ISSN:0041-1337    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

The behavior of urinary thromboxane B2(TXB2) during acute rejection of lung allotransplants was evaluated. Unmatched mongrel dogs were submitted to a left lung orthotopic allotransplantation (groups I and II), or a sham operation (group III). All animals had an initial significant elevation of TXB2excretion due to surgical trauma; however, in sham-operated animals (group III) this elevation returned to basal levels after 3 days. All transplanted animals (groups I and II) had persistent TXB2elevation with 2 important peaks on postop days 5 and 9. The elevated TXB2excretion persisted in spite of immunosuppressive treatment with azathioprine and prednisone (group II). Rejection was followed by means of an objective grading system applied to chest roentgenograms taken on all animals. It was found that TXB2levels correlated directly with the grade of radiographic changes seen, thus indicating degree of rejection. TXB2can be useful as a noninvasive indicator for surveillance of lung allograft rejection.

ISSN:0041-1337    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Heterotopic renal allografts following bilateral nephrectomies were placed in 21 healthy mongrel dogs. One group of 11 dogs received cyclosporine (5 mg/kg/ 24 hr, orally), and 1 group of 10 dogs received cyclosporine and mizoribine (5 mg/kg and 3 mg/kg/24 hr, orally). Body weights, blood cell counts, serum chemistry profiles, serum electrolyte levels, urinalysis with cytology and culture, lymphocyte stimulation assays, immunoglobulin levels, whole blood levels of cyclosporine, and serum levels of mizoribine were followed. At the end of each survival period, necropsy and histopathologic examinations were performed.The mean survival time for the cyclosporine group was 12.8 ± 7 days. The mean survival time for the cyclo-sporine/mizoribine group was 33.6 ± 16.4 days, significantly longer (P=.0006) than the cyclosporine group. Death in the cyclosporine/mizoribine group was attributed to the combined effects of renal allograft rejection and development of a mizoribine-dependent enteritis. Serum levels of mizoribine were greater in the last half of the survival period due to compromised renal excretion of the drug. There were no complications due to infection, myelosuppression, or hepatotoxicity.Combination cyclosporine/mizoribine immunosuppression enhanced canine renal allograft survival in this study. Monitoring serum concentrations of mizoribine is imperative to determine toxic (enteritis) levels. Availability of an intravenous form of mizoribine would facilitate immunoregulation during periods of variable intestinal absorption or renal excretion.

ISSN:0041-1337    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

In a rat experimental study we investigated whether the atrial natriuretic peptide by itself is able to improve early renal function after an ischemic injury. Two groups of Wistar male rats underwent a right nephrectomy and a left renal artery occlusion for 30 min and were infused for 2 hr after ischemia with isotonic saline or rat atrial natriuretic peptides (αANF: 28 amino acids (AP 28) and atriopeptin III (AP 24): 24 amino acids). ANF infusion increased the urinary flow (P<0.001), the urinary sodium concentration (P<0.001), the sodium excretion rate (P<0.0001), and improved the glomerular filtration rate (GFR) recovery (P<0.02) determined at the end of the 2-hr infusion period. AP 24 exhibited higher natriuretics activities than AP 28. The effect of both peptides upon GFR recovery was equivalent. These effects of ANF observed after acute ischemia suggest that this peptide may be beneficial on the resumption of renal function in the early phases following transplantation.

ISSN:0041-1337    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Bronchiolitis obliterans has emerged as the most significant long-term complication of human heart-lung transplantation. Possible causes include rejection, infection, altered bronchial circulation, and denervation. We attempted to assess the role of some of these possibilities by reviewing the airway histology in nonimmunosup-pressed orthotopic rat left lung allografts in three strain combinations: BN-to-LEW (major histocompatibility complex [MHC]-incompatible) n=27; (LEW × BN)Fi-to-LEW, n=11; and F344-to-LEW (minor loci-incompatible) n=18. Fifteen syngeneic transplants (LEW-to-LEW) served as controls. After assigning the lungs to a rejection phase (latent, vascular, alveolar, or destructive), the airway pathology was specifically examined. In the latent phase, only changes attributable to transplantation per se were identified. In the vascular phase in the BN-to-LEW rats and (LEW × BN)F1-to-LEW rats, the bronchioles were surrounded by dense cuffs of activated lymphocytes. The lymphocytic infiltrate then progressively involved the lamina propria and epithelium, where it became associated with focal epithelial cell necrosis. Eventually the epithelium became ulcerated (alveolar phase), and the submucosa and luminal surface became replaced by granulation tissue, which frequently protruded into the lumen in a bronchiolitis obliterans pattern. In the destructive phase the changes were similar to those in the alveolar phase, but were more severe. In the F344-to-LEW rats the airway changes were less prominent, although the remainder of the lungs was at comparable phases of rejection. These changes were not observed in the right (nontransplanted) lungs or the control (LEW-to-LEW) lungs. The findings in these animals suggest that the process of rejection affects the airways and may result in posttransplantation bronchiolitis obliterans.

