Further evidence for allergic pathophysiology in allergic fungal sinusitis

Controversy continues over whether allergic fungal sinusitis represents a true allergy, an infection, or a point somewhere along a spectrum between allergy and infection. The present study describes two experiments that add weight to the argument that allergic fungal sinusitis (AFS) is truly an immunologically mediated hypersensitivity and not a form of infection. In the first experiment, eight patients with Bipolaris culture-positive AFS were prospectively evaluated with Bipolaris antigen skin testing and with inhibition radioallergosorbent (RAST) and enzyme-linked immunosorbent assay (ELISA) for Bipolaris-specific IgE and IgG antibodies. The Bipolaris AFS cases were compared with 10 control patients with no history of AFS. All eight AFS cases demonstrated positive skin testing to Bipolaris and in addition, all tested positive by RAST and ELISA for IgE and IgG Bipolaris antibodies, respectively. In the control group one patient had a positive skin test, ELISA, and RAST and one additional patient had a positive ELISA only. Good correlation was noted between skin test, RAST, and ELISA results. In the second experiment, sinus mucosa from 14 AFS patients and 10 control patients with other forms of surgical sinus disease was analyzed by immunohistocytochemistry for the eosinophilic inflammatory mediators major basic protein (MBP) and eosinophil derived neurotoxin (EDN) and the neutrophil mediator neutrophil elastase. All AFS cases demonstrated evidence of eosinophilic mediator release, and MBP and EDN predominated over neutrophil elastase. In the control group eosinophil and neutrophil mediator release in sinus mucosa was equal. The two experiments support the concept that AFS is an antigen-triggered, IgE- and IgG-mediated hypersensitivity response with a late-phase inflammatory reaction involving release of eosinophilic mediators.     

Allergenic fungi in allergic fungal sinusitis

The lung relies upon epithelial active transport of Na+ to aid in the clearance of fluid from its air spaces. Because it is unknown whether the rate of active Na+ transport by the distal lung epithelium varies during early postnatal age, we performed studies in young guinea pigs (7 and 30 days after birth). We used a single pass isolated perfused lung model in which a Krebs Ringer bicarbonate solution containing 22Na+, [14C]sucrose, and FITC-dextran was placed into the air spaces of the lungs, and apparent permeability-surface area (PS) products were calculated after determining the changes in lung weight and the concentrations of the isotopes in the vascular effluent. The PS product for 22Na+, but not [14C]sucrose, decreased significantly at both ages when amiloride was infused (final concentration of 10(-4) M). Amiloride also decreased the rate of fluid clearance, as assessed by changes in organ weight, at both ages. Although the absolute rate of amiloride-sensitive 22Na+ transport increased with age, morphometric measurement of the alveolar region demonstrated that the rate of amiloride-sensitive 22Na+ transport per unit alveolar surface area was similar. These data indicate that although the guinea pig lung undergoes significant growth shortly after birth, the rate of amiloride-sensitive active Na+ transport per unit surface area remains constant. Since a component of weight loss was insensitive to amiloride, these in vivo studies suggest that the amiloride-insensitive Na+ transport pathways previously identified in cultured lung epithelium exist in the intact lung.     

The origins of basophils and eosinophils in allergic inflammation

The bone marrow actively participates in the production of IgE-positive inflammatory cells (eosinophils, basophils, and mast cells), which are typically recruited to tissues in atopic individuals. Understanding the signaling between the tissue and the bone marrow at the molecular level may well open up new avenues of therapy for allergic inflammation.     

Local and systemic eosinophil activation in allergic fungal sinusitis

Research into the genetics of migraine remains difficult because of the involvement of polygenetic and environmental factors. The discovery of the gene for familial hemiplegic migraine on chromosome 19p 13 is an important step forward. This brain specific P/Q-type calcium channel alpha 1-subunit gene opens new avenues for studying the genetics of migraine, the pathophysiology of the onset of migraine attacks and the development of novel specific prophylactic drugs.     

