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N E Goeken

Publications and source records attributed to N E Goeken.

53 records · Page 3Linked to original sources
PubMed1981

Human suppressor cells: evidence of functionally distinct subsets.

Human suppressor cells (SC) differing in both kinetic characteristics and degree of specificity were induced in vitro either by Concanavalin A (CON A) (10 microgram/ml) or by repeated stimulation with allogeneic cells. CON A SC caused a characteristic early peak in blastogenesis (Day 2) when cocultured with fresh autologous cells in the presence of either CON A or augmented response fell rapidly to values 50--90% below positive controls by the usual optimal day for the particular stimulus. Treatment with 5-bromodeoxyuridine and light during rapid proliferation ablated the early responses but increased the later responses (i.e., reduced the suppression). The cells mediating both the early rise and late suppression were found to belong to a subset of T cells that lost their ability to form SRBC rosettes (theophylline sensitive) in the presence of the phosphodiesterase inhibitor, theophylline, and were inactivated by mitomycin C. In contrast, SC induced by repeated allogenic stimulation were suppressive in MLC but not CON A cultures, did not initiate early blastogenesis in the presence of naive cells and were partially mitomycin resistant. The mitomycin resistant SC induced by allogeneic stimulation are found in the theophylline resistant T-cell subset. These data are consistent with a model of human SC differentiation in which at least two subsets may be present: (1) a mitomycin sensitive, nonspecific cell that participates in an obligatory early autologous recognition event (induction?) and (2) a later occurring, more mitomycin resistant effector cell that appears to acquire specificity for the response that it affects.

Bromodeoxyuridine↗
PubMed1981

A 2-year trial of prospective HLA-DR matching: effects on renal allograft survival and rate of transplantation.

In a 2-year trial at a single center, prospective HLA-DR matching for cadaver renal transplantation exerted a stronger effect than either HLA-A and B matching or blood transfusion. One-year cumulative graft survivals for two-DR-matched organs was 92%. Grafts matched for one DR antigen had a cumulative 1-year graft survival of 65% whereas grafts matched for zero DR antigens had a cumulative 1-year survival of 41%. When all cadavers with less than two identifiable DR antigens were excluded from this analysis, however, the graft survivals of the groups known to be mismatched for one or two DR antigens were similar (61% versus 59%). Grafts matched for three or four HLA-A and B antigens did somewhat better than those matched for only zero, one, or two HLA A and B antigens (74% versus 59%, 1-year survival). This effect was only demonstrable in the zero- and one-DR-matched group. Similarly, prior blood transfusion exerted a modest effect (transfused versus nontransfused, 71% versus 56% 1-year graft survival) that was also most evident in the zero- and one-DR-matched groups. The institution of this trial was also associated with a 35% annual increase in the rate of transplantation and a 50% reduction in median patient waiting time. DR typing of cadaveric donors is feasible and highly desirable. Multicenter pooling of DR-typed donors is thus predicted to lead to optimal matching for a high proportion of renal transplant candidates.

Graft Survival↗
PubMed1981

Functional cell mediated lympholysis I. Description of the assay.

The anamnestic response by human bi-directional (BD) mixed lymphocyte cultures (MLC) to restimulation by cells of the original stimulating type is generally strikingly reduced as compared to that of standard one-way cultures. This difference was shown not to be related to a change in kinetics nor was it due to exhaustion of the media or soluble factors since fresh media did not ameliorate the effect nor were supernatants from BD cultures found to be suppressive. The relative inhibition was also not reversed by removal of the allogeneic cells by phenotype specific antiserum. Cytotoxic tests with donor and responder specific antisera revealed that the cells bearing that phenotype were dramatically reduced in BD as compared to one-way cultures. Thus, the diminished secondary response appears to be due to cytotoxic elimination of the responder cells. This allogeneic cytotoxicity is dependent on non-T, phagocytic, adherent cells. The phenomenon is called Functional Cell Mediated Lympholysis (F-CML).

