A History of Recurrent Episodes of Prolonged Cough as a Predictive Value for Determining Cough Variant Asthma in a Primary Care Setting

Background: Many patients visit primary care clinics with a complaint of cough. General practitioners (GPs) developed a list of the causative diseases of cough that can produce a patient’s symptoms and signs. Then, the patients’ medical histories were evaluated to determine whether the diagnosis of cough variant asthma (CVA) or post-infectious cough (PIC) could have been predicted. Methods: We retrospectively investigated 195 outpatients with a complaint of cough. Medical histories of “recurrent episodes of prolonged cough” and “upper respiratory infection” were obtained during the initial visit. The accuracy of medical histories in predicting CVA and PIC was calculated on the area under the curve (AUC). Results: Among eligible patients with cough, PIC was diagnosed in 99 patients (50.8%), CVA in 40 patients (20.5%), upper airway cough syndrome in 28 patients (14.4%), and chronic obstructive pulmonary disease in 11 patients (5.6%). Among the patients with CVA and those with PIC, 93% and 12%, respectively, had a history of recurrent episodes of prolonged cough. For the diagnosis of CVA, having a history of recurrent episodes of prolonged cough showed a moderately accurate AUC (0.76, 95% CI: 0.71–0.82). On the other hand, for the diagnosis of PIC, having no history of recurrent episodes of prolonged cough also showed a moderately accurate AUC (0.87, 95% CI: 0.82–0.92). Conclusion: The medical history of recurrent episodes of prolonged cough is useful for the prediction of CVA as well as PIC

Hybrid dynamic/static method for large-scale simulation of metabolism

BACKGROUND: Many computer studies have employed either dynamic simulation or metabolic flux analysis (MFA) to predict the behaviour of biochemical pathways. Dynamic simulation determines the time evolution of pathway properties in response to environmental changes, whereas MFA provides only a snapshot of pathway properties within a particular set of environmental conditions. However, owing to the large amount of kinetic data required for dynamic simulation, MFA, which requires less information, has been used to manipulate large-scale pathways to determine metabolic outcomes. RESULTS: Here we describe a simulation method based on cooperation between kinetics-based dynamic models and MFA-based static models. This hybrid method enables quasi-dynamic simulations of large-scale metabolic pathways, while drastically reducing the number of kinetics assays needed for dynamic simulations. The dynamic behaviour of metabolic pathways predicted by our method is almost identical to that determined by dynamic kinetic simulation. CONCLUSION: The discrepancies between the dynamic and the hybrid models were sufficiently small to prove that an MFA-based static module is capable of performing dynamic simulations as accurately as kinetic models. Our hybrid method reduces the number of biochemical experiments required for dynamic models of large-scale metabolic pathways by replacing suitable enzyme reactions with a static module

A microarray data-based semi-kinetic method for predicting quantitative dynamics of genetic networks

BACKGROUND: Elucidating the dynamic behaviour of genetic regulatory networks is one of the most significant challenges in systems biology. However, conventional quantitative predictions have been limited to small networks because publicly available transcriptome data has not been extensively applied to dynamic simulation. RESULTS: We present a microarray data-based semi-kinetic (MASK) method which facilitates the prediction of regulatory dynamics of genetic networks composed of recurrently appearing network motifs with reasonable accuracy. The MASK method allows the determination of model parameters representing the contribution of regulators to transcription rate from time-series microarray data. Using a virtual regulatory network and a Saccharomyces cerevisiae ribosomal protein gene module, we confirmed that a MASK model can predict expression profiles for various conditions as accurately as a conventional kinetic model. CONCLUSION: We have demonstrated the MASK method for the construction of dynamic simulation models of genetic networks from time-series microarray data, initial mRNA copy number and first-order degradation constants of mRNA. The quantitative accuracy of the MASK models has been confirmed, and the results indicated that this method enables the prediction of quantitative dynamics in genetic networks composed of commonly used network motifs, which cover considerable fraction of the whole network

