Ultrastructural sequences during liver iron overload in genetic hemochromatosis
Identifieur interne : 000501 ( Istex/Corpus ); précédent : 000500; suivant : 000502Ultrastructural sequences during liver iron overload in genetic hemochromatosis
Auteurs : Theodore C. Iancu ; Yves Deugnier ; June W. Halliday ; Lawrie W. Powell ; Pierre BrissotSource :
- Journal of Hepatology [ 0168-8278 ] ; 1997.
English descriptors
- KwdEn :
- Acinar, Acinar zone, Acinar zones, Bile, Bile bodies, Bile canaliculi, Bile canaliculus, Biliary route, Biochemical data, Biopsy, Canaliculus, Cell death, Chronic iron overload, Collagen deposition, Collagen fibers, Critical level, Critical threshold, Curved arrows, Cytoplasmatic ferritin particles, Cytosol, Cytosolic ferritin, Deugnier, Early stages, Electron micrographs, Electron microscopy, Entire hepatocyte, Ferritin, Ferritin particles, Ferritin synthesis, Fiver iron overload, Genetic hemochromatosis, Hemochromatosis, Hemosiderin, Hemosiderin aggregates, Hepatic, Hepatic iron concentration, Hepatic iron index, Hepatic stellate cells, Hepatocyte, Hepatocytes, Hexagonal paracrystalline arrangements, Histopathological, Histopathological data, Histopathological findings, Iancu, Idiopathic hemochromatosis, Incoming iron, Individual ferritin particles, Iron deposition, Iron loading, Iron metabolism, Iron overload, Iron research, Iron storage, Iron toxicity, Kupffer cells, Laser microprobe mass analysis, Light microscopy, Lipid peroxidation, Liver biopsies, Liver cell damage, Liver cells, Liver iron overload, Liver ultrastructure, Lysosomal, Lysosomal disruption, Lysosomal membrane fragility, Lysosome, Massive siderosis, Mild overload, Mitochondrion, Moderate overload, Numerous siderosomes, Organelle, Organelle damage, Overload, Pericanalicular polarization, Periportal hepatocytes, Phospholipid membranes, Plenum press, Present study, Protein coat, Rappaport faculty, Reference range, Reticuloendothelial cells, Rough endoplasmic reticulum, Same investigator, Severe overload, Siderosis, Siderosomes, Sinusoidal, Sinusoidal cell siderosis, Sinusoidal cells, Special reference, Stellate, Stellate cells, Subcellular, Subcellular changes, Thin sections, Ultrastructural, Ultrastructural changes, Ultrastructural evidence, Ultrastructural pathology, Ultrastructure, Unstained magnification.
- Teeft :
- Acinar, Acinar zone, Acinar zones, Bile, Bile bodies, Bile canaliculi, Bile canaliculus, Biliary route, Biochemical data, Biopsy, Canaliculus, Cell death, Chronic iron overload, Collagen deposition, Collagen fibers, Critical level, Critical threshold, Curved arrows, Cytoplasmatic ferritin particles, Cytosol, Cytosolic ferritin, Deugnier, Early stages, Electron micrographs, Electron microscopy, Entire hepatocyte, Ferritin, Ferritin particles, Ferritin synthesis, Fiver iron overload, Genetic hemochromatosis, Hemochromatosis, Hemosiderin, Hemosiderin aggregates, Hepatic, Hepatic iron concentration, Hepatic iron index, Hepatic stellate cells, Hepatocyte, Hepatocytes, Hexagonal paracrystalline arrangements, Histopathological, Histopathological data, Histopathological findings, Iancu, Idiopathic hemochromatosis, Incoming iron, Individual ferritin particles, Iron deposition, Iron loading, Iron metabolism, Iron overload, Iron research, Iron storage, Iron toxicity, Kupffer cells, Laser microprobe mass analysis, Light microscopy, Lipid peroxidation, Liver biopsies, Liver cell damage, Liver cells, Liver iron overload, Liver ultrastructure, Lysosomal, Lysosomal disruption, Lysosomal membrane fragility, Lysosome, Massive siderosis, Mild overload, Mitochondrion, Moderate overload, Numerous siderosomes, Organelle, Organelle damage, Overload, Pericanalicular polarization, Periportal hepatocytes, Phospholipid membranes, Plenum press, Present study, Protein coat, Rappaport faculty, Reference range, Reticuloendothelial cells, Rough endoplasmic reticulum, Same investigator, Severe overload, Siderosis, Siderosomes, Sinusoidal, Sinusoidal cell siderosis, Sinusoidal cells, Special reference, Stellate, Stellate cells, Subcellular, Subcellular changes, Thin sections, Ultrastructural, Ultrastructural changes, Ultrastructural evidence, Ultrastructural pathology, Ultrastructure, Unstained magnification.
Abstract
Abstract: Background/Aims: The pathway through which iron contributes to liver cell damage and cirrhosis in genetic hemochromatosis is not clear. The objective of the present study was to describe the ultrastructural changes in liver biopsies of patients in various stages of this condition and to correlate these with clinical, histopathological and biochemical data. Methods: Liver biopsies from 20 patients with genetic hemochromatosis were examined by transmission electron microscopy. The use of unstained thin (60 nm) sections facilitated the identification and localization of the electron-opaque compounds of ferritin and hemosiderin in various liver cells. Stained thin sections permitted evaluation of the concomitant subcellular damage and collagen deposition. The ultrastructural observations were corroborated with the histopathological findings and biochemical data. Results: All patients had liver iron overload, which was classified as mild, moderate or severe. In the stage of mild overload (hepatic iron concentration HIC 93.5±23.3 μmol/g and hepatic iron index HII 2.3±0.7), cytosolic ferritin and scarce pericanalicular lysosomes (siderosomes) were seen in periportal hepatocytes (acinar zone 1), without evidence of organelle damage, and in the absence of sinusoidal cell siderosis. In moderate overload (HIC 190.8± 41.5 μmol/g and HII 4.3±1.9), ferritin was identified in hepatocytes of all acinar zones, and the pericanalicular siderosomes were abundant, especially in acinar zone 1. Single hepatocytes showed organelle damage and occasional sinusoidal cells showed siderosis. In severe overload (HIC 308±49.0 μmol/g and HII 7.5±1.7), hepatocytes of all acinar zones were-filled with large, hemosiderin-containing siderosomes, and changes in mitochondria, smooth and rough endoplasmic reticulum and nuclei were conspicuous. Marked sinusoidal cell siderosis and collagen deposition were observed predominantly in this stage. Conclusions: Electron microscopy has shown that during the long, latent stage of “compensated” genetic hemochromatosis, hepatocytes display only minimal subcellular changes, other than iron overload. “Decompensated” overload, characterized by extensive subcellular pathology and focal necrosis, is reached when 1) the hepatocytic siderosis is generalized (i.e. beyond pericanalicular polarization of siderosomes in hepatocytes, and beyond zone 1 in the acinus); and 2) there is evidence of massive siderosis of sinusoidal cells. These findings support the concept of a critical level of hepatic iron concentration beyond which organelle damage is conspicuous and liver cell injury may become irreversible.
