Search PubMed⌕ Search

Biomedical subjects

P Alexander

Publications and source records attributed to P Alexander.

At least 109 records · Page 6Linked to original sources
PubMed1980

Variability in heparin effect on serum drug binding.

Heparinized saline was given to seven men and one woman, aged 21 to 42 yr, after a 14-hr fasting period and 2 hr after breakfast; blood was collected in nonoheparinized tubes. Diazepam (D alpha) and warfarin (W alpha) free fractions were determined in serum by equilibrium dialysis to which radiolabeled drug was added. After 50 U heparin (Harris LO14) intravenously, the maximum effect on D alpha, W alpha, and free fatty acids (FFA) developed in 5 min and lasted 20 to 30 min. D alpha rose and W alpha fell (p < 0.01) at 5 min. Cumulative doses of heparin increased FFAs (F4,16 = 18.29, p < 0.0005). D alpha rises (r = 0.73, p < 0.001) and W alpha falls (r = -0.74, p < 0.001) correlated with changes in FFAs. D alpha rises and W alpha falls were greater postprandially than in the fasted state (p < 0.01). Five subjects were randomly assigned up to 400 U intravenously of each of two different heparin lots (Harris LO14, and Organon LA39.) The FFA rises (reflecting heparin lipolytic activity, F1,32 = 179.62, p < 0.0005), D alpha rises (F1,32 = 34.22, p < 0.0005), and the W alpha falls (F1,32 = 33.20, p < 0.0005) by heparin Harris LO14 were greater than those by heparin Organon LA39. Although small doses of heparin, such as those in heparin locks, can affect drug binding, the extent and variability of the effect depends on the biologic activity of the heparin, and varies with manufacturer and lot, exact time of sampling, and eating.

Adult↗
PubMed1979

The nature of remission in acute myeloblastic leukaemia.

15 patients with acute myeloblastic leukaemia (AML) in remission were given immunotherapy and 17 similar patients were given immunotherapy plus chemotherapy with the drugs used to induce remission. Median remission length was 245 days for both groups and median survival was 465 days for patients given chemoimmunotherapy and 476 days for patients given only immunotherapy. The failure of remission chemotherapy in AML cannot be attributed to induced resistance because the same drugs induced a second remission in 60% of the patients. From laboratory studies with human AML cells it is suggested that in AML the residual leukaemic cells mature after induction chemotherapy and are then refractory to further drug treatment. Relapse occurs when the leukaemic population proliferates and the environment permits dedifferentiation into frank blast cells.

Adolescent↗
PubMed1979

Immunity as the predominant factor determining metastasis by murine lymphomas.

The metastatic behaviour of the L5178E (non-M) lymphoma and a highly metastatic subline L51787ES (M) were studied in syngeneic DBA2 mice. The non-M tumour rarely metastasizes in intact syngeneic mice, but produces extensive and rapidly lethal metastases when implanted into irradiated recipients. The metastatic behaviour of the M subline is unaffected by irradiation of the host. By conventional transplantation criteria, the non-M tumour is more immunogenic than the M subline. Both tumours, however, produce similar responses in a lymphnode weight-gain assay. Host-cell infiltration of the tumours growing s.c. is much greater in the non-M than the M, the infiltrating cells being Fc-receptor-positive and maturing into macrophages after 2 days in vitro. Although spontaneous in vitro motility of the M cells is much greater than that of the non-M, the metastatic behaviour of the tumours is clearly determined by host immunological responses.

Animals↗
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↗
PubMed1979

Induction of haemorrhagic necrosis in a murine tumour by products from the culture fluid of Azotobacter.

Macromolecules in the supernatant from cultures of the nitrogen-fixing bacterium Azotobacter chroococcum when given systemically induce permanent regression of established grafts of a syngeneic murine lymphoma. The effect mimics that produced by endotoxin in that haemorrhagic necrosis is induced in the tumour, but the ratio of the toxic dose to the dose needed to cause tumour regression is greater than for this culture supernatant than for endotoxin.

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

Failure of suckling to transfer immunity to a syngeneic rat sarcoma.

Young born to and suckled by mothers rendered immune to a syngeneic sarcoma showed no acquired resistance to challenge with tumour. Whilst other workers had found that allograft immunity could be transferred by milk, we conclude (1) that lymphocytes present in the milk cannot transfer immunity to tumour-specific antigens when absorbed by suckling, and (2) that transfer of maternal immunoglobulins either pre- or postnatally also does not protect against s.c. inoculated tumour.

Animals↗
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

Maintenance of remission in acute myelogenous leukaemia by a mixture of B.C.G. and irradiated leukaemia cells.

Thirty patients with acute myelogenous leukaemia (A.M.L.) in full haematological remission were allocated alternately to two groups of fifteen patients each. All patients received immunotherapy, given weekly as intradermal and subcutaneous injections of killed allogeneic A.M.L. cells, plus Glaxo B.C.G. given by Heaf gun at a separate site. One group also received a mixture of A.M.L. cells and B.C.G. on 4 occasions early in remission. Four patients in this group have remained in remission for 92 to 134 weeks, whereas all patients in the other group had relapsed by 68 weeks. The findings suggest that cells mixed with B.C.G. may be effective in prolonging remission.

Adolescent↗
PubMed1977

Back to the drawing board--the need for more realistic model systems for immunotherapy.

In experimental animals the growth of tumors which display strong immunogenicity can be slowed by immunological maneuvers that increase the magnitude of the host response to the specific tumor antigens. Such immunogeneic tumors do not, in general, cause distant metastases and may, therefore, not be relevant to the treatment of disseminated disease in man. This may explain why the current experience with immunotherapy based on such animal models has, with very few exceptions, been disappointing. Animal tumors which are not immunogenic by standard transplantation tests frequently disseminate and it seems likely that clinically useful immunotherapy has to be based on procedures which are effective against such tumors. The lack of immunogenicity detectable by transplantation may be due to the absence of tumor-specific transplantation antigens (TSTAs), in which case if there is to be any immunotherapy it will have to be direct at boosting some innate type of host resistance. Alternatively, the lack of immunogenicity may be attributable to the intervention of "escape mechanisms" which pervert the immunologically specific host response to TSTAs. In this case, the immunological maneuvre should be directed at overcoming the escape problem and not at boosting the magnitude of the specific host reaction to the TSTAs.

Animals↗