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At least 19 recordsLinked to original sources

Analysis of lectin receptors in normal nasal mucosa, nasal polyp, inverted papilloma and papillary adenocarcinoma.

In order to investigate the changes in glycoprotein structure in the process of cellular differentiation of the nasal mucosa, formalin-fixed, paraffin-embedded biopsy specimens of normal nasal mucosae, nasal polyps, inverted papillomas and papillary adenocarcinomas were analysed by the Avidin Biotin-Peroxidase Complex technique for the demonstration of peanut agglutinin (PNA) receptors, concanavalin ensifomis agglutinin (ConA) receptors, ulex europeaus agglutinin (UEA-I) receptors, wheat germ agglutinin (WGA) receptors, carcino-embryonic antigen (CEA) and keratin. The quantity and distribution of PNA receptors, ConA receptors, UEA-I receptors and CEA were different, in relation to the varying pathological changes. The results suggest that the glycoprotein structure in the cells of the nasal mucosa will change following their differentiation and malignant transformation, which may be helpful in establishing the diagnosis.

Adenocarcinoma, Papillary↗

Inflammatory cells in nasal mucosa and nasal polyps.

OBJECTIVE: Since some controversy exists concerning the frequency of inflammatory cells in nasal polyps, we have compared the frequency of tissue inflammatory cells (lymphocytes, neutrophils, eosinophils and plasma cells) including 11 kinds of lymphocyte subsets in the same specimens of nasal mucosa and nasal polyps. METHODS: Histopathological observations and flow cytometric analyses were performed on eight mucosal specimens of the inferior turbinates of patients with nasal polyps and on 13 polyp specimens. RESULTS: Nasal polyps contained significantly more eosinophils, neutrophils and plasma cells than nasal mucosa, and EG2+ cells (activated eosinophils) were significantly more frequent in nasal polyps than in nasal mucosa. Flow cytometric analysis showed that there were no significant differences in the frequencies of lymphocytes and lymphocyte subsets (CD1+, CD2+, CD3+, CD5+, CD7+, CD4+, CD8+, CD10+, CD19+, CD20+ and HLA-DR+ cells) including CD4/8 ratios between nasal mucosa and polyps, though, both nasal mucosa and polyps contained significantly more lymphocytes than eosinophils, neutrophils or plasma cells. The T cell lineage (CD2+, CD3+, CD5+ and CD7+ cells) was found in high frequency and B cell lineage (CD10+, CD19+ and CD20+ cells) in low frequency in both nasal mucosa and polyps. The frequency of HLA-DR+ cells (most of which were activated T cells) was not significantly different between nasal mucosa and nasal polyps. CONCLUSION: Histopathological and flow cytometric analyses were performed on the composition of inflammatory cells in nasal mucosa of the inferior turbinates and in polyps from the same patients. The elevated numbers of activated eosinophils, neutrophils and plasma cells in nasal polyps compared with nasal mucosa suggest that inflammatory processes play important roles in the pathophysiology of nasal polyps. The frequencies of lymphocytes and lymphocyte subsets were not significantly different between these two tissues.

Adolescent↗

Occurrence, distribution and possible role of the regulatory peptide endothelin in the nasal mucosa.

Nasal blood flow is finely regulated by local release of neurotransmitters, neuropeptides and other bioactive molecules acting via paracrine mechanisms. We have investigated the occurrence and distribution in human nasal mucosa of endothelin, a potent vasoconstrictor peptide, by immunocytochemistry and the effect of systemic administration of endothelin-1 on vascular perfusion of rabbit nasal mucosa by laser Doppler flowmetry. Endothelin-like immunoreactivity was demonstrated within vascular endothelial cells in both developing and mature human mucosa. Nasal epithelial cells and some connective tissue cells, presumed to be macrophages, also displayed specific immunostaining. In rabbits injected with endothelin-1, a potent and prolonged nasal vasoconstriction was observed. It is suggested that endothelin released locally may participate in the regulation of nasal blood flow via paracrine mechanisms. Since endothelin has growth-promoting actions on several cell types, it is also tentatively proposed that this regulatory peptide may play a role during development of the nose.

