Involvement of galanin and galanin receptor 2 in a mouse model of allergic rhinitis.

BACKGROUND: Allergic rhinitis (AR) is caused by allergic reaction to allergens such as pollen. Galanin (GAL), a neuropeptide that regulates inflammatory processes, is widely expressed in the central and peripheral nervous systems. Although neuropeptides are implicated in arthritis and chemically induced ileitis, their roles in AR remain unclear. METHODS: We developed a murine model of AR and generated control, systemic sensitization, mild AR, and severe AR groups. We examined GAL and GAL receptor (GALR) mRNA and protein levels and localization patterns in each group using reverse transcription PCR, western blotting, and immunohistochemical analyses. Additionally, we evaluated the effects of M871, a GALR2 antagonist, on mice with severe AR. RESULTS: Gal and Galr2 are expressed in nasal mucosa and brain (control) samples from control and AR mice. GAL and GALR2 were expressed at similar levels and localized to ciliated epithelial and submucosal gland cells of the nasal mucosa in all four groups. Intranasal M871 administration significantly reduced the incidence of nose rubbing behaviors and sneezing (p < 0.001 in 30 min, respectively) in severe AR mice relative to that in controls. Mechanistically, we postulate that GALR2 is expressed in B cells, and M871 administration reduces IgE production, as well as the number of B cells in tissues. CONCLUSIONS: GAL signaling may not change progressively with increasing nasal sensitization, suggesting that this signaling process exacerbates, rather than directly trigger, AR. GAL-GALR2 signaling likely mediates AR development, suggesting that its inhibition represents a novel therapeutic strategy for AR.

Biphasic low-grade nasopharyngeal papillary adenocarcinoma: a case report and literature review.

BACKGROUND: Low-grade nasopharyngeal papillary adenocarcinoma (LGNPPA) is distinctly rare. We report a patient with a uniquely biphasic LGNPPA; additionally, we review similar tumors reported in the literature. CASE PRESENTATION: A 56-year-old man presented with an asymptomatic pedunculated tumor in the vault of the nasopharynx, at the junction of the nasal septum and the roof, which was discovered during screening for laryngeal cancer. To obtain a definitive diagnosis, the patient underwent endoscopic endonasal surgery under general anesthesia. Immunohistochemical analysis of the tumor revealed it to be an LGNPPA with a prominent spindle cell component. CONCLUSION: To our knowledge, this is the fourth reported LGNPPA exhibiting a spindle cell component and the second with a prominent pathological condition. The prognosis of LGNPPA is usually excellent. Therefore, it is important for clinicians to scrutinize the lesion's pathology to avoid unnecessary, disfiguring surgery.

[Emergency Care System in Otolaryngology].

Otolaryngologists play a very important role in the field of emergency care in otolaryngology because their field requires a particular expertise in dealing with a variety of diseases. However, the emergency medical service system at night or during holidays has not yet been completely organized. Clarification of the present problems is essential to improve our emergency medical service system. Thus, we investigated the present state of otolaryngological emergency care in Tokyo and in Kyorin University Hospital. In Tokyo, outpatient clinics and hospitals see the emergency patients in the otolaryngology field by rotation during holidays. More than 13,000 patients were referred to the outpatient clinics, and more than 2, 000 patients were referred to the hospitals per year using this emergency care system. There are some problem with this system. One is that patients have to rush to a hospital in consecutive holidays and the other is that only a few clinics and hospitals see patients at night. Otolaryngologists have to regard these problem as an otolaryngologist-wide issue. For both public administration or academic societies a site for discussion needs to be provided.

Barrier Factors of Adherence to Dupilumab Self-Injection for Severe Allergic Disease: A Non-Interventional Open-Label Study.

