Cognitive Function in Patients With Mild Idiopathic Pulmonary Fibrosis: A Case-Control Pilot Study.

This case-control study examined cognitive function in patients with mild idiopathic pulmonary fibrosis (IPF), in comparison with controls or moderate-to-severe IPF. Ten mild IPF, 10 moderate-to-severe IPF, and 16 controls were enrolled, and performance on seven different cognitive function tests was compared in each group. IPF showed decreased cognitive function compared to controls in verbal memory, cognitive flexibility and information processing speed. As the scores were lower even in mild IPF, this study suggests that cognitive function declines early in the disease process of IPF. Thus, occupational therapy for IPF should require an assessment of cognitive function and assistance appropriate to the client's function.

Progression of Smoking-Induced Emphysema in a Case with Indium Lung.

Recently, it has become clear that inhaled indium-tin oxide causes emphysematous as well as interstitial changes in the lung. Here, we present a 59-year-old male ex-smoker, quitting smoking at the age of 55. He had been engaged in indium-tin oxide processing from 27 to 37 years of age, with 22 years having passed since the final exposure to indium. He was found to have a high serum indium concentration and Krebs von den Lungen-6 (KL-6). Furthermore, bilateral centrilobular emphysema was recognized in high-resolution computed tomography (HRCT). After transferring jobs to a non-indium-tin oxide section, KL-6 returned to a normal level within 4 years, whereas neither serum indium concentration nor emphysema had decreased to normal despite 22 years having passed since the exposure ended. At the age of 59, a thoracoscopic lung biopsy was performed to assess the contribution of smoking and that of indium to the lung destruction. The pathological findings demonstrated cholesterol granulomas with the accumulation of macrophages and multinucleated giant cells that had phagocytosed particles. Together with the typical findings of indium lung, fibrotic and emphysematous changes were observed. The elemental analysis of the biopsied specimens revealed excessive deposition of indium throughout the airways, interstitial spaces and alveoli. The pathological findings of this case may be the result of two kinds of pulmonary damage, i.e., smoking and indium. This report indicates that occupationally-inhaled indium could remain in the lung for as long as 22 years and continue to insult the lung tissue with inflammation caused by smoking.

Construction of Ultrathin Layer-by-Layer Films of Oligothiophene Derivatives on an Electrode.

Oligothiophene derivatives, which are known as p-type materials, have been synthesized, and their ultrathin layer-by-layer films have been constructed on an electrode using a simple and convenient dipping method. The stepwise deposition behavior of quaterthiophene and sexithiophene derivatives on the electrode via hydrogen bonding was monitored by electronic spectra measurement, and the constructed films were evaluated by X-ray photoelectron spectroscopy, grazing-incidence small-angle X-ray scattering, and cyclic voltammetry. It has been clarified that the constructed layer-by-layer films were electroactive and photoelectroactive.

Prognostic evaluation of branch atheromatous disease in the pons using carotid artery ultrasonography.

BACKGROUND: Branch atheromatous disease is an ischemic stroke, involving occlusion or severe stenosis of the perforating artery, causing neurologic symptoms and serious sequelae. We aimed to investigate initial morphometric and hemodynamic characteristics of the vertebral artery immediately post-onset to predict lesion expanding. METHODS: This case-control study collected demographic, historical, and physical examination data from 44 patients with branch atheromatous disease in the pons at admission. The maximum ischemic pons area and stenosis rate in the basilar artery were calculated using magnetic resonance images. Diameter, velocity, and flow volume of the vertebral arteries were measured using carotid artery ultrasonography. Correlations between ischemic lesion extent and these parameters were investigated. RESULTS: Patients were assigned to groups of less (Group 1) or more (Group 2) than the median maximum ischemic area in the pons, calculated from magnetic resonance images (121.6 mm2). Modified Rankin scale scores were significantly worse in Group 2. Blood pressure and blood findings were similar between groups. Group 2 showed significantly higher basilar artery stenosis rates. Flow volume, velocity, peak systolic velocity, and end-diastolic velocity in the vertebral artery on both sides were significantly decreased in Group 2. CONCLUSIONS: Deteriorated vertebral artery hemodynamics caused a more extensive ischemic lesion in branch atheromatous disease in the pons. Evaluation of the vertebral using carotid artery ultrasonography in the acute phase may be useful for predicting disease progression.

Effect of Yokukansan and Yokukansankachimpihange on Aggressive Behavior, 5-HT Receptors and Arginine Vasopressin Expression in Social Isolation-Reared Mice.

