摘要:

AbstractAn increased influx and/or a decreased extrusion of calcium across the plasma membrane resulting in an increase in cytosolic‐free calcium could play an important role in the initiation of irreversible cell injury. Therefore, the translocation of calcium across the plasma membrane was probed in the perfused rat liver using multiple indicator dilution methodology. The sucrose space corresponding to the extracellular space amounted to 0.35 ± 0.13 ml per gm liver, and the water space corresponding to the extra‐ and intracellular spaces was 0.97 ± 0.08 ml per gm. The calcium space was always slightly larger (0.42 ± 0.10 ml per gm) than the sucrose space. The calcium space further increased during perfusion with the calcium ionophore A 23187, whereas the sucrose space remained unchanged. Two hours after administration to intact rats of acetaminophen (2 gm per kg) and carbon tetrachloride (2 ml per kg), respectively, the calcium space had increased markedly relative to the sucrose space and relative to the water space, indicating an increased accessibility of the cells to extracellular calcium. Similarly, reperfusion of livers after 90 min of ischemia was associated with an increase in calcium space relative to the sucrose and water spaces. These studies indicate that, in three models of acute liver injury, the net influx of calcium across the plasma membrane is increased early in the evolution of the injury before irreversible damage

ISSN:0270-9139    

DOI:10.1002/hep.1840070602

出版商:W.B. Saunders    

年代:1987

数据来源: WILEY

摘要:

AbstractWhen a small amount of Gram‐negative lipopolysaccharide was intravenously injected into mice which had been injected with heat‐killedPropionibacterium acnes7 days before, massive hepatic cell necrosis was induced and most of the mice died 24 hr later. However, when prostaglandin E1was administered with lipopolysaccharide, remarkable improvements in the survival rate and in the histological changes of the liver were observed. In order to find out how prostaglandin E1suppressed the induction of massive hepatic cell necrosis in this experimental model, we studied the effects of prostaglandin E1on the activation of liver adherent cells, from which the cytotoxic factor is released, and on the protection of hepatocytes from the cytotoxic factor. As a result, prostaglandin E1not only inhibited the activation of liver adherent cells and suppressed the release of the cytotoxic factor, but it also directly affected the hepatocytes and protected them from the cytotoxic fac

ISSN:0270-9139    

DOI:10.1002/hep.1840070603

出版商:W.B. Saunders    

年代:1987

数据来源: WILEY

摘要:

AbstractThe effects of several treatments involving α‐adrenergic mechanisms upon the early stages of rat liver regeneration were examined. Catecholamine concentrations in rat plasma were measured at various times after hepatectomy and were found to be elevated relative to those in plasma from sham‐operated rats. Surgical hepatic denervation or injection of an α1‐adrenergic receptor antagonist (prazosin) reduced incorporation of [3H] thymidine into liver DNA during the first 24 hr after partial hepatectomy. Chronic guanethidine injections (3 to 6 weeks) reduced liver catecholamine levels, but did not affect its ability to regenerate.The inhibition of regenerative DNA synthesis by prazosin was preceded by an alteration in the binding of epidermal growth factor to regenerating liver, which was apparently the result of an increased number of epidermal growth factor receptors. Thus, α1‐adrenergic blockade, which affects both epidermal growth factor receptor binding and subsequent DNA synthesis in hepatocyte primary cultures, can also modulate these processes during liver regenerat

ISSN:0270-9139    

DOI:10.1002/hep.1840070604

出版商:W.B. Saunders    

年代:1987

数据来源: WILEY

摘要:

AbstractRats fed chow containing finely divided elemental iron (from carbonyl‐iron) develop hepatic iron overload resembling human hereditary hemochromatosis in that deposition of iron is primarily in periportal hepatocytes and with hepatic iron concentrations sufficiently high to be associated in the human disease with hepatic fibrosis or cirrhosis. In recent studies using this model, we reported changes in hepatic hemoproteins and heme oxygenase, the rate‐controlling enzyme of heme breakdown. We now report effects of iron‐loading on three enzymes of heme synthesis: 5‐aminolevulinate synthase; the first and rate‐controlling enzyme of the pathway, 5‐aminolevulinate dehydrase (or porphobilinogen synthase), and uroporphyrinogen decarboxylase, the activity of which is decreased in porphyria cutanea tarda, a liver disease in which iron is known to play an important but still poorly understood role. Of the three enzymes, only activity of the dehydrase was altered by iron‐loading: it was decreased significantly as early as 1 week after starting iron feeding, and with marked iron overload was 30 to 32% of control values. The degree of decrease was inversely related (r = −0.77 to −0.88) to the degree of iron overload and was partially reversed within 1 to 3 days when feeding of the iron‐supplemented diet was stopped. The decrease in dehydrase activity was not attributable to lack of reduced glutathione or other disulfide‐reducing agents or to zinc deficiency; nor was evidence found for inhibition by iron compounds or other possible inhibitors present in iron‐loaded livers. Immunochemical studies showed that the amount of 5‐aminolevulinate dehydrase protein decreased in parallel to its decrease in activity, suggesting that iron‐loading produced a reversible imbalance between the rate of synthesis

