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Biomedical subjects

J R Schmidtke

Publications and source records attributed to J R Schmidtke.

At least 19 recordsLinked to original sources
PubMed1988

Histamine type-2 receptor antagonist immune modulation. I. Increased cell-mediated cytotoxicity in normal and in down-regulated systems.

Cimetidine, a histamine type-2 receptor antagonist, is capable of immunoregulating T cell-mediated proliferative responses in both man and mouse. We present data that show that cell-mediated cytotoxicity (CMC) is also increased by cimetidine in normal and down-regulated murine splenocytes. Timed addition and removal of cimetidine from CMC generation cultures localizes the cimetidine effect to the first 24 hours of the alloantigen sensitization process. Cimetidine partially reverses CMC suppression by suppressor cells generated in vitro in a dose response manner; the result depends on the number of suppressor cells added. Mixed tumor lymphocyte cytotoxicity of splenocytes from syngeneic-tumor-bearing mice is increased by in vivo cimetidine treatment, which results in prolongation of concomitant tumor immunity. These data support the concept that cimetidine may have potential as a clinical immunofacilitator in down-regulated states of immunity.

Animals↗
PubMed1985

Cyclosporin A inhibits helper/inducer surface antigen expression on activated human lymphocytes.

Helper/inducer (H/I) and cytotoxic/suppressor (C/S) subpopulations of human peripheral blood mononuclear lymphocytes (PBL) were cultured with Concanavalin A (Con A) and Cyclosporin A (CsA) to determine effects on proliferation and surface marker expression. After 72 h in culture, CsA strongly inhibited Con A induced proliferation of H/I and C/S subpopulations in a manner similar to that observed for whole PBL. By flow cytometric analysis, enhanced expression of both the Leu-2a (C/S) and Leu-3a (H/I) surface markers was observed on PBL from con A treated cultures. Addition of CsA to these cultures inhibited the enhanced expression of Leu-3a more than that of Leu-2a. Studies showed that this CsA inhibition of enhanced Leu-3 antigen expression occurred in a concentration dependent manner, was statistically significant throughout a 4 day culture period and did not require addition of C/S cells to mediate the effect. The data suggest that CsA blocks Con A induced blastogenesis at an early stage of activation.

Adult↗
PubMed1985

Alterations in lymphocyte subpopulations in copper-deficient mice.

Analyses of cell surface determinants of splenocytes from copper-deficient C58 mice indicate alterations in lymphocyte subpopulation characteristics. Both the absolute number and the relative percentage of surface immunoglobulin-bearing (B) cells from copper-deficient mice were significantly greater than those from copper-supplemented controls. The relative percentage of Thy 1.2-positive (T) cells was decreased, and the decrease was most prominent within the Lyt 1-positive (helper) T-cell subset. The functional responsiveness of both B cells and T cells was decreased in copper deficiency.

Animals↗
PubMed1983

Effects of methylprednisolone on concanavalin A-induced human lymphocyte blastogenesis: a comparative analysis by flow cytometry, volume determination and 3H-thymidine incorporation.

The inhibition of concanavalin A-induced human peripheral blood lymphocyte blastogenesis by methylprednisolone (MP) was studied by using flow cytometry and tritiated thymidine (3H-TdR) incorporation. Flow cytometric determinations of volume, low angle forward light scatter, and nucleic acid showed MP to be a potent inhibitor of blastogenesis. The effects were concentration-dependent and correlated with 3H-TdR uptake. By using the single cell analytic capability of flow cytometry, the target stages of the cell cycle where MP affects lymphocyte activation were determined. Evidence is presented that steroids can block both early and late phases of this process.

Adult↗
PubMed1982

The immunomodulatory action of frentizole, a novel immunosuppressive agent.

The in vitro effects of frentizole and methylprednisolone on human PBL were examined. Both drugs exhibited differential effects on lymphocyte subpopulations. Frentizole was more effective in suppressing human lymphocytes responding to Con A and PWM, than it was in cells activated by PHA, specific antigen, or alloantigen. Methylprednisolone, on the other hand, was more inhibitory for cells stimulated by PHA, specific antigen, or alloantigen. These data suggest that frentizole has a preferential effect on the cytotoxic/suppressor subpopulation of human T lymphocytes while methylprednisolone appears to preferentially affect the helper/inducer subset. Differences in potency between the two drugs were also observed. Methylprednisolone was better able to maintain its inhibitory effects during longer periods of culture than frentizole. Both agents were less effective if their addition to the culture was delayed 24-48 hrs and neither drug was very effective in overcoming the adjuvant action of poly A:U on mitogenically activated human PBL.

Adjuvants, Immunologic↗
PubMed1981

Schultz-Dale reaction in mouse trachea.

A method was developed to induce contraction of immunologically sensitized mouse trachea by antigen (Schultz-Dale reaction). The response was mediated by immunoglobulin (Ig) E antibody directed against either the hapten DNP, the hapten carrier conjugate DNP-keyhole limpet hemocyanin (KLH), or the unmodified carrier KLH. Tracheal contractions were elicited by DNP-KLH, KLH, or DNP-bovine serum albumin (BSA) but not by DNP or BSA alone. This procedure represents a useful index of in vitro anaphylaxis in mouse airway smooth muscle.

Anaphylaxis↗
PubMed1981

Synergistic effects of lipopolysaccharide on phytohemagglutinin- and concanavalin A-induced deoxyribonucleic acid synthesis in human peripheral blood lymphocytes: participation of T lymphocytes.

