Munehiko Onda

Defined localization of nestin-expressing cells in L-arginine-induced acute pancreatitis.

Objective: Nestin is a stem cell marker originally described as an intermediate filament protein expressed in neuroepithelial stem cells. In the pancreas, a small number of nestin-expressing cells, which are believed to represent either stem cells or progenitor cells, are known to be present in islets, as well as in some stellate cells, pericytes, and endothelial cells. We monitored pancreatic nestin expression to delineate the location of stem cells/progenitor cells in the pancreas after l-arginine-induced pancreatitis. Methods: Male Wistar rats received 2 intraperitoneal injections of l-arginine, each consisting of 250 mg/100 g of body weight, and were killed 3, 6, and 12 hours and 1, 4, 7, and 14 days later. Results: Serum amylase and lipase levels increased after l-arginine injection, maximal levels occurring at 3 and 12 hours postinjection, respectively. Six hours after l-arginine injection, interstitial edema was observed in the pancreas, whereas on day 4 postinjection, there was severe pancreatic necrosis. Neovascularization and ductal-ductular proliferation were also present in the pancreas. Immunohistochemical analysis revealed increased Ki-67 labeling in acinar cells and capillary endothelial cells. Immunoblotting using antinestin antibody revealed increased nestin expression after l-arginine injection. In the control rat pancreas, nestin immunoreactivity was detected in a few capillary endothelial cells in some islets. After l-arginine injection, nestin was expressed in proliferating capillary endothelial cells, in stellate cells surrounding ductular structures and in submesothelial cells. Conclusions: Transient nestin expression occurs in specific cell types during the proliferative stage after recovery from l-arginine-induced pancreatitis and may represent the contribution of stem cells and/or progenitor cells to the regenerative capacity of the pancreas.

Magnetic resonance imaging of myelofibrosis STIR and gadolinium-enhanced MR images

MR images of myelofibrosis were assessed in twelve patients. Myelofibrosis showed low intensity in T1-weighted images, high intensity in STIR images, and enhancement after gadolinium injection. MR spectroscopy detected a large water resonance. MR imaging was consistent with histological findings and useful in evaluating the extracellular space in bone marrow of myelofibrosis, but it was of no value in differentiating between primary and secondary myelofibrosis.

Invasive pulmonary aspergillosis occluding the descending aorta and left pulmonary artery: CT features.

Invasive pulmonary aspergillosis (IPA) has been recognized as an infectious complication in immunocompromised patients. We present a case of IPA, which occluded the descending aorta and left pulmonary artery and led to death after antileukemic chemotherapy. Contrast-enhanced CT demonstrated thrombi in the great vessels as low attenuation areas. These thrombi became extensive despite intensive antibiotic and antifungal therapy. Microscopic examination revealed that the thrombi contained aspergillus hyphae, and occlusions of both great vessels were induced by direct extension of aspergillus. This case illustrates that IPA can be the cause of great vessel occlusion in immunocompromised patients. We describe the CT and autopsy findings of this case and emphasize the virulence of this fungus.

Ultrastructural changes and immunohistochemical localization of advanced glycation end products in the heart of streptozotocin-treated Mongolian gerbils.

This study was designed to clarify the developing mechanism of cardiomyopathy and vasculopathy in streptozotocin-treated Mongolian gerbils. Twenty male Mongolian gerbils (MG; 10–12 weeks old) were used, and 150 mg/kg of streptozotocin (STZ) was injected into the left femoral vein. Six control male MG were injected intravenously with normal saline. The animals showed severe hyperglycemia (up to 330 ± 96.4 mg/dl) by 1 week after streptozotocin administration. At 1 week after STZ treatment, cardiomyocytes revealed no significant change, but unclear striated structures were demonstrated in cardiomyocytes at 4 weeks. After 1 year, anisocytosis was observed, and in the perinuclear region granular components were stained positively with periodic acid-Schiff reagent. Ultrastructurally, at 4 weeks and 1 year after STZ treatment, cardiomyocytes were irregular in size, and oval amorphous and lysosomal electron-dense bodies were observed in perinuclear and cytoplasmic regions. In coronary arteries, endothelial and medial cells revealed increased vesicles and intercellular collagen fibrils. Capillaries showed slight swelling of endothelial cells associated with the lamellar thickening of basement membrane and collagen fibrils in the perivascular regions. Immunohistochemically, advanced glycation end products (AGE) were observed in the cytoplasm of vascular and heart cells, and ultrastructurally the reaction products were demonstrated in the endoplasmic reticulum and lysosomes of cardiomyocytes and vascular cells in the STZ-treated Mongolian gerbils. AGE may play an important role not only in angiopathy but also in cardiomyopathy of STZ-treated Mongolian gerbils after STZ treatment.

Expression of keratinocyte growth factor receptor (KGFR/FGFR2 IIIb) in vascular smooth muscle cells.

