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Biomedical subjects

Toshio Fukusato

Publications and source records attributed to Toshio Fukusato.

At least 19 recordsLinked to original sources
PubMed2007

Long-term effects of subcutaneously injected 2,3,7,8-tetrachlorodibenzo-p-dioxin on the liver of rhesus monkeys.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) accumulates and remains stable in the fatty tissues and liver of rodents for a long time. Considering the pronounced difference between species, long-term, low dose hepatic effects of TCDD were investigated after subcutaneous administration of TCDD into rhesus monkeys during pregnancy. Macroscopic and histopathological examination of the liver carried out 4 y after TCDD administration demonstrated intrahepatic focal fatty changes, infarction, hemorrhage, microthrombi-formation, sinusoidal ectasia, small hepatocyte hyperplasia, and increased number of alpha-smooth muscle actin (alpha-SMA)-positive cells. An electron microscopic study disclosed sinusoidal endothelial cell degeneration and injury in the liver of TCDD-treated monkeys. Western blot analysis showed downregulation of aryl hydrocarbon receptor (AhR) protein expression and decreased level of vascular endothelial (VE) cadherin but increased expression levels of CYP1A1 and transforming growth factor beta (TGF-beta) protein in the liver tissues. These changes observed in TCDD-exposed monkeys indicated sinusoidal endothelial cell injury and impairment in intrasinusoidal microcirculation. Infarction, focal fatty change, and microthrombi-formation are considered to be closely associated with intrahepatic circulatory impairment. Increased number of alpha-SMA-positive cells and decreased level of VE cadherin expression in the liver tissues might also be associated with sinusoidal endothelial cell injury. In addition, downregulation of AhR expression and increased CYP1A1 protein levels in the liver were consistent with persistent effects of TCDD. Although it has been reported that TCDD induced endothelial cell injury, this is the first report to describe vascular disorders and protein expression in the liver after injection with TCDD in a primate model.

Animals↗
PubMed2006

Adenomyoma with goblet and Paneth cells of the ileum.

A case of ileal adenomyoma with goblet and Paneth cells is reported. A 75-year-old man died of ruptured hepatocellular carcinoma. As an incidental finding at autopsy, a 9 x 7 x 6 mm(3)-sized nodule was found in the ileal wall. Histologically, the lesion occupied the submucosa and muscularis propria, and consisted of glandular structures of various sizes and interlacing smooth muscle bundles surrounding the glandular elements. Goblet cells and Paneth cells were interspersed in the glandular element. Immunohistochemically, the glandular element was positive for cytokeratin (CK) 7 and negative for CK 20. This is the first reported case of adenomyoma of the gastrointestinal tract that contained Paneth cells. The result of the immunohistochemical staining favored the heterotopic pancreas theory concerning its pathogenesis. The appearance of goblet and Paneth cells might be the result of metaplasia.

Adenomyoma↗
PubMed2006

Spontaneous regression of hepatic inflammatory pseudotumor with primary biliary cirrhosis: case report and literature review.

Hepatic inflammatory pseudotumor (IPT) is a rare benign non-neoplastic lesion characterized by proliferating fibrous tissue infiltrated by inflammatory cells. The exact etiology of IPT remains unclear. Although the association of IPT with systemic inflammatory disorders has been well established, a specific relationship with cholangitis is distinctly rare. We report a case of spontaneous regression of hepatic IPT with primary biliary cirrhosis (PBC). To date, only two cases of IPT with PBC have been reported. In our case, however, IPT developed during the course of improvement of cholangitis of PBC induced by effective treatment, differing from two previously reported cases. Our case indicates that the development of IPT does not also relate to the activity of cholangitis and/or hyper gamma-globulinemia, since our case was confirmed radiologically to be free of IPT when biliary enzymes and immunoglobulins were much higher than the corresponding values on admission. Comparison of our case with the two previously reported cases suggests that IPT occurring with PBC does not represent the same disease entity or be a bystander for PBC.

