bluuebunny/crossref_metadata_2025 huggingface dataset:
Hepatocellular carcinoma associated with second primary malignancy
Authors: Lin Deng‐Yn , Liaw Yun‐Fan , Wu Cheng‐Shyong , Chang‐Chien Chi‐Sin , Chen Pang‐Chi , Chen Tong‐Jong
Published: August 2010

ABSTRACT— In a consecutive series of 562 patients with pathologically documented hepatocellular carcinoma (HCC), 12 patients (2.1%) were found to have a second primary malignancy elsewhere. Of these, eight were male, four female, with ages ranging from 49 to 76 years (mean 60.7 ± 9.3 years). The associated cancers included eight cases of gastric cancers, an esophageal cancer, a stump cancer, a case of myelocytic leukemia and a histiocytic lymphoma. Eight cases had both malignancies diagnosed at the same admission. In the other four, HCC were detected after an interval of 4, 10, 12 and 39 months. Two had received previous chemotherapy or radiotherapy. Fifty percent of the 12 patients were hepatitis B surface antigen (HBsAg) positive. Their liver function tests and alpha‐fetoprotein levels were consistent with those of patients with HCC alone. The results suggest that the occurrence of HCC concomitant with or arising after another primary malignancy in Taiwan is not rare.
Systemic haemodynamics, renal and platelet function during chronic propranolol administration in patients with compensated cirrhosis
Authors: Meacci Egidio , La Villa Giorgio , Laffi Giacomo , Cominelli Fabio , Di Donato Marisa , Dabizzi Piero , Albani Fiorenzo , Gentilini Paolo
Published: August 2010

ABSTRACT— Chronic propranolol administration is followed by some haemodynamic alterations, which may impair renal function. It has also been suggested that it may reduce platelet production of proaggregatory thromboxane (TX) A2. We therefore evaluated cardiac index (CI), systemic vascular resistance (SVR), creatinine clearance, daily sodium excretion under controlled sodium intake, platelet aggregation and platelet TXA2 production during whole blood clotting in eight patients with cirrhosis, portal hypertension and no ascites, before and after 3 months of propranolol administration. Liver function was also assessed by evaluating the galactose elimination capacity (GEC) and galactose clearance (Cgal). The expected, significant reduction of CI and increase of SVR was observed. Creatinine clearance and sodium balance were unchanged throughout the study. Furthermore, the renal prostaglandin system, as reflected by urinary prostaglandin E2 and TXB2 excretion, was also unaffected by the drug. No modification of platelet aggregation, platelet TXA2 production during whole blood clotting, GEC and Cgal was observed. We conclude that chronic propranolol administration is followed by alterations of CI and SVR, but it does not impair renal function and platelet aggregation in patients with cirrhosis, portal hypertension and no ascites. The maintenance of renal function during beta‐adrenergic blockade is not due to an increased renal production of vasodilating prostaglandins.
The prognostic significance of bacteremia in hepatic cirrhosis
Authors: Graudal Niels , Hubeck Berit , Bonde Jan , Thomsen Åge Chr.
Published: August 2010

ABSTRACT— In order to investigate whether bacteremic cirrhosis patients generally have a more serious prognosis than non‐bacteremic cirrhosis patients the survival rates of 43 bacteremic and 43 matched non‐bacteremic cirrhosis patients were compared. No difference in survival existed between the two groups from the time of cirrhosis diagnosis. However, the survival rate of the bacteremic patients calculated from the onset of bacteremia was significantly shorter than the survival rate of the non‐bacteremic cirrhosis patients calculated from the time of random selection (p < 0.05). Thus the bacteremic patients at the time of bacteremia were generally in a later phase of their disease than the controls at the time of selection. Therefore, bacteremia when it occurs in cirrhosis is a severe prognostic sign, not because of its influence on survival but because of its occurrence late in the course of cirrhosis.
Lymphokines and bile secretion in the rat
Authors: Rustgi Vinod K. , Jones D. Brian , Dinarello Charles A. , Hoofnagle Jay H.
Published: August 2010

ABSTRACT— Sepsis is occasionally accompanied by jaundice which is marked by an intrahepatic cholestasis and scant hepatocyte necrosis. The pathogenesis is unknown. The bile fistula rat was used in this study to investigate the possibility that intrahepatic cholestasis is one of the many systemic effects of the major endogenous pyrogen, interleukin‐1. The effect of acute administration of endotoxin, interleukin‐2 and recombinant rat interferon gamma on biliary secretion and biliary transport mechanisms was also studied. Basal bile flow, peak bile flow and peak sodium taurocholate output were measured after 1 h in all cases, except with recombinant rat interferon gamma where the time interval was 3 h. Endotoxin significantly reduced basal and sodium taurocholate‐stimulated bile flow, as well as sodium taurocholate secretion. No such effect was noted after acute administration of any of these lymphokines or chronic administration of interleukin‐1. The cholestasis induced by endotoxin administration is not mediated by interleukin‐1, interleukin‐2 or recombinant interferon gamma.
Hepatitis B core and surface antigen expression in HBeAg and HBV DNA positive chronic hepatitis B: correlation with clinical and histological parameters
Authors: Dusheiko Geoffrey , Paterson Alan
Published: August 2010