Purpose: The status of dupilumab self-injection at home is not well understood. We therefore aimed to identify the barriers to adherence to dupilumab self-injection. Patients and Methods: This non-interventional open-label study was conducted between March 2021 and July 2021. Patients with atopic dermatitis, bronchial asthma, and chronic rhinosinusitis with nasal polyps receiving dupilumab, from 15 sites, were requested to complete a self-administered questionnaire regarding the frequency and effectiveness of dosing as well as their use and satisfaction with dupilumab. Barriers to adherence were assessed using the Adherence Starts with Knowledge-12. Results: We included 331 patients who used dupilumab for atopic dermatitis (n = 164), chronic rhinosinusitis with nasal polyps (n = 102), and bronchial asthma (n = 65). The median efficacy of dupilumab scored 9.3 on the visual analog scale. Overall, 85.5% of the patients self-injected dupilumab, and 70.7% perfectly complied with the established injection dates. The pre-filled pen was significantly superior to the conventional syringe in terms of usability, operability, ease of pushing the plunger, and patient satisfaction. However, the pre-filled pen caused more pain during self-injection than did the syringe. Multivariate logistic regression analysis showed that adherence decreased with longer dupilumab treatment duration (p = 0.017) and was not associated with age, sex, underlying disease, or device type. There was a difference in responses related to "inconvenience/forgetfulness" between the good and poor adherence groups. Conclusion: The pre-filled dupilumab pen was superior to the syringe in terms of usability, operability, ease of pushing the plunger, and satisfaction. Repetitive instructions are recommended for preventing poor adherence to dupilumab self-injection.

Tonsillar TLR9 expression and efficacy of tonsillectomy with steroid pulse therapy in IgA nephropathy patients.

BACKGROUND: Patients with IgA nephropathy (IgAN) often show aggravation of renal injury with macroscopic hematuria after mucosal infections, especially tonsillitis. We previously demonstrated the important role of mucosal Toll-like receptor 9 (TLR9) activation in the pathogenesis of murine IgAN. Moreover, a single nucleotide polymorphism (SNP) in TLR9 was significantly associated with pathological severity in human IgAN. In this study, we investigated correlations between tonsillar TLR9 messenger RNA expression, TLR9 SNP genotypes and clinical outcomes following tonsillectomy with steroid pulse therapy (SPT) in IgAN patients. METHODS: Tonsillar TLR9 expression was examined in IgAN (n = 49) and control (n = 15) patients who had undergone tonsillectomy. The correlations between tonsillar TLR9 expression level, TLR9 SNP genotypes and clinical outcomes after tonsillectomy with SPT were examined. RESULTS: High expression of tonsillar TLR9 was observed in ∼23% of IgAN patients. These patients showed stronger and earlier remission of hematuria and proteinuria than those with low TLR9 expression. Patients with the TT genotype of TLR9 SNP (rs352140) had more severe renal damage than those with other genotypes. Patients whose serum IgA level decreased more than average after tonsillectomy (large ΔIgA) showed higher cumulative remission rates of proteinuria than patients with a smaller decrease in these levels (small ΔIgA). CT/CC genotypes were more dominant and tonsillar TLR9 expressions significantly higher in large ΔIgA patients than in small ΔIgA patients. CONCLUSION: In IgAN patients, expression levels of tonsillar TLR9 and TLR9 SNP were well correlated with the efficacy of tonsillectomy with SPT.

Antimicrobial peptides human beta-defensins and cathelicidin LL-37 induce the secretion of a pruritogenic cytokine IL-31 by human mast cells.

In addition to their microbiocidal properties, human beta-defensins (hBDs) and cathelicidin LL-37 stimulate a number of mammalian cell activities, including migration, proliferation, and cytokine/chemokine production. Because hBDs and LL-37 cause mast cells to release pruritogens such as histamine and PGs, we hypothesized that these peptides would stimulate the secretion of a novel pruritogenic mediator IL-31, predominantly produced by T cells. hBDs and LL-37 enhanced IL-31 gene expression and IL-31 protein production and release in the human mast cell line LAD2, as well as in peripheral blood-derived cultured mast cells, suggesting that mast cells are another source of IL-31. Moreover, the expression of IL-31 was elevated in psoriatic skin mast cells, and hBD-2-4 and LL-37, but not hBD-1, enhanced its expression in vivo in rat skin mast cells. hBDs and LL-37 also induced the release of other pruritogenic mediators, including IL-2, IL-4, IL-6, GM-CSF, nerve growth factor, PGE(2), and leukotriene C(4), and increased mRNA expression of substance P. hBD- and LL-37-mediated IL-31 production/release was markedly reduced by pertussis toxin and wortmannin, inhibitors of G-protein and PI3K, respectively. As evidenced by the inhibitory effects of MAPK-specific inhibitors, hBD-2-4 and LL-37 activated the phosphorylation of MAPKs p38, ERK, and JNK that were required for IL-31 production and release. The ability of hBDs and LL-37 to stimulate the production and release of IL-31 by human mast cells provides a novel mechanism by which skin-derived antimicrobial peptides/proteins may contribute to inflammatory reactions and suggests a central role of these peptides in the pathogenesis of skin disorders.

