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Biomedical subjects

H Enzan

Publications and source records attributed to H Enzan.

At least 91 records · Page 5Linked to original sources

Superficial angiomyxoma of the right inguinal region: report of a case.

We report one rare case of superficial angiomyxoma of the right inguinal region, in a 67-year-old man. The tumor, measuring 4.5 x 4.0 x 3.0 cm, had a finger-like shape, was composed of a well circumscribed conglomerate of multiple myxomatous nodules and was located partially in the dermis and partially in the subcutaneous tissue. Microscopically, in contrast to previously reported cases, the tumor was composed mainly of oval plump stromal cells with an amphophilic cytoplasm. Spindle-shaped stromal cells were scattered throughout the tumor. The tumor border was not infiltrative and was well defined by thick hyalized collagen bundles. Neither hyperchromasia nor pleomorphism was apparent. No mitotic figures were detected in the specimens prepared. Small to medium-sized blood vessels showed a scattered distribution, but large vessels, seen frequently in aggressive angiomyxoma, were absent. Moreover, no plexiform capillary pattern was evident. These findings were diagnostic of superficial angiomyxoma. Although this disease entity is considered as including cutaneous focal mucinosis, follicular fibroma, trichofolliculoma and trichogenic adnexal tumor, we propose that these tumors should be excluded.

Aged↗

Metaplastic shadow cells in rectal adenocarcinoma: report of a case with immunohistochemical study.

We report a case of adenocarcinoma of the rectum with foci of metaplastic shadow cells. The patient was a 65 year old man with anemia. Macroscopically the tumor was an ordinary rectal cancer. Microscopically, in addition to the features of moderately differentiated adenocarcinoma invading the subserosa, islands of shadow cells in tumor nests were detected in both primary and one of three pericolic metastatic lymph node lesions. Neoplastic glandular cells showed gradual transition to shadow cells. An antibody specific for high-molecular-weight cytokeratins reacted with the shadow cells and intermediate zone epithelial cells surrounding them, but no CEA, low-molecular-weight cytokeratins or cyclin D1 was detectable in them. Cytokeratin 14 was expressed only in the transitional zone epithelial cells. The intermediate zone epithelial cells were regarded as metaplastic squamous cells, from which the shadow cells were derived. The patient died of multiple liver metastases nine and a half months after surgery. To our knowledge, this is the first report of an immunohistochemical study of rectal adenocarcinoma containing shadow cells not only in the primary lesion but also in a metastatic lymph node.

Adenocarcinoma↗

Sequential changes in human Ito cells and their relation to postnecrotic liver fibrosis in massive and submassive hepatic necrosis.

To examine the relationship of Ito cells to postnecrotic liver fibrosis, liver specimens, obtained at autopsy from 17 patients with acute massive necrosis (AMN) and acute submassive hepatic necrosis (ASMN), were examined immunohistochemically. In normal adult livers, Ito cells positive for alpha-smooth muscle actin isoform (ASMA) were rarely seen, scattered along hepatic sinusoids. In contrast, in AMN the Ito cells in necrotic areas became strongly positive for ASMA. They were swollen with elongated cytoplasmic processes along collapsed sinusoidal walls. Around these ASMA-positive Ito cells, there were numerous infiltrated macrophages and lymphocytes present. There was no significant alteration of fibroblasts in the portal tracts. In the middle and late stages of ASMN, the spindle-shaped ASMA-positive Ito cells formed a continuous cellular network. New fibre formation was predominantly around them. In this immediate postnecrotic fibrosis, ASMA-positive stromal cells of Ito cell origin were distributed irregularly and were closely associated with reticulin and newly-formed collagen fibres. Regenerative nodules were surrounded by dense layers of ASMA-positive stromal cells. Throughout the stages of ASMN, portal fibroblasts remained negative for ASMA. We believe that Ito cells in necrotic areas show myofibroblastic transformation and play a central role in the postnecrotic liver fibrosis. Portal fibroblasts play no significant part in this type of fibrosis.

Actins↗

Changes in various tissues in the arterial wall of spontaneously hypertensive rats.

