Mikako Aoki

Mast Cells in Basal Cell Carcinoma Express VEGF, IL-8 and RANTES

Background: Basal cell carcinoma (BCC) is the most common malignant tumor of the skin. Although an increase in mast cell infiltration was observed in BCC lesions, definite evidence of an active role of mast cells in the pathogenesis of BCC is still lacking. BCC is accompanied by cellular infiltrates. Moreover, the stroma in the BCC lesions is characterized by an increased number of mast cells and increased vascularity. The aim of this study was to elucidate the probable role of mast cells in BCC, especially focusing on the relationship between mast cells and lymphocytic infiltration as well as angiogenesis. Methods: We examined the expression and distribution of VEGF, IL-8 and RANTES in 16 nodular BCC lesions by immunohistochemistry. We also examined the lymphocyte subset, and the correlation between VEGF expression and microvessel density in the BCC lesion. mRNA expression of IL-8 and RANTES was examined by the reverse transcriptase-polymerase chain reaction. Results: T cells, especially CD4+/CD45RO+ memory T cells were the predominant infiltrating lymphocyte population in BCC lesions. An increased number of tryptase+ cells (mast cells) was found in the stroma. VEGF+/IL-8+/RANTES+ cells were also found abundantly in the stroma of all BCC lesions. The number of VEGF+, IL-8+ and RANTES+ cells was significantly higher than that in controls. By immunohistochemistry of serial sections, tryptase+ cells were found to express VEGF, IL-8 or RANTES. Messenger RNA expression of IL-8 and RANTES was also observed in the BCC lesions. Conclusion: This study suggests that mast cells may play an active role in the angiogenesis of BCC through the production of VEGF and IL-8. Furthermore, mast cells may also regulate lymphocytic infiltration through the production of IL-8 and RANTES.

Successful treatment of Kimura's disease with cyclosporine

We report the case of a 29-year-old Japanese woman presenting with recurring Kimuras disease. We began treatment with cyclosporine within 7 days, the nodular lesion had almost cleared. The cyclosporine dose was then gradually reduced and discontinued after 6 months. The patient was reassessed 18 months after the cessation of treatment and there was no evidence of recurrence of the disease. We speculate that the effects of cyclosporine on T helper-2 cells improves Kimuras disease.

Persistent Plaques and Linear Pigmentation in Adult-Onset Still’s Disease

A 25-year-old Japanese man presented with high spiking fever, arthralgia and a skin rash. A pruritic edematous erythema with persistent plaques was found mainly on the trunk; these lesions persisted even when the fever subsided, with prominent linear pigmentation. As marked neutrophilia and a high level of serum ferritin were detected, a diagnosis of adult-onset Still’s disease (AOSD) was made, even though the persistent eruption was not characteristic of the disease. Oral prednisolone, together with low-dose methotrexate, was given with good results. In the literature, a similar atypical rash has been reported in 11 cases in Japan. All of them required high-dose administration of corticosteroids or other immunosuppressive agents. Severe systemic complications were seen in 3 patients, and 2 cases died of the disease. Persistent plaques and linear pigmentation are some of the manifestations of AOSD, which cannot be overlooked. This appearance could be an indication that suggests an increased risk of systemic complications and a prolonged time to clinical remission.

Tumor Necrosis Factor Alpha Immunoreactivity of Rat Peritoneal Mast Cell Granules Decreases during Early Secretion Induced by Compound 48/80: An Ultrastructural Immunogold Morphometric Analysis

We used fast (seconds) and ultrafast (milliseconds) microwave energy-assisted chemical fixation protocols, postembedding immunogold staining, and a morphometric analysis to investigate the early morphological changes and the TNF-alpha immunoreactivity in the cytoplasmic granules of rat peritoneal mast cells that had been stimulated to secrete by exposure to compound 48/80. Exposure to compound 48/80 induced the development of increased numbers of cytoplasmic granules that exhibited decreased electron density; these granules often also appeared swollen. These granule alterations were accompanied by a significantly decreased proportion of granules that were positive for TNF-alpha immunoreactivity. We also calculated the density of TNF-alpha labeling/mu 2 in both dense (unaltered) and altered granules in specimens. TNF-alpha immunoreactivity was present in dense granules (regardless of whether or not the specimens had been stimulated with compound 48/80) and in cells that were fixed with either fast or ultrafast microwave energy. However, altered granules exhibited a decreased density of TNF-alpha label. These findings show that changes in the immunolocalization and/or density of TNF-alpha immunoreactivity occur very rapidly upon stimulation of rat peritoneal mast cells with compound 48/80.

Two Cases of Lymphomatoid Papulosis in Children

Abstract: An 8‐year‐old Japanese boy had a 4‐month history of self‐healing crops of violaceous, scaling papules and several small indurated areas of erythema on his limbs, buttocks, and trunk. Histologically there was an infiltration of small lymphocytic cells with scattered large atypical cells expressing CD30. Characterization of T‐cell receptor gene rearrangement showed monoclonality of the infiltrating cells. The second patient, a 15‐year‐old Japanese girl, had a 2‐week history of self‐healing papulovesicular eruptions on her face and limbs. Large CD30+ atypical cells were also noted in the perivascular lymphocytic infiltration. Immunohistochemical studies revealed CD8 expression on almost all CD30+ cells in the second case. In the literature, there have been two reports of children with large CD30+ atypical cells expressing CD8 and two cases expressing CD4, whereas all adult cases reported have had cells expressing only CD4.

