Victor Ankoma-Sey , Christina Tzagarakis , Kun Bee Chang , Scott L. Friedman
{"title":"Downregulation of matrix and β-PDGF receptor gene expression by anti-TGFβ antibody in rat hepatic stellate cells during experimental liver injury","authors":"Victor Ankoma-Sey , Christina Tzagarakis , Kun Bee Chang , Scott L. Friedman","doi":"10.1016/S0928-4346(96)00341-6","DOIUrl":"10.1016/S0928-4346(96)00341-6","url":null,"abstract":"<div><p>Excess matrix in hepatic fibrosis results from both fibrogenic stimulation of stellate cells by TGFβ1 and cell proliferation due to induction of β-platelet derived growth factor receptor (β-PDGFR). In this paper, treatment of culture-activated rat stellate cells with anti-TGFβ inhibited collagen and fibronectin mRNA expression by 82 and 58%, respectively, versus control cells. In vivo, anti-TGFβ inhibited collagen I gene expression by 86% in stellate cells isolated from rats treated with CC14 compared with control antibody. In contrast to stellate cells, anti-TGFβ had no effect on collagen I gene expression in isolated sinusoidal endothelial cells. Anti-TGFβ administered in vivo to rats with liver injury also reduced expression of stellate cell β-PDGFR mRNA to that of control animals. Anti-TGFβ antibody had no effect on the histologic appearance of the tissue. These data support a role for TGFβ in stellate cell matrix expression and provide evidence for transmodulation of PDGF receptor by TGFβ in vivo. However, inhibition of TGFβ alone may not be adequate to attenuate severe hepatic injury and fibrosis.</p></div>","PeriodicalId":13746,"journal":{"name":"International Hepatology Communications","volume":"6 3","pages":"Pages 144-152"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0928-4346(96)00341-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91098131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Conserved nucleotide sequence of NS5A in hepatitis G virus or GB virus C in Japan and China","authors":"Toshikazu Hada , Weidong Liu , Hiroyasu Imanishi , Kohya Fukui , Xiaohui Zhou , Zhancheng Yao , Qianhao Wu , Jiewen Qiu , Masao Ohno , Arata Iwasaki , Yoshiki Amuro , Yinrong Wu , Kazuya Higashino","doi":"10.1016/S0928-4346(96)00338-6","DOIUrl":"10.1016/S0928-4346(96)00338-6","url":null,"abstract":"<div><p>A semi-nested PCR method was designed for detecting the NS5A region of hepatitis G virus (HGV) or GB virus C (GBV-C) using specific oligonucleotide primers. Patients, 14 of 69, suffering from hepatic diseases in Japan and 5 of 21 in China showed strong positive signals for HGV or GBV-C by this method. The PCR products were directly sequenced. The nucleotide sequences identified differed from one another by 0–5%, from HGV by 3–9% and GBV-C by 2–7%, the percentages of the latter two being compared with the sequences reported previously. Amino acid sequences were the same or had only one alteration compared with HGV and two to three alterations compared with GBV-C. These results indicate that the nucleotide sequence of NS5A of HGV (or GBV-C) is more conserved than that of NS3 of GBV-C (or HGV) which has been reported to show variations of 0–23%.</p></div>","PeriodicalId":13746,"journal":{"name":"International Hepatology Communications","volume":"6 3","pages":"Pages 130-136"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0928-4346(96)00338-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81285078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Detection of telomerase RNA component in human liver tissues","authors":"Hisashi Hisatomi, Yoshimi Ohmura, Kumi Nagao, Naomi Mori, Emi Wada, Yasuko Kawaoto, Toshiyasu Yamauchi, Kazumasa Hikiji","doi":"10.1016/S0928-4346(96)00344-1","DOIUrl":"10.1016/S0928-4346(96)00344-1","url":null,"abstract":"<div><p>This study investigated the relationship between telomerase activity and telomerase RNA component (telomerase RNA) in human liver tissues. Telomerase RNA was detected in all hepatocellular carcinoma (HCC) tissues (<span><math><mtext>20</mtext><mtext>20</mtext></math></span>), and telomerase activity was detected in 18 (90.00%) of the 20 HCC tissues. Telomerase RNA was detected in 17 (89.47%) of 19 livers with liver cirrhosis, and telomerase activity was detected in eight (42.11%) of the 19 tissues. In livers with chronic hepatitis, telomerase RNA was detected in 11 (64.71%) of 17, and telomerase activity was detected in six (35.29%) of the 17 tissues. Telomerase RNA was detected in all the tissues with telomerase activity detected, i.e. 19 HCC tissues, 17 liver cirrhosis tissues and 11 chronic hepatitis tissues. In all normal tissues (<em>n</em> = 3), telomerase RNA and activity were not detected. From our results, one can deduce that the production of telomerase is thought to be under the control of telomerase RNA, the possibility is great that chronic hepatitis tissues and liver cirrhosis tissues become HCC when the telomerase RNA is positive.</p></div>","PeriodicalId":13746,"journal":{"name":"International Hepatology Communications","volume":"6 3","pages":"Pages 175-178"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0928-4346(96)00344-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78649556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sandra Hirsch, Carlos Muñoz, María Pía de la Maza, Margarita Petermann, Marcelo López, Liana Schlesinger, Daniel Bunout
