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Biomedical subjects

G Mahrle

Publications and source records attributed to G Mahrle.

At least 55 records · Page 3Linked to original sources
PubMed1991

Localization of calmodulin in epidermis and skin glands: a comparative immunohistological investigation in different vertebrate species.

The study deals with the immunolocalization of calmodulin-reactive epithelial cells in different vertebrates (Tinca tinca, Ambystoma mexicanum, Xenopus laevis, Rana ridibunda, Columba domestica, Sus scrofa domestica, Homo sapiens sapiens). The immunoperoxidase technique was performed on acetone fixed frozen sections using monoclonal (BF8) and polyclonal (ACAM) anti-calmodulin antibodies. We were able to differentiate 2 major types of staining patterns: 1. A more superficial epidermal staining in species adapted to an aqueous environment and 2. a staining along the epidermal-dermal junction in species adapted to a terrestrial environment. It seems most likely that epithelial cells immunoreactive for calmodulin are involved in skin permeability control.

Ambystoma↗
PubMed1991

Immunohistochemistry of porcine skin.

The present paper reports immunohistological findings in porcine skin, which were obtained by use of mono- and polyclonal antihuman antibodies and either alkaline phosphatase anti-alkaline phosphatase (APAAP) or peroxidase (POX) technique. Epidermal staining was observed with antibodies to keratins (K 8.12, RSKE 60), filaggrin, and calmodulin (ACAM). Staining of connective tissue and vessels was achieved using antibodies to vimentin (V9(1)), collagen type IV, and fibronectin. In general, these antibodies gave a staining pattern similar to that of normal human skin. The similarities of immunoreactivity to poly- and monoclonal antihuman antibodies in porcine and human skin render porcine skin a reliable model in biomedical research.

Animals↗
PubMed1991

Increase of lipid fluidity and suppression of proliferation resulting from liposome uptake by human keratinocytes in vitro.

The in vitro effects of liposomes on HaCaT human keratinocytes were studied with regard to their uptake, lipid fluidity and proliferation of the cells. Oligolamellar liposomes, prepared from soya bean phospholipids, had a mean size of 150 mm and consisted predominantly of phosphatidylcholine (83%) and phosphatidylethanolamine (10%) and the fatty acids comprised mainly linoleic acid (66%) or other unsaturated fatty acids. After 6 and 24 h of incubation with 1 and 0.1% w/v of liposomal lipids, phase-contrast microscopy revealed marked cytoplasmic vacuolization of the cells. Keratinocytes treated with the liposomes contained aggregations of multilaminated lipid material without delimiting cell membranes. The cellular lipid fluidity (reciprocal of diphenylhexatriene fluorescence polarization P-value) correlated with liposomal concentration and incubation time. A significant elevation of lipid fluidity (P less than 0.05) was observed with 1 and 0.1% liposomes after 1 h of incubation (81.8 +/- 4.7 and 95.7 +/- 1.2% of control P value) and for 0.01% liposomes after 3 h (96.2 +/- 1.5%). Maximum fluidity occurred after 48 h of exposure to 1% liposomes (42.1 +/- 3.1%). Exposure to liposomal lipids for 24 and 48 h resulted in suppressed cell proliferation with 50% inhibition concentrations (IC50), being 0.06% for incorporation of [3H]-thymidine. 0.08% for [14C]-amino-acid incorporation and greater than 1% for protein content per well after 24 h of exposure. The cells were able to proliferate and lipid fluidity returned to normal within 7 days following discontinuation of incubation with liposomal lipids.

Cell Division↗
PubMed1991

Induction and inhibition of NAD(P)H: quinone reductase in murine and human skin.

