Neuropeptide Y-like immunoreactivity in Langerhans cells from patients with atopic dermatitis.
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Biomedical subjects
Publications and source records attributed to A Giannetti.
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Cell-cell and cell-substratum interactions are mediated by surface glycoproteins, members of the vast family of "adhesion molecules". These cellular receptors influence many biological processes, including cell-substratum adhesion phenomena, cellular migration during embryogenesis, haemostasis and immune reactions. Among these molecules, in the last few years the integrin family has been extensively studied. Integrins are widely distributed on several cell types, and are also present in the skin with distinct extracellular binding specificities. In the skin, the various members of this family play multiple functions, intervening in keratinocyte adhesion to the basement membrane, in the maintenance of cell polarity, in inflammatory processes and during wound healing.
In the last fifteen years various epidermal cell (EC) culture systems have been developed suitable both for investigation purposes and for clinical applications. In organ and explant cultures skin pieces are grown to obtain in the first case vertical proliferation of epidermis and in the second outward migration and proliferation of EC. In isolated EC cultures, EC suspensions are seeded on plastic or specific substrates (collagens, fibronectin, 3T3 fibroblasts). EC attach to the substrate, proliferate to form a confluent multilayered epithelium and can be subcultured. Using a serum-free medium (MCDB 153) EC can be grown in culture free of any undefined supplement. In organotypical culture systems, EC are seeded on a biological matrix (dermis, dermal equivalent) and lifted at the air-liquid interface. Under these conditions a high level of differentiation of the cultured epidermis can be obtained. The availability of a culture-grown epithelium, similar to the in vivo epidermis, has led to the use of cultured epidermal sheets for the treatment of wounds, in particular burns. The therapeutic results have been quite promising.
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The transmission of the human immunodeficiency virus (HIV) was studied in 647 subjects who presented no apparent risk factors for the infection other than having had promiscuous heterosexual relations, heterosexual relations with people with an elevated risk of infection, or heterosexual relations with people infected by human immunodeficiency virus. Thirty subjects were found to be seropositive for anti-human immunodeficiency virus antibodies. The elevated risk factors included being the habitual partner of a person at risk of infection or of a person who was infected by human immunodeficiency virus, or being the partner of a patient with acquired immunodeficiency syndrome. The transmission of the virus was verified in 13 of 284 subjects (4.57%) who had had heterosexual intercourse three or more times with persons at risk and in 16 of 101 subjects (15.84%) who had had heterosexual intercourse three or more times with persons who were seropositive for human immunodeficiency virus antibodies. No significant correlation between human immunodeficiency virus infection and a history of sexually transmitted infections, nor between human immunodeficiency virus infection and female subjects was found. These data suggest that the epidemic of acquired immunodeficiency syndrome can also spread through heterosexual relations, even if the possibility of becoming infected in this way seems at the moment limited to particular risk behaviors.
Adults with atopic dermatitis (AD), with respiratory atopy only and healthy non-atopic controls were given intradermal injections of substance P (SP), neurokinin A (NKA), neurotensin (NT), vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP) and histamine into the normal-appearing skin on the back. The weal and flare responses were evaluated after 3, 5 and 15 min and the areas calculated using an automatic image analyser. With the three different concentrations used (1, 3 and 30 pmols) a statistically significant (P less than 0.05) reduction in both the weal and flare response to SP, NKA, NT and histamine and a reduced flare to CGRP was observed only in AD patients. Among those with AD there was no uniformity of response to the individual neuropeptide and in general the more severely affected showed a lower reactivity. Dose-response relationships were evaluated for SP and NT (10-320 pmols) in AD and healthy controls. In AD dose-response curves and time-course relationships were similar to controls, but at significantly reduced levels. The itch response to the neuropeptides and histamine was not different in atopics and controls. We suggest that this hyporesponsiveness in AD is the result of natural tachyphylaxis of the target structures (mast cells and blood vessels) and possibly due to a higher availability of neuropeptides in the skin or to a primary abnormal sensitivity of the blood vessels and mast cells to these peptides.
Six male patients with extensive psoriasis, resistant to conventional treatment, were treated orally with low-dose Cyclosporin A (CsA) (5 mg/kg/day). One patient had generalized pustular psoriasis, three psoriatic erythroderma, and two disseminated chronic plaque psoriasis. All patients, with the exception of one, were treated for at least twelve weeks. Nearly complete remission was obtained in four cases. In one patient the response was incomplete, while treatment in one case was suspended after two weeks because of the onset of cutaneous pyogenic infections and oral candidiasis. In each case a relapse was observed with the suspension of treatment.
