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Biomedical subjects

G Mahrle

Publications and source records attributed to G Mahrle.

At least 127 records · Page 7Linked to original sources

[One-hour-treatment of psoriasis with anthralin and UV-light (author's transl)].

A total of 66 patients with psoriasis was treated with one percent anthralin for one hour (one-hour-treatment) and UV-light. 17 out of 26 out-patients treated with anthralin and UVB showed a good response. In 40 in-patients the one hour regimen was administered in combination with UVA or UVB, in part in right-left side comparison in order to evaluate whether anthralin with UV-light is more effective than anthralin alone. Within six weeks remission was obtained with anthralin alone as well as with combined treatment with anthralin and UVA or UVB. In right-left side comparison UV-light had no significant additional effect in this regimen. The one-hour-treatment was effective but did not seem to be superior to the conventional therapy with anthralin in in-patients. However, the one-hour-treatment is advantageous and convenient for out-patients.

Anthracenes↗

[Antitumor effect of retinoids (author's transl)].

Retinoids given in a high dosage are able to reduce or prevent the growth of experimental skin tumors in animals. Our study on the systemic effect of aromatic retinoid (Ro 10-9359) on DMBA-induced skin tumors in rabbits supported these findings. The antitumor effect seems to be independent of the type of tumor induction. Previous reports and the possibility of using this retinoid effect in the treatment of skin tumors in man are discussed.

Animals↗

Concanavalin-A binding sites, pemphigus antigens, and beta 2 microglobulin in epidermal hyperproliferation, premalignant and malignant lesions.

Three cell surface parameters of epidermal cells have been studied by immunofluorescence, pemphigus antigens, concanavalin-A binding sugars, and beta 2 microglobulin. Biopsy specimens were taken from a total of 59 patients with psoriasis, seborrheic and solar keratosis, squamous cell carcinoma, and basal cell epithelioma. We found a loss of demonstrability of all parameters in dedifferentiated tumors or tumor areas in squamous cell carcinoma, premonitory changes in solar keratosis, and no changes in seborrheic keratosis. In the psoriatic epidermis a granular redistribution of the cell surface parameters was occasionally observed in circumscribed areas of the epidermis. A selective loss of the demonstrability of beta 2 microglobulin was the prominent feature in basal cell epithelioma. Our findings demonstrate that the alterations of the cell surface differ in malignant and premalignant skin tumors, in basal cell epithelioma, and in benign psoriatic hyperplasia.

Antigens↗

Domain turnover of junctional membrane areas in the epidermis.

To investigate the turnover of complete junctional membrane areas ("domain turnover"), psoriatic epidermis, keratoacanthoma, and squamous cell carcinoma were studied with an electron microscope and compared with the normal epidermis. Three types of domain turnover of junctions were observed. First, the uptake of intact intercellular junctions, which occurred as complete or incomplete annular junctions in the cytoplasm. Mainly gap junctions were involved. Second, the formation of autojunctions bridging an infolding at the surface of a cell, which is then incorporated and occurs partly with an attached saccule in the cytoplasm. This type was confined to desmosomes. Finally, the loss of intercellular desmosomes into the intercellular space was observed. Proliferating epidermis was associated with an increased domain turnover of gap junctional membrane areas. Domain turnover of desmosomes prevailed in tumors.

Carcinoma, Squamous Cell↗

DMBA-induced tumors and their prevention by aromatic retinoid (Ro 10-9359).

Both auricles of 21 domestic rabbits were painted with dimethylbenzanthracene (DMBA). Eleven animals of this group were additionally fed aromatic retinoid (AR) by an esophageal tube. Two control animals were not treated at all. Eight or 9 weeks after the beginning of the study six of the seven remaining animals, which had only been painted with DMBA, developed a total of 25 keratoacanthoma-like tumors (KA). On the other hand, none of the seven animals left, which were painted with DMBA and fed AR showed any tumor by this time. The systemic effect of AR was studied in biopsies from the snout and the back. The epidermis of the snout showed 'mucous mataplasia' by histochemical and electron-microscopic criteria, whereas the epidermis of the back was not significantly altered. The production of intra- and extracellular lamellated material indicated an additional effect of AR on epidermal lipid metabolism. The effect of AR in the prevention of DMBA-induced tumors was characterized by 'mucoid cytolysis' and karyolysis.

