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Biomedical subjects

P Fritsch

Publications and source records attributed to P Fritsch.

At least 199 records · Page 11Linked to original sources

[Use of systemic retinoids in dermatology].

The naturally occurring retinoids (vitamin A alcohol = retinol and all-trans-retinoic acid) have been largely replaced by synthetic retinoids in recent years as systemic drugs for use in dermatology. At the present time, two synthetic retinoids are commercially available: etretinate (Tigason) and isotretinoin (Accutane). These compounds-which have a more favourable therapeutic index than the naturally occurring retinoids-ushered in a new era of dermatological therapy by their potent antikeratinizing, antiseborrhoeic (only isotretinoin) and antineoplastic action. The broadest indications for the use of these retinoids are psoriasis (etretinate) and cystic acne (isotretinoin), whereas the most dramatic effects are encountered in a number of severe ichthyosiform disorders. Another important, although at present not clearly defined role of the retinoids is in the prophylaxis of skin tumours.

Acne Vulgaris↗

Distribution of anionic surface sites on human melanocytes and human melanoma cells in culture.

With cationized ferritin (CF) as an ultrastructural marker for anionic cell surface sites, cultured guinea pig melanocytes display a uniquely homogeneous labelling pattern and a striking absence of redistribution of marker material. In the present study, we applied the same technique to normal human melanocytes and melanoma cells. Unfixed primary human mixed epidermal cell cultures displayed CF labelling patterns identical to those in guinea pig epidermal cells: on keratinocytes, CF was found in distinct aggregations which, upon prolonged incubation, clustered and were shed. Melanocytes, in contrast, bound CF to the cell surface as a uniform diffuse monolayer. There were no signs of cluster formation or shedding. Melanoma cell cultures were derived from 10 primary (2 lentigo maligna, 1 lentigo maligna melanoma, 4 superficial spreading melanomas, 2 nodular portions of superficial spreading melanomas, 1 nodular melanoma) and from 7 metastatic melanomas (4 cutaneous, 3 lymph node metastases). The CF labelling patterns encountered were heterogeneous. Three out of 10 primary tumors and 5 out of 7 metastases showed alterations of the normal melanocyte labelling pattern: regions of typical CF distribution were irregularly interrupted by stretches of membrane free of marker. In some areas, CF occurred in small globular aggregates. There was considerable heterogeneity of CF labelling patterns in different clones of a given culture. Altered CF binding patterns in melanoma cells appear to be associated with high metastasizing protential of the cell clones and may thus represent an unfavourable prognostic sign.

Binding Sites↗

Identical lectin binding patterns of human melanocytes and melanoma cells in vitro.

Cell surface glycoconjugate patterns of human epidermal cells and of melanoma cells (MC) in primary culture derived from 11 primary and metastatic melanomas were investigated using fluorescent and horseradish peroxidase conjugated lectins for visualization at the light and electron microscopic level. The lectin labeling profiles of human melanocytes (M) and MC were found to be identical. According to their binding patterns, the lectins tested were grouped into three categories: (1) lectins binding to both keratinocytes (K) and M/MC, irrespective of neuraminidase pretreatment (concanavalin-A, wheatgerm agglutinin, succinylated wheatgerm agglutinin); (2) lectins binding to K but not to M/MC, irrespective of neuraminidase pretreatment (Ulex europaeus agglutinin I); (3) lectins binding to K, but to M/MC only after neuraminidase pretreatment (soybean, Helix pomatia, and peanut agglutinins). Untreated M were reactive for soybean and peanut agglutinins only at contact sites with K. Since the lectins from soybean, Helix, and peanut bind specifically to D-galactose and N-acetyl-D-galactosamine residues, we conclude that these particular glycoconjugates are normally masked by sialic acid on M/MC surfaces and can be unmasked by neuraminidase. These features, which have been previously observed in guinea pig M, appear to be interspecies surface markers of melanocytic cells which remain unaltered in the course of malignant transformation.

Animals↗

In vitro complement binding in human skin cells with altered differentiation.

