bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk factors for ulcerative reflux oesophagitis: A case‐control study
Authors: RYAN PHILIP , HETZEL DAVID J. , SHEARMAN DAVID J. , McMICHAEL ANTHONY J.
Published: March 2008

Abstract A case‐control study was undertaken to investigate the effects of smoking, alcohol consumption, use of non‐steroidal anti‐inflammatory and other analgesic medications and family and medical history on the risk of ulcerative reflux oesophagitis (URO). We recruited 191 cases with URO diagnosed at endoscopy, 162 hospital controls who had also undergone endoscopy and 140 community controls from the Adelaide metropolitan area. From these three groups of subjects, 134 case‐community control pairs, matched on age, sex and postcode of residence and 142 case‐hospital control pairs, matched on age, sex, hospital and endoscopist, were formed. Elevated non‐significant risks were found in those smoking at least 20 cigarettes per day relative to those who never smoked (relative risk = 1.9, 95% confidence interval: 0.9‐3.9 in case‐hospital control pairs; relative risk = 1.9, 95% confidence interval: 0.9‐3.7 in case‐community control pairs). There was no elevation in risk associated with the use of non‐steroidal anti‐inflammatory drugs, with alcohol consumption, factors related to medical and reproductive history, nor with family history except for paternal history of heartburn (relative risk = 2.5, 95% confidence interval: 1.2‐5.4 in case‐hospital control pairs; relative risk = 1.9, 95% confidence interval: 1.0‐4.0 in case‐community control pairs). With the possible exception of smoking, no other risk factors for ulcerative reflux oesophagitis related to lifestyle are apparent.
Hepatic portal infiltrates in mice immunized with syngeneic lymphoid cells: Connotations for models of autoimmune liver disease
Authors: KARANIKAS VAIOS , MACKAY IAN R , ROWLEY MERRILL J , VEITCH BARRY , LOVELAND BRUCE E
Published: March 2008

The aim of this study was to investigate liver histology in mice after immunization with the conserved self molecule dihydrolipoamide dehydrogenase, E3, a subunit of the mitochondrial 2‐OADC enzyme family identified as the M2 autoantigen in the liver disease, primary biliary cirrhosis. Mice were immunized by a novel procedure. The autoantigen E3 was introduced by pinocytosis into hypertonically treated syngeneic lymphoid cells to facilitate intracellular antigen processing and presentation and the generation of a cytolytic T cell response. Liver sections were examined and scored for evidence of an inflammatory response by two independent procedures: standard microscopy with visual scoring, and automated scanning with computerized scoring. There was a close correlation between read‐outs of liver histology by standard microscopy and automated scanning, using the index of mononuclear cellular infiltrations in hepatic portal tracts. Such infiltrates were prominent in the immunized mice, but, unexpectedly, the degree of infiltration was similar in mice injected with autoantigen (E3)‐loaded syngeneic cells, or syngeneic cells treated only with hypertonic medium. The equivalent changes in the liver with the experimental and control protocol is indicative of the reactivity of the liver to any provocative immune stimulus, and is cautionary for protocols designed for the induction of autoimmune liver disease in experimental animals.
Infection of human hepatocyte cell lines with hepatitis C virus in vitro
Authors: TAGAWA M. , KATO N. , YOKOSUKA O. , ISHIKAWA T. , OHTO M. , OMATA M.
Published: March 2008

Hepatocyte related cell lines, namely human embryonic hepatocyte cell line (WRL68) and hepatoblastoma cell line (Hep G2), were tested for their ability to support hepatitis C virus (HCV) replication in vitro. The replicative intermediate of the minus strand HCV RNA was newly transcribed from the inoculated virus, and was stable in WRL68 cells over a period of 62 days. HCV RNA detected in the culture medium at 62 days after infection suggested a long period of virus secretion from this cell line. In Hep G2, transcription of the minus strand HCV RNA was also detected until 39 days after infection, but transcription and secretion of viral progeny could not be demonstrated. Although HCV infection of WRL68 was not high, this cell line might prove to be a useful tool for studying HCV replication in vitro.
Epithelioid granulomas in chronic hepatitis C: A transient pathological feature
Authors: OKUNO TADAO , ARAI KEN , MATSUMOTO MASAYUKI , SHINDO MICHIKO
Published: March 2008

Multiple hepatic granulomas in chronic hepatitis C patients treated with alpha interferon were recently observed. To assess the presence of hepatic granulomas in chronic hepatitis C, and to determine whether their presence is related to interferon therapy or primarily related to chronic hepatitis C viral (HCV) infection, 446 liver biopsy specimens from 239 Japanese patients with chronic hepatitis C were reviewed. Well‐formed non‐caseating epithelioid granulomas were found in five (1.1%) of 446 liver biopsy specimens from five (2.0%) of 239 patients. All five patients had been followed up for 1 to 3 years, having between one and six liver biopsy specimens taken at intervals of 6 months to 1 year. Four of these five patients received alpha interferon therapy during the follow‐up period. Hepatic granulomas were found in one of the pretherapy liver biopsy specimens in four patients and in one of the post‐therapy specimens in one patient. Extensive investigation of the aetiology of hepatic granulomas yielded no conclusive findings. The presence of hepatic granulomas could not be demonstrated in follow‐up liver biopsy specimens taken from the four patients who had undergone alpha interferon therapy. These findings suggest that hepatic granulomas may appear as an expression of non‐specific reaction in HCV‐related chronic hepatitis, and are not related to alpha interferon therapy.
Epidemiology of genotypes of hepatitis C virus in Japanese patients with type C chronic liver diseases: A multi‐institution analysis
Authors: TANAKA EIJI , KIYOSAWA KENDO , MATSUSHIMA TAKASHI , ISHIKAWA KAZUYOSHI , HINO KUNIHIKO , TANAKA SATOSHI , NOSE HARUHIKO , KUMADA HIROMITSU , IINO SHIRO , KAMIMURA TOMOTERU , UNOURA MASASHI , MIZOKAMI MASASHI , OKANOUE TAKESHI , KUROKI TETSUO , YAMADA GOTARO , MIURA TOHRU , YANO MICHITAMI , TSUBOUCHI HIROHITO , KOHARA MICHINORI , SATO SHUNICHI , HATTORI NOBU , GROUP GNOTYPING ELISA STUDY
Published: March 2008