Aged↗
PubMed2006

High expression of eosinophil chemoattractant ecalectin/galectin-9 in drug-induced liver injury.

BACKGROUND: Ecalectin/galectin-9 (ECL/GL9) is an eosinophil chemoattractant isolated from T lymphocytes. Drug-induced liver injury (DILI), often caused by an allergic mechanism, is occasionally accompanied by eosinophilic infiltration. In this study, we intended to determine whether DILI can induce augmentation of ECL/GL9 expression. Further, we investigated whether this augmentation is associated with tissue eosinophilia. METHODS: We examined the expression of ECL/GL9 in biopsy specimens of DILI using the immunohistochemical technique. A rabbit anti-ECL/GL9 antibody was produced by immunizing rabbits with synthetic peptide corresponding to a molecular epitope of ECL/GL9. Thereafter, immunohistochemical staining with the use of this antibody was performed on 16 DILI needle biopsy specimens, and on biopsy specimens of chronic viral hepatitis, liver cirrhosis, and normal liver tissues as controls. RESULTS: In all cases of DILI specimens, but not in control liver specimens, a clear positive staining for ECL/GL9 was observed. Such positive staining was noted on Kupffer cells, fibroblasts, and histiocytes, but not on lymphocytes or hepatocytes. However, the intensity of immunolabeling did not correlate with the extent of eosinophile leukocyte infiltration. CONCLUSION: High expression of ECL/GL9 is suggested to be a specific finding of DILI. However, tissue eosinophilia in DILI cannot be explained by the augmentation of ECL/GL9 expression.

Adult↗
PubMed2005

Histological study on comparison between NASH and ALD.

We examined the histological findings of non-alcoholic steatohepatitis (NASH) and ALD to study resemblance and difference of these two diseases. At a glance of H&E staining, they looked same, however, careful examination on silver impregnation histology, the fibrosis of NASH showed lattice fibrosis on the other hand ALD showed solid fibrosis. The appearance of fibrosis was different due to qualitative difference. More examination on the change of hepatocytes, there were some difference in incidence of the findings such as megamitochondria, bile stasis, hemosiderin deposition, vacuolic nuclei, and lipogranuroma. So we are able to differentiate NASH and ALD histologically.

Journal Article↗
PubMed2005

Prevalence of ischemic enterocolitis in patients with acute pancreatitis.

BACKGROUND: A considerable number of acute pancreatitis cases have been reported to be complicated by nonocclusive mesenteric ischemia. However, no reports have ever referred to the incidence of ischemic enterocolitis in patients with acute pancreatitis, using a series of autopsy cases. Here, we report our review of autopsy cases of patients with acute pancreatitis to examine the incidence of associated ischemic enterocolitis. METHODS: The intestinal and pancreatic slides of 48 autopsy cases of patients with acute pancreatitis were reviewed and the incidence of ischemic enterocolitis was determined. Clinical case records were also reviewed. RESULTS: Thirteen (27%) of 48 autopsy cases of patients with acute pancreatitis were complicated by ischemic enterocolitis. The frequency of shock was significantly higher in patients with ischemic enterocolitis than in those without ischemic enterocolitis. The intestinal lesion was diffuse in many cases and gangrene was not an unusual finding. CONCLUSIONS: The incidence of ischemic enterocolitis in patients with acute pancreatitis was much higher than that in the previous reports. Clinicians who treat patients with acute pancreatitis should consider ischemic enterocolitis as one of the frequent and severe complications of this condition.

Acute Disease↗
PubMed2005

Interobserver variation in the histopathological assessment of nonalcoholic steatohepatitis.