ABSTRACT— The interrelationship between hepatitis B virus (HBV) infection, hepatic injury and clinical activity in chronic HBV infection is incompletely understood. We have scored histologic activity, the expression of hepatitis B core (HBcAg) and hepatitis B surface antigen (HBsAg) and assessed HBV replication to correlate HBV antigen expression with histologic disease. Forty‐seven formalin‐fixed, percutaneous liver biopsies from HBeAg carriers were studied. Twenty‐nine were Black, 16 Caucasian and two Oriental. Fifty‐nine percent had chronic active, 35% chronic persistent hepatitis and 14% cirrhosis. None were positive for antibodies to Human Immunodeficiency Virus (HIV). HBsAg and HBcAg in tissue were detected by immunochemical staining. Diffuse HBsAg staining was observed in 10/15 patients with CPH, but there was no correlation between histologic score and HBsAg expression. Intracytoplasmic HBcAg was observed in patients seroconverting to anti‐HBe, but was also detected in patients with minimal hepatitis. An inverse correlation between histologic score and HBcAg expression was observed. HBcAg expression was more widespread in patients with CPH (mean 37%) than in CAH (mean 18%). A positive correlation was observed between serum aminotransferase concentrations and histologic score. Although no consistent pattern can be discerned, HBcAg expression and hepatic injury are frequently dissociated in patients with chronic HBV infection; complex host responses may determine the variable degree of disease activity and hepatic injury.
Lack of evidence for increased lipid peroxidation in ethanol‐induced centrilobular necrosis of rat liver
Authors: Inomata Tomoo , Rao G. Ananda , Tsukamoto Hidekazu
Published: August 2010

ABSTRACT— The pathogenetic role of lipid peroxidation in ethanol‐induced liver injury was previously supported by demonstration of increased formation of diene conjugates and decreased hepatic levels of reduced glutathione in ethanol‐fed animals and alcoholic patients with liver injury. The present study was carried out to investigate whether these findings can be extended to a rat model that was shown to produce a spontaneous ethanol‐induced liver injury progressing from steatosis to necrosis and fibrosis (Hepatology 6: 814, 1986). Despite the histological evidence of progression from hepatic steatosis to centrilobular necrosis in these animals, diene conjugate formation in mitochondrial and microsomal lipids was not enhanced when compared to pair‐fed controls. In addition, hepatic levels of neither methionine nor glutathione were decreased in the ethanol‐fed animals. The fatty acid composition of mitochondrial phospholipids from these animals was similar to that in the controls. However, in the microsomal phospholipids, the level of arachidonate (20:4) was depressed by about 50% as compared to the controls. These results demonstrate the lack of evidence for a pathogenetic relationship between lipid peroxidation and ethanol‐induced liver injury progressing to centrilobular necrosis. They further suggest that the decreased levels of 20:4 commonly seen after chronic ethanol intake may not be due to a peroxidative loss.
DNA clonal heterogeneity of hepatocellular carcinoma demonstrated by Feulgen‐DNA analysis
Authors: Kuo Sow‐Hsong , Sheu Jin‐Chuan , Chen Ding‐Shinn , Sung Juei‐Low , Lin Chi‐Chung , Hsu Hey‐Chi
Published: August 2010

ABSTRACT— To demonstrate DNA clonal heterogeneity of hepatocellular carcinomas (HCC), the DNA histographic pattern of both primary HCCs and their recurrent or metastatic lesions were studied among 36 patients (33 men and 3 women). Thirty‐six paired aspirations or imprints taken from primary, recurrent or metastatic lesions were stained, using the modified Feulgen method, and the DNA content was measured with a scanning microdensitometer at a wavelength of 550 nm. Paired aspirations or imprints taken from different parts of the same HCC were examined in 17 cases; the DNA distribution patterns were similar in 15 (88%) and differed in only two (12%). A similar DNA histogram was also shown among different tumors in 10 (71%) of 14 patients with multiple HCCs, with a DNA ploidy discrepancy in only four (29%). Two of two subcutaneous metastases and two of three recurrent tumors showed DNA distribution patterns similar to those in their primary HCCs. In summary, a DNA clonal heterogeneity of HCC was found in 19% (7/36). In contrast, the similar DNA histographic patterns found in most instances among different parts of the HCC and between the primary and recurrent or metastatic lesions suggest that HCC may derive from a single cell clone in the majority of cases.
Pressure profile in liver sinusoids
Authors: Henriksen Jens H. , Lassen Niels A.
Published: August 2010

ABSTRACT— A model of pressure profile along the sinusoids in the liver is presented. The major prerequisite is a converging sinusoidal flow pattern through a network of tubes with almost equal diameter. In this case the main hemodynamic resistance is located downstream at the outlet. Different geometric configurations (sphere, cylinder, and sections of these) are considered, and it is concluded that the precise shape of the microcirculatory unit is not crucial. The applicability in cirrhosis is considered in relation to a decreased diameter and number of the sinusoids in this condition. Estimated pressure profiles along the sinusoids indicate a steep downstream pressure fall in cirrhosis, implying that the spatial average of sinusoidal pressure is close to that of the inlet, i.e. portal pressure. Another prediction is an increased blood flow rate (flow rate per vessel) in the region near the outlet of the sinusoids.
Simultaneous detection of epidermal growth factor receptor (EGF‐R), epidermal growth factor (EGF) and ras p21 in cholangiocarcinoma by an immunocytochemical method
Authors: Nonomura Akitaka , Ohta Goroku , Nakanuma Yasuni , Izumi Ryohei , Mizukami Yuji , Matsubara Fujitsugu , Hayashi Morimoto , Watanabe Kishichiro , Takayanagi Nobutatsu
Published: August 2010

