bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of iron toxicity in human hepatocyte cultures by pyoverdins Pa A and Pf, the peptidic siderophores of Pseudomonas aeruginosa and fluorescens
Authors: Jégo Patrick , Chenoufl Norchen , Loréal Olivier , Morel Isabelle , Pasdeloup Nicole , Abdallah Mohamed A. , Brissot Pierre , Lescoat Gérard
Published: August 2010

Abstract: The protective effect of pyoverdins Pa A and Pf, peptidic siderophores secreted respectively by Pseudomonas aeruginosa and fluorescens, was studied in primary cultures of human hepatocytes exposed to iron (50 or 100 μM of iron‐citrate). AST, ALT and MDA releases were measured as indexes of cytotoxicity. In order to demonstrate that these chelators were able to decrease iron uptake or increase iron release from the hepatocytes, labelled cells were obtained by maintaining the cultures in the presence of 1 μM 55Fe ferric chloride plus 50 μM iron citrate. One day after iron treatment, an increase in AST, ALT and MDA release was observed with 50 or 100 μM of iron citrate; it appeared that the concentrations 50 and 100 μM of iron were highly toxic for human hepatocytes. In the presence of 50 or 100 μM of iron, the addition of 50 or 100 μM of Pa A or Pf was effective to inhibit the increase observed in the enzyme leakage and the MDA production resulting from iron exposure. In human hepatocytes cultured for 1 day in the presence of 1 μM 55Fe‐50 μM iron citrate plus 50 or 100 μM Pa A or Pf, a net decrease of iron uptake by the cells was observed, as demonstrated by the low intracellular iron level. When the hepatocytes were cultured for 1 day in the presence of 1 μM 55Fe‐50 μM iron citrate and then for a further day in the presence of 50 or 100 μM Pa A or Pf without additional iron, the chelators increased the extracellular iron level, indicating their iron release from the loaded cells; however, the effects of Pa A and Pf on iron release did not differ significantly. In conclusion, iron loading achieved by adding iron citrate to the culture medium is highly toxic for human hepatocytes. Pyoverdins Pa A and Pf are effective in protecting human hepatocytes against the toxic effect of iron by both decreasing the uptake of the metal and increasing its release from the loaded cells.
Clinical and histological features of cytomegalovirus hepatitis in previously healthy adults
Authors: Kanno Atsushi , Abe Masahide , Yamada Miki , Murakami Kazuhiro
Published: August 2010

Abstract: It is well known that cytomegalovirus infection is often accompanied by hepatitis, but there have been few comparative studies with respect to clinical features of cytomegalovirus‐associated hepatitis and other acute viral hepatitides. In the present study, clinical and pathological features of 11 acute sporadic cytomegalovirus hepatitis infections in previously healthy adults were compared with those of 45 acute sporadic viral hepatitis, including type A, type B and type C. As a result, the characteristics of cytomegalovirus hepatitis were a long‐lasting fever, splenomegaly, atypical lymphocytosis, a mild transaminasemia, a low ratio of alanine aminotransferase level to lactate dehydrogenase level, and mild hepatic histopathological changes.
Virological characterization and liver histology in HCV positive subjects with normal and elevated ALT levels
Authors: Rossini Angelo , Ravaggi Antonella , Agostinelli Enrica , Bercich Luisa , Gazzola Gian Biattista , Radaeli Enrico , Callea Francesco , Cariani Elisabetta
Published: August 2010

Abstract: We analyzed HCV genotype and RNA titer in 36 chronically infected subjects, 20 with persistently normal or near‐normal alanine aminotransferase (ALT) activity and 16 with raised ALT activity. All subjects underwent liver biopsy and evaluation of the histological activity index (HAI) by both Knodell's and Ishak's scoring systems. Genotype 2 was detected in most subjects with normal ALT activity, whereas genotype 1 was more frequent among subjects with raised ALT activity. HCV‐RNA titer was higher in subjects with increased ALT. Histological evidence of chronic hepatitis was documented in all cases, but higher scores for grading and for staging were associated with increased ALT activity. HCV genotype had no statistical relationship with RNA titer or with liver histology. In logistic regression analysis, viral genotype, RNA titer and histological scores for grading and staging were correlated independently with the ALT profile. The evidence of chronic hepatitis in all subjects with persistently normal ALT activity suggests that healthy HCV carriage is a rare event.
Gene expression in liver after toxic injury: analysis of heat shock response and oxidative stress‐inducible genes
Authors: Schiaffonati Luisa , Tiberio Laura
Published: August 2010

Abstract: In the liver, CC14 induces cell necrosis followed by regeneration. Cell injury is caused by free radical damage and may be due, at least in part, to oxidative stress and the subsequent formation of reactive oxygen intermediates (ROIs). In a rat model of acute CCl4‐induced hepatic injury, we examined the expression of genes involved in cellular response to different kinds of stress, including oxidative stress (hsp70 family, heme oxygenase), in free radical detoxification (Mn superoxide dismutase and Cu/Zn superoxide dismutase), in iron homeostasis (H and L ferritin subunits) and in the cell cycle (c‐fos, c‐jun, histone H3). As an experimental approach, we first analysed the pattern of protein synthesised by liver slices in vitro. Then we studied the mechanisms regulating the expression of different genes, by analysing both mRNA steady state levels and transcription rates. Activation of the specific heat shock transcription factor (HSF) by CC14 was also investigated. We observed that different members of the hsp70 family (hsp70, hsc73, grp78) are activated by different kinetics and are regulated mainly at the transcriptional level. Induction of the hsp70 gene occurs rapidly and transiently and is preceded by the activation of HSF DNA‐binding activity. We demonstrated an increase in the steady‐state levels of mRNAs for heme oxygenase, Mn and Cu/Zn superoxide dismutases and H and L ferritin subunits. However, different kinetics and regulatory mechanisms occurred with different genes. We showed that induction of c‐fos and c‐jun protooncogenes is the earliest event after CCl4 administration, whereas histone H3 expression peaked at 24–48 h. The results of this study are interpreted as evidence that activation of specific stress response genes is primarily related to the defence against the rapidly occurring cell damage, but may also be related to subsequent processes of tissue inflammation and cell proliferation.
Comparison of angiography, CT arteriography and MR imaging in assessment of liver metastases treated by percutaneous transcatheter intraarterial chemotherapy
Authors: Mahfouz Ahmed‐Emad , Häring Georg , Hamm Bernd
Published: August 2010