9,10-Dimethyl-1,2-benzanthracene↗

Use of the fluorescence-activated cell sorter to quantitate and enrich for subpopulations of human skin cells.

A variety of immunologic staining techniques were compared in a quantitative study of antigen expression by human epidermal cells. Virtually all nucleated epidermal cells express beta 2-microglobulin, which is associated with HLA-A, -B, and -C antigens, whereas only about 4% expressed T6, an antigen expressed by Langerhans cells but not other cells in the skin. With the fluorescence-activated cell sorter (FACS), epidermal cell suspensions were selectively enriched 10- to 15-fold for T6-positive Langerhans cells. An average of 6.5% of cells were specifically stained by anti-HLA-DR antibody. When dispersed cells stained with anti-DR plus peroxidase were examined with the technique of immunoelectron microscopy, only mononuclear leukocytes (probably Langerhans cells) were stained. After separating HLA-DR positive skin cells with the FACS, the DR-positive population but not the DR-negative population stimulated proliferation of allogeneic responder lymphocytes, indicating that sorted cells are metabolically active. We conclude that HLA-DR antigen is not expressed by keratinocytes in normal human skin cell suspensions and that the FACS can be used to selectively enrich or deplete skin cell suspensions of antigenically distinct subpopulations such as Langerhans cells.

Antibodies, Monoclonal↗

Expression of HLA-DR antigen in skin from patients with psoriasis.

Using murine monoclonal antibodies against human HLA-DR antigen and against human T cells, we investigated the indirect immunofluorescence staining pattern of involved and uninvolved skin from patients with psoriasis. The staining pattern of involved psoriatic epidermis is different from the pattern seen in uninvolved skin from the same patient and consists of scattered, single HLA-DR positive cells alternating with groups of HLA-DR positive cells. These HLA-DR positive cell clusters can be seen at any level of the epidermis. In some patients, the dermis of involved skin shows prominent accumulations of T cells which are HLA-DR positive and thus represent activated T cells.

Fluorescent Antibody Technique↗

Oral treatment of keratinizing disorders of skin and mucous membranes with etretinate. Comparative study of 113 patients.

This study reports comparative results of the effects of an aromatic retinoid, etretinate (RO 10-9359), on various disorders of the skin and mucous membranes. One hundred thirteen patients suffering from psoriasis, lichen planus, keratosis follicularis, and various other disorders were treated and examined. The patients received 25 to 100 mg/day of oral etretinate for up to 30 months. Patients with erythrodermic psoriasis, pustular psoriasis, and keratosis follicularis showed the best response. The conditions of patients with psoriasis vulgaris, palmoplantar psoriasis, and lichen planus also improved, but less impressively. The mucous membrane lesions of lichen planus and leukoplakia showed only moderate improvement. The most striking adverse clinical reactions observed were cheilitis (70%), dryness of the mucous membranes (27%), and hair loss (27%).

Administration, Oral↗

[Combined 1-hour therapy of psoriasis using anthralin and UV light].

