NAD(P)H oxidase plays a crucial role in PDGF-induced proliferation of hepatic stellate cells

The proliferation of hepatic stellate cells (HSCs) is a critical step in hepatic fibrogenesis. Platelet-derived growth factor (PDGF) is the most potent mitogen for HSCs. We investigated the role of nonphagocytic NAD(P)H oxidase-derived reactive oxygen species (ROS) in PDGF-induced HSC proliferation. The human HSC line, LI-90 cells, murine primary-cultured HSCs, and PDGF-BB were used in this study. We examined the mechanism of PDGF-BB-induced HSC proliferation in relation to the role of a ROS scavenger and diphenylene iodonium, an inhibitor of NAD(P)H oxidase. We also measured ROS production with the aid of chemiluminescence. We showed that PDGF-BB induced proliferation of HSCs through the intracellular production of ROS. We also demonstrated that HSCs expressed key components of nonphagocytic NAD(P)H oxidase (p22phox, gp91phox, p47phox, and p67phox) at both the messenger RNA and protein levels. Diphenylene iodonium suppressed PDGF-BB-induced ROS production and HSC proliferation. Coincubation of H2O2 and PDGF-BB restored the proliferation of HSCs that was inhibited by diphenylene iodonium pretreatment. Phosphorylation of the mitogen-activated protein kinase (MAPK) family constitutes a signal transduction pathway of cell proliferation. Our data demonstrate that NAD(P)H oxidase-derived ROS induce HSC proliferation mainly through the phosphorylation of p38 MAPK. Moreover, an in vivo hepatic fibrosis model also supported the critical role of NAD(P)H oxidase in the activation and proliferation of HSCs. In conclusion, NAD(P)H oxidase is expressed in HSCs and produces ROS via activation of NAD(P)H oxidase in response to PDGF-BB. ROS further induce HSC proliferation through the phosphorylation of p38 MAPK.     

Metastatic hypopharyngeal and esophageal cancer to a percutaneous endoscopic gastrostomy site

The patient was a 63-year-old man who underwent percutaneous endoscopic gastrostomy (PEG) for nutritional management while undergoing radiochemotherapy for hypopharyngeal and esophageal cancer. At about 6 months after PEG, redness and swelling were seen around the gastrostomy site, and pathological testing confirmed the same poorly differentiated squamous cell carcinoma as the hypopharyngeal and esophageal cancer. The tumor caused symptoms associated with buried bumper syndrome to increase significantly.     

Development of diabetes in Japanese subjects with impaired glucose tolerance: A seven year follow-up study

Summary Five hundred and seven subjects with postprandial glycosuria underwent a 50 g oral glucose tolerance test in an epidemiological survey of diabetes mellitus carried out in 1964–1965 in the town of Osaka, Japan. The oral glucose tolerance test was repeated 7 years later in 207 (40.8%) of the subjects. The results of the initial and the follow-up test were classified into three categories according to the new WHO criteria: normal, impaired glucose tolerance and diabetes. Most of the diabetic subjects (84.8%) remained unchanged between the initial and follow-up test. Of the subjects with impaired glucose tolerance at the time of the initial test, 38.5% showed diabetes in the follow-up test, while another 38.5% returned to normal. On the other hand, 13.5% of the normal subjects in the initial test developed impaired glucose tolerance or diabetes in the follow-up test. The rate of worsening to diabetes was related closely to the 2-h blood glucose value at the initial test. In addition, the rate of worsening was higher in males and obese subjects than in females and non-obese subjects. A multiple logistic analysis indicated that the fasting and 2-h glucose values were significantly predictive of worsening to diabetes.     

A case of accessory mitral valve leaflet associated with solitary mitral cleft.

Accessory mitral valve leaflet is a rare congenital anomaly. More than half of the cases show other congenital cardiac defects and almost all of the cases show subaortic obstruction. We report a case of an accessory mitral valve tissue without outflow obstruction associated with mitral cleft of the posterior mitral leaflet. To our knowledge, this is the first reported case of the combination of these two congenital anomalies.     

