bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of multiple mutations in the core promoter and pre‐core/core region of hepatitis B virus genome on the response to interferon in e antigen‐positive chronic hepatitis B
Authors: Zhang Xinxin , Han Yongnian , Lu Zhimeng , Gao Jian , Luo Zhenghui , Zhang Donghua 
Published: March 2003

AbstractBackground and Aims: Hepatitis B virus (HBV) genomic mutations may be one of the factors that influence the efficacy of interferon (IFN) therapy. The aim of this study was to investigate the effects of mutations in different parts of the HBV genome on IFN therapy.Methods: We studied the baseline clinical, biochemical, serologic and virologic parameters in 17 patients with e antigen‐positive chronic hepatitis B. The DNA sequence of the X gene and pre‐core/core gene in serum samples of these patients was analyzed before the initiation of IFN therapy.Results: All five patients with the T1762–A1764 mutation were IFN responsive, while among the 12 remaining patients, only two responded to therapy. Among five patients with both a pre‐core A1896 mutation and a mutation in the epitope aa 107–118 of the core region, four were non‐responders whereas the fifth responded to therapy. In three other patients with A1896 mutations, one with simultaneous mutations in five lymphocytic epitopes did not respond to therapy; the two remaining patients with concomitant mutations in one or two epitopes were responsive. Serum HBV‐DNA levels were lower and titers of antibody to hepatitis B virus core antigen‐immunoglobin M (anti‐HBc‐IgM) were higher in the responders than in the non‐responders. Hepatitis B virus genotypes B and C were found to be in all these Chinese patients.Conclusions: These results suggest that HBV genomic mutations, serum viral loads and titers of anti‐HBc‐IgM might be predictive of the efficacy of IFN therapy. These clinical findings should be further investigated by in vivo and in vitro experiments.
Iron overload impairs pro‐inflammatory cytokine responses by Kupffer cells
Authors: Olynyk John K , Clarke Sharon L 
Published: March 2003

AbstractAim: The aim of the present study was to determine the effect of chronic iron overload on Kupffer cell cytokine production.Methods: Kupffer cells were isolated from rats that were fed either a control or iron‐supplemented diet for 12 months. Cytokine mRNA and protein levels were determined by using a ribonuclease protection assay and ELISA, respectively.Results: Baseline levels of tumor necrosis factor‐α, transforming growth factor‐β1, interleukin‐6 and granulocyte macrophage colony stimulating factor were similar in iron‐loaded and control Kupffer cells. Following the addition of lipopolysaccharide to control cells, tumor necrosis factor‐alpha, interleukin‐1α and interleukin‐6 mRNA levels increased. Tumor necrosis factor‐alpha mRNA and protein levels were reduced by 40 and 60%, respectively, in iron‐loaded cells compared with controls following the addition of lipopolysaccharide. Interleukin‐6 mRNA levels in iron‐loaded Kupffer cells were also reduced. Granulocyte macrophage colony stimulating factor mRNA levels remained unchanged in controls, but were significantly elevated in iron‐loaded cells. Tumor growth factor‐β1 mRNA and protein levels were similar in control and iron‐loaded cells.Conclusion: Deposition of iron in Kupffer cells in chronic dietary iron overload results in an impaired pro‐inflammatory cytokine response to lipopolysaccharide. Our observations may have relevance to the altered immune function observed in chronic iron‐overload syndromes.
Modulation of doxorubicin sensitivity by cyclosporine A in hepatocellular carcinoma cells and their doxorubicin‐resistant sublines
Authors: Shiraga Kunihiro , Sakaguchi Kohsaku , Senoh Tomonori , Ohta Takeyuki , Ogawa Shin , Sawayama Tomoyuki , Mouri Hirokazu , Fujiwara Akiko , Tsuji Takao 
Published: March 2003

