Hideaki Enzan

Capital Medical University, Peping, Beijing, China

Are you Hideaki Enzan?

Claim your profile

Publications (212)647.74 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: To study the early stages of hyaline membrane (HM) formation, diffuse alveolar damage (DAD) was thoroughly investigated using immunohistochemical methods in 15 autopsy cases, which consisted of various types of interstitial pneumonias and pulmonary diseases derived from nonmalignant or malignant diseases. Alveolar mouths (AMs) that were presumed to be normal were ultrastructurally examined in detail, by using pulmonary tissues in the pneumothorax. It is interesting to note that during the initial stages of HM formation in AMs, fragmented eosinophilic masses were closely attached to AMs as irregular fragments or by a cap-like structure. The ultrastructure revealed some distance between the capillary spaces and surface epithelium of the AMs, indicating that the epithelial cells at the AMs might be often easily damaged even by minor stimuli; they can be considered as "locus minoris resistentiae." HMs were found to be formed initially at the site of AMs derived from fragmented eosinophilic masses in not only pulmonary but also extrapulmonary diseases, including both nonmalignant and malignant diseases. These irregular eosinophilic masses, representing the early shape of HMs, were immunohistochemically positive for the epithelial membrane antigens, namely, surfactant protein A and factor VIII antigen, and occasionally for KL-6 and cytokeratins. These results suggested that fragmented irregular masses represent the initial phase of HM formation. Five of 15 cases were focally negative for KL-6 at the initial irregular mass of HMs. Because KL-6 is one of the fundamental components of pulmonary surface elements, it needs to be studied further by detailed clinicopathological examination. © The Author(s) 2015.
    International Journal of Surgical Pathology 07/2015; 23(7). DOI:10.1177/1066896915582262 · 0.95 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Diffuse pulmonary ossification (DPO) is a rare pulmonary lesion. DPO is typically detected at autopsy rather than premortem. Recently, however, several cases were diagnosed antemortem using computed tomography, high-resolution computed tomography, or video-assisted thoracic surgery. In the present study, we evaluated DPO at autopsy from two patients with post-myocardial infarction (cases 1 and 3) and one patient with duodenal cancer (case 2). Multiple metaplastic bones (nodular in case 1 and 3 or dendriform in case 2) were detected in these three cases. In an attempt to detect aluminum and iron deposition in these metaplastic bones, histochemical investigations were performed. The two nodular types of one and three cases were positive for aluminum and iron, but the dendriform type of case 2 was positive only for aluminum. The depositions occurred in a linear pattern along the calcifying front. It is of great interest that these deposition patterns were similar to those of bones from three previously reported DPO cases and from the bones of hemodialysis patients. It is suggested that these abnormal metal depositions in the calcifying front might disturb the normal mineralization processes of the metaplastic bones, although no morphological abnormality was detected, except for dense black color of calcifying front lines. Further investigations are needed in more patients with DPO to obtain more information on this topic.
    Medical Molecular Morphology 01/2015; DOI:10.1007/s00795-015-0096-1 · 1.46 Impact Factor
  • Hirofumi Nakayama · Hideaki Enzan · Wataru Yasui ·
    [Show abstract] [Hide abstract]
    ABSTRACT: To investigate the difference of surrounding stromal structure between the polypoid and flat adenomas in the colorectum, we performed microscopic study including immunohistochemistry in a total of 32 colorectal adenomas (typical 24 polypoid and eight flat adenomas), especially focusing on vessels around muscularis mucosa. All 24 polypoid adenomas accompanied vasculo-smooth muscle hamartomatous structure in association with muscularis mucosa and submucosal vessels, whereas none of eight flat adenomas had vasculo-smooth muscle hamartomatous structure; surrounding muscularis mucosa and submucosa of the flat adenomas are identical to those of normal colorectal tissue. Vasculo-smooth muscle hamartomatous structure is linked to the morphogenesis of colorectal polypoid adenomas.
    Medical Molecular Morphology 09/2014; 48(2). DOI:10.1007/s00795-014-0087-7 · 1.46 Impact Factor

