Biomedical subjects

W Diezel

Publications and source records attributed to W Diezel.

At least 19 recordsLinked to original sources

PubMed1992

Inhibition of skin allograft rejection and acute graft-versus-host disease by cis-urocanic acid.

Ultraviolet B radiation initiates a suppression of the delayed-type hypersensitivity response accompanied by a generation of antigen-specific suppressor cells and an alteration of antigen-presenting function. In previous studies we and other investigators could achieve a prolongation of graft survival by a treatment of the recipient with UVB light or 8-methoxy-psoralen plus UVA light (PUVA). One of the mediators of the systemic immunomodulatory effects of ultraviolet light or PUVA may be urocanic acid, which is isomerized in the skin by ultraviolet light from its cis- to the trans-isomer. In this work we present evidence that cis-urocanic acid, generated in vitro by a treatment with UVB light or PUVA, is able to prolong the survival of allogeneic MHC disparate skin grafts in mice. In contrast, the rejection of second set grafts was not suppressed. Unirradiated (trans-urocanic acid) had no effect on allograft rejection. In a murine model cis-, but not trans-urocanic acid, prevented or delayed an acute lethal graft-versus-host disease. These experiments demonstrate the potent systemic immunomodulatory effects of cis-urocanic acid in vivo.

Animals↗

PubMed1992

[ATPase positive epidermal Langerhans cells: inhibition of ATPase by ammonium bituminosulfonate (Ichthyol) and pix lithanthracis].

Both, ammonium bituminosulfonate (Ichthyol) and Pix lithanthracis reduce the number of ATPase-positive epidermal Langerhans cells (ELC) in the epidermis of BALB/c mice: vaselinum flavum alone vs vaselinum flavum +5% Ichthyol: P less than 0.01; vaselinum flavum vs vaselinum flavum +5% Pix lithanthracis: P less than 0.001. In contrast to this, the number of Ia-positive cells was not changed under identical conditions. These results allow the conclusion that Ichthyol and Pix lianthracis are able to inhibit the enzyme ATPase on the surface of ELC. We infer that inhibition of ELC ATPase may be important in the regulation of ELC function (inhibition of cutaneous contact hypersensitivity).

Adenosine Triphosphatases↗

PubMed1992

[Ammonium bituminosulfonate (Ichthyol). Anti-inflammatory effect and inhibition of the 5-lipoxygenase enzyme].

Ammonium bituminosulphonate (Ichthyol) inhibits 5-lipoxygenase activity in human polymorphonuclear neutrophils. The inhibition is dose-dependent and occurs at non-cytotoxic concentrations of the drug. This results in a decreased release of Leukotriene B4 from polymorphonuclear neutrophils. Furthermore, when applied to the ear skin of AB/Bln mice pretreated with croton oil, Ichthyol reduces the inflammatory reaction.

Animals↗

PubMed1992

[In vitro proliferation of human bone marrow cells--inhibition by components of Candida albicans].

Candida albicans (CA) components influence the proliferation of human bone marrow cells in vitro (colony-forming assay). Number of colonies per 10(5) bone marrow cells after cultivation with rHuGM-CSF (maximal plateau colony formation): 46.2 +/- 9.1 (n = 6); after cultivation with rHuGM-CSF in combination with CA proteins: 0.05 mg protein/ml: 33.4 +/- 4.6 (n = 3); 0.10 mg protein/ml: 20.8 +/- 3.6 (n = 3).

Bone Marrow Cells↗

PubMed1991

Inhibition of Langerhans cell ATPase and contact sensitization by lanthanides--role of T-suppressor cells.

Lanthanides are rare earths, elements 55-71 in the periodic table, that are of interest in biologic systems as isomorphic competitors for calcium binding sites. Lanthanides were tested for their inhibitory influence on the Ca++/Mg(++)-dependent ATPase of epidermal langerhans cells in vitro, and on the immunologic function of Langerhans cells in vivo. The trivalent ions of lanthanides, lanthanum, and cerium completely inhibited the ATPase staining of Langerhans cells in vitro. When mice were sensitized with dinitrofluorobenzene on skin sites pretreated with topical lanthanum chloride, and challenged on untreated ear skin, a markedly reduced contact hypersensitivity response was observed. This hyporesponsiveness was found to be antigen specific, and could be passively transferred to naive syngeneic animals recipients by CD4-CD8+ spleen cells. These results suggest that inhibition of the epidermal Langerhans cell surface ATPase by application of topical lanthanum and the induction of antigen-specific immunologic tolerance may be related events.

Adenosine Triphosphatases↗

PubMed1990

Cytofluorometric and cytomorphologic analysis of human bone marrow cells derived from stromal cultures stimulated by granulocyte-macrophage colony-stimulating factor, interferon-gamma and splenopentin pentapeptide.