Pathological assessment is considered as the gold standard for the diagnosis of nonalcoholic steatohepatitis (NASH). However, there is no agreement of histological features required for the diagnosis of NASH. In the present study, eight experienced hepatopathologists read liver biopsy specimen slides of 21 cases of NASH and suspected NASH independently and were asked to assess histopathological features and render a diagnosis. Interobserver variation among pathologists was evaluated by kappa statistics. Significant, good agreement was present in evaluation of the extent of steatosis and grade of fibrosis. Agreement was moderate concerning the localization of steatosis, localization of fibrosis, and glycogen nuclei. Only slight or poor agreement was seen in evaluation of type of steatosis, ballooning, intralobular necroinflammatory change, portal inflammation, and degree of neutrophilic infiltration. Thus the agreement varied for histological variables. Significant, moderate agreement was seen in the diagnosis of NASH but agreement was poor in the diagnosis of suggestive NASH. The agreement for the diagnosis of NASH was not high as for the individual histological findings that were thought to be the basis of the diagnosis. In conclusion, some histological features in NASH might prove useful for the development of a standardized and reliable pathological diagnosis and scoring system.

Journal Article↗
PubMed2005

Solid pseudopapillary tumor of the pancreas with metastases to the lung and liver.

Presented herein is the case of a 41-year-old woman who was admitted to Teikyo University Hospital with abdominal and back pain. Clinical examination revealed a large mass of the pancreas and multiple nodules in the liver. After surgical resection of the pancreatic and liver tumors, liver nodules recurred repeatedly, and a solitary mass lesion occurred in the right lung. Grossly, the pancreatic tumor was large and partially cystic. Histologically, small and uniform tumor cells proliferated, having solid and pseudopapillary patterns. These pathological findings enabled a pathological diagnosis of solid pseudopapillary tumor (SPT) of the pancreas to be made. The pathological appearance of the liver and lung tumors was similar to that of the pancreatic tumor. This is the first report of a case of pancreatic SPT that showed lung metastasis. It should be kept in mind that pancreatic SPT may take such an aggressive clinical course, although they are usually benign in nature.

Adult↗
PubMed2005

Correlation of gamma-catenin expression with good prognosis in medulloblastomas.

OBJECT: Medulloblastoma is a malignant cerebellar tumor of childhood and is difficult to cure due to frequent cerebrospinal fluid dissemination. Amplification of the c-myc gene (4%) and messenger (mRNA) overexpression (50%) are known to be adverse prognostic indicators. Because mRNA overexpression cannot be explained by gene amplification alone, mechanisms other than gene amplification are postulated. Molecules on the Wnt signal pathway in primary tumors were examined. METHODS: Immunohistochemical and cytogenetic examinations of beta- and gamma-catenin, c-myc, N-myc, and cyclin D1 in 24 primary medulloblastomas were conducted, and their clinical relevance was evaluated. Cytoplasmic/membranous staining of beta- and gamma-catenin was detected in 19 (79%) and nine (37%) cases, respectively, and nuclear expression of cyclin D1 and c-myc was detected in six (25%) and 21 (83%) cases, respectively. The expression levels of gamma-catenin in Western blot analysis and immunohistochemistry were similar. By differential polymerase chain reaction, c-myc and N-myc were amplified separately in two large cell/anaplastic medulloblastomas. No cyclin D1 amplification, or beta- or gamma-catenin mutations were found. Kaplan-Meier analysis revealed no dissemination at diagnosis (Chang Grade M0) and gamma-catenin expression was correlated with good prognosis (p = 0.0002 and 0.003, respectively). Expression of gamma-catenin was also significant in the M0 group (p = 0.022). Expression of cyclin D1 showed a trend toward adverse outcome (p = 0.057) and all patients in whom cyclin D1 expression was found died of disease. CONCLUSIONS: Expression of gamma-catenin is of great prognostic value and its immunohistochemistry may be useful for further stratification of treatment. Cyclin D expression may have the potential to be an adverse prognostic indicator.

Adolescent↗
PubMed2004

Biliary excretion of bile acids and organic anions in rats with dichloroethylene-induced bile canalicular injury.

