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Biomedical subjects

A Mayer-da-Silva

Publications and source records attributed to A Mayer-da-Silva.

11 recordsLinked to original sources
PubMed1991

Genetically determined coincidence of Kaposi sarcoma and psoriasis in an HIV-negative patient after prednisolone treatment. Spontaneous regression 8 months after discontinuing therapy.

We report the case of drug-induced, acrolocalized Kaposi sarcoma (KS), arising multicentrically in both palms and soles of a male patient who has had widespread psoriasis since 12 years of age. This 59-year-old man, of Mediterranean origin, was HIV antibody-negative and had received oral prednisolone treatment over 5 months for chronic obstructive lung disease (initial dose: 75 mg/d). Eight months after discontinuing oral treatment the KS nodules regressed spontaneously and finally disappeared completely without additional treatment. Light and electron microscopic investigations confirmed the diagnosis of KS, whereas laboratory tests excluded HIV infection and suggested mild immune dysfunction. The existence of HLA loci predisposing to KS and to psoriasis (A1, DR5, DR7, DR11) was characteristic for the simultaneous occurrence of these two diseases. This case report demonstrates the complex interrelationships between genetic predisposition, drugs leading to immune suppression, and the evolution of an unusual neoplasm.

Disease Susceptibility↗
PubMed1990

Initial hyperproliferation and incomplete terminal differentiation of cultured human keratinocytes from lesional and uninvolved psoriatic skin.

Human epidermal keratinocytes (KCs) were isolated from lesional and from uninvolved skin of 8 patients with chronic plaque-like psoriasis and from the normal skin of 8 healthy volunteers. Primary KC cultures, grown on 3T3 cell feeder layers, were examined over a period of 4 weeks and their plating efficiency, colony growth area, DNA synthesis and ultrastructural cell differentiation were evaluated. Psoriatic KCs formed colonies one day earlier than non-psoriatic controls and proliferated faster during the first 2 weeks, as assessed by the mean colony growth area and 3H-thymidine incorporation. After 4 weeks, however, no significant differences were observed between the in vitro proliferation parameters of normal and psoriatic KCs. At the ultrastructural level, cultures of lesional psoriatic KCs consisted of more cell layers with adherent transitional cells and incomplete formation of cornified envelopes, even after 4 weeks, while KCs from uninvolved psoriatic skin were characterized by a transient delay of in vitro maturation. These results indicate that the characteristic hyperproliferation of psoriatic KCs may only be maintained over a short period of primary culture, whereas defective terminal differentiation of lesional psoriatic KCs was maintained throughout the culture period.

Biopsy↗
PubMed1989

Interferons in dermatology.

Interferons are a large family of proteins and glycoproteins, naturally occurring or artificially produced by recombinant biotechnology. Their antiviral, antiproliferative, antitumoral, and immunomodulatory activities are induced by alterations in cell metabolism after binding to specific membrane receptors. Interferons have been used for the treatment of viral papillomas (e.g., verruca vulgaris and condyloma acuminatum), human immunodeficiency virus (HIV)-associated Kaposi's sarcoma and cutaneous tumors (e.g., melanoma, cutaneous T cell lymphoma, and basal cell carcinoma), and inflammatory dermatoses (e.g., Behçet's syndrome and psoriatic arthropathy). Clinical trials have been performed worldwide with various regimens and have not always led to conclusive results. In our experience long-term therapy with high doses of subcutaneously injected, recombinant interferon-alpha-2a in patients with HIV-associated Kaposi's sarcoma induces a remission or stabilization of the disease. In malignant melanoma a low response rate is obtained in metastatic disease with the use of interferon as a single therapeutic agent. Combined with other antitumor agents, however, interferon seems to be a useful drug. Excellent control of Behçet's disease has been obtained, and the treatment of condylomata acuminata has been effective.

Humans↗
PubMed1989

Effects of azelaic acid on proliferation and ultrastructure of mouse keratinocytes in vitro.

The effects of azelaic acid (C9-dicarboxylic acid, AZA) on the proliferation and ultrastructure of neonatal NMRI mouse keratinocyte cultures were studied to clarify the mechanisms of AZA action on normal and diseased epidermis. The dose- and time-dependency of the drug effects on DNA synthesis was examined by 3H-thymidine incorporation into DNA and by autoradiography. Electron microscopy was used to detect the target cell organelles of the drug. Azelaic acid decreased DNA synthesis in a dose- and time-dependent manner with a 50% inhibitory concentration of 20 mM. The inhibition of DNA synthesis was already observed after 1 h of treatment, reached its maximum after 4 h, and was stable for 24 h. A complete reversibility of the inhibitory effects was observed within 2 h after discontinuation of the treatment, and, interestingly, a rebound effect occurred with a temporary increase of DNA synthesis. Furthermore, treatment with AZA reduced the RNA and protein synthesis of the cells. Electron microscopic evaluation of treated cultures showed early marked damage of the mitochondria, followed by dilation of the rough endoplasmic reticulum (RER). These alterations were completely reversible after discontinuation of the treatment. Our findings show that AZA exerts a dose- and time-dependent, reversible antiproliferative effect on keratinocytes, acting primarily on mitochondria and RER. The antiproliferative action of AZA could explain its beneficial effect in some skin disorders characterized by alteration of keratinocytic differentiation.

Animals↗
PubMed1989

Effects of azelaic acid on sebaceous gland, sebum excretion rate and keratinization pattern in human skin. An in vivo and in vitro study.

