bluuebunny/crossref_metadata_2025_split huggingface dataset:
High‐dose natural interferon‐α therapy for chronic hepatitis C with a high viral load: Predictors of efficacy
Authors: Komatsu Masafumi , Suto Toshiyuki , Ishikawa Kazuyoshi , Sato Shunichi ,   THE AOMORI, AKITA and IWATE AREAS VIRAL HEPATITIS RESEARCH GROUP
Published: March 2003

Background: The effectiveness of interferon against hepatitis C has been found to be greatly affected by viral factors. However, few controlled interferon trials have involved seemingly intractable cases of chronic hepatitis C. Methods: In 44 patients with high hepatitis C virus RNA levels (≥ 105 copies/mL), we carried out a prospective, controlled study of two natural interferon‐α regimens, seeking predictors of therapeutic efficacy. Total natural interferon‐α doses over 6 months in two groups were 780 and 840 million units, respectively. Results: High therapeutic efficacy was achieved with no significant outcome difference between the regimens. The virus eradication rate was 35% and the rate of sustained biochemical response was 45% for both regimens. Multivariate logistic regression analysis identified viral genotype as the only significant predictor of success in viral eradication. Conclusions: Hepatitis C virus genotype 2 showed high sensitivity to interferon‐α and this therapy can be recommended even for patients with a high viral load of this genotype. In contrast, with genotype 1b, cure was extremely difficult in cases with 107 or more copies/mL with a single 6‐month course of interferon‐α.
Modelling the hepatitis C virus epidemic in Australia
Authors: Law1 Matthew G 
Published: March 2003

Abstract
Introduction
: In Australia, to the end of 1997, more than 110 000 people have been diagnosed with hepatitis C virus (HCV) antibodies and reported to State/Territory surveillance systems. The available data indicate that the overwhelming majority (around 80%) of people with HCV antibodies were infected through injecting drug use.
Methods
: Models of the HCV epidemic in Australia were developed based on estimates of the pattern of injecting drug use in Australia. Estimates of HCV infections due to injecting drug use thus obtained were then adjusted to allow for HCV infections resulting from other transmission routes. Projections of cirrhosis and hepatocellular carcinoma (HCC) resulting from HCV were obtained by combining modelled HCV incidence with estimates of the progression rates to these outcomes.
Results
: Based on the models, it was estimated that there were 196 000 (lower and upper limits of 149 000 and 234 000) people in Australia living with HCV antibodies at the end of 1997, with HCV incidence in 1997 estimated to be 11 000 (8500–13 500). It was estimated that 8500 (4000–13 000) people were living with HCV‐related cirrhosis in 1997 and that there were 80 (40–125) incident cases of HCV‐related HCC.
Discussion
: Model‐based estimates were broadly consistent with other sources of information on the HCV epidemic in Australia. These models suggest that the prevalence of HCV‐related cirrhosis and the incidence of HCV‐related HCC will more than double in Australia by 2010.© 1999 Blackwell Science Asia Pty Ltd
Genetically distinct strains of Candida albicans with elevated secretory proteinase production are associated with diarrhoea in hospitalized children
Authors: Mathaba Leslie T , Paxman Adrian E , Ward Peter B , Forbes David A , Warmington John R 
Published: March 2003

Abstract
Background
: Candida albicans has been implicated as the aetiological agent in a significant percentage of children with diarrhoea. The virulence properties of C. albicans strains associated with acute and chronic diarrhoea in hospitalized children were investigated.
Methods
: The genotypic relationships between the isolates were determined using restriction enzyme analysis and hybridization with a C. albicans‐specific DNA probe, 27A.
Results and Conclusion
: In patients with acute and chronic diarrhoea, there is evidence for selection of specific, genetically distinct strains of C. albicans. Higher levels of secretory Candida acid proteinase produced by isolates from patients with acute diarrhoea may account for the more severe symptoms. However, the lower adherence of these isolates may predispose to the rapid (within 2 to 4 days) resolution of the condition. In patients with chronic diarrhoea the lower levels of proteinase produced correlate with the less severe symptoms, while the increased adherence may account for the persistence of the infection.
Acute hepatic failure in India: A perspective from the East
Authors: Acharya Subrat K , Panda Subrat K , Saxena Alka , Gupta S Datta 
Published: March 2003

