Biomedical subjects
Publications and source records attributed to B E Johnson.
A quantitative study of 8-methoxypsoralen plasma profiles in patients with psoriasis undergoing photochemotherapy shows that a poor response to the treatment may be explained in terms of abnormal pharmacokinetic behaviour. However, not all 'poor responders' exhibit an abnormal pattern and for these an alternative explanation is required.
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Osteomalacia due to vitamin D deficiency is common in elderly women. It has been suggested that ultraviolet light may have a place in its prevention but our studies with Vita-Lite fluorescent tubes have given no support to the view that these can play a useful role in the promotion of vitamin D synthesis.
Blood was cultured and chromosome preparations were examined for sister chromatid exchanges and chromosome aberrations in eighteen patients receiving photochemotherapy with 8-MOP and UV-A for the treatment of psoriasis, both before starting treatment and again 6 months later. The UV-A was administered both by means of low output (irradiance: 1.1--2.25 mW/cm2) and high output (irradiance: 6.1--7.6 mW/cm2) UV-A radiation cubicles. Irrespective of the intensity of irradiation or the total dose of UV-A administered there was no evidence of chromosome damage in lymphocytes following treatment.
Of sixty-nine examples of the photosensitivity dermatitis and actinic reticuloid syndrome, nine were found to be allergically sensitive to chrysanthemum oleoresin extract. Although this extract showed evidence in vitro of a phototoxic action we were unable with in vivo studies to explain the connection between the contact allergic sensitivity and the photosensitivity. The fractions responsible for the in vitro phototoxicity appear to be different from those involved in the in vivo contact allergic sensitivity. This study provides further support for the view that in the photosensitivity dermatitis and actinic reticuloid syndrome contact allergic sensitivity is of importance.
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Contact allergic sensitivity to oleoresin extracts from Compositae plants was found to be usually present in individuals suffering from the photosensitivity dermatitis and actinic reticuloid syndrome. It was demonstrated in forty-seven out of fifty-five examples of this syndrome. These results provide support for the view that contact allergic sensitivity is an important aspect of the state of chronic photosensitivity in the middle-aged and elderly male.
The yield of thymine-containing dimers produced in mouse skin DNA in vivo by 290 nm ultraviolet radiation was shown to increase with dose up to around 2000 J/m2 and subsequently at a much slower rate up to 8000 J/m2. The study of wavelength dependence of dimer formation in skin indicated that 290 nm was the most effective wavelength of those investigated, followed by 300, 280 and 260 nm, with 310 nm being by far the least effective. A reduction in the number of dimers present in skin DNA was shown to occur by 24 h post-irradiation in a dose-dependent manner. A significant percentage of the dimers was, however, found to persist in the skin until at least 72 h post-irradiation.
Nuclear DNA appears to be the major molecular target for the inhibitory, mutagenic and lethal effects of ultraviolet radiation on cells in culture. Cyclobutyl dimers between adjacent pyrimidine bases, the major photochemical lesions for these effects in prokaryotes, also play a part in UVR effects on eukaryote cells. Pyrimidine dimers have been isolated from in vivo UV-irradiated guinea pig and mouse skin. The wavelength dependence for dimer induction is similar to that for acute skin reactions but no direct causal relationship has been established. Sunlight UVA may induce dimers in skin DNA. Excision of dimers from mouse skin in vivo is deficient as it is for most rodent cells in culture; human cell excision is efficient and the difficulties in interpretation of UV-carcinogenesis results with mice in terms of human skin cancer are therefore, increased.
Human lymphocytes exposed to the effects of long wave UV radiation in the presence of 8-methoxypsoralen prior to stimulation by PHA show dose related sister chromatid exchanges after 2 replication cycles in vitro. This has implications for interpreting the processes involved and for monitoring DNA damaging agents in vivo.
This article describes the satisfactory clinical improvement obtained in the majority of a group of 72 patients with psoriasis of various types as a result of the oral and/or topical administration of 8-methoxypsoralen followed by long wavelength ultraviolet irradiation. The irradiation source used was that of conventional longwave UV fluorescent tubes mounted in a specially constructed cubicle. Until such time as the long term effect of this form of photochemotherapy on the cell has been evaluated and the most appropriate regime worked out, it would seem to be important to restrict the amount of irradiation used to that required to produce acceptable maintained clinical improvement.
It is important in the technique of photopatch testing, using oil of bergamot, to have determined the concentration of the active psoralen, bergapten, so as to avoid false negative responses in the assessment of phototoxic reactions. Techniques for assessing the phototoxic components of oil of bergamot are described and quantitative analyses of bergapten, the only significant photoactive compound in the samples examined, are reported. The phototoxicity of bergapten was found to be nearly the same as that of xanthotoxin (8-MOP) in tests on human skin.
Sister chromatid exchange rates in cultured cells from the blood of patients receiving photochemotherapy have been examined as an indicator of possible genetic hazards of the treatment to patients with psoriasis. Lymphocytes of untreated patients with psoriasis appear to have sister chromatid exchange rates after 72 h of culture indistinguishable from normal subjects and there is no evidence from these studies that sister chromatid exchanges are significantly increased in the lymphocytes of patients receiving photochemotherapy. Cells from blood taken from patients who had been given 8-methoxypsoralen orally 2 h before and then irradiated with UV-A in vitro were found to have an increased exchange rate which could be related to the presence of the drug in the peripheral circulation.
In a group of 19 subjects suffering from erythropoietic protoporphyria the administration of beta-carotene appeared to produce improvement based on a subjective assessment of alterations in exposure times required to produce the symptoms and signs of the condition. This clinical improvement however failed to show a direct correlation with the prophyrin levels in blood and faeces, or with the estimation by phototesting of the minimal response dose within the action spectrum of 400-600 nm.
Using a standardized open photopatch test technique, the phototoxic reactions produced by bergamot oil bergapten (5-methoxypsoralen) the active component of the oil, and xanthotoxin (8-methoxypsoralen) were studied. The reaction was affected by a range of factors such as the vehicle (PMF or ethanol), the concentration of ethanol in the vehicle, the skin site, the interval between application of the psoralen and irradiation, the hydration of the skin, and the degree of natural or sun-induced pigmentation. Repeated photopatch testing at the same skin site produced an increase in sensitivity. Eye colour, natural susceptibility to suntanning, age, and sex, had no effect on the phototoxic response to psoralens.
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Quindoxin (quinoxaline di-N-oxide) is a photosensitizer capable of producing photocontact dermatitis. The study of a group of seven affected subjects has provided evidence of persistent light reaction and "photoallergy", most probably to the parent substance and not to any photoproduct or contaminant. Clinical and photobiological similarities to the photosensitivity dermatitis and actinic reticuloid syndrome were demonstrated.
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