bluuebunny/crossref_metadata_2025 huggingface dataset:
Subclass restriction of immunoglobulin G in liver cirrhosis
Authors: AKBAR S. M. F. , ONJI MORIKAZU , MASUMOTO TOSHIKAZU , OHTA YASUYUKI
Published: March 2008

Abstract The serum immunoglobulin G (IgG) subclasses were determined in 41 patients with liver cirrhosis (LC) and in 15 normal controls. In 19 cases of LC and in 6 normal controls, the IgG subclasses were also determined in lymphocyte culture supernatants. The determinations were performed by enzyme immunoassay. It was found that the absolute mean IgG1 and IgG3 levels were increased in all LC due to various causes. The mean IgG1 increase was most pronounced in post‐hepatitic LC, and the mean percentage of IgG1 to total IgG was also increased in this type of LC in comparison with the normal controls and the other types of LC. The IgG3 fraction was significantly increased in primary biliary cirrhosis (PBC). In alcoholic LC, all IgG subclasses were increased significantly in comparison with normal controls. In lymphocyte culture supernatants from PBC patients, the mean IgG1 and IgG3 levels were increased in supernatants from unstimulated cultures, and the mean IgG1, IgG3, and IgG4 were increased after pokeweed mitogen (PWM) stimulation. In post‐hepatitic LC, the mean IgG4 level was increased in both unstimulated culture supernatants and after PWM stimulation. In alcoholic LC, the mean IgG4 level was increased in unstimulated culture supernatants, whereas the mean IgG1 level was increased after PWM stimulation. These findings showed that LC of differing aetiologies exhibited different profiles of IgG subclasses. This may be related to the different aetiological agents and the pathogenesis of the different types of LC.
Defects in the precore region of hepatitis B virus DNA in a plasma pool from carriers seropositive for antibody against e antigen and with infectivity in chimpanzees
Authors: OMI SHIGERU , OKAMOTO HIROAKI , TSUDA FUMIO , MAYUMI MAKOTO
Published: March 2008

Abstract A plasma pool from 12 asymptomatic carriers seropositive for antibody against hepatitis B e antigen (anti‐HBe) contained hepatitis B virus (HBV) with chimpanzee infectious doses of 1–100/mL, and another pool from 12 carriers positive for hepatitis B e antigen (HBeAg) contained 108/mL doses or more. The HBeAg‐positive pool contained 106‐fold more HBV DNA than the anti‐HBe‐positive pool, reflecting the difference in infectivity in chimpanzees. The precore region sequences of HBV DNA in the two plasma pools were amplified by polymerase chain reaction, and separate HBV DNA clones were propagated for determining the nucleotide sequence. Of 114 clones from the anti‐HBe‐positive pool, 113 displayed a point mutation from guanine to adenine at nucleotide 83 in the precore region, which converted codon 28 for tryptophan (TGG) to a stop codon (TAA), and the remaining clone had a point mutation from adenine to cytosine at the first letter of codon 1 (CTG) to inhibit the translation initiation of the precore region. Precore region defects, in contrast, were observed in only 10 (8%) of 119 clones from the HBeAg‐positive pool. These results indicate the infectious capacity of HBV mutants, defective in the precore region and incapable of directing the synthesis and secretion of HBeAg, which prevail in the circulation of hosts after they seroconvert from HBeAg to anti‐HBe.
Achalasia of the oesophagus: Treatment with pneumatic dilatation
Authors: PREWETT EMILY J. , DESMOND PAUL V. , BREEN KERRY J.
Published: March 2008

Abstract A series of 51 patients with achalasia of the oesophagus treated by pneumatic dilatation between 1980 and 1988 is reported. Treatment was assessed as effective (no or minimal dysphagia) in 78% of patients, followed for a mean of 30 months. Thirty‐four patients required only one dilatation and only two patients had more than 3 dilatations. There were no deaths, but perforation occurred in seven patients, four of whom required early surgical repair. A further five patients were referred for elective surgery. Factors possibly contributing to oesophageal perforation are discussed.
Enzymes degrading bacterial chemotactic F‐met peptides in human ileal and colonic mucosa
Authors: CHADWICK V. S. , SCHLUP M. M. T. , COOPER B. T. , BROOM M. F.
Published: March 2008

