Yoshiki Miyachi

Photoaging from an oxidative standpoint

The free radical theory proposes that photoaging, which is both qualitatively and quantitatively different from chronological aging, may result from imperfect protection against cumulative stress of free radicals produced by chronic and repeated ultraviolet irradiation. Since the skin is always in contact with oxygen and is occasionally exposed to ultraviolet light, skin is one of the best target organs of environmental photo-oxidative stress. A growing body of evidence suggests that reactive oxygen species are generated by ultraviolet irradiation resulting in the structural and functional alteration of cutaneous components which should affect the photoaging process over a long period. The age-related alteration of cutaneous antioxidant defense capacity against cumulative effects of continual photo-oxidative stress to the skin may also affect the photoaging. Thus the possible use of antioxidants that attenuate photo-oxidative toxicity is believed to be an important strategy modulating photoaging. Several antioxidants have readily been proved to work in the experimental conditions. This paper reviews photoaging from a photo-oxidative standpoint and discusses the possible regulation of photoaging by antioxidants that is an important issue in the photodermatological field.

Epidemiological Analysis of Prognosis of 496 Japanese Patients with Progressive Systemic Sclerosis (SSc)

For the first time, we performed an epidemiological study of SSc in Japan to study the factors influencing prognosis, survival rate and cause of death of Japanese SSc patients and to compare our data with those from foreign countries.

Morphological and biochemical analyses on fibroblasts and self-produced collagens in a novel three-dimensional culture

The addition of l‐ascorbic acid 2‐phosphate (Asc 2‐P). which is active and stable under a conventional culture condition. could render dermal fibroblasts to the organization of a dermislike structure on a plastic dish without any prior treatment. The cell layer was composed of multilayered fibroblasts surrounded by dense extracellular matrices. Confocal microscopic examination disclosed that the fibroblasts in the upper layer were spindle‐shaped and those in the lower layer were polygonal. Electron microscopic examination revealed the accumulation of mature collagen fibrils in the intercellular space. These morphological observations suggest that the cell layer may resemble the dermis‐like structure. Biochmical analyses revealed that the hydroxyproline content of the cell layer increased in a time‐dependent manner. while the monolayer culture system without Asc 2‐P yielded no measurable amount of hydroxyproline. On sodium dodecylsulphate‐polyacryl‐amide gel electrophoresis. neutral insoluble collagens extracted from the cell layer showed the identical electrophoretic pattern to those from the human dermis. In addition. these bands were completely digested by bacterial collagenase. This novel culture system could provide a simple tool with which to investigate the collagen metabolism by fibroblasts under more physiological conditions.

Time-dependent effect of chronic UV irradiation on superoxide dismutase and catalase activity in hairless mice skin.

Reactive oxygen species are produced by ultraviolet (UV) exposure and cause oxidative damage. Enzymic antioxidants such as superoxide dismutase (SOD) and catalase (CAT) may play important defensive roles in vivo. The previous studies have focused on the acute effects after single UV irradiation on those enzyme activities. In this study, we investigated the chronic effects of ultraviolet-A (UVA) or ultraviolet-B (UVB) exposure on the skin SOD and CAT activities using hairless mice. Accumulated doses of UVA and UVB after 36-week irradiation conducted 3 times a week were 3240 J/cm2 and 4320 mJ/cm2, respectively. SOD activity was increased by UVB irradiation and gradually returned to control levels, but was unaffected by UVA irradiation. In contrast, CAT activity was suppressed by UVA irradiation, indicating that the skin SOD and CAT activities are not coordinately regulated by long-term UV irradiation. These findings suggest that SOD activity is induced by repeated exposures to UVB in response to chronic photooxidative stress. However, continual cumulative stress may overwhelm the capacity of this system. These time-dependent changes of the cutaneous antioxidant system by chronic UV irradiation should provide us with important information on photooxidative events in cutaneous photoaging.

Perianal hidradenitis suppurativa: early surgical treatment gives good results in chronic or recurrent cases

Hidradenitis suppurativa (HS) represents a chronic, recurrent, deep‐seated folliculitis resulting in abscesses followed by the formation of sinus tracts and scarring. It is an uncommon disorder frequently involving the perianal region. We review the clinical and pathological features of 12 patients (10 men and two women) with perianal HS (PHS). The mean age at presentation was 43 years (range 24–65), and the mean duration of illness was 14 years (range 2–30). Two patients exhibited multiple areas of involvement, including the axilla and the nape of the neck, in addition to the perianal region. Histological examinations showed epidermis‐lined sinuses surrounded by dense plasma cell infiltration in four of nine specimens. The complications related with PHS included anal fistula (seven patients), diabetes mellitus (four), malignant tumour (two) and sepsis (one). Three patients died of the complications. Eight patients underwent wide local excision. The defects were managed with a meshed split‐thickness skin graft in five patients, and open treatment in the remainder. New lesions developed in untreated skin of two patients. However, no patient relapsed in the surgically treated sites. PHS is frequently complicated with anal fistula and is occasionally life‐threatening as a result of the occurrence of malignant tumours or sepsis. Early surgical excision followed by meshed split‐thickness skin graft can successfully cure the lesion without functional disturbance.

