Akira Ohkawara

A survey of psoriasis patients in Japan from 1982 to 2001

BACKGROUND The Japanese Society for Psoriasis Research has conducted an annual survey of psoriasis patients in Japan from 1982 to 2001. OBJECTIVE To perform the epidemiological study about a survey of psoriasis patients conducted in Japan for twenty years. METHODS A sample of 28628 cases was collected from 148 dermatology centers throughout Japan. The reports from each center were analyzed. RESULTS Males (65.8%) were predominant over females (34.2%) in number. The vast majority of cases (86.0%) had plaque-form of psoriasis vulgaris, and 812 cases (2.8%) showed guttate psoriasis. Psoriatic erythroderma (0.8%), generalized pustular psoriasis (0.9%), and localized pustular psoriasis (0.5%) were rare. Three hundred of the patients (1.0%) manifested psoriatic arthritis. Local corticosteroids (67.8%) were the most used modalities, whereas local vitamin D(3) preparations (2.4%) were rarely used. For photo-therapeutic treatments, topical (12.1%) and systemic (7.5%) PUVA were predominant over UVB therapy (0.5%). In systemic treatments, drugs from the herbal medicine was the first (14.2%), followed by etretinate (7.6%), nonsteroidal anti-inflammatory drugs (4.4%), oral corticosteroids (4.1%), methotrexate (2.8%), cyclosporine (1.6%), and anti-cancer drugs (1.4%). CONCLUSION This survey was the first epidemiological study throughout Japan.

HTLV-I-associated myelopathy in a patient with adult T-cell leukemia

Disseminated erythematous papules and plaques developed in a 60-year-old man 3 years before the appearance of neurologic manifestations. A biopsy specimen of the plaque revealed Pautriers microabscess and a dense mononuclear cell infiltration with atypical convoluted nuclei in the papillary dermis. These cells were helper/inducer T lymphocytes that expressed the interleukin 2 receptor. The patients white blood cell count was normal, but 1% atypical lymphocytes and a high titer of anti-human T-lymphotropic virus (HTLV)-I antibody were detected in his serum. A smoldering type of adult T-cell leukemia was diagnosed. While he was being treated with PUVA, a gait disturbance developed. A high titer of anti-HTLV-I antibody, characteristic of HTLV-I-associated myelopathy, was demonstrated in his cerebrospinal fluid.

Glucocorticoid-induced alteration of beta-adrenergic adenylate cyclase response of epidermis.

SummaryIt has been reported that the beta-adrenergic adenylate cyclase system of the pig epidermis is regulated by glucocorticoids, resulting in the augmentation of epinephrine-induced cyclic-AMP accumulations. Using this phenomenon, we compared the glucocorticoidal potency of three typical glucocorticoids: hydrocortisone, prednisolone and dexamethasone. There was a considerable variation in the magnitude of the glucocorticoid-induced augmentation of the beta-adrenergic response when pig skin that had been obtained on different occasions was used. In each experimental series (using the same pig skin), however, the maximal augmentation effects obtained with these glucocorticoids were approximately the same. The potent glucocorticoid, dexamethasone, demonstrated its effect at lower concentrations than were required for prednisolone, while hydrocortisone required a much higher concentration before its effect was detectable. Thus, despite considerable variations in the magnitude of the glucocorticoid effects, the concentrations required for the glucocorticoid effect were closely associated with the established glucocorticoidal potency which has previously been described.

Topical PUVA treatment increases epidermal beta‐adrenergic adenylate cyclase responsiveness

The effects of topical PUVA treatment on the epidermal cyclic AMP system were investigated. 8‐methoxypsoralen (8‐MOP), 0.3% in ethanol was applied to the backs of pigs which were then irradiated with UVA. A significant increase in the epidermal beta‐adrenergic adenylate cyclase response was observed 24 h after low (1.1 J/cm2) and moderate (2.1 J/cm2) dose irradiation. There was no significant change in the adenosine‐ or histamine‐mediated adenylate cyclase responses. 8‐MOP application or UVA irradiation alone had no effect on the beta‐adrenergic adenylate cyclase response. PUVA treatment with a higher irradiation dose (4.2 J/cm2) produced no increase in the beta‐adrenergic response and adenosine‐ and histamine‐mediated adenylate cyclase responses were decreased. Cyclic AMP phosphodiesterase activity was decreased by PUVA treatments using UVA doses of 1.1 and 2.1 J/cm2; however, the change was not statistically significant. The increased beta‐adrenergic response was also observed in the presence of the cyclic AMP phosphodiesterase inhibitor, isobutylmethylxanthine. These results indicate that epidermal adenylate cyclase responsiveness is affected by topical PUVA treatment in vivo.

