Glimpses into the molecular pathogenesis of Peyronie's disease

Peyronie's disease (PD) is a fibroproliferative disease of the penis. Since little is known about the molecular pathogenesis of PD, we compared the biochemical make-up of PD plaques with normal tunica albuginea to clarify pathological processes in the scarred tissue. Protein and mRNA levels were measured in plaques and in unaffected pieces of the tunica albuginea. We investigated the presence of myofibroblasts, the deposition of collagens, and some key elements of Wnt and YAP1 signaling at protein level. The expression of 45 genes, all related to collagen homeostasis and extracellular matrix proteins, was quantified. In plaques, more myofibroblasts were present, and we observed an activation of Wnt signaling and YAP1 signaling. Increased levels of the collagens types I and III confirm the fibrotic nature of plaques. The mRNA ratio of collagen types III, IV, and VI to type I was increased. The expression of lysyl hydroxylase 3 was higher, whereas a decreased expression level was seen for fibronectin and cathepsin K. The biochemical composition of plaques was different from unaffected tunica albuginea: the relative and absolute abundance of various extracellular matrix proteins were changed, as well as the quality of collagen and the level of the collagen-degrading enzyme cathepsin K

SAFEGUI: resampling-based tests of categorical significance in gene expression data made easy

Summary: A large number of websites and applications perform significance testing for gene categories/pathways in microarray data. Many of these packages fail to account for expression correlation between transcripts, with a resultant inflation in Type I error. Array permutation and other resampling-based approaches have been proposed as solutions to this problem. SAFEGUI provides a user-friendly graphical interface for the assessment of categorical significance in microarray studies, while properly accounting for the effects of correlations among genes. SAFEGUI incorporates both permutation and more recently proposed bootstrap algorithms that are demonstrated to be more powerful in detecting differential expression across categories of genes

BAGEL:a web-based bacteriocin genome mining tool

A common problem in the annotation of open reading frames (ORFs) is the identification of genes that are functionally similar but have limited or no sequence homology. This is particularly the case for bacteriocins, a very diverse group of antimicrobial peptides produced by bacteria and usually encoded by small, poorly conserved ORFs. ORFs surrounding bacteriocin genes are often biosynthetic genes. This information can be used to locate putative structural bacteriocin genes. Here, we describe BAGEL, a web server that identifies putative bacteriocin ORFs in a DNA sequence using novel, knowledge-based bacteriocin databases and motif databases. Many bacteriocins are encoded by small genes that are often omitted in the annotation process of bacterial genomes. Thus, we have implemented ORF detection using a number of published ORF prediction tools. In addition, BAGEL takes into account the genomic context, i.e. for each potential bacteriocin-encoding ORF, the sequence of the surrounding region on the genome is analyzed for genes that might encode proteins involved in biosynthesis, transport, regulation and/or immunity. These innovations make BAGEL unique in its ability to detect putative bacteriocin gene clusters in (new) bacterial genomes. BAGEL is freely accessible at:

How Do Patients Understand Questions about Lower Urinary Tract Symptoms?:A Qualitative Study of Problems in Completing Urological Questionnaires

Lower urinary tract symptoms are common complaints in ageing people. For a urological evaluation of such complaints in men, the International Prostate Symptom Score (IPSS) is used worldwide. Previous quantitative studies have revealed serious problems in completing this questionnaire. In order to gain insight into the nature and causes of these problems, we conducted a qualitative study. Not only the purely verbal IPSS was studied but also two alternatives, including pictograms: the Visual Prostate Symptom Score (VPSS) and the Score Visuel Prostatique en Image (SVPI). Men aged 40 years and over with an inadequate level of health literacy (IHL; n = 18) or an adequate level of health literacy (AHL; n = 47) participated. Each participant filled out one of the three questionnaires while thinking aloud. The analysis of their utterances revealed problems in both health literacy groups with form-filling tasks and subtasks for all three questionnaires. Most noticeable were the problems with the IPSS; the terminology and layout of this form led to difficulties. In the VPSS and SVPI, the pictograms sometimes raised problems. As in previous research on form-filling behavior, an overestimation by form designers of form fillers' knowledge and skills seems to be an important explanation for the problems observed

Fabry disease with atypical phenotype identified by massively parallel sequencing in early-onset kidney failure

Background. The cause of chronic kidney disease (CKD) remains unknown in ∼20% of patients with kidney failure. Massively parallel sequencing (MPS) can be a valuable diagnostic tool in patients with unexplained CKD, with a diagnostic yield of 12%–56%. Here, we report the use of MPS to establish a genetic diagnosis in a 24-year-old index patient who presented with hypertension, nephrotic-range proteinuria and kidney failure of unknown origin. Additionally, we describe a second family with the same mutation presenting with early-onset CKD. Results. In Family 1, MPS identified a known pathogenic variant in GLA (p.Ile319Thr), and plasma globotriaosylsphingosine and α-galactosidase A activity were compatible with the diagnosis of Fabry disease (FD). Segregation analysis identified three other family members carrying the same pathogenic variant who had mild or absent kidney phenotypes. One family member was offered enzyme therapy. While FD could not be established with certainty as the cause of kidney failure in the index patient, no alternative explanation was found. In Family 2, the index patient had severe glomerulosclerosis and a kidney biopsy compatible with FD at the age of 30 years, along with cardiac involvement and a history of acroparesthesia since childhood, in keeping with a more classical Fabry phenotype. Conclusion. These findings highlight the large phenotypic heterogeneity associated with GLA mutations in FD and underline several important implications of MPS in the work-up of patients with unexplained kidney failure.</p

Fabry disease with atypical phenotype identified by massively parallel sequencing in early-onset kidney failure

Background. The cause of chronic kidney disease (CKD) remains unknown in ∼20% of patients with kidney failure. Massively parallel sequencing (MPS) can be a valuable diagnostic tool in patients with unexplained CKD, with a diagnostic yield of 12%–56%. Here, we report the use of MPS to establish a genetic diagnosis in a 24-year-old index patient who presented with hypertension, nephrotic-range proteinuria and kidney failure of unknown origin. Additionally, we describe a second family with the same mutation presenting with early-onset CKD. Results. In Family 1, MPS identified a known pathogenic variant in GLA (p.Ile319Thr), and plasma globotriaosylsphingosine and α-galactosidase A activity were compatible with the diagnosis of Fabry disease (FD). Segregation analysis identified three other family members carrying the same pathogenic variant who had mild or absent kidney phenotypes. One family member was offered enzyme therapy. While FD could not be established with certainty as the cause of kidney failure in the index patient, no alternative explanation was found. In Family 2, the index patient had severe glomerulosclerosis and a kidney biopsy compatible with FD at the age of 30 years, along with cardiac involvement and a history of acroparesthesia since childhood, in keeping with a more classical Fabry phenotype. Conclusion. These findings highlight the large phenotypic heterogeneity associated with GLA mutations in FD and underline several important implications of MPS in the work-up of patients with unexplained kidney failure.</p

Home measures of anxiety, avoidant coping and defence as predictors of anxiety, heart rate and skin conductance level just before invasive cardiovascular procedures

The question was whether anxiety, heart rate and skin conductance level just before invasive cardiac procedures could be predicted by anxiety related measures obtained at patients homes approximately 3 weeks before treatment. Trait measures of avoidant coping and defence were provided by sixty-three male and thirty-three female patients who were scheduled for a diagnostic or interventional heart catheterization. In hospital physiological measures were registered continously during a 20 min interview and subsequently patients reported their anxiety. Results with hierarchical regres