bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractThe 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

AbstractPrimary 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

AbstractIn 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

ABSTRACTInterferon 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

ABSTRACTA 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.
Cellular iron processing
Authors: MORGAN EVAN H. 
Published: March 2008

ABSTRACTIron is transported in the blood plasma, mainly bound to transferrin, but in abnormal conditions other iron containing compounds may become important. These include ferritin, haemopexin‐haem, haptoglobin‐haemoglobin and non‐specific non‐transferrin‐bound iron, all of which are taken up from the circulation by the liver. Transferrin‐bound iron can be used by all types of cells in amounts that depend on their complement of transferrin receptors. Immature erythroid cells are the most active in this function. Investigations using reticulocytes as an example of erythroid cells have demonstrated the presence of two mechanisms for the uptake of ferrous iron. One, a high affinity process disappears as reticulocytes mature. It probably represents the mechanism by which iron derived from transferrin is transported into the cytosol after receptor‐mediated endocytosis of the iron‐transferrin complex. The other mechanism has a lower affinity for iron, is retained when reticulocytes mature and is probably associated with Na+ transport across the cell membrane. The physiological characteristics of the two iron transport processes and the evidence for the above conclusions are summarized in the present paper.
Review: Molecular pathogenesis of hepatic acute porphyrias
Authors: GRANDCHAMP BERNARD , PUY HERVÉ , LAMORIL JÉROME , DEYBACH JEAN CHARLES , NORDMANN YVES 
Published: March 2008

ABSTRACTThe molecular cloning of cDNA and genes encoding enzymes of the haem biosynthetic pathway have permitted the genetic defects underlying acute intermittent porphyria (AIP) and hereditary coproporphyria to be unravelled. In AIP, many different gene abnormalities have been documented since 1989. The prevalence of specific defective alleles among AIP families depends on which human population is studied. Founder effects are likely to account for a high frequency of a single mutation in Finland and, to a lesser extent, in Holland, while many other mutations have only been found once, each of them in a single family. In hereditary coproporphyria several different mutations have already been identified since 1994, suggesting that a large allelic heterogeneity also exists. The search for mutations in variegate porphyria has just started since the recent publication of the human cDNA sequence. Direct detection of the mutations using DNA analysis brings a growing contribution to the detection of asymptomatic carriers among relatives of porphyric patients and will, therefore, improve the prevention of acute attacks.
Keratinocyte growth factor is an endogenous stimulant of rabbit gastric epithelial cell proliferation and migration in primary culture
Authors: TAKAHASHI MORIO , OTA SHINICHI , NISHIMURA SHUJI , OGURA KEIJI , MAEDA SHIN , TODA NOBUO , HAMADA EIJI , TERANO AKIRA , OMATA MASAO 
Published: March 2008

ABSTRACTMesenchymal‐epithelial interactions are important in the gastric mucosal repair. However, specific factors responsible for such interactions have not been established. In the present study, keratinocyte growth factor (KGF) significantly stimulated proliferation of gastric epithelial cells dose dependently and synergistically with hepatocyte growth factor (HGF), epidermal growth factor (EGF) and insulin. Restitution of gastric epithelial monolayers was also assessed, using a round wound restitution model. Keratinocyte growth factor facilitated the restitution of gastric epithelial cells significantly but did not have any effects on gastric fibroblasts. Keratinocyte growth factor receptor mRNA was expressed by gastric epithelial cells, indicating that these effects were elicited by the specific receptor mediated pathway. Northern blot analysis revealed the expression of KGF mRNA in gastric fibroblasts but not in gastric epithelial cells, indicating the production of KGF. These results suggest that KGF might be involved in gastric mucosal repair, through mesenchymal‐epithelial interaction.
Lubrication of visceral movement and gastric motility by peritoneal surfactant
Authors: HILLS BA 
Published: March 2008

AbstractFour studies are described as a means of evaluating the hypothesis that surface‐active phospholipid (SAPL) enhances the lubrication of gastric motility and visceral movement in general. In the first two studies, a lipid extract from ovine peritoneal rinsings was found to have remarkable antiwear capabilities ex vivo and to reduce friction to a remarkably low level as quantified by a coefficient of kinetic friction of 0.008 ± 0.002 (n= 10). Moreover, this lipid extract demonstrated both these features of lubrication at high load. In other studies, peritoneal lipid extract was found to be highly surfaceactive, while many lamellar bodies (LB) have been identified in omentum and, by analogy with the lung and the stomach, would therefore appear to be a source of SAPL. Lubrication by peritoneal surfactant is discussed as another example of a ubiquitous barrier to abrasion and other potential insults common to all visceral surfaces.
Cytotoxin and urease activities of Helicobacter pylori isolates from Japanese patients with atrophic gastritis or duodenal ulcer
Authors: MURAKITA HAJIME , HIRAI MASAMICHI , ITO SHIGEJI , AZUMA TAKESHI , KATO TAKUJI , KOHLI YOSHIHIRO , KURIYAMA MASARU 
Published: March 2008