Sixteen medical institutions in Japan collaborated in this study of the epidemiology of hepatitis C virus (HCV) genotypes. A total of 4176 patients with type C chronic liver disease, from the four main islands of Japan, were evaluated. Of those evaluated, 2794 had chronic hepatitis, 727 had liver cirrhosis and 655 had hepatocellular carcinoma. The HCV genotype of the patients was determined by an enzyme‐linked immunosorbent assay based on serological genotype 1‐ and 2‐specific recombinant peptides (SG‐1 and SG‐2, respectively) of the NS4 region. The prevalence of SG‐1 and SG‐2 HCV was similar in the four main islands of Japan. SG‐1 HCV predominated in each disease category (69–76%). The percentage of patients with SG‐1 HCV increased by 7%, while that of patients with SG‐2 HCV decreased by 7%, as liver disease progressed in severity from chronic hepatitis to carcinoma (P < 0.001). Patients with either SG‐1 or SG‐2 had a similar mean age and history of blood transfusion. In conclusion, SG‐1 HCV was found to predominate in Japan, and the HCV genotype was found to be related to the stage of hepatitis C disease.
Effect of nizatidine and ranitidine on 24 hour intragastric pH, pepsin, prostaglandin E2 and serum gastrin concentrations in healthy volunteers
Authors: THOMSON ABR , KIRDEIKIS P. , JAMALI F. , TAVERNINI M. , ZUK L. , MARRIAGE B. , SIMPSON I. , MAHACHAI V.
Published: March 2008

In order to achieve possible greater therapeutic efficacy, ranitidine 300 mg bid (R2) may be given rather than 300 mg qhs (R1), or nizatidine 300 mg bid (N2) may be given rather than 300 mg qhs (N1). A randomized placebo‐controlled crossover study was performed in six healthy volunteers (four males, two females) who ranged in age from 23 to 43 years, comparing R1 R2, N1, and N2 versus placebo (P), measuring 24 h intragastric pH by the aspiration technique, gastric juice pepsin and prostaglandin E2 (PGE2) concentrations, as well as serum gastrin concentrations. In all treatment groups, 24‐h intragastric pH was higher than with P; the 24 h and daytime (0800–2200 h) pH was higher with N2 than with N1 but not with R2 versus R1. The percentage pH ≥ 3 was greater with N2 than with N1 during the daytime. Night‐time (2200–0800 h) and 24 h pepsin concentrations were higher in R2 than in R1, were similar in N1 and N2, and were lower in these treatment groups than in P. The gastric juice PGE2 concentration at night‐time, but not at daytime, was increased in the four treatment groups compared with P. Despite the higher pH values at night‐time in the treatment groups, the night‐time concentrations of serum gastrin were unchanged, and yet during the daytime the higher values of pH were associated with increased gastrin concentrations when R2 or N2 were given, but not with R1 and N2. There was a negative correlation between intragastric juice pH and pepsin concentration during the daytime, and a positive correlation between pH and PGE2 concentration during the night‐time. The slopes and y‐axis intercepts between pH and pepsin or PGE2, concentrations differed between the placebo and the treatment groups, suggesting that these H2‐receptor antagonists may have an effect on lowering pepsin and raising PGE2 concentrations in addition to their effects on pH. As the percentage of time over the 24 h period and night‐time periods when the pH was greater than 3 was not different between ranitidine and nizatidine, the two regimens will likely have similar clinical efficacy.
The contrasting influence of chronic nicotine intake on gastrin and gastric acid secretion
Authors: WONG D. , OGLE CW
Published: March 2008

The effects of chronic nicotine treatment on gastric acid secretion stimulated by subcutaneous injection of pentagastrin, as well as on serum gastrin levels and the stomach parietal cell population, were examined. Rats drank a solution of nicotine 25 μg/mL tap water for periods of 10, 30 or 45 days. Pentagastrin increased the gastric secretory volume and acid output in pylorus‐ligated control animals that drank tap water. Animals given nicotine in their drinking water for 10, 30 or 45 days showed increased basal gastric secretion and acid output. Pentagastrin produced maximum stimulatory effects at lower dose levels of 50 μg/kg in the 10‐day treatment group and 25 μg/kg in the 30‐ or 45‐day treatment groups; however, the maximum responses to pentagastrin in all nicotine‐treated batches were comparable to those of their corresponding controls. Serum gastrin levels remained unchanged from the 10th day of nicotine treatment, whereas the levels in the control animals continued to rise with age. Nicotine 25 μg/mL drinking water given for 10, 30 or 45 days caused no significant changes in the parietal cell population, mucosal surface area or mucosal thickness. These findings are consistent with the idea that chronic nicotine administration, for at least 10 days, will lead to increased muscarinic receptor sensitivity; basal acid secretion is consequently elevated, and this in turn may depress gastrin secretion.
Comparison of lansoprazole and omeprazole in the short‐term management of duodenal ulcers in Taiwan
Authors: CHANG F‐Y , CHIANG C‐Y , TAM T‐N , NG W‐W , LEE S‐D
Published: March 2008

