Time Sequence of Airway Remodeling in a Mouse Model of Chronic Asthma: the Relation with Airway Hyperresponsiveness

During the course of establishing an animal model of chronic asthma, we tried to elucidate the time sequence of airway hyperresponsiveness (AHR), airway inflammation, airway remodeling, and associated cytokines. Seven-week-old female BALB/c mice were studied as a chronic asthma model using ovalbumin (OVA). After sensitization, mice were exposed twice weekly to aerosolized OVA, and were divided into three groups depending on the duration of 4 weeks, 8 weeks, and 12 weeks. At each time point, airway responsiveness, inflammatory cells, cytokines in bronchoalveolar lavage fluids (BALF), serum OVA-specific IgE, IgG1, IgG2a, and histological examination were carried out. AHR to methacholine, increased levels of OVA-specific IgG1 and IgG2a, and goblet cell hyperplasia were continuously sustained at each time point of weeks. In contrast, we observed a time-dependent decrease in serum OVA-specific IgE, BALF eosinophils, BALF cytokines such as IL-13, transforming growth factor-beta1, and a time-dependent increase in BALF promatrix metalloproteinase-9 and peribronchial fibrosis. In this OVA-induced chronic asthma model, we observed airway remodelings as well as various cytokines and inflammatory cells being involved in different time-dependent manners. However, increased airway fibrosis did not directly correlate with a further increase in airway hyperresponsiveness

Functional Assay of Cancer Cell Invasion Potential Based on Mechanotransduction of Focused Ultrasound

Cancer cells undergo a number of biophysical changes as they transform from an indolent to an aggressive state. These changes, which include altered mechanical and electrical properties, can reveal important diagnostic information about disease status. Here, we introduce a high-throughput, functional technique for assessing cancer cell invasion potential, which works by probing for the mechanically excitable phenotype exhibited by invasive cancer cells. Cells are labeled with fluorescent calcium dye and imaged during stimulation with low-intensity focused ultrasound, a non-contact mechanical stimulus. We show that cells located at the focus of the stimulus exhibit calcium elevation for invasive prostate (PC-3 and DU-145) and bladder (T24/83) cancer cell lines, but not for non-invasive cell lines (BPH-1, PNT1A, and RT112/84). In invasive cells, ultrasound stimulation initiates a calcium wave that propagates from the cells at the transducer focus to other cells, over distances greater than 1 mm. We demonstrate that this wave is mediated by extracellular signaling molecules and can be abolished through inhibition of transient receptor potential channels and inositol trisphosphate receptors, implicating these proteins in the mechanotransduction process. If validated clinically, our technology could provide a means to assess tumor invasion potential in cytology specimens, which is not currently possible. It may therefore have applications in diseases such as bladder cancer, where cytologic diagnosis of tumor invasion could improve clinical decision-making

Prognostic Significance of Multidrug Resistance Gene 1 (MDR1), Multidrug Resistance-related Protein (MRP) and Lung Resistance Protein (LRP) mRNA Expression in Acute Leukemia

The prognostic significance of multidrug resistance (MDR) gene expression is controversial. We investigated whether multidrug resistance gene 1 (MDR1), multidrug resistance-related protein (MRP) and lung resistance protein (LRP) mRNA expression are associated with outcomes in acute leukemia patients. At diagnosis we examined MDR1, MRP and LRP mRNA expression in bone marrow samples from 71 acute leukemia patients (39 myeloid, 32 lymphoblastic) using nested RT-PCR. The expression of each of these genes was then expressed as a ratio in relation to β-actin gene expression, and the three genes were categorized as being either 0, 1+, 2+ or 3+. MDR1, MRP and LRP mRNA expression was detected in 23.9%, 83.1% and 45.1%, respectively. LRP mRNA expression was significantly associated with resistance to induction chemotherapy in acute leukemia patients, and in the AML proportion (p=0.02 and p=0.03, respectively). MRP and high MDR1 mRNA expression was associated with poorer 2-yr survival (p=0.049 and p=0.04, respectively). Patients expressing both MRP and LRP mRNA had poorer outcomes and had worse 2-yr survival. The present data suggest that MDR expression affects complete remission and survival rates in acute leukemia patients. Thus, determination of MDR gene expression at diagnosis appears likely to provide useful prognostic information for acute leukemia patients

Inflammatory and Remodeling Events in Asthma with Chronic Exposure to House Dust Mites: A Murine Model

