Search PubMed⌕ Search

Biomedical subjects

J L Rees

Publications and source records attributed to J L Rees.

At least 109 records · Page 6Linked to original sources
PubMed1993

p53 protein expression in benign and malignant skin tumours.

The skin affords an excellent model of human carcinogenesis because a variety of lesions from benign tumours to invasive malignancy, with or without metastatic potential, are commonly found, and are accessible to biopsy. To date, few genetic alterations have been observed in skin neoplasia. In this study we have used a recently developed monoclonal antibody (DO7) to examine p53 protein expression in a wide variety of benign and malignant skin lesions. Benign skin lesions were negative, but a significant number of malignant epithelial lesions showed detectable p53; 56% of squamous carcinomas and 42% of basal cell carcinomas were positive. A smaller proportion of dysplastic epithelial lesions were positive (27%), and only 3.6% of malignant melanomas were positive. Thus, although detectable p53 protein is a common occurrence in malignant epithelial lesions, it does not correlate with the malignant phenotype or with metastatic potential. The finding of a lower proportion of positivity in dysplastic lesions, and absence of staining in benign tumours, suggests that p53 mutation may be involved in the progression towards invasive malignancy in human squamous skin lesions.

Bowen's Disease↗
PubMed1993

The relation between p53 mutation and p53 immunostaining in non-melanoma skin cancer.

Extensive study of the p53 gene has established its role as a tumour-suppressor gene, and the involvement of mutant p53 in a wide spectrum of human malignancy. Many mutations of p53 result in a protein product that is abnormally stable, so that it becomes readily detectable by immunocytochemistry. In contrast, under normal conditions, it has been considered that levels of wild-type p53 were too low to be detectable. Although positive immunocytochemistry has been used as a marker of mutation, recent evidence suggests that this assumption may not always be valid. We have carried out both PCR-sequencing of exons 5-8 of the p53 gene in 20 basal cell carcinomas (BCC), and immunocytochemistry of these tumours with the anti-p53 antibody DO7. Twenty cases of Bowen's disease, in which we had previously documented mutations, were also immunostained. We report a low rate of p53 mutation in the BCCs we examined (2/20), and a discrepancy between tumours with positive immunostaining and those with mutation in both Bowen's disease and BCC. Of eight tumours in which we detected mutation, only four were immunopositive: of 19 immunopositive samples, only four showed detectable mutation. We discuss the implications of our results for the use of positive immunostaining in clinical diagnosis, and the involvement of p53 in skin carcinogenesis.

Aged↗
PubMed1993

Codon 12 Harvey-ras mutations are rare events in non-melanoma human skin cancer.

ras mutations have been reported as an early event in some human malignancies and in the mouse skin model of multistep carcinogenesis; early studies in human non-melanoma skin cancers have reported variable rates of ras mutations. A recent study, however, has reported a high frequency of activating mutations of the Harvey-ras proto-oncogene in non-melanoma skin cancers, and the site specificity of the mutation at the second position of codon 12 prompted us to re-examine the importance of Ha-ras codon 12 mutations as an early event in the development of these tumours, using a combination of PCR and restriction fragment polymorphism of codon 12 of the Ha-ras gene. Dilution experiments confirmed that the method was sensitive and capable of detecting mutations at this codon when only 4% of the total alleles are mutated. We were surprised to find no mutations in the 40 basal cell carcinomas, 12 squamous cell carcinomas and 12 cases of Bowen's disease studied. We conclude that Ha-ras codon 12 mutations are rare events in human non-melanoma skin cancer in the U.K. The marked differences in the frequency of codon 12 Ha-ras mutations in published studies may relate to either technical artefacts, or differences in the molecular epidemiology between areas of low and high sun exposure.

Base Sequence↗
PubMed1992

Delayed type hypersensitivity is abnormal in patients with lichen planus.