Measurement of skin elastic properties with a new suction device (I): Relationship to age, sex and the degree of obesity in normal individuals.

We measured skin elastic properties (distension ability, retraction ability, and the skin elasticity) of 4 different body sites, finger, hand, forearm, and chest, in 191 normal individuals by means of a new suction device and investigated the correlation of skin elastic properties with sex, site, age, and the degree of obesity. Neither sex nor the degree of obesity were correlated with skin elastic properties. The skin elastic property of the chest was significantly higher than those of the other three sites. Decrease in the skin elasticity of the hand, forearm and chest were associated with aging. This simple and non‐invasive device can provide an objective method for evaluating skin elastic property.

Antineutrophil cytoplasmic autoantibodies in patients with systemic sclerosis

Perinuclear type of antineutrophil cytoplasmic antibodies (p‐ANCA) have been found in patients with periarteritis nodosa. Churg‐Strauss arteritis. or pauci‐immune idiopathic crescentic glomerulonephritis. Recently, the association of p‐ANCA and normotensive renal failure, in patients with systemic sclerosis (SSc), was reported. We have studied the incidence of p‐ANCA in patients with SSc and have investigated its relationship to clinical and laboratory findings. Sera from 77 patients with SSc were examined by the indirect immunofluorescence (IIF) test, employing an ethanol‐fixed human neutrophil and enzyme‐linked immunosorbent assay, using purified myeloperoxidase (MPO) as an antigen (MPO‐ELISA). The sera from seven patients (9‐1%) were p‐ANCA positive, by both IIF and MPO‐ELISA. One patient died from systemic necrotizing angiitis but the remaining six patients have shown no symptoms of systemic vasculitis or of renal involvement. There was a tendency for patients positive for p‐ANCA (anti‐MPO antibody) to also be positive for other autoantibodies. such as anti‐Sc1‐70 antibody, anti‐centromere antibody, anti‐microsome antibody, anti‐thyroglobulin antibody and rheumatoid factor. Although the incidence of p‐ANCA (anti‐MPO antibody) is low in patients with SSc, and its clinical significance in SSc needs further investigations, this could be a serological marker for certain symptoms in SSc.

Membranocystic changes in the panniculitis of dermatomyositis

Summary Clinically apparent paniculatus is rare in dermatomyositis. The common histopathological landings are infiltration of lymphocytes, epithelioid cells and plasma cells in the fat lobules, along with varying degrees of fat degeneration and fibrosis. We report a 65‐year‐old woman with dermatomyositis who developed paniculatus with a characteristic histological change known as a membranocystic lesion. Although this change has been observed in various diseases affecting the subcutaneous fat tissue, it has rarely been reported in dermatomyositis. Dermatomyositis should be included in the diseases showing a membranocystic lesion.

Psoriasis vulgaris coexistent with epidermolysis bullosa acquisita

Summary Autoimmune bullous diseases, such as bullous pemphigoid or pemphigus vulgaris. occasionally develop in psoriatic patients. In addition, a novel subepidermal bullous disease with autoantibodies against a lower lamina lucida antigen of 200kDa has recently been reported in association with psoriasis. We describe here a patient with psoriasis vulgaris who developed epidermolysis bullosa acquisita (EBA). Direct immunofluorescence revealed linear deposition of IgCl and C3 at the basement membrane zone. The patients serum bound to the dermal side of salt‐split normal human skin. However, immnumohlol analysis demonstrated that the patients serum reacted with an EBA antigen of 290 kDa. EBA should be included in the list of autoimmune diseases associated with psoriasis vulgaris.

Disaccharide analysis of human skin glycosaminoglycans in sun-exposed and sun-protected skin of aged people

The total amount of main disaccharide units of skin glycosaminoglycans was compared between sun-exposed (n = 12) and sun-protected skin (n = 14) of aged people using high performance liquid chromatography after labeling with 1-phenyl-3-methyl-5-pyrazolone. The total amount of main disaccharide units in sun-exposed skin was comparable to sun-protected skin presumably due to the diversity of individuals. Consequently, we compared sun-exposed skin with sun-protected skin in identical individuals (n = 6). The total amount of main disaccharide units in sun-exposed skin was significantly greater than that in sun-protected skin (P < 0.05). In addition, the ratio of delta Di-HA (hyaluronic acid, HA)/delta Di-4S (dermatan sulfate, DS) in sun-exposed skin showed a decreasing trend as compared with sun-protected skin in four of six individuals. These results are in agreement with our previous results obtained in animal experiments of photoaging, i.e., hairless mouse skin exposed to repeated UV irradiation showed an increase in total amount of main disaccharide units and a decrease in the ratio of delta Di-HA(HA)/delta Di-4S(DS). We could confirm similar changes in skin glycosaminoglycans both in human and murine photoaging supporting the appropriate rationale for using the hairless mouse as an animal model for photoaging. Again, disaccharide analysis should provide a useful method to examine the biochemical changes of skin glycosaminoglycans in human photoaging.