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Biomedical subjects

J Shelby

Publications and source records attributed to J Shelby.

At least 73 records · Page 4Linked to original sources
PubMed1987

Pregnancy after tubo-ovarian transplantation.

A rat model was developed for microsurgical en bloc vascularized adnexal isografts and allografts. Transplantation of the fallopian tube and ovary from donors to syngeneic, bilaterally tubo-oophorectomized recipients was technically successful in six of eight animals, and four litters of healthy offspring were delivered at 44, 45, 85, and 105 days after transplantation. Twelve tubo-ovarian allografts using cyclosporine for immunosuppression resulted in seven viable grafts and three pregnancies. Cyclosporine at 15 mg/kg/day was found to be teratogenic, but normal progeny were delivered when the dose was lowered to 5 mg/kg/day during pregnancy. These results suggest that microsurgical tubal transplantation with an appropriate immunosuppressive regimen warrants further investigation as potential treatment for certain infertility problems in the human.

Animals↗
PubMed1986

Immunosuppressive effects of burn injury and nonspecific blood transfusion.

Burn injuries and blood transfusions both have been implicated as causes of suppressed immune responses. Skin allograft survival in a burned mouse model was studied to determine the relationships among burn injury, blood transfusion, and phlebotomy before transfusion as they affected immunocompetence. At 7 days after 20% TBSA full-thickness burn injury, allograft skin survival was prolonged compared to nonburned control. When increasing volumes of blood were transfused, allograft survival times decreased accordingly. Phlebotomy before transfusion tended to enhance this response. Similar results were seen at 14 days after burn injury, although phlebotomy before transfusion did not further decrease allograft survival time at 14 days. This study demonstrated that blood transfusions were not additively immunosuppressive over burn injury alone. Increased amounts of transfused blood restore allogeneic responsiveness. Phlebotomy may enhance this response when performed early after burn injury.

Animals↗
PubMed1986

Transfusion-induced sensitization to skin allografts in burned mice.

Blood transfusions are known to improve allograft survival times, and this effect is enhanced with recipient immunosuppression. The focus of the present study was to determine the effect of pretransplant and perioperative donor-specific (DST) or nonspecific (NST) blood transfusion on skin allograft survival in thermally injured mice. Allogeneic immune responsiveness was suppressed in 20% TBSA burned mice, but not to a degree which was protective against DST-induced sensitization. Pretransplant DST resulted in accelerated graft rejection in burned recipients, although high-dose cyclosporine partially reversed this sensitization. Additionally, burn-related immunosuppression in this model did not enhance perioperative transfusion-induced graft prolongation. However, when burn-injured perioperatively transfused mice were further immunosuppressed with cyclosporine, significant graft prolongation occurred. These data suggest that perioperative NST may contribute to prolonged skin graft survival in burned recipients, provided that the mice are sufficiently immunosuppressed.

Animals↗
PubMed1985

[Effects of cyclosporine and blood transfusion on cardiac xenografts in combination of rat and mouse].

Transplant surgeons have been interested in the transplantation of vasculized organ xenografts. We studied the effects of Cyclosporine and blood transfusion on rat heart xenografts in mice and in reverse combination. B6AF1 mouse recipients were transfused with C3D2F1 mouse blood, presenting H-2k/d antigen and with B10.BR mouse blood transfusion, presenting H-2D and H-9 antigen to recipients. All rejected on day 5 in control group and C3D2F1 group. Prolongation of xenograft survival occurred with MST (Mean Survival Time) of 7.0 +/- 1.7 days (p less than 0.01), when primed by B10.BR blood transfusion. The survival time (MST = 14.4 +/- 3.2 days (p less than 0.001) of rat heart xenografts was prolonged in mice recipients treated with i.m. injection of 20 mg/kg/day of Cyclosporine for 14 days (short term). When B6AF1 mouse hearts were grafted into Lewis rats, however, no significant prolongation of graft survival occurred in any of Cyclosporine-treated rats. Cyclosporine did not prove to beneficial in this combination because of rat natural antibodies or species-specific barriers to mouse.

Animals↗
PubMed1984

Suppressor cell induction in donor-specific transfused mouse heart recipients.

Administration of donor-specific blood presenting major or minor foreign histocompatibility antigens to the mouse recipient improved heart allograft survival when a single transfusion of 0.25 ml was given to the recipient prior to transplantation. Multiple transfusions did not prolong allograft survival, which suggested a presensitization effect. In addition, when the single transfusion volume was reduced to 0.025 ml, no significant effect in prolongation of graft survival was observed. Thus the amount of blood transfused seemed to be a critical factor in achieving the transfusion effect. Splenic suppressor cells after transfusion and transplantation (as determined by adoptive transfer) were present during the stable maintenance phase of graft survival in transfused recipients with long-term surviving heart allografts. Also, an intact spleen was required to achieve improved allograft survival in mice transfused with donor-specific blood. Thus a mechanism for the favorable effect of blood transfusion may be the generation of splenic suppressor cells in response to transfusion followed by transplantation.

Animals↗
PubMed1983

Abrogation of second-set rejection with cyclosporine.