ABSTRACT— Expression of the epidermal growth factor (EGF), EGF receptor (EGFR) and ras oncogene product p21 was simultaneously examined in 37 cases with intrahepatic cholangiocarcinoma (CC) by means of an immunocytochemical method. While normal livers were all negative for any of the antigens at the concentration of the antibodies used, EGF‐R was positive in 12 (32.4%) CCs, EGF in 22 (59.5%), and ras p21 in 33 (89.2%). The positive incidence of the three antigens was not different among the histologic subtypes of the tumor. However, the number of EGF‐R‐ and ras p21‐positive tumor cells decreased with progressing histologic tumor grade, but the expression of EGF was not associated with the tumor grade. Expression of the three antigens was not related to the degree of metastatic spread of the tumor. Simultaneous expression of the three antigens was seen only in 4 CCs, and that of EGF‐R and EGF in 4, EGF‐R and ras p21 in 12, and EGF and ras p21 in 20. These data suggest that the expression of EGF, EGF‐R and ras p21 on CC cells is not related to the tumor aggressiveness, and the activation of each respective gene is independent. Furthermore, the data also indicate that an autocrine model for tumor growth, as suggested by a combination of EGF and EGF‐R, may be applicable only to very limited cases of CCs.
Liver adenosine triphosphate and pH in fasted and well‐fed mice after infusion of adenine nucleotide precursors
Authors: Lee Robert G. L. , Clouse Melvin E. , Lanir Amos
Published: August 2010

ABSTRACT— Nutrition is a factor which may affect the liver energy charge. Experiments were performed to determine the effect of starvation and of ATP precursors, adenine and ribose on liver energy stores. The 31P NMR spectra of well‐fed and starved mice livers were studied in a perfusion system using Krebs‐Henseleit buffer (KHB). The ATP precursors, adenine (20 mmol/1) and ribose (80 mmol/1), were then added to determine their effect. Their effect on the ATP dynamics during ischemia and reperfusion were then evaluated. The effects of adenine alone and ribose alone were then determined. The 31P spectra of well‐fed mice demonstrated high ATP content relative to Pi, phosphoesters and phospholipids. Animals starved for 24 h showed very low ATP, high Pi and little or no detectable phospholipids. In starved animals, ATP rose steadily to approximately 50% above the baseline level when precursors were added. Pi decreased to 30% of the baseline after 40 min. Little change was noted in well‐fed animals. The rate of ATP decay did not change with the onset of ischemia, whether the livers were perfused with KHB alone or KHB with precursors. Upon reperfusion, precursors improved the recovery of ATP (81% vs 49% after 20 min ischemia, 44% vs 34% after 30 min ischemia). Addition of adenine alone produced similar results, but addition of ribose alone did not significantly alter ATP recovery. In conclusion, supplying starved or post‐ischemic livers with adenine or ribose and adenine does improve ATP levels.
DNA synthesis in cultured adult rat hepatocytes: effect of serum and calcium
Authors: Sand Tor‐Erik , Gladhaug Ivar Prydz , Refsnes Magne , Christoffersen Thoralf
Published: August 2010

ABSTRACT— We have investigated the influence of serum and of varying Ca2+ concentrations on the DNA synthesis in primary monolayer cultures of adult rat hepatocytes, using a defined basic medium. Supplementation of the medium with 10% horse serum did not significantly affect the time course of the DNA synthesis induced by insulin and epidermal growth factor. Dose effect curves showed that serum moderately sensitized the cells to low concentrations of insulin and slightly sensitized them to epidermal growth factor, but was not required for full responses to maximal concentrations of the hormones. In the serum‐free cultures a wide range of Ca2+ concentrations (0.4–1.8 mmol/1) yielded maximal DNA synthesis, suggesting a broad Ca2+ optimum of the S phase entry in the hepatocyte monolayers.
Liver cell rosettes: structural differences in cholestasis and hepatitis
Authors: Nagore N. , Howe S. , Boxer L. , Scheuer P. J.
Published: August 2010

ABSTRACT— Cholestatic and hepatitic liver cell rosettes, gland‐like formations found respectively in chronic cholestasis and in chronic active hepatitis, represent structural modifications of liver cell plates in response to injury. Differences in cytokeratin expression, ultrastructure and three‐dimensional (3‐D) configuration have been investigated. Cholestatic rosettes are considered to be a form of biliary metaplasia of hepatocytes, linking with newly‐formed bile ductules in adjacent septa and probably providing some protection from injury caused by abnormal bile constituents. Hepatitis rosettes, by contrast, are a form of liver cell regeneration developing in isolated surviving hepatocytes or small groups of hepatocytes within areas of collapse.
Hepatic reticulo‐endothelial function: a correlation of radioisotopic and immunohistochemical assessment
Authors: Triger D. R. , Bialas M. C. , Segasby C. A. , Underwood J. C. E.
Published: August 2010

Using an immunoperoxidase staining technique for muramidase (lysozyme)‐containing cells in liver biopsies, the Kupffer cell population has been compared with the isotope liver scan abnormalities in 43 patients with various liver diseases. A significantly greater degree of scintigraphic abnormality was seen in cirrhotics compared with non‐cirrhotics using both a visually assessed scan scoring technique (p< 0.001) and computer‐generated spleen‐to‐liver (S‐L) relative activity ratios (p<0.01). The mean muramidase‐positive cell count in cirrhotic biopsies was not significantly different from that in non‐cirrhotics, neither was there any significant difference between alcoholic and non‐alcoholic liver disease. The liver mass was shown to be significantly greater (p<0.02) in alcoholic compared with non‐alcoholic disease, but even if corrections were made for this, no significant differences were found. A significant (p<0.02) negative correlation was found between liver scan score and muramidase‐positive cell count in patients with cirrhosis but not in non‐cirrhotic disorders. No significant correlations were observed if the computer‐derived liver mass was taken into consideration. These results suggest that the scan defect seen in liver disease cannot be explained by loss of Kupffer cells alone, although they are consistent with the hypothesis that intrahepatic shunting plays a significant role. Chronic alcohol ingestion does not in itself appear to be a major independent influence.
Expression and clinical significance of pre‐S1 and S2 proteins of HBV in sera of patients with chronic liver disease
Authors: HU KE‐QIN , YU ZHI‐QUN , LI FANG‐HE , HAO LIAN‐JIE
Published: August 2010

