Sonic hedgehog is a critical mediator of erythropoietin-induced cardiac protection in mice

Erythropoietin reportedly has beneficial effects on the heart after myocardial infarction, but the underlying mechanisms of these effects are unknown. We here demonstrate that sonic hedgehog is a critical mediator of erythropoietin-induced cardioprotection in mice. Treatment of mice with erythropoietin inhibited left ventricular remodeling and improved cardiac function after myocardial infarction, independent of erythropoiesis and the mobilization of bone marrow–derived cells. Erythropoietin prevented cardiomyocyte apoptosis and increased the number of capillaries and mature vessels in infarcted hearts by upregulating the expression of angiogenic cytokines such as VEGF and angiopoietin-1 in cardiomyocytes. Erythropoietin also increased the expression of sonic hedgehog in cardiomyocytes, and inhibition of sonic hedgehog signaling suppressed the erythropoietin-induced increase in angiogenic cytokine expression. Furthermore, the beneficial effects of erythropoietin on infarcted hearts were abolished by cardiomyocyte-specific deletion of sonic hedgehog. These results suggest that erythropoietin protects the heart after myocardial infarction by inducing angiogenesis through sonic hedgehog signaling.     

Prostatic adenocarcinoma with marked neuroendocrine differentiation

A case is presented of prostatic cancer with marked neuroendocrine differentiation. Double-labeled immunohistochemical staining was performed with prostate-specific antigen and Chromogranin A. Both antibodies were localized to some of the cancer cells with Paneth cell-like features. Furthermore, most of the cancer cells were positively stained with luminal cell marker CAM 5.2, suggesting that neuroendocrine cells originated from the prostatic luminal cells.     

Trichoblastic infundibular cyst

We report 4 cases of an infundibular cyst that histopathologically showed small papillary projections of follicular germinative cells emanating from the basal layer of the cyst wall. Some of these projections branched and formed a reticulated pattern. This cystic lesion is histopathologically distinctive. We propose to designate it as a trichoblastic infundibular cyst because its lining resembles that of an infundibular cyst, yet it has cells that resemble those of the follicular germ in its wall.     

Interleukin-15 inhibits smooth muscle cell proliferation and hyaluronan production in rat ductus arteriosus

Neointimal cushion formation (NCF) is an important vascular remodeling for anatomical closure of the ductus arteriosus (DA). Inflammatory responses to vascular injury or atherosclerosis are known to be associated with the pathogenesis of NCF. We found that the expression of interleukin (IL)-15 mRNA was significantly higher in rat DA than in the aorta. IL-15 immunoreactivity was detected predominantly in the internal elastic laminae (IEL) and to a lesser extent in smooth muscle cells (SMCs) in rat DA. Prostaglandin E (PGE) increased the expression of IL-15 mRNA in cultured DA SMCs. IL-15 significantly attenuated the platelet-derived growth factor (PDGF)-BB-mediated SMC proliferation, but did not change SMC migration. IL-15 significantly attenuated PGE1-induced hyaluronic acid (HA) production in a dose-dependent manner, which is a potent stimulator of NCF. Accordingly, IL-15 might have an inhibitory effect on the physiologic vascular remodeling processes in closing the DA.     

Composite Tumor with Papillary Adenocarcinoma and Squamous Cell Carcinoma of the Esophagus: Report of a Case

(Received for publication on Mar. 2, 1999; accepted on Nov. 11, 1999)     

Results of a survey of community-acquired-pneumonia and evaluation of old and new Japanese Respiratory Society guidelines]

We evaluated the usefulness of domestic and foreign guidelines for the diagnosis and treatment of patients with community-acquired-pneumonia at 23 institutions in 6 prefectures of the Tohoku Area, from December 2003 to November 2004. Based on the old and new Japanese Respiratory Society (JRS) guidelines, we evaluated severity, clinical efficacy and detection of atypical pneumonia. As for severity, the old guidelines led to the diagnosis of an excessive number of 'severe' cases. On the other hand, patients were appropriately diagnosed as having mild, moderate, severe, or very severe disease based on the new JRS guidelines (2005). The severity classification often correlated with the Pneumonia Severity Index (PSI) of the IDSA guidelines. The efficacy rate for patients who were prescribed the recommended drug according to the old JRS guidelines was 85.7% and for those who did not use the recommended drug it was 68.7% (p < 0.001).     

Therapeutic Effects of Benzoxazinorifamycin KRM-1648 Administered Alone or in Combination with a Half-Sized Secretory Leukocyte Protease Inhibitor or the Nonsteroidal Anti-Inflammatory Drug Diclofenac Sodium against Mycobacterium avium Complex Infection in Mice

The effects of half-sized secretory leukocyte protease inhibitor or diclofenac sodium administered alone or in combination with the benzoxazinorifamycin KRM-1648 on the therapeutic efficacy of KRM-1648 against Mycobacterium avium complex (MAC) in mice were studied. Neither of the two anti-inflammatory drugs affected the efficacy of KRM-1648, while they exerted significant modulating effects on tumor necrosis factor alpha production by MAC-infected macrophages.