Cyclosporine was evaluated for its ability to delay or prevent accelerated rejection in a model of the second-set immune response. Lewis rats sensitized by LBN skin grafts or subcutaneous heart fragments experienced accelerated rejection of heterotopic, vascularized LBN hearts with a mean survival time (MST) of approximately 5 days versus MST of 9.5 days for primary grafts. A short course of cyclosporine (10 mg/kg/day for 10 days) significantly prolonged graft survival in presensitized hosts to approximately 12 days (P less than 0.01) as compared with the nontreated controls. Adjunctive splenectomy failed to further extend graft survival; MSTs were 12.0 and 5.7 days with and without cyclosporine, respectively. A comparable abrogation of second-set rejection was also achieved with a short course of antithymocyte serum (MST of 10.6 days). Rejection promptly ensued in all of the above groups shortly after cessation of immunosuppression. In contrast, a maintenance regimen of cyclosporine, given in a tapering dose, markedly extended graft survival to from 77 to 100+ days. Again, however, rejection eventually occurred following withdrawal of the cyclosporine. These data suggest that cyclosporine can indeed effectively prolong allograft survival in presensitized hosts.

Animals↗
PubMed1983

Human skin storage techniques: a study utilizing a nude mouse recipient.

The nude mouse model is an excellent technique for studying the viability of stored human skin. In this study Roswell Park Memorial Institute (RPMI) tissue culture medium provided reliable storage of viable human skin for 20 days. Antibiotic concentration plays a role in stored skin viability with low concentrations of penicillin and streptomycin providing adequate bacterial control and improved viability when compared to identical media with high concentrations of the same antibiotics. Addition of fetal calf serum to the storage medium did not improve human skin viability in this experiment.

Animals↗
PubMed1981

Biology of human skin transplanted to the nude mouse: I. Response to agents which modify epidermal proliferation.

To accept human skin transplanted to the congenitally athymic (nude) mouse as a system to study human skin and its physiologic and pathologic states, it must be demonstrated that skin so maintained retains its function as a biologic unit. We have found that responses of grafted human skin and nude mouse skin to various agents differ. This difference in response has been utilized to assess barrier function and proliferative capacity of human skin grafts. Human skin grafts undergo a proliferative response when 10 ng of the tumor promoter, 12-O-tetradecanoyl phorbol 13-acetate (TPA) is applied. Nudes do not respond to this dose. Increasing the dose to 100 ng of TPA evokes a response in both. However, only in the human skin grafts can this response be blocked with betamethasone valerate (BV). In that human skin grafts do not take on their hosts' responsiveness, and the response of domestic pig skin to these agents before and after grafting is identical, the conclusion is reached that human skin appears to retain its inherent biologic unit function. The data also demonstrate some of the potential of this system to study kinetics of the epidermis of human skin.

Animals↗
PubMed1981

Involved and uninvolved skin from psoriatic subjects: are they equally diseased? Assessment by skin transplanted to congenitally athymic (nude) mice.

A highly significant, but unanswered, question in the pathogenesis of psoriasis relates to how normal appearing and diseased skin can coexist, undergo spontaneous flares and remissions, and yet appear to be genetically acquired. A plausible explanation for these disparate observations is that there is a basic defect in epidermal proliferation of skin of subjects with psoriasis and that disease expression is governed by other host factors. To address this question, we compared epidermal proliferation of skin involved and uninvolved with psoriasis with normal skin before and after transplantation to congenitally athymic (nude) mice, a biologic milieu free of humoral factors unique to the donor host. Results demonstrated that (a) before transplant, synthesis of DNA by the epidermal cells from skin uninvolved and involved with psoriasis is significantly higher than normal, 1.6 and 3.6 times, respectively; (b) 6 wk after transplantation, synthesis of DNA by epidermal cells is unchanged for normal skin, increased for uninvolved skin, and decreased for involved skin. These increases and decreases are of such a magnitude that at 6 wk the number of epidermal cells synthesizing DNA per 1,000 basal cells is identical, and is 2.2 times that of normal skin. When removed from the milieu of the afflicted host, skin involved and uninvolved with psoriasis appear equally "diseased." These data support the notion that there is aberrant epidermal proliferation in skin of patients with psoriasis and that host factors appear to play a role both in the expression and nonexpression of this disease.

Adult↗
PubMed1980

Epidermal proliferation of nude mouse skin, pig skin, and pig skin grafts. Failure of nude mouse skin to respond to the tumor promoter 12-O-tetradecanoyl phorbol 13-acetate.

Human skin transplanted to nude mice offers a possible experimental system for the study of normal epidermal proliferation and differentiation, and for their pathological counterparts. Crucial to the development of such a system is the demonstration that such grafts retain the responsive features of donor skin. To document that donor proliferative characteristics are maintained in the grafts, a comparative analysis of agents that induce proliferation was made on skin of mice homozygous and heterozygous for nude, on pig skin, and on pig skin transplanted onto nude mice. A wave of epidermal proliferation could be induced in pig skin and pig skin grafted onto nude mice, but not in nude mouse skin after the topical application of 10 ng 12-O-tetradecanoyl phorbol 13-acetate (TPA). A 10-fold greater concentration of TPA or 5% croton oil induced proliferation in all species of epidermis studied. Mice, heterozygous for nude, showed a normal response to 10 ng TPA, suggesting that the ability to respond to TPA may be related, in part, to a recessive genetic trait. Nude mouse skin transplanted to a heterozygous littermate capable of responding to 10 ng TPA does not respond. These observations argue that: the graft retains its donor proliferative characteristics when transplanted to the nude, and the inability of the nude mouse to respond to lower doses of TPA may be related to absorption, the nude gene(s), or an inherent threshold to response. The lack of response to the promoter TPA provides a plausible explanation for the decreased incidence of tumors arising in nude mice during two-stage carcinogenesis experiments.

Animals↗