Abstract: The purpose of this study was to compare results of digital subtraction angiography (DSA), computed tomographic arteriography (CTA), and magnetic resonance imaging (MRI) in the assessment of patients with liver metastases subjected to percutaneous transcatheter intra‐arterial chemotherapy. Forty‐four patients with liver metastases treated by cyclic percutaneous transcatheter intra‐arterial chemotherapy were examined before each cycle by an imaging protocol consisting of DSA and CTA. MRI was added to this protocol in 18 patients. DSA and CTA equally detected thrombosis of the catheter or arteries distal to the catheter tip in 16 examinations. DSA detected arterial reflux in 15 examinations, while CTA detected only one case of reflux. CTA was superior to DSA in demonstrating perfusion abnormalities and superior to MRI in detecting metastases. CT was the only method that demonstrated intratu‐moral calcification. In conclusion, in patients with liver metastases subjected to percutaneous transcatheter intra‐arterial chemotherapy, DSA is the best method for detection of arterial reflux, whereas CTA is the best method for detection of metastases and demonstration of perfusion abnormalities.
Effects of intravenous immunoglobulins on T‐cell mediated, concanavalin A‐induced hepatitis in mice
Authors: Shirin Haim , Bruck Rafael , Aeed Hussein , Hershkoviz Rami , Lider Ofer , Kenet Gabriel , Avni Yona , Halpern Zamir
Published: August 2010

Abstract: Concanavalin A (ConA) activates T lymphocytes and causes T‐cell mediated hepatic injury in mice. The intravenous administration of human immunoglobulins has beneficial effects in T‐cell mediated diseases such as experimental autoimmune encephalomyelitis and adjuvant arthritis. In the present study, we examined the effects of intravenous immunoglobulins in a mouse model of T‐cell mediated, acute liver injury induced by concanavalin A. Balb/c mice were inoculated with 12 mg/kg concanavalin A with or without intravenous immunoglobulins at doses of 0.4, 0.6, 0.8 g/kg body wt. The serum levels of liver enzymes, tumor necrosis factor‐α, interferon‐γ and interleukin‐6 were assayed 2, 6 and 24 h after concanavalin A administration. Intravenous immunoglobulins did not prevent concanavalin A‐induced hepatitis, as manifested by elevation of serum aminotransferases and histopathological evaluation. The serum levels of tumor necrosis factor‐α in mice pretreated with immunoglobulins, measured 2 h after ConA treatment were reduced, while interferon‐γ levels measured 6 h after ConA inoculation were 5‐fold higher than control levels. There was no effect of intravenous immunoglobulins on the release of interleukin 6. In conclusion, these results indicate that intravenous immunoglobulin is not effective in preventing T‐cell mediated concanavalin A‐induced hepatitis. The increased secretion of interferon‐γ and the incomplete suppression of tumor necrosis factor‐α release may explain the lack of efficacy of intravenous immunoglobulin in this experimental model.
Spontaneous intrahepatic portosystemic venous shunt in a patient with cirrhosis: diagnosis by combined color Doppler and pulsed Doppler ultrasonography
Authors: Grattagliano Anna , Rapaccini Gian Ludovico , Camaldo Giuseppe , Pompili Maurizio , Marino Patrizia , Mastromatteo Angela Maria , Cotroneo Antonio Raffaele , Gasbarrini Giovanni
Published: August 2010

Abstract:Large spontaneous intrahepatic portosystemic venous shunts are occasionally found and their diagnosis by Doppler sonography is rarely reported. The authors describe a case of spontaneous intrahepatic porto‐systemic venous shunt in liver cirrhosis diagnosed by color Doppler and characterized by an unusual pulsed Doppler spectrum: a continuous flat portal‐like pattern of flow in the portal branch, and in both the shunt and the hepatic vein,
Regeneration of the hepatic nerves following surgical denervation of the liver in dogs
Authors: Ito Yoshiya , Takahashi Tsuyoshi , Tadokoro Fumihiko , Hayashi Keiko , Iino Zen‐ichiro , Sato Koshi , Akira Kakita
Published: August 2010

ABSTRACT— This study was conducted to examine the regeneration process of hepatic nerves following surgical hepatic denervation in dogs. A denervation model was surgically created by removing all visible nerves around the hepatoduodenal ligament along with the peri‐hepatic tissues. The hepatic nerves were examined on the hepatic specimens taken at 1 week, 1 month and 3 months post‐denervation by means of immuno‐histochemical staining, and also electron microscopy. At 1 week post‐denervation, the extrinsic hepatic nerves were observed not to have regenerated. However, at 1 month post‐denervation, GAP‐43‐positive nerves were identified and regenerating axons were shown to be present on electron microscopic observation. The immunoreactivity for anti‐GAP‐43 antibody was not shown any longer at 3 months post‐denervation, and the regenerated nerve axons were shown to be similar to those at pre‐denervation on ultrastructural study. Results of the present study suggested that regeneration of the extrinsic hepatic nerves began to appear about 1 month after the hepatic denervation, and was completed by 3 months post‐denervation.
Autonomic nervous system activity during infusion of L‐arginine in patients with liver cirrhosis
Authors: Saijyo Tetsuya , Nomura Masahiro , Nakaya Yutaka , Saito Ken , Ito Susumu
Published: August 2010