Pattern of circulating eosinophils in allergic children suffering from infectious disease

We report a patient presenting with melena. Endoscopic examination showed gastric fundal varices as well as colonic varices. The latter is rarely encountered and is usually associated with portal hypertension. On angiography there appeared to be a splenic vein thrombosis which is only reported once earlier as a cause of colonic varices. A short review of the literature concerning colonic varices is added.     

Clinical features and characteristics of paranasal sinus effusion in allergic sinusitis

Paraproteins or monoclonal proteins are the result of clonal B-cell or plasma cell proliferation of a malignant, premalignant or non-malignant nature. Monoclonal proteins may consist of intact immunoglobulin molecules or of heavy or light chains only. Depending on their rate of production and/or secretion they may accumulate in the serum and/or urine of patients. Their presence in the circulation may remain silent, as in monoclonal gammopathy of undetermined significance (MGUS), or may lead to clinical syndromes such as Hyperviscosity, Acrocyanosis, Cold hemagglutination, hemolysis and hemorrhagic manifestations. Their tissue deposition may be localized, with the kidney being the most frequent target as in Myeloma Cast Nephropathy or systemic, as in AL amyloidosis where heart, liver, nerves, tongue are usual targets, in addition to the kidneys.     

Inhibitory effect of F-1322 on allergic eosinophil infiltration in airways

The effects of F-1322 (N-[2-[4-(benzhydryloxy)piperidino]ethyl]-3-hydroxy-5-(3-pyridy lmethoxy)-2-naphthamide) on antigen-induced eosinophil infiltration and interleukin-5 production in the airways and on in vitro eosinophil migration were investigated. F-1322 (10-30 mg/kg, p.o.) inhibited antigen-induced eosinophil infiltration and interleukin-5 production in the airways of sensitized mice in a dose-dependent manner. Furthermore, F-1322 (0.1-10 microM) prevented the in vitro migration of eosinophils from guinea-pigs and humans induced by recombinant human interleukin-5, platelet-activating factor, and leukotriene B4 in a concentration-dependent manner. These results indicate that F-1322 has an inhibitory effect on allergic eosinophil infiltration of the airways by preventing both eosinophil migration and interleukin-5 production. These pharmacological profiles suggest that F-1322 will be a useful therapeutic for allergic diseases, especially asthma.     

The role of powered instrumentation in the surgical treatment of allergic fungal sinusitis

Allergic fungal sinusitis is a chronic disorder that is being more frequently recognized by otolaryngologists. It is a recurrent illness characterized by frequent exacerbations, and requires aggressive medical and surgical treatment. When surgical therapy is employed, it is necessary to ensure adequate debridement and removal of edematous tissue. We have been using powered dissection as our primary method in sinus surgery over the past three year. We have treated 11 patients with allergic fungal sinusitis, and find powered instrumentation to be very effective in removing the polypoid tissue from the nose and sinuses, and in providing a clear surgical field. The procedure can be performed safely with minimal trauma to normal tissue. We believe that the use of powered dissection greatly enhances the comprehensive treatment of allergic fungal sinusitis.     

Solution structure of eotaxin, a chemokine that selectively recruits eosinophils in allergic inflammation

The solution structure of the CCR3-specific chemokine, eotaxin, has been determined by NMR spectroscopy. The quaternary structure of eotaxin was investigated by ultracentrifugation and NMR, and it was found to be in equilibrium between monomer and dimer under a wide range of conditions. At pH 相似文献   

IL-5 production by NK cells contributes to eosinophil infiltration in a mouse model of allergic inflammation

IL-5 production in vivo plays a unique role in the production, activation, and localization of eosinophils in a variety of allergic conditions. The current paradigm suggests that allergen-specific Th2 cells are the main source for the IL-5 production. The experiments outlined in this work, however, suggest that in vivo production of IL-5 by NK cells can separately influence eosinophil-associated inflammatory responses. Specifically, a mouse model of allergic inflammation was used in which C57BL/6 mice were immunized and challenged with a short ragweed Ag extract, known to induce a selective eosinophilia within the peritoneal cavity. Peritoneal lavage fluids from these mice also contained increased numbers of T cells and NK cells, as well as significantly elevated levels of IL-4, IL-5, and IFN-gamma. Flow-cytometric analysis of cytokine-producing cells in peritoneal lavage fluid revealed increased numbers of IL-5-producing cells in both T cell and NK cell populations following allergen exposure. Depletion of NK cells by treatment with NK1.1 Abs selectively reduced the number of infiltrating eosinophils by more than 50%. Moreover, the inhibition of the infiltration of eosinophils was accompanied by a complete loss of IL-5-producing NK cells and significantly reduced levels of peritoneal lavage fluid IL-5, whereas the number of IL-5-producing T cells was not affected. Thus, the results presented in this study provide clear evidence for a novel immunoregulatory function of NK cells in vivo, promoting allergen-induced eosinophilic inflammatory responses by the production of IL-5.     