The traditional herbal medicines yokukansan (YKS) and yokukansankachimpihange (YKSCH) are prescribed for neurosis, insomnia or night crying and irritability in children. YKSCH comprises YKS and two additional herbs, a chimpi and a hange, and is used to treat digestive function deficiencies. However, the differences between the effects of YKS and YKSCH on brain function are unclear. The present study examined the effects of YKS and YKSCH on aggressive behavior in mice reared under a social isolation (SI) condition. Mice were housed individually for 6 weeks. YKS and YKSCH were administered orally for 2 weeks before aggression tests. SI increased aggressive behavior against naïve mice, and YKS, but not YKSCH, significantly attenuated this aggressive behavior. Because serotonin (5-HT)2A and 5-HT3A receptor antagonists are reported to have anti-aggressive effects, the mRNA levels of these receptors were examined. YKS attenuated the SI-induced increase in 5-HT2A and 5-HT3A receptor mRNA in the amygdala. On the other hand, YKSCH attenuated the SI-induced increase in 5-HT1A receptor mRNA. YKS and YKSCH did not affect 5-HT and its metabolite 5-hydroxyindoleacetic acid content in the amygdala. However, YKSCH increased the mRNA level of arginine vasopressin (AVP), which is a neuropeptide that has been implicated in aggression, in the amygdala. These results suggest that YKS ameliorates aggressive behavior by decreasing 5-HT2A and 5-HT3A receptor expression. The YKSCH-induced increase in AVP may disrupt the anti-aggressive effect of YKS. YKS may be more effective than YKSCH for treating irritability if digestive function deficiencies are not considered.

Progressive plasterer's pneumoconiosis complicated by fibrotic interstitial pneumonia: a case report.

BACKGROUND: Although the prevalence of pneumoconiosis has been decreasing due to improvements in working conditions and regular health examinations, occupational hygiene measures are still being established. Plasterers encounter a number of hazardous materials that may be inhaled in the absence of sufficient protection. CASE PRESENTATION: A 64-year-old man who plastered without any dust protection for more than 40 years was referred to our hospital with suspected interstitial pneumonia. Mixed dust pneumoconiosis and an unusual interstitial pneumonia (UIP) pattern with fibroblastic foci were diagnosed by video-assisted thoracoscopic surgery, and an elemental analysis detected elements included in plaster work materials. Despite the cessation of plaster work and administration of nintedanib, the patient developed advanced respiratory failure. CONCLUSION: Plasterers are at an increased risk of pneumoconiosis and may have a poor prognosis when complicated by the UIP pattern. Thorough dust protection and careful monitoring are needed.

Evaluation of Yanagihara facial nerve grading system based on a muscle fiber analysis of human facial muscles.

PURPOSE: We morphometrically analyzed human facial muscles, and evaluated the Yanagihara facial nerve grading system using our data. METHODS: We used 15 types of human facial muscle, 2 types of masticatory muscle and 2 types of skeletal muscle. The materials were obtained from 11 Japanese male cadavers aged 43-86 years. We counted the muscle fibers and measured the transverse area of the muscle fibers (TAMF), and then calculated the number of muscle fibers (NMF) per mm2 and the average TAMF. RESULTS: We found a significant correlation between average TAMF and NMF (r = - 0.70; p < 0.01). We classified facial muscles into three types based on the correlational results. Type A had a low average TAMF and high NMF. Type C had a high average TAMF and low NMF. Masticatory and skeletal muscles were characterized as Type C. Type B was intermediate between Types A and C. CONCLUSIONS: Pathological changes in the facial muscles in facial nerve palsy seem to vary according to the type of facial muscle, because each facial muscle has a unique fiber-type composition. As the nine discrete facial expressive states evaluated in the Yanagihara system involve all three facial muscle types of our classification, the Yanagihara system is an outstanding system for grading facial nerve palsy in terms of the facial muscle morphology.

Octaalkoxyfullerenes: Widely LUMO-Tunable C2 v-Symmetric Fullerene Derivatives.

C2 v-Symmetric octaalkoxyfullerenes, C60(OR)8 (R = CH3, C2H5, CH2CF3), were synthesized by reacting octabromofullerene with the corresponding alcohols in the presence of AgBF4. The reactions occurred with no change in the addition pattern, and the compounds were unambiguously characterized by NMR spectroscopy and X-ray structure analysis. Electrochemical measurements revealed not only that these derivatives have stable redox properties but also that their LUMO levels can be tuned over a very wide range.

