Peroxisome proliferator-activated receptors(PPARs) are ligand-activated transcription factors belonging to the nuclear receptor superfamily, which is composed of four members encoded by distinct genes(α, β, γ, and ...Peroxisome proliferator-activated receptors(PPARs) are ligand-activated transcription factors belonging to the nuclear receptor superfamily, which is composed of four members encoded by distinct genes(α, β, γ, and δ). The genes undergo transactivation or transrepression under specific mechanisms that lead to the induction or repression of target gene expression. As is the case with other nuclear receptors, all four PPAR isoforms contain five or six structural regions in four functional domains; namely, A/B, C, D, and E/F. PPARs have many functions, particularly functions involving control of vascular tone, inflammation, and energy homeostasis, and are, therefore, important targets for hypertension, obesity, obesity-induced inflammation, and metabolic syndrome in general. Hence, PPARs also represent drug targets, and PPARα and PPARγ agonists are used clinically in the treatment of dyslipidemia and type 2 diabetes mellitus, respectively. Because of their pleiotropic effects, they have been identified as active in a number of diseases and are targets for the development of a broad range of therapies for a variety of diseases. It is likely that the range of PPARγ agonist therapeutic actions will result in novel approaches to lifestyle and other diseases. The combination of PPARs with reagents or with other cardiovascular drugs, such as diuretics and angiotensin Ⅱ receptor blockers, should be studied.This article provides a review of PPAR isoform characteristics, a discussion of progress in our understanding of the biological actions of PPARs, and a summary of PPAR agonist development for patient management. We also include a summary of the experimental and clinical evidence obtained from animal studies and clinical trials conducted to evaluate the usefulness and effectiveness of PPAR agonists in the treatment of lifestyle-related diseases.展开更多
A 61-year-old male was referred to our hospital with a three-month history of persistent epigastralgia and right hypochondralgia. Initial examination revealed a fist-size mass at the epigastric fossa. Ultrasonography ...A 61-year-old male was referred to our hospital with a three-month history of persistent epigastralgia and right hypochondralgia. Initial examination revealed a fist-size mass at the epigastric fossa. Ultrasonography showed a hemangioma and a mosaic echoic lesion in the ventromedian with poor blood-flow signal and linear hyperechoic part inside, and a clear border to the surroundings. Dynamic computed tomography revealed a highly enhanced effect from the portal-venous phase continuing to the equilibrium phase. T1-weighted gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced image revealed a high intensity effect at the early phase that continued to the next phase. On the other hand, it contained a low intensity area by a fat suppression of that image. In addition, a T2-weighted image did not show a high intensity effect. Laparotomy was performed on the second day of hospitalization. The tumor had arisen from the ligamentum teres of the liver, and no metastasis or invasion of other organs was noted. It consisted of a lipid component of mature adipocytes and a fibrous component of deep dyeing pleomorphic or multinuclear atypical stromal cells. Immunohistochemical study of the atypical stromal cells demonstrated that they were positive for MDM2 and CDK4. A pathological diagnosis of atypical lipomatous tumor(ALT) was made, and the patient was discharged on the eighth day following the procedure. At the 6-mo follow-up dynamic CT, the patient was free of recurrence or metastasis. We experienced a patient with ALT in the ligamentum teres of the liver. This case suggests the need for a careful and detailed examination when encountering patients presenting with a mass; when neoplastic lesion is confirmed by image inspection, we should thoroughly investigate, including further image investigations and pathologic examination. The latter is the most important.展开更多
The interstitial pneumonia (IP) associated with myeloperoxidase anti-neutrophil cytoplasmic autoantibody (MPO-ANCA) showed characteristic histology dominated by usual IP pattern. We showed a 94-year-old woman, whose p...The interstitial pneumonia (IP) associated with myeloperoxidase anti-neutrophil cytoplasmic autoantibody (MPO-ANCA) showed characteristic histology dominated by usual IP pattern. We showed a 94-year-old woman, whose prognosis was poor by severity of IP by MPO-ANCA associated vasculitis. The median age at diagnosis of IP by MPO-ANCA associated vasculitis was over 60 years, with a male predominance. Most patients died related to respiratory insufficiency. Our case would be the oldest patient in IP by MPO-ANCA associated vasculitis in the literature.展开更多