ABSTRACT—Patients with liver cirrhosis exhibit a hyperdynamic circulatory state as evidenced by tachycardia and an increase in cardiac output accompanied by an elevation of sympathetic tone. This condition is due to the excessive release of nitric oxide (NO), an endogenous vasodilator, which is in turn related to the abnormal induction of NO synthase. The present study investigated whether the intravenous infusion of L‐arginine, the precursor of NO, may cause a similar hyperdynamic circulatory state. A new method, the analysis of power spectrum heart rate variability, was used to evaluate autonomic nervous activity. Twenty patients with liver cirrhosis underwent continuous Holter monitoring of the ECG during the intravenous administration of L‐arginine (10 g) (Fisher's solution) infused over 60 min. Power spectral analysis was computed from 512 beats of the Holter ECG data. Low frequency (LF; 0.04–0.15 Hz) and high frequency (HF; 0.15–0.40 Hz) spectral powers and the ratio of LF to HF (LF/HF) were calculated every 10 min before and after the infusion of L‐arginine. The LF power, which reflects sympathetic tone modified by vagal tone, and the LF/HF, an indicator of sympathetic tone, were both significantly increased during the infusion (p<0.05). HF power, an indicator of parasympathetic tone, showed no significant change in the early stage of the infusion but was significantly increased in the late stage (p<0.05). The administration of L‐arginine thus led to an elevation of sympathetic tone. Fisher's solution, which is administered to patients with hepatic insufficiency, contains L‐arginine, and may also produce a hyperdynamic circulatory state as an adverse effect related to an elevation of the plasma level of NO by L‐arginine. The monitoring of such patients is thus indicated.
HGV: the identification, biology and prevalence of an orphan virus
Authors: Mphahlele M. Jeffrey , Lau George K. K. , Carman William F.
Published: August 2010

ABSTRACT— Hepatitis G virus (HGV) and GB virus C (GBV‐C) (both hereinafter referred to as HGV) were independently identified in patients with hepatitis of unknown aetiology. HGV is a positive‐sense RNA virus of the family Flaviviridae. The virus can establish both acute and chronic infection and appears to be sensitive to interferon. Horizontal transmission is mainly parenteral, although other routes such as vertical have been well documented. High risk groups include intravenous drug users (IVDUs), the multiply transfused, haemodialysis patients and haemophiliacs. Up to 90% of IVDUs are positive for either HGV‐RNA or antibodies to HGV envelope‐2 protein (anti‐E2). HGV is frequently detected in patients with HBV and HCV infection. Its link to hepatitis has now become less certain. Only around 3–6% of non‐A–E hepatitis cases are HGV viraemic, clearly showing that HGV is not the major cause of idiopathic hepatitis as originally hoped. Around 1–5% of volunteer blood donors in developed countries are HGV viraemic, but the prevalence is 10–20% in the general population in some developing countries. At present, it is not known whether HGV is associated with other diseases in humans, is a passenger virus, or only becomes virulent under certain conditions.
Determination of plasma alpha‐glutathione S‐transferases in patients with HCV‐related chronic infection: its significance and possible clinical relevance
Authors: Loguercio Carmela , Tuccillo Concetta , Caporaso Nicola , Blanco Giovanna Del Vecchio , Morisco Filomena , Guerriero Ciro , DI Santolo Salvatore Scotto , Valenza Lucio Mario , Blanco Camillo Del Vecchio
Published: August 2010

ABSTRACT— Aims/Background: Alpha‐glutathione S‐transferases (α‐GST) are the cytoplasmatic class of enzymes responsible for cellular detoxifying processes. We evaluated the plasma α‐GST activity in relation to chronic infection caused by hepatitis C virus (HCV). Methods: Eighteen anti‐HCV‐negative healthy subjects (controls), 32 anti‐HCV‐positive subjects with a constant normality of alanine aminotransferases (ALT) and gamma‐glutamyl transpeptidase (γ‐GT) levels (“apparently healthy carriers”), and 85 patients with HCV‐related chronic liver disease (40 chronic hepatitis, 27 cirrhosis, and 18 with hepatocellular carcinoma) were studied. We assayed plasma α‐GST in all subjects upon their entry into the study; and every 6 months for 3 years in the control group and in anti‐HCV apparently healthy carriers. Results: Alpha‐GST values were significantly higher than normal values in 57% of the 21 HCV‐RNA‐positive apparently healthy carriers and in none of 11 persistently HCV‐RNA‐negative subjects; the highest increment of α‐GST was documented in patients with chronic hepatitis. We did not observe correlation among HCV‐RNA, histological activity, γ‐GT and ALT or α‐GST values. Conclusions: Therefore, the increment of plasma α‐GST indicates a liver involvement even when ALT levels are normal. This may be clinically relevant to “apparently healthy carriers” whose plasma α‐GST values, when increased, might need further evaluation.
Effects of orthotopic liver transplantation on body composition
Authors: Hussaini S. H. , Oldroyd B. , Stewart S. P. , Soo S. , Roman F. , Smith M. A. , Pollard S. , Lodge P. , O'Grady J. G. , Losowsky M. S.
Published: August 2010

