bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor progression in hepatocellular carcinoma: Relationship with tumor stroma and parenchymal disease
Authors: LOCKWOOD DAVID SR , YEADON TRINA M , CLOUSTON ANDREW D , CRAWFORD DARRELL G , FAWCETT JONATHAN , CALLAGHAN SHIRLEY A , GOTLEY DAVID C 
Published: May 2003

AbstractBackground: Encapsulation in hepatocellular carcinoma is associated with decreased invasiveness and improved survival in several series. Although active fibrogenesis by myofibroblasts has been demonstrated in the capsule, it is unclear if the capsule results from a general increase in peritumoral fibrosis, or an inherently less invasive tumor phenotype. The relationship between collagen deposition within tumor stroma, presence of cirrhosis and invasiveness also needs clarification.Methods: We performed immunohistochemistry for collagens I, III, IV and VI on sections of encapsulated and non‐encapsulated hepatocellular carcinoma, arising in cirrhotic and non‐cirrhotic livers. Staining was graded semi‐quantitatively in tumor stromal elements and adjacent parenchymal sinusoids. The relationship of this staining with encapsulation, cirrhosis, and vascular invasion was analyzed.Results: Formation of a discrete capsular layer was associated with reduced vascular invasion, but not with a pervasive increase in peritumoral fibrosis. Increased collagen I content of tumor stroma and adjacent parenchymal sinusoids was associated with non‐encapsulated tumors and vascular invasion. The presence of cirrhosis had little effect on capsule composition.Conclusions: Encapsulation of hepatocellular carcinoma reflects reduced invasiveness, rather than increased peritumoral collagen synthesis, which may instead enhance invasion. Increased intratumoral collagen I protein is also associated with increased tumor invasiveness. Pre‐existing cirrhosis has little effect on tumor progression, possibly because the characteristics of cirrhosis are overwhelmed by tumor‐induced changes in the adjacent parenchyma.
Effects of interferon alpha therapy on the catalytic domains of the polymerase gene and basal core promoter, precore and core regions of hepatitis B virus
Authors: CHEN ROBERT YUNG MING , BOWDEN SCOTT , DESMOND PAUL VINCENT , DEAN JO , LOCARNINI STEPHEN A 
Published: May 2003

AbstractAims: The aim of the present study was to examine the catalytic domains of the polymerase gene, the basal core promoter and the precore and core regions of the hepatitis B virus (HBV) genome for specific mutations. These may account for the response to interferon alpha (IFN‐α) treatment, which may have prognostic value.Methods: Multiple serum samples were collected prospectively from 30 patients with chronic active hepatitis B who were treated with IFN‐α. Patients were assigned to one of three groups: group A (n = 11) and group B (n = 10) individuals were hepatitis B e antigen (HBeAg)‐positive prior to treatment. Group A patients underwent HBeAg seroconversion after treatment while group B patients did not. Group C (n = 9) patients were HBeAg‐negative prior to treatment. The HBV DNA was extracted from the sera collected before, during and after treatment and the various genomic regions were amplified, sequenced and examined for mutations.Results: During IFN‐α therapy, multiple changes were found in the catalytic domains of the HBV polymerase gene in all groups. The frequency of mutations and associated amino acid changes were highest in virus from group C patients and lowest in group A patients. The interdomain regions of the viral polymerase were the most affected. Multiple mutations were also found in the precore, core and core promoter regions. However, no specific mutations were associated with clinical response or outcome.Conclusions: During IFN‐α treatment, multiple mutations occurred in the HBV genome, including the catalytic domains of the polymerase gene. Changes that did occur could not be correlated to the clinical response or treatment outcome. However, no mutations were found that have been linked to lamivudine escape, indicating that lamivudine therapy would be effective in IFN‐α non‐responder patients.
Gross appearance of hepatocellular carcinoma reflects E‐cadherin expression and risk of early recurrence after surgical treatment
Authors: INAYOSHI JUN , ICHIDA TAKAFUMI , SUGITANI SOICHI , TSUBOI YASUNORI , GENDA TAKUYA , HONMA NOBUYUKI , ASAKURA HITOSHI 
Published: May 2003

