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Biomedical subjects

R Stadler

Publications and source records attributed to R Stadler.

At least 109 records · Page 6Linked to original sources
PubMed1987

Growth of human hair follicle keratinocytes in vitro. Ultrastructural features of a new model.

A simple experimental technique was developed to provide an in vitro model for the study of human follicular keratinocytes. Anagen-phase human hairs were plucked from the scalp of healthy individuals; the follicles were separated, plated on coverslips coated with collagen G, and cultivated in McCoy 5A Medium in a CO2-incubator at 37 degrees C. Light and electron microscopy after 1, 2, 3, and 6 weeks showed selective and progressive cell growth with keratinocyte differentiation, producing multilayered cultures of cells joined with fully developed desmosomes. Three distinct patterns of differentiation, leading to the formation of an incomplete horny layer, were seen. The particular arrangement of tonofilaments, the considerable amounts of cytoplasmic glycogen, and the absence of malpighian differentiation were ultrastructural indicators of the follicular origin of the cultured cell population, which most likely grew from the outer root sheath of the hair. This technique may provide a promising model on which to base further studies of hair biologic processes and hair growth.

Cell Differentiation↗
PubMed1987

Disseminated Kaposi's sarcoma in AIDS: histogenesis-related populations and influence of long-term treatment with rIFN-alpha A.

Lesions (n = 19) of cutaneous Kaposi's sarcoma in different stages of development were obtained from 13 patients with acquired immunodeficiency syndrome (AIDS), and studied by light and electron microscopy. Six additional biopsies from 4 patients treated with recombinant alpha A interferon were obtained after treatment. Varying amounts of two proliferating cell populations were found: (1) Large cells showing cytologic and histochemical characteristics of endothelial cells. They were seen in close proximity to normal vessels, forming new vascular structures and large aggregates found in papular and nodular lesions. (2) Smaller spindle-shaped cells, probably of pericytic origin. They appeared in bundles and fascicles in the papillary dermis of the cutaneous Kaposi's sarcoma lesions and, in part, gave origin to thin-walled, bizarre-shaped vessels that show incomplete lumina proliferating from the upper to the deep dermis and are surrounded by extravasate erythrocytes and siderophages. After long-term systemic treatment with recombinant alpha A interferon, the endothelial type of tumor cell aggregates mostly disappeared, whereas most of the spindle-shaped pericytic-like cells were still present. Our findings lead us to suggest that some cellular product may, as a promoter factor, induce the proliferation and growth of endothelial cells. This factor may be blocked by alpha A interferon and cause regression of endothelial cell proliferation observed in AIDS patients undergoing long-term systemic therapy.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Retinoids and keratinocyte differentiation in vitro.

Standard retinoids (e.g. etretinate, isotretinoin) are successful in the treatment of a variety of dermatological disorders. However, they are handicapped by an unfavorable ratio between activity and toxicity. In order to find more successful substances new promising compounds were recently synthesized. The aim of this study was to screen new monoaromates (etretin (Ro 10-1670) ), demethyletretin (Ro 12-7310), 13-cis-etretin (Ro 13-7652) and the polyaromates arotinoid (Ro 15-0778), arotinoid acid (Ro 13-7410) and arotinoid ethyl sulfone (Ro 15-1570) for their effect on keratinocyte differentiation in vitro and to compare these results with differentiation data of retinoids currently used clinically. It was found that the second generation of retinoids had a lower antikeratinizing potential than the third generation of retinoids. They markedly inhibited crosslinked keratins and envelope proteins. Arotinoid acid was found to be the most potent derivative. In contrast to this, differences with regard to the synthesis of keratohyalingranule macroaggregates were detected between the retinoid derivatives. Arotinoid acid and arotinoid sulfone stimulated this protein fraction, whereas arotinoid left this fraction uninfluenced. If the data obtained were considered the selection criterion for the future therapeutic application of the new arotinoids in psoriasis therapy, it should be more useful to employ arotinoid acid or arotinoid sulfone rather than arotinoid in clinical psoriasis studies.

Animals↗
PubMed1987

[Pemphigus vegetans of the Hallopeau type. Detection of pemphigus antibodies with direct and indirect immunofluorescence].

