Loss of chromosome 16 from renal epithelial cells in humans.
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This work explores the notion that low-frequency, acquired aneuploidy may play a role in complex genetic traits such as essential hypertension. To this end, renal epithelial cells in urinary sediments and in renal cysts were examined by fluorescent in situ hybridization with DNA probes specific for the heterochromatic and centromere regions of chromosomes 16 and 1. Chromosome 16 was probed because it harbors variant genes causing monogenic hypertension. These genes have also been investigated for their role in essential hypertension. Chromosome 1 was also probed as an internal control. Higher proportions of renal epithelial cells in the urinary sediments showed monosomy of chromosome 16 than monosomy of chromosome 1 (P<0.001). We also observed in epithelial cells of renal cysts a preponderance of monosomy for chromosome 16 over monosomy for chromosome 1 (P<0.024). Low-frequency loss of heterozygosity that results from acquired monosomy of chromosome 16 and perhaps other chromosomes may contribute to expression of complex genetic traits such as essential hypertension, in which the diverse phenotypic manifestations are poorly understood. (+info)
Expression analyses and interaction with the anaphase promoting complex protein Apc2 suggest a role for inversin in primary cilia and involvement in the cell cycle.
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Homozygous inv mice lack a functional inversin protein and exhibit situs inversus plus severe cystic changes in the kidney and pancreas. Although the inversin sequence has provided few clues to its function, we and others have previously identified calmodulin as a binding partner. We now provide evidence that inversin interacts with the anaphase promoting complex protein Apc2. As expected of an Apc2 target, inversin possesses D-boxes and site-directed mutagenesis of the well-conserved D-box residues abrogates inversin-Apc2 interaction. An inversin-specific antibody reveals a dynamic expression pattern throughout the cell cycle and strong expression in the primary cilia of renal epithelium. Our data support a role for inversin in primary cilia and involvement in the cell cycle. Mutations of the proteins polaris, cystin and polycystin-2 which are expressed in renal epithelium primary cilia, lead to renal cystic changes. Aberrant cell proliferation is also involved in cyst development. The data reported here suggest that inversin may provide a link between these two mechanisms. (+info)
Function and structure in the diphenylamine-exposed kidney.
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Standard micropuncture and microdissection techniques were used to examine the function and structure of nephrons in rats whose kidneys were made cystic by dietary exposure to diphenylamine. Heterogeneity characterized the lesion, with dilation and frank cyst formation occurring in 5-30% of nephrons. Elevated intraluminal hydrostatic pressures, occurring in the absence of increased glomerular filtration or decreased net water reabsorption, were recorded in dilated, but not in nondilated nephrons. Structural studies demonstrated communication of dilated nephrons with cysts, concretions of debris within tubular lumens, evidence of extrinsic pressure by cysts on adjacent tubules, and apparent luminal narrowing of some proximal tubules. These observations were used to explain prolonged loop of Henle transit times and occasional failure to detect [3H]inulin excretion after microperfusion into dilated tubules. It was concluded that the elevated hydrostatic pressures in the dilated nephrons of diphenylamine-exposed kidneys were the consequence of variably severe and frequently incomplete tubular occlusion. These findings support the hypothesis that cyst formation is a consequence of partial obstruction and elevated intratubular pressure in this model and perhaps in other susceptible mammalian kidneys. (+info)
Steroid-induced polycystic kidneys in the newborn rat.
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The ability of prednisolone, prednisolone tertiary butyl acetate, and tertiary butyl acetate to induce cysts in the kidneys of 8-day-old rats has been examined following single intramuscular injection of the chemicals into newborn rats. The results indicate that only prednisolone tertiary butyl acetate-treated rats developed cysts to any marked extent. The daily injection of potassium chloride (from Day 2 to Day 7) into the prednisolone tertiary butyl acetate-treated rats prevented the formation of cysts. Similar injection of potassium bicarbonate failed to provide protection. Serum and urine electrolyte (potassium, sodium, and chloride) concentrations were also studied on the day of necropsy. The steroid-treated rats did not develop the hypokalemia observed by previous workers. Changes in electrolyte concentrations were noted in a number of instances, but these could not be causally related to cyst formation. (+info)
Hypertensive retinopathy in a cat.