{"title":"Increased cytokine production is associated with acute inflammation in cirrhotic alcoholic patients","authors":"Sandra Hirsch, Carlos Muñoz, María Pía de la Maza, Margarita Petermann, Marcelo López, Liana Schlesinger, Daniel Bunout","doi":"10.1016/S0928-4346(96)00346-5","DOIUrl":"10.1016/S0928-4346(96)00346-5","url":null,"abstract":"<div><p>The role of cytokines in the etiology of liver injury and their contribution to the systemic manifestations that occur in patients with liver disease, are not clearly understood. <em>Aim:</em> To study if serum levels and in vitro blood mononuclear cell (BMC) production of IL-Iβ and TNFα are related to the severity of alcoholic liver cirrhosis, and identify potential factors that can modify cytokine production in these patients. Serum levels, spontaneous and in vitro LPS stimulated BMC production of Interleukin-Iβ (IL-Iβ) and Tumor Necrosis Factor α (TNFα), were measured in 38 patients with alcoholic cirrhosis Child B or C, and nine normal volunteers. Serum levels and spontaneous in vitro production of IL-Iβ and TNFα were below detection limits. There were no differences between normal controls and Child B or C patients in LPS-stimulated production of IL-Iβ or TNFα. However eight patients with alcoholic hepatitis or infections superimposed on cirrhosis, had higher levels on LPS-stimulated BMC production of IL-Iβ (12.9 ± 5.8 ng/ml) and TNFα (4.9 ± 2.3 ng/ml) than the rest of cirrhotic patients (5.3 ± 3.5 and 1.8 ± 0.9 ng/ml). There was no association between IL-Iβ and TNFα BMC production and parameters of liver function or recent alcohol ingestion. Increased levels of IL-Iβ and TNFα production by stimulated BMC are associated with acute inflammatory events in cirrhotic alcoholic patients and not with the severity of liver disease.</p></div>","PeriodicalId":13746,"journal":{"name":"International Hepatology Communications","volume":"6 3","pages":"Pages 166-174"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0928-4346(96)00346-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81540425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Development of local necrosis, side-effects and histopathological study after hepatic injection of acetic acid solutions","authors":"Toru Tamai , Toshihito Seki , Masato Imamura , Taiichi Nakagawa , Akira Nishimura , Kouji Kunieda , Tomohiro Shiro , Kyoichi Inoue , Akiharu Okamura","doi":"10.1016/S0928-4346(96)00342-8","DOIUrl":"10.1016/S0928-4346(96)00342-8","url":null,"abstract":"<div><p>Intratumoral injection of 50% acetic acid solution has recently been performed as a new local therapy for hepatocellular carcinoma. The use of ethanol in this therapy has problems of high dosage, frequent injections, and local tumor recurrence. Probably, in these regards the usefulness of acetic acid with potent coagulating and necrotizing effects cannot be denied. We have previously reported the acute toxicity of acetic acid injected into the normal rat liver at various concentrations. In the present study, we assessed the acute toxicity and necrotizing effect of 50% acetic acid solution and its effect on other organs after injection into the normal rat liver in different volumes. With increases in the volume of acetic acid, the size of the necrotic zone tended to increase and the mortality rate rose. The LD<sub>50</sub> of 50% acetic acid calculated with Behrens' method was 0.279 ml/kg. Histopathological examination of rats died immediately after acetic acid injection revealed acute pulmonary edema and marked congestion of the kidneys and spleen. Therefore, if this agent is used clinically, sufficient attention must be paid to its dose level and its acute toxicity.</p></div>","PeriodicalId":13746,"journal":{"name":"International Hepatology Communications","volume":"6 3","pages":"Pages 153-157"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0928-4346(96)00342-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87946171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rafael García-Cañero, Javier Pérez de Diego, Carolina Trilla, Miguel de Foronda, Juan José Díaz-Gil, Rosa M. Cereceda, Maricarmen Guijarro
