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SummaryThe correlation between the amount of lipid peroxide and squalene in skin surface lipid was observed by statistical analysis. To investigate the mechanism of skin surface lipid peroxidation, es

Lipid peroxide in human skin surface lipids was investigated. The correlation between the amount of lipid peroxide and the total amount of lipids in skin surface lipids was determined by statistical analysis. Furthermore, the correlation between lipid peroxide and squalene in skin surface lipids was also proved. These results suggest that the major source of lipid peroxide in skin surface is squalene, and that lipid peroxidation is enhanced by external factors such as ultraviolet light irradiation.

Patients with pemphigus vulgaris (PV) have circulating anti-desmoglein (Dsg) 3 immunoglobulin G (IgG) autoantibodies that induce blister formation. We developed an in vitro quantitative assay to evaluate the pathogenic strength of anti-Dsg3 IgG autoantibodies in blister formation. To obtain intercellular adhesion mediated dominantly by Dsg3, we used primary cultured normal human keratinocytes expressing low level of Dsg2 in the presence of exfoliative toxin A that specifically digests Dsg1. After incubation with various antibodies, monolayers released by dispase were subjected to mechanical stress by pipetting, and the number of cell fragments were counted. When anti-Dsg3 monoclonal antibodies (mAb) obtained from pemphigus model mice were tested, pathogenic AK23 mAb yielded significantly higher number of cell fragments than AK7 or AK20 non-pathogenic mAb. Dissociation scores, defined with AK23 mAb as the positive control, were significantly higher with active stage PV sera (n=10, 77.4 ± 21.4) than controls (n=11, 16.0 ± 9.6; p=0.003). When pair sera obtained from 6 PV patients in active stage and in remission were compared, the dissociation scores reflected well the disease activity as those in active stage were four to 17 times higher than those in remission. When sera from different patients showing similar ELISA scores but different clinical severity were tested (n=6), the dissociation scores with sera from severe disease activity were significantly higher than those with sera in remission. These findings indicate that this dissociation assay will provide a simple and objective biological method to measure the pathogenic strength of pemphigus autoantibodies.

アトピコオイルローションは，精製ツバキ油を配合した無香料，無着色の乳液タイプの全身用保湿製剤である。乾燥性皮膚疾患患者26例を対象とした4週間にわたる臨床試験を行い，その安全性と有用性の検討を行った。最終観察日に観察した乾燥，鱗屑，潮紅，毛孔性角化，そう痒の皮膚症状は，使用前と比較して有意な改善が認められた(p＜0.01)。有用性は，極めて有用が38.5％，有用以上が100.0％であった。全ての症例に副作用は無く安全に使用できた。また，使用感については，しっとり感があり，のびがよく，使い心地のよい製剤であることが確認された。96.2％が継続使用を希望した。以上のことより，アトピコオイルローションは，乾燥性皮膚疾患患者の日常のスキンケア剤として，安全かつ有用に使用できる保湿剤であると考えられた。

Keratin 10 (K10) is known to be tightly bound to the cornified cell envelope (CCE) and this binding is thought to play an important role in enhancing the structural integrity of the cornified cells. Bullous congenital ichthyosiform erythroderma (BCIE) is a genetic disorder of keratinization caused by gene mutations in the conserved sequences of keratin 1 (K1) or K10, which leads to abnormal suprabasal keratin network assembly. In BCIE patients' skin, the keratin network abnormalities make the upper spinous and granular keratinocytes fragile and result in blister formation. However, the exact pathomechanism of the hyperkeratosis seen in BCIE is still unknown. The involvement of the CCE in the pathomechanism of hyperkeratosis in BCIE is controversial. Abnormal CCE assembly may cause hyperkeratosis as reported in cases of lamellar ichthyosis. Binding of K10 to CCE is thought to be a vital connection between the suprabasal keratin filament network and CCE. We hypothesize that abnormal suprabasal keratin assembly caused by either K1 or K10 mutations can disrupt CCE formation, resulting in the hyperkeratosis observed in BCIE. To clarify whether K10 and keratin network defects affect CCE formation in vivo, the ultrastructural and immunohistological features of CCE were studied in the epidermis of two Japanese BCIE patients from two independent families carrying an identical missense mutation M150T in the helix initiation motif of K10. Ultrastructurally, a 15-nm-thick, dense, normal-appearing CCE was formed at the cell periphery of the keratinized epidermal cells. Light and electron microscopic immunolabeling revealed that the major CCE precursor proteins, involucrin and loricrin, were normally distributed and restricted to CCE of the epidermis. Immunofluorescent labeling showed that epidermal TGases, TGase 1, TGase 2 and TGase 3, were expressed normally in the epidermis. These findings suggest that a normal CCE is formed during the process of human epidermal keratinization, even if the suprabasal keratin filament network is disrupted as with this particular K10 mutation, M150T in BCIE.

