bluuebunny/crossref_metadata_2025 huggingface dataset:
Randomised, controlled study of transhepatic obliteration of varices and oesophageal stapling transection in uncontrolled variceal haemorrhage
Authors: Burroughs A. K. , Bass N. M. , Osborne D. , Dick R. , Hobbs K. F. , Sherlock S.
Published: August 2010

ABSTRACT— Percutaneous transhepatic obliteration and surgical stapling transection of the oesophagus with the EEA gun were compared prospectively in the treatment of uncontrolled oesophageal variceal haemorrhage unresponsive to conservative measures. Twenty patients with cirrhosis, with a patent portal vein and who were considered suitable for general anaesthesia and surgery, were randomised to two treatment groups (10 patients each). Immediate arrest of haemorrhage was achieved in 17 patients (nine surgery, eight obliteration). In one other patient, stapling transection succeeded where attempted transhepatic obliteration failed, and in another patient obliteration succeeded where attempted transection had failed. One patient continued to bleed and died following attempts at both procedures. Two other patients also died in hospital, without rebleeding following surgery. Variceal rebleeding during the same hospital admission occurred in two patients in the obliteration group and in none after surgery. Oesophageal stapling transection compares very favourably with a non‐surgical technique such as transhepatic obliteration of varices in the emergency treatment of uncontrolled variceal haemorrhage in patients with moderate liver failure.
Acute viral hepatitis with bridging necrosis. Collaborative study on chronic hepatitis
Authors: Tandon B. N. , Nayak N. C. , Tandon H. D. , Bijlani L. , Joshi Y. K. , Gandhi B. M. , Madanagopalan N. , Panchanadam M. , Bose S. L. , Mishra G.
Published: August 2010

ABSTRACT— Bridging necrosis was recorded in 14% of 361 patients with acute viral hepatitis on examination of the liver biopsy. The clinical and biochemical features of acute viral hepatitis with bridging necrosis were compared with acute viral hepatitis with no bridging necrosis (NBN). It was noted that fever of more than 8 days' duration in the pre‐icteric phase, the presence of mild ascites and pedal edema during the icteric phase, increasing or persistently high levels of serum bilirubin even 4 weeks after the onset of the icteric phase and positive hepatitis‐B surface antigen were significantly more common in acute viral hepatitis with bridging necrosis. Hepatitis‐B surface antigen clearance was slow in this group. The long‐term complication of chronic hepatitis was more frequent in patients with acute viral hepatitis with bridging necrosis.
The biliary excretion and pharmacokinetics of mezlocillin in jaundiced patients with external bile drainage
Authors: Dooley J. S. , Gooding A. , Hamilton‐Miller J. M. T. , Brumfitt W. , Sherlock S.
Published: August 2010

ABSTRACT— The biliary excretion and pharmacokinetics of mezlocillin have been studied in jaundiced patients with total external bile drainage through a percutaneous transhepatic catheter. In 10 of 11 studies, 2 g mezlocillin intravenously resulted in biliary concentrations sufficient to exceed the minimum inhibitory concentrations of most common biliary pathogenic organisms. In 6 h, 0.2–6.2% of the dose given was recovered in bile. The biliary clearance was 0.21–7.82 ml/min and increased with the duration of biliary decompression. The serum half‐life of mezlocillin was prolonged (1.81 ± 0.23 h, mean ± SD), and was due to reduced biliary and renal clearance.
The plasma membrane origin of liver‐specific protein (LSP)
Authors: Jensen Donald M. , Hall Cathie , Majewski Terrance
Published: August 2010

ABSTRACT— Liver‐specific lipoprotein (LSP) is a potentially important target antigen for autoimmune liver cell injury, but the complexity of LSP “the preparation” has hindered investigation of anti‐LSP immune responses. In the present study, rabbit LSP and isolated liver plasma membranes (LPM) were compared using electron microscopy and marker enzyme analysis to determine the subcellular site of origin of LSP. These results suggest that LSP “the preparation” is highly enriched with plasma membrane.
A monoclonal antibody reactive with human hepatocytes
Authors: Holmes C. H. , Hawkey C. J. , Gunn Barbara , Austin E. B. , Fisk Alyson , Smith P. G. , Embleton M. J. , Baldwin R. W. , Toghill P. J.
Published: August 2010

ABSTRACT— A monoclonal antibody, RL23/36, reacting preferentially with a determinant expressed on normal human hepatocytes is described. Use of an immunohistochemical technique on frozen sections from a range of 75 human liver biopsy specimens revealed that the determinant detected by RL23/36 was not expressed on hepatocytes from a number of patients with biopsy‐proven liver disease. Although a normal staining pattern was observed in 28 of 29 biopsy specimens from patients with no evidence of liver disease, the antibody did not bind to hepatocytes in some cases of chronic active hepatitis (2/13), alcoholic liver disease (2/9), haemochromatosis (1/1), cirrhosis (1/2) and liver metastases (2/8). Furthermore, as in a previous study undertaken in the rat, the antibody failed to bind to tumour cells in the single human hepatoma observed in this study. These results suggest that further studies using RL23/36 may shed light on the pathogenesis of a number of liver diseases, including primary hepatocellular carcinoma.
Failure to induce selective cholestasis in the rat after long‐term extrahepatic selective biliary obstruction
Authors: Bioulac‐Sage P. , Dubuisson L. , Bedin C. , Balabaud C.
Published: August 2010

