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Thomas Horn - One of the best experts on this subject based on the ideXlab platform.

  • DETECTION OF EARLY ZONE 3 LIVER FIBROSIS IN CHRONIC ALCOHOLICS A Comparison of Four Connective Tissue Staining Methods
    Apmis, 2009
    Co-Authors: Mogens Vyberg, Jette Junge, Thomas Horn
    Abstract:

    Fibrous deposits in the Perisinusoidal Space in the acinar zone 3 are early and prognostically important features of the alcoholic liver lesion. Four connective tissue staining methods: van Gieson's Picro-Fuchsin (VG), Gordon & Sweets' reticulin (GS), Chromotrope Aniline Blue (CAB), and Picro-Sirius (PS) were evaluated concerning their relative sensitivity in the detection of early zone 3 fibrosis. A selected area in 60 liver biopsies with preserved architecture, obtained from chronic alcoholics, were studied. A semiquantitative registration of the degree of fibrosis was made. A comparison between the scores of the various staining methods by means of Pratt's test revealed PS to be significantly the most sensitive method. GS was insignificantly more sensitive than CAB while VG (which in contrast to the other three methods leaves reticulin unstained) was the least sensitive. In five biopsies which only revealed fibrosis in PS, Perisinusoidal collagenization was confirmed by transmission electron microscopy. In the histological detection of early zone 3 fibrosis, PS is therefore recommended.

  • The blood hepatocytic barrier: a light microscopical, transmission- and scanning electron microscopic study.
    Liver, 2008
    Co-Authors: Thomas Horn, Hans Lyon, Per Christoffersen
    Abstract:

    - The normal blood hepatocytic barrier (BHB), comprised by the endothelial lining cells and the Perisinusoidal Space, was investigated, and it was concluded that the BHB is a complex structure in which each individual part serves several functions. Immunohistochemical staining for factor VIII showed endothelial lining cells to be positive. By TEM and SEM the endothelial cells were seen to be fenestrated without a basal lamina. They possess numerous endocytotic vesicles. The Perisinusoidal Space contains the lipocytes and a matrix composed of fibrils, and a microfilamentous to granular material. The nature of these matrix components was poorly analyzable by conventional methods. Lipocytes were visualized by LM in: 1) sections stained with oil red 0 after fixation in Baker's formol-calcium and following post-fixation in dichromate, and 2) toluidine-blue-stained Epon-embedded sections. TEM revealed numerous cytoplasmic processes rich in microfilaments encircling the sinusoids.

  • Early alcoholic liver injury: changes of the Disse Space in acinar zone 3
    Liver, 2008
    Co-Authors: Thomas Horn, Jette Junge, Per Christoffersen
    Abstract:

    — One hundred and twelve consecutive liver biopsies were studied by transmission electron microscopy. In 18 out of 23 biopsies from chronic alcoholics showing preserved architecture by light microscopy, basal laminas were found in acinar zone 3 applied to endothelial cells as well as to hepatocytes. Basal laminas occurred independently of Mallory bodies and lipogranulomas, and were observed even in cases where light microscopy showed no fibrosis in zone 3. In addition to basal laminas, deposition of collagen and defenestration of the endothelial cells were observed. Basal laminas were seen only rarely in biopsies from non-alcoholics. We suggest that basal lamina formation in acinar zone 3 is initiated by changes in the Perisinusoidal Space and that it may contribute to impaired liver cell function and possibly initiate liver cell necrosis.

Per Christoffersen - One of the best experts on this subject based on the ideXlab platform.

  • The blood hepatocytic barrier: a light microscopical, transmission- and scanning electron microscopic study.
    Liver, 2008
    Co-Authors: Thomas Horn, Hans Lyon, Per Christoffersen
    Abstract:

    - The normal blood hepatocytic barrier (BHB), comprised by the endothelial lining cells and the Perisinusoidal Space, was investigated, and it was concluded that the BHB is a complex structure in which each individual part serves several functions. Immunohistochemical staining for factor VIII showed endothelial lining cells to be positive. By TEM and SEM the endothelial cells were seen to be fenestrated without a basal lamina. They possess numerous endocytotic vesicles. The Perisinusoidal Space contains the lipocytes and a matrix composed of fibrils, and a microfilamentous to granular material. The nature of these matrix components was poorly analyzable by conventional methods. Lipocytes were visualized by LM in: 1) sections stained with oil red 0 after fixation in Baker's formol-calcium and following post-fixation in dichromate, and 2) toluidine-blue-stained Epon-embedded sections. TEM revealed numerous cytoplasmic processes rich in microfilaments encircling the sinusoids.