AbstractAcute hepatic failure (AHF) in India almost always presents with encephalopathy within 4 weeks of the onset of acute hepatitis. Further subclassification of AHF into hyperacute, acute and subacute forms may not be necessary in this geographical area, where the rapidity of onset of encephalopathy does not seem to influence survival. Viral hepatitis is the cause in approximately 95–100% of patients, who therefore constitute a more homogeneous population than AHF patients in the West. In India, hepatitis E (HEV) and hepatitis B (HBV) viruses are the most important causes of AHF; approximately 60% of cases are caused by to these viruses. Hepatitis B virus core mutants are very important agents in cases where hepatitis B results in AHF in this country. Half of the patients with AHF admitted to our centre are female, one‐quarter of whom are pregnant. Therefore, pregnant females who contract viral hepatitis constitute a high‐risk group for the development of AHF. However, the outcome of AHF in this group is similar to that in non‐pregnant women and men. No association with any particular virus has been identified among sporadic cases of AHF. In our centre, approximately one‐third of AHF patients survive with aggressive conservative therapy, whereas two‐thirds of deaths occur within 72 h of hospitalization. Cerebral oedema and sepsis are the major fatal complications. Both fungal and Gram‐negative bacteria are major causes of sepsis. Among patients with AHF, despite the presence of sepsis, its overt clinical features (i.e. fever, leucocytosis) may be absent and objective documentation of the presence of sepsis in such patients is achieved by repeated culture of various body fluids. It should be possible to develop simple, clinical prognostic markers for AHF in this geographical region, in order to identify patients suitable for liver transplantation.
Treatment of chronic liver diseases with traditional Chinese medicine
Authors: Wang Bao‐En 
Published: March 2003

AbstractTraditional Chinese medicine is still being extensively used for treatment of liver disease in China. The anti‐viral herbs, Phyllanthus amarus, P. niruri and P. urninaria, and Oxymatrine extracted from Sophora flavecientis and S. subprostratae, have been shown to have a remarkable HBV suppressing effect with a serum conversion rate for HBeAg and HBV DNA around 45%, similar to that of IFN‐α. The anti‐inflammatory compound, Stronger NeoMinophagen C (SNMC), is a Japanese preparation of glycerrhizin, extracted from Glyceriza glabra, which has shown an effective rate of ALT and AST normalization and reduction to < 60 U/L in 65.6% and 73.5% of patients. Compound 861, made of 10 herbs with Salvia miltiorrhiza as its chief component, has been shown experimentally to be effective in suppressing fibrogenesis, enhancing collagen degradation, and inhibiting TIMP expression. Clinically, an open trial of 2000 patients showed improvement of symptoms in 83% and normalization of serum ALT in 82%. In a controlled study of 107 patients with HBV‐related diseases, double liver biopsies showed that the fibrosis reversal rate after 6 months treatment with Cpd 861 was 78% in S2, 82% in S3 (precirrhotic stage) and 75% in S4 (early cirrhosis), as assessed by Scheuer’s and Chevallier’s criterion. In conclusion, traditional Chinese medicine has great potential in the treatment of chronic hepatitis B.
Relationship between histological prognosis of chronic hepatitis C and amount of hepatitis C virus core protein in serum
Authors: Iijima Akihiro , Tanaka Eiji , Kobayashi Masanori , Yagi Shintaro , Mizokami Masashi , Kiyosawa Kendo 
Published: March 2003

Abstract
Background
: Hepatitis C virus (HCV) viraemia is one of the factors for histological prognosis of chronic hepatitis C.
Methods
: One hundred and thirty‐five patients who received hepatic biopsies twice at intervals of 5 years or longer were followed up for a mean of 9.7 ± 4.0 years were studied retrospectively. The amount of HCV viraemia present was measured as the concentration of HCV core protein by using the fluorescence enzyme immunoassay method.
Results
: Multiple‐regression analysis, using deterioration of the histological stage as a dependent variable, showed that greater age (P = 0.041), higher stage of hepatic histology at the start of follow up(P = 0.029), and higher serum concentration of core protein (P < 0.001) were independent factors affecting the deterioration of the liver’s histological stage. At follow up, no significant difference in histological stage was seen between patients with serum HCV core protein ≥ 100 pg/mL (n = 60) and those with serum core protein < 100 pg/mL (n = 75). The histological grade in patients with high serum core‐protein levels tended to be significantly worse and the deterioration rate of the histological stage was significantly higher than in those with low HCV core protein levels (68 vs 35%, P < 0.001). The mutation rate of the HCV envelope‐2/non‐structural 1 (E2/NS1) nucleotide region was compared in two patients who had high serum concentrations of HCV core protein and whose histological stage had deteriorated with two patients who had low serum concentrations of the core protein and whose histological stages remained unchanged. No significant difference in E2/NS1 mutation was found.
Conclusions
: The amount of HCV viraemia was suggested to be a significant factor for determining histological outcome in patients with chronic hepatitis C. The mutation rate in the E2/NS1 region did not seem to be associated with the prognosis of chronic hepatitis C.© 2000 Blackwell Science Asia Pty Ltd
Molecular biology of hepatitis A virus: Significance of various substitutions in the hepatitis A virus genome
Authors: Yokosuka Osamu 
Published: March 2003