Lichen planus is characterized by the histological features of a cell-mediated attack on the epidermis. To see whether there is any defect in cutaneous immunity in non-lesional skin, we measured the response to a contact sensitizer in 17 patients with lichen planus and 27 control subjects. Sensitization was induced with 30 micrograms dinitrochlorobenzene applied to the thigh. The subjects were challenged 4 weeks later with three doses of dinitrochlorobenzene (8.8, 12.5 and 17.7 micrograms), and responses were quantified with calipers as the change in skinfold thickness at 48 h. Patients with lichen planus were significantly less responsive with smaller reactions at all challenge doses. These abnormalities suggest that the skin is abnormal in areas unaffected by the rash, and raise the possibility that there may be a primary defect in the cutaneous immune system in lichen planus.

Female↗
PubMed1992

Quantifying anti-inflammatory agents' potency by measurement of response to dinitrochlorobenzene challenge.

Classical assays of topical corticosteroid potency based on the induction of vasoconstriction are unsatisfactory for a number of reasons. These include the doubtful relevance of vasoconstriction to immune inflammation, and more importantly, the inability to compare non-steroidal agents with corticosteroids. Here we describe a simple assay in which the inhibitory effect of agents upon delayed type hypersensitivity response to dinitrochlorobenzene can be quantified by measurements of reaction as skinfold thickness with Harpenden callipers. Using this system we have confirmed the greater potency of clobetasol propionate (Dermovate) compared with betamethasone valerate (Betnovate), but the evidence for an inhibitory effect of topical cyclosporin (10% cream) compared with base on this response is less convincing.

Administration, Topical↗
PubMed1992

The unexpectedly rapid response of fungal nail infection to short duration therapy.

To test our hypothesis that, by laying down a fungicidal barrier in the growing nail, a short course of antifungal therapy should be effective against onychomycosis, we treated 8 subjects with Trichophyton rubrum nail infection with terbinafine 125 mg b.d. for 14 days. All but one patient showed marked improvement, and 80% of fingernails and 37% of toenails were clinically cured after 6 months. Although this confirmed our prediction, the onset of response measured by outward movement of affected nail and negative cultures from distal nail clippings occurred after as little as 4 weeks. This was too soon for a fungicidal barrier to have grown out and indicates that the drug must have been carried directly into the diseased distal nail, presumably from newly formed ventral nail beneath it. The findings show that 1) short duration therapy, perhaps even a single dose, is possible in fungal nail infections; 2) the ventral nail provides unexpectedly rapid access of drugs to the site of distal disease.

Adult↗
PubMed1990

The influence of area of application on sensitization by dinitrochlorobenzene.

We have investigated the effect on sensitization of altering the area of application of 2,4,dinitrochlorobenzene (DNCB) at a constant dose per unit area. We showed that, when an area of less than 1 cm2 is used, this area is critical in determining the degree of sensitization. This contrasts with previous work that showed, for larger areas, an alteration in the area of application had little effect on sensitization, whereas keeping the area constant and increasing the concentration of DNCB increased the degree of sensitization. We suggest that not only is the amount of antigen important in determining response, but also the distribution of the antigen as presented to the afferent limb of the immune system.

Dermatitis, Contact↗
PubMed1989

Differential expression of the alpha and beta retinoic acid receptors in tissues of the rat.

We have compared the expression of alpha and beta retinoic acid receptors (RAR-alpha and RAR-beta) in different rat tissues. The two cDNA probes for RAR-alpha and RAR-beta each specifically detect two different transcripts. RAR-alpha was expressed in all tissues examined, but, in contrast, the expression of RAR-beta was undetectable in some tissues. The data do not support the idea that RAR-beta is specific to epithelial tissues.

Animals↗
PubMed1989

Expression of the alpha and beta retinoic acid receptors in skin.

Retinoic acid receptor (RAR) -alpha and -beta transcripts are expressed in rat and human skin, and in rat and human dermal fibroblasts and keratinocytes in vitro. RAR-alpha transcripts (ca. 2.8 and 3.6 kb) were expressed in all tissues but were more abundant in dermis and dermal fibroblasts than in epidermis or keratinocytes. RAR-beta mRNA was expressed in skin, but patterns of expression differed between human and neonatal rat samples. In human dermal fibroblasts, keratinocytes and whole skin, two RAR-beta transcripts (ca. 3.1 and 3.4 kb) were expressed. Conversely, in neonatal rat skin, dermal fibroblasts, and keratinocytes only the smaller transcript was detectable and was more abundant in cultured cells than in whole tissue. These results suggest that retinoic acid may have complex, as yet undefined, RAR-mediated regulatory functions in both dermis and epidermis.