Pollen Allergy Screening with Allergen-Specific and Total Immunoglobulin E Titers.

Background: Allergic rhinitis is a typical type I hypersensitivity reaction, commonly caused by inhalant allergens. Accurate identification of the causative antigen is important for rapid diagnosis and treatment initiation. Objective: This study examined the efficiency of serum-based allergen-specific immunoglobulin E and total immunoglobulin E antibody titers in screening for pollen allergy. We also examined the effect of cross-reactive carbohydrate determinants on specific immunoglobulin E titers in screening for pollen allergy, one of the causes of false positivity in specific immunoglobulin E measurements. Methods: A questionnaire was used to evaluate the symptoms of pollinosis among participants who underwent a medical examination. One hundred and thirty-two participants reported pollen allergy symptoms and 127 reported an absence of symptoms. Specific immunoglobulin E levels were measured using the AlaSTAT 3g Allergy method. Seventeen components, including four types of cross-reactive carbohydrate determinant-specific immunoglobulin E antibodies, were measured and evaluated comparatively. Results: The sensitivity and specificity of the tests in predicting the presence or absence of pollen allergy were analyzed. The values of the areas under the curves for immunoglobulin E antibody levels against cedar, cypress, orchard grass, and ragweed pollen were 0.87, 0.82, 0.63, and 0.56, respectively. A cross-reactive carbohydrate determinant-related false-positive effect on the pollen specific immunoglobulin E titer was noted in pollen screening. Conclusion: Cedar pollen-specific immunoglobulin E titers showed sufficient accuracy for use in pollen allergy screening. The study of cross-reactive carbohydrate determinants suggested that subjects who tested positive for pollen often had false-positive results due to the impact of cross-reactive carbohydrate determinants.

[Virus-associated hemophagocytic syndrome (VAHS) as an initial manifestation in HIV infection].

A 21-year-old man admitted for idiopathic fever and sore throat was diagnosed with virus-associated hemophagocytic syndrome (VAHS) when bone marrow aspirate showed hemophagocytosis. ELISA for HIV antibodies was negative, although HIV RNA was positive. VAHS is extremely rare as an initial manifestation in HIV infection, being reported, to our knowledge, in only 4 subjects in Japan. Hemophagocytic syndrome (HPS) features fever and hepatosplenomegaly associated with pancytopenia, hypertriglyceridemia, and hypofibrinogemia, due to hypercytokinemia. Physicians should thus be aware that primary HWV infection may involve glandular-fever-like illness and should start prompt diagnosis to contain AIDS spread.

The Prevalence of Odontogenic Pathology in Patients With Bilateral Rhinosinusitis.

OBJECTIVE: We investigated cases with opacification on maxillary sinus computed tomography (CT) among patients with rhinosinusitis with opacification in both paranasal sinuses (bilateral rhinosinusitis) to confirm the involvement of odontogenic infections. METHODS: This study included 75 patients who were diagnosed with bilateral rhinosinusitis based on clinical examination and evident opacification on at least one side on maxillary sinus imaging with computed tomography CT. The definition of odontogenic sinusitis was determined by examining EPT and oral findings, in addition to the CT and orthopantomography (OP), by one oral surgeon and two otolaryngologists. RESULTS: We found that 45.3% of patients had odontogenic infections, which were associated with multiple infected teeth in some cases. Odontogenic infection was observed in both sinuses in some patients. Sinusitis with polyps was frequently associated with dental infection, and some cases were also associated with mycosis. Almost no oral symptoms were observed. CONCLUSIONS: The results suggest that clinicians should consider odontogenic infection in patients with bilateral rhinosinusitis with opacification, on at least one side on maxillary sinus imaging. This means that accurate diagnosis may be challenging for otolaryngologist or dentists alone, suggesting that a collaboration between the two would be suitable for this task.

