Fc+ and Fc- cells, both of which were replicating. The Fc- population was capable of producing tumours, whereas the Fc+ was not. Of 23 assessable xenograft tumours produced by the AML cells, 14 regressed completely, 4 grew progressively and 5 grew progressively after initial regression. Progressive tumours could be further transplanted. The regression may arise as a result of maturation in vivo similar to that seen in vitro.

Animals↗
PubMed1978

Immunotherapy of human acute leukaemia.

Conclusions are difficult to draw. In the six studies of immunotherapy of AML discussed, all the three employing BCG and cells showed a prolongation of survival and the major contributing factor to this prolongation of survival was extension of life after relapse. In the three studies using BCG alone only one shows a beneficial effect, but some more time must be allowed to elapse before this can be concluded with confidence.

Acute Disease↗
PubMed1978

Inability to demonstrate lytic antibodies to autologous leukaemia cells in the sera from remission patients with acute myelogenous leukaemia treated with active specific immunotherapy.

The sera from seven patients with acute myelogenous leukaemia (AML) who had achieved a clinical remission and who were being maintained by weekly immunotherapy using irradiated allogeneic AML cells and BCG, were examined for the presence of antibodies which were lytic to autologous AML cells using either a complement- or cell-dependent assay. The AML cells had been stored at --179 degrees C and put into a short-term tissue culture prior to testing. At no time during the period of remission or relapse could cytotoxic activity to the autologous cells be detected, although all of the sera had lytic antibodies for some allogenic leukaemia cells. We concluded that the patients were capable of raising lytic antibodies to histocompatibility antigens but did not raise comparable lytic antibodies directed against a leukaemia-specific membrane antigen.

Adult↗
PubMed1977

Early deaths in acute myelogenous leukemia.

In a series of 84 patients with acute myelogenous leukemia, 24 died within 6 weeks of starting treatment. Twenty of the 24 patients had failed to achieve remission at the time of death. Death was due to infection in 20 patients and in 17 of these to septicemia; but whereas severe local infection with septicemia accounted for 12 deaths, only five patients died of septicemia without local infection. Bleeding was the direct cause of death in only four patients and an associated terminal event in another three; of these four patients three had disseminated intravascular coagulopathy. Surprisingly, in this group of patients age and overall clinical status at the time of admission were of no prognostic value in the first 6-week period. The importance of drug resistent disease associated with intractable local infection as a major cause of early death is emphasized.

Adult↗
PubMed1976

The effect of immunotherapy on survival of patients with acute myelogenous leukaemia after relapse.

A randomized controlled clinical trial for the use of immunotherapy for maintaining patients with acute myelogenous leukaemia has been conducted involving 52 patients. All patients received short pulsed maintenance chemotherapy but 30 of the patients received additional immunotherapy consisting of BCG and irradiated allogeneic myeloblastic leukaemia cells. Of the 22 patients who received chemotherapy alone, 19 died with a medium survival of 39 weeks, whereas 20 of the 30 patients who received chemotherapy plus immunotherapy died with an estimated median survival of 74 weeks. The value for the significance of the difference in death rates of patients was less than .01. The main effect of this immunotherapy was, however, due to a prolongation of survival after the patients had relapsed; the median survival for the immunotherapy patients being 23 weeks compared with only 11 weeks for the chemotherapy alone patients (p less than .005). The overall results also show that there was a slight prolongation of first remission in patients who received immunotherapy with a median duration of 44 weeks compared with 27 weeks for patients who received only chemotherapy. The possible mechanisms of action of this form of immunotherapy are discussed.

Adolescent↗
PubMed1974

Adult acute leukaemia.

Seventy-eight adult patients with acute leukaemia were classified cytologically into 3 categories: acute lymphoblastic leukaemia (ALL), acute myelogenous leukaemia (AML) or acute undifferentiated leukaemia (AUL). The periodic acid-Schiff stain was of little value in differentiating the 3 groups. The treatment response in each group was different: 94% of patients with ALL (16/17) achieved complete remission with prednisone, vincristine and other drugs in standard use in childhood ALL; 59% of patients with AML (27/46) achieved complete remission with cytosine arabinoside and daunorubicin (22 patients), or 6-thioguanine and cyclophosphamide (2 patients), 6-thioguanine, cyclophosphamide and Adriamycin (1 patient), and cytosine and Adriamycin (1 patient); only 2 out of 14 patients (14%) with acute undifferentiated leukaemia achieved complete remission using cytosine and daunorubicin after an initial trial of prednisone and vincristine had failed. Prednisone and vincristine would seem to be of no value in acute undifferentiated leukaemia. It would seem also that no benefit is obtained by classifying all patients with acute leukaemia over 20 years of age as "adult acute leukaemia" and treating them with the same polypharmaceutical regimen. The problems posed by each disease are different and such a policy serves only to obscure them.

Acute Disease↗