RAD51 separation of function mutation disables replication fork maintenance but preserves DSB repair.

Homologous recombination (HR) protects replication forks (RFs) and repairs DNA double-strand breaks (DSBs). Within HR, BRCA2 regulates RAD51 via two interaction regions: the BRC repeats to form filaments on single-stranded DNA and exon 27 (Ex27) to stabilize the filament. Here, we identified a RAD51 S181P mutant that selectively disrupted the RAD51-Ex27 association while maintaining interaction with BRC repeat and proficiently forming filaments capable of DNA binding and strand invasion. Interestingly, RAD51 S181P was defective for RF protection/restart but proficient for DSB repair. Our data suggest that Ex27-mediated stabilization of RAD51 filaments is required for the protection of RFs, while it seems dispensable for the repair of DSBs.

Compact Measurement of the Optical Power in High-Power LED Using a Light-Absorbent Thermal Sensor.

LED (Light-Emitting Diode) presents advantages such as luminescence, reliability, durability compared with conventional lighting. It has been widely applied for life, healthcare, smart farm, industry, and lighting from indoor to the automotive headlamp. However, the LED is vulnerable to thermal damage originated from the high junction temperature, especially in high power applications. Hence, it requires precise qualification on the optical power and the junction temperature from the pilot line to secure reliability. In this study, the photo-thermal sensor is proposed by employing a sheet-type thermocouple composed of photo-absorbent metal film and thermocouple. This sensor aims low-cost qualification in pilot line for high-power luminous devices and optical monitoring of costly luminaire such as automobile LED headlamp. The sensor is designed to detect the increased temperature response of LED hot spots from the transferred thermal power and absorbed optical power. The temperature response of each sheet-type thermocouple is utilized as a signal output of the absorbed optical power and hot spot temperature based on the introduced sensor equation. The proposed thermal sensor is evaluated by comparing the experiment with the measured reference value from the integrating sphere and the attached thermocouple at a junction. The experiment result reveals 3% of the maximum error for the optical power of 645 mW.

Importance of microbial extracellular vesicle in the pathogenesis of asthma and chronic obstructive pulmonary disease and its diagnostic potential.

There are rising evidences of the human microbiome as a potentially influential player that is actively engaged in shaping the pathogenetic processes and other unresolved issues both in asthma and other chronic respiratory diseases, particularly of the airways. The biological components such as microbiome in inhaled air can induce immune dysfunction and inflammation, leading to inflammatory pulmonary disorders such as asthma and chronic obstructive pulmonary disease (COPD). Microbe-derived extracellular vesicles (EVs) with biologically active information or functions can reprogram their respective target cells and EV may have a role for the development of asthma and COPD. To evaluate the role of microbe-derived EV in the pathogenesis of asthma and COPD and its role in diagnosis, the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement method was used for the study. An electronic search was performed using PubMed, PubMed Central, and Embase up to 2020. EVs serve as an intercellular transporter of miRNAs for cell-to-cell communication in the lungs. Bacteria-derived EVs have distinctive characteristics in the lungs of patients with asthma and COPD compared to healthy controls. Furthermore, bacterial EV IgG antibody titers in serum were significantly higher in patients with asthma and COPD than in healthy controls, suggesting that antibacterial EV antibodies titers can be used as a diagnostic tool for lung disease. Taken together, microbial EVs and miRNAs have important roles in the pathogenesis of asthma and COPD and they can provide novel diagnostic biomarkers for asthma and COPD.

Lung Disease Diagnostic Model Through IgG Sensitization to Microbial Extracellular Vesicles.