Bacterial chemotactic F‐met peptides have been identified in culture supernatants of intestinal bacteria and in human faecal dialysates. These potent inflammatory agents could play a role in intestinal inflammatory disorders should they cross the epithelial barrier of the gut. We have identified mucosal peptidases which degrade F‐met‐leu‐phe (FMLP) in ileal and colonic mucosal biopsies obtained at colonoscopy. A carboxypeptidase, inhibited by D‐L‐benzyl succinate (BzS), accounted for more than 60% of total FMLP‐ase activity, other uncharacterized peptidases contributing the rest of the activity against the intact peptide. An F‐met deformylase, inactive against di‐ and tri‐peptides, cleaves released F‐met completing the degradation. Total FMLP‐ase, carboxypeptidase and F‐met deformylase activities were measured in serial mucosal biopsies from 15 control patients undergoing colonoscopy for occult bleeding with negative findings and from 15 patients with ulcerative colitis (UC) and 10 with Crohn's disease (CD). Highest activities were found in terminal ileum and lowest in the rectum. Total FMLP‐ase and carboxypeptidase activities were similar in controls and UC patients but were substantially reduced in CD, especially in the terminal ileum (controls 493 ± 146 and 116 ± 73 nmol/100 μg protein per h, respectively and CD 231 ± 96 and 41 ± 36 nmol/100μg protein per h, respectively (P= 0.0018 and 0.015). F‐met deformylase activities were similar in all groups. There was no correlation between enzyme activity and severity of inflammation. FMLP degrading peptidases probably contribute to the mucosal barrier of the gut in regions of high bacterial colonization, limiting intestinal absorption and inflammatory responses to these potent bacterial products in the intestinal lumen.
Liver copper concentration in Wilson‘s disease: Effect of treatment with ‘anti‐copper’ agents
Authors: GIBBS K. , WALSHE J. M.
Published: March 2008

Serial copper determinations have been made on the livers of 10 patients with Wilson's disease. Two were studied before and eight after the start of treatment in order to assess the effect, if any, on the concentration of the metal. In two patients who were receiving no therapy and in one in whom it had been discontinued, the level of copper rose. In the latter patient, resumption of treatment then resulted in a fall in the level of copper in the liver. A similar fall was seen in seven patients on continuous therapy. In one patient, a very poor complier, there was a tendency for the liver copper concentration to rise over a 5‐year period.

All three therapies investigated—penicillamine, trientine and tetrathiomolybdate—when taken regularly, appear to be effective in reducing liver copper levels.

Sixty‐nine single determinations of liver copper have been plotted against time on treatment. This shows that the copper concentration falls rapidly in the first year. Thereafter, there is no linear relationship between the duration of treatment and liver copper. Poor compliers have a higher liver copper concentration than do good compilers.

Determinations made from different portions of the liver showed that in only one of 19 examples was there an overlap between the near normal and the abnormal range.

The principal mechanism of action of ‘anti‐copper’ agents in Wilson's disease appears to be the mobilization of copper from the tissues, but a secondary detoxifying action may come into play later.
Primary biliary cirrhosis in Taiwan
Authors: CHAN CHO‐YU , LEE SHOU‐DONG , HUANG YI‐SHIN , WU JAW‐CHING , TSAI YANG‐TE , TSAY SHYH‐HAW , LO KWANG‐JUEI
Published: March 2008