Fifty-one patients with psoriasis were treated with 1% anthralin for 1 h (1-h treatment) and UV-light. Seven of 11 out-patients treated with anthralin and UV-B showed a good response. In 40 in-patients the 1-h regimen was administered in right-left side comparison to evaluate (1) whether UV-A or UV-B combined with anthralin was more effective than anthralin alone and (2) whether anthralin was photoactivated by UV-A or UV-B. As to the latter, one body side of the patients was exposed to UV radiation before and the other body side after application of anthralin. In in-patients the response to therapy was monitored by a defined score system. We did not find any significant differences in the paired comparisons. We therefore summarized the different treatment regimens and rated 42% with very good or good, 26% with fair, and 32% with poor. The results show that the 1-h treatment with 1% anthralin seems to be advantageous especially for the treatment of out-patients with circumscribed chronic psoriatic lesions. UV-light did not improve considerably the therapeutic effect of anthralin in the regimen of this study.

Adult↗

Epidermal changes induced by oral excess of aromatic retinoid in guinea pigs.

The effect of oral aromatic retinoid Ro 10-9359 in a high dosage (25 mg/kg/day) on guinea pig epidermis was investigated by light and electron microscopy. The induced morphological alterations showed two different stages: (a) In the injury stage, seen aftr one week of retinoid administraion, the epidermis was mainly characterized by lack of the horny layer and vacuolar cytoplasmic disintergration of the malpighian layer with intracellular edema and accumulation of some PAS-positive material. Tonofilaments and desmosomes were markedly reduced, keratinosomes were increased in number. (b) In the recovery stage, seen after 3 weeks of administration, the horny layer had reappeared, the edematous and vacuolar changes were diminished and the epidermis became slightly acanthotic. Hypergranulosis with numerous spongiform keratohyalin granules was a prominent feature. The number of tonofilaments, desmosomes, and keratinosomes showed a clear tendency to normalization. In conclusion, high systemic doses of aromatic retinoid initially exert a cytotoxic, keratolytic, and mucoplastic effect on the normal guinea pig epidermis. Nevertheless, the affected keratinocytes adapt themselves, despite the further administration of the drug, showing a gradual restoration of these changes and a stimulation of epidermal proliferation, leading to acanthosis.

Animals↗

[Reversible impairment of spermatogenesis induced by aromatic retinoid in guinea pigs (author's transl)].

Forty-one male guinea pigs were treated orally with high doses of aromatic retinoid (Ro 10-9359) 25 mg/kg/day in oleum arachidis for 6 weeks. Twenty-three animals were investigated at the end of this treatment. The remaining 18 animals were investigated after an additional retinoid-free interval of 6 weeks. A control group of 13 animals received oleum arachidis only. The histological investigation of the testes of the 23 animals studied immediately after the 6-week application of retinoid revealed reduced diameters of the seminiferous tubules, disorganization and desquamation of the seminiferous epithelium with decreased spermatogenetic activity and lack of mature elements. On the other hand, the 18 animals which were investigated 6 weeks after completion of retinoid treatment did not show any alterations, as compared to the control animals. Our results show that high systemic doses of aromatic retinoid clearly induce impairment of the spermatogenesis; however, all changes were reversible within 6 weeks after withdrawal of the drug.

Animals↗

Increased elongated and stabilized microtubules in psoriatic keratinocytes.

Microtubules (MT) occur in the keratinocytes as 20 nm broad tubular structures with an electron-lucent core surrounded by an electron-dense wall. The number and the length of the MT increased to the upper epidermal layers. In the normal keratinocytes the MT were relatively short (maximal length 2.2 microns) and slightly tortuous. Their outline was tenuous and irregular. Sometimes the MT were interrupted indicating a high fragility. In the upper layers of the psoriatic epidermis the MT reached a maximal length of 3.1 microns, showing a greater elongation than in the normal epidermis. The MT were stright and distinctly limited, most likely resulting from a higher grade of stabilization or polymerisation. By their interaction with the tonofilaments the MT may contribute to the stability of the cell shape, delaying the flattening of the psoriatic keratinocytes in the upper epidermal layers. Nowhere did the MT make direct contact with the cell membrane. At some places they did gain access to the cell membrane by short microfilaments.

Epidermis↗

[Hair growth, liver function and light sensitivity during oral retinoid therapy for psoriasis (author's transl)].

