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Biomedical subjects

D Steinmuller

Publications and source records attributed to D Steinmuller.

At least 55 records · Page 3Linked to original sources
PubMed1984

Cloned LYT-2+ cytolytic T lymphocytes destroy allogeneic tissue in vivo.

The long-accepted notion that alloimmune cytolytic T cells (CTL) mediate transplantation immunity has recently been called into question. In order to ascertain directly whether alloimmune CTL can mediate destruction of foreign tissue, we tested the ability of mouse CTL expanded as cloned populations in vitro to destroy allogeneic skin in vivo. The results of these studies prove unequivocally that cloned Lyt-2+ CTL can perform this task in an immunologically specific, H-2-restricted, and dose-dependent fashion.

Animals↗
PubMed1984

Lysis of mouse macrophages, fibroblasts, and epidermal cells by epidermal alloantigen-specific cytotoxic T lymphocytes: effect of culture and inflammatory agents on Epa-1 expression.

The expression of Epa-1, a tissue-restricted non-major histocompatibility complex (MHC) alloantigen, on CBA epidermal cells (EC), fibroblasts (FB), and macrophages (M phi) was investigated using bulk-cultured and clonally-derived anti-Epa-1 cytotoxic T lymphocytes (CTL). Epa-1 was readily detected on freshly trypsinized and 24-hr-cultured EC, and on skin FB cultured for 1-3 weeks. In contrast, fresh peritoneal (PE) M phi were specifically resistant to Epa-1 CTL but became susceptible after 12-24 hr in culture. Epa-1 expression by PE M phi also could be induced in vivo by M phi-activating agents such as concanavalin A or Bacillus Calmette-Guérin (BCG), but not by the sterile inflammatory agents peptone broth or thioglycolate, suggesting a correlation between Epa-1 phenotype and M phi activation. From this and from parallel studies of spleen cell M phi it is concluded that Epa-1 may be a strain-specific marker for activated M phi in the mouse, as well as an inducible histocompatibility antigen in vivo.

Animals↗
PubMed1984

Improved results of cadaver renal transplantation with azathioprine, prednisone and antilymphoblast globulin.

From 1980 to 1982, 100 consecutive cadaver renal transplants were performed. All but 2 recipients received preoperative transfusion and all received an initial 2-week course of antilymphoblast globulin. A prospective controlled evaluation of high versus low maintenance prednisone, and antilymphoblast globulin versus intravenous methylprednisolone for first rejection therapy was done. Over-all 1-year graft and patient survivals were 77 and 96 per cent, respectively. Graft survival was equal in the high and low steroid groups. Antilymphoblast globulin was as effective as intravenous methylprednisolone in reversing first rejections. Graft survival was improved with better donor-recipient matched grafts. We conclude that excellent results can be obtained in transfused cadaver renal allograft recipients managed with azathioprine, prednisone and antilymphoblast globulin. The regimen of prophylactic antilymphoblast globulin, low maintenance prednisone and antilymphoblast globulin alone for first rejections is immunologically effective and steroid sparing.

Antilymphocyte Serum↗
PubMed1984

Skin grafting.

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Animals↗
PubMed1984

Renal transplantation of patients on chronic peritoneal dialysis.

A retrospective review of patients transplanted from peritoneal dialysis was performed to assess the risk of this form of dialysis for patients awaiting renal transplantation. Eighteen transplants have been performed in 16 patients, ages 6 to 57 years, undergoing chronic peritoneal dialysis over the past 4 years. Sixteen were from cadaver donors, and two were from living related donors (LRD). The patients had been undergoing intermittent peritoneal dialysis or continuous ambulatory peritoneal dialysis (CAPD) using permanent silastic catheters, from five days to 4 years. No patient had clinical evidence for peritonitis at the time of transplantation. The peritoneal catheter was removed at the time of transplant in all cadaver donor recipients without complication. One recipient of a LRD kidney had the catheter removed two days prior to transplant. Cultures of the catheter were sterile in 16 cases. Two patients had positive peritoneal catheter cultures at the time of transplant but were treated with appropriate antibiotics and never developed clinical peritonitis. Fourteen transplants had postoperative fevers. No definite source was found in 13; one had fever in relation to acute graft rejection. The fevers resolved in all patients either spontaneously or subsequent to therapy. Other complications were similar to those seen in patients transplanted from hemodialysis. Hemodialysis was performed as needed pretransplant and posttransplant using a temporary femoral vein catheter or arteriovenous fistula without complication. Nine patients are alive with a functioning kidney 1 to 36 months posttransplant (mean 17 months). Six transplants rejected (five patients), and one failed secondary to renal vein thrombosis. Two patients died posttransplant, one after a cerebrovascular accident, and one due to an unknown cause 1 month postnephrectomy for rejection. In conclusion, patients undergoing chronic peritoneal dialysis can be successfully transplanted without a significant incidence of complications related to their peritoneal dialysis.

