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Biomedical subjects

N E Goeken

Publications and source records attributed to N E Goeken.

At least 37 records · Page 2Linked to original sources
PubMed1985

Outcome of renal transplantation following a positive cross-match with historical sera: the ASHI survey.

Analysis of retrospective data, obtained on 216 patients from 27 centers transplanted across some form of positive lymphocyte cross-match in a noncurrent serum, revealed that actuarial 1-yr graft survival was 69% in first transplants and 53% in recipients of second or subsequent transplants. Graft outcome did not correlate with peak antibody levels, change in antibody from peak to current, remoteness in time of the most recent positive serum, the number or timing of sera cross-matched, the technique or target cell cross-matched, or the degree of positivity of the most recent positive serum. Although a concurrent control population was not available, these results support the concept that acceptable graft survival can be achieved despite a positive cross-match with noncurrent sera.

Graft Survival↗
PubMed1985

The use of partially matched, unrelated donors in clinical bone marrow transplantation.

It is estimated that 60-70% of patients who might benefit from a bone marrow transplant will not have a suitably matched, related donor. We have, therefore, designed a clinical experiment to test the safety and feasibility of using marrow from partially matched, unrelated donors. This paper details our transplant experience in the first eight patients with leukemia. The first four patients had advanced leukemia at the time of transplantation. Each showed hematopoietic recovery, but all died from septic complications largely related to extended neutropenia encompassing both the pre-marrow-grafting and the post-marrow-grafting period. The next four patients were in remission at the time of transplantation. Each showed prompt and sustained hematopoiesis with variable graft-versus-host disease (GVHD). No acute or chronic GVHD was seen in two patients, grade II (skin only) was seen in one patient, and grade IV (skin, liver, and gut) was seen in one patient. One patient has died from sepsis five-and-one-half months following transplantation, and three are alive and well six-and-one-half to nine-and-one-half months postengraftment. This preliminary experience, together with several case reports in the literature, leads us to conclude that bone marrow transplantation with partially matched, unrelated marrow is a safe and feasible approach. If these results are confirmed by longer follow-up in a larger group of patients, the development of marrow donor pools would appear to be justified.

Adolescent↗
PubMed1985

Failure of cyclosporine to prevent in vivo T cell priming in man. Studies in allogeneic spleen transplantation.

Cyclosporine is a potent new immunosuppressive agent utilized in clinical organ transplantation. Available evidence suggest that it interferes with the secretion of interleukin-2. However, the long term efficacy of cyclosporine in preventing allograft rejection may depend on a relative sparing of suppressor cells early in the allogeneic response, allowing them to mature and effect a state of operational tolerance. If this is the case, cyclosporine must not affect antigen priming or recognition. Two patients in our center underwent allogeneic spleen transplant in conjunction with renal and pancreatic transplant. Both patients were treated with therapeutic levels of cyclosporine during the course of transplant. Neither developed any clinical signs of renal or pancreatic transplant rejection. Both patients developed graft-versus-host disease and eventually required allogeneic (donor) splenectomy. Studies performed on the splenocytes recovered from these specimens demonstrate alloantigen-specific cytotoxic T cell precursors. These studies demonstrate that although cyclosporine can prevent allograft rejection it does not necessarily prevent or ameliorate graft-versus-host disease. Furthermore, cyclosporine does not prevent in vivo T cell priming of alloantigen recognition. The primed cytotoxic precursors can be expanded in the presence of exogenous interleukin-2 to become fully active cytoxic cells.

Cells, Cultured↗
PubMed1985

Ia molecular localization of the DRw52 allodeterminant and the DRw52-like determinants defined by monoclonal antibodies.

DRw52 (formerly MT2) is a human Ia alloantigen that is expressed in linkage disequilibrium with DR3, 5, w6, and w8. Although there is general agreement that the DRw52 determinant resides on biochemically defined DR molecules, conflicting evidence exists regarding whether DRw52 resides on one or both DR molecules, DQ and DR molecules, or DR and BR molecules. Six anti-DRw52 allosera and three DRw52-like monoclonal antibodies were used to identify the Ia molecules that bear the DRw52 and DRw52-like determinants from DR5 and DRw6 homozygous cells. Based on these two-dimensional gel studies, the DRw52 allodeterminant appears to reside on a subset of DR molecules from DR5 and DRw6 cells. In contrast, the determinants defined by the three anti-DRw52-like monoclonal antibodies were found to reside on one DR molecule, on the second DR molecule, or on both DR molecules, respectively. Therefore, there is considerable complexity of Ia antigenic determinants that are associated with DR3, 5, w6, and w8 at the population level.