We report the case of a 25-year-old woman with bullous lesions diagnosed as the rare pustular type of pemphigus described by Hallopeau. Direct immunofluorescence studies revealed deposits of IgG and C3 in the intercellular spaces of the epidermis; the indirect immunofluorescence technique revealed circulating antiepithelial IgG antibodies. The skin lesions cleared completely following treatment with systemic corticosteroids and azathioprine. These findings indicate the disease first described by Hallopeau as "pyodermite végétante" does indeed belong to the pemphigus group, being a rare type of pemphigus vegetans.

Adult↗
PubMed1987

[Behçet disease and exogenous interferon. A successful treatment study using recombinant alpha-A-IFN].

Up till now no standard therapy for Behçet syndrome has existed. Long-term corticoid therapy is often necessary, although side-effects cannot be avoided. Recent investigations have shown a correlation between high endogenous gamma-interferon serum levels and low activity of the syndrome. A 20-year-old male with severe Behçet's syndrome was therefore treated with recombinant alpha-A-interferon (IFN). The general condition of the patient improved rapidly, together with rapid clearing of the skin lesions. Over a 10.5 week-period the patient received a total dose of 792 million IU recombinant alpha-A-interferon.

Behcet Syndrome↗
PubMed1987

[Disseminated mucocutaneous Kaposi sarcoma in AIDS. Clinical and therapeutic experiences in 13 patients].

Since 1980 a new epidemic form of disseminated mucocutaneous Kaposi's sarcoma (KS) with a progressive clinical course has been observed in populations at risk. Since 1982, 13 cases of AIDS-associated KS have been seen in our department; all of them were in young homosexual males with circulating HIV antibodies and a reduction in the ratio of T-helper to T-suppressor lymphocytes (0.05-1.3). Following systemic treatment with recombinant alpha A-interferon (rIFN-alpha A) over a period of 6 months (18 million IU/day for 3 months; later 18 million IU/3 X weekly) together with other concomitant measures (superficial X-ray radiation, argon laser radiation, surgical excision of isolated lesions) we registered complete remission of the remaining lesions in 2 cases, progression of the disease in 4 cases, and at least temporary stabilization of the disease in 7 cases. In 4 patients opportunistic infections occurred during rIFN treatment: Pneumocystis carinii pneumonia (PCP) with lethal outcome in 2 cases, atypical mycobacteriosis in 2 cases, and Legionella pneumoniae infection in 1 case. Two additional deaths were registered due to PCP appearing during the post-treatment period. Life-threatening virus infections were not observed during rIFN treatment. Out of 9 patients receiving prophylactic trimethoprim/sulfamethoxazole medication, only 1 developed allergic exanthema as a result of this drug combination. Occasionally, rIFN-induced leukopenia was seen and pronounced thrombocytopenia appeared in 1 patient during treatment. Overall, systemic rIFN therapy was well tolerated; its long-term administration in patients with AIDS-associated mucocutaneous KS seems to be well justified according to these preliminary observations.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1987

[Therapeutic use of alpha interferon in metastasizing malignant melanoma, disseminated Kaposi sarcoma and severe Behçet disease].

Three types of human interferons (IFNs) are differentiated: alpha-interferon (with about 20 subtypes), beta-interferon, and gamma-interferon. In addition to their antiviral properties, these IFN types exert numerous other biological effects, which are increasingly exploited for therapeutic purposes. From 1982 to 1985 long-term recombinant alpha 1-interferon (rIFN-alpha A) was administered systemically in 39 patients with various severe dermatoses. In this study we report our preliminary experiences with systemic administration of rIFN-alpha A in malignant melanoma (MM, 9 patients), in disseminated Kaposi's sarcoma (KS, 8 patients), and in severe Behçet's disease (2 patients). In metastatic MM (clinical stage IV) the result was only moderate; the administration of IFN in earlier stages, for instance as a postoperative adjuvant therapy, appears more promising. In disseminated KS with acquired immune deficiency syndrome (AIDS) our experience was encouraging. In 7/8 patients the general condition was stabilized and partial remission of skin lesions was observed. In Behçet's disease both patients had good or excellent responses to IFN treatment. The side effects of systemic rIFN-alpha A were moderate, dose-dependent, and tolerable.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Effect of recombinant alpha A-interferon on DNA synthesis and differentiation of human keratinocytes in vitro.

