Socio-economic deprivation and outcomes following radical nephroureterectomy for clinically localized upper tract transitional cell carcinoma.

BACKGROUND: Little is known about the effects of socio-economic deprivation on the oncological outcomes of surgically treated upper tract transitional cell carcinoma. METHODS: From January 1998 to December 2012, 161 patients underwent nephroureterectomy for upper urinary tract cancer at our tertiary medical centre. We included 124 patients where complete data were available for further analysis. This study also analysed the impact of the reported risk factors such as grade, stage, multifocality in addition to socio-economic deprivation on the long-term oncological outcomes after nephroureterectomy. RESULTS: One hundred and twenty-four (77 %) patients with complete data for socio-economic status were analysed in this study. The median age of the cohort was 73 years (interquartile range 45-86). There were 20, 18, 17, 40 and 29 patients in different socio-economic categories ranging from 1 to 5, respectively. The median duration of follow-up was 68 months (9-174). A statistically higher grade (p value 0.005) and higher stage (p value 0.0005) disease was seen in patients from less deprived categories on both univariate and multivariate analyses. The cancer-specific mortality and follow-up recurrences, however, did not significantly differ between the different socio-economic categories on multivariate analysis (p value 0.13; 0.6) and on univariate and multivariate analyses. A higher number of patients with multifocal disease and concomitant carcinoma in situ (CIS) had disease recurrences which were statistically significant (p values 0.026 and 0.014, respectively) on multivariate analysis. CONCLUSIONS: A lower recurrence-free survival was observed in patients with multifocal disease and those with concomitant CIS following nephroureterectomy for clinically localized disease. Long-term follow-up did not show any significant differences in cancer-specific survival between different deprivation categories.

Bradykinin B1 receptor-mediated vasodilation is impaired in myometrial arteries from women with pre-eclampsia.

OBJECTIVE: To investigate the vascular functional activity, localisation and expression of B1 and B2 kinin receptors in normal pregnancy and pre-eclampsia. METHODS: Kinin receptor-mediated relaxation of myometrial arteries was assessed using wire myography. Immunohistochemical staining and gene expression of kinin receptors in the myometrium was determined. RESULTS: B2 receptor-mediated relaxation was reduced in pre-eclampsia. B1 receptor-mediated relaxation was observed in a proportion of healthy women and was impaired in pre-eclampsia. Receptor expression and localisation was unaltered in pre-eclampsia. CONCLUSION: Here, we demonstrate a novel B1 receptor-mediated vasodilatation in healthy myometrial vessels that is absent in pre-eclampsia.

Impact of multiple deprivations on detection, progression and interventions in small renal masses (less than 4 cm) in a population based study.

BACKGROUND AND OBJECTIVES: A relatively unknown associations exists between the detection, progression and rate of interventions in small renal masses in the context of socioeconomic status. The study explored the impact of socioeconomic status on the detection, progression and intervention rate in SRMs. PARTICIPANTS AND METHODS: A population-based cohort of patients with SRMs was identified using various hospital databases in well-defined geographical area between January 2007 and December 2011. A list of patients with unique 10-digits Community Health Index (CHI) number and their follow-up was recorded on a pre-designed electronic database sheet. Correlation between the socioeconomic status and detection, progression and pattern of interventions of small renal masses was the primary outcome. The postcode of each patient was identified and linked to the Scottish Index of Multiple Deprivation (SIMD) scoring system, and a deprivation category number assigned to each patient, allowing potential links to become apparent between small renal masses and deprivation. RESULTS: Two hundred and seventeen patients were diagnosed with small renal masses in 150,820 abdominal imaging carried out in a population of 117,600. The detection of SRMs in relation to SIMD status showed no statistically significant differences across different categories. Similarly, interventions, type of surgery and progression remained unaffected by socioeconomic status. The group on active surveillance showed slow or no-growth at a mean follow-up of more than 2 years. CONCLUSIONS: The detection of small renal masses is very small compared with the amount of imaging investigations of abdomen in 5 years in this cohort. Detection, progression and rate of intervention did not differ in different socioeconomic strata of the cohort. The majority of small renal masses on active surveillance did not change or grew in size very slowly when observed over time.

New aspects of hepatic fibrosis.

Hepatic stellate cells are the major source of extracellular matrix proteins in hepatic fibrosis, including Type I collagen. In response to liver injury, the hepatic stellate cells change from a quiescent to an activated phenotype. This activation process includes a phenotypic change to a myofibroblast-like cell, increased proliferation rate, loss of retinoid stores, increased production of extracellular matrix proteins, chemokines, and cytokines, and contractility. Ongoing studies are characterizing the genes that are differentially expressed in the quiescent and activated hepatic stellate cells. We have also investigated the regulation of Type I collagen expression, the cleavage of collagen propeptides, and the formation of collagen cross-links. Understanding these pathways may provide new insights into the molecular pathogenesis of hepatic fibrosis.

Far upstream regulatory elements enhance position-independent and uterus-specific expression of the murine alpha1(I) collagen promoter in transgenic mice.

The stage- and tissue-specific expression of many eukaryotic genes is regulated by cis-regulatory elements, some of which are located in proximity to the start site of transcription whereas others have been identified at considerable distances. In previous studies we have identified far upstream DNase I-hypersensitive sites in the murine alpha1(I) collagen (Col1a1) gene, which may play a role in the regulation of this abundantly expressed gene. Here we have cloned several of these sites into reporter gene constructs containing the Col1a1 promoter driving the green fluorescent protein (GFP) reporter gene and tested their possible functions in transfection experiments and transgenic mice. In transient and stable transfections none of the hypersensitive sites had a significant effect on Col1a1 promoter activity, indicating that they do not contain a classical transcriptional enhancer. In transgenic animals one element located at -18 to -19.5 kb enhanced the position-independent activity of the linked Col1a1 promoter and may be part of a locus control region. Another element located at -7 to -8 kb specifically enhanced reporter gene expression in the uteri of transgenic mice, suggesting that it contains a novel transcriptional enhancer that may be involved in the regulation of type I collagen expression in tissue remodeling in the uterus during the estrous cycle. Our studies also demonstrate the versatility of the GFP reporter gene for use in transgenic animals because it can be analyzed in live animals, whole mount embryos, histological thin sections, or primary cell cultures, and it can be quantified very sensitively in tissue or cell extracts using a fluorometer.

Site-selected mutagenesis of the Drosophila second chromosome via plasmid rescue of lethal P-element insertions.

This paper describes a fast and efficient approach to correlating cloned genes with mutant phenotypes in Drosophila. We make use of a large collection D. melanogaster lines with recessive lethal insertions of a P[lacW] transposon on their second chromosome. Within this collection there clearly must be many insertions corresponding to Drosophila genes that have been cloned and characterized, e.g., via homology with cloned mammalian genes, but for which mutant phenotypes have yet to be identified. We have made use of the fact that P[lacW] contains a plasmid replicon to establish a collection of rescued plasmids containing genomic DNA flanking the sites of transposon insertion. Plasmids representing a total of 1836 lines were independently rescued and pooled in batches of 10 and 100. Pools of 100 plasmids were screened by hybridization with cDNAs corresponding to cloned second chromosome loci. Hybridizing pools were then narrowed down to single plasmids by a process of subdivision and rehybridization, and corresponding mutant lines were obtained. The success rate was better than one in four. This rate would undoubtedly be improved by the use of genomic DNA probes.