Makoto Seiji

Lysosome destruction and lipoperoxide formation due to active oxygen generated from haematoporphyrin and UV irradiation.

The lysosomal enzymes, acid‐phosphatase and β‐glucuronidase, were released from rat liver lysosome when exposed to 400 nm irradiation in the presence of haematoporphyrin, and the release was prevented by adding vitamin E., diazabicyclo‐octane, bovine serum albumin, superoxide dismutase or d‐mannitol to the reaction mixture. Monochromatic irradiation with wavelengths from 380 to 410 nm caused no significant differences in the release of lysosomal enzymes, but 420 nm irradiation caused three fifths of that of 400 nm irradiation. The malondialdehyde level in rat liver homogenate increased after 400 nm irradiation in the presence of haematoporphyrin. Reduction of nitroblue‐tetrazolium was not observed when haematoporphyrin was excited by 400 nm; it was considered that superoxide anion radical (O–2) was not primarily generated.

Pigmentary incontinence in fixed drug eruptions: Histologic and electron microscopic findings

Pigmentary incontinence is a phenomenon observed in some inflammatory skin disorders. Clinically it may be seen as a slate-colored pigmentation. Histologically it is seen as an accumulation of melanin in the upper dermis. The possible mechanism for development of pigmentary incontinence is discussed based on a review of the literature and electron microscopic studies of fixed drug eruption.

HISTIDINE-RICH PROTEIN AS A POSSIBLE ORIGIN OF FREE AMINO ACIDS OF STRATUM CORNEUM

Pulse‐chase labeling experiments with 3H‐histidine and 3H‐arginine were performed in hairless mice to investigate the origin of free amino acids in the stratum corneum. Time‐course labeling of epidermal proteins was examined by sodium dodecyl sulfate‐polyacryl amide gel electrophoresis (SDS‐PAGE). The radioactivity was also measured in the following three epidermal fractions; 0.1 N HClO4 soluble‐ethanol soluble fraction (Fr. I), 0.1 N HClO4 soluble‐ethanol insoluble fraction (Fr. II, histidine‐rich protein fraction) and 0.1 N HClO4 insoluble‐8M urea soluble fraction (Fr. III).

Primary cutaneous cryptococcosis.

A 53-year-old man, a pigeon fancier, with long-standing asthma, treated for years with systemic corticosteroids, developed a fast-growing mass on his right wrist. The diagnosis of cryptococcosis was established by histology and culture of tissue which yielded Cryptococcus neoformans. Oral treatment with ketoconazole for 3 months resulted in a complete cure with residual hyperpigmentation and minute scars. During a 10-month follow-up, the patient was free of recurrences.

Transfer of tyrosinase to melanosomes in Harding-Passey mouse melanoma.

The transfer of tyrosinase from microsomes into melanosomes, without passing through the cytosol in the Harding-Passey mouse melanoma cell, was confirmed by experiments carried out using a combination of radioisotope tracer techniques and immunoprecipitation. 3H-Labeled amino acid incorporation into tyrosinase present in the microsome, melanosome, and soluble fractions confirmed the precursor-product relationship of the enzyme in the microsome fraction and in the melanosome fraction. However, two forms of the enzyme, Ts1- and Ts2-tyrosinase, separated from the soluble fraction by polyacrylamide gel electrophoresis, were shown to play no role in the transfer since little or no incorporation of radioactivity into tyrosinase in this fraction was found. It is suggested that most tyrosinase observed in the soluble fraction does not leak from the melanosomes or the microsomes during homogenization, but comes from necrotic tumor cells. It appears that melanosomal and microsomal tyrosinase might be released from the membrane of necrotic cells modified by various degradation enzymes, considering the data on the recovery of tyrosinase from the soluble fraction, where one-third of total enzyme activity in the postnuclear fraction could not be increased, even when the postnuclear fraction of the tumor was further homogenized radically.

A case of lichen amyloidosus with Riehl's melanosis-like lesion on the face: a histological and electron microscopic study of Civatte body and amyloid.