In a multicentre, cooperative study into the treatment of extensive psoriasis with a new aromatic retinoid (Ro 10--9359) trichogram, liver function tests and the light erythema threshold were investigated. In some of the patients hair loss occurred, usually in the fifth to eighth week after a total dose of 1.9 g retinoid. In all cases this improved an average of six weeks after dose reduction or cessation of treatment. The trichogram in 27 patients showed a diffuse toxic hair loss. In 70% the effluvium was telogenic, in 22% telogen-dystrophic. GPT, GOT, alkaline phosphatase and prothrombin index showed no significant alterations during retinoid treatment. However, in individual cases there was a rise in GOT and GPT up to 80 U/l. Furthermore there was a statistical tendency in rising bilirubin levels. Finally there was no evidence for an increase in light sensitivity after three weeks of retinoid treatment. Measurement of the erythema threshold showed rather more a reduction in light sensitivity under treatment.

Alanine Transaminase↗

The phospholipid pattern in the involved and the uninvolved psoriatic epidermis.

The phospholipid pattern of the involved and the uninvolved epidermis from 48 psoriatic patients and of the normal epidermis from 23 healthy controls was determined by thin-layer chromatography. A higher amount of total phospholipids was found only in the involved psoriatic epidermis, whereas significant alterations in the phospholipid pattern were observed in the psoriatic lesion and in the lesion-free epidermis. Namely, the decrease of phosphatidylserine and the increase of phosphatidylinositol were identically present in both the involved and the uninvolved psoriatic epidermis. It seems likely that these alterations in the phospholipid pattern in psoriasis may be related to subclinical alterations of the epidermis in this disease.

Adult↗

Laboratory investigations in patients with generalized psoriasis under oral retinoid treatment. A multicenter study of computerized data.

Numerous laboratory parameters were examined 235 patients with generalized psoriasis treated orally with retinoid and in 35 patients treated topically with anthralin as control. Computer evaluation of the obtained data revealed statistical trends to elevation of the total serum bilirubin level and increasing number of blood monocytes after long-term oral treatment. No other statistically significant changes of the laboratory data were found. Particularly, the liver function tests (transaminases, prothrombin and alkaline phosphatase) showed no significant alterations. Only in a few cases did the retinoid compound have an influence on the GPT and GOT levels. The reasons for this individual sensitivity to the drug remain unknown. No significant alterations were found in the control group treated topically with anthralin.

Administration, Oral↗

[Importance of the plasma membrane for epidermal regulation processes].

In this review the general structure and the properties of the plasma membrane are described with respect to the recent findings on the membrane of the keratinocyte. A structural and functional model of the plasma membrane of the keratinocyte is proposed based on biochemical, electron microscopic and fluorescence microscopic findings. The plasma membrane is obviously involved in the control of intercellular adhesion, growth and differentiation of normal epidermal cells. Under pathological conditions an alteration of the plasma membrane of the keratinocyte may affect the intercellular communication and/or the cellular control by mediators.

Carbohydrates↗

Demonstration of giant and anular nexus in the psoriatic epidermis.

In the psoriatic skin, nexus were most prominent in the upper layers of the viable epidermis, using the Alcian blue-Lanthanum technique. There, they reached double and manifold the length (giant nexus) of those in normal epidermis. According to the villous transformation of the epidermal cell surface in psoriasis, the nexus showed a great variation in their shape. Undulating nexus were seen beside invagination--and anular nexus. On ther other hand, nexus were lacking in the deepest layers of the psoriatic epidermis in contrast to normal epidermis. From these findings it seems that the intercellular communication by specialized low resistant junctions is reduced in the deepest layers of the psoriatic epidermis. In the upper epidermal layers, however, the extensive formation and the variable configuration of the nexus express a high synthetic activity and a well developed intercellular information in these areas of the psoriatic epidermis.

Epidermis↗