Interferons are known to protect cells against virus infection, to inhibit cell growth in a number of cell lines and also to modulate cell differentiation. Their possible clinical application has now entered its final phase. The aim of this investigation was to study the effect of recombinant alpha A-interferon (r IFN-alpha A) on human keratinocyte DNA synthesis and differentiation in vitro. [3H]-TdR incorporation into DNA was used to quantify DNA synthesis in keratinocyte cultures at varying concentrations of rIFN-alpha A. Cell differentiation was determined using polyacrylamide gel electrophoresis of six specific protein fractions extracted from the keratinocytes. Our results indicate that rIFN-alpha A is a potent inhibitor of keratinocyte DNA synthesis in vitro; it also decreases significantly the amount and synthesis of non-covalently bound keratins while increasing the disulphide cross-linked keratins. No qualitative changes in keratinocyte proteins were observed.

Cell Differentiation↗
PubMed1986

[Prognosis-oriented therapy of malignant melanoma. New concepts].

Similar to other countries, the incidence of malignant melanoma (MM) is significantly increasing in the Federal Republic of Germany. In established MM, curative therapeutic measures are limited. Current worldwide effort is therefore being directed toward its early recognition and the immediate surgical removement of the primary tumor, with a safety margin of at least 3 cm from the edge of the tumor in all cases. General anesthesia seems preferable and is used in most German university departments of dermatology. Another essential requirement is to subdivide clinical stage I into several risk groups since the 5-year survival rate of each individual case included in this stage may vary from greater than 90% to less than 50%; this can be accomplished by analyzing two main prognostic criteria that will largely determine the final outcome: tumor thickness, and tumor localization. Sex may also play a role in some cases. Other prognostic factors should also be considered. The selection of postoperative therapeutic measures (including prophylactic immunotherapy, prophylactic chemotherapy, and prophylactic regional lymphadenectomy) will then depend on the prognostic risk expected for each patient. This approach means that all of the main individual parameters must be carefully evaluated, and this is time-consuming, but it seems to be more appropriate than any other method for achieving optimal therapeutic results. When MM are in the late metastasizing clinical stages only palliative measures are currently possible, and there is little hope, if any, for a final cure.

Adult↗
PubMed1986

[Dicarboxylic acids inhibit the growth of keratinocytes in vitro].

The antiproliferative effect of three straight-chained saturated dicarboxylic acids was examined with neonatal mouse keratinocyte cultures. Adipic acid (C6), azelaic acid (C9), and sebacic acid (C10) were added to the cultures in concentrations ranging from 1 to 50 mmol/l. Proliferation was assayed by liquid-scintillation counting of 3H-thymidine incorporation into DNA and by autoradiography. Fifty percent inhibition of 3H-thymidine incorporation was observed with 50 mmol/l adipic acid, 20 mmol/l azelaic acid, and 10 mmol/l sebacic acid, respectively. The antiproliferative effect was completely reversible after cessation of treatment. Moreover, treated cultures then showed a rebound effect with increased DNA synthesis. These results show that dicarboxylic acids exert reversible antiproliferative effects on keratinocytes.

Adipates↗
PubMed1985

Effects of arotinoid ethyl ester on epithelial differentiation and proliferation.

In recent years the search for new retinoids, safer and more potent than the available compounds, has led to the development of arotinoids. In preliminary clinical trials, arotinoid ethyl ester [(E)-4-[2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1- propenyl]benzoic acid ethyl ester; TTNPB ethyl ester] was found to be highly effective in the treatment of severe and etretinate-resistant dermatoses. Using adult hairless mice, embryonic mouse limb-bud cultures and keratinocyte cultures as experimental models, we have performed morphological, autoradiographic and biochemical studies on the effects of arotinoid ethyl ester on epithelial differentiation in vivo and in vitro. Arotinoid ethyl ester stimulates proliferation of both embryonic and adult mouse epidermis. However, it inhibits the differentiation of embryonic epidermis and enhances that of adult epidermis. Arotinoid ethyl ester induces a decrease in the cyclic AMP content of cholera toxin-stimulated keratinocytes but fails to alter cyclic AMP concentrations in keratinocytes not treated with cholera toxin.

Aging↗
PubMed1984

Effect of a new retinoid, arotinoid (Ro 13-6298), on in vitro keratinocyte proliferation and differentiation.

