Georges Choufani

Galectin-1 Is Overexpressed in Nasal Polyps under Budesonide and Inhibits Eosinophil Migration

Because of the importance of galectins for various cellular activities, the influence of the glucocorticoid budesonide on the level of expression of galectins-1 and -3 was investigated in human nasal polyposis. Ten nasal polyps obtained from surgical resection were maintained for 24 hours in the presence of various concentrations of budesonide. As quantitatively demonstrated by means of computer-assisted microscopy, 250 ng/ml (the highest dose tested) induced a pronounced increase of galectin-1 expression. This feature was observed in nasal polyps from allergic patients but not in those from nonallergic patients. Since eosinophils represent the main inflammatory cell population in nasal polyps, we investigated the effect of galectin-1 on their migration levels by means of quantitative phase-contrast computer-assisted videomicroscopy. Our results show that galectin-1 (coated on plastic supports) markedly reduced the migration levels of eosinophils in comparison to P-selectin. On the cellular level, marked modifications in the polymerization/depolymerization dynamics of the actin cytoskeleton (as revealed by means of computer-assisted fluorescence microscopy) and, to a much lesser extent, an increase in the adhesiveness of eosinophils to tested substrata were detectable. The present study therefore reveals a new galectin-1–mediated mechanism of action for glucocorticoid-mediated anti-inflammatory effects.

Left Superior Temporal Gyrus Is Coupled to Attended Speech in a Cocktail-Party Auditory Scene.

Using a continuous listening task, we evaluated the coupling between the listeners cortical activity and the temporal envelopes of different sounds in a multitalker auditory scene using magnetoencephalography and corticovocal coherence analysis. Neuromagnetic signals were recorded from 20 right-handed healthy adult humans who listened to five different recorded stories (attended speech streams), one without any multitalker background (No noise) and four mixed with a “cocktail party” multitalker background noise at four signal-to-noise ratios (5, 0, −5, and −10 dB) to produce speech-in-noise mixtures, here referred to as Global scene. Coherence analysis revealed that the modulations of the attended speech stream, presented without multitalker background, were coupled at ∼0.5 Hz to the activity of both superior temporal gyri, whereas the modulations at 4–8 Hz were coupled to the activity of the right supratemporal auditory cortex. In cocktail party conditions, with the multitalker background noise, the coupling was at both frequencies stronger for the attended speech stream than for the unattended Multitalker background. The coupling strengths decreased as the Multitalker background increased. During the cocktail party conditions, the ∼0.5 Hz coupling became left-hemisphere dominant, compared with bilateral coupling without the multitalker background, whereas the 4–8 Hz coupling remained right-hemisphere lateralized in both conditions. The brain activity was not coupled to the multitalker background or to its individual talkers. The results highlight the key role of listeners left superior temporal gyri in extracting the slow ∼0.5 Hz modulations, likely reflecting the attended speech stream within a multitalker auditory scene. SIGNIFICANCE STATEMENT When people listen to one person in a “cocktail party,” their auditory cortex mainly follows the attended speech stream rather than the entire auditory scene. However, how the brain extracts the attended speech stream from the whole auditory scene and how increasing background noise corrupts this process is still debated. In this magnetoencephalography study, subjects had to attend a speech stream with or without multitalker background noise. Results argue for frequency-dependent cortical tracking mechanisms for the attended speech stream. The left superior temporal gyrus tracked the ∼0.5 Hz modulations of the attended speech stream only when the speech was embedded in multitalker background, whereas the right supratemporal auditory cortex tracked 4–8 Hz modulations during both noiseless and cocktail-party conditions.

The levels of retinoid RARβ receptors correlate with galectin-1, -3 and -8 expression in human cholesteatomas

Cholesteatoma is a benign disease characterized by the presence of an unrestrained growth and the accumulation of keratin debris in the middle ear cavity. This often recurs, even when surgical resection is thought to be complete. In a previous study we showed that cholesteatomas with the highest apoptotic indices recurred more rapidly and also exhibited a high level of p53 immunopositive cells. In view of their relevance to the characterization of the cell differentiation status, the present study focuses on the expression of retinoid acid receptors (RARs) and galectins in human cholesteatomas. Retinoids control the differentiation processes in keratinocytes while galectins play strikingly modulatory roles at apoptosis and cell adhesion levels in a wide variety of tissue (embryonic, normal and neoplastic). To clarify the expression of these two protein families in human cholesteatomas we examined and quantified the levels of immunohistochemical expression of RARalpha, beta and gamma, and also galectin-1, -3 and -8 in a series of 70 human cholesteatomas. Our data show clearly that predominantly RARbeta and galectin-1 were expressed. The RARgamma concentration was significantly lower than that of the RARalpha; this was also observed for the galectin-8 concentration in comparison with the galectin-3 one. Furthermore, the level of RARbeta expression correlated highly (P=0.00001) with the level of galectin-8 expression, which also correlated significantly with the level of RARalpha and RARgamma expression. In addition, this parameter also correlated with the level of galectin-1 and galectin-3 expression. These data suggest that cholesteatomas may originate in an undifferentiated population of keratinocytes, and that a relation may exist between retinoid activity and galectins.

