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Biomedical subjects

J B Grogan

Publications and source records attributed to J B Grogan.

At least 55 records · Page 3Linked to original sources

Experimental small bowel transplantation utilizing cyclosporine.

Cyclosporine prolonged the survival of ectopic small bowel allografts in a canine model. A 9-fold increase in mean survival as compared with controls was obtained. Addition of prednisone to cyclosporine did not result in further graft prolongation, but improved the gross and histological appearance of the allograft. Monitoring the motility and histology of the allograft appears to be useful in predicting approaching rejection. Xylose absorption was not helpful in this regard. A new technique for measuring fat absorption in the transplant is described. Following allografting, fat absorption is resumed by 14 days posttransplantation.

Animals↗

T-lymphocyte analysis in the early diagnosis of adult respiratory distress syndrome.

Adult respiratory distress syndrome occurs concomitantly with a number of clinical conditions but has no known cause. At present, there is no generally acceptable method for establishing the early diagnosis. In the course of studying immune aberrations by means of monoclonal antibody staining and fluorescence-activated cell sorting in injured patients, we noted an apparent specific T-lymphocyte response to this syndrome in one patient. There was an increase in suppressor T-cells and a decrease in helper/suppressor T-lymphocyte ratio (normal = 1.57). When the patient recovered, the helper/suppressor ratio rose to above 3.0. T-lymphocyte analysis offers a promising means of evaluating patients considered highly susceptible to adult respiratory distress syndrome, i.e., victims of massive trauma. Further studies will be required to fully elucidate this possibility.

Adult↗

Immunoregulation by antigenic stimulation via the anterior chamber of the eye.

The presentation of alloantigen to the host via the anterior chamber of the eye can alter the host's immune response. Spleen cells from Lewis rats bearing Brown Norway skin implants in the anterior chamber demonstrated a mildly depressed in vitro blastogenic response to MLC and to PHA stimulation 7-28 days after implantation, a normal response by 35 days, and a slightly greater than normal response by 42 days after implantation. In addition, serum from rats bearing implants for 7-24 days demonstrated a significant depressant effect on the blastogenic response of normal spleen cells to MLC and to PHA stimulation, but the "blocking" effect was absent by 42 days postimplantation. These results indicate that antigen presentation via the anterior chamber of the eye can produce a state of active immunosuppression within the host which could contribute to the privileged nature of the anterior chamber of the eye.

Animals↗

Polymorphonuclear leukocyte function in cancer patients treated with total body hyperthermia.

This study was performed to determine if the ingestive and bactericidal capacity of peripheral blood polymorphonuclear leukocytes (PMN) was altered in cancer patients treated with total body hyperthermia (TBH). TBH of either 41.5 or 42.0 C was induced and maintained for periods up to 6 hours by extracorporeal circulation of the patient's blood through a very sensitive temperature regulating device via a shunt in the patient's leg. In vitro studies performed at 37 C showed that the bactericidal capacity of the PMN from cancer patients was initially generally lower than values obtained from control individuals, but most of the patients' PMN exhibited an increased bactericidal capacity following TBH. Function was not diminished by multiple hyperthermia treatments. Similar studies performed in vitro at 42 C showed that the bactericidal capacity of PMN from both control individuals and cancer patients was significantly less than those obtained at 37 C. These data indicate that the bactericidal capacity of peripheral blood PMN may be transiently increased after TBH, but during the period of elevated temperature, the phagocytic process may be retarded.

Body Temperature↗

Transient defect in the bactericidal capacity of rabbit alveolar macrophages following sublethal shock.

The phagocytic function of alveolar macrophages obtained from rabbits after they were given sublethal shock by tumbling in a modified Noble-Collip drum was studied. As compared to the phagocytic function of alveolar macrophages from normal rabbits, tumbling produced a statistically significant reduction in in vitro bactericidal capacity for both Pseudomonas aeruginosa and Escherichia coli. However, there was no alteration in the ingestive phase. The reduced bactericidal capacity was evident within 15 minutes after the stress, but the bactericidal capacity had returned to normal in rabbits that were allowed to recover for 24 hours before the studies were performed.

Animals↗

Suppression of graft-versus-host reactions in rats bearing implants in the anterior chamber of the eye.

