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.

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.

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.

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.

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.

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.

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.

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.

Two-radiograph reconstruction using six geometrical solution sets and least-squares method.

When two radiographic projections are available for reconstruction, it was found that six different combinations of equations could be used to obtain the geometrical solutions for the position of any point. No errors in the image coordinates read from the radiographs resulted in identical solutions for the six equations. Inaccuracies or errors present in the image coordinates generated differences among the six solutions. In this case, a least-squares method could be used to determine the optimum position. The utility of such a least-squares optimizing approach is presented in the context of a clinical example.

Correction functions for optimizing the reconstructed image in transverse section scan.

Two correction functions are derived for one- and two-dimensional convolution methods for reconstructing a section image from multiple projections. The functions are optimized to yield a maximum 'signal-to-noise power ratio' for a given RMS resolution width, where 'signal power' is the integrated squared line spread function (signal power regarding one-dimensional position information per count) and 'noise power' is the variance of the image density at the centre of a locally uniform source. The point spread function of the reconstructed image is Gaussian, and the standard deivation of noise associated with a locally uniform image is found to be proportional to D-3/2, where D is the RMS resolution width. The autocovariance function for uniform noise is also given.

A method for calculating the optimum irradiation condition for intracavitary radiotherapy using quadratic programming.

A method of calculating optimum irradiation conditions for intracavitary radiotherapy using quadratic programming has been formulated and then modified for practical application. The allowable range of obtained dose, which is usually fixed in advance, is automatically computed to be as small as possible. The variance of the product of the activity and the irradiation time of the tandem source is also minimised to avoid the occurrence of cold and/or hot spots. Optimum irradiation conditions for conventional intracavitary radiotherapy of carcinoma of the uterine cervix were obtained on the basis of isodose curves passed through the points A of the Manchester system. Those for carcinoma of the other organs and special cases of carcinoma of the uterine cervix can be determined after consideration of the tumour state.

Noninvasive quantification of regional myocardial blood flow and ammonia extraction fraction using nitrogen-13 ammonia and positron emission tomography.

This report describes the theoretical basis and a method to quantitate regional myocardial blood flow (RMBF) and ammonia extraction fraction (E) in man, noninvasively, with N-13 ammonia and positron emission tomography (PET). Two patients with hypertrophic cardiomyopathy, whose left ventricular (LV) walls were markedly thick, were employed in this study to avoid partial volume effects and cross contamination between LV walls and blood pool. RMBF and E were calculated from time-activity curves of myocardial tissue and left atrium derived from serial 6-second PET images of the heart. The time-activity curve of left atrium was used as an arterial input function. The results were RMBF = 67 +/- 4 ml/min/100 g, E = 80 +/- 13% and 65 +/- 10 ml/min/100 g, 81 +/- 16% for each patient. The validity of the present method was discussed.

Quantitative measurement of uptake of radiolabeled monoclonal antibody by means of planar data.

Data obtained from planar images were used to measure the uptake of monoclonal antibody in organs and tumors. Background counts included in the region of interest were eliminated, and the attenuation of the photons emitted by the radionuclide through the intervening tissues was compensated for. The background counts and the intensity of the attenuation were determined from the results of phantom studies and numerical integration with a personal computer. The quantitative uptake of 111In labeled anti-melanoma Monoclonal Antibody (ZME-018) in a melanoma lesion, the liver, and the bone marrow of a patient was measured by the planar method which we developed.

A new phantom for evaluation of low-contrast detectability of X-ray CT scanner.

It is possible to produce Xyron (styrene grafted polyphenylene ether) having different electron densities but virtually the same effective atomic number. The difference between the CT numbers obtained with two Xyron types of different electron densities was shown both theoretically and experimentally to be constant, regardless of the effective photon energy. A phantom for evaluation of low-contrast detectability of X-ray CT scanners was produced from these two types of Xyron and was shown to be effective for both comparative studies and daily quality assurance.

Medical use of radiation and particle accelerators.

Recently, medical use of radiation has progressed markedly with the application of newly developed techniques and modalities. And the progress of radiation diagnosis too, has felt the impact of imaging techniques since the introduction of X-ray computerized tomography (X-ray CT). In radiation therapy, efforts have been concentrated on studies to improve local control rates of radioresistant cancers and locally advanced cancers, which remained a problem even after the introduction of megavoltage radiation therapy machines. Particle radiation, characterized by an excellent dose distribution as well as the features of high LET radiation, has been introduced in to clinical research for use in radiation therapy. Other studies with particle radiation suggests that the short lived radioisotopes produced by accelerators will open up a new era for nuclear medicine. This paper looks at the present status and some of the future problems in the medical use of radiation and radioisotopes in Japan.

