Community Clinical Psychological Support of an Evening High School (VIII)

ある定時制高校への大学院生による地域臨床的な支援活動は今年で8年目となった。今年度も「改訂版支援モデル（循環型）」に基づいて、校内巡回、教室内支援、グループワークの実施、先生方との共有ファイルによる情報共有、広報活動を行った。今年度は従来の週2日から週3日の支援体制としたことにより、不登校気味の生徒と会う機会が増え、我々の活動の周知にも繋がった。しかし、8年目という長期にわたる支援活動にも関わらず、活動の浸透化や先生方との連携が未だ不十分であると感じた。特に、我々が考える支援と先生方のニーズを上手くすり合わせることに難しさがあった。今後の支援継続にあたり、先生方と関わる機会を積極的に設けるべきである。充実した支援活動を行うために、環境に働きかけることが必要不可欠であろう。It has been 8 years since a team of graduate students began offering psychological support to an evening high school. This year, we continued to enhance support activities based on "the revised support model (circulation type)" from the previous year, by moving throughout the school, supporting students during class, producing a group work project, sharing students\u27 information with the teachers through shared files, and making our activities known through a newsletter and personal communications. By changing our support activities from twice a week, to one to three times a week this year, we were able to increase our contact with students who tend to be absent from school. Consequently, awareness of our activities among students increased from the previous year. Despite this increase, our activities do not seem to have been sufficiently integrated into the school system, even after 8 years. Specifically, there are difficulties in matching the activities of our support model with the teachers\u27 requests. It is discussed that, for the benefit of the students, we should have more opportunities to interact with teachers

Community Clinical Psychological Support of an Evening High School (VIII)

ある定時制高校への大学院生による地域臨床的な支援活動は今年で8年目となった。今年度も「改訂版支援モデル（循環型）」に基づいて、校内巡回、教室内支援、グループワークの実施、先生方との共有ファイルによる情報共有、広報活動を行った。今年度は従来の週2日から週3日の支援体制としたことにより、不登校気味の生徒と会う機会が増え、我々の活動の周知にも繋がった。しかし、8年目という長期にわたる支援活動にも関わらず、活動の浸透化や先生方との連携が未だ不十分であると感じた。特に、我々が考える支援と先生方のニーズを上手くすり合わせることに難しさがあった。今後の支援継続にあたり、先生方と関わる機会を積極的に設けるべきである。充実した支援活動を行うために、環境に働きかけることが必要不可欠であろう。It has been 8 years since a team of graduate students began offering psychological support to an evening high school. This year, we continued to enhance support activities based on "the revised support model (circulation type)" from the previous year, by moving throughout the school, supporting students during class, producing a group work project, sharing students\u27 information with the teachers through shared files, and making our activities known through a newsletter and personal communications. By changing our support activities from twice a week, to one to three times a week this year, we were able to increase our contact with students who tend to be absent from school. Consequently, awareness of our activities among students increased from the previous year. Despite this increase, our activities do not seem to have been sufficiently integrated into the school system, even after 8 years. Specifically, there are difficulties in matching the activities of our support model with the teachers\u27 requests. It is discussed that, for the benefit of the students, we should have more opportunities to interact with teachers

Overexpression of Chitinase 3-Like 1/YKL-40 in Lung-Specific IL-18-Transgenic Mice, Smokers and COPD

We analyzed the lung mRNA expression profiles of a murine model of COPD developed using a lung-specific IL-18-transgenic mouse. In this transgenic mouse, the expression of 608 genes was found to vary more than 2-fold in comparison with control WT mice, and was clustered into 4 groups. The expression of 140 genes was constitutively increased at all ages, 215 genes increased gradually with aging, 171 genes decreased gradually with aging, and 82 genes decreased temporarily at 9 weeks of age. Interestingly, the levels of mRNA for the chitinase-related genes chitinase 3-like 1 (Chi3l1), Chi3l3, and acidic mammalian chitinase (AMCase) were significantly higher in the lungs of transgenic mice than in control mice. The level of Chi3l1 protein increased significantly with aging in the lungs and sera of IL-18 transgenic, but not WT mice. Previous studies have suggested Chi3l3 and AMCase are IL-13-driven chitinase-like proteins. However, IL-13 gene deletion did not reduce the level of Chi3l1 protein in the lungs of IL-18 transgenic mice. Based on our murine model gene expression data, we analyzed the protein level of YKL-40, the human homolog of Chi3l1, in sera of smokers and COPD patients. Sixteen COPD patients had undergone high resolution computed tomography (HRCT) examination. Emphysema was assessed by using a density mask with a cutoff of −950 Hounsfield units to calculate the low-attenuation area percentage (LAA%). We observed significantly higher serum levels in samples from 28 smokers and 45 COPD patients compared to 30 non-smokers. In COPD patients, there was a significant negative correlation between serum level of YKL-40 and %FEV1. Moreover, there was a significant positive correlation between the serum levels of YKL-40 and LAA% in COPD patients. Thus our results suggest that chitinase-related genes may play an important role in establishing pulmonary inflammation and emphysematous changes in smokers and COPD patients

Endogenous and Exogenous Thioredoxin 1 Prevents Goblet Cell Hyperplasia in a Chronic Antigen Exposure Asthma Model

