bluuebunny/crossref_metadata_2025_split huggingface dataset:
Projections of nitric oxide synthase and vasoactive intestinal polypeptide‐reactive submucosal neurons in the human colon
Authors: Porter Anthony J , Wattchow David A , Brookes Simon Jh , Costa Marcello 
Published: March 2003

Abstract
Background
: The submucosal plexus is important in the control of secretomotor and motor function of the intestine. Our aim was to describe the projections of submucosal neurons to the mucosa within the submucosal plexus and to the circular muscle of human colon and to determine whether submucosal neurons that projected to different layers were located at different levels of the submucosa.
Methods
: A retrogradely transported fluorescent dye was applied to the mucosa, submucosa or circular muscle layer of human colon which was then maintained in organotypic culture for 5 days. The submucosa was then dissected into two preparations, one containing the inner layer of the submucosal plexus and the other containing both the intermediate and outer layers. The dissected preparations were labelled with antibodies to nitric oxide synthase (NOS) or vasoactive intestinal peptide (VIP).
Results
: Submucosal neurons projected to the mucosa, submucosa and circular muscle layers for mean distances of 3.7, 3.0 and 4.3 mm, respectively. Ninety‐seven per cent of submucosal neurons labelled from the circular muscle were located in the outer or the intermediate layers, while 51% of those projecting to the mucosa were in inner layer and 49% in the intermediate/outer layers of the submucosal plexus. Eleven per cent of submucosal neurons projecting to the circular muscle were immunoreactive for NOS and 12% were immunoreactive for VIP. Forty‐five per cent of those projecting within the submucosa were immunoreactive for VIP and 38% of those projecting to the mucosa were immunoreactive for VIP.
Conclusions
: Submucosal neurons in the human colon innervate the mucosa, circular muscle and submucosa and different functional classes of neurons are located in different layers of the submucosal plexus.© 1999 Blackwell Science Asia Pty Ltd
Augmentative effects of L‐cysteine and methylmethionine sulfonium chloride on mucin secretion in rabbit gastric mucous cells
Authors: Watanabe Tomoe , Ohara Susumu , Miyazawa Shitirou , Saigenji Katunori , Hotta Kyoko 
Published: March 2003

Abstract
Background
: Our previous study showed that
L‐cysteine (Cys) and methylmethionine sulfonium chloride (MMSC) inhibited ethanol‐induced gastric mucosal damage and increased the amount of surface mucin in rats. This study examined whether Cys and MMSC augmented mucin secretion and changed distribution of mucin vesicles ultrastructurally in mucous cells by using primary cultured mucous cells from rabbit glandular stomach. Changes in intracellular cyclic adenosine 3′,5′‐monophosphate (cAMP) and in levels of cytosolic free Ca2+ were investigated by treatment with Cys and MMSC.
Methods
: Mucin content was measured by an enzyme‐linked lectin assay. Transmission electron micrography was used to examine ultrastructural distribution of mucin granules. The amount of cAMP or levels of free Ca2+ were measured by enzyme immunoassay or by fura‐2. 16,16‐Dimethyl prostaglandin E2 (dmPGE2) or ATP was used as the positive control.
Results
:
L‐Cysteine and MMSC increased mucin secretion and decreased cellular mucin content. The same was noted for dmPGE2. Accelerated mucin granule movements toward the plasma membrane were shown by these agents. Intracellular cAMP increased with exposure to dmPGE2 for 20 min, while neither Cys nor MMSC increased cAMP. No increase in cytosolic free Ca2+ levels occurred after treatment with Cys or MMSC, but an increase was induced 10 s after the addition of ATP.
Conclusions
: The present findings indicate that the increase in mucin secretion by Cys and MMSC was not mediated through the cAMP or Ca2+ signal transduction pathway, but might occur through non‐receptor‐mediated mechanisms.
Cavographic study of an early stage of obstruction of the hepatic portion of the inferior vena cava
Authors: Shrestha Santosh M , Joshi Bishnu L , Shrestha Shobhana , Maharajan Krishna G 
Published: March 2003

