Local fungus-specific Immunoglobulin E production in chronic rhinosinusitis with nasal polyps.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous disease, and its pathogenesis remains controversial. This study aimed to examine the involvement of fungi in CRSwNP pathogenesis. METHODS: We enrolled 29 controls and 111 CRSwNP patients. We analyzed fungi in the nasal secretions, serum fungus-specific immunoglobulin E (IgE) levels, and nasal polyp (NP) IgE levels. Moreover, we evaluated the correlation between patients' IgE levels and computed tomography (CT) scores. RESULTS: There was no difference in fungal detection rate between CRSwNP patients with and without asthma. Specific IgEs against various antigens were highly detectable in NPs of CRSwNP patients. In CRSwNP patients, fungus-specific IgE levels in NPs were correlated with CT scores. Serum fungus-specific IgEs became undetectable after operation in more than half of the CRSwNP patients without asthma but not in those with asthma. Other serum airborne antigen-specific IgEs did not become undetectable after operation. CONCLUSIONS: Fungus-specific IgEs were highly detectable in NPs of CRSwNP patients, and NPs comprised a major region of specific IgE production. Fungi may therefore play an important role in CRSwNP pathogenesis by inducing Th2 immune responses, including IgE synthesis.

Coupled afterslip and transient mantle flow after the 2011 Tohoku earthquake.

Modeling of postseismic deformation following great earthquakes has revealed the viscous structure of the mantle and the frictional properties of the fault interface. However, for giant megathrust events, viscoelastic flow and afterslip mechanically interplay with each other during the postseismic period. We explore the role of afterslip and viscoelastic relaxation and their interaction in the aftermath of the 2011 M w (moment magnitude) 9.0 Tohoku earthquake based on a detailed model analysis of the postseismic deformation with laterally varying, experimentally constrained, rock rheology. Mechanical coupling between viscoelastic relaxation and afterslip notably modifies both the afterslip distribution and surface deformation. Thus, we highlight the importance of addressing mechanical coupling for long-term studies of postseismic relaxation, especially in the context of the geodynamics of the Japan trench across the seismic cycle.

Involvement of transient receptor potential vanilloid 2 in intra-oral incisional pain.

OBJECTIVE: To examine whether transient receptor potential vanilloid 2 (TRPV2) contributes to the changes in intra-oral thermal and mechanical sensitivity following the incision of buccal mucosa. MATERIALS AND METHODS: Buccal mucosal pain threshold was measured after the incision. Changes in the number of TRPV2-immunoreactive (IR) trigeminal ganglion (TG) neurons which innervate the whisker pad skin and buccal mucosa, changes in the number of isolectin B4-negative/isolectin B4-positive TRPV2-IR TG neurons which innervate the whisker pad skin and the buccal mucosa, and the effect of peripheral TRPV2 antagonism on the pain threshold of incisional whisker pad skin and buccal mucosa were examined after these injuries. RESULTS: Buccal mucosal pain hypersensitivities were induced on day 3 following the incision. The total number of TRPV2-IR TG neurons and the number of isolectin B4-negative TRPV2-IR TG neurons which innervate the whisker pad skin and buccal mucosa were increased. Buccal mucosal TRPV2 antagonism completely suppressed the heat and mechanical hypersensitivities, but not cold hypersensitivity. TRPV2 antagonist administration to the incisional whisker pad skin only partially suppressed pain hypersensitivities. CONCLUSION: The increased expression of TRPV2 in peptidergic TG neurons innervating the incisional buccal mucosa is predominantly involved in buccal mucosal heat hyperalgesia and mechanical allodynia following buccal mucosal incision.

Identification of specifically reduced Th2 cell subsets in allergic rhinitis patients after sublingual immunotherapy.

BACKGROUND: Although Th2 cells are well known to play important roles in allergic diseases including allergic rhinitis (AR), the factors that induce and sustain the pathogenesis of AR remain unclear. The recent development of sublingual immunotherapy (SLIT) is expected to allow changes to the underlying pathogenesis of AR. However, which Th2 cell subsets are important in house dust mite-induced AR (HDM-AR), the influence of SLIT on the pathogenic Th2 cells, and the association of Th2 cell subsets with SLIT efficacy have not been clarified. METHODS: The cytokine production and frequency of HDM-reactive T-cell subsets in peripheral blood mononuclear cells (PBMCs) were evaluated using flow cytometry in 89 HDM-AR patients (placebo [n = 43] and HDM 300 IR [n = 46]) who participated in a placebo-controlled study of SLIT with HDM tablets. All patients provided samples both before treatment as a baseline and at the end of the 52-week study. The PBMCs were stained with CellTrace™ Violet (CTV) before culture with HDM extract, and HDM-reactive T cells were detected as the proliferated cells with diminished CTV. RESULTS: HDM-reactive IL-5+ IL-13+ CD27- CD161+ CD4+ cells and ST2+ CD45RO+ CD4+ cells were observed in the peripheral blood from each patient with HDM-AR; these cells significantly decreased after SLIT in the group treated with active tablets. HDM-reactive ST2+ CD45RO+ CD4+ cells were significantly lower in active-responders. CONCLUSION: Allergen-reactive ST2+ CD45RO+ CD4+ cells or those combined with IL-5+ IL-13+ CD27- CD161+ CD4+ cells may be useful as markers indicating the successful treatment of SLIT. These cells may play a crucial role in the pathogenesis of AR as pathogenic memory Th2 cells.