Adult↗

Expression and distribution of ion transport mRNAs in human nasal mucosa and nasal polyps.

CONCLUSIONS: Our results indicate that the electrogenic kidney Na(+)/HCO(3)(-) cotransporter (kNBC), KCl cotransporter (KCC1 and -4) and Ca(2+)-activated Cl(-) channel (CaCC1, -2, -3) mRNAs are expressed in normal nasal mucosa and nasal polyp, suggesting that altered expression of all CaCC mRNAs in nasal polyp may cause impaired electrolyte and water transport across the epithelial cells. OBJECTIVE: Electrolyte transport by nasal epithelia has been suggested to be important for controlling the quantity and composition of the nasal fluid and may play an important role in the development of nasal polyps. Transepithelial transport of ions and water in various fluid-transporting epithelia is strictly dependent on the localization of specific membrane proteins in the polarized epithelial cells. In this study we investigated the expression and distribution of mRNA transcripts for kNBC, pancreatic NBC, KCC1, -2, -3, -4 and CaCC1, -2, -3 gene families in human nasal mucosa and nasal polyp. MATERIAL AND METHODS: The expression and localization of these gene families were investigated in inferior turbinate tissues and nasal polyp using reverse transcriptase polymerase chain reaction (RT-PCR), semiquantitative RT-PCR and in situ hybridization. RESULTS: mRNAs for kNBC, KCC1 and -4 and all the CaCC families (CaCC1, -2 and -3) are expressed in human turbinate mucosa and nasal polyp. The expression levels of kNBC and KCC1 and -4 mRNAs did not differ between nasal mucosa and nasal polyp. However, the expression levels of all the CaCC genes were significantly decreased in nasal polyp. In situ hybridization revealed that the expression of these genes was mainly localized in the epithelial layer and submucosal glands of inferior turbinate mucosa and in the epithelial layer of nasal polyp.

Adult↗

Dynamics of COX-2 in nasal mucosa and nasal polyps from aspirin-tolerant and aspirin-intolerant patients with asthma.

BACKGROUND: Only dynamic studies can elucidate the discrepancies concerning the expression of the inducible COX-2 gene in inflammatory airway diseases. OBJECTIVES: To quantify the expression and spontaneous regulation of COX-1 and COX-2 mRNAs in nasal polyps and nasal mucosa by real-time PCR. METHODS: Nasal polyps were obtained from 16 aspirin-tolerant patients with asthma/rhinitis (ATAR) and 18 aspirin-intolerant patients with asthma/rhinitis (AIAR) undergoing nasal polypectomy. Nasal mucosa was obtained from 12 subjects undergoing nasal corrective surgery. All specimens were cut into 3 pieces. One was immediately snap-frozen in liquid nitrogen, and the remaining 2 were left at room temperature for 30 or 60 minutes before freezing. Data are presented as medians and 25th to 75th percentiles of 10 6 cDNA molecules/microg total RNA. RESULTS: Baseline COX-2 mRNA levels were significantly lower in both ATAR (0.45; 0.13-1.20; P <.05) and AIAR (0.24; 0.12-0.41; P <.001) nasal polyps than in nasal mucosa (1.35; 0.52-3.90). COX-2 mRNA expression did not change over time in nasal mucosa but increased significantly in ATAR nasal polyps ( P <.05), reaching similar levels to nasal mucosa after 60 minutes. In contrast, COX-2 mRNA showed no significant change over time in AIAR nasal polyps. COX-1 mRNA was higher in nasal polyps than in nasal mucosa, and its expression was not modified over time in any group of patients. CONCLUSION: These results suggest differential kinetics of COX-2 mRNA between nasal mucosa and nasal polyps. AIAR nasal polyps appear to have a greater abnormality of the COX-2 pathway than ATAR.