Abstract
Background
: Liver disease caused by a chronic lesion of the hepatic portion of the inferior vena cava (IVC) is clinically characterized by dilated superficial veins in the body trunk with cephalad flow, hepatomegaly and splenomegaly. Cavography shows stenosis or complete obstruction near the cava‐atrial junction.
Methods
: Early (acute and subacute) forms of the disease were recognized. The early stage of the disease manifested as jaundice, hepatomegaly or ascites and fever. Patients with acute and subacute onset of the illness with no past history of liver disease were studied with inferior vena cavography. Some of the patients had repeat cavography at 6 months and at 1 year after the initial investigations.
Results
: Three types of cavographic lesions were observed in the early stages of the disease: type 1, linear lucent area in the IVC close to cava‐atrial junction; type 2, a smooth or irregular narrowing of almost the whole segment of the hepatic portion of the IVC; and type 3, a constriction or narrowing of a segment of the IVC near the cava‐atrial junction. The first two types were associated with the acute stage of the disease and type 3 with the subacute stage. Type 2 and 3 lesions were associated with post‐stenotic dilatation (PSD) close to the atrium. Lucent areas resulting from thrombosis are common in PSD. The acute and subacute hepatic IVC diseases in Nepal are commonly associated with bacterial infection.
Conclusions
: It is postulated that the early cavographic lesions are consistent with thrombosis and thrombophlebitis of the hepatic portion of the IVC, and that resolution of the lesions leads to the development of stenosis and to complete obstruction.
Putative role of hepatitis B virus X protein in hepatocarcinogenesis: Effects on apoptosis, DNA repair, mitogen‐activated protein kinase and JAK/STAT pathways
Authors: Arbuthnot Patrick , Capovilla Alexio , Kew Michael 
Published: March 2003

AbstractChronic infection with hepatitis B virus (HBV) is a major risk factor for the development of hepatocellular carcinoma (HCC). The pathogenesis of HBV‐induced malignant transformation is, however, incompletely understood. HBx, the protein encoded by the X open reading frame, is a transcriptional activator that has been implicated in hepatocarcinogenesis. HBx inhibits the function of the tumour suppressor protein p53 in what is thought to be an early event in hepatocyte transformation before the later accumulation of inactivating p53 point mutations. HBx inhibits apoptosis but also exerts pro‐apoptotic effects. The effects of HBx on apoptosis may be important not only for the development of HCC but also for the establishment of HBV infection. Further implication of HBx in hepatocyte transformation has been the demonstration that it inhibits the repair of damaged hepatocyte DNA. This effect may be mediated by interaction with p53 or through binding to the damaged DNA binding protein (DDB), which plays an accessory role in nucleotide excision repair. In addition, HBx activates cell signalling cascades involving mitogen‐activated protein kinase (MAPK) and Janus family tyrosine kinases (JAK)/signal transducer and activators of transcription (STAT) pathways. The implications of these modulating effects of HBx are not fully understood, but they are likely to have wide‐ranging effects on hepatocyte proliferation, apoptosis and the regulation of cell growth checkpoints. The cellular functions ascribed to HBx are unusually diverse, and defining the biologically important role of HBx during HBV replication will go some way to understanding the sequelae of chronic HBV infection.
Extracorporeal shock wave lithotripsy of gallstones revisited: Current status and future promises
Authors: Mulagha Eneya , Fromm Hans 
Published: March 2003

AbstractThe improvement and refinement of extracorporeal shock wave lithotripsy (ESWL) has made this non‐invasive treatment modality not only more effective, but also applicable to a larger population of gallstone patients. It can be performed safely on an outpatient basis. Advances in lithotripsy technology have made it possible to fragment stones into very small, sand‐like particles (pulverization), which clear the gall‐bladder faster than large fragments. Recent studies provide evidence that adjuvant bile acids may not be necessary in most cases in which pulverization is achieved. Good gall‐bladder emptying appears both to promote the clearance of gallstones after ESWL and to decrease their recurrence. Although generally found to be more expensive than surgery if bile acids are used, ESWL should be cost‐effective, as bile acids may not be necessary in all patients. Elderly patients with radiolucent, solitary and less than 30 mm gallstones can particularly benefit from lithotripsy.© 2000 Blackwell Science Asia Pty Ltd
Firstline treatment for hepatitis C: combination interferon/ribavirin versus interferon monotherapy
Authors: Lai Ming‐Yang 
Published: March 2003

