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Biomedical subjects

D Steinmuller

Publications and source records attributed to D Steinmuller.

At least 19 recordsLinked to original sources
PubMed1991

Long-term follow-up after partial removal of a solitary kidney.

BACKGROUND: The removal of more than one kidney in animals leads to proteinuria and progressive renal failure due to focal segmental glomerulosclerosis. This injury may be the result of chronic glomerular hyperfiltration. The purpose of this study was to determine the effect of a reduction in renal mass of more than 50 percent on residual renal function and morphology in humans. METHODS: We evaluated long-term renal function in 14 patients with a solitary kidney who had undergone partial nephrectomy for renal-cell or transitional-cell carcinoma. In 12, the first kidney had been removed 2 months to 21 years previously for the same type of cancer; in 2, the other kidney was congenitally atrophic. Before surgery, no patient had clinical or histopathological evidence of primary renal disease. All 14 patients underwent partial nephrectomy to remove a localized tumor, with 25 to 75 percent of the solitary kidney being excised. They were evaluated 5 to 17 years after surgery (mean, 7.7). RESULTS: Twelve patients had stable postoperative renal function, and end-stage renal failure developed in two. There were no changes in blood pressure in any patient during follow-up. Nine patients had proteinuria, which was mild (0.15 to 0.8 g of urinary protein per day) in five. The extent of proteinuria was inversely correlated with the amount of remaining renal tissue (P = 0.0065) and directly correlated with the duration of follow-up (P = 0.0005). Four patients with moderate-to-severe proteinuria had renal biopsies, which revealed focal segmental glomerulosclerosis in three patients and global glomerulosclerosis in one. CONCLUSIONS: Long-term renal function remains stable in most patients with a reduction in renal mass of more than 50 percent. These patients are, however, at increased risk for proteinuria, glomerulopathy, and progressive renal failure.

Adult↗
PubMed1991

Evidence that epidermal alloantigen Epa-1 is an immunogen for murine heart as well as skin allograft rejection.

Epa-1 is a non-H-2 mouse alloantigen defined by MHC-restricted, CD8+ cytotoxic T cells. In vitro it is a strong determinant for the lysis of epidermal cells, fibroblasts, and macrophages but not lymphocytes, and in vivo it functions as a target for skin allograft rejection and cutaneous graft-versus-host reactions. Genetically, Epa-1 appears to be the nonpolymorphic manifestation of a loss mutation. The establishment of C3H.Epa-1 (Epa), an Epa-1+ congenic strain on the Epa-1- C3H/HeJ (C3H) inbred strain background, facilitated the investigation of the role of Epa-1 in skin and heart allograft rejection. C3H females and males rejected first-set Epa skin grafts with median survival times (MSTs) of 20 and 30 days, respectively. However, there was a strong factor of immunization, because all second-set skin allografts were rejected by hosts of both sexes within 10 days. In contrast, all Epa hosts of both sexes permanently accepted C3H skin allografts, consistent with Epa-1 arising from a loss mutation. C3H hosts of both sexes rejected primarily vascularized first-set Epa heart allografts in similar tempo to first-set Epa skin allografts, with MSTs of about 30 days. However, in contrast to the accelerated rejection of skin allografts, sensitized C3H hosts rejected Epa heart allografts in chronic fashion, with some transplants showing very prolonged survival. Thus, Epa-1 is a relatively strong determinant of skin allograft rejection but a weaker determinant of heart allograft rejection.

Animals↗
PubMed1991

The outcome of renal transplantation in children without prolonged pre-transplant dialysis.