Url:
DOI: 10.1016/S0168-8278(97)80079-7
Links to Exploration step
ISTEX:1A4E538F0BCA10EF2E4EF72E58762BA3FA387790Le document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title>Ultrastructural sequences during liver iron overload in genetic hemochromatosis</title>
<author><name sortKey="Iancu, Theodore C" sort="Iancu, Theodore C" uniqKey="Iancu T" first="Theodore C." last="Iancu">Theodore C. Iancu</name>
<affiliation><mods:affiliation>E-mail: tiancu@techunix.technion.ac.il</mods:affiliation>
</affiliation>
<affiliation><mods:affiliation>Electron Microscopy Unit, B Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Deugnier, Yves" sort="Deugnier, Yves" uniqKey="Deugnier Y" first="Yves" last="Deugnier">Yves Deugnier</name>
<affiliation><mods:affiliation>Clinique des Maladies du Foie and INSERM Unit 49, University Hospital Pontchaillou, Rennes, France</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Halliday, June W" sort="Halliday, June W" uniqKey="Halliday J" first="June W." last="Halliday">June W. Halliday</name>
<affiliation><mods:affiliation>Liver Unit, Queensland Institute of Medical Research and The University of Queensland, Brisbane, Australia</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Powell, Lawrie W" sort="Powell, Lawrie W" uniqKey="Powell L" first="Lawrie W." last="Powell">Lawrie W. Powell</name>
<affiliation><mods:affiliation>Liver Unit, Queensland Institute of Medical Research and The University of Queensland, Brisbane, Australia</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Brissot, Pierre" sort="Brissot, Pierre" uniqKey="Brissot P" first="Pierre" last="Brissot">Pierre Brissot</name>
<affiliation><mods:affiliation>Clinique des Maladies du Foie and INSERM Unit 49, University Hospital Pontchaillou, Rennes, France</mods:affiliation>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">ISTEX</idno>
<idno type="RBID">ISTEX:1A4E538F0BCA10EF2E4EF72E58762BA3FA387790</idno>
<date when="1997" year="1997">1997</date>
<idno type="doi">10.1016/S0168-8278(97)80079-7</idno>
<idno type="url">https://api.istex.fr/document/1A4E538F0BCA10EF2E4EF72E58762BA3FA387790/fulltext/pdf</idno>
<idno type="wicri:Area/Istex/Corpus">000501</idno>
<idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">000501</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title level="a">Ultrastructural sequences during liver iron overload in genetic hemochromatosis</title>
<author><name sortKey="Iancu, Theodore C" sort="Iancu, Theodore C" uniqKey="Iancu T" first="Theodore C." last="Iancu">Theodore C. Iancu</name>
<affiliation><mods:affiliation>E-mail: tiancu@techunix.technion.ac.il</mods:affiliation>
</affiliation>
<affiliation><mods:affiliation>Electron Microscopy Unit, B Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Deugnier, Yves" sort="Deugnier, Yves" uniqKey="Deugnier Y" first="Yves" last="Deugnier">Yves Deugnier</name>
<affiliation><mods:affiliation>Clinique des Maladies du Foie and INSERM Unit 49, University Hospital Pontchaillou, Rennes, France</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Halliday, June W" sort="Halliday, June W" uniqKey="Halliday J" first="June W." last="Halliday">June W. Halliday</name>
<affiliation><mods:affiliation>Liver Unit, Queensland Institute of Medical Research and The University of Queensland, Brisbane, Australia</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Powell, Lawrie W" sort="Powell, Lawrie W" uniqKey="Powell L" first="Lawrie W." last="Powell">Lawrie W. Powell</name>
<affiliation><mods:affiliation>Liver Unit, Queensland Institute of Medical Research and The University of Queensland, Brisbane, Australia</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Brissot, Pierre" sort="Brissot, Pierre" uniqKey="Brissot P" first="Pierre" last="Brissot">Pierre Brissot</name>
<affiliation><mods:affiliation>Clinique des Maladies du Foie and INSERM Unit 49, University Hospital Pontchaillou, Rennes, France</mods:affiliation>
</affiliation>
</author>
</analytic>
<monogr></monogr>
<series><title level="j">Journal of Hepatology</title>
<title level="j" type="abbrev">JHEPAT</title>
<idno type="ISSN">0168-8278</idno>
<imprint><publisher>ELSEVIER</publisher>
<date type="published" when="1997">1997</date>
<biblScope unit="volume">27</biblScope>
<biblScope unit="issue">4</biblScope>
<biblScope unit="page" from="628">628</biblScope>
<biblScope unit="page" to="638">638</biblScope>
</imprint>
<idno type="ISSN">0168-8278</idno>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt><idno type="ISSN">0168-8278</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Acinar</term>
<term>Acinar zone</term>
<term>Acinar zones</term>
<term>Bile</term>
<term>Bile bodies</term>
<term>Bile canaliculi</term>
<term>Bile canaliculus</term>
<term>Biliary route</term>
<term>Biochemical data</term>
<term>Biopsy</term>
<term>Canaliculus</term>
<term>Cell death</term>
<term>Chronic iron overload</term>
<term>Collagen deposition</term>
<term>Collagen fibers</term>
<term>Critical level</term>
<term>Critical threshold</term>
<term>Curved arrows</term>
<term>Cytoplasmatic ferritin particles</term>
<term>Cytosol</term>
<term>Cytosolic ferritin</term>
<term>Deugnier</term>
<term>Early stages</term>
<term>Electron micrographs</term>
<term>Electron microscopy</term>
<term>Entire hepatocyte</term>
<term>Ferritin</term>
<term>Ferritin particles</term>
<term>Ferritin synthesis</term>
<term>Fiver iron overload</term>
<term>Genetic hemochromatosis</term>
<term>Hemochromatosis</term>
<term>Hemosiderin</term>
<term>Hemosiderin aggregates</term>
<term>Hepatic</term>
<term>Hepatic iron concentration</term>
<term>Hepatic iron index</term>
<term>Hepatic stellate cells</term>
<term>Hepatocyte</term>
<term>Hepatocytes</term>
<term>Hexagonal paracrystalline arrangements</term>
<term>Histopathological</term>
<term>Histopathological data</term>
<term>Histopathological findings</term>
<term>Iancu</term>
<term>Idiopathic hemochromatosis</term>
<term>Incoming iron</term>
<term>Individual ferritin particles</term>
<term>Iron deposition</term>
<term>Iron loading</term>
<term>Iron metabolism</term>
<term>Iron overload</term>
<term>Iron research</term>
<term>Iron storage</term>
<term>Iron toxicity</term>
<term>Kupffer cells</term>
<term>Laser microprobe mass analysis</term>
<term>Light microscopy</term>
<term>Lipid peroxidation</term>
<term>Liver biopsies</term>
<term>Liver cell damage</term>
<term>Liver cells</term>
<term>Liver iron overload</term>
<term>Liver ultrastructure</term>
<term>Lysosomal</term>
<term>Lysosomal disruption</term>
<term>Lysosomal membrane fragility</term>
<term>Lysosome</term>
<term>Massive siderosis</term>
<term>Mild overload</term>
<term>Mitochondrion</term>
<term>Moderate overload</term>
<term>Numerous siderosomes</term>
<term>Organelle</term>