Adult↗

Changes of adrenergic and muscarinic cholinergic receptors in nasal mucosa in nasal allergy.

Receptor-binding assays were performed to evaluate the changes of beta- and alpha 1-adrenergic and muscarinic receptors in the nasal mucosa of subjects with nasal allergy and in guinea pigs sensitized with ovalbumin using radioligands 3H-DHA, 3H-prazosin and 3H-QNB, respectively. In subjects with nasal allergy, a decrease in density of beta- and alpha 1-adrenergic receptors and an increase in density of muscarinic cholinergic receptors were observed. An increase in density of muscarinic cholinergic receptors could be reproduced in the nasal mucosa of guinea pigs which were sensitized with ovalbumin and had typical hyperreactive nasal symptoms. These results indicate that the increase in the density of muscarinic receptors observed in the nasal mucosa of subjects with nasal allergy has been induced secondarily by an allergic reaction in the nasal mucosa with hyperreactive nasal symptoms, which in turn acts as an aggravating factor in the vicious circle promoting hyperreactivity of the nasal mucosa.

Adolescent↗

Expression and distribution of thioredoxin and thioredoxin reductase in human nasal mucosa and nasal polyp.

CONCLUSIONS: The results of this study indicate that thioredoxin (Trx) and thioredoxin reductase (TrxR) may play a role in the defense of normal human nasal mucosa against external noxious stimuli. Based on the fact that normal nasal mucosa is continuously exposed to inhaled toxicants and contains a considerable number of inflammatory cells, Trx and TrxR may be upregulated even in normal nasal mucosa and perhaps the difference in their expression levels between normal nasal mucosa and nasal polyp, if it exists at all, is small and therefore difficult to detect. Further studies will be needed to clarify the roles of Trx and TrxR in the pathogenesis of nasal polyp. OBJECTIVES: The cellular antioxidant defense system includes thiol-containing proteins such as Trx and TrxR, which have recently attracted much attention due to their strong antioxidant radical quenching capabilities and other important biological functions related to the regulation of the cellular redox state. This study was undertaken to investigate the expression and distribution of Trx and TrxR in normal human nasal mucosa and nasal polyp, and to improve understanding of the significance of the Trx system in these conditions. MATERIAL AND METHODS: The expression and distribution of Trx and TrxR in normal human inferior turbinate mucosa and nasal polyp were investigated using reverse transcriptase polymerase chain reaction (RT-PCR), semiquantitative RT-PCR, Western blotting and immunohistochemistry. RESULTS: mRNAs and protein for both Trx and TrxR were detected in normal human inferior turbinate mucosa and nasal polyp. Semiquantitative RT-PCR and Western blotting revealed that there was no significant difference in the expression levels of Trx and TrxR between inferior turbinate mucosa and nasal polyp. Immunoreactivity for both Trx and TrxR was seen in nasal epithelial cells, glands and vascular endothelium of inferior turbinate mucosa and nasal polyp. Trx and TrxR immunoreactivity was also found in inflammatory infiltrating cells in inferior turbinate mucosa and nasal polyp.

Adult↗

Drug metabolism in the nasal mucosa.

