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Biomedical subjects

A A Schothorst

Publications and source records attributed to A A Schothorst.

At least 19 recordsLinked to original sources

Pyrimidine dimer induction and repair in cultured human skin keratinocytes or melanocytes after irradiation with monochromatic ultraviolet radiation.

We compared the susceptibilities of cultured melanocytes and keratinocytes to dimer induction in DNA by monochromatic ultraviolet (UV) radiation. Keratinocytes as well as melanocytes were derived from human foreskin, grown as a monolayer in petri dishes, covered with phosphate-buffered saline containing 0.1% glucose, and irradiated. UV irradiation was carried out at 254, 297, and 302 nm as well as with a light source emitting predominantly 312 nm. The induction of pyrmidine dimers was assessed by determination of the number of T4 endonuclease V-sensitive sites (ESS). We found a slightly higher response for dimer induction in melanocytes at 254, 297, and 302 nm; this difference was only significant at the 297-nm wavelength. Action spectra for pyrimidine dimer induction were derived from the exposure-response data obtained. The action spectra mimic to a large degree the action spectra for dimer induction in other cultured mammalian cells. The repair rate during a post-irradiation period lasting up to 24 h was substantially the same for the two cell types. The percentage of T4 endonuclease V-sensitive sites (ESS) remaining 9 and 24 h after irradiation was 45% and 30%, respectively.

Cells, Cultured

'High single-dose' European PUVA regimen also causes an excess of non-melanoma skin cancer.

We report the results of a long-term (12.8 years) follow-up study of the detection of malignant and benign skin tumours in patients with psoriasis, who were treated with PUVA according to the European, 'high single-dose' regimen. A total of 13 squamous cell carcinomas (SCC) and 24 basal cell carcinomas (BCC) were diagnosed in 11 of 260 patients. The incidence of both SCC and BCC was increased in comparison with the general Dutch population. The ratio of SCC to BCC in the general population was 1:8 but was 1:2.5 in our study group. A positive correlation was observed between the development of SCC and the total UVA dosage, the age of the patient at the start of the PUVA treatment and a history of arsenic use. This dose-related increase in the incidence of SCC, reported in studies from the U.S.A., has not been found in earlier European studies. The average time period between the start of PUVA therapy and the diagnosis of the first malignant skin tumour was 6.0 years for SCC and 4.7 years for BCC. Among the 49 benign skin tumours were actinic keratoses, a keratoacanthoma and 'PUVA keratoses', a newly described hyperkeratotic lesion, especially found in PUVA-treated patients.

Age Factors

Differential immune response of congenic mice to ultraviolet-treated major histocompatibility complex class II-incompatible skin grafts.

The influence of ultraviolet (UVB) irradiation on the survival of H-2 class II-disparate skin grafts was studied in congenic mouse strains. Isolated skin was UVB irradiated in vitro at a dose of 40 mJ/cm2 from both sides to remove Ia immunogenicity. Immediately after irradiation the skin was transplanted onto the flank of allogeneic mice. When B10.AQR grafts were transplanted onto B10.T(6R) recipients, a significant prolongation of the survival time was observed, while 50% of the UVB-treated grafts were not rejected at all. However, in the opposite direction--i.e., B10.T(6R) grafts onto B10.AQR recipients, no significant prolongation of the survival was observed. To test whether this effect was due to a difference in susceptibility of the donor skin to UVB irradiation or to a different immune response in the recipients, (B10.T(6R) x B10.AQR) grafts were transplanted onto the parent strains. Similar results were obtained, in that UVB-treated grafts did not show a prolonged survival in B10.AQR recipients, whereas a significant prolongation (50% of the grafts survived more than 100 days) was observed in B10.T(6R) recipients. UVB-treated (B10.T(6R) x B10.AQR)F1 grafts were also transplanted onto (B10.T(6R) x C57B1/10)F1, (B10.AQR x C57B1/10)F1, (B10.T(6R) x Balb/c)F1 and (B10.AQR x Balb/c)F1 recipients--but in none of these combinations was a prolonged survival time observed. These data suggest that, in contrast to all in vitro experiments, the abrogation of the immune response by UVB treatment of the stimulator cells is, in vivo, not a general phenomenon. The genetic constitution of the responder mice seems to play an important role in determining whether or not an immune response takes place.

Animals

Plastic blankets and heat shields decrease transmission of phototherapy light.

An in vitro study showed that the use of transparent plastic insulation to decrease heat loss from newborn infants substantially decreases the transmission of phototherapy light. The decrease is proportional to the number of plastic layers between the light source and the baby because of reflection from the surface of the plastic. This increases if the surface is irregular. Thickness and the type of plastic used had no effect.

