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Biomedical subjects

W K Silvers

Publications and source records attributed to W K Silvers.

At least 145 records · Page 8Linked to original sources
PubMed1969

Studies on the immunotherapy of runt disease in rats.

Using rats of the Lewis and BN (Ag-B locus incompatible) isogenic strains, a comparative study has been made of the capacity to prevent or mitigate the development of runt disease with: (a) lymph node cell suspensions from normal adult BN rats, (b) node cells, or (c) serum from donors sensitized against Lewis tissue antigens, or (d) heterologous anti-lymphocyte serum (ALS) raised in rabbits against rat thymocytes. Following a standard intravenous or intraperitoneal inoculation of 20 x 10(6) Lewis node cells into neonatal BN hosts, there are cutaneous manifestations of runt disease within 11-15 days and death invariably takes place within 20 days. However, complete protection is afforded by administration of a similar number of normal BN node cells via a different vein, or admixed with the otherwise harmful Lewis node cells. However, timing of the administration was crucially important-precedence or delay by as little as 4 hr resulted in a great impairment of protection. When the inoculations of the two cell suspensions were separated by 24 hr, no protection was afforded. These and other observations suggested that a necessary condition for protection of the hosts by unsensitized isologous cells requires that they establish a prompt and intimate confrontation with the homologous target cells. At the same dosage level, suspensions of node cells from sensitized isologous donors were much more effective therapeutically, saving the lives of 92% of treated subjects when administered after a delay of 3 days, and of 19% when the delay was 4 or 5 days. Of the various immunotherapeutic agents studied, daily injections of 0.2 ml of isoantiserum gave the best results, and could totally reverse the course of the disease even when initiated at age 10-13 days and subjects already presented symptoms. ALS, although inferior to isoantiserum at the dosage levels tested, proved to be superior to sensitized isologous cells as a protective agent, since the initiation of daily injections after delays of 6 or 8 days were still effective. The observations that delayed treatments of infant rats with isoantisera or ALS resulted in complete recoveries sustain the thesis that the lesions responsible for the fatal outcome of runt diseases are not inflicted at a very early stage. The efficacy of both isoantisera and ALS as a means of inhibiting the progression of homologous disease also suggests that they may have therapeutic value in situations where this condition is encountered.

Animals↗
PubMed1968

Studies on the induction of tolerance of the H-Y antigen in mice with neonatal skin grafts.

In contrast to the uniform rejection of adult male skin isografts by C57BL/6 females, neonatal male skin isografts are frequently accepted. Moreover, 50% of all females which accept a neonatal male skin graft for 50 days accept a subsequent adult male skin graft as well. This ability of neonatal skin to produce tolerance has been investigated under a variety of experimental conditions. The results indicate: (a) Even when a newborn male skin graft is transplanted concomitantly with an adult graft, it can produce tolerance of the latter although it is less effective in this regard than when transplanted beforehand. (b) The continued exposure of the host to the newborn graft is vitally important in maintaining the unresponsive state; and most females deprived of these grafts for 50 days manifest an immune response when challenged with adult male skin. (c) Newborn male skin isografts raised on adult females are not as antigenic as normal male skin grafts. (d) Occasionally, even a presensitized female can be rendered tolerant by grafting with neonatal male skin. (e) Neonatal male skin grafts are not accepted when transplanted to the spleens of adult females although they may occasionally induce tolerance of a subsequent orthotopic adult male skin graft. The failure of these intrasplenic grafts to survive can be attributed at least partly to their small size since orthotopic grafts of comparable size usually do not survive. (f) Females bearing neonatal male skin grafts are not perceptible cellular chimeras. Because the unresponsive condition induced with neonatal skin is similar to that which results from multiparity, this latter condition has also received attention. In this regard it has been established that unlike the removal of a neonatal male skin isograft, the delayed grafting of isolated females with a previous history of multiparity does not result in many of them manifesting what may be considered an immune response. However, this delay in grafting does seem to impair the tolerance multiparity produces. The results are discussed in relation to other methods of producing tolerance in adult animals.

Age Factors↗
PubMed1967

"Intrinsic" immunological tolerance in allophenic mice.