Background: While squamous cell carcinoma and pseudocarcinomatous hyperplasia have been documented as pre-existing lesions in cases of reactive eccrine syringofibroadenoma (ESFA), to the best of our knowledge carcinoma occurring in a solitary ESFA has not yet been reported. We present one such case in a 91-year-old female who had a dome-shaped, reddish tumor on the extensor side of the left forearm. Methods: We review the histopathological, immunophenotypical and ultrastructural findings of this tumor, including the keratin expression profile. Results: Histopathologically, long, branching, anastomosing, thin and thick strands of small cuboidal epithelial cells were extending from the surface epidermis into the dermis. In the center of the tumor, there were irregular-shaped nests of atypical tumor cells invading downward into the dermis. Ultrastructurally, duct-like lumina lined with cuboidal tumor cells were present in the epithelial cords. From these findings, the present case was diagnosed as solitary eccrine syringofibroadenocarcinoma (ESFAC). Keratin expression studies revealed that cells of the thick strands, except for the luminal and basal cells, were positive for differentiation-specific keratins, keratins 1 and 10, and that cells of the thin strands were positive for keratins 5 and 14. Conclusions: Histopathological, immunophenotypical and ultrastructural evidence, as well as the pattern of keratin expression, suggest differentiation of the present malignant tumor towards the eccrine dermal duct. This case is the first reported case of ESFAC as far as we know.

We describe a case of photosensitivity due to pyridoxine hydrochloride (vitamin B6) in a heterozygote of hypophosphatasia. Photopatch tests using pyridoxine hydrochloride and pyridoxal 5′-phosphate, compounds referred to as vitamin B6, with ultraviolet light A irradiation were positive. Laboratory examination showed low serum alkaline phosphatase. Tissue-nonspecific alkaline phosphatase exon amplification from DNA of the patient’s lymphocytes detected deletion 1154–1156 hypophosphatasia mutation, indicating that this patient was diagnosed to be a heterozygote of hypophosphatasia. The seric pyridoxal 5′-phosphate level of this patient with hypophosphatasia was higher than in normals. Furthermore, after oral administration of vitamin B6 this level increased greatly and long-lastingly, and this might be related to the low level of alkaline phosphatase in this patient. Photosensitivity in this patient may have been caused by abnormal metabolism of vitamin B6 under the hypophosphatic condition.

To elucidate photosensitization potentials of new quinolone antibacterial agents, production of active oxygen species and peroxidation of squalene after ultraviolet A exposure were investigated. Production of singlet oxygen and/or hydrogen peroxide was estimated by bleaching of p-nitroso-N, N-dimethylaniline. Lomefloxacin showed the greatest ability to produce active oxygen species, and this ability was reduced by the addition of the singlet oxygen quencher sodium azide. Ciprofloxacin and fleroxacin also had strong activity. Photosensitized peroxidation of squalene was evaluated by measurement of thiobarbituric acid-reactive substances. Lomefloxacin was the strongest sensitizer, followed by fleroxacin and ciprofloxacin. These results suggest that certain new quinolones are involved in phototoxicity via the mechanism of active oxygen species.

40歳の女性, 主婦。初診の約1年前, 左乳房下の腫瘍に気付く。次第に増大したため来院した。腫瘍の生検像より乳癌の皮膚転移と診断したが, 触診では原発腫瘍は触れず, マンモグラフィーでも原発腫瘍は認めなかった。超音波検査で辺縁不整な低エコーの原発と思われる腫瘍像を発見, 組織学的に乳癌と確定診断した。精査の結果, 乳癌は左腋窩リンパ節に転移していた。

46歳,男性.初診の約20年前から右足関節外果の小さい皮下腫瘤に気づいていた.自覚症状がないため放置していたが,腫瘤が急激に増大したため受診した.腫瘤は,直径2×1.5cmの淡紅色,軽度隆起した硬い皮下腫瘤で,一部に面靤様皮疹を認めた.組織学的検査では,真皮にPAS,Grocott染色に陽性のセメント様物質を中心とした肉芽腫性病巣が散在していた.生検時に排出された多数の黒色顆粒と組織片をサブロー培地で培養したところ,それらのいずれからも黒色の真菌集落を得た.菌の特徴は,1) 組織内顆粒は直径1mm大の黒色で硬い,2) 分離菌の集落の表面は灰褐色,短絨毛状,裏面は黒色,3) 培地への色素拡散は殆どない,4) 分生子は容易に産生されず,5)発育に温度依存がある,室温(約27℃),30℃の順に発育は良好,37℃では発育せず,であった.以上の結果とexoantigen test1)より,Madurella griseaと同定した.病変部は全摘術にて完治した.本症例は,本邦での同菌種による足菌腫の第1例である.

