Immunohistologic localization of ras p21 in normal, hyperplastic, and neoplastic epidermis.

BACKGROUND: Ras p21, a ras oncogene product, plays an important role in tumorigenesis, proliferation, and differentiation in various tissues and cells. METHODS: Using a monoclonal antibody raised against ras p21 (RASK 4), localization of ras p21 in normal epidermis and involved epidermis of various skin diseases was examined immunohistologically. RESULTS: Ras p21 was not present in basal cells of normal epidermis or basaloid cells of basal cell epithelioma but was found almost evenly in the cytoplasm of squamous cells and granular cells. This suggests that ras p21 is concerned with differentiation of epidermal cells. The mode of distribution of ras p21 differed from one cell to another in epidermal cells that turned to malignancy. The distribution was uneven and irregular in the tumorous region on the whole. CONCLUSIONS: This result might possibly represent abnormal differentiation of epidermal cells that turned to malignancy, deviating from the regular mode of the distribution of ras p21, which is necessary for normal differentiation.

Cutaneous eruptions induced by granulocyte colony-stimulating factor in two cases of acute myelogenous leukemia.

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) induced cutaneous eruptions in two cases of acute myelogenous leukemia. In both cases, the eruptions appeared during rhG-CSF therapy for neutropenia induced by the remission-induction chemotherapy and disappeared rapidly after the discontinuance of rhG-CSF therapy. Histopathology of those eruptions revealed dermal cell infiltrations consisting of some neutrophils and atypical cells. It was interesting that, although there were no leukemic cells in the peripheral blood or bone marrow, eruptions containing many leukemic cells appeared. The mechanism of the appearance of these eruptions was unclear, but it was considered that a few leukemic cells might have responded to rhG-CSF and proliferated in the skin.

Reactivity and persistence of local immunological memory on murine contact hypersensitivity.

In a rechallenge system examining murine contact hypersensitivity to DNFB in BALB/c mice, the reactivity to the specific antigen at the previously responded site and the persistence of an immunological memory were investigated. Flare-up reactions were induced 4 weeks after the first challenge only at the previously responded site by local or systemic administrations of minute quantities of a specific antigen. The intensity of ear swelling was dependent on the quantity of applied antigen at the time of the rechallenge. The local hypersensitivity to the specific antigen observed in the previously responded site and the regional lymph node persisted for at least 1 year. These results suggest that the sensitivity to a specific antigen at the previously responded site is intensified and the immunological memory persists for a long time. This may explain the mechanisms by which chronic contact dermatitis recurs readily at the limited site by exposure to minute quantities of causative antigens.

Allergic granulomatosis and angiitis of Churg-Strauss. A case of high serum level of eosinophil cationic protein.

We report a case of allergic granulomatosis and angiitis of Churg-Strauss. The patient is a 40-year-old woman who satisfied the clinico-pathological triad of asthma, tissue and blood eosinophilia, and granulomatous vasculitis. We also measured serum eosinophil cationic protein (ECP) levels in this patient. In the active stage, the serum ECP level was higher than in healthy controls, declining in the remission stage, a finding suggesting that ECP is involved in the pathogenesis and course of Churg-Strauss disease.

Dermal nerve sheath myxoma.

A case of dermal nerve sheath myxoma on the left palm of 26-year-old Japanese man is presented. We examined this tumor by light and electron microscopies. On light microscopic examination, this tumor was characterized by a multilobulated myxoid tumor composed of stellate cells in an abundant mucous matrix. This histological feature resembled previously reported cases of dermal nerve sheath myxoma. On electron microscopic examination, the findings of these tumor cells were similar to those of the perineurial cells. These microscopical examinations have provided evidence for an origin from perineurial cells rather than Schwann cells.

Interleukin-2 production of T cells in atopic dermatitis.

Patients with atopic dermatitis (AD) were treated with Tranilast, Interleukin-2 (IL-2) (production of T cells in vitro) and blood histamine values, before and after Tranilast therapy, were measured, and the following results were obtained: 1) Compared with healthy controls, the IL-2 producing ability of T cells in patients with AD was increased. 2) After Tranilast therapy, IL-2 production of T cells in AD decreased in quantity to the control level. 3) Skin lesion severities of AD were correlated with the quantity of IL-2 production of T cells. 4) Serum histamine levels were not significantly different between AD patients and healthy controls, before or after Tranilast therapy.

Immunohistochemical localization of desmosomal and cytoskeletal proteins in the epidermis of healthy individuals and patients with Hailey-Hailey's disease.

