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Stuart B Bauer

Publications and source records attributed to Stuart B Bauer.

6 recordsLinked to original sources
PubMed2025

Trio exome sequencing identifies de novo variants in novel candidate genes in 19.62% of CAKUT families.

PURPOSE: Congenital anomalies of the kidney and urinary tract (CAKUT) encompass heterogenous malformations arising from defective nephrogenesis. To date, approximately 50 monogenic genes are known to cause CAKUT if mutated. Recent studies show the impact of de novo variants in genetic disease etiology. Trio exome sequencing identifies de novo variants in novel candidate genes in 19.62% of CAKUT families. METHODS: We performed trio-based exome sequencing in 209 families with CAKUT to detect novel candidate disease genes. RESULTS: Trio analysis yielded in the identification of CAKUT candidate genes in 96 of 209 trio families (45.93%). In 41 of 209 cases, we detected strong de novo variants in 45 potential novel CAKUT candidate genes (19.62%). We developed a prioritization approach that highlights a truncating de novo variant in SOX13 (HGNC:11192) as a promising cause for CAKUT. In addition, further allele carriers for the candidate gene CHD1L (HGNC:1916) were identified, thus supporting the role of CHD1L in the pathogenesis of CAKUT. CONCLUSION: We conclude that de novo variants in potential novel CAKUT candidate genes contribute to the disease etiology and present SOX13 as a potential novel cause for CAKUT.

Humans↗
PubMed2003

Fibroepithelial polyps causing ureteropelvic junction obstruction in children.

PURPOSE: Fibroepithelial polyps are benign mucosal projections that can be found throughout the urinary system. We review our experience with fibroepithelial polyps of the ureteropelvic junction in children to define more clearly this entity and its outcome following treatment. METHODS: We reviewed the records of all children with fibroepithelial polyps causing ureteropelvic junction obstruction treated at our institution between December 1967 and February 2002. RESULTS: Nine patients 6 weeks to 9 years old had 11 ureteropelvic junction obstructions secondary to fibroepithelial polyps, representing a 0.5% incidence of all ureteropelvic junction obstructions seen during that period. The majority of the patients were male (89%) and had obstruction on the left side (78%). Only 22% of the patients had a diagnosis of obstructing polyps suggested preoperatively. All patients underwent dismembered pyeloplasty but 1 required subsequent nephrectomy due to progressive loss of renal function. All lesions were characterized microscopically by polypoid projections of fibrous tissue covered by epithelium and demonstrating varying degrees of inflammation. No recurrences were seen during a mean followup of 44 months. CONCLUSIONS: Fibroepithelial polyps are rare lesions that cause ureteropelvic junction obstruction in children, primarily in males and on the left side. Filling defects were diagnosed preoperatively in 22% of the patients in this series. Excision and dismembered pyeloplasty were curative, and recurrences were not observed. The etiology of this disease remains obscure.

Child↗
PubMed2003

Signaling through PI3K/Akt mediates stretch and PDGF-BB-dependent DNA synthesis in bladder smooth muscle cells.

PURPOSE: Smooth muscle cells (SMC) of the bladder undergo hypertrophy and hyperplasia following exposure to sustained mechanical overload. Although superficial similarities in the response of the heart and bladder to hypertrophic stimuli suggest that similar molecular mechanisms may be involved, this remains to be demonstrated. In this study we compared signal transduction pathway activation in primary culture bladder SMC and cardiac myofibroblasts in response to cyclic stretch. The effects of growth factor stimulation on pathway activation in bladder SMC were also investigated. MATERIALS AND METHODS: Primary culture rodent bladder SMC or cardiac myofibroblasts were subjected to cyclic stretch-relaxation in the absence or presence of pharmacologic inhibitors of the phosphoinositide-3-kinase, (PI3K)/Akt, extracellular signal-regulated kinase-mitogen activated protein kinase (Erk-MAPK) or the p38 stress-activated protein kinase-2 (SAPK2) pathways. In parallel experiments human bladder SMC were treated with platelet-derived growth factor-BB (PDGF-BB), heparin-binding EGF-like growth factor (HB-EGF) or fibroblast growth factor-2 (FGF-2). In each case the extent of DNA synthesis was determined by uptake of tritiated thymidine, and activation of specific signaling intermediates was determined by immunoblot analysis using antibodies to the non-phosphorylated and phosphorylated (activated) forms of Akt, p38 and Erk1/2. RESULTS: Akt and p38 were rapidly phosphorylated in stretched bladder SMC and cardiac myofibroblasts, and stretch-induced DNA synthesis in these cells was ablated with inhibitors of PI3K or p38 but not Erk-MAPK. Similarly, PDGF-BB up-regulated DNA synthesis in bladder SMC in a p38 and Akt-dependent manner. CONCLUSIONS: We conclude that distinct stimuli, such as mechanical stretch and PDGF-BB, promote DNA synthesis in bladder SMC through shared downstream signaling pathways. Furthermore, phenotypically similar cells from the bladder and heart show comparable pathway activation in response to stretch. These findings suggest that similar molecular mechanisms underlie the altered growth responses of the bladder and heart to mechanical overload. This study also provides the first report of Akt activation in bladder SMC and suggests that Akt, consistent with its pivotal role in cardiac hypertrophy, may also be a key regulator of remodeling in the SMC compartment of the bladder exposed to hypertrophic/hyperplastic stimuli in vivo.

