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J R Schmidtke

Publications and source records attributed to J R Schmidtke.

At least 37 records · Page 2Linked to original sources
PubMed1979

Improved renal allograft survival with selected HLA antigen matching.

We examined the influence of the three most frequent linkage disequilibrium antigen combinations, HLA 1-8, 2-12, and 3-7, on renal allograft survival. We reviewed the results of 214 first transplants to recipients sharing exactly two HLA-A or -B antigens with the donor, excluding failures caused by hyperacute rejection or technical factors. Actuarial graft survival for matches having HLA 1-8, 2-12 or 3-7 was compared with all other two-antigen matches within the group. Improved graft survival, occurred with HLA 1-8 matches (85% and 80% at 2 and 5 years, respectively) and with HLA 2-12 matches (80% at both 2 and 5 years), compared to all other two-antigen matches (71% and 58% at 2 and 5 years, respectively). Allografts matched for HLA 3-7 had poorer graft survival (44% at both 2 and 5 years). We compared nondiabetic and diabetic recipients and found similar improved graft survival with HLA 1-8 or 2-12 matches in nondiabetic recipients. There was no difference, however, in graft survival in diabetic recipients with HLA 1-8 or 2-12 matches, as compared to other two-antigen matches. We conclude that HLA antigen matches of 1-8 or 2-12 between donor and recipient have demonstrated improved graft survival in nondiabetic recipients, while HLA 3-7 matches have poorer survival, as compared to other two-antigen matches. Thus, unlike single antigen serotyping, selected HLA antigen matching appears to afford superior graft survival.

Antilymphocyte Serum↗
PubMed1977

Chemiluminescence response of human leukocytes: influence of medium components on light production.

Light-producing reactions have been reported to occur after phagocytosis of opsonized particles by human polymorphonuclear neutrophils, eosinophils, and monocytes. Such chemiluminescence appears to be related to the generation of singlet oxygen, superoxide, and hydroxyl radicals, which have also been implicated as microbicidal agents. In examining the influences of various medium components on leukocyte chemiluminescence, we have observed that the amount of light measured is increased by addition of soluble protein, the amino acids tyrosine and tryptophane, or excess zymosan to the reaction medium. These agents appear to produce their effect not by increasing the rate of phagocytosis, but by providing substrate for secondary light-producing reactions. Polystyrene particles do not provide a suitable substrate for such secondary light-producing reactions. This is evidenced by the failure of ingested latex to stimulate high levels of chemiluminescence in the cellular system and their failure to augment light production in two noncellular chemiluminescent reactions. Some of the light generated in the cellular chemiluminescence response may derive from secondary reactions, which occur outside of the phagocyte. Support for this phenomenon is provided by two experiments. In one, addition of supplementary, nonopsonized zymosan to the reaction, after phagocytosis of opsonized zymosan is complete, resulted in an increased level of chemiluminescence. In another, addition of nonopsonized zymosan, together with latex particles, resulted in a significant increase in chemiluminescence. The results of the latter experiment also support our hypothesis that latex does not provide an appropriate substrate for secondary light-producing reactions. These observations suggest that leukocytes activated by phagocytosis generate electronically activated radicals which act intra- and extracellularly and that the amino acids tyrosine and trytophane may provide one substrate through which these agents act.

Culture Media↗
PubMed1976

Differential effects of chlorpromazine on the in vitro generation and effector function of cytotoxic lymphocytes.

Allograft rejection represents a cytotoxic response mediated to a large degree by thymus-derived T lymphocytes (1). The study of such cell-mediated cytotoxic phenomena has been greatly facilitated by the discovery first noted by Hayry and Defendi (2) and Wunderlich and Cany (3), that a natural consequence of allogeneic stimulation in an unidirectional mixed lymphocyte culture (MLC) was the appearance of cytotoxic lymphocytes specific for antigens present on the stimulator cells. Subsequent studies have shown that such in vitro generation of cytotoxic lymphocytes was dependent on the proliferative response in an MLC (4), was genetically determined (5), and possibly required the interaction of several subpopulations of T cells (6). We now report that the surface active agent chlorpromazine: (a) inhibits allogeneic stimulation of the proliferative response in an MLC; (b) inhibits the MLC generation of cytotoxic lymphocytes, (c) has no effect on the recognition, binding, or lysis of target cells by already sensitized lymphocytes; and (d) blocks a postproliferative membrane-mediated event, independent of proliferation, and necessary for the MLC generation of cytotoxic lymphocytes.

Animals↗
PubMed1976

Seven years' experience with antilymphoblast globulin for renal transplantation from cadaver donors.