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A 12-year-old cat presented for sudden blindness was diagnosed with hypertensive retinopathy on the basis of ophthalmologic and ultrasonic examination. Renal failure due to a large intranephric cyst obstructing the right ureter and renal artery was the suggested cause of the systemic hypertension. The cat died 8 hours after unilateral nephrectomy. (+info)
Extended field-of-view sonography: advantages in abdominal applications.
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OBJECTIVE: To show the advantages of extended field-of-view sonography in abdominal applications. METHODS: Thirty-one cases were prospectively analyzed in our study. Extended field-of-view images were obtained when the radiologist decided that they would offer potential advantages for the examination. When extended field-of-view scanning was used, the radiologist determined prospectively whether it was useful according to several categories. Images were obtained with a 2- to 5-MHz curved array transducer or 4- to 9- and 5- to 12-MHz linear array transducers. RESULTS: Extended field-of-view sonography provided several potential benefits over conventional sonography in the abdominal area. The advantages of extended field-of-view sonography were better demonstration of the spatial relationship between lesions and adjacent normal structures in 18 cases (58%), accurate quantification of sizes or volumes of large organs or lesions in 16 (52%), better display of the extended and tubular structures in 6 (19%), usefulness for clinical consultations in 7 (23%), and documentation comparable with that of computed tomography or magnetic resonance imaging in 10 (32%). CONCLUSIONS: Extended field-of-view sonography provided the anatomic context of the lesion in its surroundings and allowed precise measurement and tracing of the extended and tubular structures. The method has notable advantages and clinical applications. (+info)
Mutations in INVS encoding inversin cause nephronophthisis type 2, linking renal cystic disease to the function of primary cilia and left-right axis determination.
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Nephronophthisis (NPHP), an autosomal recessive cystic kidney disease, leads to chronic renal failure in children. The genes mutated in NPHP1 and NPHP4 have been identified, and a gene locus associated with infantile nephronophthisis (NPHP2) was mapped. The kidney phenotype of NPHP2 combines clinical features of NPHP and polycystic kidney disease (PKD). Here, we identify inversin (INVS) as the gene mutated in NPHP2 with and without situs inversus. We show molecular interaction of inversin with nephrocystin, the product of the gene mutated in NPHP1 and interaction of nephrocystin with beta-tubulin, a main component of primary cilia. We show that nephrocystin, inversin and beta-tubulin colocalize to primary cilia of renal tubular cells. Furthermore, we produce a PKD-like renal cystic phenotype and randomization of heart looping by knockdown of invs expression in zebrafish. The interaction and colocalization in cilia of inversin, nephrocystin and beta-tubulin connect pathogenetic aspects of NPHP to PKD, to primary cilia function and to left-right axis determination. (+info)
Description, nomenclature, and mapping of a novel cerebello-renal syndrome with the molar tooth malformation.
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Cerebello-oculo-renal syndromes (CORSs) and Joubert syndrome (JS) are clinically and genetically heterogeneous autosomal recessive syndromes that share a complex neuroradiological malformation resembling a molar tooth on brain axial images, a condition referred to as "molar tooth on imaging" (MTI) or the "molar tooth sign." The current literature on these syndromes is complex, with overlapping and incomplete phenotypes that complicate the selection of clinically homogeneous cases for genetic purposes. So far, only one locus (JBTS1 on 9q34) has been mapped, in two families with JS. Here, we describe a large consanguineous family with JS and nephronophthisis, representing a novel cerebello-renal phenotype. We have mapped this condition to the pericentromeric region of chromosome 11 and have named the locus "CORS2." The acronym "CORS" is proposed for all loci associated with JS, CORSs, and related phenotypes sharing the MTI, because this neuroradiological sign seems to be the unifying feature of these clinically heterogeneous syndromes. (+info)