The purpose of this study was to characterize the human cutaneous NAD(P)H: quinone reductase (NQR) activity by known inhibitors of different reductases and to compare it with the murine skin and liver NQR activity. This enzyme plays a major role in the defence of cells against oxygen stress because it inhibits the 1-electron reduction of quinones to semiquinones and their subsequent oxidation to quinones termed as quinone redox cycle. It belongs to the aromatic hydrocarbon-responsive (Ah) battery. This gene battery includes Cyp1a1 (cytochrome P-450 IA1), Cyp1a2 (cytochrome P-450 IA2) and Nmo-1 [NAD(P)H: quinone reductase]. In the skin cytochrome P-450 IA1-dependent activity is about 1-5% compared to the corresponding activity in the liver, whereas NQR has the same activity in skin and liver. NQR was determined in the cytoplasm of murine skin, liver, and human keratinocytes using 2,6-dichlorophenolindophenol as the substrate. The Ah-receptor binding compounds, such as coal tar constituents, or 3-methylcholanthrene induce cytochrome P-450-dependent activities such as aryl hydrocarbon hydroxylase or 7-ethoxyresorufin-O-de-ethylase and NQR, whereas butyl hydroxytoluol, which does not bind to the Ah receptor, induces only NQR. For inhibition studies several known inhibitors of dihydrodiol dehydrogenase, aldo-keto and carbonyl reductase activities were used. There was a similar pattern of inhibition of the basal and induced activity in all tissues investigated. Pyrazole, progesterone and phenobarbital did not inhibit, whereas dicoumarol, rutin and indomethacin inhibited NQR activity in murine skin and liver as well as in human keratinocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Lactate dehydrogenase release as an indicator of dithranol-induced membrane injury in cultured human keratinocytes. A time profile study.

HaCaT cells, a rapidly multiplying human keratinocyte line, were tested for their sensitivity to antipsoriatic dithranol with regard to classical proliferation parameters and for the drug's action on the plasma membrane integrity by the dose- and time-dependent release of cytosolic lactate dehydrogenase (LDH). In the case of 3H thymidine as well as 14C amino acid incorporation the 50% inhibition concentration (IC50) was 0.2 microM dithranol 24 h after initial exposure to the drug. For protein content of attached cells the IC50 proved to be greater than 3.0 microM. Using 0.3, 1.0 and 3.0 microM dithranol, significant (p less than 0.05) dose dependent LDH release of 0.866 +/- 0.387, 1.842 +/- 1.127 and 2.938 +/- 1.635 mU per hour and cm2 confluent culture area was measured between the 5th and the 24th hour, compared to an acetone control of 0.504 +/- 0.299 mU/h x cm2. Between the 2nd and the 4th hour as well as from the 25th to the 48th hour and the 49th to the 72nd hour the LDH release after dithranol treatment did not exceed the control value. In accordance with these findings dose-dependent morphological signs of cell injury were detected by phase contrast microscopy beyond the 4th hour. The data reveal that: HaCaT cells are a very sensitive target for the antiproliferative action of dithranol; the drug causes considerable plasma membrane damage even at concentrations as low as 0.3 microM; and this membrane damage becomes evident after a latency of at least 4 h and for a limited period of up to 24 h.

Anthralin↗
PubMed1990

Recombinant interferon-gamma (rIFN-gamma) in dermatology.

This paper gives a short review on the function, pharmacokinetics, and therapeutic application of recombinant interferon-gamma (rIFN-gamma) in dermatology. Simultaneously, our own experiences are presented for 57 patients (phase II study) suffering from genital warts (21 patients), psoriatic arthritis (10 patients), psoriasis vulgaris (three patients), malignant melanoma (six patients), bowenoid papulosis (four patients), Behcet's disease (four patients), basal cell carcinoma (six patients), as well as herpes simplex recidivans, epidermodysplasia verruciformis, and mycosis fungoides (one patient each). We conclude that there might be an indication for treatment with rIFN-gamma in genital warts, bowenoid papulosis, Behcet's disease, and microbial infections, such as leprosy and cutaneous leishmaniasis. Even though there are reports of a limited beneficial effect of rIFN-gamma on arthritis and skin lesions in psoriasis, we failed to observe any in 10 patients. The main side effects in our low-dose study (50-100 micrograms/d) were mild fever (78%), fatigue (78%), and myalgia (65%). Laboratory tests revealed an increase in the serum triglyceride level, in particular, in psoriatic patients.

Bacterial Infections↗
PubMed1990

[Increased expression of proliferation keratins K 6 and K 16 in unaffected skin in exacerbated psoriasis].

The in vivo expression of the proliferation keratins K 6 and K 16 is characteristic for hyperproliferative diseases and positive in psoriatic lesions. Our study was performed in order to investigate the in vitro expression of proliferation keratins and to settle the question whether they are also inducible in organ cultures of uninvolved psoriatic skin, possibly differing from normal skin.

Adult↗
PubMed1990

[Cyclosporin A--dermatologic indications].