Adolescent↗
PubMed1984

Expression of cell-defined H-Y antigen on mouse epidermal cells.

Cytotoxic T lymphocytes (CTL)5 of female origin that readily lysed syngeneic male lymphoid cells in specific, dose-dependent, H-2 restricted fashion had little or no activity against syngeneic male epidermal cells (EC) in short-term or long-term chromium-release assays. Moreover, although male EC were quite capable of priming syngeneic female lymphocytes in vivo for the accelerated rejection of male-specific skin grafts and for the subsequent generation of H-Y-specific CTL by exposure of primed female spleen cells (SC) to irradiated, syngeneic male SC in vitro, male EC themselves were incapable of stimulating the development of H-Y CTL when cocultured with primed female SC. Tests of EC from reciprocal male-female radiation chimeras revealed that keratinocytes, not marrow-derived EC (Langerhans cells), were responsible for the priming ability of EC in vivo. Moreover, H-Y antigen was serologically defined on EC that failed to express H-Y-specific CTL target-cell determinants. Alternative explanations of these findings are discussed, including the possibility that the inability of H-2-restricted T cells to lyse male EC results from the lack of association of H-Y antigen and H-2 restricting elements on the EC membrane.

Animals↗
PubMed1983

Improved results of cadaver renal transplantation in the diabetic patient.

The results of 54 renal transplants performed on 48 patients with end stage renal disease and insulin-dependent diabetes mellitus are reported. Pre-transplant screening with coronary angiography was done to determine the presence and severity of coronary artery disease and left ventricular dysfunction. There were 12 living related donor (group 1) and 42 cadaver renal transplants. The cadaver transplant recipients were grouped further into those who received additional prophylactic immunosuppression with antilymphoblast globulin (group 2, 18 patients) and those who received standard immunosuppression with azathioprine and prednisone (group 3, 18 patients). The 2-year patient and graft survival rates in groups 1 to 3 were 81 and 67, 88 and 69, and 61 and 32 per cent, respectively. The use of prophylactic antilymphoblast globulin for adjunctive immunosuppression resulted in significantly improved graft survival among cadaver recipients (p less than 0.003). Selection of patients for transplantation on the basis of preliminary screening with coronary angiography was found to have a major impact on patient survival.

Adult↗
PubMed1983

Simultaneous structural and functional imaging of the transplant kidney using digital subtraction angiography.

We herein describe our preliminary experience with digital subtraction angiography in the noninvasive evaluation of renal transplant structure and function. A single digital subtraction angiography study was obtained in 38 patients with transplant kidneys and various levels of renal function. The main renal artery was demonstrated well in all studies. Stored digital information was used to generate appearance and clearance rates of contrast medium to produce a functional renal image. There was good correlation between the functional image pattern on digital subtraction angiography and the known degree of renal functional impairment. No adverse effects resulted from the small dose of intravenous contrast material used for angiography. This initial study suggests that digital subtraction angiography is a rapid, safe and noninvasive method for visualization of the transplant kidney, and can afford clinically relevant structural and functional information.

Adult↗
PubMed1983

Extended cadaver renal preservation with combined simple cold storage and hypothermic pulsatile perfusion.

Although simple cold storage and hypothermic pulsatile perfusion are each accepted methods of cadaver kidney preservation the efficacy of combining these techniques for extended renal preservation is unclear. In 18 patients cadaver allografts were used that had been preserved with combined simple cold storage (range 6 to 20 hours) and hypothermic pulsatile perfusion (range 9 to 38 hours). The total interval of preservation for these kidneys ranged from 25 to 48 hours. Excellent post-transplant graft function was achieved in all cases, with a mean serum creatinine nadir of 1.4 mg./dl. In 14 patients (78 per cent) grafts continued to function at intervals of 3 to 38 months after transplantation. Of the remaining 4 patients 3 lost the grafts to rejection, while 1 died 7 months after transplantation with a well functioning graft. These data suggest that the combination of simple cold storage and hypothermic pulsatile perfusion provides a safe and effective method for extended renal preservation.

Adolescent↗
PubMed1983

A controlled randomized double-blind study of antilymphoblast globulin in cadaver renal transplantation.

Herein are presented the results of a controlled prospective randomized double-blind evaluation of antilymphoblast globulin as an immunosuppressive adjunct to azathioprine and prednisone in cadaver renal transplantation. There were 31 patients and 36 patients randomly assigned to therapeutic and control groups, respectively. ALG-treated patients experienced no major side-effects, a delayed onset of rejection following transplantation (P less than .005), a reduced total number of rejection episodes (P less than .05), fewer days in the hospital (P less than .05), a reduced cost of transplantation (P less than .02), improved graft survival (P less than .05), and patient survival equivalent to that of the control group. These data indicate that ALG is safe, cost-effective, and of immunologic benefit in cadaver renal transplantation.