ISSN:0041-1337    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Graft-versus-host disease (GVHD) has been evaluated in partially inbred miniature swine in order to study this complication of allogeneic bone marrow transplantation (BMT) in a major histocompatibility complex (MHC) genetically defined large animal model. Bone marrow from MHC homozygous (“parental”) swine was injected into irradiated (900 rads total-body irradiation) MHC heterozygous (“F1”) swine that shared one haplo-type with the donor. All 18 animals successfully engrafted with donor bone marrow, and 17 of these devel-

ISSN:0041-1337    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Ex vivo T cell depletion of donor marrow grafts in humans and mice has virtually eliminated severe graft-versus-host disease (GVHD). However, as a consequencl of T cell depletion, sustained donor cell engraftment is likely compromised. Since the majority of T cell depletion techniques also deplete natural killer (NK) cells, we investigated the role of donor NK cells in engraftment and GVHD in a murine model. Using a monoclonal antibody directed against an NK-specific epitope, we have selectively depleted NK cells while preserving donor marrow T cells. In an established model of engraftment, selective NK depletion demonstrated that removal of donor NK cells did not impair the engraftment process under conditions in which donors and recipients are major histocompatibility complex–disparate. In contrast, recipients of anti-Thy 1.2 plus complement (entreated marrow grafts had a significantly higher incidence of either partial engraftment or graft rejection as compared with recipients of selective NK-depleted donor grafts or control grafts. In addition, we have observed that NK-specific depletion of donor marrow/ splenocyte inocula does not alter the incidence of GVHD. Recipients of NK-depleted donor grafts developed lethal acute GVHD, whereas recipients of anti-Thy 1.2–depleted donor grafts did not (P< 0.0001). Interestingly, NK 1.1–depleted donor graft recipients had a significantly increased mortality in comparison with control groups receiving C‘-treated grafts (P =0.04) or anti-Thy 1.2 plus C’-treated grafts (P< 0.05). Thus, NK depletion may reduce immunosurveillance, thereby increasing the risk of posttransplant infection. We conclude from these results that donor NK cells play an insignificant role in engraftment as well as in the afferent phase of GVHD, but may be important in immunosurveillance when murine bone marrow is transplanted across the major histocompatibility barrier.

ISSN:0041-1337    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

The clinical usefulness of cyclosporine (CsA) in organ transplantation and autoimmune diseases is limited by its intrinsic nephrotoxicity. The mechanism of this renal impairment was examined utilizing an animal model in which male Sprague-Dawley rats were administered oral CsA in doses of 25, 37.5, and 50 mg/kg/day for 7 days and 50 mg/kg/day for 2, 4, and 7 days. Urinary thromboxane B2(TXB2) excretion increased from 30.6± 2.3 to 60.8±4.4 ng/24 hr I<0.001, following 48 hr of CsA dosing. In addition, a concomitant rise in proximal tubular sodium reabsorption was observed with fractional excretion of sodium decreasing from 0.502±0.091 to 0.223 ± 0.037% P<0.05. Urinary prostaglandin E2and 6-keto-prostaglandin F1αexcretion increased twofold, although plasma levels of all 3 prostanoids did not vary from cpntrols. Functional changes included decreases in the relative renal blood flow of 53% P<0.05, and the clearance of creatinine and urea of 46% and 42%, respectively on day 7 of treatment, while renal

ISSN:0041-1337    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Flow cytometric analysis of mononuclear cell surface antigens identified 2 distinct populations of CD8/11 cells in the peripheral blood of recovering bone marrow transplant (BMT) recipients. These populations were distinguished based on differential CD8 antigen expression. One population expressed high-surface density CD8 (CD8brigh,/ll); the other population expressed low-surface density CD8 (CD8dim/ll). The surface expression of CD11, the C3bi receptor on lymphocytes, is similar in CD8brigh7H and CD8dimcells. Thus, although 13 BMT recipients had elevated CD8/11 cells (&OV0335;=27%±9%; normal range &OV0335;=7.4±3.3%), the percent of CD8bright/ll cells versus CD8dim/ll cells varied. The majority of cells in patients with a predominant CD8bright/ll phenotype did not express CD 16 (FcTreceptor). In contrast, the CD8dim/ll cells coexpressed CD16. When functional studies were performed, we observed high numbers of CD8bright/l 1 cells correlated with low natural killer (NK) lytic activity, while patients with <25% CD8bright/ll cells had high NK activity. Analysis of interleukin 2 (IL-2) production revealed that none of the peripheral blood mononuclear cells (PBMC) from BMT patients synthesized IL-2 at <1.5 months posttransplant. However, cells from some patients began to synthesize IL-2 at approximately 2 months posttransplant. It is likely that both populations of CD8/11 cells have an impact on the regeneration and regulation of the immune system in BMT recipients

ISSN:0041-1337    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Between 1/1/76 and 12/31/86, 448 patients underwent transplantation (360 first transplants). Of these, 286 (230 first) were referred by 5 dialysis centers, each referring more than 40 recipients. The remainder were referred by a large number of centers. Using our 5 largest referral centers, we studied the effect of dialysis center on graft and patient survival. There was no difference between dialysis centers in patient survival. Actuarial graft survival differed significantly for all cadaver transplants and for first cadaver transplants (P< 105). Significant differences persisted when groups were subdivided by type of immunosuppression (azathioprine vs cyclosporine). Demographic (age, race, cause of renal disease) and immunologic (transfusions, PRA, matching) differences between groups did not explain the difference in graft survival.

ISSN:0041-1337    

出版商:OVID    

年代:1988

数据来源: OVID