1. Using stroke-prone spontaneously hypertensive rats (SHRSP), stroke-resistant spontaneously hypertensive rats (SHRSR) and Wistar-Kyoto rats (WKY), vascular complications and the longevity of rats were investigated. 2. SHRSP aged more than 9.5 months tended to suffer from severe vascular complications such as periarteritis nodosa (PN) of mesenteric artery, while SHRSR very rarely showed severe vascular complications and WKY did not show any complications, because of the different level of systolic blood pressure. 3. Among some tissues PN tended to occur early in the small arteries of the testes and then in mesenteric artery, when these tissues of SHRSP were investigated microscopically. 4. Concerning the influence of systolic blood pressure on arterial smooth muscle layer, the deviation force of this layer was larger in SHRSR compared to WKY (44.7 times in Y axis), which was calculated mathematically and physically using computer analysis. 5. The arterial wall area of PN was enlarged, resulting in the low ratio of lumen/wall. The ratio of arterial lumen/wall was lower in SHRSP when compared to the age-matched WKY. 6. In search for myocardial ischaemia, ECG was recorded. There were positive correlations between PQ interval or SV1 + RV5 and age in the three strains of rats. ST depression more than 1 mm on ECG was most prevalent in old SHRSP, indicating probably the presence of myocardial ischaemia.

Animals↗

Mucinous cholangiocarcinoma featuring a unique microcystic appearance.

An autopsy case is presented of a peculiar type of intrahepatic 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. Macroscopically, the cut surface of the lesion revealed a characteristic honeycomb-like appearance, consisting purely of microcysts, 0.2-0.4 cm in diameter, lined by prolific mucin-producing adenocarcinoma cells. The lesion did not have large cystic space, fibrous capsule, or benign cystadenomatous 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 clinicopathological findings, we consider the present tumor to be a variant of mucinous cholangiocarcinoma with characteristic microcyst formation rather than a type of cystadenocarcinoma.

Aged↗

Hepatic sinusoidal endothelial cells can store and metabolize serum immunoglobulin.

Sinusoidal inclusion-containing endothelial cells in the liver were investigated with particular interest in their capacity of metabolizing immunoglobulin. Formalin-fixed deparaffinized liver specimens were used for immunohistochemistry, and pronase digestion was proved to be effective for antigen retrieval of immunoglobulin. The inclusions in sinusoidal endothelial cells were strongly immunostained with anti-immunoglobulin (Ig)G, IgA, and IgM antibodies in predigested sections. The complements were not identified immunohistochemically in the inclusions even after pronase treatment. Two women with autoimmune liver disease, who initially represented high levels of serum gamma globulin and abundant inclusion-containing endothelial cells, were studied. The subsequent biopsy after effective corticosteroid therapy demonstrated significant histological improvement as well as the disappearance of inclusion-containing endothelial cells (ICECs). During and after treatment, their serum gamma globulin levels were drastically reduced. In conclusion, the hepatic sinusoidal endothelial cells can take up serum immunoglobulin, probably through a receptor-mediated pathway, and its excessive storage results in the formation of cytoplasmic inclusions that are easily recognized by a light microscope. The stored immunoglobulin may be degraded in the cytoplasm, and the inclusions would disappear in association with the reduction of sinusoidal gamma globulin content. In other words, the intralobular density of inclusion-containing endothelial cells is a morphological predictor for the serum gamma globulin level.

Adrenal Cortex Hormones↗

Hitherto unrecognized arterioles within hepatocellular carcinoma.

The distribution of blood vessels in human hepatocellular carcinoma was studied with the anti-a-smooth muscle actin monoclonal antibody by light and electron microscopy, and with morphometric analysis. a-Smooth muscle actin-positive arterioles were never observed in lobules or pseudolobules of non-cancerous areas, but were frequently seen within hepatocellular carcinomas. Morphometric analysis revealed that most of these arterioles measured between 10 and 25 microns in diameter. The morphology of intratumoural arterioles differed considerably from that of conventional arteries in the portal tracts of the non-cancerous area. The presence of abundant intratumoural arterioles can explain the angiographic hypervascularity of hepatocellular carcinoma and provides a pathological basis for its susceptibility to hypoxia and for arterial embolization as a therapeutic strategy.

Adult↗

Immunoelectron microscopic observations on Leu-7 positive cells in virus-related chronic liver diseases.

