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Biomedical subjects

S F Oluwole

Publications and source records attributed to S F Oluwole.

At least 73 records · Page 4Linked to original sources
PubMed1992

Intestinal allograft survival in the rat following pretreatment with donor-specific UV-B-irradiated leukocytes and peritransplant immunosuppression with cyclosporine.

Previous studies from our laboratory showed that pretreatment with ultraviolet-B-irradiated donor leukocytes (UV-B DL) combined with brief peritransplant cyclosporine (CyA) resulted in indefinite survival of Wistar/Furth rat cardiac allografts in Lewis recipients. This study was designed to examine the effect of pretransplant UV-B DL with or without peritransplant CyA on orthotopic intestinal allografts in the same rat strain combination. The results showed that while low-dose CyA treatment alone (10 mg/kg i.m. on days 0, +1, and +2) had no effect on intestinal allograft rejection, 20 mg/kg (on days 0, +1, and +2) CyA significantly (P less than or equal to 0.001) prolonged graft survival, with 33% of the hosts surviving indefinitely. The highest dose of CyA (30 mg on days 0, +1, and +2) abrogated rejection, but most transplant recipients succumbed to infection and functional ileus due to a toxic side effect of CyA. Pretreatment with UV-B DL on days -14 and -7 alone did not prolong intestinal allograft survival. Combination of a subtherapeutic CyA dose (20 or 10 mg/kg) given on days 0, +1, and +2 with pretransplant UV-B DL on days -14 and -7 did not alter the survival of intestinal allografts compared to treatment with CyA alone. This suggests that pretreatment with UV-B DL with or without peritransplant administration of CyA has no effect on intestinal allograft survival, in contrast to the effect of such combined treatment on cardiac allograft survival, where indefinite graft survival is observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Differential effects of pretreatment with ultraviolet-B modified or unmodified donor-specific leukocyte transfusions on intestinal and cardiac allograft survival in the rat.

This study compares the effects of pretreatment with donor-specific leukocytes (DL) or UV-B irradiated donor-specific (UV-B DL) transfusion on day -7 relative to organ transplantation, in the induction of specific immunologic unresponsiveness to intestinal and cardiac allografts in the Lewis-to-ACI rat strain combination. Recipients of orthotopic small intestinal allografts, who were pretreated with UV-B DL survived for 7.2 +/- 3.6 days compared with 7.5 +/- 0.5 days in the control group. Pretreatment with unmodified DL induced hyperacute rejection of intestinal allografts, suggesting a sensitizing effect of DL in this model. In contrast, pretreatment with DL and UV-B DL transfusions significantly prolonged cardiac allograft survival with 25% (DL) and 50% (UV-B DL) of the grafts surviving indefinitely (greater than 120 days). To define the underlying mechanisms of the differential effects of DL and UV-B DL pretreatment on intestinal and cardiac allograft survival, we evaluated the ability of DL and UV-B DL transfusions to induce alloantibodies and donor-directed cytotoxic T lymphocytes (CTL). The finding that recipients of DL developed donor-specific cytotoxic alloantibodies and CTL may partially explain the accelerated rejection of intestinal allografts in such recipients while the disparity of the findings in cardiac and intestinal transplantation may be due to a higher affinity of the induced cytotoxic alloantibodies to antigens on the intestine than on the heart. Since UV-B DL pretreatment prevents the induction of cytotoxic alloantibodies and CTL, there is a significant difference in recipients transfused with DL as compared with UV-B DL. The proliferative response to donor alloantigens (MLR) of lymphocytes obtained from DL and UV-B DL pretreated animals was down-regulated as compared with the MLR response of lymphocytes obtained from unmodified animals. Subsequent coculture experiments demonstrated the appearance of suppressor cells following pretreatment with DL and UV-B DL. While DL and UV-B DL transfusions significantly increased cardiac allograft survival, there was no prolongation of intestinal allografts in our model despite the abrogation of the sensitizing effect of DL transfusions by prior UV-B irradiation. These differential effects on graft survival emphasize the importance of specific organ immunogenicity.