Exposure of cytoskeletal intermediate-sized filaments (ISF) of various cell populations in normal human skin to normal human serum (NHS) results in the deposition of C3 upon these structures; this phenomenon most likely occurs antibody-independently, is initiated by Clq binding to ISF, and is followed by the activation of the classical complement pathway. In the present study we investigated the cytoplasmic C3-binding properties of skin cells undergoing altered differentiation. Incubation of cryostat skin sections of dermal melanocytic nevi with NHS and, subsequently, with fluorescein isothiocyanate-conjugated rabbit antihuman C3 resulted in a bright cytoplasmic staining of the vast majority of nevus cells. Immunoelectron microscopic studies demonstrated that ISF within nevus cells represented the only cytoplasmic C3-binding structures. In contrast, ISF within melanoma cells, basal cell carcinoma cells, and keratinocytes constituting psoriatic lesions lacked C3-binding properties. We propose that changes in structure and subunit protein composition of ISF in certain cells undergoing altered differentiation results in a decrease or loss of their C3-binding capacity.

Basal Cell Carcinoma↗

Application of the tyrosinase assay to normal melanocytes in culture.

Using a special selection technique, normal guinea-pig melanocytes were maintained in highly purified but sparse cultures (approximately 10(4) cells/25 cm2 culture vessel) which showed little proliferative activity. The applicability of the Pomerantz tyrosinase assay was tested in this in vitro model system using three different approaches, namely crude cell extracts and viable cell cultures either in situ or in suspension. The latter modifications both proved too insensitive, whereas crude cell extracts allowed accurate measurements of the basal tyrosinase activity and its stimulation by various agents. In unstimulated cultures basal tyrosinase activities ranged from 30% to 700% (mean 260%) above the blank values; intra-assay and inter-assay variability were 4.2% and 77.5%, respectively. Stimulation with alpha-MSH (10(-5) M, 10(-6) M), beta-MSH (10(-5) M), choleratoxin (10(-11) M) and cAMP (10(-4) M) plus theophylline (10(-4) M) resulted in an increase of tyrosinase activity 30-65% above basal values. Melanotropin potentiating factor (10(-8) M) enhanced the effects of alpha-MSH (10(-6) M) by 20%. This assay modification provides a sensitive tool for comparative studies of melanogenesis in normal melanocytes, malignant melanocytes and otherwise altered melanocytes.

Animals↗

Junctional blisters in acquired bullous disorders of the dermal-epidermal junction zone: role of the lamina lucida as the mechanical locus minoris resistentiae.

The level of cleavage was determined in a variety of acquired bullous diseases of the dermal-epidermal junction zone (bullous pemphigoid, dermatitis herpetiformis, porphyria cutanea tarda and epidermolysis bullosa acquisita). We used an indirect immunofluorescence technique to examine the basal membrane zone with anti-type IV collagen and anti-laminin antisera and bullous pemphigoid sera. The majority of blisters examined proved to be junctional, including those from disorders hitherto considered to be dermolytic. Dermolytic cleavage was encountered only sporadically in microvesicles of dermatitis herpetiformis, in one small vesicle and in one out of five large blisters of porphyria cutanea tarda and in a large lesion of epidermolysis bullosa acquisita. We conclude that in acquired bullous disorders of the dermal-epidermal junction zone the preferential site of split formation is the lamina lucida which appears to act as a locus minoris resistentiae; dermolytic split formation of substantial extent occurs only when the sublaminal fibrillar apparatus is mechanically compromised.

Blister↗

[Experience in pair-feeding of rats treated with nitrate or sodium nitrite].

A nutritional and toxicological study has been made of rats, using the pair-feeding technique. The animals were fed a diet containing 5% of NO-3 ion or 0.5% of NO-2 ion (in the form of sodium salts). Under these conditions, a decrease was noted in the consumption of solid food which caused a net loss of weight. Besides, nitrates notably increase liquid intake and diuresis while nitrites induce a significant decrease in the protein retention coefficient.

Animals↗

Effects of dietary nitrite and nitrate on experimentally-induced inflammation in the rat.

