Gene Expression Analysis of a Murine Model with Pulmonary Vascular Remodeling Compared to End-Stage IPAH Lungs

BACKGROUND: Idiopathic pulmonary arterial hypertension (IPAH) continues to be one of the most serious intractable diseases that might start with activation of several triggers representing the genetic susceptibility of a patient. To elucidate what essentially contributes to the onset and progression of IPAH, we investigated factors playing an important role in IPAH by searching discrepant or controversial expression patterns between our murine model and those previously published for human IPAH. We employed the mouse model, which induced muscularization of pulmonary artery leading to hypertension by repeated intratracheal injection of Stachybotrys chartarum, a member of nonpathogenic and ubiquitous fungus in our envelopment. METHODS: Microarray assays with ontology and pathway analyses were performed with the lungs of mice. A comparison was made of the expression patterns of biological pathways between our model and those published for IPAH. RESULTS: Some pathways in our model showed the same expression patterns in IPAH, which included bone morphogenetic protein (BMP) signaling with down-regulation of BMP receptor type 2, activin-like kinase type 1, and endoglin. On the other hand, both Wnt/planar cell polarity (PCP) signaling and its downstream Rho/ROCK signaling were found alone to be activated in IPAH and not in our model. CONCLUSIONS: Activation of Wnt/PCP signaling, in upstream positions of the pathway, found alone in lungs from end stage IPAH may play essential roles in the pathogenesis of the disease

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研究報告書ページ（49）-（50

Bulk inflaton shadows of vacuum gravity

We introduce a $(5+m)$-dimensional vacuum description of five-dimensional bulk inflaton models with exponential potentials that makes analysis of cosmological perturbations simple and transparent. We show that various solutions, including the power-law inflation model recently discovered by Koyama and Takahashi, are generated from known $(5+m)$-dimensional vacuum solutions of pure gravity. We derive master equations for all types of perturbations, and each of them becomes a second order differential equation for one master variable supplemented by simple boundary conditions on the brane. One exception is the case for massive modes of scalar perturbations. In this case, there are two independent degrees of freedom, and in general it is difficult to disentangle them into two separate sectors.Comment: 22 pages, 4 figures, revtex; v2: references adde

Use of the index of pulmonary vascular disease for predicting long-term outcome of pulmonary arterial hypertension associated with congenital heart disease

AimsLimited data exist on risk factors for the long-term outcome of pulmonary arterial hypertension (PAH) associated with congenital heart disease (CHD-PAH). We focused on the index of pulmonary vascular disease (IPVD), an assessment system for pulmonary artery pathology specimens. The IPVD classifies pulmonary vascular lesions into four categories based on severity: (1) no intimal thickening, (2) cellular thickening of the intima, (3) fibrous thickening of the intima, and (4) destruction of the tunica media, with the overall grade expressed as an additive mean of these scores. This study aimed to investigate the relationship between IPVD and the long-term outcome of CHD-PAH.MethodsThis retrospective study examined lung pathology images of 764 patients with CHD-PAH aged <20 years whose lung specimens were submitted to the Japanese Research Institute of Pulmonary Vasculature for pulmonary pathological review between 2001 and 2020. Clinical information was collected retrospectively by each attending physician. The primary endpoint was cardiovascular death.ResultsThe 5-year, 10-year, 15-year, and 20-year cardiovascular death-free survival rates for all patients were 92.0%, 90.4%, 87.3%, and 86.1%, respectively. The group with an IPVD of ≥2.0 had significantly poorer survival than the group with an IPVD <2.0 (P = .037). The Cox proportional hazards model adjusted for the presence of congenital anomaly syndromes associated with pulmonary hypertension, and age at lung biopsy showed similar results (hazard ratio 4.46; 95% confidence interval: 1.45–13.73; P = .009).ConclusionsThe IPVD scoring system is useful for predicting the long-term outcome of CHD-PAH. For patients with an IPVD of ≥2.0, treatment strategies, including choosing palliative procedures such as pulmonary artery banding to restrict pulmonary blood flow and postponement of intracardiac repair, should be more carefully considered

FEDSM2003-45225 EXPERIMENTAL STUDY ON COMPOUND SWIRL JET

ABSTRACT This paper concerns the fundamental study on the push-pull type ventilator, especially applied to the smoking table. In order to achieve more effective cleaning of the dirty air, a compound swirl jet, which consists of a round free jet having thick rim and a coaxial annular swirl jet was proposed by the authors. It was found that the compound flow is very useful for the push flow of the push-pull type ventilator selecting the suitable flow rate ratio of the annular swirl jet to the free jet. As a fundamental study on the compound swirl jet, the flow visualization was also carried out using the smoke method. At the same time, the mean velocity components were measured using the cobra Pitot tube. It was found from the results of these experiments that the unique flow structure by the interaction of two jets is created in the compound swirl jet choosing the adequate flow rate ratio, which is suitable for the push flow of the push-pull type ventilator