To assess the significance of pre‐S proteins expression during chronic hepatitis B virus (HBV) infection, we developed a sensitive labeled avidin biotin ELISA to detect pre‐S1 and pre‐S2 proteins. In serum specimens from 80 patients with chronic liver disease, the frequency of pre‐S1 and S2 proteins was 53.7% and 47.5%, respectively. Furthermore, it reached 87.8% and 77.6%, respectively, in cases with chronic HBV infection, indicating that pre‐S proteins are usually expressed in sera with chronic HBV infection. We found that the expression of pre‐S proteins is closely associated with HBV replicating markers, such as HBV DNA, HBcAg and HBeAg, in sera of patients with chronic HBV infection. Both pre‐S1 and S2 proteins were often concurrently expressed in liver and serum with chronic HBV infection. However, the frequency was slightly higher in liver than in serum, suggesting that it may be clinically valuable to detect pre‐S proteins in serum and liver simultaneously to determine the status of HBV infection. Our results also indicated that pre‐S proteins expression in serum can serve as markers of HBV infection, but cannot be used to estimate the severity and activity of hepatic pathology.
Copper overload in the developing guinea pig liver: a histological, histochemical and biochemical study
Authors: Chesta Jaime , Srai Surjit K. S. , Burroughs Andrew K. , Scheuer Peter J. , Epstein Owen
Published: August 2010

ABSTRACT— The copper profile in Wilson's disease resembles that of human and guinea pig neonates. Microvesicular steatosis is characteristic of early histological damage in Wilson's disease. The aim of this study was to relate the histological, histochemical and ultrastructural changes seen in developing guinea pig liver to the developmental pattern of liver copper in these animals. Copper‐stressed and control guinea pigs were studied. Liver biopsies were stained with haematoxylin and eosin, rhodanine (for copper), orcein (for copper‐associated protein) and oil Red 0 (for fat). Selected specimens were examined by electron microscopy. Liver and serum copper levels and copper oxidase activity were also determined. Fetal liver copper increased during the last trimester of pregnancy, reaching five times the adult level in the perinatal period and falling rapidly in the 4 days after birth. Marked steatosis developed in both control and copper‐stressed guinea pig liver. The fat score correlated strongly with liver copper concentration (r: 0.60; p < 0.001). Orcein and rhodanine staining correlated with liver copper concentration (r: 0.52 and r: 0.40 respectively, p < 0.01). Marked prenatal hepatic steatosis and its postnatal clearance correlates with changes in liver copper concentration. This experimental model provides an opportunity to study the pathogenesis of hepatic steatosis and the relationship between copper retention and steatosis.
Serum antibodies to thymus epithelial cells in non‐A, non‐B and cryptogenic chronic liver disease
Authors: Cassaniy Fabio , Tremolada Federico , Bianchi Francesco B. , Baffoni Laura , Selleri Luca , Benvegnu‘ Luisa , Craxi‘ Antonio , Realdi Giuseppe , Zauli Daniela , Pisi Emilio
Published: August 2010

ABSTRACT—Antibodies against thymus epithelial cells (anti‐TEC) and the basal cell layer (BCLA) of squamous epithelia have been described in association with HDV‐related chronic liver disease (CLD). Data are lacking on their presence during nAnB virus infection. Sera from 51 patients with nAnB post‐transfusion hepatitis, including acute and chronic cases diagnosed during a prospective study on candidates for cardiac surgery, and 167 with various forms of CLD were tested for the presence of anti‐TEC and BCLA using indirect immunofluorescence on human thymus and rat forestomach sections. Both antibodies mainly occurred in nAnB, HDV and cryptogenic CLD (anti‐TEC: 51%, 47% and 42%; BCLA: 29%, 38% and 31%, respectively). The prevalence of anti‐TEC in nAnB CLD turned out to be higher than that recorded in alcoholic, HBV‐related, autoimmune, liver and kidney microsomal antibody positive CLD and primary biliary cirrhosis (p ranging from < 0.03 to < 0.0004). Two monoclonal antibodies (Mabs) to cytokeratins gave a pattern superimposable on that of spontaneous anti‐TEC (both Mabs) and BCLA (only one). Antibodies against epithelial constituents, presumably targeting cytokeratin‐associated antigens, occur not only in HDV CLD, as previously reported, but also in nAnB CLD, where they might represent a diagnostic aid, due to the unavailability of reliable serological markers of nAnB infection. The close similarity of anti‐TEC and BCLA status between nAnB and cryptogenic CLD suggests a nAnB etiology of at least a proportion of chronic liver patients at present scored as cryptogenic.
Effects of repeated atrial natriuretic peptide bolus injections in cirrhotic patients with refractory ascites
Authors: Laffi Giacomo , Marra Fabio , Pinzani Massimo , Meacci Egidio , Tosti‐Guerra Cristina , De Feo Maria Laura , Gentilini Paolo
Published: August 2010