Lansoprazole is a novel H +/K + ‐ATPase inhibitor which exhibits a very potent and long‐acting suppression of acid secretion. The object of this randomized, controlled trial was to compare duodenal ulcer healing rates after 4 weeks of treatment with a once‐daily regimen of either 30 mg lansoprazole or 20 mg omeprazole. Of a total of 111 patients 57 received lansoprazole, whereas 54 received omeprazole. In intention‐to‐treat analysis at 4 weeks, 89.5% patients showed ulcer healing following treatment with lansoprazole compared with 83.3% of patients treated with omeprazole. Per protocol analysis indicated that 96.1% of patients treated with lansoprazole showed ulcer healing, compared with 93.6% of patients treated with omeprazole (NS). Age, smoking or ulcer size did not affect the ulcer healing rate. Both agents could effectively and quickly resolve ulcer symptoms. The Helicobacter pylori clearance was seen in 36 (73.5%) patients in the lansoprazole group and in 40 (80%) patients in the omeprazole group after four weeks of treatment (NS). In addition, both agents led to hypergastrinaemia, by approximately 1.6 fold. Adverse side effects included a few occurrences of reversible skin rash and constipation. It is concluded that lansoprazole elicits an adequate healing response and resolves symptoms of duodenal ulcer as well as omeprazole. Furthermore, lansoprazole is well tolerated with a few adverse side effects.
Acute hepatitis C transmitted by needlestick accident despite short duration interferon treatment
Authors: NAKANO YOSHIYUKI , KIYOSAWA KENDO , SODEYAMA TAKESHI , TANAKA EIJI , MATSUMOTO AKIHIRO , ICHIJO TETSUYA , MIZOKAMI MASASHI , FURUTA SEIICHI
Published: March 2008

Hepatitis C virus (HCV) transmission by needlestick accidents involving hospital employees has become an important problem. The present report is of a case of acute hepatitis C that developed after a needlestick injury, despite short duration interferon treatment performed just after the accident in a trial effort to prevent HCV transmission. Nosocomial infection of HCV in medical employees is reviewed, and the current prospects for protecting them from HCV transmission after needlestick accident are discussed.
Interferon treatment for chronic hepatitis C in haemodialysis patients: Suggestions based on a small series
Authors: OKUDA KUNIO , HAYASHI HARUYUKI , YOKOZEKI KAZUO , KONDO TOMOKO , KASHIMA TAKASHI , IRIE YASUBUMI
Published: March 2008

Chronic hepatitis C is endemic among chronic haemodialysis patients. There have been a number of reports on hepatocellular carcinoma developing in such patients in Japan. The present study reports on the treatment of 15 patients who showed elevated ALT levels due to biopsy proven chronic hepatitis C with interferon α‐2a (IFN). The dose schedule was 6 mega units (MU) daily for the first two weeks followed by 3 doses per week for 5.5 months. Side effects were so severe that IFN treatment was discontinued early in one patient, the dosage reduced in 11 and only tolerated in the original schedule by three patients. Excluding one patient who only recently completed the therapy, 13 were able to be evaluated for therapy efficacy by assessment of serum ALT and viral RNA. The overall results showed that IFN was effective in eight of 13 patients, a rate somewhat higher than the reported figures in this country. It is concluded that IFN therapy is indicated in haemodialysis patients with progressive chronic hepatitis C, but the dose administered should be lower and the dose schedule more flexible, perhaps 3 MU three times a week, in order to minimize untoward side effects.
Bile acid‐induced depolarization of mitochondrial membrane potential preceding cell injury in cultured gastric mucosal cells
Authors: MIURA SOICHIRO , FUKUMURA DAI , SHIOZAKI HIROSHI , SUZUKI MASAYUKI , KUROSE IWAO , SUEMATSU MAKOTO , TSUCHIYA MASAHARU , ISHII HIROMASA
Published: March 2008

Changes in energy metabolism elicited by sodium taurocholate and their relation to cell viability were determined in gastric mucosal cells. Cultured mucosal cells were labelled with rhodamine‐123, a mitochondrial energization‐sensitive fluorescence probe, or by propidium iodide, a fluorochrome which labels the nuclei of non‐viable cells. The cells were observed under a fluorescence microscope with a laser scanning confocal imaging system. After the addition of sodium taurocholate at concentrations > 5 mol/L, mucosal cells showed a rapid and significant decrease in rhodamine‐123 fluorescence. A decrease to 40% of the pretreated values at 30 min was seen with a concentration of sodium taurocholate of 7.5mmol/L. A marked increase in the percentage of propidium iodide‐positive cells was noted when the concentration of sodium taurocholate exceeded 5mmol/L. However, the extent of the decrease in rhodamine‐123 fluorescence was always greater than the increase in the percentage of propidium iodide‐positive cells, suggesting that most of these gastric mucosal cells remained viable. It is therefore suggested that the decrease in rhodamine‐123 fluorescence is largely due to the disturbed oxidative phosphorylation of mitochondria. Pretreatment of gastric mucosal cells with low concentrations of ethanol resulted in a significant cytoprotective effect against sodium taurocholate injury with significant prevention of a decrease in rhodamine‐123 fluoresence. It is concluded that sodium taurocholate induces a depolarization of the mitochondrial membrane potential preceding cell injury and that the cytoprotective effect of ethanol relates to its attenuation of the uncoupling effect.
Dyspepsia and Helicobacter pylori in Japanese employees with and without ulcer history
Authors: SCHLEMPER RONALD J , VAN DER WERF SJOERD DJ , BIEMOND IZÄK , LAMERS CORNELIS BHW
Published: March 2008

