Chidori Asagami

Electron microscopic studies of most cells of human fetal skins

Electron microscopic study of human fetal skins revealed thick-type and elongated-type mast cells which seem similar to those in postpartum skin. Four types of mast cell granules were distinguished in these mast cells: granules presumed to be in mid-stage of maturation, with internal structures not contained inside a membrane-limited vacuole; granules of an undetermined nature, with internal structures contained inside a membrane-limited vacuole; electron dense granules presumed to be fully mature; compound-form granules presumably representing lysosomal structures. Among these granules, structures probably representing an earlier stage of granule formation were found. They consisted of membranous components, coarse granular components, and fine granular components. Based on the morphology of these granules and structures, a sequence in granule formation was postulated. Ultrastructural comparison between mast cells and dermal melanocytes in the same fetal skins revealed that these two mesenchymal cells were similar but not identical in the process of specific granule formation.

Inhibitory effect of azelastine, a potent antiallergic agent, on release of tumor necrosis factor-alpha from activated human peripheral blood mononuclear cells and U937 cells.

Abstract It is generally accepted that tumor necrosis factor‐α (TNF‐α) is a multifunctional cytokine which is involved in the regulation of inflammation as well as immunity. In the present study, we investigated whether azelastine, a potent antiallergic agent, affects release of TNF‐α from peripheral blood mononuclear cells (PBMC) and U937 cell line in vitro. When human PBMC and U937 cells were stimulated by phytohemagglulinin (PHA) and 12‐0‐letradecanoyl‐phorbol‐13‐acetate (TPA). respectively, the cells released significant amounts of TNF‐α as determined by TNF‐α‐specific enzyme immunoassay. TNF‐α levels in the culture supernatant of PHA‐stimulated human PBMC and TPA‐activated U937 cells decreased in a dose‐dependent manner when these cells were cultured in the presence of azelastine. This inhibitory effect of azelastine was obtained at concentrations where the drug produced no toxicity. Moreover, azelastine also inhibited release of TNF‐α from U937 cells which were already activated by TPA. These results suggest that the inhibitory effect of azelastine on TNF‐α release plays an important role in its antiallergic action in addition to inhibition and/or antagonism of histamine and leukolriens, which has been previously reported.

Successful Treatment of Vitiligo with a Sex Steroid‐Thyroid Hormone Mixture

Four patients with generalized vitiligo were successfully treated by oral administration of a sex steroid‐thyroid hormone (Metharmon‐F®, 2 tablets daily). Histopathologically, the repigmented skin showed increased numbers of melanocytes and melanin granules in the keratinocytes.

Association of apolipoprotein allele ε2 with psoriasis vulgaris in Japanese population

Abstract We studied phenotypic variations of apolipoprotein E (apoE) and the corresponding allele frequencies in 100 Japanese patients with psoriasis vulgaris (PV). The phenotypes of apoE were examined using analytical isoelectric focusing followed by immunoblotting with goat anti-apoE antibody and alkaline phosphatase-conjugated rabbit antigoat IgG. The phenotypic frequency of apoE3/2 in PV was significantly higher than in healthy controls, and this elevation was associated with an increased frequency of the ε2 allele. Therefore, it is suggested that the apoE molecule plays an important role in the development of PV.

Structure determination of glycosphingolipids of cultured human keratinocytes

From cultured human keratinocytes, seven glycolipid fractions were isolated by DEAE and silica-gel column chromatographies, and further by HPLC on a silica-gel column. By means of 1H-NMR spectroscopy, fast atom bombardment mass spectrometry and GLC-mass spectrometry, one fraction was determined to contain acylglucosylceramides, which consist of amide linked omega-hydroxy fatty acids (C30:0, C30:1, C32:1 and C34:1), fatty acids linked to the omega-hydroxy fatty acids through ester linkages (C14:1, C16:1, C18:1 and C18:2), a long-chain base (d18-sphingenine), and beta-glucose. Five of the other fractions contained glucosylceramides, and the seventh fraction contained a mixture of glucosylceramides and galactosylceramides. Glucosylceramides containing long-chain omega-hydroxy fatty acids, which are assumed to be immediate precursors of the acylglucosylceramides, were hardly detected in these glycolipid fractions. Six glucosylceramide fractions were separated due to differences in their fatty acids and sphingosines. On comparison with the results reported in our previous paper, the acylglucosylceramide content of the cultured human keratinocytes was about half that of human epidermis. Under the culture conditions used, the human keratinocytes did not differentiate into granular or horny cells. Taken together, the results suggest that the synthesis of acylglucosylceramides is not activated much in the cultured keratinocytes, but would be more activated in differentiated cells.