AbstractBackground and Aims: Correlation between the gross classification of hepatocellular carcinoma (HCC) and its vascular invasion or intrahepatic metastasis has been reported previously. Because E‐cadherin‐mediated epithelial cell‐to‐cell adhesion is thought to suppress cancer cell invasion, the present study was performed to analyze the correlation between E‐cadherin expression and the gross classification of HCC.Methods: Thirty‐six resected solitary HCC <6 cm in diameter were each classified as single nodular type (type 1), single nodular with extranodular growth type (type 2) or contiguous multinodular type (type 3), and the clinicopathological and prognostic differences between type 1 HCC and the other types were analyzed. The expression of E‐cadherin in each tumor was examined by immunoblotting and immunohistochemical analysis.Results: Vascular invasion and microscopic intrahepatic metastasis were observed more frequently in types 2 and 3 (61%) than in type 1 (13%) HCC. Immunoblot analysis indicated that the relative level of E‐cadherin expression in cancerous tissue was significantly lower in type 2 and 3 (0.75 ± 0.49) than in type 1 (1.46 ± 0.79) HCC. Immunohistochemical examination revealed decreased and partially absent E‐cadherin expression in the tumorous area of type 2 and 3 HCC. The recurrence‐free survival rate was higher for patients with type 1 HCC than for those with the other types.Conclusions: Types 2 and 3 HCC have marked metastatic and invasive potential and reduced expression of E‐cadherin, predicting a high risk of recurrence after surgical treatment.
Role of elevated platelet‐associated immunoglobulin G and hypersplenism in thrombocytopenia of chronic liver diseases
Authors: SANJO AKIRA , SATOI JUJIN , OHNISHI AKIHIRO , MARUNO JUNKO , FUKATA MASAYUKI , SUZUKI NAOKI 
Published: May 2003

AbstractBackground and Aim: Thrombocytopenia typically worsens with the progression of liver disease and can become a major clinical complication. Several mechanisms that contribute to thrombocytopenia have been proposed, including hypersplenism accompanied by increased platelet sequestration, platelet destruction mediated by platelet‐associated immunoglobulins (PAIgG), and diminished platelet production stimulated by thrombopoietin (TPO). The purpose of the present study was to evaluate the role of each of these mechanisms in patients with liver disease‐associated thrombocytopenia.Methods: Twenty‐nine patients with liver cirrhosis (LC), 20 of whom were hepatitis C virus (HCV)‐seropositive, 29 chronic hepatitis (CH) patients, 24 of whom were HCV‐seropositive, and 16 control patients without liver or hematopoetic disease were enrolled in this study. Serum TPO levels, PAIgG, and liver‐spleen volumes were determined and correlation analyses were performed.Results: No differences in serum TPO levels were observed among the three groups. The PAIgG levels were significantly elevated in CH and LC patients (mean ± SD: 56.5 ± 42.3 and 144.6 ± 113.6 ng/107 cells, respectively) compared with the controls (18.9 ± 2.5 ng/107 cells, P < 0.001 for both). Spleen volume was significantly higher only in LC (428 ± 239) compared with CH (141 ± 55) and control (104 ± 50 cm3) (P < 0.001), while liver volume was not significantly different between the three groups. Correlation analyses demonstrated a significant negative correlation between platelet count with PAIgG (r = − 0.517, P < 0.001) and spleen volume (r = − 0.531, P < 0.001), and no relationship between platelet count and serum TPO level (r = 0.076).Conclusions: Serum TPO level may not be directly associated with thrombocytopenia in patients with chronic hepatitis and liver cirrhosis. In contrast, spleen volume and PAIgG are associated with thrombocytopenia in such patients, suggesting that hypersplenism and immune‐mediated processes are predominant thrombocytopenic mechanisms.
Tolerance to famotidine and ranitidine treatment after 14 days of administration in healthy subjects without Helicobacter pylori infection
Authors: KOMAZAWA YOSHINORI , ADACHI KYOICHI , MIHARA TAKAFUMI , ONO MASAHIRO , KAWAMURA AKIRA , FUJISHIRO HIROFUMI , KINOSHITA YOSHIKAZU 
Published: May 2003

AbstractBackground and Aim: The attenuated antisecretory activity observed during continuous administration of ranitidine has been described as tolerance. However, it remains unclear whether a similar phenomenon occurs with other histamine H2 receptor antagonists (H2RA). We investigated whether tolerance to famotidine, a stronger H2RA than ranitidine, occurs during long‐term administration.Methods: Seven healthy male Japanese subjects without Helicobacter pylori infection participated in a randomized cross‐over study in which ranitidine and famotidine were administered for 14 days with a 4‐week wash‐out period. We performed 24‐h intragastric pH monitoring on the first and 14th days of administration of each drug, and measured serum gastrin and plasma drug concentrations on the first, seventh and 14th days.Results: The acid‐inhibiting activity of ranitidine and famotidine declined during continuous administration. In particular, the potent nocturnal pH‐increasing effect of the H2RA, which was observed on day 1, declined on day 14. Serum gastrin concentrations on day 14 were significantly lower than those on day 7, although plasma drug concentrations remained unchanged.Conclusion: Tolerance to famotidine occurs during continuous administration for 14 days, as previously shown in ranitidine studies.
Nutritional benefits of enteral alanyl‐glutamine supplementation on rat small intestinal damage induced by cyclophosphamide
Authors: SATOH JIN , TSUJIKAWA TOMOYUKI , FUJIYAMA YOSHIHIDE , BAMBA TADAO 
Published: May 2003

