Smooth-muscle-associated contractile protein in renal mesenchymal tumour cells and in transformed cells from DMN-injected rats.

Cryostat sections and established in vitro cultures of dimethylnitrosamine(DMN)-induced renal mesenchymal tumours and monolayer cultures of transformed kidney cells derived from rats treated with a carcinogenic dose of DMN were examined by indirect immunofluorescence with human serum containing smooth muscle antibody. Eight mesenchymal tumours examined showed filamentous cytoplasmic staining of spindle cells infiltrating between renal tubules, whilst in normal kidneys interstitial cells were only weakly positive. In established in vitro cultures from 6 mesenchymal tumours, different patterns of staining were observed in morphologically different cell forms, ranging from fine filamentous staining in giant cells to diffuse cytoplasmic fluorescence in small bipolar cells, and cell outline staining in polygonal cells. In addition filamentous staining of microvillous projections and nucleolar staining were observed in some tumour cells. Monolayer cultures of transformed kidney cells showed strong staining of coarse, randomly-orientated cytoplasmic filaments, whilst fibroblasts cultured from normal rat kidney demonstrated an ordered array of fine, parallel filaments. Specificity of the immunofluorescent staining reaction was established by failure to obtain staining with normal serum, with smooth muscle antibody serum neutralized by homogenates of smooth muscle or extracts containing actin derived from smooth muscle. These results indicate that there is an apparent increase of actin-like contractile microfilaments in transformed cells and in renal mesenchymal tumours. The cytoplasmic contracile microfilaments in these cells may play a role in tumour cell mobility and invasion

Contribution of type 2 diabetes associated loci in the Arabic population from Tunisia: a case-control study

<p>Abstract</p> <p>Background</p> <p>Candidate gene and genome-wide association studies have both reproducibly identified several common Single Nucleotide Polymorphisms (SNPs) that confer type 2 diabetes (T2D) risk in European populations. Our aim was to evaluate the contribution to T2D of five of these established T2D-associated loci in the Arabic population from Tunisia.</p> <p>Methods</p> <p>A case-control design comprising 884 type 2 diabetic patients and 513 control subjects living in the East-Center of Tunisia was used to analyze the contribution to T2D of the following SNPs: E23K in <it>KCNJ11/Kir6.2</it>, K121Q in <it>ENPP1</it>, the -30G/A variant in the pancreatic β-cell specific promoter of Glucokinase, rs7903146 in <it>TCF7L2 </it>encoding transcription factor 7-like2, and rs7923837 in <it>HHEX </it>encoding the homeobox, hematopoietically expressed transcription factor.</p> <p>Results</p> <p><it>TCF7L2</it>-rs7903146 T allele increased susceptibility to T2D (OR = 1.25 [1.06–1.47], <it>P </it>= 0.006) in our study population. This risk was 56% higher among subjects carrying the TT genotype in comparison to those carrying the CC genotype (OR = 1.56 [1.13–2.16], <it>P </it>= 0.002). No allelic or genotypic association with T2D was detected for the other studied polymorphisms.</p> <p>Conclusion</p> <p>In the Tunisian population, <it>TCF7L2</it>-rs7903146 T allele confers an increased risk of developing T2D as previously reported in the European population and many other ethnic groups. In contrast, none of the other tested SNPs that influence T2D risk in the European population was associated with T2D in the Tunisian Arabic population. An insufficient power to detect minor allelic contributions or genetic heterogeneity of T2D between different ethnic groups can explain these findings.</p

‘Left behind places’: a geographical etymology

‘Left behind places’ has become the leitmotif of geographical inequalities since the 2008 crisis. Yet, the term’s origins, definition and implications are poorly specified and risk obscuring the differentiated problems and pathways of different kinds of areas. This paper explicates the geographical etymology and spatial imaginary of ‘left behind places’. It argues that the appellation and its spatial expression have modified how geographical inequalities are understood and addressed by recovering a more relational understanding of multiple ‘left behind’ conditions, widening the analytical frame beyond only economic concerns, and opening up interpretations of the ‘development’ of ‘left behind places’ and their predicaments and prospects. While renewing interest in fundamental urban and regional concerns, what needs to endure from the ascendance of the ‘left behind places’ label is the terminology and spatial imaginary of reducing geographical inequalities and enhancing social and spatial justice