<term>Organelle damage</term>
<term>Overload</term>
<term>Pericanalicular polarization</term>
<term>Periportal hepatocytes</term>
<term>Phospholipid membranes</term>
<term>Plenum press</term>
<term>Present study</term>
<term>Protein coat</term>
<term>Rappaport faculty</term>
<term>Reference range</term>
<term>Reticuloendothelial cells</term>
<term>Rough endoplasmic reticulum</term>
<term>Same investigator</term>
<term>Severe overload</term>
<term>Siderosis</term>
<term>Siderosomes</term>
<term>Sinusoidal</term>
<term>Sinusoidal cell siderosis</term>
<term>Sinusoidal cells</term>
<term>Special reference</term>
<term>Stellate</term>
<term>Stellate cells</term>
<term>Subcellular</term>
<term>Subcellular changes</term>
<term>Thin sections</term>
<term>Ultrastructural</term>
<term>Ultrastructural changes</term>
<term>Ultrastructural evidence</term>
<term>Ultrastructural pathology</term>
<term>Ultrastructure</term>
<term>Unstained magnification</term>
</keywords>
<keywords scheme="Teeft" xml:lang="en"><term>Acinar</term>
<term>Acinar zone</term>
<term>Acinar zones</term>
<term>Bile</term>
<term>Bile bodies</term>
<term>Bile canaliculi</term>
<term>Bile canaliculus</term>
<term>Biliary route</term>
<term>Biochemical data</term>
<term>Biopsy</term>
<term>Canaliculus</term>
<term>Cell death</term>
<term>Chronic iron overload</term>
<term>Collagen deposition</term>
<term>Collagen fibers</term>
<term>Critical level</term>
<term>Critical threshold</term>
<term>Curved arrows</term>
<term>Cytoplasmatic ferritin particles</term>
<term>Cytosol</term>
<term>Cytosolic ferritin</term>
<term>Deugnier</term>
<term>Early stages</term>
<term>Electron micrographs</term>
<term>Electron microscopy</term>
<term>Entire hepatocyte</term>
<term>Ferritin</term>
<term>Ferritin particles</term>
<term>Ferritin synthesis</term>
<term>Fiver iron overload</term>
<term>Genetic hemochromatosis</term>
<term>Hemochromatosis</term>
<term>Hemosiderin</term>
<term>Hemosiderin aggregates</term>
<term>Hepatic</term>
<term>Hepatic iron concentration</term>
<term>Hepatic iron index</term>
<term>Hepatic stellate cells</term>
<term>Hepatocyte</term>
<term>Hepatocytes</term>
<term>Hexagonal paracrystalline arrangements</term>
<term>Histopathological</term>
<term>Histopathological data</term>
<term>Histopathological findings</term>
<term>Iancu</term>
<term>Idiopathic hemochromatosis</term>
<term>Incoming iron</term>
<term>Individual ferritin particles</term>
<term>Iron deposition</term>
<term>Iron loading</term>
<term>Iron metabolism</term>
<term>Iron overload</term>
<term>Iron research</term>
<term>Iron storage</term>
<term>Iron toxicity</term>
<term>Kupffer cells</term>
<term>Laser microprobe mass analysis</term>
<term>Light microscopy</term>
<term>Lipid peroxidation</term>
<term>Liver biopsies</term>
<term>Liver cell damage</term>
<term>Liver cells</term>
<term>Liver iron overload</term>
<term>Liver ultrastructure</term>
<term>Lysosomal</term>
<term>Lysosomal disruption</term>
<term>Lysosomal membrane fragility</term>
<term>Lysosome</term>
<term>Massive siderosis</term>
<term>Mild overload</term>
<term>Mitochondrion</term>
<term>Moderate overload</term>
<term>Numerous siderosomes</term>
<term>Organelle</term>
<term>Organelle damage</term>
<term>Overload</term>
<term>Pericanalicular polarization</term>
<term>Periportal hepatocytes</term>
<term>Phospholipid membranes</term>
<term>Plenum press</term>
<term>Present study</term>
<term>Protein coat</term>
<term>Rappaport faculty</term>
<term>Reference range</term>
<term>Reticuloendothelial cells</term>
<term>Rough endoplasmic reticulum</term>
<term>Same investigator</term>
<term>Severe overload</term>
<term>Siderosis</term>
<term>Siderosomes</term>
<term>Sinusoidal</term>
<term>Sinusoidal cell siderosis</term>
<term>Sinusoidal cells</term>
<term>Special reference</term>
<term>Stellate</term>
<term>Stellate cells</term>
<term>Subcellular</term>
<term>Subcellular changes</term>
<term>Thin sections</term>
<term>Ultrastructural</term>
<term>Ultrastructural changes</term>
<term>Ultrastructural evidence</term>
<term>Ultrastructural pathology</term>
<term>Ultrastructure</term>
<term>Unstained magnification</term>
</keywords>
</textClass>
<langUsage><language ident="en">en</language>
</langUsage>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Abstract: Background/Aims: The pathway through which iron contributes to liver cell damage and cirrhosis in genetic hemochromatosis is not clear. The objective of the present study was to describe the ultrastructural changes in liver biopsies of patients in various stages of this condition and to correlate these with clinical, histopathological and biochemical data. Methods: Liver biopsies from 20 patients with genetic hemochromatosis were examined by transmission electron microscopy. The use of unstained thin (60 nm) sections facilitated the identification and localization of the electron-opaque compounds of ferritin and hemosiderin in various liver cells. Stained thin sections permitted evaluation of the concomitant subcellular damage and collagen deposition. The ultrastructural observations were corroborated with the histopathological findings and biochemical data. Results: All patients had liver iron overload, which was classified as mild, moderate or severe. In the stage of mild overload (hepatic iron concentration HIC 93.5±23.3 μmol/g and hepatic iron index HII 2.3±0.7), cytosolic ferritin and scarce pericanalicular lysosomes (siderosomes) were seen in periportal hepatocytes (acinar zone 1), without evidence of organelle damage, and in the absence of sinusoidal cell siderosis. In moderate overload (HIC 190.8± 41.5 μmol/g and HII 4.3±1.9), ferritin was identified in hepatocytes of all acinar zones, and the pericanalicular siderosomes were abundant, especially in acinar zone 1. Single hepatocytes showed organelle damage and occasional sinusoidal cells showed siderosis. In severe overload (HIC 308±49.0 μmol/g and HII 7.5±1.7), hepatocytes of all acinar zones were-filled with large, hemosiderin-containing siderosomes, and changes in mitochondria, smooth and rough endoplasmic reticulum and nuclei were conspicuous. Marked sinusoidal cell siderosis and collagen deposition were observed predominantly in this stage. Conclusions: Electron microscopy has shown that during the long, latent stage of “compensated” genetic hemochromatosis, hepatocytes display only minimal subcellular changes, other than iron overload. “Decompensated” overload, characterized by extensive subcellular pathology and focal necrosis, is reached when 1) the hepatocytic siderosis is generalized (i.e. beyond pericanalicular polarization of siderosomes in hepatocytes, and beyond zone 1 in the acinus); and 2) there is evidence of massive siderosis of sinusoidal cells. These findings support the concept of a critical level of hepatic iron concentration beyond which organelle damage is conspicuous and liver cell injury may become irreversible.</div>