Analysis of psoriatic patients registered in Asahikawa Medical College Hospital from 1983 to 2007

Psoriasis is a chronic inflammatory skin disease, which has been increasing during the last 50 years in Japan. The aim of the present study is to analyze psoriatic patients registered from 1983–2007 in Asahikawa Medical College Hospital, which is located in the northern part of Japan. A total of 607 cases were registered at the first inspection in the Department of Dermatology, Asahikawa Medical College. Men (403 cases, 66.4%) were predominant over women (204 cases, 33.6%). The clinical types of psoriasis were psoriasis vulgaris (91.5%), guttate psoriasis (4.2%), psoriasis arthropathica (2.8%), psoriatic erythroderma (0.6%), generalized pustular psoriasis (0.6%), localized pustular psoriasis (0.15%) and infantile psoriasis (0.15%). Topical corticosteroids (78.1%) and vitamin D3 (18.1%) products were the main previous topical agents. Previous systemic treatments included etretinate (7.7%), cyclosporine (1.5%) and methotrexate (0.3%). Use of topical vitamin D3 and cyclosporine therapies have been gradually increasing during the past 25 years. Regarding the previous phototherapy, topical psoralen and ultraviolet A therapy (PUVA) (4.9%) was predominant over ultraviolet B (0.9%), and systemic PUVA (0.7%). Use of ultraviolet B phototherapy has been increasing during the past 5 years. The results are essentially similar to those of a survey of psoriasis in Japan from 1982–2001. Although the incidence of psoriasis might be higher in Hokkaido Prefecture, there is essentially no variation in the disease profile of psoriatic patients.

Pig-skin epidermal calmodulin: Effects of antagonists of calmodulin on DNA synthesis of pig-skin epidermis

SummaryAlthough epidermal keratinocytes contain significant amounts of calmodulin, the exact role of calmodulin in epidermal biological activity remains to be determined. Pig-skin (epidermal) calmodulin was purified to homogeneity by DEAE/Sepharose- and phenothiazine-affinity-column chromatography. The characteristics of the purified calmodulin proved to be in good agreement with those of calmodulin obtained from other sources. Phenothiazines (trifluoperazine and chlorpromazine), mepacrine, propranolol, and colchicine inhibited the effect of the purified epidermal calmodulin on the calmodulin-deficient phosphodiesterase of bovine heart. These calmodulin antagonists all had inhibitory effects on the thymidine incorporation of pig-skin epidermal keratinocytes. These observations support the assumption that calmodulin might play an important role in epidermal keratinocyte proliferation.

Modulation of pig epidermal adenylate-cyclase responses by protein-synthesis inhibitors: Its relation to glucocorticoid and colchicine effects