AbstractBackground: Glutamine is the principal fuel used by the small intestine. Although the parental administration of glutamine promotes intestinal mucosal growth, it is controversial whether enteral glutamine is effective against small intestinal damage caused by chemotherapy. To further evaluate the benefits of enteral supplementation, peptide and amino acid transporter functions must be considered.Method: Rats were given cyclophosphamide (CPM) intraperitoneally (300 mg/kg). Expression of the amino acid transporter, B0 and peptide transporter (PepT1) in the jejunal mucosa was initially examined by northern blot analysis. Rats received a bolus oral supplement of an alanine (1.22 g/kg/day) plus glutamine (2.0 g/kg/day) mixture, alanyl‐glutamine (2.972 g/kg/day) or saline as a control, for 7 days after CPM administration.Results: Levels of B0 mRNA remained unchanged at both 3 and 7 days after CPM administration. Conversely, PepT1 mRNA increased significantly after CPM administration, and reached 200% of the initial level 7 days later. In rats given alanyl‐glutamine, the mucosal wet weight and protein content increased significantly with increasing villus height at 3 and 7 days, compared with the alanine plus glutamine mixture. The plasma glutamine concentration in the alanyl‐glutamine group, but not the alanine plus glutamine mixture group, increased significantly compared with that in the saline group.Conclusion: Enteral supplementation with an alanyl‐glutamine but not alanine plus glutamine mixture prevents intestinal damage, as demonstrated by increased peptide transport expression and an elevated plasma glutamine concentration after CPM administration.
Autonomic nervous dysfunction in patients with liver cirrhosis using 123I‐metaiodobenzylguanidine myocardial scintigraphy and spectrum analysis of heart‐rate variability
Authors: IGA AKIKO , NOMURA MASAHIRO , SAWADA YUKI , ITO SUSUMU , NAKAYA YUTAKA 
Published: May 2003

AbstractBackground: It has been reported that nitric oxide (NO) synthase is induced in patients with liver cirrhosis (LC), and that an excessive production of NO enhances sympathetic nervous function. The present report describes a study of the feasibility of evaluation of abnormalities of autonomic nervous function by 123I‐metaiodobenzylguanidine (MIBG) myocardial scintigraphy and heart‐rate variability in patients with LC.Methods: Low‐frequency (LF) power, high‐frequency (HF) power, LF/HF, and 1/f fluctuations of heart rate variability were examined in 50 patients with LC (LC group), and 50 normal subjects (N group). Echocardiogram, urinary nitrite and nitrate, and cathecholamines were examined.Results: Fractional shortening was observed for the hyperdynamic state of patients in the LC group according to Child's A–C classification. Washout rate of MIBG, LF/HF, and blood levels of norepinephrine increased and HF power decreased with the progression of LC. However, the urinary secretion of nitrite and nitrate were significantly increased only in cirrhotic patients with Child C.Conclusions: The present results indicate that autonomic abnormalities appear early in LC, and that these abnormalities can be detected by MIBG myocardial scintigraphy and analysis of heart‐rate variability. We consider these methods to be clinically useful for the quantitative detection of hyperdynamic circulation of liver cirrhosis.
Novel human and mouse genes encoding a shank‐interacting protein and its upregulation in gastric fundus of W/WV mouse
Authors: DAIGO YATARO , TAKAYAMA ICHIRO , WARD SEAN M , SANDERS KENTON M , FUJINO MASAYUKI A 
Published: May 2003

