Biomedical subjects

I Ariel

Publications and source records attributed to I Ariel.

98 records · Page 6Linked to original sources

PubMedDate not supplied

Renal pathology in WAGR syndrome.

The Wilms' tumor-aniridia-genital anomalies-mental retardation (WAGR) syndrome is associated with an increased risk for developing Wilms' tumor. A right nephrectomy was performed following the diagnosis of Wilms' tumor in a 2-year-old girl with WAGR syndrome and chromosome 11, del 11p13. Pathologic examination revealed intralobar nephrogenic rests and a peripelvic multicystic mass, sharply delineated from the adjacent typical intralobar nephrogenic rests and renal parenchyma, which may represent a cystic Wilms' tumor (cystic partially differentiated nephroblastoma). We studied the expression of the H19 gene by in-situ hybridization performed on paraffin sections of the kidney. H19 is an imprinted maternally-expressed gene that is not translated to protein and functions as a regulatory RNA molecule. It is tightly linked with the paternally-imprinted gene of insulin-like growth factor 2. While IGF2 presumably plays a role in tumorigenesis of Wilms' tumor, H19 is not expressed in the majority of Wilms' tumors. The expression of H19 in the intralobar nephrogenic rests was found to be prominent in the component of the blastema and markedly reduced with differentiation to tubular structures similar to the fetal kidney. The differential diagnosis of hyperplastic intralobar nephrogenic rests from a small Wilms' tumor arising in intralobar nephrogenic rests is difficult. Complete understanding of the chain of molecular events occurring in the evolution of Wilms' tumors may lead to the development of tumor markers to be used on paraffin sections and so help in the differential diagnosis of hyperplasia versus malignant transformation.

Child, Preschool↗

PubMedDate not supplied

H19 and IGF2 gene expression in human normal, hyperplastic, and malignant endometrium.

We examined H19 and insulin-like growth factor 2 (IGF2) gene expression in normal endometrium (12 cases), hyperplasia (27 cases), and cancer (27 cases) by non-radioactive in situ hybridization. H19 was not expressed in the epithelium of normal endometrium, but its frequency of expression was 15% in hyperplastic and 60% in neoplastic epithelium. In stroma cells, H19 frequency of expression was 75% in normal endometrium, 55% in hyperplasia, and 37% in carcinoma. According to the grade of endometrial cancer cell differentiation, H19 showed increased frequency and level of expression in the epithelium from well to moderately and poorly differentiated tissues. Our results indicate that H19 expression in epithelial cells of endometrial hyperplasia and cancer merits further investigation and could be useful as a complementary histopathologic and prognostic marker among other modalities in endometrial cancer. IGF2 expression did not appear useful for diagnostic or prognostic purposes.

Case-Control Studies↗

PubMedDate not supplied

High levels of maternal serum human chorionic gonadotropin in Down syndrome pregnancies: the possible role of a transcription factor on chromosome 21.

Increased levels of human chorionic gonadotropin (hCG) are used as markers for Down syndrome (DS) screening of low-risk populations. The pathophysiology for increased hCG levels remains unknown. In general, hCG synthesis is limited by the rate of beta-chain formation. In the placenta, 2 of a total of 6 hCG beta-genes are expressed. We hypothesized that in DS, a transcriptional factor may upregulate beta-chain transcription by interacting with the beta5-promoter. Primary cell cultures of skin fibroblasts from both normal and DS midtrimester fetuses were established and transfected with the beta5-promoter linked to the chloramphenicol-acetyl-transferase reporter gene. The chloramphenicol-acetyl-transferase activity was measured. Three of six DS-derived cell cultures showed a three-fold increase in acetylation. The increase in hCG promoter activity in DS-derived fibroblasts suggests a possible role for a transcriptional factor located on the human chromosome 21 by either directly or indirectly interacting with the beta5-promoter.

Biomarkers↗

PubMedDate not supplied

Synaptogenesis and myopathy under acetylcholinesterase overexpression.