Bedding and Linens

Risk evaluation of UVB therapy for psoriasis: comparison of calculated risk for UVB therapy and observed risk in PUVA-treated patients.

A descriptive dose-response model is presented to evaluate the long-term risk with respect to non-melanoma skin cancer associated with UVB therapy. The model is based on the results of animal dose-response studies and epidemiological data. A number of factors that influence the risk associated with therapy are evaluated: annual dose applied, solar exposure, therapeutic period, age at start of therapy. Shielding from therapeutic exposures of the skin areas that normally receive the most sun exposure could effectively reduce the risk. The model calculations were compared with observational data, as far as available. The calculated risk corresponded within the limits of statistical error with observed long-term risk of UVB therapy in Sweden; as far as there was a deviation, the model calculations tended to over-estimate the risk. A comparison of the model prognoses for UVB therapy with the observed risk among PUVA-treated patients in the USA shows a much higher observed risk for squamous cell carcinoma among the PUVA-treated patients.

Adult

Influence of ultraviolet radiation treatment on the survival of heterotopic skin grafts in the mouse.

Isolated mouse tail skin was UV-irradiated in vitro at a dose of 40 mJ/cm2 from both sides to remove the Ia immunogenicity. Immediately after irradiation the skin was transplanted onto the flank of allogeneic mice. When there was a total H-2 difference between donor and recipient, the UV-irradiated skin did not show a prolonged survival compared to control grafts. In the case of an I-region difference only, i.e., B10.AQR grafts onto B10.T (6R) recipients, a significant prolongation of the survival time was observed, whereas 50% of the UV-treated grafts were not rejected at all.

Animals

UVB doses in maintenance psoriasis phototherapy versus solar UVB exposure.

A possible increase in the risk of skin cancer in psoriatic patients treated with long-term maintenance UVB phototherapy was assessed by comparing the cumulative doses of UVB with the amount of UVB received from sunlight by normal healthy people. The biologically-effective UVB dose (termed UVB(EE) ) was measured using polysulphone film and worn as a badge by individuals with either an indoor or an outdoor occupation during 4 summer months of 1983 in The Netherlands (52 degrees N). The calculated mean annual UV-B(EE) doses were 5.9 J/cm2 for persons with an indoor occupation and 134 J/cm2 for those with an outdoor occupation. The UVB(EE) doses received by psoriasis patients during an initial course of phototherapy, as well as during maintenance treatment, were also estimated and gave a mean value of 22 J/cm2. Mean annual amounts of solar UVB(EE) exposure were calculated and compared with the administered doses of UVB(EE) during maintenance phototherapy. A dose-response model is described in order to estimate the increased incidence of non-melanoma skin cancer associated with such therapy. The cumulative incidence among patients who received maintenance phototherapy for several decades was calculated to be a factor of 2.5 to 7.5 higher than the incidence among individuals with an outdoor occupation.

Humans

[Solaria].

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Cholecalciferol

In vitro studies on the protoporphyrin uptake and photosensitivity of normal skin fibroblasts and fibroblasts from patients with erythropoietic protoporphyria.

Fibroblasts derived from patients with erythropoietic protoporphyria (EPP) are not sensitive to violet light and do not contain an excess of protoporphyrin (PP). Fibroblasts from both normal individuals and patients with EPP can take up very low concentrations of PP from culture medium. Cells grown in PP-containing medium showed a gradually increasing but limited uptake of PP and also an increased sensitivity to light. A sensitive scanning microfluorometric method has made it possible to demonstrate that the PP is mainly localized in the perinuclear granules. After exposure to violet light, cells photosensitized by PP in a culture medium showed increased membrane permeability as well as reduced reproductive capacity. Both of these photodamage effects can be repaired during postirradiation incubation in culture medium at 37 degrees C.

Cell Division

The role of oxygen in the photodamaging effect on erythrocytes of some photoallergic and phototoxic compounds.

Red blood cells irradiated with longwave ultraviolet light in the presence of a number of photoallergic or phototoxic compounds showed a marked loss of K+ ions. This process was strongly restricted by anaerobic conditions. During irradiation, oxygen was consumed. Since pre-irradiated photosensitizers were not toxic to erythrocytes, it is concluded that during irradiation, oxidative processes take place in the erythrocyte. The concentrations of the investigated photoallergic compounds required to induce photohaemolysis, were several times higher than those required for the phototoxic compound protoporphyrin. These findings indicate that photoallergic compounds, like the photodynamic compounds, also have photo-oxidative capacities, but to a much lower degree.

Erythrocytes