We investigated the liver biopsies of 78 patients with hepatitis virus-related chronic liver diseases (B type; 14 patients, C type; 64 patients) by immunoelectron microscopy with the Leu-7 monoclonal antibody in order to determine the association of NK/K cells in virus-related chronic liver diseases. Most Leu-7 positive cells in the liver had the Pit cell morphology but a few Pit cells were Leu-7 negative. A few Leu-7 positive cells had neither Pit cell nor typical T cell morphology. No ultrastructural difference was observed in Leu-7 positive cells between hepatitis B virus- and hepatitis C virus-related chronic liver diseases. Regardless of virus type and hepatitis activity, the fine morphology of extravascular Leu-7 positive cells differed considerably from intravascular cells. Leu-7 positive cells were regularly seen in the cellular infiltrates but the ratio of Leu-7 positive cells/whole infiltrates was low. There was no correlation between the inflammatory activity of the disease and the level of Leu-7 positive cell infiltration. A virus aetiology (hepatitis-C or hepatitis-B) did not affect Leu-7 positive cell infiltration. We conclude that NK cells play only a small role in the pathogenesis of hepatitis B virus or hepatitis C virus-related hepatocytolysis, during the chronic stage.

Adult↗

Immunohistochemical identification of Ito cells and their myofibroblastic transformation in adult human liver.

To identify Ito cells in normal and pathological adult human livers, immunohistochemical studies were performed by the avidin-biotin-peroxidase complex method using monoclonal antibodies for alpha-smooth muscle actin (ASMA), desmin, and vimentin. Fifty one needle biopsies, 7 surgically resected specimens, and 5 autopsy specimens were studied. In the normal adult liver vascular smooth muscle cells and pericytes, together with perisinusoidal cells with thin cytoplasmic processes were positive for ASMA. These latter cells formed a loose and discontinuous layer along the sinusoidal walls. Immunoelectron microscopy showed that the ASMA-positive perisinusoidal cells were Ito cells containing fat droplets. The other sinusoidal lining cells were negative for ASMA. In chronic liver disease, ASMA-positive Ito cells showed an increase in number, size, and the intensity of immunostaining in areas of piece-meal necrosis), and formed a continuous cellular network. These cells were dendritic in shape with irregularly elongated cytoplasmic processes and contained an increased amount of microfilaments, in association with loss of the characteristic fat droplets. Thus, their ultrastructural features corresponded to those of myofibroblastic cells. Ito cells showed no staining for desmin in both normal and pathological livers. These results indicate that immunohistochemistry using an anti-ASMA antibody is a sensitive and reliable method for the identification of both normal and transformed Ito cells in adult human livers.

Actins↗

Alpha-smooth muscle actin-positive perisinusoidal stromal cells in human hepatocellular carcinoma.

The purpose of this study is to clarify the morphological characteristics and functional significance of the perisinusoidal stromal cells in hepatocellular carcinoma. The liver specimens surgically resected from 24 patients with hepatocellular carcinoma were studied by electron microscopy and immunohistochemistry using monoclonal antibodies against alpha-smooth muscle actin, vimentin and desmin. In the tissue space between endothelial cells and trabeculae of cancer cells, the stromal cells were frequently found. They were strongly positive for alpha-smooth muscle actin, weakly and less frequently positive for vimentin but negative for desmin. They varied in shape, size and distribution, stretching cytoplasmic processes and occasionally surrounding the trabeculae of cancer cells. They contained considerable amounts of microfilaments that were positive for alpha-smooth muscle actin and condensed in cell periphery. Along the cell membrane, the short dense areas and pinocytotic vesicles were seen. The external lamina incompletely invested the stromal cells. They were always surrounded by amorphous material. In the granulation tissue and fibrotic areas around necrotic cancer tissue, they were increased in size and number. On the other hand, immunohistochemically and ultrastructurally, they closely resembled the Ito cells in the piecemeal necrosis that showed myofibroblastic transformation. These results suggest that the perisinusoidal stromal cells in nonnecrotic cancer tissue produce the extracellular matrix in the tissue space and maintain the cancerous trabecular structure. After necrosis of cancer tissue, they may become activated and actively participate in the fibrosis.