Lipopolysaccharide induces a synergistic uptake of tritiated thymidine in peripheral blood lymphocytes (PBL) when cultured with phytohemagglutinin or concanavalin A as compared to PBL incubated only with phytohemagglutinin or concanavalin A. In this study we investigated which subpopulations(s) of PBL is involved in this synergistic increase in deoxyribonucleic acid synthesis. Separation of PBL into sheep erythrocyte rosette-forming cells (T cells) and non-rosette-forming cells (B cells) showed that the T cells were responsible for the increased uptake of radiolabel. PBL and T cells had similar dose-response profiles and kinetic patterns. Paralleling this augmented tritiated thymidine uptake was an increase in the number of cells undergoing blast transformation. Delayed-addition experiments showed that the two mitogens must be added within 12 h of each other for maximal augmentation to occur. Finally, preincubation of T cells with lipopolysaccharide had no demonstrable effect on the amount of concanavalin A uptake by these cells. This model may provide unique information about the activation of human peripheral blood T cells compared to activation of these cells by one mitogen.

Biological Transport↗
PubMed1980

Cimetidine-induced augmentation of human lymphocyte blastogenesis by mitogen, bacterial antigen, and alloantigen.

The effect of Cimetidine, a histamine-type 2 receptor antagonist, was evaluated on the in vitro proliferative response of normal human peripheral blood lymphocytes (PBLs). Cimetidine (10(-3) to 10(-8) M) increased mitogen-induced blastogenesis by 22% (phytohemagglutinin (PHA) and by 27% (pokeweed) over nondrug-treated control values (P less than 005 for PHA and pokeweed). Preincubation of PBLs with Cimetidine further augmented blastogenesis as much as 2- to 3-fold (P less than 0.005 for both mitogens). Multiple testing of the same normal subject demonstrated consistent reproducibility of increased proliferation by Cimetidine. Similar statistically significant amplifications of the proliferative res-ponse were observed when bacterial antigen (streptokinase-streptodornase) or alloantigen was used to induce blastogenesis. Optimally effective concentrations of Cimetidine ranged from 10(-5) to 10(-7) M, which corresponds to expected clinical serum levels. These observations suggest that a histamine-type 2 receptor antagonist is capable of modulating the proliferative response of PBLs in the absence of exogenously added histamine. The immunoregulatory implication of this Cimetidine-induced proliferative augmentation is discussed in relation to clinical transplantation and cancer immunotherapy.

Antigens, Bacterial↗
PubMed1980

Lipopolysaccharide-induced immunomodulation of the generation of cell-mediated cytotoxicity. I. Suppression of the development of cytotoxic lymphocytes.

Bacterial lipopolysaccharide from a variety of Gram-negative organisms suppresses the development of cytotoxic killer cells in the murine MLC. Cytotoxic T lymphocytes were generated in vitro by incubating BALB/c responder spleen cells with irradiated C57BL/6 stimulator cells for 5 days in mixed lymphocyte culture (MLC). The addition of LPS at the initiation of MLC suppressed killing of 51Cr-labeled target cells in a dose-dependent manner. LPS was active only during the afferent phase of CMC, since it did not interfere with the efferent phase of the assay. Furthermore, timed addition and timed removal studies suggested that the presence of LPS during the first 48 hr of MLC was critical for maximal suppression of CMC. Lipid A extracted from LPS, which had been shown to be highly suppressive when added to the sensitization phase of the CMC assay, was also inhibitory. Moreover, when LPS was added to MLC in the presence of tritiated thymidine, the proliferative activity of the responder cells increased markedly after 72 hr of culture. These data suggest that LPS, a known B cell mitogen, can modulate the complex sequence of cellular interactions that leads to the generation of cell-mediated cytotoxicity.

Animals↗
PubMed1979

Intralesional immunotherapy of malignant melanoma with mycobacterium smegmatis cell wall skeleton combined with trehalose dimycolate (P3).

The clinical efficacy of intralesional immunotherapy utilizing Mycobacterium smegmatis cell wall skeleton (CWS) and trehalose dimycolate attached to oil droplets was investigated in 15 patients with advanced malignant melanoma. Patients received 300 microgram to 1050 microgram of the CWS combined with one-half that amount of trehalose dimycolate every 1 to 2 weeks for a total of 8 treatments. Therapy was continued if regression of injected lesions only occurred. Therapy was discontinued if regression of noninjected disease also occurred. Six of the 15 patients had regression of at least one injected lesion. Four of these 6 patients also had regression of noninjected disease lasting 4+, 6, 16 and 18+ months. Response was highly related to immune status. Six (83%) of 7 patients who reacted to one of a battery of skin tests responded. All 8 patients who did not react to skin tests failed to respond to therapy. There was no correlation of response with sex, prior therapy, disease-free interval or presence of visceral disease. Mycobacterial CWS and trehalose dimycolate is an effective immunotherapeutic agent. Additional studies of purified immunoadjuvants are warranted.

Cell Wall↗
PubMed1979

Differential susceptibility of human peripheral blood lymphocyte subpopulations to mitogenic activation. Influence of methylprednisolone.

The inhibition of the mitogenic activation of human peripheral blood lymphocyte (PBL) subpopulations by methylprednisolone (MP) was dependent on the mitogen used. Purified human T cells were more sensitive to the effects of MP than were B cells or PBLs, especially when these cells were activated by pokeweed mitogen (PWM). MP did not function by inhibiting binding of mitogen to the cell surface. After being mitogenically activated, human lymphocytes were resistant to the effects of MP. These effects of MP were shown to be reversible. Monocytes did not provide a significant degree of protection to mitogenically activated human T cells incubated with MP. These data suggest that MP-induced inhibition of the mitogenic activation of human PBLs may be a reflection of lymphocyte heterogeneity, and that the differential sensitivity of PBLs to MP may be used to isolate functionally different subpopulations of these cells.

Classification↗