AbstractBackground and Aims: Cyclosporine A (Cys) and verapamil (Ver) sensitize multidrug‐resistant (MDR) cells to various anticancer drugs by interacting with membrane glycoproteins involved in the drug efflux. In the present study, we assessed the effect of Cys on the modulation of doxorubicin (DOR) sensitivity in hepatocellular carcinoma (HCC) cell lines, and their DOR‐resistant sublines.Methods: The sensitivity to DOR and the chemosensitizing effects of Cys were assessed by using two human HCC cell lines, PLC/PRF/5 and Hep‐3B, and their DOR‐resistant sublines, PLC/DOR and 3B/DOR. The expression of multidrug resistance 1 (MDR1) and multidrug resistance‐associated protein (MRP) mRNA in these cells were detected by using a RT‐PCR. The HCC cell lines grown in individual wells of 24‐well plates were incubated with DOR that were sequentially diluted in culture medium in combination with 5 μmol/L Cys for 24 h. The cell viability in each well was measured by using a 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay.Results: The mRNA of MDR1 and that of MRP were readily detectable in the HCC cell lines by RT‐PCR. When 5 μmol/L Cys was added to the culture, the 50% inhibiting concentration (IC50) of DOR was reduced from 0.93 ± 0.29 μg/mL to 0.32 ± 0.10 μg/mL in PLC/PRF/5, and from 0.25 ± 0.07 μg/mL to 0.09 ± 0.04 μg/mL in Hep‐3B. Furthermore, in the presence of 5 μmol/L Cys, the IC50 of DOR was reduced from 48.63 ± 17.04 μg/mL to 0.49 ± 0.14 μg/mL in PLC/DOR, and from 4.60 ± 1.22 μg/mL to 0.15 ± 0.06 μg/mL in 3B/DOR. The amounts of PCR products of MDR1 mRNA in PLC/DOR and 3B/DOR were greater than those in PLC/PRF/5 and Hep‐3B, respectively.Conclusions: In HCC, the amplification of MDR1 mRNA is probably the main mechanism underlying acquired DOR resistance. Cyclosporine is also indicated to be highly active in potentiating the anticancer activity of DOR in HCC cells and their DOR‐resistant sublines.
Prevalence and natural history of subclinical hepatic encephalopathy in cirrhosis
Authors: Das Ananya , Dhiman Radha K , Saraswat Vivek A , Verma Meera , Naik Subhash R 
Published: March 2003

AbstractBackground and Aims: The natural history of subclinical hepatic encephalopathy (SHE) is unknown. The present study was conducted to study the prevalence and the natural history of SHE in patients with cirrhosis of the liver.Methods: One hundred and sixty‐five patients with cirrhosis of the liver were studied. A total of nine psychometric tests (trail making and Wechsler adult intelligence scale‐performance (WAIS‐P) tests) were administered. Subclinical hepatic encephalopathy was present if two or more psychometric tests were abnormal. Seventy‐two patients (SHE 40, without SHE 32) also underwent serial psychometric testing on follow‐up visits at 6–8 week intervals.Results: Subclinical hepatic encephalopathy was present in 103 (62.4%) patients. The number and figure connection, block design and picture completion tests were the most useful in the detection of SHE. Severity of SHE, as assessed by the number of abnormal tests, was greater in patients with more severe liver disease. During follow up, SHE tended to persist or worsen in patients with poorer liver function. Although other clinical complications were similar in different groups, overt hepatic encephalopathy developed more commonly in those patients who had SHE at entry compared to those who did not (22.6 vs 5.6%, P = 0.044). Among the patients with SHE, the development of overt hepatic encephalopathy was more common in patients with Child's score of > 6 than with Child's score of ≤ 6 (40 vs 5%, P = 0.019).Conclusions: We conclude that SHE is common in cirrhosis. The natural history of SHE is worse in patients with advanced cirrhosis and SHE probably predisposes the cirrhotic patient to overt hepatic encephalopathy.
High risk of Helicobacter pylori infection in young Japanese dentists
Authors: Honda Kimio , Ohkusa Toshifumi , Takashimizu Ichizen , Watanabe Mamoru , Amagasa Mitsuo 
Published: March 2003

AbstractBackground and Aim: The route of person‐to‐person transmission of Helicobacter pylori may be either fecal–oral or oral–oral, because the bacterium is found in both dental plaque and feces. We assessed the prevalence of H. pylori seropositivity, which reflects present or past infection, in Japanese dentists exposed occupationally to dental plaque.Methods: We examined the sera of 60 dentists (34 who were 20–29 years or older, and 26 who were over 30 years of age) and 60 age‐matched controls by using quantitative ELISA for antibodies of the immunoglobulin G class to H. pylori.Results: The proportion of dentists seropositive for H. pylori (42 of 60, 70%) was higher than in controls (23 of 60, 38%). The odds ratio for H. pylori seropositivity (3.8; 95% CI, 1.76–8.02) was high in the dentists. When dentists were classified in terms of the length of their practice, the odds ratio for seropositivity (10.4; 95% CI, 3.26–32.85) was high in the dentists practising for fewer than 4 years. The proportion of dentists in their 20s who were seropositive was greater than that in the group of age‐matched controls.Conclusion: Japanese young dentists are at a high risk for H. pylori infection, with the oral–oral transmission route being possibly the most common.
Significance of serum soluble Fas antigen level in chronic hepatitis C patients treated with interferon: Relationship to the therapeutic response
Authors: Ohkawa Kazuyoshi , Hiramatsu Naoki , Mochizuki Kiyoshi , Mita Eiji , Iio Sadaharu , Yoshihara Harumasa , Kato Michio , Masuzawa Manabu , Kasahara Akinori , Sasaki Yutaka , Hori Masatsugu , Hayashi Norio 
Published: March 2003