Cell Adhesion↗
PubMed1981

Functional cell mediated lympholysis: II. Genetics.

The diminished response to secondary stimulation of human lymphocytes primed in bi-directional (BD) mixed lymphocyte culture (MLC) has been demonstrated to be due to cytotoxic destruction of the responder cells by the numerically superior allogeneic stimulating cell population. This phenomenon is called Functional Cell Mediated Lympholysis (F-CML). Matching for HLA-A and B, HLA-DR or for MLC non-responsiveness (HLA-D) in unrelated pairs does not ablate F-CML, indicating that none of these loci serve as the exclusive target for this activity. One locus appears to be centromeric from HLA-A in an A/B recombinant family and a B/D recombinant family demonstrates a target centromeric from HLA-B. A special family with homozygous for HLA-A, B and D provided evidence for an additional locus other than HLA-A, B or D. Thus, genetic studies indicate that at least one target antigen of F-CML may be coded for by a locus that is centromeric from HLA-B and which may be distinct from HLA-D or DR.

Antigens, Surface↗
PubMed1979

Acquired agranulocytosis with granulocyte specific cytotoxic autoantibody.

Multiple infections and severe neutropenia were found in a previously healthy 29 year old man with no history of similar syndromes in the family, drug ingestion or exposure to environmental toxins. There was no evidence at the time of presentation of diseases previously associated with agranulocytosis (e.g., neoplasia, thyrotoxicosis, chronic infection, collagen-vascular disease or leukoagglutinating antibody). His serum contained a nonagglutinating, complement-dependent, cytotoxic antibody, however, reactive with peripheral blood granulocytes from 35 per cent of normal donors. The neutropenia was not affected by steroids but resolved promptly after splenectomy. Microscopic examination of the spleen revealed ingestion of polymorphonuclear leukocytes by splenic macrophages. Family studies indicated that the target antigen was non-HLA and that the antibody was not absorbed by lymphocytes or platelets. We conclude that the agranulocytosis was autoimmune in origin and suggest that similar myeloid-specific immune responses could influence granulocyte tranfusion and bone marrow transplantation by alloimmune "rejection" that would not be avoided by matching only for HLA specificities.

Adult↗
PubMed1978

Immunosuppressive activity of isolated rat and human fetoproteins.

Alpha-fetoprotein (AFP) was purified from rat hepatoma sera and pooled human cord sera. Both AFP-rich fractions prepared by consecutive ion exchange and gel filtration chromatography and pure rat AFP prepared by liquid phase immunoabsorption lacked in vitro suppressive activity. Human AFP purified by affinity chromatography was suppressive, but so was similarly purified human cord albumin. Alteration of ionic conditions was shown to affect the activity of both human AFP and cord albumin. The primary mixed lymphocyte response, the generation of the secondary response, and the memory cell, per se, were all found to be sensitive to active human AFP under the appropriate culture conditions.

Animals↗
PubMed1977

Conditions affecting the immunosuppressive properties of human alpha-fetoprotein.

The hypothesis that alpha-fetoprotein (AFP) is immunosuppressive in vitro was tested with immunoabsorbent purified human cord AFP in human lymphocyte cultures. Albumins were purified identically from cord plasma and pooled adult plasma. No preparations were suppressive in phytohemagglutinin-stimulated cultures. Both AFP and human cord albumin (HCA) produced 50% suppression of allogeneic lymphocyte cultures at 50 to 100 microgram/ml final concentrations, whereas adult and commercial albumins were not suppressive. When AFP was eluted from the immunoabsorbent column in 0.15 M NaCl rather than the conventional 0.5 M NaCl, activity was greatly diminished or lost, but could be restored by dialysis against 0.5 M KCl. Previously, inactive lots of HCA also demonstrated the same phenomenon. It appears, therefore, that the immunosuppressive activity of AFP (and albumin) may depend both on its source and the procedure by which it is isolated. Whether analogous conditions occur in vivo is unknown at this time.

Animals↗
PubMed1977

Microgranulocytotoxicity.

