H Enzan

Capital Medical University, Peping, Beijing, China

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Publications (192)585 Total impact

  • [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.
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    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. · 2.28 Impact Factor
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    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. · 1.17 Impact Factor
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    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. · 10.73 Impact Factor
  • Atherosclerosis Supplements - ATHEROSCLER SUPPL. 01/2009; 10(2).
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    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. · 1.72 Impact Factor
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    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. · 1.72 Impact Factor
  • Hideaki Enzan
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    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. · 1.72 Impact Factor
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    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. · 1.72 Impact Factor
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    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. · 3.68 Impact Factor
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    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. · 3.87 Impact Factor
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    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. · 2.28 Impact Factor
  • Hideaki Enzan
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    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 01/2008; 37(2):225-230. · 1.72 Impact Factor
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    ABSTRACT: We studied the distribution of myofibroblasts in the stroma of normal seminal vesicles. Twelve normal seminal vesicles obtained by surgery on the diagnosis of some diseases were selected, and we evaluated the distribution of myofibroblasts in the seminal vesicles using immunohistochemical and electron and immunoelectron microscopic techniques. Immunohistochemically, myofibroblasts, which were positive for alpha-smooth muscle actin (ASMA) and negative for high molecular weight caldesmon (h-CD), were observed in the stroma just beneath the epithelium of normal seminal vesicles. Moreover, an electron microscope examination revealed the presence of spindle or stellate cells in the stroma of the lamina propria beneath the seminal vesicle epithelium, and an immunoelectron microscopic examination showed that these cells were positive for ASMA. Finally, myofibroblasts are distributed in the lamina propria of human normal seminal vesicles and may play an important role in the ejection of sperm plasm.
    Medical Molecular Morphology 01/2008; 40(4):208-11. · 1.17 Impact Factor
  • Nihon Naika Gakkai Zasshi 09/2007; 96(8):1697-9.
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    ABSTRACT: Adenoid basal carcinomas of the uterine cervix are uncommon neoplasms and generally run a favorable clinical course. Although it is well known that these tumors do not evoke the stromal reaction, we immunohistochemically examined a stromal reaction in a case of adenoid basal carcinoma. A 40-year-old woman was found to have a cervical polyp during a medical checkup and underwent polypectomy. Histological examination revealed the finding of adenoid basal carcinoma. Immunohistochemically, a smaller number of CD34-positive and CD31-negative stromal cells, namely fibroblasts, in the stroma of tumor center than in normal cervical stroma were observed. On the other hand, alpha-smooth muscle actin-positive and h-caldesmon-negative stromal cells, namely myofibroblasts, were completely absent in the stroma of tumor center. Finally, our preliminary report suggests that the decrease of CD34-positive fibroblasts in adenoid basal carcinoma may show an early stromal reaction to tumor invasion. Gynecologists and pathologists should bear in mind that adenoid basal carcinoma may arise in a cervical polyp.
    Medical Molecular Morphology 07/2007; 40(2):112-4. · 1.17 Impact Factor