医薬品として使用されているフェノチアジン誘導体には,長波長紫外線を吸収してヒト皮膚に光線過敏症を誘起するものがある.10位に3-dimethylaminopropyl基をもつクロルプロマジンおよび3-qUinuclidinylmethyl基をもつメキタジンによる皮表脂質スクアレンの光増感酸化反応を調べ,この反応は一重項酸素が関与するTypeII反応であることを明らかにした.両薬剤による不飽和脂質の光増感酸化反応と一重項酸素生成の量子収率に対する溶媒依存性を比較検討した.生体内で起こる光増感反応を生体外でシミュレートするには,反応基質や光増感剤をとりまくミクロな環境を十分に考慮する必要があることを明らかにした.

Human red blood cells (RBCs) were lysed by in vitro irradiation in the presence of the antifungal drug griseofulvin (GF). Effects of UVA fluence and GF concentration on photohaemolysis were examined under aerobic conditions. The photohaemolysis occurred at much lower fluence than that necessary for oxidation of the membrane lipids. UVA-irradiated solution of GF did not cause haemolysis. The photohaemolysis was colloid osmotic in nature because it was preceded by K+ leakage from the cells and was delayed in the presence of 30 mM sucrose in the medium. Even under anaerobic conditions, RBCs were lysed by irradiation with higher fluence than that required for aerobic photohaemolysis. Therefore, some phototoxic mechanism other than photosensitized oxidation is also involved in the photohaemolysis.

The mechanism and active species of drug-induced photosensitive reactions were investigated by measuring the absorption spectra of the transient species on photoexcitation as well as by determining the efficiency of singlet oxygen production on quenching by oxygen of the excited state of drugs. The quantum yields of singlet oxygen production were determined for chlorpromazine hydrochloride, mequitazine, and afloqualone as 0.27, 0.28, and 0.14, respectively. These rather high yields of singlet oxygen suggest its important role in photosensitivity of the drugs. On the basis of the transient-spectroscopic investigations the quenching mechanism of excited-state drugs by oxygen was discussed.

Causative gene defects have not been demonstrated in the majority of nonbullous congenital ichthyosiform erythroderma (NBCIE) cases. The purpose of this study was to further elucidate the pathogenesis of NBCIE. Immunohistochemical and ultrastructural observations, transglutaminase activity assays and sequencing of TGM1 were performed in five patients from four NBCIE families. Transglutaminase 1 (TGase 1), involucrin and loricrin expression and in situ transglutaminase activity were present in all of the cases. Ultrastructurally, two cases out of five showed incomplete thickening of the cornified cell envelope (CCE) during keratinization and the other three exhibited abnormal lipid droplets in the cornified cells and malformed lamellar granules. No TGM1 mutation was found in any of the four families by direct sequence analysis. NBCIE cases with normal TGase 1 seemed to have two distinct patterns of abnormality, one with abnormal lipid droplets and malformed lamellar granules and the other with defective CCE formation.

We report here a case of Bowen's disease that developed in the periungual area of the left ring finger of a 55-year-old Japanese male. Because the histology of the lesion mimicked in part the features of a common wart, a PCR-based analysis of human papillomavirus (HPV) DNA and sequencing of viral DNA of PCR-amplified fragments were performed. The lesion contained HPV11 and 16 DNA, and HPV was suspected to play a role in the development of the lesion.

Oesophageal involvement of pemphigus vulgaris had been considered an exceptional event. However, our endoscopic study found oesophageal lesions in seven of eight (87.5%) patients with pemphigus vulgaris.