Actins↗

Acetylsalicylate (ASA)-induced mitochondrial dysfunction and its potentiation by Ca2+.

Although it has been suggested that acetylsalicylate (ASA)-induced mitochondrial dysfunction plays an important role in the pathogenesis of Reye's syndrome, administration of ASA alone does not cause this syndrome in therapeutic doses. We noted, however, that Ca2+ plays important roles in the regulation of cellular functions. ASA at concentrations of 250 microM or less, which had little effect on succinate-linked respiration, impaired Ca2+ accumulation in liver mitochondria by causing an increase in Ca2+ release. ASA plus Ca2+, which in concentrations of 150 microM or less alone had little effect on mitochondrial respiration, inhibited state 3 respiration and dinitrophenol-induced uncoupling of respiration. In addition, ASA plus Ca2+ increased state 4 respiration and ATPase activity. These results indicate that ASA plus Ca2+ impaired mitochondrial ATP synthesis, and suggest that ASA and ASA-induced Ca2+ increases in cytosol form a vicious circle of effects. Furthermore, oral administration of ASA (150 mg/kg for 5 days running) to rats did not affect mitochondrial structure or liver function, but resulted in aberrations of mitochondrial respiration. These results suggest that even therapeutic doses of ASA may induce alteration in mitochondrial function.

Adenosine Triphosphatases↗

Serum alpha-L-fucosidase activity and tumor size in hepatocellular carcinoma.

The serum level of alpha-L-fucosidase activity has been suggested as a useful marker in the diagnosis of hepatocellular carcinoma, although the precise mechanism behind the elevation of this parameter has not been determined. We found that the serum alpha-L-fucosidase activity level was significantly higher in 67 patients with hepatocellular carcinoma (695.1 +/- 245.5 nmol/ml/hr) than in 47 patients with cirrhosis (389.1 +/- 188.2 nmol/ml/hr; p < 0.001) and in 54 controls (202.0 +/- 104.6 nmol/ml/hr; p < 0.001). However, alpha-L-fucosidase activity was not correlated with tumor size (r = 0.134), whereas the alpha-fetoprotein level was correlated with tumor size (r = 0.580, p < 0.001). When 515.8 nmol/ml/hr was taken as the cutoff value (mean value in the controls plus 3 standard deviations), alpha-L-fucosidase activity was above the cutoff value in 12 of the 17 patients with a hepatocellular carcinoma less than 2 cm in diameter, in 28 of the 37 patients with a hepatocellular carcinoma less than 3 cm in diameter and in 52 of the 67 patients with hepatocellular carcinoma. In contrast, only 10 of the 47 patients with cirrhosis had levels above the cutoff value. These findings suggest that an increase in serum alpha-L-fucosidase activity in patients with cirrhosis may be a marker for detecting a hepatocellular carcinoma, especially a small tumor, because alpha-fetoprotein and des-gamma-carboxy-prothrombin are less promising as tumor markers.

Biomarkers↗

Appearance of sinusoidal inclusion-containing endothelial cells in liver disease.

Sinusoidal "inclusion-containing endothelial cells" were studied histopathologically and immunohistochemically in various liver diseases, and their clinical importance was investigated. A total of 498 needle liver biopsies were examined. Endothelial inclusions inside the cells were recognized as eosinophilic granules in hematoxylin-eosin-stained sections. Electron microscopy showed that these inclusions corresponded to round cytoplasmic dense bodies with a single limiting membrane. The contents of these bodies were generally homogeneous, but sometimes heterogeneous. The inclusions appeared to contain protein, but were resistant to trypsin digestion, and immunohistochemistry failed to identify any immunoglobulins or hepatocyte-derived proteins. These endothelial cells also contained an increased number of micropinocytotic vesicles when compared with ordinary cells. The inclusion-containing endothelial cells appeared frequently in chronic hepatitis, but were relatively rare in other liver diseases. The incidence was higher in chronic aggressive hepatitis than in chronic persistent hepatitis or inactive cirrhosis. Although the density of these cells varied considerably even among patients with the same histological diagnosis and the phenotypical changes of these endothelial cells, assessed by monoclonal antibodies, were not apparent, the serum gamma globulin level tended to increase in relation to the density of inclusion-containing endothelial cells and the correlation was significant in hepatitis C.