ISSN:0270-9139    

DOI:10.1002/hep.1840070605

出版商:W.B. Saunders    

年代:1987

数据来源: WILEY

摘要:

AbstractThe etiology of malnutrition and the metabolic effect of aggressive nutritional support by enteral feeding were evaluated in patients with moderately severe alcoholic hepatitis. Among 21 patients presenting with jaundice, ascites, coagulopathy and low grade encephalopathy, the mean digestibilities (intake – fecal excretion/intake × 100) of total energy and fat were subnormal at 74.6 ± 2.9 and 64.5 ± 4.4%, respectively, and nitrogen balance was negative in half the patients with a mean value of +0.74 gm per day ± 1.2. Based on initialad libitumintake of hospital diet, patients were grouped as six patients with adequate caloric intake who underwent a repeated 3‐day balance study to assess the effect of hospitalization (Group I) and eight anorectic patients who underwent a repeat balance study during constant nasoduodenal infusion of the liquid formula Isocal‐HCN in an amount sufficient to provide 35 kcal per kg ideal body weight (Group II). During the initial phase of hospital tray diet, the mean digestibilities of energy, fat, protein and carbohydrate, and the mean nitrogen balance were similar in each group. The digestibilities of each diet constituent and nitrogen balance were similar in both phases of hospital tray diet in patients in Group I. On the other hand, the infusion of Isocal‐HCN to patients in Group II resulted in significant increases over their baseline values in intakes of energy and protein and in digestibilities of energy, fat and protein, and in a 5‐fold increase in nitrogen balance. Provision of essential nutrients by enteric infusion had no effect on fluid balance or degree of encephalopathy. These short‐term studies provide a metabolic basis for enteric formula feeding in improving the intestinal absorption and nitrogen balance of anorectic patients with alco

ISSN:0270-9139    

DOI:10.1002/hep.1840070606

出版商:W.B. Saunders    

年代:1987

数据来源: WILEY

摘要:

AbstractAcetaldehyde, the primary metabolite of ethanol, binds covalently to proteins forming condensation products which have been recently shown to be immunogenic. To assess whether an antibody response against acetaldehyde‐modified protein epitopes is associated with alcoholic liver disease, the serum immunoreactivity against proteins modifiedin vitroby acetaldehyde and against the corresponding unmodified proteins was measured by an enzyme‐linked immunosorbent assay in 58 alcoholics with varying degrees of liver damage. Alcoholics showed significantly higher titers against protein‐acetaldehyde conjugates than against the unmodified protein, independent of the nature of the carrier protein. The highest titers occurred in alcoholic hepatitis patients. Sera of patients with chronic hepatitis of nonalcoholic origin and of healthy controls also reacted with acetaldehyde conjugates, but their titers were significantly lower than those in alcoholic hepatitis patients. Our data support the idea that binding of acetaldehyde to proteins in humans generates antigenic determinants which trigger a corresponding immune response against such epitopes and suggest that this humoral immune response may be implicated in autoantibody formation and liver damage associated with excessive alcohol consum

ISSN:0270-9139    

DOI:10.1002/hep.1840070607

出版商:W.B. Saunders    

年代:1987

数据来源: WILEY

摘要:

AbstractMouse and human extracted liver tissue were examined by indirect immunofluorescent staining and transmission electron microscopy in order to study the alteration of cytokeratin intermediate filaments associated with Mallory body formation. Frozen sections of griseofulvin‐fed mouse liver and human liver of primary biliary cirrhosis and primary sclerosing cholangitis were extracted by Triton X‐100 and nuclease. Indirect immunofluorescent staining was performed by using anticow hoof keratin antibody for mouse liver and anti‐human epidermal keratin antibody (AE1 and AE3) for human liver. Transmission electron microscopy was also performed on extracted and critical point‐dried samples. The griseofulvin‐fed mouse hepatoma cells showed four different types of altered staining pattern based on the indirect immunofluorescent staining of the cytoplasm and Mallory bodies: Type I—cytoplasm(+), Mallory body(−); Type II—cytoplasm(+), Mallory body(+); Type III—cytoplasm(−), Mallory body(+), and Type IV—cytoplasm(−), Mallory body(−). Types I and III were predominant, however, some hepatoma cells which contain Mallory bodies revealed bright cytoplasmic staining (Type II). The nuclear rims were strongly stained. In human liver, AE1 stained Mallory bodies and the bile duct epithelium intensely, but did not stain normal hepatocytes. AE3 mainly stained Mallory bodies and normal hepatocytes, but also stained bile duct epithelium weakly. Indirect immunofluorescent staining for human liver showed the same staining patterns as found in mouse liver, except that Type IV was not observed. Although many hepatocytes which contained Mallory bodies did not react with either of these two antibodies (Type III), some of the hepatocytes were stained, not only with AE3, but also with AE1 (Type II). Transmission electron microscopy revealed that Mallory bodies were often surrounded by numerous intermediate filaments, which is equivalent to the Type II pattern in indirect immunofluorescent staining. This was true of mouse liver frozen sections and primary cultures, as well as human liver studied. The results clearly show that cells associated with Mallory bodies show changes in the expression of cytokeratins as well as rearrangement of intermediate filaments within the cell. Hepatocytes forming Mallory bodies often contain a variable density of intermediate filaments which fail to stain with cytokeratin antibodies, indicating that the antigenic determinants of the intermediate fila

