Search PubMed⌕ Search

Biomedical subjects

R D Barnes

Publications and source records attributed to R D Barnes.

At least 55 records · Page 3Linked to original sources

Murine leukaemia virus group-specific antigen in tumor-resistant tetraparental AKR reversible CBA/H-T6 chimaeras.

Various facts are now known about the relative lymphoma resistance of a group of tetraparental AKR reversible CBA/H-T6 chimaeras derived by early embryo aggregation. Firstly, their tumour resistance is not due to the lack of the lymphomaprone AKR cells. Secondly, results showing titres of MuLV-gs antigen comparable with, and occasionally in excess of, those in the AKR suggest that the tumour resistance of the chimaeras is unlikely to be due to a lack of oncogenic leukaemia virus. However, in marked contrast to the AKR, antibody-viral antigen renal complexes in the chimaeras were minimal. Lack of viral antigens could not explain the relative lack of renal complexes. Absence of the corresponding anti-viral antibody is the most likely explanation and this has to be attributed to the CBA component of the tetraparental AKR reversible CBA/H-T6 chimaeras. We suggest that with tolerance to the leukaemia virus being maintained and in the absence of anti-viral antigenic complexes, tumour-specific sites can be recognized and thus tumours are eliminated. This hypothesis remains to be proven.

AKR murine leukemia virus↗

The innate resistance of CBA mice to endogenous murine leukaemia virus infection.

The incidence of lymphomata in CBA mice is low and furthermore is unaltered by transplantation at the early blastocyst stage and being born from the lymphoma-prone AKR. The number of C-type murine leukaemia virus particles in CBA derived in this manner and milk-fostered by AKR mice in no way differs from normal CBA. The results suggest that the oncogenic Gross virus does not pass through either the transplacental or transmammary routes, or alternatively that viral replication in the CBA was in some way inhibited. Both possibilities have still to be distinguished.

Animals↗

The use of early embryo aggregation derived chimaeras. I. To study immunological tolerance.

Early embryo aggregation mouse chimaeras have proven an invaluable tool to study mechanisms involved in tolerance. Such chimaeras are most commonly derived following the aggregation of two undifferentiated embryos and therefore not suprisingly they were originally considered examples of classic immunological tolerance. Since this time alternative mechanisms including humoral and cell suppressor activity have been suggested and until recently tolerance in tetraparental chimaeras has remained a controversy. This controversy is now reviewed in the light of recent findings which has suggested that such mice are in fact examples of classic tolerance with the possibility that this is achieved by heterogenous elimination of the clones of potentially self in equilibrium self auto-reactive cells.

Animals↗

The use of early embryo aggregation derived mouse chimaeras. II. The study of disease processes.

Early embryo aggregation derived mouse chimeras have proven an extremely valuable tool to study development of disease processes. In this respect chimaeras prove a unique opportunity to study the interaction between cells genetically pre-destined to become diseased and a normal cell population within the same animal. In this situation chimaeras can be studied in view of possible 'correction' of the disease by the provision of a population of normal host cells and/or their products. Various host deficiency states including classic immune deficiency, potentially 'deficient' anemias and tumours have been studied--the subject of the review here.

Aging↗

The use of early embryo aggregation derived mouse chimaeras. III. A tool of immunogenetics.

Early embryo aggregation derived chimaeras have proven a valuable tool to biologists concerned with various aspects of mammalian development. The use of this model is discussed here in respect of its application to the field of immunogenetics and also to possible future exploitation. Chimaeras have already provided information concerning various areas of immunogenetics ranging from tolerance, control of antibody response, allotype expression, gene transfer and its possible influence upon the immune response. These are reviewed here.

Aging↗

Autoimmune implications of vasectomy in man.

The frequent development of sperm antibodies following vasectomy does not appear to be related to the formation of other autoantibodies. We have examined serum taken from 346 men before and 6 months after vasectomy for seven different autoantibodies. The occurrence of positive results is comparable to any normal population.

Antibody Formation↗

Levels of C-type viral p30 antigens in lymphoma-resistant mice.

