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Biomedical subjects

W Diezel

Publications and source records attributed to W Diezel.

At least 37 records · Page 2Linked to original sources

Splenopentin-induced reconstitution of the immune response after total body irradiation: optimization of treatment regime.

In former investigations our group obtained an immuno-reconstituting effect in mice treated by immunosuppression after a continuous treatment with splenopentin (SP5). The goal of the present study was to test whether a small number of injections right after immunosuppression possibly produces the same result in the sense of an initial effect. Although a short-term therapy induced an increase of antibody formation which was measurable after 4 weeks, the study clearly showed that only a continuous treatment by SP5 led to an optimum, i.e. complete reconstitution of antibody formation.

Adjuvants, Immunologic

[Immunostimulants--therapeutic aspects].

A survey is given about the so far known mode of action and the therapeutic application of the following agents with immunostimulatory effects: Interleukin-2, Interferon-gamma, Tumor necrosis factor, Thymosin alpha 1, Thymopentin, Splenopentin, Thymulin, Thymostimulin, Muramyl dipeptide, Bestatin, Tuftsin and Levamisole. The treatment of patients suffering from immunodeficiency disorders and cancer with such agents seems to be possible in the near future.

Acetylmuramyl-Alanyl-Isoglutamine

Inhibition of cutaneous contact hypersensitivity by calcium transport inhibitors lanthanum and diltiazem.

Epidermal Langerhans cells (ELC) are bone marrow-derived immune cells that are important in allergic contact dermatitis. We examined the influence of calcium transport inhibitors, lanthanum and diltiazem hydrochloride, on allergic contact dermatitis induced by 1-chloro-2,4-dinitrobenzene (DNCB) in BALB/c mice. Systemic lanthanum at a dose of 0.08 mg/kg and topical lanthanum (50 microliters of 10% solution) were given 5 d before DNCB sensitization. Systemic diltiazem (30 mg/kg per dy) was given for 3 d during sensitization with DNCB. In all animals, challenge with topical DNCB to the ear skin was performed 5 d after sensitization and ear swelling was measured. Twenty four hours post-DNCB challenge, animals receiving systemic lanthanum demonstrated a 56% decrease in contact hypersensitivity (ear swelling) compared with non-lanthanum-treated animals (0.08 +/- 0.03 mm vs 0.18 mm +/- 0.02 mm, p less than 0.01). Topical lanthanum produced a 58% decrease in contact hypersensitivity (0.20 +/- 0.02 mm vs 0.41 +/- 0.03 mm, p less than 0.01). The DNCB-induced ear swelling also resolved more quickly in animals treated with lanthanum. Systemic diltiazem produced a 67% decrease in ear swelling (0.05 +/- 0.01 mm vs 0.15 +/- 0.02 mm, p less than 0.001). A decrease in epidermal Langerhans cell density of 13 to 14% was produced by systemic lanthanum, detected by both ATPase staining and Ia staining, respectively (p less than 0.05). Approximately 20% of the Langerhans cells were morphologically abnormal, having become "rounded," and lacking normal dendritic processes. From these results, we infer that calcium transport across the cell membrane of ELC may be important in the regulation of their function. Lanthanides and other calcium-channel blockers may be useful pharmacologic agents to probe these phenomena.

Adenosine Triphosphatases

[Contact hypersensitivity (DNCB test) and inhibition by the calcium channel blocker diltiazem].

We studied the influence of the calcium transport inhibitor diltiazem on epidermal Langerhans cell-induced contact dermatitis against 1-chloro-2.4-dinitrobenzene (DNCB) in Balb/c mice. Diltiazem administered systemically was found to be able to decrease allergic reactions against DNCB. Twenty four hours post challenge animals treated with diltiazem demonstrated a 36% decreased ear swelling compared with non diltiazem-treated animals (p less than 0.001). From these results, we conclude that calcium is important in regulating epidermal Langerhans cell functions and in activating these cells.

Animals

[The effect of the peptide dalargin on wound healing].