  • Nihon Rinsho Geka Gakkai Zasshi (Journal of Japan Surgical Association) 01/2014; 75(1):190-196. DOI:10.3919/jjsa.75.190
  • Hirofumi Nakayama · Hideaki Enzan · Wataru Yasui ·
    [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study is to investigate the distribution and roles of podoplanin/D2-40-positive pericryptal stromal cells in superficial colorectal epithelial neoplasia. A total of 105 superficial colorectal epithelial tumors were examined: 65 tubular/tubulovillous adenomas, 32 adenocarcinomas in situ, and 8 submucosally invasive adenocarcinomas. Immunohistochemical analysis was performed using the monoclonal antibody to podoplanin/clone D2-40, which is reactive in both lymphatic endothelial cells and activated stromal cells, but negative in vascular endothelial cells. We found 50 (78 %) of 65 tubular/tubulovillous adenomas, 30 (94 %) of 32 adenocarcinomas in situ, and all 8 (100 %) submucosally invasive adenocarcinomas had podoplanin/D2-40-positive pericryptal stromal cells, whereas all normal colorectal mucosae had no podoplanin/D2-40-positive pericryptal stromal cells. The presence of podoplanin/D2-40-positive pericryptal stromal cells is associated with epithelial tumorigenesis in the colorectum.
    Medical Molecular Morphology 01/2013; 46(1). DOI:10.1007/s00795-012-0004-x · 1.46 Impact Factor

  • Nihon Rinsho Geka Gakkai Zasshi (Journal of Japan Surgical Association) 01/2013; 74(1):173-178. DOI:10.3919/jjsa.74.173
  • [Show abstract] [Hide abstract]
    ABSTRACT: To investigate the relationship between mast cell and hepatic fibrosis by histopathological method and semi-quantitative measurement. Seventy-two Wistary male rats, the control group and the normal group of each only 16, experimental group of 40 rat liver fibrosis was induced by injection of DMN and was sampled at eight different time points. HE, histochemistry, immunohistochemistry (ABC method) and immunofluorescence were performed. The size of fibrosis and the number of mast cells were counted. The expression of MMP-2 and TIMP-2 was documented and electron microscopic examination was performed. After injection of DMN, the fibrosis was the most severe in the 2 week (3.72%) and the first month (3.73%, P = 0.2626), and then gradually diminished, although residual fibrosis was still present at 12 months (1.42%, P = 0.0003). The appearance of mast cells began at 2 weeks (1.73 per 200 power field in average by light microscope) after the injection and reached the peak at 4 months (3.06, P = 0.008). Residual amount of mast cells were present at 12 months (1.04, P = 0.045). However, the degree of fibrosis was not proportional or overlapping with the number of mast cells in this experiment model. Mast cells expressed MMP-2 but not TIMP-2. In the DMN-induced rat liver fibrosis model, mast cell may be an integral player in the pathogenesis of liver fibrosis and may contribute to the degradation of fibrosis by synthesizing and secreting MMP-2.
    Zhonghua bing li xue za zhi Chinese journal of pathology 04/2012; 41(4):260-4. DOI:10.3760/cma.j.issn.0529-5807.2012.04.010
  • [Show abstract] [Hide abstract]
    ABSTRACT: To clarify the clinical implications of neutrophils in vulnerable plaques we evaluated the function and activity of infiltrated neutrophils in an atherosclerotic plaque, focusing on oxidant production. A histopathological investigation was performed using carotid arterial samples obtained from seven patients. The atherosclerotic plaques were examined cytochemically for naphthol-ASD-chloroacetate esterase activity and oxidant-production, and immunohistochemically using N-formyl peptide receptor-like 1 (fPRL1)-, CD66b-, CD68- or p22phox-specific antibodies. The cytoplasmic fPRL1 intensity value of the neutrophils in the plaque was estimated using an activity index. Naphthol-ASD-chloroacetate esterase activity was found in cells located in the atherosclerotic plaque, indicating that the cells were neutrophils. The cytoplasmic fPRL1 intensity value of the neutrophils in the plaque decreased to approximately 60% of the intensity observed in the capillary vessels. Oxidant-production was also detected in the plaques, and both neutrophils and macrophages were observed at the corresponding oxidant-production sites. p22phox expression was also located in the same areas in which oxidant-production was observed in these plaques. We could not directly evaluate how much ROS generated from the infiltrated neutrophils contributed the plaque vulnerability followed by its rupture. However, the infiltrated neutrophils in the atherosclerotic plaques morphologically appeared activated and were actively generating oxidant, implying that neutrophils, together with macrophages, infiltrate into atherosclerotic plaques and contribute to plaque vulnerability.
    Histology and histopathology 01/2011; 26(1):1-11. · 2.10 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Methotrexate-associated lymphoproliferative disorder (MTX-LPD) is a lymphoid proliferation or lymphoma in patients treated with MTX. We report a case of Epstein-Barr virus (EBV)-positive subcutaneous panniculitis-like T-cell lymphoma (SPTCL) in a 60-year-old Japanese man treated with MTX for rheumatoid arthritis (RA). SPTCL is a rare cytotoxic T-cell lymphoma characterized by involvement of subcutaneous fat mimicking panniculitis. The patient, who had been on MTX therapy for RA, manifested high fever and lumbago. Physical examination showed multiple subcutaneous nodules on the trunk including axillary and inguinal regions. Biopsy of the inguinal nodule showed profuse infiltration of CD8(+) T-cell lymphoma cells in the subcutaneous adipose tissues. A diagnosis of SPTCL was made according to the diagnostic criteria of World Health Organization classification. EBV-encoded small RNA in situ hybridization revealed that the lymphoma cells contained EBV genome. The cells were positive for EBV latent membrane protein 1, but not for EBNA2. After discontinuation of MTX, the nodules regressed spontaneously. Studies have reported that most MTX-LPDs are B-cell type lymphomas and Hodgkin lymphoma. To the best of our knowledge, EBV-positive SPTCL has not been reported in patients receiving MTX. Our case emphasizes the importance of clinical and virological characterization of MTX-associated SPTCL.
    International journal of hematology 09/2010; 92(2):364-8. DOI:10.1007/s12185-010-0642-5 · 1.92 Impact Factor