HLA alleles in generalized pustular psoriasis (GPP) were investigated to clarify the etiology and/or pathogenesis of this disease. Not only serological typing of HLA class I and II antigens but also genotyping of HLA class II alleles were carried out in twenty-six unrelated Japanese patients with GPP. These patients were classified according to their history of psoriasis vulgaris (PV). Serological typing revealed a significantly high incidence of HLA-Cw1 (Pc = 0.04) in the patients as compared with Japanese healthy controls. The frequency of HLA-B46 was particularly high in the patients with GPP and a previous history of PV. Genotyping of HLA class II alleles showed a highly significant increase in HLA-DQB1*0303 (Pc = 0.01) in the patients vs. the healthy controls. In particular, HLA-DQB1*0303 was significantly more frequent in the patients with no prior history of PV than in those with a history of PV. Analysis on linkage disequilibrium showed remarkably different patterns for HLA class II haplotypes between the patients and the healthy controls. Based on the comparative analysis among the amino acid sequences of the beta 1-domain of the HLA-DQB1*03 alleles, proline at residue 55 was suggested to be important as a common amino acid for determination of the susceptibility to GPP. These results revealed not only an association between the etiology and/or pathogenesis of GPP and HLA, but also different mechanisms of the immune response between the patients with GPP and PV.

Patients showing coexistent linear IgG and IgA deposition along the basement membrane zone on direct immunofluorescence have been described as either bullous pemphigoid, epidermolysis bullosa acquisita, linear IgA bullous dermatosis, or cicatricial pemphigoid, depending on the clinical features and laboratory findings. In the present report, we describe two cases showing atypical clinical features distinct from those of other known bullous diseases. No circulating antibodies were detected by indirect immunofluorescence of normal human skin. Indirect immunofluorescence of 1 M NaCl split skin revealed IgG and/or IgA antibodies reactive with the dermal side of the split. Immunoblotting of normal human epidermal and dermal extracts showed no apparent reactivity with known autoantigens. The results suggest that there may be a unique and distinct bullous disease with linear IgG and IgA deposition at the basement membrane zone.

Dry skin, atrophy, pigmentation and nail disorders are well known side effects of hemodialysis. A porphyria cutanea tarda-like syndrome 1 and Kyrle-like lesions 2 have also been observed. Porokeratosis has also beeen reported in some immunosuppressed patients. 3,4 We describe a case of porokeratosis localized to the flexor aspect of the left forearm near the site where hemodialysis was performed

— Fluorospectroscopic behavior of chlorpromazine, mequitazine, afloqualone and piroxicam, which are known to induce skin photosensitivity, was examined in both homogeneous solutions and human buccal mucosal cells. Each drug showed large Stokes' shifts and their fluorescence intensities increased in hydrophobic solvents. These results indicated that the drugs tested can be used as hydrophobic fluorescence probes. Fluorescence microscopic observations of buccal mucosal cells treated with these drugs showed that all the drugs, especially chlorpromazine and mequitazine, were distributed in intracellular membranous regions.

We would like to respond to theArchivesarticles by O'Connor et al 1 and Cribier et al. 2 O'Connor et al reported on the porphyrin abnormalities found in the acquired immunodeficiency syndrome and suggested that the contribution of the hepatitis C virus (HCV) to abnormal porphyrin excretion patterns were characteristic of porphyria cutanea tarda (PCT). In 1994, we analyzed the urinary excretion patterns of porphyrin derivatives in patients with HCV-induced liver disease and HCV carriers using high-performance liquid chromatography. 3 The levels of urinary porphyrins of 63 HCV-positive patients who had liver diseases (including acute hepatitis, chronic hepatitis, liver cirrhosis, and hepatoma), 37 HCV carriers, and 32 healthy volunteers are summarized in the Table. The levels of uroporphyrin were below the detection limit and a coproporphyrin-predominant excretion pattern was observed in all these groups. Only secondary coproporphyria was observed and no PCT-like excretion pattern was observed. To clarify the

— When a suspension of Escherichia coli was irradiated with near-UV light in the presence of chlorpromazine (at a concentration below a cytotoxic level), the cells were killed. Efficiency of the photodynamic killing was not influenced by the deficiency of the uvrA gene or the recA gene. Neither phenotypic reversion of E. coli Hs30R (arginine auxotroph) nor induction of lambda prophage in lysogenic bacteria was detected after this treatment.

Nineteen patients with psoriasis vulgaris underwent the 8 MOP-BLB therapy combined with steroid ODT. 1. Twenty-six psoriatic lesions were improved after one to seven exposures (average time is 3.8 exposures). Seventeen psoriatic lesions were completely healed after three to thirteen exposures (average time is 9.9 exposures). 2. After psoriatic lesions were moderately improved by only steroid ODT, the 8 MOP-BLB therapy combined with steroid ODT was attempted. Seventeen psoriatic lesions were improved after two to three exposures (average time is 2.5 exposures). Eleven psoriatic lesions were completely healed after five to ten exposures (average time is 7.3 exposures). 3. Relapses of the lesions which had completely healed have not been observed until at this moment for three months.