An Inhibitory Effect of Dexamethasone on A549 Cell Adhesion to Neutrophils: Possible Involvement of Nuclear Factor-Kappa B

In order to clarify the effects of dexamethasone on epithelial cells at the transcription factor level, protein synthesis level and functional level, we examined neutrophil adhesion to A549 cells (an immortalized human type II alveolar epithelial cell line), expression of intercellular adhesion molecule-1 (ICAM-1), and translocation of nuclear factor-kappa B (NF-κB) into nuclei. The intranuclear localization of fluorescently stained NF-κB and an adhesion assay between neutrophils and A549 cells was analyzed quantitatively using laser scanning cytometry. ICAM-1 expression on A549 cells was measured by flow cytometric analysis. Stimulation of A549 cells with tumor necrosis factor (TNF)-α caused a time- and dose-dependent increase in their adhesiveness for neutrophils. ICAM-1 expression on A549 cells after stimulation with TNF-α for 12 h was significantly up-regulated, compared with unstimulated cells (P< 0.05). Intranuclear NF-κB was induced 10 min after stimulation with TNF-α and was increased in a TNF-α-dose-dependent manner. Dexamethasone suppressed TNF-α-induced NF-κB translocation in A549 cells by approximately 60%, ICAM-1 expression on A549 cells by approximately 40%, and A549 adhesiveness for neutrophils completely. Therefore, we suggest that the inhibition of A549 adhesiveness for neutrophils by dexamethasone may be due in part to the suppression of NF-κB entry into nuclei and ICAM-1 expression in A549 cells

4.Rocks and minerals

金沢大学COEポストドクターDepartment of Earth and Planetary Science, Tokyo Institute of technology鹿児島大学Editor : Tazaki, Kazue, Cover:Scanning electoron microscopic photograph of Gallionella sp. in biomats of Aso caldera, Kyusyu, Japan. Various shapes of Gallonella sp. are shown (image:Moriichi, Shingo).COE, 金沢大学 水・土壌環境領域シンポジウム「地球環境における微生物の役割」, 日時：2002年12月4日（水）13：00～, 場所：金沢大学理学部3階第一実験

Alveolar Epithelial Cell Line, A549 Cells Inhibit Neutrophil Apoptosis

Though cellular localization at the site of an inflammatory challenge is the critical first step in a neutrophil response, little has been known about the effects of alveolar epithelial cells on the dynamics of neutrophils. To investigate these effects, we used human purified neutrophils incubated with monolayers of human alveolar epithelial cells (A549), quiescent or preactivated with recombinant human tumor necrosis factor (TNF)-α for 24 h. Laser scanning cytometry (LSC) was employed to detect nuclear morphological changes and quantitate DNA strand breaks in neutrophils. The experiments revealed that A549 cells inhibited neutrophil apoptosis, and that this inhibitory effect was enhanced when the A549 cells were preactivated with TNF-α for 24 h. These results suggest that alveolar epithelial cells may be potentially able to contribute to promote inflammatory mechanisms by delaying neutrophil apoptosis

Effect of a Nitric Oxide Donor on Intracellular Cytokine Production in Normal Human Peripheral Lymphocytes

It has been recently suggested that nitric oxide (NO) plays an important role in modulating immune responses including helper T (Th) cell differentiation. To investigate the effect of NO on cytokine production in T cells, we examined in vitro the percentage of interferon (IFN)-γ and interleukin (IL)-4 producing cells by the intracellular cytokine staining method with flow cytometry. The percentage of IFN-γ and IL-4 producing cells reached maximal value 8 h after stimulation by phorbol 12-myristate 13-acetate (PMA) and ionomycin. When an NO donor, sodium nitroprusside (SNP), was co-incubated with PMA and ionomycin for 8 h, nitrite levels increased in a dose dependent manner for SNP (P = 0.007; Friedman test). The percentage of IFN-γ producing cells was diminished in consequence of the increasing doses of SNP (P = 0.002; Friedman test). While the percentage of IL-4 producing cells tended to be diminished by SNP, this difference, however, was statistically not significant (P = 0.062; Friedman test). Therefore, we have suggested that NO might affect Th cell differentiation through inhibition of Th1-cytokine production and might cause a Th2 cell predominant state