Antibodies, Monoclonal↗
PubMed1984

Granulocytotoxic antibodies in a patient with propylthiouracil-induced agranulocytosis.

Agranulocytosis developed in a patient who was receiving propylthiouracil. Using a microgranulocytotoxicity assay, serum taken from the patient was shown to be strongly granulocytotoxic when tested against the patients granulocytes and those obtained from two of eight normal subjects. Tests for granulocyte agglutinins and for lymphocytotoxicity were negative. Granulocytotoxic activity decreased as the patient's peripheral granulocyte count recovered. Cytotoxicity was shown to be mediated by a complement-dependent IgM antibody.

Adult↗
PubMed1984

Differential stimulatory requirements and regulation of naive and primed human lymphocytes.

In these investigations, human lymphocytes primed in vitro in MLR have been employed as a model for human memory cells and have been compared to naive lymphocytes from the same donor. Both the stimulatory requirements and the regulation of these cells were found to differ significantly. The dose of stimulators giving a maximal primary (I) response was less than 10% the dose of restimulating cells giving a maximal secondary (II) response. II responses were further found to be inversely related to the original I response. This was associated with at least two separate regulatory phenomena. Suppressor cell induction was enhanced at high priming doses while memory cell precursors were preferentially stimulated at very low priming doses. Priming of memory cells could also be demonstrated to occur in the absence of any detectable I proliferation by utilizing platelets or heat treated stimulators. Memory cells were also a much more resistant than naive cells to both alloantigen induced suppressor cells and to culture activated monocyte suppressor cells. This in vitro model suggests that the human I and II responses to alloantigen have both distinct triggering requirements and differential sensitivity to regulatory cells. It is suggested that preferential formation of memory cells under conditions that require no proliferation and which are suboptimal for suppressor cell generation and the acquired resistance of memory cells to down regulation by suppressor cells may contribute to the poor graft prognosis of sensitized renal transplant patients.

HLA Antigens↗
PubMed1984

Successful DR-incompatible cadaver kidney transplantation. Combined effect of HLA A and B matching and blood transfusion.

The purpose of this retrospective analysis of DR-incompatible cadaver renal transplantation was to evaluate the effect of HLA A and B matching and blood transfusion status on actual one-year graft survival. There were 31 2-DR, 111 1-DR, and 27 0-DR grafts at risk during the study period. First, a comparison was made between preoperative (PRE) and peroperative (PER) transfusions alone. Graft survivals were 70% vs. 92% (2 DR), 67% vs. 52% (1 DR) and 71% vs. 39% (0 DR) for the PRE and PER groups, respectively. Statistical significance was not found between the two values in each DR subgroup, although the difference approached significance in the O DR group (0.1 greater than P greater than 0.05). Matching for greater than or equal to 2 A and B antigens significantly improved graft survival in the 1 DR-matched group when compared with those matched for less than 2 antigens (76% vs. 44%, P less than 0.005). While marked differences between the greater than or equal to 2 and less than 2 A and B matched groups were observed for both the 2 DR (92% vs. 68%, P greater than 0.1) and O DR groups (59% vs. 40%, P greater than 0.3) these differences were not significant. Stratifying the data for transfusion status revealed that the positive influence of HLA A and B matching in the 1 DR group was dependent upon the presence of preoperative blood administration. Graft survival of 87% for the PRE transfused recipients of grafts matched for greater than or equal to 2 A and B antigens was significantly better (P less than 0.001) than the 42% survival observed in similarly transfused recipients of poorer matched organs. Conversely, A and B matching was not significantly beneficial in the 1 DR recipients transfused only at the time of transplant with graft survivals of 57% vs. 43% for those matched for greater than or equal to 2 or less than 2 A and B antigens, respectively (P greater than 0.3). This analysis suggests that a combined effect of both HLA A and B matching and preoperative blood transfusions may allow for highly successful first cadaver renal transplantation in the face of DR incompatibility.