PURPOSE: Recently, there has been a rise in the interest to understand the composition of indoor dust due to its association with lung diseases such as asthma, chronic obstructive pulmonary disease (COPD) and lung cancer. Furthermore, it has been found that bacterial extracellular vesicles (EVs) within indoor dust particles can induce pulmonary inflammation, suggesting that these might play a role in lung disease. METHODS: We performed microbiome analysis of indoor dust EVs isolated from mattresses in apartments and hospitals. We developed diagnostic models based on the bacterial EVs antibodies detected in serum samples via enzyme-linked immunosorbent assay (ELISA) in this analysis. RESULTS: Proteobacteria was the most abundant bacterial EV taxa observed at the phylum level while Pseudomonas, Enterobacteriaceae (f) and Acinetobacter were the most prominent organisms at the genus level, followed by Staphylococcus. Based on the microbiome analysis, serum anti-bacterial EV immunoglobulin G (IgG), IgG1 and IgG4 were analyzed using ELISA with EV antibodies that targeted Staphylococcus aureus, Acinetobacter baumannii, Enterobacter cloacae and Pseudomonas aeruginosa. The levels of anti-bacterial EV antibodies were found to be significantly higher in patients with asthma, COPD and lung cancer compared to the healthy control group. We then developed a diagnostic model through logistic regression of antibodies that showed significant differences between groups with smoking history as a covariate. Four different variable selection methods were compared to construct an optimal diagnostic model with area under the curves ranging from 0.72 to 0.81. CONCLUSIONS: The results of this study suggest that ELISA-based analysis of anti-bacterial EV antibodies titers can be used as a diagnostic tool for lung disease. The present findings provide insights into the pathogenesis of lung disease as well as a foundation for developing a novel diagnostic methodology that synergizes microbial EV metagenomics and immune assays.

Lactobacillus plantarum-derived Extracellular Vesicles Protect Atopic Dermatitis Induced by Staphylococcus aureus-derived Extracellular Vesicles.

PURPOSE: The microbial environment is an important factor that contributes to the pathogenesis of atopic dermatitis (AD). Recently, it was revealed that not only bacteria itself but also extracellular vesicles (EVs) secreted from bacteria affect the allergic inflammation process. However, almost all research carried out so far was related to local microorganisms, not the systemic microbial distribution. We aimed to compare the bacterial EV composition between AD patients and healthy subjects and to experimentally find out the beneficial effect of some bacterial EV composition. METHODS: Twenty-seven AD patients and 6 healthy control subjects were enrolled. After urine and serum were obtained, EVs were prepared from samples. Metagenomic analysis of 16s ribosomal DNA extracted from the EVs was performed, and bacteria showing the greatest difference between controls and patients were identified. In vitro and in vivo therapeutic effects of significant bacterial EV were evaluated with keratinocytes and with Staphylococcus aureus-induced mouse AD models, respectively. RESULTS: The proportions of Lactococcus, Leuconostoc and Lactobacillus EVs were significantly higher and those of Alicyclobacillus and Propionibacterium were lower in the control group than in the AD patient group. Therefore, lactic acid bacteria were considered to be important ones that contribute to the difference between the patient and control groups. In vitro, interleukin (IL)-6 from keratinocytes and macrophages decreased and cell viability was restored with Lactobacillus plantarum-derived EV treatment prior to S. aureus EV treatment. In S. aureus-induced mouse AD models, L. plantarum-derived EV administration reduced epidermal thickening and the IL-4 level. CONCLUSIONS: We suggested the protective role of lactic acid bacteria in AD based on metagenomic analysis. Experimental findings further suggest that L. plantarum-derived EV could help prevent skin inflammation.

Clinical course of asthma patients with H1N1 influenza infection and oseltamivir.