Among 30 consecutive patients diagnosed with primary biliary cirrhosis (PBC) in Taiwan, 27 were females and the median age of symptom onset was 54.5 years. Most had similar clinical manifestations to those reported in the Western countries, but ascites and oesophageal varices as commonly found at the late stages of cirrhosis of liver were noted in nine patients (30%) and 13 patients (43%) respectively. Only one patient was asymptomatic. Hyperbilirubinaemia was noted in 21 patients (70%) and hypoalbuminaemia in 8 patients (27%). All patients had elevated serum alkaline phosphatase and alanine aminotransferase and 28 (93%) had antimitochondrial antibodies. Ten out of 21 patients (48%) were positive in antinuclear antibodies, of which most were of speckled type. Sixteen out of 18 patients (89%) had elevated serum IgM levels. Interestingly, only one of 26 patients (3.8%) was positive for hepatitis B surface antigen, in contrast to its high prevalence (15%) in the Taiwan population. Special associated diseases, including systemic lupus erythematosus, scleroderma, malignant lymphoma and hepatocellular carcinoma, were each noted in one patient respectively. Eight patients had a history of gallstones before the diagnosis of PBC. The mean follow‐up period was 23.6±19.8 months, and nine patients died during that period. In conclusion, the clinical manifestations of PBC in Taiwan are similar to those in Western countries, but most of our cases were at later stages.
Pre‐operative nutritional support in children with end‐stage liver disease accepted for liver transplantation: An approach to management
Authors: CHIN S. E. , SHEPHERD R. W. , CLEGHORN G. J. , PATRICK M. , ONG T. H. , WILCOX J. , LYNCH S. , STRONG R.
Published: March 2008

Pre‐operative nutritional support was studied in 28 children with end‐stage liver disease awaiting orthotopic liver transplantation. Nasogastric supplemental administration of a standard semi‐elemental enteral nutritional formula was compared with a similar formula enriched with branched chain amino acids, and with a group receiving oral nutrition only. The duration of treatment in all groups was similar (mean 90 days). Energy intakes in the supplemented groups were 120–150% of recommended daily intakes (RDI), whereas ad libitum intakes in the oral group ranged 58–100% RDI. A significant improvement in mean Z‐score for body weight (denoting catch‐up) was noted only in those children who received nasogastric supplements enriched with branched‐chain amino acids. The standard enterally‐fed group maintained their body weight and Z‐scores did not change significantly. In contrast, body weight Z‐scores in those fed orally declined significantly. Nutritional supportive therapy of malnourished children with end‐stage liver disease can minimize or improve nutritional status in children awaiting liver transplantation. The use of nutritional formulae rich in branched‐chain amino acids may have nutritional advantages in children with chronic liver disease which require further study and evaluation.
Polymerized albumin binding to serum in various liver diseases: Its significance and relation to hepatitis B virus infection
Authors: DASH SRIKANTA , PANDA SUBRAT K. , NAYAK NABEEN C.
Published: March 2008

Sensitive and specific enzyme‐linked immunosorbent assays (ELISA) were developed to detect separately the binding of polymerized human serum albumin (PHSA) to its antibody (A‐PHSA) and to the hepatitis B surface antigen (HBsAg). A‐PHSA was not detected in normal serum, whereas more than one‐third to about half of sera from patients with acute liver cell injury showed this antibody. Frequency of A‐PHSA positivity was low in chronic liver diseases, being relatively higher in those with continuing liver injury. A‐PHSA detection was not related to seropositivity for HBsAg.

PHSA binding of HBsAg positive sera showed a higher frequency of positivity in chronic carriers than acute hepatitis B. Of 172 asymptomatic HBsAg carriers, PHSA binding was demonstrated in 25 (15%), the frequency being significantly high if HBeAg was also present (84%). Binding was infrequent in sera having anti‐HBe (2.9%) and in those negative for both HBeAg and anti‐HBe (2.7%). Binding of HBsAg to PHSA was significantly higher than to human serum albumin (HSA). Immunoblotting of separated HBsAg components showed PHSA binding specifically to the high molecular weight peptide. PHSA binding in HBsAg positive serum may indicate the latter's infectivity as detected in a study of maternal‐fetal transmission, where it demonstrates 100% infectivity in HBsAg and HBeAg positive mothers.