Odontogenic infection and antiresorptive agent-related osteonecrosis of the jaw with facial subcutaneous abscess formation: A retrospective clinical study of difficult-to-diagnose cases.

OBJECTIVE: The objective of this study was to analyze difficult-to-diagnose cases of odontogenic infection and antiresorptive agent-related osteonecrosis of the jaw (ARONJ) with facial subcutaneous abscesses by otolaryngologists. METHODS: The study was conducted in the department of otolaryngology of a university hospital. Seven patients exhibiting odontogenic infection and ARONJ with facial subcutaneous abscesses diagnosed at the department of otolaryngology in our hospital from January 2008 to December 2018 were included in the study. We investigated the following information obtained from the patients: clinical department for initial treatment, sex, age, offending tooth, causative disease, site of the fistula, symptoms, methods of diagnoses, and therapy. RESULTS: Odontogenic infection with facial subcutaneous abscess formation can occur in individuals in a wide range of age groups; however, the pathological manifestations of ARONJ are often observed in older women, frequently at the chin and accompanied by nodules and pain in the adjacent teeth. Computed tomography and orthopantomography are useful for diagnosis and are especially indicated for patients under long-term follow-up or with frequent recurrences. Magnetic resonance imaging, cytodiagnosis, and histological analysis might be necessary to exclude the possibility of tumors. Management of such facial subcutaneous abscesses comprises dental treatment and infection control, and f surgical removal of the abscess is usually not required. Treatments such as sequestrectomy and sitafloxacin administration are useful for patients with ARONJ. CONCLUSION: Our results demonstrated that for patients with facial subcutaneous abscesses, involvement of odontogenic infection and ARONJ should be considered.

Diagnosing odontogenic sinusitis: An international multidisciplinary consensus statement.

BACKGROUND: Odontogenic sinusitis (ODS) is distinct from non-odontogenic rhinosinusitis, and often requires multidisciplinary collaboration between otolaryngologists and dental providers to make the diagnosis. The purpose of this study was to develop international multidisciplinary consensus on diagnosing ODS. METHODS: A modified Delphi method was used to assess for expert consensus on diagnosing bacterial ODS. A multidisciplinary panel of 17 authors with ODS expertise from 8 countries (8 otolaryngologists, 9 dental specialists) was assembled. Each author completed 2 of 3 surveys (2 specialty-specific, and 1 for all authors). Thirty-seven clinical statements were created, focusing on 4 important diagnostic components: suspecting ODS; confirming sinusitis in ODS; confirming different dental pathologies causing ODS; and multidisciplinary collaborative aspects of diagnosing ODS. Target audiences were all otolaryngologists and dental providers. RESULTS: Of the 37 clinical statements, 36 reached consensus or strong consensus, and 1 reached no consensus. Strong consensus was reached that certain clinical and microbiologic features should arouse suspicion for ODS, and that multidisciplinary collaboration between otolaryngologists and dental providers is generally required to diagnose ODS. To diagnose ODS, otolaryngologists should confirm sinusitis mainly based on nasal endoscopic findings of middle meatal purulence, edema, or polyps, and dental providers should confirm dental pathology based on clinical examination and dental imaging. CONCLUSION: Based on multidisciplinary international consensus, diagnosing ODS generally requires otolaryngologists to confirm sinusitis, and dental providers to confirm maxillary odontogenic pathology. Importantly, both dental providers and otolaryngologists should suspect ODS based on certain clinical features, and refer patients to appropriate providers for disease confirmation.