BACKGROUND: H1N1 influenza virus prevailed throughout the world in 2009. However, there are few reports on the clinical features of H1N1 influenza infection in adult asthma patients. We evaluated the clinical features in asthma patients with H1N1 influenza infection who took oseltamivir and compared them to those with other upper respiratory infections. METHODS: We reviewed asthma patients over 15 years of age who had visited Seoul National University Hospital and Seoul National University Bundang Hospital for suspected H1N1 influenza infection from August 2009 to March 2010. Various clinical features such as hospital admission days, respiratory symptoms, basal lung function, and past history was compared between H1N1 influenza PCR positive and negative groups. RESULTS: A total of 111 asthmatics were enrolled. All patients took oseltamivir. H1N1 RT-PCR was positive in 62 patients (55.9%), negative in 49 patients (44.1%). Wheezing developed more frequently in the H1N1 positive group. (43.5 vs. 16.7%, P=0.044). The rate of acute asthma exacerbations and pneumonia development were higher in the H1N1 positive group (59.7 vs. 51%, P=0.015, 25.0% vs. 0%, P<0.001). The rates for emergency room visit, hospital admissions, intensive care unit admissions, hospital days were not different between the groups. Underlying medical conditions were accompanied more frequently in the H1N1 negative patients (21.6% vs. 30.6%, P=0.002), especially cardiac disease (7.2% vs. 15.3%, P=0.011). CONCLUSIONS: H1N1 influenza infection may affect the clinical course of asthma combined with more severe manifestations; however, Oseltamivir could have affected the clinical course of H1N1 infected patients and made it milder than expected.

The age-related characteristics of adults with asthma who visited emergency departments in Korea from 2007 to 2012.

BACKGROUND: Understanding the patterns of emergency department (ED) visits of patients with asthma is important for disease control and prevention of exacerbations. OBJECTIVE: This study aimed to investigate the characteristics of adult patients who visited EDs because of their asthma. METHODS: Patients with asthma, ages ≥19 years old, who visited 117 EDs throughout Korea between January 2007 and December 2012 were identified in the National Emergency Department Information System (NEDIS) data base using the International Classification of Disease, 10th revision, codes J45 (asthma) and J46 (status asthmaticus). RESULTS: A total of 97,835 adult patients with asthma visited 117 EDs throughout Korea during the study period. There was a slight female preponderance (male-to-female ratio, 1:1.09). The number of patients aged 70-79-years-old was 28,031 (28.7%), the highest among the patients with asthma. ED visits showed a seasonal distribution, with most occurring in winter and spring, followed by autumn. The seasonal distribution varied by age; most patients ages 19-49 years presented in autumn (September), whereas those patients ages ≥50 years presented to the ED most often in winter. Overall, 65.5% of patients were admitted to the hospital, including 12.6% admitted to an intensive care unit (ICU). Overall, 209 patients (0.2%) died. The rates of hospital admission to general wards and ICUs were highest in those patients ≥70 years old; this group also had the highest mortality rate. CONCLUSION: In this nationwide study, which spanned 6 years, of adult patients with asthma, we observed an age-specific seasonal pattern of ED visits. Identifying the causes of age-related deterioration and seasonal visits to the ED will help prevent asthma symptoms and reduce medical costs.

Importance of indoor dust biological ultrafine particles in the pathogenesis of chronic inflammatory lung diseases.

The role of infectious agents in the etiology of inflammatory diseases once believed to be non-infectious is increasingly being recognized. Many bacterial components in the indoor dust can evoke inflammatory lung diseases. Bacteria secrete nanometer-sized vesicles into the extracellular milieu, so-called extracellular vesicles (EV). which are pathophysiologically related to inflammatory diseases. Microbiota compositions in the indoor dust revealed the presence of both Gram-negative and Gram-positive bacteria. Escherichia coli is a model organism of Gram-negative Enterobacteriaceae. The repeated inhalation of E. coli-derived EVs caused neutrophilic inflammation and emphysema in a dose-dependent manner. The emphysema induced by E. coli-derived EVs was partially eliminated by the absence of Interferon-gamma or interleukin-17, suggesting that Th1 and/or Th17 cell responses are important in the emphysema development. Meanwhile, the repeated inhalation of Staphylococcus aureus-derived EVs did not induce emphysema, although they induced neutrophilic inflammation in the lung. In terms of microbial EV compositions in the indoor dust, genera Pseudomonas, Acinetobacter, Enterobacter, and Staphylococcus were dominant. As for the clinical significance of sensitization to EVs in the indoor dust, EV sensitization was closely associated with asthma, chronic obstructive pulmonary disorder (COPD), and lung cancer. These data indicate that biological ultrafine particles in the indoor dust, which are mainly composed of microbial EVs, are important in the pathogenesis of chronic lung diseases associated with neutrophilic inflammation. Taken together, microbial EVs in the indoor dust are an important diagnostic and therapeutic target for the control of chronic lung diseases, such as asthma, COPD, and lung cancer.