We studied the influence of human recombinant granulocyte-macrophage colony-stimulating factor (hrGM-CSF), human recombinant interferon-gamma (hrIFN-gamma) and splenopentin pentapeptide (Sp-5), either alone or in combination, on the proliferation and differentiation of human bone marrow cells in modified Dexter's cultures. After 10, 14 and 21 days cells were analyzed by classical staining according to Pappenheim and by cytofluorometry with a set of different monoclonal antibodies. IFN-gamma inhibited the proliferation of progenitor cells and provided signals promoting monocytic differentiation, whereas GM-CSF induced the proliferation of blastoid elements which expressed HLA-DR and M2 (VIM-2 monoclonal antibody), but progressively lost surface CD34. Furthermore, an increase of CD15+ cells was also observed. When GM-CSF was tested in combination with IFN-gamma, it abolished the inhibitory effect of IFN-gamma and both cytokines synergized to promote the expression of CD11c, CD14 and M2 surface antigens. Sp-5 alone had only a marginal activity, but it potentiated the effects of GM-CSF. These findings suggest that GM-CSF may induce the transition from stem cells to committed myeloid progenitors. In contrast to IFN-gamma, Sp-5 can serve as an additional proliferative signal with negligible effects on cell maturation.

Amino Acid Sequence↗

PubMed1990

Inhibition of rat heart allograft rejection by a PUVA treatment of the graft recipient. Role of cisurocanic acid.

Treatment of rat heart grafts with PUVA, the combination of the photosensitizer 8-methoxypsoralen and longwave ultraviolet light, leads to a prolonged transplant survival in allogeneic recipients. A PUVA treatment of the recipient rats, performed for 7 consecutive days after transplantation, prolonged graft survival even more effectively. This may be due to the systemic immunomodulatory effects of PUVA in the recipient. One of the mediators is urocanic acid, which is transformed by ultraviolet light in the skin from its trans- to the cis-isomer, which, in turn, acts as a mediator on the immune system. An injection of cisurocanic acid into graft recipients for 7 consecutive days after transplantation resulted in prolonged graft survival; in 40% of the rats, permanent graft acceptance was observed. The significance of these results for clinical organ transplantation is discussed.

Analysis of Variance↗

PubMed1990

Stimulation of the recruitment of epidermal Langerhans cells by splenopentin.

Splenopentin (SP-5: Arg-Lys-Glu-Val-Tyr), a pentapeptide corresponding to the residues 32-36 of the splenic hormone splenin, increases dose-dependently the number of bone marrow colonies (M and GM colonies). Therefore, we tested the stimulatory effect of SP-5 on the recruitment of epidermal Langerhans cells in skin deprived of these cells. A high dose of cyclophosphamide or dexamethasone led to a drastic decrease of LC density in murine skin with slow and incomplete restoration. SP-5 accelerated Langerhans cell recruitment and led to pretreatment levels of Langerhans cell density in the skin. These results indicate that SP-5 may possibly be used to treat disorders (e.g., HIV infection) where impaired Langerhans cell density and function can lead to secondary cutaneous infections.

Animals↗

PubMed1990

Splenopentin (DAc-SP-5) accelerates the restoration of myelopoietic and immune systems after sublethal radiation in mice.

In 1981 a new splenic hormone was described by Audhya et al. (Biochemistry, 20, 6195-6200, 1981). At first designated as thymopoietin III, the complete amino acid sequence had been described as splenin in 1984. For the pentapeptide corresponding to amino acids 32-36 of splenin was shown to be active in immunological systems. The synthetic pentapeptide splenopentin (DAc-SP-5) and the sequence 32-36 of splenin are identical. In this study the recovery of immunocompetence in mice following sublethal irradiation is shown to be enhanced by DAc-SP-5. The treatment effects of DAc-SP-5 were verified by splenic plaque-forming response to a T-cell dependent antigen and in the hematopoietic colony-forming assay. These effects were associated with an accelerated recovery of leukocyte counts in peripheral blood and spleen without significant changes in the relation between leukocyte and lymphocyte subpopulations. Furthermore, in comparison to control animals DAc-SP-5 treated mice showed in the first weeks postexposure a significantly higher number of bone marrow derived cells as well as granulocyte-macrophage and macrophage colony-forming cells (GM-CFC and M-CFC). Therefore, DAc-SP-5 may be a useful substance for treating secondary forms of bone marrow depression.

Animals↗

PubMed1990

Splenopentin (DAc-SP5)--influence on engraftment and graft-vs-host reaction after non-H-2 bone marrow transplantation in mice.

The influence of DAc-SP5 on engraftment and graft-vs-host reaction (GVHR) was studied in different non-H-2 strain combinations. The engraftment was more or less enhanced in every case, whereas the situation in the GVHR was completely different. In one case splenopentin did not influence the course of the GVHR so much, in a second case the symptoms of the GVHR were completely abolished, and in a third case the GVHR was dramatically enhanced up to a great mortality. Therefore, before application of DAc-SP5 to the bone marrow transplantation in humans in order to improve the engraftment, parameters have to be found which allow an exact prediction about the influence of splenopentin on the GVHR in each single case.

Animals↗

PubMed1990

[The effect of Tomesa therapy on epidermal Langerhans cells in experimental animals].