AbstractHepatitis A virus (HAV) is the sole member of the hepatogenus of Picorna viridae. This virus can now be propagated in cell culture and in primates. Molecular biological studies of HAV have disclosed its genomic structure and the functional significance of the viral proteins to some extent. Hepatitis A virus has a positive‐stranded RNA of approximately 7.5 kb that encodes a large polyprotein. Translation of the protein is influenced by the function of the internal ribosomal entry site in the 5′ non‐translating region. It is generally agreed that the polyprotein is processed to four structural and seven non‐structural proteins by the proteinase encoded in the 3C region. Replication efficiency seems to be controlled by amino acid substitutions in the 2B and 2C regions. The virulence of HAV in primates may be determined by substitutions in the 2C region. Although the severity of hepatitis A was thought to be determined by immunological reactions of the host to the virus, the potential virulence of the variant viruses themselves may need further examination. Recent progress in polymerase chain reaction technology has made possible an analysis of the HAV sequence in clinical specimens; such analysis is of importance in the disclosure of differences in HAV subspecies in different clinical conditions.
Mechanism of gastric mucosal proliferation induced by gastrin
Authors: Kinoshita Yoshikazu , Ishihara Shunji 
Published: March 2003

AbstractGastrin has a potent trophic effect on gastric fundic mucosa. When serum concentrations of gastrin are elevated, proliferation of both the progenitor cells in the glandular neck zone and enterochromaffin‐like (ECL) cells in the bottom of the glands is stimulated. Because ECL cells have gastrin receptors, their proliferation is directly stimulated by gastrin. However, because the proliferation of progenitor cells cannot be directly stimulated (so far there has been no gastrin receptor demonstrated on these proliferating cells), some indirect mechanisms must be involved. Enterochromaffin‐like and parietal cells are only two types of cells that have demonstrated a strong gene expression of the gastrin receptor. Furthermore, they secrete several growth factors, such as Reg protein, heparin‐binding epidermal growth factor‐like growth factor (HB‐EGF) and amphiregulin (AR). Reg protein production by ECL cells, as well as HB‐EGF and AR production by parietal cells, is stimulated by gastrin and these growth factors are potent trophic agents of progenitor cells in the neck zone of the gastric fundic mucosa. Accordingly, gastrin may stimulate the proliferation of gastric mucosal cells indirectly via these growth factors in addition to its direct trophic effect on ECL cells.
Gastrointestinal metastasis in hepatocellular carcinoma: Radiological and endoscopic studies of 11 cases
Authors: Lin Chi‐Pin , Cheng Jin‐Shiung , Lai Kwok‐Hung , Lo Gin‐Ho , Hsu Pin‐I , Chan Hoi‐Hung , Hsu Jui‐Hung , Wang Ya‐Yu , Pan Huay‐Ben , Tseng Hui‐Hwa 
Published: March 2003

Abstract
Background
: From October 1990 to January 1999, 11 of 2237 hepatoma patients at our hospital had gastrointestinal tract metastasis. We describe the radiological and endoscopic features, clinical course and prognoses of those patients.
Methods
: All patients were male. Six patients were hepatitis B carriers, and cirrhosis was noted in eight patients on admission. We reviewed all available radiological, endoscopic and pathological features.
Results
: The commonest clinical presentation was frank gastrointestinal bleeding. Histological proof of gastrointestinal involvement was seen in six patients. Endoscopic features included ulcerative tumours mimicking advanced gastric carcinoma (43%) and submucosal tumours (29%). The sites of organ involvement were stomach (five), duodenum (two), colon (three) and duodenum and colon (one). Direct invasion by a contiguous neoplasm was the major route of gastrointestinal tract metastasis. Portal vein thrombosis may be the key point of haematogenous spread to other sites.
Conclusions
: The prognosis in these patients was extremely poor. Almost all patients died within 5 months if no further aggressive management was performed. Surgical intervention may be the optimal choice for palliative treatment of HCC with gastrointestinal tract involvement.
Detection of vascular endothelial growth factor and its receptor expression in human hepatocellular carcinoma biopsy specimens
Authors: Shimamura Takeshi , Saito Satoru , Morita Katsumi , Kitamura Takehiko , Morimoto Manabu , Kiba Takayoshi , Numata Kazushi , Tanaka Katsuaki , Sekihara Hisahiko 
Published: March 2003