AbstractIn the initial treatment of chronic hepatitis C, interferon‐alfa (IFN‐α) monotherapy for 24–48 weeks induces sustained response rates of only 10–20%. Combination therapy with IFN‐α plus ribavirin induces a sustained response in 40–50% of patients, and can be now recommended as the firstline therapy for chronic hepatitis C. Stopping therapy at week 12 because of persistent viraemia is unnecessary with the combination therapy because later clearance of HCV RNA can still occur with a sustained response. Patients with HCV genotype 1 should receive 48 weeks of combination therapy, in contrast to 24 weeks for patients with genotypes 2 or 3. For patients who cannot tolerate the side effects of ribavirin, such as anaemia, IFN‐α at 3 MU three times weekly for 48 weeks is preferred as the initial therapy. The long‐acting pegylated IFN can be expected to enhance the efficacy of combination therapy in the treatment of chronic hepatitis C and appears to be much more potent as monotherapy. Further studies are needed to improve the current ‘half‐full’ status of chronic hepatitis C treatment.
Role of Kupffer cells and gut‐derived endotoxins in alcoholic liver injury1
Authors: Enomoto Nobuyuki , Ikejima Kenichi , Bradford Blair U , Rivera Chantal A , Kono Hiroshi , Goto Moritaka , Yamashina Shunhei , Schemmer Peter , Kitamura Tsuneo , Oide Hirosumi , Takei Yoshiyuki , Hirose Miyoko , Shimizu Hidetake , Miyazaki Akihisa , Brenner David A , Sato Nobuhiro , Thurman Ronald G 
Published: March 2003

AbstractThe hepatotoxic effects of alcohol have been described in detail, but factors responsible for its hepatotoxicity have only partially been characterized. For example, it is known that chronic ethanol ingestion increases hepatotoxicity and produces fatty liver, hepatitis and cirrhosis. However, acute ethanol consumption reduces endotoxin hepatotoxicity. It now appears that Kupffer cells participate in several aspects of these phenomena. Previously, most studies on the effects of alcohol on liver function have focused chiefly on the hepatocyte. Recently, attention has been directed towards the effect of ethanol ingestion on Kupffer cell function, which is stimulated by gut‐derived endotoxins (lipopolysaccharides) via mechanisms dependent on increased gut permeability and the possible relationship between Kupffer cells and alcohol‐induced liver injury. Here we will review new evidence for the proposal that Kupffer cells and endotoxins play a pivotal role in hepatotoxicity following alcohol exposure, based on studies using the continuous intragastric enteral feeding model developed by Tsukamoto and French and an acute model developed by us.
Effect of branched‐chain amino acids on the composition and cytolytic activity of liver‐associated lymphocytes in rats
Authors: Tsukishiro Takashi , Shimizu Yukihiro , Higuchi Kiyohiro , Watanabe Akiharu 
Published: March 2003

Abstract
Background
: Although branched‐chain aminoacids (BCAA) are reported to be effective in prolongation of the mean survival time of patients with liver cirrhosis, it is not clear whether BCAA could influence the immune function in those patients.
Methods
: Branched‐chain amino acids were given as a supplement to carbon tetrachloride‐induced cirrhotic rats, and an aminogram of the liver and kinetics of liver‐associated lymphocytes (LAL) were then analysed.
Results
: Liver cirrhosis was established at the 12th week, and glutathione S‐transferase placental form (GST‐P)‐positive lesions, which are known to be pre‐neoplastic lesions, occupied 1.72 ± 0.84% of the liver at the 16th week in the controls. At this time the LAL showed an increase in the number of CD5‐, CD8‐ and CD18‐positive cells and augmentation of lectin‐dependent cellular cytotoxicity (LDCC) activity. Furthermore, supplementation of BCAA increased the number of LAL, especially CD8‐positive cells and natural killer cells, and augmented LDCC activity of LAL at the 16th week. The number of LAL was positively correlated with the valine concentration in the plasma and liver, and the area of GST‐P‐positive lesions tended to be decreased in the BCAA group.
Conclusion
: These findings suggest that BCAA administration has stimulatory effects on the local immune systems of the liver, which may have a potential to inhibit hepatocarcinogenesis. Moreover, among all amino acids valine might be an important amino acid for enhancing the immune function of LAL.
Biliary excretory function is regulated by canalicular membrane fluidity associated with phospholipid fatty acyl chains in the bilayer: Implications for the pathophysiology of cholestasis
Authors: Hyogo Hideyuki , Tazuma Susumu , Kajiyama Goro 
Published: March 2003