</front>
</TEI>
<istex><corpusName>elsevier</corpusName>
<keywords><teeft><json:string>ferritin</json:string>
<json:string>siderosomes</json:string>
<json:string>hepatocytes</json:string>
<json:string>hepatic</json:string>
<json:string>hemochromatosis</json:string>
<json:string>ultrastructural</json:string>
<json:string>organelle</json:string>
<json:string>iron overload</json:string>
<json:string>subcellular</json:string>
<json:string>lysosomal</json:string>
<json:string>siderosis</json:string>
<json:string>acinar</json:string>
<json:string>ferritin particles</json:string>
<json:string>iancu</json:string>
<json:string>overload</json:string>
<json:string>ultrastructure</json:string>
<json:string>stellate</json:string>
<json:string>genetic hemochromatosis</json:string>
<json:string>moderate overload</json:string>
<json:string>cytosol</json:string>
<json:string>lysosome</json:string>
<json:string>liver biopsies</json:string>
<json:string>severe overload</json:string>
<json:string>sinusoidal cells</json:string>
<json:string>hepatocyte</json:string>
<json:string>hepatic iron concentration</json:string>
<json:string>acinar zone</json:string>
<json:string>organelle damage</json:string>
<json:string>canaliculus</json:string>
<json:string>deugnier</json:string>
<json:string>mitochondrion</json:string>
<json:string>histopathological</json:string>
<json:string>present study</json:string>
<json:string>electron microscopy</json:string>
<json:string>hemosiderin</json:string>
<json:string>collagen deposition</json:string>
<json:string>acinar zones</json:string>
<json:string>cytoplasmatic ferritin particles</json:string>
<json:string>bile canaliculi</json:string>
<json:string>ultrastructural pathology</json:string>
<json:string>liver ultrastructure</json:string>
<json:string>mild overload</json:string>
<json:string>kupffer cells</json:string>
<json:string>iron toxicity</json:string>
<json:string>early stages</json:string>
<json:string>biopsy</json:string>
<json:string>sinusoidal</json:string>
<json:string>rough endoplasmic reticulum</json:string>
<json:string>numerous siderosomes</json:string>
<json:string>hepatic iron index</json:string>
<json:string>biliary route</json:string>
<json:string>bile canaliculus</json:string>
<json:string>liver cells</json:string>
<json:string>incoming iron</json:string>
<json:string>ultrastructural changes</json:string>
<json:string>hemosiderin aggregates</json:string>
<json:string>collagen fibers</json:string>
<json:string>phospholipid membranes</json:string>
<json:string>stellate cells</json:string>
<json:string>lipid peroxidation</json:string>
<json:string>iron metabolism</json:string>
<json:string>bile</json:string>
<json:string>cytosolic ferritin</json:string>
<json:string>massive siderosis</json:string>
<json:string>laser microprobe mass analysis</json:string>
<json:string>electron micrographs</json:string>
<json:string>histopathological findings</json:string>
<json:string>reticuloendothelial cells</json:string>
<json:string>thin sections</json:string>
<json:string>critical level</json:string>
<json:string>biochemical data</json:string>
<json:string>fiver iron overload</json:string>
<json:string>sinusoidal cell siderosis</json:string>
<json:string>liver iron overload</json:string>
<json:string>individual ferritin particles</json:string>
<json:string>pericanalicular polarization</json:string>
<json:string>periportal hepatocytes</json:string>
<json:string>hepatic stellate cells</json:string>
<json:string>protein coat</json:string>
<json:string>entire hepatocyte</json:string>
<json:string>subcellular changes</json:string>
<json:string>hexagonal paracrystalline arrangements</json:string>
<json:string>unstained magnification</json:string>
<json:string>iron deposition</json:string>
<json:string>iron loading</json:string>
<json:string>iron storage</json:string>
<json:string>bile bodies</json:string>
<json:string>curved arrows</json:string>
<json:string>light microscopy</json:string>
<json:string>liver cell damage</json:string>
<json:string>lysosomal membrane fragility</json:string>
<json:string>rappaport faculty</json:string>
<json:string>histopathological data</json:string>
<json:string>cell death</json:string>
<json:string>chronic iron overload</json:string>
<json:string>reference range</json:string>
<json:string>ultrastructural evidence</json:string>
<json:string>critical threshold</json:string>
<json:string>idiopathic hemochromatosis</json:string>
<json:string>ferritin synthesis</json:string>
<json:string>special reference</json:string>
<json:string>lysosomal disruption</json:string>
<json:string>same investigator</json:string>
<json:string>iron research</json:string>
<json:string>plenum press</json:string>
</teeft>
</keywords>
<author><json:item><name>Theodore C. Iancu</name>
<affiliations><json:string>E-mail: tiancu@techunix.technion.ac.il</json:string>
<json:string>Electron Microscopy Unit, B Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel</json:string>
</affiliations>
</json:item>
<json:item><name>Yves Deugnier</name>
<affiliations><json:string>Clinique des Maladies du Foie and INSERM Unit 49, University Hospital Pontchaillou, Rennes, France</json:string>
</affiliations>
</json:item>
<json:item><name>June W. Halliday</name>
<affiliations><json:string>Liver Unit, Queensland Institute of Medical Research and The University of Queensland, Brisbane, Australia</json:string>
</affiliations>
</json:item>
<json:item><name>Lawrie W. Powell</name>
<affiliations><json:string>Liver Unit, Queensland Institute of Medical Research and The University of Queensland, Brisbane, Australia</json:string>
</affiliations>
</json:item>
<json:item><name>Pierre Brissot</name>
<affiliations><json:string>Clinique des Maladies du Foie and INSERM Unit 49, University Hospital Pontchaillou, Rennes, France</json:string>
</affiliations>
</json:item>
</author>
<subject><json:item><lang><json:string>eng</json:string>
</lang>
<value>Electron microscopy</value>
</json:item>
<json:item><lang><json:string>eng</json:string>
</lang>
<value>Ferritin</value>
</json:item>
<json:item><lang><json:string>eng</json:string>
</lang>
<value>Genetic hemochromatosis</value>
</json:item>
<json:item><lang><json:string>eng</json:string>
</lang>
<value>Hemosiderin</value>
</json:item>
<json:item><lang><json:string>eng</json:string>
</lang>
<value>Liver iron overload</value>
</json:item>
</subject>
<arkIstex>ark:/67375/6H6-Q2QJSWMB-L</arkIstex>
<language><json:string>eng</json:string>
</language>
<originalGenre><json:string>Full-length article</json:string>
</originalGenre>