Relationship between olfactory acuity and peak expiratory flow during postoperative follow-up in chronic rhinosinusitis associated with asthma.

OBJECTIVES: The link between nasal and bronchial disease has been studied extensively for chronic rhinosinusitis and asthma. The concept of "united airway allergy" has become widely accepted in the past decade. We evaluated the relationship between the upper and lower airways during follow-up after endoscopic sinus surgery by monitoring sinonasal and pulmonary functions. METHODS: Thirty-nine subjects with chronic rhinosinusitis associated with bronchial asthma were entered in this study. A self smell test using stick-type odorant materials was carried out daily to evaluate postoperative recurrence of sinonasal disease. Each patient was assessed for peak expiratory flow (PEF) 3 times daily. RESULTS: The average (+/- SD) scores of initial symptoms were 8.3 +/- 2.2, which was significantly decreased to 1.5 +/- 1.4 by 3 months after operation. During postoperative follow-up, 25 of 39 patients showed no decrease in PEF, whereas the other 14 patients had at least 1 episode of a significant decline in PEF. In the postoperative course, with respect to the self smell test, 24 patients showed no aggravation of smell, but 15 patients had episode(s) of decreased olfaction. Twelve patients demonstrated worsening on the smell test concomitant with a decreased PEF. A discrepancy between olfactory acuity and pulmonary function was recognized in 5 patients. There were 22 patients with a good prognosis of parameters of both the upper and lower airways. CONCLUSIONS: Daily monitoring of both upper and lower respiratory tract functions clearly revealed dual relationships, indicating that worsening of sinusitis accompanies asthma exacerbation. Appropriate measures of the upper and lower airways following endoscopic sinus surgery can be used to predict patient outcome.

A randomized prospective study of oral levofloxacin vs intravenous flomoxef prophylaxis in postoperative infection after endoscopic sinus surgery.

OBJECTIVE: The clinical efficacy and cost effectiveness of oral antimicrobial prophylaxis with levofloxacin (LVFX) on endoscopic sinus surgery (ESS) was evaluated. MATERIALS AND METHODS: Ninety-three patients undergoing ESS were prospectively enrolled in the present study. The patients were randomly divided into 2 groups, LVFX and flomoxef (FMOX). Two hundred milligrams of LVFX was orally given 2 hours before the start of surgery and 6 hours after the end of surgery, which was followed by the administration of 200 mg every 12 hours for 2 days. One gram of FMOX was dissolved in 100 ml of physiological saline and given intravenously at the induction of anesthesia and 6 hours after the end of surgery, followed by infusion twice daily for 2 days. RESULTS: There were no statistically significant differences between 2 groups in terms of age, sex, systemic complications, surgical procedures, the duration of the operation, the length of hospitalization, the amount of blood loss, body temperature, or the number of white blood cells or C-reactive protein. Although no statistical significance was observed in the bacterial resistance between the two antibiotics, LVFX seems to show a low rate of resistance pattern change as compared to FMOX. The present study demonstrated that no patients treated with LVFX or FMOX were afflicted with postsurgical infection. CONCLUSION: Oral administration of LVFX is a simple, cost-effective and safe alternative to intravenous prophylaxis in ESS based on clinical efficacy and bacteriological study.

Relationships of opacification in the nasal sinuses, rhinosinusitis, and antiresorptive agent-related osteonecrosis of the jaw.

OBJECTIVE: Bone turnover suppression agents are widely used for prophylaxis of bone metastases from cancer and osteoporosis; the occurrence of their side effect, antiresorptive agent-related osteonecrosis of the jaw (ARONJ), has been increasing. We investigated the relationships between opacification in the nasal sinuses, rhinosinusitis, and ARONJ based on data obtained from oral surgeons. METHODS: We examined 132 patients who had been clinically diagnosed with ARONJ based on clinical observations; all patients had undergone treatment at the Departments of Otorhinolaryngology and Oral Surgery. In 16 of the 132 patients, we confirmed a diagnosis of osteonecrosis of the upper jaw and the presence of ipsilateral opacification of the maxillary sinus. We analyzed the data of these 16 patients in detail. RESULTS: Five of the 16 patients had some nasal symptoms and had been diagnosed with rhinosinusitis. The opacification of the rhinosinuses improved, partially improved, and remained unchanged after treatment in 10, three, and two patients, respectively; notably, imaging assessment could not be conducted after treatment in one case. CONCLUSIONS: Although there is no consensus regarding the treatment of sinusitis accompanying ARONJ, attempts to improve the causal foci and conservative treatment may offer favorable results; thorough investigation is necessary in refractory cases before determining the use of surgery.