Acral Lentiginous Melanoma Associated with Down's Syndrome

To the Editor: It is well known that Downs syndrome is associated with malignant tumors (l) and several dermatoses, such as syringomas (2). There has been, however, no previous report of malignant melanoma associated with Downs syndrome. We describe a patient with Downs syndrome and an acral lentiginous melanoma. Case Report: A 39-year-old Japanese woman with Downs syndrome visited the Dermatology Clinic ofYamaguchi University School ofMedicine for evaluation of an asymptomatic black lesion on the third interdigital space of her right foot present for one year. On physical examination, the lesion consisted of a dark brownish, elastic nodule 22 x 8 x 10 mm containing a central ulcer, in the midst of a 33 x 18 mm, irregularly shaped blackish plaque (Fig. 1). The right inguinal lymph nodes were palpable. Although they were elastic hard, the lymph nodes were smaller than rice grains, and there was no adhesion. The typical features of Downs syndrome were present, including severe mental retardation, epilepsy, an epicanthal fold, a flat-bridged nose, and short phalanges. Chromosome analysis (G-banding) of peripheral blood lymphocytes revealed trisomy 21 but no other chromosomal abnormalities. The lesion was excised with a wide margin of more than 5 ern around it. Syme amputation was performed together with the radical ileoinguinal dissection. The thickness of the tumor was 7.2 mm. A microscopic examination showed typical findings of acral lentiginous melanoma with radial and vertical invasion, irregular acanthosis, reaching Clarks level V (Fig. 2). There was no evidence of metastasis. Chromosome analysis of the excised melanoma cells was not done. Three years after the surgical therapy, she remains well without disease. Comment: Chromosomes of patients with Downs syndrome are known to be more sensi59

Immune response to Streptococcus pyogenes and the susceptibility to psoriasis

Monoclonal antibodies directed against type 12 Group A streptococcal cell wall antigens cross‐react with nuclei and cytoplasm of cells from skin and synovium from controls, uninvolved skin of psoriatics and psoriatic plaques. Patients with psoriasis had high serum titres of antibody against the M12 (C‐region) streptococcal antigen compared to controls. An abnormal immune response directed against a ‘self’ antigen after initiation by Group A streptococcal infection may play an important role in the exacerbation or development of psoriasis.

Experimental study of the potential for contact sensitization and cross-reaction of imidazole antifungals

We examined the potential for contact sensitization of miconazole nitrate and croconazole hydro‐chloride and the cross‐reaction between them in guinea pigs by the maximization lest of Mugnsson and Kligman. Contact sensitivity was induced by croconazole hydrochloride in 5 out of 7 animals which, after being injected with 5% croconazole hydrochloride, underwent a closed patch with 25% croconazole hydrochloride. Contact sensitivity was not induced by miconazole nitrate. The 5 animals sensitized to croconazole hydrochloride were tested with 8 other imidazole antifungals and positive reactions were observed to oxiconazole nitrate in 2 of the 5 animals. This response may be a cross‐reaction.

A JAPANESE CASE OF NEU-LAXOVA SYNDROME

A 5‐day‐old Japanese female with Neu‐Laxova syndrome was presented. The patient had severe edema throughout the body, desquamation, and erosion of the skin. She also exhibited microcephaly, exophthalmos, and rocker‐bottom feet. Histologic examinations of a cutaneous specimen showed atrophy of the dermis and absence of the sebaceous glands. These represent embryonic abnormalities. Even though there was no hypoplasia of the cerebellum and lungs or hydramnios, we evaluated this patient as the first Japanese case of this sporadic disease. With intensive care, including dermatological treatment, the patient survived for 134 days.

A disease with features of cutis laxa and Ehlers-Danlos syndrome

SummaryA mother and daughter are described with light and electron microscopic, and biochemical abnormalities of their connective tissue characteristic of both cutis laxa and the Ehlers-Danlos syndrome. The mother was clinically normal, while her 8-year-old daughter exhibited loose, wrinkled skin and other clinical features of cutis laxa, and also fragility, bruisability and hyper-extensibility of the skin and poor healing of wounds, leaving “cigarette paper” scars, features characteristic of the Ehlers-Danlos syndrome. Light and electron microscopic studies of skin biopsy specimens and cultured skin fibroblasts from both individuals revealed reduced and distorted elastic fibres, a finding usually seen in cutis laxa. Electrophoretic studies of collagen excreted from cultured skin fibrobasts revealed in both individuals and alpha 2(I) chain with a molecular size smaller than usual. The father and elder daughter were normal by clinical, light and electron microscopic and electrophoretic studies. It was concluded from these findings that the mother and daughter represented a hitherto undescrbed disease of the connective tissue with dominant inheritance and variable expressivity.