<abstract>Abstract: Background/Aims: The pathway through which iron contributes to liver cell damage and cirrhosis in genetic hemochromatosis is not clear. The objective of the present study was to describe the ultrastructural changes in liver biopsies of patients in various stages of this condition and to correlate these with clinical, histopathological and biochemical data. Methods: Liver biopsies from 20 patients with genetic hemochromatosis were examined by transmission electron microscopy. The use of unstained thin (60 nm) sections facilitated the identification and localization of the electron-opaque compounds of ferritin and hemosiderin in various liver cells. Stained thin sections permitted evaluation of the concomitant subcellular damage and collagen deposition. The ultrastructural observations were corroborated with the histopathological findings and biochemical data. Results: All patients had liver iron overload, which was classified as mild, moderate or severe. In the stage of mild overload (hepatic iron concentration HIC 93.5±23.3 μmol/g and hepatic iron index HII 2.3±0.7), cytosolic ferritin and scarce pericanalicular lysosomes (siderosomes) were seen in periportal hepatocytes (acinar zone 1), without evidence of organelle damage, and in the absence of sinusoidal cell siderosis. In moderate overload (HIC 190.8± 41.5 μmol/g and HII 4.3±1.9), ferritin was identified in hepatocytes of all acinar zones, and the pericanalicular siderosomes were abundant, especially in acinar zone 1. Single hepatocytes showed organelle damage and occasional sinusoidal cells showed siderosis. In severe overload (HIC 308±49.0 μmol/g and HII 7.5±1.7), hepatocytes of all acinar zones were-filled with large, hemosiderin-containing siderosomes, and changes in mitochondria, smooth and rough endoplasmic reticulum and nuclei were conspicuous. Marked sinusoidal cell siderosis and collagen deposition were observed predominantly in this stage. Conclusions: Electron microscopy has shown that during the long, latent stage of “compensated” genetic hemochromatosis, hepatocytes display only minimal subcellular changes, other than iron overload. “Decompensated” overload, characterized by extensive subcellular pathology and focal necrosis, is reached when 1) the hepatocytic siderosis is generalized (i.e. beyond pericanalicular polarization of siderosomes in hepatocytes, and beyond zone 1 in the acinus); and 2) there is evidence of massive siderosis of sinusoidal cells. These findings support the concept of a critical level of hepatic iron concentration beyond which organelle damage is conspicuous and liver cell injury may become irreversible.</abstract>
<qualityIndicators><score>10</score>
<pdfWordCount>5355</pdfWordCount>
<pdfCharCount>34237</pdfCharCount>
<pdfVersion>1.2</pdfVersion>
<pdfPageCount>11</pdfPageCount>
<pdfPageSize>576 x 792 pts</pdfPageSize>
<refBibsNative>true</refBibsNative>
<abstractWordCount>361</abstractWordCount>
<abstractCharCount>2652</abstractCharCount>
<keywordCount>5</keywordCount>
</qualityIndicators>
<title>Ultrastructural sequences during liver iron overload in genetic hemochromatosis</title>
<pmid><json:string>9365038</json:string>
</pmid>
<pii><json:string>S0168-8278(97)80079-7</json:string>
</pii>
<genre><json:string>research-article</json:string>
</genre>
<serie><title>Pathology of the liver</title>
<language><json:string>unknown</json:string>
</language>
<pages><first>219</first>
<last>241</last>
</pages>
<editor><json:item><name>RNM MacSween</name>
</json:item>
<json:item><name>PP Anthony</name>
</json:item>
<json:item><name>PJ Scheuer</name>
</json:item>
<json:item><name>AD Burt</name>
</json:item>
<json:item><name>BC Portmann</name>
</json:item>
</editor>
</serie>
<host><title>Journal of Hepatology</title>
<language><json:string>unknown</json:string>
</language>
<publicationDate>1997</publicationDate>
<issn><json:string>0168-8278</json:string>
</issn>
<pii><json:string>S0168-8278(00)X0009-8</json:string>
</pii>
<volume>27</volume>
<issue>4</issue>
<pages><first>628</first>
<last>638</last>
</pages>
<genre><json:string>journal</json:string>
</genre>
</host>
<namedEntities><unitex><date><json:string>1997</json:string>
<json:string>1975</json:string>
</date>
<geogName></geogName>
<orgName><json:string>Medical Research and The University of Queensland, Brisbane, Australia Background</json:string>
<json:string>Milman Research Fund</json:string>
<json:string>National Health and Medical Research</json:string>
</orgName>
<orgName_funder></orgName_funder>
<orgName_provider></orgName_provider>
<persName><json:string>T. C. Iancu</json:string>
<json:string>Mrs Hanna</json:string>
<json:string>Deugnier</json:string>
<json:string>Ghadially</json:string>
<json:string>Linda Fletcher</json:string>
<json:string>Cleton</json:string>
<json:string>Britton</json:string>
<json:string>In</json:string>
<json:string>I. Pt</json:string>
<json:string>June W. Halliday</json:string>
<json:string>Yves Deugnier</json:string>
<json:string>Kim Bridle</json:string>
<json:string>W. Powell</json:string>
<json:string>Pierre Brissot</json:string>
<json:string>Lynne Reid</json:string>
<json:string>Hepatocyte</json:string>
<json:string>Pt</json:string>
</persName>
<placeName><json:string>Brisbane</json:string>
<json:string>Australia</json:string>
<json:string>Rennes</json:string>
<json:string>Helsinki</json:string>
<json:string>Haifa</json:string>
<json:string>Israel</json:string>
<json:string>France</json:string>
<json:string>Copenhagen</json:string>
</placeName>
<ref_url></ref_url>
<ref_bibl><json:string>Hultcrantz et al.</json:string>
<json:string>Trump et al.</json:string>
<json:string>T. C. Iancu et al.</json:string>
<json:string>Brissot et al.</json:string>
<json:string>Bassett et al.</json:string>
<json:string>Ramm et al.</json:string>
<json:string>Peters et al.</json:string>
<json:string>Sthl et al.</json:string>
</ref_bibl>
<bibl></bibl>
</unitex>
</namedEntities>
<ark><json:string>ark:/67375/6H6-Q2QJSWMB-L</json:string>
</ark>
<categories><wos><json:string>1 - science</json:string>
<json:string>2 - gastroenterology & hepatology</json:string>
</wos>
<scienceMetrix><json:string>1 - health sciences</json:string>
<json:string>2 - clinical medicine</json:string>
<json:string>3 - gastroenterology & hepatology</json:string>
</scienceMetrix>
<scopus><json:string>1 - Health Sciences</json:string>
<json:string>2 - Medicine</json:string>
<json:string>3 - Hepatology</json:string>
</scopus>
<inist><json:string>1 - sciences appliquees, technologies et medecines</json:string>
<json:string>2 - sciences biologiques et medicales</json:string>
<json:string>3 - sciences medicales</json:string>
</inist>
</categories>
<publicationDate>1997</publicationDate>
<copyrightDate>1997</copyrightDate>