Animals↗
PubMed1992

Induction of stable chimerism and transplantation tolerance to rat islet and heart allografts by ultraviolet-B modulation of bone marrow cells.

Ultraviolet-B irradiation (UV-B) (700 J/m2) of BM cells prior to transplantation into lethally gamma-irradiated (1050 rads) allogeneic rats prevents the development of GVHD and results in stable chimerism. This study was developed to determine if UV-B modulation of BMT is useful for preconditioning recipients for the induction of tolerance to donor islets and heart allografts. Lethally irradiated Lewis rats that received UV-B irradiated (700 J/m2) WF BMT (10(8) BM cells) demonstrated stable chimerism without any evidence of GVHD. The stable Lewis chimeras were made diabetic with streptozotocin (STZ) at 28-35 days after BMT and subdivided into 3 experimental groups that received 1000-1200 islets from WF, Lewis, or BN (third-party), respectively. The results showed that group I diabetic Lewis chimeras accepted permanently (greater than 300 days) BM donor WF islets and became normoglycemic. When 3 of 6 Lewis chimeras transplanted with WF islets were rechallenged with WF hearts 60 days after islet grafts, they accepted both islets and cardiac allografts permanently (greater than 240 days). Similarly, the remaining 3 animals accepted Lewis cardiac allografts permanently, thus indicating tolerance to both donor and recipient alloantigens. Group II diabetic chimeras accepted permanently (greater than 300 days) recipient (Lewis) islets. In contrast, group III chimeras rejected acutely (7-8 days) third-party (BN) islets. However, when these animals that rejected BN islets and again became diabetic were retransplanted with BM donor-type (WF) islets, they became permanently normoglycemic (greater than 200 days). This finding emphasizes the specificity of the induction of tolerance in this model and the apparent lack of organ-specific sensitization. To define the underlying mechanism of tolerance, in vivo adoptive transfer of 10(8) spleen cells to naive Lewis or WF recipients, obtained from tolerant Lewis chimeras carrying donor islets and heart allografts, showed no prolongation of cardiac allografts in the unmodified syngeneic hosts, thus questioning the role of suppressor mechanisms in the tolerant rats. Furthermore, cells from the tolerant chimeras that showed no mixed lymphocyte reaction (MLR) response to Lewis or; WF alloantigens failed to suppress anti-Lewis and anti-WF MLR-response in coculture MLR. These results suggest that tolerance to donor alloantigens in the UV-B BMT model is most likely due to selective elimination of anti-BM donor helper or effector cell precursors (clonal deletion) rather than induction of suppressor cell activity. This study demonstrates that this relatively simple and effective approach to modulation of T cells in BM treatment may be potentially useful in the induction of tolerance to donor organs.

Animals↗
PubMed1991

Migration patterns of dendritic cells in the rat: comparison of the effects of gamma and UV-B irradiation on the migration of dendritic cells and Lymphocytes.

To further define the underlying mechanisms of immune suppression induced by UV-B irradiation, we have examined the kinetics of homing patterns of in vitro UV-B-irradiated and gamma-irradiated-thoracic duct lymphocytes (TDL) compared to dendritic cells (DC). Our findings show that 111In-oxine-labeled TDL specifically home to the spleen, liver, lymph nodes, and bone marrow with subsequent recirculation of a large number of cells from the spleen to lymph nodes. In contrast, DC preferentially migrate to the spleen and liver with a relatively insignificant distribution to lymph nodes and an absence of subsequent recirculation. Splenectomy prior to cell injection significantly diverts the spleen-seeking DC to the liver but not to the lymph nodes, while the homing of TDL to lymph nodes is significantly increased. In vitro exposure of 111In-oxine labeled TDL to gamma irradiation does not significantly impair immediate homing to lymphoid tissues but inhibits cell recirculation between 3 and 24 hr. In contrast, gamma irradiation does not affect the tissue distribution of labeled DC, suggesting that DC are more radioresistant to gamma irradiation than TDL. Unlike the findings in animals injected with gamma-irradiated cells, UV-B irradiation virtually abolished the homing of TDL to lymph nodes and significantly reduced the homing of the spleen-seeking DC to the splenic compartment while a large number of cells were sequestered in the liver. The results of in vitro cell binding assay show that TDL, unlike DC, have the capacity to bind to high endothelial venules (HEV) within lymph node frozen sections while gamma and UV-B irradiation significantly inhibit the binding of TDL to lymph node HEV. These findings suggest that: (i) DC, unlike TDL, are unable to recirculate from blood to lymph nodes through HEV; (ii) although gamma irradiation impairs TDL recirculation, it does not affect DC tissue distribution; and (iii) UV-B irradiation impairs both TDL and DC migration patterns. We conclude that the lack of capacity of irradiated TDL to home to lymph nodes is due to damage to cell surface homing receptors and that the failure of DC to home to the lymph node microenvironment is related to the absence of HEV homing receptors on their cell surface.