文摘Peroxisome proliferator-activated receptors(PPARs) are ligand-activated transcription factors belonging to the nuclear receptor superfamily, which is composed of four members encoded by distinct genes(α, β, γ, and δ). The genes undergo transactivation or transrepression under specific mechanisms that lead to the induction or repression of target gene expression. As is the case with other nuclear receptors, all four PPAR isoforms contain five or six structural regions in four functional domains; namely, A/B, C, D, and E/F. PPARs have many functions, particularly functions involving control of vascular tone, inflammation, and energy homeostasis, and are, therefore, important targets for hypertension, obesity, obesity-induced inflammation, and metabolic syndrome in general. Hence, PPARs also represent drug targets, and PPARα and PPARγ agonists are used clinically in the treatment of dyslipidemia and type 2 diabetes mellitus, respectively. Because of their pleiotropic effects, they have been identified as active in a number of diseases and are targets for the development of a broad range of therapies for a variety of diseases. It is likely that the range of PPARγ agonist therapeutic actions will result in novel approaches to lifestyle and other diseases. The combination of PPARs with reagents or with other cardiovascular drugs, such as diuretics and angiotensin Ⅱ receptor blockers, should be studied.This article provides a review of PPAR isoform characteristics, a discussion of progress in our understanding of the biological actions of PPARs, and a summary of PPAR agonist development for patient management. We also include a summary of the experimental and clinical evidence obtained from animal studies and clinical trials conducted to evaluate the usefulness and effectiveness of PPAR agonists in the treatment of lifestyle-related diseases.
文摘A 61-year-old male was referred to our hospital with a three-month history of persistent epigastralgia and right hypochondralgia. Initial examination revealed a fist-size mass at the epigastric fossa. Ultrasonography showed a hemangioma and a mosaic echoic lesion in the ventromedian with poor blood-flow signal and linear hyperechoic part inside, and a clear border to the surroundings. Dynamic computed tomography revealed a highly enhanced effect from the portal-venous phase continuing to the equilibrium phase. T1-weighted gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced image revealed a high intensity effect at the early phase that continued to the next phase. On the other hand, it contained a low intensity area by a fat suppression of that image. In addition, a T2-weighted image did not show a high intensity effect. Laparotomy was performed on the second day of hospitalization. The tumor had arisen from the ligamentum teres of the liver, and no metastasis or invasion of other organs was noted. It consisted of a lipid component of mature adipocytes and a fibrous component of deep dyeing pleomorphic or multinuclear atypical stromal cells. Immunohistochemical study of the atypical stromal cells demonstrated that they were positive for MDM2 and CDK4. A pathological diagnosis of atypical lipomatous tumor(ALT) was made, and the patient was discharged on the eighth day following the procedure. At the 6-mo follow-up dynamic CT, the patient was free of recurrence or metastasis. We experienced a patient with ALT in the ligamentum teres of the liver. This case suggests the need for a careful and detailed examination when encountering patients presenting with a mass; when neoplastic lesion is confirmed by image inspection, we should thoroughly investigate, including further image investigations and pathologic examination. The latter is the most important.
文摘The interstitial pneumonia (IP) associated with myeloperoxidase anti-neutrophil cytoplasmic autoantibody (MPO-ANCA) showed characteristic histology dominated by usual IP pattern. We showed a 94-year-old woman, whose prognosis was poor by severity of IP by MPO-ANCA associated vasculitis. The median age at diagnosis of IP by MPO-ANCA associated vasculitis was over 60 years, with a male predominance. Most patients died related to respiratory insufficiency. Our case would be the oldest patient in IP by MPO-ANCA associated vasculitis in the literature.