ISSN:0270-9139    

DOI:10.1002/hep.1840070608

出版商:W.B. Saunders    

年代:1987

数据来源: WILEY

摘要:

AbstractHepatic stellate cells play a quantitatively important role in hepatic retinoid metabolism and storage in rats maintained under normal nutritional conditions. Studies were conducted to further explore the biochemical characteristics of hepatic stellate cells. Stellate cells were isolated in high purity and yield from the livers of normal rats. The isolated cells had the morphology expected (on electron micrographs) for stellate cells, and were enriched in retinoids and in the intracellular retinoid‐binding proteins. The composition of the stellate cell lipid droplets was examined. These lipid droplets were isolated in high purity and integrity from frozen and thawed stellate cell preparations by differential centrifugation. We estimate that the lipid composition of stellate cell lipid droplets consisted of approximately 42% retinyl ester, 28% triglyceride, 13% cholesterol (total) and 4% phospholipid. Thus, stellate cell lipid droplets contain substantial levels of both cholesterol and triglyceride, in addition to retinyl esters. Stellate cell homogenates were assayed for both retinol‐binding protein and transthyretin by specific radioimmunoassays. Within the detection limits of these radioimmunoassays, we were unable to detect the presence of either retinol‐binding protein (<9 ng per 106cells) or transthyretin (<11 ng per 106cells) in the stellate cell preparations. Total RNA, prepared from the isolated stellate cells, was examined by Northern blot analysis for retinol‐binding protein mRNA and transthyretin mRNA, using cDNA probes for retinol‐binding protein and transthyretin. Within the sensitivity of these assays, retinol‐binding protein mRNA and transthyretin mRNA were not detected in stellate cells. These findings suggest that stellate cells do not synthesize or accumulate retinol‐bi

ISSN:0270-9139    

DOI:10.1002/hep.1840070609

出版商:W.B. Saunders    

年代:1987

数据来源: WILEY

摘要:

AbstractEndothelial cells of the hepatic sinusoid isolated from mice livers and maintained in culture display typical fenestrae grouped in sieve plates. Treatment with cytochalasin B led to no significant change in the mean diameter of the fenestrae but to an increase in their number and in the porosity of the cells (percentage of the cellular surface opened by the fenestrae) which attained up to 300% of that of the controls. Scanning electron microscopic observations of Triton‐extracted cells revealed that these modifications were related to an alteration of the cytoskeleton. The effect of cytochalasin B could be reversed; 3 hr after removal of the drug, the cells recovered their original aspect with sieve plates scattered over their surface.These observations demonstrate that endothelial fenestrae are inducible structures and that the cytoskeleton seems to be involved in their formatio

ISSN:0270-9139    

DOI:10.1002/hep.1840070610

出版商:W.B. Saunders    

年代:1987

数据来源: WILEY

摘要:

AbstractThe hepatocyte plasma membrane presents a morphological and functional regionalization into three domains: the sinusoidal; the lateral, and the canalicular. The mechanisms responsible for the biogenesis and maintenance of this regionalization are poorly understood. In this work, we have used colchicine and phalloidin, two drugs known to interfere with the secretory processes in hepatocytes, to study whether they also affect the transport of membrane proteins. The localization of three plasma membrane antigens was studied by light and electron microscopy using monoclonal antibodies identifying either the sinusoidal (A39) or the lateral (B1) or the canalicular (B10) domains in normal hepatocytes. In rats injected with colchicine (0.25 mg per 100 gm), A39 moved from the sinusoidal membrane to the lateral and canalicular ones, whereas B10 was displaced from the canalicular to the sinusoidal and lateral membranes, resulting after 8 hr in an almost equal labeling of the three domains with both antibodies. In rats injected daily for 7 days with phalloidin (50 μg per 100 gm), A 39 became mainly localized on the bile canalicular membrane instead of the sinusoidal one; B10 predominated on the canalicular membrane as in controls but in places it labeled the sinusoidal and lateral domains as well. In bile duct‐ligated rats studied for comparison for 4, 10 or 21 days, A39 and B10 localizations evolved as after phalloidin, but the changes were more marked. B1 was not affected by any of the treatments. In conclusion, colchicine, phalloidin and bile duct ligation do not seem to hinder the antigens in reaching the plasma membrane, but induce a redistribution of two of them, suggesting a disturbance in the biogenesis and/or control of the plasma membrane regionalization. Such an abnormal distribution could be involved in—or contribute to—the initiation of chole

ISSN:0270-9139    

DOI:10.1002/hep.1840070611

出版商:W.B. Saunders    

年代:1987

数据来源: WILEY