Search PubMed⌕ Search

Biomedical subjects

D Steinmuller

Publications and source records attributed to D Steinmuller.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1988

Tissue destruction resulting from the interaction of cytotoxic T cells and their targets.

In vitro and in vivo-generated cytotoxic T lymphocytes (CTL) specific for major and minor histocompatibility antigens evoked antigen-specific full-thickness skin necrosis when injected intradermally into allogeneic mice in a variety of strain combinations. In addition, CTL-target-cell mixtures injected intradermally into hosts syngeneic to the CTL also evoked destruction of host tissue. These "innocent bystander" reactions were evoked with alloreactive CTL as well as with CTL directed against hapten (TNP)-modified and virus (influenza A)-infected target cells. Unlike the direct reactions, the bystander reactions in histocompatibility-antigen systems occurred in spite of H-2 incompatibility of the CTL, admixed target cells, and the hosts. One explanation for these results, currently under investigation, is that some bystander reactions may occur without MHC restriction. In aggregate, our findings indicate that nonspecific as well as antigen-specific reactions initiated by CTL-target-cell interactions may contribute to tissue destruction in allograft rejection, in severe forms of delayed-type hypersensitivity, and in certain viral infections.

Animals↗
PubMed1987

Renal transplantation for end-stage polycystic kidney disease.

From 1963 to 1984, 56 renal transplants were performed in 51 patients with end-stage renal failure due to autosomal dominant polycystic kidney disease (ADPKD). There were 49 cadaver and 7 living-related transplants. Overall patient and graft survival was 88 per cent and 66 per cent at one year, 59 per cent and 49 per cent at five years, respectively. There was no significant difference in patient or graft outcome with cadaver versus living-related donor kidneys. One-year graft success with and without pretransplant bilateral nephrectomy (BN) was 78 per cent versus 58 per cent, respectively (n.s.). Patient survival after return to dialysis after graft loss was not compromised by the earlier performance of BN. In patients who did not undergo pretransplant BN, there were no complications from the retained native kidneys after transplantation. In cadaver recipients, the two-year graft success rate with and without preliminary blood transfusions was 54 per cent versus 61 per cent, respectively (n.s.). Cadaver graft survival with and without adjunctive antilymphocyte globulin (ALG), excluding 3 recipients managed with cyclosporine, was 88 per cent versus 50 per cent at one year, and 70 per cent versus 32 per cent at five years, respectively (p less than 0.05). This beneficial effect of ALG was still evident when only transfused cadaver recipients were analyzed and was achieved with no resulting compromise in patient survival. Follow-up computerized tomography (CT) scanning of the transplant kidney in 10 recipients with a long-term (1-9 years) functioning allograft showed no evidence of recurrent ADKPKD.

Adult↗
PubMed1986

Renal transplantation in end stage renal disease patients with existing urinary diversion.

From 1971 to 1984 renal transplantation was performed in 20 patients with end stage renal disease who presented with an existing form of urinary diversion. These patients were evaluated with a cystometrogram, voiding cystourethrogram and cystoscopy. In some cases bladder function was studied further by cycling through a suprapubically placed catheter. The bladder was considered unstable in 13 patients and undiversion was done at transplantation. The period of prior diversion ranged from 3 to 20 years (mean 12.7 years). There were no surgical complications postoperatively and normal bladder function returned in all patients. Currently, 8 patients have a functioning renal allograft 16 months to 9 years after transplantation (mean 4.2 years). Seven patients were considered to have a nonusable bladder owing to severe neurogenic disease or refractory contracture. In these patients transplantation was done into a pre-fashioned intestinal conduit (5) or cutaneous ureterostomy (2). Currently, 4 patients have a functioning renal allograft 16 months to 6.2 years after transplantation (mean 3.8 years). Transplantation candidates who present with an existing form of urinary diversion should be evaluated carefully, since many will have a usable bladder. Regardless of whether the bladder is usable, transplantation can be performed safely with no increased surgical or immunological risk.

Adult↗
PubMed1986

A prospective analysis of the accuracy and cost-effectiveness of digital subtraction angiography for living-related renal donor evaluation.

