Differential gene expression in the developing mouse ureter

In many instances, kidney dysgenesis results as a secondary consequence to defects in the development of the ureter. Through the use of mouse genetics a number of genes associated with such malformations have been identified, however, the cause of many other abnormalities remain unknown. In order to identify novel genes involved in ureter development we compared gene expression in embryonic day (E) 12.5, E15.5 and postnatal day (P) 75 ureters using the Compugen mouse long oligo microarrays. A total of 248 genes were dynamically upregulated and 208 downregulated between E12.5 and P75. At E12.5, when the mouse ureter is comprised of a simple cuboidal epithelium surrounded by ureteric mesenchyme, genes previously reported to be expressed in the ureteric mesenchyme, foxC1 and foxC2 were upregulated. By E15.5 the epithelial layer develops into urothelium, impermeable to urine, and smooth muscle develops for the peristaltic movement of urine towards the bladder. The development of these two cell types coincided with the upregulation of UPIIIa, RAB27b and PPAR gamma reported to be expressed in the urothelium, and several muscle genes, Acta1, Tnnt2, Myocd, and Tpm2. In situ hybridization identified several novel genes with spatial expression within the smooth muscle, Acta1; ureteric mesenchyme and smooth muscle, Thbs2 and Co15a2; and urothelium, Kcnj8 and Adh1. This study marks the first known report defining global gene expression of the developing mouse ureter and will provide insight into the molecular mechanisms underlying kidney and lower urinary tract malformations. (c) 2005 Elsevier B.V. All rights reserved.

Asymptomatic bacteriuria Escherichia coli strain 83972 carries mutations in the foc locus and is unable to express F1C fimbriae

Escherichia coli is the most common organism associated with asymptomatic bacteriuria (ABU). In contrast to uropathogenic E. coli (UPEC), which causes symptomatic urinary tract infection (UTI), very little is known about the mechanisms by which these strains colonize the urinary tract. Bacterial adhesion conferred by specific surface-associated adhesins is normally considered as a prerequisite for colonization of the urinary tract. The prototype ABU E coli strain 83972 was originally isolated from a girl who had carried it asymptomatically for 3 years. This study characterized the molecular status of one of the primary adhesion factors known to be associated with UTI, namely F1C fimbriae, encoded by the foc gene cluster. F1C fimbriae recognize receptors present in the human kidney and bladder. Expression of the foc genes was found to be up-regulated in human urine. It was also shown that although strain 83972 contains a seemingly intact foc gene cluster, F1C fimbriae are not expressed. Sequencing and genetic complementation revealed that the focD gene, encoding a component of the F1C transport and assembly system, was non-functional, explaining the inability of strain 83972 to express this adhesin. The data imply that E. coli 83972 has lost its ability to express this important colonization factor as a result of host-driven evolution. The ancestor of the strain seems to have been a pyelonephritis strain of phylogenetic group B2. Strain 83972 therefore represents an example of bacterial adaptation from pathogenicity to commensalism through virulence factor loss.

Urinary arsenic, porphyrins and malondialdehyde in a population 16 years after arsenic mitigation program in Xinjian, China

Arsenic contamination of groundwater (0.05 to 0.84 mg/L) in Kuitun, Xinjiang was first found in 1970’s. Alternative clean surface water was introduced in 1985. We aimed to assess the exposure and heath outcome since the mitigation. In 2000, we collected a total of 360 urine samples from villagers from the endemic area and a nearby control area for arsenic (As), porphyrins and malondialdehyde (MDA) measurements. The averaged urinary As level of villagers from the endemic site (117±8.3 μg/g creatinine; 4.2 to 943.8 μg/g creat) was higher than that of the control site (73.6±3.2 μg/g creat). No significant differences were found in urinary porphyrins or MDA between the endemic and control sites. However, when the urinary arsenic was higher than 150 μg/g creat, these two biomarkers were higher in the exposed group than the control. Within the exposed group, villagers with arsenic-related skin symptoms had higher arsenic, uroporphyrin and MDA compared to those who had not shown symptoms. Sine the water mitigation, villagers whose urinary arsenic levels were 270 μg/g creat dropped from 20% to 10% of the population. Population with arsenic-related skin symptoms remained unchanged at 31%. We noted that 7.8% of those who had skin lesions were born after the implementation of intervention and that some villagers still prefer to drink the groundwater. Further, in the dry season, lack of surface water and electrical power breakdowns are to blame for failure to ensure continuous supply of clean water. It is concluded that despite the prompt action and successful water mitigation program to curb arsenic poisonings, it is essential to continue to monitor the health outcome of this population.

Urinary excretion of cadmium among Torres Strait Islanders (Australia) at risk of elevated dietary exposure through traditional foods

This study explored urinary cadmium levels among Torres Strait Islanders in response to concerns about potential health impact of high levels of cadmium in some traditional seafood (dugong and turtle liver and kidney). Cadmium levels were measured by inductively coupled mass spectrometry in de-identified urine samples collected during general screening programs in 1996 in two communities with varying dugong and turtle catch statistics. Statistical analysis was performed to identify links between cadmium levels and demographic and background health information. Geometric mean cadmium level among the sample group was 0.83 mu g/g creatinine with 12% containing over 2 mu g/g creatinine. Cadmium level was most strongly associated with age (46% of variation), followed by sex (females > males, 7%) and current smoking status (smokers > non-smokers, 4.7%). Adjusting model conditions suggested further positive associations between cadmium level and diabetes (p = 0.05) and residence in the predicted higher exposure community (p = 0.07). Positive correlations between cadmium and body fat in bivariate analysis were eliminated by control for age and sex. This study found only suggestive differences in cadmium levels between two communities with predicted variation in exposure from traditional foods. However, the data indicate that factors linked with higher cadmium accumulation overlap with those of renal disease risk (i.e. older, females, smokers, diabetes) and suggest that levels may be sufficient to contribute to renal pathology. More direct assessment of exposure and health risks of cadmium to Torres Strait Islanders is needed given the disproportionate level of diet-related disease and the cultural importance of dugong and turtle. This study highlights the need to consider social and cultural variation in exposure and to de. ne "safe'' cadmium levels during diabetes given its rising global prevalence.