The wound-healing agent Dalargin, a hexapeptide and varios of its cleavage products were tested in a wound-healing model on the basis of granulation in rat. Three days after wounding (p.op.) an increase in granulation was observed at Dalargin concentrations of 10 micrograms/ml and 50 micrograms/ml. Seven days p.op. an increase was observed already at a Dalargin concentration of 5 micrograms/ml. The cleavage products of Dalargin had no stimulating effect on granulation. A histologic differentiation of the different cell parts in the granulation tissue led to an increased total number of cells. The concentration of 5 micrograms/ml induced both an increase in the number of endothelial cells and fibroblasts, the concentration of 50 micrograms/ml induced just an increase of the number of endothelial cells. The possible bases of the mode of operation are being discussed. The stimulating effect on wound healing as described could be confirmed by the results obtained in our animal experiments.

Animals

Prevention of graft-vs-host reaction induced immunodeficiency by treatment with splenopentin (DAc-SP5).

Early experiments had shown that splenopentin, the active part of the splenic hormone splenin, stimulates the differentiation of virgin B- and T-lymphocytes and significantly enhanced the reconstitution of immune reactions after immune suppression. The present study investigates the influence of splenopentin on the course of the graft-vs-host reaction (GVHR). The experimental model used were adult hybrid mice which received intravenously parental spleen cells. During the GVHR which has an chronical course in the strain combinations used a short stimulatory phase is followed by a long-lasting immunosuppression detected by antibody formation against sheep erythrocytes. Furthermore, the splenomegaly in the first weeks after spleen cell injection changed to a drastic decrease of the spleen weight up to strongly beyond normal values. Continuous treatment with splenopentin significantly prevented both symptoms of the GVHR: The suppression of the antibody formation was diminished widely, and no loss of spleen weight occurred. Furthermore, during the stimulatory phase anti-DNA-autoantibodies were produced in the untreated animals, while the splenopentin therapy prevented this reaction. During the further course of the experiment no increase of autoantibody production was detected later on.

Animals

Splenopentin--influence on antibody formation in immunosuppressed animals and on phagocytic capability of human granulocytes.

Sublethally x-ray irradiated C57 Bl/6 Bln. mice (whole body irradiation with 600 cGy) were treated with or without a splenopentin derivative (DA SP-5: N alpha-acetyl-L-arginyl)-(N alpha-acetyl-L-lysyl)-L-glutamyl-L-valyl-L-tyrosine and compared for their capacity to produce antibodies against target sheep red blood cells. As demonstrated DA SP-5 treated mice produced antibodies earlier and in a higher level than animals untreated. Furthermore, DA SP-5 influences the phagocytic capability of human granulocytes in a dose dependent matter.

Animals

[Anti-psoriasis and phototoxic effect of a hematoporphyrin derivative following topical administration and irradiation with visible light].

An ointment, consisting of 100 micrograms hematoporphyrin derivative +5.0 ml dimethylsulfoxide +95.0 ml Unguentum Alcoholum lanae SR, was checked for both phototoxic and antipsoriatic efficacy. After topical application and irradiation with visible light or ultraviolet radiation, healthy skin showed delayed erythemas, whereas psoriasis plaques improved markedly.

Adolescent

The influence of interferon-gamma, interleukin-2, prostaglandin E2, and cyclosporine on the polyclonal and anti-DNA antibody secretion in lymphocyte cultures derived from patients with systemic lupus erythematosus.