  • 01/2010; 49(4):262-267. DOI:10.5795/jjscc.49.262
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The pathogenesis of non-alcoholic fatty liver disease (NAFLD) is incompletely understood. Kupffer cells (KCs), phagocytic liver-resident macrophages, provide a protective barrier against egress of endotoxin from the portal to the systemic circulation. It is not known if KC phagocytic function is impaired in NAFLD. Super-paramagnetic iron oxide (SPIO) magnetic resonance imaging is a comparative technology dependent on KC phagocytic function. To evaluate KC uptake function, in patients and experimental animals with NAFLD, using SPIO. Abdominal CT and histological examination of liver biopsy specimens were used to estimate the degree of steatosis in patients with NAFLD and controls with chronic hepatitis C. SPIO-MRI was then performed in all patients. Normal rats fed a methionine-choline-deficient diet to induce non-alcoholic steatohepatitis (NASH), the more severe stage of NAFLD, and obese, insulin resistant, Zucker fa/fa rats with steatohepatitis, were also studied with SPIO-MRI and analysed for hepatic uptake of fluorescent microbeads. Immunohistochemical analysis evaluated the numbers of KCs in patients and rat livers. Relative signal enhancement (RSE), inversely proportional to KC function, was higher in patients with NAFLD than in controls and with the degree of steatosis on CT. RSE also positively correlated with the degree of steatosis on histology and was similarly higher in rats with induced severe NAFLD (NASH). On immunohistochemistry, defective phagocytic function was the result of reduced phagocytic uptake and not due to reduced KC numbers in rats or patients with NAFLD. KC uptake function is significantly impaired in patients with NAFLD and experimental animals with NASH, worsens with the degree of steatosis and is not due to a reduction of KC numbers.
    Gut 11/2009; 59(2):258-66. DOI:10.1136/gut.2009.176651 · 14.66 Impact Factor

