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Biomedical subjects

E Macher

Publications and source records attributed to E Macher.

At least 55 records · Page 3Linked to original sources

Modulation of suppressor mechanisms in allergic contact dermatitis: 5. Evidence that inhibition of suppressor T lymphocytes by Corynebacterium parvum is mediated by interferon.

Using a contact hypersensitivity model in BALB/c mice we have previously been able to show that Corynebacterium parvum or C. parvum serum (C.p.s.) of mice treated 24 hr before with C. parvum inhibited the suppressor T-lymphocyte (Ts-cell) response induced by epicutaneous antigen overload with 2,4-dinitrofluorobenzene (DNFB) or by i.v. injection of 2,4-dinitrobenzene sulfonic acid (DNBSO3) without inhibition of the T effector cell response (TDH-cell). In the present investigation we further analyzed the factor responsible for Ts-cell inhibition. Treatment of the C.p.s. with sheep-antimouse interferon (IFN) globulin neutralized its Ts-cell inhibitory effect. Intravenous (i.v.) injection of a crude mouse fibroblast IFN (340 U per mouse) 2 hr after i.v. application of a dose of DNBSO3 inducing tolerance had a similar Ts-cell inhibitory effect as observed with C.p.s. Injection of an electrophoretically pure alpha- and beta-IFN preparation (1000 U per mouse) increased contact sensitivity in mice sensitized with an antigen overload and inhibited the induction of Ts-cells by DNBSO3 i.v. This result is highly suggestive that the Ts-cell inhibitory factor in serum of C. parvum-treated mice is IFN and it shows that Ts-cells as compared to TDH-cells are susceptible to the inhibitory effect of highly purified IFN. This finding suggests that IFN may be an important immunoregulatory factor of delayed hypersensitivity not only in contact allergy but also in bacterial and viral defense.

Animals↗

[The effect of anaesthesia and surgery on immune function. A review (author's transl)].

This paper reviews the literature concerning the question, how the immune functions might be affected by anaesthesia and surgery. General and local anaesthetics inhibit in vitro and in vivo important functions of lymphocytes, granulocytes, and macrophages. However, the postoperative immunosuppression is not attributable to the anaesthesia but rather appears to depend on the tissue trauma itself.

Age Factors↗

Adjuvant reactivity predicts survival in patients with "high-risk" primary malignant melanoma treated with systemic BCG. EORTC Malignant Melanoma Cooperative Group Writing Committee.

We report the prognostic importance of strength of reaction to BCG, tumor histology and clinical factors in patients with previously untreated high-risk (Clark, III, IV and V) primary malignant melanoma. One hundred and one such patients receive high-dose BCG (1 x 10(8) viable units) by Heaf gun as an adjuvant to standardized primary surgery according to EORTC Protocol 18741. Univariate analysis of disease-free interval (DFI) indicates that the degree of maximum reaction to BCG (p = 0.0003), Breslow thickness (p = 0.0003) and Clark level (p = 0.002) are highly significant prognostic factors. When a multivariate model using Cox's proportional hazard regression was used for DFI, the degree of maximum reaction to BCG and Breslow thickness were by far the most significant criteria. A prognostic equation wa obtained to predict DFI from maximum BCG reaction and Breslow thickness. From analysis of the "scores" calculated in this way it appears that the two variables act independently. This technique permits the determination of values that are predictive of DFI and discriminate between subgroups of patients with different DFI characteristics (5 groups, p less than 0.0001). This exercise was repeated for survival and similar results were obtained. The degree of a patient's immune reaction to BCG administered therapeutically is of paramount importance in determining the likelihood of survival. This factor and the Breslow thickness can be integrated to produce a mathematical equation which accurately predicts survival for appropriately treated melanoma patients.

Adolescent↗

Monoclonal gammopathies in Sézary syndrome: a report of four new cases and a review of the literature.

Clinical and laboratory findings of four patients with Sézary syndrome and monoclonal gammopathy are presented. In the literature five cases with the association of these symptoms have been reported. Among the authors' series of 13 patients with Sézary syndrome, monoclonal gammopathy was observed far more often than could be expected from its natural incidence. It appears likely that monoclonal gammopathy is related to Sézary syndrome.

Aged↗

Monoclonal gammopathy in scleredema. Observations in three cases.