From 1982 to 1984, we conducted a prospective study to evaluate the usefulness of i.v. renal digital subtraction angiography (DSA) for living-related donor (LRD) evaluation. Twenty-eight LRDs were evaluated with the traditional approach of intravenous pyelography (IVP) and standard catheter arteriography (SCA) (group 1). During the same period, 33 LRDs underwent renal DSA and IVP from a single i.v. contrast injection (group 2). If renal arterial imaging with DSA was considered satisfactory, no further radiographic studies were done (group 2-A, n = 23). If renal arterial imaging with DSA was not satisfactory, SCA was then obtained (group 2-B, n = 10). DSA alone accurately defined the number and location of renal arteries in 21 of 23 patients from group 2-A, and in 5 of 10 patients from group 2-B. The major limitation of DSA was in patients with multiple renal arteries; accurate imaging was obtained in only 7 of these 13 patients (54%). In group 2 overall, preoperative renal imaging was not accurate in 2 of 33 patients (6%); in both cases, an unsuspected polar artery was found at nephrectomy. The mean cost per patient of all radiographic renal imaging studies was $953.00 for group 2 and $1721.00 for group 1. These data suggest that the approach of preferentially evaluating LRDs with DSA-IVP, and obtaining SCA only if DSA yields poor visualization, is more cost-effective but not as accurate as the traditional policy of obtaining SCA and IVP in all cases.

Angiography↗
PubMed1986

Detrimental effect of cyclosporine on initial function of cadaver renal allografts following extended preservation. Results of a randomized prospective study.

We report herein the results of a randomized prospective trial comparing maintenance cyclosporine (CsA)-prednisone immunosuppression to a regimen of azathioprine-prednisone-antilymphocyte globulin (ALG) in cadaver renal transplant recipients. Fifty-six patients were entered into this study with 31 assigned to the ALG group and 25 to the CsA group. These two groups were well matched for most major determinants of graft outcome and the mean renal preservation time was 37 hr in each group. The incidence of acute tubular necrosis (ATN) was high in both groups (58% ALG, 72% CsA, NS). There were five cases of primary nonfunction in the CsA group and only one in the ALG group (P = .05). Of the kidneys that functioned, the mean serum creatinine nadir (1.5 vs. 2.2 mg/dl, P = .06) and the mean number of days to reach the serum creatinine nadir (24.2 vs. 43.3 days, P = .03) were both less in the ALG group. The actuarial one-year graft survival rate in the ALG and CsA groups is 78% and 48%, respectively (P less than .05). This difference is mainly due to the large number of primary nonfunctioning grafts in the latter group, which we attribute to the effect of CsA's nephrotoxicity superimposed on renal ischemia incurred prior to transplantation. These data emphasize that, in order to realize the full benefit of CsA in cadaver transplantation, renewed emphasis must be placed on minimizing ischemic renal damage.

Adolescent↗
PubMed1986

In vitro and in vivo cytotoxicity of T cells cloned from rejecting allografts.

Epa-1 is a tissue-restricted, non-major histocompatibility (MHC) antigen that may be responsible for the extreme sensitivity of skin to allograft rejection and graft-versus-host disease (GVHD), especially with MHC-compatible donors and recipients. To confirm that Epa-1 serves as a target in allograft rejection and GVHD, we isolated Epa-1-specific cytotoxic T lymphocyte (CTL) clones completely in vivo from sponge-matrix allografts and from lymph nodes draining rejecting skin allografts. These clones induced GVHD-like skin lesions in antigen-specific, MHC-restricted fashion following intradermal inoculation into appropriate hosts. The in vivo-derived clones are conventional CTL since they are IL-2-dependent and express the Thy-1.2+, Lyt-1-, Lyt-2+, L3T4- phenotype. The results of this study also are pertinent to the controversy over which T-cell subset actually mediates allograft immunity, since the intragraft isolation and subsequent cloning of conventional CTL that induce necrotizing skin lesions are direct evidence that CTL are the proximal mediators of allograft rejection.

Animals↗
PubMed1985

Renal transplantation in the older recipient.

From 1976 to 1983, 13 living related and 54 cadaver renal transplants were done in 62 patients more than 50 years old. Patients with no coronary or myocardial disease upon coronary angiography were selected preferentially for transplantation. Over-all 1-year patient and graft survival rates were 88 and 70 per cent, respectively. Among cadaver recipients graft survival was improved (p less than 0.001) when prophylactic antilymphoblast globulin was used. There were fewer steroid-related complications (p less than 0.001) in recipients managed with a low dose rather than a high dose maintenance prednisone regimen. With careful patient selection and a steroid-sparing immunosuppressive regimen, renal transplantation can be done safely in older recipients with no increased risk of death or graft loss.

Age Factors↗