  • Atherosclerosis Supplements 06/2009; 10(2). DOI:10.1016/S1567-5688(09)70826-8 · 2.29 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: An autopsy case is presented of a peculiar type of intrahe-patic mucinous adenocarcinoma with microcyst formation arising In a 78 year old Japanese man who died of hepatic coma and renal failure 4 months after onset. Macroscopi-cally, the cut surface of the lesion revealed a characteristic honeycomb-like appearance, consisting purely of micro-cysts, 0.2–0.4 cm in diameter, lined by prolific mucin-producing adenocarclnoma cells. The lesion did not have large cystic space, flbrous capsule, or benign cystadenoma-tous component other than neoplastic microcyst formation. The carcinoma cells showed various proliferating patterns, such as irregularly shaped nest-like, trabecular, papillary and tubular ones, directly Invaded the hepatic parenchyma and portal tract with loose or thick fibrosis, and infiltrated extensively into both intrahepatic and extrahepatic stroma along the vascular structures. From these clinicopathologi-cal ffndlngs, we conslder the present tumor to be a variant of mucinous cholangiocarcinoma with characteristic microcyst formation rather than a type of cystadenocarcinoma.
    Pathology International 12/2008; 45(4):292 - 296. DOI:10.1111/j.1440-1827.1995.tb03459.x · 1.69 Impact Factor
  • Hideaki Enzan ·
    [Show abstract] [Hide abstract]
    ABSTRACT: The proliferative activity of Ito cells in acute liver injury induced by carbon tetrachloride (CCl4) was studied by light and electron microscopic autoradio-graphy. At 48 hours after a single intraperitoneal injection of CCl4, the livers of the mice given vitamin A per os for preceding 9 days and those of the mice without vitamin A-pretreatment were removed. Small tissue blocks of each group were respectively incubated at 37°CC for 1 hour in culture medium containing 3H-thymidine. After CC14, injection, perisinusoidal and sinusoidal cells adjacent to centrilobular necrotic liver cells increased in number and size. Some of them were labelled by 3H-thymidine. On the other hand, the perisinusoidal and sinusoidal cells in the peripheral zone in which liver cells are not markedly degenerated nor necrotic showed no noticeable increase in number. They contained very few or no silver grains after 3H-thymidine. In control mice the labelling of perisinusoidal cells was hardly observed. Electron microscopic autoradiography revealed that most of the labelled perisinusoidal cells in the centrilobular zone possess characteristics of Ito cells in their location and in the fine structures such as the presence of small fat droplets, well-developed rough endoplasmic reticulum, and Golgi complex in the cytoplasm. These findings indicate that Ito cells incorporate 3H-thymidine in DNA synthesis after hepatocellular necrosis resulting in cell proliferation. ACTA PATHOL. JPN. 35: 1301–1308, 1985.
    Pathology International 12/2008; 35(6):1301 - 1308. DOI:10.1111/j.1440-1827.1985.tb01429.x · 1.69 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Focusing on hematopoiesis, especially granulocytopoiesis, livers from ten human fetuses between 7 to 13 weeks of gestation were observed with light and electron microscpe. In the hepatic mesenchymal tissue variable number of granulocytes in varying stage of maturation were found from 10 to 13 weeks of gestation. The granules of neutrophils in human fetal livers were classified into three distinct types. The first granules appeared in myeloblasts. The second granules, possibly formed in Golgi complex, were more larger and observed after the promyelocytic stage. The third granules, predominant in mature neutrophils, were pleomorphic. Other than granulo-cytic, erythrocytic and stromal cells, unclassifiable cells were occasionally encountered. The role of mesenchymal tissues in the granulocytopoiesis, the development of fetal neutrophfls and the problem of hematopoietic stem cells were discussed.
    Pathology International 12/2008; 28(3):411 - 426. DOI:10.1111/j.1440-1827.1978.tb01265.x · 1.69 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Liver tissues obtained from 78 human fetuses between 5 weeks and 10 months of gestation were observed with light and electron microscope. In the third month of gestation hepatic megakaryocytopoiesis reached the maximum level and then appeared to decline. At the maximum level immature to mature megakaryocytes were usually smaller than those from adult bone marrow. They were observed between growing liver cells, within hepatic sinusoids and in the mesenchyme surrounding the liver parenchyma in the given order of frequency. Immature megakaryocytes were characterized by the presence of both demarcation vesicles or tubules and a few small round specific granules. The nucleus was mononuclear but frequently indented. With cell maturation, the megakaryocytes were stained intensely by PAS-technique. The nuclei were multilobulated. Large cytoplasm was dominated by numerous specific granules and well-developed demarcation membrane system. Some megakaryocytes passed through the sinusoidal wall and possibly to hepatic sinusoids. These observations indicate that the main site of hepatic megakaryocytopoiesis may be extravascular and more likely between liver cells. Small megakaryocytes in fetal livers are discussed in relation to the occurrence of similar megakaryocytes in various blood dyscrasias.
