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Biomedical subjects

P Alexander

Publications and source records attributed to P Alexander.

At least 127 records · Page 7Linked to original sources
PubMed1977

Non-specific cytotoxicity of spleen cells in mice bearing transplanted chemically induced fibrosarcomas.

Spleen cells collected from mice bearing transplanted chemically induced syngeneic fibrosarcomas non-specifically inhibited DNA synthesis of sarcoma and lymphoma target cells in vitro. Splenocytes from mice hyper-immunized against a syngeneic sarcoma specifically inhibited DNA synthesis of the tumour used for immunization. The impairment of tumour-cell DNA synthesis was associated in vitro with cytostasis, and lysis of the target cells was not seen. Since treatment with anti-theta serum and complement did not impair cytostatic action of the spleen cells, and since thymus-deprived animals showed similar activity to normal mice, T lymphocytes were not involved in non-specific cytostasis. Removal of phagocytic adherent cells by carbonyl iron markedly inhibited the cytostatic activity of the spleen cells, suggesting a role in this reaction for cells of the monocyte-macrophage series. The presence of an actively growing sarcoma was a prerequisite for the expression of non-specific cytostasis, since surgical excision resulted in complete disappearance of this activity of spleen cells.

Animals↗
PubMed1977

Immunotherapy for acute myelogenous leukaemia: a controlled clinical study 2 1/2 years after entry of the last patient.

One hundred and thirty-nine untreated patients with acute myelogenous leukaemia (AML) were admitted between August 1970 and December 1973 and allocated into two remission treatment regimens: one to receive chemotherapy alone and the other chemotherapy with immunotherapy. Of the patients who attained remission. 22 were in the chemotherapy group and in September 1975 2 remained alive, the median survival time being 270 days and after relapse 75 days. Twenty-eight patients received immunotherapy during remission, and 5 remained alive; the median survival time of the group being 510 days and after relapse 165 days. Ongoing acturial analysis precisely predicted early in the study the median survival of the two groups, but it took a 2-year follow-up after entry of the last patient before it became clear that there were very few long-term survivors. The increase in survival time produced by the immunotherapy is apparently made up of two components: prolongation of the first remission and length of survival after the first relapse. It must be notted that the chemotherapy for this study was devised 6 years ago and the results of the control arm (chemotherapy alone) may be poorer than those obtained in contemporary studies.

Adolescent↗
PubMed1977

Further evidence of response by leukaemia patients in remission to antigen(s) related to acute myelogenous leukaemia.

Fifteen patients with acute myelogenous leukaemia were studied to determine if their remission blood leucocytes could be stimulated into taking up [3H] thymidine after in vitro culture with their own cryo-preserved irradiated AML leukaemia cells. In 6/15 patients it was possible to show autologous recognition and equal recognition of their stored leukaemia cells, even when they had previously been maintained in in vitro proliferative cultures in liquid suspension and undergoing myeloid maturation for one week. After in vitro proliferative culture, 4 populations of leukaemia cells produced material in the supernatant media between 3 and 7 days capable of inducing [3H] thymidine uptake in autologous (2 pts, 5 supernatants) and allogeneic (2 pts, 2 supernatants) AML remission lymphocytes, but not in normal donor lymphocytes. The relevance of these observations to tumour-associated AML antigen is discussed.

Antigens, Neoplasm↗
PubMed1977

Selective mobilization of specifically cytotoxic T-lymphocytes at sites of inflammation in relation to BCG-induced resistance to implants of syngeneic sarcoma in mice.

The heightened and long-persisting resistance of BCG--immunized C57BL/6 mice (10-week-old males and females) to challenge with syngeneic sarcoma cells was largely restricted to the site of inoculation of the BCG. The specific cytotoxicity of peritoneal T-cells and the total number of T-cells that could be recovered from the peritoneal cavity were more than ten times greater in mice that had received BCG ip 2-4 weeks prior to inoculation of tumor than in non-BCG-treated mice. The specific T-cell-mediated cytotoxic potential of the peritoneal exudate of mice immunized with tumor was therefore at least 100 times greater in mice that had received BCG ip. This effect was detectable by 3 days after inoculation of BCG and reached a maximum 2-4 weeks later. The protection against tumor offered by pretreatment with BCG could be explained by the selective recruitment of committed T-lymphocytes to sites of chronic inflammation. The induction of nonspecifically cytotoxic macrophages and systemic changes such as generalized stimulation of the reticuloendothelial system were not contributing factors.