CD30+ lymphoproliferative disorder: primary cutaneous anaplastic large cell lymphoma followed by lymphomatoid papulosis

CD30+ large anaplastic lymphoid cells are seen in anaplastic large cell lymphoma (ALCL), and also in lymphomatoid papulosis (LyP) and other lymphoproliferative disorders. It can be difficult precisely to categorize these disorders with CD30+ cells. We report a case of primary cutaneous CD30+ ALCL with systemic metastases in whom the clinical disease subsequently evolved into LyP. The patient was initially administered cisplatin and etoposide and made a good response. Eighteen months later, recurrent, self‐healing cutaneous small nodules appeared around the original tumour site without any systemic involvement. Histopathological examination of the recurrent lesions revealed infiltration with a mixture of cells that included neutrophils, eosinophils and CD30+ large anaplastic cells cytologically identical with those in the primary lesion. The anaplastic cells in both the primary and recurrent lesions were positive for monoclonal antibodies CD30, CD25 and a monoclonal antibody directed against the chimeric protein p80NPM‐ALK. These observations suggest the possibility that the ALCL and the subsequent LyP represent different clinical manifestations of proliferation of the same clone.

Case of anaphylaxis caused by ingestion of royal jelly

Anaphylaxis is a severe form of allergic disease. Royal jelly is widely consumed in Japan, but a few cases of anaphylaxis caused by royal jelly have been reported. We encountered a 26‐year‐old Japanese woman who developed anaphylaxis after drinking a beverage of crude royal jelly including honey. She had a history of bronchial asthma, allergic rhinitis, allergic conjunctivitis, atopic dermatitis and food allergy (abalone). Prick tests were performed with the beverage of crude royal jelly including honey and with two other beverages including honey. Only the crude royal jelly beverage showed a positive reaction. An oral challenge test with the crude royal jelly beverage was not performed, but a similar test with a beverage including honey caused no symptoms. A positive response to the beverage of crude royal jelly was not observed in normal volunteers. A positive diagnosis of anaphylaxis due to royal jelly was made based on the positive prick test, systemic clinical symptoms and the negative prick tests in healthy volunteers. Moreover, the patient had no symptoms when taking lemon and orange, which were present as essences in the crude royal jelly beverage, and also had no response to honey after anaphylaxis. Increased consumption of royal jelly in health food supplements may increase the incidence of royal jelly‐related allergic reactions. Therefore, royal jelly should be considered as a causative allergen in food‐induced anaphylaxis.

Granulocyte adsorptive apheresis for leg ulcers complicated by rheumatoid arthritis: a report on three successfully treated cases

Background  The treatment of inflammatory leg ulcers complicated by rheumatoid arthritis (RA), which are unresponsive to conventional care, can be frustrating. Furthermore, as granulocytes and monocytes (GM) are major sources of inflammatory cytokines, they have the potential to initiate and perpetuate inflammatory skin lesions. Accordingly, a recent study reported the remission of pyoderma gangrenosum following the reduction of activated peripheral blood GM by adsorptive apheresis (GMA).

IMMUNOCYTOCHEMICAL LOCALIZATION OF CHYMASE TO CYTOPLASMIC VESICLES AFTER RAT PERITONEAL MAST CELL STIMULATION BY COMPOUND 48/80

The subcellular events responsible for release of mediators by mast cells may help to clarify roles for mast cells in health and disease. In this study we show that the granule-associated protease chymase is also within cytoplasmic vesicles in appropriately stimulated rat peritoneal mast cells. Rat peritoneal mast cells were recovered before or 1–10 sec after exposure to the secretogogue compound 48/80 (10 μg/ml) and then were examined by radioimmunoassay to quantify histamine release or were processed, using routine methods for postembedding immunoelectron microscopy, to identify the subcellular localization of chymase. In comparison to unstimulated cells, compound 48/80 stimulated cells in two independent experiments showed an increase (15%, 28%) in the surface area of the cell and a decrease (12%, 6%) in the surface area of the total granule compartment before degranulation channel formation. These global cellular changes occurred in a background of transient but significant (p<0.01) increases in the area and number of chymase-immunoreactive vesicles per μ2 cytoplasm. These changes were detectable at 5 or 7 sec after stimulation with compound 48/80 but returned to near prestimulation levels by 9 or 10 sec after addition of compound 48/80 (total cumulative histamine release was 28% by 8 sec and 47% by 14 sec). These observations suggest that vesicles participate in the early stages of regulated secretion of chymase from rat peritoneal mast cells.

Bilateral chalazia of the lower eyelids associated with pulmonary tuberculosis

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