Use of the analysis of the volatile faecal metabolome in screening for colorectal cancer

Diagnosis of colorectal cancer is an invasive and expensive colonoscopy, which is usually carried out after a positive screening test. Unfortunately, existing screening tests lack specificity and sensitivity, hence many unnecessary colonoscopies are performed. Here we report on a potential new screening test for colorectal cancer based on the analysis of volatile organic compounds (VOCs) in the headspace of faecal samples. Faecal samples were obtained from subjects who had a positive faecal occult blood sample (FOBT). Subjects subsequently had colonoscopies performed to classify them into low risk (non-cancer) and high risk (colorectal cancer) groups. Volatile organic compounds were analysed by selected ion flow tube mass spectrometry (SIFT-MS) and then data were analysed using both univariate and multivariate statistical methods. Ions most likely from hydrogen sulphide, dimethyl sulphide and dimethyl disulphide are statistically significantly higher in samples from high risk rather than low risk subjects. Results using multivariate methods show that the test gives a correct classification of 75% with 78% specificity and 72% sensitivity on FOBT positive samples, offering a potentially effective alternative to FOBT

The genetic susceptibility to type 2 diabetes may be modulated by obesity status: implications for association studies

<p>Abstract</p> <p>Background</p> <p>Considering that a portion of the heterogeneity amongst previous replication studies may be due to a variable proportion of obese subjects in case-control designs, we assessed the association of genetic variants with type 2 diabetes (T2D) in large groups of obese and non-obese subjects.</p> <p>Methods</p> <p>We genotyped <it>RETN</it>, <it>KCNJ11</it>, <it>HNF4A</it>, <it>HNF1A</it>, <it>GCK</it>, <it>SLC30A8</it>, <it>ENPP1</it>, <it>ADIPOQ</it>, <it>PPARG</it>, and <it>TCF7L2 </it>polymorphisms in 1,283 normoglycemic (NG) and 1,581 T2D obese individuals as well as in 3,189 NG and 1,244 T2D non-obese subjects of European descent, allowing us to examine T2D risk over a wide range of BMI.</p> <p>Results</p> <p>Amongst non-obese individuals, we observed significant T2D associations with <it>HNF1A </it>I27L [odds ratio (OR) = 1.14, <it>P </it>= 0.04], <it>GCK </it>-30G>A (OR = 1.23, <it>P </it>= 0.01), <it>SLC30A8 </it>R325W (OR = 0.87, <it>P </it>= 0.04), and <it>TCF7L2 </it>rs7903146 (OR = 1.89, <it>P </it>= 4.5 × 10^-23), and non-significant associations with <it>PPARG </it>Pro12Ala (OR = 0.85, <it>P </it>= 0.14), <it>ADIPOQ </it>-11,377C>G (OR = 1.00, <it>P </it>= 0.97) and <it>ENPP1 </it>K121Q (OR = 0.99, <it>P </it>= 0.94). In obese subjects, associations with T2D were detected with <it>PPARG </it>Pro12Ala (OR = 0.73, <it>P </it>= 0.004), <it>ADIPOQ </it>-11,377C>G (OR = 1.26, <it>P </it>= 0.02), <it>ENPP1 </it>K121Q (OR = 1.30, <it>P </it>= 0.003) and <it>TCF7L2 </it>rs7903146 (OR = 1.30, <it>P </it>= 1.1 × 10^-4), and non-significant associations with <it>HNF1A </it>I27L (OR = 0.96, <it>P </it>= 0.53), <it>GCK </it>-30G>A (OR = 1.15, <it>P </it>= 0.12) and <it>SLC30A8 </it>R325W (OR = 0.95, <it>P </it>= 0.44). However, a genotypic heterogeneity was only found for <it>TCF7L2 </it>rs7903146 (<it>P </it>= 3.2 × 10^-5) and <it>ENPP1 </it>K121Q (<it>P </it>= 0.02). No association with T2D was found for <it>KCNJ11</it>, <it>RETN</it>, and <it>HNF4A </it>polymorphisms in non-obese or in obese individuals.</p> <p>Conclusion</p> <p>Genetic variants modulating insulin action may have an increased effect on T2D susceptibility in the presence of obesity, whereas genetic variants acting on insulin secretion may have a greater impact on T2D susceptibility in non-obese individuals.</p