The pharmacology, the biological action, as well as the clinical indications for systemic or topical application of cyclosporin A (CSA) is reviewed. Our studies yielded the following results: In chronic stationary psoriasis, systemic treatment with CSA in very low doses (2.5 mg/kg/d, 13 patients, 10 weeks) led to a 75% reduction of the PASI score without any side reactions. After topical application of CSA (40 patients, 1/5/10% gel and ointment), we observed a subclinical effect. CSA permeated into the deeper layers of the skin and accumulated up to a concentration of 3.880 ng/g (80-39.000 ng/g, polyclonal RIA); these quantities correspond with those found after systemic administration. In spite of this, CSA was not measurable in the blood. Topical CSA reduced the neutrophils in psoriatic skin both selectively and significantly, but did not affect the epidermal synthesis of DNA.

Administration, Topical↗
PubMed1990

[Cutaneous administration of liposomes--a review of the literature with special reference to findings from keratinocyte cultures, animal experiments and clinical studies].

Recent findings regarding the topical application of liposomes are reviewed under 3 headings: (1) keratinocyte cultures, (2) animal experiments, and (3) clinical studies. Under cell culturing conditions, liposomes are able to get into direct contact with living keratinocytes--just as in cutaneous application when the barrier of the horny layer is missing (i.e. in case of superficial skin defects or unkeratinized mucocutaneoaus surfaces). Under these circumstances, keratinocytes show liposomal alterations of the cell structure, proliferation, and lipid fluidity. Animal experiments and clinical studies have pointed out that, in comparison with a conventional formulation, a liposomal way of application can enhance the penetration of various substances as well as their toposelective enrichment in the skin, since the dermal-vascular absorption is diminished.

Animals↗
PubMed1990

[The effect of initial external glucocorticoid administration on cignolin treatment of psoriasis].

In a randomized open study we compared the effect of conventional dithranol therapy (CSV-therapy, 7 patients) with a combination regimen, in which patients were pretreated with a 0.064% betametason dipropionate ointment (Diprosis) for 1 week before the onset of dithranol therapy (B + CSV-therapy). Clinical evaluation was performed by grading 4 representative lesions per patient for erythema, plaque thickness and scaling every week (EPS-score). After one week of therapy glucocorticoid was superior to dithranol (reduction of EPS-scores 68% vs. 35%). Thereafter the benefit of CSV-therapy surpassed that of B + CSV-therapy. 33 days after onset of therapy there was a 95% reduction of skin lesions in the CSV-group compared to a 75% reduction in the B + CSV-group. In terms of a 95% reduction the CSV-group required 32.9 +/- 5.5 days versus 45.1 +/- 19.7 days of the B + CSV-group. During the 6 months follow-up relapses occurred in 3 of 7 patients of the CSV-group 15.32 and 34 days after discontinuation of therapy and in 2 of 7 patients of the B + CSV-group 64 and 82 days after discontinuation of therapy. The present findings reveal that a pretreatment of psoriasis with topical glucocorticoids reduces the response to dithranol and the duration of remission.

Administration, Topical↗
PubMed1990

[Topical administration of cyclosporin in psoriasis vulgaris].

Two groups of patients with chronic plaque psoriasis were topically treated either with 10% cyclosporin in a jelly base or with 5% cyclosporin in an ointment base under occlusion. We found that cyclosporin penetrates into the lower epidermis and the dermis, when it is applied under occlusion. Obviously, the target cells are neutrophil granulocytes, since they decrease in number under cyclosporin, whereas the other inflammatory cells as well as the epidermal proliferation remain unchanged. In contrast to systemic application of cyclosporin, we did not observe any clinical differences between plaques treated with cyclosporin and those treated with placebo.

Administration, Topical↗
PubMed1990

[Effect of cignolin and infrared irradiation on the patch test and lymphocyte transformation test].

In a study on the effect of anthralin and infrared irradiation (IR) on the allergic patch test in vivo and the lymphocyte transformation test in vitro, we observed that anthralin enhanced the local test reaction. Our findings suggest an additive reaction of toxic anthralin dermatitis and allergic test reaction. Immunohistology showed that additional treatment with anthralin resulted in elevated numbers of the OKT-6+ dendritic cells in the epidermis. Anthralin in concentrations of greater than or equal to 10(-5) M inhibited the lymphocyte transformation in vitro. IR irradiation-either before or during patch testing-did not significantly influence the allergic test reaction or the lymphocyte transformation, if the temperature was adjusted to 37 degrees C. In comparison to convective heat, we found no specific effect of IR irradiation.