BACKGROUND: Hepatocytes in zone 1 of the hepatic lobule play a role in the uptake and biliary excretion of bile acids and organic anions under physiological conditions, and hepatocytes in zone 3 may play a role only when there is a high-dose load. To further elucidate the role of hepatic zonation in the hepatic handling of bile acids and organic anions, the biliary excretion of these compounds was studied in rats with dichloroethylene (DCE)-induced selective zone 3 bile canalicular injury. METHODS: Biliary excretion of various bile acids and organic anions was studied in rats 1 h after oral administration of DCE (5 mg/100 g). The effect of DCE on the immunostaining of multidrug resistance protein 2 (Mrp2; an important canalicular organic anion transporter) in the liver was also examined. RESULTS: The biliary excretory maximum of taurocholate and tauroursodeoxycholate was decreased in DCE-treated rats, whereas the biliary excretion of taurolithocholate-sulfate and phenolphthalein-glucuronide was unchanged in DCE-treated rats, and DCE treatment decreased the biliary excretion of sulfobromophthalein and pravastatin. DCE decreased Mrp2 staining in the canalicular membrane of zone 3 hepatocytes on immunohistochemistry. CONCLUSIONS: These findings indicate that canalicular transport in zone 3 hepatocytes is important in the biliary excretion of bile acids and organic anions, when they are administered at high doses.

ATP-Binding Cassette Transporters↗
PubMed2004

Myolipoma of the retroperitoneum.

A case of retroperitoneal myolipoma is reported. A 55-year-old woman with the main complaint of an abdominal mass was admitted to Teikyo University Hospital, Tokyo, Japan. Retroperitoneal liposarcoma was suspected based on magnetic resonance imaging, and the tumor was resected. The resected tumor was well encapsulated and 30 x 15 x 8 cm in size. Histologically, it consisted of mature adipose cells and smooth muscle cells. Neither nuclear atypia nor mitosis was observed in either component. The tumor was pathologically diagnosed as myolipoma of the retroperitoneum. Retroperitoneal myolipoma is often misdiagnosed radiologically as liposarcoma because the overwhelming majority of large retroperitoneal tumor containing fat is liposarcoma, however, the clinical course of myolipoma is quite different from that of liposarcoma. Although myolipoma is very rare, pathologists should consider it in the differential diagnosis of fat-containing retroperitoneal masses.

Diagnosis, Differential↗
PubMed2004

Sarcomatoid carcinoma with components of small cell carcinoma and undifferentiated carcinoma of the gallbladder.

We report a case of sarcomatoid carcinoma with components of small cell carcinoma and undifferentiated carcinoma of the gallbladder. An 84-year-old woman was admitted to our university hospital with right upper abdominal pain and back pain. Clinical diagnosis of a gallbladder tumor was made based on the findings of abdominal ultrasonography, computed tomography and endoscopic retrograde cholangiopancreatography, and a cholecystectomy was carried out. On gross examination a pedunculated polypoid tumor protruded into the lumen of the gallbladder. Histologically the tumor was composed of carcinomatous and sarcomatous components; the carcinomatous component consisted mainly of small cell carcinoma and undifferentiated carcinoma. In general, the carcinomatous component of sarcomatoid carcinoma of the gallbladder consists of adenocarcinoma, and there have only been two previously reported cases in which the carcinomatous component consisted of small cell carcinoma or undifferentiated carcinoma. Because the patient's prognosis may be influenced by the peculiar carcinomatous component in such cases, it is important to accumulate case reports that clarify their clinicopathological features.

Aged↗
PubMed2003

Pericardiectomy to treat constrictive pericarditis in a patient with hyperbilirubinemia: report of a case.

An 18-year-old man was admitted to our hospital with abdominal distension and edema of both legs. His total serum bilirubin level was 5.2 mg/dl. Echocardiography showed impaired left ventricular contraction, and computed tomography showed a thickened pericardium with massive pleural effusion and ascites. Cardiac catheterization showed both a dip and a plateau in the right ventricle pressure curve, based on which we diagnosed constrictive pericarditis. The selected treatment option was a pericardiectomy. We dissected the thickened pericardium, which was about 7-10 mm thick, and removed as much as possible through a median sternotomy without cardiopulmonary bypass. Postoperatively, his hemodynamics and renal dysfunction improved, and the serum bilirubin level gradually decreased. We report this case to show how pericardiectomy was effective not only for improving this patient's hemodynamics, but also for resolving his hyperbilirubinemia. The relevant literature is reviewed following this case report.