Aldosterone-producing adenoma with prolonged amelioration by dexamethasone

Secretion of aldosterone from aldosterone-producing adenoma (APA) is to some degree under the control of ACTH and the suppressible effect of glucocorticoid on plasma aldosterone concentration (PAC) and blood pressure has been reported to be transient. We report a rare case of aldosteronism due to APA in which PAC and blood pressure were well controlled with small dose dexamethasone for over one year. No chimeric gene of glucocorticoid-remediable aldosteronism (GRA) was found in DNA of APA and leukocytes from peripheral blood and 17alpha-hydroxylase deficiency (17-OH-D) was ruled out by endocrinological examinations, this case indicates the possibility of an unknown mechanism of ACTH-dependent APA.     

A case of pulmonary embolic metastasis of choriocarcinoma presenting with multiple pulmonary infiltrative shadows]

A 34-year-old woman visited our hospital complaining of dry cough. Chest radiography and computed tomography showed bilateral multiple infiltrative shadows over the lung field. After an initial diagnosis of pneumonia, antibiotics were administered, but the therapy failed to improve the symptoms and abnormalities observed on the chest radiograph. The patient was then admitted to our hospital. The bronchoalveolar lavage fluid (BALF) was slightly bloody, but we were not able to make any specific findings in BALF. In order to confirm the pathological diagnosis, video-assisted thoracoscopic lung biopsy was performed aiming at the right middle and lower lobes. There were bleeding pulmonary infarctions in a biopsy specimen from the right middle lobe. Atypical cells positive for human chorionic gonadotropin (hCG) proliferated in the pulmonary arteries, and so a diagnosis of pulmonary embolic metastasis of choriocarcinoma was made. After the diagnosis, it became clear that urine and serum hCG values were very high. The patient has since received systemic chemotherapy in the gynecology unit at our hospital. Pulmonary embolic metastasis of choriocarcinoma diagnosed by video-assisted thoracoscopic lung biopsy has never been reported in the literature. However, early hCG measurement may have detected this syndrome in the earlier stages, and pulmonary metastasis of choriocarcinoma should be considered in the differential diagnosis of women with past pregnancy presenting with intractable multiple pulmonary shadows.     

Relationship between efficacy of antiarrhythmic drug therapy and structural remodeling in patients with paroxysmal atrial fibrillation

OBJECTIVES: To evaluate whether the response to antiarrhythmic drug therapy in patients with paroxysmal atrial fibrillation affects the development of structural remodeling in the left atrium and ventricle. METHODS: This study included 230 patients (158 men and 72 women, mean age 67 +/- 11 years) in whom antiarrhythmic drug therapy was attempted for > or = 12 months to maintain sinus rhythm (mean follow-up period 45 +/- 27 months). The patients were divided into three groups according to the response to antiarrhythmic drug therapy: group A consisted of 78 patients without recurrence of atrial fibrillation, group B consisted of 87 patients with recurrence of atrial fibrillation and electrical and/or pharmacological cardioversion to restore sinus rhythm, and group C consisted of 65 patients with permanent conversion despite antiarrhythmic drug therapy. RESULTS: In group A, left atrial dimension (LAD), left ventricular end-diastolic dimension (LVDd), and left ventricular ejection fraction (LVEF) did not change after antiarrhythmic drug therapy. In group B, LAD increased significantly after antiarrhythmic drug therapy (from 32.6 +/- 6.4 to 36.0 +/- 6.5 mm, p < 0.01), Whereas either LVDd or LVEF did not change after antiarrhythmic drug therapy. In group C, LAD increased significantly after antiarrhythmic drug therapy (from 37.3 +/- 7.0 to 40.5 +/- 7.9 mm, p < 0.01) and LVEF was significantly reduced after antiarrhythmic drug therapy (from 69.4 +/- 6.2% to 66.5 +/- 8.9%, p < 0.05). LVDd did not change after antiarrhythmic drug therapy. The plasma concentration of human atrial natriuretic peptide during sinus rhythm at the initiation of antiarrhythmic drug therapy in group A (30.5 +/- 26.7 pg/ml) was significantly lower than those in group B (48.0 +/- 49.7 pg/ml) and group C (49.7 +/- 39.5 pg/ml). CONCLUSIONS: The development of structural remodeling in human myocardium can be prevented with antiarrhythmic drug therapy if sinus rhythm is maintained without recurrence of atrial fibrillation in patients with paroxysmal atrial fibrillation.