Enhancer-bound LDB1 regulates a corticotrope promoter-pausing repression program.

Substantial evidence supports the hypothesis that enhancers are critical regulators of cell-type determination, orchestrating both positive and negative transcriptional programs; however, the basic mechanisms by which enhancers orchestrate interactions with cognate promoters during activation and repression events remain incompletely understood. Here we report the required actions of LIM domain-binding protein 1 (LDB1)/cofactor of LIM homeodomain protein 2/nuclear LIM interactor, interacting with the enhancer-binding protein achaete-scute complex homolog 1, to mediate looping to target gene promoters and target gene regulation in corticotrope cells. LDB1-mediated enhancer:promoter looping appears to be required for both activation and repression of these target genes. Although LDB1-dependent activated genes are regulated at the level of transcriptional initiation, the LDB1-dependent repressed transcription units appear to be regulated primarily at the level of promoter pausing, with LDB1 regulating recruitment of metastasis-associated 1 family, member 2, a component of the nucleosome remodeling deacetylase complex, on these negative enhancers, required for the repressive enhancer function. These results indicate that LDB1-dependent looping events can deliver repressive cargo to cognate promoters to mediate promoter pausing events in a pituitary cell type.

Genetic control of pituitary development and hypopituitarism.

The pituitary gland functions as a relay between the hypothalamus and peripheral target organs that regulate basic physiological functions, including growth, the stress response, reproduction, metabolism and lactation. The development of the pituitary gland has been studied extensively in mice, and has begun to be explored in zebrafish, an animal model system amenable to forward genetics. Multiple signaling molecules and transcription factors, expressed in overlapping but distinct spatial and temporal patterns, are required at various stages of pituitary development. Defects in this precisely regulated genetic program lead to diverse pituitary dysfunction. The animal models have greatly enhanced our understanding of molecular mechanisms underlying pituitary development in addition to congenital pituitary disorders in humans.

Outcome of prenatally diagnosed fetal hydronephrosis.

OBJECTIVE: To demonstrate the postnatal investigation, treatment and outcome of infants with hydronephrosis prenatally diagnosed by ultrasound between 1994 and 1996. STUDY DESIGN: In a two-year period we studied 20 infants who presented with hydronephrosis diagnosed by prenatal ultrasound and confirmed by postnatal ultrasound. Unilateral hydronephrosis was diagnosed in 17 infants and bilateral hydronephrosis in 3. An anteroposterior renal pelvic diameter > 7 mm after 33 weeks of pregnancy was used to predict abnormal outcomes. In the postnatal follow-up period, the infants were followed with sequential ultrasound and urinalysis. 99mTc-diethylene triamine pentaacetic acid scan, intravenous pyelography and voiding cystourethrography were performed in selected cases. Pyeloplasty was performed only if there was evidence of renal compromise. RESULTS: A male predilection was found. The left kidney was more commonly involved. Ultrasonic follow-up of the 20 infants showed that hydronephrosis resolved in 9, who were all in the unilateral hydronephrosis group. The range of fetal renal pelves on prenatal ultrasound was 7-15 mm in the resolution group. Pyeloplasty was performed in three unilateral hydronephrosis infants. Follow-up ranged from 36 to 72 months. CONCLUSION: When the fetal renal pelvis was < 15 mm on prenatal ultrasound, it never progressed. Prenatally diagnosed hydronephrosis may be safely observed, and surgical correction should be performed only if renal compromise occurs.

A highly luminescent spiro-anthracenone-based organic light-emitting diode exhibiting thermally activated delayed fluorescence.

Efficient thermally activated delayed fluorescence was observed from a spiro-anthracenone derivative (ACRSA). An organic light-emitting diode containing ACRSA exhibited blue-greenish electroluminescence with a maximum external quantum efficiency of 16.5%.

Antibiotic resistance patterns of community-acquired urinary tract infections in children with vesicoureteral reflux receiving prophylactic antibiotic therapy.

OBJECTIVE: The goal was to examine bacterial antimicrobial resistance of recurrent urinary tract infections in children receiving antibiotic prophylaxis because of primary vesicoureteral reflux. METHODS: We reviewed data retrospectively for children with documented vesicoureteral reflux in 2 hospitals during a 5-year follow-up period. The patients were receiving co-trimoxazole, cephalexin, or cefaclor prophylaxis or prophylaxis with a sequence of different antibiotics (alternative monotherapy). Demographic data, degree of vesicoureteral reflux, prophylactic antibiotics prescribed, and antibiotic sensitivity results of first urinary tract infections and breakthrough urinary tract infections were recorded. RESULTS: Three hundred twenty-four patients underwent antibiotic prophylaxis (109 with co-trimoxazole, 100 with cephalexin, 44 with cefaclor, and 71 with alternative monotherapy) in one hospital and 96 children underwent co-trimoxazole prophylaxis in the other hospital. Breakthrough urinary tract infections occurred in patients from both hospitals (20.4% and 25%, respectively). Escherichia coli infection was significantly less common in children receiving antibiotic prophylaxis, compared with their initial episodes of urinary tract infection, at both hospitals. Children receiving cephalosporin prophylaxis were more likely to have an extended-spectrum beta-lactamase-producing organism for breakthrough urinary tract infections, compared with children with co-trimoxazole prophylaxis. Antimicrobial susceptibilities to almost all antibiotics decreased with cephalosporin prophylaxis when recurrent urinary tract infections developed. The extent of decreased susceptibilities was also severe for prophylaxis with a sequence of different antibiotics. However, antimicrobial susceptibilities decreased minimally in co-trimoxazole prophylaxis groups. CONCLUSIONS: Children receiving cephalosporin prophylaxis are more likely to have extended-spectrum beta-lactamase-producing bacteria or multidrug-resistant uropathogens other than E coli for breakthrough urinary tract infections; therefore, these antibiotics are not appropriate for prophylactic use in patients with vesicoureteral reflux. Co-trimoxazole remains the preferred prophylactic agent for vesicoureteral reflux.