AbstractThe vacuolating cytotoxin and urease secreted by Helicobacter pylori are thought to be virulent factors. Because vacuolation is potentiated by the presence of ammonium ion, which is produced by urease in vitro, it is of interest to examine whether cytotoxin and urease work reciprocally in the development of atrophic gastritis or duodenal ulcer. In the present study, patients (all H. pyloripositive) were divided into four groups: mild atrophic gastritis (group 1; nine patients), severe atrophic gastritis (group 2; 36 patients), duodenal ulcer with mild atrophic gastritis (group 3; 19 patients) and duodenal ulcer with severe atrophic gastritis (group 4; 12 patients). Cytotoxin production and urease activity of H. pylori isolated from these patients were analysed. Cytotoxin production was observed in four of nine (44.4%), 28 of 36 (77.8%), 11 of 19 (57.9%) and eight of 12 (66.7%) isolates from groups 1, 2, 3 and 4, respectively. Cytotoxin‐producing H. pylori isolates were found significantly more in patients with severe atrophy than in patients with mild atrophy (P= 0.048). The mean of relative activity of cytotoxin in H. pylori isolate was 1. 6. ± 2. 3, 7. 9. ± 7. 4, 5. 8. ± 6. 0 and 9. 0 ± 9. 1 in groups 1, 2, 3 and 4, respectively. Helicobacter pylori isolates from severe atrophy or duodenal ulcer patients in groups 2 or 4 possessed significantly higher activity than those from non‐ulcer patients in group 1 (P= 0.017 and 0.030, respectively). The mean of urease activity was 8. 6 ± 4. 6, 10. 0 ± 5. 9, 10. 0 ± 8. 5 and 11. 2 ± 7. 7 IU/mg in groups 1, 2, 3 and 4, respectively. These differences indicated no statistical significance. In each H. pylori isolate, the production of cytotoxin and urease were independent, which indicated that there was no reciprocal effect between them in vivo. Thus, cytotoxin‐producing H. pylori isolates were more prevalent in patients with severe atrophic gastritis and the cytotoxin activities of H. pylori isolates from the patients with severe atrophic gastritis or duodenal ulcer were much higher than those from the patients with mild atrophic gastritis, which suggested that vacuolating cytotoxin may be a disease‐inducing factor.
Reduced liver function is the trigger for renal sodium retention following portal vein ligation in the rat
Authors: MURAKAMI SHIGETO , OHNO TOSHIYUKI , BERNARDO JOSÉ F. , PFEIFER CYNTHIA A. , LI TIMEO , ZHANG YONG , DUBEY RAGHVENDRA K. , BRANCH ROBERT A. , SABRA RAMZI 
Published: March 2008

AbstractSodium retention along with peripheral vasodilation are features of prehepatic portal hypertension. In several models of experimental liver damage, sodium retention occurs only when hepatic function, measured by the aminopyrine breath test (ABT‐k), falls below a critical threshold. The relationship between renal sodium handling, ABT‐k and systemic and renal haemodynamics in partial portal vein ligated (PVL) rats was examined to test the hypothesis that peripheral vasodilation was responsible for initiating sodium retention. Haemodynamic measurements were conducted early after surgery in portal hypertensive rats with and without sodium retention and in sham‐operated controls. Compared with control, both PVL groups of rats had elevated portal pressure and lower peripheral vascular resistance (P<0.05). Sodium retaining‐PVL rats had both lower ABT‐k (0.95 ± 0.05 vs 1.38 ± 0.06 times 10‐2/min; P<0.05) and higher sodium balance (1.38 ± 0.09 vs 0.43 ± 0.09 mmol/day; P< 0.05) than non‐sodium retaining PVL rats. No differences in plasma renin activity or noradrenaline concentrations were observed. In a separate group of rats, hydralazine‐induced peripheral vasodilation did not induce sodium retention. These results suggest that the presence of peripheral vasodilation alone is not sufficient to trigger a sodium‐retaining status. A factor, probably liver function‐dependent, acting directly on renal tubules may be necessary for changes in renal sodium handling in this model.
Renal and haemodynamic responses to a novel kappa opioid receptor agonist, niravoline (RU 51,599), in rats with cirrhosis
Authors: MOREAU RICHARD , CAILMAIL STEPHANE , HAMON GILLES , LEBREC DIDIER 
Published: March 2008

AbstractBecause renal water retention is a complication of cirrhosis, niravoline (RU 51,599), a novel kappa (κ) opioid receptor agonist which is known to cause a water diuresis under normal conditions, may be useful in the therapy of chronic liver diseases. Thus, the present study examined the effects of niravoline on renal function in rats with cirrhosis. Urine was collected during the 2 h period following the administration of vehicle (saline) in one group of animals or niravoline (3 mg/kg, i.v.) in auother group. Urinary and plasma osmolality were measured prior to and 2 h after niravoline in a third group of animals. Urine flow and natraemia were significantly higher after niravoline (147±12 μL/min and 153±2 mmol/L, respectively) than after vehicle (27 ± 7 μL/min and 146 ± 1 mmol/L, respectively). Niravoline significantly decreased urinary osmolality and significantly increased plasma osmolality and free water clearance. This substance did not significantly change urinary sodium excretion. In conclusion, this study shows that niravoline, a κ opioid receptor agonist, induced a water diuresis in rats with cirrhosis.
Career paths for clinical scientists
Authors: FARRELL GEOFFREY C. 
Published: March 2008