The graft-versus-host (GVH) response of spleen cells from rats bearing either orthotopic skin grafts or allogeneic implants in the anterior chamber of the eye was evaluated using popliteal lymph node (PLN) assay. When a viable implant remained in the anterior chamber, the spleen cells of these rats produced a popliteal lymph node enlargement in F1 hybrids which was approximately 50% of that produced by a similar number of cells from a normal animal. Conversely, the GVH response of spleen cells from orthotopically skin-grafted rats was noted to be significantly increased over the response of spleen cells from normal animals. The decrease in the GVH response of implanted rat spleen cells was a specific reaction and not because of trauma or implantation, since spleen cells from rats bearing syngeneic implants had shown no reduction in their GVH-inducing ability. The PLN weights of rats receiving mixed population of normal and implanted rat spleen cells were always less than the weights observed with an equal number of normal spleen cells. These findings permit the assumption that implant-bearing rats may be lacking or low in cells that induce GVH reactions or that there is a delayed conversion of effector cells after early immune recognition.

Animals↗

Host response to allogeneic implants in the anterior chamber of the rat eye.

The anterior chamber of the eye has long been considered an immunologically privileged site, but the nature of this privilege has been re-examined recently. In our study, we used rats with defined genetic differences as the donors and the recipients. Implants were from split-ear sections, and the host response was measured both in vivo, by implant survival time, and in vitro, by the mixed-leukocyte reaction and the 51Cr-release cytotoxicity assay. Controls consisted of syngeneic implants and allogeneic orthotopic skin grafts. This study has shown that (1) host sensitization occurs approximately 7 days after implantation, (2) cytotoxic effector cells are produced by day 14, with a peak on day 21, (3) implant survival time is long in spite of the presence of competent effector cells, and (4) the survival time of implants is directly related to the degree of genetic histoincompatibility. The reasons for the long implant survival in hosts with a demonstrable immune reactivity has not been established, but the survival time appears to be related to the route of sensitization (vascular rather than lymphatic), which lends itself to the production of serum blocking factors and the procurement of supressor T cells.

Animals↗

Orthotopic skin graft survival in rats that have harbored skin implants in the anterior chamber of the eye.

Allogeneic tissue implantation to the anterior chamber of the eye indicated that the host response varies with the size of the implant. Small implants (0.5 mm2) placed in the anterior chamber prolonged the survival of subsequent orthotopic skin allografts across major histocompatibility differences. In contrast, large implants (2.0 mm2) accelerated the rejection of specific skin grafts. The observed delay in graft rejection of small implant-bearing rats was specific to the implant donor, since the third-party unrelated skin grafts on these animals showed neither increase nor decrease in survival times.

Animals↗

Immunologic study of the brain as a privileged site.

A number of experimental findings reported here indicate that the brain functions as a privileged site not because of an afferent arc blockade, as hitherto thought, but because of an efferent arc blockade, with some afferent arc delay. There appears to be a quantitative deficiency in the efferent arc, but a qualitative defect is not ruled out. Implants survive four times as long in the brain as in the anterior chamber.

Animals↗

Altered neutrophil phagocytic function in burn patients.

Neutrophil ingestion and bactericidal capacity were studied in 35 burn patients. Using Pseudomonas aeruginosa as the test microorganism, it was found that defects in bactericidal capacity were common, particularly in phagocytes of patients with burns greater than 30% of the body surface. Even though reduced neutrophil ingestion was observed in a significant number of assays the incidence was low in comparison to the incidence of reduced bactericidal capacity. Defects in phagocytic function were not detected until at least 5 days after injury and at the time of discharge all patients that were studied had resumed normal phagocytic function.

Blood Bactericidal Activity↗

Suppressed in vitro chemotaxis of burn neutrophils.

A comparison of the chemotactic response of peripheral blood neutrophils between burn patients and control individuals was performed. Beginning approximately 5 days postburn a decreased chemotactic response of neutrophils from burned patients was noted. The most severely reduced chemotaxis was noted in the burn patients who died. No evidence of a burn serum factor which inhibited the chemotactic response of control neutrophils was found in this study.

Adolescent↗

Pseudomonas aeruginosa infection in mice after treatment with cyclophosphamide.

This study attempted to determine if the antineoplastic alkylating agent, cyclophosphamide (Cytoxan), altered the host response to Pseudomonas aeruginosa infection in mice. The effect of cyclophosphamide was evaluated by an increased mortality or enhanced bacterial growth in the liver, lungs, spleen, and kidneys. The mice that were treated with either single or multiple doses of 25 mg/kg cyclophosphamide showed no increase in mortality, nor did they exhibit an enhanced localization of P aeruginosa in any of the organs studied. Higher dose levels of cyclophosphamide produced a statistically significant increase in mortality and greater distribution of bacteria in the mouse organs, but there appeared to be no organ that was particularly susceptible to infection.

Animals↗