Pathogenicity of memory Th2 cells is linked to stage of allergic rhinitis.

BACKGROUND: Allergic rhinitis (AR) consists of three developmental stages that are based on the presence/absence of antigen-specific IgE and symptoms. The pathogenic Th2 (Tpath2) cells constitute a population of Th2 cells with additional potentially pathogenic characteristics. We examined the relationship between Tpath2 cells and the stages of allergic rhinitis by focusing on ST2, which is an IL-33 receptor. METHODS: Patients with Japanese cedar pollen-induced AR (JCP-AR) and healthy volunteers were divided into "nonsensitized," "asymptomatic sensitized (AS)," and "JCP-AR" groups. We analyzed the ST2 expression and the Th2 function of cultured CD4+ T cells. Next, we observed the progress of patients in the AS stage around the time of seasonal pollen dispersal, with the characteristics of Th2 cells. RESULTS: The ST2 expression of T cells was only upregulated in the AR group. The production of IL-4 and IL-13 was found in CD4+ T cells obtained from AS by stimulation with JCP, but reactivity to IL-33 was not observed. Although IL-33 did not induce the elevation of IL-4 production in the JCP-AR group, IL-33 substantially increased the production of IL-5 and IL-13 in comparison with antigen stimulation alone. In newly afflicted patients, the increased expression of ST2 and elevated reactivity to IL-33 was observed, even before the pollen dispersal season. CONCLUSIONS: Our study demonstrated that the pathogenicity of memory Th2 cells is linked to sensitization and the stage of allergic rhinitis. Therefore, Tpath2 cells may provide useful insights into the mechanism of the onset and progression of allergic rhinitis.

Sublingual immunotherapy for allergic rhinitis: subjective versus objective tools to evaluate its success.

BACKGROUND: Biomarkers that enable objective evaluation of the clinical effects of immunotherapy for allergic rhinitis have yet to be identified. METHODS: This study included 40 patients who were enrolled in a large randomized, double-blind, placebo-controlled, multicenter study examining the efficacy of sublingual immunotherapy (SLIT) using Japanese cedar (JC) pollen extract during two consecutive pollen seasons from 2010 to 2012. Based on changes in total nasal symptom medication score, patients in the SLIT and placebo groups were subdivided into two subgroups: good responders and poor responders. The levels of JC pollen-specific IL-10+Foxp3+ cells and specific Th2 cytokine-producing cells were measured and the association with the efficacy of SLIT was analysed. RESULTS: The total nasal symptom medication score was significantly lower in the SLIT group compared with the placebo group. The number of JC pollen-specific Th2 cytokine-producing cells increased during the pollen season in the placebo group and in poor responders in the SLIT group; however, the increases were inhibited in the good responders in the SLIT group. The number of JC pollen-specific IL-10+Foxp3+ cells increased only in these good responders. CONCLUSIONS: Changes in levels of allergen-specific Th2 cytokine-producing cells and IL-10+Foxp3+ cells could be objective biomarkers for SLIT.

Denture wearing during sleep doubles the risk of pneumonia in the very elderly.