Adjunct effect of loratadine in the treatment of acute sinusitis in patients with allergic rhinitis

Recently, it has been recognized that cell-bound heparan sulfate (HS) proteoglycans (HSPG) are able to bind and subsequently initiate degradation of lipoproteins. Two mediators of lipoprotein catabolism, both with HS binding capacity, lipoprotein lipase (LPL) and apolipoprotein E (apoE), are involved in this process. This mechanism is known as the secretion-capture process of apoE. Lipoprotein(a) [Lp(a)] was shown to have a strong binding capacity to cell-associated HSPG. This binding capacity was increased by LPL addition. We investigated the effects of recombinant apoE (r-apoE) enrichment of Lp(a) on the binding to HS. Lp(a), isolated by ultracentrifugation and gel filtration, was incubated with r-apoE and reisolated by ultracentrifugation, resulting in r-apoE-enriched Lp(a). ApoE-enriched Lp(a) and control Lp(a) were coated to microtiter plates. The capacity to bind biotin-conjugated HS (b-HS) in the presence or absence of inactivated bovine LPL was studied. R-apoE-enriched Lp(a) showed increased b-HS binding capacity versus control Lp(a). Addition of LPL resulted in an increased b-HS binding capacity of both control and r-apoE-enriched Lp(a). To investigate whether binding of Lp(a) to endothelial cell HSPG occurred in vivo, 39 volunteers were injected with heparin (50 U/kg) and plasma lipid and Lp(a) levels were determined before and 20 minutes after heparin injection. No significant increase in plasma Lp(a) concentrations was found. The results showed that Lp(a) can be enriched with apoE and that this resulted in increased LPL-enhanced binding to HSPG. From the in vitro studies, it can be concluded that the secretion-capture process of apoE is a possible catabolic route for Lp(a). However, whether this also occurs in vivo remains to be confirmed.     

Evaluation and treatment of allergic fungal sinusitis. I. Demographics and diagnosis

BACKGROUND: Few cases of allergic fungal sinusitis have been systematically evaluated to conclusively confirm working clinical, histopathologic, and serologic diagnostic criteria. OBJECTIVES: The objective of this study was to describe 67 consecutive cases of allergic fungal sinusitis, the largest number of cases yet published. METHODS: Cases from 1 practice over 8 years were evaluated with a consistent protocol, including skin testing, serum chemistries and serologies, and surgical specimen analysis. RESULTS: All patients were atopic (100 %) and had nasal polyposis (100%). They tended to be young (33.3+/-13.1 years, mean +/-SEM), immunocompetent (92 %; remaining 8 % with low quantitative immunoglobulin but normal function), have slight female preponderance (58%), have a history of hypertrophic rhinosinusitis (100%), report nasal cast production (75%), and have developed their disease in the southwestern United States. Bipolaris spicifera was the most prevalent fungus involved (67%). Total serum IgE (mean 668 IU/mL) and fungal-specific IgG were generally elevated, whereas fungal-specific precipitins and specific IgE were generally negative despite positive fungal-specific immediate hypersensitivity skin tests. CONCLUSIONS: Patients with allergic fungal sinusitis tend to have elevated total serum IgE and fungal-specific IgG at diagnosis but not fungal-specific IgE or precipitins. Histopathologic criteria for allergic fungal sinusitis diagnosis are discussed. The southwestern United States appears to be a "hot spot" for the disease, particularly caused by B spicifera.     