Until relatively recently, interest has largely centered upon the causal role of oncogenic viruses especially with respect to the development of murine lymphomas. Host factors have recently come to the fore and are considered to be effective here, where we note that, in spite of relatively high levels of C-type viral antigen in the AKR X CBA F1 mouse, this hybrid remains relatively lymphoma resistant. Evidence points to an overriding host factor in this situation that is dominant with respect to tumor resistance and furthermore independent of the viral load at least as judged by levels of p30 viral antigen, an assumption confirmed by xc plaque assay.

Animals↗

Cross-reaction of antibodies present in sera of vasectomized mice with human swollen spermheads.

Vasectomy induced anti-sperm antibodies in mice were seen to cross react with human spermatozoa. Similarly anti-sperm antibodies in an infertile human male subject were found not only to react with human but also with bovine, porcine and murine sperm. Both observations made with preparations of swollen spermatozoa demonstrate the cross-reactivity of anit-sperm protamine activity of different species. Therefore in spite of known species dependent differences in amino acid composition and sequence of protamines, they appear to have common antigenic determinants.

Animals↗

Tolerance and leukaemogenesis.

Two subjects are considered here separately. Both are related to findings in the early embryo aggregation derived mouse chimaera model. Such chimaeras are most commonly derived following the aggregation of two undifferentiated embryos and therefore not suprisingly they were originally considered examples of "classic" immunological tolerance. Since this time alternative mechanisms including humoral and cell suppressor activity have been suggested and until recently tolerance in tetraparental chimaeras has remained a controversy. This controversy is now reviewed in the light of recent findings which has suggested that such mice are in fact examples of classic tolerance with the possibility that this is achieved by heterogeneous elimination of the clone of potentially self in equilibrium self auto-reactive cells. Chimaeras have also been studied in respect of leukaemogenesis. Results in a group of AKR reversible CBA leukaemia susceptible reversible resistant chimaeras suggest resistance is dominant. Moreover evidence now points to lack of anti-viral antibody activity in these chimaeras which I wish to suggest may be related to apparent resistance to leukaemia. In this context it may be envisaged that in the absence of masking anti-viral antigen complexes "normal" tumour immunity may have been effected. Although this has yet to be proven evidence points to tolerance to the oncogenic virus being maintained in the chimaeras furthermore also in the naturally derived (AKR X CBA) F1. This in turn leads me to suggest that "intolerance" to the oncogenic virus, the spontaneous development of anti-viral antibodies and tumour development might well be related in the AKR. This in turn enables me to propose that tolerance and leukaemogenesis, at least in this stiuation, appear to be related.

AKR murine leukemia virus↗

Failure to detect antibody against Gross virus in tetraparental AKR reversible CBA mouse chimaeras.

In spite of early acquisition upon the germ line, tolerance to the Gross (gs) virus is short-lived in the AKR. From about the age of 3 months anti-gs antibodies occur and these complex with the corresponding viral antigens. Such complexes are best seen in the glomeruli by means of immunofluorescence. In marked contrast to the AKR, renal complexes were minimal in a group of AKR reversible CBA/H-T6 chimaeras derived by early embryo aggregation. This was particularly surprising since large numbers of type C murine leukaemia virus-like particles were identified in the chimaeras and the tissues were found to be saturated with gs antigen. The lack of renal antigen-antibody complexes was the first suggestion that anti-gs antibody might not be present in the chimaeras and renal elution studies here support this assumption. In contrast to the AKR where "split " renal eluates have been shown to have anti-gs activity, no activity was demonstrated in eluates from any of the chimaras. Tolerance to the oncogenic Gross virus in the chimaeras has to be attributed to the CBA parental strain component and since this component is also held responsible for the tumour resistance of these chimaeras, both phenomena could well be related. In this context it would appear that in the absence of masking by antibody viral antigenic complexes, tumour specific sites can be recognized in the chimaeras and unlike the AKR "normal" tumour immunity can be effected. This hypothesis is currently bei-ng tested.

AKR murine leukemia virus↗

Murine leukaemia virus expression in the AKR following thymectomy.

Thymectomy effectively prevents the development of spontaneous lymphoma in the AKR but how this effect is achieved remains to be determined. One possible mechanism, namely suppression of genomic expression of the oncogenic murine leukaemia virus now seems unlikely since levels of the group specific MuLV antigen were in comparision with their sham operated controls unaltered in both neonatally and adult thymectomized AKR.

Age Factors↗