The first case of multiple pulmonary granulomas with amyloid deposition in a dental technician; a rare manifestation as an occupational lung disease.

BACKGROUND: Occupational lung diseases, such as pneumoconiosis, are one of the health problems of dental workers that have been receiving increasing interest. Pulmonary amyloidosis is a heterogenous group of diseases, and can be classified into primary (idiopathic) and secondary (associated with various inflammatory diseases, hereditary, or neoplastic). To date, the development of pulmonary amyloidosis in dental workers has not been reported. CASE PRESENTATION: A 58-year-old Japanese female presented with chest discomfort and low-grade fever that has persisted for 2 months. She was a dental technician but did not regularly wear a dust mask in the workplace. Chest X ray and computed tomography revealed multiple well-defined nodules in both lungs and fluorodeoxyglucose (FDG)-positron emission tomography revealed abnormal FDG uptake in the same lesions with a maximal standardized uptake value (SUV [max]) of 5.6. We next performed thoracoscopic partial resection of the lesions in the right upper and middle lobes. The histological examination of the specimens revealed granuloma formation with foreign body-type giant cells and amyloid deposition that was confirmed by Congo red staining and direct fast scarlet (DFS) staining that produce apple-green birefringence under crossed polarized light. Because there were no other causes underlying the pulmonary amyloidosis, we performed electron probe X-ray microanalysis (EPMA) of the specimens and the result showed silica deposition in the lesions. Based on these results, we finally diagnosed the patient with pulmonary granulomas with amyloid deposition caused by chronic silica exposure. Afterward, her symptoms were improved and the disease has not progressed for 2 years since proper measures against additional occupational exposure were implemented. CONCLUSIONS: Our case presented three important clinical insights: First, occupational exposure to silica in a dental workplace could be associated with the development of amyloid deposition in lung. Second, EPMA was useful to reveal the etiology of amyloid deposition in the lungs. Last, proper protection against silica is important to prevent further progression of the disease. In conclusion, our case suggested that occupational exposure to silica should be considered when amyloid deposition of unknown etiology is found in the lungs of working or retired adults.

[A Case of Drug-Induced Organizing Pneumonia Caused by Dasatinib].

A 52-year-old man with chronic myelogenous leukemia (CML) received dasatinib after the failure of imatinib and nilotinib therapy. Two years after the initiation of dasatinib, he developed shortness of breath that gradually worsened. Chest X-ray and computed tomography scan showed pulmonary infiltrative shadows and bilateral pleural effusion. We performed a transbronchial lung biopsy and diagnosed organizing pneumonia caused by dasatinib treatment. Corticosteroid therapy was initiated after the discontinuation of dasatinib and all his symptoms were significantly improved. Because of the exacerbation of CML, the patient was treated with imatinib and then nilotinib; however, these drugs failed to decrease the leukemic cells. Re - administration of dasatinib in combination with corticosteroid therapy successfully controlled CML without recurrence of organizing pneumonia.

Risk factors for stomatitis in patients with lymphangioleiomyomatosis during treatment with sirolimus: A multicenter investigator-initiated prospective study.

PURPOSE: Lymphangioleiomyomatosis is a rare lung disease caused by proliferation of abnormal smooth muscle-like cells and typically occurs in premenopausal women. Sirolimus is now the first-line drug for the treatment of lymphangioleiomyomatosis. Sirolimus-induced stomatitis is the most frequent adverse event experienced during treatment. To identify risk factors, we investigated the association of stomatitis incidence with patient background data and treatment parameters, using data from the multicenter long-term sirolimus trial. METHODS: Subjects received sirolimus for 2 years at doses adjusted to maintain a trough blood level of 5 to 15 ng/mL. The incidence of stomatitis was correlated with baseline demographics, clinical characteristics, and changes in the longitudinal data. Risk factors at baseline were assessed by using univariate and multivariate analyses. RESULTS: The most frequent adverse event was stomatitis, with the cumulative rate reaching 88.9% by 9 months, higher than that reported in postrenal transplant patients. The repetition, the duration, and the severity of stomatitis events were variable among patients. We found that patients with low hemoglobin (Hb) (<14.5 g/dL) showed significantly higher incidence than those with high Hb (≥14.5 g/dL, P < .01). The cumulative rate for stomatitis incidence was significantly associated with a decrease in the mean corpuscular volume, while the Hb level was constant; thus, red blood cell count in patients increased during the study. CONCLUSIONS: Baseline Hb levels and a decrease in mean corpuscular volume during treatment were correlated with the incidence of stomatitis.