AbstractBackground and Aims: A division of labor exists between different classes of interstitial cells of Cajal (ICC) in the gastrointestinal tract. In the stomach and small intestine, ICC at the level of the myenteric plexus (IC‐MY) act as slow wave pacemaker cells, whereas intramuscular ICC (IC‐IM) in the stomach act as intermediaries in enteric motor neurotransmission. The muscle layers of the gastric fundus do not have IC‐MY, therefore electric slow waves are not generated. Intramuscular ICC are absent in the gastric fundus of W/WV mutant mice, and excitatory and inhibitory motor nerve responses are reduced in these tissues. The absence of IC‐IM in W/WV mutants in the fundus provides a unique opportunity to study the molecular changes that are associated with the loss of these cells.Methods: The tissue gene expression of wild‐type and W/WV mice from gastric fundus was assayed using a murine microarray chip analysis displaying a total of 8734 elements.Results: Twenty‐one queries were differentially expressed in wild‐type and W/WV mice. One candidate gene, encoding a novel protein homologous to rat Shank‐interacting protein (Sharpin) was significantly upregulated in fed and starved W/WV mice. The full‐length clone of the murine gene and its human counterpart were isolated and designated as Shank‐interacting protein‐like 1 (SIPL1). Human SIPL1 complementary DNA encodes a protein of 345 amino acids. This gene was localized to chromosome 8. SIPL1 was abundantly expressed in human stomach and small intestine, and scarcely expressed in cecum and rectum.Conclusions: Gene analysis showed that SIPL1 differentially express in the gastric fundus of normal and W/WV mice. The upregulation of SIPL1 in the fundus of W/WV mice, and expression in the upper gastrointestinal tract suggest that the SIPL1 gene could be associated with ICC function in mice and humans.© 2003 Blackwell Publishing Asia Pty Ltd
Loss of heterozygosity on chromosome 17p predicts neoplastic progression in Barrett's esophagus
Authors: DOLAN KEVIN , MORRIS ANTHONY I , GOSNEY JOHN R , FIELD JOHN K , SUTTON ROBERT 
Published: May 2003

AbstractBackground and Aim: Endoscopic surveillance for adenocarcinoma in patients with Barrett's esophagus is costly, with one cancer detected every 48–441 patient years of follow up. Genetic abnormalities, including loss of heterozygosity at sites of tumor suppressor genes, have been detected in malignant and premalignant Barrett's esophagus. The aim of this prospective study was to determine if loss of heterozygosity analysis could identify patients with Barrett's esophagus at greatest risk of adenocarcinoma, for whom endoscopic surveillance is most appropriate.Methods: Loss of heterozygosity analysis was performed on endoscopic biopsies from 48 patients as part of a Barrett's surveillance program using 14 microsatellite markers shown previously to detect loss of heterozygosity in more than 30% of esophageal adenocarcinomas. Patients were followed up endoscopically for a median of 5 years.Results: Loss of heterozygosity was detected in nine patients. Three patients with loss of heterozygosity on chromosome 5q or 9p did not progress beyond metaplasia. Loss of heterozygosity at 17p11.1–p13 was detected in six patients, all of whom demonstrated dysplasia and/or carcinoma during follow up (four low‐grade dysplasia, one high‐grade dysplasia and one adenocarcinoma).Conclusion: Loss of heterozygosity at 17p11.1–p13 on chromosome 17p identifies patients with Barrett's esophagus at risk of neoplastic progression and can supplement histology in determining the frequency of endoscopy during surveillance.
Delta 13C‐urea breath test value is a useful indicator for Helicobacter pylori eradication in patients with functional dyspepsia
Authors: CHANG YOUNG‐WOON , MIN SUN‐KEE , KIM KYUNG‐JIN , HAN YO‐SEOB , LEE JOO‐HEE , DONG SEOK‐HO , KIM HYO‐JONG , KIM BYUNG‐HO , LEE JOUNG‐IL , CHANG RIN 
Published: May 2003

AbstractBackground: Eradication of Helicobacter pylori is not routinely recommended for the symptomatic relief and the prevention of gastric cancer in patients with functional dyspepsia. The present study investigated a useful indicator of H. pylori eradication in such patients by determining the optimal cutoff value of a 13C‐urea breath test (UBT).Methods: One hundred dyspeptic patients participated in the study. Dyspepsia was scored, and a 13C‐UBT administered. A level of delta 13C‐UBT of>4‰ was diagnosed as H. pylori‐positive. After the stomach was endoscopically sprayed with phenol red, biopsy specimens were taken from the antrum, body and cardia of the stomach for the assessment of H. pylori density, and activity (neutrophil infiltration) and degree (lymphocyte infiltration) of gastritis.Results: Correlation between delta 13C‐UBT and dyspepsia score was not found. Delta 13C‐UBT significantly correlated with H. pylori density score in the total stomach (r = 0.53, P < 0.0001), neutrophil (r = 0.34, P = 0.0005) and lymphocyte score (r = 0.69, P < 0.0001). Twenty‐six of the 100 subjects had a neutrophil score of ≥4, lymphocyte score of ≥4, and H. pylori score of ≥4. Their 95% confidence interval of mean was 58.2‰, which reflects moderate to marked acute and chronic gastritis, and dense H. pylori colonization.Conclusions: The 13C‐UBT is a reliable semiquantitative test to assess H. pylori density and the activity and degree of gastritis. It is proposed that H. pylori eradication therapy might be beneficial for patients with functional dyspepsia with a delta 13C‐UBT of >58.2‰.
Decreased ratio of CD4/CD8 lymphocytes might be predictive for successful interferon alpha and lamivudine combined therapy in childhood chronic hepatitis B infection: A preliminary study
Authors: GENEL FERAH , UNAL FATIH , OZGENC FUNDA , AKSU GUZIDE , AYDOGDU SEMA , KUTUKCULER NECIL , YAGCI RASIT V 
Published: May 2003