ABSTRACT— The renal and hormonal effects of repeated atrial natriuretic peptide (ANP) boli (1 μg/kg of body weight) were studied in eight cirrhotic patients with refractory ascites. Under basal conditions the patients showed a striking activation of the renin‐angiotensin‐aldosterone system (plasma renin activity 19.3 ± 3.0 μg/ml±h, plasma aldosterone concentration 3.87 ± 0.58 ng/ml) and a tenfold elevation in plasma ANP levels compared to healthy subjects (131.7, range 47.0–288.6, vs. 9.8, range 5.0–15.0, fmol/ml, p < 0.001). The first ANP injection was followed by a remarkable increase in plasma ANP levels and by a slight increase in urinary cyclic guanosine‐monophosphate excretion (from 1050.8 ± 454.8 to 1446.6 ± 822.2 pmol/min). A significant reduction of mean blood pressure (MBP) occurred 5 min after the first injection (from 86.7 ± 7.2 to 79.9 ± 5.8 mmHg, p < 0.05), but values gradually returned to the baseline after 30 min. Heart rate (HR) increased 10 min after the first bolus injection (from 83.75 ± 4.7 to 88.1 ± 4.6 beats/min) and reached baseline values after 30 min. Similar behaviour of MBP and HR was observed after the second, third and fourth bolus injections. Urinary sodium excretion, urinary flow, glomerular filtration rate, plasma renin activity, and plasma aldosterone concentration did not show any significant modification during ANP administration, nor did these parameters change in the following 12‐h recovery period. The striking activation of the renin‐angiotensin‐aldosterone system and probably of other vasoconstricting and sodium‐retaining systems observed in basal conditions in patients with cirrhosis and refractory ascites seems the most likely explanation for the lack of any appreciable natriuretic and diuretic effect after repeated ANP boli.
Persistence of hepatitis B virus DNA after serological clearance of hepatitis B virus
Authors: Tanaka Yuji , Esumi Mariko , Shikata Toshio
Published: August 2010

ABSTRACT— Using Southern blot technique, the state of hepatitis B virus (HBV) DNA in liver tissue was investigated in 16 patients who were sero‐negative for hepatitis B surface antigen (HBsAg) but positive for its antibody (anti‐HBs). In only one case, was HBV DNA found in liver tissue in a heterogeneously integrated form. In this case, digestion with Taq I demonstrated integrated HBV DNA as two definite bands at 1.8 and 0.5 kbp. This suggests that HBV DNA in some cases persists even after HBV infection has been cleared serologically. It is possible that this persistence of HBV DNA plays an important role in hepatocarcinogenesis.
Evidence for the involvement of organelles in the mechanism of ketone‐potentiated chloroform‐induced hepatotoxicity
Authors: Hewitt L. Arthur , Palmason Carol , Masson Solange , Plaa Gabriel L.
Published: August 2010

ABSTRACT—Ketones can potentiate the hepatotoxicity of haloalkanes in animals. This may be due, in part, to changes in organelle susceptibility. Male Sprague‐Dawley rats were administered 15 mmol/kg (po) acetone, 2‐butanone, 2‐hexanone or 50 mg/kg (po) chlordecone or mirex (a nonketonic analog of chlordecone). Eighteen hours later, tests of organelle structure/function were performed (osmotic stress, respiration, and calcium pump activity). Other rats were given14CHCl3(0.5 or 1.0 ml/kg, po) 18 h after chlordecone or mirex administration. Three hours later, the organelle distribution of14C was evaluated. In a final experiment, ketone‐pretreated (chlordecone or 2‐hexanone) animals were killed 6 h after CHCl3administration and evaluated morphologically for evidence of modified organelle response. Acetone and chlordecone, when given alone, enhanced lysosomal fragility to osmotic stress; no changes in functional capacity of mitochondria or microsomes were observed. CHCl3‐derived14C in the mitochondrial fraction increased 2‐fold in chlordecone‐treated rats. Morphological evaluation suggested mitochondria respond differently to CHCl3in ketone‐pretreated (chlordecone or 2‐hexanone) animals compared to corn oil‐pretreated controls. These results support the concept that modifications of organelles contribute to the mechanism of ketone‐potentiation of CHCl3‐induced hepatotoxicity.
Detection of HBeAg/anti‐HBe immune complexes in the reactivation of hepatitis B virus replication among anti‐HBe chronic carriers
Authors: Castillo Inmaculada , Bartolomé Javier , Quiroga Juan Antonio , Porres Juan Carlos , Carreño Vicente
Published: August 2010

ABSTRACT—Sixty‐four chronic hepatitis B surface antigen (HBsAg) carriers with hepatitis B e antibody (anti‐HBe) were followed in order to detect reactivations of hepatitis B virus (HBV) infection and to assess the incidence and specificity of hepatitis B e antigen/hepatitis B e antibody (HBeAg/anti‐HBe) immune complexes (ICs). In 18 out of 19 patients who suffered an increase in alanine transaminase (ALT) values, serum HBV‐DNA reappeared co‐occurring with the peak(s) of transminases. HBeAg/anti‐HBe immune complexes were detected in 17/18 (94.4%) patients positive for HBV‐DNA. In nine of them, the appearance of immune complexes co‐occurred with prednisone therapy, in two following seroconversion after recombinant interferon alpha‐2A treatment, and spontaneously in the remaining seven patients. When ALT levels dropped to normal values, immune complexes as well as HBV‐DNA became undetectable. In conclusion, the detection of HBeAg/anti‐HBe immune complexes seems to be a specific method to detect HBV replication among anti‐HBe positive patients.
Streaming liver VII: DNA turnover in acinus zone‐3
Authors: Zajicek G. , Schwartz‐Arad D.
Published: August 2010

