The influence of tonsillectomy on allergic diseases in pediatric patients.

BACKGROUND: The influence of tonsillectomy on allergic airway diseases is not well known. OBJECTIVES: In the present study, the influence of tonsillectomy on perennial allergic rhinitis (PAR) and bronchial asthma (BA) among pediatric subjects was prospectively investigated. METHODS: The tonsillectomy (surgery group) and the age-matched non-surgical subjects (control group) were examined and followed prospectively. In addition, immunological analysis was conducted. RESULTS: After in vitro allergen stimulation, the production of a small number of allergen-specific Th2 cells was induced in the tonsillar cells, even in sensitized subjects. Flow cytometry analysis detected more effector regulatory T cells (Tregs) in the tonsils than in peripheral blood. Clinically, after surgery, the PAR and BA symptoms improved in the surgery group but not in the control group. The total IgE in the surgery group was significantly lower than in the control group; after surgery, IgE levels slightly increased but remained lower. The postoperative Dermatophagoides farina (Der f)-specific IgE level increased in the sensitized subjects but not in the non-sensitized subjects. CONCLUSION: Tonsillectomy did not improve the underlying mechanisms of the allergy, however the decreased risk of infection and upper airway obstruction could lead to improved symptoms of allergic airway diseases.

The first sporadic case of DFNA11 identified by next-generation sequencing.

We report the first sporadic case of nonsyndromic autosomal dominant hearing loss (DFNA11). The patient was a 5-year-old boy with moderate bilateral hearing loss. Targeted next-generation sequencing analysis of patient DNA identified a known heterozygous DFNA11 mutation, c.689C > T, in MYO7A, encoding p.Ala230Val. The mutation was not detected in the parents of the patient and is considered to be de novo. This mutation is identical to the one reported previously in an Italian family. Accumulation of mutation data increases the feasibility of identifying autosomal dominant mutations in sporadic sensorineural hearing loss.

GJB2-associated hearing loss undetected by hearing screening of newborns.

The hearing loss caused by GJB2 mutations is usually congenital in onset, moderate to profound in degree, and non-progressive. The objective of this study was to study genotype/phenotype correlations and to document 14 children with biallelic GJB2 mutations who passed newborn hearing screening (NHS). Genetic testing for GJB2 mutations by direct sequencing was performed on 924 individuals (810 families) with hearing loss, and 204 patients (175 families) were found to carry biallelic GJB2 mutations. NHS results were obtained through medical records. A total of 18 pathological mutations were identified, which were subclassified as eight inactivating and 10 non-inactivating mutations. p.I128M and p.H73Y were identified as novel missense GJB2 mutations. Of the 14 children with biallelic GJB2 mutations who passed NHS, eight were compound heterozygotes and 3 were homozygous for the c.235delC mutation in GJB2, and the other three combinations of non-c.235delC mutations identified were p.Y136X-p.G45E/p.V37I heterozygous, c.512ins4/p.R143W heterozygous, and p.V37I/p.R143W heterozygous. These 14 cases demonstrate that the current NHS does not identify all infants with biallelic GJB2 mutations. They suggest that the frequency of non-penetrance at birth is approximately 6.9% or higher in DFNB1 patients and provide further evidence that GJB2 hearing loss may not always be congenital in onset.

Suppression of inflammation by dexamethasone prolongs adenoviral vector-mediated transgene expression in murine nasal mucosa.

CONCLUSION: The results of this study demonstrate that suppression of inflammation by dexamethasone attenuates the host immune response against adenoviral-mediated gene transfection and thereby prolongs transgene expression in murine nasal mucosa. OBJECTIVES: Gene transfer using a recombinant adenovirus is a good tool for research and clinical applications, but the immune response to adenoviral vectors can induce inflammation and loss of transgene expression in transfected tissues. In this study we investigated the effects of dexamethasone-induced immunosuppression on adenovirus gene transfer in the nasal mucosa of the mouse. MATERIAL AND METHODS: We administered the recombinant adenovirus Ax1CAlacZ, which encodes Escherichia coli beta-galactosidase (lacZ gene), to the nasal mucosa of mice treated with or without i.p. dexamethasone and evaluated the expression of the lacZ gene on Days 2, 4, 7, 14 and 28. The nasal mucosa was dissected out, and the mRNA level was measured using a LightCycler. The expression of the exogenous beta-galactosidase was detected by means of histochemistry. RESULTS: Dexamethasone treatment significantly increased the mRNA level compared with that in the controls at Days 4, 7 and 14. Histochemistry showed that the expression of beta-galactosidase protein persisted in the dexamethasone-treated mice at Days 7 and 14 but had diminished almost to nothing in the control group.

Effects of adenoviral vector-mediated BDNF expression on the bulbectomy-induced apoptosis of olfactory receptor neurons.

The expression of adenoviral vector (Ad)-mediated lacZ and brain-derived neurotrophic factor (BDNF) in mouse olfactory epithelium (OE) was examined, and the effect of BDNF on the survival of the bulbectomized OE was evaluated. A recombinant adenovirus, Ax1CAlacZ, was administrated into the mouse OE after bulbectomy, and the expression of a transferred E. coli beta-galactosidase (beta-gal) gene was confirmed by X-gal staining. The expression and effects of exogenous BDNF in the OE after bulbectomy were examined using immunohistochemistry and the TUNEL method. The adenoviral vector-mediated expression of beta-gal in the mouse OE was detectable for up to 14 days after bulbectomy in vivo. The Ad-mediated expression of BDNF was also observed in the OE after bulbectomy. Exogenously induced BDNF suppressed the degenerative changes of bulbectomized OE. TUNEL staining indicated that the exogenous BDNF enhanced the survival of the bulbectomized OE by inhibiting apoptosis. Ad-mediated expression of BDNF in the mouse nasal mucosa alleviated degenerative changes in bulbectomized OE. Ad-mediated transfer of neurotrophic factors might be applicable in the treatment of olfactory disorders.

In vivo expression of adenovirus-mediated lacZ gene in murine nasal mucosa.

Adenovirus is a good tool for transferring exogenous genes into various organs because the virus has a wide spectrum of infection. In this report, we demonstrate that a recombinant adenovirus, Ax1CAlacZ, can transfer an exogenous lacZ gene into murine nasal mucosa in vivo. The efficiency of the exogenous gene expression varied for different cell types and was improved by optimizing the method of administration. In the olfactory region, the olfactory epithelia, sustentacular cells and olfactory nerve efficiently expressed lacZ gene transferred by Ax1CAlacZ using either of two administration methods, dripping or injecting. In contrast, in the respiratory region, the respiratory epithelia but not the subepithelial tissues expressed lacZ gene transferred by Ax1CAlacZ, and the efficiency of the gene transfer, which was low when the virus was administered by nasal drops, was improved when the virus was administered by injection. Our study demonstrated that gene transfer mediated by adenovirus is more efficient in the olfactory epithelia than in the respiratory epithelia, and may be applicable to nasal or paranasal diseases such as olfactory epithelial disturbances.