AbstractBackground: In the development of chronic hepatitis with hepatitis B virus infection and in response to therapy, the immune status of the infected host plays a critical role. In this study, immunological variables were assessed in patients before interferon alpha and lamivudine therapy to determine if any pretreatment immunological parameter could be an indicator of response to therapy in childhood chronic hepatitis B infection.Methods: Forty‐four patients with chronic hepatitis B virus infection, aged 9.0 ± 3.9 years, were enrolled in the study. The pretreatment clinical features, biochemical test results, histological activity indexes and immunological parameters were evaluated. All patients received interferon alpha for 6 months and lamivudine for 52 weeks. Four patients who could not be followed up were excluded from the study. The other 40 patients have been followed for a mean period of 27.5 ± 9.7 months after therapy discontinuation.Results: Seventeen patients showed loss of hepatitis B early antigen (HBeAg) with appearance of anti‐HBe (42.5%) and six of those who responded also showed loss of hepatitis B surface antigen (HBsAg) with the presence of anti‐HBs (15%). Except elevated aspartate aminotransferase levels, there was no significantly correlation between response and sex, age, pretreatment duration of disease and histological activity indexes. Pretreatment immunoglobulins (Ig), IgG subclasses, complement C3, C4 and secretory IgA levels were also not found to be significantly related to response. The evaluation of lymphocyte subsets showed that therapy responders had significantly reduced pretreatment ratios of CD4/CD8+ lymphocytes due to prominent increased percentages of CD8+ cells. The other cellular immunity parameters and some cell surface adhesion molecules were similar in both groups.Conclusion: This study emphasizes the importance of increased pretreatment CD8+ lymphocyte percentages leading to a significant decrease in CD4/CD8 ratio in chronic hepatitis B virus infection of childhood as an immunological factor predicting response to treatment.
Scirrhous changes in dysplastic nodules do not indicate high‐grade status
Authors: AN HEE J , ILLEI PETER , DIFLO THOMAS , JOHN DEVON , MORGAN GLYN , TEPERMAN LEWIS , THEISE NEIL 
Published: May 2003

AbstractBackground and Aims: Dysplastic nodules (DN) may be divided into high‐grade and low‐grade, and the former has been known as a precancerous or borderline lesion. Recently many morphological characteristics concerning these types of DN have been reported. In the present study we attempted to evaluate the scirrhous change in DN as an indicative feature of high‐grade DN, based on the morphological and cell‐kinetic analyses using immunohistochemical stains for Ki‐67.Methods: We reviewed 35 livers with DN and selected 15 DN with scirrhous change. We stained DN‐bearing sections of each case with hematoxylin and eosin, trichrome, reticulin and Perls’ stain. We tried to subclassify and characterize the scirrhous change according to the fibrosis pattern. We also stained with Ki‐67 immunohistochemically to assess the proliferative activity of DN with scirrhous change.Results: We found two types of scirrhous change, that is, pericellular and stellate. The pericellular type was related to the Mallory body‐forming cholestatic degeneration, whereas the stellate type was associated with extensive portal fibrosis probably induced by ischemic damage. Among DN with scirrhous change, high‐grade DN comprised five nodules (33%) and there were 10 (67%) low‐grade nodules. There was no significant relationship between the presence or the types of scirrhous change and the grade of DN. The significant differences of Ki‐67 labeling indices between types of scirrhous change were not shown in this study. We also could not find the differences between Ki‐67 labeling indices of scirrhous DN (high and low grades) and those of surrounding regenerative nodules.Conclusions: This evidence indicated that the scirrhous change in DN was not a specific feature of high‐grade DN. We also found that scirrhous DN have two morphological varieties that may represent biologically different processes, that is, pericellular scirrhous type and stellate scirrhous type.