In a Dutch working population, the apparent association between dyspeptic symptoms and Helicobacter pylori infection was found to be entirely due to subjects with an ulcer history. In general populations with a much higher prevalence of H. pylori infection and peptic ulcer disease, such as in Japan, the relationship between dyspepsia and H. pylori has yet to be clarified. A questionnaire on ulcer history and dyspeptic symptoms during the preceding 3 month period was obtained from apparently healthy Japanese employees who underwent a periodic medical examination. In addition, serum samples were analysed for anti‐H. pylori IgG antibodies. A total of 196 men and 35 women, aged 23–71 years, participated in the study. Seven women (20%) and 49 men (25%) had a diagnosis of peptic ulcer disease. Among 41 subjects with verified duodenal (26) and/or gastric (17) ulcer, 95% were H. pylori positive while 32% had had frequent dyspeptic symptoms in the 3 months prior to the study (29% of the 35 men and 50% of the 6 women). Among the 147 men and 28 women without an ulcer history, the 3 month period prevalence of frequent dyspepsia was 14 and 32%, respectively. The rate of H. pylori positivity was 80% in non‐ulcer dyspeptics and 68% in all other non‐ulcer subjects (95% confidence intervals: 61–92 and 61–76%, respectively). Significant differences in symptoms between H. pylori positive and negative subjects could not be detected, neither in the whole population nor in the non‐ulcer group. In conclusion, in this Japanese working population, no association was found between dyspeptic symptoms and H. pylori infection, irrespective of the inclusion of subjects with a peptic ulcer history.
Ultrasound‐guided fine needle aspiration biopsy of portal vein thrombosis in liver cirrhosis: Results in 15 patients
Authors: DE SIO ILARIO , CASTELLANO LUIGI , CALANDRA MARIA , ROMANO MARCO , PERSICO MARCELLO , DEL VECCHIO‐BLANCO CAMILLO
Published: March 2008

Between 1988 and 1992 ultrasound‐guided fine needle aspiration biopsies of thromboses in the main branches of the portal vein were carried out in 15 patients with liver cirrhosis. The aims of the study were to evaluate the usefulness, feasibility and diagnostic accuracy of this procedure in cirrhotics with known or suspected hepatocellular carcinoma. The procedure was carried out only in patients with a platelet count ≥40 000/μL and prothrombin activity ≥40%. A single pass, with a 22 gauge spinal needle, was performed in the portal vein lumen. Diagnosis of the aetiology of the portal vein thrombosis was obtained in all 15 cases. In 12 cases, a cytological diagnosis of hepatocellular carcinoma was made. In one case, the neoplastic cells aspirated were compatible with adenocarcinoma, and a subsequent colonoscopy confirmed the presence of colonic cancer. The material aspirated was compatible with chemically‐induced thrombosis in one patient who had undergone several percutaneous ethanol injection sessions for treatment of hepatocellular carcinoma, and in the last case only blood was aspirated, thus ruling out the coexistence of hepatic cancer. We conclude that fine needle aspiration biopsy of portal vein thrombosis is a feasible, low risk procedure that facilitates the diagnosis of hepatocellular carcinoma when fine needle biopsy of focal liver lesions fails. Fine needle aspiration biopsy of portal vein thrombosis is also useful in excluding neoplastic aetiology of portal vein thrombosis.
Secondary prevention of hepatocellular carcinoma
Authors: TANG ZHAO‐YOU , YANG BING‐HUI
Published: March 2008

Two decades have gone by since the earlier trials of alpha‐fetoprotein (AFP) screening for hepatocellular carcinoma (HCC) were conducted in Africa and China. It is accepted that early detection, diagnosis and treatment of HCC remains an important target to be achieved before a breakthrough appears on the primary prevention of HCC. In the present study, screening investigations were performed in a high risk population of HCC, defined as persons who had hepatitis, blood transfusions, a family history of HCC, and were hepatitis B virus carriers. Ultrasonography combined with AFP serosurvey was accepted as an effective screening procedure to detect small HCC. Early diagnosis of HCC was not difficult if tumour markers and medical imaging were combined. Early resection has been proven to prolong survival of patients with small HCC. Repeated intralesional ethanol injection is an alternative treatment to surgery, while transcatheter arterial embolization is a less effective alternative. Re‐resection of subclinical recurrence after curative resection has proven of merit in prolonging survival even further. Resection of small HCC remains an important approach in getting long‐term HCC survival and to improving 5‐year survival rates. It is more effective than treatment of large HCC. Studies on the secondary prevention of HCC have stimulated research into tumour markers, the natural history and cellular origin of HCC and oncogenes. However, the issue of ‘cost‐effectiveness’ remains to be evaluated.
Gastric microcirculatory disturbance and behaviour of leucocytes after thermal injury: Intravital observation of arteriovenous shunting channels in the gastric submucosal layer
Authors: YOSHIDA MASASHI , FUKUMURA DAI , WAKABAYASHI GO , OTANI YOSHIHIDE , OSHIMA ATSUSHI , SHIMAZU MOTOHIDE , KUBOTA TETSURO , KUMAI KOICHIRO , KUROSE IWAO , MIURA SOICHIRO , KITAJIMA MASAKI
Published: March 2008

In order to investigate the pathogenesis of acute gastric mucosal lesion after thermal injury, microcirculatory disturbance was assessed and observation of the behaviour of leucocytes was performed. Gastric blood flow decreased at 15 min post‐thermal injury, and partially improved at 2 h; however, it decreased again at 5 h post‐thermal injury. Mucosal microcirculatory disturbance was observed by using vascular labelling with monastral blue B. Deposits of monastral blue B were observed centring mainly on collecting venules but were also observed in the capillaries. Submucosal microcirculatory disturbance was observed through an intravital microscope. The irregularity of the wall and segmental constriction in the venules and presence of an arteriovenous shunting channel was observed in the submucosal layer at 5 h post‐thermal injury. The percentage of rolling or sticking leucocytes that passed the confluence of a prevenule and a venule were significantly increased at 5 h after thermal injury. The present study revealed depression of gastric blood flow, mucosal and submucosal microcirculatory disturbance, and a significant increase of rolling and sticking leucocytes in the peripheral part of venules after thermal injury. Leucocyte‐endothelial interactions may occur under such conditions and this interaction may play an important role in inducing the microcirculatory disturbance that results in an acute gastric mucosal lesion after thermal injury. The present study also demonstrated the possibility of intravital study of gastric submucosal arteriovenous shunting channels.
Role of mucosal microcirculation in gastric lesions induced by lateral hypothalamic lesions in rats
Authors: SAITA HIROSHI , MURAKAMI MOTONOBU , KITA TORU
Published: March 2008