Phytochemical analysis and effects of Pteris vittata extract on visual processes.

The present study was designed to explore the possible effects of Pteris vittata on visual sensitivity, ERG waves, and other components of the visual system. Electrophysiological techniques including electroretinography (ERG) were used in the present study. The phytochemical composition of the extract was investigated using liquid chromatography-mass spectrometry (LC-MS) techniques. The results indicated that the extract significantly augmented dark- and light-adapted ERG b-wave amplitude. Furthermore, these findings showed that P. vittata extract does not have Gamma-aminobutyric acid receptor antagonistic activity but may function as a retinal neural antagonist in bullfrog retina. P. vittata extract improved the visual sensitivity by 0.8 log unit of light intensity, and reduced the regeneration time for rhodopsin. The six main peaks obtained through LC-MS were identified as flavonoids. Based on these results, it was concluded that P. vittata extract or its constituents may be used to treat eye diseases.

MicroRNA and diseases: therapeutic potential as new generation of drugs.

MicroRNA (miRNA) is a small non-coding regulatory RNA of 21-25 nucleotides (nts) in length. miRNA works as a post-transcriptional regulator of a specific mRNA by inducing degradation or translation repression resulting in gene silencing. A large number of miRNA have been reported and many more are yet to be discovered. Aberrant expression of miRNA has been linked to numerous diseases. Attempts have been made to attenuate miRNA misregulation under pathophysiological conditions. Additionally, the potential use of miRNA in the diagnosis and treatment of diseases has been studied. Several preclinical and clinical results have been obtained, and miRNA-based therapeutics are still under investigations. In this review, the role of miRNA in a variety of pathological conditions has been summarized. Recent findings from preclinical and clinical investigations examining the role of miRNA as diagnostic markers, and their potential as drug candidates, are also highlighted. The current results summarized in this review may elucidate new dimensions of miRNA therapeutic and diagnostic techniques for biomedical academic and industry research.

Stimulatory effects of zinc oxide nanoparticles on visual sensitivity and electroretinography b-waves in the bullfrog eye.

During the last decade, a large number of studies have focused on the development of nanomaterials for medical applications. Therefore, the present study was designed to evaluate the stimulatory effects of zinc oxide nanoparticles in the vertebrate visual system. Zinc oxide nanoparticles were synthesized and characterized through photoluminescence, ultraviolet (UV)-visible spectroscopy, field emission scanning electron microscopy and X-ray diffraction measurements. Furthermore, various electrophysiological recordings were obtained from the bullfrog eyecup preparations under various treatment conditions. Photoluminescence data showed a central peak at 386 nm while the UV-visible spectrum showed a sharp absorption band centered around 367 nm. Field emission scanning electron microscopy and X-ray diffraction measurements showed that synthesized zinc oxide nanoparticles have a polycrystalline wurtzite structure, with a round to oval shape and an average particle size of > 40 nm. Electroretinography (ERG) demonstrated that zinc oxide nanoparticles significantly increased the ERG b-wave amplitude in dark-adapted bullfrog eyecups and in the presence of background illumination. Zinc oxide nanoparticles also improved the visual sensitivity by 0.7 log unit of light intensity and shortened the duration of rhodopsin regeneration. Based on the results obtained, it was concluded that zinc oxide nanoparticles may be used to improve visual functions. The present study may add new dimensions to the biomedical applications of nanomaterials in eye research.