[Pulmonary Mucoepidermoid Carcinoma with Hilar Lymph Node Metastasis Complicated by Myelodysplastic Syndrome].

A 65-year-old woman was found to have a mass shadow on chest computed tomography. The patient had been diagnosed as having myelodysplastic syndrome 3 years before admission. She was transferred to our hospital for further examination of the mass in the lower lobe of left lung. The mass was positron emission tomography-positive (SUVmax of 8.6)suggesting a malignant neoplasm. Serum concentrations of carcinoembryonic antigen was elevated to 8.7 ng/ml. Preoperative laboratory studies showed anemia (hemoglobin 6.9 g/dl). Transfusion of red blood cells was performed prior to surgery. Under the video-assited thoracoscopic surgery, left lower lobectomy and lymph node dissection were perfomed. The histopathological diagnosis was mucoepidermoid carcinoma, and the hilar lymph node metastasis positive. There were no postoperative complications, such as infection or bleeding. Chemotherapy with tegafur/uracil was performed after the operation. The patient is currently alive without any recurrence 2 years after the operation.

Kamishoyosan reduces conditioned fear-induced freezing behavior in socially isolated ovariectomized rats.

In the present study, we investigated the effect of kamishoyosan (KSS) on conditioned fear-induced freezing in ovariectomized (OVX) rats. Socially isolated OVX rats showed the longest freezing time among the following four groups: group-housed sham-operated (Sham), isolated Sham, group-housed OVX, and isolated OVX rats. Repeated oral administration of KSS (30-300 mg/kg) reduced conditioned fear-induced freezing in socially isolated OVX rats. The reduction of freezing by KSS was reversed by flumazenil (3 mg/kg) and bicuculline (3 mg/kg). These findings suggest that the GABAA-benzodiazepine receptor complex is involved in the anxiolytic effect of KSS in socially isolated OVX rats.

A mathematical model to predict protein wash out kinetics during whole-lung lavage in autoimmune pulmonary alveolar proteinosis.

Whole-lung lavage (WLL) remains the standard therapy for pulmonary alveolar proteinosis (PAP), a process in which accumulated surfactants are washed out of the lung with 0.5-2.0 l of saline aliquots for 10-30 wash cycles. The method has been established empirically. In contrast, the kinetics of protein transfer into the lavage fluid has not been fully evaluated either theoretically or practically. Seventeen lungs from patients with autoimmune PAP underwent WLL. We made accurate timetables for each stage of WLL, namely, instilling, retaining, draining, and preparing. Subsequently, we measured the volumes of both instilled saline and drained lavage fluid, as well as the concentrations of proteins in the drained lavage fluid. We also proposed a mathematical model of protein transfer into the lavage fluid in which time is a single variable as the protein moves in response to the simple diffusion. The measured concentrations of IgG, transferrin, albumin, and ß2-microglobulin closely matched the corresponding theoretical values calculated through differential equations. Coefficients for transfer of ß2-microglobulin from the blood to the lavage fluid were two orders of magnitude higher than those of IgG, transferrin, and albumin. Simulations using the mathematical model showed that the cumulative amount of eliminated protein was not affected by the duration of each cycle but dependent mostly on the total time of lavage and partially on the volume instilled. Although physicians have paid little attention to the transfer of substances from the lung to lavage fluid, WLL seems to be a procedure that follows a diffusion-based mathematical model.

Presynaptic protein Synaptotagmin1 regulates the neuronal polarity and axon differentiation in cultured hippocampal neurons.

