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Biomedical subjects

A E Beer

Publications and source records attributed to A E Beer.

99 records · Page 6Linked to original sources
PubMed1972

Further evidence concerning the autoantigenic status of the trophoblast.

Heterologous antisera were raised by inoculation of rabbits with fairly pure suspensions of trophoblast, lymphoid, fetal (excluding placental components), epidermal, decidual, and renal cells from Fischer rats. After absorption of hemagglutinins, these antisera were assayed for abortifacient activity by intramuscular inoculation into time-mated Fischer females. The anti-trophoblast serum aborted all the recipients, but had some nonspecific activity in that it caused the deaths of 12% of them. Anti-lymphocyte serum was more toxic and less potent as an abortifacient. None of the other sera harmed either the mothers or their fetuses. However, the anti-kidney cell serum caused kidney lesions. Absorption of the anti-trophoblast serum with lymphoid cells completely removed its toxicity for the pregnant females without perceptible impairment of its abortifacient activity. However, the latter could be removed by absorption with trophoblast cells. (a) The lymphocyte-absorbed anti-trophoblast serum was equally effective in aborting rats over the range 7-18 days postconception; (b) a single injection of 1 ml was sufficient in most cases, and (c) it was equally efficacious in terminating gestation in rats irrespective of their genetic constitution, and (d) its effect was highly species-specific. These findings support the premise that a unique antigen (or antigens), of possible clinical significance, is associated with trophoblast cells.

Abortion, Induced↗
PubMed1972

Maternally induced transplantation immunity, tolerance, and runt disease in rats.

A previous report that the offspring of outbred Sprague-Dawley rats, born of mothers presensitized or tolerant with respect to tissue antigens of the Lewis strain, and reinoculated with Lewis cells during their pregnancy, reject test grafts of Lewis skin in an accelerated manner has been confirmed. This "maternally induced" alteration in reactivity of the progeny has been found to be long lasting, immunologically specific, and probably not due to transfer of humoral antibody. It has been established that the reexposure of the mothers to donor cellular antigen during pregnancy augmented the influence of the prior states of tolerance or sensitivity. To obviate the complications inherent in working with the outbred Sprague-Dawley rats, the key experiments summarized above were repeated with isogenic Fischer rats as parents and Lewis rats as the tissue donors as before. With this combination it was found that a state of prior sensitization or tolerance in the mothers resulted in the apparent induction of tolerance in some of their progeny. Reinoculation of either the tolerant or sensitized mothers during pregnancy slightly increased the incidence and degree of impairment of their offsprings' capacity to reject Lewis skin grafts. A single intraperitoneal injection of 100 x 10(6) million Lewis lymphoid cells into normal Fischer rats in the 14th-16th day of pregnancy also weakened the reactivity of their progeny to Lewis test grafts. Further to test the premise that this weakened reactivity might be due to maternal induction of tolerance, by antenatal transmission of alien cells, the lymphohematopoietic tissue system of adult Fischer females was replaced by that from Lewis donors with the aid of cyclophosphamide. It was anticipated that when these animals were mated with Fischer males, sufficient Lewis leukocytes might cross the placentas to induce high degrees of tolerance. Although normal sized healthy litters were born, about 50% of the infants succumbed to graft-versus-host (GVH) or runt disease within 40 days, many of them giving evidence of being tolerant of Lewis grafts. The mothers, too, developed chronic GVH disease. The offspring of Fischer females made chimeric with cells from (Fischer x Lewis)F(1) hybrid donors, as well as their mothers, remained healthy. Intraperitoneal injection of normal Fischer females, in the 15th-17th day of pregnancy, with 100 million lymphoid cells from specifically sensitized Lewis rats, also caused fatal runt disease to develop in about 50% of their offspring, but left the mothers unscathed. Taken together, these various findings indicate that in some genetic contexts at least the extent of the natural surreptitious transplacental cellular traffic can be considerably augmented experimentally, though how this comes about and why lymphocytic cells that are foreign to the mother can apparently gain access to fetuses more readily than her own cells remain to be determined.

Animals↗
PubMed1970

Implantation, transplantation, and epithelial-mesenchymal relationships in the rat uterus.

Free tail skin grafts or suspensions of viable epidermal cells have been placed in the atraumatized uterus of isologous rat hosts and allowed to "implant" of their own accord to study the possible uniqueness of this site for other than nature's transplants, i.e. conceptuses, and its response to unnatural grafts. Despite the presence of an intact endometrial epithelium, free skin grafts heal-in rapidly, provided that a state of estrogen excess is established at the time of transplantation. In the absence of estrogen most of the grafts failed to implant. Once established, the grafts survive indefinitely without further estrogen. However, if at any stage a state of continual estrus is established, skin epidermis migrates centrifugally from the graft perimeter invasively replacing the native uterine epithelium. The results of an analysis of the modus operandi of this estrogen-facilitated epidermal migration in utero sustain the view that the hormone acts upon the uterine stroma rather than upon the epidermal cells. When grafts of lingual mucosa or vaginal "skin" were placed in the uteri of rats maintained in chronic estrus, migration of epidermis took place even more vigorously than from tail skin. These epithelia conserved their distinctive histologic specificities indefinitely when growing as heterotypic recombinants on the alien mesenchymal stroma of the uterus. Monodisperse suspensions of epidermal cells appear to "implant" and establish small epidermal plaques in the uterus only at sites predestined to accept conceptuses. That the endocrinologic parameters for the establishment of skin grafts in the uterus are similar to those for blastocysts is suggested by the finding that both kinds of graft can become established in the same uterine horn in the absence of exogenous hormones.

Animals↗