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Adrian Spencer Woolf: Influence Statistics

Development of epithelial organs requires co-ordinated interactions between epithelial and mesenchymal tissues. Studies using null mutant mice have indicated that the ret receptor and its ligand, glial cell line-derived neurotrophic factor (GDNF), are crucial for initiation of development of the metanephric kidney. However, the role of this signalling system in other branching organs has not been analysed. Here we describe expression studies of ret, GDNF, and a co-receptor for GDNF ...

Renal parenchymal disease after urinary tract infection (UTI) has been associated with the development of hypertension and renal functional impairment. A systematic literature review and meta-analysis was performed to determine how effectively the finding of primary vesicoureteric reflux (VUR) on micturating cystography (MCU) in children hospitalized with UTI predicted renal parenchymal disease on (99m)Technetium-dimercaptosuccinic acid ((99m)Tc-DMSA) scintigraphy. Medline, Embase, and ...

Several lines of evidence suggest that hepatocyte growth factor/scatter factor (HGF/SF), a soluble protein secreted by embryo fibroblasts and several fibroblast lines, may elicit morphogenesis in adjacent epithelial cells. We investigated the role of HGF/SF and its membrane receptor, the product of the c-met protooncogene, in the early development of the metanephric kidney. At the inception of the mouse metanephros at embryonic day 11, HGF/SF was expressed in the mesenchyme, while met ...

Fraser syndrome (OMIM 219000) is a multisystem malformation usually comprising cryptophthalmos, syndactyly and renal defects1. Here we report autozygosity mapping and show that the locus FS1 at chromosome 4q21 is associated with Fraser syndrome, although the condition is genetically heterogeneous. Mutation analysis identified five frameshift mutations in FRAS1, which encodes one member of a family of novel proteins related to an extracellular matrix (ECM) blastocoelar protein found in ...

Mutations in hepatocyte nuclear factor 1B (HNF1B), which is a transcription factor expressed in tissues including renal epithelia, associate with abnormal renal development. While studying renal phenotypes of children with HNF1B mutations, we identified a teenager who presented with tetany and hypomagnesemia. We retrospectively reviewed radiographic and laboratory data for all patients from a single center who had been screened for an HNF1B mutation. We found heterozygous mutations in 21 ...

A critical role for Tie1, an orphan endothelial receptor, in blood vessel morphogenesis has emerged from mutant mouse studies. Moreover, it was recently demonstrated that certain angiopoietin (Ang) family members can activate Tie1. We report here that Ang1 induces Tie1 phosphorylation in endothelial cells. Tie1 phosphorylation was, however, Tie2 dependent because 1) Ang1 failed to induce Tie1 phosphorylation when Tie2 was down-regulated in endothelial cells; 2) Tie1 phosphorylation was ...

Autosomal dominant polycystic kidney disease (ADPKD) in children is sometimes considered to be a benign condition, with morbidity manifesting in adulthood. Therefore, diagnostic screening of children at risk is controversial. The aim of our study was to to compare the manifestations of ADPKD in children diagnosed by postnatal ultrasound (US) screening versus those presenting with symptoms. This was a retrospective chart review of children with ADPKD assessed in a single centre between ...

BACKGROUND: In rats, offspring born to mothers supplied low protein diets during pregnancy have fewer glomeruli than normal. We hypothesized that such nephron deficits are associated with altered cell turnover in the metanephros, the embryonic precursor of the adult kidney.

METHODS: Wistar rats were supplied with one of three isocaloric diets from day 0 of pregnancy: control (18% protein) or low protein (9% or 6%) diets. All had a normal chow after birth. Groups were compared by ...

Previous studies have demonstrated that hepatocyte growth factor/scatter factor (HGF/SF) is secreted by mesenchymal cells and that it elicits motility, morphogenesis and proliferation of epithelia expressing the met receptor. We now report that HGF/SF may act as an autocrine factor in fibromuscular renal mesangial cells. These cells mechanically support glomerular endothelia, control the rate of plasma ultrafiltration and are implicated in the pathogenesis of a variety of chronic renal ...

BACKGROUND: Renal tract malformations are, on occasion, associated with uterine malformations. The transcription factor hepatocyte nuclear factor (HNF)-1beta is expressed from the earliest stages of development of the Wolffian duct, the mesonephros and metanephros, and the Müllerian ducts in the mouse. In adult mice HNF-1beta is expressed in the kidney tubules, collecting ducts, and in the oviducts and uterus in the female (Müllerian duct derivatives) and in the epididymis, vas deferens ...

Congenital anomalies of the kidney and urinary tract (CAKUT) include vesicoureteral reflux (VUR). VUR is a complex, genetically heterogeneous developmental disorder characterized by the retrograde flow of urine from the bladder into the ureter and is associated with reflux nephropathy, the cause of 15% of end-stage renal disease in children and young adults. We investigated a man with a de novo translocation, 46,X,t(Y;3)(p11;p12)dn, who exhibits multiple congenital abnormalities, ...

The hepatocyte nuclear factor-1beta (HNF-1beta) transcription factor controls endoderm development. Human mutations cause early-onset diabetes mellitus and have recently been associated with dysplastic, hypoplastic, and glomerulocystic kidneys. A new kindred with this "renal cysts and diabetes" syndrome is described, and nephrogenic HNF-1beta expression is defined. The proband had congenital cystic kidneys: over the next 12 yr, his renal function was impaired, but he was normoglycemic. ...

The planar cell polarity (PCP) pathway, incorporating non-canonical Wnt signalling, controls embryonic convergent (CE) extension, polarized cell division and ciliary orientation. It also limits diameters of differentiating renal tubules, with mutation of certain components of the pathway causing cystic kidneys. Mutations in mouse Vangl genes encoding core PCP proteins cause neural tube defects (NTDs) and Vangl2 mutations also impair branching of embryonic mouse lung airways. Embryonic ...

OBJECTIVES: To determine whether vascular endothelial growth factor A (VEGF) and its receptors are expressed during bladder development in mice when capillaries are forming, and whether exogenous VEGF might enhance the growth of endothelia and other types of bladder cells, using an embryonic organ-culture model.

MATERIALS AND METHODS: Whole bladders from wild-type mice, at embryonic day (E) 14, were grown in serum-free organ culture in an air/5% CO2 atmosphere; some cultures were ...

Familial glomerulocystic kidney disease (GCKD) is a dominantly inherited condition characterized by glomerular cysts and variable renal size and function; the molecular genetic etiology is unknown. Mutations in the gene encoding hepatocyte nuclear factor (HNF)-1beta have been associated with early-onset diabetes and nondiabetic renal disease-particularly renal cystic disease. We investigated a possible role for the HNF-1beta gene in four unrelated GCKD families and identified mutations ...