ABSTRACT— Livers of four young, male, random‐bred rats weighing 250 g were fixed in formalin and stained with Feulgen. In each section, 50 hepatocytes were randomly selected and their distance from the nearest terminal hepatic vein was measured with an eye‐piece micrometer. Distance was expressed in two units: 1. micrometer and, 2. cell location, or the cell number separating a sampled cell from the terminal hepatic rim. The sections were scanned with an image cytometer. The tissue was magnified × 400 and digitized into 512 × 512 pixels. The software determined the nuclear boundary and estimated its area and optical absorbance, which was expressed in relative DNA units. One unit equals the absorbance of a diploid lymphocyte. Nuclear area and optical absorbance measurements were made up to 220 μm distance from the terminal hepatic vein which roughly covers zones 2 and 3. Previously we have shown that in zones 1 and 2 hepatocyte nucleus enlarges and becomes polyploid. The present study demonstrates that in zone‐3 this trend is reversed, nuclear area and DNA absorbance decline. The average hepatocyte advances 2 μm daily. In zone‐1 it accumulates daily 0.005 DNA absorbance units and in zone‐3 it loses daily 0.24 DNA absorbance units. It is proposed that in zone‐3 DNA leaves the intact cell in a physiological way. DNA accumulation and polyploidy are regarded here as forms of gene amplification which may be reversed, so that under these circumstances amplified DNA may be “deamplified” and the excess DNA leaves the cell.
Relative risk of hepatocellular carcinoma in HBsAg positive vs alcoholic cirrhosis. A cross‐sectional study
Authors: Hadengue A. , N'dri N. , Benhamou J. P.
Published: August 2010

ABSTRACT— The etiological link between hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC) has been suggested on epidemiologic, serologic and molecular grounds. This link has, however, recently been questioned by prospective studies suggesting that HBV infection also causes cirrhosis and that whatever the cause of cirrhosis, the risk of developing HCC could be roughly similar. All male patients first admitted to Hôpital Beaujon with cirrhosis or HCC from 1983 to 1987 were included in a cross‐sectional study. A total of 277 new patients with cirrhosis (but free of HCC) were admitted, of whom 55 were HBsAg positive, and 181 were alcoholic. During the same period, 117 new patients with HCC were admitted, 48 in association with alcoholic cirrhosis, 36 with HBsAg positive cirrhosis. The relative risk (odds ratio) of HCC was 2.5 (95% confidence interval, 1.46–4.37; p=0.0011) in patients with HBsAg positive cirrhosis as compared to patients with alcoholic cirrhosis. HBsAg positive patients were significantly younger than their alcoholic counterparts (48 ± 14 vs 54 ±10 years in the cirrhotic group; 49 ± 12 vs 62 ± 8 years in the HCC group). We conclude that, using the methodology of a cross‐sectional study, the relative risk of HCC was about twice greater in HBV‐associated than alcoholic cirrhosis. The results of longitudinal prospective studies examining this issue might be biased by selecting patients older than the mean age of HCC occurrence or excluding patients with HCC when present at first admission.
Identification of nucleolar organizer regions in non‐neoplastic and neoplastic hepatocytes by the silver‐staining technique
Authors: Nonomura Akitaka , Mizukami Yuji , Matsubara Fujitsugu , Nakanuma Yasuni
Published: August 2010

Abstract— The silver staining technique to demonstrate nucleolar organizer region (NOR)‐associated proteins (AgNORs) was applied to a variety of liver tissues, including chronic persistent hepatitis (CPH), chronic active hepatitis (CAH), liver cirrhosis (LC), liver cell dysplasia (LCD), focal nodular hyperplasia (FNH), adenomatous hyperplasia (AH) and hepatocellular carcinoma (HCC). In the present study, only discrete, easily counted black dots within nuclei and silver‐stained nucleolus were counted under a magnification of X 400 without oil‐immersion objectives. The mean AgNOR counts of HCC and LCD were significantly higher than that of normal hepatocytes, and 77% of cases of LCD and 56% of HCC had mean AgNOR counts more than 2, whereas those in CPH, CAH, LC, FNH and AH were always less than 2 and were not different from that of normal hepatocytes. Among HCC, the mean number of AgNORs increased with the grade of the tumor. However, the AgNOR counts of grade I HCC were always less than 2 and overlapped with those of normal hepatocytes and other benign categories. All cases with mean AgNOR counts of more than 2 turned out to be HCC, except LCD which exhibited characteristic histologic appearances easily distinguished from HCC. These findings suggest that AgNORs could be quantitatively useful in evaluating the grade of HCC, even under routine microscopic examination without oil‐immersion objectives, and mean AgNOR counts of more than 2 per nucleus are hallmarks of HCC.
Immunohistochemical identification of proliferating cells following dimethylnitrosamine‐induced liver injury
Authors: Paolucci F. , Mancini R. , Marucci L. , Benedetti A. , Jezequel A. M. , Orlandi F.
Published: August 2010

Abstract— The present study is concerned with changes in the number and localization of S‐phase cells in the liver of rats exposed to dimethylnitrosamine (DMN). S‐phase cells were detected by immunohistochemistry after injection of bromodeoxyuridine (BrdU) and exposure of paraffin sections of liver tissue to the antibody anti‐BrdU. With respect to controls, the number of S‐phase cells increased four to fivefold in DMN‐treated animals in the first week of treatment and remained significantly higher thereafter, in association with the formation of septa. At all times, the labelling index was higher in littoral cells than in hepatocytes. No labelling was observed in biliary cells. This behaviour is different from that reported in other situations, for instance in regeneration after partial hepatectomy, which suggests that besides hepatocytes and littoral cells replacement, an involvement of the latter cell line in the inflammatory reaction, synthesis of extracellular matrix components and formation of septa may account for this particular pattern.
Changes in sensitivity of hepatocytes isolated from regenerating rat liver to the growth inhibitory action of transforming growth factor beta
Authors: Strain Alastair J. , Hill David J.
Published: August 2010