ABSTRACT— Forty‐eight hours after extra‐hepatic selective biliary obstruction (SBO), there is evidence of cholestasis in the obstructed lobes (OL). However, some major ultrastructural features of cholestasis are missing. The aim of this work was to investigate the long‐term effect of SBO. One month after surgery, and in comparison with sham‐operated rats, bile flow, liver weight, and liver weight ratio of obstructed/nonobstructed lobes were normal. Furthermore, there was no evidence of cholestasis in OL by light and electron microscopy. Bile duct communications between obstructed and non‐obstructed lobes were evidenced by Indian ink injection. In sham‐operated rats, bile duct communications between ducts of the different lobes were involved in bile drainage. It appears, therefore, that the main reason for the lack of cholestasis 1 month after SBO is the drainage of bile from OL through accessory bile ducts.
Binding properties of mechanically and enzymatically isolated hepatocytes for IgG and C3
Authors: Ramadori G. , Lenzi M. , Dienes H. P. , zum Büschenfelde K. H. Meyer
Published: August 2010

ABSTRACT— The presence of Fc and C3 receptors was studied on mechanically and enzymatically isolated rabbit, mouse and rat hepatocytes as well as on hepatocytes derived from primary cultures. The same cell preparations were used for studying the uptake of an antibody against nuclear antigens. Mechanically isolated hepatocytes were able to bind AIgG and activate complement. However, the same cells were not able to form rosettes with EA or with EAC. Enzymatically isolated hepatocytes did not bind AIgG or activate complement nor did they form rosettes with EA or with EAC. The mechanically isolated cells and the nonviable fraction of the enzymatically isolated cells showed a nuclear fluorescence when incubated with an antibody against nuclear antigens. We conclude that enzymatically isolated hepatocytes lack Fc and C3 binding sites. Furthermore, the damage to the plasma membrane of the non‐viable cells allows the penetration of antibodies against intracellular antigens.
Simultaneous infection with non‐A, non‐B and B viruses in a patient exhibiting different histologic patterns of acute hepatitis
Authors: Dienes Hans‐P. , Grün Martin , Hess Georg , John Hans Dieter
Published: August 2010

ABSTRACT— We present the case of an elderly female patient who developed acute and severe hepatitis with two distinct peaks following blood transfusion. The serological markers and histopathology during the first attack were characteristic for hepatitis non‐A, non‐B (NANBH), whereas the second peak was due to hepatitis B virus (HBV) infection. Electron microscopy revealed morphologic equivalents for both hepatitis agents.
The cellular distribution of vitamin A in the liver
Authors: Wanless Ian R.
Published: August 2010

ABSTRACT— Hepatic vitamin A (VA) is concentrated in lipocytes (fat‐storing cells) but the actual concentration in various cell types has not been measured. In this study hepatocytes from normal and VA‐pre‐treated rats were isolated and the VA content was measured. Because most lipocytes were lysed in the procedure, VA content within lipocytes was estimated indirectly by subtracting total hepatic VA from hepatocellular VA. Hepatocytes contained 10.9% of the total hepatic VA (7.2% in VA‐treated rats). The volume density of lipocytes in whole liver was 0.23% as determined morphometrically (1.45% in VA‐treated rats). From these results it is estimated that the VA concentration in lipocytes is 39 mg/ml (3015 times that in hepatocytes) in normal rats and 69 mg/ml in VA‐treated rats. Lipocyte lipid droplets are estimated to be 26% retinyl palmitate (by volume) in normal rats and 31% in VA‐treated rats.
Chronic hepatitis with nonspecific histological changes. Is it a distinct variant of chronic hepatitis?
Authors: Liaw Yun‐Fan , Sheen I‐Shyan , Chu Chia‐Ming , Chen Tong‐Jong
Published: August 2010

ABSTRACT— A longitudinal follow‐up study has been undertaken in 62 patients with clinicopathologically verified chronic hepatitis with non‐specific reactive histological changes (NSRH) in comparison with 28 patients with chronic persistent hepatitis (CPH), the clinical features of which are quite similar to NSRH. In contrast to the stationary and non‐progressive course of CPH, 45.2% of patients with NSRH, either HBsAg positive or negative, ran a fluctuating course with moderate to marked elevation of SGPT (>200 IU/l). In HBsAg‐positive patients, only those positive for HBeAg and a few negative for both HBeAg and anti‐HBe had fluctuating courses. In addition, patients with apparent clinical and biochemical changes could show histological features of chronic lobular hepatitis (CLH). A few developed chronic active hepatitis and/or cirrhosis on follow‐up biopsy. It is concluded that NSRH is a form of chronic hepatitis different from CPH, but similar to or representing a phase of CLH. It is suggested that NSRH should be categorized as CLH in the classification of chronic hepatitis.
Immunohistochemical demonstration of the cytoplasmic copper‐associated protein in the liver in primary biliary cirrhosis: its identification as metallothionein
Authors: Janssens A. R. , Bosman F. T. , Ruiter D. J. , Van Den Hamer C. J. A.
Published: August 2010

ABSTRACT— Metallothionein was isolated from the liver of rats pretreated with cadmium. Monospecific anti‐metallothionein antibodies were produced in rabbits. Twenty‐six primary biliary cirrhosis (PBC) liver samples and three control liver samples were stained for metallothionein by an indirect immunoperoxidase technique. Nineteen of the PBC samples and the control samples were also stained for copper by Timm's silver sulphide method. In all PBC samples the copper concentration was determined. In addition, the zinc, cadmium, and mercury concentrations were measured in some samples. Eighteen of the PBC samples stained for metallothionein showed marked diffuse cytoplasmic and nuclear staining of a varying number of periportal hepatocytes. In none of them was granular staining detected. None of the control samples showed staining. Fourteen of the PBC samples stained for copper showed diffuse cytoplasmic and granular staining of the periportal hepatocytes. In none of them was nuclear staining detected. None of the control samples showed staining. No elevated zinc, cadmium, or mercury concentrations were found but the copper concentration was increased in 21 of the 26 PBC samples. The number of cells staining for copper and metallothionein was assessed semiquantitatively. Significant correlations were found between the grade of metallothionein staining and the liver copper concentration; the grade of Timm's staining and the liver copper concentration; and the grades of metallothionein staining and Timm's staining. The data suggest that the accumulation of copper induces synthesis of cytoplasmic and nuclear metallothionein, and that the increased amount of cytoplasmic copper is bound to a similarly increased amount of metallothionein.
Alcoholic hyalin‐containing hepatocytes — a characteristic morphologic appearance
Authors: Uchida Toshikazu , Kronborg Ian , Peters Robert L.
Published: August 2010

