Generation of neuroendocrine chromaffin cells from sympathoadrenal progenitors: beyond the glucocorticoid hypothesis.
ABSTRACT The developmental diversification of neural crest-derived sympathoadrenal (SA) progenitor cells into neuroendocrine adrenal chromaffin cells and sympathetic neurons has been thought to be largely understood. Based on two decades of in vitro studies with isolated SA progenitor and chromaffin cells, it was widely assumed that chromaffin cell development crucially depends on glucocorticoid hormones provided by adrenal cortical cells. However, analysis of mice lacking the glucocorticoid receptor has revealed that the chromaffin cell phenotype develops largely normally in these mice, except for the induction of the adrenaline synthesizing enzyme phenylethylamine N-methyl transferase. In a search for novel candidate genes that might be involved in triggering the sympathetic neuron/chromaffin cell decision, we have studied putative contributions of transforming growth factor (TGF)-alpha, BMP-4, and the transcription factor MASH-1, molecules with distinct expressions in SA progenitor cells, in their migratory pathways and final destinations. TGF-beta2 and -beta3 and BMP-4 are highly expressed in the wall of the dorsal aorta and in the adrenal anlagen during and after immigration of SA progenitors but expressed at much lower levels in sympathetic ganglia. We found that neutralizing antibodies against all three TGF-beta isoforms applied to the chorionic-allantoic membrane (CAM) of quail embryos interfere with proliferation of immigrated adrenal chromaffin cells but do not affect their specific neuroendocrine ultrastructural phenotype. Grafting of noggin-producing cells to the CAM, which scavenges BMPs, interferes with visceral arch and limb development but does not overtly affect the chromaffin phenotype. The transcription factor MASH-1 promotes early differentiation of SA progenitors. Mice deficient for MASH-1 lack sympathetic ganglia, whereas the adrenal medulla previously has been reported to be present. We show here that most adrenal medullary cells in MASH-1(-/-) mice identified by Phox2b immunoreactivity lack the catecholaminergic marker tyrosine hydroxylase. More surprisingly, most cells do not contain chromaffin granules and display a neuroblast-like ultrastructure and show strongly enhanced expression of c-RET comparable to that observed in sympathetic ganglia. Together, our data suggest that TGF-betas and BMP-4 do not seem to be essential for chromaffin cell differentiation. In contrast with previous reports, however, MASH-1 apparently plays a crucial role in chromaffin cell development.
Article: Posterior semicircular canal benign paroxysmal positional vertigo presenting with torsional downbeating nystagmus: an apogeotropic variant.[show abstract] [hide abstract]
ABSTRACT: The aim of this study is to verify the hypothesis that free-floating particles could sometimes localize into the distal portion of the non ampullary arm of the posterior semicircular canal (PSC) so that assuming the Dix-Hallpike's positions, the clot could move towards the ampulla eliciting a inhibitory torsional-down beating paroxysmal positional nystagmus (PPNy), instead of typical excitatory torsional-up beating PPNy. Among 45 patients with vestibular signs suggesting anterior semicircular canal paroxysmal positional vertigo (PPV), collected from February 2003 to August 2006, we detected a group of 6 subjects whose clinical findings showed a singular behaviour during follow-up. At the first check-up, all patients were submitted to different types of physical manoeuvres for ASC canalolithiasis. Patients were controlled during the same session and after one week. When we found that nystagmus was qualitatively changed we adopted the appropriate physical therapies for that sign. At a next check-up, after having performed some physical therapies, all patients had a typical PSC PPNy of the opposite side, with respect to that of the ASC initially diagnosed. Basing on these observations we conclude that PSC PPV, similarly to lateral semicircular canal PPV, could manifests in a apogeotropic variant.International Journal of Otolaryngology 01/2012; 2012:413603.
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ABSTRACT: Benign paroxysmal positional vertigo (BPPV) is a mechanical peripheral vestibular disorder which may involve any of the three semicircular canals but principally the posterior. In as much as the literature has described theories to explain the mechanism of BPPV and also contains scholarly works that elucidate BPPV; its management remains an enigma to most clinicians. To this end, this work was aimed at outlining an evidence-based best practice for most common form of BPPV. A systematic review of the literature was conducted between 1948 and June 2011 in PubMed, Embase, Ovid, and Cochrane database through the online Library of the University of Cape Town. Seventy-nine worthy articles that addressed the study were selected on consensus of the two authors. There is consensus for the use of canalith repositioning procedures as the best form of treatment for posterior canal canalolithiasis. However, successful treatment is dependent on accurate identification of the implicated canal and the form of lithiasis. Furthermore, clinicians should note that there is no place for pharmacological treatment of BPPV; unless it is to facilitate repositioning.Journal of the Nigeria Medical Association 04/2012; 53(2):94-101.
Article: Performance of DHI Score as a Predictor of Benign Paroxysmal Positional Vertigo in Geriatric Patients with Dizziness/Vertigo: A Cross-Sectional Study.[show abstract] [hide abstract]
ABSTRACT: Dizziness/vertigo is one of the most common complaint and handicapping condition among patients aged 65 years and older (Geriatric patients). This study was conducted to assess the impact of dizziness/vertigo on the quality of life in the geriatric patients attending a geriatric outpatient clinic. A cross-sectional study was performed in a geriatric outpatient clinic of a rural teaching tertiary care hospital in central India. In all consecutive geriatric patients with dizziness/vertigo attending geriatric outpatient clinic, DHI questionnaire was applied to assess the impact of dizziness/vertigo and dizziness associated handicap in the three areas of a patients' life: physical, functional and emotional domain. Later, each patient was evaluated and underwent Dix-Hallpike maneuver by the physician who was blind of the DHI scoring of the patient. We compared means and proportions of variables across two categories of benign paroxysmal positional vertigo (BPPV) and non-BPPV. For these comparisons we used Student's -test to test for continuous variables, chi-square test for categorical variables and Fisher's exact test in the case of small cell sizes (expected value<5). The magnitude of dizziness/vertigo was 3%. Of the 88 dizziness/vertigo patients, 19 (22%) and 69(78%) cases, respectively, were attributed to BPPV and non-BPPV group. The association of DHI score ≥50 with the BPPV was found to be statistically significant with x value = 58.2 at P<0.01. DHI Score is a useful tool for the prediction of benign paroxysmal positional vertigo. Correct diagnosis of BPPV is 16 times greater if the DHI Score is greater than or equal to 50. The physical, functional and emotional investigation of dizziness, through the DHI, has demonstrated to be a valuable and useful instrument in the clinical routine.PLoS ONE 01/2013; 8(3):e58106. · 4.09 Impact Factor