Modified Lothrop (Draf III) procedure for the treatment of a recurrent orbitofrontal cholesterol granuloma: A case report.

Orbitofrontal cholesterol granuloma is a rare occurrence. Here, we present a case involving a 64-year-old man with a recurrent orbitofrontal cholesterol granuloma treated by the Modified Lothrop (Draf III) procedure. The patient, who had a history of trauma and previous sinus surgery, presented with chief complaints of nasal congestion, olfactory impairment, and diplopia. We suspected chronic sinusitis; computed tomography showed a soft-tissue shadow extending from the bilateral frontal sinuses to the ethmoid sinuses, with a cyst in the right orbitofrontal region. We performed endoscopic surgery for removal of the mass, and histopathological analysis of the resected specimen confirmed a diagnosis of cholesterol granuloma. The lesion recurred 2 months later, and we performed revision surgery using the Modified Lothrop or Draf III procedure. The patient showed no relapse at the 5-year follow-up. These findings suggest that the Draf III procedure is an effective surgical treatment for cholesterol granulomas.

Abducens Nerve Paralysis Induced by a Primary Solitary Sphenoid Sinus Mucocele with Broad Osseous Thinning at the Cranial Base.

Primary solitary sphenoid sinus mucocele is rare, generally presenting with headaches or eye symptoms at the anatomical site. We report the case of a 39-year-old woman incidentally diagnosed with sphenoid sinus mucocele during a complete medical checkup. Imaging revealed that the cystic wall had developed from the rear sphenoid sinus and had spread expansively to diminish the clivus; however, no symptoms were reported, and the patient was managed with close observation. During the follow-up period, diplopia developed suddenly due to isolated left-sided abducens nerve paralysis. An endoscopic endonasal approach was used to open the frontal cystic wall, and fascia lata and fat were used for cranial base reinforcement to avoid future cerebrospinal fluid leakage, resulting in improvement during the early stages of follow-up. Treatment options for sphenoid sinus mucoceles include close observation or surgery. In our case, we chose surgery because of an acute symptomatic manifestation during observation.

Inhibitory action of roxithromycin on histamine release and prostaglandin D2 production from beta-defensin 2-stimulated mast cells.

The long-term, low-dose therapy with the 14-membered macrolides is well known to be effective for treatment of chronic airway inflammation. Although the mode of macrolides on neutrophils, monocytes, and epithelial cells has been investigated, the effect of macrolides on mast cell function is sparsely reported on. We first examined the effect of roxithromycin (RXM) on mast cell functions activated by human beta-defensin-2 (hBD-2). In this study, histamine release, prostaglandin D2 (PGD2) production, and intracellular Ca2+ concentration ([Ca2+]i) were measured in the absence and presence of RXM, using rat peritoneal mast cells stimulated with hBD-2. RXM, at doses of 12.5 and 25 microg/ml, significantly inhibited the histamine release from mast cells (p<0.05). In addition, PGD2 production induced by hBD-2 was significantly reduced by RXM at 6.25 (p<0.05) and 12.5 microg/ml (p<0.01). Furthermore, the hBD-2-induced increase of [Ca2+]i in mast cells was inhibited by 6.25 and 12.5 microg/ml of RXM (p<0.05). The present findings suggest that RXM modulates mast cell activation induced by hBD-2 via a Ca2+ signal pathway, thereby possibly alleviating chronic airway inflammation.

Prevention of ultrasonic coagulator-mediated mucoperiosteal flap injury and defects by using a clip manipulation in the resection of the posterior nasal nerve.