AbstractBackground and Aim: Fas system‐mediated cytotoxicity is thought to be involved in the development of liver injury in hepatitis C virus (HCV) infection. In this study, we investigated serum soluble Fas antigen levels in chronic hepatitis C patients treated with interferon and their correlation with the therapeutic response.Methods: The subjects were 67 chronic hepatitis C patients who underwent a 24‐week course of α‐interferon therapy. Patients were categorized into three groups; sustained responders (n = 22), transient responders (n = 24), and non‐responders (n = 21), according to changes in the serum alanine aminotransferase level during and after therapy. The viral genotype, viremic level and diversity in the hypervariable region were examined before therapy. Serum soluble Fas antigen levels were assayed by using serum samples taken at the beginning and the end of therapy.Results: In the univariate analysis, serum soluble Fas antigen levels tended to be higher in non‐responders (10.0 ± 3.4 ng/mL) than in sustained responders (8.5 ± 3.0 ng/mL) and transient responders (8.2 ± 2.1 ng/mL; P = 0.13 and P < 0.05). The non‐response to therapy was observed in eight of the 15 (53%) patients with serum soluble Fas antigen ≥ 11 ng/mL, compared with 13 of the 52 (25%) patients with serum soluble Fas antigen < 11 ng/mL (P < 0.05). As for the multivariate analysis, the only significant factor contributing to the sustained response was a low HCV viremic level (P = 0.0046). Significant factors contributing to the non‐response were a high serum alanine aminotransferase (P = 0.0407) and a high serum soluble Fas antigen level (P = 0.0483).Conclusions: High production levels of soluble Fas antigen may be associated with a poor response to interferon therapy in chronic hepatitis C patients.
Clinician opinion on the management of patients with hepatic colorectal metastases
Authors: Moore Katrina , Bokey Les , Chapuis Pierre , Tait Noel 
Published: March 2003

AbstractBackground and Aims: Clinical practice is determined by many different factors, but with the advent of evidence‐based medicine, there may be a tendency to concentrate upon the scientific facts when decision‐making rather than focusing on the patient. Furthermore, individual clinician opinion or bias may potentially influence patient management. This study outlines clinician opinion with regard to management of patients with hepatic colorectal metastases, and compares it to present practice in the Sydney metropolitan area.Methods: Clinician opinion was assessed by using a questionnaire and compared to results from a prospective multicenter study looking at patterns of care of patients with hepatic colorectal metastases.Results: Clinicians participating in the present study had a good knowledge of the current evidence concerning hepatic colorectal metastases and its treatment. However, there was a discrepancy between clinician knowledge that matched scientific evidence and actual clinical practice.Conclusions: This study suggests that clinician bias/opinion does influence patterns of care for patients with hepatic colorectal metastases.
An evaluation of the PyloriTek test for the diagnosis of Helicobacter pylori infection in Chinese patients before and after eradication therapy
Authors: Wong Wai Man , Wong Benjamin Chun Yu , Tang Vera Shun Yim , Lai Kam Chuen , Yuen Siu Tsan , Leung Suet Yi , Hu Wayne Hc , Lam Shiu Kum 
Published: March 2003