Abstract— Transforming growth factor beta (TGFB) is a potent inhibitor of DNA synthesis in adult rat hepatocytes in vitro. In the present study, the response of hepatocytes from normal or regenerating rat liver to TGFB was determined. TGFB inhibited DNA synthesis uniformly in hepatocytes from both groups in the absence of EGF. However, hepatocytes from 3 h regenerating liver maintained for 3 days in the presence of EGF were less sensitive to the growth‐inhibitory action of TGFB. [3H]‐thymidine incorporation was inhibited at 20 pM TGFB by only 7% in hepatocytes from 3 h regenerating liver compared with 70% in normal hepatocytes. By increasing the dose of TGFB to 100 pM, however, the full inhibitory response was restored. Reduced sensitivity was also found when the nuclear labelling index was determined, but no change was observed in cells from rats 3 h following sham hepatectomy. The change in sensitivity to TGFB required the presence of 5 ng/ml EGF or greater. Within a further 24–48 h in culture, the response to lower doses of TGFB was at least partially restored. While the present experimental design cannot directly confirm the role of TGFB as a paracrine inhibitor of liver growth in vivo, the data are compatible with this hypothesis.
Different outcomes of chronic hepatitis delta virus infection in woodchucks
Authors: Schlipköter U. , Ponzetto A. , Fuchs K. , Rasshofer R. , Choi S. S. , Roos S. , Rapicetta M. , Roggendorf M.
Published: August 2010

Abstract— Hepatitis delta virus (HDV) superinfection of woodchuck chronic carriers of woodchuck hepatitis virus (WHV) results in acute and chronic disease. The different courses of disease mimicked the outcome of human HDV superinfection, making woodchucks valuable models for clinical studies of HDV. Ten of 11 woodchuck chronic carriers of WHV superinfected with HDV developed acute HDV infection with markers of viral replication in the serum and liver. One animal (DW128) had no serological markers of acute HDV infection. Nine of 11 (82%) superinfected animals developed chronic HDV infection. An unusual course of chronic HDV infection occurred in one woodchuck (DW128): no serum markers of acute or chronic HDV infection appeared but HDV RNA was detected in the liver, indicating that chronic HDV infection can occur without serological markers.
DNA measurements in chronic hepatitis, cirrhosis and hepatocellular carcinoma
Authors: Lin Hsien‐Hong , Shyu Wei‐Chue , Chen Gu‐Ling , Lin Yn‐Huei , Chen Tong‐Jong , Liaw Yun‐Fan
Published: August 2010

Abstract— It has been documented that chronic hepatitis may progress to cirrhosis and then develop hepatocellular carcinoma (HCC). To test whether abnormal cellular DNA increases along this line of development, liver tissues from 48 patients with chronic hepatitis, 17 with cirrhosis, and 8 with HCC were investigated for cellular DNA content with a scanning microdensitometer. Seven of 8 HCCs and 2 cirrhotic livers adjacent to HCC had abnormally increased cellular DNA content. Only 4 livers from patients with chronic liver diseases other than HCC had abnormal cellular DNA content. The cellular DNA content in livers not accompanying HCC was not related to the patient's age, histological diagnosis, and hepatitis inflammatory activity. The results confirmed the increase of cellular DNA content in HCC, but did not provide evidence of a progressively increasing DNA content from chronic hepatitis to liver cirrhosis. However, cirrhotic livers with abnormal hepatocytic DNA content deserve careful follow‐up for the early detection of HCC.
Immunohistochemical demonstration of β‐hexosaminidase in cirrhotic and cholestatic human livers with a monoclonal antibody
Authors: ELSAFI MOHAMED ELHASSAN , HULTBERG B. , HÄGERSTRAND I. , ISAKSSON A. , STENRAM U.
Published: August 2010

ABSTRACT— The lysosomal enzyme β‐hexosaminidase (Hex) was studied immunohisto‐chemically with a monoclonal antibody in normal human livers and in livers with cirrhosis and cholestasis. No reaction was detected in sections from normal livers. The reaction in diseased livers was prominent mainly in degenerating hepatocytes, whereas Kupffer cells and bile duct epithelium showed faint reactivity. The reaction product was intense in degenerated hepatocytes, especially in the periphery of the pseudolobules in cirrhotic livers. In cholestatic livers the positivity was localized around central veins in cells with bile pigment. The more pigment, the stronger was the reaction. It is suggested that the elevated level of serum Hex found in cirrhosis and cholestasis derives from degenerating hepatocytes and activated Kupffer cells.
Calcium staining by the glyoxal‐bis‐(2‐hydroxyanil)‐method in the livers of rats treated with CCl4, diltiazem, and with both agents together
Authors: ITOH SUSUMA , GOHARA SHINJI , INOMATA REIKO , MATSUYAMA YASUHISA , YAMAGISHI FUJIO
Published: August 2010

ABSTRACT—We studied the histochemistry of Ca in livers treated with CCl4, diltiazem (one of the Ca antagonists), and both agents together to determine whether hepatocytes or other parts of the liver in liver lesions show Ca staining and whether the grade or location of Ca in these injuries varies. For Ca staining, cryostat sections were treated by the glyoxal‐bis‐(2‐hydroxyanil) (GBHA)‐method using O.C.T. imbedding compound instead of paraffin. Diltiazem‐treated rats showed Ca granules in the bile canaliculi around the terminal hepatic veins and Kupffer cells 6 h after intragastric injection. Rats treated with CCl4showed fine red granules in the cytoplasm of the hepatocytes around the terminal hepatic veins as soon as 5 min mildly and 2 h moderately after intraperitoneal injection. Hepatocytes around the terminal hepatic veins showed positive Ca granules 6 to 30 h after intragastric injection of CCl4. Hepatocytes stained by Ca showed acidophilic degeneration and coagulative necrosis. The hepatocytes of rats treated with both diltiazem and CCl4revealed fewer Ca granules than those treated with CCl4alone. In summary, Ca was stained by the GBHA method from the early stage of liver injury by CCl4and was closely involved in acidophilic degeneration and coagulative necrosis of hepatocytes. The Ca staining in liver cells in CCl4‐treated rats was decreased by diltiazem.
Von Willebrand factor antigen is not an accurate marker of rat and guinea pig liver endothelial cells
Authors: LENZI RENATO , ALPINI GIANFRANCO , LIU MARGARET H. , RAND JACOB H. , TAVOLONI NICOLA
Published: August 2010

