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Biomedical subjects

E Macher

Publications and source records attributed to E Macher.

At least 37 records · Page 2Linked to original sources
PubMed1985

Phenotypic dynamics of tumor progression in human malignant melanoma.

The phenotypic changes in human melanoma cells during the course of tumor progression were studied with monoclonal antibodies (MAbs) against the melanoma-associated antigens (MAA) M.2.2.4, H.2.8.10, K.1.2, A.1.43, and A.10.33, and HLA-(A,B,C and D). Cryostat sections of 172 primary melanomas of the skin, 157 melanoma metastases and 56 nevi were investigated with an indirect immunoperoxidase method. Phenotypic heterogeneity was observed within lesions at all stages, and also within different tumors of the same patients. Despite this heterogeneity, principles of antigen expression were found. From the reaction pattern of MAbs, the following classifications of antigens were derived: "constitutive" markers of nevomelanocytic cells (M.2.2.4 and H.2.8.10) were found expressed over a wide range of local and systemic tumors. One MAA, K.1.2 (Suter et al., 1985), that declines with progression of melanoma, was classified as an "early" antigen, whereas MAA that appear in primary melanoma in proportion to invasiveness, and which are expressed in metastases of lymph nodes and visceral organs (A.1.43, and A.10.33), were classified as "late" markers of tumor progression. HLA-antigens were classified as "intermediate" markers, HLA-A,B,C, as an "early-intermediate", and HLA-DR as a "late-intermediate" marker. The occurrence of class II HLA, A.1.43-, and A.10.33-positive tumor cells in primary melanoma indicates a high metastatic potential of tumors, independent of tumor thickness. The data show that local and systemic progression of melanoma is associated with qualitative changes in tumor cells which can be recognized by MAbs.

Antibodies, Monoclonal↗
PubMed1985

[Information before basaloma surgery--results of an inquiry].

We report on the results of an empirical investigation on medical information before surgery of basaliomas. The study comprised 42 patients who had been informed. The given information was documented by consent forms. In the second year after surgery, all patients received a detailed questionnaire. One aim of the investigation was to find out which particulars of the verbal and written information they still kept in mind. 26 questionnaires were returned. Evaluation showed that some patients had completely forgotten that information about complications of surgery had been given at all. Only one of the patients could name a special complication of treatment.

Basal Cell Carcinoma↗
PubMed1984

[Internal versus topical tetracycline therapy of acne].

The study comprised 49 patients suffering from acne who were treated over a period averaging 4.7 +/- 1.2 months with tetracyclines administered either orally (1000 mg daily for 5 days, then 250 mg daily) or locally (2% alcoholic solution). Randomization was carried out by means of random numbers. The percentage of pustules among the total acne efflorescences was chosen as clinical parameter for the efficacy of the antibiotic therapy. After treatment, both collectives showed the same significant decline of pustulation. The therapy was finally evaluated on a six-point scale both by the doctor and the patient. In total, there could not be detected any significant difference in the evaluation of local and oral medication.

Acne Vulgaris↗
PubMed1984

Selective induction of delayed hypersensitivity T-effector and T-suppressor lymphocytes in vitro by haptenized bone marrow-derived macrophages.

The role of various subpopulations of antigen-presenting macrophages in the induction of T-lymphocyte subpopulations has been difficult to study in the past. We have used an in vitro system of bone marrow cell culture both to induce T-effector (TDH) and T-suppressor (Ts) cells active in delayed-type hypersensitivity. Bone marrow-derived macrophages (BM-MA) grown in Teflon bag cultures were allowed to attach to culture dishes and were pulse-labeled with 2,4-dinitrobenzene sulfonate (DNBSO3). Spleen cell lymphocytes from nonsensitized BALB/c mice were cocultured with antigen-pulsed or control BM-MA for 3 days. The lymphocytes were harvested, and injected iv into BALB/c mice which were challenged within 1 hr after injection by painting the right ear with 2,4-dinitrofluorobenzene (DNFB, effector test) or sensitized with DNFB on 2 days following iv injection of the cells and challenged 5 days later (suppressor test). Ear swelling was measured 24 hr later to assess the effector or suppressor function of the in vitro educated lymphocytes. BM-MA grown for 5 days (BM-MA 5) in L-cell conditioned medium induced only TDH cells (Thy 1+, Lyt 1+2-) whereas BM-MA grown for 10 days in conditioned medium induced only Ts cells (Thy 1+, Lyt 1-2+). In both cases, induced TDH and Ts cells were antigen specific. Functionally, induced Ts cells suppressed the afferent limb of the delayed response. When DNP-BM-MA 5 and DNP-BM-MA 10 were used to induce TDH or Ts cells in vivo by subcutaneous or intravenous injection respectively, only BM-MA 5 were able to sensitize recipient mice. Both 5- and 10-day macrophage populations induced Ts cells in vivo. Functionally, these Ts cells appeared to act on the efferent limb of the delayed reaction. We conclude that different populations of antigen-presenting macrophages can preferentially induce TDH or Ts cells, perhaps depending on antigen presentation in association with class II antigens or on the functional state of the antigen-presenting cell.