Abstract
Background
: Vascular endothelial growth factor (VEGF) exerts its actions on the microvasculature, by interacting with specific endothelial cell receptors, and thus, contributes to angiogenesis and growth in many tumours.
Methods
: Using nested reverse‐transcription–polymerase chain reaction, we examined the biopsy specimens of 14 patients with human hepatocellular carcinoma (HCC) and cirrhosis, for the expression of hepatic VEGF, and the VEGF receptors KDR and flt‐1. To avoid the influence of hypoxia or ischaemia induced by surgical manipulation, we used biopsy specimens of the liver instead of resected specimens.
Results
: Vascular endothelial growth factor mRNA expression was detected in the tumour portion of the specimens in 13 of 14 patients (93%), and in the corresponding non‐tumour portion of the specimens in eight patients (57%; P = 0.08). No differences were found between the tumour portion and the corresponding non‐tumour portion in relative concentrations of VEGF mRNA. However, mRNA expression of the VEGF receptors, KDR and flt‐1, was detected in 14 (100%) and 11 (79%) of the tumour portions, respectively, and in four (29%) and five (36%) of the corresponding non‐tumour portions, respectively (χ2 test: KDR, P < 0.01; flt‐1, P = 0.08). The relative concentration of KDR mRNA in the tumour portions was significantly higher than in the non‐tumour portions (Mann–Whitney U‐test: P < 0.001) but no differences were detected for flt‐1.
Conclusions
: KDR mRNA is significantly overexpressed in HCC lesions and could be associated with the angiogenesis and tumour growth induced by VEGF.
Spontaneous regression of hepatocellular carcinoma and review of literature
Authors: Takeda Yoshio , Togashi Hitoshi , Shinzawa Haruhide , Miyano Shintaro , Ishii Rika , Karasawa Tetsuru , Takeda Yumiko , Saito Takafumi , Saito Koji , Haga Hiroko , Matsuo Taku , Aoki Masanori , Mitsuhashi Hideki , Watanabe Hisayoshi , Takahashi Tsuneo 
Published: March 2003

AbstractA 68‐year‐old man presented with multiple hepatocellular carcinoma, which was considered to be unresectable at the first admission in January 1994. Pathological diagnosis was made by biopsy of the one lesion among them. From January 1994 to December 1997, 10 transarterial chemoembolizations and six percutaneous ethanol injection therapies were performed on the tumours in the cirrhotic liver. In February 1998 the tumour situated in the right lobe began to increase in size. The maximum tumour diameter was 6.3 cm measured by computed tomography (CT). In the beginning of May 1998 moderate ascites was present and mild hepatic encephalopathy was noticed. The patient was in the terminal stage of hepatocellular carcinoma and no further treatment was possible at that time. However, serum α‐fetoprotein and protein induced by vitamin K absence or antagonist II dramatically decreased in June 1998. The CT scan also showed that the tumour had completely regressed without specific treatment. In February 1999 a new biopsy‐proven hepatocellular carcinoma, 2 cm in diameter, developed in the lateral segment of the liver. It was well treated by percutaneous ethanol injection therapy. The patient was alive in good condition without any symptoms or tumour recurrence in June 1999. It was concluded that a rare case of spontaneous regression of hepatocellular carcinoma had occurred.
Duodenal ulcer prevalence: Experimental evidence for the possible role of dietary lipids
Authors: Jayaraj A Paul , Tovey Frank I , Lewin Michael R , Clark Charles G 
Published: March 2003