ABSTRACT— To determine whether von Willebrand Factor (vWF) is a valid marker of liver endothelial cells, we determined vWF immunoreactivity in rat and guinea pig liver sections and in smears of elutriated nonparenchymal cells isolated from these two species. In frozen sections, positive staining for vWF was seen only in the endothelium lining large hepatic vessels in both species, and no immunoactivity was detected in the sinusoids. On the other hand, immunohistochemical staining for vimentin (a marker of mesenchymal cells) showed positive reaction throughout the vascular and sinusoidal endothelial cells in both the rat and guinea pig liver. In fractions of elutriated rat and guinea pig nonparenchymal liver cells, which included almost exclusively liver endothelial cells, only 25–40% of the cells displayed a positive reaction for vWF. However, when these same fractions were stained for vimentin, 70–95% of the cells exhibited immunoreactivity. Most of the vWF‐negative cells were not red and white blood cells, biliary epithelial and Kupffer cells, and hepatocytes, and had ultrastructural features of sinusoidal endothelial cells. We conclude that in both the rat and guinea pig, liver sinusoidal endothelial cells do not exhibit vWF immunoreactivity. Thus, in routine immunohistochemical assays, vWF is not an accurate marker of rat and guinea pig liver endothelial cells. Vimentin is more appropriate for this purpose, provided that other mesenchymal cells are separated or independently identified.
B‐N‐acetyl hexosaminidase (B‐NAH) serum levels after endotoxin administration into the portal vein in the rat
Authors: Scapa E. , Orda R. , Neuman M. , Sayfan J. , Abramovici J. , Eshchar J.
Published: August 2010

ABSTRACT— Endotoxin was injected directly into the portal vein in rats with and without common bile duct (CBD) ligation. B‐N‐acetyl hexosaminidase (B‐NAH) activity levels in the serum were found to be significantly elevated 24 h later in both groups. Serum bile acid levels were found to be significantly higher in the endotoxin‐injected groups of rats compared to controls. Thus, endotoxin, as well as bile acids, may cause damage to Kupffer cell membranes, resulting in accumulation of B‐NAH in rat serum.
Detection of serum inhibitory factor for lymphocyte stimulation in chronic viral hepatitis: relationship with the replication level
Authors: Martinez M. Gracia , Castillo Inmaculada , Quiroga Juan Antonio , Porres Juan Carlos , Carreño Vicente
Published: August 2010

ABSTRACT— Sera from 111 patients with chronic viral hepatitis and from 55 cases with other liver disorders were assayed for serum inhibitory factor. The prevalence of this immunosuppressive factor was very similar between chronic hepatitis B (61%), chronic hepatitis delta (57%) and chronic hepatitis C (68%). At the same time, serum inhibitory factor was never detected in the other disorders studied. The presence of this inhibitory factor was detected in a significantly higher percentage (p < 0.05) of HBeAg, HBV‐DNA positive cases (75%) than in anti‐HBe positive, HBV‐DNA negative cases (44.4%). In chronic hepatitis delta, this immunosuppressive factor was also related to HDV‐RNA positivity. The detection of this serum immunosuppressive factor in chronic viral hepatitis and its association with a high viral replication level implies a possible role of this factor in the immune pathogenic mechanism in infectious viral hepatitis.
Thyroid gland size and function in patients with cirrhosis of the liver
Authors: Bianchi G. P. , Zoli M. , Marchesini G. , Volta U. , Vecchi F. , Iervese T. , Bonazzi C. , Pisi E.
Published: August 2010

ABSTRACT— Thyroid dysfunction has long been reported in patients with liver disease, but limited information is available on thyroid gland size in cirrhosis. Most studies were carried out on small, selected series of patients, and no study has measured thyroid volume in relation to the etiology of liver disease. Thyroid volume was measured at ultrasound in 118 consecutive patients with cirrhosis of different etiology and 48 healthy subjects matched for age and sex. No subject had evidence of overt thyroid disease. The mean volume was increased by 17% (from 16.0 [SD 5.2] ml in controls to 18.8 [7.6] in cirrhosis; P < 0.025), and thyroid enlargement (antero‐posterior diameter > 20 mm) was present in 38% of cases, in the presence of hormone values indicative of low‐T3 syndrome. No significant differences in thyroid gland size were observed in relation to the extent of liver dysfunction or to the etiology of liver disease. The prevalence of thyroid nodules was similar in controls and in patients with cirrhosis. In only 8% of cases were laboratory values indicative of hypothyroidism, with low free triiodothyronine and raised thyroid‐stimulating hormone levels; in these patients thyroid volume was decreased on average by 26%. This was mainly the case with patients with primary biliary and alcoholic cirrhosis. The largest mean thyroid volume was observed in patients with HBsAg + ve postnecrotic cirrhosis, whose thyroid volume was increased on average by 37%, and 53% of subjects had thyroid enlargement. This finding raises the question of a possible direct involvement of the thyroid in hepatitis B virus infection.
Liver changes in patients with hyperthyroidism
Authors: Sola J. , Pardo‐Mindán F. J. , Zozaya J. , Quiroga J. , Sangro B. , Prieto J.
Published: August 2010

ABSTRACT— We studied liver changes in the hepatic biopsies of five patients with hyperthyroidism. A characteristic histopathologic picture consisting of mild to moderate intrahepatocytic cholestasis, lobular inflammatory infiltrate with some eosinophils, and Kupffer cell hyperplasia was found in all cases. We discuss the specificity, clinico‐pathological correlations and the possible pathophysiology of these lesions.