ABSTRACT— Aims/Background: The effects of orthotopic liver transplantation on body composition are unclear. We aimed to assess changes in body composition after transplantation using dual energy x‐ray absorptiometry and total body potassium. Methods: Dual energy x‐ray absorptiometry and total body potassium counting to assess muscle mass were performed in 55 patients before and up to 24 months after liver transplantation and the results expressed as paired data before and at time intervals after transplantation. Results: The results showed that total body weight fell by 3.6 ± 1.3 kg (p<0.02) at 1 month, with a maximal fall in lean tissue mass at 2–5 months of 4.8 ± 1.2 kg (p<0.003). Thereafter, no change in lean tissue mass was recorded, although there were increases at 12 and 24 months of total body weight (11.5 ± 2.4 kg, 7.8 ± 3.1 kg; p<0.03, respectively) and fat mass (12.9 ± 2.2 and 10.5 ± 2.7 kg; p<0.003). A fall in total body potassium was seen at 1 month (118 ± 12 mmol; p<0.003) and 2–5 months (176 ± 9.9 mmol; p<0.03), which mirrored the fall in lean mass. Conclusions: After liver transplantation there is an initial fall in body weight due to a loss of lean mass. Lean mass does not recover after transplantation, although there is an increase in fat mass that leads to the observed increase in total body weight.
Massive liver necrosis associated with hyperamylasemia
Authors: Galus Maria , Schiffman Raymond , Olkowska Danuta
Published: August 2010

ABSTRACT— In North America, massive liver necrosis is due mainly to viral infection or exposure to hepatotoxins. We report an unusual case of massive liver necrosis due to diffuse liver infiltration by small cell carcinoma of the lung. The unusual presentation included hyperamylasemia due to ectopic amylase production by the tumor. In this era of liver transplantation it is important to consider malignancy in the differential diagnosis of fulminant or acute liver failure prior to liver transplantation.
Portal‐systemic encephalopathy from a spontaneous gastrorenal shunt diagnosed by three‐dimensional computed tomography and treated effectively by percutaneous vascular embolization
Authors: Kuramitsu Tomoyuki , Komatsu Masafumi , Matsudaira Naoya , Naganuma Toshio , Niizawa Makoto , Zeniya Akira , Yoshida Tsukasa , Toyoshima Itaru , Chiba Mitsuro , Masamune Osamu
Published: August 2010

ABSTRACT— A 67‐year‐old man with a portal‐systemic shunt confirmed by three‐dimensional computed tomography (3D‐CT) was successfully treated by percutaneous vascular embolization. The patient had aggravated loss of memory, disorientation, and hyperammonemia. A gastrorenal shunt 16 mm in diameter was found by 3D‐CT reconstructed by helical computed tomography (CT). Embolization was performed only in the shunt percutaneously through the inferior vena cava. One year after the embolization, no recurrence of portal‐systemic encephalopathy and no portal hypertension have appeared, and the clinical course has been good.
CA 19–9 production by a cystadenoma with mesenchymal stroma of the common hepatic duct: a case report
Authors: Caturelli Eugenio , Bisceglia Michele , Villani Maria Rosaria , De Maio Giovanni , Siena Domenico Angelo
Published: August 2010

ABSTRACT— A case of a CA 19–9 producing cystadenoma with mesenchymal stroma originating from the common hepatic duct is presented, with a review of the literature. The findings of ultrasound and CT scans and the endoscopic retrograde cholangiopancreatography picture allowed the establishment of a confident pre‐operative diagnosis. Although there was an elevation of CA 19–9 serum levels, the resected specimen did not show any malignant focus at pathologic examination. After surgical excision, CA 19–9 serum levels returned to normal.
Activated sub‐populations of lymphocytes and natural killer cells in normal liver and liver grafts before transplantation
Authors: Navarro F. , Portalès P. , Pageaux J. P. , Perrigault P. F. , Fabre J. M. F. , Domergue J. , Clot J.
Published: August 2010

ABSTRACT— Aims/Background: The anatomic structure of the liver suggests that it is a place of intense trafficking between intra‐hepatic and peripheral blood compartment leukocytes. Furthermore, the liver contains a large number of passenger leukocytes that may play a role in the appearance of donor‐type microchimerism after transplantation. In this study, we aimed to define the principal lymphocyte sub‐populations contained in donor peripheral blood and liver grafts and in normal liver removed during minimally invasive surgery. Methods: Liver biopsies were taken at the time of vascular clampage during liver extraction from donors in a brain dead state (GI: n=14). Normal liver biopsies were removed during minimaly invasive surgery (GII: n=10). Results: We observed evidence of the presence of lymphocytic activation associated with the two major CD8+ lymphocyte and natural killer (NK) cell populations in the two groups, with a significant increase in TCR γδ‐bearing lymphocyte receptors between normal liver and the liver graft. Conclusions: The presence of activated leukocytes in the graft could have a fundamental role in induction of peripheral tolerance. This activation could be the result of a basic immunological response linked to the interaction of T cells and NK cells, and of secondary activation due to stress and the conditions necessary for organ removal from donors in a brain dead state.
Cell‐kinetic study of proliferating bile ductules in various hepatobiliary diseases
Authors: Harada Kenichi , Kono Naoko , Tsuneyama Koichi , Nakanuma Yasuni
Published: August 2010

