Expansion of a 12-kb VNTR containing the REXO1L1 gene cluster underlies the microscopically visible euchromatic variant of 8q21.2

Copy number variants visible with the light microscope have been described as euchromatic variants (EVs) and EVs with extra G-light material at 8q21.2 have been reported only once before. We report four further patients with EVs of 8q21.2 ascertained for clinical (3) or reproductive reasons (1). Enhanced signal strength from two overlapping bacterial artificial chromosomes (BACs) and microarray analysis mapped the EV to a 284-kb interval in the reference genome. This interval consists of a sequence gap flanked by segmental duplications that contain the 12-kb components of one of the largest Variable Number Tandem Repeat arrays in the human genome. Using digital NanoString technology with a custom probe for the RNA exonuclease 1 homologue (S. cerevisiae)-like 1 (REXO1L1) gene within each 12-kb repeat, significantly enhanced diploid copy numbers of 270 and 265 were found in an EV family and a median diploid copy number of 166 copies in 216 controls. These 8q21.2 EVs are not thought to have clinical consequences as the phenotypes of the probands were inconsistent, those referred for reproductive reasons were otherwise phenotypically normal and the REXO1L1 gene has no known disease association. This EV was found in 4/3078 (1 in 770) consecutive referrals for chromosome analysis and needs to be distinguished from pathogenic imbalances of medial 8q. The REXO1L1 gene product is a marker of hepatitis C virus (HCV) infection and a possible association between REXO1L1 copy number and susceptibility to HCV infection, progression or response to treatment has not yet been excluded.     

Prevalence of Schistosoma intercalatum and S. haematobium Infection among Primary Schoolchildren in Capital Areas of Democratic Republic Of S?o Tomé and Príncipe,West Africa

Background

A parasitological survey of Schistosoma haematobium and S. intercalatum infection among primary schoolchildren in capital area of Democratic Republic of São Tomé and Príncipe (DRSTP) was undertaken.

Methods

Subjects with positive infection were confirmed by the detection of S. haematobium ova in the urine or S. intercalatum ova in the stool by using centrifugation concentration or merthiolate-iodine-formalin concentration method. Totally, 252 urine and stool samples, respectively, were obtained from apparently healthy schoolchildren, of which 121 from boys (9.8 ± 1.4 yr) and 131 from girls (9.7 ± 1.3 yr).

Results

None of participating schoolchildren were found having S. haematobium ova in the urinary specimen. While, among 4 primary schools studied, only schoolchildren from Saint Marçal were detected with S. intercalatum ova in the fecal specimen, making the overall prevalence of S. intercalatum infection among schoolchildren was 2.4% (6/252) and girls had insignificantly higher prevalence (3.1%, 4/131) than that (1.7%, 2/121) in boys (χ² = 0.5, P = 0.5).

Conclusion

Water control and sanitation as well as snails eliminated by molluscicides are urgently needed to reduce S. intercalatum infection in DRSTP inhabitants.     

Clinical utility of histopathology data: cancers of the testis and urinary bladder

Histopathology data form the basis of most oncological patient management. Pathology guidelines therefore recommend sets of core data items that should be reported in each specimen. The clinical utility of a particular data item depends on the clinical scenario. Awareness of how these data are used to guide patient management could enable pathologists to focus their resources on clinically important issues. For example, it is generally critical to identify even a minor nonseminomatous component in a predominantly seminomatous testicular germ cell tumour as such patients would be managed as a nonseminoma. However, this finding would be less important in a patient with a raised serum alpha fetoprotein level as such a patient would generally be managed as a nonseminoma even if the histological diagnosis is pure seminoma. In this review, we discuss the clinical utility of various histopathology parameters in the management of bladder and testicular cancer.     

Community acquired fulminant Pseudomonas infection of the gastrointestinal tract in previously healthy infants

Three previously healthy infants presented with diarrhoea and pyrexia and deteriorated rapidly. Two patients had necrotizing bowel disease requiring aggressive surgical intervention. All survived. P. aeruginosa gastrointestinal infection in previously healthy children is an extremely rare condition with a high mortality. Ecthyma gangrenosum was present in over 60% of reported cases although often not recognized initially. A high index of clinical suspicion, including prompt recognition of ecthyma gangrenosum, is mandatory for an early diagnosis of P. aeruginosa gastrointestinal infection. Early diagnosis and treatment may improve the prognosis.     

EXPLAINED VARIATION FOR LOGISTIC REGRESSION

Different measures of the proportion of variation in a dependent variable explained by covariates are reported by different standard programs for logistic regression. We review twelve measures that have been suggested or might be useful to measure explained variation in logistic regression models. The definitions and properties of these measures are discussed and their performance is compared in an empirical study. Two of the measures (squared Pearson correlation between the binary outcome and the predictor, and the proportional reduction of squared Pearson residuals by the use of covariates) give almost identical results, agree very well with the multiple R² of the general linear model, have an intuitively clear interpretation and perform satisfactorily in our study. For all measures the explained variation for the given sample and also the one expected in future samples can be obtained easily. For small samples an adjustment analogous to R²_adj in the general linear model is suggested. We discuss some aspects of application and recommend the routine use of a suitable measure of explained variation for logistic models.     

Essential role for Smad3 in angiotensin II‐induced tubular epithelial–mesenchymal transition

Angiotensin II (Ang II) is a key mediator of chronic kidney disease, in which epithelial–mesenchymal transition (EMT) is a critical process mediated by the TGFβ/Smad signalling pathway. The present study examined the specific role of Smads in Ang II‐induced EMT in vitro and in vivo. We found that Ang II signalled through the receptor of AT1, not AT2, to activate Smad2/3 and induce EMT in a normal rat tubular epithelial cell line (NRK52E). Activation of Smads by Ang II was attributed to degradation of an inhibitory Smad7, which was mediated by the AT1‐Smurf2‐dependent ubiquitin degradation mechanism because blockade of AT1 receptor or knockdown of Smurf2 inhibited Smad7 loss, thereby reducing Smad2/3 activation and EMT in response to Ang II. In contrast, over‐expression of Smad7 inhibited Ang II‐induced Smad2/3 activation and EMT in NRK52E cells and in a rat model of remnant kidney disease. Moreover, knockdown of Smad3, not Smad2, attenuated Ang II‐induced EMT. In conclusion, Ang II activates Smad signalling to induce EMT, which is mediated by a loss of Smad7 through the AT1‐Smurf2‐dependent ubiquitin degradation pathway. Smad3, but not Smad2, may be a mediator of EMT, while Smad7 may play a protective role in EMT in response to Ang II. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.