Deletion 2q37: an identifiable clinical syndrome with mental retardation and autism

Terminal deletion of the long arm of chromosome 2 is a rare chromosomal disorder characterized by low birth weight, delayed somatic and mental development, craniofacial defects, short neck, heart and lung congenital defects, and autistic features. We report on a girl with 46,XX.ish del(2)(q37.1) de novo karyotype, mental retardation, dysmorphic features, gastrointestinal anomalies, and autistic traits and compare her clinical manifestations with patients with the same deletion previously described in literature.     

Gene expression profiling of childhood adrenocortical tumors

Pediatric adrenocortical tumors (ACT) are rare and often fatal malignancies; little is known regarding their etiology and biology. To provide additional insight into the nature of ACT, we determined the gene expression profiles of 24 pediatric tumors (five adenomas, 18 carcinomas, and one undetermined) and seven normal adrenal glands. Distinct patterns of gene expression, validated by quantitative real-time PCR and Western blot analysis, were identified that distinguish normal adrenal cortex from tumor. Differences in gene expression were also identified between adrenocortical adenomas and carcinomas. In addition, pediatric adrenocortical carcinomas were found to share similar patterns of gene expression when compared with those published for adult ACT. This study represents the first microarray analysis of childhood ACT. Our findings lay the groundwork for establishing gene expression profiles that may aid in the diagnosis and prognosis of pediatric ACT, and in the identification of signaling pathways that contribute to this disease.     

Evolution of the endoplasmic reticulum during spermiogenesis of the rooster: An electron microscopic study

The endoplasmic reticulum (ER) of rooster's spermatids was analyzed during spermiogenesis, which was subdivided into eight distinct steps on the basis of changes observed with the electron microscope in the nucleus, acrosome-perforatorium system, manchette, and flagellum. In steps 1 and 2, spermatids' ER cisternae presented the following specializations: (1) A loose network of tubular cisternae was distributed throughout the cytoplasm. (2) Six to eight tight networks of anastomosed tubular cisternae parallel to each other were closely stacked to form a discoid body (1.5–2.5 μm in diameter and 0.5–0.8-μm thick) in which spheroidal vesicles (0.4 μm in diameter) were inserted. Close to and connected with this body, called the alveolar body, there was a stack of annulate lamellae. (3) Large, flattened ER cisternae were seen singly or in piles of two or three running parallel to the nuclear surface. (4) A collection of tubular ER cisternae faced plaques of thickened plasma membranes. These elements of the ER system appear continuous with each other. During steps 3–5 of spermiogenesis, no modification of the alveolar body-annulate lamellae complex was noted; the large flattened ER cisternae disappeared, however, and the broad network of tubular cisternae developed markedly. During steps 6 and 7, the latter network of tubular cisternae fragmented into vesicles that swelled to give a vacuolated appearance to the cytoplasm. The alveolar body-annulate lamellae complex remained visible until late step 7, when it disintegrated just before spermiation. Thus the system of ER cisternae underwent marked structural modifications during spermiogenesis.     

Natural paniceins from mediterranean sponge inhibit the multidrug resistance activity of Patched and increase chemotherapy efficiency on melanoma cells

Multidrug resistance has appeared to mitigate the efficiency of anticancer drugs and the possibility of successful cancer chemotherapy. The Hedgehog receptor Patched is a multidrug transporter expressed in several cancers and as such it represents a new target to circumvent chemotherapy resistance. We report herein that paniceins and especially panicein A hydroquinone, natural meroterpenoids produced by the Mediterranean sponge Haliclona (Soestella) mucosa, inhibit the doxorubicin efflux activity of Patched and enhance the cytotoxicity of this chemotherapeutic agent on melanoma cells in vitro. These results are supported by the molecular docking performed on the structure of the bacterial drug efflux pump AcrB and on the Patched model built from AcrB structure. Docking calculations show that panicein A hydroquinone interacts with AcrB and Patched model close to the doxorubicin binding site. This compound thus appears as the first antagonist of the doxorubicin efflux activity of Patched. The use of inhibitors of Patched drug efflux activity in combination with classical chemotherapy could represent a novel approach to reduce tumor drug resistance, recurrence and metastasis.     

Amplification of the steroidogenic factor 1 gene in childhood adrenocortical tumors

Southern Brazil has one of the highest incidences of childhood adrenocortical tumors (ACTs), occurring 10-15 times more frequently than worldwide estimates. The reasons for this increase remain elusive. In an attempt to further characterize the genetic changes in childhood ACTs, we recently detected a consistent gain of 9q (or a portion of it) in eight of nine cases of pediatric ACTs and amplification of 9q34 in the majority of these cases using comparative genomic hybridization. Other studies involving both childhood and adult ACTs have corroborated these findings. To follow up on these results, we examined whether the steroidogenic factor 1 (SF-1) gene, which is located in this chromosomal region and plays an important role in the development and function of the adrenal cortex is amplified in these ACT cases. We detected increased copy number of the SF-1 gene in all eight cases with 9q gain, suggesting an association between an increased copy number of the SF-1 gene and adrenocortical tumorigenesis.     

Increased gait variability in diabetes mellitus patients with neuropathic pain

AimsGait dysfunction in subjects with diabetes mellitus (DM) contributes to falling and subsequent injuries. Using a portable device (GaitMeter^TM), we measured gait parameters in DM patients with and without diabetic peripheral neuropathy (DPN) during flat surface walking. We hypothesized that DM patients with DPN and neuropathic pain (NeP) would have greater gait step variability than those with DPN without NeP.MethodsSubjects with DPN and at least moderate NeP (DPN-P), DPN without NeP (DPN-NoP), DM without DPN, and control subjects without DM were assessed. Our outcome measure was gait variability for step length and velocity. DPN severity was quantified using the Toronto Clinical Scoring System and the Utah Early Neuropathy Score. Falls and their outcomes were retrospectively quantified.ResultsEach cohort contained ≥ 20 subjects. Durations of DM and HbA1C were greatest amongst DPN cohorts. DPN-P participants had greater variability of step length and step velocity, except for DM only participants. DPN-P participants also reported greater risk of hospitalizations for fall-related injuries, and greater fear of falling. Modest negative relationships emerged for step length with step velocity, reported falls and pain severity.ConclusionsNeP contributes to gait variability, potentially contributing to the risk of falling in DM patients.     

Latest advances in diagnostic urologic radiology

Magnification renal arteriography results in a moderate degree of improvement in its diagnostic accuracy. The differential diagnosis of cyst versus tumor can be made with great accuracy. Various parenchymal renal diseases can be identified and staged so that accurate prognoses can be made. Technical advances in x-ray tubes and electronic imaging systems will result in angiograms of higher resolution and further improve the accuracy of magnification arteriography.