The inflammatory reaction was studied through changes in the weights and the constituents of granulomas induced by turpentine. The investigation used young rats fed ad lib for two months with diets containing 0.1% NO2-, 0.5% NO2-, 0.5% NO3- (w/w dry food). The NO2- and NO3- were incorporated into the diet in the form of their sodium salts. One normal control group was used as well as two groups which were "iso-sodium" with the treated groups (they received 0.636 g and 4.718 g NaCl/100 g dry food). Variance analysis was used for the statistical comparison of each group with its iso-sodium control. The growth of the animals dropped very significantly on nitrite treatment at both levels but for the nitrates only the stronger dose caused growth inhibition. The fresh weight of the granulomas decreased under the influence of the various treatments whereas the weight of the thymus was lower than the controls only in rats receiving the higher dose of nitrite. This decrease in the weights of the granulomas was paralleled by that of certain hydrosoluble and insoluble constituents of the inflamed tissue--in particular the total mucopolysaccharides and the collagen--but to a lesser extent by the non-fibrillar proteins. All these variations indicate a decrease in the defence mechanisms under the action of nitrites and nitrates. Various mechanisms could be involved: competition with iodine for capture by the thyroid, the hypoxic consequences of methaemoglobinaemia general nutritional effects, metabolic action during oxidations and peroxidations in the liver, or hormonal regulation of the adrenal glands. Analysis of the results also shows that the inflammatory reaction induced is a sensitive test in alimentary toxicology since effects are visible at doses of nitrates and nitrites which do not have nutritional consequences.

Animals↗

[Stimulation of mitotic activity of bone marrow cells in an acute inflammatory reaction. Implication of serum factors].

A nonspecific acute inflammatory reaction, induced in mice by an intrapleural injection of dextran, is able to increase, in vivo, the mitotic index of bone marrow cells. The transfer of this phenomenon to normal mice can be obtained by the injection of pure or diluted sera from animals developing an acute non-specific inflammation. This activity may also be found in the serum of normal mice but at a much lower level. The stimulatory activity is also observable in vitro when bone marrow cells are incubated with inflammatory serum. This activity is recoverable after ultrafiltration in the fraction less than 10 000 daltons. These results suggest the existence in sera of stimulating factors for hematopoiesis and furthermore that these stimulatory activities are increased during the process of inflammation.

Acute Disease↗

In vitro complement binding on cytoplasmic structures in normal human skin: immunoelectronmicroscopic studies.

We have previously provided evidence that suggests that exposure of cryostat skin sections to normal human serum (NHS) results in the antibody-independent Clq binding to cytoplasmic structures of various cell types, leading to classical complement pathway activation as evidenced by cytoplasmic C3 deposition. In the present study, we have employed immunoelectronmicroscopic methods to clarify the exact nature of cytoplasmic C3 binding structures. Incubation of cryostat skin sections with NHS followed by peroxidase-labeled rabbit anti-human C3 serum (HRP-R/Hu C3) revealed that intracytoplasmic binding of C3 occurred in suprabasal keratinocytes, melanocytes, fibroblasts, smooth muscle cells, endothelial cells, pericytes, Schwann cells, and nerve axons, but not in basal keratinocytes, Langerhans cells, and other cellular constituents of the skin. C3 binding, as revealed by the deposition of HRP reaction product, was exclusively confined to intermediate-sized filaments (ISF), which can therefore be considered to represent the subcellular site for classical complement pathway activation. Under experimental conditions that do not allow classical complement pathway activation, ISF were not decorated. Our observation that ISF of ontogenetically different cell types share the capacity of complement fixation is in accordance with the recent finding that different ISF types, despite their biochemical and antigenic heterogeneity, have common alpha-helical domains and may provide a clue to the mechanism and site of interaction between complement components and ISF.

Axons↗

[Epidermolysis bullosa acquisita: diagnosis by optic immunofluorescent demonstration of junctional antigens and vitamin E treatment].