PHSA possibly mediates the attachment of the HBV to the hepatocyte and a competitive binding between A‐PHSA with HBsAg for PHSA may modulate the course of HBV infection.
Immunohistochemical studies on the localization of cancer associated antigens DU‐PAN‐2 and CA19‐9 in carcinomas of the digestive tract
Authors: OHSHIO G. , OGAWA K. , KUDO H. , YAMABE H. , NAKASHIMA Y. , KIM Y. C. , ENDO K. , WATANABE Y. , MANABE T. , TOBE T.
Published: March 2008

The immunohistochemical localization of DU‐PAN‐2 antigen and CA19‐9 antigen in carcinomas of the digestive tract was studied using an immunoperoxidase technique. Staining for DU‐PAN‐2 antigen and CA19‐9 antigen was observed in 104 (79%) and 96 (73%) of 131 carcinomas of the digestive tract, respectively. Diffuse staining (more than 20% of carcinoma cell stained) for DU‐PAN‐2 was detected in 14 of 21 (67%) pancreatic carcinomas and 11 of 19 (58%) carcinomas of the biliary tract (including cholangiocarcinoma). Diffuse staining for CA19‐9 was detected in 15 (71%) of pancreatic carcinomas and nine (47%) of the carcinomas of the biliary tract. In colon carcinomas, no diffuse staining for DU‐PAN‐2 was observed, whereas diffuse staining for CA19‐9 was found in 41%. There was a positive correlation between the differentiation degree (or grade) of the adenocarcinomas of the colon and the expression of CA19‐9, but not that of DU‐PAN‐2.

These immunohistochemical studies showed that DU‐PAN‐2 antigen is expressed diffusely in most cases of adenocarcinoma of the pancreas and biliary tract and is more specific for adenocarcinomas of the pancreas and biliary tract than CA19‐9.
Persistence of anti‐HBs and protective efficacy after administration of hepatitis B vaccine
Authors: YOSHIDA KEN , FUJIYAMA SHIGETOSHI , SATO TATSUO
Published: March 2008

AbstractTo evaluate the effect of hepatitis B vaccine on the persistence of anti‐HBs and its efficacy in preventing hepatitis type B, anti‐HBs and anti‐HBc levels were studied over a period of 5.5 years.

Plasma‐derived hepatitis B vaccine, containing 20 μg of HBsAg protein, was injected subcutaneously in 122 healthy medical staff members, followed by two identical injections 1 and 6 months later. Anti‐HBs and anti‐HBc levels were then measured by radio‐immunoassay. The anti‐HBs titres were expressed as the sample/negative (S/N) ratios, and an S/N ratio of more than 2.1 was considered positive.

The mean (and s.d.) anti‐HBs titre peaked 7 months after the first vaccination with an S/N ratio of 153.6 ±149.8, after which it decreased with time. The mean anti‐HBs titre dropped to an S/N ratio of 8.0 ±5.1 5.5 years after the first vaccination. The percentage of vaccinees who were anti‐HBs positive also gradually decreased with time after a peak of 84.2% at 7 months following the first vaccination. The percentage of vaccinees who were anti‐HBs positive was 38.9% 5.5 years after the first vaccination. The anti‐HBc level was not positive in all subjects during the observation period.

Five vaccinated volunteers who had developed anti‐HBs after the basic vaccination, but whose acquired antibody level became negative within 4.5 years following the first vaccination, were administered a booster dose of 20 μg of HBsAg 4.5 years after the first vaccination. Only one of these subjects did not respond to the booster vaccination. The peak anti‐HBs titre of this subject was very low following the initial vaccination.

From these observations, it was concluded that, although the acquired antibody titres and percentage of vaccinees who were anti‐HBs positive decreased with time, the incidence of hepatitis B infection would be lower in vaccinees than that in other non‐vaccinated general medical staff members in Japan. This was probably due to the persistence of immunological memory in vaccinees who had responded well after basic vaccination.
Effect of verapamil on splanchnic haemodynamics in a portal hypertensive rat model
Authors: LAY CHII‐SHYAN , TSAI YANG‐TE , YANG CHUEN‐MAY , CHEN HSING‐I. , SIMCHON SHLOMOH , CHIEN SHU , LO KWANG‐JUEI
Published: March 2008