To evaluate the pathophysiology underlying gastric mucosal lesions induced by lateral hypothalamic (LH) lesions, we investigated the changes in acid secretion, gastric mucosal blood flow, gastric mucus and mucosal integrity in the corpus during the 4 h period and 48 h after the production of bilateral electrolytic LH lesions in male Sprague‐Dawley rats. Gastric mucosal lesions were macroscopically produced 24 h (63%) and 48 h (83%) after LH lesions, although there were no visible lesions at 7 h. Gastric acid secretion was significantly increased 48 h after LH lesions, compared with that in the control group. Gastric mucosal blood flow and transmucosal potential difference (PD) in the LH lesion group immediately decreased after LH lesions and did not recover during 4 h and at 48 h. On the contrary, in the control group, gastric mucosal blood flow decreased after the brain surgery but soon recovered, and there was no significant change in PD. LH lesions resulted in the reduction of intramucosal mucus to 50% 3 h after LH lesions. Moreover, we exposed the stomach to 10 mmol/L taurocholic acid (TCA) 3 h after LH lesions to examine the disruption in gastric mucosal defensive function in rats with LH lesions. The recovery of the reduced PD by TCA was slow and gastric mucosal lesions were easily formed in the LH lesion group. These results suggest that gastric mucosal ischaemia after lesioning of LH immediately results in the disruption of mucosal defensive function before the formation of visible gastric lesions, and predisposes to the formation of gastric mucosal lesions by a delayed increase in acid secretion.
Intestinal absorption of lithocholate and its sulfate and glucuronide in rats
Authors: TAKIKAWA HAJIME , YOKOTE MICHIKO , SANO NAOYO , NAKAKI MOTOE , YAMANAKA MASAMI
Published: March 2008

The absorption of lithocholate and its sulfate and glucuronide in rat jejunum and terminal ileum was studied. Tracer amounts of radiolabelled bile acids were administered to the ligated intestinal segments, and their absorption was monitored by biliary excretion through a bile duct catheter. Absorption of lithocholate was faster in the terminal ileum than in the jejunum. Although the sulfation reduced lithocholate absorption in the jejunum, it did not affect lithocholate absorption in the terminal ileum. This was due to the Na+‐dependency of ileal absorption of lithocholate‐sulfate assessed by perfusion studies. In contrast, the glucuronidation markedly reduced lithocholate absorption both in the jejunum and the terminal ileum. These findings indicate that the glucuronidation is more effective than sulfation in detoxifying lithocholate as far as the prevention of its intestinal absorption is concerned.
Serum pepsinogen I and pepsinogen II, and the ratio of pepsinogen I pepsinogen II in peptic ulcer diseases: With special emphasis on the influence of the location of the ulcer crater
Authors: WU MING‐SHIANG , WANG HSIU‐PO , WANG JIN‐TOWN , WANG TEH‐HONG , LIN JAW‐TOWN
Published: March 2008

To investigate the effect of the location of the ulcer crater on the serum levels of pepsinogen I (PGI), pepsinogen II (PGII) and the ratio of PGI/PGII, these parameters were determined in 161 healthy controls, 29 patients with gastric ulcer in the gastric body (GU‐I), 65 with coexistent gastroduodenal ulcer (GU‐II), 104 with gastric ulcer in the prepyloric region (GU‐III), and 116 with duodenal ulcer (DU). Serum PGI levels were significantly higher (P<0.01) in patients with GU‐III (110.6 ± 65.1 ng/mL), GU‐II (100.0 ± 46.6 ng/mL), and DU (92.2 ± 35.2 ng/mL) than in the controls (77.4 ± 31.4 ng/mL), while there were no significant differencs between GU‐I (82.5 ± 36.3 ng/mL) and the controls. Patients with gastric ulcer in any region had significantly higher (P<0.01) serum PGII levels (GU‐I, 20.0 ± 15.7 ng/mL; GU‐II, 15.5 ± 10.9 ng/mL; GU‐III, 14.3 ± 10.0 ng/mL) than the controls (10.6 ± 6.0 ng/mL) and the patients with DU (10.0 ± 5.5 ng/mL), whereas no significant differences existed between the latter two. The ratio of PGI/PGII in GU‐I (5.86 ± 3.90) was significantly lower (P<0.01) than any other group (controls, 8.83 ± 4.70; GU‐II, 8.33 ± 4.99; GU‐III; 9.64 ± 6.13; DU, 10.45 ± 4.49), while patients with DU it was significantly higher (P<0.01) than any other groups. These findings indicate that peptic ulcer is comprised of a heterogeneous group of diseases. A normal level of serum PGI, an increased level of PGII, and a decreased ratio of PGI/PGII in GU‐I patients reflected extensive atrophic gastritis, while an elevated level of PGI, a normal level of PGII, and an increased ratio of PGI/PGII in DU patients implicated hypersecretory status coexistent with superficial fundic gastritis. These findings suggest functional heterogeneity of the gastric mucosa according to the different locations of the ulcer crater.
Secretory and biosynthetic responses of gastrin and somatostatin to acute changes in gastric acidity
Authors: KAPUSCINSKI MIREK , SHULKES ARTHUR
Published: March 2008

