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Biomedical subjects

J D Ansell

Publications and source records attributed to J D Ansell.

At least 37 records · Page 2Linked to original sources

Specificity of tumour associated transplantation antigens (TATA) of different clones from the same tumour.

The TATA of two clones from the same murine methylcholanthrene-induced fibrosarcoma have been investigated by immunizing syngeneic mice with irradiated cells of one or both clones and challenging them 14 days later with viable cells. The tumour had been induced in a female backcross CBA mouse heterozygous for the A and B alloenzymes of phosphoglycerate kinase-1 (PGK-1). One clone expressed A and the other B, and both A and B hosts were used in the experiments. Each clone was found to possess strong TATA but there was no demonstrable cross reactivity. The clonal composition of tumours produced by inoculating mice with a mixture of the two clones was profoundly altered by prior immunization with one of them. A second experiment was performed with 3 clones from another tumour; these expressed PGK-1 A, B and AB respectively. Again, there was no evidence of immunological cross reactivity between the A and B clones, but there was some cross reactivity between the A clone and AB clone. These results, coupled with previous observations of changes in the clonal composition of pleoclonal murine fibrosarcomas in culture and on transplantation, suggest that the antigenic specificity of these tumours is less stable than is commonly supposed.

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Suppressive effects of Corynebacterium parvum on primary and secondary antibody responses in mice.

The splenic plaque forming cell (PFC) response of mice to an intraperitoneal injection of sheep erythrocytes was severely depressed by prior treatment with Corynebacterium parvum given four days beforehand by the same route. However, total antibody levels were less affected, and soon attained near normal titres. This implied that the effects of C. parvum were limited to the spleen, and that other tissues gave a substantial response during the period when the splenic response was suppressed. Equally, this apparently local immunosuppressive effect of C. parvum failed to inhibit the eventual development of a normal memory cell pool. It was also shown that primed cells in the spleen, challenged during the period when C. parvum inhibited primary IgG responses, were relatively refractory to its suppressive effects.

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Clonal interaction in tumours.

The development of cancer is contingent on the emergence of at least one clone of transformed cells. One method used to investigate whether human tumours are monoclonal depends on the mosaicism in the normal tissues of women heterozygous for the two forms of the enzyme glucose-6-phosphate dehydrogenase (G-6-PD). This mosaicism results from the inactivation of one X chromosome in all somatic cells and should not exist in a monoclonal population. Following the discovery in feral mice of an electrophoretic variant (A) of the X-coded enzyme phosphoglycerate kinase (PGK-1) which differs from the form (B) found in common laboratory mouse strains it was reported that fibrosarcomas induced chemically in hybrids of feral and laboratory-bred mice expressed both enzyme phenotypes, but the conclusion that both were expressed by neoplastic cells was based solely on morphological evidence. The development of histocompatible substrains of mice homozygous for one or other alloenzyme has made it possible to study the clonal composition of tumours under experimental conditions in which the neoplastic status of subpopulations of cells can be verified by transplantation. The experiments we now report, while confirming that murine fibrosarcomas are often pleoclonal, show that the clonal composition may change markedly during tissue culture and on transplantation to congenic hosts. These changes presumably reflect changes in the growth kinetics of differentiating subpopulations of the tumour. Cloned sublines are less readily transplantable than uncloned tumour cell populations, and some sublines are less readily transplantable than others; this suggests that sublines resistant to a host's attack are selected on transplantation or that some sublines require the cooperation of others to survive. We postulate that changes in clonal composition occur also during tumour development, metastasis and recurrence.

Animals↗

Special proliferative sites are not needed for seeding and proliferation of transfused bone marrow cells in normal syngeneic mice.

The widely held view that transfused bone marrow cells will not proliferate in normal mice, not exposed to irradiation or other forms of bone marrow ablation, was reinvestigated. Forty million bone marrow cells from male donors were given to female recipients on each of 5 consecutive days, 5 to 10 times the number customarily used in the past. When the recipients were examined 2-13 weeks after the last transfusion, donor cells were found to average 16-25% of total marrow cells. Similar percentages of donor cells were found when variants of the enzyme phosphoglycerate kinase determined electrophoretically were used for identification of donor and recipient cells. Evidence is presented that the proportion of donor cells is compatible with a linear dependence on the number of cells transfused over the range tested--i.e., 20-200 million bone marrow cells injected intravenously. Special proliferative sites thus do not appear to be required.

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Age-related changes in cell localization and proliferation in lymph nodes and spleen after antigenic stimulation.

Antigen-dependent localization of 51Cr-labelled lymphocytes, and the subsequent uptake of IUdR into lymphoid organs has been studied as a function of age. Measures of cell localization indicated that while old age can alter the patterns of entry of lymphocytes into lymph nodes and spleen, these changes are variable and probably not sufficient alone to explain decreased primary antibody responses in old animals. Proliferation of cells, however, was consistently affected in both organs and this phenomenon is discussed in terms of abnormal T-cell function.

Aging↗

Changes in lymphocyte accumulation and proliferation in the lymph nodes draining the pregnant uterus.

Changes in weight, lymphocyte accumulation and cellular proliferation have been measured in the lymph nodes draining the uterus during inter- and intra-strain pregnancies and compared with similar effects after other antigenic stimuli. From the data obtained it was concluded that "paternal" antigenic stimulation from the conceptus initiated an immune response in these nodes. The mechanisms of the subsequent suppression of this response are discussed.

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The development of trophoblast in vitro from blastocysts containing varying amounts of inner cell mass.

When intact mouse blastocysts are cultured in vitro in medium supplemented with foetal calf serum, trophoblast cells proliferate and undergo giant cell transformation such as occurs in vivo. If the amount of inner cell mass in the blastocyst is decreased by culture with [3H]-thymidine then giant cell transformation occurs normally but proliferation is reduced. In the absence of inner cell mass no proliferation occurs, and giant cell transformation is more rapid than in undamaged blastocysts.

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C-terminal truncation of WT1 delays but does not abolish hematopoiesis in embryoid bodies.

The effect of mutations that truncate the WT1 protein on in vitro hematopoietic differentiation from embryonal stem cells has been examined by CFU-A assay, o-dianisidine staining for heme, and RT-PCR analysis of the expression of fetal and adult globins. In two independently isolated ES cell lines the mutations delay but do not abolish hematopoiesis. Analysis of replated CFU-A colonies indicates that the delay occurs prior to the formation of hematopoietic stem cells. The results demonstrate a role for WT1 at the onset of hematopoiesis.

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