[Role of Candida allergen in atopic dermatitis and efficacy of oral therapy with various antifungal agents].

We studied whether fungal allergens play a role in exacerbating the clinical symptoms of atopic dermatitis (AD). We found that the percentage of the patients who showed CAP-RAST positive (2 < or = score) to Candida albicans (Ca) was significantly higher in the patients with severe symptoms and high serum IgE level than those with mild symptoms and lower IgE. This was also true for the patients with CAP-RAST positive to Pityrosporum ovale (Po). AD patients with their symptoms localized to head and neck showed significantly higher tendency to have positive CAP-RAST (2 < or = score) to Ca and Po when compared to those with their eruption distributing to the extremities. We then evaluated the efficacy of oral therapy with antifungal agents in 140 cases of refractory AD with positive CAP-RAST to Ca. Good or excellent response was obtained in 60% with fluconazole, 35% with itraconazole, 31% with amphotericin B, 28% with nystatin. The present finding that amphotericin B and nystatin, both of which are not absorbed through intestine, were effective for approximately a third of the patients indicates that Ca in the intestine plays an important role in triggering AD symptoms. Fluconazole was more effective than amphotericin B and nystatin, suggesting that fungal colonizing in other parts of the body but the digestive tract also play a role in the exacerbation of AD symptoms.

Microsomal alcohol oxygenase: purification and characterization of a cytochrome P450 responsible for oxidation of 7-hydroxy-delta 8-tetrahydrocannabinol to 7-oxo-delta 8-tetrahydrocannabinol in guinea pig liver.

Guinea pig hepatic enzyme, microsomal alcohol oxygenase, was able to oxidize both 7 alpha- and 7 beta-hydroxy-delta 8-tetrahydrocannabinol (7 alpha- and 7 beta-hydroxy-delta 8-THC) to 7-oxo-delta 8-THC. A cytochrome P450, named P450GPF-B, which mediates this oxidative metabolism was purified from hepatic microsomes of untreated female guinea pigs. The purified enzyme showed a single protein band of molecular mass 50,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The NH2-terminal amino acid sequence of P450GPF-B is highly homologous with those of several cytochrome P450s belonging to the CYP3A subfamily. 18O derived from atmospheric oxygen was incorporated into 31 and 6%, respectively, of 7-oxo-delta 8-THC formed from 7 alpha- and 7 beta-hydroxy-delta 8-THC when the substrates were incubated with P450GPF-B under 18O2. The antibody against P450GPF-B significantly suppressed the oxidative activities of 7 alpha- and 7 beta-hydroxy-delta 8-THC to 7-oxo-delta 8-THC in hepatic microsomes of guinea pig. These results indicate that P450GPF-B is a major enzyme responsible for the hepatic microsomal alcohol oxygenase activities in the guinea pig.

Potential efficacy of low metal diets and dental metal elimination in the management of atopic dermatitis: an open clinical study.

We performed an open clinical study on the effects of low metal diets and/or dental metal elimination on 27 patients with moderate to severe atopic dermatitis (AD), who showed positive patch tests for metal allergens and/or clinical exacerbation by oral provocation tests with metal salts. All the patients were recommended to ingest low metal diets for 3 months and/or undergo dental metal elimination. Marked or moderate improvement was noted in 18 patients (67%); 7 patients (26%) showed marked improvement and 11 patients (41%), moderate improvement. Nine patients (33%) showed minimal improvement or no change. In the patients who showed marked or moderate improvement, we observed statistically significant decreases (p < 0.05) in both peripheral blood eosinophil counts and serum LDH levels after 3 months of treatment. The present study suggests that restriction of ingested metal allergens to which patients have positive patch tests and/or oral challenge tests may be useful in the management of some patients with AD who have metal sensitivity.

Dermatomyofibroma (Plaqueförmige Dermale Fibromatose).

We reported a patient with dermatomyofibroma and reviewed the literature to characterize the immunohistochemical features of dermatomyofibroma. A 25-year-old woman presented with an asymptomatic, well-circumscribed, red-brown plaque on the left posterior shoulder. Microscopic examination revealed a non-encapsulated but well-circumscribed tumor in the mid-dermis extending into the upper subcutaneous fatty tissue. The tumor was composed of faintly eosinophilic, thin, wavy collagen fibers arranged as intersecting fascicles with an arrangement predominantly parallel to the skin surface. Embedded among the wavy fibers, there were a fair number of nuclei that were elongated, vesicular, and uniform in size. Immunohistochemical studies using a peroxidase-antiperoxidase technique disclosed that the cytoplasm of the tumor cells was positive for muscle actin. The tumor cells were negative for alpha-smooth muscle actin, desmin, factor XIIIa, S-100 protein, and CD34. Clinical, histopathologic, and immunohistochemical analysis confirmed dermatomyofibroma.

