Hiroko Miyauchi

Phototoxicity and photoallergenicity of quinolones in guinea pigs

Clinical reports indicate that the fluoroquinolone group of antibiotics can induce cutaneous photosensitivity reactions. In the present study, phototoxicity and photoallergenicity of quinolones including nalidixic acid (NA) norfloxacin (NFLX), ofloxacin (OFLX), enoxacin (ENX), ciprofloxacin (CPFX), lomefloxacin (LFLX), and tosufloxacin (TFLX) were experimentally examined in an in vivo system using the guinea pig. Phototoxicity of all quinolones tested was demonstrated after a single, oral administration of the drugs and subsequent exposure to long-wave ultraviolet (UVA) at a dose of 30 J/cm2. The phototoxic potencies were: ENX, LFLX > OFLX > NA, TFLX > NFLX, CPFX. Photoallergic reaction was also induced to LFLX and NA by pretreatment with cyclophosphamide, an immunoadjuvant. No cross-reactions in photoallergy were observed among quinolones. The photo-ingestion test was positive in photoallergically sensitized animals, while the photopatch test was negative. This is the first report which demonstrated experimentally the photoallergenicity of quinolones. Clinical features of the photosensitivity due to quinolones can be explained by the results of the present experiments.

The effect of ultraviolet (UVB and PUVA) radiation on the expression of epidermal keratins

Using a panel of monoclonal antibodies directed against keratins (PKK2. CK8.12 and KL1). the effects of ultraviolet B (UVB) and psoralen plus ultraviolet A (PUVA) irradiation on keratin expression in guinea‐pig skin were examined immunohistoehemically. Following irradiation, whether by UVB or PUVA, rapid alterations in the distribution pattern of keratins were observed in the epidermis. The alterations included the induction of basal cell‐type keratins (PKK2 and CK8.12 staining) in the suprabasal layers, with concomitant reduction ofthe suprabasal‐type keratins (KL1 staining). These alterations in keratin expression were observed during the period when DNA synthesis appears to be accelerated by ultraviolet light exposure (5 h–5 days after LIVB, and 2–10 days after PUVA irradiation). Therefore, these changes are probably reflections ofa proliferative or regenerative state of keratinocytes. This explanation was supported by the result of an experiment involving tape stripping of the epidermal horny layers, which also accelerates DNA synthesis hy keratinocytes. Immunohistochemistry appears to be a useful and sensitive method of detecting the effect of ultraviolet light on keratinization.

A new animal model for contact dermatitis : The hairless guinea pig

Allergic and irritant contact reactions were evaluated in the recently identified hairless guinea pig, Crl:IAF(HA)BR, a mutant from the Hartley strain. The cutaneous changes were observed macro‐ and microscopically. The irritant contact dermatitis was induced by croton oil, 2,4‐dinitrochlorobenzene (DNCB), or anthralin. Both hairless and hairy guinea pigs developed similar reactions to these chemicals. The density of the epidermal Langerhans cells (LC) of hairless guinea pigs was significantly higher than that in the hairy strain. Allergic contact sensitization was easily induced with DNCB. Photoallergic contact sensitization was also induced with tetrachlorosalicylanilide (TCSA) but not with tribromosalicylanilide (TBS). However, by administration of cyclophosphamide before sensitization, positive photocontact responses were seen with TBS. These results indicate that hairless guinea pigs can be used as animal models for investigation of immunologic and nonimmunologic contact reactions.

The distribution of IgG subclass autoantibodies in bullous pemphigoid analysed by immunofluorescence and immunoblotting

SummaryThe distribution of IgG subclasses in bullous pemphigoid (BP) autoantibodies in 14 BP sera and four biopsies was analysed by immunofluorescence (IF) and immunoblotting (IB). Three clones of monoclonal antibodies (MoAbs) to each IgG subclass were used. All 14 sera showed linear fluorescence in the basement membrane zone with IF, and 240 kDa and/or 180 kDa protein bands in human epidermal extract were detected by IB using a polyclonal antibody to total IgG. BP antibody in IgG4 subclass was found to be predominant, as it was detected most frequently and intensively in all positive sera and lesions studied by both techniques. In the IgG1 to IgG3 subclasses, a range of proportions of positive sera was obtained among MoAbs to the same IgG subclass in both techniques. However, one MoAb could detect IgG1 subclass BP antibody with a high frequency in both techniques. No difference in IgG subclass distribution of BP antibodies was observed during the course of the disease. In each serum, any IgG subclass of BP antibody recognized the identical BP antigen(s). These results suggest the predominance of IgG4 subclass and the possible presence of IgG1 subclass in BP antibodies.

The ATPase-staining of Langerhans Cells in Previously Stored Skin Tissues

The ATPase‐staining of Langerhans cells is usually done on fresh, unfixed biopsy specimens. In the present study, we attempted to stain these cells in previously stored tissues of guinea pig skin. The ATPase activity disappeared after freezing or preservation in formalin or ethanol. In contrast, tissue specimens which had been stored in physiological saline at 4°C stained as well as fresh cells even after 14 days.