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Biomedical subjects

J Handley

Publications and source records attributed to J Handley.

At least 19 recordsLinked to original sources

Analysis of prostate tissue DNA for the presence of human papillomavirus by polymerase chain reaction, cloning, and automated sequencing.

We have analysed the DNA from 24 prostate tissue biopsies, spanning a range of Gleason grading from benign to grade 5 and mixed randomly with cervical cancer samples of known human papillomavirus (HPV) status, for the prevalence of HPV DNA, in a double-blind study to ensure complete objectivity. Polymerase chain reactions (PCR) were performed using general E1 open reading frame primers for HPV under low stringency conditions, in addition to reactions containing primers specific for HPV16, E2, and E6 open reading frames under higher, more stringent PCR conditions. The presence of cellular DNA was verified by the use of primers for hypoxanthine guanine phosphoribosyl transferase. DNA bands were not detected in the prostate biopsies using the HPV16-specific primers under high-stringency PCR conditions, however a predominant band in the 400 bp region was observed in 15 of the prostate biopsies using the general primers and the low annealing temperature of 40 degrees C. This fragment was excised and cloned into the pT7 blue vector and the sequence of the insert determined. Although the cloned sequences initiated and terminated with the two authentic PCR primers, they did not contain a significant HPV-related open reading frame. Our results indicate that HPV type 16 and closely related types, as detected by the general primer pair, are unlikely initiators of prostate carcinogenesis within our population.

Amino Acid Sequence↗

Co-ordinated changes in expression of cell adhesion molecules in prostate cancer.

The expressions of E-cadherin, the integrin subunits beta 1, beta 2, beta 3, CD44 and alpha-catenin were studied in parallel by immunohistochemistry in a series of 40 prostate biopsies comprising one normal, 11 benign prostatic hyperplasia (BPH), and 28 prostatic adenocarcinomas. As reported by others, there was a consistent loss of E-cadherin expression with increasing tumour grade and de-differentiation. However, a significant proportion of losses occurred at earlier grades than previously reported. The parallel nature of this study showed, for the first time in human prostate carcinoma, a reciprocal expression pattern of E-cadherin and beta 1 integrin in the higher grades of prostate cancer. A reciprocal expression pattern was also found for E-cadherin and CD44 between moderately and poorly differentiated tumours. alpha-Catenin expression was downregulated only in those cells which had previously lost E-cadherin expression, and beta 2 and beta 3 integrin were rarely expressed in prostate tumours. A loss of expression of the luminal epithelial specific keratins CK8 and CK18 was also observed in advanced stage, poorly differentiated carcinomas.

Adenocarcinoma↗

Effect of percutaneous local anaesthetics on pain reduction during pulse dye laser treatment of portwine stains.

We have used EMLA, 4% amethocaine gel and placebo for facial portwine stains, for a period of 1 h, in a double-blind study. After removal of the preparations from the skin surface, each area was treated with six pulses of the laser, each 5 mm in diameter. Any pain noted immediately after treatment was recorded using both visual analogue (VAS) and verbal rating (VRS) scores. Twenty nine patients completed the study and statistical analysis of the results indicated that both EMLA and 4% amethocaine gel were superior to placebo (P < 0.001). However, when EMLA and 4% amethocaine gel were compared, the amethocaine preparation was significantly better (P < 0.05, VAS; P < 0.005 VRS) than EMLA in reducing pain caused by the laser treatment.

Adolescent↗

Cutaneous neoplasia following PUVA therapy for psoriasis.

To determine the risk of cutaneous neoplasia following photochemotherapy (PUVA), we reviewed patients with psoriasis treated at our unit between 1979 and 1991. Two hundred and forty-five patients were assessed, with a median duration of follow-up of 9.5 years. Fifty-nine per cent were male, and 41% female. The median number of exposures was 59, and the median total dose was 133 J/cm2 for the group as a whole. Non-melanoma skin cancers (NMSC) occurred in six individuals (2.4%). Basal cell carcinoma occurred in all six and one individual also developed four squamous cell carcinomas and Bowen's disease of the penis. No cases of malignant melanoma were recorded. Patients who developed NMSC received a median number of 225 exposures and a median cumulative dose of 654 J/cm2. Compared with a control study population in West Glamorgan, Wales, there was a 1.4 (95% confidence limits (CL) 0.5 and 3.1) times increased risk of NMSC. A statistically significant increased incidence of NMSC was found for patients who had received 100 or more exposures, and 250 or more J/cm2, with risks of 3.7 (95% CL 1.0 and 9.5), and 4.0 (95% CL 1.1 and 10), respectively. A PUVA dose of < 250 J/cm2 or < 100 exposures conferred a minimal increase in risk of NMSC in our study population.

Adult↗

Long-lasting allergic patch test reactions to nickel sulfate: analysis by nickel quantification and immunocytochemistry.

We previously showed the median duration of positive patch test reactions to nickel sulfate (5% pet.) was 9 days, and defined as long-lasting (LLAPTR) the 14.3% of reactions that persisted for 17 days or longer. The pathomechanisms of LLAPTR are unclear, but may involve either localized antigen persistence or abnormal downregulation of the cellular immune response. In this study, we compared (a) the nickel concentration and (b) the immunocytochemical nature of the local immune reaction, between biopsies from LLAPTR (n = 8) and normally resolving allergic patch test reactions (NRAPTR) (n = 8) to nickel sulfate. The concentration of nickel in LLAPTR (median 0.56 microgram/g, range 0.25-3.87 micrograms/g, mean 0.83 microgram/g, 95% CI 0.35-1.31) and NRAPTR (median 0.58 microgram/g, range 0.2-1.85 micrograms/g, mean 0.88 microgram/g, 95% CI 0.02-1.74) was similar. Activated T lymphocytes, expressing surface IL-2 receptor, HLA DR, DR alpha 1, DP, DQ, and CD2 > CD8 > CD4 antigens, were seen throughout the dermis and occasionally infiltrating the suprabasal layer of the epidermis in all biopsies. CD1 and HLA DR, DR alpha 1, DP, and DQ-expressing Langerhans cells were present throughout the epidermis and occasionally seen in the papillary dermis. HLA DR, DR alpha 1, DP, and DQ antigen expression were also seen on the surface of non-dendritic cells in the epidermis (probably either keratinocytes or T lymphocytes) and vascular endothelial cells in the papillary dermis. There were no significant qualitative or quantitative differences in the immunocytochemical nature of the localized immune reaction between LLAPTR and NRAPTR. These findings suggest that the pathomechanism of LLAPTR to nickel sulfate is unlikely to be explained simply on the basis of nickel concentration or the nature of the localized immune reaction at the patch test site.

Adult↗

Day 4 is better than day 3 for a single patch test reading.

Readings were performed on day (D) 2, D3 and D4 after application of patch tests in 88 patients. 90 patch test reactions in 49 patients were interpreted as allergic and of past or present relevance. A single D2 reading detected 58 of the allergic reactions with 32 false-negatives and 23 false-positives. A single D3 reading detected 77 allergic reactions, with 13 false-negatives and 17 false-positives. A single D4 reading detected 85 allergic reactions, with 5 false-negatives and 9 false-positives. Therefore, if only a single reading is feasible, it is better performed on D4 than on D3.

Allergens↗