Nasal delivery is a potential alternative for systemic availability of drugs restricted to intravenous administration, such as peptide and protein drugs. Although nasal delivery avoids the hepatic first-pass effect, the enzymatic barrier of the nasal mucosa creates a pseudo-first-pass effect. The xenobiotic metabolic activity in the nasal epithelium has been investigated in several species including humans. The Phase I, cytochrome P-450 enzymes have been studied extensively for their toxicological significance, since these enzymes metabolize inhaled pollutants into reactive metabolites which may induce nasal tumors. The cytochrome P-450 activity in the olfactory region of the nasal epithelium is higher even than in the liver, mainly because of a three- to fourfold higher NADPH-cytochrome P-450 reductase content. Phase II activity has also been found in the nasal epithelium. The delivery of peptides and proteins has been hindered by the peptidase and protease activity in the nasal mucosa. The predominant enzyme appears to be aminopeptidase among other exopeptidases and endopeptidases. The absorption of peptide drugs can be improved by using aminoboronic acid derivatives, amastatin, and other enzyme inhibitors as absorption enhancers. It is possible that some of the surfactants, e.g., bile salts, increase absorption by inhibiting the proteolytic enzymes. Thus, in addition to the permeation barriers, there also exists an enzymatic barrier to nasal drug delivery, which is created by metabolic enzymes in the nasal epithelium.

Absorption↗

Nitric oxide and parasympathetic vascular and secretory control of the dog nasal mucosa.

Nasal vascular and secretory responses to local intra-arterial injection of acetylcholine (ACh) and vasoactive intestinal polypeptide (VIP) and to electrical stimulation of the nasal parasympathetic nerve fibres were recorded in dogs anaesthetized with pentobarbital. The influence of pretreatment with atropine and propranolol and the nitric oxide synthetase (NOS) inhibitor Nomega-nitro-L-arginine (L-NNA) was analysed. As a marker for NOS, NADPH-diaphorase (NADPH-d) histochemistry was studied in the sphenopalatine ganglion, trigeminal nerve and nasal mucosa. Local intra-arterial infusion of ACh and VIP evoked dose-dependent vasodilatation and nasal secretion which were not modified in the presence of L-NNA. The NO donor nitroprusside induced dose-dependent vasodilatation but no secretion. Atropine did not reduce the vasodilatation evoked by the parasympathetic nerve stimulation, but did reduce the secretory response by 55% (p < 0.05). During L-NNA infusion, the atropine-resistant vasodilatation evoked by parasympathetic nerve stimulation was reduced by a further 80% (p < 0.01) and the non-cholinergic secretory response was reduced by a further 30% (p < 0.05). Simultaneous infusion of the NO donor nitroprusside reversed the secretory response but not the vasodilator response to parasympathetic nerve stimulation. Histochemical studies revealed that NADPH-d activity was co-localized with VIP in parasympathetic axons. These observations suggest that NO could act as a non-cholinergic parasympathetic neurotransmitter in the vascular and secretory control of the dog nasal mucosa.

Acetylcholine↗

Distribution of NADPH-diaphorase positive nerve fibers in the rat nasal mucosa.

Nasal mucosa was investigated by NADPH-diaphorase histochemistry. Positive fibers were distributed around blood vessels, seromucous glands and in the subepithelial layer. The pterygopalatine, trigeminal and superior cervical ganglia were also studied to examine the origin of these fibers. Many neurons in the pterygopalatine ganglion were labeled, and a few neurons were stained in the trigeminal ganglion. No perikarya were labeled in the superior cervical ganglion. Therefore, most of the labeled fibers must be originating from the pterygopalatine ganglion, and the rest of them may originate from the trigeminal ganglion. These results suggest that nitric oxide may have some role in the nervous control of the nasal mucosa.

Animals↗

Keratinocyte growth factor and its receptor messenger RNA expression in nasal mucosa and nasal polyps.

To examine the potential biologic role of fibroblast growth factors (FGFs) in nasal polyps and nasal mucosa during chronic inflammatory conditions, we investigated messenger RNA (mRNA) expression of three members of the FGF family -- acidic FGF, basic FGF, and keratinocyte growth factor (KGF)-- in nasal polyp tissues, as well as in hyperplastic nasal mucosa. Using the sensitive method reverse transcription-polymerase chain reaction (RT-PCR), we demonstrated that of the examined FGFs, KGF had the most abundant mRNA expression in nasal polyps and nasal mucosa. We also found that significantly higher levels of KGF mRNA were expressed in nasal polyps than in nasal mucosa, whereas mRNA expression of acidic FGF and basic FGF was relatively low in these tissues. In addition, we showed that KGF receptor mRNA was present in most of the nasal mucosa; however, none or little was expressed in nasal polyps. These results suggest that KGF might play an important role in nasal epithelial proliferation and that excessive synthesis of KGF in nasal polyp stroma may contribute to hypertrophy of the nasal mucosa in patients with chronic sinusitis associated with nasal polyposis.