SummaryThe effects of protein-synthesis inhibitors (actinomycin D, puromycin, and cycloheximide) on epidermal adenylate-cyclase responses were investigated. When pig skin (epidermis) was incubated in RPMI-1640 medium, the β-adrenergic adenylatecyclase response (epinephrine-induced cyclic-AMP accumulations) decreased, whereas the adenosine and histamine responses increased after long-term (up to 48 h) incubation. The addition of actinomycin D or puromycin to the incubation medium resulted in a marked increase in epinephrine-induced cyclic-AMP accumulations and a decrease in adenosine- and histamine-induced cyclic-AMP accumulations. Cycloheximide had a weak effect on the epinephrine response, and had apparently stronger effects on the adenosine and histamine responses than actinomycin D or puromycin. Histologically, various degenerative changes of keratinocytes (with or without acantholytic changes) were observed after long-term incubation with these protein-synthesis inhibitors. Both low- and high-Kmcyclic-AMP phosphodiesterase activities were moderately decreased by the protein-synthesis inhibitors. However, augmentation effects on the β-adrenergic response were also observed in the presence of the cyclic-AMP phosphodiesterase inhibitor, theophylline. We have described previously similar augmentation effects on the β-adrenergic response caused by glucocorticoids and colchicine. Comparison of the effects of these chemicals with those of protein-synthesis inhibitors revealed that the most marked effects on the β-adrenergic response were produced by actinomycin D, puromycin and colchicine; glucocorticoid had a moderate effect (hydrocortisone), while cycloheximide had only a weak effect. Furthermore, the simultaneous addition of actinomycin D (or puromycin) and colchicine (or hydrocortisone) at their optimal concentrations produced a more marked (additive or synergistic) increase in the β-adrenergic response than the addition of each chemical alone. The simutaneous addition of actinomycin D and puromycin at their optimal concentrations resulted in neither an additive nor a synergistic effect. Our results indicate that, as well as being affected by glucocorticoids and colchicine, epidermal adenylatecyclase responses are affected by various protein-synthesis inhibitors, the mechanism of which seems to be independent of that of glucocorticoids or colchicine.

Human skin epidermal adenylate cyclase systems: defective beta-adrenergic responsiveness in the involved epidermis of Darier's disease.

It has been reported that pig skin epidermis contains at least four independent adenylate cyclase systems, i.e. 1) beta-adrenergic-, 2) histamine H2-, 3) adenosine and, 4) prostaglandin E-adenylate cyclase systems, resulting in the accumulation of cyclic AMP. Using human skin epidermis, we investigated the responses of adenylate cyclase to epinephrine, histamine, and adenosine. In normal human skin, all three agents increased cyclic AMP levels of the skin. The epinephrine effect was inhibited by a beta-adrenergic blocking agent, propranolol. The histamine effect was inhibited by a histamine H2 inhibitor, cimetidine. The adenosine effect was inhibited by theophylline. The effects of epinephrine and histamine were augmented by the addition of the cyclic AMP phosphodiesterase inhibitor, theophylline. Another phosphodiesterase inhibitor, papaverine, augmented the effects of all three agents. In contrast to pig skin epidermis, where histamine and adenosine-induced cyclic AMP accumulations were marked, in human skin, epinephrine-induced cyclic AMP accumulation was more marked than those induced by histamine and adenosine. Using the epidermis of Dariers disease, we also investigated the effects of epinephrine, histamine and adenosine on the cyclic AMP levels of the skin. The involved skin of Dariers disease was shown to be characterized by a defective beta-adrenergic responsiveness. These findings show that normal human skin possesses at least three independent adenylate cyclase systems (beta-adrenergic, histamine H2-, and adenosine-adenylate cyclase), as in pig skin epidermis, with a different responsiveness pattern to these stimulators. Our data also show that the responsiveness to each receptor-adenylate cyclase system may be modified in a pathological condition of epidermis such as in Dariers disease. The significance of decreased beta-adrenergic responsiveness in the involved skin in Dariers disease was discussed in relation to our previous finding of the same type of defect in the psoriatic-involved epidermis.

The action of topical vitamin A acid on normal epidermis and non-involved epidermis of psoriatics. A morphological and enzymatic study.

Topical application under occlusion of 0.1% Vitamin A Acid (VAA) in polyethylene glycol to the non‐involved skin of psoriatics and to the skin of normal controls resulted in keratolysis, acanthosis, glycogen accumulation, and increased enzyme activity, though the changes are more marked in the former. Those changes occurred during the first week of application and did not progress further, in fact continued application resulted in a biochemical return toward normal.

Erythema gyratum repens accompanied by essential thrombocythemia, followed by a blastic crisis.

Crisis Takahiro Kiyohara, Masanobu Kumakiri, Hitoshi Kobayashi, Mariko Mayuzumi and Akira Ohkawara Department of Dermatology, Fukui Medical University, 23 – 3 Shimoaizuki, Matsuoka-cho, Yoshida-gun, Fukui 910 – 1193, Japan, Department of Dermatology, Hokkaido University Graduate School of Medicine, N15 W7 Sapporo, JP-060-8638, Japan. E-mail: kiyo @ fmsrsa.fukui-med.ac.jp Accepted November 18, 2002.