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Biomedical subjects

Peter Selby

Publications and source records attributed to Peter Selby.

9 recordsLinked to original sources
PubMed2003

Uroplakin gene expression in normal human tissues and locally advanced bladder cancer.

The uroplakins are widely regarded as urothelium-specific markers of terminal urothelial cytodifferentiation. This study investigated the expression of the four uroplakin genes, UPIa, UPIb, UPII and UPIII, in a wide range of normal human tissues to determine tissue specificity and in advanced transitional cell carcinoma (TCC) to examine gene expression in primary and metastatic disease. In the urinary tract, all four uroplakins were expressed by urothelium and UPIII was also expressed by prostatic glandular epithelium. UPIa and UPII appeared to be urothelium-specific, but UPIb was detected in several non-urothelial tissues, including the respiratory tract, where it was associated with squamous metaplasia of tracheal and bronchial epithelia. The ten cases of primary TCC and corresponding lymph node metastases demonstrated that each uroplakin gene could be expressed at the mRNA level. No single uroplakin gene was expressed in all primary tumours or metastases, but 80% of the primary tumours and 70% of the lymph node metastases expressed at least one uroplakin gene. UPIII mRNA was often expressed in the absence of UPIII protein. These results confirm that in human tissues the expression of UPIa and UPII genes is highly specific to urothelium and suggest that the tight differentiation-restricted expression of uroplakin genes in normal urothelium is lost following malignant transformation.

Carcinoma, Transitional Cell↗
PubMed2003

Association between vertebral fracture and increased mortality in osteoporotic patients.

UNLABELLED: Determinants of mortality were studied in a prospective study of 677 women and men with primary or secondary osteoporosis. Prevalent vertebral fractures were associated with increased mortality, but other known predictors of mortality explain a significant proportion of the excess risk. INTRODUCTION: In population studies, prevalent vertebral fractures are associated with increased mortality. It is unknown whether this excess mortality is related to low bone mineral density or its determinants or whether there is an additional component associated with fracture itself. METHODS: We studied 677 women and men with osteoporosis, 28-88 years old, of whom 352 had morphometrically determined vertebral fracture, to examine the risk and causes of mortality in patients with osteoporosis (defined densitometrically as a spine bone mineral density T-score < -2.5 and -3.0 for women and men, respectively, and/or one or more prevalent vertebral fractures without a history of significant trauma). The participants had enrolled in a double-blind placebo-controlled study in osteoporosis and were comprised of 483 women with postmenopausal osteoporosis, 110 women with secondary osteoporosis, and 84 men with osteoporosis of any cause. Demographics, medical history, and other measures of skeletal and nonskeletal health status were assessed at entry. RESULTS: During a median follow-up of 3.2 years, 37 (5.5%) participants died, with 31 of these deaths occurring in those with prevalent vertebral fractures. Compared with participants who did not have a prevalent vertebral fracture, those with one or more fractures had a 4.4-fold higher (95% CI, 1.85, 10.6) mortality rate. After adjustment for predictors for poor health--including number of medications, number of diseases, use of oral corticosteroids, alcohol intake, serum albumin and erythrocyte sedimentation rate (ESR), renal function, height, weight, gender, and age--the point estimate of risk remained elevated but was no longer statistically significant (hazard ratio, 2.4; 95% CI, 0.93, 6.23). CONCLUSIONS: Prevalent vertebral fractures in osteoporotic patients are associated with increased mortality. Other known predictors of mortality can explain a significant proportion of the excess risk.

Adult↗
PubMed2002

Human uroplakin lb gene structure and promoter analysis.

The uroplakin Ib (UPIb) gene is predominantly expressed in urothelium and is overexpressed in 50% of transitional cell carcinoma (TCC). Molecular cloning of the genomic 5' region and comparison to a chromosome 3q genomic contig determined that the gene spans 31 kb and has eight exons including a noncoding exon 1. Multiple transcription start sites were identified in exon 1 by 5'RACE and ribonuclease protection assay (RPA). In vitro reporter gene analysis was performed with 2.3 kb of genomic DNA sequence flanking the 5' end of UPIb. A 235-bp 5' fragment that included UPIb exon 1 generated strong transcriptional activity in normal and malignant human urothelial cell lines. Established malignant cell lines had greater transcriptional activity from the UPIb promoter than normal human cells. The identification of a functional human UPIb gene promoter may find application in targeting gene therapy strategies for bladder cancer.

5' Untranslated Regions↗
PubMedDate not supplied

Paternal alcohol exposure and Turner syndrome.

AIMS: Turner syndrome (TS) is a sex chromosome aneuploidy that occurs as a result of a non-disjunctional error in meiosis I or anaphase lag; however, the aetiology of this disorder remains unknown. Anecdotal evidence suggests that paternal alcoholism may play an unidentified role in the aetiology of TS. Accordingly, the primary objective of this study was to determine the potential association between paternal alcohol exposure and TS. METHODS: The questionnaire was designed to solicit information about the parents' health and lifestyle habits occurring 1 year prior to and throughout the pregnancy of their daughter with TS. Alcohol dependence was assessed by the Brief Michigan Alcohol Screening Test (BMAST). The study population was solicited from the Turner's Syndrome Society of Canada and included any parent(s) having a child with TS who was of any age. Two hundred and twelve families completed and returned the survey. RESULTS: This provided a response rate of 86.5%. Six of the fathers (3.6%; n = 166) and six of the mothers (3.6%; n = 165) had scores of 5 or more on the BMAST (scores of 5+ are considered to be in the 'alcoholic range'). This is considerably lower than the population norm of 9.5%. CONCLUSIONS: Our study has suggested there is no association between paternal or maternal alcohol consumption and TS.

Adolescent↗
PubMedDate not supplied

Hypercalcaemia.

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Adult↗