  • Early alcoholic liver injury: changes of the Disse Space in acinar zone 3
    Liver, 2008
    Co-Authors: Thomas Horn, Jette Junge, Per Christoffersen
    Abstract:

    — One hundred and twelve consecutive liver biopsies were studied by transmission electron microscopy. In 18 out of 23 biopsies from chronic alcoholics showing preserved architecture by light microscopy, basal laminas were found in acinar zone 3 applied to endothelial cells as well as to hepatocytes. Basal laminas occurred independently of Mallory bodies and lipogranulomas, and were observed even in cases where light microscopy showed no fibrosis in zone 3. In addition to basal laminas, deposition of collagen and defenestration of the endothelial cells were observed. Basal laminas were seen only rarely in biopsies from non-alcoholics. We suggest that basal lamina formation in acinar zone 3 is initiated by changes in the Perisinusoidal Space and that it may contribute to impaired liver cell function and possibly initiate liver cell necrosis.

Reidar Albrechtsen - One of the best experts on this subject based on the ideXlab platform.

  • Carcinoma-associated Perisinusoidal laminin may signal tumour cell metastasis to the liver
    Virchows Archiv A, 1992
    Co-Authors: Ulla M. Wewer, Reidar Albrechtsen
    Abstract:

    The Perisinusoidal Space of the liver shows extensive modulation of the extracellular matrix in response to various pathological conditions. We studied Perisinusoidal laminin expression immunohistochemically using polyclonal and monoclonal antibodies in 110 human liver specimens obtained at autopsy. In normal adult liver the Perisinusoidal Spaces contained only minimal amounts of immunoreactive laminin. In 86% of patients dying from cancer with liver metastasis, however, a distinct increase in the amount of Perisinusoidal laminin could be demonstrated. The Perisinusoidal Space also contained laminin in cancer patients without liver metastasis. In 3 cases of leukaemia sinusoids were laminin negative. In cirrhosis and chronic passive congestion there was, as expected, laminin immunoreactivity in the Perisinusoidal Space. The results obtained using polyclonal antibodies against laminin were confirmed using chain-specific monoclonal antibodies against B2 laminin. In an ex vivo assay, viable tumour cells (Panc-1 and clone A) were found to bind with remarkable specificity to frozen sections of liver tissue containing Perisinusoidal laminin as opposed to liver tissues without laminin. We suggest that this Perisinusoidal laminin may directly on indirectly mediate tumour cell metastasis to the liver.

  • Laminin A, B1, B2, S and M subunits in the postnatal rat liver development and after partial hepatectomy
    Laboratory Investigation, 1992
    Co-Authors: Ulla M. Wewer, Engvall E, Paulsson M, Yoshihiko Yamada, Reidar Albrechtsen
    Abstract:

    The expression of laminin subunits (A, B1, B2, S and M) in the Perisinusoidal Space of the rat liver was studied in early postnatal life, in the adult, and after partial hepatectomy. In the Perisinusoidal Space of the normal adult rat, laminin was detected with polyclonal antibodies only in small streaks of basement membranes extending from the portobiliary tract and to a lesser degree from the central vein. Occasionally, droplets of laminin immunoreactivity were also found along the intervening portions of the Perisinusoidal Spaces. All morphologically identifiable basement membranes of the rat liver (biliary ducts and blood vessels) irrespective of the age of animals exhibited B1, B2 and S immunoreactivity. Laminin A was restricted to the larger blood vessels and could not be detected in the biliary ducts. In the adult rat, immunoreactivity for the A-like M subunit was absent except for some negligible immunostaining of the blood vessels. In the neonatal rat strong linear laminin immunoreactivity was present in the Perisinusoidal Spaces throughout the entire lobule. Structurally, this laminin is not organized into a basement membrane as defined by electron microscopy. The Perisinusoidal laminin was reactive with antibodies to B1, B2, S and M but the A subunit was absent. Sequential immunohistochemical studies of progressively older animals revealed that B1, B2, S and M immunoreactivity was weak in the Perisinusoidal Spaces before birth but during the postnatal life distinct linear immunoreactivities appeared. Most intense immunoreactivity was present at 1 to 2 weeks after birth. The Perisinusoidal laminin gradually disappeared in growing animals and by 6 to 8 weeks basically no laminin could be detected in this location. By Northern blot analysis increased levels of B1 and B2 were detected in neonatal rats as compared to adult rats. S-laminin mRNA could readily be demonstrated in neonatal rat livers by Northern blot analysis, whereas A and M could not. Expression of S and M-laminin transcripts were demonstrated by polymerase chain reaction, but we were unable to obtain a laminin A product. After partial hepatectomy a transient laminin immunoreactivity, comparable to that in the neonatal rats, was detected in the Perisinusoidal Spaces. Laminin was most prominent 3 days after resection and reacted with antibodies to B1, B2, S and M. No A subunit could be detected in this extracellular matrix.(ABSTRACT TRUNCATED AT 400 WORDS)