ABSTRACT— Aims and Methods: Proliferat bile ductules are classifiable histologically into typical and atypical types. To clarify their histogenesis and regulation, we examined their phenotype, proliferating and degrading characteristics, using liver sections from 58 patients with various hepatobiliary diseases. Results: Typical ductules were found in all cases. Atypical ductules were also frequently found in extrahepatic biliary obstruction (EBO), chronic hepatitis (CH), as well as in primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). Typical ductules completely expressed biliary‐type cytokeratins, while atypical ductules lacked complete biliary‐type cytokeratins and often connected with periportal hepatocytes. Proliferative indices of typical ductules in diseased livers were higher than those in normal livers, while those of atypical ductules were low in PBC and PSC and high in EBO and CH. Apoptosis was detected in typical and atypical ductules. Perforin was preferably expressed on typical and atypical ductules, compared with CD95. Conclusions: These findings suggest that typical ductules reflect active proliferation of preexisting ductules. Atypical ductules might be classifiable into two categories: those in PBC and PSC primarily reflect ductular transformation (metaplasia) of periportal hepatocytes, while those in EBO and CH reflect active proliferation and transformation of hepatocytes. Apoptosis via perforin/granzyme B pathway may be involved in the maintenance of homeostasis in ductular proliferation as degrading fraction.
Taurocholate induces preferential release of phosphatidylcholine from rat liver canalicular vesicles
Authors: Gerloff Thomas , Meier Peter J. , Stieger Bruno
Published: August 2010

Abstract: Aims/Background: Biliary phospholipid secretion involves predominant segregation of canalicular phosphatidylcholine into bile. We tested the hypothesis that micellar concentrations of the major physiologic bile salt taurocholate can preferentially solubilize phosphatidylcholine from the canalicular rat liver plasma membrane. Methods: Subcellular fractions from rat liver and kidney were isolated with standardized procedures, incubated in vitro with taurocholate or 3‐[(3‐cholamidopropyl)dimethylammonio]‐propane‐1‐sulphonate (CHAPS) and released phospholipids determined after centrifugation. Results: After incubation of canalicular (cLPM) and basolateral (blLPM) rat liver plasma membrane vesicles with 6 and 8 mM taurocholate, the proportion of phosphatidylcholine released was about two‐fold higher as compared with its relative contribution to the overall lipid composition of the membranes. Quantitatively, this taurocholate‐induced preferential phosphatidylcholine release was about four‐fold higher in cLPM (117 nmol) as compared with blLPM (28 nmol). Comparison of membranes from different organs showed that increased sphingomyelin content reduced taurocholate‐induced phosphatidylcholine release. Furthermore, phosphatidylcholine release from cLPM did not fit an inverse exponential relationship between membrane sphingomyelin content and phosphatidylcholine release from different starting material, indicating that cLPM is especially prone to taurocholate‐induced phosphatidylcholine release. In contrast, in rat liver microsomes and kidney brush border membranes, taurocholate released phospholipids in proportion of their membrane contents, indicating an unspecific membrane solubilizing effect only. Similarly, CHAPS had an unselective lipid solubilizing effects in cLPM and blLPM. Conclusion: These results support the concept that the very last step of canalicular phospholipid secretion is mediated in vivo by bile salt‐induced vesiculation of phosphatidylcholine‐enriched microdomains from the outer leaflet of cLPM.
Expression of pancreatic alpha‐amylase protein and messenger RNA in hilar primitive bile ducts and hepatocytes during human fetal liver organogenesis: an immunohistochemical and in situ hybridization study
Authors: Terada Tadashi , Kato Masako , Horie Satoshi , Endo Kanenori , Kitamura Yukisato
Published: August 2010

Abstract: Aims/Background: This study was conducted to evaluate the expression of pancreatic digestive enzymes in hilar bile ducts and hepatocytes during human fetal liver organogenesis. Methods: We investigated the expression of pancreatic alpha‐amylase protein and messenger RNA (mRNA) in hilar primitive bile ducts and hepatocytes by immunohistochemistry and in situ hybridization techniques, using 11 human fetal livers of various gestational ages. The specificity of the immunohistochemistry and in situ hybridization procedures was confirmed by Western blot analysis and in situ hybridization using sense probes, respectively. Results: Immunoreactivity of pancreatic alpha‐amylase protein and expression of pancreatic alpha‐amylase mRNA were present not only in the primitive ductal cells of the hilar region including the ductal plate, remodelling bile ducts and remodeled bile ducts but also in primitive hepatocytes of the hilar region, though the immunoreactivity and mRNA signals in the primitive hepatocytes disappeared in the third trimester. There was perfect correlation between immunohistochemistry and in situ hybridization. Conclusions: These results suggest that primitive biliary cells and hepatocytes of the hilar region in the human fetus do express pancreatic alpha‐amylase protein and mRNA, and that the primitive biliary epithelial cells and hepatocytes in the hilar region share a common cell lineage with exocrine pancreatic cells.
Fungal colonisation and fluconazole therapy in acute liver disease
Authors: Fisher Neil C. , Cooper Mike A. , Hastings J. G. Mark , Mutimer David J.
Published: August 2010

Abstract: Background/Aims: Fungal infection, particulary with Candida spp., has been identified as an important cause of morbidity and mortality in patients with acute liver failure. Fungal colonisation of superficial mucosal sites usually precedes invasive infection. We investigated colonisation patterns in patients with acute liver disease receiving fluconazole therapy in order to investigate the possibility of emergence of fluconazole‐resistant C. albicans or other species. Methods: During a 6‐month study period, we studied all patients referred to our unit with acute liver disease by twice‐weekly sampling and mycological analysis of specimens from superficial mucosal and other sites as appropriate. Patients were treated with prophylactic antimicrobials including 100 mg fluconazole daily in accordance with our usual protocol. Results: Twenty‐two patients with acute liver disease were studied, eight of whom underwent transplantation. Eighteen patients were colonised by fungi at presentation, and six developed secondary colonisation during fluconazole therapy. Four of these patients (all transplanted) became colonised by resistant species; one of these was Aspergillus fumigatus, which led to death. There were no other invasive fungal infections identified during the study period, and no fluconazole‐resistant C. albicans were identified. Conclusions: Resistance to fluconazole is unlikely to develop in C. albicans during short‐term fluconazole prophylaxis in acute liver disease, and in this study we did not find evidence of invasive disease from other Candida spp. during fluconazole therapy. However, in patients at particularly high risk, other strategies are required to prevent infection with Aspergillus spp.
Comparative study of 5‘ UTR and NS3R primers for the detection of GB virus C/ hepatitis G virus RNA in Japanese
Authors: Tanaka Hiroto , Miyano Motoshige , Ueda Hiroki , Doi Ryohei , Mimura Keiji , Nishide Iwao , Yukawa Susumu
Published: August 2010