Abstract To elucidate the effects of verapamil on splanchnic haemodynamics in rats with portal hypertension, verapamil was given at a low dose (0.2 mg/kg) and a high dose (2 mg/kg) to the rat model after portal vein ligation. Approximately 10% decrease in arterial pressure was caused by the low dose of verapamil, with significant decreases in cardiac output and portal venous inflow as well as reduced portal pressure; these were all indicative of a rise in portal vascular resistance. In contrast, the marked fall in both arterial pressure and cardiac output in the high dose, accompanied by a significant decrease in the portal pressure and the unchanged portal venous inflow, suggested a reduction in portal vascular resistance. This study shows that the acute effects of verapamil on portal hypertension may vary with the dosage used. These results also demonstrate that, since the therapeutic efficacy and safety of verapamil is only in a very limited range of dose, caution should be taken in its clinical use in the treatment of cirrhosis with portal hypertension.
Clinicopathological staging for colorectal cancer: An International Documentation System (IDS) and an International Comprehensive Anatomical Terminology (ICAT)
Authors: FIELDING L. P. , ARSENAULT P. A. , CHAPUIS P. H. , DENT O. , GATHRIGHT B. , HARDCASTLE J. D. , HERMANEK P. , JASS J. R. , NEWLAND R. C.
Published: March 2008

The purpose of tumour staging for colorectal cancer (CRC) is to help define clinical management, facilitate communication between physicians, provide a basis for stratification and analysis of treatment results in prospective studies, and provide some prognostic information for patients and their families. The World Congresses of Gastroenterology, Digestive Endoscopy, and Coloproctology, Working Party on staging for CRC studied six commonly used systems to review their strengths and weaknesses. Although it was concluded that defining a new staging system was unnecessary, it was recognized that there is a need to define a terminology to describe the full anatomic extent of spread of CRC. Furthermore, we note that there are several additional features, derived from both clinical and pathology information, which have had prognostic significance shown by appropriately constructed multivariate analyses and which can be used to formulate a more accurate prognostic index than that provided by a description of anatomical tumour spread.

Thus the Working Party came to two principal conclusions. First, a standard format should be adopted for the collection of the essential data required for prospective studies, and we recommend the ‘International Documentation System (IDS) for CRC’ for this purpose. Second, a nomenclature which describes the full anatomical extent of tumour spread and residual tumour status in CRC has been defined and should be adopted, from which all currently used staging systems can be derived. We have called this nomenclature the ‘International Comprehensive Anatomical Terminology (ICAT) for CRC'.

In the event that these recommendations are adopted, we envision that there will be improved clarity in the documentation of treatment outcome for patients with CRC and improved communication of results derived from prospective studies. Furthermore, an acceptance of IDS and ICAT would set the scene to develop a prognostic index for individual patients with CRC by the expansion of anatomical clinicopathology staging information to include additional factors which have independent prognostic significance.
Diagnostic utility of ultrasonography in hepatic venous outflow tract obstruction in a tropical country
Authors: ARORA A. , SHARMA M. P. , ACHARYA S. K. , PANDA S. K. , BERRY M.
Published: March 2008

The present study was undertaken to define the role of ultrasonography (US) in screening and diagnosis of hepatic venous outflow tract obstruction. Forty‐five consecutive patients clinically suspected to have hepatic venous outflow tract obstruction were included in the study for screening by US and for assessment of patency or block in the hepatic vein (HV) and/or inferior vena cava (IVC). Four patients were excluded from the study. Eleven patients had a diagnosis other than hepatic venous outflow tract obstruction and all these patients were found to have patent HV and IVC. Thirty patients were finally diagnosed to have hepatic venous outflow tract obstruction. Using US, as a screening test 27 (90%) out of 30 such cases were correctly identified as cases of hepatic venous outflow tract obstruction and in these cases the site of block in hepatic venous outflow tract (major HV and/or IVC) was correctly diagnosed in 90% of the cases.

