bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization and accumulation of ferritin in hepatocyte nuclei of mice with iron overload
Authors: Smith Andrew G. , Carthew Philip , Francis Jean E. , Edwards Richard E. , Dinsdale David 
Published: March 2007

After a single subcutaneous dose of iron-dextran (600 mg of iron/kg), iron overload developed in C57BL/10ScSn mice. At 4, 24 and 78 wk liver nonheme iron concentrations were 67-, 42- and 21-fold higher than controls, respectively. Much of the iron was in macrophages, but hepatocytes were also strongly positive for Perls' stainable iron. One feature was the development of iron-positive nuclear inclusions in hepatocytes. After a delay of at least 8 wk when no stainable iron was evident, a maximum of 37% of periportal hepatocytes contained inclusions by 24 wk. Although this proportion remained constant for the remainder of the study, the size of the inclusions (which were not membrane-limited) increased to > 3 μm in diameter, occupying > 25% of the nuclear volume. The presence of iron in the inclusions was confirmed by energy dispersive x-ray microanalysis. Immunocytochemical studies showed that the iron was present as aggregates of ferritin. Quantitation of nonaggregated ferritin molecules by image analyses after electron microscopy demonstrated that within 4 wk ferritin levels in cytoplasm and nucleoplasm had greatly increased but that there was a concentration gradient of approximately one order of magnitude across the nuclear envelope.
These findings are consistent with the hypothesis that in iron-loaded mouse hepatocytes there is a slow passage of ferritin-molecules through the nuclear pores; the gradient is maintained by the continual aggregation of ferritin within the nucleus. Intranuclear ferritin may provide a source of iron for catalyzing hydroxyl radical formation in nuclei during some toxic, carcinogenic and aging processes. (HEPATOLOGY 1990;12:1399-1405).
Quantification of hepatic iron with CT and MRI: Practical considerations
Authors: Kier Ruben 
Published: March 2007

The diagnostic efficacy of magnetic resonance (MR) and computed tomography (CT) for detection and quantification of hepatic iron was assessed in a series of patients under investigation for clinical or biochemical evidence of hepatic iron overload. Thirty patients underwent MR imaging (SE 30,60/1000 or SE 30,60/2000) at 0.5 Tesla with calculation of hepatic T2 and liver to paraspinous muscles signal intensity ratios. Twenty-nine patients also had measurement of hepatic attenuation on noncontrast CT images. Results of these imaging studies were correlated in all patients with quantitative iron determination from liver biopsy specimens. The best predictor of liver iron among parameters studied was the ratio of the signal intensities of liver and paraspinous muscle (L/M) on a SE 60/1000 sequence. Both MR using L/M ratios and CT were sensitive methods for detection of severe degrees of hepatic iron overload with 100% of patients with hepatic iron on biopsy > 600 μg/100 mg liver dry weight detected on the basis of L/M < 0.6 or CT attenuation > 70 Hounsfield units (HU). The MR parameter, however, was more specific than CT (100 vs 50%) and showed a higher degree of correlation with quantitated hepatic iron from biopsy. T2 measurements showed poor correlation with hepatic iron, due to difficulty in obtaining precise T2 measurements in vivo when the signal intensity is low. None of the parameters utilized was sensitive for detecting mild or moderate degrees of hepatic iron overload.
We conclude that MR and CT are sensitive techniques for noninvasive detection of severe hepatic iron overload, with MR providing greater specificity than CT. Lesser degrees of iron deposition, however, may go undetected by our current imaging techniques.
Detection of hepatitis C viral RNA by the polymerase chain reaction
Authors: Lucey Michael , Traber Peter G. 
Published: March 2007