Adolescent↗
PubMed2003

Molecular analysis of the rhabdoid predisposition syndrome in a child: a novel germline hSNF5/INI1 mutation and absence of c-myc amplification.

The authors report a case of the rhabdoid predisposition syndrome (RPS) secondary to a germline hSNF5/INI1 mutation, whose brain tumor was originally unclassified but finally diagnosed as an atypical teratoid/rhabdoid tumor (AT/RT) by molecular analysis. A 7-month-old infant presented with hydrocephalus secondary to a huge pineal tumor and subsequently developed a renal rhabdoid tumor. The histology of the brain tumor was initially undetermined; however, an AT/RT was strongly suspected because of her clinical course. Mutational screening of the hSNF5/INI1 gene by heteroduplex and direct sequence analysis detected a missense mutation at codon 53 (CGA --> TGA, arginine --> stop) in both tumors, as well as in normal tissue of the kidney. Polymerase chain reaction (PCR)-based microsatellite analysis showed in both tumors allelic loss on chromosome arm 22q to which the hSNF5/INI1 gene maps. c-myc amplification was examined by differential PCR but not detected. Histologic review of the brain tumor by immunohistochemistry confirmed focal expression of epithelial membrane antigen and smooth muscle actin. These findings suggest that the brain tumor was really an AT/RT as a component of RPS secondary to a germline hSNF5/INI1 mutation. The present mutation has never been reported in the literature.

Brain Neoplasms↗
PubMed2002

Coexpression of glucose transporter 1 and matrix metalloproteinase-2 in human cancers.

BACKGROUND: Cancer cells express higher levels of glucose transporter proteins (Gluts) than do normal cells. Glut-1 overexpression is associated with invasiveness. Because matrix metalloproteinase-2 (MMP-2) is also overexpressed in cancer cells and is associated with invasiveness, we tested the hypothesis that Glut-1 may regulate MMP-2 expression. METHODS: We transiently transfected Glut-1 complementary DNA (cDNA) or Glut-1 antisense oligonucleotides in the human rhabdomyosarcoma cell line RD and analyzed MMP-2 mRNA expression and cell invasiveness. Empty vector and sense oligonucleotides were used for controls. We analyzed MMP-2 promoter activity in transfectants with a luciferase reporter assay and with p53 and Ets-1 gel mobility shift assays. Eight human cancer cell lines and 80 human cancer specimens were analyzed for coexpression of Glut-1 and MMP-2 by western blot and immunohistochemical analyses, respectively. RESULTS: Overexpression of Glut-1 in RD cells increased MMP-2 expression 4.3-fold (95% confidence interval [CI] = 3.7-fold to 4.9-fold) and invasiveness 3.2-fold (95% CI = 2.6-fold to 3.8-fold) relative to control transfected cells. Conversely, suppression of Glut-1 expression by antisense oligonucleotides decreased MMP-2 expression by 71.5% (95% CI = 71.1% to 71.9%) and invasiveness by 53.0% (95% CI = 47.5% to 58.5%). Glut-1-mediated MMP-2 expression involved the binding of the transcription factor p53 but not Ets-1. All eight human cancer cell lines coexpressed Glut-1 and MMP-2 by western blotting, and 45 of 80 human tumor tissues coexpressed Glut-1 and MMP-2 by immunohistochemistry. CONCLUSIONS: MMP-2 expression and cell invasiveness are tightly associated with Glut-1 expression in human cancer cell lines. Because suppression of Glut-1 decreased MMP-2 expression and cancer cell invasion, Glut-1 could be a target for therapy of various cancers that overexpress Glut-1.

Blotting, Northern↗