Adolescent↗
PubMed1984

Differential requirements for class II MHC antigen in human T cell activation.

We have employed three different models of major histocompatibility complex (MHC) antigen to investigate the role of these antigens in some aspects of human T cell activation in in vitro; specifically the induction of lymphokine synthesis and receptors, and in antigen presentation. Those models were (1) allogeneic platelets (class I alone); (2) D/DR compatible lymphocytes (class I plus nonimmunogenic class II); and (3) allogeneic heat-treated lymphocytes. After heating at 45 C for 1 hr, the latter are completely viable and express both class I (HLA A and B) and class II (HLA, DR, MT/MB) MHC antigens but do not stimulate in the mixed lymphocyte reaction (MLR). These models were compared with conventional irradiated MLR stimulating or antigen-presenting cells. Only the conventional cells were able to stimulate the synthesis of interleukin-1 and interleukin-2. Also, irradiated but not heat-treated non-T cells could present soluble antigen to autologous T cells. This implies that intact and unmodified Ia molecules are required for those responses. On the other hand, heat treated allogeneic lymphocytes and D/DR-compatible lymphocytes but not allogeneic platelets could induce responsiveness to interleukin-2. This function appears to require a heat stable but nonallogeneic component of the class II molecules. Our previous observations employing these models have also shown that there is yet a third category of T cell responses, including memory cell priming and suppressor cell induction, that can occur in the presence of predominantly class I antigen. Taken together, these data illustrate the functional heterogeneity of T cell responses to Ia-like antigens. The possible relevance of these findings to clinical transplantation is discussed.

Antigen-Presenting Cells↗
PubMed1984

Acute graft-versus-host disease resulting from normal donor blood transfusions.

2 fatal cases of graft-versus-host disease (GvHD) occurred following blood product transfusions given to patients receiving standard chemotherapy for Hodgkin's disease. GvHD was established by HLA typing, clinical course, and compatible skin biopsy. 23 cases of GvHD following transfusion of blood products from normal donors are also reviewed. It should be suspected when fever or rash appear 1-2 weeks after transfusion of unirradiated blood products into a compromised host or when pancytopenia following chemotherapy is prolonged or unexpectedly severe. Prevention of GvHD by irradiation of granulocytes, platelets and packed red blood cells given to immunosuppressed patients is recommended to prevent this often fatal disease.

Adult↗
PubMed1984

Human suppressor cell induction in vitro: preferential activation by class I MHC antigen.

Human peripheral blood lymphocytes heated at 45 degrees C for 1 hr were found to continue to express all the serologically detected class II MHC antigens (HLA DR, MT, MB) but not to stimulate proliferation in primary or secondary MLR. Such cells did, however, stimulate the formation of potent suppressor cells. Three additional stimulator cell models for the presentation of either class I antigen only (purified platelets and purified T cells) or class I antigen plus nonimmunogenic class II antigen (D/DR-compatible cells) gave identical results. Supernatants from cultures stimulated with any of these cell types had significantly reduced IL 2 activity when compared to control MLR. The suppressor cells generated in such cultures were not restricted to the class I or class II MHC antigen of the original stimulator. These data are interpreted to mean that 1) the class II epitopes detected by alloantisera and the epitopes that serve as lymphocyte-activating determinants are metabolically or conformationally distinct, and 2) that presentation of class I MHC antigen alone or in conjunction with nonimmunogenic class II MHC antigen preferentially stimulates the formation of suppressor cells. It is hypothesized that the latter may be an additional mechanism that contributes to the efficacy of matching for class II determinants in human renal transplantation.

Antilymphocyte Serum↗
PubMed1983

Nosocomial Legionnaires' disease. Occurrence in recipients of bone marrow transplants.