Controversy in the literature exists over whether or not it is beneficial to maintain a patient on dialysis for a prolonged time before transplantation. Because no data exist comparing children who have had prolonged dialysis before transplantation to those who have none, we reviewed the charts of all children transplanted at the Children's Hospital of the Cleveland Clinic Foundation. Of those, we selected three groups for analysis: group one (n = 12) consisted of patients who had had less than or equal to 10 weeks of dialysis before transplantation (6.8 +/- -2.2 weeks, +/- = SD); group two (n = 21) were patients who had had more than 10 weeks of dialysis (142 + +/- -148 weeks). Both groups had two years of follow-up data. Group three (n = 13) consisted of patients who had had less than two years of follow-up (18.7 +/-/-7 months) but no dialysis before transplantation. There were no differences in mode of dialysis between groups one and two nor in the type of transplant (living-related donor vs. cadaveric). Significantly, the patients in group three received more cyclosporine A and less anti-lymphocyte globulin than the other two groups (p less than 0.05). Patients in group two received more transfusions (11.9 +/- 14.3) than patients in group one (4.0 +/- 2.7) and group three (3.5 +/- 7.3). There were no differences in number of patients who experienced at least one rejection episode among the three groups. Although the mean serum creatinine concentration at two years of follow-up was higher in group two (3.6 +/- -3.9 mg/dl), this was not significantly different from group one (1.7 +/- -0.7 mg/dl) or group three (1.9 +/- -0.5, n = 7). Sixty-three percent of patients in group one, 60% of patients in group two and 91% in group three had functioning allografts at two years follow-up. Although there may be other considerations, our data do not indicate any increase in rejection or decrease in graft survival in children who do not receive prolonged dialysis.

Adolescent↗
PubMed1990

Dissociation of tissue destruction induced by cytolytic T cells in vivo and cytotoxicity as measured in vitro.

Two forms of local cutaneous graft-versus-host reactions were used to examine the in vivo activity of cytolytic T cells in a large number of antigen systems and mouse strain combinations. In immune lymphocyte transfer reactions (TrRs), CTL were injected intradermally into allogeneic hosts to which they were sensitized; in bystander reactions (ByRs), CTL were mixed with target cells and the mixture injected into hosts syngeneic to the CTL. Both reactions frequently culminate in full-thickness skin destruction. However, CTL highly active in cell-mediated lympholysis assays in vitro sometimes failed to induce significant reactions in vivo, and CTL with negligible CML activity often induced severe, necrotizing lesions. In addition, Clone 58, a non-MHC-specific CD8+ clone that originated from cells extracted from a sponge matrix allograft, lost its CML activity but continued to induce necrotizing TrRs and ByRs. Insofar as these reactions may exemplify the specific (TrR) and nonspecific (ByR) tissue injury that occurs in the rejection process, these findings question the reliability of CML for predicting the ability of CTL to induce the tissue destruction seen in allograft rejection.

Animals↗
PubMed1989

Recent results of cadaver kidney retransplantation.

The results of secondary cadaver renal transplantation in 42 patients treated from 1980 to 1986 have been reviewed. The initial graft was from a cadaver donor in all cases. All patients were managed with a maintenance immunosuppressive regimen, including either antilymphoblast globulin and/or cyclosporine. The over-all 1 and 2-year patient survival rates were 97 and 94 per cent, respectively. The over-all 1 and 2-year graft survival rates were 69 and 63 per cent, respectively. Graft success was not influenced by patient age greater than 50 years, diabetes, initial graft removal, interval between initial graft removal and retransplantation, duration of initial graft function, level of presensitization or HLA-Dr antigen matching. Currently, cadaver renal retransplantation can be performed safely and with an improved opportunity for graft success. Patients who return to dialysis after losing an allograft should be encouraged to consider another transplant for the same reasons that prompted initial transplantation.

Adolescent↗
PubMed1989

Endoscopic correction of vesicoureteral reflux in the renal transplant candidate.

High grade vesicoureteral reflux is a well recognized risk factor for post-transplant infection that has been managed commonly with native nephrectomy. Recent reports have described the successful correction of vesicoureteral reflux by the subtrigonal injection of polytetrafluoroethylene (Teflon) paste. We treated 5 transplant candidates with vesicoureteral reflux with this technique. Ureteral reflux was corrected in 80 per cent of the treated ureters with 6 months of followup. Of the patients 3 have undergone successful renal transplantation without complication. This procedure is well suited to the end stage renal disease patient preparing for renal transplantation, since it avoids an open operation on the pre-transplant bladder and preserves the native kidney, thus, facilitating pretransplant dialysis.