Abstract: Aims/Background: Many epidemiological studies of new hepatitis viruses, including GB virus C (GBV‐C) and hepatitis G virus (HGV), have used polymerase chain reaction (PCR) primers designed for the third nonstructural region (NS3R). However, a homology study of GBV‐C and HGV genomes revealed that the 5′ untranslated region (5'UTR) was more conserved than NS3R. Methods: We attempted to detect GBV‐C/HGV using PCR primers corresponding to the 5′ UTR, and compared its incidence to that derived from NS3R primers. Furthermore, PCR products amplified using the 5′ UTR primers were sequenced and subjected to phylogenetic analysis. Results: In patients with chronic hepatitis C, the prevalence of GBV‐C/HGV by PCR with the NS3R and 5′ UTR primers was 5.1% (4/78) and 17.9% (14/78), respectively, and in patients on hemodialysis, it was 0% (0/81) and 5.9% (5/85), respectively. We could not detect GBV‐C/HGV in patients with non‐A‐C liver disease. The incidence of GBV‐C/HGV by 5′ UTR primers was higher than by NS3R primers. After DNA sequencing at 5′ UTR, phylogenetic analysis showed two types of GBV‐C/HGV, Jap and HGV types. Conclusion: 5′ UTR primers proved highly sensitive for detection of GBV‐C/HGV and were superior to the NS3R primers.
Areas of sinusoidal surface hepatocyte nuclear predominance in type C chronic hepatitis
Authors: Tanaka Yasuki , Ichida Takafumi , Nomoto Minoru , Matsuda Yasunobu , Asakura Hitoshi
Published: August 2010

Abstract: Aims/Background: Thick hepatic plates have been considered one of the morphological characteristics of hepatocyte regeneration in cirrhotic nodules. They can be recognized by the sinusoidal surface predominance of their nuclei. We have investigated the prevalence of this in HBV and HCV infections. Methods and Results: This feature was more frequently present in type C chronic hepatitis with low activity of inflammation and low grade of fibrosis, than with type B chronic hepatitis. Additionally, this area of sinusoidal surface hepatocyte nuclear predominance (ASSHNP) was seen in zone II, rather than in periportal zones, in type C chronic hepatitis. Clinical data were analyzed statistically. Immunohistochemical reactivity of type IV collagen, laminin, Ulex europaeus agglutinin 1 lectin (UEA‐1), and factor VIII‐related antigen were increased in ASSHNP. Immunohistochemical staining of Ki‐67 antigen was performed in order to assess the regenerative capacity of this area and showed a low level of regeneration. Ultrastructure of this area in type C chronic hepatitis showed a decrease in the number of mitochondria and an increase of nuclear pleomorphism together with basement membrane formation in the space of Disse. Conclusion: Although the cause of these abnormalities was not clarified in this study, it is suggested that they are related to chronic hepatitis C virus (HCV) infection per se, rather than regeneration or inflammatory activity. These changes may be significant in HCV‐associated hepatocarcinogenesis.
TUMOUR GROWTH AND SPONTANEOUS METASTASIS SPREAD IN TWO SYNGENEIC SYSTEMS
Authors: Hagmar Björn
Published: August 2010

In two syngeneic tumour‐host systems, MCGl‐AS in CBA mice and melanoma B16 in C57BL/6J mice, the time of onset of spontaneous metastasis spread was determined, so was how removal of the primary tumours affected the amount of metastases. Treatment with two anticoagulants (heparin and phenprocoumon) and an antifibrinolytic (EACA) was instituted for 6 days, when metastatic spread was beginning. Heparin increased metastasis formation from MCGl‐AS and a similar trend was found in the case of melanoma B16. The coumarin anticoagulant, phenprocoumon, had no such effect. None of the substances seemed to affect the growth of MCGl‐AS metastases, when the treatment was instituted after resection of the primary tumours. This was the case also of EACA, but this substance tended to reduce tumour weights and metastasis formation in both systems, if applied before removal of tumours. The results seem to offer evidence against the concept that thrombosis around disseminated tumour cells promotes the development of metastases. The location of fibrin in subcutaneously transplanted tumours was also studied in histological sections.
GUINEA PIGS AND CARCINOGENS
Authors: Stenbäck Frej
Published: August 2010

The reaction of guinea pig skin to topical and subcutaneous administration of four carcinogens administered in different dosages to newborn and adult animals, has been investigated histologically and histochemically. The transplantability of the sarcomas produced, and the occurrence of spontaneous tumours in the strain used, was studied too. The guinea pig was resistant to topical carcinogen treatment, but large doses administered during a long period did induce tumorigenesis. The resulting tumours were all fibrosarcomas. The newborn animals were as resistant as adults. The transplantation of the tumours was successfull, but the percentage of positive “takes” was small. A single dermal tumour occurred spontaneously in the control group consisting of 500 animals.
BASAL CELL CARCINOMA WITHIN A SEBORRHOEIC KERATOSIS
Authors: Andersen Johan
Published: August 2010