Takashi Umemura - One of the best experts on this subject based on the ideXlab platform.

  • Idiopathic hepatic fibrosis with cholestasis in broiler chickens: immunohistochemistry of hepatic stellate cells
    Avian Pathology, 2002
    Co-Authors: Kenji Ochiai, E. Handharyani, Takashi Umemura
    Abstract:

    Immunohistochemical examinations of hepatic stellate cells (HSCs) were performed on six enlarged livers from broiler chickens with malformation of the extrahepatic biliary tract (group 1) and on eight broiler livers affected with naturally occurring cholangiohepatitis without biliary malformation (group 2). The livers from both groups were grossly enlarged, firm and tan-coloured, and histologically revealed severe diffuse fibrosis with proliferation of bile ductules. HSCs positive for muscle actin and desmin actively proliferated in the Perisinusoidal Space and around newly formed bile ductules. There was no difference in the immunohistochemical reactivities and location of HSCs between the two groups. The findings suggest that the diffuse hepatic fibrosis found in group 2 as well as group 1 results from reactive proliferation of HSCs.

  • Immunohistochemical and Ultrastructural Study of Ito Cells (Fat-Storing Cells) in Response to Extrahepatic Bile Duct Ligation in Broiler Chickens
    Journal of Veterinary Medical Science, 2001
    Co-Authors: Ekowati Handharyani, Kenji Ochiai, Naoko Iwata, Takashi Umemura
    Abstract:

    The Ito cell (fat-storing cell) lies in Perisinusoidal Space of liver and has a variety of functions. We investigated the immunohistochemistry and ultrastructure of Ito cells in normal and cholestatic livers of broiler chickens. Immunohistochemistry demonstrated that Ito cells expressed HHF35 muscle actin, vimentin, desmin, glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), chromogranin A and cytokeratins in normal livers. These cells were diffusely scattered throughout the lobules. Livers treated with extrahepatic bile duct ligation (BDL) showed cholestasis, fibrosis, proliferation of biliary ductules and Ito cells. The Ito cells were frequently found in fibrotic areas and were larger in size with more extensive immunoreactivity than those of normal livers. Ultrastructural study demonstrated that Ito cells were closely associated with the production of collagen fibers in BDL livers. These findings suggest that Ito cells actively react against hepatocytic injuries and play a major role in the hepatic fibrogenesis of cholestatic livers of chickens.

Haruki Senoo - One of the best experts on this subject based on the ideXlab platform.

  • Induction of cellular process elongation in hepatic stellate cells cultured on interstitial collagen gel: intracellular signaling mechanism
    Japanese Journal of anatomy, 2001
    Co-Authors: Mitsuru Sato, Haruki Senoo
    Abstract:

    Hepatic stellate cells (HSCs), located in the Perisinusoidal Space of Disse, extend long cellular processes, which surround the hepatic sinusoids. However, after primary culture and following subculture using ordinary polystyrene culture dishes, HSCs lost their cellular processes and exhibited myofibroblast-like phenotypes. HSCs displayed rounded shapes when cultured on Matrigel containing the basement membrane components. On the other hand, HSCs exhibited the elongated cellular processes when cultured on interstitial collagen gel. This process elongation was induced by integrin-binding and the subsequent intracellular signaling pathways including protein kinases, protein phosphatases, PI 3-kinases, small G proteins, and microtubule-associated protein (MAP) subtype, MAP2C, and finally resulted from the reorganization of microtubules. The cellular processes contained vitamin A and matrix metalloproteinase-1. Such an HSC culture system using extracellular matrix components would be useful to study HSC functions in vivo, such as retinoid metabolism and reorganization of extracellular matrix.