Animals↗
PubMed1977

Innate resistance and specific immunity in host control of cancer.

A review of the role of immune mechanisms in neoplasia is presented. The role of macrophages in innate resistance, the involvement of T-Lymphocytes and other aspects are discussed. Innate resistance to sporadically occurring malignant cells may be exercised by mononuclear phagocytes. While there is no support for the hypothesis that specific immune processes involving T-lymphocytes determine the incidence of cancer, they influence the biological behavior and natural history of some tumors once they have become clinically evident.

Animals↗
PubMed1977

A psychotherapist's reaction to his patient's death.

A case history of a patient who died during the course of psychotherapy is initially presented in the form of an essay. Three therapeutic points (one related to the therapist's awareness of his anger toward the patient) are focused on in regard to working with the dependent, suicidal patient: the importance of being in touch with one's own anger toward the suicidal patient; the need to vary one's attitude and approach toward the dependent patient as he travels through different emotional phases; the importance of promptly involving significant friends and relatives in close observation of and relating to the acutely suicidal person. The emotions and psychodynamic factors in the author and other psychotherapists in response to the death of a patient are then examined with particular emphasis on the therapist's allowing himself to mourn the personal loss.

Attitude of Health Personnel↗
PubMed1976

Macrophages and tumours.

The interplay between the reticuloendothelial system and the growth of tumours is complex. Tumours stimulate the output of monocytes from the bone-marrow leading in some instances to a marked monocytosis. While tumours contain varying numbers of normal macrophages, and in some rat sarcomata they may constitute up to 60% of the total cells of the tumour, the monocytes in tumour bearers are abnormal in so far as they fail to enter sites of inflammation probably because they have bound immune complexes. There is an inverse correlation between the macrophage content of animal tumours and their capacity to metastasize and this may be related to the capacity of macrophages to kill tumour cells as a result of cell-to-cell contact. Macrophage cytotoxicity can be immunologically specific and this, co-operation with T-lymphocytes is required. In addition, macrophages can also be induced to express an immunologically non-specific anti-tumour cell activity.

Animals↗
PubMed1976

A long-term effect of adult thymectomy on cortisone sensitivity and alkaline RNAse activity of murine lymphoid cells.

The alkaline RNAse content of lymphoid cells was measured in two year old mice that had been thymectomized at six to seven weeks of age and found to be three times higher in spleen and four times in lymph nodes than in sham thymectomized age-matched controls. There was, however, no difference in the content of alkaline RNAse in the liver between the two groups of mice. Following administration of cortisone, the RNAse level in the lymphoid organs was increased to a much greater extent in the control than in the thymectomized mice.

Animals↗
PubMed1976

Monocytosis associated with the growth of transplanted syngeneic rat sarcomata differing in immunogenicity.

The effect of the growth of two syngeneic transplanted sarcomata of widely differing biological properties on the number of monocytes in the blood of rats was measured (1) by binding of a specific antimacrophage serum to leucocytes, and (2) by sedimenting in a density gradient rosettes between mononuclear cells and antibody-coated sheep red cells under conditions in which B-cells are not brought down. For the 4 syngeneic sarcomata studied there was a progressive increase in the number of monocytes with tumour growth and the values returned to normal a few days after their surgical removal. The extent of monocytosis was related to the immunogenicity of the tumour and was most pronounced for the HSBPA sarcoma, which is highly immunogenic, has a low rate of spontaneous metastasis and contains many macrophages, and least for the MC-3 sarcoma which is essentially non-immunogenic, invariably gives rise to distant metastases and contains only about 8% macrophages. The growth of sarcomata had previously been found to reduce the number of monocytes which enter inflammatory lesions, both non-specific and due to a delayed hypersensitivity reaction. This "anti-inflammatory" action of sarcomata which is related to their immunogenicity cannot be ascribed to the preferential uptake of monocytes by the tumours and it is concluded that the monocytes in the blood of tumour-bearers, though increased in number, are modified so that they do not enter sites of inflammation.

Animals↗
PubMed1976

Estimation in sera by radioimmunoassay of a specific membrane antigen associated with a murine lymphoma.