Animals↗
PubMed1989

Sex differences in susceptibility to development of contact hypersensitivity to dinitrochlorobenzene (DNCB).

We have investigated the differences between the sexes in the development of contact sensitivity induced by dinitrochlorobenzene (DNCB). Ten male and 12 female subjects were sensitized with DNCB (30 micrograms applied on a 1 cm patch test disc) and challenged 1 month later with doses of 8.8, 12.5, 17.7 and 25 micrograms. The responses were measured after 48 h as increase in skinfold thickness with Harpenden callipers. Females showed a larger response at all challenge doses studied, and the slope of the log-dose response curve was significantly steeper in females. We conclude that there are significant differences in delayed type hypersensitivity between males and females.

Adult↗
PubMed1989

Stimulated eccrine gland function in primary Sjögren's syndrome.

Sweat secretion rate, stimulated by iontophoresis of pilocarpine, was measured in 22 patients with primary Sjögren's syndrome and 22 age- and sex-matched normal control subjects. There was no significant difference in measured sweat rates (P = 0.45). We conclude that the complaint of dryness of the skin in patients with Sjögren's syndrome is not due to decreased eccrine gland secretion.

Adult↗
PubMed1989

Nuclear retinoic-acid-binding proteins and receptors in retinoic-acid-responsive cell lines.

Nuclear retinoic-acid-binding activity and the expression of retinoic acid receptor mRNA (RAR-alpha and RAR-beta) were assayed in the F9 embryonal carcinoma, HeLa, HL-60 promyelocytic leukaemia and S91 melanoma cell lines. A 4-svedberg nuclear retinoic-acid-binding activity was detected in all 4 cell lines, but the levels in the HeLa and HL-60 cells were lower than in the F9 and S91 lines. RAR-alpha mRNA was expressed in all 4 cell lines, although at a very low level in S91 cells. Conversely, RAR-beta mRNA was expressed in S91 cells and, at a lower level, in F9 cells but was undetectable in HeLa and HL-60 cells. RAR-beta, transcribed and translated in vitro from the cloned cDNA coding region, sedimented at 4 S and this suggests that the 4-svedberg nuclear retinoic-acid-binding activity may represent the retinoic acid receptors.

Blotting, Northern↗
PubMed1988

Effect of isotretinoin on eccrine gland function.

Sweat secretion rate, stimulated by iontophoresis of pilocarpine, was measured before and during treatment with isotretinoin in 20 patients. Sweat secretion was increased during treatment in 15 patients (75%), but the mean increase of 15% was not statistically significant (P = 0.085, paired t-test; 95% confidence limits-0.2% to +30%) and no patients had a clinically apparent alteration of sweating. We conclude that there is no important change in stimulated sweating associated with isotretinoin therapy.

Adolescent↗
PubMed1987

Effects of benzodiazepines on laryngeal reflexes. Comparison of lormetazepam and Diazemuls.

Of 20 volunteers, five were given intravenous Diazemuls 15 mg over 15 seconds, and three groups of five were given lormetazepam 2 mg intravenously over 10, 20 and 60 seconds, respectively. Laryngeal reactivity and psychomotor function were tested at intervals from prior to injection until 4 hours after injection. For equivalent degrees of depression of psychomotor function, lormetazepam depressed the laryngeal reflex less than Diazemuls (p = 0.004). Lormetazepam give over 60 seconds depressed the laryngeal reflex more than when given over 10 seconds (p = 0.008) or over 20 seconds (p = 0.048), although a significant difference was not demonstrated between the 10-second and 20-second groups. These results concur with experimental evidence that benzodiazepine receptor multiplicity exists, which allows various members of the benzodiazepine group of drugs to exhibit differing therapeutic ratios for their various effects.

Adolescent↗