We previously reported on the clinical effectiveness of functional inferior turbinosurgery utilizing modified vidian neurectomy, the resection of the posterior nasal nerve (PNN), combined with inferior turbinoplasty. In order to prevent re-innervation of the PNN after resection and to avoid postoperative massive hemorrhage--presumably resulting from insufficient fixation and unexpected exposure of the bony or cartilaginous fragments covered on the resected neurovascular bundle containing the sphenopalatine vessels and the PNN--we designed a surgical technique during which a vascular clip was used in order to provide traction of the mucoperiosteal flap. Then we compared it with the previous procedure (without the use of the clip). The injury and defects of the mucoperiosteal flap were evaluated by the degree of exposure to the bony or cartilaginous fragments and scored on a scale of 0 to 2 points. The defects of the mucoperiosteal flap were reduced by using a vascular clip. The average score of the defects was 0.97 +/- 0.73 (n = 64) in the conventional procedure without any manipulation and 0.27 +/- 0.45 (n = 60) in the procedure using a vascular clip. The difference observed between the two gropups was statistically significant (p < 0.001). These results demonstrated that this is a safe technique to prevent injury and defects of the mucoperiosteal flap in gaining access to expose the PNN. This should promote early wound healing, reduce the chance of recurrence and of postoperative massive hemorrhage.

Inhibition of FcepsilonRI-dependent mediator release and calcium flux from human mast cells by sialic acid-binding immunoglobulin-like lectin 8 engagement.

BACKGROUND: Sialic acid-binding immunoglobulin-like lectins (Siglecs) are a family of glycan-binding inhibitory receptors, and among them, Siglec-8 is selectively expressed on human eosinophils, basophils, and mast cells. On eosinophils, Siglec-8 engagement induces apoptosis, but its function on mast cells is unknown. OBJECTIVE: We sought to study the effect of Siglec-8 engagement on human mast cell survival and mediator release responses. METHODS: Human mast cells were generated from CD34+ precursors. Apoptosis was studied by using flow cytometry. Mast cell mediator release or human lung airway smooth muscle contraction was initiated by FcepsilonRI cross-linking with or without preincubation with Siglec-8 or control antibodies, and release of mediators was analyzed along with Ca++ flux. RBL-2H3 cells transfected with normal and mutated forms of Siglec-8 were used to study how Siglec-8 engagement alters mediator release. RESULTS: Siglec-8 engagement failed to induce human mast cell apoptosis. However, preincubation with Siglec-8 mAbs significantly (P < .05) inhibited FcepsilonRI-dependent histamine and prostaglandin D(2) release, Ca++ flux, and anti-IgE-evoked contractions of human bronchial rings. In contrast, release of IL-8 was not inhibited. Siglec-8 ligation was also shown to inhibit beta-hexosaminidase release and Ca++ flux triggered through FcepsilonRI in RBL-2H3 cells transfected with full-length human Siglec-8 but not in cells transfected with Siglec-8 containing a tyrosine to phenylalanine point mutation in the membrane-proximal immunoreceptor tyrosine-based inhibitory motif domain. CONCLUSION: These data represent the first reported inhibitory effects of Siglec engagement on human mast cells.

Two Cases of Allergic Fungal Sinusitis with Differing Postoperative Course.

Allergic fungal sinusitis (AFS) often develops in unilateral paranasal sinuses, which must be differentiated from tumors. When AFS develops on both sides, however, it must be differentiated from eosinophilic chronic sinusitis with evident eosinophilic infiltration at nasal/paranasal sinus mucosa; both conditions are highly recurrent and commonly considered intractable paranasal sinusitis. Surgical correction is the primary treatment method for AFS, as it is essential to connect the paranasal sinus communication to ensure exhaustive resection of the pathologic mucosa and for nasal steroids to reach each paranasal sinus. We recently encountered two AFS cases with differing postoperative courses. Case 1 showed evident exacerbation in the computed tomography findings, which suggests progression to eosinophilic sinusitis. Case 2 showed a benign prognosis without recurrence. Close long-term follow-up should be mandatory after surgery for the treatment of AFS.