{"title":"Changes in rat liver microsomal enzyme activities induced by injection of rat liver growth factor into male rats","authors":"Rafael García-Cañero, Javier Pérez de Diego, Carolina Trilla, Miguel de Foronda, Juan José Díaz-Gil, Rosa M. Cereceda, Maricarmen Guijarro","doi":"10.1016/S0928-4346(96)00335-0","DOIUrl":"10.1016/S0928-4346(96)00335-0","url":null,"abstract":"<div><p>Microsomal cytochromes P450 and b<sub>5</sub> and enzyme activities linked to P450 isoforms <span><math><mtext>IA1</mtext><mtext>2</mtext></math></span>, <span><math><mtext>IIB1</mtext><mtext>2</mtext></math></span>, IIC11 and IIIA were assessed over a 72 h period in male Wistar rats after intraperitoneal injection of a single dose of 4 μg/100 g body weight of rat liver growth factor (r-LGF) and compared with those of partially hepatectomized and sham-operated animals. The injection provoked a marked decrease in the activities of cytochrome P450 isozymes <span><math><mtext>IIB1</mtext><mtext>2</mtext></math></span>, IIC11 and IIIA and about a 50% reduction in cytochrome P450 and b<sub>5</sub> contents during the first 48 h postinjection, which were slowly restored to the levels observed in control or sham-operated animals. The findings in partially hepatectomized rats were similar. These results suggest that, alone, the rat liver growth factor selectively mimics the effects of the initial stages of in vivo liver regeneration in certain hepatic microsomal detoxifying enzymes.</p></div>","PeriodicalId":13746,"journal":{"name":"International Hepatology Communications","volume":"6 2","pages":"Pages 92-98"},"PeriodicalIF":0.0,"publicationDate":"1996-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0928-4346(96)00335-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76209775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Alcohol hepatic toxicity in rat: evidence of the utility of gastric ethanol metabolism","authors":"Lucia Battiston , Michèle Moretti , Patrizia Tulissi , Massimiliano Fanni-Canelles , Gabriele Pozzato","doi":"10.1016/S0928-4346(96)00330-1","DOIUrl":"10.1016/S0928-4346(96)00330-1","url":null,"abstract":"<div><p>Since a fraction of ingested ethanol (EtOH) is metabolized by gastric mucosa, different amounts of alcohol should reach the liver, when the same dose is administered by oral or intravenous route. Accordingly, we demonstrated that the hepatic depletion of glutathione induced by EtOH is lower when it is administered orally rather than intraperitoneally (i.p.). In the present study we investigated, after EtOH load, the time-course of common serum liver damage tests and of α-glutathione-<em>S</em>-transferase (αGST) levels as a new indicator of hepatocellular injury in rats. The tests were also performed in Cimetidine-treated rats. Oral EtOH administration was followed by a less pronounced decrease and by a quicker recovery of hepatic glutathione than after i.p. route. After oral EtOH load, Cimetidine, a potent inhibitor of gastric alcohol-dehydrogenase, produced a decrease of hepatic glutathione significantly (<em>P</em> < 0.005) more pronounced than in controls. Serum αGST increased significantly (<em>P</em> < 0.05) 6 h after i.p. EtOH administration, whereas no modifications were found after oral EtOH load. Common liver damage tests did not show any modification. In Cimetidine-treated rats, oral EtOH load was followed by an increase of serum αGST similar to that after i.p. administration. This study demonstrates the beneficial effects of gastric EtOH metabolism on the liver. The lack of gastric alcohol metabolism resulted not only in decreased content and delayed recovery of liver glutathione, but in potential hepatocellular damage.</p></div>","PeriodicalId":13746,"journal":{"name":"International Hepatology Communications","volume":"6 2","pages":"Pages 61-70"},"PeriodicalIF":0.0,"publicationDate":"1996-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0928-4346(96)00330-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86797330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Ursodeoxycholic acid decreases the serum transaminase levels of chronic liver disease patients treated with glycyrrhizin","authors":"Hironori Mitsuyoshi, Toshiaki Nakashima, Koji Inaba, Hiroki Ishikawa, Yoshikuni Sakamoto, Ninko Matsumoto, Takeshi Okanoue, Kei Kashima","doi":"10.1016/S0928-4346(96)00334-9","DOIUrl":"10.1016/S0928-4346(96)00334-9","url":null,"abstract":"<div><p>The effects of ursodeoxycholic acid (UDCA) on the liver function test values were investigated in patients with chronic hepatitis (CH) and liver cirrhosis (LC) in whom treatment with glycyrrhizin (SNMC) for more than 6 months had failed to improve serum transaminase levels. Twenty-six patients treated with Stronger neo minophagen C (SNMC), 60 ml, i.v., three times/week) for more than 6 months were given UDCA (Urso, 600 mg/day) in addition (SNMC + UDCA group) and 22 patients were given UDCA (Urso, 600 mg/day) alone (UDCA group). The mean AST, ALT, γ-GTP and total bile acid (TBA) values during the 3 months before UDCA treatment and the 3 months after the start of UDCA treatment were compared in each case. The results showed that AST, ALT and γ-GTP were improved by 28, 34 and 46%, respectively in the 24 patients with CH, type C in the SNMC + UDCA group, and 27, 30 and 39%, respectively in the 14 patients with CH, type C in the UDCA group. UDCA was also effective in improving AST and ALT in the patients in the SNMC + UDCA group who were resistant to interferon therapy. The percentages of improvement in AST, ALT and γ-GTP in the 10 LC patients were lower than in the CH patients in both SNMC + UDCA and UDCA group. In conclusion, UDCA is useful in decreasing the serum transaminase levels of patients with CH, even when they are being treated with SNMC.