Our results indicate that US is a sensitive and accurate test and should be the initial investigation for screening and identifying the site of obstruction in patients with hepatic venous outflow tract obstruction.
Non‐steroidal anti‐inflammatory drug associated ulcer: Epidemiology, causation and treatment
Authors: LANGMAN M. J. S. , BROOKS P. , HAWKEY C. J. , SILVERSTEIN F. , YEOMANS N.
Published: March 2008

Epidemiological evidence consistently indicates that aspirin or non‐aspirin non‐steroidal anti‐inflammatory drug use is associated with the occurrence of gastric ulceration, gastric and duodenal ulcer bleeding, and ulcer death. Evidence on duodenal ulcer occurrence conflicts, possibly because of differences in study populations.

A wide range of mechanisms could explain the occurrence of non steroidal‐induced damage. These include inhibition of bicarbonate secretion, effects on mucus formation, and vascular actions. Not all effects are dependent on cyclo‐oxygenase inhibition.

Short‐term studies in humans provide indications of likely therapeutic effects, but cannot demonstrate clinical efficiency.

Although anti‐secretory drugs and prostaglandins can protect patients against the development of duodenal or gastric ulcers, but not both, there is no clinical evidence which bears upon the critical issue of protection against complications.
Time as a factor in the expression of ethanol injury to the gastric mucosa
Authors: FRYDMAN GARY M. , PENNEY ANGELA G. , MALCONTENTI CATHY , O'BRIEN PAUL E.
Published: March 2008

A technique of quantitative histology was used to assess the influence of time after injury on the histological expression of gastric mucosal damage. Rats, pretreated with either natural prostaglandin E2 or saline, were subjected to intragastric administration of either 50% or 100% ethanol. Fifteen minutes later the ethanol was removed from the stomach. Rats were sacrificed at either 30 min or 24 h after ethanol instillation. In rats pretreated with saline and subjected to 100% ethanol with or without prostaglandin pretreatment, the extent of deep mucosal damage was markedly underestimated by early evaluation. Only 5.4% of the volume of the gastric mucosa showed evidence of damage at 30 min after ethanol, compared with 57.3% of the volume of the mucosa, at 24 h after 100% ethanol exposure.

Assessment of gastric mucosa 24 h after ethanol injury showed that PGE2 reduces the extent of surface area damaged and the volume of the mucosal damage. When 50% ethanol was used as the injurious agent, no difference was noted in the volume of the mucosa damaged when the stomach was assessed at either 30 min or 24 h after injury.

These results indicate that full histological expression of injury is not present 30 min after 100% ethanol instillation, at least in part because of fixation of the gastric mucosa by 100% ethanol. Fifty per cent ethanol, which does not cause mucosal fixation, may be better as a test agent.
Clinicopathological study of liver involvement in cytomegalovirus infection in infant autopsy cases
Authors: KOSAI KEN‐ICHIRO , KAGE MASAYOSHI , KOJIRO MASAMICHI
Published: March 2008

To clarify the pathogenesis of hepatic cytomegalovirus (CMV) infection, we clinicopathologically investigated 18 infants and 10 adults with cytomegalic inclusion bodies (CIB) in the liver among a total of 75 autopsy cases with CIB in any organ of the body. CMV infection was confirmed by immunohistochemistry and in situ hybridization. When CIB were present in the liver, CMV infection also tended to be systemic. All the adults were immunocompromised patients, but diseases inducing immunodeficiency were present in only two of the infants. The severe and systemic CMV infections we found in infants might have been associated with congenital CMV infection. Histotogically, hepatocyte necrosis, cholestasis, extramedullary hematopoiesis and fatty degeneration were more frequent and prominent in infants than in adults. However, inflammatory cell infiltration was only slight. In addition, the frequent association with premature birth and hypoplasia of the thymus suggested that insufficient development of immunity may result in hepatic CMV involvement in infants. CIB were most frequently observed in hepatocytes in both infants and adults, but in infants they were also frequently seen in the bile duct epithelium. These histopathological findings and the high incidence of jaundice in infant patients suggest that the bile duct is also an important site of CMV proliferation in infants, and that CMV infection may be one cause of infantile jaundice.
Immunoglobulin G subclasses of antibodies to hepatitis B core antigen in HBs antigen positive liver diseases
Authors: AKBAR S. M. F. , HORIIKE NORIO , ONJI MORIKAZU , OHTA YASUYUKI
Published: March 2008