Adult↗

Scanning electron microscopy of the human nasal mucosa.

Nasal biopsies are taken from normals and from patients suffering from perennial rhinitis, nasal polyps, hay fever or atrophic rhinitis. The biopsies from the inferior nasal turbinate are studied in a scanning electron microscope. In conclusion, allergic reactions have only a slight, direct influence on the ultrastructure of the mucous membrane. Contrary to this, the surface of the nasal mucosa is characteristically altered in atrophic rhinitis. By chance it was observed how flagellated bacteria invades the mucous membrane by fastening to the epithelial cells, which consequently are expelled.

Bacteria↗

Comparative study of the effects of different glucocorticosteroids on eosinophil survival primed by cultured epithelial cell supernatants obtained from nasal mucosa and nasal polyps.

BACKGROUND: Supernatants from epithelial cell cultures enhance eosinophil survival in vitro, this effect being abrogated by previous incubation of eosinophils with glucocorticosteroids. This property has resulted in the development of an in vitro test to compare the potency of these drugs. A comparative study was performed with dexamethasone, methylprednisolone, deflazacort, and budesonide. METHODS: Human epithelial cell conditioned media (HECM) was generated from cultured epithelial cells obtained from healthy nasal mucosa and polyps. Eosinophils isolated from the peripheral blood were incubated with different corticosteroids for one hour before the addition of HECM. The inhibitory potency of the four steroids on the eosinophil survival index was compared using the concentration of steroid causing 50% inhibition (IC50). RESULTS: Eosinophil survival was increased by HECM from both healthy nasal mucosa and polyps. All four steroids blocked HECM-induced eosinophil survival in a dose-dependent manner. On healthy nasal mucosa methylprednisolone was the least potent (IC50 = 536 nM), deflazacort (IC50 = 264 nM) was twice as potent as methylprednisolone, while budesonide and dexamethasone were approximately nine times as potent (both IC50 = 58 nM). When potency was evaluated on the promoting effects of the HECM obtained from nasal polyps, the inhibitory potencies were lower and consequently the IC50 values were higher when compared with HECM generated from healthy nasal mucosa: methylprednisolone (IC50 = 546 nM), deflazacort (IC50 = 390 nM), dexamethasone (IC50 = 76 nM), and budesonide (IC50 = 78 nM). CONCLUSIONS: The potencies of glucocorticosteroids can be compared by evaluating their effects on the survival of eosinophils previously primed by supernatants obtained from epithelial cell culture. The different effects of steroids on eosinophils primed by HECM obtained from healthy nasal mucosa compared with HECM obtained from nasal polyps suggest that polyps might represent more active tissue which is relatively resistant to treatment with corticosteroids.

Administration, Topical↗

Analysis of proteoglycan gene messages in human nasal mucosa and nasal polyp using dot blot hybridization.

It has been suggested that the formation and growth of nasal polyp require the remodeling of extracellular matrix. Proteoglycans (PGs) are major components of the extracellular matrix that maintain the integrity of structural tissue. The leucine-rich repeat PGs include lumican, decorin and biglycan and have many important biologic activities in various pathologic conditions, including the remodeling of the extracellular matrix. Therefore, these small-PG families may be involved in the formation and growth of nasal polyp. In the present study, surgical specimens of nasal polyps and nasal mucosa were assessed for expression of mRNA coding for lumican, decorin and biglycan using reverse transcriptase-polymerase chain reaction followed by dot blot hybridization. Lumican, decorin and biglycan mRNA were expressed in all tissue samples examined. Semiquantitative dot blot hybridization revealed that the levels of the lumican and biglycan messages are lower in nasal polyp tissues than in nasal mucosa. The decorin messages in nasal polyp were expressed at levels similar to those in nasal mucosa. These results suggest that lumican, decorin and biglycan may be important components of the extracellular matrix in nasal mucosa. Considering the function of these PGs, normal levels of decorin associated with low levels of biglycan and lumican may play a role in the pathogenesis of nasal polyposis.