Efficacy of lodoxamide eye drops on mast cells and eosinophils after allergen challenge in allergic conjunctivitis

PURPOSE: The purpose of the study is to evaluate in a double-blind, randomized study the efficacy of lodoxamide tromethamine 0.1% versus placebo. METHODS: Signs and symptoms, tear tryptase, and tear fluid cytology were evaluated in 20 asymptomatic subjects with allergic conjunctivitis. The study included three allergen challenges in skin test-positive patients. At the first visit, a threshold dose of allergen was established. At the second visit, a bilateral ocular challenge was performed without pretreatment. At the third visit, either lodoxamide or placebo eye drops were used for 1 week before ocular challenge. RESULTS: Lodoxamide significantly reduced tryptase levels (P < 0.01), neutrophils (P < 0.04), and eosinophils (P < 0.01) in the tear fluid and significantly inhibited ocular itching (P < 0.02) when compared with that of placebo. CONCLUSIONS: Lodoxamide is effective in reducing tryptase levels and the recruitment of inflammatory cells in the tear fluid after allergen challenge.     

Diagnostic use of enzymatic RAST skin tests and determination of eosinophils in nasal mucosa in allergic rhinitis

AIMS: Allergic rhinitis is the most frequent disease mediated by immunoglobulin E (IgE). Nasal challenge is the gold standard for the diagnosis of allergic rhinitis. Skin tests (ST) are the most used diagnostic method to detect the presence of specific IgE bind to skin mast cells. The exposition of the nasal mucous membrane to the allergen is followed by an increase of the local eosinophils; the count of eosinophils in nasal mucous (ENM) is a diagnostic test for allergic rhinitis. Enzymatic RAST or enzymatic allergo-sorbent test (ESA) measures the level of serum allergen-specific IgE. OBJECTIVE: To measure the sensitivity, specificity, and diagnostic precision of ST, EAST and ENM in allergic rhinitis. METHOD: We studied 241 individuals, 162 of them had allergic rhinitis, and 79 were healthy controls. They underwent nasal challenge and intradermic ST for Dermatophagoies spp (acarus). Fraxinus americana (Ash-tree), Amaranthus palmieri (quelite), Cynodon Dactylon (capriola) and Felis catus (cat), EAST for Dermatophagoides pteronyssinus (acarus), and ENIVI. Results of ST, EAST and ENIVI were compared with their corresponding nasal challenge, and the prevalence of allergic rhinitis for each allergen was calculated. The best cut point was assessed by means of receiver-operator curves (ROC), and sensitivity, specificity, positive predictive value, negative predictive value, inter-observer concordance coefficient, area under ROC (0), standard error of 0 (SEO), and 95% confidence interval of 0 of each test were calculated using the best cut point. RESULTS: ST and EAST had the best sensitivity and specificity. ENM had the lowest sensitivity and specificity. CONCLUSION: For the diagnosis of Dermatophagoides spp allergic rhinitis ST for Dermatophagoides spp and EAST for Dermatophagoides pteronyssinus have the same diagnostic precision. According to the indexes for diagnostic precision, and inter-observer concordance coefficient, ST and EAST are useful to diagnose allergic rhinitis induced by the evaluated allergens. ENIVI is a test that is not very useful for the diagnosis of allergic rhinitis.     

Increased calpain expression in activated glial and inflammatory cells in experimental allergic encephalomyelitis

In demyelinating diseases such as multiple sclerosis (MS), myelin membrane structure is destabilized as myelin proteins are lost. Calcium-activated neutral proteinase (calpain) is believed to participate in myelin protein degradation because known calpain substrates [myelin basic protein (MBP); myelin-associated glycoprotein] are degraded in this disease. In exploring the role of calpain in demyelinating diseases, we examined calpain expression in Lewis rats with acute experimental allergic encephalomyelitis (EAE), an animal model for MS. Using double-immunofluorescence labeling to identify cells expressing calpain, we labeled rat spinal cord sections for calpain with a polyclonal millicalpain antibody and with mAbs for glial (GFAP, OX42, GalC) and inflammatory (CD2, ED2, interferon gamma) cell-specific markers. Calpain expression was increased in activated microglia (OX42) and infiltrating macrophages (ED2) compared with controls. Oligodendrocytes (galactocerebroside) and astrocytes (GFAP) had constitutive calpain expression in normal spinal cords whereas reactive astrocytes in spinal cords from animals with EAE exhibited markedly increased calpain levels compared with astrocytes in adjuvant controls. Oligodendrocytes in spinal cords from rats with EAE expressed increased calpain levels in some areas, but overall the increases in calpain expression were small. Most T cells in grade 4 EAE expressed low levels of calpain, but interferon gamma-positive cells demonstrated markedly increased calpain expression. These findings suggest that increased levels of calpain in activated glial and inflammatory cells in EAE may contribute to myelin destruction in demyelinating diseases such as MS.     

