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Biomedical subjects

J B Grogan

Publications and source records attributed to J B Grogan.

At least 37 records · Page 2Linked to original sources
PubMed1989

Experimental small-bowel transplantation: alternative strategies for graft prolongation.

Alternative combined immunosuppressive therapy was tested in canine orthotopic bowel transplantation. Despite sporadic long-term survival, cyclosporine is still questionably effective. Triple-drug therapy (cyclosporine, azathioprine, and prednisone) combined with antilymphocyte serum or with a short segment graft was effective in reducing the early postoperative mortality due to acute rejection but did not alter the long-term survival rate. There was no apparent relationship between the serum cyclosporine levels and survival. The long-term survivors (longer than 100 days) maintained relatively low serum trough levels of cyclosporine. These suggest that orthotopic bowel transplantation in the dog, and probably in the human as well, requires improved immunosuppressive regimens.

Animals↗
PubMed1989

A successful model of small bowel autotransplantation in the dog.

Experimental small bowel transplantation has continued to be a complex procedure with high mortality. We investigated the technical aspects of small bowel transplantation in an effort to define a procedure that would result in an improved survival rate. Three methods of graft harvesting were examined in a model of canine small bowel autotransplantation. Harvesting the graft by first flushing with room-temperature lactated Ringer's followed by iced lactated Ringer's resulted in the best preservation and subsequently the best survival rate (71%). Flushing with iced lactated Ringer's alone resulted in survival rates of 22 and 50% in two additional groups. We also investigated two methods of graft reanastomosis. Although either venous drainage regimen appears to be suitable, graft venous reanastomosis to the host portal vein resulted in a slightly higher postoperative weight than reanastomosis to the host inferior vena cava. A model of small bowel transplantation with a high long-term survival rate has been developed. This model can now be applied to studies of the various physiological aspects of small bowel transplantation.

Animals↗
PubMed1988

Glutaraldehyde-preserved venous valve transplantation in the dog.

Transplantation of femoral vein grafts was performed on 33 mongrel dogs to assess graft patency and valvular function after storage in glutaraldehyde. The grafts were removed from the donor, flushed with room temperature heparinized lactated Ringer's solution, and then stored in a 0.2% glutaraldehyde solution for 16 hr. At the time of grafting, the veins were again flushed with lactated Ringer's and anastomosed orthotopically to the recipient. An arteriovenous fistula was also created. Postoperatively the animals received daily doses of aspirin (2 mg/kg) and dipyridamol (50 mg). The following groups were studied: Group I (n = 10) served as controls and received fresh autografts. Group II (n = 13) received autografts stored for 16 hr in 0.2% glutaraldehyde. Group III (n = 10) received allografts stored similarly in glutaraldehyde for 16 hr. The grafts were monitored for evidence of patency. All grafts were removed for histological evaluation when patency was no longer detected or at the end of 7 weeks. Of the fresh and glutaraldehyde-preserved autografts (Group 1), 100% were patent at 7 weeks, and generally retained valve function. Patency of allografts was only slightly inferior but valve function was disappointingly poor at 7 weeks.

Animals↗
PubMed1988

Profound suppression of lymphocyte function in early biliary obstruction.

The blastogenic response to mitogens was studied in spleen and lymph node cells from four groups of Lewis rats at 1 to 2, 3 to 5, 6 to 9 and 10 to 14 days, respectively, after common bile duct ligation (CBD) or sham celiotomy (SC). Suppression in the splenocytes' mitogenic response to concanavalin A and phytohemagglutinin was noted as early as 3 days after common bile duct ligation. The response remained suppressed during the period of observation. Lymph node cells manifested a suppressed response to concanavalin A and phytohemagglutinin after 4 days of jaundice. No alteration in splenocyte response to lipopolysaccharide was observed. There was no correlation with the level of serum bilirubin.

Animals↗
PubMed1988

Twelve-hour and twenty four-hour preservation of small bowel allografts by simple hypothermia. Survival utilizing cyclosporine.

Canine small bowel was harvested and stored by simple hypothermic technique. After 12- and 24-hr storage, respectively, the small bowel graft was allotransplanted into recipients. All animals receiving 12-hr stored grafts (n = 9) survived beyond 5 days. In the 24-hr storage group, 67% of the animals (n = 9) survived beyond 5 days. Successful storage for such extended periods by simple hypothermia has not been achieved previously. Donor pretreatment with antibiotics as well as extensive intraluminal irrigation of the harvested small bowel are considered to be important technical features in this successful preservation.

Animals↗
PubMed1988

Long-term survival of orthotopic bowel allografts in the rat treated with short-term low-dose cyclosporine.