ABSTRACT— We studied the morphologic appearance of alcoholic hyalin (AH)‐containing hepatocytes in liver biopsies from 14 patients with alcoholic liver disease. Most hepatocytes had a characteristic appearance. The cells were swollen and hydropic with an intact cell membrane. The mitochondria had variable‐sized cristae which were both shortened and elongated. The smooth endoplasmic reticulum was markedly decreased. The rough endoplasmic reticulum was bizarre, with detachment of the ribosomes that surrounded the AH. The hepatocytes that contained AH bodies had lost almost all the glucose‐6‐phosphate activity but had variable amounts of succinic dehydrogenase and diphosphopyridine nucleotide diaphorase activities. The neutrophils admixed with mononuclear cells attached themselves to the hepatocytes and then invaginated into the hepatocytic cytoplasm with focal lysis of the cell membrane mediated via the release of neutrophilic lysosomes. The distortion of protein‐synthesizing organelles and decrease in glucose‐6‐phosphatase activity suggest that the AH‐containing hepatocyte is metabolically decompensated. The final cell death may be related to the neutrophilic attack, rather than the metabolic derangement.
Infection of murine hepatocyte cultures by herpes simplex virus (HSV) 1 and 2
Authors: Ramadori G. , Dienes H. P. , zum Büschenfelde K. H. Meyer , Falke D.
Published: August 2010

ABSTRACT— A study was undertaken of the interaction between liver cells and Herpes Simplex Virus (HSV) in vitro. Hepatocytes were obtained from HSV–resistant (C57/B16) and from HSV‐susceptible (BALB/c, A/J, C3H) mouse strains and cultured according to standard methods. Each culture was infected with several strains of HSV‐type 1 or of HSV‐type 2, respectively. The multiplicity of infection was 5. The cytopathic effect was evaluated by light‐ and electron‐microscopy. The number of infectious particles was determined using rabbit kidney or Vero cell cultures. All evaluations were made at different time intervals after infection. No difference concerning the replication rate of HSV‐1 and 2 in isolated hepatocytes from resistant and susceptible mouse strains was detected. However, a marked difference was observed with respect to the production of infectious particles: HSV‐1 exhibited a good multiplication rate, whereas no production of virus particles was observed with HSV‐2. The data show that mice hepatocytes fail to bear the genotype for resistance to HSV infections.
Effects of short‐term, high‐dose prednisone treatment of patients with HBsAg‐positive chronic active hepatitis
Authors: NAIR PREM V. , TONG MYRON J. , STEVENSON DOUGLAS , ROSKAMP DEBORAH , BOONE CISSY
Published: August 2010

ABSTRACT— We conducted a clinical trial to study the effects of a 10‐week course of prednisone therapy and its withdrawal on serum aminotransferase levels and on hepatitis B virus (HBV) markers in patients with hepatitis B surface antigen (HBsAg) positive chronic active hepatitis (CAH‐B). Eighteen patients with CAH‐B were treated with prednisone, while another 18 patients matched for age, sex, race and sexual preference were followed simultaneously without treatment for the same duration. Nine of 18 prednisone‐treated patients became transiently DNA polymerase positive. All nine patients developed a transient rise in serum alanine aminotransferase (ALT) levels of greater than 300 U/L above baseline values, which was associated with a drop in HBsAg levels from a mean of 186 μg/ml prior to therapy to 92 μg/ml at 6 months following treatment. Six of these patients developed fatigue, anorexia and dark urine, and four also developed either ascites or hemorrhage from esophageal varices, which was accompanied by hepatic encephalopathy. All six of these patients had histologic evidence of CAH with cirrhosis. In comparison, none of the control, untreated patients with CAH‐B had any change in either HBV markers or serum ALT levels. Therefore, even a short course of prednisone in patients with CAH‐B with cirrhosis is detrimental and its use should be discouraged.
Posttransfusion non‐A, non‐B hepatitis. A prospective study
Authors: Barcena R. , Suarez‐Garcia E. , Gil L. A. , Moreira V. F. , Garcia‐Hoz F. , Milicua J. M. , De Miquel D. Boixeda , del Arbol L. Ruiz , Pascasio J. M. , Garcia‐Plaza A.
Published: August 2010

ABSTRACT— We have prospectively studied the clinical data, prognostic factors and chronic liver sequelae in 68 patients who developed posttransfusion non‐A, non‐B hepatitis. The mean incubation period was 5.9 weeks with a range from 2.1 to 12 weeks; 63.5% of the patients were asymptomatic and 60.6% anicteric. The chronicity rate (elevated ALT values for a period of more than 6 months) was 67.6%. The chronicity rate of symptomatic hepatitis (95.5%) was significantly higher than that of asymptomatic hepatitis (54.5%) (P<0.01). Monophasic hepatitis, characterized by a rapid elevation in serum ALT followed by a rapid decline with no further fluctuations, had a chronicity rate (42.5%) significantly lower than polyphasic hepatitis (86.6%) (P<0.05) and plateau type hepatitis (94.4%) (P<0.01). Results of 35 liver biopsies carried out among 46 patients with elevated ALT after 6 months were as follows: chronic active hepatitis, 15 cases; prolonged acute hepatitis, 12 cases; chronic persistent hepatitis, 6 cases; posthepatitis liver changes, 1 case; and secondary hemosiderosis, 1 case.
Immunoglobulin‐containing plasma cells in acute hepatitis
Authors: Mietkiewski J. M. , Scheuer P. J.
Published: August 2010