We have studied the immunohistochemical localization of desmosomal and cytoskeletal proteins in the epidermis of healthy individuals and patients with Hailey-Hailey's disease. It was found that the localization of desmosomal proteins (desmoplakin, desmoglein) and keratin filaments in the involved epidermis of patients with Hailey-Hailey's disease was almost same as that in the normal epidermis of healthy individuals. In contrast, the localization of actin filaments in the involved epidermis of patients with Hailey-Hailey's disease differed from that in the normal epidermis of healthy individuals.

Flow cytometric analysis of protein kinase C in lymph node cells during the induction phase of contact hypersensitivity reaction.

On the fourth day after a single painting of 2,4,6-trinitro-chlorobenzene on the abdominal skin, inguinal lymph nodes were removed, and a single-cell suspension was prepared. The cells were analyzed flow cytometrically, using monoclonal anti-protein kinase C antibody. It was found that the number of lymph node cells in which protein kinase C was detected on the cell surface was significantly increased over that in non-treated mice (p less than 0.01). On the basis of our results and discussions in the literature, it is thought that protein kinase C is related to the initiation of the contact hypersensitivity reaction.

Flow cytometric analysis of murine splenic cells after DNFB painting on Langerhans cell deficient skin.

One week after a single painting of 50 microliters of 0.5% DNFB in acetone-olive oil on the tail skin of C3H mice, the spleens were removed from the animals. A single cell suspension was prepared from the spleens, and flow cytometric analysis was performed for L3T4 and Lyt2 positive cells, as well as for the IJk expression of the Lyt2+ cells. Results showed that the percentages and absolute numbers of Lyt2+ L3T4- cells, Lyt2- L3T4+ cells, Lyt2+ IJk+ cells, and Lyt2+ IJk- cells in the spleens of the DNFB-treated mice were not significantly different from those in the non-treated mice. However, in the treated mice, the IJk expression of Lyt2+ cells intensified. These results indicate that, following a single painting of DNFB onto Langerhans cell-deficient skin, the numbers of Lyt2+ cells do not change significantly, but do change functionally.

Flare-up reaction on murine contact hypersensitivity. I. Description of an experimental model: rechallenge system.

In this experiment, a 'rechallenge system' was established in BALB/c mice to study a local immunological reaction of contact hypersensitivity (CH). Briefly, mice were sensitized by a single painting with 25 microliters of 0.5% dinitrofluorobenzene (DNFB) on the shaved back skin on Day 0. On Day 5, they were challenged with 20 microliters of 0.2% DNFB on each left ear, and on Day 33 challenged again with either painting 20 microliters of 0.2% DNFB on their both ears or intravenous administration of 15 mg of dinitrobenzene sulphonic acid (DNBS). As the result, marked ear swelling was observed by the second challenge only on the first challenged site and these responses were clarified to be antigen specific. In in vitro experiments, it was shown that only the cells from the regional lymph node of the skin, which were previously elicited on challenge, were enhanced to proliferate by DNBS, which was added into the culture medium. These results suggest that there is a local immunological mechanism to respond to the specific antigen only on the site in which CH reaction has been elicited previously. The results from this 'rechallenge system' may help to explain some pathological mechanisms of such chronic diseases as fixed drug eruption or chronic contact dermatitis, which recur easily in skin lesions involved previously.

IL-1 and PGE2 productions by the regional lymph node cells from DNFB-sensitized mice.

Interleukin 1 (IL-1) and Prostaglandin E2 (PGE2) are mainly produced by macrophage/monocytes. In this experiment, we investigated the immunological role of macrophage/monocytes in the lymph nodes (LNs) by measuring IL-1 and PGE2 productions of regional LN cells from dinitrofluorobenzene (DNFB)-sensitized and -tolerant mice. LN cells from sensitized mice produced IL-1 in remarkable amounts after in vitro antigen stimulation. On the other hand, the LN cells from tolerant mice failed to produce IL-1 or PGE2. These data indicate that, by modifying cytokine production, macrophage/monocytes in the regional LNs play a key role in the pathomechanism of contact hypersensitivity.

Ultrastructural studies of the skin and cultured fibroblasts in I-cell disease.

The skin and cultured fibroblasts from a patient with I-cell disease were examined by electron microscopy. Multiple vacuolations were seen in fibroblast and/or histiocyte-like cells, secretory cells of eccrine glands, and Schwann cells of the skin. Vacuolar inclusions were single membrane-limited, and contained a few reticulo-floccular and vesicular materials, endothelial cells of the dermal capillaries contained other types of inclusions, which were also membrane-limited, more electron dense, and multivesicular. The epidermis and pilosebaceous appendages seemed to be normal. Cultured skin fibroblasts contained prominent inclusions which varied in size and morphology. Acid phosphatase activity was seen in some of those inclusions, indicating their derivation from lysosomes. These findings suggest that the I-cell disease is a type of lysosomal storage disease and that electron microscopic examination of normal-appearing skin in this disease may contribute to the diagnosis.