Murine subcutaneous immunotherapy models with beneficial immunological and physiological effects.

BACKGROUND: Immunotherapy was introduced 100 years ago and has a unique role in the treatment of allergic diseases in that only immunotherapy can induce long-term immunological tolerance. However, only a few mouse models of immunotherapy have been developed so far. OBJECTIVE: We tried to establish murine immunotherapy models that have similar findings in human using subcutaneous rush immunotherapy-like schedule. METHODS: To determine the maximal safe or maximal tolerable dose, injection dose was doubled twice a day from the dose of sensitization. Mice with established asthma using ovalbumin (OVA) were repeatedly injected with OVA from the dose of sensitization subcutaneously twice a day: after reaching to the maximal safe or maximal tolerable dose, mice were injected with each dose either 10 times or 24 times. RESULTS: Short term immunotherapy (10 times) with the maximal safe and tolerable dose of OVA showed decreased IL-5 production, decreased IL-5/INF-γ ratio, and increased IgG2a/IgG1 but there was no significant difference in airway hyperresponsiveness (AHR) or airway inflammation. Prolonged immunotherapy (24 times) with the maximal tolerable dose not only decreased cytokine productions of IL-5 and even INF-γ, but also decreased IgE, IgG1 and even IgG2a production. Remarkably, the prolonged immunotherapy provided a protective effect on AHR. CONCLUSION: This study suggested immunotherapy models with some beneficial immunological and physiological effects in murine asthma.

Influence of the Adjuvants and Genetic Background on the Asthma Model Using Recombinant Der f 2 in Mice.

Der f 2 is the group 2 major allergen of a house dust mite (Dermatophagoides farinae) and its function has been recently suggested. To determine the optimal condition of sensitization to recombinant Der f 2 (rDer f 2) in murine model of asthma, we compared the effectiveness with different adjuvants in BALB/c and C57BL/6 mice. Mice from both strains sensitized with rDer f 2 by intraperitoneal injection or subcutaneous injection on days 1 and 14. The dosage was 20 µg. Freund's adjuvants with pertussis toxin (FP) or alum alone were used as adjuvants. On days 28, 29, and 30, mice were challenged intranasally with 0.1% rDer f 2. We evaluated airway hyperresponsivenss, eosinophil proportion in lung lavage, airway inflammation, and serum allergen specific antibody responses. Naive mice were used as controls. Airway hyperresponsiveness was increased in C57BL/6 with FP, and BALB/c with alum (PC200: 13.5±6.3, 13.2±6.7 vs. >50 mg/ml, p<0.05). The eosinophil proportion was increased in all groups; C57BL/6 with FP, BALB/c with FP, C57BL/6 with alum, BALB/c with alum (24.8±3.6, 20.3±10.3, 11.0±6.9, 5.7±2.8, vs. 0.0±0.0%, p<0.05). The serum allergen specific IgE levels were increased in C57BL/6 with FP or alum (OD: 0.8±1.4, 1.1±0.8, vs. 0.0±0.0). C57BL/6 mice were better responders to rDer f 2 and as for adjuvants, Freund's adjuvant with pertussis toxin was better.

Differences in airway inflammation according to atopic status in patients with chronic rhinitis.