The influence of various immunoregulatory substances was studied in lymphocyte cultures derived from patients suffering from systemic lupus erythematosus (SLE) by using the model of spontaneous secretion of polyclonal immunoglobulin G (IgG)/immunoglobulin M (IgM) and anti-DNA autoantibodies. Compared with healthy donors, lymphocytes derived from patients with active SLE disease showed an elevated secretion of total IgG as well as anti-DNA-IgG in vitro, which was associated with an increase in the proportion of activated (HLA-class II +) T cells in their peripheral blood. Recombinant interferon-gamma increases the total IgG/IgM as well as anti-DNA-IgG/IgM secretion, which suggests that it has a possible role in the pathogenesis of SLE disease. Recombinant interleukin-2 and prostaglandin E2 normalize the high, spontaneous total IgG secretion, but elevate anti-DNA-IgG/IgM secretion. These results suggest that autoreactive B-cell clones are regulated differently in SLE patients. Cyclosporine inhibits total IgG/IgM secretion in all patients and anti-DNA-IgG/IgM secretion in six of eight patients. The possible therapeutic use of such immunomodulatory substances in SLE disease is discussed.

Adolescent

The effect of PUVA treatment on acid hydrolases in human polymorphonuclear leukocytes.

The activity of intracellular acid hydrolases in polymorphonuclear leukocytes (PMNL) from psoriatic patients and normal control subjects was determined. No significant differences between healthy and psoriatic individuals were detected, but a slight decrease in acid hydrolase activity was found in PMNL of psoriasis patients during PUVA therapy. PUVA treatment of PMNL in vitro at intensities that may be achieved in situ in the epidermis led to intracellular inactivation of acid hydrolases, which was not due to secretion of the enzymes or cell damage. The decrease in PMNL hydrolase activity appeared to be evoked by PUVA-generated reactive oxygen species because reduced glutathione prevented this decrease. The activity of free extracellular acid hydrolases was not affected by PUVA, and the superoxide production of PUVA-treated PMNL was increased. These results suggest that intracellular inactivation of acid hydrolases and possibly other lysosomal enzymes in PMNL or monocytes infiltrating the epidermis may contribute to the antipsoriatic activity of PUVA therapy.

Acetylglucosaminidase

Effect of splenopentin (SP-5) on the antibody formation in immunosuppressed mice.

Sublethally irradiated C57Bl/6 mice (whole body irradiation with 600 cGy) were treated with or without diacetyl splenopentin and compared for their capacity to produce antibodies against target sheep red blood cells. As demonstrated, mice treated with splenopentin produced antibodies earlier and in a higher level than animals untreated.

Animals

Serum-mediated inhibition of the interferon-gamma-induced HLA-DR expression on monocytes in patients with psoriasis.

Psoriatic patients have a decreased proportion of monocytes expressing class II major histocompatibility complex antigens (DR+ monocytes) in their peripheral blood. The expression of the DR antigen on monocytes after culture in the presence of either autologous lymphocytes (endogenous interferon-gamma, IFN-gamma) or exogenous IFN-gamma was investigated. In normal AB serum the lymphocytes of the majority of the patients showed a spontaneous IFN-gamma production which was sufficient for DR antigen induction, while the monocytes displayed approximate normal susceptibility to exogenous IFN-gamma as judged by DR antigen expression. However, the sera of psoriatic patients contained one or more factors that interfered with the IFN-gamma-mediated DR antigen expression on cultured monocytes of the same patients. Restoration of IFN-gamma-induced DR antigen expression on monocytes in the presence of the patient's sera was achieved by the addition of superoxide dismutase, 2-mercaptoethanol, or indomethacin. The clinical significance of these observations is discussed.

Antigens, Surface

Histamine receptor-bearing lymphocytes (HRL). VIII. Splenopentin-accelerated reconstitution of the immunoresponsiveness after elimination of HRL.

The maturation effect of DA-SP5 on a spleen cell population depleted of immunocompetent, histami nereceptor-bearing lymphocytes was examined. Conjugates of histamine and the A-chain of the mistletoe lectin I killed in vitro these cells and abolished, as shown in a previous paper, their humoral and cellular capacity by around 90%. Sublethally irradiated mice were reconstituted with the remaining cells and treated with DA-SP5 (3 intraperitoneally injections of 10 micrograms DA-SP5 per week). The strong accelerating action of DA-SP5 on the restoration of the antibody response is interpreted as an effect of DA-SP5 on the maturation of B- and T-cells under in vivo conditions.

Animals