These studies used the polymerase chain reaction (PCR) to identify hepatitis C virus (HCV) RNA in clinical samples collected from patients with chronic liver disease or from blood donors. The relative role of this assay compared with detection of HCV antibodies in serum was evaluated. Weiner and colleagues found that 9 of 15 patients with non-A, non-B (NANB) chronic hepatitis and the only patient with cryptogenic cirrhosis had persistent antibodies to a nonstructural protein of HCV (C100-3). Seven of the 10 antibody-positive patients had HCV RNA detected by a highly sensitive PCR assay; two of the antibody-negative patients also had HCV RNA. The pattern of viral RNA and antibody was evaluated in one patient with acute posttransfusion NANB hepatitis (PTNANB) and in three chimpanzees with acute infection. Viral RNA was detected early after infection and, in each case, before the appearance of antibody. In one chimpanzee, viral RNA disappeared when antibody became detectable. The authors conclude that most patients with chronic NANB liver disease have HCV infection.
Garson and colleagues found that 6 of 1,100 donor blood units were repeatedly positive for antibodies to the C100-3 antigen (anti-C100-3). Only one of these six donor units was found to contain HCV RNA by a “nested PCR” assay. Nested PCR refers to the use of two successive rounds of amplification, with the second round using primers internal to, or nested within, the original two primers. The positive donor unit was the only one of the six antibody-positive units to cause posttransfusion hepatitis in a recipient. Sera from three other confirmed cases of posttransfusion hepatitis were evaluated and in each case one donor unit of blood was found to contain HCV RNA and anti-C100-3. The authors concluded that anti-C100-3 may not be a good predictor of infectivity in blood donors and that direct identification of viral RNA may be required.
Omeprazole and aryl hydrocarbon hydroxylases: Should we be worried?
Authors: Kolars J. C. , Turgeon D. K. , Watkins P. B. 
Published: March 2007

Diaz and colleagues have carefully studied the effects of omeprazole on the expression of cytochrome P-450 in primary cultures of human hepatocytes. When omeprazole was added to the culture medium in varying concentrations, there was an increase in P-450IA2 protein and mRNA concentrations, an increase in de novo synthesis of P-450IA2 protein, and an increase in microsomal catalytic activities characteristic of P-450IA2 (phenacetin deethylase and acetanilide hydroxylase). Omeprazole treatment also resulted in an increase in both enzymatic activity characteristic of P-450IA1 (ethoxyresorufin deethylase and benzpyrene hydroxylase) and concentration of P-450IA1 mRNA. In contrast, omeprazole appeared to have no significant effect on expression of other P-450s within the P-450II or P-450III families in the hepatocytes. To validate these in vitro observations, liver biopsy specimens were obtained from five patients before and after a 4-day course of pharmacological doses of omeprazole. In each patient, omeprazole treatment appeared to result in a two- to eightfold increase in P-450IA2 immunoreactive protein and P-450IA1 and P-450IA2 enzymatic activities.
The authors conclude that omeprazole is an inducer of P-450IA2 and probably P-450IA1 in human liver. Induction of these enzymes could potentiate the bioactivation of carcinogens or the hepatotoxicity of some drugs such as acetaminophen.
Cholestasis and changes of portal pressure caused by chlorpromazine in the perfused rat liver
Authors: Akerboom Theodorus , Schneider Ingo , vom Dahl Stephan , Sies Helmut 
Published: March 2007

Chlorpromazine (10 μmol/L) causes a marked increase in portal pressure in perfused rat liver. Simultaneously, oxygen consumption, hepatic clearance of taurocholate and bile flow are diminished. These effects are prevented by the cyclooxygenase inhibitors indomethacin (15 μmol/L), acetylsalicylate (3 mmol/L) or ibuprofen (200 μmol/L). On addition of chlorpromazine the liver releases increased amounts of prostaglandin D2; this increase does not occur in the presence of indomethacin.
At higher concentrations of chlorpromazine (100 μmol/L) the inhibition of taurocholate clearance and bile flow is accompanied by only a moderate increase of portal pressure, and indomethacin is without effect. At this high concentration, substantial cell damage, as indicated by the release of lactate dehydrogenase, is present.
We conclude that arachidonic acid—derived metabolites, notably prostanoids, are involved in the inhibition of bile flow and of taurocholate clearance observed at low concentrations of chlorpromazine. The data suggest that changes in the microcirculation are responsible for the impairment of the liver functions. At higher concentrations of chlorpromazine the cell toxicity of the drug becomes prominent. (Hepatology 1991;13:216-221).
Ultrastructural localization of interferon-producing cells in the livers of patients with chronic hepatitis B
Authors: Dienes Hans P. , Hess Georg , Wöorsdörfer Marita , Rossol Siegbert , Gallati Harald , Ramadori Giuliano , Büschenfelde Karl-Hermann Meyer Zum 
Published: March 2007