<doi><json:string>10.1016/S0168-8278(97)80079-7</json:string>
</doi>
<id>1A4E538F0BCA10EF2E4EF72E58762BA3FA387790</id>
<score>1</score>
<fulltext><json:item><extension>pdf</extension>
<original>true</original>
<mimetype>application/pdf</mimetype>
<uri>https://api.istex.fr/document/1A4E538F0BCA10EF2E4EF72E58762BA3FA387790/fulltext/pdf</uri>
</json:item>
<json:item><extension>zip</extension>
<original>false</original>
<mimetype>application/zip</mimetype>
<uri>https://api.istex.fr/document/1A4E538F0BCA10EF2E4EF72E58762BA3FA387790/fulltext/zip</uri>
</json:item>
<istex:fulltextTEI uri="https://api.istex.fr/document/1A4E538F0BCA10EF2E4EF72E58762BA3FA387790/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a">Ultrastructural sequences during liver iron overload in genetic hemochromatosis</title>
</titleStmt>
<publicationStmt><authority>ISTEX</authority>
<publisher>ELSEVIER</publisher>
<availability><p>ELSEVIER</p>
</availability>
<date>1997</date>
</publicationStmt>
<sourceDesc><biblStruct type="inbook"><analytic><title level="a">Ultrastructural sequences during liver iron overload in genetic hemochromatosis</title>
<author xml:id="author-0000"><persName><forename type="first">Theodore C.</forename>
<surname>Iancu</surname>
</persName>
<email>tiancu@techunix.technion.ac.il</email>
<note type="correspondence"><p>Correspondence: Prof. T. C. Iancu, Electron Microscopy Unit, B Rappaport Faculty of Medicine, P.O. Box 9649, Haifa 31096, Israel. Tel: 972-4-829-5219. Fax: 972-4-851 7008.</p>
</note>
<affiliation>Electron Microscopy Unit, B Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel</affiliation>
</author>
<author xml:id="author-0001"><persName><forename type="first">Yves</forename>
<surname>Deugnier</surname>
</persName>
<affiliation>Clinique des Maladies du Foie and INSERM Unit 49, University Hospital Pontchaillou, Rennes, France</affiliation>
</author>
<author xml:id="author-0002"><persName><forename type="first">June W.</forename>
<surname>Halliday</surname>
</persName>
<affiliation>Liver Unit, Queensland Institute of Medical Research and The University of Queensland, Brisbane, Australia</affiliation>
</author>
<author xml:id="author-0003"><persName><forename type="first">Lawrie W.</forename>
<surname>Powell</surname>
</persName>
<affiliation>Liver Unit, Queensland Institute of Medical Research and The University of Queensland, Brisbane, Australia</affiliation>
</author>
<author xml:id="author-0004"><persName><forename type="first">Pierre</forename>
<surname>Brissot</surname>
</persName>
<affiliation>Clinique des Maladies du Foie and INSERM Unit 49, University Hospital Pontchaillou, Rennes, France</affiliation>
</author>
<idno type="istex">1A4E538F0BCA10EF2E4EF72E58762BA3FA387790</idno>
<idno type="DOI">10.1016/S0168-8278(97)80079-7</idno>
<idno type="PII">S0168-8278(97)80079-7</idno>
</analytic>
<monogr><title level="j">Journal of Hepatology</title>
<title level="j" type="abbrev">JHEPAT</title>
<idno type="pISSN">0168-8278</idno>
<idno type="PII">S0168-8278(00)X0009-8</idno>
<imprint><publisher>ELSEVIER</publisher>
<date type="published" when="1997"></date>
<biblScope unit="volume">27</biblScope>
<biblScope unit="issue">4</biblScope>
<biblScope unit="page" from="628">628</biblScope>
<biblScope unit="page" to="638">638</biblScope>
</imprint>
</monogr>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><creation><date>1997</date>
</creation>
<langUsage><language ident="en">en</language>
</langUsage>
<abstract xml:lang="en"><p>Background/Aims: The pathway through which iron contributes to liver cell damage and cirrhosis in genetic hemochromatosis is not clear. The objective of the present study was to describe the ultrastructural changes in liver biopsies of patients in various stages of this condition and to correlate these with clinical, histopathological and biochemical data. Methods: Liver biopsies from 20 patients with genetic hemochromatosis were examined by transmission electron microscopy. The use of unstained thin (60 nm) sections facilitated the identification and localization of the electron-opaque compounds of ferritin and hemosiderin in various liver cells. Stained thin sections permitted evaluation of the concomitant subcellular damage and collagen deposition. The ultrastructural observations were corroborated with the histopathological findings and biochemical data. Results: All patients had liver iron overload, which was classified as mild, moderate or severe. In the stage of mild overload (hepatic iron concentration HIC 93.5±23.3 μmol/g and hepatic iron index HII 2.3±0.7), cytosolic ferritin and scarce pericanalicular lysosomes (siderosomes) were seen in periportal hepatocytes (acinar zone 1), without evidence of organelle damage, and in the absence of sinusoidal cell siderosis. In moderate overload (HIC 190.8± 41.5 μmol/g and HII 4.3±1.9), ferritin was identified in hepatocytes of all acinar zones, and the pericanalicular siderosomes were abundant, especially in acinar zone 1. Single hepatocytes showed organelle damage and occasional sinusoidal cells showed siderosis. In severe overload (HIC 308±49.0 μmol/g and HII 7.5±1.7), hepatocytes of all acinar zones were-filled with large, hemosiderin-containing siderosomes, and changes in mitochondria, smooth and rough endoplasmic reticulum and nuclei were conspicuous. Marked sinusoidal cell siderosis and collagen deposition were observed predominantly in this stage. Conclusions: Electron microscopy has shown that during the long, latent stage of “compensated” genetic hemochromatosis, hepatocytes display only minimal subcellular changes, other than iron overload. “Decompensated” overload, characterized by extensive subcellular pathology and focal necrosis, is reached when 1) the hepatocytic siderosis is generalized (i.e. beyond pericanalicular polarization of siderosomes in hepatocytes, and beyond zone 1 in the acinus); and 2) there is evidence of massive siderosis of sinusoidal cells. These findings support the concept of a critical level of hepatic iron concentration beyond which organelle damage is conspicuous and liver cell injury may become irreversible.</p>
</abstract>
<textClass><keywords scheme="keyword"><list><head>Keywords</head>
<item><term>Electron microscopy</term>
</item>
<item><term>Ferritin</term>
</item>
<item><term>Genetic hemochromatosis</term>
</item>
<item><term>Hemosiderin</term>
</item>
<item><term>Liver iron overload</term>
</item>
</list>
</keywords>
</textClass>
</profileDesc>
<revisionDesc><change when="1997-05-12">Modified</change>
<change when="1997">Published</change>
</revisionDesc>
</teiHeader>
</istex:fulltextTEI>
<json:item><extension>txt</extension>
<original>false</original>
<mimetype>text/plain</mimetype>
<uri>https://api.istex.fr/document/1A4E538F0BCA10EF2E4EF72E58762BA3FA387790/fulltext/txt</uri>