AbstractBackground and Aim: The PyloriTek Test Kit (a 1‐h rapid urease test) was developed for the rapid diagnosis of Helicobacter pylori (H. pylori) during endoscopy. Most studies were performed in Western populations. The aim of this study was to evaluate the PyloriTek test for the diagnosis of H. pylori infection in Chinese population.Methods: Eligible patients without prior treatment or who had had recent eradication of H. pylori were recruited. During endoscopy, biopsies were taken from the antrum and corpus for an in‐house rapid urease test (RUT), histology and for the PyloriTek test (one antral and one corpus biopsy). Results of the PyloriTek test were compared with the gold standard (RUT and histology).Results: Analysis of PyloriTek test results from the antrum alone (101 patients before eradication and 52 patients after eradication) showed a sensitivity, specificity, and accuracy of 96.3, 97.9, and 97.0%, respectively, for cases before eradication, and an accuracy of 100% for cases after eradication. The benefit of an additional body biopsy was marginal and only occurred in the pre‐eradication group.Conclusion: The PyloriTek test was highly accurate for the diagnosis of H. pylori infection before and after eradication therapy, with a final result available at 1 h, which is unmatched by any invasive test so far. It enhances clinical decision‐making by allowing the clinicians or endoscopists to start therapy on the same day of an endoscopy visit. One biopsy from the antrum is highly reliable for this purpose.
Hyposplenism in alcoholic cirrhosis, facts or artifacts? A comparative analysis with non‐alcoholic cirrhosis and extrahepatic portal venous obstruction
Authors: Satapathy Sanjay K , Narayan Sajith , Varma Neelam , Dhiman Radija K , Varma Subhash , Chawla Yogesh 
Published: March 2003

AbstractBackground and Aims: Hyposplenism has been described in patients with alcoholic cirrhosis (AC). However, no data are available regarding hyposplenism in patients with non‐alcoholic cirrhosis (NAC) and other forms of portal hypertension such as extrahepatic portal venous obstruction (EHPVO). The aim is to study the splenic functions in patients with AC, NAC, and EHPVO.Methods: Splenic functions were assessed consecutively in 22 patients with AC, 21 with NAC, and 23 with EHPVO. The tests included pitted red blood cells (RBC; %) and Howell–Jolly bodies in the peripheral smear. Pitted RBCs > 2% with or without the presence of Howell–Jolly bodies were taken as indicators of hyposplenism. The splenic function in each group was compared with age‐matched controls.Results: Hyposplenism was found in 10 (45.45%) patients with AC, six (28.57%) with NAC and one (4.34%) with EHPVO. The mean pitted RBCs were significantly increased in patients with AC (mean 4.93 ± 1.36%vs control 1.22 ± 0.17%, P < 0.05), but not so with NAC (2.01 ± 0.69%) and EHPVO (mean 0.99 ± 0.1%vs control 0.66 ± 0.1%, P > 0.05). Howell–Jolly bodies were seen in only four patients. The mean pitted RBCs were significantly higher among patients who were actively consuming alcohol (9.14 ± 3.35%) compared to those who abstained at least for more than 24 weeks (2.0 ± 1.3%, P < 0.05).Conclusion: Hyposplenism is more common in AC patients, particularly those who are actively consuming alcohol compared with those who abstain. Patients with NAC have a lower incidence of hyposplenism, while in EHPVO patients, it is uncommon.
Cisapride improves gallbladder emptying in patients with type 2 diabetes mellitus1
Authors: Dhiman Radha K , Arke Leishangthem , Bhansali Anil , Gupta Sanjay , Chawla Yogesh K 
Published: March 2003

AbstractBackground and Aims: Gallbladder motor function is impaired in many patients with diabetes, and may be related to cholinergic nerve damage. Cisapride is a prokinetic drug of the gastrointestinal tract and acts by releasing acetylcholine from cholinergic nerve endings. The aim of this study was to determine the effect of cisapride on gallbladder emptying in patients with type 2 diabetes mellitus (DM).Methods: Gallbladder emptying and tests for autonomic neuropathy (AN) were performed in 27 patients with type 2 DM and in 10 healthy subjects. Gallbladder emptying was studied by using real‐time ultrasonography after an overnight fast, and after the subjects received a breakfast that contained 2500 J. Gallbladder emptying was repeated after the treatment with cisapride (10 mg t.i.d.) for 1 week in all subjects.Results: Abnormal gallbladder emptying was present in 14 (51.9%) patients. The residual gallbladder volume (mean ± SEM) was higher (9.3 ± 1.0 vs 4.6 ± 0.6; P = 0.002), and ejection fraction was lower (57.4 ± 4.0 vs 74.2 ± 2.4; P = 0.015) in diabetic patients than it was in healthy subjects. Cisapride produced a reduction in fasting and residual volumes (24.6 ± 2.4 vs 20.0 ± 1.4; P = 0.034 and 9.3 ± 1.0 vs 5.9 ± 1.1; P = 0.00003, respectively), and an improvement in ejection fraction (57.4 ± 4.0 vs 72.6 ± 3.8; P = 0.000007). The improvement in gallbladder emptying after cisapride therapy was confined to the patients with AN (n = 13) (57.3 ± 5.4 vs 80.4 ± 2.9; P = 0.0017), suggesting denervation supersensitivity with an upregulation of cholinergic receptors. There was no significant change in the ejection fraction in patients without AN (57.5 ± 6.1 vs 65.4 ± 6.5; P = NS). Sex, duration of diabetes, peripheral neuropathy, diabetic retinopathy and serum cholesterol level did not influence gallbladder emptying.Conclusion: Impaired gallbladder emptying is common in patients with type 2 DM. Cisapride significantly improves gallbladder emptying in patients with autonomic neuropathy.
Autoimmune hepatitis in the Indian subcontinent: 7 years experience
Authors: Gupta Rajesh , Agarwal Shri Ram , Jain Monika , Malhotra Veena , Sarin Shiv Kumar 
Published: March 2003