In preliminary clinical trials, a new retinoid, Arotinoid Ro 13-6298, was found highly effective in hyperproliferation and keratotic disorders. The aim of this investigation was to study the effect of Arotinoid on in vitro neonatal mouse keratinocyte proliferation and differentiation. Five doses of Arotinoid were tested. [3H]-Tdr labeling techniques and autoradiography were used to quantitate proliferation. Differentiation was assessed using one-dimensional polyacrylamide gel electrophoresis and autoradiography of six specific protein fractions extracted from the cells using a series of buffers. Our results indicate that Arotinoid is an extremely potent inhibitor of keratinocyte proliferation. Arotinoid significantly decreases the amount and synthesis of non-covalently and disulfide cross-linked keratins and cell envelopes while increasing the quantity of keratohyalin granule-associated proteins. No qualitative change in keratinocyte proteins was observed.

Animals↗
PubMed1983

[Acantholysis and eosinophilic spongiosis: pemphigus herpetiformis. Successful retinoid therapy].

Pemphigus herpetiformis is an unusual variant of the pemphigus group, showing acantholytic bulla formation together with marked eosinophilic spongiosis. The clinical picture shows erythematous and pruritic papulovesicular bullous lesions affecting the skin and the oral mucosa. It most closely resembles dermatitis herpetiformis or bullous pemphigoid. In contrast, the presence of acantholysis and of antiepithelial antibodies indicate pemphigus. Three patients, all women, showing this unusual variant of pemphigus, were seen during the last 3 years, a fourth is reported here. One patient responded well to dapsone; the three others did not. Oral treatment with aromatic retinoid (Ro 10-9359) was clearly effective in the last patient, leading to full remission of the skin lesions in a few days. The oral mucosa improved only partly. Discontinuation of the aromatic retinoid treatment and replacement of the drug by placebo was followed by a relapse both of mucosal and skin lesions. Aromatic retinoid possibly inhibits eosinophilic migration into the epidermis and impedes acantholysis associated with this phenomenon.

Acantholysis↗
PubMed1982

[Immunological staging in lupus erythematosus. Basic data and practical significance].

A complete staging of immunity in lupus erythematosus includes immunoserologic, immunocytologic, and immunohistologic findings. However, not all of these laboratory findings are of clinical relevance. The most important immunologic parameters for lupus erythematosus can be summed up in three obligatory and two facultative tests. This "immunologic staging" is considered to be of decisive importance for the risk classification of patients with lupus erythematosus and for the choice of the therapeutic procedure.

Antibodies, Anti-Idiotypic↗
PubMed1982

[Drug-induced pellagra].

In industrialized countries pellagra may nowadays be induced by inappropriate diet schedules, alcohol abuse, endogenous disorders of metabolism, and also intake or abuse of drugs. In particular, INH, hydantoine, and other anticonvulsive drugs may induce pellagra by causing disorders in vitamin B metabolism. On this pathway disorders of tryptophan metabolism may also occur. We report here on a woman who developed pellagra after long-term abuse of analgetics and psychopharmaca obviously due to disorders in gastrointestinal resorption and liver metabolism. Phenobarbital, salicylic amide, phenacetin, possible also diazepam, induced the disease most likely. The clinical diagnosis was confirmed by low blood levels of niacinamide. Discontinuation of drug medication and systemic application of vitamin preparations were followed by full remission in 6 weeks.

Diazepam↗
PubMed1981

[Oro-mandibular-limb-hypogenesis-syndrome (author's transl)].

The Oro-mandibular-limb-hypogenesis-syndrome is a combination of rare malformations. The etiology is unknown. Early reconstruction of the mouth and orthopedical care are described. The psychological management of the parents and the early contact between mother and child are important.

Abnormalities, Multiple↗
PubMed1981

[Erythema anulare centrifugum with pustulation. Successful oral retinoid therapy].

Erythema anulare centrifugum with pustulation (EACP) is an unusual sterile pustulosis, which is believed to represent a rare type of pustular psoriasis. HLA-examination in this patient did not show, however, the typical pattern of vulgar of pustular psoriasis. No other signs of psoriasis were found either, except for the spongiform pustule. The EACP most likely corresponds to a special entity in the large group of psoriatic skin diseases. Oral retinoid therapy revealed full remission of the skin lesions.

Erythema↗