</p></div>","PeriodicalId":13746,"journal":{"name":"International Hepatology Communications","volume":"6 2","pages":"Pages 85-91"},"PeriodicalIF":0.0,"publicationDate":"1996-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0928-4346(96)00334-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76727710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Regulation of liver cell polarity by retinoic acid in vitro: bile canaliculi formation","authors":"Annie Claude , Samuel W. French","doi":"10.1016/S0928-4346(96)00336-2","DOIUrl":"10.1016/S0928-4346(96)00336-2","url":null,"abstract":"<div><p>The mechanisms which regulate liver cell polarity and the formation of the bile canaliculi are unknown. Retinoic acid may, like dexamethasone, regulate cell polarity through its effects on the development of the bile canaliculus. We examined these effects on hepatocytes in primary culture by observing the formation of bile canaliculi and the pericanalicular sheath. The hypothesis is that retinoic acid induces organizational changes in cellular polarity in hepatocytes in vitro. To test this hypothesis, we added <em>trans</em>-retinoic acid 10<sup>−5</sup> M to monolayers of hepatocyte cultures derived from preweanling rats. After 48 h the organization of the cytokeratin intermediate filament cytoskeleton was visualized by immunofluorescence on partially extracted preparations, by unembedded whole mount electron microscopy and gel electrophoresis on detergent extracted preparations. Quantitative measurements of the bile canaliculi were performed. Under the influence of retinoic acid, the number and size of bile canaliculi formed were significantly increased and formed a more complex architecture such as branching. The bile canaliculi were functional as demonstrated by the fluorescein diacetate dye uptake and excretion. In conclusion, retinoic acid enhanced cell polarity as indicated by the increase in the size and complexity of the bile canaliculi and the pericanalicular sheaths.</p></div>","PeriodicalId":13746,"journal":{"name":"International Hepatology Communications","volume":"6 2","pages":"Pages 99-111"},"PeriodicalIF":0.0,"publicationDate":"1996-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0928-4346(96)00336-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76529820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Antithrombin III stimulates prostaglandin I2 production by cultured rat hepatic sinusoidal endothelial cells","authors":"Hiromasa Ohira, Katsutoshi Obara, Masahito Kuroda, Jun Tojo, Hironobu Ochiai, Masae Kokubun, Masayuki Miyata, Tomoe Nishimaki, Reiji Kasukawa","doi":"10.1016/S0928-4346(96)00332-5","DOIUrl":"10.1016/S0928-4346(96)00332-5","url":null,"abstract":"<div><p>We examined the production of prostanoids, specifically prostaglandin (PG) I<sub>2</sub> and thromboxane (TX) A<sub>2</sub>, in cultured rat hepatic sinusoidal endothelial cells treated with antithrombin (AT) III. When cells were treated for 3 h with various concentration of AT III, production of 6-keto-PGF<sub>1α</sub> (a stable metabolite of PG I<sub>2</sub>) increased significantly and in a dose-dependent manner, compared with production by untreated cells. In terms of kinetics, significant increases were noted at 3 h (20.13 ± 1.38 pg/ml), 4 h (21.23 ± 0.63 pg/ml) and 24 h (36.58 ± 4.93 pg/ml) with AT III (300 μg/ml) stimulation, compared with production by the untreated cells (10.29 ± 1.21, 10.34 ± 1.66 and 22.64 ± 2.59 pg/ml, respectively). Moreover, this production was significantly reduced with increasing concentrations of heparin. On the other hand, TX B<sub>2</sub> (a stable metabolite of TX A<sub>2</sub>) production was unaffected by AT III treatment. These data suggest that AT III may ameliorate the liver damage or disturbances in the sinusoidal microcirculation by stimulating the PG I<sub>2</sub> production of hepatic sinusoidal endothelial cells.</p></div>","PeriodicalId":13746,"journal":{"name":"International Hepatology Communications","volume":"6 2","pages":"Pages 71-78"},"PeriodicalIF":0.0,"publicationDate":"1996-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0928-4346(96)00332-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77969397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}