Analysis of signal transduction pathways in human eosinophils activated by chemoattractants and the T-helper 2-derived cytokines interleukin-4 and interleukin-5

Activation and recruitment of eosinophils in allergic inflammation is in part mediated by chemoattractants and T-helper 2 (Th2)-derived cytokines. However, little is known concerning the signal transduction mechanisms by which this activation occurs. We have investigated tyrosine kinase-mediated activation of phosphatidylinositol 3-kinase (PI3K) and compared this with the activation of the p21ras-ERK signaling pathway in human eosinophils. The related cytokines interleukin-3 (IL-3), IL-5, and granulocyte-macrophage colony-stimulating factor (GM-CSF), all induced PI3K activity detected in antiphosphotyrosine immunoprecipitates. Furthermore, the chemoattractants platelet-activating factor (PAF), RANTES, and C5a were also able to induce phosphotyrosine-associated PI3K activity. Protein kinase B (PKB) is a downstream target of PI3K activation by growth factors. Induction of PKB phosphorylation in human eosinophils was transiently induced on activation with the cytokines IL-4 and IL-5, as well as the chemoattractants PAF, C5a, and RANTES showing a broad activation profile. Surprisingly, analysis of the activation of the mitogen-activated protein (MAP) kinases p44(ERK1) and p42(ERK2), showed that ERK2, but not ERK1, was transiently activated in human eosinophils after stimulation with IL-5 or PAF. Activation kinetics correlated with activation of p21ras by both cytokines and chemoattractants as measured by a novel assay for guanosine triphosphate (GTP)-loading. Finally, using specific inhibitors of both the p21ras-ERK and PI3K signaling pathways, a role was demonstrated for PI3K, but not p21ras-ERK, in activation of the serum-treated zymosan (STZ)-mediated respiratory burst in IL-5 and PAF-primed eosinophils. In summary, these data show that in human eosinophils, Th2-derived cytokines differentially activate both PI3K and MAP kinase signal transduction pathways with distinct functional consequences showing complex regulation of eosinophil effector functions.     

Antigen-induced airway hyperresponsiveness is associated with infiltration of eosinophils in lung tissue, but not with bronchoalveolar lavage eosinophilia or neutrophilia

Hemimicropsia is a rare disorder of visual perception characterized by an apparent reduction of the size of objects when presented in one hemifield. We report two cases of hemimicropsia resulting from focal brain lesions. The first patient was an art teacher and could accurately depict his abnormal visual perception. He subsequently died and his brain was examined post mortem. In the second patient, micropsia was assessed by a quantified size comparison task. The size of a given object is normally perceived as constant across any spatial position. Hemimicropsia may thus be considered a limited violation of the size constancy principle. Behavioural and anatomical data are discussed in relation to the neural basis of visual object perception in humans.     

Apoptosis in rat prostatic adenocarcinoma is associated with rapid infiltration of cytotoxic T-cells and activated macrophages

The laser has played a valuable primary and adjunctive role in the management of nasal and sinus disorders. When using the laser there must be appropriate knowledge about safety, instrumentation, and types of pathologic conditions in which the laser is effective. The laser is effective for turbinate dysfunction of various causes. Its coagulating, cutting, and vaporization ability make it useful in managing intranasal vascular disorders such as hereditary hemorrhagic telangiectasia and hemangioma. There is some promise in using the laser for nasal polyposis with eosinophilia.