    Pathology International 12/2008; 30(6):937 - 954. DOI:10.1111/j.1440-1827.1980.tb03282.x · 1.69 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Fascin-1 is an actin-bundling protein localized at the core actin bundles within microvillar projections and filopodial extensions in migrating cells. It is expressed at a low level in normal epithelial cells, but at a high level in tumor cells, indicating its importance in the invasion and motility of tumor cells. In addition, fascin-1 is expressed in human and murine embryos, occurring at high levels especially in developing nervous tissues. In this study, we have investigated the expression patterns of fascin-1 immunohistochemically during the early stages of rat hepatogenesis. A high expression of fascin-1 was detected in the liver bud and hepatoblasts at embryonic day (ED) 10.5, ED11.5, and ED12.5. Expression fell by ED13.5 and was not detectable at ED14.5. These observations demonstrate that the expression of fascin-1 is correlated with the migration activity of hepatoblasts during the early stages of liver development in rats.
    Cell and Tissue Research 11/2008; 334(2):219-26. DOI:10.1007/s00441-008-0683-8 · 3.57 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To determine the extent to which hepatic stellate cell (HSC) activation contributes to liver fibrosis, it was found necessary to develop an alternative structural and functional stellate cell marker for in situ studies. Although several HSC markers have been reported, none of those are associated with particular HSC functions. The present study was undertaken to examine whether lecithin:retinol acyltransferase (LRAT), the physiological retinol esterification enzyme of the liver, is a potential and relevant tissue marker for HSC. An antibody specific to mouse and human LRAT was prepared based on the amino acid sequences. Antibodies to LRAT were used for immunohistochemical studies to assess the distribution of LRAT-positive cells in the liver with the aid of fluorescence and immunogold electron microscopy. LRAT-positive cells were found to be confined in the space of Disse, corresponding with the location of desmin-positive HSC in rodent liver, also in human liver. Interestingly, LRAT-positive staining was also observed along the liver sinusoidal endothelial lining. Furthermore, immune electron microscopic studies revealed that LRAT was mainly distributed in HSC within the rough-endoplasmic reticulum (RER) and multivesicular bodies, whereas LRAT staining within the endothelial cells was largely confined to the perinuclear area and to some extent to the RER. Evidence has been accumulated that LRAT might serve as an excellent alternative HSC marker for future structural and functional studies. Furthermore, the presence of LRAT in endothelial cells might suggest a currently unknown function of this enzyme in liver endothelial biology.
    Liver international: official journal of the International Association for the Study of the Liver 07/2008; 29(1):47-54. DOI:10.1111/j.1478-3231.2008.01773.x · 4.85 Impact Factor
  • H Nakayama · H Itoh · S Kunita · N Kuroda · M Hiroi · H Matsuura · W Yasui · H Enzan ·
    [Show abstract] [Hide abstract]
    ABSTRACT: Elastic fibers appear in extensive old fibrotic foci in general. We examined an association between hepatic fibrosis stage and the presence of perivenular elastic fibers in nonalcoholic steatohepatitis (NASH). A total of 48 liver needle biopsy specimens were used, taken from 48 cases with NASH. Fibrosis Stage (Brunt E, et al. Am. J. Gastroenterol. 1999) of the cases was as follows; six Fibrosis Stage I, twenty-two Fibrosis Stage II, and twenty Fibrosis Stage III. We examined Orcein stain sections in all of the liver needle biopsy specimens. In all twenty Fibrosis Stage III cases, perivenular elastic fiber bundles were observed. In contrast, perivenular elastic fibers were detected only in one of the six Fibrosis Stage I and two of the twenty-two Fibrosis Stage II cases. In liver needle biopsy specimens of NASH, detection of perivenular elastic fibers is useful in deciding Fibrosis Stage III.
    Histology and histopathology 05/2008; 23(4):407-9. · 2.10 Impact Factor
  • Hideaki Enzan ·
    [Show abstract] [Hide abstract]
    ABSTRACT: Small tissue blocks of livers obtained from normal and CCI4 -treated mice were incubated in culture medium supplemented with 3H-leucine for one hour to observe the protein synthesis of Ito cells in acute carbon tetrachloride liver injury by a light and electron microscopic autoradtography. In normal mouse liver very few Ito cells are labeled with 3H-leucine. On the contrary, in acutely damaged mouse liver by a single intraperitoneal Injection of CCI4, the Ito cells in the centrilobular zones where liver cells show marked degeneration and necrosis are densely labeled. No labeling, however occurs over the Ito cells in the intermediate and peripheral zones of the same liver lobules, where liver cells showed no cellular degeneration. These findings show that the Ito cells are inactive in 3H-leucine incorporation under physiological conditions. After acute liver cell injury the Ito cells located in the necrotic areas of liver cells are markedly activitated for protein synthesis.
    Pathology International 02/2008; 37(2):225-230. DOI:10.1111/j.1440-1827.1987.tb03058.x · 1.69 Impact Factor

Publication Stats

3k Citations
647.74 Total Impact Points


  • 2012
    • Capital Medical University
      • Department of Pathology
      Peping, Beijing, China
  • 2004-2011
    • Kochi University
      • Department of Pathology
      Kôti, Kochi, Japan
  • 1982-2009
    • Kochi Medical School
      Kôti, Kōchi, Japan
  • 1974-2004
    • Hiroshima University
      • • Department of Molecular Pathology
      • • Department of Hematology
      Hirosima, Hiroshima, Japan
  • 2001
    • First Solar
      Tempe, Arizona, United States
  • 2000
    • Kure Medical Centre
      Kure, Hiroshima, Japan
  • 1976
    • University of Freiburg
      • Department of Pathology
      Freiburg, Baden-Württemberg, Germany