The activity of gastric parietal cells in terms of hydrochloric acid (HCl) secretion is regulated by the interaction of stimulatory substances (e.g. gastrin) and inhibitors (e.g. somatostatin) acting in an endocrine and paracrine mode, as well as luminal factors. In the present study the following parameters were measured: the synthesis (mRNA), storage (tissue peptide concentration) and secretion (plasma peptide concentration) of somatostatin and gastrin following short‐term treatment of rats with pentagastrin (acid stimulant), secretin, omeprazole (reduces gastric acidity by inactivating gastric H/K ATPase) and the somatostatin analogue octreotide (reduces gastric acidity by inhibiting both the parietal cell and gastrin). The mRNA coding for H/K ATPase and carbonic anhydrase II (CA II), the two enzymes responsible for the generation of hydrogen ions from the parietal cell, were also quantitated. In response to octreotide, somatostatin peptide and mRNA levels in the fundus rose to 180 ± 16% (P < 0.001) and 1073 ± 356% (P < 0.05) of control, respectively. In contrast, octreotide caused a decrease in antral somatostatin peptide and its mRNA did not change significantly. No significant changes in synthesis, secretion or storage of gastrin were observed except for omeprazole induced hypergastrinaemia (580 ± 76%, P < 0.001). H/K ATPase and CA II mRNA were largely unaffected except for an increase in CA II mRNA following octreotide and a decrease in H/K ATPase mRNA after pentagastrin. These data support the concept of the differential control of antral and fundic somatostatin synthesis and provide evidence for a regulatory loop by which somatostatin can influence its own synthesis. H/K ATPase and CA II mRNA were not regulated in concert, as reported to occur in isolated canine parietal cells, a result that reiterates the need for these type of whole animal studies.
Detection of hepatitis B virus precore stop codon mutants by selective amplification method: Frequent detection of precore mutants in hepatitis B e antigen positive healthy carriers
Authors: NAKAHORI SUSUMU , YOKOSUKA OSAMU , EHATA TOSHIKI , CHUANG WANG‐LONG , IMAZEKI FUMIO , ITO YOSHIMI , OHTO MASAO
Published: March 2008

The precore region of hepatitis B virus (HBV) is indispensable for secretion of e antigen protein. Therefore, the precore stop codon mutants may play an important role in the process of e antigen seroconversion. However, the presence of the mutants in hepatitis B e antigen positive carriers has not been fully studied because of difficulties in detecting the mutants in the presence of large amounts of wild‐type viruses. To overcome this, a sensitive method has been developed to detect the presence of G to A stop codon mutants at codon 28 of precore region. Primers for polymerase chain reaction (PCR) were devised to introduce restriction enzyme site Sty I for wild‐type viruses and Dde I for the mutants. The amplification products with these primers were digested with Sty I to exclude the products from wild‐type viruses. The remaining amplicon from precore mutants were re‐amplified, and the presence of precore mutant was confirmed with Dde I digestion. The presence of precore mutants was examined in 61 HBV carriers by the method combining PCR and restriction enzyme digestion. Approximately 0.1% of precore mutant DNA among 106 copies of wild‐type virus DNA was detectable by this method. The presence of the precore mutants was detected in seven of 10 (70%) e antigen positive asymptomatic carriers, and in 29 of 36 (81%) e antigen positive patients with chronic liver diseases, and in all 15 (100%) anti‐e antibody positive patients with chronic liver diseases.

This study revealed that a small amount of the precore mutants was present in the majority of HBV carriers.
Cytokines, nitric oxide synthesis and liver regeneration
Authors: DECKER KARL F , OBOLENSKAYA MARIA Y
Published: March 2008

During the prereplicative period of liver regeneration the changes in the levels of mRNA for tumour necrosis factor‐α (TNF‐α) and its receptors were nearly synchronous. The mRNA levels reached their maximum 1 – 3 h after operation and exceeded the values for intact animals about tenfold. Lipopolysaccharide stimulation induced an increase in TNF‐α and TNF receptor production comparable with that occurring during regeneration.

Nitric oxide (NO) production in the regenerating liver was determined by electron paramagnetic resonance (EPR) spectroscopy. The first increase in NO production occurred approximately 1 h after partial hepatectomy (PHE). The second and more pronounced peak of NO production was observed about 6 h after PHE when the hepatocytes entered the first cell cycle; it originated mainly from these cells. The consequent minimum of NO synthesis coincided with the maximal rate of DNA synthesis. The third gradual rise of NO production was seen at the transit from the first to the second cell cycle of the hepatocytes and the entrance of the non‐parenchymal cells into proliferation.

Hepatocytes, Kupffer and endothelial cells were isolated from livers after PHE. They were found to start their main NO production in the described sequence at the times corresponding to their respective entrance into the cell cycle. The maxima of NO synthesis were inversely correlated to the DNA‐synthesizing activity of the individual cell type.
Role of sinusoidal endothelial cells in liver disease
Authors: OKANOUE TAKESHI , MORI TAKASHI , SAKAMOTO SHINICHI , ITOH YOSHITO
Published: March 2008