Abstract
Background and Aims
: Mapping the geographical distribution of duodenal ulcer in relation to staple diets, and experiments on animal peptic ulcer models suggested that the lipid fraction in certain foodstuffs had a protective effect which was most marked in the lipid obtained from Horse gram (Dolichos biflorus). Lipid obtained from stored polished rice or rice bran was ulcerogenic. Further animal experiments were designed to investigate the protective and healing effects of Horse gram lipid (HGL) against peptic ulceration.
Methods
: Three effects were investigated in rats: (i) the protective effect of HGL on peptic ulceration produced by using pyloric ligation in combination with South Indian diet or rice bran oil, or by cysteamine, alcohol or aspirin; (ii) the effect of HGL on mast cell degranulation in response to pyloric ligation and rice bran oil; and (iii) the healing effect of HGL on acute gastric ulceration produced by alcohol, on chronic gastric ulceration produced by topical acetic acid or on chronic duodenal ulcer following cysteamine.
Results
: Horse gram lipid was shown to be protective and to promote ulcer healing in all the models used. Mast cell degranulation was inhibited.
Conclusion
: The experiments confirm the presence of a lipid in certain staple foods that have protective and healing properties in experimental peptic ulcer animal models. The differences in the prevalence of duodenal ulceration between different regions in some developing countries with a high prevalence of Helicobacter pylori infection might be explained by the presence or absence of protective lipids or ulcerogenic factors in the staple diet.
Dendritic cell‐based cancer immunotherapy: Potential for treatment of colorectal cancer?
Authors: Chen Wangxue , Rains Natalie , Young David , Stubbs Richard S 
Published: March 2003

AbstractHuman tumours including those of the gastrointestinal tract express a number of specific antigens that can be recognized by T cells, thus providing potential targets for cancer immunotherapy. Dendritic cells (DC) are rare leucocytes that are uniquely potent in their ability to capture, process and present antigens to T cells, and so selectively migrate through tissues to reach lymph nodes and spleen where initiation of immune responses takes place. Studies in murine tumour models have shown clearly that DC are capable of presenting tumour antigens to initiate tumour‐specific cytotoxic T cell responses, and DC vaccination can induce anti‐tumour activity against both primary tumours and pre‐established tumour metastases. These findings together with the ability to culture sufficient numbers of DC from human bone marrow or blood progenitors have prompted the current major interest in their potential use in human tumour vaccination. Vaccine production involves harvesting autologous DC from cultured peripheral blood mononuclear cells in the presence of a cocktail of cytokines, ex vivo exposure of the DC to tumour antigens and return of pulsed DC to the patient to induce tumour immunity. Reports from Phase I/II clinical trials indicate that DC vaccines are safe with little or no side effect, and are capable of initiating antigen‐specific T cell responses. Furthermore, defined tumour antigens are not necessarily required, which may make the process more applicable to human cancers, including many gastrointestinal cancers that lack well‐characterized tumour‐specific antigens. Additional trials of DC vaccination for a variety of human cancers including colorectal cancers are under way, and refinement of vaccine protocols and methods for targeting tumour antigens to DC in vivo are also being explored. There is reason to believe that DC‐based vaccination could become an adjunct to current treatments for human cancers including colorectal cancer in the foreseeable future.
Cyclo‐oxygenase‐2 inhibitors suppress epithelial cell kinetics and delay gastric wound healing in rats
Authors: Sun Wei‐Hao , Tsuji Shingo , Tsujii Masahiko , Gunawan Edhi S , Sawaoka Hitoshi , Kawai Naoki , Iijima Hideki , Kimura Arata , Kakiuchi Yoshimi , Yasumaru Masakazu , Sasaki Yutaka , Kawano Sunao , Hori Masatsugu 
Published: March 2003

Abstract
Background and Aims
: The present study examined the effects of NS‐398, a specific cyclo‐oxygenase‐2 inhibitor, on gastric mucosal cell kinetics and gastric wound healing following acid‐induced injury.
Methods
: Male Sprague‐Dawley rats were fasted for 24 h and then 0.6 mol/L hydrochloric acid (HCl; 1 mL) was administered into the stomach; NS‐398 or indomethacin was administered to the animals 10 min after the acid. Levels of constitutive cyclo‐oxygenase (COX‐1) and mitogen‐inducible cyclo‐oxygenase (COX‐2) in the gastric mucosa were analysed using western blotting and immunohistochemical staining. The grade of the lesion was assessed using planimetry and histological examination, including immunohistochemistry for proliferating cell nuclear antigen (PCNA).
Results
: Although there was strong expression of COX‐1, there was minimal expression of COX‐2 in the gastric mucosa. Expression of COX‐2 was enhanced mainly in surface epithelial cells and neck cells following HCl administration. Gastric mucosal ulcers and erosions healed within 48 h, during which time the proliferative zone expanded in the control animals. Indomethacin and NS‐398 suppressed the expansion of the proliferative zone and delayed the healing of the gastric injury.
Conclusion
: The present study demonstrated that cyclo‐oxygenase‐2 inhibitors delay gastric wound healing by suppressing expansion of the mucosal proliferative zone. These results provide evidence that cyclo‐oxygenase‐2 has an important role in gastric mucosal regeneration.