Poor oral health and hygiene are increasingly recognized as major risk factors for pneumonia among the elderly. To identify modifiable oral health-related risk factors, we prospectively investigated associations between a constellation of oral health behaviors and incident pneumonia in the community-living very elderly (i.e., 85 years of age or older). At baseline, 524 randomly selected seniors (228 men and 296 women; mean age, 87.8 years) were examined for oral health status and oral hygiene behaviors as well as medical assessment, including blood chemistry analysis, and followed up annually until first hospitalization for or death from pneumonia. During a 3-year follow-up period, 48 events associated with pneumonia (20 deaths and 28 acute hospitalizations) were identified. Among 453 denture wearers, 186 (40.8%) who wore their dentures during sleep were at higher risk for pneumonia than those who removed their dentures at night (log rank P = 0.021). In a multivariate Cox model, both perceived swallowing difficulties and overnight denture wearing were independently associated with an approximately 2.3-fold higher risk of the incidence of pneumonia (for perceived swallowing difficulties, hazard ratio [HR], 2.31; and 95% confidence interval [CI], 1.11-4.82; and for denture wearing during sleep, HR, 2.38; and 95% CI, 1.25-4.56), which was comparable with the HR attributable to cognitive impairment (HR, 2.15; 95% CI, 1.06-4.34), history of stroke (HR, 2.46; 95% CI, 1.13-5.35), and respiratory disease (HR, 2.25; 95% CI, 1.20-4.23). In addition, those who wore dentures during sleep were more likely to have tongue and denture plaque, gum inflammation, positive culture for Candida albicans, and higher levels of circulating interleukin-6 as compared with their counterparts. This study provided empirical evidence that denture wearing during sleep is associated not only with oral inflammatory and microbial burden but also with incident pneumonia, suggesting potential implications of oral hygiene programs for pneumonia prevention in the community.

Activation of invariant natural killer T cells in regional lymph nodes as new antigen-specific immunotherapy via induction of interleukin-21 and interferon-γ.

Invariant natural killer T (iNKT) cells play important immunoregulatory functions in allergen-induced airway hyperresponsiveness and inflammation. To clarify the role of iNKT cells in allergic rhinitis (AR), we generated bone marrow-derived dendritic cells (BMDCs), which were pulsed by ovalbumin (OVA) and α-galactosylceramide (OVA/α-GalCer-BMDCs) and administered into the oral submucosa of OVA-sensitized mice before nasal challenge. Nasal symptoms, level of OVA-specific immunoglobulin (IgE), and T helper type 2 (Th2) cytokine production in cervical lymph nodes (CLNs) were significantly ameliorated in wild-type (WT) mice treated with OVA/α-GalCer-BMDCs, but not in WT mice treated with OVA-BMDCs. These anti-allergic effects were not observed in Jα18(-/-) recipients that lack iNKT cells, even after similar treatment with OVA/α-GalCer-BMDCs in an adoptive transfer study with CD4(+) T cells and B cells from OVA-sensitized WT mice. In WT recipients of OVA/α-GalCer-BMDCs, the number of interleukin (IL)-21-producing iNKT cells increased significantly and the Th1/Th2 balance shifted towards the Th1 dominant state. Treatment with anti-IL-21 and anti-interferon (IFN)-γ antibodies abrogated these anti-allergic effects in mice treated with α-GalCer/OVA-BMDCs. These results suggest that activation of iNKT cells in regional lymph nodes induces anti-allergic effects through production of IL-21 or IFN-γ, and that these effects are enhanced by simultaneous stimulation with antigen. Thus, iNKT cells might be a useful target in development of new treatment strategies for AR.

[The influence of septal perforation on measurement by acoustic rhinometry].

The influence of septal perforation on results of acoustic rhinometry was studied using cases of septal perforation and a human-nose model. Acoustic rhinometry was conducted before and after closing the perforation (average 16 mm in diameter, 23 mm from the nostril) by thin cotton patches in 33 cases (19 men and 14 women). The decrease in cross-sectional area and volume after closure was statistically significant. A human-nose model with septal holes ranging from 5, 10, 15, to 20 mm and locations ranging from 20, 40, to 50 mm from the nostril was studied by acoustic rhinometry. Our results suggest that the effect of perforations on the measurement is much greater in anterior perforations than in posterior perforations.

[Anterior turbinectomy: experimental and clinical study].

INTRODUCTION: Minimal cross-sectional areas situated at the anterior end of the inferior turbinate have the most influence on nasal patency. To improve persistent nasal obstruction, 2 types of inferior turbinectomies--conventional complete resection including the anterior and posterior mucosa and anterior resection of the anterior mucosa--were conducted and preoperative and postoperative nasal patency and stuffy sensation were compared and analyze. OBJECTS AND METHODS: Cases undergoing 2 types of turbinectomies between July 1997 and March 2000 numbered 63--conventional in 32 (64 sides) and anterior in 31 (62 sides). Anterior, posterior, and total nasal volume and minimal cross-sectional area were evaluated pre- and postoperatively using an acoustic rhinometer. The stuffy sensation was similarly evaluated by the visual analog scale (VAS). RESULTS: All nasal volumes showed postoperative increase under conventional treatments. Anterior and posterior volumes significantly increased under anterior treatment. Comparing the results of postoperative volume posterior volume was significantly larger under conventional treatment than under anterior treatment. Stuffy sensation significantly improved by VAS in both types of turbinectomy, with no significant difference between them. CONCLUSION: Anterior treatment to solely increase nasal volume at the minimal cross sectional area showed equal postoperative improvement in VAS under conventional treatment.