Background: Goblet cell hyperplasia with mucus hypersecretion contribute to increased morbidity and mortality in bronchial asthma. We have reported that thioredoxin 1 (TRX1), a redox (reduction/oxidation)-active protein acting as a strong antioxidant, inhibits pulmonary eosinophilic inflammation and production of chemoki- nes and Th2 cytokines in the lungs, thus decreasing airway hyperresponsiveness (AHR) and airway remodeling in mouse asthma models. In the present study, we investigated whether endogenous or exogenous TRX1 inhibits goblet cell hyperplasia in a mouse asthma model involving chronic exposure to antigen. Methods: We used wild-type Balb/c mice and Balb/c background human TRX1-transgenic mice constitutively overproducing human TRX1 protein in the lungs. Mice were sensitized 7 times (days 0 to 12) and then challenged 9 times with ovalbumin (OVA) (days 19 to 45). Every second day from days 18 to 44 (14 times) or days 35 to 45 (6 times), Balb/c mice were treated with 40 μg recombinant human TRX1 (rhTRX1) protein. Goblet cells in the lungs were examined quantitatively on day 34 or 45. Results: Goblet cell hyperplasia was significantly prevented in TRX1-transgenic mice in comparison with TRX1 transgene-negative mice. rhTRX1 administration during OVA challenge (days 18 to 44) significantly inhibited goblet cell hyperplasia in OVA-sensitized and -challenged wild-type mice. Moreover, rhTRX1 administration after the establishment of goblet cell hyperplasia (days 35 to 45) also significantly ameliorated goblet cell hyperplasia in OVA-sensitized and -challenged wild-type mice. Conclusions: Our results suggest that TRX1 prevents the development of goblet cell hyperplasia, and also ameliorates established goblet cell hyperplasia

IL-18 induces airway hyperresponsiveness and pulmonary inflammation via CD4+ T cell and IL-13.

IL-18 plays a key role in the pathogenesis of pulmonary inflammatory diseases including pulmonary infection, pulmonary fibrosis, lung injury and chronic obstructive pulmonary disease (COPD). However, it is unknown whether IL-18 plays any role in the pathogenesis of asthma. We hypothesized that overexpression of mature IL-18 protein in the lungs may exacerbate disease activities of asthma. We established lung-specific IL-18 transgenic mice on a Balb/c genetic background. Female mice sensitized- and challenged- with antigen (ovalbumin) were used as a mouse asthma model. Pulmonary inflammation and emphysema were not observed in the lungs of naïve transgenic mice. However, airway hyperresponsiveness and airway inflammatory cells accompanied with CD4(+) T cells, CD8(+) T cells, eosinophils, neutrophils, and macrophages were significantly increased in ovalbumin-sensitized and challenged transgenic mice, as compared to wild type Balb/c mice. We also demonstrate that IL-18 induces IFN-γ, IL-13, and eotaxin in the lungs of ovalbumin-sensitized and challenged transgenic mice along with an increase in IL-13 producing CD4(+) T cells. Treatment with anti-CD4 monoclonal antibody or deletion of the IL-13 gene improves ovalbumin-induced airway hyperresponsiveness and reduces airway inflammatory cells in transgenic mice. Overexpressing the IL-18 protein in the lungs induces type 1 and type 2 cytokines and airway inflammation, and results in increasing airway hyperresponsiveness via CD4(+) T cells and IL-13 in asthma

Overproduction of IL-18 in lungs increases Th1 and Th2 cytokines, and airway hyperresponsiveness.

<p>(A) The concentrations of IFN-γ, IL-13, IL-1β, and eotaxin in the bronchoalveolar lavage fluids (BALFs) were measured by specific ELISA kits. (n = 4 to 6 per each group) *: p<0.05 (B) On day 19, BALF cells were isolated from OVA-sensitized and challenged mice. Three-color analysis was performed for intracellular cytokine staining. Isolated BALF cells were stained with FITC-anti-mouse CD4 mAb, PE-anti-mouse IL-13 mAb, PC7-anti-mouse IFN-γ mAb, and/or control isotype matched mAbs, as reported previously <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0054623#pone.0054623-Hoshino4" target="_blank">[14]</a>. The lymphocyte population was gated for intracellular cytokine analysis. (C) Mice were anesthetized intraperitoneally with sodium pentobarbital, and their tracheas were cannulated via tracheostomy. The mice were ventilated mechanically (tidal volume, 325 µl; frequency, 120 breaths/minute). A paralytic agent (pancuronium bromide) was administered and airway opening pressure was measured with a differential pressure transducer and was recorded continuously. Stepwise increases of acetylcholine chloride (ACh, catalog no. A-6625, Sigma–Aldrich Chemical) in 0.9% saline (0.6 to 160 mg/ml) were given by an ultrasonic nebulizer (30 seconds). The data were expressed as the provocative concentration 200 (PC200); the concentration at which airway pressure was 200% of its baseline. PC200 was calculated by log-linear interpolation for individual mice. The data were also expressed as airway resistance changes from baseline in response to 9 different doses of Ach (0, 0.625, 1.25, 2.5, 5, 10, 20, 40, 80, and 160 mg/ml). (n = 6 to 10 per each group) *: p<0.05. (D) Serum Total IgE and OVA-specific IgE concentrations were measured. (n = 5 to 12 per each group) *: p<0.05.</p

Treatment with anti-CD4 mAb decreased airway inflammation, Th1 and Th2 cytokines, and airway hyperresponsiveness in IL-18 Tg mice.

<p>In group 3, OVA-sensitized mice were treated with 500 µg of rat anti-mouse CD4 mAb or rat IgG on day 17, and OVA-challenged on day 18. (A) Cell populations in the BALFs. (n = 5 to 7 per each group) *: p<0.05. (B) The concentrations of mouse IFN-γ and IL-13 in the BALFs were measured. (n = 5 to 7 per each group) *: p<0.05. (C) Airway responsiveness to aerosolized acetylcholine was examined as described above. The data were also expressed as airway resistance changes from baseline in response to 9 different doses of Ach (0, 0.625, 1.25, 2.5, 5, 10, 20, 40, 80, and 160 mg/ml). (n = 7 to 10 per each group) *: p<0.05.</p