1 alpha,25-dihydroxyvitamin D3 modulates Ia antigen expression induced by interferon-gamma and prostaglandin E2 production in Pam 212 cells.

Recent investigations suggest that 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3] has an effect on the regulation of immune responses and that keratinocyte (KC) expression of major histocompatibility complex class II antigens may be involved in immune responses. We investigated the modulation by 1 alpha,25(OH)2D3 of Ia antigen expression induced by interferon-gamma (IFN-gamma) and prostaglandin E2 (PGE2) production in Pam 212 cells. 1 alpha,25(OH)2D3 at 10(-6), 10(-8) or 10(-10) M significantly decreased the levels of IFN-gamma-induced Ia antigen expression in Pam 212 cells. Pam 212 cells produced PGE2 and 1 alpha,25-(OH)2D3 enhanced Pam 212 cell PGE2 production. However, indomethacin (1, 5 and 10 micrograms/ml) did not abrogate the inhibitory effect of 1 alpha,25(OH)2D3 on IFN-gamma induction of Ia antigen expression in Pam 212 cells, indicating that the products of the cyclo-oxygenase pathway do not mediate 1 alpha,25(OH)2D3 inhibition of IFN-gamma induction of Pam 212 cell Ia antigen expression. Our studies suggest that in Pam 212 cells the levels of Ia antigen expression induced by IFN-gamma and PGE2 production are negatively and positively regulated by 1 alpha,25(OH)2D3, respectively, and that 1 alpha,25(OH)2D3 may play a role in the regulation of immune responses.

Hair follicle nevus.

We present a case of hair follicle nevus, a rare hamartoma composed of vellus hair follicles. Hair follicle nevus should be differentiated from accessory auricle, trichofolliculoma and hair nevus.

Thermal neutron capture therapy of malignant melanoma using 10B-monoclonal antibodies: in vitro and in vivo analysis.

We have established methods of targeting a sufficient number of 10B atoms on human melanoma cells to allow selective destruction of the cancer cells by thermal neutron irradiation. Thermal neutron capture therapy (NCT)1-3 requires the presence of at least 10(9) 10B atoms on each target cell for specific killing of that cell without injuring normal tissues. In order to accumulate an adequate number of 10B atoms on target cells, we first created an effective compound containing 12 atoms of 10B per molecule (10B12-chlorpromazine) and 10B-dopa analogue (10B1-paraboronophenylalanine). In the present study, about three molecules of our newly synthesized 10B12-compound were conjugated to an avidin molecule. The resulting 10B38.5-avidin compound can be specifically directed to human melanoma cells by biotinated monoclonal antibodies (MAbs) specific for the cells. We were able to accumulate 2.6 x 10(8) 10B atoms on a melanoma cell using this method. Cultured human melanoma cells treated with 10B-avidin-biotin-MAb (10B-AB-MAb) were selectively damaged by thermal neutron irradiation in vitro. This is the first study to indicate that thermal neutrons selectively damage target cells boronated by MAbs.

Specific killing of human melanoma cells with an efficient 10B-compound on monoclonal antibodies.

We previously established methods which have enabled us to target a sufficient number of 10B atoms on human melanoma cells to destroy them by thermal neutron irradiation. Monoclonal antibodies were here used as vector of 10B atoms on the target cell. Thermal neutrons require at least 10(9) 10B atoms to destroy the cell. In order to accumulate an adequate number of 10B atoms on target cells, our first approach was to make an effective compound that contains 12 atoms of 10B in a molecule. The second step was to conjugate the compound with an avidin molecule (10B12-avidin). One molecule of the 10B12-avidin carries about 30 atoms of 10B. This 10B12-avidin can be specifically targeted on human melanoma cells by biotinated monoclonal antibodies specific for the cells. Furthermore, the number of 10B atoms on target cells can be augmented by a hapten-antihapten monoclonal antibody system. The cultured human melanoma cells treated with these methods were damaged by thermal neutron irradiation. This is the first study that indicates thermal neutrons do injure target cells boronated by monoclonal antibodies.