BACKGROUND: Hippocampal neurons in the brain polarize to form multiple dendrites and one long axon. The formation of central synapses remains poorly understood. Although several of the intracellular proteins involved in the clustering of central neurotransmitter receptors and ion channels have been identified, the signals involved in pre- and postsynaptic differentiation remain elusive. Synaptotagmin1 is an abundant and important presynaptic vesicle protein that binds Ca(2+) (J Biol Chem 277:7629-7632, 2002) in regulation of synaptic vesicle exocytosis at the synapse. Synapse consists of the formation of synaptic connections and requires precise coordination of Synaptotagmin1. It was reported Synaptotagmin1 plays an important roles in the formation of axonal filopodia and branches in chicken forebrain neurons (Dev Neurobiol 73:27-44, 2013). To determine if Synaptotagmin1 could have a role in formation of axon in hippocampal neurons, we investigated the effects of Synaptotagmin1 overexpression and knockdown using the shRNA on the growth and branching of the axons of primary hippocampal neurons. We showed that overexpression of Synaptotagmin1 leads to abnormal multiple axon formation in cultured rat hippocampal neurons. RESULTS: We first examined the effects of Synaptotagmin1 on the numbers of axon and dendrites. We found that the overexpression of Synaptotagmin1 led to the formation of multiple axons and induced an increase in the number of endogenous postsynaptic protein Homer1c clusters in cultured hippocampal neurons. Endogenous initial segment of axon was detected with anti-sodium channel (anti-NaCh) antibody and with anti-Tau1 (J Neurosci 24: 4605-4613, 2004). The endogenous initial segment of axon was stained with anti-NaCh antibodies and with anti-Tau1 antibodies. Then the numbers of prominence dyed positive were counted as axon. We attempted to specifically knockdown the endogenous Synaptotagmin1 with small hairpin RNAs (shRNAs). To further dissect the functions of endogenous Synaptotagmin1 in neuronal polarity, we used the shRNA of Synaptotagmin1 that specifically blocks the existence of endogenous Synaptotagmin1. When the shRNA of Synaptotagmin1 was introduced to the cells, the number of axons and dendrites did not change. CONCLUSIONS: These results indicate that the accumulation of Synaptotagmin1 may play an important role in axon/dendrite differentiation.

Relationship between crystallization tendencies during cooling from melt and isothermal storage: toward a general understanding of physical stability of pharmaceutical glasses.

The lack of protocols to predict the physical stability has been one of the most important issues in the use of amorphous solid dispersions. In this paper, the crystallization behaviors of pharmaceutical glasses, which have large variations in their crystallization tendencies, have been investigated. Although each compound appears to have a wide variation in their crystallization time, the initiation time for crystallization could be generalized as a function of only Tg/T, where Tg and T are the glass transition temperature and storage temperature, respectively. All compounds in which crystallization was mainly governed by temperature had similar activation energies for crystallization initiation, ca. 210-250 kJ/mol, indicating that physical stability at any temperature is predictable from only Tg. Increased stability is expected for other compounds, where crystallization is inhibited by an large energetic barrier, and stochastic nucleation plays an important role in initiating crystallization. The difference in the dominant factor, either temperature or pressure, appeared to correlate with the nucleation mechanism, and this could be determined by a cool-heat cycle after melting using thermal analysis. This conclusion should make prediction of physical stability of amorphous formulations easier, although the investigation was conducted under ideal conditions, which eliminated surface effects.

Effects of the density difference between water and oil on stabilization of powdered oil-in-water emulsions.

A powdered oil-in-water (o/w) emulsion is a dispersed system in which the continuous phase of a particle-stabilized o/w emulsion is dispersed in air by encapsulating the water globules with hydrophobic particles. During their preparation, oil droplets in water globules are forced to move because of high-shear mixing, leading to creaming of the oil droplets and possible wetting of the hydrophobic particles with the oil droplets, which induces destabilization. To prepare powdered o/w emulsions efficiently, the extent of creaming of the oil droplets has to be suppressed. We describe how to achieve this by mixing two oils of different densities and preparing powdered o/w emulsions from oil mixtures exhibiting a decreasing density difference with water. As the extent of creaming is reduced, enhanced stabilization of the powdered emulsions occurs.

Study on distribution of terminal branches of the facial nerve in mimetic muscles (orbicularis oculi muscle and orbicularis oris muscle).

There have been many anatomical reports to date regarding the course of the facial nerve to the mimetic muscles. However, reports are relatively scarce on the detailed distribution of the terminal branches of the facial nerve to the mimetic muscles. In this study, we performed detailed examination of the terminal facial nerve branches to the mimetic muscles, particularly the branches terminating in the orbicularis oculi muscle and orbicularis oris muscle. Examination was performed on 25 Japanese adult autopsy cases, involving 25 hemifaces. The mean age was 87.4 years (range, 60-102 years). There were 12 men and 13 women (12 left hemifaces and 13 right hemifaces). In each case, the facial nerve was exposed through a preauricular skin incision. The main trunk of the facial nerve was dissected from the stylomastoid foramen. A microscope was used to dissect the terminal branches to the periphery and observe them. The course and distribution were examined for all terminal branches of the facial nerve. However, focus was placed on the course and distribution of the zygomatic branch, buccal branch, and mandibular branch to the orbicularis oculi muscle and orbicularis oris muscle. The temporal branch was distributed to the orbicularis oculi muscle in all cases and the marginal mandibular branch was distributed to the orbicularis oris muscle in all cases. The zygomatic branch was distributed to the orbicularis oculi muscle in all cases, but it was also distributed to the orbicularis oris muscle in 10 of 25 cases. The buccal branch was not distributed to the orbicularis oris muscle in 3 of 25 cases, and it was distributed to the orbicularis oculi muscle in 8 cases. There was no significant difference in the variations. The orbicularis oculi muscle and orbicularis oris muscle perform particularly important movements among the facial mimetic muscles. According to textbooks, the temporal branch and zygomatic branch innervate the orbicularis oculi muscle, and the buccal branch (or the buccal branch and marginal mandibular branch) innervates the orbicularis oris muscle. In this study, we performed dissection of the terminal facial nerve branches that terminate in the orbicularis oculi muscle and orbicularis oris muscle and performed detailed examination of their courses. The results revealed 5 multiple anomalies not in conventional books, and the movements of the muscles might be compensated.