Endoscopy↗
PubMed1989

Two-color immunofluorescence flow cytometric analysis of lymphocytes in long-term renal allograft recipients.

We used 2-color immunofluorescence flow cytometry (FACS 440) and monoclonal antibodies (Becton-Dickinson) to study peripheral blood lymphocytes subsets from 26 patients with well functioning renal allografts for longer than 5 years. Comparisons were made to a group of 25 healthy volunteers and 25 dialysis patients awaiting renal transplantation. As anticipated, there was no significant difference with respect to the absolute number or percentage of activated (T11+ and HLA-DR+) and cytotoxic (Leu-2+ and Leu-15-)T lymphocytes among the 3 groups. However, there was a significantly decreased absolute number (p equals 0.0001) and percentage (p equals 0.0001) of suppressor cells (Leu-2+ and Leu-15+) in the transplant patients compared to the healthy control group. No significant differences existed between the transplant and dialysis groups. There also was an increase in the percentage (p equals 0.000) but not in the absolute number of T helper lymphocytes (Leu-3+ and Leu-8-) in the transplant population compared to healthy controls. No significant difference existed between the transplant and dialysis groups. These findings suggest that a normal value of cytotoxic (Leu-2+ and Leu-15-) and activated (T11+ and HLA-DR+) T lymphocytes may be a good prognostic indicator of long-term survival of renal allografts. Also, the highly significant decrease in the number of Leu-2+ and Leu-15+ cells in long-term, well functioning allografts indicates that additional functional characterization of this subset may be necessary.

Adult↗
PubMed1989

Use of digital subtraction fluorography in screening for coronary artery disease in patients with chronic renal failure.

The diagnosis of coronary artery disease remains a major problem in patients with end-stage renal disease. Screening with conventional noninvasive techniques is limited by the poor exercise capacity of these patients. This study evaluated the accuracy of digital subtraction fluorography in detecting coronary calcification as a noninvasive, nonexercise screening test for coronary artery disease. Eighty-six patients under evaluation for renal transplantation and considered at increased risk of coronary artery disease were studied by coronary arteriography and digital subtraction fluorography for coronary calcification. Significant coronary disease (greater than or equal to 50% obstruction in at least one vessel) was present in 36 (42%) patients. The detection of coronary calcification by digital subtraction fluorography had a sensitivity of 78% and a specificity of 66%. The probability of disease being present in the absence of coronary calcification in this group was 18%. The detection of coronary calcification by digital subtraction fluorography appears to be a satisfactory and inexpensive screening test in this setting.

Calcinosis↗
PubMed1989

Blocking of interleukin-2 production, but not the tissue destruction induced by cytotoxic T cells, by cyclosporine.

Cytotoxic T lymphocytes generated against epidermal alloantigen-1 (Epa-1), a tissue-restricted, non-H-2 alloantigen that is a target-cell determinant of both skin allograft rejection and cutaneous graft-versus-host reactions, directly produce full-thickness ulcerative skin lesions in Epa-1+ mice. Anti-Epa-1 CTL also indirectly cause extensive damage of "innocent bystander" tissue when injected admixed with Epa-1+ target cells into the skin of Epa-1- hosts. Unlike the direct destruction of host tissue by CTL in "immune lymphocyte transfer reactions" (TrR), "bystander reactions" (ByR) apparently are initiated by the release of lymphokines that recruit host inflammatory cells to the injection site. Treatment of CTL with cyclosporine in vitro prevents their production of lymphokines like interleukin 2 but has no effect on cell-mediated cytotoxicity. However, little is known about the function of CsA-treated CTL in vivo. We confirmed the differential effect of CsA on CTL function in vitro with bulk-culture anti-Epa-1 CTL-CsA pretreatment of CTL abrogated IL-2 production but did not affect CMC. Moreover, we found that CsA pretreatment did not affect the ability of CTL to evoke TrR, nor did it significantly impair their ability to mediate ByR. Therefore, when CTL are treated with CsA in such a way that they lose their capacity to produce IL-2, their cytotoxic activity in vitro as well as their ability to directly and indirectly mediate tissue destruction in vivo are left intact. These results suggest that the ability of CTL to mediate allograft rejection is not dependent on their ability to produce IL-2 and that CMC plays a role in the rejection process.