ABSTRACT— Immunoglobulin(Ig)‐containing plasma cells in human liver were investigated in different aetiological and histological forms of acute hepatitis. Liver specimens from 93 patients with acute hepatitis (A, B, non‐A, non‐B and drug‐induced) were studied by conventional microscopy and by immunoperoxidase staining for IgG, IgA and IgM in paraffin sections. Plasma cells were found in 78 of 93 specimens and Ig‐containing cells in 75. IgG‐containing cells were significantly more abundant in acute hepatitis with bridging necrosis than in other forms (p<0.01), and there were more IgA‐containing cells than in the classical and periportal forms (p<0.05). IgG‐containing cells were more numerous in acute hepatitis with periportal or panacinar necrosis than in the classical form (p<0.05). IgG‐ and IgA‐containing cells were less abundant in drug‐induced hepatitis than in viral hepatitis (p<0.05). Among the viral groups the largest number of IgG‐containing cells was found in non‐A, non‐B hepatitis, while IgA‐containing cells were most abundant in type A. These differences were not statistically significant. IgM‐containing cells were very scanty in all groups studied. It is concluded that Ig‐producing plasma cells are common in acute viral hepatitis and presumably play a part in antibody‐dependent immune reactions in this disease.
The role of prostacyclin in patients with portal hypertension
Authors: Hashizume Makoto , Inokuchi Kiyoshi , Tanaka Kenzo
Published: August 2010

ABSTRACT— The serum levels of prostacyclin in portal venous blood samples from patients with portal hypertension were measured by radioimmunoassay to assess the role of prostacyclin in this clinical entity. Portal venous prostacyclin activity exceeded peripheral venous activity 2–3 fold in both cirrhotics and non‐cirrhotics. The size of esophageal varices showed an inverse relation to the concentration of portal venous prostacyclin in the cirrhotics. There was no significant difference between the portal vein pressure and the size of varices, and the portal vein pressure did not correlate with the concentration of 6 keto‐PGF1a. Thus, serum levels of portal venous prostacyclin may depend on the development of collateral circulation in cirrhotics and increased splanchnic blood flow probably accelerates the washout effect.
Sexual dysfunction in men with alcoholic liver cirrhosis. A comparative study
Authors: Jensen Søren Buus , Gluud Christian ,   The Copenhagen Study Group for Liver Diseases
Published: August 2010

ABSTRACT— Sexual dysfunction in men with alcoholic cirrhosis was investigated in young (< 56 years) outpatients with steady female partners. Sixty‐one per cent (11/18) claimed sexual dysfunction, with erectile dysfunction and/or reduced sexual desire being the most common symptoms. Comparing patients with (n=11) and without (n = 7) sexual dysfunction, no significant differences were found concerning a number of pertinent clinical variables. This should be interpreted with caution, however, owing to the small number of patients in each group. The prevalence and type of sexual dysfunction were not significantly different comparing alcoholic cirrhotic men to chronic alcoholic men without overt liver disease (matched for duration of alcoholism, age and duration of partnership) and to insulin‐dependent diabetic men (matched for age and duration of partnership). However, all groups had a significantly (p< 0.025) raised prevalence of sexual dysfunction when compared to men without chronic disease (matched for age and duration of partnership).
Colchicine effect on bile canalicular motility: long‐term study using isolated cultured hepatocytes and time‐lapse cinephotomicrography
Authors: Oshio C. , Miyairi M. , Watanabe S. , Smith C. R. , Phillips M. J.
Published: August 2010

ABSTRACT— The effect of colchicine on spontaneous in vitro contractions of bile canaliculi was assessed using time‐lapse cinephotomicrography. Colchicine 2.5 μM and/or taurocholate 5 μM were added to the culture medium. The experiment was long‐term, lasting for 13 h. Frame‐by‐frame analysis revealed that colchicine, after a lag period of 4 h, suppressed the number of contractions over the remainder of the 13‐h experimental period, even in the presence of taurocholate (p<0.001). The number of contractions per hour decreased in both the colchicine and combined colchicine‐plus‐taurocholate‐treated groups compared to untreated and taurocholate‐treated controls. These results do not necessarily mean that colchicine has an effect on the contractile process per se, since the contractions, when they occurred, appeared normal. It is likely that the canalicular motility events are related to bile secretion. The reduction in contractions after a lag period likely indicates that secretion is impaired, and hence the need for contractions is reduced. These results support the view that for normal canalicular bile secretory function, microtubules as well as a normal microfilament system are required.
Diagnostic value of the fibrosis of the terminal hepatic venule in fatty liver and chronic hepatitis due to ethanol or other aetiology
Authors: BRUNELLI E. , MACARRI G. , JEZEQULE A. M. , ORLANDI F.
Published: August 2010

ABSTRACT— The frequency of fibrosis of the terminal hepatic venule (FTHV) has been investigated by two observers unaware of the patient's history, in needle biopsy specimens showing normal histology (n = 23), alcoholic steatosis (n = 23), steatosis in diabetes or overweight (n = 26), alcoholic hepatitis (n = 21), or virus‐related chronic active hepatitis (n = 44). FTHV was coded following a scale from 0 to 3 of severity. Minimal (grade 1) FTHV was seen in most venules of biopsies with a normal histological pattern, and was considered a normal feature. Grade 2 of FTHV was absent in the group showing normal histology but was evident in 17.4% – 39.7% of the venules observed in the other groups without attaining diagnostic relevance. The percentage rate of severe (grade 3) FTHV was 0.0, 4.9, 6.6, 18.7 and 2.9 in the respective groups as delineated above. In alcoholic hepatitis, severe FTHV therefore showed a higher frequency than in virus‐related chronic hepatitis (p<0.001), with high values of sensitivity (0.75), specificity (0.93), and predictivity (0.84 positive, 0.98 negative) for ethanol aetiology. The ethanol‐related diagnostic value of FTHV however, was low in steatosis.
Influence of nutritional state on ischemic damage in rat liver
Authors: FREDERIKS WILMA M. , FRONIK GERARD M. , MAR FRANS , JAMES JAN
Published: August 2010