AbstractBackground: Autoimmune hepatitis (AIH) is presumed to be rare in India. The present prospective study was carried out to determine the prevalence, clinical, biochemical and histological profile of patients with AIH in India.Methods: Consecutive patients with chronic liver disease suspected to be AIH, were screened for antinuclear antibodies (ANA), antismooth muscle antibodies (ASMA), antimitochondrial antibody (AMA), and anti‐liver kidney microsomal antibodies (anti‐LKM‐1). Serum protein electrophoresis and liver biopsy were done. Autoimmune hepatitis was diagnosed according to the International Autoimmune Hepatitis Group criteria.Results: Fifty of 1358 (3.43%) patients with chronic liver disease were diagnosed as autoimmune liver disease; 39 with AIH, two with overlap syndrome, five with primary sclerosing cholangitis, and four with primary biliary cirrhosis. Twenty‐nine patients were categorized as definite AIH and 10 as probable AIH. Autoimmune hepatitis was common in females (males : females 1:3), with a mean age of 31 ± 17 years. Patients often presented with fatigue, jaundice and anorexia. Skin lesions (58%), joint symptoms (30%), and menstrual abnormalities (26%) were not uncommon. Mildly elevated alkaline phosphatase and hyper gamma globulinemia were seen in 78 and 91% patients, respectively. Eighty percent of patients were type I AIH, while 20% of cases remained unclassified. Histopathological changes included piecemeal necrosis (100%), plasma cell infiltration (91%), rosette formation (82%), and cirrhosis (76%). Overall mortality was 25% during a mean follow up of 15.7 ± 17.0 months.Conclusions: Our results clearly demonstrate that: (i) AIH is not uncommon in India; and (ii) while the profile and spectrum of AIH resembles that seen in the West, Indian patients present late, often in a cirrhotic state.
Effect of omeprazole‐induced achlorhydria on trefoil peptide expression in the rat stomach
Authors: Kang Baolin , Alderman Barbara M , Nicoll Amanda J , Cook Greg A , Giraud Andrew S 
Published: March 2003

AbstractBackground:Omeprazole is an inhibitor of the H+K+ ATPase of the gastric parietal cell, which is used clinically to suppress gastric acid secretion. It has also been found to inhibit gastric mucin production; however, its effects on the synthesis and secretion of the trefoil peptides, which are also expressed by mucus cells, and which play a key role in cytoprotection and epithelial repair, are unknown.Methods:Rats (n = 8) were given either omeprazole (30 mg/kg per day; p.o.) or inert carrier for 1 week, and the effects on synthesis and peptide expression of the gastric trefoil peptides, TFF1/pS2 and TFF2/SP, were compared.Results:As expected, omeprazole treatment abolished H+ ion production with a mean gastric juice pH of 7.2 compared with 2.4 for controls. The omeprazole group had elevated total protein levels of 35‐fold and TFF1/pS2 peptide levels elevated fourfold, respectively, but not TFF2/SP peptide in gastric juice, suggesting that the increased pH reduced the viscosity of adherent mucus, thereby increasing gastric juice concentrations by dissolution of adherent TFF1/pS2 and increased secretion. Concomitant with increased TFF1/pS2 secretion was a fall in predominantly antral mucosal trefoil peptide concentrations. In contrast to trefoil secretory rates, the steady‐state synthesis of both TFF1/pS2 and TFF2/SP was unchanged after omeprazole treatment, implying both a large cellular pool of processed peptide and rapid secretion.Conclusion:The increase in the concentration of TFF1/pS2 in gastric secretions during chronic omeprazole‐induced achlorhydria may be important in preventing tissue injury and promoting repair in response to an increased luminal bacterial population.