Cells expressing α- and γ-interferon were localized in the liver tissue of patients with chronic hepatitis B by means of light and electron microscopy using monoclonal antibodies. Interferon-positive cells were regularly seen in the infiltrating mononuclear cells, and the number showed a good correlation with the degree of the necroinflammatory activity of the disease. In chronic persistent hepatitis and in normal livers, they were infrequent or virtually absent. α-Interferon was shown to be positive in lymphocytes, polymorphonuclear leukocytes and fibroblasts, Kupffer cells and, weakly, in the cytoplasm of a few hepatocytes in cases of active hepatitis, whereas γ-interferon was demonstrated only in lymphocytes. The expression of human leukocyte class I antigens on hepatocytes showed a close association with the number of interferonproducing cells, but not with the presence of virus particles and HBcAg in liver cells, when studied using electron microscopy and double-labeling.
Interferon seems to be an important regulator of the local immune response in the liver in patients with chronic hepatitis B. Its functions may play a role in inducing the human leukocyte class I antigen expression on hepatocytes, thus enhancing the elimination of virus-containing hepatocytes by major histocompatibility complex-restricted cytotoxic lymphocytes. (Hepatology 1991;13:321-326).
The role of methanethiol in the pathogenesis of hepatic encephalopathy
Authors: Blom Henk J. , Ferenci Peter , Grimm Georg , Yap Sing H. , Tangerman Albert 
Published: March 2007

Mixed disulfides of methanethiol represent a relative estimate for an exposure to methanethiol. The concentrations of methanethiol-mixed disulfides, methionine, 4-methylthio-2-oxobutyrate and ammonia were measured in patients with different stages of hepatic encephalopathy, in patients with chronic kidney failure and in healthy subjects. In patients with hepatic encephalopathy, the mean serum concentrations of all these compounds were elevated. However, the elevations of methanethiol-mixed disulfides were small and partly caused by decreased renal function. In addition, the levels of methanethiol-mixed disulfides did not differ significantly between the different grades of hepatic encephalopathy. The concentrations of methanethiol-mixed disulfides were substantially lower than those previously observed in healthy subjects after an oral methionine load or in a patient with a deficiency in methionine adenosyltransferase, the latter without causing encephalopathy. We concluded that the role of methanethiol in the pathogenesis of hepatic encephalopathy is probably minor, if not insignificant.
In the patients with hepatic encephalopathy, a significant correlation was found between the concentrations of methionine and 4-methylthio-2-oxobutyrate and between 4-methylthio-2-oxobutyrate and methanethiol-mixed disulfides, supporting the theory that methanethiol is formed by way of the methionine transamination pathway. Evidence is provided that, besides the methionine transsulfuration pathway, the transamination pathway is also impaired in patients with hepatic encephalopathy. (Hepatology 1991;13:445-454.)
Localizing glucose transport proteins: Active investigation of passive carriers
Authors: Gumucio Jorge J. , Kaunitz Jonathan D. 
Published: March 2007

The “liver” isoform of the facilitated diffusion glucose transporter is expressed predominantly in liver, intestine, kidney, and pancreatic islet α-cells. The apparent molecular mass of the transporter in liver, kidney, and intestine is different, as detected by Western blot analysis of membrane proteins using antipeptide antibodies. However, as assessed by Northern blot analysis and molecular cloning, the same mRNA is expressed in these tissues, indicating that there are tissue-specific posttranslational modifications of the same transporter polypeptide. As determined by immunofluorescence analysis on frozen tissue sections, the liver glucose transporter is present on the sinusoidal membrane of hepatocytes, on the basolateral membrane of fully differentiated absorptive intestine epithelial cells, and on the basolateral membrane of proximal tubule cells of the kidney nephron. This localization is consistent with the involvement of the liver glucose transporter in several key steps of glucose metabolism: glucose uptake and release by the liver and absorption or reabsorption by epithelial cells of the intestine and kidney, respectively.
The localization of two glucose transporter isoforms was mapped in the rat kidney: the high-Michaelis constant (Km; 15-20mM) low-affinity “liver” transporter and the low-Km (1-2mM) high-affinity erythroid/brain transporter. Both are basolateral membrane proteins, but the liver transporter was present exclusively in the S1 part of the proximal tubule, whereas the erythroid/brain transporter was expressed at variable levels in different nephron segments. Staining intensity was low in the straight proximal tubule (S3), intermediate in the medullary thin and thick ascending limbs, and highest in connecting segments and collecting ducts. In the collecting duct, the erythroid/brain glucose transporter was expressed at the highest level in intercalated cells; less was present in principal cells. In the papilla, only intercalated cells expressed this transporter isoform. These results suggest specific involvement of each transporter isoform in transepithelial glucose reabsorption by different segments of the proximal tubule. They also indicate that while the liver glucose transporter is present in gluconeogenic cells, there is a good correlation between the level of expression of the erythroid/brain glucose transporter and the glycolytic activity of the different nephron segments.
Increased tumor necrosis factor-α receptor number in chronic hepatitis B virus infection
Authors: Lau Johnson Y. N. , Sheron Nick , Nouri-Aria Kayhan T. , Alexander Graeme J. M. , Williams Roger 
Published: March 2007