Orthotopic bowel transplantation continues to be a "difficult" procedure, both experimentally and clinically, despite the advent of cyclosporine. Even with high-dosage CsA administration, long-term survival has been sporadic and short-term mortality high. In the present study, a low-dosage CsA regimen (5 mg/kg/day for 2 weeks postoperatively) produced prolonged survival in BN-Lewis donor/recipient combinations utilizing an orthotopic bowel transplantation model with portal venous anastomosis. The transplanted bowel continued to survive despite the lack of maintenance dosage after initial induction. The recipient animals evinced donor-specific hyporesponsiveness as donor skin grafts were rejected in a slow, indolent fashion. Third-party skin grafts acutely rejected in normal fashion. It was remarkable that the bowel grafts continued to survive in good condition despite the rejection of donor-specific and nonspecific challenging skin grafts placed on the animals. The precise mechanism of this donor-specific hyporesponsiveness is not known.

Animals↗
PubMed1988

Orthotopic nonauxiliary total bowel transplantation using rats: technical procedure.

A procedure for nonauxiliary orthotopic total bowel transplantation is described, in which the graft from jejunum to distal colon is transplanted with portal venous drainage in end-to-end fashion in a one-stage procedure. The early postoperative mortality (within 4 days) was 23.8% in this study and presently is approximately 20% in our laboratory. It is noteworthy that the incidence of venous thrombosis is very low in this model. Continuous venous infusion, vascular perfusion, and luminal irrigation with Euro-Collins solution were employed in this preparation. The technique described is expected to prove useful for orthotopic nonauxiliary bowel transplant investigation because of its technical simplicity, low early postoperative mortality, and low incidence of vascular complications.

Animals↗
PubMed1987

Total orthotopic small bowel transplantation with cyclosporine.

The efficacy of immunosuppression including intravenous cyclosporine was assessed in a dog model of total orthotopic small bowel transplantation. Without immunosuppression, allografted animals died before the thirteenth postoperative day. Cyclosporine and prednisone therapy afforded a sixfold increase in survival of allografted animals. Bowel preparation, such as ex-vivo irradiation, treatment of the donor animal with antithymocyte globulin (ATG), or bowel preservation, did not appear to affect survival. However, a preliminary study of combination therapy using azathioprine, ATG, prednisone, and cyclosporine indicated that there were fewer early deaths as compared with other groups. Histologically, allografted bowel showed various degrees of mucosal change to which poorer nutritional aspects were attributed. "Intestinal death" caused by rejection was considered to be the principal cause of death in animals with advanced mucosal changes, in particular those who were long-term survivors. However, other debilitating factors (e.g., superimposed infection, endotoxemia, or possibly graft-versus-host reaction) may be present in nonsurvivors demonstrating fewer pathological changes in the graft.

Aged↗
PubMed1987

Total orthotopic small bowel allotransplantation in the dog. Features of atypical rejection and graft-versus-host reaction.

The critical histologic review of our experience with small bowel allotransplantation in the dog is presented. While "classical" rejection with dense small cell infiltration and mucosal destruction does occur, more common is the "atypical" rejection reaction in which cellular infiltration is sparse. This "atypical" rejection was characterized by a significant decrease of mucosal epithelial structures with increased mitotic figures in crypt cells and frequent vascular changes, including segmental fibrinoid necrosis and thrombosis with or without overlying mucosal destruction. Substantial regenerating capacity of bowel mucosa tends to compensate for the destruction, complicating the histology. The host lymph nodes and spleen present a histologic picture highly suggestive of GVH reaction. The reduction in host lymphocytes in these organs from karyorrhexis with replacement by histiocytes and subsequently by plasma cells is described. It is emphasized that rejection and GVH are not mutually exclusive and occur simultaneously. The decrease of functional mucosal mass could well account for the nutritional malsequelae. Also, the weakening of immune structures on the host and the graft side may predispose to catastrophic enterogenous infections, perhaps explaining the large number of animals that die without overt signs of rejection following small bowel transplantation.

Animals↗
PubMed1987

Suppressed cellular cytotoxic response in rats bearing skin implants in the anterior chamber of the eye.

The ability of allogeneic skin implants placed into the anterior chamber of the eye to elicit splenic cell cytotoxicity was studied in Le rats. No cellular cytotoxicity was detected in the rats bearing either small (0.5 mm2) or massive (greater than 5 mm2) skin implants, but the injection of allogeneic splenocytes into the anterior chamber readily induced cytotoxic spleen cells. Since the presence of an allogeneic skin implant in the anterior chamber appeared to suppress the production of host cytotoxic cells, studies were performed to determine whether the host's cellular cytotoxic response to an orthotopic allogeneic skin graft could be suppressed by the presence of the implant. It was found that the production of splenic cell cytotoxicity was severely suppressed in rats that were implanted 8-21 days before receiving an orthotopic skin graft from the implant donor strain. No suppression occurred if the implant and the skin graft were performed on the same day. The suppression was specific for the alloantigens present on the implant in the anterior chamber because third party implants did not suppress cytotoxicity. It appears that alloantigen presentation via the anterior chamber of the eye can modulate the host's cellular immune response to systemically administered alloantigens.

Animals↗
PubMed1986

Depressed host response to skin implants in the anterior chamber of the eye.

