Induction of unscheduled DNA synthesis in hairless mouse epidermis by ultraviolet light. (17/527)

The activity of ultraviolet (UV) light to induce unscheduled DNA synthesis (UDS) was investigated in hairless mouse epidermis by means of an in vivo-in vitro assay using a liquid scintillation counting method. Groups of three to five 8-week-old female hairless mice were irradiated with UV-B or UV-A, then skin samples were taken and cultured individually in medium containing [3H]thymidine with or without hydroxyurea (HU) for 2 hr. DNA of the epidermis was extracted, and incorporation of [3H]thymidine and the DNA content were determined with a liquid scintillation counter and a fluorescence spectrophotometer, respectively. Induction of UDS was judged in terms of the UDS index [(the ratio of DNA synthesis in the presence of HU to that in its absence) x 100]. UV-B increased the UDS index 1 hr after irradiation of 500 J/m2, which corresponds to approximately 1 minimal erythema dose or 1 minimal edema dose, and showed a dose-dependent increase up to 17-fold in the UDS index at irradiation doses of 500 to 2,000 J/m2. In a time-course study, UV-B also increased replicative DNA synthesis (RDS) 48 hr after irradiation at 1,000 J/m2. On the other hand, UV-A did not increase the UDS index at irradiation doses of 2 x 10(5) to 8 x 10(5) J/m2. These results show that induction of UDS by UV irradiation depends on wavelength and an increase of RDS in the epidermis exposed to UV-B irradiation appears after induction of UDS.  (+info)

Clinical constellation of annular erythema associated with anti-Ro/La autoantibodies. (18/527)

Annular erythema (AE) associated with anti-Ro (SSA) and/or La (SSB) autoantibody in patients with Sjogren syndrome (SS) or with SS/systemic lupus erythematosus overlap syndrome (SS/SLE), has recently been described in Orientals, and it may be a counterpart of annular skin lesion of the subacute cutaneous LE seen mostly in Caucasians. The author examined five Korean AE patients in respect to dinical diversity. In this small-sample study, subtle differences appeared between individual cases regarding the serologic features and the diagnoses of the disease. Among the five cases, four had circulating anti-Ro and anti-La antibodies, and one had only anti-La. Regarding the diagnosis, one was SS/SLE, two were primary SS, and the remaining two were only "AE associated with anti-Ro/La antibody". There seem to be a wide clinical spectrum in the disease expression of AE associated with anti-Ro/La autoantibody than previously thought.  (+info)

Cross-sensitivity reaction between tacrolimus and macrolide antibiotics. (19/527)

A patient with an allergy to a macrolide antibiotic was given tacrolimus and developed a sudden cutaneous reaction.  (+info)

Transcription-coupled and global genome repair differentially influence UV-B-induced acute skin effects and systemic immunosuppression. (20/527)

Exposure to UV-B radiation impairs immune responses in mammals by inhibiting especially Th1-mediated contact hypersensitivity and delayed-type hypersensitivity. Immunomodulation is not restricted to the exposed skin, but is also observed at distant sites, indicating the existence of mediating factors such as products from exposed skin cells or photoactivated factors present in the superficial layers. DNA damage appears to play a key role, because enhanced nucleotide excision repair (NER) strongly counteracts immunosuppression. To determine the effects of the type and genomic location of UV-induced DNA damage on immunosuppression and acute skin reactions (edema and erythema) four congenic mouse strains carrying different defects in NER were compared: CSB and XPC mice lacking transcription-coupled or global genome NER, respectively, as well as XPA and TTD/XPD mice carrying complete or partial defects in both NER subpathways, respectively. The major conclusions are that 1) transcription-coupled DNA repair is the dominant determinant in protection against acute skin effects; 2) systemic immunomodulation is only affected when both NER subpathways are compromised; and 3) sunburn is not related to UV-B-induced immunosuppression.  (+info)

Protection by ultraviolet A and B sunscreens against in situ dipyrimidine photolesions in human epidermis is comparable to protection against sunburn. (21/527)