Production of the antiviral cytokine, tumor necrosis factor-α is increased in chronic hepatitis B virus infection, and clinical studies of tumor necrosis factor-α have indicated a proviral effect at higher doses. To determine whether this might be related to abnormal cell surface tumor necrosis factor-α receptor expression, binding characteristics of cell surface tumor necrosis factor-α receptor on peripheral blood mononuclear cells in chronic hepatitis B virus carriers were studied using radioiodinated recombinant tumor necrosis factor-α. The specific binding curves generated were analyzed according to the method of Scatchard to determine cell surface receptor numbers and dissociation constants.
A single class of cell surface tumor necrosis factor-α receptor was demonstrated on peripheral blood mononuclear cells and mononuclear subsets. The median number (range) of cell surface tumor necrosis factor-α receptors on peripheral blood mononuclear cells from controls (n = 11), chronic hepatitis B virus patients seropositive for hepatitis B virus DNA (n = 8) and seronegative for hepatitis B virus DNA (n = 8) were 2,329 (range = 1,538 to 3,133), 3,375 (range = 2,300 to 6,718) (p < 0.01) and 3,113 (range = 2,229 to 5,246) (p < 0.05) sites/cell, respectively. They all had similar dissociation constants of 8.4 × 10−10 mol/L (range = 4.1 to 16.9), respectively. Further dissection of the peripheral blood mononuclear cells showed that this increase in cell surface receptor number was confined to the monocyte fraction (p < 0.01). Plasma tumor necrosis factor-α levels in five patients with increased monocyte cell surface tumor necrosis factor-α receptor numbers were also elevated. No correlation between cell surface tumor necrosis factor-α receptor number and serum AST, HBsAg, hepatitis B virus DNA or liver histology was observed.
These data indicate that cell surface tumor necrosis factor-α receptor number is increased in monocytes but normal in lymphocytes and support previous observations that monocytes are activated in chronic hepatitis B virus infection. (HEPATOLOGY 1991;14:44-50.)
Visualization of the interaction of native and modified lipoproteins with parenchymal, endothelial and Kupffer cells from human liver
Authors: Kleinherenbrink-Stins Monique F. , van de Boom Hans J. , Schouten Donald , Roholl Paul J. M. , van der Heyde Niels M. , Brouwer Adriaan , Berkel Theo J. C. V. , Knook Dick L. 
Published: March 2007