BACKGROUND: Chronic rhinitis is a heterogeneous group of diseases that cause nasal inflammation. And the nose may be a window into the lung in the concept of "one airway one disease." OBJECTIVE: This study was conducted to evaluate differences between the different forms of chronic rhinitis in terms of lower airway inflammation. METHODS: Patients that attended the allergy clinic and presented with moderate/severe persistent rhinitis symptoms for more than 1 year were enrolled. The patients with chronic rhinitis were classified into two groups (house dust mites [HDM]-sensitive allergic rhinitis [AR] or non-allergic rhinitis [NAR]) according to the presence of atopy, and additionally according to nasal polyposis and airway hyperresponsiveness, respectively. Medical records were reviewed and the mRNA expression levels of IL-5, IFN-γ, TGF-ß1, IL-17A, and IL-25 were evaluated in induced sputum samples in each group. RESULTS: Induced sputum samples of 53 patients were evaluated. Patients with NAR were significantly older than patients with HDM-sensitive AR (p < 0.05). Nasal polyposis was more prevalent in NAR patients than in HDM-sensitive AR patients (10.2% vs. 62.5%, p < 0.001). The expression levels of IL-17A mRNA were higher in NAR patients, regardless of the presence of airway hyperresponsiveness (p = 0.005). CONCLUSION: These results suggest that patients with different forms of chronic rhinitis could have different inflammatory environments in their lower airway and NAR patients might have bronchial inflammation related to the elevated levels of IL-17A compared to HDM-sensitive AR patients.

Surveillance of contrast-media-induced hypersensitivity reactions using signals from an electronic medical recording system.

BACKGROUND: Contrast-media (CM) hypersensitivity is a well-known adverse drug reaction. Surveillance of adverse drug reactions usually depends on spontaneous reports. However, the rate of spontaneous reports is low. Recent progress in information technology enables the electronic search on signals of adverse drug reactions from electronic medical recording (EMR) systems. OBJECTIVES: To analyze the incidence and clinical characteristics of CM hypersensitivity using an EMR-based surveillance system. METHODS: The surveillance system used signals from standardized terms within the international classification of nursing practice terms that can indicate symptoms of CM hypersensitivity and from the order codes for procedures that used contrast media, antihistamine, and epinephrine. The search strategy was validated by allergists comparing the electronic search strategy versus manually reviewing medical charts over one month. The main study covered for one year period. RESULTS: Detection rate of the electronic search method was 0.9% (7/759), while that of the manual search method was 0.8% (6/759). EMR-based electronic search method was highly efficient: reduced the charts that needed to be reviewed by 96% (28/759). The sensitivity of electronic screening was 66.7%, specificity was 99.6%, and the negative predictive value was 99.7%. CM hypersensitivity reactions were noted in 266 among 12,483 cases (2.1%). Urticaria was the most frequent symptom (74.4%). CT was the most frequent procedure (3.6%) that induced CM hypersensitivity. CONCLUSION: A surveillance system using EMR may be a useful tool in the study of drug hypersensitivity epidemiology and may be used in an adverse drug reaction alarm system and as a clinical, decision making support system.

Effects of Rubus coreanus extract on visual processes in bullfrog's eye.

ETHNOPHARMACOLOGICAL RELEVANCE: The fruit of Rubus coreanus (Rosaceae) is traditionally used as an aphrodisiac, astringent, restorative and tonic in Asian countries. It is advised for treating diseases related to liver, kidney and urinary dysfunction, premature greying, blurred vision, infertility, impotence and premature ejaculation. Additionally, there is a long history of different parts of the plants being used in the treatment of ophthalmic diseases. However, no scientific studies have been undertaken to determine the effects of Rubus coreanus in visual processes of the vertebrate retina. AIM OF STUDY: The purpose of the present study was to investigate the positive effects of Rubus coreanus extracts on visual processes in the vertebrate's eye. MATERIALS AND METHODS: Electroretinogram (ERG) techniques were used to record the responses from a bullfrog's eye cup preparations. Active pharmacological agents were used to block specific receptors in the retina and to leave others unaffected. Lipid peroxidation in the retina was generated by adding FeSO(4)+Na-ascorbate. RESULTS: It was observed that both dark- and light-adapted ERG b-wave peak amplitude significantly increases with Rubus coreanus treatment. It was found that Rubus coreanus acts as a retinal neural antagonist but not as GABA receptor antagonist. Rubus coreanus treatment lowered the duration of rhodopsin regeneration. The results obtained indicated that Rubus coreanus protects against lipid peroxidation drop off ERG amplitude in retina. CONCLUSION: Based on results obtained, it is suggested that Rubus coreanus can potentially improve visual sensitivity and can be used to treat pathophysiological conditions of eye.