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Several non-opioid regulatory peptides have been described in normal human skin localized both in neural fibres and in cellular elements. These include substance P, neurokinin A, neurotensin, calcitonin gene-related peptide, vasoactive intestinal polypeptide, peptide histidine methionine, neuropeptide Y, somatostatin, galanin and atrial natriuretic peptide. In the present review the morphological aspects and distribution of peptidergic nerves in normal human skin are presented. The main functional roles on nociception, pruritus, cutaneous blood flow and sweat production are discussed in regard to neuropeptides. The relationships between neuropeptides, mast-cells and neurogenic inflammation are discussed in detail. Pathological conditions are reported in which an alteration in the peptidergic control might be of importance in their pathogenesis. Some working hypothesis are discussed.
Skin biopsy specimens from five patients with pityriasis lichenoides et varioliformis acuta and from six patients with pityriasis lichenoides chronica were studied by direct immunofluorescence and by an immunoperoxidase technique using a panel of monoclonal antibodies. The dermal inflammatory infiltrate was composed of T cells, macrophages, and a small proportion of CD1a+ cells, mostly perivascular. CD8+ cells (cytotoxic/suppressor phenotype) predominated in the epidermis according to the degree of epidermal necroses, whereas CD4+ cells (helper/inducer phenotype) were superior in number among dermal T cells. A few B cells and Leu7+ cells were detected in only a small proportion of lesions. The results obtained confirm that the two conditions are variants of a single disease process and suggest that cell-mediated immune mechanisms may be important in the pathogenesis of the epidermal and vascular damage. Endothelial cells (HLA-DR+ and HLA-DQ+) and CD1a+ cells (epidermal and possibly dermal) could be primarily involved, acting as antigen-presenting cells.
13 patients of both sexes, affected by a severe form of papular rosacea, were treated with 13-cis retinoic acid (1 mg/kg/day) for 2 months. One patient interrupted the treatment after 15 days because of severe blepharitis. The size and number of papules were progressively reduced from the 2nd week, reaching complete regression at the 6th week. Three patients complained of mild blepharitis, 9 patients developed dry cheilitis.
Two cases of cutaneous phaeohyphomycosis due to Alternaria tenuissima in patients affected with primitive myeloproliferative syndrome and lymphocytic lymphoma respectively are reported. Following a review of the specific literature, the authors discuss the etiopathogenic mechanisms, the clinical and histologic aspects of the lesions and the therapeutic problems.
In the present study we have stained for alfa-naphthyl acetate esterase (ANAE) cord blood lymphocytes (CBL) as well as cord blood E rosetting cells. The results obtained showed that the percentage of E rosettes (E+) is lower in cord blood than in adult peripheral blood when rosetting is carried out with untreated sheep red blood cells (SRBC), while there is no significant difference if SRBC are previously treated with 2-aminoethylisothiouronium bromide (AET). ANAE-positive cells (A+) were higher in cord than in adult blood. ANAE staining of E+ cells showed that CBL include a high percentage of A+ cells with low avidity for SRBC which could represent immature lymphocytes related to the T-cell lineage.
Serum and CSF levels of penicillin have been determined in 13 syphilitic patients treated with relatively high doses of penicillin G by the intravenous route. Wide individual variability in the CSF/serum concentration ratio was observed. In all patients the concentration of the antibiotic in the CSF was equal to or greater than 0.03 IU/ml., which is considered to be the minimal therapeutic concentration. The potential clinical usefulness of different therapeutic regimens in the treatment of neurosyphilis is discussed.
Squaric acid dibutyl ester was used in the treatment of 26 cases of alopecia areata (AA). The results are related to different types of AA.
Secretory-IgA (SIgA) concentrations were determined in whole saliva, unstimulated or stimulated by lemon juice, of thirty-eight children with atopic dermatitis, which comprised three adolescents, sixteen with IgE detected by RAST to one or more common allergen and twenty-two without specific IgE by RAST. There were thirty healthy controls matched for age and sex. The mean amount of total IgE was significantly greater in the RAST-positive than in the RAST-negative group. The mean SIgA concentration in unstimulated saliva of the RAST-positive atopic dermatitis group was less than that of the RAST-negative atopic dermatitis group and control groups, through the mean concentrations of SIgA of stimulated saliva were not significantly different in the three groups. It is suggested that the pathogenesis of atopic dermatitis may differ in children with or without specific-IgE antibodies; in those who were RAST-positive deficient exclusion of allergen by the intestinal barrier contributed to the pathogenesis, but not in those who were RAST-negative.
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The incidence of histocompatibility antigens HLA-A, B, C, DR was studied in 32 Italian children with dermatitis herpetiformis. A significantly increased relative risk was found for B8 (R.R.=6.2), which was present in 50% of the patients as against 14% of the controls and for DR3 (R.R.=11.7), present in 69% of the patients as against 16%. DR7 also appeared to be increased, but only among DR3-negative patients. There was no significant difference in the incidence of DR3 between children with abnormal and normal jejunal biopsy, though there does seem to be a difference in expressivity of the intestinal involvement between DR3 apparent homozygous, DR3 heterozygous and DR3-negative patients.