10,371 research outputs found
Transflective device with a transparent organic light-emitting diode and a reflective liquid crystal device
Mechanisms of Lung Injury in a Mouse Model of Bronchopulmonary Dysplasia
Bronchopulmonary dysplasia (BPD) is a chronic lung disease that affects preterm infants. Increased levels of inflammatory mediators in the amniotic fluid and in the lungs of preterm infants are associated with the development of BPD. It has been shown that infant transgenic mice that express interleukin (IL)-1β in the lung epithelium from approximately embryonal day 14 (pseudoglandular stage of lung development) develop a pulmonary injury that resembles BPD, supporting the idea that inflammation plays an important role in the pathogenesis of BPD. The mechanisms by which inflammation causes lung injury have not been identified.
The aim of this thesis was to define mechanisms by which perinatal inflammatory lung injury develops by using transgenic mice that express IL-1β in the lung epithelium in an inducible manner.
The β6 integrin subunit has previously been shown to be involved in the progression of pulmonary diseases in adult mice. To investigate the involvement of the β6 integrin subunit in IL-1β-induced lung disease in the neonate, lung development of IL-1β-expressing mice lacking the β6 integrin subunit were compared with that of IL-1β-expressing mice with wild-type β6 loci. Absence of the β6 integrin subunit alleviated the IL-1β-induced lung injury, as demonstrated by smaller alveoli, thinner alveolar walls, and a milder lung inflammation than IL-1β-expressing mice with wild-type β6 integrin loci. The results suggest that the β6 integrin subunit plays a role in the development of neonatal lung disease.
Increased levels of matrix metalloproteinase (MMP)-9 and an imbalance between proteases and antiproteases in the lungs of infants and animals developing BPD have led to the hypothesis that MMP-9 may be involved in the pathogenesis of the disease. No differences in lung histology were detected between mice with wild-type MMP-9 loci and mice with null MMP-9 loci, implying a non-essential role of MMP-9 during lung development. However, IL-1β caused a more severe alveolar hypoplasia in mice deficient in MMP-9 than in MMP-9 wild-type mice, suggesting that MMP-9 may have a protective role during inflammatory lung injury.
A short-term exposure of IL-1 has been shown to accelerate development of the surfactant system in fetal rabbits and lambs. Using transgenic mice where the expression of IL-1β is restricted to the distal lung epithelium, the effects on lung development and function of chronic prenatal IL-1β production were studied. Distal lung expression of IL-1β disrupted acinar bud formation prior to birth and decreased the expression of the important surfactant proteins SP-B and SP-C. The 100% mortality observed among the IL-1β-expressing mice was probably due to the inflammation-induced structural changes and to deficient surfactant function. The results suggest that an early and continuous inflammatory stimulus in the distal lung epithelium causes severe lung injury and disrupts surfactant production
Nrf2 deficiency influences susceptibility to steroid resistance via HDAC2 reduction
Abnormal lung inflammation and oxidant burden are associated with a significant reduction in histone deacetylase 2 (HDAC2) abundance and steroid resistance. We hypothesized that Nrf2 regulates steroid sensitivity via HDAC2 in response to inflammation in mouse lung. Furthermore, HDAC2 deficiency leads to steroid resistance in attenuating lung inflammatory response, which may be due to oxidant/antioxidant imbalance. Loss of antioxidant transcription factor Nrf2 resulted in decreased HDAC2 level in lung, and increased inflammatory lung response which was not reversed by steroid. Thus, steroid resistance or inability of steroids to control lung inflammatory response is dependent on Nrf2-HDAC2 axis. These findings have implications in steroid resistance, particularly during the conditions of oxidative stress when the lungs are more susceptible to inflammatory response, which is seen in patients with chronic obstructive pulmonary disease, asthma, rheumatoid arthritis, and inflammatory bowel disease
Deletion of vitamin D receptor leads to premature emphysema/COPD by increased matrix metalloproteinases and lymphoid aggregates formation
Deficiency of vitamin D is associated with accelerated decline in lung function. Vitamin D is a ligand for nuclear hormone vitamin D receptor (VDR), and upon binding it modulates various cellular functions. The level of VDR is reduced in lungs of patients with chronic obstructive pulmonary disease (COPD) which led us to hypothesize that deficiency of VDR leads to significant alterations in lung phenotype that are characteristics of COPD/emphysema associated with increased inflammatory response. We found that VDR knock-out (VDR(-/-)) mice had increased influx of inflammatory cells, phospho-acetylation of nuclear factor-kappaB (NF-κB) associated with increased proinflammatory mediators, and up-regulation of matrix metalloproteinases (MMPs) MMP-2, MMP-9, and MMP-12 in the lung. This was associated with emphysema and decline in lung function associated with lymphoid aggregates formation compared to WT mice. These findings suggest that deficiency of VDR in mouse lung can lead to an early onset of emphysema/COPD because of chronic inflammation, immune dysregulation, and lung destruction