A monoclonal gammopathy was observed in three patients with long-term and widespread scleredema (Buschke's disease). There was no evidence of multiple myeloma in any patient. Deposition of monoclonal immunoglobulins in the skin was not detected by direct immunofluorescence microscopy. In contrast to scleromyxedema (lichen myxedematosus), from which scleredema can be distinguished clinically and histologically, the monoclonal immunoglobulins in two cases were of IgG2-kappa and IgG3-kappa type. Only one of the three patients had IgG1-lambda paraproteinemia, which is frequently seen in scleromyxedema. Our findings suggest that diffuse scleredema may be characterized by paraproteinemia but that the possible role of monoclonal immunoglobulins in the pathogenesis of this disease has yet to be resolved.

Adult↗

Modulation of suppressor mechanism in allergic contact dermatitis. IV. Selective inhibition of suppressor T-lymphocytes by serum obtained from Corynebacterium parvum treated mice.

We have previously shown that Corynebacterium parvum treatment reduced tolerance induced by intravenous injection of 2,4-dinitrobenzene sulfonic acid (DNBSO3) or by sensitizing BALB/c mice with a supraoptimal dose of 2,4-dinitrofluorobenzene (DNFB). Further analysis by transfer experiments revealed that the generation and/or functional expression of suppressor T-lymphocytes (Ts-cells) was inhibited in both tolerance models. Inhibition of Ts-cells was not entirely correlated with suppression of mitogen induced lymphocyte proliferation mediated by C. parvum activated macrophages. In this investigation we studied the effect of serum obtained at various times after C. parvum injection on tolerance and Ts-cells in DNFB contact allergy. Serum obtained 6 and 24 hr, however, not 72 hr after C.parvum injection inhibited Ts-cells, induced by DNBSO3 and tested by transfer to naive recipients, as efficiently as C. parvum itself. The serum had following characteristics: (1) It inhibited the functional expression of Ts in the recipient animal. (2) It inhibited tolerance induction by an epicutaneous supra-optimal dose of DNFB. (3) It did not inhibit the induction and functional expression of T-effector cells of delayed hypersensitivity (TDH-cells) as shown by transfer experiments. (4) The Ts-inhibitory factor was heat resistant (56 degrees C), not destroyed or lost by dialysis against tris-glycine buffer pH 2 and could not be detected in the serum of NMRI-mice injected 24 hr before with C parvum. (5) The C parvum serum did not significantly increase the spleen weight or suppress mitogen-induced spleen lymphocyte proliferation. The nature of this Ts-cells inhibitory factor is unknown, although the results suggest that cortisone or transfer of bacteria are not responsible. Factors mediating selective inhibition of Ts-cells may be of important regulatory function in delayed type hypersensitivity.

Animals↗

Modulation of suppressor mechanisms in allergic contact dermatitis: 2. Inhibition of suppressor T-lymphocytes by Corynebacterium parvum.

Pretreatment of BALB/c mice with Corynebacterium parvum inhibited the induction of tolerance to the contact sensitizing agent 2,4-dinitrofluorobenzene induced by intravenous injection of DNBSO3. The suppressive effect on tolerance induction has further been analyzed by adoptive transfer experiments. Injection of C. parvum intraperitoneally (0.7-2.8 mg/mouse) before injection of the tolergen inhibited the generation of T-suppressor cells as shown by transfer of spleen cells from the tolerized donor to naive recipients. Pretreatment of the recipients of the suppressor T-cells from tolerized animals with C. parvum also inhibited the function of these cells in the recipient animals. Time-kinetic experiments suggested that more than one mechanism appeared to be responsible for the tolerance induced by DNBSO3; C. parvum (probably via activated macrophages) suppressed tolerance which is mediated by T-suppressor lymphocytes. These results suggest that T-suppressor lymphocytes may--similarly as T-helper cells--be modulated by an activated monocytic-phagocytic system.

Adjuvants, Immunologic↗

Modulation of suppressor mechanisms in allergic contact dermatitis: 1. Effect of C. parvum on the induction phase of contact allergy.

The effect of a pretreatment with corynebacterium parvum (C. parvum) on contact allergy in BALB/c mice was studied. Mice sensitized with 50 microliter (supraoptimal dose) 2.4-dinitrofluorobenzene (DNFB, 0.5%) showed a suppressed response as measured by ear swelling after painting the right ear with 0.3% DNFB in comparison to an allergic response obtained with an optimal sensitization dose (15 microliter DNFB 0.5%). By transfer of spleen cells from donors sensitized with a supraoptimal or an optimal dose to recipients either challenged ro sensitized shortly afterwards with DNFB it could be shown that less functionally active immune T-lymphocytes of the delayed hypersensitivity type and significantly more suppressor T-cells were induced in supraoptimally sensitized mice in comparison to the optimally sensitized animals. Intraperitoneal injection of C. parvum (2.8 mg/mouse) one week before sensitization enhanced the contact allergic response in mice sensitized with a supraoptimal dose of DNFB, with little effect on the response in optimally sensitized animals. Further analysis of this enhancement in transfer experiments showed that C, parvum selectively suppressed the generation and/or functional expression of T-suppressor cells and, probably by this mechanism, increased the number of functionally active T-immune lymphocytes. It is proposed that possibly by activation of the immune system C. parvum will suppress suppressor cells in contact allergy and by this mechanism might facilitate sensitization to the contact allergen.