Abstract
Background and Aims
: Bile canalicular membrane fluidity is modulated by phospholipid molecular species within membrane lipid bilayers. Thus, organellar membrane lipid composition is a determinant of canalicular function. In this study, the effect of phalloidin‐induced cholestasis on bile lipid composition and liver subcellular membrane fraction composition in rats was examined to clarify the relationship between cholestasis and hepatic lipid metabolism.
Methods and Results
: Each rat received one phalloidin dose (400 μg/kg, i.v.). After the bile was collected, liver microsomes and canalicular membranes were analysed. The bile flow rate decreased by 50% 3.5 h after phalloidin administration. Although the bile acid output remained almost the same, the phospholipid and cholesterol output were significantly decreased (by 40.3 ± 5.97% and 76.9 ± 5.56%, respectively). Thus, the cholesterol : phospholipid (C : P) ratio in bile was significantly decreased by 80.4 ± 10.1%. Phalloidin administration also increased the saturated : unsaturated fatty acid ratio (S : U) in bile for phosphatidylcholine by 25.5 ± 3.2%. In the canalicular membrane, the C : P and S : U ratios for phosphatidylcholine were increased (24.8 ± 4.2% and 34.4 ± 6.9%, respectively), while the S : U for sphingomyelin was decreased by 61.0 ± 6.2%. In microsomes, the C : P was decreased by 41.0 ± 6.0%, but the S : U for both phosphatidylcholine and sphingomyelin were unaffected. Canalicular membrane fluidity, assayed by 1,6‐diphenyl‐1,3,5‐hexatriene fluorescence depolarization, decreased significantly. Therefore, increased secretion of hydrophobic phosphatidylcholine into bile was associated with more hydrophobic canalicular membrane phosphatidylcholine, while sphingomyelin in the canalicular membrane was less hydrophobic.
Conclusions
: These results indicate that phalloidin uncouples secretion of cholesterol and phospholipids, which causes a redistribution of fatty acyl chain species among canalicular membrane phospholipids that alters membrane fluidity. These changes may be a homeostatic response mediated by the phospholipid translocator in the canalicular membrane, although direct evidence for this is unavailable.
Effect of a calcium channel blocker and antispasmodic in diarrhoea‐predominant irritable bowel syndrome
Authors: Lu Ching‐Liang , Chen Chih‐Yen , Chang Full‐Young , Chang Shen‐Shong , Kang Lih‐Jiun , Lu Rei‐Hwa , Lee Shou‐Dong 
Published: March 2003

Abstract
Background
: Irritable bowel syndrome (IBS) is a colonic function disorder. Both pinaverlum bromide (a selective calcium channel blocker) and mebeverine (an antispasmodic) are reported to be effective in the long‐term (12–16 weeks) treatment of IBS patients. Their efficacy in the short‐term treatment of IBS patients and colonic transit time is unclear. Furthermore, substance P and neuropeptide Y have either excitatory or inhibitory effects on colonic motility. Whether the efficacy of both drugs is mediated through these neuropeptides remains unknown.
Methods and Results
: A clinical trial was conducted with 91 patients with diarrhoea‐predominant IBS. After basal measurement of the total colonic transit time, IBS patients were randomized to receive either pinaverlum bromide (50 mg, t.i.d.) or mebeverine (100 mg, t.i.d.) for 2 weeks. The symptomatic scores regarding defaecation, total colonic transit time and serum levels of substance P and neuro‐peptide Y were measured before and after treatments. The daily defaecation frequency was markedly decreased after treatment (pinaverlum bromide, 2.9 ± 1.2 vs 2.0 ± 1.0, P < 0.05; mebeverine, 2.7 ± 1.1 vs 2.1 ± 1.0, P < 0.05). The stool consistency became well formed after both treatments (P < 0.05). Both drugs similarly improved the global well‐being in these IBS patients (pinaverlum bromide vs mebeverine 73.4 vs 71.8%, P > 0.05). The total colonic transit time was significantly prolonged only after pinaverlum bromide treatment (21.4 ± 15.5 vs 30.8 ± 14.8 h, P < 0.01). Neither substance P nor neuropeptide Y serum level was significantly changed after either treatments.
Conclusion
: Pinaverlum bromide and mebeverine have similar therapeutic efficacies on diarrhoeapredominant IBS patients. Prolonged colonic transit time may be one of the factors responsible for the efficacy of pinaverlum bromide on the IBS patients. Substance P and neuropeptide Y appear less important in the pathogenesis of diarrhoea‐predominant IBS.© 2000 Blackwell Science Asia Pty Ltd
Measurement of serum hyaluronic acid in patients with chronic hepatitis C and its relationship to liver histology
Authors: McHutchison John G , Blatt Larry M , De Medina Maria , Craig John R , Conrad Andrew , Schiff Eugene R , Tong Myron J , Group The Consensus Interferon Study 
Published: March 2003

