Shigeo Nishiyama

Inhibitory effect of magnesium l-ascorbyl-2-phosphate (VC-PMG) on melanogenesis in vitro and in vivo

BACKGROUND An inhibitory effect of ascorbic acid (AsA) on melanogenesis has been described. However, AsA is quickly oxidized and decomposed in aqueous solution and thus is not generally useful as a depigmenting agent. OBJECTIVE Our purpose was to examine the effect on pigmentation of magnesium-L-ascorbyl-2-phosphate (VC-PMG), a stable derivative of AsA. METHODS Percutaneous absorption of VC-PMG was examined in dermatomed human skin, and its effect on melanin production by mammalian tyrosinase and human melanoma cells in culture was also measured. A 10% VC-PMG cream was applied to the patients. RESULTS VC-PMG suppressed melanin formation by tyrosinase and melanoma cells. In situ experiments demonstrated that VC-PMG cream was absorbed into the epidermis and that 1.6% remained 48 hours after application. The lightening effect was significant in 19 of 34 patients with chloasma or senile freckles and in 3 of 25 patients with normal skin. CONCLUSION VC-PMG is effective in reducing skin hyperpigmentation in some patients.

Annular erythema: A possible association with primary Sjögren's syndrome

In four patients with primary Sjögrens syndrome a distinct annular erythema developed, which was characterized by a wide, elevated border (which can be likened to a doughnut ring) and central pallor. Histologically, there was a coat sleeve-like infiltration of lymphocytes around blood vessels and nuclear debris in the connective tissue. Vasculitis or epidermal changes suggestive of lupus erythematosus were not observed, and there was no immunoglobulin deposition along the basement membrane zone. This annular erythema may be a cutaneous manifestation of Sjögrens syndrome.

Clinical and Histopathologic Analysis of the Relationship between Lichen Planus and Chronic Hepatitis C

A prospective clinical investigation of 45 patients with lichen planus (LP) demonstrated a significant association between LP and chronic hepatitis C. Anti‐hepatitis C virus (HCV) antibodies were found in 17 (37.8%) of the 45 LP patients. This was significantly higher than in the controls. This higher prevalence of anti‐HCV antibodies was found equally in both male and female patients in the three types of LP; cutaneous only type, mucous only type, and both cutaneous and mucous type. Most of the patients with positive anti‐HCV antibodies had abnormal values of transaminase enzymes and/or a past history of chronic hepatitis. Histological and immunohistological investigations of three cases with LP and chronic hepatitis C demonstrated some morphologic similarities between these two diseases. Histopathologic findings of both LP and chronic hepatitis C were based on a T lymphocytic infiltrate with keratinocyte or hepatocyte damage. The degrees of infiltrating cells positive to UCHL‐1, MX‐panB, Leu‐7, and human leukocyte antigen (HLA)‐DR antibodies in the chronic hepatitis C lesions seemed to be similar to those in the LP lesions. These results may support a possible relationship between LP and chronic hepatitis C and the hypothesis that LP may be associated with chronic liver diseases as a result of a cytotoxic attack on the hepatocytes.

In situ expression of messenger RNA of interleukin-1 and interleukin-6 in psoriasis: interleukin-6 involved in formation of psoriatic lesions

SummaryPsoriasis is a disease of abnormal proliferation and differentiation of epidermal cells. Several cytokines released by keratinocytes are implicated as factors responsible for this pathological condition of the epidermis. In order to elucidate the role of these cytokines in psoriasis, messenger RNA (mRNA) expression of interleukin-1 (IL-1) and IL-6 in psoriatic epidermis was investigated using biotin-labelled complementary DNA (cDNA) of the cytokines. Messenger RNA of IL-1α was weakly detected in some normal healthy epidermis specimens and more strongly in all the perilesional uninvolved psoriatic epidermis specimens. It was also expressed in the transitional zone between uninvolved and fully developed psoriatic skin, but was not expressed in lesional skin. In contrast, IL-6 mRNA was rarely expressed in normal healthy epidermis, but was expressed in perilesional uninvolved psoriatic epidermis, in the transitional zone and in the fully developed lesional epidermis, with the maximum intensity in the transitional zone. Expression of mRNA of IL-6 receptor showed a similar tendency to that of IL-6. It was expressed in psoriatic epidermis, most strongly in the transitional zone, but not in normal healthy epidermis. IL-6 was demonstrated immunohistochemically in psoriatic epidermis, but IL-6 receptor was demonstrated only in the transitional zone. Thus IL-6 and its receptor expression correlated well with the formation of psoriatic lesions where IL-1 may initiate their expression. IL-6 may play an important role in the pathogenesis of psoriasis.