Animals↗
PubMed1991

Mechanical and electrophysiologic changes in rat cardiac allografts during immunologic rejection.

We studied the relationship between immunologic rejection and changes in contractility of isolated perfused papillary muscle, using heterotopically transplanted rat hearts. Rejection assessed by mononuclear cell infiltration was associated with depressed twitch amplitude and lower rates of tension development and relaxation. The relationship between maximum developed tension and [Ca2+]o was attenuated in muscle from the rejecting allografted heart, as compared with muscle of normal or isografted hearts. To determine the effects of rejection on ventricular electrophysiologic properties, we recorded transmembrane action potentials in isolated ventricular myocardium. We found that in rejecting allografted hearts the resting potential, action potential amplitude, and maximum upstroke velocity of phase zero were significantly reduced compared with normal and isografted hearts. The attenuation in the mechanical and electrophysiologic properties was largely prevented by treating the transplanted rat with anti-lymphocyte-globulin on days 0, 1, and 2 after transplantation. In summary, the present study demonstrates that immunologic rejection of the heterotopically allotransplanted rat heart is associated with marked attenuation of both mechanical and electrophysiologic properties of the ventricular myocardium.

Action Potentials↗
PubMed1991

Serum thyroglobulin autoantibody titres and immunoglobulin concentrations in Nigerians with goitre.

Using the tanned turkey red blood cell haemaglutination test, blood samples from 327 Nigerians with goitre were screened for the presence of thyroglobulin autoantibody. 15 (4.6%) were found to have significantly positive autoantibody titres while none of the 50 age and sex-matched normal controls and autoantibody. Of the 15 with significantly positive thyroglobulin autoantibody titres, only 2 were males, giving a male:female ratio of 1 to 6.5. The mean serum concentration of IgG in the positive cases (4,163 +/- 53.5 mg/100 ml) was significantly higher than either that of normal controls (3,044 +/- 147.6 mg/100 ml) of goiterous subjects with no thyroglobulin autoantibody (2,196 +/- 116.5mg/100ml). It was found that thyroglobulin autoantibody is an IgG immunoglobulin. It is concluded that autoimmune thyroid disease occurs in Nigerians with goitre and that females are affected more than males.

Adolescent↗
PubMed1990

Prevention of GVHD by modulation of rat bone marrow with UV-B irradiation: II. Kinetics of migration of UV-B-irradiated bone marrow cells in naive and lethally irradiated rats.