Animals↗
PubMed1988

Cellular autoimmunity in psoriasis and lichen planus.

The objective of this investigation was to determine whether specific cellular recognition of the epidermis is associated with the human skin diseases, psoriasis and lichen planus. Epidermal cells (EC) obtained from biopsies of involved and uninvolved skin of patients with these diseases were used as stimulators and targets for autologous peripheral blood mononuclear cells (PBMC) in assays of three conventional manifestations of cellular immunity: lymphocyte transformation, leukocyte migration-inhibition and cell-mediated cytotoxicity. Parallel tests were conducted with autologous PBMC as stimulators to ascertain the tissue specificity of the reactions evoked by autologous EC. Similar assays were conducted with EC and PBMC from a large group of normal subjects, and the results were compared to those of the dermatology patients by rigorous statistical analyses. No evidence of lymphocyte-mediated cytotoxicity towards autologous EC was obtained with any of the subject groups, but autologous EC, and to a lesser extent PBMC, of the psoriasis patients, but not of the other two groups, evoked significant lymphocyte transformation. These results were obtained only with patients on Goeckerman therapy, raising the possibility that they were a manifestation of the treatment (topical coal-tar and ultraviolet light irradiation) rather than of the disease, although reasons are presented why this is unlikely. Clearer evidence of disease-associated autoimmunity was obtained in the leukocyte migration-inhibition assays, where autologous EC, and to a lesser extent, PBMC, of the psoriasis patients in general, not just those on Goeckerman therapy, and not those of the lichen planus patients or of the normal subjects, stimulated the release of a leukocyte migration-inhibition factor. These results support the concept of a central role for T-cell mediated autoimmunity in the pathogenesis of psoriasis.

Adult↗
PubMed1988

Monoclonal antibodies to tissue-restricted autoantigens in the mouse epidermis.

The humoral response to allogeneic epidermal cells (EC) in the mouse is dominated by the response to autoantigens. To investigate this phenomenon, several hybridoma clones that secrete monoclonal antibodies (MoAbs) that reacted specifically with EC were isolated. Three of these MoAbs--A3.1-6, A4.1-2 and A4.2-5--were further characterized. Competitive blocking assays were utilized to show that A4.1-2 and A4.2-5 recognize the same or closely associated determinants and that A3.1-6 recognizes a unique determinant. MoAb A3.1-6 reacts equally well with mouse and human EC; A4.2-5 shows little, if any, reactivity with human EC. In immunofluorescence assays of mouse skin, A3.1-6 stained the perinuclear cytoplasm of keratinocytes in most, if not all, layers of the epidermis whereas A4.2-5 strongly stained an extracellular antigen expressed in the middle cell layers. Immunoblot analysis showed that the target antigen of A3.1-6 is a keratin polypeptide of approximately 55 kd.

Animals↗
PubMed1988

Domination by epidermal cell-reactive autoantibodies in attempts to raise antibodies to Epa-1 alloantigens.

Despite extensive efforts to produce polyclonal sera and monoclonal antibodies (MoAbs) to Epa-1, a non-H-2 alloantigen expressed by murine epidermal cells (EC) but not lymphoid cells (LC), we were unsuccessful. In total, we screened nearly 3000 hybridoma culture supernatants--a sampling of B cells from 37 mice in 27 fusions--without finding significant evidence of Epa-1-reactive antibodies, an effort greater than that made to produce antibodies to other histocompatibility (H) antigens. Although mice immunized with Epa-1+ contained high levels of EC-reactive antibodies that showed little crossreactivity with LC targets, these were autoantibodies rather than alloantibodies because they reacted as strongly with syngeneic as with allogeneic EC targets. In the course of these studies, we found that even sera of normal mice contain EC-reactive autoantibodies, and that these could be further boosted by immunization with allogeneic EC. These data indicate that the humoral response to allogeneic EC is dominated by the response to a group of tissue-restricted autoantigens expressed on EC. These findings are discussed in the light of the general inability to produce antibodies to minor H antigens.

Animals↗