9 research outputs found
Suppression of contact hypersensitivity after repeated exposures of humans to low doses of solar simulated radiation
Although it is generally recognised that UV radiation (UVR) can induce suppression of contact hypersensitivity (CHS) in human subjects, most protocols to date have not tested the effect of low daily doses of solar simulated radiation (SSR). In the present study, healthy individuals, divided into four groups each consisting of approximately 34 subjects, were whole-body irradiated with 1.2 standard erythema doses of SSR for 2, 10 or 30 consecutive days, or were unirradiated. They were sensitised with diphenylocyclopropenone (DPCP) on one exposed body site 24 h after the final UVR. The occurrence and severity of the primary allergic response were noted, and both parameters were shown to be significantly lowered in the group irradiated for 30 days compared with the unirradiated group. Elicitation of CHS was undertaken 3 weeks after the sensitisation, using a range of concentrations of DPCP on a UV-protected body site. The extent of the CHS at 48 h was assessed by the clinical score, by an erythema meter and by histological examination of a biopsy taken from the site challenged with one selected concentration of DPCP. Although erythema and pigmentation did not differ between the groups, a significant negative correlation was found between the clinical CHS score and the number of days of UV exposure, at the lowest challenge dose of DPCP. In addition a significant negative correlation was revealed between the intensity of spongiosis (intraepidermal oedema and vesicles, as evaluated by histology) and the number of days of UV exposure. Thus small daily doses of SSR induce suppression of CHS in human subjects and the effect is cumulative, indicating that there is no adaptation to the immunomodulating effects of UVR, at least over the test period of 30 days
Germline mutations in the von Hippel-Lindau (VHL) gene in patients from Poland: disease presentation in patients with deletions of the entire VHL gene
\u2022 Thirty-four Polish families with a clinical diagnosis of
VHL disease were studied in order to describe: (1) the
frequency of germline mutations in these families; (2) the
spectrum of germline VHL mutations in the Polish population; (3) the proportion of de novo mutations; and (4)
genotype-phenotype correlations in patients with a
deletion of the entire VHL gene.
\u2022 The coding region of the VHL gene was tested using
direct sequencing. Large deletions were analysed using
quantitative Southern blotting and/or multiplex PCR.
\u2022 (1) Germline VHL mutations were observed in 30/34
(88%) families. Mutations were not identified in 4/34
(12%) probands (five subjects/four families) with central
nervous system haemangioblastoma (cHAB) and/or
retinal angioma (rHAB). (2) Small intragenic mutations
were detected in 18/30 (60%) families; all were
located 3\u2032 of codon 53. Partial and complete gene
deletions were detected in 7/30 (23%) and 5/30
(17%) families, respectively. Five mutations were unique
to the Polish population. (3) Five of 30 (17%) VHL mutation positive probands were found to have no family
history of VHL. (4) Of 11 patients with complete
deletions, all developed cHAB, two presented with
rHAB, and none developed renal cell carcinoma (RCC).
\u2022 (1) Some patients with predominantly brain tumours
and/or retinal angioma do not have identifiable germline mutations in the VHL gene and may have somatic
mosaicism, or may be affected by mutations of different
nature or localisation than the mutations for which the
study assays are designed, or may be phenocopies of
the disease. An alternative explanation is the presence
of additional haemangioblastoma susceptibility genes.
(2) The main characteristics of germline VHL mutations
in the Polish population are similar to those reported in
other populations. However, we observed a higher proportion of patients with complete deletions (5/30,
17%), compared to those reported in other populations
(3-9%). There was no evidence of a founder effect for
complete deletions in our patients. (3) The apparent de
novo mutation rate is 3c20%. (4) A complete deletion of
the VHL gene results primarily in brain tumours. This
result may be useful in genetic counselling for subjects
with complete deletions