[Evaluation of nasal valve by CT imaging].

UNLABELLED: The nasal valve was studied using coronal scans by computed tomography (CT). SUBJECTS: Coronal images were 5 mm thick obtained from 133 subjects 93 men and 40 women averaging 46 years of age. METHODS: The valvular area was studied in 2 slices containing nasal valve, anterior and posterior slices 5 mm apart. After defining standard points for evaluation, breadth, height and area were evaluated using NIH Image Version 1.59 from left and right as an unit. RESULTS: Results were follows: 1. The breadth of the nasal valvular area is larger in men than in women, and the height greater. The angle of valvular area is similar in both. 2. A comparison of anterior and posterior slices showed the smallest breadth of valvular area in the anterior slice to be smaller than in the posterior slice. The breadth of the vestivular area below the valvular area is larger in the anterior than posterior slice. The angle in the anterior slice is larger than that in the posterior slice. The area of valvular area in the anterior slice is smaller than that in the posterior slice.

[Nose bleeds and nitric oxide in the nose].

Most of the nitric oxide (NO) in expiratory air is produced by the nose and its accessory sinuses, and nasal allergies related to NO have been often reported. In the present study, we postulated that nose bleeds may be somehow related to reactive oxygen species. The expression of NO synthase (NOS) by the nasal mucosa was evaluated using the RT-PCR method, and the concentration of NO in air expired through the nose was measured. The activity of superoxide dismutase, which scavenges superoxide anions, was also evaluated. The genetic expression of iNOS was observed in the nasal mucosa, and a significantly lower level of expression was noted in subjects with a nosebleed, compared to that of the controls. This result was interpreted as indicating a decrease in NO levels as a result of the nosebleed, leading to an elevation in blood pressure. Transient elevations in blood pressure caused by oxidative stress may lead to the rupture of nasal vessels if hypertension preexists. Serum levels of superoxide dismutase increased significantly in subjects with nose bleeds. This finding might be related to the activity of the superoxide anion, which is released in large amounts during nose bleeds. Serum superoxide dismutase levels increase in response to the high concentration of superoxide anions. The concentration of NO in air expired through the nose was significantly lower in subjects with nose bleeds, compared to that of the control subjects. We suggest that NO production decreases in subjects experiencing nose bleeds and that this reduction is induced by preexisting hypertension and injury from reactive oxygen species, contributing to the resulting nose bleed.

[Nasal foreign bodies in 299 cases].

Although nasal foreign bodies very commonplace in daily clinical practice, their simplicity in pathology and diagnosis is so unique that case reports based upon a large number have been rather scarce. We report 299 verified cases of nasal foreign bodies seen during the past 13 years from January 1986 to December 1998, at our institute, together with clinical and statistical analysis. The total number of first visits during the surveyed period was 55,312 and nasal foreign bodies comprised 0.54%. Of these 217 subjects (72.6%) appeared in emergencies. Man comprised 172 (58%) and woman 127 (42%), with the right side comprising 166 cases (57%), the left side 123 (42%) and bilateral 3 cases (1%). In monthly distribution, cases are more often seen in November and December and less often seen in January, with the monthly average being 25. In age distribution, the majority were seen in those under 10 years old, excluding 6 cases. The average age was 4.0 and the range 1 month to 81 years. In the majority of cases, foreign bodies remained only a short time (with in 24 hour) but in 15 cases stayed rather a long time (over 24 hour). In specificity, the majority of foreign bodies were toys, with plastic bullets used with air guns most frequent, in 46 cases (15.3%), followed by beads in 36 cases (12.0%). Other foreign bodies seen comparatively often were pieces of tissue paper, buttons, and plastic toys components.

[A clinical treatise upon the nasal septal perforation].

Thirty nine cases of septal perforation of various origins were presented using clinical such as backgrounds age, gender, possible causes, and size of septal perforation evaluated by diameter. The cases included 26 males and 13 females with a mean age of 35 years range: 8 to 85 years. Possible causative factors were as follows: septal surgeries (9), other nasal and paranasal surgeries (17), nasal cautery or tamponade (2), occupational (2), collagen disease (2), inflammatory (1) and idiopathic (5). Signs and symptoms related to perforations were minor, such as stuffy nose (3), running nose (3), nosebleed (5), dry sensation (4), nasal pain (1), and asymptomatic (23). Sizes of perforations by largest diameter were small (less than 10 mm) in 7, moderate (11-20 mm) in 13, and large (more than 21 mm) in 6. The size of perforations tended to be variable, but two cases with collagen disease showed large perforations 35 mm. Although iatrogenic and idiopathic cases comprised the majority of cases (80%), such a few cases of grave significases as collagen and hematological diseases showed unusually large perforations.

