Expression Pattern of α-Tubulin, Inversin and Its Target Dishevelled-1 and Morphology of Primary Cilia in Normal Human Kidney Development and Diseases.

The spatiotemporal expression of α-tubulin, inversin and dishevelled-1 (DVL-1) proteins associated with the Wnt-signaling pathway, and primary cilia morphology were analyzed in developing kidneys (14th-38th developmental weeks), healthy postnatal (1.5- and 7-years old) and pathologically changed human kidneys, including multicystic dysplastic kidneys (MCDK), focal segmental glomerulosclerosis (FSGS) and nephrotic syndrome of the Finnish type (CNF). The analysis was performed by double immunofluorescence, electron microscopy, semiquantitative and statistical methods. Cytoplasmic co-expression of α-tubulin, inversin and DVL-1 was observed in the proximal convoluted tubules (pct), distal convoluted tubules (dct) and glomeruli (g) of analyzed tissues. During kidney development, the overall expression of α-tubulin, inversin and DVL-1 decreased, while in the postnatal period slightly increased. The highest expressions of α-tubulin and inversin characterized dct and g, while high DVL-1 characterized pct. α-tubulin, inversin and DVL-1 expression pattern in MCDK, FSGS and CNF kidneys significantly differed from the healthy control. Compared to healthy kidneys, pathologically changed kidneys had dysmorphic primary cilia. Different expression dynamics of α-tubulin, inversin and DVL-1 during kidney development could indicate that switch between the canonical and noncanonical Wnt-signaling is essential for normal kidney morphogenesis. In contrast, their disturbed expression in pathological kidneys might be associated with abnormal primary cilia, leading to chronic kidney diseases.

Epidemiology of renal disease in children in the region of southern Croatia: a 10-year review of regional renal biopsy databases.

BACKGROUND: Epidemiological data on some renal diseases in children are available from world national registries of renal biopsies. However, there is no publislhed study of biopsy-proven childhood glomerulonephritis in Croatia. This report is the first review of pathohistological data covering a pediatric population over a 10-year period in the Croatian region of Dalmatia. MATERIAL/METHODS: A retrospective study was done on all renal biopsies from 65 children under 18 years of age received by the Clinical Hospital Split between 1995 and 2005. The histopathological findings were reviewed to determine the pattern of biopsy-proven glomerulonephritis. Indications for renal biopsy and clinico-pathological correlations were studied. Data on serum creatinine concentration, 24-h proteinuria, hematuria, clinical diagnosis, pathohistological diagnosis, and post-biopsy complications were collected. RESULTS: The main indications for biopsy were nephrotic syndrome (41.5%), hematuria with proteinuria (23.1%), and isolated hematuria (12.3%). The most frequent renal diseases in decreasing order were mesangioproliferative glomerulonephritis (27.7%), IgA nephropathy (13.8%), and Henoch-Schönlein nephritis (10.8%). Tubulointerstitial nephritis, focal segmental glomerulosclerosis, and endoproliferative glomerulonephritis each accounted for 6.2%. Alport syndrome, fibrillary glomerulonephritis, and minimal change diseases were each found in 4.6% of cases. Other forms of glomerulonephritis were rarely found. CONCLUSIONS: The present data represent the basis for a future Croatian Registry of Renal Biopsies and are an important contribution to the epidemiology of renal diseases in south-eastern Europe. Three cases of fibrillary glomerulonephritis in children with steroid-dependent nephrotic syndrome, not reported in other countries' registries, were also found. The importance of ultrastructural analysis of biopsy specimens is emphasized.

Variations in ATM protein expression during normal lymphoid differentiation and among B-cell-derived neoplasias.

The ataxia telangiectasia mutated (ATM) protein plays a central role in the cellular response to DNA double-strand breaks (DSBs). Developmentally programmed DSBs are restricted to cellular subsets within lymphoid tissues and we asked whether ATM expression is differentially regulated during lymphoid differentiation. We showed that immature B cells in bone marrow and immature T cells of the thymic cortex were negative or weakly ATM-positive. T cells of thymic medulla and peripheral tissues strongly expressed ATM. High levels of ATM were present in the B lymphocytes of the mantle zone and in plasma cells, while the majority of germinal center B cells were negative or weakly labeled. Therefore, ATM expression appears to be down-regulated at those stages of lymphoid development where physiological DNA DSBs occur. In B-chronic lymphocytic leukemia and mantle cell lymphoma we observed two categories: ATM-negative tumors, most likely reflecting the presence of ATM mutation, and tumors with abundant ATM expression. Most follicular center-cell lymphomas and diffuse large B-cell lymphomas, which rarely show inactivation of the ATM gene, were negative or weakly ATM-positive. Tumor cells from most cases of Hodgkin's disease were ATM-negative. Therefore, unless ATM inactivation occurs, ATM expression in lymphoid tumors is likely to reflect their cellular origin. As a result, immunostaining to identify lymphoid neoplasias with ATM inactivation might only be feasible for tumors derived from the stages where ATM is constitutively highly expressed.

Pulmonary alveolar microlithiasis in childhood: clinical and radiological follow-up.

This report describes a case of pulmonary alveolar microlithiasis that was diagnosed in an 8.5-year-old girl by high-resolution computed tomography (CT) and open lung biopsy. Presence of symptoms (productive cough, fever), their periodic occurrence (lasting up to 1 week), and comparatively long asymptomatic periods should be emphasized. Despite extensive X-ray abnormalities, tests of pulmonary interstitium involvement and exercise tests revealed normal results. A therapeutic regimen, including disodium etidronate, was administered for 18 months with no significant clinical or radiological improvement.