UV-B irradiation (700 J/m2) of bone marrow (BM) cells prior to transplantation into lethally gamma-irradiated (1050 rad) allogeneic rats prevents the development of GVHD and results in a stable mixed lymphohematopoietic chimerism. To better understand the underlying mechanisms of the development of stable radiation chimeras in this model, this study was designed to examine whether the dose (700 J/m2) of UV-B irradiation used for the modulation of the BM inoculum would affect the homing pattern of radiolabeled BM cells compared to that of thoracic duct lymphocytes (TDL) in the naive and lethally irradiated recipients. The results showed that intravenously administered, 111Indium-oxine-labeled, unmodified TDL home specifically to the spleen, lymph nodes, and BM compartments with a subsequent recirculation of a large number of cells from the spleen to the lymph nodes. In contrast, radiolabeled, unmodified BM cells migrate specifically to the spleen, liver, and BM with the lymph nodes, thymus, and nonlymphoid organs containing very little amounts of radioactivity. The stable concentrations of radioactivity in the lymphoid and nonlymphoid compartments between 3 and 72 hr after injection suggest that BM cells, unlike TDL, do not recirculate. The migration pattern of BM cells in the naive recipient was not significantly different from that seen in lethally irradiated animals except for the higher concentration of radioactivity in the spleen and BM of irradiated animals compared to that seen in naive recipients. The similarity of tissue localization of BM cells in naive or in irradiated syngeneic recipients to that of allogeneic recipients suggests that the homing of BM cells is not MHC restricted. Our findings of similarity between tissue localization of UV-B-irradiated labeled BM cells and unmodified BM cells in naive and lethally irradiated recipients suggest that a dose of 700 J/m2 of UV-B irradiation is not capable of impairing BM cell migration although it is sufficient to abolish the homing of TDL to the HEV-bearing organs. Thus, our results show that BM cells are less susceptible to cell damage by UV-B irradiation than lymphocytes thereby providing the rationale for ex vivo modulation (rather than elimination) of mature T-lymphocytes in the donor BM inoculum with UV-B irradiation. This relatively simple and effective approach to modulation of T-cells in donor BM inoculum may be potentially useful in preventing GVHD without endangering successful engraftment in larger animals and in man.

Animals↗
PubMed1990

Mn (III) hematoporphyrin. A potential MR contrast agent.

Manganese (III) hematoporphyrin (MnHP), a new and stable complex, was prepared, and its toxicity and magnetic resonance (MR) imaging properties were evaluated. In tests of acute and subacute toxicity, no deaths resulted from bolus intravenous injections of 13 or 19 mumols/kg of MnHP, but there was a 33% mortality when the dose was 38 mumols/kg. Laboratory results were normal in the surviving rats. Ultraviolet- visible spectroscopy of the urine and serum of two rats injected 24 hours previously with 38 mumols/kg MnHP revealed no free HP, suggesting in vivo stability of MnHP. Finally, using a standardized imaging protocol, there was a mean increase of 37% in the liver-to-muscle intensity ratios in four rats injected 24 hours previously with 25 mumols/kg MnHP when compared to paired controls (P less than .005). In addition, obvious visual increase in the signal intensity of the liver on T1-weighted images was seen in animals tested with 13 and 19 mumols/kg of MnHP. The results suggest that further evaluation of MnHP as an MR contrast agent for the liver is warranted.

Animals↗
PubMed1990

Interstitial class II-positive cell depletion by donor pretreatment with gamma irradiation. Evidence of differential immunogenicity between vascularized cardiac allografts and islets.