Nosocomial pneumonia caused by Legionella pneumophila serogroup 1 occurred in five patients after bone marrow transplantation for hematologic malignancies. Two patients died as a result of the infection despite treatment with erythromycin. Serologic screening revealed no other cases of Legionnaires' disease in 40 consecutive recipients of bone marrow transplants, giving a frequency of infection of 13 percent. These five cases represent 23 percent of the pneumonia occurring in this group of patients. Patients undergoing bone marrow transplantation are highly susceptible to infectious complications. Legionnaires' disease must now be added to the list of pathogens infecting this group of patients. Erythromycin is not generally a part of standard empiric antibiotic regimens in febrile neutropenic patients, but appears to be a reasonable addition when pneumonia does not respond to conventional, empiric treatment. Even with appropriate therapy, Legionnaires' disease remains a highly lethal infection in immunocompromised hosts.

Adolescent↗
PubMed1983

Immunoregulatory activity of T-cell subsets activated in human mixed lymphocyte reaction.

Unseparated human T cells or isolated OKT4+ and OKT8+ subsets were stimulated in allogeneic MLR and subsequently tested for their capacity to suppress fresh autologous responding cells in a second MLR. Contrary to the bulk of evidence regarding the immunoregulation of B-cell function, both OKT4+ and OKT8+ cells could be activated to form suppressors of the MLR and were equally radioresistant. An early peak of blastogenesis was observed when OKT4+ suppressors were used, and this event was completely radiosensitive. When the fresh responding cells were also fractionated into OKT4+ and OKT8+ subsets, no preference for suppressibility of either subset could be demonstrated, indicating that OKT4+ suppressors were acting directly and not through an inductive mechanism requiring OKT8+ effectors. It is suggested that when alloantigenic responses are involved, the human T-cell subsets defined by these monoclonal antibodies may be more accurately defined by the class of MHC antigen to which they respond than by their effector function.

Antibodies, Monoclonal↗
PubMed1982

Suppressor cells induced in the human autologous mixed lymphocyte reaction.

Theophylline, a phosphodiesterase inhibitor, also reversibly inhibits the SRBC receptor of a subpopulation of human T lymphocytes. We have previously reported that the precursor for the Concanavalin A (Con A) inducible suppressor cell (SC) is found predominantly in the theophylline-sensitive (Ts) population; whereas, the precursor of the mitomycin resistant suppressor cell induced in the allogeneic mixed lymphocyte reaction (MLR) is predominantly in the theophylline-resistant (TR) subset. This study examines the theophylline sensitivity and functional characteristics of suppressor cells induced in autologous MLR (AMLR). Both TS and TR proliferate moderately in AMLR but differ in their ability to form suppressors. AMLR activated Ts and TR cells demonstrate early blastogenesis and weak suppression in the Con A assay system, but suppression in an MLR assay system appeared to be confined largely to the TR subset. AMLR suppressors were mitomycin sensitive. These data illustrate that suppressors generated in allogeneic and autologous MLR have significant functional and phenotypic similarities, and strengthen the association between these two immunologic phenomena.

Cell Differentiation↗
PubMed1982

Activity of concanavalin A-induced suppressor cells in human MLR: differential effects on primary MLR, secondary MLR, and memory cell precursors.

The relative sensitivity of the MLR responses of freshly isolated human lymphocytes to Con A-induced suppressor cells (SC) was compared to that of lymphocytes that had been primed previously in vitro. Fresh and primed cells were suppressed 72 and 17%, respectively, when cultured under similar conditions (p less than 0.0005). Titration of SC indicated that equivalent suppression in the two populations would require greater than a 50-fold excess of SC in the primed cells. Neither preincubation of the primed cells for 24 or 72 hr with the SC before restimulation, addition of fresh autologous cells to the primed cells, nor preincubation of the SC with fresh cells before addition to the primed cells increased suppression of primed cells. SC added at the beginning of a primary MLC were, however, very suppressive for both the primary response (67% suppression) and the subsequent secondary response (81% suppression). These data indicate that although the human primary MLR and the precursor of the memory cell are both sensitive to the suppressors induced by Con A, the memory cell itself possess an intrinsic resistance to such suppressors that is not related to simple kinetic phenomena nor to the loss in vitro of an intermediate regulatory cell. Cell depletion experiments suggest that resistance to nonspecific suppression may occur at the level of the helper cell.

Antibodies, Monoclonal↗