Abstract
Background and Aims
: Chronic hepatitis C is a slowly progressing inflammatory disease of the liver that can lead to cirrhosis and its complications. Assessment of liver damage in hepatitis C has been primarily via histological evaluation. Liver biopsy, while useful in determining the extent of liver damage, has associated costs and places patients at a small but finite risk of bleeding. Studies in small patient populations have identified serum markers shown to correlate with liver histology, including pro‐collogen III peptide and hyaluronic acid (HA). To determine whether serum HA was a reliable predictor of cirrhosis and fibrosis, we examined serum HA concentrations from 486 chronic Hepatitis C virus (HCV) patients.
Methods and Results
: Patients were anti‐HCV and HCV RNA positive, with elevated alanine aminotransferase values and underwent a liver biopsy. Sera were obtained at the baseline for HA using radioimmunoassay methodology. Patients with cirrhosis had significantly higher serum HA concentrations compared with non‐cirrhotic patients (382 ± 31 vs 110 ± 9 μg/L respectively, P < 0.001). Patients with fibrosis had significantly higher mean serum HA concentrations (179 ± 11 μg/L) compared with patients without fibrosis (62 ± 20 μg/L; P < 0.001). The correlation between HA concentration and the components of the Knodell histological activity index score revealed no strong associations with the exception of fibrosis, which showed moderate correlation (R = 0.5421, P < 0.001). The clinical value of HA measurement appears to be its ability to exclude cirrhosis. A HA value of < 60 μg/L excluded the presence of cirrhosis or significant fibrosis with a predictive value of 99 and 93%, respectively.
Conclusions
: Serum HA measurement may be clinically useful to non‐invasively assess the degree of fibrosis and cirrhosis. Further prospective studies are warranted to determine the clinical utility of HA as a non‐invasive marker of liver fibrosis.
Use of tamoxifen in hepatocellular carcinoma: A review and paradigm shift
Authors: Tan Chee Kiat , Chow Pierce Kh , Findlay Michael , Wong Camilla , Machin David 
Published: March 2003

AbstractHepatocellular carcinoma is often diagnosed at a late, inoperable stage for which there are no uniformly efficacious treatment available presently. The oral anti‐oestrogen drug, tamoxifen, has been used in such patients, based on the belief that the growth of hepatocellular carcinoma is promoted by endogenous oestrogen via a receptor‐mediated process. In this review, we examine the trials reported in the literature using tamoxifen in hepatocellular carcinoma. Randomized controlled trials with tamoxifen have so far revealed mixed results. We propose that this may be due to the fact that the mechanism of action of tamoxifen in hepatocellular carcinoma is via an oestrogen‐receptor independent pathway that requires much higher doses of tamoxifen for activation than those used in the trials so far. Thus there must be a paradigm shift to dissociate the action of tamoxifen from oestrogen receptors in hepatocellular carcinoma. This means that future trials with tamoxifen in hepatocellular carcinoma should use higher doses of tamoxifen, at least four to eight‐fold that of the dose that is efficacious in an oestrogen‐receptor dependent mechanism.
Expression of human telomerase catalytic subunit gene in cancerous and precancerous gastric conditions
Authors: Suzuki Kaori , Kashimura Hiromasa , Ohkawa Jun , Itabashi Masayuki , Watanabe Teruo , Sawahata Tatuo , Nakahara Akira , Muto Hiroshi , Tanaka Naomi 
Published: March 2003

Abstract
Background and Aims
: Telomerase activity is thought to be necessary for cellular immortality and carcinogenesis. The mRNA that encodes the telomerase catalytic subunit (hTERT) has recently been identified, and expression of hTERT mRNA is thought to regulate activation of telomerase. To determine at what stage of carcinogenesis cells begin to express hTERT, we analysed hTERT mRNA expression in gastric carcinoma and precancerous conditions, focusing on chronic gastritis with or without intestinal metaplasia.
Methods
: Using reverse transcription‐polymerase chain reaction, hTERT gene expression was investigated in 18 gastric cancers and 60 specimens of chronic gastritis. Telomerase activity was evaluated using telomeric repeat amplification protocol.
Results
: Sixteen of 18 (89%) gastric carcinomas expressed hTERT mRNA, and this expression was unrelated to histological type or depth of invasion. Telomerase activity was found in seven of eight (88%) gastric cancer tissues, all of which expressed hTERT mRNA. Expression of hTERT mRNA was positive in 14 of 60 (23%) specimens of chronic gastritis, and was most prominent in seven of 15 (47%) specimens of gastric mucosa with intestinal metaplasia. Expression of the hTERT gene was significantly more frequent in chronic gastritis with intestinal metaplasia than in gastritis without intestinal metaplasia (P = 0.030). In addition, hTERT gene expression was not correlated with age, sex, biopsy site, histological grade of inflammatory cells, glandular atrophy and lymph follicles, or infection with Helicobacter pylori. None of eight normal gastric mucosa expressed hTERT mRNA.
Conclusions
: Our results indicate that hTERT mRNA is expressed in precancerous conditions as well as in gastric cancer, and that hTERT gene expression is induced at an early stage of gastric carcinogenesis.