Ultrasonography of small hepatic tumors.

The differential accuracy of ultrasonographic examinations of small hepatic tumours was analyzed by receiver-operating characteristics. Using only one image of a single hepatic tumor under 3 cm in diameter as revealed by real-time scanner, the readers were requested to select one out of five diagnoses (hepatocellular carcinoma, metastatic tumor, cavernous hemangioma, cyst, or miscellaneous) and to choose the credibility from five levels of confidence. The averaged diagnostic accuracy was 68% in hepatocellular carcinoma, 70% in metastatic tumor, and 77% in cavernous hemangioma. Hepatic tumors were classified retrospectively into eight ultrasonographic patterns, based on mutual consent. The mosaic and hypoechoic patterns were relatively characteristic of hepatocellular carcinoma (91% and 92% respectively). Except for these two patterns, ultrasonographic findings in small liver tumors were nonspecific, including frequently reported hyperechoic pattern for cavernous hemangioma.

Analysis of bone scintigram data using speech recognition reporting system--data analysis with speech recognition system.

Five hundred eighty bone scintigram reports were stored using a voice pattern recognition system in a general-purpose, middle-sized computer (ACOS-650). Bone scintigraphy carried out in our institute was examined by analyzing these data. The results of the examination showed that the introduction of this system made it possible to analyze all the data quickly. Before the introduction of this system, the data able to be analyzed had been restricted because of their complexity. The results also showed that this system would be useful for understanding the examinations carried out in the whole hospital as well as for analyzing metastatic tumors and the number of patients receiving examinations. Furthermore, this system would be helpful in the logical analysis of reports prepared by doctors.

Use of B95a cells for isolation of canine distemper virus from clinical cases.

Canine distemper virus (CDV) was readily isolated at high rate with marked cytopathic effect (CPE) in B95a cells, a marmoset lymphoid cell line, from the peripheral blood leukocytes, cerebrospinal fluid cells and brain of dogs. Difference in type of CPE, i.e. syncytium type and round-cell one, among the virus isolates indicate the presence of heterogeneity of virus populations in prevalent CDV. Thus, this cell system is expected to be useful for ecological studies on CDV in the field.

Orbital wall fractures. Conventional views and CT.

In order to evaluate the benefit derived by conventional views in the initial diagnosis of fractures of the orbital walls, a clinical study was designed to compare the results of evaluations by plain films and coronal CT scans. The conventional Caldwell's and Waters' views will provide a fairly reliable result as to the presence of orbital fractures: orbital floor (anterior in 78%, posterior in 73%), medial orbital wall (anterior in 71%, posterior in 72%), and ethmoid-maxillary plate in 64%. False-negative diagnosis was seen at the anterior portion of the floor in 13%, at the anterior portion of the medial orbital wall in 7%, and at the ethmoid-maxillary plate in 11%. False-negative diagnosis was seen at the orbital floor (anterior in 9%, posterior in 10%), at the medial orbital wall (anterior in 21%, posterior in 29%), and at the ethmoid-maxillary plate in 21%. Our results agree well with those of the past reports.

Radio-opacity of the paranasal sinuses. Conventional views and CT.

In order to examine the reliability of conventional views in predicting the degree of radio-opacity, irrespective of soft tissue or fluid seen in chronic sinusitis in adults, a comparison has been made between the results of evaluations by two routine views (Caldwell's and Waters') and by CT in axial scans. Ninety-seven sides (61 case) were included in the study. The radio-opacity was classified into three groups according to the degree of aeration or radiolucency. The diagnosis of plain films were classified into three categories (matched diagnosis, over-diagnosis, and under-diagnosis) in comparison to the radio-opacity depicted by corresponding CT scans. The incidences of matched diagnosis are, in the order of percentages: maxillary sinus (78.4%), frontal sinus (71.1%), nasofrontal area (66.0%), anterior ethmoidal cells (52.6%), and posterior ethmoidal cells (52.6%). The incidence of over-diagnosis is highest in the posterior ethmoidal cells (52.6%) and lowest in the maxillary sinus (20.6%). The incidence of under-diagnosis is highest in the anterior ethmoidal cells (24.7%) and lowest in the maxillary sinus (1.0%).