Hironori Minami

A preliminary report of the treatment of blue nevus with dermal injection of riboflavin and exposure to near-ultraviolet/visible radiation (ribophototherapy).

Dye lasers are useful for treating pigmented skin lesions, but their equipment is expensive and bulky. A simple and cheap phototherapy would be acceptable to dermatologists for treating pigmented skin lesions such as nevus of Ota. We investigated as a pilot study whether dermal injection of riboflavin and exposure to near-ultraviolet/visible radiation (ribophototherapy) decreases the dermal pigment of blue nevi which are recalcitrant to laser therapy. The therapeutic efficacy was assessed by comparison of the amount of dermal pigment in hematoxylin-eosin specimens taken before and after treatment. Pigmentation of the nevus became faint to the depth of 1 mm with little noticeable epidermal change after 21 treatments. At the deeper dermis somewhere between 3 and 4 mm from the epidermis, ballooning degeneration of the dermal cells was observed in hematoxylin-eosin specimens. Ribophototherapy is hopeful for treating pigmented skin lesions.

Chronological difference in walking impairment among Japanese group A xeroderma pigmentosum (XP‐A) patients with various combinations of mutation sites

Almost all Japanese group A xeroderma pigmentosum (XP‐A) patients have nonsense and/or nonsense codon‐leading mutations in the XP group A (XPA) gene, and develop neurological abnormalities. Walking ability is one of the most important neuromuscular functions of the patients, because it determines their daily activities. We studied the correlation between the various combinations of mutations found by PCR‐RFLP in Japanese XP‐A patients and their chronological walking impairment. We classified these patients into six groups. Group I: A patient who was homozygous for the mutation at codon 116 in exon 3 (Type 1 mutation) could never walk unaided. Group III: Typical patients who were homozygous for the mutation at intron 3 (Type 2 mutation) could walk unaided till 7–16 years of age. Group V: Patients who were compound heterozygous for Type 2 mutation and for the mutation at codon 228 in exon 6 (Type 3 mutation) began to develop some walking difficulty at 5–13 years of age and became unable to walk at 25–28 years of age. Group VI: A patient who was homozygous for Type 3 mutation could walk unaided without any difficulty till the age of 21. The walking ability of group II and IV patients is not known yet.

Elevated plasma superoxide dismutase activity in patients with systemic sclerosis

Injury to vessel walls, especially microvascular damage due to free radicals, has been a focus of interest concerning the pathogenesis of systemic sclerosis. Excess reactive oxygen species may induce antioxidant defenses. We therefore measured plasma superoxide dismutase (SOD) activity in patients with systemic sclerosis and found average SOD activity of plasma in 16 patients with systemic sclerosis (5.00 +/- 3.10 U/ml) to be significantly (P < 0.001) higher than those in 89 healthy volunteers (1.56 +/- 0.234 U/ml). Patients with Raynauds phenomenon and/or skin sclerosis had particularly high SOD activity. These findings suggest that plasma SOD activity may serve as a useful parameter for assessment of sclerotic progression and the presence of Raynauds phenomenon.

Vitamin B6 phototoxicity induced by UVA radiation

Abstract We have previously reported that pyridoxine shows UVA-induced cytotoxicity. Four other vitamin B6 compounds (pyridoxal, pyridoxamine, pyridoxal phosphate, and pyridoxamine phosphate) are metabolically more important in vivo than pyridoxine. These compounds were examined for UVA phototoxicity to cultured human fibroblasts. The cytotoxicity was measured by post-UVA irradiation colony-forming ability. All the B6 compounds except pyridoxal phosphate showed cytotoxicity. Pyridoxamine phosphate, which is the most important form of vitamin B6 in vivo, had the strongest cytotoxic effect. To examine the involvement of reactive oxygen species in the phototoxicity, we performed an electron spin resonance study using the spin trapping agent, 5,5-dimethyl-1-pyrroline N -oxide, and diethylenetriaminepentaacetic acid. We failed to detect radicals derived from vitamin B6. The cytotoxic effect remained in UVA-irradiated solutions for at least 30 min after the end of UVA irradiation. Hydrogen peroxide was produced in the solution, but the amount was not enough to cause cytotoxicity. In addition, the cells from xeroderma pigmentosum patients who belong to group A or C showed survival curves similar to those of normal fibroblasts. This suggests that cyclobutane pyrimidine dimers or 6-4 photoproducts of DNA were not involved in this damage. These findings suggest that UVA-induced vitamin B6 cytotoxicity is caused by toxic photoproducts resulting from irradiated vitamin B6.

Severe neurological abnormalities associated with a mutation in the zinc-finger domain in a group A xeroderma pigmentosum patient

All the reported Japanese patients with group A xeroderma pigmentosum (XP) have two or three mutations at codon 116 in exon 3, codon 228 in exon 6, and the splicing acceptor site of intron 3 of XP group A complementing (XPAC) gene. A homozygote (XP390S) with a nonsense mutation at codon 228 has less severe neurological abnormalities than patients with the splicing mutation at the acceptor site of intron 3. As homozygotes for the nonsense mutation at codon 116, which truncates a carboxyl‐terminal site of XPAC protein at an early part of its zinc‐finger domain, have not been reported previously, the possible severity of associated neurological abnormalities was not known. We report a group A XP patient, XP180S, who had neurological abnormalities which were more severe than those in patients homozygous for the splicing mutation. The polymerase chain reaction product from exon 3 of the patients XPAC gene was digested completely into three fragments by MseI restriction endonuclease. Thus, the patient was homozygous for the mutation at codon 116.