We characterized the structural changes of sinusoidal endothelial cells in chronic ethanolfed rats and rats with cirrhosis induced by thioacetamide. The phenotypic changes of sinusoidal endothelial cells in fibrotic rats induced by thioacetamide and the reversibility of these changes were also investigated under transmission and scanning electron microscopy, regular microscopy and by immunohistochemistry with laminin and von Willebrand factor antibodies. The diameter and porosity of sinusoidal endothelial fenestrations were increased in chronic ethanol‐fed rats without liver fibrosis, however, they decreased within 4 weeks of the cessation of thioacetamide treatment. A basement membrane‐like structure in Disse's space was noted 6 weeks after thioacetamide treatment. Laminin was detected in Disse's space after 4 weeks and von Willebrand factor was detected in the cytoplasm as granular fluorescence after 6 weeks of thioacetamide treatment. Reversibility of the phenotypic changes of the sinusoidal endothelial cells was demonstrated in fibrotic liver of rats that received thioacetamide for 6 weeks after long‐term discontinuation of thioacetamide administration. These results indicate that the structural and immunohistochemical characteristics of sinusoidal endothelial cells change in chronic ethanol‐fed rats and fibrotic rats and these changes are reversible.
Role of adhesion between activated macrophages and endothelial cells in the development of two types of massive hepatic necrosis in rats
Authors: MOCHIDA SATOSHI , OHNO AKIHIKO , ARAI MASAHIRO , FUJIWARA KENJI
Published: March 2008

Sinusoidal endothelial cell damage is produced by activation of hepatic macrophages after endotoxin administration in rats pretreated with Cornyebacterium parvum or undergoing 70% hepatectomy. Such damage causes fibrin deposition in the hepatic sinusoids leading to massive hepatic necrosis. In the C. parvum model, cytotoxic mediators, such as tumour necrosis factor (TNF)α and superoxide anions released from activated hepatic macrophages directly destroy sinusoidal endothelial cells. In contrast, in the partial hepatectomy model, endothelial cell damage occurs as a result of fibrin deposition due to derangement of the coagulation equilibrium regulated by tissue factor and thrombomodulin expressed on hepatic macrophages and sinusoidal endothelial cells, respectively. Immunohistological examination revealed that the expression of ICAM‐1 in sinusoidal endothelial cells and LFA‐1 in hepatic macrophages was greater in both models than in normal rats preceding the development of hepatic necrosis. The extent of liver injury was significantly attenuated by treatment with monoclonal antibodies against both adhesion molecules in the C. parvum model, but aggravated in the partial hepatectomy model, compared to control rats. We conclude that adhesion of activated macrophages to endothelial cells via LFA‐1 and ICAM‐1 in the hepatic sinusoids is essential for endothelial cell destruction in the C. parvum model, but can act protectively against provocation of fibrin deposition in the hepatectomy model.
Roles of oxidative stress in activation of Kupffer and Ito cells in liver fibrogenesis
Authors: TSUKAMOTO HIDEKAZU , RIPPE RICHARD , NIEMELÄ ONNI , LIN MIN
Published: March 2008

An increasing body of experimental evidence is emerging to incriminate oxidative stress as a pivotal signal for liver fibrogenesis. This paper reviews the results from our studies testing this hypothesis. In the rat model of alcoholic liver disease, the importance of oxidative stress was supported by marked accentuation of liver fibrosis by dietary supplementation of iron, a pro‐oxidant, and the significant correlation of the liver malondialdehyde (MDA) and 4‐hydroxynonenal (4HNE) levels with the hepatic collagen accumulation. Both MDA and 4HNE adduct epitopes were detected intensely and diffusely in close association with collagen deposition. The direct cause and effect relationship between MDA/4HNE and Ito cell stimulation was indicated by the demonstration of Ito cell collagen gene induction by these aldehydes in culture. In primary cultures of rat Kupffer cells (KC), addition of antioxidants such as α‐tocopherol acetate and succinate suppressed mRNA expression and the release of interleukin (IL)‐6 and tumour necrosis factor alpha (TNFα). In rats with biliary fibrosis, an increase in the liver MDA level was accompanied by enhanced mRNA expression of procollagen α 1 (I) and transforming growth factor β 1 in Ito cells; and that of TNFα and IL‐6 in KC. Furthermore, the gel shift assay of KC nuclear extracts showed enhanced NF‐kB DNA binding activity. These results support the proposal that enhanced oxidative stress constitutes an important signal for activation of Kupffer and Ito cells in experimental liver fibrogenesis.
Integrity of myosin light chain kinase is essential for Ito cell contraction
Authors: WATANABE SUMIO , WANG XIAN‐EN , HIROSE MIYOKO , OIDE HIROSUMI , SHIMIZU HIDETAKE , KITAMURA TSUNEO , YUMOTO ATUKO , SUZUKI SATOKO , MIYAZAKI AKIHISA , SATO NOBUHIRO
Published: March 2008

Hepatic sinusoidal Ito cells (fat storing cells) are believed to play a regulatory role on hepatic sinusoidal blood flow through their contraction. The detailed mechanism of contraction of Ito cells, however, is still unknown. The present study was undertaken to clarify the effect of new myosin light chain kinase inhibitor, wortmannin, on Ito cell contraction. Ito cells prepared from rat liver were cultured for 4 days before the study. The contraction of Ito cells, which was monitored and analysed by time‐lapse video tape recording, was triggered by addition of endothelin‐1. Wortmannin pretreatment for 1 h inhibited endothelin‐induced Ito cell contraction dose‐dependently. Therefore, the integrity of the actomyosin system is essential for Ito cell contraction and normal sinusoidal blood flow.
Possible cause of primary graft non‐function after orthotopic liver transplantation: A hypothesis with rat models
Authors: FUJIWARA KENJI , MOCHIDA SATOSHI , OHNO AKIHIKO , ARAI MASAHIRO
Published: March 2008