Mice experimentally derived from pairs of conjoined, undifferentiated, cleavage-stage embryos of different histocompatibility genotypes can retain cells of each strain, which still produce their characteristic antigenic products. The animals are permanently tolerant of cells of both original types, remain free of runt disease, and display a normal and specific immune response to introduction of a foreign antigen. Absence of autoimmunity in development of ordinary animals is explainable by the "intrinsic" kind of tolerance found here.

Alleles↗
PubMed1967

Quantitative studies on the mixed lymphocyte interaction in rats. II. Relationship of the proliferative response to the immunologic status of the donors.

The influence of the immunologic status of the cell donors on the proliferative behavior of rat lymphocytes in the mixed lymphocyte interaction has been studied. Mixed cultures of cells from various parental and F(1) combinations having morphologically distinguishable sex chromosomes exhibited unidirectional proliferative reactivity. The mitotic figures were predominately of parental origin. Lymphocytes from donors made tolerant at birth to homologous transplantation isoantigens were specifically unreactive against cells bearing antigens of the tolerance inducing strain, but not to indifferent third party homologous lymphocytes. Cells from animals that had been surgically thymectomized at birth exhibited a markedly and sometimes totally diminished reactivity against homologous lymphocytes. Presensitization of the cell donors resulted in a curtailment of proliferative reactivity in cultures with cells bearing the immunizing antigens. This may reflect the destructive properties that lymphocytes from sensitized animals are known to possess. The results of these experiments show that the proliferative activity of lymphocytes in the mixed lymphocyte interaction accurately reflects the immunologic status of the cell donors, and these findings provide further support for the premise that the mixed lymphocyte interaction represents a primary immunologic response by cells in culture against homologous cells bearing histocompatibility antigens.

Animals↗
PubMed1967

Studies on the conservation of epidermal specificies of skin and certain mucosas in adult mammals.

To determine whether the factor(s) responsible for the conservation of epidermal specificities in adult guinea pigs and hamsters resides in the germinal layer of the epidermis or in the dermis, thin grafts of skin, possessing qualitatively distinct regional characteristics, were separated into their superficial epidermal and dermal components with the aid of trypsin. Dermis of one type was combined with epidermis of another to produce "recombinant" grafts which were then transplanted to small, full thickness cutaneous sites on the thorax of geneticaily compatible hosts. A variant of this procedure involved transplanting sheets of superficial epidermis of various types to shallow split thickness recipient areas in the skin of the thorax. All grafts were maintained for 100 days before they were excised and examined histologically. The results indicate that, whereas the dermis determines the kind of epidermis produced in recombinant grafts involving the ear, the sole of the foot, and the trunk, this is not the case in recombinants which include tongue, esophageal, or cheek pouch epithelia. The one exception to this occurred when tongue or esophagus epithelia were transplanted to split thickness beds in trunk skin. Here they appeared to produce an epidermis characteristic of their new location. It is believed that this exception is probably due to the fact that the native follicular epidermis present in trunk dermis made such a substantial contribution to the new superficial epidermis that it behaved overtly as body skin epidermis. Taken together, these results suggest that basal layer cells of the superficial epidermis of sole of foot skin, ear skin, and the hair-bearing skin of the general integument behave as if they are equipotential, and that in adult life maintenance of these particular epidermal specificities is the outcome of persistent specific inductive stimuli from the underlying dermis. The results of subsidiary experiments are reported which indicate that the epithelial component of mammary gland tissue is also pluripotential, being capable of producing, under appropriate conditions, a normal-looking, fully stratified superficial epidermis.

Animals↗
PubMed1967

Mixed leukocyte reactions and histocompatibility in rats.

Mixed leukocyte culture tests have been carried out on two hetero geneous but genetically defined backcross populations of rats to determine whether the reactions observed can provide the basis for histocompatibility matching. The experiments were designed so that only-one-way reactions could occur. Only when the donors of individual leukocyte mixtures differed at the important Ag-B histocompatibility locus was there any in vitro reactivity, and differences at this locus were invariably associated with the prompt rejection of skin homografts. Determination of compatibility at this locus proved to be important in that it facilitated the prolongation of survival of skin homografts by immunosuppressive therapy.

Animals↗