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Biomedical subjects

M Seiji

Publications and source records attributed to M Seiji.

At least 19 recordsLinked to original sources

Clinical and biological studies of 26 cases of xeroderma pigmentosum in northeast district of Japan.

Twenty-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.

Adolescent

Radical production during tyrosinase reaction, dopa-melanin formation, and photoirradiation of dopa-melanin.

It has been suggested that superoxide anion (O2-) may be produced during eumelanin formation and during the photoirradiation of eumelanin , but no direct evidence for this has yet been reported (although O2- production during photoirradiation of pheomelanin has been shown). In this report, the production of O2- was investigated during the formation and photoirradiation of dopa-melanin, a synthetic eumelanin . It was found that cytochrome c was reduced during the tyrosinase reaction and dopa-melanin formation in vitro; this reduction could not be inhibited by superoxide dismutase (SOD). When dopa-melanin was irradiated by UV radiation or by visible light, high nitroblue tetrazolium (NBT) reduction was observed; this reduction was proportional to the light energy and the amount of dopa-melanin. NBT reduction by visible light could be slightly inhibited by SOD, but a 12% decrease of NBT reduction by UV radiation could be shown with the addition of SOD. These observations indicate that some radicals were produced during the tyrosinase reaction and dopa-melanin formation. Further, when dopa-melanin was irradiated, radicals were also produced, some of which were thought to consist of O2-, but others were unknown.

Catechol Oxidase

Inhibition of aminoacyl-transfer RNA formation by low-molecular substances from melanoma extract.

Two partially purified fractions of the ethanol precipitate (70-95%) of the water extract of Harding-Passey mouse melanoma, which inhibit protein and DNA syntheses of B-16 melanoma cells in culture, also inhibit protein synthesis in various cell-free systems. By examining their inhibitory effects on limited reactions of protein synthesis, it was found that one of them (ME II) inhibits protein synthesis by blocking aminoacyl-tRNA formation, while the other (ME IV) does not. This inhibition of aminoacyl-tRNA formation was not limited to specific amino acids. Since the amino acid-dependent pyrophosphate (PPi)-ATP exchange reaction catalyzed by aminoacyl-tRNA synthetases was not inhibited, it was concluded that some factor(s) in ME II inhibits amino acid transfer from aminoacyl-AMP to tRNA. ME II contains more than 20 proteins from 10,000 to 90,000 daltons. EDTA treatment of this fraction caused the release of low-molecular substances with inhibitory activity from the proteins. The molecular weights of the active substances are less than 5,000 daltons. The active low-molecular substances are apparently not peptides or nucleotides.

Adenosine Triphosphate

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.

Animals

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.

Drug Eruptions

Immunoelectron microscopic examination of IgA deposition in dermatitis herpetiformis.

Ultrastructural localization of IgA in the skin of three Japanese patients with dermatitis herpetiformis (DH) was studied with the immunoelectron microscopic technique using periodate-lysine-paraformaldehyde fixation. In direct immunofluorescence studies, two of the three cases showed fine fibrillar deposition of IgA and the other case fine granules in the dermal papillae. In the former, the reaction products of IgA were present in the upper dermis forming various-sized aggregates which were occasionally arranged perpendicularly to the epidermis and appeared to be associated with microfibrillar bundles of the elastic tissue. Reaction products were also deposited to a lesser extent on the microfibrillar component of the elastic fibers at the lower part of the dermal papillae. However, in the latter, the reaction products were found to form smaller aggregates on and around the collagen fibrils rather than on the elastic tissue. Such a localization of IgA reaction products has not yet been reported in DH. The difference of the distribution patterns of IgA and the possible singularity of Japanese DH cases are discussed.

Adult

Acral melanoma in Japan.

Clinical records and histologic materials from 81 patients with malignant melanoma at the Department of Dermatology at Tohoku University School of Medicine were reviewed. In addition, a statistical study on 1597 cases of malignant melanoma collected from the Japanese literature from 1961 to 1982 was performed. The annual mortality rate has been increasing almost linearly over the past 20 years. The mortality rate per year for 1980 was 0.21 per 100,000. Five-year survival rate at Tohoku University was 35 percent. The most common site of melanoma was acral, especially the plantar surfaces. The clinical and histologic study of acral melanomas showed that clinicopathologic features are the same as those reported for acral lentiginous melanoma in the United States.

Extremities

Chemiluminescence of UV-irradiated linolenic acid and squalene.

An emission spectral analysis was carried out on ultraweak chemiluminescence emitted from UVB-irradiated linolenic acid and squalene. The main emission species produced by the transition of (1 delta g) (1 delta g) dimer and an additional weak band near 477.5 nm (0, 0) by the transition of (1 delta g (1 epsilon g+) to (3 epsilon g-) (3 epsilon g-) were found by spectroscopic analysis of chemiluminescence in both cases of irradiated linolenic acid and of squalene. A distinct peak around 410-420 nm was observed in irradiated squalene and the emitter seems to be due to the excited carbonyl compound.

Linolenic Acids

Immunofluorescence studies on civatte bodies and dyskeratotic cells with anti-keratin antibody.