Although animal models with ovalbumin have been used to study chronic asthma, there are difficulties in inducing recurrence as well as in maintaining chronic inflammation in this system. Using a murine model of house dust mite (HDM)-induced bronchial asthma, we examined the airway remodeling process in response to the chronic exposure to HDM. During the seventh and twelfth weeks of study, HDM were inhaled through the nose for three consecutive days and airway responsiveness was measured. Twenty-four hours later, bronchoalveolar lavage and histological examination were performed. The degree of overproduction of mucus, subepithelial fibrosis, and the thickness of the peribronchial smooth muscle in the experimental group was clearly increased compared to the control group. In addition, HDM-exposed mice demonstrated severe airway hyperreactivity to methacholine. In the bronchoalveolar lavage fluid, the number of total cells and eosinophils was increased; during the twelfth week, the number of neutrophils increased in the experimental group. With regard to changes in cytokines, the concentrations of IL-4, IL-13, and transforming growth factor-beta (TGF-β) were increased in the experimental group. The data suggest that eosinophils, IL-4, IL-13, and TGF-β might play an important role in the airway remodeling process and that neutrophils may be involved with increased exposure time

Pseudomonas segetis sp. nov., isolated from soil

A Gram-negative, aerobic bacterium, designated strain FR1439(T), was isolated from the soil of Dokdo in the Republic of Korea. The cells of strain FR1439(T) were catalase- and oxidase-positive, motile and rod-shaped. Phylogenetic analysis of the 16S rRNA gene sequence revealed that it represents a distinct line of descent within the genus Pseudomonas. The levels of DNA-DNA relatedness between strain FR1439(T) and type strains of phylogenetically related species, namely Pseudomonas flavescens, Pseudomonas mendocina, Pseudomonas pseudoalcaligenes and Pseudomonas straminea, ranged from 28 to 37%. Several phenotypic characteristics, together with the cellular fatty acid composition, can be used to differentiate strain FR1439(T) from related pseudomonads. On the basis of the polyphasic taxonomic evidence presented in this study, strain FR1439(T) represents a novel species, for which the name Pseudomonas segetis sp. nov. is proposed. The type strain is FR1439(T) (= IMSNU 14101(T) = CIP 108523(T) = KCTC 12331(T)).

Evaluation on the Restoration Effects in the River Restoration Projects Practiced in South Korea

This study evaluated the effects of the restoration of rivers carried out by the central government on streams located in major cities in South Korea. The effects of the restoration were evaluated based on the morphological and ecological characteristics, species composition and richness of vegetation, and a Riparian Vegetation Index of the restored streams. The naturalness of the streams, based on both the morphological and ecological characteristics, as well as the Riparian Vegetation Index of the restored streams was significantly lower than that of the reference rivers. The vegetation profiles of the restored streams did not reflect the flooding regimen of the river. Furthermore, the herbaceous plants found on the streambanks give way to shrubs and then to tree-dominated vegetation, respectively. The species composition of the vegetation in the restored streams showed a significant difference from that of the reference streams and this difference was particularly more significant with regards to the herbaceous plant-dominated vegetation types. The species richness of the restored streams showed a difference among the different streams but was lower than that of the reference streams. The ratio of exotic and gardening plants occupied in the species composition of the restored streams tended to be higher than that in the reference streams. Considering the above results, the restoration effects were usually low in the restored streams. Accordingly, an active adaptive management plan was recommended to improve those problems

Molecular Genetic Characterization of the Merozoite Surface Protein 1 Gene of Plasmodium vivax from Reemerging Korean Isolates▿

Plasmodium vivax merozoite surface protein 1 (PvMSP-1) has been considered a major candidate for the development of an antimalaria vaccine, but the molecule exhibits antigenic diversity among isolates. The extent of genetic polymorphism in the region between interspecies conserved blocks 4 and 5 (ICB4 and ICB5) of the PvMSP-1 gene was analyzed for 30 Korean isolates. Two genotypes, SK-A and SK-B, were identified on the basis of amino acid substitution. Almost all the amino acid sequences of the Korean isolates were nearly identical to those of the Solomon Island isolate Solo-83 (97.8 to 99.9% similarity) and Philippine isolates Ph-79, Ph-52-2, and Ph-49 (97.3 to 99.8% similarity). Also, we report two sequences in the isolates that were characterized on the basis of restriction fragment length polymorphism (RFLP). The RFLP profiles following digestion with the DraI restriction enzyme produced two distinguishable patterns. This study might be the first report of the region between ICB4 and ICB5 of the MSP-1 gene of P. vivax in South Korea