Indispensable roles of OX40L-derived signal and epistatic genetic effect in immune-mediated pathogenesis of spontaneous pulmonary hypertension

<p>Abstract</p> <p>Background</p> <p>Pulmonary hypertension (PH) refers to a spectrum of diseases with elevated pulmonary artery pressure. Pulmonary arterial hypertension (PAH) is a disease category that clinically presents with severe PH and that is histopathologically characterized by the occlusion of pulmonary arterioles, medial muscular hypertrophy, and/or intimal fibrosis. PAH occurs with a secondary as well as a primary onset. Secondary PAH is known to be complicated with immunological disorders. The aim of the present study is to histopathologically and genetically characterize a new animal model of PAH and clarify the role of OX40 ligand in the pathogenesis of PAH.</p> <p>Results</p> <p>Spontaneous onset of PAH was stably identified in mice with immune abnormality because of overexpression of the tumor necrosis factor (TNF) family molecule OX40 ligand (OX40L). Histopathological and physical examinations revealed the onset of PAH-like disorders in the C57BL/6 (B6) strain of OX40L transgenic mice (B6.TgL). Comparative analysis performed using different strains of transgenic mice showed that this onset depends on the presence of OX40L in the B6 genetic background. Genetic analyses demonstrated a susceptibility locus of a B6 allele to this onset on chromosome 5. Immunological analyses revealed that the excessive OX40 signals in TgL mice attenuates expansion of regulatory T cells the B6 genetic background, suggesting an impact of the B6 genetic background on the differentiation of regulatory T cells.</p> <p>Conclusion</p> <p>Present findings suggest a role for the OX40L-derived immune response and epistatic genetic effect in immune-mediated pathogenesis of PAH.</p

A case of Mallory-Weiss syndrome confirmed by endoscopy

A case of Mallory-Weiss syndrome confirmed by endoscopic observation. A 46-year-old man was admitted by emergency because of hematemesis and melena. An endoscopic examination revealed a laceration and bleeding at the esophago-gastric junction. The patient was recovered by blood transfusion. The authors emphasized that endoscopic examination in emergency is useful for diagnosis of Mallory-Weiss syndrome

A case of Mallory-Weiss syndrome confirmed by endoscopy

A case of Mallory-Weiss syndrome confirmed by endoscopic observation. A 46-year-old man was admitted by emergency because of hematemesis and melena. An endoscopic examination revealed a laceration and bleeding at the esophago-gastric junction. The patient was recovered by blood transfusion. The authors emphasized that endoscopic examination in emergency is useful for diagnosis of Mallory-Weiss syndrome