We used an allograft pretreatment regimen involving lethal total-body gamma irradiation of donor rats eight days prior to transplantation to compare directly the immunogenicty of immediately-vascularized heart allografts with isolated, neovascularized pancreatic islet allografts. TBI pretreatment of heart donors (IHT) caused a modest prolongation in cardiac allograft survival compared with controls in a low-responding fully-allogeneic strain combination, Lewis-to-ACI. The addition of 10(5) donor-type dendritic cells (DCs) at the time of transplantation reversed the prolongation of IHT in this strain combination. Donor pretreatment with TBI did not lead to prolonged cardiac allograft survival in either a high-responding combination, ACI-to-Lewis, or in an MHC class II-compatible strain combination, F344-to-Lewis. In contrast, islets from irradiated donors (IIT) showed markedly prolonged survival in both low-responding (Lewis-to-ACI) and high-responding (W/F-to-Lewis) strain combinations. The addition of 10(5) donor-type DCs to the islets at the time of transplantation caused the rejection of only two of six IIT in the Lewis-to-ACI combination. Combined pretreatment regimens involving TBI-pretreated cardiac allografts--such as recipient immunosuppression with peritransplant cyclosporine (10 mg/kg on days 0, 1, and 2) or the combination of TBI (1000 cGy on day -3) and cyclophosphamide (300 mg/kg on day -5) in a pretreatment regimen--did not lead to synergistic graft prolongation in the low-responding Lewis-to-ACI combination. Immunohistologic studies showed that eight days after TBI rat hearts and islet were both greater than 90% depleted of class II (0X6+) interstitial dendritic cells while class I (0X18+) expression was unchanged. IIT are able to increase class II expression when donors are treated with recombinant gamma interferon (4000 U/day on days -3, -2, and -1). MLR data showed that ACI recipients of Lewis IIT reacted normally to donor (Lewis) and third-party (W/F) stimulator cells greater than 100 days after transplantation. The apparent greater immunogenicity of heart allografts as compared with islets in this model could be due to (1) a quantitative difference between the number of residual class II-positive cells in hearts and islets or a greater nnon-MHC antigenic load in the heart grafts given its larger size, or (2) a quanlitative difference between hearts and islets due to the presence of a vascular endothelium in the immediately vascularized heart that can present alloantigen and provide a major stimulus to rejection.

Animals↗
PubMed1990

Specific immunosuppression by local lymphoid irradiation using subcutaneous injection of palladium-109 labeled allogeneic lymphocytes.

We have previously shown that intravenously administered palladium-109 labeled lymphocytes (Pd-L) migrated specifically to peripheral lymphoid organs where they caused selective lymphoid irradiation resulting in significantly prolonged cardiac allograft survival. This study evaluates the biodistribution of subcutaneously injected allogeneic Pd-L and the capacity of such labeled cells carrying a large dose of irradiation at a local site to attract and subsequently delete alloreactive T lymphocytes. It was hypothesized that subcutaneously administered allogeneic lymphocytes labeled with a large dose of palladium-109 will attract and then kill by irradiation the host effector cells which might permit prolongation of donor-specific allograft via partial clonal deletion. The results showed that 80% (injected dose) of subcutaneously injected allogeneic Pd-L remained at the site of administration while 20% of injected dose/gram was localized in the ipsilateral popliteal lymph node. No significant radioactivity was found in the other lymphoid and nonlymphoid organs. Pd-L effectively deleted the donor-specific effector cells, as measured by specific unresponsiveness to donor lymphocytes in mixed lymphocyte reaction. Donor cardiac allograft survival, however, was not prolonged over that found in naive recipient controls, although it was significantly prolonged when compared to cardiac allograft survival in controls sensitized by identical injections of unmodified subcutaneous allogeneic lymphocytes (mean survival time +/- SD of 6.5 +/- 0.8 vs. 3.0 +/- 0.6 days). These results suggest that partial clonal deletion of specific alloreactive cells achieved by this approach alone is insufficient to induce unresponsiveness to allografts in vivo.

Animals↗
PubMed1990

The predictive value of bacterial contamination at operation in post-operative wound sepsis.

Wounds of 53 surgical patients were studied prospectively both clinically and bacteriologically. There were 26 males and 27 females with a mean age of 38.3 yr. Culture of fascia-deep wound swabs at closure of wound at the end of operation was related to culture if postoperative wound infection occurred. Overall wound infection rate was 15.1% with an infection rate for clean wounds of 3.7% being lowest and the dirty wound infection rate of 60% being highest. Pathogenic organisms in seven of eight infected wounds had been isolated at wound closure while in one instance they were different from organisms in the wound at closure. Risk of development of subsequent infection was significant if enteric organisms rather than Staphylococcus were isolated from the wound at closure. Wounds that had negative culture at the end of operation had no post-operative infection. The study underlines the importance of bacteriological analysis of wounds at the end of operation in identifying those at risk of post-operative infection and the probable causative pathogenic organisms. This will be useful in the choice of prophylactic antibodies for treatment of high-risk patients.

Adolescent↗