ABSTRACT— The influence of the nutritional state of rats on the volume of necrosis in the liver at 24 h after 60 min ischemia has been estimated using fresh liver slices incubated in tetranitro BT. The volume of necrosis is about 30% in an animal fed ad libitum and about 10% in rats fasted for 24 h. Standardization of the time of feeding using a food dispensing apparatus did not reduce the relatively high individual variation in the extent of liver cell necrosis after ischemia. The beneficial effect of fasting on the extent of liver cell necrosis induced by ischemia may be due to decreased acidosis and/or a change in metabolic status.
Immunohistochemical characterization of inflammatory infiltrates at the site of bile duct injury in primary biliary cirrhosis
Authors: Shimizu M. , Yuh K. , Aoyama S. , Ichihara I. , Watanabe H. , Shijo H. , Okumura M.
Published: August 2010

ABSTRACT— Surgically obtained liver specimens from four patients with primary biliary cirrhosis (PBC), Stages I–II, were studied immunohistochemically using a broad panel of monoclonal antibodies. At the site of bile‐duct injury (CNSDC), the inflammatory cells were recognized to be Coulter T‐11+ (directed against all T‐cells) and OKT‐8+ (directed against cytotoxic/suppressor: C/S T‐cells) cells. The MHC‐class I antigen (i.e. HLA‐A, B, C) was expressed weakly in the cytoplasm of the minority of damaged bile‐duct epithelial cells, and the MHC‐class II antigen (i.e. HLA‐DR) was not expressed. Thus, OKT‐8+ cells may play an important role in the immunologically mediated destruction of ductular epithelium in PBC. Strong MHC‐antigen expression and OKT‐8+ cell infiltration in destructive bile‐duct lesions were not simultaneously observed. In the portal lymphocyte‐rich areas, OKT‐4+ (directed against helper/inducer: H/I T‐cells) predominated over OKT‐8+ cells. B‐lymphocytes were present predominantly in the peripheral zones of the lymphoid aggregates. The distribution of helper/inducer T‐cells and B‐lymphocytes indicates that they may play a role in the induction of immunoglobulin in the lymphocyte‐rich areas. The inflammatory mononuclear cells within the granuloma observed in one patient were Coulter T‐11+, OKT‐8+ and Leu‐3a+3b+ (directed against helper/inducer T‐cells) cells.
Serial transmission of a human non A—non B hepatitis viral strain to HBV‐protected chimpanzees: successive histological and ultrastructural studies
Authors: Degott C. , Trepo C. , Durand‐Schneider A. M. , Degos F. , Potet F. , Feldmann G.
Published: August 2010

ABSTRACT— 1) A NANB agent of human origin was inoculated in HBV‐immunized chimpanzees. Infection was proven in two animals and serially passed to two others. The absence of anti‐HBc in serum and the absence of HBsAg and HbcAg in liver are arguments against the HBV nature of the transmitted infection. Moreover, the reproducible appearance of the NANBcAg/Ab system at each passage from man to chimpanzee and from chimpanzee to chimpanzee, a response not elicited in control animals, suggests that this reaction may be a specific immunologic marker for the strain. 2) NANB infection was transmitted in all chimpanzees. 3) Distinctive hepatic morphologic features were obtained in the liver biopsies of the human donor and the inoculated chimpanzees: eosinophilic alterations of hepatocytes and numerous inflammatory cells. Inflammation was more prominent than necrosis, appearing earlier and lasting longer, but was not topographically close to the eosinophilic changes. 4) On electron microscopy, particles characteristic of NANB agent were observed in the cytoplasm of the hepatocytes. No particles were demonstrated in the nucleus of these cells.
Insulin dependence of M2 pyruvate kinase in primary culture of human liver
Authors: Gali Paule , Wolfrom Claire , Gautier Marthe , Hartmann Lucien
Published: August 2010

ABSTRACT— In the basal state, the presence of L pyruvate kinase (LPK) was constantly observed in primary human liver cell cultures initiated from explants, when cells were examined by immunofluorescence and double labelling. After short‐term insulin incubation, M pyruvate kinase (MPK) appeared. Therefore, both LPK and MPK were located in the same cells. We previously obtained the same results in isolated rat hepatocytes in which we demonstrated that short‐term regulation of M2PK by insulin was a function of dose and/or incubation time. The present work established that similar conditions govern the regulation of this isozyme in vitro in human hepatocytes.
Glafenine‐associated hepatic injury
Authors: STRICKER BRUNO H. CH. , BLOK A. P. ROELAND , BRONKHORST FRANS B.
Published: August 2010