In a typical seborrhoeic keratosis removed from a 79‐year‐old woman a smaller area with transition to basal cell carcinoma is found. Invasion from the surrounding skin may be excluded, just as a primary Pinkus' fibroepithelioma is out of the question. The possibility of secondary epithelial changes above a subepidermal fibrosis is unlikely.
ULTRASONIC EQUIPMENT FOR APPLICATION OF ULTRASOUND WITH HIGH EFFECT TO ANIMALS USED FOR EXPERIMENTS
Authors: Bang Jens , Northeved Allan
Published: August 2010

In the light of the increasing application of ultrasonics for diagnostic purposes, it seems reasonable, in order to obtain a qualitative and quantitative evaluation, to investigate the teratogenic effects, if any, of ultrasound with frequencies equalling those applied for diagnostic purposes in comprehensive animal experiments. The object of the present study is to define the construction of an apparatus and the development of a methodology by which to demonstrate harmful effect, if any, involved in the application of continuous 2.25 MHz ultrasound to experimental animals and their products of conception. Furthermore the present study is to define a method for determination of level of action in the uterus of experimental animals.
DILUTION ANAEMIA
Authors: Thorling E. B.
Published: August 2010

Mice of the strain BALB/c develop a dilution anaemia when transplanted with the plasmocytoma PC 5. The total red cell mass remains unchanged during growth of the tumour whereas the haematocrit comes steadily downwards to 2/3 of the normal value. In spite of the apparent “anaemia”, the mice do not invoke compensatory increases in erythropoiesis as demonstrated by lack of reticulocytosis and lack of erythropoietin production in increased amounts. The animals have retained the capacity to respond to a hypobaric hypoxic stimulus, and it is, therefore, tentatively assumed that the oxygen transport is not decreased in case of dilution anaemia and that the tissue oxygen tension will remain normal.
CHANGING PATTERNS OF BACTERIAL ENDOCARDITIS IN NORWAY
Authors: Capoferro Renato
Published: August 2010

An analysis is made of the patterns of bacterial endocarditis in a Norwegian autopsy material from the period 1939–67. This material is compared with that of Harbitz from 1894–97. The main findings include a decreased frequency, an increased average age, a greater variety of aetiologic agents, a lesser importance of rheumatism as predisposing factor, and a very high incidence of embolic phenomena.
TUBULAR AND INTERSTITIAL NEPHRITIS PRODUCED BY HOMOLOGOUS HEART HOMOGENATE IN RABBITS
Authors: Wegelius Otto , Jokinen E. J.
Published: August 2010

Repeated intraperitoneal and subcutaneous injections of undenatured homologous myocardial homogenates into rabbits results in an irreversible kidney disease in the majority of the animals. The lesion starts about eighteen weeks after the start of the experiment in the cells of the proximal convoluted tubules and around these structures as an interstitial infiltration of mononuclear cells. At forty weeks kidney impairment is obvious, as shown by elevated serum creatinine, changes in serum protein level and electrophoretic pattern, electrolyte disturbances and protein in the urine. The kidneys are partly shrunken, resembling “peach stones”. Myoglobin and/or some other component in the homologous homogenate is thought to be the agent responsible. The findings are interpreted as an experimental model of chronic tubular and interstitial nephritis in man.
HISTOCHEMICAL OBSERVATIONS OF THE DEVELOPING GLOMERULUS AND JUXTAGLOMERULAR APPARATUS
Authors: Kazimierczak Jerzy
Published: August 2010

Non‐mitochondrial adenosine triphosphatase, acid (glucose‐6‐)phosphatase, alkaline phosphatase, glucose‐6‐phosphate dehydrogenase, and the metalophilic reaction were followed histochemically during the development of the glomerulus and the juxtaglomerular apparatus of the kidney of the new‐born pig. It was found that the rudimentary structures already exhibit activity of those enzymes which are characteristic of the particular structures of the adult nephron. Thus adenosine triphosphatase was located in the progenitorial cells of the glomerular mesangium, of the lacis, and of the vascular media, while acid (glucose‐6‐)phosphatase was restricted to the vascular endothelium both inside and outside the differentiating glomeruli; glucose‐6‐phosphate dehydrogenase was always present in the tubular segment closely applied to the differentiating renal corpuscle (the macula densa segment) while alkaline phosphatase was already abundant in the prospective segment of the proximal tubule in the S‐shaped body. The histological and histochemical observations indicated furthermore that the mesangium and the contiguous cells of the juxtaglomerular apparatus are very similar to each other from the earliest stages of differentiation and appear to have the same origin in the local mesenchymal cells. The glomerular endothelium differs from the latter structures but has much in common with the endothelium of the interstitial vessels where it presumably originates.
RECKLINGHAUSEN'S DISEASE: A MULTIFACETTED SYNDROME
Authors: Schönebeck Jan , Ljungberg Otto
Published: August 2010

A case of multiple neurofibromatosis associated with café‐au‐lait coloured skin spots, a metastasizing para‐aortic phaeochromocytoma and a parathyroid adenoma is reported. Investigation of the patient's family has revealed seven further cases of multiple neurofibromatosis. In four of these café‐au‐lait coloured skin spots and in one bilateral opticus glioma have also been found. The relationship between von Recklinghausen's disease and allied conditions such as the “neuro‐cutaneous”—, “medullary thyroid carcinoma‐phaeochromocytoma”—and “pluriglandular” syndrome is discussed.
PLACE OF RENIN FORMATION IN RABBIT UTERUS
Authors: Eskildsen Peter Claes
Published: August 2010