Chronic Disease↗

Acute hepatic failure with swollen mitochondria and microvesicular fatty degeneration of hepatocytes triggered by free radical initiator.

BACKGROUND: Reye syndrome and acute fatty liver of pregnancy are characterized by acute hepatic failure associated with characteristic pathologic changes of hepatocytes, i.e., microvesicular fatty degeneration with severe mitochondrial swelling. Several animal models of these conditions have been proposed, although none has demonstrated sufficiently similar laboratory and pathologic features. EXPERIMENTAL DESIGN: A single dose of 2,2'-azobis-(2-amidinopropane) dihydrochloride, a free radical initiator, 100 mg/kg of body weight, injected intraperitoneally to BALB/c mice induced a transient decrease in hepatic energy charge, liver mitochondrial respiratory activity, and succinate dehydrogenase activity and a transient increase in blood ammonia level, suggesting hepatic failure. RESULTS: The hepatocytes displayed microvesicular fatty degeneration with severely swollen mitochondria. CONCLUSIONS: This is the first model of acute hepatic failure with microvesicular fatty degeneration of hepatocytes. It suggests a role of free radicals in the pathogenesis of certain types of acute hepatic failure.

Adenine Nucleotides↗

The evidence of human herpesvirus 6 infection in the lymph nodes of Hodgkin's disease.

Human herpesvirus 6 (HHV-6), the causative agent of exanthem subitum, has been implicated in other diseases. Recently HHV-6-specific sequences have been detected by Southern blot analysis and polymerase chain reaction in the lymph nodes of three patients with Hodgkin's disease. The pathological localization of HHV-6, however, is still unknown. In order to study the pathological role of HHV-6 in Hodgkin's disease, we investigated, by immunohistochemical and molecular methods, two lymph node biopsies taken from a 7-year-old boy with Hodgkin's disease during the course of disease evolution. Although the histopathological findings of the first biopsy differed from those of the second, HHV-6 antigens and sequences could be detected in both lymph nodes by immunohistochemistry and in situ hybridization, respectively. HHV-6 was localized in macrophages, predominantly in lymphoid follicles, but not in Reed-Sternberg cells. Antibody titres to HHV-6 were consistent with reactivation of latency. Neither cytomegalovirus nor Epstein-Barr virus was present. Our data suggest a role for HHV-6 in the pathogenesis of Hodgkin's disease.

Antibodies, Viral↗

Cytotoxic activity of spleen-derived T lymphocytes against autologous biliary epithelial cells in autopsy patients with primary biliary cirrhosis.

Autoimmunity against biliary epithelial cells is considered to be involved in the pathogenesis of primary biliary cirrhosis (PBC). However, cytotoxic activity of T lymphocytes against biliary epithelial cells has not previously been examined. This study has demonstrated that spleen-derived T lymphocytes were cytotoxic for autologous biliary epithelial cells in all of five patients with PBC, even though it was only detectable at high effector to target ratios. Such cytotoxicity was not found in non-PBC patients. CD8-positive T lymphocytes were shown to be responsible for the cytotoxicity by negative selection, and its inhibition was dependent on the ratio of cold to hot target cells. These observations may support a current hypothesis that the pathogenesis of PBC is partly due to T cell autoimmunity directed against the bile duct epithelium.

Aged↗

[Recent studies on Ito cells with molecular biology].

By Northern blot analysis of total RNA, extracted from normal human and rat Ito cells, either freshly isolated or in culture, recent studies demonstrated the expression of mRNA for collagen type I, III, IV, fibronectin, laminin, transforming growth factor-beta (TGF-beta), hepatocyte growth factor, nuclear retinoic acid receptor-beta and alpha-smooth m muscle actin. Moreover, Ito cells isolated from experimentally induced fibrotic livers exhibited a marked increase in mRNA for collagen type I, associated with a moderate increase in mRNA of collagen type III and TGF-beta. Although endothelial cells from the same liver also showed moderate increase in mRNA for collagen type I alone, hepatocytes showed no changes. From these results it is concluded that Ito cells are the most important cells in hepatic fibrogenesis.

Animals↗