ABSTRACT— Glafenine was associated with hepatic injury in 38 cases. The causal relationship was assessed on the basis of the temporal relationship with drug use, course and exclusion of other causes. In 27 cases a causal relationship was considered likely, i.e. ‘probable’ (12 cases) or ‘possible’ (15 cases), whereas in 11 cases it was either unlikely or unclassifiable. In both the ‘probable’ and ‘possible’ groups 60–70% of individuals were women. Jaundice was present in three‐quarters of cases in both groups. Eosinophilia was more frequent in the group of ‘probable’ cases, and this group had the highest case‐fatality rate (42%). Onset varied from 2 days (after a rechallenge) to 8 months, but most cases appeared between 2 weeks and 4 months after starting therapy. Histology in 22 cases showed a predominantly hepatocellular pattern, varying from spotty panlobular necrosis, centrilobular and (sub)massive necrosis (acute pattern) to fibrosis and cirrhosis (chronic pattern). The chemical structure of glafenine and the clinicopathological pattern it induces resemble that of cinchophen. The incidence is unknown. Either metabolic idiosyncrasy or an immunoallergic mechanism seems to be responsible.
Use of indirect immunofluorescence to show changes in liver actin microfilament staining in inbred mice strains exposed to the mycotoxin sporidesmin
Authors: JORDAN T. W.
Published: August 2010

ABSTRACT— The distribution of microfilaments in cryostat sections of liver from BALB/c and C57BL/6 mice was compared using the F‐actin binding probe rhodaminyl phalloidin and indirect immunofluorescence using a human serum containing anti‐actin autoantibodies. The immunological reactivity of this serum was established by its capacity to immunoprecipitate purified skeletal muscle actin and by its ability to immunoprecipitate a protein which migrated electrophoretically with actin from 35S‐labeled liver cells. Oral administration of the liver toxin sporidesmin did not substantially alter the binding of rhodaminyl phalloidin to microfilaments but the reactivity of the anti‐actin serum with the liver cytoskeleton was diminished 3 h after, and enhanced within 24 h of toxin ingestion. Amounts of actin measured by DNAase inhibition were not altered. The results are assessed in terms of their significance for understanding the way in which sporidesmin causes liver damage.
Trace elements in normal and cirrhotic human liver tissue I. Iron, copper, zinc, selenium, manganese, titanium and lead measured by X‐ray fluorescence spectrometry
Authors: MILMAN N. , LAURSEN J. , PØDENPHANT J. , ASNAES S.
Published: August 2010

ABSTRACT— Trace elements (Fe, Cu, Zn, Se, Mn, Ti, Pb) were measured by X‐ray fluorescence spectrometry in normal liver tissue obtained at autopsy from 74 subjects (44 ♀, 30 ♂), median age 62 years (range 20–87), and in tissue from 27 cirrhotic livers (14 alcoholic, 13 non‐alcoholic cirrhosis). The element content (median and 5–95 percentile interval) in normal livers in mmol/kg dry tissue was: Fe, 16.51 (7.82–39.03); Cu, 0.378 (0.189–0.629); Zn, 4.01 (2.59–9.33); Se, 0.018 (<0.004–0.035); Mn, <0.055 (<0.055–0.237); Ti, <0.146 (<0.146–0.919); Pb, <0.0005 (<0.0005–0.0154). Only copper content showed a sex difference, being higher in males than in females (P<0.04). In both groups of cirrhotic liver, Fe content was within normal, Cu content above normal (P<0.05, P<0.02), and Se content below normal (P<0.0001, P<0.04). Alcoholic cirrhotic livers had lower Zn levels (P<0.02), higher Mn levels (P<0.06), and higher Pb levels (P<0.03) than normal livers.
Prolonged inhibition of hepatitis B virus replication with vidarabine monophosphate in chronic active type B hepatitis
Authors: GUARDIA J. , ESTEBAN R. , BUTI M. , JARDI R. , ALLENDE H. , ESTEBAN J. I.
Published: August 2010

ABSTRACT— Eight patients with chronic (mean 52 months) type B hepatitis (chronic active hepatitis and active cirrhosis) and markers of active viral replication (presence of HBeAg and HBV‐DNA in serum) were treated with Ara‐AMP for 7–12 weeks. The mean follow‐up time was 18.3 months. All but one patient responded to treatment. In seven patients, HBeAg and HBV‐DNA became negative and developed anti‐HBe. One patient lost HBsAg as well as HBeAg and HBV‐DNA. HBcAg in liver tissue became undetectable or greatly reduced in the seven patients in whom it was strongly positive. Aminotransferase and immunoglobulin levels reverted to normal in the seven responders and remained normal through the entire follow‐up period. A second liver biopsy, performed after completion of therapy, showed improvement in six of eight cases, with disappearance of lobular activity. Two patients treated for 12 weeks developed a severe polyneuropathy lasting for 6 months. A 7‐week course of Ara‐AMP seems to induce long‐lasting inhibition of viral replication, along with an improvement in liver function tests and liver histology, without significant side effects. On the other hand, a 12‐week course was associated with the development of a severe and prolonged polyneuropathy.
Transferrin receptor on rat Kupffer cells in primary culture
Authors: KUMAZAWA MASATSUGU , MISAKI MORIHARU , BABA MASARU , SHIMA TERUO , SUZUKI SHIRO
Published: August 2010

ABSTRACT— Kupffer cells may play a role in the turnover of iron in acute viral hepatitis. The transferrin receptor of rat Kupffer cells in primary culture was therefore investigated in this study. Daily specific bindings on 125I‐diferric transferrin (Tf) to rat Kupffer cells in primary culture from day 3 to day 6 of culture were 1.64±0.08%, 4.16±0.05%, 4.34±0.07% and 2.63±0.07%, respectively. The specificity of the Tf binding sites was examined by competition studies showing that galactose (30 mmol·1‐1) and ovalbumin (90 μmol·l‐1) did not compete for the binding sites, but human lactoferrin (50 μmol·l‐1) competed for the binding sites by about 30%. The affinity and capacity of Tf receptor on rat Kupffer cells in 5‐day culture were analyzed according to the method of Scatchard. A single class of 125I‐diferric Tf binding sites with an affinity constant of 1.65 times 107 l·mol‐1 and a capacity of 6.86 times 106 sites/cell was found. After zymosan (500 μg/ml) preincubation for 30 min, the binding capacity increased about 1.7‐fold, and this increase depended upon the increase of the affinity of Tf receptor. These data suggest that Kupffer cells in the activated state accelerate the removal of elevated serum iron.
Human extrahepatic biliary atresia: portal connective tissue activation related to ductular proliferation
Authors: De Freitas L. A. R. , Chevallier Michèle , Louis Dominique , Grimaud Jean‐Alexis
Published: August 2010