Ureteral reimplantation for vesicoureteral reflux: comparison of minimally invasive extravesical with transvesical and conventional extravesical techniques.

OBJECTIVES: To analyze and compare the different ureteral reimplantation techniques to clarify the decision making for surgical treatment of vesicoureteral reflux. METHODS: From July 1995 to December 2000, 218 patients underwent antireflux surgery. The first 92 cases (143 ureters) were performed with the transvesical technique of Cohen (group 1), the next 37 cases (49 ureters) with the conventional extravesical technique (group 2), and the last 89 cases (113 ureters) with the new minimally invasive technique (group 3). The surgical time, length of hospital stay, postoperative side effects, frequency of pain control, and voiding cystogram findings to ensure the cessation of reflux for all patients were retrospectively analyzed. RESULTS: The success rates were similar among the different procedures. All patients in group 1 required a suprapubic cystostomy, and three had blood clot retention. Four patients in group 2 had bladder inefficiency. The surgical time ranged from 139 to 181 minutes in group 1, 58 to 94 minutes in group 2, and 40 to 61 minutes in group 3. The length of hospital stay ranged from 2.8 to 5.5 days in groups 1 and 2, and no hospital stay was needed in group 3. The frequency of analgesic administration was significantly less in group 2 compared with group 1; however, no analgesia was required in group 3. CONCLUSIONS: The results from our comparison show that the minimally invasive technique can be used as a simple and highly effective interventional procedure with less morbidity for the patient.

Poststreptococcal glomerulonephritis with pulmonary edema presenting as respiratory distress.

Acute poststreptococcal glomerulonephritis(PSGN) is characterized by an abrupt onset of edema,hypertension, and hematuria. Although the association of pulmonary edema with acute glomerulonephritis has been established, it is uncommon for children with PSGN to present with respiratory distress due to pulmonary edema. We encountered six such patients, aged 6-10 years, during a 10-month period. The demographic data, clinical manifestations, laboratory data, radiographic pictures, and clinical courses were collected. All patients presented to the primary pediatricians with dyspnea and alveolar infiltrates with bilateral pleural effusions on plain chest radiographs that were misinterpreted as pneumonia initially. The diagnosis of PSGN was de-layed until the awareness of the presence of pulmonary edema complicating PSGN. Subsequent urinalysis and blood pressure measurement all showed microscopic hematuria and hypertension. Elevated serum antistreptolysin 0 titers and depressed serum complement C3 levels confirmed the diagnosis of PSGN. Two patients progressed to respiratory failure because of a delayed diagnosis of PSGN. All patients recovered without sequelae following appropriate diuresis and antihypertensive therapy. We conclude that in preschool and school-age children who present with dyspneic respirations and a chest radiograph showing radiographic features of pulmonary edema, proper evaluation including blood pressure recording and urinalysis should be performed immediately. Prompt diagnosis and early therapy of PSGNmay avoid mortality and unnecessary therapeutic intervention.

Acute myeloid leukemia complicated with staghorn calculus.

An 11-year-old girl who presented with hyperleukocytosis accompanied by significant increases in serum uric acid and lactate dehydrogenase levels was discovered to be suffering from acute myeloid leukemia (AML). Subsequently a staghorn calculus was identified 22 months after the start of chemotherapy. The diagnosis of staghorn calculi was suggested by plain abdominal X-ray and ultrasonography. This paper describes the course of an adolescent patient with AML and focuses specifically upon her urological complications. To the best of our knowledge, this is the first reported pediatric case of AML complicated with staghorn calculi, which developed following repeated episodes of septicemia.

Identification of a Wnt/Dvl/beta-Catenin --> Pitx2 pathway mediating cell-type-specific proliferation during development.

Understanding the cell type-specific molecular mechanisms by which distinct signaling pathways combinatorially control proliferation during organogenesis is a central issue in development and disease. Here, we report that the bicoid-related transcription factor Pitx2 is rapidly induced by the Wnt/Dvl/beta-catenin pathway and is required for effective cell-type-specific proliferation by directly activating specific growth-regulating genes. Regulated exchange of HDAC1/beta-catenin converts Pitx2 from repressor to activator, analogous to control of TCF/LEF1. Pitx2 then serves as a competence factor required for the temporally ordered and growth factor-dependent recruitment of a series of specific coactivator complexes that prove necessary for Cyclin D2 gene induction. The molecular strategy underlying interactions between the Wnt and growth factor-dependent signaling pathways in cardiac outflow tract and pituitary proliferation is likely to be prototypic of cell-specific proliferation strategies in other tissues.