Keratinocyte growth factor receptor (KGFR), also known as fibroblast growth factor receptor (FGFR)2 IIIb, is located in many types of epithelial cells and is activated by four known ligands (FGF‐1, FGF‐3, FGF‐7 (also known as KGF) and FGF‐10) that are predominantly synthesized by mesenchymal cells. In the early stage of atherosclerosis, vascular smooth muscle cells (VSMC) transform from a contractile to a synthetic phenotype, proliferate and migrate into the intima. Previously, FGF‐7 mRNA expression was reported in VSMC, but KGFR mRNA was not detected. In the present study, we attempted to determine whether KGFR is localized in VSMC cultured from rat aorta and VSMC in human normal and atherosclerotic coronary arteries. Expression of KGFR mRNA and its protein was detected in cultured rat VSMC by reverse transcription–polymerase chain reaction and western blot analysis, respectively. Immunohistochemically, KGFR was localized in the VSMC of the outer layer of the media in normal human coronary arteries. Furthermore, it was localized in the VSMC of the media and thickened intima of atherosclerotic arteries. Recombinant FGF‐7 and/or FGF‐10 proteins stimulated the growth of cultured rat VSMC. These findings indicate that KGFR localized in VSMC may contribute to the proliferation of VSMC in normal and atherosclerotic arteries.

Comparison of Epirubicin-Iodized Oil Suspension and Emulsion for Transcatheter Arterial Chemoembolization in VX2 Tumor

To compare the antitumor efficacy and safety of transcatheter arterial chemoembolization (TACE) by epirubicin suspension (epirubicin suspension: epirubicin-iodized oil mixture without solution) to that by epirubicin emulsion (epirubicin emulsion: epirubicin-iodized oil mixture with solution), the efficacy of treatment by administration of either an epirubicin suspension or emulsion was examined in an animal model. Changes in plasma epirubicin concentration were compared over 24 h immediately after treatment, and enhanced ultrasonographic and histopathological analysis subsequently conducted 7 days after treatment to determine the growth ratio and proportion of viable tumor cells. The growth ratio and proportion of viable tumor cells were found to be significantly lower in the suspension group than in the emulsion group while the plasma epirubicin concentration was found to be significantly higher in the suspension group than in the emulsion group. These results indicate that administration of an epirubicin suspension is a superior form of TACE compared to that of administration of an epirubicin emulsion.

Solitary Fibrous Tumor of the Cervical Esophagus

Solitary fibrous tumors (SFTs), so-called localized fibrous tumors or fibrous mesotheliomas, are rare tumors originating from the mesenchymal tissue, and were first described as a distinct entity in 1931 by Klemperer and Rabin [1]. SFT has received different names, such as subpleural fibroma and benign or localized (fibrous) mesothelioma because of controversy surrounding its histogenesis (mesothelial versus submesothelial). About 700 cases of SFTs were described from 1942; in 85–90% of cases they arose from the pleura, but have also been described in other locations in the body, including the pelvic cavity, nasal cavity, pulmonary parenchyma, meninges, kidney, lung, mediastinum, retroperitoneum, temporal region, neck, groin, buttock, and thigh [2–16]. We report a case with an SFT arising from the cervical esophagus accidentally discovered by endoscopic examina-

Assessment of adventitial involvement of esophageal carcinoma by endoscopic ultrasonography

SummaryThe adventitial involvement (AI) of esophageal squamous cell carcinoma in 20 patients was analyzed by endoscopic ultrasonography (EUS) and computed tomography (CT). The findings were compared with the histologic evidence of tumor invasion in the resected specimens. AI was detected as an irregularity or interruption of the third layer of the esophageal wall on ultrasound examination. The overall accuracy in the assessment of depth of tumor invasion by EUS and CT scan was 80% and 68%, respectively. EUS diagnosed AI in 17 patients and detected direct tumor invasion of either the aorta, trachea or pericardium in 7 of them. In 4 patients who had severe stenotic lesions, EUS underestimated the depth of tumor invasion when compared to the histologic findings. Overall, these results, show that EUS when combined with CT scanning is a useful means of preoperatively evaluating tumor invasion in patients with esophageal carcinoma.

Comparative study of cisplatin-iodized oil suspension and emulsion for transcatheter arterial chemoembolization of rabbit VX2 liver tumors

Aim:  To evaluate the antitumor effects and hepatotoxicity of transcatheter arterial chemoembolization (TACE) with cisplatin‐iodized oil suspension and emulsion in a rabbit tumor model.

Crystalloid Granuloma of Parotid Gland: A Case Report With Review of the Literature

Crystalloid granuloma (CG) of salivary gland is an extremely rare inflammatory disease, and only 6 cases have been reported in the English literature. CG is histologically characterized by a granulomatous reaction to amylase crystalloid deposition. A 73-year-old woman presented with a painful left neck mass. Computed tomography depicted a mass located in the lower pole of the left parotid gland, suspicious for a tumoral lesion. Preoperative fine needle aspiration cytology found amylase crystalloid deposition with a few inflammatory cells. Surgical sections of the mass revealed formation of a granuloma containing abundant eosinophilic but glassy and transparent amorphous crystalloids, suggestive of α-amylase crystalloid. No neoplastic elements were detected. The case was eventually diagnosed with CG in the parotid gland. Our findings suggest that when we identify amylase crystalloids in fine needle aspiration cytology smears from the salivary gland, CG should be considered even if neoplasm is clinically or radiographically suspected.