  • Adhesion between Cells and Extracellular Matrix with Special Reference to Hepatic Stellate Cell Adhesion to Three-dimensional Collagen Fibers
    Cell Structure and Function, 2000
    Co-Authors: Katsuyuki Imai, Takeya Sato, Haruki Senoo
    Abstract:

    Hepatic stellate cells are located in the Perisinusoidal Space (Space of Disse), and extend their dendritic, thin membranous processes and fine fibrillar processes into this Space. The stellate cells coexist with a three-dimensional extracellular matrix (ECM) in the Perisinusoidal Space. In turn the three-dimensional structure of the ECM regulates the proliferation, morphology, and functions of the stellate cell. In this review, the morphology of sites of adhesion between hepatic stellate cells and extracellular matrix is described. Hepatic stellate cells cultured in polystyrene dishes spread well, whereas the cells cultured on or in type I collagen gel become slender and elongate their long cellular processes which adhere directly to the collagen fibers. Cells in type I collagen gel form a large number of adhesive structures, each adhesive area forming a face but not a point. Adhesion molecules, integrins, for the ECM are localized on the cell surface. Elongation of the cellular processes occurs via integrin-binding to type I collagen fibers. The signal transduction mechanism, including protein and phosphatidylinositol phosphorylation, is critical to induce and sustain the cellular processes. Information on the three-dimensional structures of ECM is transmitted via three-dimensional adhesive structures containing the integrins.

  • Molecular mechanisms in the reversible regulation of morphology, proliferation and collagen metabolism in hepatic stellate cells by the three-dimensional structure of the extracellular matrix.
    Journal of Gastroenterology and Hepatology, 1998
    Co-Authors: Haruki Senoo, Katsuyuki Imai, Yoshikazu Matano, Mitsuru Sato
    Abstract:

    Hepatic stellate cells (vitamin A-storing cells, lipocytes, interstitial cells, fat-storing cells, Ito cells) exist in the Perisinusoidal Space of the hepatic lobule and store 80% of the body's retinoids as retinyl palmitate in lipid droplets in the cytoplasm. Under physiological conditions, these cells play pivotal roles in the regulation of retinoid homeostasis; they express specific receptors for retinol-binding protein (RBP), a binding protein specific for retinol, on their cell surface, and take up the complex of retinol and RBP by receptor-mediated endocytosis. However, in pathological conditions such as liver fibrosis, these cells lose retinoids and synthesize a large amount of extracellular matrix (ECM) components including collagen, proteoglycan and adhesive glycoproteins. The morphology of these cells also changes from star-shaped stellate cells to that of fibroblasts or myofibroblasts. The three-dimensional structure of ECM components was found to regulate reversibly the morphology, proliferation and functions of hepatic stellate cells. Molecular mechanisms in the reversible regulation of stellate cells by ECM imply cell surface integrin binding to ECM components followed by signal transduction processes and then cytoskeleton assembly.

  • Hepatic stellate cells--from the viewpoint of retinoid handling and function of the extracellular matrix.
    Japanese Journal of anatomy, 1997
    Co-Authors: Haruki Senoo, Mitsuru Sato, Katsuyuki Imai
    Abstract:

    Hepatic stellate cells (vitamin A-storing cells, lipocytes, fat-storing cells, Ito cells) exist in the Perisinusoidal Space of the hepatic lobule, and store 80% of retinoids in the whole body as retinyl palmitate in lipid droplets in the cytoplasm. In physiological conditions, these cells play pivotal roles in the regulation of retinoid homeostasis; they express specific receptors for retinol-binding protein (RBP), a binding protein specific for retinol, on their cell surface, and take up the complex of retinol and RBP by receptor-mediated endocytosis. By contrast, in pathological conditions such as liver fibrosis, these cells lose retinoids, and synthesize a large amount of extracellular matrix (ECM) components including collagen, proteoglycan and adhesive glycoproteins. The morphology of these cells also changes from the star-shaped stellate cells to that of fibroblasts or myofibroblasts. It is concluded that three-dimensional structure of the ECM components reversibly regulates the morphology, proliferation, and functions of the hepatic stellate cells.