The interaction of low density lipoprotein, acetylated low density lipoprotein and apolipoprotein E—free high density lipoprotein with parenchymal, endothelial and Kupffer cells of human liver was visualized. For this purpose, the fluorescent phospholipid analog 1,1′-dioctadecyl-3,3,3′,3′-tetramethyl indocarbocyanine perchlorate was used to label the lipoproteins. The involvement of both parenchymal and nonparenchymal cells in the uptake of 1,1′-dioctadecyl-3,3,3′,3′-tetramethyl indocarbocyanine perchlorate—labeled low density lipoprotein and acetylated low density lipoprotein was studied using in vitro perfusion of human liver tissue blocks. In addition, primary hepatocyte cultures were used to visualize the interaction with 1,1′-dioctadecyl-3,3,3′,3′-tetramethyl indocarbocyanine perchlorate-labeled apolipoprotein E—free high density lipoprotein and (modified) low density lipoprotein.
1,1′-dioctadecyl-3,3,3′,3′-tetramethyl indocarbocyanine perchlorate-low density lipoprotein showed a time-dependent and concentration-dependent interaction with both hepatocytes and Kupffer cells, although the intensity of the interaction with parenchymal cells varied strongly among the liver donors. Uptake of 1,1′-dioctadecyl-3,3,3′,3′-tetramethyl indocarbocyanine perchlorate-low density lipoprotein by both cell types was strongly inhibited by the presence of excess unlabeled low density lipoprotein in the (perfusion) medium. Methylation and hydroxyac-etaldehyde treatment of low density lipoprotein prevented the uptake of low density lipoprotein. This indicated that the uptake of low density lipoprotein by Kupffer and parenchymal cells was mediated by the low density lipoprotein receptor.
1,1′-dioctadecyl-3,3,3′,3′-tetramethyl indocarbocyanine perchlorate-acetylated low density lipoprotein was mainly taken up in situ by liver endothelial cells and by a minor population of Kupffer cells. Polyinosinic acid, a known inhibitor of the scavenger receptor, prevented the uptake by liver endothelial cells. Therefore human liver endothelial cells express active scavenger receptors on their surface.
Apolipoprotein E—free 1,1′-dioctadecyl-3,3,3′,3′-tetramethyl indocarbocyanine perchlorate-high density lipoprotein was found to be associated with the membrane of cultured liver parenchymal cells but was not taken up intracellularly, indicating a cholesterol exchange process occurring extracellularly at the plasma membrane. The cellular localization of lipoprotein receptors and uptake of the various classes of lipoproteins are comparable with the situation in rats. (HEPATOLOGY 1991;13:79-90.)
Evaluation of laser spallation as a technique for measurement of cell adhesion strength
Authors: Hagerman Elizabeth , Shim Jaewoo , Gupta Vijay , Wu Ben 
Published: March 2007

AbstractCell adhesion to material surfaces is one of the fundamental phenomena of cellular response to implanted devices. Controlling the strength, dynamics, and mechanics of cell adhesion offer opportunities for designing novel biomaterials for tissue engineering and biotechnology. Many techniques have been developed for the purpose of quantifying various types of cell–biomaterial interaction. One method to evaluate cell affinity for a biomaterial is to measure the stress required to remove adherent cells from the material. This study investigates the possibility of using laser spallation, a technique previously developed for measuring the tensile strength of thin film interfaces, for evaluation of initial cell attachment strength. MC3T3‐E1 preosteoblasts were cultured on fibronectin‐coated polystyrene, a surface known to engage cells in receptor mediated adhesion, and untreated polystyrene, which elicit nonspecific adhesion mechanisms during early stages of cell attachment. The laser spallation technique effectively detached cells from polymer substrates and also distinguished relative cell adhesion strengths to surfaces with known differences in cell binding affinities. Scanning electron micrographs determined that cell detachment resulting from laser spallation left a cleaner surface than jet impingement, possibly suggesting a more complete detachment mechanism. Absolute values of adhesion strengths determined by laser spallation were significantly higher than those found using jet impingement, a previously reported hydrodynamic technique. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2007
Mechanism of degradation of AgCL coating on biopotential sensors
Authors: Shih Chun‐Che , Shih Chun‐Ming , Chou Kuang‐Yi , Lin Shing‐Jong , Su Yea‐Yang , Gerhardt Rosario A. 
Published: March 2007

AbstractAgCl coated Ag foil has been widely used as the biopotential sensor to diagnose problems of the human heart. Evidence shows that quality of AgCl on the electrode could experience degradation during the process of long‐term monitoring for irregular activities of the heart. To study the degradation of AgCl/Ag electrode, new and used electrodes were collected. Electrochemical tests such as open‐circuit potential (OCP), cathodic stripping, electrochemical impedance spectroscopy (EIS), scanning electron microscopy (SEM), and X‐ray mapping of elemental distribution were applied to understand the electrochemical properties of the sensors during the progress of degradation. Results revealed that OCP values shift from positive potential of new sensor to negative potential of used sensor (OCPnew: +30 mV; OCPused: −300 mV, p < 0.05) and a significant difference in impedance (Impedancenew: 3000 Ω; Impedanceused: 1 MΩ, p < 0.05). Ratio of the average AgCl thickness on good and bad eletrocardiographic (ECG or EKG) electrodes is 4.83 (p < 0.05). Simulated degradation by exposing the biosensor to deaerated sweat solution and by cathodic stripping of AgCl proposed that the degradation occurs by cathodic reduction of AgCl due to the presence of hydrogen ions in the low pH value of human sweat under deaerated condition. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2007