Ultrastructural studies were carried out on the patient who developed lichen amyloidosus and Riehls melanosis‐like lesion on the legs and face, respectively. In the skin specimens from the face, there were many masses of aggregations of wavy or net‐like filaments which appeared to correspond to Civatte bodies as recognized under the light microscope at the dermo‐epidermal junction. Sometimes, an other kind of filament mass was present in the papilla. These were aggregations of straight and non‐branching filaments and were very similar to so‐called amyloid masses. These amyloid‐like masses, which seemed to be in a developmental stage, consisted of net‐like filaments as well as straight and non‐branching filaments. Therefore, the net‐like filament masses or Civatte bodies seemed to serve a particular role in the formation of these amyloid‐like filament masses. On the other hand, in the skin specimens from the leg, there were many amyloid masses in the papillae and few Civatte bodies in the dermo‐epidermal junction, but no features suggesting that Civatte bodies may serve a role in the formation of amyloid. From these observations, it may be concluded that Civatte bodies will contribute to the formation of amyloid under certain conditions like Riehls melanosis; however, it is still uncertain whether Civatte bodies also contribute to the formation of amyloid filaments of lichen amyloidosus.

Clinical and biological studies of 26 cases of xeroderma pigmentosum in Northeast District of Japan

SummaryTwenty-six patients with xeroderma pigmentosum (XP), who live in the Northeast (Tohoku) District of Japan, were examined for the clinical characteristics of UV-induced DNA synthesis (unscheduled DNA synthesis, UDS) and UV sensitivity of skin fibroblasts or lymphoblastoid cells, or both. A history of consanguineous marriage within two generations was found in 19 of 26 cases (73%). Two pairs of siblings showed similar manifestations and almost the same levels of UDS and of UV sensitivity. Squamous cell carcinoma, basal cell carcinoma, or both were observed on the exposed skin in 14 patients, but no malignant melanoma was found. Cancer had developed in approximately 71% (10/14) of the cancer-bearing patients by the age of 20, and 8 of them belonged to the UDS-deficient group. Neurological manifestations were associated with nine patients, including 3 with typical de Sanctis-Cacchione syndrome (DSC), and most of the cells derived from these patients had a UDS level less than 10% of that of the normal cells. A clear correlation between the levels of UDS and UV sensitivity, on the one hand, and the severity of clinical manifestations on the other could not be detected, but it seems that the UDS-deficient group is generally much more sensitive to UV in terms of cell killing and the induction of sister chromatid exchange (SCE) than the UDS-proficient group. After a photosensitivity test, one patient with mild skin manifestations showed distinct skin tanning without preceding erythema.

Plantar malignant melanoma. Statistical and clinicopathological studies.

Among 51 cases of malignant melanoma seen at the Department of Dermatology, Tohoku University School of Medicine, from 1966 to 1978, 16 cases had had the primary lesion on the sole. The average age of these 16 cases was 63 and the sex ratio (M:F) was 11:5. The common sites of involvement on the sole were the heel (in 9 cases) and the toes and metatarsal region (in 5 cases). In 14 cases the lesions arose on the right sole; furthermore, 6 cases had had histories of trauma before or after the development of tumor and 7 cases had received insufficient excisions of their lesions, all of which showed a recurrence and/or lymph node metastasis within a year. These data suggest that traumatic stimulation may have some effect up on the pathogenesis of plantar melanoma.

INACTIVATION MECHANISM OF TYROSINASE IN MOUSE MELANOMA

Tyrosinase [EC 1.14.18.1] isolated from mouse melanoma was inactivated during the dopatyrosinase reaction. When ascorbate was added to the reaction system, in which dopa‐quinone is immediately converted back to dopa by ascorbate thus preventing the formation of melanin, tyrosinase inactivation similarly occurred. If superoxide anions (O2–) or singlet oxygens (1O2), are generated during the reaction they can attack the enzyme protein to be inactivated. Therefore an estimate was made with scavengers for oxygen radicals and with a liquid scintillation counter but neither was detectable. Thus the inactivation involved is not due to reaction products nor oxygen radicals.

Electron microscopic studies of porokeratosis Mibelli --Civatte bodies and amyloid deposits in the dermis.

Electron microscopic investigations of lesions from 5 cases of porokeratosis Mibelli clarified that the cornoid lamella was composed of two types of abnormal horny cells, the precursors of which were detected as dyskeratotic cells and autolytic cells in the epidermis directly beneath the cornoid lamella. Therefore, it was concluded that the cornoid lamella might be caused by a disturbance of keratinization of genetically fragile keratinocytes. On the other hand, some sort of repair mechanism might be present in the epidermis of the lesion by which degenerated epidermal cells (Civatte bodies) are transferred from the epidermis into the cutis. In the cutis of the lesion, Civatte bodies were found in one case and amyloid in three cases. However, neither the coexistence of both nor an intermediate form was detected. These findings strongly suggest a possible conversion of Civatte bodies into amyloid.