Immune alterations in the host following alloantigenic skin implantation into the anterior chamber (AC) of the eye were studied in inbred rats. Splenocytes from implant-bearing rats showed significantly reduced mixed lymphocyte culture (MLC) reaction. The reduced response was consistently evident when the implant was viable in the AC, indicating a constant presence of antigen is needed for elicitation of suppressed MLC responses. No comparable suppression was achieved when host sensitization was mediated by other routes. Low dose cyclophosphamide (CP) and enucleation (removal of implant) resulted in loss of suppression of MLC reactivity, indicating a role of suppressor cell involvement. These observations are compatible with the hypothesis that the presentation of alloantigen via AC results in profound immunological alterations of the host.

Animals↗
PubMed1985

Cell-mediated immunity in rats bearing allogeneic skin in the anterior chamber of the eye. I. Response to mitogens.

Early studies have indicated that presentation of donor antigen via the anterior chamber (AC) of the eye diminished the host's ability to react immunologically in vivo. In the present study this reduced immunological activity has been studied in vitro. Compared to spleen cells from control rats, the spleen cells from Lewis rats bearing Brown Norway skin implants in the AC had a mild but consistently reduced in vitro blastogenic response to phytohemagglutinin 10-35 days postimplantation. Either a normal or slightly greater than normal response occurred thereafter. The implant-induced suppression of the mitogenic stimulation was evident only in splenocytes; lymph nodes and thymic lymphocytes from AC-implanted rats responded similarly to controls. The suppressed mitogenic reactivity appears to be specific for the T-cell population since the stimulation in the presence of lipopolysaccharide was no different from that in controls. Furthermore, the reduced activity was greatly enhanced in the T-cell-enriched population. These results suggest that allogeneic skin placed in the AC of the eye depresses the immune activity of the host's splenocytes which may contribute to the privileged nature of the anterior chamber.

Animals↗
PubMed1985

Stimulating effect of fructose 1-6 diphosphate on the phagocytic function of rat RES and on human leukocyte carbohydrate metabolism.

The phagocytic behavior of the reticuloendothelial system in the rat was assessed by a quantitative technique following fructose-1,6-diphosphate (FDP) administration. In addition, the effect of FDP on the carbohydrate metabolism of human leukocytes was investigated. The rate of colloidal carbon clearance from the blood was increased significantly in the FDP-treated rats as compared to dextrose and saline controls (p less than 0.001). FDP also attenuated the hepatic decrease of ATP (p less than 0.005) and creatine phosphate (p less than 0.005) that has been observed after intravenous administration of colloidal carbon. Carbohydrate metabolism in human leukocytes was enhanced by FDP, with a concomitant increase in ATP content (p less than 0.001). Experimental evidence suggests that FDP intervenes in the Embden-Meyerhof pathway both as a metabolic regulator and as a high energy substrate. These properties of FDP in stimulating the carbohydrate metabolism have recently been described in man.

Adenosine Triphosphate↗
PubMed1985

Antigen nonspecific rejection of allogeneic skin implants in the anterior chamber of sensitized rats.

As expected, skin implants placed in the anterior chamber of the eye of rats systemically sensitized with alloantigen from the antigen specific (second party) donor implants are rapidly rejected, indicating that the anterior chamber offers no barrier to the efferent immune response. However, during our studies it was noted that antigen nonspecific (third party) skin implants placed in the anterior chamber of the eye of similarly sensitized rats were also rejected in accelerated fashion. In all of the donor-recipient rat strain combinations tested which were sensitized by orthotopic skin grafts, third party skin implants placed in the anterior chamber of the eye were rejected within 14 days. A similar rejection pattern was noted in the anterior chamber of rats that were sensitized by the foot pad injection of graded doses of RT1 incompatible spleen cells. Rats sensitized with mouse skin grafts also rejected RT1 histoincompatible allogeneic implants within the anterior chamber, a result not noted in rats sensitized with either dog, rabbit, or pig skin grafts.

Animals↗
PubMed1985

Augmentation of suppression in cyclophosphamide-treated rats bearing allogeneic skin implants in the anterior chamber of the eye.

This study shows that alloantigen presentation via the anterior chamber (AC) of the eye coupled with a single high dose cyclophosphamide (CP) (100 mg/kg) treatment effectively suppresses the skin graft rejection reaction of the recipient. Lewis (Le) rats bearing allogeneic Brown Norway (BN) skin implants in the AC of the eye demonstrate a modest increase in the survival time of orthotopic BN skin grafts. A slight prolongation of the survival of orthotopic BN skin grafts was also demonstrated in nonimplant or syngeneic implant-bearing Le recipients which received a single injection of a large dose of CP. Augmentation of suppression was evident in rats which were treated with a single dose of 75 mg/kg CP but not 25 mg/kg. The augmentation of suppression was evident when CP treatment and skin grafting of the recipient occurred on either 0, 7, or 14 days postimplantation. Recipient splenectomy did not interfere with the augmentation of suppression.

Animals↗