Animals↗
PubMed1984

The pattern of the mononuclear infiltrate as a prognostic parameter in flat superficial spreading melanomas.

The mononuclear cell infiltrate of 90 superficial spreading melanomas (SSM) of less than or equal to 1.5 mm thickness was analyzed at different locations around and within the tumors. All patients had been followed for at least 5 years, and 20 (22%) had developed metastases. A correlation between the overall inflammatory response in the histologic sections and the prognosis was not observed, nor could a significant distinction be made between metastasizing and nonmetastasizing melanomas when the mononuclear cell infiltrate was analyzed at different locations. A significant clustering of metastasizing tumors was, however, observed in the subgroup with a relatively strong infiltrate within the tumor compared with the overall infiltrate. From this observation, a semiquantitative description of the pattern of the infiltrate was established. It provides an additional parameter for prognostication in flat SSMs and it raises new questions about the role of the local host-tumor interaction.

Adult↗
PubMed1984

A double blind trial of H1 and H2 receptor antagonists in the treatment of atopic dermatitis.

Eighteen patients with atopic dermatitis were randomly chosen for a clinical trial to compare the action of the H2 receptor antagonist cimetidine in combination with the H1 receptor antagonist chorpheniramine against the chlorpheniramine alone and against placebo. Each treatment period lasted for 4 weeks. Intensity of puritus was recorded daily by the patient on an analogue scale. Global clinical assessment was graded on a 5-point scale every 2 weeks by the investigators and weekly by the patient himself. Further study parameters were: quantity of the corticosteroid ointment used for 'emergencies'. immunoglobulin E level, and eosinophil count. The data of 16 patients was evaluated. There was no significant difference in any of the study parameters during the three treatment periods. On the basis of this study, the combined administration of H1 and H2 receptor antagonists is of no benefit in the treatment of atopic dermatitis.

Adolescent↗
PubMed1984

Clinical features of superficial spreading melanomas with zones of regression.

To assess the significance of spontaneous regression in superficial spreading melanoma (SSM), 36 patients with clinical signs of regression in their primary tumor were compared to 200 patients with regular SSMs (controls). SSMs with regression were found to have the following, distinctive clinical features, which were significantly different from controls (P less than 0.05): (1) male predominance (69%), (2) preferential localization on the trunk (80.6%), (3) lower tumor thickness (Breslow), (4) clustering in Clark levels II and III, and (5) a larger surface area. The incidence of metastases was lower in patients with regressing SSMs (13.9%) compared to controls (20.5%) although the time until relapse was slightly shorter (20.6 months versus 28.1 months for controls). These prognostic parameters were not significantly different. However, of the patients who died, 2 of 4 with zones of regression had thin melanomas (less than or equal to 1.5 mm), compared to only 1 of 27 without regression zones (P less than 0.05). SSMs with regression therefore have unique clinical features, which may be related to their pathogenesis, and they may have some prognostic significance.

Adult↗
PubMed1984

Inhibition of the T suppressor circuit of delayed-type hypersensitivity by interferon.

The effects of electrophoretically pure murine interferon (Mu-IFN-alpha beta) on the T suppressor pathway and on the T effector cell of delayed hypersensitivity (TDH) were investigated in BALB/c mice, in a 2,4-dinitrofluorobenzene (DNFB) contact-sensitivity model. Various T cell subpopulations, suppressor T cells of the afferent (Ts-aff) and efferent (Ts-eff) types, an auxiliary Ts (Ts-aux), as well as TDH were induced, and their function was assessed in transfer experiments. The results were as follows. At a dose of 5 X 10(3) U, IFN was shown to inhibit the Ts-aff response, when given to the donor animal shortly after induction of the Ts-aff subpopulation or when injected into the recipient 2 hr after spleen cell transfer. Pretreatment in vitro with IFN of the splenic cells to be transferred also abolished the Ts-aff response. Similar amounts of IFN were able to inhibit the generation of Ts-eff in the donor animals, whereas 10-fold-higher amounts were needed in vivo or in vitro to block the functional expression of Ts-eff in the recipient animal. Intravenous injection of IFN into recipients of Ts-eff on day 0 and 1 after sensitization inhibited the expression of the Ts-eff transferred 1 day before ear challenge. This suggests that the Ts-aux response required for the TDH suppression by Ts-eff is blocked by IFN. Secretion of a suppressor factor by Ts in vitro was not blocked by IFN. Treatment of the donor of suppressor factor-secreting Ts with IFN, however, blocked the induction of this Ts. The TDH were not sensitive to IFN even at amounts approximately 100 times higher than those used for the Ts inhibition in vivo as well as in vitro. These results demonstrate that low amounts of IFN may selectively block the suppressor pathway, because induction of these regulatory T cell subsets appears to be particularly sensitive to IFN. The exact mechanism of the IFN-mediated inhibition of Ts is not yet clear. The data suggest an important regulatory function of IFN in delayed-type hypersensitivity (DTH) reactions.

