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A C Cavanagh

Publications and source records attributed to A C Cavanagh.

25 records · Page 2Linked to original sources

Monoclonal antibodies to early pregnancy factor perturb tumour cell growth.

The pregnancy-associated substance early pregnancy factor (EPF) has previously been reported as a product of tumours of germ cell origin. More recently EPF (or an EPF-related substance, tEPF) has also been detected in the serum of patients bearing tumours of non-germ cell origin. We report here the production of tEPF by a variety of cultured transformed and tumour cell lines, of both germ and non-germ cell origin. Antibodies specific for EPF remove all tEPF activity from tumour cell conditioned medium. tEPF production is found to be associated with cell division; tEPF is no longer detected after growth arrest or differentiation. Co-culture of tumour cells with increasing doses of anti-EPF monoclonal antibodies resulted in a significant, dose-dependent decrease in rate of cell growth and viability. Similar anti-EPF concentrations had no effect on the concanavalin A induced proliferation of mouse spleen cells. These studies suggest, therefore, that tEPF is a growth-regulated product of cultured tumour and transformed cells. These cells are also dependent upon tEPF for continued growth, i.e. tEPF is acting in the autocrine mode.

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Passive immunization of pregnant mice against early pregnancy factor causes loss of embryonic viability.

Early pregnancy factor (EPF) is a monitor of the incidence of fertilization and the progress of the early embryo. To determine whether, as well as being a marker of embryonic viability, EPF is also necessary for embryonic survival, passive immunization studies with monoclonal and polyclonal antibodies to EPF were carried out on pregnant mice. In the preparation of monoclonal antibodies, it was noted that most anti-EPF producing hybridomas failed to grow in vitro, while those that did grow produced only low yields of specific IgM antibodies. Two stable hybridoma cell lines were established both producing low affinity anti-EPF IgM; polyclonal anti-EPF IgG was prepared in rabbits. Mice were passively immunized with 500 micrograms monoclonal anti-EPF IgM at 32 and 56 h post coitum (total dose 1 mg) or with 500 micrograms polyclonal anti-EPF IgG at 8, 16, 32 and 40 h post coitum (total dose 2 mg). At 10 days, only 6/18 and 3/6 mice receiving monoclonal antibodies and 2/7 and 1/6 mice receiving polyclonal antibodies had maintained their pregnancies. In contrast, all mice receiving control IgM (N = 14) or control IgG (N = 4) and 22/23 receiving saline were still pregnant at Day 10.

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Identification of two suppressor factors induced by early pregnancy factor.

The binding of EPF to lymphocytes stimulates the release of soluble mediators, active in T cell dependent reactions, namely the rosette inhibition test and the adoptive transfer of contact sensitivity. On the basis of their ability to inhibit the delayed type hypersensitivity reaction in this latter assay, they have been classified as suppressor factors. This paper describes the identification of two EPF-induced suppressor factors. Unlike EPF which is neither species-restricted nor strain-restricted, these factors are genetically restricted in their action in the rosette inhibition test. EPF-S1 (estimated Mr 14,000) is restricted to the 1 region of the mouse MHC, while EPF-S2 (estimated Mr 55,000) is restricted to a locus (or loci) outside the MHC. Like other antigen non-specific factors, release of these suppressor factors can be stimulated also by Con A.

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Production in vitro of mouse early pregnancy factor and purification to homogeneity.

Early pregnancy factor (EPF) has been produced in vitro by culture of oestrous mouse oviducts and ovaries in RPMI, with the addition of prolactin and mouse embryo culture medium. The pooled harvested medium was then subjected to immunoabsorption, electrofocusing and gel filtration. A fraction was isolated with pI 6.83 and molecular weight 21 000 which was responsible for 90% of the recovered biological activity. It appeared to be homogeneous when analysed by high-performance gel-permeation chromatography. SDS treatment showed that the molecule could be split into 3 peptides of molecular weights 10 500, 7200 and 3400, the first having activity equivalent to the EPF component EPF-A from the oviduct, while the last two combined to give activity corresponding with the ovarian component EPF-B.

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Detection of an early pregnancy factor-like substance in sera of patients with testicular germ cell tumors.

Early pregnancy factor (EPF) is produced by both maternal and fetal tissue1,2 and has been detected previously only during pregnancy.3,4 The present report describes the detection of EPF, or an EPF-like substance (tEPF), in serum from patients with germ cell tumors of the testis. tEPF, or its free components, tEPF-A and tEPF-B, were detected in all 11 patients with nonseminomatous tumors and in 5 of 10 patients with seminoma. It was not detected in serum from healthy male controls nor in patients with non-germ cell tumors or benign testicular disease. It is suggested that tEPF may be an additional serum marker for germ cell tumors and may expand the group already detectable by such markers.

Chaperonin 10↗

Ovum factor: a first signal of pregnancy?

Previous studies have shown that, in the mouse, a factor is produced by the fertilized ovum within 24 h of mating. It cooperates with prolactin to stimulate ovarian production of component B or early pregnancy factor (EPF). This paper presents an initial characterization of the substance, termed ovum factor (OF). An indirect assay based on the rosette inhibition test for EPF has shown that OF is first released upon penetration of the ovum by the fertilizing spermatozoon. OF continues to be produced at least until blastulation. Processes which parthenogenetically activate the ovum are also capable of stimulating OF release from unfertilized ova. Gel filtration studies reveal that OF exists in multiple MW forms of approximately 160,000; 2,800; and 1,500. A substance with these characteristics has not been described previously; it may represent the first embryonic signal to the mother.

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