ABSTRACT— Surgical bile flow restoration in extrahepatic biliary atresia (EHBA) does not prevent the development of ongoing hepatic fibrosis and cirrhosis. Portal connective matrix was studied on liver biopsies obtained from seven children submitted to portoenterostomy. Electron microscopy and immunohistochemical techniques (using specific antibodies directed against collagen isotypes and associated glycoproteins) were performed. The study of extracellular and cellular components of connective mat ix demonstrated the existence of two distinct areas according to their situation with regard to ductular proliferation: loose connective matrix – mainly composed of finectin, type III collagen, type IV collagen and laminin – associated with microvessels and myofibroblasts proliferation characterized periportal zones adjacent to bile ductules; in areas distant from ductular proliferation, connective matrix appeared dense, composed of type I and type III collagen associated with fibroblasts. The connective matrix pattern observed in periductular areas can be compared to that described in cicatricial and hypertrophic processes where the myofibroblastic cell population is known to play an important role in fibrosis development. Although the connective matrix activation process remains unclear in EHBA, it may be suggested that activation of a connective tissue cellular clone might be responsible for this portal fibromatosis.
Bacteremia in cirrhosis of the liver
Authors: Graudal Niels , Milman Nils , Kirkegaard Erik , Korner Bent , Thomsen Åge Chr.
Published: August 2010

ABSTRACT— In a retrospective study the average yearly incidence of bacteremia in cirrhosis patients was found to be 4.5%. This is about 5–7 times higher than in two general materials of all bacteremic patients from the same hospital. There was no difference between the distribution of bacterial strains in the 43 bacteremic cirrhosis patients and the two general materials of all bacteremic patients.
In situ characterisation of the (peri)portal inflammatory infiltrate in acute hepatitis A
Authors: Sciot R. , Van den Oord J. J. , De Wolf‐Peeters C. , Desmet V. J.
Published: August 2010

ABSTRACT— The portal and acinar zone 1 (periportal) inflammatory infiltrate in acute hepatitis A (HA) strongly resembles piecemeal necrosis (PMN) in chronic hepatitis B (HB). The latter infiltrate has been characterized in detail previously, and a predominance of suppressor/cytotoxic T cells has been demonstrated. For comparison we analyzed the infiltrate in acute HA in three liver biopsies, applying a broad panel of monospecific and monoclonal antibodies. In two cases, helper/inducer T cells surrounded by B lymphoid cells represented the main lymphoid subset in all portal areas. In the third liver biopsy, a case of acute HA superimposed on a pre‐existing chronic HB, the cellular composition of the inflammatory infiltrate varied from one portal tract to another. Despite the morphological resemblance between the inflammatory infiltrate in acute HA and PMN in chronic HB, a clear‐cut difference in the composition of both infiltrates is obvious from our results. By virtue of the presence of numerous suppressor/cytotoxic T cells, PMN in chronic HB represents the morphological expression of a cellular immune response, whereas the predominance of helper/inducer T cells, admixed with B cells and plasma cells in acute HA represents the morphological expression of a humoral immune response.
Lack of hepatitis B virus DNA sequences in sera from patients with acute and chronic liver diseases diagnosed as non‐A, non‐B‐hepatitis
Authors: Slusarczyk J. , Hess G. , Hansson B. G. , Zum Büschenfelde K.‐H. Meyer
Published: August 2010

ABSTRACT— The sera of 15 individuals with transfusion‐associated acute or chronic non A, non B hepatitis, which lacked hepatitis B virus markers, were tested for hepatitis B virus DNA by dot blot hybridization test. Three sera of two patients positive in this test, however, also gave positive results when the labeled plasmid was used as probe instead of labeled HBV‐DNA, indicating false positive results in the initial test. In conclusion, the data indicated that sera of patients with confirmed non A, non B hepatitis do not contain DNA‐sequences in the serum hybridizing with HBV‐DNA.
The fate of electron opaque tracers (horseradish peroxidase and lanthanum chloride) during valproic acid‐induced choleresis
Authors: Jezequel A. M. , Macarri G. , Rinaldesi M. L. , Venturini C. , Lorenzini I. , Orlandi F.
Published: August 2010

ABSTRACT—Horseradish peroxidase (HRP) and lanthanum chloride (LaCl3) are useful tools for, respectively, the study of vesicular transport through the hepatocyte and the study of the permeability of junctional complexes. These tracers have been used to detect the changes associated with the choleresis independent of bile acids induced by valproic acid (VPA) in rats. The animals were given a single dose of VPA (600 mg/kg, ip). HRP (100 mg/kg) or 5 mM LaCl3were given intraportally after 1 h, when bile flow had increased twofold. The excretion of HRP in bile was measured colorimetrically up to 2 h after HRP. Ultrastructural morphometry was conducted on liver of intact rats taken from 1 to 40 min after HRP. The volume density (VD) of HRP‐containing vesicles and of HRP‐containing multivesicular bodies (MVB) was counted. In VPA‐treated rats, HRP appeared in bile with a peak showing at 5 min against 20 min in controls, but the total amount of HRP excreted was less than in controls. The intrahepatocytic vesicular transport of HRP was also modified, showing a peak at 3 min in VPA‐treated rats compared to 10 min in controls, together with a decreased VD of pericanalicular vesicles. This was accompanied by an increase of HRP‐containing MVB, already evident at 5 min. VPA‐induced changes in HRP transport through the hepatocytes appeared twofold: 1) during VPA‐induced stimulation of bile flow, there was an early and short‐lived increase of transcellular transport and biliary elimination of HRP: 2) a diversion of HRP towards the indirect, lysosomal pathway apparently occurred, in agreement with previous findings concerning the formation of numerous cytolysomes induced by VPA (Hepatology1984:4: 1159–1166). The decreased amount of HRP excreted in bile could be accounted for by a diversion of HRP towards the degradation pathway. The pattern of distribution of LaCl3was similar in VPA‐treated animals and in controls, suggesting that gross structural alterations of the junctional complexes are unlikely to occur during VPA‐induced choleresis.
Natural killer (NK) cell activity and its in vitro response to interferon‐α(Le) in chronic liver diseases and hepatocellular carcinoma
Authors: Hirai Nobuyuki , Kato Yasuhiro , Kobayashi Kenichi , Hattori Nobu
Published: August 2010