Anthralin↗
PubMed1990

[Tuberculosis cutis luposa gigantea with Mycobacterium bovis detection].

In an 80-year-old woman, retired farmworker, we observed lupus vulgaris extending over more than half of her leg. The extreme size of the affected area made us talk of a giant form in this case. Bacteriological investigation revealed Mycobacterium bovis. The minimal amount of tuberculin required to induce a positive intradermal reaction was 10 IU (GT Behring). Another case with similar dimensions (reported by Christiansen in 1967) had been caused by Mycobacterium avium and developed over a period of at least 5 years. The vast cutaneous affection of our patient, in contrast, had developed within only one year, starting from a brownish macula of the size of a palm on her upper leg. This macula - presumably the manifestation of quiescent lupus vulgaris - had not changed for more than 40 years. This late exacerbation of post-primary tuberculosis might have been favored by the patient's reduced immunologic resistance on account of her advanced age. In addition, local cofactors - namely ankylosis of her knee and contact eczematous dermatitis - have to be considered. In accordance with the resistogram, the disease responded to monotherapy with isoniazide.

Aged↗
PubMed1989

[Systemic photochemotherapy (PUVA) in acanthosis nigricans maligna: regression of keratosis, hyperpigmentation and pruritus].

We report on a 60-year-old patient, who developed malignant acanthosis nigricans (MAN) with intense itching 2 years after a large-cell bronchial carcinoma had been diagnosed and found inoperable. The MAN became manifest at a phase of full clinical remission of the lung tumor, which had been treated with cytostasis (cisplatin, vindesine), high energy irradiation, and extirpation of the lymph node metastases. One year after onset of MAN, the lung tumor relapsed, accompanied by an elevated serum level of carcinoembryonic antigen (CEA). The patient was slightly obese, but not diabetic. The generalized MAN was treated with 18 exposures to systemic PUVA (photochemotherapy) over 9 weeks. The patient received 8-methoxypsoralene (8-MOP) orally and a total UVA dose of 52 J/cm2; the last exposure amounted to a maximum dose of 4 J/cm2. Under this treatment, the patient was completely relieved from tormenting pruritus; in addition, we observed significant regression of the pigmented keratoses as well as the intertriginous maceration.

Acanthosis Nigricans↗
PubMed1989

[Cytokinetics and keratins of keratinocytes from skin of the elderly].

Regarding the keratin pattern of non-exposed skin, we found no significant qualitative or quantitative differences between 6 old persons (mean age 85 years) and 4 young adults (mean age 20 years). There was, however, a slight increase of proliferation keratins (K6, K16) in aged skin. In non-exposed skin taken from 6 old (mean age 70 years) and 5 young persons (mean age 37 years), longterm primary submersion cultures of keratinocytes did not show any significant differences as far as the classical parameters of growth behavior were concerned (i.e. plating efficiency, cell count, and labeled thymidine incorporation). In accordance with these findings, daily measurements of the thymidine kinase activity in the supernatants revealed discrete but not significant differences between keratinocytes in aged people and those in young persons.

Adolescent↗
PubMed1989

[Optimized interval treatment of eczema with fluprednidene. A multicenter double-blind study].

In a multicenter double-blind study, 44 patients suffering from eczema were bilaterally treated with 0.1% fluprednidene-21-acetate over 21 days. Continuous application twice a day was compared with intermittent therapy, i.e. 1 day intermission (15 patients), 2 days intermission (16 patients) and 3 days intermission (13 patients) using the cream base. Final evaluation was based on 11 criteria. All regimens, continuous and intermittent, proved effective (at least 90% reduction of the lesions). Treatment with 3 days intermission showed the same favorable results as continuous application, although the amount of glucocorticoids applied was 75% less. Measurements of the skin fold thickness (SFT) in healthy controls did not indicate any atrophy after treatment with fluprednidene under the same conditions as the eczema patients or under occlusion for up to 21 days. Clobetasol-17-propionate, in contrast, significantly reduced the SFT already after application of only 1 week.

Administration, Topical↗