Comparative immunohistochemical study of multicystic dysplastic kidneys with and without obstruction.

Etiology of multicystic dysplastic kidney (MCDK) remains unknown. Not all cases are associated with obstruction. We compared by immunohistochemistry 17 cases of MCDK (10 cases with and seven without obstruction) to 17 controls and 20 fetal kidneys. TGF-ß was negative in obstructive MCDKs and positive in nonobstructive MCDK. IGF2 was overexpressed in obstructive and underexpressed in nonobstructive MCDKs. PAX2, BCL-2, and ß-catenin were expressed equally in obstructive and nonobstructive dysplasia. TGF-ß and IGF2 work by different mechanisms in obstructive and nonobstructive MCDKs, but there are no differences among PAX 2, BCL-2, and ß-catenin in obstructive versus nonobstructive dysplasia.

Differential changes in TGF-ß/BMP signaling pathway in the right ventricular myocardium of newborns with hypoplastic left heart syndrome.

BACKGROUND: Hypoplastic left heart syndrome (HLHS) is characterized by underdevelopment of the left ventricle (LV) and increased biomechanical stress on the right ventricle (RV) from single ventricle physiology. Despite the clinical significance, the signaling pathways active during RV remodeling and disease progression are not known. To address this, we examined differential changes in expression of genes associated with transforming growth factor-beta (TGF-beta)/bone morphogenetic protein (BMP) signaling in RV tissue isolated from HLHS patients relative to RV and LV tissue from control subjects. METHODS AND RESULTS: Quantitative real-time polymerase chain reaction was used to detect changes in expression of 84 genes involved in TGF-beta/BMP-mediated cardiac development, cell growth, and differentiation in RV tissue collected from 6 neonates with HLHS undergoing stage 1 Norwood procedure (age, 1-7 days; mean, 4 days) and RV and LV tissue obtained from 5 infants with noncardiac pathology (age range, 1-135 days: mean, 85 days) that served as controls. Analysis of gene expression profiles between control-LV and control-RV revealed significant depression of TGF-beta/BMP signaling in RV compared with LV. Of the 84 genes analyzed, 38 were differentially expressed between HLHS-RV and control-RV, whereas only 22 compared with control-LV. Significant changes were observed in: tissue remodeling genes including Activin receptor type IIA (ACVR2A) (+2.13) and Activin receptor-like kinase 1 (ACVRL1) (+2.22); and cell survival, growth, and differentiation genes including CDC25A (+2.18), p21 (-3.64), p15 (+2.15), BMP5 (+4.58), BMP3 (+2.16), GDF3 (+8.59), NODAL (+2.32), and BMP binding endothelial regulator (BMPER) (+4.58). The most significant changes common to HLHS-RV versus control-RV and control-LV sample groups is observed for Anti müllerian hormone receptor 2 (AMHR2) (+18.79 control-RV, +3.38 control-LV), and the BMP antagonist Inhibin alpha (INHA) (+11.47 control-RV, +5.73 control-LV). CONCLUSIONS: Although this descriptive study does not allow cause-effect inferences, our results suggest changes in cardiac development pathways and upregulation of genes associated with cell growth and differentiation in the neonatal RV of children with HLHS. These molecular profiles are more closely related to those observed in the normal LV rather than normal RV at similar maturational age. This work provides the basis for future mechanistic studies to elucidate the molecular mechanisms regulating RV remodeling in HLHS.

Intestinal candidiasis: an uncommon cause of necrotizing enterocolitis (NEC) in neonates.

Candida albicans produces intestinal perforation and necrotizing enterocolitis (NEC) in preterm newborns. We reviewed pathology files in neonates with a diagnosis of NEC (10-year period), gathered history, and reviewed histological materials. Of 249 autopsies, two (0.8%) had systemic candidiasis. From 66 surgical cases with a diagnosis of NEC, five cases (7.5%) had intestinal candidiasis. Candida albicans grew in pre- and post-mortem blood, lung, or peritoneal fluid in all cases. Histologically, the small bowel revealed fungi, sometimes intravascular. Systemic candidiasis with intestinal involvement is an important complication of prematurity and a prevalent cause of sepsis. The presence of intraluminal fungi with associated vascular occlusion may lead to bowel ischemia, necrosis, and perforation.