</json:item>
</fulltext>
<metadata><istex:metadataXml wicri:clean="Elsevier, elements deleted: tail"><istex:xmlDeclaration>version="1.0" encoding="utf-8"</istex:xmlDeclaration>
<istex:docType PUBLIC="-//ES//DTD journal article DTD version 4.5.2//EN//XML" URI="art452.dtd" name="istex:docType"></istex:docType>
<istex:document><converted-article version="4.5.2" docsubtype="fla"><item-info><jid>JHEPAT</jid>
<aid>97800797</aid>
<ce:pii>S0168-8278(97)80079-7</ce:pii>
<ce:doi>10.1016/S0168-8278(97)80079-7</ce:doi>
<ce:copyright type="unknown" year="1997"></ce:copyright>
</item-info>
<head><ce:title>Ultrastructural sequences during liver iron overload in genetic hemochromatosis</ce:title>
<ce:author-group><ce:author><ce:given-name>Theodore C.</ce:given-name>
<ce:surname>Iancu</ce:surname>
<ce:cross-ref refid="COR1"><ce:sup>∗</ce:sup>
</ce:cross-ref>
<ce:cross-ref refid="AFF1"><ce:sup>a</ce:sup>
</ce:cross-ref>
<ce:e-address>tiancu@techunix.technion.ac.il</ce:e-address>
</ce:author>
<ce:author><ce:given-name>Yves</ce:given-name>
<ce:surname>Deugnier</ce:surname>
<ce:cross-ref refid="AFF2"><ce:sup>b</ce:sup>
</ce:cross-ref>
</ce:author>
<ce:author><ce:given-name>June W.</ce:given-name>
<ce:surname>Halliday</ce:surname>
<ce:cross-ref refid="AFF3"><ce:sup>c</ce:sup>
</ce:cross-ref>
</ce:author>
<ce:author><ce:given-name>Lawrie W.</ce:given-name>
<ce:surname>Powell</ce:surname>
<ce:cross-ref refid="AFF3"><ce:sup>c</ce:sup>
</ce:cross-ref>
</ce:author>
<ce:author><ce:given-name>Pierre</ce:given-name>
<ce:surname>Brissot</ce:surname>
<ce:cross-ref refid="AFF2"><ce:sup>b</ce:sup>
</ce:cross-ref>
</ce:author>
<ce:affiliation id="AFF1"><ce:label>a</ce:label>
<ce:textfn>Electron Microscopy Unit, B Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel</ce:textfn>
</ce:affiliation>
<ce:affiliation id="AFF2"><ce:label>b</ce:label>
<ce:textfn>Clinique des Maladies du Foie and INSERM Unit 49, University Hospital Pontchaillou, Rennes, France</ce:textfn>
</ce:affiliation>
<ce:affiliation id="AFF3"><ce:label>c</ce:label>
<ce:textfn>Liver Unit, Queensland Institute of Medical Research and The University of Queensland, Brisbane, Australia</ce:textfn>
</ce:affiliation>
<ce:correspondence id="COR1"><ce:label>*</ce:label>
<ce:text>Correspondence: Prof. T. C. Iancu, Electron Microscopy Unit, B Rappaport Faculty of Medicine, P.O. Box 9649, Haifa 31096, Israel. Tel: 972-4-829-5219. Fax: 972-4-851 7008.</ce:text>
</ce:correspondence>
</ce:author-group>
<ce:date-received day="23" month="1" year="1997"></ce:date-received>
<ce:date-revised day="12" month="5" year="1997"></ce:date-revised>
<ce:date-accepted day="26" month="5" year="1997"></ce:date-accepted>
<ce:abstract><ce:section-title>Abstract</ce:section-title>
<ce:abstract-sec><ce:simple-para><ce:italic>Background/Aims:</ce:italic>
The pathway through which iron contributes to liver cell damage and cirrhosis in genetic hemochromatosis is not clear. The objective of the present study was to describe the ultrastructural changes in liver biopsies of patients in various stages of this condition and to correlate these with clinical, histopathological and biochemical data.</ce:simple-para>
<ce:simple-para><ce:italic>Methods:</ce:italic>
Liver biopsies from 20 patients with genetic hemochromatosis were examined by transmission electron microscopy. The use of unstained thin (60 nm) sections facilitated the identification and localization of the electron-opaque compounds of ferritin and hemosiderin in various liver cells. Stained thin sections permitted evaluation of the concomitant subcellular damage and collagen deposition. The ultrastructural observations were corroborated with the histopathological findings and biochemical data.</ce:simple-para>
<ce:simple-para><ce:italic>Results:</ce:italic>
All patients had liver iron overload, which was classified as mild, moderate or severe. In the stage of mild overload (hepatic iron concentration HIC 93.5±23.3 μmol/g and hepatic iron index HII 2.3±0.7), cytosolic ferritin and scarce pericanalicular lysosomes (siderosomes) were seen in periportal hepatocytes (acinar zone 1), without evidence of organelle damage, and in the absence of sinusoidal cell siderosis. In moderate overload (HIC 190.8± 41.5 μmol/g and HII 4.3±1.9), ferritin was identified in hepatocytes of all acinar zones, and the pericanalicular siderosomes were abundant, especially in acinar zone 1. Single hepatocytes showed organelle damage and occasional sinusoidal cells showed siderosis. In severe overload (HIC 308±49.0 μmol/g and HII 7.5±1.7), hepatocytes of all acinar zones were-filled with large, hemosiderin-containing siderosomes, and changes in mitochondria, smooth and rough endoplasmic reticulum and nuclei were conspicuous. Marked sinusoidal cell siderosis and collagen deposition were observed predominantly in this stage.</ce:simple-para>
<ce:simple-para><ce:italic>Conclusions:</ce:italic>
Electron microscopy has shown that during the long, latent stage of “compensated” genetic hemochromatosis, hepatocytes display only minimal subcellular changes, other than iron overload. “Decompensated” overload, characterized by extensive subcellular pathology and focal necrosis, is reached when 1) the hepatocytic siderosis is generalized (i.e. beyond pericanalicular polarization of siderosomes in hepatocytes, and beyond zone 1 in the acinus); and 2) there is evidence of massive siderosis of sinusoidal cells. These findings support the concept of a critical level of hepatic iron concentration beyond which organelle damage is conspicuous and liver cell injury may become irreversible.</ce:simple-para>
</ce:abstract-sec>
</ce:abstract>
<ce:keywords><ce:section-title>Keywords</ce:section-title>
<ce:keyword><ce:text>Electron microscopy</ce:text>
</ce:keyword>
<ce:keyword><ce:text>Ferritin</ce:text>
</ce:keyword>
<ce:keyword><ce:text>Genetic hemochromatosis</ce:text>
</ce:keyword>
<ce:keyword><ce:text>Hemosiderin</ce:text>
</ce:keyword>
<ce:keyword><ce:text>Liver iron overload</ce:text>
</ce:keyword>
</ce:keywords>
</head>
</converted-article>
</istex:document>
</istex:metadataXml>
<mods version="3.6"><titleInfo><title>Ultrastructural sequences during liver iron overload in genetic hemochromatosis</title>
</titleInfo>
<titleInfo type="alternative" contentType="CDATA"><title>Ultrastructural sequences during liver iron overload in genetic hemochromatosis</title>
</titleInfo>
<name type="personal"><namePart type="given">Theodore C.</namePart>
<namePart type="family">Iancu</namePart>
<affiliation>E-mail: tiancu@techunix.technion.ac.il</affiliation>
<affiliation>Electron Microscopy Unit, B Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel</affiliation>