ABSTRACT‐ The natural killer (NK) cell activity of peripheral blood lymphocytes (PBL) in patients with various chronic liver diseases, and its in vitro response to human interferon‐α(Le) were investigated using a 16‐h 51‐Cr releasing cytotoxicity assay against YAC‐1 or RSa target cells. The NK cell activity was found to be higher in chronic active hepatitis (CAH) and liver cirrhosis (LC) patients without HCC, whereas it was slightly lower in LC patients with hepatocellular carcinoma (HCC), than in normal controls. By the addition of IFN‐α(Le) in vitro, the NK cell activity was clearly and dose‐dependently augmented, even in chronic liver diseases, as well as in normal controls. The magnitude of this augmentation by 10000 IU/ml of IFN‐α(Le) in the various chronic liver diseases was not significantly different from that in normal controls. The results suggested that the response of NK cells to IFN‐α(Le) is not impaired even in chronic liver disease conditions, while the level of NK cell activity may vary according to the type of chronic liver disease and may decrease in patients with HCC.
The blood hepatocytic barrier: a light microscopical, transmission‐ and scanning electron microscopic study
Authors: Horn Thomas , Lyon Hans , Christoffersen Per
Published: August 2010

ABSTRACT‐ The normal blood hepatocytic barrier (BHB), comprised by the endothelial lining cells and the perisinusoidal space, was investigated, and it was concluded that the BHB is a complex structure in which each individual part serves several functions. Immunohistochemical staining for factor VIII showed endothelial lining cells to be positive. By TEM and SEM the endothelial cells were seen to be fenestrated without a basal lamina. They possess numerous endocytotic vesicles. The perisinusoidal space contains the lipocytes and a matrix composed of fibrils, and a microfilamentous to granular material. The nature of these matrix components was poorly analyzable by conventional methods. Lipocytes were visualized by LM in: 1) sections stained with oil red 0 after fixation in Baker's formol‐calcium and following post‐fixation in dichromate, and 2) toluidine‐blue‐stained Epon‐embedded sections. TEM revealed numerous cytoplasmic processes rich in microfilaments encircling the sinusoids.
Malignancies following long‐term azathioprine treatment in chronic liver disease
Authors: Tage‐Jensen U. , Schlichting P. , Thomsen H. F. , Høybye G. , Thomsen Aa. C. ,   The Copenhagen Study Group for Liver Diseases
Published: August 2010

ABSTRACT— One hundred and fifty‐four patients with histologically verified nonalcoholic chronic liver disease were randomized to azathioprine or prednisone treatment. After a median of 91 months observation time, the cause of death was assessed retrospectively. Autopsy was performed in 82% of 71 deaths. In the azathioprine group 33% (13/39) died from malignant neoplasia, and in the prednisone group (13%) (4/32) (p = 0.08). Considering a possible fatal outcome as a consequence of treatment, this finding urges caution in the long‐term application of azathioprine at the usual dose level.
Serum aminoterminal procollagen type III peptide in acute viral hepatitis. A long‐term follow‐up study
Authors: Bentsen Kirsten D. , Hørslev‐Petersen KIM , Junker Peter , Juhl Erik , Lorenzen Ib ,   The Copenhagen Hepatitis Acuta Programme
Published: August 2010

ABSTRACT— The development of chronic viral liver disease is associated with increased deposition of connective tissue in the liver. The aminoterminal propeptide of procollagen type III (P‐III‐NP) is considered to reflect the metabolism of collagen type III, one of the major collagen types in liver fibrosis. The purpose of the present study was to elucidate, whether S‐P‐III‐NP in patients with viral hepatitis was related to injury and repair processes in the liver. S‐P‐III‐NP was determined in a prospective longitudinal study of 63 patients with acute viral hepatitis followed to healing or development of chronic liver disease. Two assays were applied. The P‐III‐NP Ria‐gnost assay, which measures mainly the intact propeptide, and the P‐III‐NP Fab‐assay, in which the antibody exhibits equal affinity to the intact propeptide as well as the degradation product col I. At the onset of viral hepatitis, S‐P‐III‐NP determined in either assay was equally elevated in the two groups. From the second month of follow‐up, significantly higher levels in both assays were observed in patients developing chronic disease. During follow‐up, the highest P‐III‐NP RIA‐gnost values were seen in patients with chronic active hepatitis, and active cirrhosis. S‐P‐III‐NP decreased towards normal levels during development of inactive cirrhosis. In the individual patient, S‐P‐III‐NP Ria‐gnost was positively related to transaminases. During follow‐up of uncomplicated hepatitis a normalization of transaminases occurred before normalization of S‐P‐III‐NP RIA‐gnost. Considering, that S‐P‐III‐NP, in contrast to the conventional laboratory variables, reflects the metabolism of type III collagen, it is assumed that determination of S‐P‐III‐NP may provide new information on fibrogenesis in viral liver disease.