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    ABSTRACT: Malignant müllerian mixed tumors (MMMTs) of the fallopian tube are very rare neoplasms, and we present such a case with unusual findings here. A 57-year-old Japanese woman, after she received a medical checkup, underwent salpingo-oophorectomy on the suspicion of ovarian cancer. At the time of operation, the main tumor was present predominantly in the fallopian tube. Microscopically, the tumor consisted of carcinoma and sarcoma components. The carcinoma showed moderately to poorly differentiated adenocarcinoma. The sarcoma consisted of predominantly undifferentiated sarcoma and focally rhabdomyosarcomatous cells with abundant eosinophilic cytoplasm. Immunohistochemically, the differentiation toward rhabdomyosarcoma was confirmed. Interestingly, the cytoplasm of undifferentiated sarcoma cells contained hyaline globule-like structures. These structures showed a positive reaction for PAS, and these structures were not digested by the diastase pretreatment. Ultrastructurally, hyaline globule-like structures corresponded to lysosomes. Finally, pathologists should keep in mind that undifferentiated sarcoma cells in MMMT of the fallopian tube may contain hyaline globule-like structures in the cytoplasm.
    Medical Molecular Morphology 04/2007; 40(1):46-9. · 1.17 Impact Factor
  • Zhonghua bing li xue za zhi Chinese journal of pathology 04/2007; 36(3):210-1.
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    ABSTRACT: In this study, we examined the distribution and origin of myofibroblasts around the perforations of appendicitis. Stromal cells of 45 cases were studied by immunohistochemistry. In the normal appendix, myofibroblasts were restricted to the mucosa, and CD34-positive stromal cells were distributed in the submucosal and subserosal layers. Some mesothelial cells were positive for cytokeratin CAM5.2, cytokeratin 5, or mesothelial cells (HBME-1). In perforation of appendicitis with both abscess and granulation tissue, a small to moderate or a moderate to large number of myofibroblasts appeared in the subserosal area around the perforation, respectively, but CD34-positive stromal cells were completely absent there. In the subserosal area of the perforation of appendicitis with abscess, cytokeratin 5-positive stromal cells were absent. However, a small to moderate number of cytokeratin CAM5.2-positive stromal cells were observed there. Double immunostaining showed the coexpression of alpha-smooth muscle actin (ASMA) and cytokeratin CAM5.2 and the coexpression of cytokeratin 5 and cytokeratin CAM5.2 in many or some stellate-shaped or spindle-shaped stromal cells existing in the subserosal area with granulation tissue around the perforation of appendicitis, respectively. Finally, many myofibroblasts appearing in the subserosal area of the perforation of appendicitis may be derived from submesothelial cells or mesothelial cells.
    Medical Molecular Morphology 01/2007; 39(4):209-13. · 1.17 Impact Factor
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    ABSTRACT: Using a developed rat model of hepatic necrosis and subsequent fibrosis induced by a high-dose intraperitoneal injection of dimethylnitrosamine (DMN), we studied iron deposition and expression of transforming growth factor-beta(1) (TGF-beta(1)) during the development of persistent liver fibrosis. Rats were sacrificed at several timepoints from 6 h to 10 months post-injection and the livers were examined for iron content and distribution, and for expression of alpha-smooth muscle actin, ED-1, TGF-beta(1), and collagen (alpha(2))I. Morphologic evidence of acute submassive hemorrhagic necrosis peaked at 36 h; on day 3 the residual parenchyma contained activated hepatic stellate cells (HSCs) and necrotic areas contained numerous macrophages; and on day 5, necrotic tissues and erythrocytes had been phagocytosed and macrophages contained abundant iron deposits. From days 7 to 10, iron-laden macrophages and activated HSCs (myofibroblasts) populated the fibrous septa in parallel. From week 2 to month 10, closely arranged macrophages and myofibroblasts were found in central-to-central bridging fibrotic tissue. TGF-beta(1) was strongly detected in both macrophages and HSCs during development of liver fibrosis. Our data suggest that increased iron deposition may be involved in the initiation and perpetuation of rat liver fibrosis. Iron-laden macrophages may influence HSCs through the action of TGF-beta(1) in DMN-induced liver fibrosis.
    Experimental and Molecular Pathology 01/2007; 81(3):255-61. · 2.13 Impact Factor

Publication Stats

2k Citations
585.00 Total Impact Points

Institutions

  • 2012
    • Capital Medical University
      • Department of Pathology
      Peping, Beijing, China
  • 2004–2008
    • Hiroshima University
      • Department of Molecular Pathology
      Hiroshima-shi, Hiroshima-ken, Japan
  • 1983–2008
    • Kochi Medical School
      Kôti, Kōchi, Japan
  • 2004–2007
    • Kochi University
      • • Department of Pathology
      • • Department of Pediatrics
      Kōchi-shi, Kochi-ken, Japan
  • 2001
    • First Solar
      Tempe, Arizona, United States
  • 2000
    • Kure Medical Centre
      Hirosima, Hiroshima, Japan