Antibody of the IgGab type can be isolated from horses immunized with cultured human lymphoblasts plus complete Freund's adjuvant. The essential steps for the production of a safe, potent anti-human lymphoblast globulin (ALG) are: A) the use of early bleedings after immunization to reduce the titer of antibodies which react with red blood cells and platelets; B) careful absorption with human red blood cell stroma and platelets; C) stabilization with non-crystalline silica dioxide; D) chromatography through QAE sephadex to remove pyrogens, microaggregates and possible inhibitors of ALG activity; E) careful safety testing in animals for toxicity and pyrogenicity; and F) testing in vitro for sterility. Such a purified horse ALG (IgGab) can be administered safely intravenously to patients to supplement a standardized immunosuppressive regimen incorporating azathioprine and prednisone. Under these circumstances, allergic reactions are very rare, antibodies to horse IgG do not develop, skin tests to horse IgG remain negative, and immune elimination of circulating horse IgG from the human circulation cannot be demonstrated. The overall results of ALG patient survival and transplant function after 184 consecutive first cadaver transplants at the University of Minnesota demonstrate a statistically significant improvement in both parameters accompanying increases in ALG dose while rigidly utilizing standardized doses of azathioprine and prednisone. There is a significant reduction in the number of grafts lost to rejection; significant reduction in the number of rejection episodes; significant delay in the onset of rejection episodes; but there is no increase in septic loss of patients or kidneys. These efforts could be seen in the gross data or when subgroups controlling for patient age, tissue typing were analyzed. Excluding patients at high risk did not alter the results. The beneficial effects of ALG were particularly striking in good matches. In the highest doses, ALG may be dangerous for older patients with poor matches who develop an increased incidence of septic loss of kidney and/or life. Thus, ALG appears to be a useful adjunct in the early management of cadaver transplants by reducing the incidence and frequency of rejection episodes. The dose should probably be reduced in the older patients who receive kidneys from badly mismatched donors. One cannot conclude from this study that ALG manufactured in other centers by this or other techniques, will accomplish the same results since the multiplicity of factors involved in the success and failure of transplants must be controlled so that the influence of intravening variables in the assessment of ALG effectiveness can be assessed.

Age Factors↗
PubMed1976

Activation of purified human T cells by mitogens: diminished mitogen-induced deoxyribonucleic acid synthesis in human T cells compared with autologous peripheral blood lymphocytes.

Human thymus-derived (T) cells were isolated from peripheral blood after rosette formation with neuraminidase-treated sheep erythrocytes (SRBC). After separation on Ficoll-hypaque, SRBC were removed from T cells by treatment with tris(hydroxymethyl)aminomethane-NH4Cl. Human T cells and autologous peripheral blood lymphocytes (PBL) were then incubated with phytohemagglutinin, concanavalin A, or pokeweed mitogen. Human T cells, in the absence of other cell types, responded with less deoxyribonucleic acid (DNA) synthesis (measured by uptake of [3H]thymidine) than equal numbers of autologous PBL. Further experimentation established that, compared with autologous PBL, the diminished capacity of human T cells to be activated by mitogens was due neither to differences in the mitogen dose-response relationship nor to the time of peak DNA synthesis of T cells or autologous PBL. Fragments or components of SRBC were not detected on human T cells, and treatment of the T cell-SRBC mixture with tris(hydroxymethyl)aminomethane-NH4Cl did not contribute to the results. Increased cell density or a period of preculture before addition of mitogen also did not influence the degree of decreased DNA synthesis in human T cells compared with the response of autologous PBL incubated with the same mitogens. When mixed with the cells remaining at the Ficoll-media interface, purified human T cells did not suppress the mitogenic response of this cell mixture to PHA or concanavalin A. The data indicated that human T cells, in the absence of other cell types, were activated by mitogens to a lesser degree than autologous PBL. Furthermore, T cells responded with DNA synthesis after direct T cell-mitogen interaction.

Cell Separation↗
PubMed1976

Activation of purified human thymus-derived (T) cells by mitogens. II. Monocyte- macrophage potentiation of mitogen-induced DNA synthesis.

Thymus-derived (T) cells from peripheral blood were purified by rosette formation with neuraminidase-treated sheep red blood cells (SRBC) and centifugation on Ficoll-Hypaque. T cells recovered from the pellet were freed of SRBC by treatment with Tris-NH4Cl. T cells purified by this method showed a diminished ability to take up 3H-thymidine (3H-TdR) after mitogen stimulation when compared to the mitogenic response of an equal number of autologous peripheral blood mononuclear lymphocytes (PBL). Autologous monocytes restored the capacity of purified T cells to take up 3H-TdR in the presence of phytohemagglutinin (PHA) or Concanavalin A (Con A). The effect was proportional to the number of monocytes added. Similar restorative effects could be obtained with allogeneic or xenogeneic monocytes. These data suggest that the mitogenic stimulation of human PBL and Con A may reflect the participation of more than one cell type: the T cells and monocyte and that the genetic origin of the monocyte is not critical for augmentation of the mitogenic activation of human T cells.