The microcytotoxicity assay technique has been extensively refined to permit the use of granulocytes as target cells in an effort to identify neutrophil-specific antigens. Virtually every aspect of the test required revision to obtain clear, reproducible results. The most radical modification was the adoption of double-fluorescent vital staining to detect cytotoxicity. The reactions detected with this new assay did not correlate with defined human histocompatibility systems (e.g., HLA, ABH, NA, NB, NC), nor were the target antigens detected on lymphocytes or platelets. Cytotoxicity was highly specific and was produced by the immunoglobulin fraction of alloantisera only in the presence of complement, thus implicating an antigen-antibody phenomenon rather than variable viability of the ephemeral PMN's in vitro. These specificities may have an impact on some aspects of human transplantation (especially of bone marrow) as well as playing a role in some febrile transfusion reactions. Of perhaps greater import is the suggested role of the antigens in immunoneutropenias and therefore in the response of myelosuppressed patients to adjunctive leukocyte transfusion therapy.

Antigen-Antibody Reactions↗
PubMedDate not supplied

A near-fatal reaction during granulocyte transfusion of a neonate.

Although reactions to granulocyte transfusions in neonates are rarely reported, we observed a near-fatal pulmonary reaction, presumably due to white cell antibodies, in a neonate with Rh hemolytic disease. The hemolytic disease was being treated with exchange transfusions, and at 2 days after the infant's birth, bacterial sepsis was suspected and granulocyte transfusions were begun. The first granulocyte transfusion (Day 3) was uneventful. Five minutes after the beginning of the second granulocyte transfusion (Day 4), severe respiratory distress, hypotension, bradycardia, cyanosis, and acidosis suddenly occurred. The infant's serum obtained after the reaction contained granulocytotoxic and B-lymphocytotoxic antibodies that reacted with leukocytes from the second granulocyte donor. Antibodies could not be detected either in the initial infant serum or in maternal serum. However, an antileukocyte antibody was present in the serum of a parous woman donor. We used plasma from this woman to prepare reconstituted whole blood for the exchange transfusion that we performed immediately preceding the second granulocyte transfusion. Despite the sequence of events, an irrefutable cause-and-effect mechanism could not be established because the properties of the donor and neonatal antibodies were similar, but not identical. However, this catastrophic event emphasizes both the potential for adverse effects of granulocyte transfusions in neonates and the need for caution when transfusing blood from parous women.

Agglutinins↗
PubMedDate not supplied

Comparing alloimmunization in preterm infants after transfusion of fresh unmodified versus stored leukocyte-reduced red blood cells.

PURPOSE: To compare the occurrence of red blood cell (RBC), platelet (PLT), and white blood cell (WBC) antibodies in preterm infants after transfusions. METHODS: A randomized, blinded trial was conducted in which preterm infants were transfused either with stored RBCs, prepared by prestorage leukocyte reduction and transfused throughout 42 days of storage to limit donor exposure (n = 18), or with fresh RBCs prepared without leukocyte reduction and transfused within 7 days after collection from as many donors as needed to guarantee freshness (n = 17). Nontransfused preterm infants of comparable birth weight were control subjects (n = 11). RESULTS: No RBC antibodies were detected in serial blood samples taken during the first 6 months of life. Similarly, no definite WBC antibodies were found, although weak reactivity was detected transiently in sera from two infants. Accordingly, RBC and WBC antibody production did not differ among groups. In all, 11% of the transfused the infants exhibited platelet antibodies: 14% of the infants given stored leukocyte-reduced RBCs and 7% of the infants given fresh nonleukocyte-reduced RBCs (difference not statistically significant). CONCLUSIONS: Preterm infants rarely produce antibodies to blood cell antigens after RBC transfusions, regardless of whether the exposure is to fresh unmodified RBCs from several donors or to stored leukocyte-reduced RBCs from a limited number of donors. Therefore, efforts to limit donor exposures or to remove WBCs from blood components cannot be justified simply for purposes of preventing alloimmunization in neonates.

Antibody Formation↗