Adult↗
PubMed1983

Low-dose maintenance prednisone and antilymphoblast globulin for the treatment of acute rejection. A steroid-sparing approach to immunosuppressive therapy.

The purpose of this prospective randomized trial was to evaluate an immunosuppressive protocol involving reduced maintenance and antirejection steroid dosages in cadaver renal transplantation. The study comprises 23 first cadaver graft recipients who experienced an acute rejection episode. All patients received an initial 14-day course of antilymphocyte globulin (ALG) and azathioprine 1.5 to 2.0 mg/kg/day. In 11 patients (group 1), a low maintenance dose of prednisone (30 mg/day) was administered and first rejection episodes were treated with a second 10-day course of ALG. The remaining 12 patients (group 2) received high maintenance doses of prednisone (2 mg/kg/day with tapering) and intravenous methylprednisolone (IVMP) for first rejection episodes. Subsequent rejections in both groups were treated with high doses of steroids. In group 1, all first rejection episodes were reversed with ALG alone, 6 patients experienced no subsequent rejection, and 10 patients currently have a functioning graft. In Group 2, the first rejection episode was reversed with IMVP alone in 10 patients; in two patients in whom IVMP therapy was unsuccessful, ALG was then administered, and subsequent rejection reversal was effected. In group 2, 4 patients experienced no subsequent rejection, and 9 patients currently have a functioning graft. Patients in group 1 received significantly lower (P less than .01) cumulative steroid doses in the first six months following transplantation, which resulted in a reduced number of major infections, as compared with patients in group 2. We conclude that the steroid-sparing regimen of low maintenance prednisone and ALG for first rejection is as effective immunologically as the established high steroid protocol.

Antilymphocyte Serum↗
PubMed1983

Functional capacity and rehabilitation of recipients with a functioning renal allograft for ten years or more.

Forty-nine renal transplant recipients who had a single functioning allograft for ten or more years are reviewed. There were 17 cadaver recipients and 32 living-related recipients. Most patients have enjoyed excellent long-term renal function with stable mean daily dosages of azathioprine and prednisone. Fifty-three percent of patients never experienced a rejection episode, and 24% of patients experienced only one rejection episode. Five recipients (10%) developed malignancy following transplantation. Based on the Karnofsky activity scale, 80% of patients enjoyed unrestricted activity at ten years posttransplant. The two major factors contributing to declining activity were progression of systemic diseases such as atherosclerosis or diabetes, and declining allograft function. Following transplantation, all patients developed renewed interest in sexual activity, all men were potent, and all women experienced regular menses. Nine men achieved fatherhood and five women underwent successful pregnancy. Currently, 46 recipients are alive with a functioning allograft. These data confirm the ability of recipients with a long-term functioning renal allograft to return to the work force, participate in preillness levels of activity, and enjoy sexual activity and parenthood.

Activities of Daily Living↗
PubMed1982

Cell-mediated cytotoxicity to non-MHC alloantigens on mouse epidermal cells. VI. Influence of the MHC on the tissue specificity of cytotoxic T-lymphocyte responses.

Mice of the C3H/He and A non-H-2 backgrounds are disparate from mice of the B10 background for the tissue-restricted, non-H-2 alloantigen of epidermal cells (EC), Epa-1, that is expressed by EC but not by lymphocytes (LC), as well as for a number of other alloantigens of the B10 background that are expressed by both EC and LC, generically referred to as "lymphocyte/epidermal alloantigens" (LEA). In this study, we compared the ability of various H-2 congenic strains on the C3H or A backgrounds to mount cytotoxic T-lymphocyte (CTL) responses to EC from H-2 compatible mice of the B10 background. High responses to Epa-1 were detected only in the H-2a and H-2k haplotypes; H-2b, H-2o1, H-2s, H-2t1, and H-2t2 haplotypes were nonresponders to Epa-1. High responses to LEA were detected in H-2a, H-2b, H-2s, H-2t1, and H-2t2 haplotypes; H-2k and H-2o1 were nonresponsive to LEA. Analysis of the H-2K, I and D region alleles of responders indicates that H-2Kk is essential for anti-Epa CTL responses, whereas Dd, Db or Ks were all permissive for strong anti-LEA responses. The ability to mount a given CTL response was not associated with differences in I-region alleles. These results are discussed in terms of K/D region products serving as Ir-gene products for CTL and in determining the apparent tissue-specificity of CTL.

Animals↗