So-called Civatte bodies and dyskeratotic cells were investigated in some skin disorders by using indirect immunofluorescence techniques with anti-human keratin antibody. In the disorders with lichenoid tissue reaction such as lichen planus and DLE, Civatte bodies were observed in the lower epidermis and upper dermis and they reacted distinctly to the anti-keratin antibody. In malignant skin tumors which show dyskeratotic cells in the epidermis, such as basal cell epithelioma and Bowen's disease, dyskeratotic cells were more clearly reacted to the antibody than other keratinocytes. These observations present additional new evidence for the hypothesis that Civatte bodies are derived from tonofilaments of keratinocytes.

Adolescent

Inhibition of cell-free protein and RNA syntheses by partially purified fractions of mouse melanoma extract.

Ethanol precipitate (70-95%) of the water extract of mouse melanoma (ME) contains suppressors for melanocyte cell division. A fraction which had preferential melanocyte cell line suppressor activity (ME IV2) was shown to inhibit protein synthesis by cell-free systems and RNA synthesis by isolated nuclei of rat liver. The separation and some characterization of the inhibitory factors in ME IV2 were carried out. Upon being boiled, the factor in ME IV2 inhibiting cell-free protein synthesis became inactive, whereas that inhibiting cell-free RNA synthesis remained active. Bio-Gel p-2 column chromatography of ME IV2 gave three distinct fractions (ME IV2-A, -B and -C). ME IV2-A was inhibitory to cell-free protein synthesis but non-inhibitory to cell-free RNA synthesis. On the contrary, ME IV2-B was non-inhibitory to cell-free protein synthesis but inhibitory to cell-free RNA synthesis. ME IV2-C was non-inhibitory to cell-free protein synthesis and seemed to be somewhat inhibitory to cell-free RNA synthesis. Preliminary analyses of the components in these subfractions are also reported.

Animals

Amyloid in localized cutaneous amyloidosis: immunofluorescence studies with anti-keratin antiserum especially concerning the difference between systemic and localized cutaneous amyloidosis.

Amyloid of localized cutaneous amyloidosis and systemic amyloidosis were subjected to study with an indirect immunofluorescence technique using anti-keratin antiserum. Anti-keratin antiserum was prepared ad modum Sun & Green. Amyloid of localized cutaneous amyloidosis was positively stained for the antiserum, whereas amyloid of systemic amyloidosis (primary and multiple myeloma-associated) was negative. There was no difference between primary localized cutaneous amyloidosis (lichen amyloidosus and macular amyloidosis) and secondary localized cutaneous amyloidosis (amyloidosis associated with skin tumor). These results indicate that amyloid of localized cutaneous amyloidosis contains components derived from epidermal fibrous protein, probably tonofilaments of keratinocytes.

Amyloid

Quantitative autoradiographic studies in RNA and protein synthesis of dyskeratotic cells in morbus Darier.

Dyskeratotic cells in morbus Darier demonstrate various fine structures indicating that the keratinization process has proceeded to a certain extent in these cells; that is, there are Odland bodies, a marginal thickening, and keratohyalin granules. Thus, acantholytic cells in the lower epidermis are supposed to perform an incomplete and premature keratinization, and eventually transform to corps ronds and grains. The biosynthesis of RNA and proteins in these dyskeratotic cells was studied by electron microscopic autoradiography after in vitro incubation. Biopsy specimens taken from typical lesions of 3 patients with morbus Darier were incubated in one of the following media for 1-2 hours at 37 degrees C in air containing 5% CO2: (1) Earle's MEM containing 200 muCi/ml of [3H]uridine; (2) Earle's balanced salt solution containing 200 muCi/ml of [3H]leucine or 200 muCi/ml of [3H]histidine. After pulse labeling of [3H]-leucine or [3H]histidine, some specimens were fixed, dehydrated, embedded in Epon, and then prepared for electron microscopic autoradiography. These 3 labeled precursors were incorporated into early acantholytic cells in the base and wall of lacunae, but they did not accumulate in completely isolated acantholytic and dyskeratotic cells including corps ronds and grains. The nuclei of corps ronds in an early stage occasionally took up uridine. The accumulation of [3H]histidine was most remarkable in the granular cells which were not dyskeratotic, and silver grains showed a strong tendency to accumulate over keratohyalin granules by 3-6 hours of chase. [3H]histidine did not incorporate in dyskeratotic cells, even though they possessed a large number of keratohyalin granules. From these findings it seems difficult to assume that these acantholytic cells keratinize themselves further by synthesizing their structural proteins under the control of the RNA system during their upward movement. On the contrary, it appears more likely that most dyskeratotic cells result from neighboring cells which have already keratinized to some extent.

Autoradiography

Immunofluorescence studies on cutaneous amyloidosis with anti-keratin antibody.

Skin specimens obtained from two cases of primary localized cutaneous amyloidosis (PLCA) were subjected to study with an indirect immunofluorescence technique using anti-keratin antibody. Distinct fluorescence was observed in stratum corneum, and in spinous and basal cells of the epidermis and also in amyloid masses located in the upper dermis. These results appear to indicate that keratinous protein is one of the constituents of amyloid masses of cutaneous amyloidosis.

Amyloidosis