[Method for determining optimal intracavitary radiotherapy conditions for carcinoma of the uterine cervix with tumor infiltration of the vaginal wall].

Stage III carcinoma of the uterine cervix is occasionally accompanied by tumor infiltration of the vaginal wall. Currently, the vaginal wall has to be irradiated in the same manner as the uterine cervix. The authors have developed a system for determining the optimal irradiation conditions for treating the two regions, uterine cervix and vaginal wall, at the same time. A comparison of two methods is shown in simulation, and then a clinical case is reported. The first method consists of two treatment plans, one for the uterine cervix without tumor infiltration of the vaginal wall, and the other for the vaginal wall without carcinoma of the uterine cervix. The second, newly developed method considers the two regions together. Irradiation times of ovoid sources obtained with the second method are 15-25% less than those of the first method. Isodose curves obtained with the two methods are very different, and thus the uterine cervix and vaginal wall must be considered together in order to determine irradiation conditions.

Topical application of capsaicin and flap survival.

A study has been undertaken to investigate the relationship of capsaicin administration to flap survival. Skin flaps measuring 9 by 2 cm in size were raised on the dorsum of rats and covered with silicone gel sheet either containing or not containing capsaicin. Topical application of capsaicin transcutaneously resulted in a significant increase in the area of flap survival (P < 0.01).

[Techniques for determining position from more than two radiographs intersecting at arbitrary angles in brachytherapy].

The least squares method and geometrical solution for calculating position were used in the two-projection method. Five coordinate systems were defined as a normal system, image system on film intersecting the beam central axes at an arbitrary angle and the projection, virtual coordinate and virtual image coordinate systems with beam central axis as one of the three coordinate axes to determine the geometrical relationship between a point and image on the film. Normal coordinates of the point were calculated by six geometrical solution sets and two forms of the least squares method using the rotation matrixes of the coordinate systems. One least squares method solves simultaneous nonlinear equations, and the other derives a strict solution from simultaneous linear equations. The latter least squares method has little physical meaning and is not as useful as the former. Although the former has physical meaning, the iterative approximation method should be used to determine position since a strict solution cannot be obtained directly. By these least squares methods, position is determined with less error using the projections at more than two focal spots.

[Determination of source position for four radiography systems with orthogonal projections in brachytherapy].

Four configurations of two X-ray tube positions are available for determining the position of a point using two orthogonal films. For each configuration, there are many formulas for calculating the coordinate of a point: the least squares methods with and without physical meaning, such as six sets of geometrical solutions, an approximation method with constant magnifications and so on. It is troublesome for a person in charge of treatment planning to directly derive a formula or select an appropriate formula from numerous ones for the four configurations. Thus, a method to easily apply the published formula for a configuration to the other three configurations is described in simulations and a clinical case using rotation matrixes of the right-handed coordinate system. Each diagonal element of the rotation matrixes is 1 or -1, and the other elements are 0.

Measurement of arterial tracer concentrations from cardiac PET images.

OBJECTIVE: Cardiac PET imaging offers the potential capability for the noninvasive measurement of arterial input function. This capability is somewhat limited, however, because of partial volume and spillover effects. The purpose of this study was to validate arterial tracer concentration measurements using PET images by assigning a region of interest (ROI) to the left ventricle, left atrium (LA), and ascending aorta. MATERIALS AND METHODS: We selected [11C]CO and [13N]ammonia as tracers, because the activity of [11C]CO is primarily in the blood pool and that of [13N]ammonia primarily in myocardial tissue. Six [11C]CO and 11 [13N]ammonia PET scans were obtained in 17 subjects. Arterial tracer concentrations determined by PET were compared with those measured by well counting of arterial blood sampling obtained at the midpoint of each image acquisition. RESULTS: Arterial tracer concentrations as determined by LA-PET imaging correlated closely with those measured by blood sampling (r = 0.996, slope = 1.00 for [11C]CO; r = 0.841, slope = 0.974 for [13N]ammonia). Partial volume and spillover effects were minimized by assigning an ROI to the LA. CONCLUSION: Arterial tracer concentrations can be measured noninvasively with cardiac PET.