Predictors of 2-Year Mortality in Patients Receiving Long-Term Oxygen Therapy: A Prospective Observational Study.

Background: Patients receiving long-term oxygen therapy are in a state of progressive respiratory dysfunction and have high mortality. However, the predictors of mortality in these patients have not yet been established. Objectives: This prospective observational study aimed to identify the predictors of two-year mortality in patients receiving long-term oxygen therapy. Design, Setting/Subjects: This two-year prospective observational study included 96 patients who received long-term oxygen therapy in the outpatient department of the National Hospital Organization Nishiniigata Chuo Hospital in Japan. Measurements: The updated Charlson Comorbidity Index, body mass index, handgrip strength, modified British Medical Research Council scale (mMRC), Barthel Index (BI), and Montreal Cognitive Assessment (MoCA) were collected in 2019 as a baseline. Outcome was defined as mortality due to chronic respiratory disease during the two-year follow-up period, and predictors were estimated using age- and sex-adjusted Cox proportional hazards model. Results: The 83 patients that were followed up, 30 (36%) died. The Cox proportional hazards model estimated handgrip strength (adjusted hazard ratio [HR]: 0.89; 95% confidence interval [CI]: 0.84-0.94; p < 0.01; Wald: 14.38.), mMRC (adjusted HR: 1.96; 95% CI: 1.36-2.83; p < 0.01; Wald: 13.16.), BI (adjusted HR: 0.95; 95% CI: 0.93-0.98; p < 0.01; Wald: 17.07.), and MoCA (adjusted HR: 2.17; 95% CI: 1.31-3.59; p < 0.01; Wald: 9.06) as predictors. Conclusions: This study indicated that handgrip strength, dyspnea, activities of daily living, and cognitive function were predictors of two-year mortality in patients receiving long-term oxygen therapy.

Alternaria inhibits double-stranded RNA-induced cytokine production through Toll-like receptor 3.

BACKGROUND: Fungi may be involved in asthma and chronic rhinosinusitis (CRS). Peripheral blood mononuclear cells from CRS patients produce interleukin (IL)-5, IL-13 and interferon (IFN)-γ in the presence of Alternaria. In addition, Alternaria produces potent Th2-like adjuvant effects in the airway. Therefore, we hypothesized that Alternaria may inhibit Th1-type defense mechanisms against virus infection. METHODS: Dendritic cells (DCs) were generated from mouse bone marrow. The functional responses were assessed by expression of cell surface molecules by FACS (MHC class II, CD40, CD80, CD86 and OX40L). Production of IL-6, chemokine CXCL10 (IP-10), chemokine CXCL11 (I-TAC) and IFN-ß was measured by ELISA. Toll-like receptor 3 (TLR3) mRNA and protein expression was detected by quantitative real-time PCR and Western blot. RESULTS: Alternaria and polyinosinic-polycytidylic acid (poly I:C) enhanced cell surface expression of MHC class II, CD40, CD80, CD86 and OX40L, and IL-6 production in a concentration-dependent manner. However, Alternaria significantly inhibited production of IP-10, I-TAC and IFN-ß, induced by viral double-stranded RNA (dsRNA) mimic poly I:C. TLR3 mRNA expression and protein production by poly I:C were significantly inhibited by Alternaria. These reactions are likely caused by heat-stable factor(s) in Alternaria extract with >100 kDa molecular mass. CONCLUSION: These findings suggest that the fungus Alternaria may inhibit production of IFN-ß and other cytokines by DCs by suppressing TLR3 expression. These results indicate that Alternaria may inhibit host innate immunity against virus infection.