Animals↗

The Duhring chamber assay for corticosteroid atrophy.

A new human model for the evaluation of the atrophogenicity of topical corticosteroids is proposed. Formulated corticosteroids (creams and ointments) were applied occlusively to normal forearm skin of human volunteers for 3 weeks using Duhring chambers. Visible atrophy and telangiectasia were rated under a stereomicroscope on a histologically validated five-point scale. There was a close correlation between the parameters of atrophy and telangiectasia. Atrophogenicity varied considerably among the tested corticosteroids, ranging from none (1% hydrocortisone) via moderate (0.1% betamethasone valerate) to very severe (0.05% clobetasol propionate). A dose-response relationship with exposure time and concentration of the corticosteroid could be demonstrated. Furthermore, the vehicle influenced the resulting atrophy and telangiectasia. Fatty ointments seem to pose less risk than oil in water creams.

Administration, Topical↗

Eosinophilic pustulosis with pemphigus-like antibody.

A 75-year-old male with eosinophilic pustulosis Ofuji complicated by superinfection with Pseudomonas aeruginosa and Proteus mirabilis is described. This is the first case of eosinophilic pustulosis with an antiepidermal antibody. This antibody was directed against the intercellular substance of the lower epidermis and it was detected by direct immunofluorescence in the patient's normal and lesional skin. As revealed by indirect immunofluorescence the patient's serum reacted with intercellular substance of human lower epidermis but not with guinea pig esophagus. Possibly the detected autoantibody is not characteristic for eosinophilic pustulosis Ofuji but rather an accompanying feature of this case similar to the antiepidermal antibodies found in patients with drug reactions and burns.

Aged↗

In vitro studies on the human cellular immune response to commercially available herpes simplex antigens.

Patients with recurrent herpes labialis and genitalis as well as normal controls were tested for the in vitro responsiveness of their lymphocytes to mitogens, to several herpes antigens and to carrier medium alone (containing chorioallantois membrane antigens). No statistically significant differences were found in the results with the direct and indirect migration inhibitory test (MIF) and in studies of the blastogenic response of lymphocytes (LTT) among the three groups. These findings held up when correlations were drawn to severity or course of the disease and suggest that immunological modulation can play at most a minor role in inducing recurrent herpes simplex infections.

Antigens, Viral↗

Interferon production by Corynebacterium parvum and BCG-activated murine spleen macrophages.

Macrophages were identified to be a major source of interferon produced in murine spleen cell cultures after intravenous injection of Corynebacterium parvum (C. parvum), strain CN 6134 or Bacille Calmette Guérin (BCG). Another strain of C. parvum, CN 5888, which lacks RES stimulating activity and adjuvant activity in vivo, was not effective when injected intravenously. Protein synthesis was required for interferon activity to be produced and protein synthesis was also required for the antiviral state to be expressed. The antiviral activity was relatively stable to pH 2 and neutralized by an antiserum against virus-induced fibroblast interferon, thus exhibiting some properties of type I interferon. In vitro only CN 6134, the biologically active strain, could induce small amounts of interferon in spleen macrophage cultures. Macrophages from CN 6134 or BCG-infected athymic nu/nu mice produced similar interferon titers as their controls. It is concluded that infection with certain immunomodulators can activate splenic macrophages via a predominantly T-cell independent mechanism. Interferon in turn may operate locally as a mediator of immunoregulation.

Animals↗

Atypical tuberous myxedema Jadassohn-Dössekker. Report of a case.

A 48-year-old male patient with atypical tuberous myxedema Jadassohn-Dössekker, characterized by nodules on both upper legs with mucin deposits, is described. Atypical tuberous myxedema Jadassohn-Dössekker can be classified together with lichen myxedematosus and scleromyxedema Arndt-Gottron as normothyrotic myxodermia. It can be distinguished from lichen myxedematosus only by the size of the lesions. The pathogenesis is unknown.

Histocytochemistry↗