[[alternative]]The Regulatory effect of Shy-Jiun-Tsi-Tang on Immunoglobulin
[[abstract]]四君子湯是補氣的基本處方,以黨參為主藥,佐以健脾利水的白朮、
茯苓,再配合有調和諸藥作用的炙甘草所構成。本實驗探討四君子湯
50%熱乙醇萃取液,對人類B淋巴球分泌免疫球蛋白(Ig)的調節作用。
四君子湯複方、單方,分別加入人類周邊血液與扁桃腺單核細胞
(PMNC、TMNC)培養基中四天後計算細胞總數與存活率,上清液測定Ig
分泌量。中藥對PMNC之實驗結果顯示,中藥均不影響細胞總數,四君子湯
抑制細胞存活率及IgE和IgM的分泌,茯苓抑制細胞存活率及IgE的分泌,
炙甘草抑制IgE分泌,黨參及白朮對細胞存活率及Ig分泌則無影響。
中藥對TMNC之實驗結果顯示,茯苓至抑制細胞總數,其餘中藥則
不影響細胞總數。茯苓、黨參、四君子湯,抑制細胞存活率,
白朮、炙甘草則不影響存活率。茯苓抑制TMNC產生IgM,
但不影響IgA、IgG之分泌。黨參抑制IgA、IgM,但不影響IgG。白朮抑制
IgA ,但不影響IgG、IgM,炙甘草抑制IgM,對IgA、IgG之分泌則無影響,
四君子湯則抑制IgA、IgG、IgM。中藥對PMNC、TMNC純化之B淋巴球的實驗
結果顯示,四君子湯複方、單方,都不影響細胞總數、存活率與Ig的分泌
。為瞭解中藥如何影響IgE的分泌,實驗進一步以U266IgE分泌細胞株(Cell
line)重複上述實驗,發現茯苓、黨參、四君子湯,都抑制細胞總數與存活
率,白朮、炙甘草則否,茯苓、黨參、白朮、四君子湯都抑制IgE的分泌,
炙甘草則無影響。本實驗結果證實,四君子湯確實對人類B淋巴球活性及
分泌免疫球蛋白(Ig)有調節作用,且依細胞來源不同,其影響程度亦有差
異。
Shy-Jiun-Tsi-Tang is one of the widely used Chinese herbal medi-
cine. In this study, human B lymphocytes were in vitro treated
with 50% hot ethanol extract of Shy-Jiun-Tsi-Tang and its four
major ingredients ( Dang-Shen, Bair-Jwu, Gan-Tsao and Fu-Ling ).
The concentration of IgM, IgG, IgA and IgE in the culture super-
natants were measured using an ELISA after four days of cultiva-
tion. Data obstaining from the experiments suggested that the
effects of the drugs on B-cell growth,viability and Ig secretion
were diverse in terms of the source and purity of the B lympho-
cytes. For the peripheral mononuclear cell ( PMNC ), the drugs
showed no effect on the total cell numbers. Shy-Jiun-Tsi-Tang
suppressed viability, IgM secretion and IgE secretion. Fu-Ling
suppressed viability and IgE secretion. Gan-Tsao suppressed IgE
secretion. Dang-Shen and Bair-Jwu had no effect on the viability
and Ig secretion. For the tonsil mononuclear cells ( TMNC ). Fu-
Ling suppressed the total cell numbers. Fu-Ling, Dang-Shen, Bair
-Jwu and Shy-Jiun-Tsi-Tang but Gan-Tsao significantly suppressed
on its viability. Fu-Ling suppressed IgM secretion, Dang-Shen
suppressed IgA and IgM secretion. Bair-Jwu suppressed IgA secre-
tion. Gan-Tsao suppressed IgM secretion. Shy-Jiun-Tsi-Tang sup-
pressed IgA, IgM and IgG secretiobn. For the B-lymphocytes(99.23
% in purity) from PMNC and TMNC, Shy-Jiun-Tsi-Tang and its four
major ingredients showed no effect on the total cell numbers,
viability and Ig secretion. To study the effect of the drugs on
IgE secretion further, an IgE-secreting line, U266, was used to
repeat the previous study. The data suggested that Fu-Ling, Dang
-Shen, and Shy-Jiun-Tsi-Tang significantly suppressed both the
total cell numbers and viability. Fu-Ling, Dang-Shen, Bair-Jwu
and Shy-Jiun-Tsi-Tang significantly suppressed IgE secretion by
U266 cells. This study demonstrated that Shy-Jiun-Tsi-Tang did
have regulatory effect on the growth, viability and Ig-secretion
of human B cells. The extent of the effect was mainly dependent
on the source of B lymphocytes.
Shy-Jiun-Tsi-Tang is one of the widely used Chinese herbal medi-
MRI of the lung (3/3)-current applications and future perspectives
BackgroundMRI of the lung is recommended in a number of clinical indications. Having a non-radiation alternative is particularly attractive in children and young subjects, or pregnant women.MethodsProvided there is sufficient expertise, magnetic resonance imaging (MRI) may be considered as the preferential modality in specific clinical conditions such as cystic fibrosis and acute pulmonary embolism, since additional functional information on respiratory mechanics and regional lung perfusion is provided. In other cases, such as tumours and pneumonia in children, lung MRI may be considered an alternative or adjunct to other modalities with at least similar diagnostic value.ResultsIn interstitial lung disease, the clinical utility of MRI remains to be proven, but it could provide additional information that will be beneficial in research, or at some stage in clinical practice. Customised protocols for chest imaging combine fast breath-hold acquisitions from a “buffet” of sequences. Having introduced details of imaging protocols in previous articles, the aim of this manuscript is to discuss the advantages and limitations of lung MRI in current clinical practice.ConclusionNew developments and future perspectives such as motion-compensated imaging with self-navigated sequences or fast Fourier decomposition MRI for non-contrast enhanced ventilation- and perfusion-weighted imaging of the lung are discussed
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