Animals↗
PubMed1976

Effect of Vibrio cholerae neuraminidase on the generation of cell-mediated cytotoxicity in vitro.

Vibrio cholerae neuraminidase (VCN))12.5 units/2 X 10(6) cells/ml) continuously present for a standard 5-day MLC will significant (p less than 0.02) increase the cytotoxic activity generated by a given number of responding spleen cells without reducing the specificity. Heat-inactiviated VCN produced no such augmentation. This augmented cytotoxicity could be reproduced by preincubating (1 hr) the responding spleen cells with VCN (25 units/2.5 X 10(6) cells/ml) before addition of stimulating spleen cells. Preincubating the stimulator spleen cells with VCN had no effect. VCN preincubation of target cells or presensitized effector cells produced no augmentation. The addition of soluble VCN to the killing assay also did not increase cytotoxicity. Thus, VCN acts only during the generation of specifically sensitized cytotoxic T cells. When the effect of VCN on MLC reactivity, cell recovery and total cytotoxicity (lytic units/10(6) cells) were compared, it became apparent that VCN increases the proliferation of responder cells after stimulation resulting in both an increased number of cells and also an increase in the proportion of specifically sensitized cytotoxic cells in the culture. VCN treatment of responder cell membrane apparently permits a more ready response to allogenic antigens in culture facilitating both increased proliferation and the increased development of specific cytotoxic killers.

Animals↗
PubMed1976

Inhibition of mitogen-induced lymphocyte transformation by local anesthetics.

Chlorpromazine (CPZ) and lidocaine were added to cultures of mouse spleen cells stimulated by concanvalin A (Con A), phytohemagglutinin (PHA), pokeweed mitogen (PWM) and lipopolysaccharide (LPS). Concentrations of CPZ greater than 5 x 10(-6)M and concentrations of lidocaine greater than 2 x 10(-3)M totally inhibited the mitogenic responses to all four mitogens. Minimal inhibitory concentrations of neither drug interferred with cell viability as determined by trypan blue uptake or 51Cr release. The effects were totally reversed by the removal of the drugs from the culture. Addition of the drug at intervals after mitogen exposure demonstrated that the inhibited event occurred relatively soon after exposure to the mitogen. For example, the addition of lidocaine or CPZ more than 24 hr after Con A stimulation had no effect on tritiated thymidine incorporation. Elevated concentrations of cyclic AMP, cyclic GMP (or their derivatives) or calciunown membrane active actions of these drugs and the rapid reversibility of the effect strongly support the idea that the local anesthetics act on the surface membrane of lymphocytes. Binding of radiolabeled Con A or LPS to lymphocyte membranes in the presence of lidocaine or CPZ was not inhibited. The possibility exists that CPZ and lidocaine disorganized cell membranes so as to interfere with the surface membrane elaboration or action of a second messenger, or interfere with cell-cell interactions.

Animals↗
PubMed1975

Augmented uptake of neuraminidase-treated sheep red blood cells: participation of opsonic factors.

Neuraminidase from Vibrio cholerae (VCN) was used to treat sheep red blood cells (SRBC) which were then incubated in vitro with murine peritoneal macrophages. The uptake of VCN-treated SRBC by macrophages was greater than the uptake of SRBC not treated with VCN. SRBC opsonized with normal mouse serum (NMS) were taken up to a greater extent than untreated SRBC. SRBC treated with VCN and opsonized with NMS were phagocytosed to a greater extent than untreated SRBC, VCN-treated SRBC, or opsonized SRBC. Evidence demonstrated that factors in serum from normal C3H/HeJ mice augmented the uptake of VCN-treated SRBC in greater amounts than of normal SRBC. These findings were discussed in relation to the increased immunogenicity of neuraminidase-treated cells.

Animals↗
PubMed1975

Synergistic effects on DNA synthesis of phytohemagglutinin or concanavalin A and lipopolysaccharide in human peripheral blood lymphocytes.

Mixtures of phytohemagglutinin (PHA) or Concanavalin A (Con A) and lipopolysaccharide (LPS) with human peripheral blood lymphocytes (PBL) resulted in a synergistic effect on DNA synthesis as measured by increased 3H-thymidine uptake. These data were compared to the mitogenic response of human PBL to PHA, Con A, or LPS alone. Various combinations of PHA and Con A usually suppressed DNA synthesis in human PBL. Titration experiments revealed that increasing amounts of LPS, in the presence of a constant amount of Con A, resulted in corresponding increases in the synergistic response of human PBL. Conversely, increasing amounts of Con A, in the presence of a constant amount of LPA did not lead to increases in the amount of synergism. The results are discussed in terms of the participation of additional cells in the synergistic response of human PBL.

Concanavalin A↗