Skin surface is covered with very thin lipid film called as skin surface lipids. Skin surface lipids are the mixture of sebum originated from sebaceous gland and epidermal lipids. Epidermal lipid is the minor component of skin surface lipids and occupies less than 5 % of skin surface lipids. However, the epidermal lipids, especially ceramide, play an important role in water barrier function of the skin.

A woman who had ingested honeybee royal jelly as a nutrient, showed an exacerbation of dermatitis when it was applied to her feet. A topical fungicide also aggravated her skin lesions. Patch testing showed positive reactions to the royal jelly, pyrrolnitrin in the fungicide and urushiol. Positive reactions to the royal jelly were found in 2 out of 10 controls, 1 of whom was sensitive to propolis.

— Both DNA bacteriophage and RNA bacteriophage were inactivated when they were irradiated with near-UV light (black light) in the presence of chlorpromazine. The far-UV sensitive mutants of T4D, i.e. T4Dv, T4Dpx and T4Dy, were no more sensitive to near-UV light plus chlorpromazine than the wild type. Electron microscopic observations showed that adsorption of T4D was greatly influenced by the treatment. The present results may indicate that the inactivation of T4D is due to the loss of adsorption caused by impairment in the tail or the tail fiber protein rather than the inactivation of DNA.

— The relative photoinduced toxicity of five benzothiadiazine diuretics was assessed with respect to their potentiality to inactivate bacteriophage lambda by exposure to near-UV light in a semi-aqueous solution of 40% N,N-dimethylformamide. The results showed the following order for the toxicity on a quantum yield basis: penflutizide > trichlormethiazide > methichlothiazide > benzylhydrochlorothiazide > hydrochlorothiazide. Since the bacteriophage was inactivated even when mixed with preirradiated solutions of the diuretics, some photoproducts are responsible for the photoinduced toxicity of the diuretics. Although a lowered pH affected the infectivity, it was a minor factor.

Purine phosphoribosyltransferase activities in normal and experimental hyperkeratotic epidermis of guinea pig skin were demonstrated quantitatively by a new microassay method. The ratio of HGPRTase with hypoxanthine as a substrate to APRTase activity in normal and hyperkeratotic epidermis was found to be 0.94 and 0.60, respectively. The HGPRTase and APRTase activities expressed as μmoles per gram wet weight per min. were increased in experimental hyperkeratotic epidermis and it is suggested that the salvage pathway for purine nucleotide biosynthesis is activated in experimental hyperkeratotic epidermis. The pH optimum of these enzymes and their stability in the frozen state were also demonstrated.

Plasmid pBR 322 was subjected to UV-A irradiation in the presence of photosensitive drugs, i.e., phenothiazines [chlorpromazine hydrochloride (CPZ), promethazine hydrochloride (PMZ) and mequitazine (MQZ)], benzothiadiazines [penflutizide (PFZ), hydrochlorothiazide (HCT) and methyclothiazide (MCT)] and afloqualone (AQ). The distribution of the closed-circular and the open-circular form of the plasmid DNA was analyzed by means of neutral agarose gel electrophoresis. All the drugs used induced more or less DNA nicking to yield the open-circular form. The nicking activities of the phenothiazines were in the order: CPZ greater than PMZ greater than MQZ. CPZ elicited extensive degradation of the DNA by photosensitization. The nicking activities of the benzothiadiazines and AQ were much weaker than CPZ and PMZ.

Evidence is presented to show that in the skin of the neonatal rat, the enzyme adenylate kinase is associated with particles. We prepared a lysosomal fraction from neonatal rat skin and then further fractionated this material by the use of a density gradient which varied from 0–16% Ficoll and 0.88–1.4 M sucrose. Three bands were isolated which had acid phosphatase, β-glucuronidase and adenylate kinase activity. Each of these fractions was then resubjected to an expanded density gradient corresponding to the range in which it had previously sedimented. When equilibrium had been reached, the particles still exhibited acid phosphatase, β-glucuronidase and adenylate kinase activity. Repeatedly washed particles retained adenylate kinase activity.

A patient with phytosterolemia and type IIa hyperlipoproteinemia with tuberous xanthomas is described. The plant sterols, beta-sitosterol, campesterol, and stigmasterol, were identified in plasma and the xanthomas; to our knowledge, this is the first case of phytosterolemia and xanthomatosis in a Japanese.