Sunscreens prevent sunburn and may also prevent skin cancer by protecting from ultraviolet-induced DNA damage. We assessed the ability of two sunscreens, with different spectral profiles, to inhibit DNA photodamage in human epidermis in situ. One formulation contained the established ultraviolet B filter octyl methoxycinnamate, whereas the other contained terephthalylidene dicamphor sulfonic acid, a new ultraviolet A filter. Both formulations had sun protection factors of 4 when assessed with solar simulating radiation in volunteers of skin type I/II. We tested the hypothesis that sun protection factors would indicate the level of protection against DNA photodamage. Thus, we exposed sunscreen-treated sites to four times the minimal erythema dose of solar simulating radiation, whereas vehicle and control sites were exposed to one minimal erythema dose. We used monoclonal antibodies against thymine dimers and 6-4 photoproducts and image analysis to quantify DNA damage in skin sections. A dose of four times the minimal erythema dose, with either sunscreen, resulted in comparable levels of thymine dimers and 6-4 photoproducts to one minimal erythema dose +/- vehicle, providing evidence that the DNA protection factor is comparable to the sun protection factor. The lack of difference between the sunscreens indicates similar action spectra for erythema and DNA photodamage and that erythema is a clinical surrogate for DNA photodamage that may lead to skin cancer.  (+info)

Levels and repair of cyclobutane pyrimidine dimers and 6-4 photoproducts in skin of sporadic basal cell carcinoma patients. (22/527)

The 32P-postlabeling method was applied to measure directly the levels and repair rates of specific cyclobutane pyrimidine dimers and 6-4 photoproducts in 10 basal cell carcinoma patients and 10 controls matched on age, skin type, and gender after exposure to 400 J per m2 of solar simulating radiation on previously unexposed buttock skin. The results showed an identical level of photoproducts at 0 h after solar simulating radiation in the basal cell carcinoma group and the control group. Erythemal response correlated with the repair of cyclobutane pyrimidine dimers within 24 h in both groups, i.e., repair was faster in those with a strong erythemal reaction. The basal cell carcinoma patients showed a somewhat slower repair of photoproducts in skin compared with the controls, but the result was not significant. Photoproducts formed at the TTC sites were repaired faster than those at the TTT sites for both cyclobutane pyrimidine dimers and 6-4 photoproducts in the basal cell carcinoma group and in the controls.  (+info)

Lack of metallothionein-I and -II exacerbates the immunosuppressive effect of ultraviolet B radiation and cis-urocanic acid in mice. (23/527)

The effect of a null mutation for the metallothionein (MT)-I and -II isoforms in mice on the immunosuppressive action of ultraviolet B (UVB; 280-320 nm) radiation has been examined. Mice were exposed to a series of increasing daily UVB doses, each dose administered to the dorsum on 3 consecutive days. Erythema was assessed, and measured as its oedema component by the post-irradiation dorsal skinfold thickness, but there was no effect of the null mutation (MT-/-) observed after 3 x 3.4 kJ/m2 of UVB radiation. Immune function was assessed by the contact hypersensitivity (CHS) response, which was initiated by sensitization on unirradiated abdominal skin, and thus demonstrated the systemic effects of dorsal treatments. In comparison with the wild-type MT+/+ mouse, the MT-/- mouse was significantly more immunosuppressed by moderate daily UVB doses (1. 75-5.9 kJ/m2). When topically applied cis-urocanic acid (cis-UCA) replaced UVB radiation as the immunosuppressive agent, contact hypersensitivity in MT-/- mice was again markedly more suppressed than in MT+/+ mice, in a dose-responsive manner. The results infer that MT, which was shown immunohistochemically to be strongly induced in the epidermis of MT+/+ mice, but to be absent in MT-/- epidermis, has the potential to protect from photoimmunosuppression, and that the mechanism of action may be via the inactivation of the epidermal UVB-photoproduct, cis-UCA.  (+info)

Mutation in the gene for connexin 30.3 in a family with erythrokeratodermia variabilis. (24/527)

Erythrokeratodermia variabilis (EKV) is an autosomal dominant keratinization disorder characterized by migratory erythematous lesions and fixed keratotic plaques. All families with EKV show mapping to chromosome 1p34-p35, and mutations in the gene for connexin 31 (Cx31) have been reported in some but not all families. We studied eight affected and three healthy subjects in an Israeli family, of Kurdish origin, with EKV. After having mapped the disorder to chromosome 1p34-p35, we found no mutations in the genes for Cx31, Cx31.1, and Cx37. Further investigation revealed a heterozygous T-->C transition leading to the missense mutation (F137L) in the human gene for Cx30.3 that colocalizes on chromosome 1p34-p35. This nucleotide change cosegregated with the disease and was not found in 200 alleles from normal individuals. This mutation concerns a highly conserved phenylalanine, in the third transmembrane region of the Cx30.3 molecule, known to be implicated in the wall formation of the gap-junction pore. Our results show that mutations in the gene for Cx30.3 can be causally involved in EKV and point to genetic heterogeneity of this disorder. Furthermore, we suggest that our family presents a new type of EKV because of the hitherto unreported association with erythema gyratum repens.  (+info)