Two cases of h(2)-receptor antagonist hypersensitivity and cross-reactivity.

H(2)-receptor antagonists, such as cimetidine, ranitidine and famotidine, are some of the most commonly prescribed medications for gastric acid-related disorders. These compounds are generally well-tolerated and anaphylactic reactions to them are rare. Here, we report two cases of H(2)-receptor antagonist-induced anaphylactic reactions: the first presented with sudden dyspnea, sneezing, urticaria, and swelling of the eyelids after ranitidine intake. The second presented with sudden severe urticaria, facial swelling, chest discomfort, dizziness, and hypotension. Possible cross-reactivity with other H(2)-receptor antagonists was assessed by oral challenge and skin tests. To date, only a few reports addressing cross-reactivity among H(2)-receptor antagonists have been published. We review the literature and summarize the data available on drug cross-reactivity in H(2)-receptor antagonist hypersensitivity.

Clinical features of clinically diagnosed eosinophilic liver abscesses.

PURPOSE: Eosinophilic liver abscesses (ELAs) are frequently encountered in the clinical field based on typical computed tomography (CT) findings and the presence of peripheral eosinophilia. In this study, the authors evaluated the clinical features and natural course of CT diagnosed ELAs. METHODS: The medical records of patients that underwent abdominal CT from July 2004 to February 2008 at Seoul National University Hospital were retrospectively evaluated. ELA was clinically diagnosed by the presence of peripheral eosinophilia (≥500 µL(-1)) and typical CT findings. The presumptive causes of clinically diagnosed ELA were divided into three categories, namely, parasitic infections, malignancies, and unidentified etiologies. Clinical courses and responses to treatment were evaluated. RESULTS: Clinically diagnosed ELAs were identified in 164 patients and the incidence of ELA was 0.68%. Of these patients, 118 (71.9%) showed radiologic resolution of clinically diagnosed ELA at a median 6.2 (0.2-33.1) months. In addition, 79 (48.2%) patients also achieved normalization of peripheral eosinophilia with radiologic resolution of clinically diagnosed ELA. In patients without identified etiologies, mean time to radiologic resolution was significantly shorter for patients treated empirically with an anti-parasitic drug than for those not treated [4.4 (0.9-26.3) vs. 12.2 (1.5-33.2) months, median (range), P = 0.001]. CONCLUSIONS: Clinically diagnosed ELA adopts a relatively benign course. Empirical anti-parasitic treatment in patients without an identified etiology may shorten the duration of clinically diagnosed ELA.

Alveolar macrophages modulate allergic inflammation in a murine model of asthma.

The role of alveolar macrophages (AMs) in the pathogenesis of asthma is still unknown. The aim of the present study was to investigate the effects of AM in the murine model of asthma. AMs were selectively depleted by liposomes containing clodronate just before allergen challenges, and changes in inflammatory cells and cytokine concentrations in bronchoalveolar lavage (BAL) fluid were measured. AMs were then adoptively transferred to AM-depleted sensitized mice and changes were measured. Phenotypic changes in AMs were evaluated after in vitro allergen stimulation. AM-depletion after sensitization significantly increased the number of eosinophils and lymphocytes and the concentrations of IL-4, IL-5 and GM-CSF in BAL fluid. These changes were significantly ameliorated only by adoptive transfer of unsensitized AMs, not by sensitized AMs. In addition, in vitro allergen stimulation of AMs resulted in their gaining the ability to produce inflammatory cytokines, such as IL-1ß, IL-6 and TNF-α, and losing the ability to suppress GM-CSF concentrations in BAL fluid. These findings suggested that AMs worked probably through GM-CSF-dependent mechanisms, although further confirmatory experiments are needed. Our results indicate that the role of AMs in the context of airway inflammation should be re-examined.