In a patient with epidermolysis bullosa acquisita the characteristic dermolytic cleavage was demonstrated by electron microscopy and by mapping of antigenic determinants (type IV collagen, laminin, bullous pemphigoid antigen) of the dermal-epidermal junction. The latter method represents a rapid and reliable way to determine the cleavage plane in diseases which display subepidermal blister formation at the light-microscopic level. The classification of epidermolysis bullosa acquisita is still under dispute. Due to its highly characteristic clinical, ultrastructural, and immunologic features and pending further experimental data, epidermolysis bullosa acquisita should be regarded as a separate disease entity; its lumping together with cicatricial pemphigoid, as proposed by some authors appears speculative. Therapy of epidermolysis bullosa acquisita is generally regarded as difficult; following a 3-year course of high dose vitamin E therapy our patient underwent complete clearing; the possibility of a spontaneous remission, on the other hand, cannot be unequivocally ruled out.

Adult↗

[Measurement of leukocyte accumulation in the capillaries in the lesser circulation of the rat: extraction of cells and characterization of enrichment in monocytes].

We have performed a qualitative and quantitative study of leucocytes in lung alveolar capillaries. This population is not an artefact induced by experimental procedure because the same population is observed after instant cardiac arrest. About 30% of these leucocytes can be extracted by perfusion, the extracted population being representative of the whole one present in capillaries. The experimental procedure used allow to collect 100.10(6) leucocytes per animal 15.10(6) of which are monocytes easily obtained as a purified population. From these results lung capillaries contain at least as many leucocytes as the whole circulating blood and 5 times more monocytes.

Animals↗

[Herpes zoster].

This paper summarizes present knowledge on pathogenesis and therapy of herpes zoster. Formerly, zoster was considered a reinfection of a partly immune individual by the varicella-zoster virus localized into a body segment of lowered resistance. Recent epidemiological and virological evidence, however, suggests a different mode of pathogenesis: in the course of varicella, VZV migrates via the sensory nerves to the dorsal root ganglia where it remains in an inactive form. It may be reactivated in response to a local or systemic lowering of the level of host resistance, resulting in painful ganglionitis and, by descension, in the characteristic segmental skin lesions of herpes zoster. Treatment with systemic corticosteroids in the early stages of zoster helps to decrease the frequency and severity of postzosteric neuralgias. Corticosteroids ought to be given at a relatively high dosage and be tapered only slowly in the course of a few weeks. They are particularly useful in older individuals, who constitute a population prone to postzosteric neuralgias. In severe cases of generalized zoster, corticosteroids should not be given to avoid further lowering of host resistance. Recently, antiviral drugs have been developed which combine high effectiveness with very tolerable side effects, namely vidarabine and acyclovir.

Adrenal Cortex Hormones↗

Immunofluorescence mapping of antigenic determinants within the dermal-epidermal junction in the mechanobullous diseases.

The classification of mechanobullous diseases often depends on the electron microscopic distinction of intradermal (dermolytic), junctional and intraepidermal sites of cleavage. Electron microscopy is tedious and time consuming. In this report we describe a different approach to the determination of the cleavage plane by using a method which recognizes subtle differences in the localization of antigenic structures relative to the cleavage plane. Cryostat sections of lesional and extralesional skin of 3 patients with dermolytic epidermolysis bullosa, 3 with epidermolytic epidermolysis bullosa and 8 with junctional epidermolysis bullosa were examined by immunofluorescence, with specific antisera against type IV collagen (localized within the basal lamina); against laminin (noncollagenous protein, localized in the lamina lucida); and with bullous pemphigoid antibodies (directed against the bullous pemphigoid antigen localized in the lamina lucida). All specimens were also examined by electron microscopy. In dermolytic epidermolysis bullosa (where cleft formation occurs intradermally) type IV collagen, laminin and the bullous pemphigoid antigen were consistently found in the roof of the blister, whereas in junctional epidermolysis bullosa (where the cleft occurs in the lamina lucida) type IV collagen and laminin were found on the floor of the blister whereas bullous pemphigoid antigen was present mainly on the roof, but focally also on the floor, of the blister. In epidermolytic epidermolysis bullosa (where the cleft is intraepidermal) all antigens were localized below the cleavage plane. In all cases electron microscopy confirmed the level of cleft formation predicted from the immunofluorescence mapping of the antigenic sites. The described method equals electron microscopy in accuracy but it is more rapid and simpler to perform.

Collagen↗