The cause of primary graft non‐function after orthotopic liver transplantation (OLTX) is uncertain, but its clinical features are similar to fulminant hepatic failure with coagulopathy. In preserved livers, endothelial cell damage in the hepatic sinusoids is characteristic, indicating that fibrin deposition in the hepatic sinusoids, which can cause massive hepatic necrosis, might occur in the liver after OLTX. When rat liver was preserved in University of Wisconsin solution at 1°C, detachment of endothelial linings into sinusoidal lumens developed with fat‐storing cell damage after 18 h. In this liver, hepatic macrophages were activated after reperfusion. Tissue factor activity in hepatic macrophages isolated from livers after OLTX was significantly increased compared to the control liver and this increase was enhanced by addition of endotoxin. In the preserved and transplanted livers, thrombomodulin expression in endothelial cells disappeared and fibrin deposition was seen in the hepatic sinusoids. Intravenous infusion therapy with antithrombin III attenuated liver injury 24 h after OLTX following preservation for 18 h. These results suggest that intravascular coagulation in the hepatic sinusoids associated with liver injury occurs in the liver after OLTX following cold preservation. This coagulopathy may be caused by sinusoidal endothelial cell damage due to regulatory imbalance in coagulation as a result of increased tissue factor activity in hepatic macrophages and decreased thrombomodulin activity in sinusoidal endothelial cells. Fat‐storing cell damage may also contribute to the endothelial cell damage. A hypothesis regarding the cause of primary graft non‐function after OLTX is proposed.
Liver transplantation and hepatic sinusoidal cells
Authors: ARII SHIGEKI , IMAMURA MASAYUKI
Published: March 2008

Primary graft non‐function of the liver is one of the common causes of retransplantation. Although the mechanism of primary graft non‐function is not fully understood, a potent elucidative pathogenesis is microcirculatory disturbance due to sinusoidal damage during cold preservation and reperfusion. In this article, we discuss the possible participation of sinusoidal endothelial cells and Kupffer cells (KC) in the cold preservation/reperfusion injury. Kupffer cell activation and endothelial damage were developed during the cold preservation with subsequent reperfusion. Activated KC produced a large quantity of tumour necrosis factor (TNF)α, and then increased ICAM‐1 expression in sinusoidal endothelial cells. The reperfusion experiment showed that hypercoagulability and leucocyte adherence in the liver are strongly involved in reperfusion injury, and that KC blockade as well as anti‐TNFα antibody and anti‐ICAM‐1 antibody ameliorate the injury in association with a reduction of both fibrin deposition and leucocyte accumulation. Ultrastructural observation also revealed the beneficial effect of KC blockade on the maintenance of sinusoidal endothelial cells. Furthermore, the thromboxane A2‐thromboxane A2 receptor system in the sinusoid was also found to participate in this pathogenesis. Thus, these results suggested that cold preservation/reperfusion injury is due to sinusoidal microcirculatory disturbance, which is, at least in part, induced by communication between activated KC and sinusoidal endothelial cells through, among others, ICAM‐1, cytokines and prostanoids.
Endotoxin induced cellular communication in the liver: Murine models for clarification of the role of LPS‐responsive macrophages in the pathogenesis of liver diseases
Authors: SHIRATORI YASUSHI , KAWASE TATEO , KOMATSU YUTAKA , HIKIBA YOHKO , OKANO KEN'ICHI , KAMII KAZUO , OMATA MASAO
Published: March 2008

In several experimental models, lipopolysaccharide (LPS) plays an important role in the pathogenesis of liver diseases. Murine models of C3H/HeN and C3H/HeJ mice have been used to elucidate the role of LPS and its responsive‐macrophages in vivo, as C3H/HeN strain mice are known to be LPS‐responsive, while C3H/HeJ strain mice are LPS‐resistant. Furthermore, release of several kinds of biologically active mediators such as interleukin‐1, tumour necrosis factor‐α, colony stimulating factor and reactive oxygen radical is not enhanced in C3H/HeJ mice even after stimulation with LPS. Thus, these murine models could be suitable for clarification of endotoxin induced cellular communication in the liver.
Effects of combination therapy with interferon and ofloxacin on chronic type C hepatitis: A pilot study
Authors: TSUTSUMI MIKIHIRO , TAKADA AKIRA , TAKASE SHUJIRO , SAWADA MAKOTO
Published: March 2008

Interferon is effective in only a limited number of patients with the 1b type of hepatitis C virus (HCV), indicating that a combination therapy with other antiviral drugs may be essential to obtain better results. In the present pilot study, the effects of a combination therapy with interferon (IFN) and an antibacterial drug, ofloxacin, were analysed. Ten patients with chronic type C hepatitis received the combination therapy (combination group). Six million units of natural IFN‐α were administered daily for 3 weeks and then three times a week for 21 weeks. The combination therapy was initiated at the beginning of the eighth week of IFN treatment and 600 mg ofloxacin per day was administered for 12 weeks. As a control, changes in HCV‐RNA were also analysed in patients who were treated with only IFN for the same period (IFN‐alone group). In the combination group, serum transaminase levels and the titres of HCV decreased significantly with ofloxacin administration. Such changes were not observed in the IFN‐alone group. The incidence of HCV‐negativity at the end of ofloxacin administration of the combination group was significantly higher than in the IFN‐alone group. The complete response rate was twice as high in the combination group as in the IFN‐alone group. In two patients who did not respond well to the IFN‐alone treatment, ofloxacin administration was commenced after the 24th week. Serum transaminase levels were normalized and HCV‐RNA became negative in these two patients after the administration of ofloxacin. These results suggest that combination therapy with IFN and ofloxacin may be an effective treatment for chronic type C hepatitis.
Case Report: Acanthosis nigricans in association with primary biliary cirrhosis: Resolution after liver transplantation
Authors: PHAM TH , KAUSHIK S. , LIN BPC , JONES DB
Published: March 2008

A case is described of a 58 year old Caucasian male with primary biliary cirrhosis (PBC) who first presented with acanthosis nigricans of both axillae, skin pigmentation, which was pronounced over the posterior surface of the neck, and generalized pruritus. Following orthotopic liver transplantation for progressive liver disease, the skin pigmentation, pruritus and acanthosis nigricans resolved. It is believed that this is the first reported case of acanthosis nigricans occurring in association with PBC, a phenomenon that resolved after liver transplantation.