The effects of azelaic acid (AZA) on the epidermis of 47 individuals (12 with normal skin, 15 with seborrheic skin and 20 suffering from acne) and on in vitro cultured keratinocytes are reported. Topical application of a 20% AZA cream significantly improved the lesions of acne patients, but failed to induce clinically detectable changes in normal or seborrheic epidermis. Complementary investigations clearly showed that AZA treatment failed to induce specific changes in sebum composition, excretion rate, or in the size of sebaceous glands, but modified epidermal keratinization. Keratohyalin granules and tonofilament bundles were reduced in size and number, mitochondria were swollen and the rough endoplasmic reticulum of malpighian keratinocytes enlarged. The infundibular epidermis of acne individuals showed marked reduction of the horny layer thickness, widening of the horny cell cytoplasm, transitional corneal cells, normalization of filaggrin distribution, and the comedo contained few bacteria and spores. In vitro, AZA exerted marked time- and dose-dependent antiproliferative cytostatic effects on cultured keratinocytes, with a 50% inhibitory dose of 20 mM, decreased some keratinocyte proteins (highly soluble fractions S2, keratohyalin macroaggregate R2, and non-cross-linked fibrous protein S4) and a 95 kD and a 35 kD protein of the cytosolic fraction. Mitochondria were frequently damaged and the rough endoplasmic reticulum enlarged. Our results indicate that AZA is an antikeratinizing agent, displaying antiproliferative cytostatic effects on keratinocytes and modulating the early and terminal phases of epidermal differentiation.

Acne Vulgaris↗
PubMed1989

Isolation of human sebaceous glands and cultivation of sebaceous gland-derived cells as an in vitro model.

An experimental technique is presented as an in vitro model for the study of human sebaceous gland-derived cells. Intact sebaceous glands were isolated from full-thickness human skin after incubation in dispase (2.4 U/ml) and in deoxyribonuclease (0.02%) by using microsurgical instruments under microscopical observation of the epidermal underface. Subsequently, the ducts of the glands were removed, the isolated gland lobules were seeded on a 3T3-cell feeder layer in Dulbecco's modified Eagle's medium and Ham's F 12 medium (3:1) supplemented with fetal calf serum (10%), L-glutamine, antibiotics, epidermal growth factor (10 ng/ml), hydrocortisone (0.4 microgram/ml), and cholera toxin (10(-9) M), and were then cultivated in a CO2-incubator at 37 degrees C. After 2-3 wk cell outgrowths resulting from the periphery of the gland lobules were obtained and dispersed cells were passaged for three subcultures with or without 3T3-cell feeder layer. The cultured cells preserved in vitro morphologic characteristics and differentiation patterns comparable to those described for normal human sebocytes in vivo, with a high rate of viable cells. Their labeling pattern with MoAb showed close similarities to the pattern reported for sebocytes in vivo but differences to the pattern of keratinocytes in vivo and in vitro. In their cytoplasm oil red and nile red stained droplets were detected, and the observed density and distribution evidenced in vitro lipogenesis. The technique presented here may provide a promising model for further experimental studies on sebaceous gland cell development and function.

Antibodies, Monoclonal↗
PubMed1988

Monoclonal antibody labeling for cytokeratins and filaggrin in the human pilosebaceous unit of normal, seborrhoeic and acne skin.

The distribution of cytokeratins and filaggrin in human pilosebaceous unit was investigated in specimens obtained from normal (n = 15), seborrhoeic (n = 6), and acne skin (n = 6), using the monoclonal antibodies CK8.12, CK8.13, CK4.62, CK8.60, KL1, PKK2, RPN 1160, and an antibody for filaggrin. The type and amount of cytokeratin content was correlated with the stage of cell differentiation in these three skin types. In all specimens studied the sebocytes. The sebaceous duct cells, and the infundibular cells contained cytokeratins, no clear differences were found between normal, seborrhoeic, and acne skin. During sebocytic maturation the amount and type of cytokeratin content changed gradually and the labeling pattern was partly different compared to the interfollicular epidermal pattern. In the sebaceous duct and the infundibulum, the labeling pattern using KL1, CK8.12, and CK8.13 was similar to that seen in interfollicular epidermis, whereas labeling with CK8.60 and PKK2 was different. These findings indicate that sebaceous duct and infundibular cells express transitional patterns of differentiation between epidermal keratinocytes and sebocytes. Filaggrin was expressed only in some sebaceous duct cells and in infundibular cells. In seborrhoeic and in acne skin, however, the reactivity of antibody to filaggrin was more intense and was already observed in the lower parts of the sebaceous duct and the infundibulum. Although no filaggrin was found in the intermediate cells of the sebaceous duct and the infundibulum in normal skin, these cell types clearly contained filaggrin in seborrhoeic and acne skin.

Acne Vulgaris↗
PubMed1988

Juvenile hyaline fibromatosis. A histologic and histochemical study.

Histochemical and routine light microscopic studies were performed in nodular skin lesions excised from one patient with juvenile hyaline fibromatosis. The lesions had different times of evolution. Recent lesions showed a high density of fibroblastlike cells embedded in an amorphous matrix of glycoproteins, hyaluronic acid, and small amounts of chondroitin sulfates A and C and of dermatan sulfate. The progressive enlargement of the lesions was due to an increase in the amount of intercellular matrix produced by the cells that progressively displayed a pattern of peripheral stratification. In the older lesions, the matrix was mainly composed by chondroitin sulfates A and C. We suggest that juvenile hyaline fibromatosis represents a disease of the connective tissue with progressive abnormal differentiation to chondroid tissue.

Alcian Blue↗
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↗