Animals↗
PubMed2002

Rate and predictors of spontaneous resolution of prenatally diagnosed primary nonrefluxing megaureter.

PURPOSE: We assessed clinical and ultrasound predictors of the spontaneous resolution of prenatally diagnosed, primary nonrefluxing megaureter. MATERIALS AND METHODS: Primary nonrefluxing megaureter was prenatally diagnosed in 54 neonates from 1993 to 1998, including 15 in whom it was bilateral (69 megaureters). Median followup period from birth to the last radiology examination was 25.8 months (range 2.3 to 72). RESULTS: Of the patients 10 underwent surgical repair for severe hydroureteronephrosis, including decreasing renal function on diuretic renography in 1, and an episode of bilateral obstruction and acute renal failure in 1. Hydroureteronephrosis resolved in 39 cases (72%) and persisted in 5 at 30 to 72 months of followup. Laterality, gender and retrovesical ureteral diameter had no significant effect on the resolution rate (p >0.05). Mean initial ureteral diameter in patients with resolution was less than in those without resolution and in those who underwent surgery (0.8 versus 1.15 and 1.32 cm., respectively). Presenting hydronephrosis grade was a significant predictor of the resolution rate (p = 0.03). Grades 1 to 3 hydronephrosis resolved at a median age of 12.9, 23.9 and 34.6 months, respectively (range 4.1 to 66). In patients in whom grades 4 and 5 hydronephrosis resolved the median age at resolution was 48.5 months. CONCLUSIONS: Most cases of prenatally diagnosed, primary nonrefluxing megaureter resolve spontaneously. Grades 1 to 3 hydronephrosis tend to resolve between ages 12 and 36 months. For these grades followup intervals may be progressively elongated after a pattern of improving hydronephrosis has been established. In children with grade 4 or 5 hydronephrosis, or a retrovesical ureteral diameter of greater than 1 cm. the condition may resolve slowly and require surgery.

Child↗
PubMed2002

Special considerations of the overactive bladder in children.

The overactive bladder (OAB) in children is defined as both involuntary detrusor contractions and urethral instability. The development of urinary control plays a key role in its incidence and in our understanding of its pathogenesis. It is seen in a number of conditions but by far is most common among patients with dysfunctional voiding. Urinary infection can be both a cause and an effect of OAB. In some instances, vesicoureteral reflux may result from detrusor overactivity because its successful resolution has been shown to depend on abolition of the hyperactivity. Early diagnosis and appropriate treatment can affect upper urinary tract function and drainage and ultimate bladder function. Recognition is noted via a thorough history and careful physical examination. Urodynamic assessment is indicated in neurologically normal children >5 years old and is combined with a voiding cystourethrogram in boys and a radionuclide cystogram in girls who have a history of recurrent urinary infection. Treatment consists of prophylactic use of anticholinergic agents in patients with neurologic dysfunction, as an early adjunctive measure in boys after ablation of posterior urethral valves, and in children with vesicoureteral reflux. The dose must be carefully titrated in children with cerebral palsy to prevent the appearance of elevated residual urine. Behavioral therapy and biofeedback techniques are effective alternatives to anticholinergic agents for children with dysfunctional voiding.

Adolescent↗