Animals↗
PubMed1983

Tumor angiogenic activity (TAA) production in vitro and growth in the nude mouse by human malignant melanoma.

The production of angiogenic activity by eleven human melanoma lines in vitro was compared with the extent of tumor growth in the nude mouse. Angiogenic activity was assayed by measuring the vascular response of the chick chorioallantoic membrane to serum-free supernatants. Growth in the nude mouse was determined after subcutaneous injection of cells 60 days later. Angiogenic activities ranged from negative to highly positive. In five lines angiogenic activity in vitro correlates with the extent of tumor growth in the nude mouse. In contrast, two lines did not show such a correlation, e.g. they produced large tumours without any detectable angiogenic activity. Histological examination of these two tumors revealed moderate degrees of vascularization and only low degrees of necrosis. It is concluded that the extent of tumor growth in the nude mouse is partly independent of the production of angiogenic activity by the tumor cells themselves.

Angiogenesis Inducing Agents↗
PubMed1983

Thalidomide in the treatment of sixty cases of chronic discoid lupus erythematosus.

The therapeutic effect of thalidomide in chronic discoid lupus erythematosus (CDLE) was studied in sixty patients who were followed up for 2 years. In fifty-four patients (90%) a complete or marked regression of the disease was observed, but when the thalidomide was stopped, thirty out of forty-one (71%) patients relapsed. Patients undergoing a second course of thalidomide treatment again responded well. Nine of the patients in whom the disease recurred after successful treatment with thalidomide and who had been unresponsive to intermittent treatment with antimalarials, showed a good response to a second or third course with thalidomide. Mild side-effects were common and 25% of patients complained of slight to moderate polyneuritic symptoms. Since electroneurological examinations had not been performed before the thalidomide therapy, the frequency of neurological side-effects cannot be accurately calculated but we recommend neurological examinations before and periodically during thalidomide treatment. Thalidomide is a very effective drug in CDLE, but in most cases it exerts its effect only whilst treatment is continued. Its use should be restricted to patients resistant to topical steroids and systemic antimalarials.

Chronic Disease↗
PubMed1983

In situ analysis of the mononuclear cell infiltrate in primary malignant melanoma of the skin.

Monoclonal antibodies, directed against functionally different lymphocyte subsets, were applied on frozen sections of primary malignant melanomas and benign nevi. Positive reaction was identified by means of an immunoperoxidase method. It was found that lymphocytic infiltrate underneath and in between malignant melanoma is composed of approximately equal numbers of OKT4 positive helper and OKT8 positive suppressor/cytotoxic T cells. The majority of these lymphocytes also expressed HLA-Dr antigen, indicating an activated state. In addition HLA-Dr, OKT6 positive dendritic cells were present in the infiltrate and between the melanoma cells. Finally, melanoma cells expressed demonstrable amounts of HLA A, B, C antigens, whereas benign nevi did not. It is concluded that all ingredients for a successful immune reaction against primary malignant melanoma are on hand. This finding is in agreement with the relatively frequent occurrence of partial or even complete regression of primary malignant melanoma of the skin.

Antibodies, Monoclonal↗
PubMed1982

Current status of melanoma chemotherapy and immunotherapy.

In the search for an improved prognosis in malignant melanoma after radical surgery, randomized trials arae being conducted examining the results of immunostimulation (BCG or levamisole) with chemotherapy dimethyl - triazeno - imidazole - carboxamide (DTIC) in stage I melanoma. So far, no significant differences between the groups are evident. In stage III melanoma, a series of new agents are being rapidly screened and some appear promising. A closer look at the basic immunopathologic process during the growth of melanomas is might lead to a more effective control of this malignancy.

Clinical Trials as Topic↗