<description>Correspondence: Prof. T. C. Iancu, Electron Microscopy Unit, B Rappaport Faculty of Medicine, P.O. Box 9649, Haifa 31096, Israel. Tel: 972-4-829-5219. Fax: 972-4-851 7008.</description>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Yves</namePart>
<namePart type="family">Deugnier</namePart>
<affiliation>Clinique des Maladies du Foie and INSERM Unit 49, University Hospital Pontchaillou, Rennes, France</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">June W.</namePart>
<namePart type="family">Halliday</namePart>
<affiliation>Liver Unit, Queensland Institute of Medical Research and The University of Queensland, Brisbane, Australia</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Lawrie W.</namePart>
<namePart type="family">Powell</namePart>
<affiliation>Liver Unit, Queensland Institute of Medical Research and The University of Queensland, Brisbane, Australia</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Pierre</namePart>
<namePart type="family">Brissot</namePart>
<affiliation>Clinique des Maladies du Foie and INSERM Unit 49, University Hospital Pontchaillou, Rennes, France</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<typeOfResource>text</typeOfResource>
<genre type="research-article" displayLabel="Full-length article" authority="ISTEX" authorityURI="https://content-type.data.istex.fr" valueURI="https://content-type.data.istex.fr/ark:/67375/XTP-1JC4F85T-7">research-article</genre>
<originInfo><publisher>ELSEVIER</publisher>
<dateIssued encoding="w3cdtf">1997</dateIssued>
<dateModified encoding="w3cdtf">1997-05-12</dateModified>
<copyrightDate encoding="w3cdtf">1997</copyrightDate>
</originInfo>
<language><languageTerm type="code" authority="iso639-2b">eng</languageTerm>
<languageTerm type="code" authority="rfc3066">en</languageTerm>
</language>
<abstract lang="en">Abstract: Background/Aims: The pathway through which iron contributes to liver cell damage and cirrhosis in genetic hemochromatosis is not clear. The objective of the present study was to describe the ultrastructural changes in liver biopsies of patients in various stages of this condition and to correlate these with clinical, histopathological and biochemical data. Methods: Liver biopsies from 20 patients with genetic hemochromatosis were examined by transmission electron microscopy. The use of unstained thin (60 nm) sections facilitated the identification and localization of the electron-opaque compounds of ferritin and hemosiderin in various liver cells. Stained thin sections permitted evaluation of the concomitant subcellular damage and collagen deposition. The ultrastructural observations were corroborated with the histopathological findings and biochemical data. Results: All patients had liver iron overload, which was classified as mild, moderate or severe. In the stage of mild overload (hepatic iron concentration HIC 93.5±23.3 μmol/g and hepatic iron index HII 2.3±0.7), cytosolic ferritin and scarce pericanalicular lysosomes (siderosomes) were seen in periportal hepatocytes (acinar zone 1), without evidence of organelle damage, and in the absence of sinusoidal cell siderosis. In moderate overload (HIC 190.8± 41.5 μmol/g and HII 4.3±1.9), ferritin was identified in hepatocytes of all acinar zones, and the pericanalicular siderosomes were abundant, especially in acinar zone 1. Single hepatocytes showed organelle damage and occasional sinusoidal cells showed siderosis. In severe overload (HIC 308±49.0 μmol/g and HII 7.5±1.7), hepatocytes of all acinar zones were-filled with large, hemosiderin-containing siderosomes, and changes in mitochondria, smooth and rough endoplasmic reticulum and nuclei were conspicuous. Marked sinusoidal cell siderosis and collagen deposition were observed predominantly in this stage. Conclusions: Electron microscopy has shown that during the long, latent stage of “compensated” genetic hemochromatosis, hepatocytes display only minimal subcellular changes, other than iron overload. “Decompensated” overload, characterized by extensive subcellular pathology and focal necrosis, is reached when 1) the hepatocytic siderosis is generalized (i.e. beyond pericanalicular polarization of siderosomes in hepatocytes, and beyond zone 1 in the acinus); and 2) there is evidence of massive siderosis of sinusoidal cells. These findings support the concept of a critical level of hepatic iron concentration beyond which organelle damage is conspicuous and liver cell injury may become irreversible.</abstract>
<subject><genre>Keywords</genre>
<topic>Electron microscopy</topic>
<topic>Ferritin</topic>
<topic>Genetic hemochromatosis</topic>
<topic>Hemosiderin</topic>
<topic>Liver iron overload</topic>
</subject>
<relatedItem type="host"><titleInfo><title>Journal of Hepatology</title>
</titleInfo>
<titleInfo type="abbreviated"><title>JHEPAT</title>
</titleInfo>
<genre type="journal" authority="ISTEX" authorityURI="https://publication-type.data.istex.fr" valueURI="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</genre>
<originInfo><publisher>ELSEVIER</publisher>
<dateIssued encoding="w3cdtf">199710</dateIssued>
</originInfo>
<identifier type="ISSN">0168-8278</identifier>
<identifier type="PII">S0168-8278(00)X0009-8</identifier>
<part><date>199710</date>
<detail type="volume"><number>27</number>
<caption>vol.</caption>
</detail>
<detail type="issue"><number>4</number>
<caption>no.</caption>
</detail>
<extent unit="issue-pages"><start>603</start>
<end>772</end>
</extent>
<extent unit="pages"><start>628</start>
<end>638</end>
</extent>
</part>
</relatedItem>
<identifier type="istex">1A4E538F0BCA10EF2E4EF72E58762BA3FA387790</identifier>
<identifier type="ark">ark:/67375/6H6-Q2QJSWMB-L</identifier>
<identifier type="DOI">10.1016/S0168-8278(97)80079-7</identifier>
<identifier type="PII">S0168-8278(97)80079-7</identifier>
<recordInfo><recordContentSource authority="ISTEX" authorityURI="https://loaded-corpus.data.istex.fr" valueURI="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-HKKZVM7B-M">elsevier</recordContentSource>
</recordInfo>
</mods>
<json:item><extension>json</extension>
<original>false</original>
<mimetype>application/json</mimetype>
<uri>https://api.istex.fr/document/1A4E538F0BCA10EF2E4EF72E58762BA3FA387790/metadata/json</uri>
</json:item>
</metadata>
</istex>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Asie/explor/AustralieFrV1/Data/Istex/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000501 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Istex/Corpus/biblio.hfd -nk 000501 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Wicri/Asie |area= AustralieFrV1 |flux= Istex |étape= Corpus |type= RBID |clé= ISTEX:1A4E538F0BCA10EF2E4EF72E58762BA3FA387790 |texte= Ultrastructural sequences during liver iron overload in genetic hemochromatosis }}
![]() | This area was generated with Dilib version V0.6.33. | ![]() |