Animal model for cholesteatoma induced in the gerbil: will the profiles of differentiation/growth-regulatory markers be similar to the clinical situation?

Introduction: Cholesteatoma is a benign tumor of the middle ear characterized by an aggressive and invasive potential. The only current treatment being surgery, it is important to have access to a reliable animal model to study and better understand cholesteatoma pathogenesis. Our study aimed to examine the biological validity of the most common experimental model of cholesteatoma: the Mongolian gerbil.

Sarcoidosis of the paranasal sinuses treated with hydroxychloroquine.

A case of sarcoidosis of the paranasal sinuses is reported. Biopsies of the sinus mucosa showed typical noncaseating granulomas. Hydroxychloroquine, which is known to be active on the cutaneous form of sarcoidosis, was used here with success and is proposed as an effective alternative to high-dose systemic steroids.

Quantitative glycohistochemical characterization of normal nasal mucosa, and of single as opposed to massive nasal polyps.

A series of 41 nasal polyps (23 single and 18 massive) and 6 normal nasal mucosa specimens was glycohistochemically investigated. Five plant lectins were used, ie, the peanut agglutinin (PNA), the wheat germ agglutinin (WGA), the gorse seed agglutinin (UEA-I), the Maackia amurensis agglutinin (MAA), and the elderberry bark agglutinin (SNA). A neoglycoconjugate and 2 animal lectins (CL-14 and CL-16) were also used. Three quantitative features were calculated by means of computer-assisted microscopy: the percentage of tissue area specifically stained by the histochemical probe, the staining intensity, and the heterogeneity level of the staining distribution. The results show that with respect to sialic acid-glycoprotein binding characteristics as determined by SNA, MAA, and WGA probes, the normal nasal mucosa differed markedly (p < .00001) from the polyposal one. The single nasal polyps exhibited glycohistochemical characteristics that differed markedly (p = .0004) from those exhibited by the massive ones. These differences related mainly to the UEA-I, PNA, and the Thomsen-Friedenreich antigen—exposing neoglycoprotein binding characteristics. In conclusion, the present study shows unambiguously that polyposal mucosa, whether of the single or the massive type, exhibits markedly distinct glycohistochemical characteristics when compared to normal nasal mucosa, and that single nasal polyps also differ markedly from massive ones.

Research paperCharacterization of patterns of expression of protein kinase C-α, -δ, -η, -γ and -ζ and their correlations to p53, galectin-3, the retinoic acid receptor-β and the macrophage migration inhibitory factor (MIF) in human cholesteatomas

Cholesteatoma is a benign disease characterized by the presence of an unrestrained growth and the accumulation of keratin in the middle ear cavity. Due to roles in cell proliferation, apoptosis and differentiation members of the protein kinase C (PKC) family could be involved in disease progression. This study focuses on the expression of protein kinase C-alpha, -delta, -eta, -gamma and -zeta in the epithelial tissues of 56 human cholesteatomas and their correlations with those of previously characterized distributions of p53, galectin-3, retinoic acid receptor-beta (RARbeta) and macrophage migration inhibitory factor (MIF). We have previously reported this marker set to be correlated with keratinocyte differentiation in human cholesteatomas. Our present data clearly show that the percentage of PKC-alpha (but not PKC-delta, -gamma, -eta and -zeta)-immunopositive cells in epithelial tissue fro recurrent cholesteatomas was significantly higher than in non-recurrent cases. Correlations between the PKC isoenzymes and the biological markers were non-uniform. PKC-alpha (but not PKC-delta, -gamma, -eta and -zeta) expression in epithelial cholesteatoma cells correlated significantly and positively with the percentages of p53-immunopositive cells. The patterns of PKC-alpha and -delta expression, but not of PKC-gamma, -eta and -zeta, correlated significantly and positively with galectin-3 expression. In addition, the correlation levels between the expression of PKC-alpha and -delta and that of galectin-3 varied depending on the infection and recurrence status. Presence of RARbeta correlated significantly (and positively) with the expression of PKC-gamma and -zeta and also in relation to the infection and recurrence status. MIF correlated presence significantly (and positively) with that of the five PKCs under study, depending on whether the cholesteatomas were non-infected or infected as well as non-recurrent or recurrent. In conclusion, the present study suggests that modifications occurring at the level of keratinocyte differentiation in human cholesteatomas involve distinct effectors, to which the activation of PKC-alpha, -delta, -eta, -gamma and -zeta can be added.