Environmental, congenital, and acquired immunological insults perturbing neuromuscular junction (NMJ) activity may induce a variety of debilitating neuromuscular pathologies. However, the molecular elements linking NMJ dysfunction to long-term myopathies are unknown. Here, we report dramatically elevated levels of mRNA encoding c-Fos and the "readthrough" (R) variant of acetylcholinesterase (AChE) in muscles of transgenic mice overexpressing synaptic (S) AChE in motoneurons and in control mice treated with the irreversible cholinesterase inhibitor diisopropylfluorophosphonate (DFP). Tongue muscles from DFP-treated and AChE-S transgenic mice displayed exaggerated neurite branching and disorganized, wasting fibers. Moreover, diaphragm muscles from both transgenic and DFP-treated mice exhibited NMJ proliferation. 2'-O-methyl-protected antisense oligonucleotides targeted to AChE mRNA suppressed feedback upregulation of AChE and ameliorated DFP-induced NMJ proliferation. Our findings demonstrate common transcriptional responses to cholinergic NMJ stress of diverse origin, and implicate deregulated AChE expression in excessive neurite outgrowth, uncontrolled synaptogenesis, and myopathology.

Acetylcholinesterase↗

PubMedDate not supplied

Streptococcus viridans infections in midgestation.

During a 14-year period Streptococcus viridans was isolated at autopsy from 18 neonates or stillborn fetuses delivered in midgestation (18-28 weeks) at Women & Infants' Hospital in Providence, Rhode Island. Evidence of swallowed and/or aspirated, infected amniotic fluid by the fetus was found in 16 of 18 cases along with chorioamnionitis and funisitis. Of the 18 cases, maternal infection was documented in 6 cases; delivery was preceded by spontaneous rupture of membranes in 9 cases and vaginal bleeding in 7 cases. Poor maternal obstetric history was indicated by only 12 living children from 42 total pregnancies in the 12 multigravidas in the study. It is concluded that S. viridans may have a significant role in the pathogenesis of second trimester amniotic fluid infections with abortions and fetal and neonatal sepsis.

Chorioamnionitis↗

PubMedDate not supplied

The urinary system in Down syndrome: a study of 124 autopsy cases.

We examined 124 autopsy cases of Down syndrome for the presence of renal and urinary tract abnormalities. The cases were divided into three groups: (I) fetuses of 16-22 weeks gestation (n = 18), (II) stillborns or newborns who died on the first day of life (n = 9), and (III) Down patients 1 day to 25 years of age (n = 97). Kidney weight was reduced by a mean of 14.4% compared with expected values. Renal hypoplasia, defined as kidney weight less than two-thirds expected, was found in 18 cases. Glomerular microcysts were found in 23 of 97 cases in group III. Focal dilatation of tubules was found in 10, simple cysts in 7, and immature glomeruli deep in the renal cortex in 18 cases. Obstructive uropathy occurred in 2 of 18 (11.1%) in group I, 2 of 9 (22.2%) in group II, and 4 of 97 (4.1%) in group III. Obstructive uropathy with bilateral cystic dysplastic kidneys resulted in Potter's sequence. We suggest that obstructive uropathy is associated with Down syndrome. When severe, it results in Potter's sequence and an early perinatal death. A chromosomal analysis is recommended in any case of obstructive uropathy in the fetal or neonatal period.

Adolescent↗

PubMedDate not supplied

Familial renal tubular dysgenesis: a disorder not isolated to proximal convoluted tubules.

The autopsy findings of a newborn with renal tubular dysgenesis, born to first cousins of Moslim Arab descent, are described. Hypocalvaria and hyperflexible joints were noted in addition to the renal lesion. A microdissection study demonstrated marked shortening of all the nephron segments from the glomeruli to the collecting tubules, rather than an isolated abnormality of the proximal convoluted tubules.

Consanguinity↗

PubMedDate not supplied

Frequent apoptosis in human kidneys after acute renal hypoperfusion.

BACKGROUND/AIMS: Apoptosis, a form of cell death characterized by DNA fragmentation and minimal inflammation, is induced by intrarenal hypoxia in rats. The objective of this study was to test whether apoptosis participates in human acute renal injury. METHODS: We examined kidneys obtained from autopsies of 40 patients following hemodynamic compromise and from 9 controls following sudden death. Nuclear DNA fragmentation was assayed by in situ 3' end labeling (TUNEL stain) and compared to histological findings. RESULTS: DNA fragmentation along renal tubular cells was observed in 23 (57%) of the study patients but in none of the controls (p < 0.005). Acute tubular necrosis was seen by formal histology in 27% of the patients and correlated with clinical acute renal dysfunction, while DNA fragmentation did not. CONCLUSION: DNA fragmentation often occurs after renal hypoperfusion and does not imply renal failure. Apoptosis may participate in the adaptive response of the kidney to hypoxia.

Acute Kidney Injury↗