Material with a molecular weight of less than 10(5) daltons has been isolated and partially purified from the ascitic fluid of DBA2 mice bearing a syngeneic lymphoma (SL2). This substance inhibits the cytotoxic action of an allogeneic antiserum directed specifically against SL2 cells. Material has been rendered radioactive with 125I and between 20 and 25% of the radioactivity is bound in a specific manner to the antiserum. The material which is referred to as 125I-TSTA has been used in a radioimmunoassay to measure the level of TSTA in the sera of mice bearing both ascitic and subcutaneous SL2 tumours. The level of circulating TSTA was found to be high immediatley following inoculation of live SL2 cells, probably because a large proportion of the injected cells autolyse. The serum concentration of TSTA then falls but 6-10 days later begins to rise again in parallel with the growth of the SL2 tumour either in the peritoneal cavity or subcutaneously. Following surgical removal of an intradermal SL2 tumour the level of TSTA in the serum falls rapidly. No evidence could be found that a significant proportion of the TSTA in the serum of tumour-bearing mice is completed with antibody. However, in the serum of DBA2 mice which have been hyperimmunized with irradiated SL2 cells there are antibodies which bind 125I-TSTA although syngeneic anti-SL2 sera, unlike alloantisera, do not show complement dependent lysis of SL2 cells.

Animals↗
PubMed1976

Spontaneous shedding and antibody induced modulation of histocompatibility antigens on murine lymphomata: Correlation with metastic capacity.

The lability of cell surface histocompatibility antigens of 2 murine lymphomata was examined. These 2 tumours differ greatly in their capacity to metastasize in syngeneic hosts. Cells of the metastatic lymphoma released histocompatibility antigens in vivo and in vitro at a greater rate than cells of the non-metastasizing lymphoma. Antigen/antibody complexes formed by the addition of allo-antiserum to intact cells disappeared more rapidly from the surface of cells of the metastatic line. We propose that the instability of surface antigens may be an integral feature of malignant cells and that there may be a quantitative relationship between the lability of membrane components and the capacity of the tumour to metastasize.

Animals↗
PubMed1976

Immunogenicity of a rat leukaemia of spontaneous origin (SAL).

The SAL rat leukaemia, which resembles acute myeloblastic leukaemia, appeared initially to be non-immunogenic since resistance to an i.p. challenge with as few as 100 cells could not be obtained using stimulation of the RES or by immunization with SAL cells exposed to x-rays, nitrogen mustard, iodoacetate or glutaraldehyde. However, immunization with SAL cells exposed to low doses of mitomycin-C slowed the growth of the challenge inoculum. Cells treated with high doses of mitomycin-C did not immunize. The results are interpreted in terms of rapid shedding of a tumour-specific antigen from the membrane of SAL cells.

Animals↗
PubMed1976

Cross reactivity of an alloantigen present on normal cells with the tumour-specific transplantation-type antigen of the acute myeloid leukaemia (SAL) of rats.

Resistance can be induced in the syngeneic host (August rats) to a myelogeneous leukaemia of spontaneous origin, called SAL, by immunization with allogeneic cells derived form both normal and malignant tissues obtained from the Hooded rat strain. Serological experiments support the conclusion that the antigen involved-referred to as "Ho-SAL"-has the properties of a tumour specific transplantation-type antigen for SAL cells but is a widely expressed alloantigen found in both normal and malignant cells derived from Hooded rats. Antisera to it can be raised in Wistar rats.

Animals↗
PubMed1976

Trapping and destruction of blood-borne syngeneic leukaemia cells in lung, liver and spleen of normal and leukaemic rats.

Leukaemic cells from rats with a lymphoid (HRL) or myeloid (SAL) leukaemia were labelled with 125IUDR and injected i.v. into either normal or leukaemic syngeneic recipients. The fate of the injected cells was studied in terms of the radioactivity in various tissues at various times up to 24 h later. In normal animals the leukaemia cells were destroyed rapidly in the reticulo-endothelial (RE) system; immediately after injection most recoverable activity was in the lung, with smaller amounts in the blood, spleen and liver but by 24 h only 20-30% of the injected activity could be recovered. In leukaemic recipients with high numbers of blasts in the blood the amount of activity recoverable from the lungs and bone-marrow was markedly reduced, while that in the blood was doubled. Nonetheless, the overall rate at which radioactivity was eliminated was not significantly different from that found in normal rats, in spite of the fact that the RE system was extensively infiltrated by leukaemia cells.

Animals↗