Adult↗

[Immunohistological study of infiltrating cells in nasal mucosa and nasal lavage fluid of perennial allergic rhinitis].

It is well known that EG2-positive cells, CD68-positive cells and other inflammatory cells significantly increase after antigen provocation in the nasal mucosa of an allergic patient. However, there are few reports of the immunohistological study if the infiltrating cells in nasal lavage fluid are not seen. In this study, the infiltrating cells in nasal mucosa as well as in nasal lavage fluid were immunohistologically examined by means of monoclonal antibodies 30 minutes after the antigen provocation. Seven patients with perennial allergic rhinitis were challenged by an antigen disk placed on one side of the inferior turbinates and each nasal cavity was irrigated separately 30 minutes after the antigen provocation. About seven days later, these patients were operated on and the nasal mucosa was removed 30 minutes after the antigen provocation. No marked change in CD4- and CD8 positive cells in the nasal mucosa and lavage fluid was found after provocation. On cytospin glass slides, there was a slight increase in the number of CD68 (P = 0.1), EG2 (P = 0.09), and neutrophil elastase positive (P = 0.2) cells. A significant increase in EG2-positive cells was also seen in the superficial layer of the lamina propria (P < 0.05) but not in the deep layer. CD22 positive cells were not seen on the cytospin glass slide, whereas many positive cells were observed in the deep layer of the lamina propria. These results indicate that EG2-positive cells participate strongly in the early phase of the allergic response after provocation in spite of the absence of significant changes in CD4- and CD8 positive cells. Immunohistological evaluation of nasal lavage is thought to be beneficial concerning the movement of each kind of cells. Each kind of cell is thought to fulfill the main physiological role in the epithelial layer or the lamina propria in early allergic inflammation.

Antigens, CD↗

Interleukin-5 upregulates intercellular adhesion molecule-1 gene expression in the nasal mucosa in nasal allergy but not in nonallergic rhinitis.

The effect of interleukin-5 (IL-5) on intercellular adhesion molecule-1 (ICAM-1) gene expression in human nasal mucosa was studied using the method of gene expression quantification. Recombinant human IL-5 was shown to induce ICAM-1 gene expression in the nasal mucosa of patients with nasal allergy, but not in the mucosa of non-allergic patients. The peak level of ICAM-1 gene expression was seen 6 h after IL-5 stimulation. In the nasal mucosa of patients with nasal allergy, IL-5 might act not only as an eosinophil chemotactic factor, but also as an enhancement factor for the expression of adhesion molecules, thereby accelerating eosinophil appearance. The results also suggest that the nasal mucosa of patients with nasal allergy somehow favors adhesion molecule induction by IL-5.

Adolescent↗

Endothelin-induced vasoconstriction in rabbit nasal mucosa.

Nasal blood flow is finely regulated by local release of neurotransmitters, neuropeptides and other bioactive molecules acting via paracrine mechanisms. We have investigated the effects of endothelin-1 (ET-1), a potent vasoconstrictor peptide, on the blood perfusion of rabbit nasal mucosa by laser Doppler flowmetry. After injection with ET-1, a potent and prolonged nasal vasoconstriction was observed. ET-immunoreactivity has previously been detected in nasal tissues and it is therefore suggested that ET-1 may participate in the regulation of nasal blood flow via paracrine mechanisms.

Animals↗