Inhibited differentiation of Langerhans cells in the rat epidermis upon systemic treatment with cyclosporin A.

The immunosuppressant drug cyclosporin A (CsA) is known to cause reduction in number, DNA synthesis and function of Langerhans cells (LC). Since also the differentiation of LC is known to be hampered in conditions of acquired immunodeficiency not due to drugs, we investigated whether this occurs with CsA. Rats were injected subcutaneously with CsA (5, 10 and 50 mgxkg(-1) x d(-1)) for three weeks; the skin was analyzed by Ia immunohistochemistry and by electron microscopy. Epidermal immunolabeled cells were 15+/-3.5 (mean +/- SEM) per 100 basal keratinocytes in untreated controls and 8.75+/-1.3, 4.75+/-1.0 and 1.7+/-1.2 upon increasing doses of CsA (p<0.01). By electron microscopy, monocytoid cells with deep invaginations of the plasma membrane and roundish LC poor in Birbeck granules appeared in the epidermis upon treatment. The results suggest that CsA inhibits the differentiation of LC precursors in the epidermis and that this can in part explain the selective increase in the risk of skin viral disease and cancer in chronically treated patients.

Colocalization of tumor necrosis factor-alpha and nitric oxide-synthase immunoreactivity in mast cell granules of nasal mucosa.

We have demonstrated, with immunohistochemical techniques, the colocalization of tumour necrosis factor-alpha (TNF alpha) with a constitutive neuronal isoform of nitric oxide-synthase (NOS) in granules of the majority (52.77%) of the mast cells (MCs) of healthy human nasal mucosa. Very few cells were positive for NOS alone (2.54%). Some cells were positive for TNF alpha alone (16.73%) or negative for both antigens (18%). Since dim degranulation occurs in MCs of healthy nasal mucosa at any time, we propose that low concentrations of TNF alpha and NOS secreted by these cells are involved not only in the regulation of homeostasis of normal human nasal mucosa, but also in the survival and function of MCs themselves.

Carcinoma of the anterior commissure of the larynx: I. Embryological and anatomic considerations.

In this study we attempt to define the organization of the anterior region of the adult larynx, on the basis of its development. For this purpose, we have studied the development of the anterior commissure region on serial sections of human larynges from embryos, fetuses, and adults. Our findings indicate that all the structures of this region derive from a single median mesenchymal band, first evident at 7 to 8 weeks of gestation, between the lateral laminae of the thyroid cartilage. This band of mesenchyme gives rise to all the structures along the midline of the thyroid cartilage and immediately beyond, including the intermediate lamina of the thyroid cartilage, the median process, and the connective tissue that connects the latter with the conoid ligament. We provide, for the first time, evidence that Broyles' ligament (commissural tendon) derives from the dorsal part of the median process and becomes intimately connected with the surrounding structures, including the insertion fibers of the vocal muscles, from early in development. On the basis of this finding we identify an independent anterior commissure region in the adult larynx, which comprises the intermediate lamina, Broyles' ligament, the connective tissue between the Broyles' and conoid ligaments, and the insertion fibers of the vocal muscles. The interpretation of all these structures as a unified region can explain the peculiar progression pathways and evolution of commissural and cordo-commissural tumors.

Localization of nitric oxide synthase immunoreactivity in mast cells of human nasal mucosa.

Nitric oxide (NO)-synthase immunoreactivity has been detected for the first time in mast cells of human normal nasal mucosa, with an antibody specific for neuronal NO-synthase. Intense immunoreactivity was revealed in secretion granules of mast cells but was found in mast cell granules free in the extracellular matrix only in some instances; no reactivity was found in the cytoplasm of this or other cell types. These findings suggest that human nasal mast cells contain a particulate isoform of NO-synthase, which shares epitopes with neuronal NO-synthase and is rapidly removed from granules upon exocytosis.

Interdigitating cells in the peritumoral infiltrate of laryngeal carcinomas: an immunocytochemical and ultrastructural study.

Interdigitating cells (IDCs) have been found in the peritumoral infiltrate of 18 patients with squamous cell carcinoma of the larynx. These cells have a dendritic shape and are characterized by the expression of S-100 protein and CD1a antigens. By electron microscopy, these cells are seen to establish intimate contacts with the apposed lymphocytes, which sometimes show signs of functional activation and proliferation. These findings indicate that IDCs may play a role in setting up a T-cell immune reaction against neoplastic cells, which may influence the biological behaviour and/or local growth of the tumour. Moreover, monocytes and cells with intermediate features between monocytes and IDCs are also found in the peritumoral infiltrate, thus suggesting that IDCs differentiate in situ from monocytic precursors, possibly under the influence of either tumour-derived factors or the local lymphoid microenvironment.

Vidian nerve resection, histamine turnover and mucosal mast cell function in patients with chronic hypertrophic non-allergic rhinitis.

Parasympathetic innervation of the respiratory tract of nasal mucosa plays an important role in the pathogenesis of chronic hypertrophic non-allergic rhinitis (C.H.N.A.R.), the vidian nerve providing the main parasympathetic nerve supply to respiratory mucosa. The present study investigates the effect of vidian nerve resection in 22 patient with intractable C.H.N.A.R. on histamine content and formation and on the number of mast cells and their degranulation in the respiratory tract. Samples were taken from respiratory mucosa for histamine and histidine-decarboxylase assay, and for microscopic observations for mast cell density and degranulation index, before and 12-24 months after vidian nerve resection. Neurectomy of the vidian nerve completely cured the clinical symptomatology, evaluated by rhinoreomanometry, and also significantly decreased both the high histamine levels and histidine-decarboxylase activity in patients with C.H.N.A.R. The density and degranulation index of mast cells were also significantly lower after surgery. These data suggest a relationship between cholinergic activity and the secretory response of mast cells and indicates a correlation between the parasympathetic nerve supply and chronic hyperthrophic non-allergic rhinitis. The significant reduction in mast cell density, histamine levels and histidine-decarboxylase activity also lends support to the hypothesis that the parasympathetic nerve supply plays a role in the regulation of mast cell histamine.

Vidian nerve resection in chronic hypertrophic non allergic rhinitis: effects on histamine content, number and rate of degranulation processes of mast cells in nasal mucosa.

The effects of Vidian nerve resection on the histamine content, number and rate of degranulation processes of mast cells in the respiratory tract of the nasal mucosa in patients with intractable chronic hypertrophic non-allergic rhinitis (CHNAR) have been investigated at various times after surgery. Preliminary data are also presented on the effects of Vidian nerve stimulation on the same parameters. The Vidian nerve was stimulated during surgery before resection. After neurotomy the histamine content was significantly lower than before but the values became less low with the passing of time. The number of mast cells per microscopic field and their degranulation index were significantly lower after surgery than before it. Stimulation determines a significant reduction in the number of mast cells per microscopic field and a parallel reduction in histamine content. These data establish a relationship between cholinergic activity and secretory response of mast cells and demonstrate a role of the parasympathetic nerve supply in the pathogenesis of CHNAR. The great reduction in the number of mast cells and histamine content also suggests that the parasympathetic nerve supply could play a role in the regulation of histamine synthesis and uptake.