In the last years a new therapy of psoriasis was developed, which consists in a treatment with salt solutions, resembling the water of the Dead Sea, and ultraviolet light (Tomesa-therapy). We studied the influence of the used salt on ATPase positive epidermal Langerhans cells in murine ear skin. An irreversible partial reduction of the Langerhans cell ATPase was found after salt treatment of separated epidermis or of full skin preparations. These results may have implications for the optimization and broader application of this therapy.

Adenosine Triphosphatases↗

PubMed1990

[Inflammation-inhibiting effect of magnesium ions in contact eczema reactions].

Water containing high concentrations of magnesium ions (e.g. Dead Sea water) is effective in the treatment of inflammatory skin diseases. Therefore, we examined the influence of Mg2+ on inflammation in allergic contact dermatitis induced by 1-chloro-2,4-dinitrobenzene (DNCB) in BALB/c mice. Animals challenged with 0.125% DNCB in the presence of magnesium chloride (28% and 14%) demonstrated significantly less pronounced contact dermatitis (ear swelling) than did animals challenged with DNCB alone (p less than 0.001 and p less than 0.01). In mice challenged with DNCB in combination with sodium chloride (14%) there was no statistically significant difference in the degree of ear swelling. These results were borne out in 5 patients known to be allergic to nickel, in whom magnesium chloride but not sodium chloride, suppressed nickel sulphate-induced contact dermatitis.

Adolescent↗

PubMed1990

[Prolonging transplant survival time by PUVA treatment of the transplant recipient. Significance of cis-urocanic acid].

A PUVA treatment of the recipients of murine tail skin grafts led to a significant prolongation of transplant survival. A possible mechanism of the systemic immunomodulatory effects of ultraviolet light in the organism is the transformation of urocanic acid in the skin from its trans- to the cis-isomer, which acts as a mediator on the immune system. A treatment of graft recipients with cis-, but not trans-urocanic acid also prolonged graft survival. The rejection of secondary grafts and the humoral immune response of mice to sheep erythrocytes were not influenced by cis-urocanic acid. These results implicate that cis-urocanic acid may be get use in clinical organ transplantation and dermatology.

Animals↗

PubMed1990

[Therapeutic use of splenopentin (DA SP-5) in patients with psoriasis arthropathica].

8 patients with confirmed psoriatic arthritis were treated with splenopentin for 12 months. A relief of joint pain could be detected under this treatment both after 6 weeks (improvement of the Ritchie-indices: 44%) and after 12 months (improvement: 28%). In contrast to this, X-ray investigations show a worsening of the disease after 12 months. Therefore we conclude that splenopentin alone is not a sufficient therapeutic drug in patients suffering from psoriatic arthritis.

Adult↗

PubMed1990

[Abnormal hematopoiesis in psoriasis--in vitro studies].

Using mononuclear cells (MNC) of patients suffering from psoriasis for production of colony-stimulating factors (CSF) an abnormal colony formation in bone marrow of healthy volunteers was detected (colony-forming assay): Number of colonies per 10(5) bone marrow cells after cultivation with 10(6) MNC of patients suffering from psoriasis vulgaris: 65 +/- 14 (n = 8); psoriasis arthropathica: 63 +/- 11 (n = 8). Control values (10(5) bone marrow cells plus 10(6) MNC of healthy donors): 116 +/- 23 (n = 10). Statistical differences: psoriasis vulgaris: p less than 0.001; psoriasis arthropathica: p less than 0.001. The mechanisms responsible for these abnormalities in hematopoiesis are still unknown. They may be of pathogenic significance in psoriasis.

Adolescent↗

PubMed1989

The dipeptide Lys-Pro restores the diminished wound healing following treatment with anti-T-helper cell monoclonal antibody.

To determine the role of T-cell subsets in wound healing, we studied the granulation tissue proliferation after depletion of CD4 or CD8 positive cells. Granulation tissue proliferation in CD8-diminished AB mice was significantly higher than in the control group as a result of depleted suppressor cell activity. The CD4-depleted mice produced granulation tissue in less than 30% of the control group. To investigate the role of dipeptidylpeptidase IV on CD4 positive cells in wound healing we used Lys-[Z(NO2)]-Pro, a chemically modified dipeptide which may result by degradation of polypeptides by this peptidase. It was possible to restore the diminished capability of granulation tissue proliferation in CD4-depleted mice by a single treatment with the dipeptide Lys-[Z(NO2)]-Pro. Our results suggest that: (i) the CD4 positive T-helper subset regulates wound healing, and (ii) products of degradation by dipeptidylpeptidase IV may bypass T-helper cell function.

Animals↗

PubMed1989

Splenopentin (DAc SP-5)-accelerated reconstitution of antibody formation after syngeneic bone marrow transplantation.

Sublethally irradiated AB/Bln, mice (800 c Gy) and supplemented with syngeneic bone marrow cells were treated with or without a splenopentin derivative (DAc SP-5) and compared for their capacity to produce antibodies. In bone marrow cell plus DAc SP-5 treated animals antibody forming cells were found earlier and in a higher frequency than in mice treated with bone marrow cells only. These findings demonstrate that DAc SP-5 is able to induce bone marrow cell maturation.

Animals↗

PubMed1989

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↗