AbstractIn the 16 years since James Wyngaarden proclaimed the clinical investigator to be an endangered species, attempts to revive this fragile beast have met with limited success in North America, the UK and Australia. The situation may be more healthy in some western European countries and Japan, but in many parts of Asia clinical investigators have vanished without trace. An analysis of the Australian context during the past 16 years suggests a gradual decline in absolute numbers of clinical scientists reaching maturation, coupled with an extraordinary diminution of their research fertility relative to that of basic scientists. In the present review, it is argued that clinical scientists have a vital role to play in medical research and, particularly, in clinical research. The reason why fewer medical graduates are entering and even fewer are being retained in medical research careers cannot be attributed to restrictions at entry, according to the availability of and competition for training scholarships. Other possible explanations include the late age of entry and the negative influence of role modelling. The latter operates directly by the attitudes and pathways of peers and indirectly through the biases of peer review. There is also a perception, possibly a realistic one, that insuperable barriers exist to obtaining a stable career position at the end of training. Finally, there is real concern about whether clinical investigators will be able to compete successfully with basic researchers for research grants. If this summation is correct, the solutions include active recruitment for research training at an earlier age, simultaneous research and medical training and truncation of postgraduate clinical training in the medical specialties with earlier introduction of medical research. In addition to these strategies, the proper training of clinical scientists must afford them generic research skills and social adaptation to a team approach with basic scientists.
Real‐time monitoring of HCV‐RNA by single tube assay kit and potential importance for predicting virological sustained response in patients with chronic hepatitis C
Authors: SHIRATORI YASUSHI , KATO NAOYA , TAMATSUKURI SHIGERU , YOSHIDA HARUHIKO , KAWABE TAKAO , NAKATA RYO , OKANO KEN'ICHI , OMATA MASAO 
Published: March 2008

ABSTRACTIn an attempt to predict virological sustained responders among patients with chronic hepatitis C after interferon therapy, HCV‐RNA in serum was measured by a one tube RT‐PCR assay kit using the RNA corresponding to 5 μL serum (standard assay) or 300 μL serum (enhanced‐sensitivity assay). Dilution analysis revealed that sensitivity of the ‘enhanced‐sensitivity assay’ increased by 10–100‐fold when compared with a ‘standard assay'. Using these assays, prospective study of interferon therapy on 38 HCV‐RNA seropositive cases with chronic hepatitis (total amount 702 MU; duration of treatment 5–6 months) was performed. At the end of treatment, six were still positive and 32 became negative by the ‘standard assay', whereas an additional eight cases became positive (total 14 cases positive; the remaining 24 cases negative) by the ‘enhanced‐sensitivity assay'. Hepatitis C viral RNA state at the end of treatment remained the same 6 months later in 23 cases (61%) by a ‘standard assay’ and in 31 (82%) by the ‘enhanced‐sensitivity assay'. Of importance was that all patients (14 cases) demonstrating HCV‐RNA in serum at the end of therapy, even by the ‘enhanced‐sensitivity assay', did not show the disappearance of HCV‐RNA in serum despite the long follow up. From these results, in order to improve our treatment efficacy, we should try to modify our treatment protocol to the extent that at least HCV‐RNA becomes undetectable. That can be only feasible during treatment by real‐time monitoring of HCV‐RNA.
Relationship between the intrahepatic expression of interferon‐α receptor mRNA and the histological progress of hepatitis C virus‐associated chronic liver diseases
Authors: ISHIMURA NORIHISA , FUKUDA RYO , FUKUMOTO SHIRO 
Published: March 2008

ABSTRACTHistological progress is one of the predictors of an unfavourable response to interferon (IFN) therapy in hepatitis C virus (HCV)‐associated chronic liver diseases (CLD). The aim of the present study was to investigate whether histological progress has an association with the expression of IFN receptor (IFN‐Rc) in the liver. Expression of mRNA of the IFN‐Rc for IFN‐α was investigated by reverse transcription polymerase chain reaction using liver biopsy specimens from 37 HCV‐associated CLD comprising 11 liver cirrhosis (LC) and 26 chronic hepatitis (CH) cases. IFN‐α and IFN‐β mRNA were detected in over 90% of subjects. In contrast, the detection rate of IFN‐Rc mRNA in chronic persistant hepatitis, chronic hepatitis 2A, chronic hepatitis 2B and liver cirrhosis (LC) was 100, 71.4, 22.2 and 0%, respectively. The absence of IFN‐Rc mRNA was significantly associated with the severity of fibrosis of the liver. These results indicated that IFN‐Rc expression decreases with the histological progress of the disease, suggesting that lower expression of IFN‐Rc mRNA may be partially responsible for the poor IFN response in LC.