Expression of Surface Markers on Mature Monocyte-Derived Dendritic Cells from Allergic Asthmatics

Dendritic cells (DCs) are one type of important inflammatory cells in the pathogenesis of asthma for early response to allergen exposure. Monocyte-derived DCs (MoDCs) are characterized by a high antigen uptake capacity and poor T-cell stimulatory activity, both features of immature DCs. By stimulation with tumor necrosis factor-alpha (TNF-alpha) or antigen capture, these cells differentiate into mature DCs with the disappearance of antigen-capturing regions, and increase in stimulatory activity. We measured the expression of some molecules on MoDCs before and after stimulation with TNF-alpha or house dust mite (HDM) antigen, from 9 house dust mite (HDM)-allergic asthmatic patients and 8 normal control subjects by flow cytometry. Primary MoDCs from HDM-allergic asthmatics showed a greater expression of histocompatibility leukocyte antigen (HLA)-DR and mannose receptor (MR), but not of CD80, CD86 or intercellular adhesion molecule-1 (ICAM-1), than those from normal subjects (P < 0.05). After stimulation with TNF-alpha or HDM, DCs from asthmatic patients showed a greater expression of HLA-DR, CD86 and ICAM-1, than those from normal subjects. In HDM-allergic asthmatic patients, MR expression on DCs significantly declined after stimulation by HDM compared with stimulation by TNF-alpha (P < 0.05). Results suggest that the reduction of MR expression may be characteristic on mature DCs after HDM exposure in allergic asthma

Predictive Model for Adverse Events and Immune Response Based on the Production of Antibodies After the Second-Dose of the BNT162b2 mRNA Vaccine

Background: The BNT162b mRNA vaccine for coronavirus disease 2019, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), mimics the immune response to natural infection. Few studies have predicted the adverse effects (AEs) after the second-dose vaccination. We present a predictive model for AEs and immune response after the second-dose of the BNT162b mRNA vaccine. Methods: To predict AEs, 282 healthcare workers (HCWs) were enrolled in this prospective observational study. The classification and regression tree (CART) model was established, and its predictive efficacy was assessed. To predict immune response, 282 HCWs were included in the analysis. Moreover, the factors affected by anti-SARS-CoV-2 spike protein RBD antibody (s-IgG) were evaluated using serum samples collected 2 months after the second-dose vaccination. The s-IgG level was assessed using Lumipulse G1200. Multiple regression analyses were conducted to evaluate variables associated with anti-s-IgG titer levels. Results: The most common AEs after the second-dose vaccination were pain (87.6%), redness (17.0%) at the injection site, fatigue (68.8%), headache (53.5%), and fever (37.5%). Based on the CART model, headache after the first-dose vaccination and age < 30 years were identified as the first and second discriminators for predicting the headache after the second-dose vaccination, respectively. In the multiple linear regression model, anti-s-IgG titer levels were associated with age, female sex, and AEs including headache and induration at the injection site after the second-dose vaccination. Conclusion: Headache after the first-dose vaccination can be a predictor of headache after the second-dose vaccination, and AEs are indicators of immune response

Molecular Dynamics Simulations of Systems Including Clay, Water and Organic Matters

金沢大学大学院自然科学研究科Tokyo Institute of Technology鹿児島大学Scedule:17-18 March 2003, Vemue: Kanazawa, Japan, Kanazawa Citymonde Hotel, Project Leader : Hayakawa, Kazuichi, Symposium Secretariat: XO kamata, Naoto, Edited by:Kamata, Naoto