Genetic and Epigenetic Alterations of the NF2 Gene in Sporadic Vestibular Schwannomas

BACKGROUND: Mutations in the neurofibromatosis type 2 (NF2) tumor-suppressor gene have been identified in not only NF2-related tumors but also sporadic vestibular schwannomas (VS). This study investigated the genetic and epigenetic alterations in tumors and blood from 30 Korean patients with sporadic VS and correlated these alterations with tumor behavior. METHODOLOGY/PRINCIPAL FINDINGS: NF2 gene mutations were detected using PCR and direct DNA sequencing and three highly polymorphic microsatellite DNA markers were used to assess the loss of heterozygosity (LOH) from chromosome 22. Aberrant hypermethylation of the CpG island of the NF2 gene was also analyzed. The tumor size, the clinical growth index, and the proliferative activity assessed using the Ki-67 labeling index were evaluated. We found 18 mutations in 16 cases of 30 schwannomas (53%). The mutations included eight frameshift mutations, seven nonsense mutations, one in-frame deletion, one splicing donor site, and one missense mutation. Nine patients (30%) showed allelic loss. No patient had aberrant hypermethylation of the NF2 gene and correlation between NF2 genetic alterations and tumor behavior was not observed in this study. CONCLUSIONS/SIGNIFICANCE: The molecular genetic changes in sporadic VS identified here included mutations and allelic loss, but no aberrant hypermethylation of the NF2 gene was detected. In addition, no clear genotype/phenotype correlation was identified. Therefore, it is likely that other factors contribute to tumor formation and growth

Foreign bodies in the ears causing complications and requiring hospitalization in children 0-14 age: results from the ESFBI study

The occurrence of foreign bodies (FBs) in otorhinolaryngological practice is a common and serious problem among patients in paediatric age. The aim of this work is to characterize the risk of complications and prolonged hospitalization due to foreign bodies in ears in terms of the characteristics of the injured patients (age, gender), typology and features of the foreign bodies, the circumstances of the accident and the hospitalization's details

The Multifunctional Host Defense Peptide SPLUNC1 Is Critical for Homeostasis of the Mammalian Upper Airway

Otitis media (OM) is a highly prevalent pediatric disease caused by normal flora of the nasopharynx that ascend the Eustachian tube and enter the middle ear. As OM is a disease of opportunity, it is critical to gain an increased understanding of immune system components that are operational in the upper airway and aid in prevention of this disease. SPLUNC1 is an antimicrobial host defense peptide that is hypothesized to contribute to the health of the airway both through bactericidal and non-bactericidal mechanisms. We used small interfering RNA (siRNA) technology to knock down expression of the chinchilla ortholog of human SPLUNC1 (cSPLUNC1) to begin to determine the role that this protein played in prevention of OM. We showed that knock down of cSPLUNC1 expression did not impact survival of nontypeable Haemophilus influenzae, a predominant causative agent of OM, in the chinchilla middle ear under the conditions tested. In contrast, expression of cSPLUNC1 was essential for maintenance of middle ear pressure and efficient mucociliary clearance, key defense mechanisms of the tubotympanum. Collectively, our data have provided the first in vivo evidence that cSPLUNC1 functions to maintain homeostasis of the upper airway and, thereby, is critical for protection of the middle ear

Tympanic membrane changes in experimental acute otitis media and myringotomy

Objective. The present experimental study explored pathomorphological changes and calcium depositions in the tympanic membrane during experimental acute otitis media caused by nontypeable Haemophilus influenzae in myringotomized and nonmyringotomized ears. Material and methods. A rat model of experimental acute otitis media caused by nontypeable Haemophilus influenzae was employed Sixteen Sprague-Dawley rats were used. Four days following middle ear inoculation, a bilateral myringotomy was performed in six randomly selected animals. Another group of 10 animals was inoculated only. On days 4, 7, 14, and 28, after inoculation, two animals from each group were sacrificed The temporal bones were removed and the tympanic membranes were dissected, followed by paraffin embedding. Adjacent sections were stained with PAS-alcian blue for basic histopathological observations and by von Kossa method for determination of calcium phosphate depositions. Results. Particularly intense invasion of polymorphonuclear neutrophil leukocytes was, seen on day 4 after inoculation. The highest infiltration of macrophages was observed on day 7. The peak number of lymphocytes was seen on day 14. No difference occurred in the number of polymorphonuclear leukocytes in myringotomized and nonmyringotomized tympanic membranes. The infiltration with lymphocytes and activated macrophages in all parts of the myringotomized tympanic membranes was statistically significantly higher than in the nonmyringotomized animals. The total amount of interstitial calcium phosphate depositions during days 7, 14, and 28 of study was statistically higher in the sections of pars tensa from myringotomized membranes compared to the nonmyringotomized membranes. Conclusion. Nontypeable Haemophilus influenzae-induced acute otitis media and myringotomy provoke more extensive inflammatory reaction with microcalcification in the tympanic membranes