Establishment of a human hemangiosarcoma cell line (ISO-HAS)

A cell line (ISO‐HAS) has been established from tumor tissue of a human hemangiosarcoma arising on the scalp by the use of conditioned medium from a murine‐phenotypic angiosarcoma cell line (ISOS‐1). Cells have been cultured for more than 2 years with up to 100 passages. The cells retained endothelial‐cell properties, such as a characteristic cobblestone appearance at confluency, contact‐inhibited growth, active uptake of acetylated low‐density lipoprotein labeled with 1,1‐dioctadecyl 1,3,3,3,3‐tetramethyl‐indocarbocyanine perchlorate (Dil‐Ac‐LDL) and CD31 expression. However, they were weakly positive for von‐Willebrand‐factor (vWf) antigen and for binding of Ulex europaeus agglutinin‐I (UEA‐1) lectin, and lacked tube‐formation activity. These findings indicate that ISO‐HAS is a poorly differentiated endothelial cell line. ISO‐HAS cells showed accumulation of p53 protein in the nuclei, and a new‐typed p53‐gene point mutation was found in exon 7 at codon 240. When inoculated s.c. into severe‐combined‐immunodeficiency (SCID) mice, the cells showed solid‐tumor growth that caused death. These properties suggest that ISO‐HAS is a malignant endothelial cell line with high tumorigenicity. Int. J. Cancer 81: 305–308, 1999.

Annular erythema : a comparative study of Sjögren syndrome with subacute cutaneous lupus erythematosus

Abstract: Annular erythema developed in 22 patients with Sjögren syndrome. Clinically, the annular erythema was subdivided into three forms: Sweet disease‐like annular erythema with an elevated border (14 cases): subacute cutaneous lupus erythematosus (SCLE)‐like marginally scaled erythema (5 cases): and papular erythema (3 cases). Histopathologically, features commonly seen in annular erythema are deep perivascular and/or periappendageal infiltration of the lymphocytes with an admixture of neutrophils or plasma cells and less frequent epidermal changes suggestive of cutaneous lupus erythematosus. Immunoglobulin or complement deposition along the dermoepidermal junction of lesional skin was observed in 8 of 18 cases, and most of the dermal infiltrates consisted of CD4(+), 4B4(+) cells. The appearance of anti‐SS‐A(Ro) (100%) and anti‐SS‐B(La) (77%) was significantly higher in patients with annular erythema. These results suggest that patients with Sjögren syndrome might have a distinct annular erythematous lesion that is both clinically and histopathologically different from SCLE, although dose immunologic abnormalities exist in these two diseases.

Significance of Elevated Serum LDH (Lactate Dehydrogenase) Activity in Atopic Dermatitis

Serum lactate dehydrogenase activity (LDH) was elevated in most cases with the severe type of atopic dermatitis (AD). We examined whether LDH correlated specifically with the clinical courses and the severity of AD skin eruptions. Blood eosinophil numbers (Eo), LDH and its isoenzymes, and serum IgE (IgE) levels in eighty patients with AD were measured before and after treatment.

Bowen's Disease: Statistical Study of a 10 Year Period

According to histological records, a total of 74 patients were diagnosed with Bowens disease (B.d.) between 1 January 1984 and 31 December 1993 at the Department of Dermatology of Kitasato University. There was slight female predominance (36 ♂, 38 ♀), and 73% of the patients were older than 60 years; the mean age was 66.8 years. Fifteen patients had multiple (two‐five) lesions. In 13 patients, other benign skin lesions were also found. Arsenic exposure as etiologic factor could have been present in 2 cases. Only 3 patients had other associated malignant tumors, which does not confirm the paraneoplastic nature of B.d. One‐fifth of the lesions were on sun‐exposed areas (head, neck and hands). Although we excluded invasive carcinomas from our statistical study, we mention the 8 invasive carcinomas developing from B.d. in that period. Histopathological classification of B.d. is uncommon. Classifying our cases by Dariers histopathological classification, 63.3% of them belonged to the lenticular type. The malignant potential of different histopathological types of B.d. needs further investigation.

Drug‐induced Chronic Pigmented Purpura

A close correlation between purpuric reaction and drugs was observed in seven cases of chronic pigmented purpura. The patients developed purpuric lesions after taking certain drugs for more than 3 years, were thiamine propyldisulfide in 2 cases, and chlordiazepoxide in 1 case. The purpuric lesions stopped recurring after removal of the drugs in the rest of the cases. It is suggested that drugs are among the etiological factors in chronic pigmented purpura.

Membrane attack complex of complement in Henoch-Schönlein purpura skin and nephritis

SummaryThe present study using direct immunofluorescence with monoclonal antibodies to C5b-9 complex-related antigens was undertaken to determine whether complement activation in Henoch-Schönlein purpura (HSP) causes assembly of the membrane attack complex of complement (MAC) in skin and nephritis lesions. The deposition of C5, C6, C7, C8, C9, and C5b-9 neoantigens was noted in the vascular walls of papillary dermis and/or subpapillary dermal plexus of the vessels in 11 out of 15 patients with HSP. Their presence in vessel walls indicates complement activation which leads to terminal complement activation. There were small deposits of S protein at the same sites in three of the 11 skin specimens. Thus, the majority of C5b-9 demonstrated in HSP skin was the cytolytically active C5b-9 complex, MAC. Granular deposits of C5b-9 related antigens without S protein were also found in the capillary walls and mesangium of the glomeruli of two out of four specimens from patients with HSP nephritis; in the other two S protein was colocalized with the deposition of C5b-9. The results of the present study indicate that complement activation leading to generation of MAC may possibly be involved in the pathogenesis of vascular injury in a significantly large number of skin lesions and of HSP nephritis.