Castration of rabbits is followed by decrease in uterine renin. After 6 hours' treatment of castrated animals with estradiol the renin concentration shows a remarkable rise which is more pronounced in the endometrium than in the myometrium. The increase is higher if the rabbits have been laparotomized 24 hours before the oestrogen treatment. This potentiation is due to addition of two different stimulations: oestrogen treatment and laparotomy. In castrated animals which are laparotomized, but not treated with oestrogen, there is only an increase of the endometrial, but not of the myometrial renin. The effect of laparotomy comes to an end in less than 4 days. Extraordinary high increase in endometrial renin is found in two of four nephrectomized rabbits.
PULMONARY AIR EMBOLIZATION IN THE DOG: POSTMORTEM FINDINGS
Authors: Dahlgren S. E. , Josephson S.
Published: August 2010

The effect of acute pulmonary air embolization on lung morphology was investigated in twenty‐eight dogs. In sixteen animals, no lesions were observed. In twelve dogs, a slight oedema formation was found on histological examination only. No relation to the pulmonary arterial pressure increase was detected. Arterial hypoxaemia had appeared in oedematous as well as non‐oedematous dogs. Thus, pulmonary oedema did not seem to depend on pulmonary arterial pressure rise or to contribute to the arterial hypoxaemia after lung embolization with air.
THE APPLICATION OF A TIDAL FLOW CULTURE METHOD TO THE STUDY OF HISTOLOGICAL AND LACTATE DEHYDROGENASE (LDH)‐ISOENZYMATIC CHANGES IN PRIMARY MOUSE LUNG CELL CULTURES
Authors: Langvad E.
Published: August 2010

A new “tidal flow” cultivation system, designed for the cultivation of large amounts of tissue in primary culture is described. In the present cultivation apparatus all explanted tissue shares a common gas phase and a common pool of nutritional medium where variations of pH and glucose concentration are largely kept within physiological limits throughout the duration of the cultivation. Oxygenation of the tissue is facilitated since oxygen diffusion may take place from all sides of the explants and since the tissue is only intermittedly submerged in nutritional medium. Morphologically, the degenerative changes occurring in primary explants of lung tissue are delayed. However, changes of the LDH isoenzyme pattern in favour of M‐LDH activity, which may be considered a sign of dedifferentiation at the molecular level, start immediately and are not prevented by an increased oxygen tension. It is concluded that morphological changes are preceded by changes at the molecular level.
LACTATE DEHYDROGENASE ISOENZYME PATTERNS IN LEUKOPLAKIA, SUBMUCOUS FIBROSIS AND CARCINOMA OF THE ORAL MUCOSA IN SOUTH INDIANS
Authors: Langvad E. , Zachariah J. , Pindborg J. J.
Published: August 2010

The lactate dehydrogenase isoenzyme pattern of biopsies from Indian oral leukoplakia, submucous fibrosis and carcinoma of the oral mucosa as well as that of oral mucous membrane biopsies from clinically normal Indian persons has been studied. The LDHIV/LDHII isoenzyme ratios found for leukoplakias, carcinomas and control biopsies did not differ significantly. The mean isoenzyme ratio of Indian control biopsies was significantly above that reported for Danish control biopsies. Submucous fibrosis was accompanied by a significant depression of the isoenzyme ratio. No clear correlation between LDH isoenzyme pattern and epithelial thickness was found. Smoking and chewing habits, which may be correlated with prevalence and localization of oral leukoplakias and carcinomas, did not significantly influence the isoenzymatic structure. Although final conclusions cannot be drawn, the high isoenzyme ratio of the Indian control material may represent an early precancerous condition, unrelated to smoking and chewing, preceding the histopathological manifestations of precancerous lesions.
THE CONTENT OF LIPOFUSCIN IN LIVER BIOPSIES FROM PATIENTS OPERATED FOR GALLSTONES
Authors: Brændstrup Otto , Dombernovsky Per
Published: August 2010

196 liver biopsies from 196 patients operated for gallstones have been semi‐quantitatively estimated as to their content of lipofuscin. The amount of lipofuscin has been evaluated in relation to the patient's age, the histological appearence, the serum alkaline phosphatase, and the icterus index. A statistical treatment of the results shows that biopsies from patients over 60 years have a significantly greater content of lipofuscin (p < 0.02). A pathological histology as fatty liver or portal fibrosis results in a non‐significant reduction in the amount of lipofuscin (p > 0.05). The content of lipofuscin has been found unchanged during operation (1–3 hours).
THE INTRARENAL VASCULAR ALTERATIONS IN NEPHROTOXIC SERUM NEPHRITIS AND THEIR RELATIONSHIP TO THE DEVELOPMENT OF HYPERTENSION
Authors: Ljungqvist Arne , Sällström Olof , Biberfeld Gunnel
Published: August 2010

Nephrotoxic serum nephritis (NTN) was induced in a series of rats through repeated intravenous injections of rabbit anti‐rat‐kidney serum. A significant number of the rats developed hypertension. Stereomicro‐angiographic and histological examinations were performed on kidneys from rats with hypertension of both short and long duration. These morphological pictures were compared with those of kidneys from normotensive rats with NTN and normotensive control rats. In the hypertensive rats the glomerular damage was found to have induced significant alterations in the intrarenal arterial pattern suggestive of a relative cortical ischaemia, whereas the glomerular damage in the normotensive rats with NTN was not sufficiently severe to have produced these vascular alterations. Obliterative lesions in the extraglomerular vessels in the NTN‐kidneys were insignificant. The development of hypertension was unrelated to the serum creatinine level. The findings suggest that hypertension is elicited in NTN when the glomerular lesion is sufficiently severe and extensive to result in alterations in the intrarenal vasculature implying a relative cortical ischaemia.