Abstract Serum immunoglobulin G (IgG) subclasses of hepatitis B core antibody (anti‐HBc) in 54 patients with different types of hepatitis B surface antigen positive (HBsAg+) liver diseases (asymptomatic carrier (ASC), acute hepatitis (AH), chronic hepatitis (CH) and liver cirrhosis (LC)) and 18 normal controls were estimated by enzyme‐linked immunosorbent assay (ELISA) using subclass specific anti‐human mouse monoclonal antibodies. In 11 cases, the estimations were carried out at both exacerbation and remission stages of chronic active hepatitis (CAH). In 4 cases of CAH, serial observations of anti‐HBc IgG subclasses were made according to the clinical course. In 5 cases of CAH, the estimations were carried out at the HBe antigen positive (HBeAg+) stage and after sero‐conversion to anti‐HBe positive (anti‐HBe+) stage. In ASC the main anti‐HBc IgG subclasses were restricted to one subclass—anti‐HBc IgGI. In AH on the other hand, all the subclasses were represented. In CH all the subclasses were detected under different diagnostic conditions but anti‐HBc IgG1 was the main subclass. In LC the mean concentration of anti‐HBc IgG3 was higher than the concentration of anti‐HBc IgG1. In exacerbation stages of CAH, the different anti‐HBc IgG subclasses had higher concentrations than in remission stages. The concentrations of different anti‐HBc IgG subclasses fell just after seroconversion from HBeAg+ stage to anti‐HBc+ stage. These data suggest that the estimation of anti‐HBc IgG subclasses may be helpful in establishing the diagnosis of different types and stages of HBsAg+ liver diseases.
Changes in serum and hepatic levels of immunoreactive prolyl hydroxylase in two models of hepatic fibrosis in rats
Authors: OKUNO MASATAKA , MUTO YASUTOSHI , KATO MICHIMASA , MORIWAKI HISATAKA , NOMA AKIO , TAGAYA OSAMU , TANABE YOSHIO
Published: March 2008

Changes in serum and hepatic levels of immunoreactive prolyl hydroxylase (IRPH) as well as cellular localization of the enzyme were studied in 2 models of hepatic fibrosis, which was induced in male rats either by subcutaneous administration of CCl4 (Group A) or by intraperitoneal injection of porcine serum (Group B). Hepatic fibrosis appeared at the 8th week in Group A and at the 12th week in Group B, and liver cirrhosis developed at the 16th week in both models. Although tissue contents of hydroxyproline (HP) and IRPH increased in both models, only HP levels correlated with the degree of fibrosis. Serum IRPH levels and serum asparate aminotransferase (AST) activities increased, showing a significant positive correlation, in group A, whereas both remained in a control range in Group B. Moreover, in another model which received a single intraperitoneal injection of CCl4, serum IRPH showed a marked increase and then a rapid decrease in parallel with the change in serum AST. Immunohistochemical analysis also showed a difference between the two fibrosis models: in group A, IRPH was positive mainly in parenchymal cells in the peripheral zone of the pseudolobulus, while in group B the staining was diffuse. These results indicate that the elevation of serum IRPH is, at least in part, due to the parenchymal cell damage, and that IRPH levels should be carefully evaluated when being used as a parameter to estimate the activity of fibrogenesis in the liver.
Significance of plasma glutathione determination in patients with alcoholic and non‐alcoholic liver disease
Authors: SHIGESAWA TATSUO , SATO CHIFUMI , MARUMO FUMIAKI
Published: March 2008

Plasma glutathione levels were determined in 79 patients with various types of liver disease and 18 healthy controls in order to study their significance in the course of liver disease. Plasma was taken at the time of needle liver biopsy. A positive linear correlation was found between plasma and hepatic glutathione concentrations, as has been suggested in experimental animals. In patients with acute viral hepatitis, chronic hepatitis, non‐alcoholic liver cirrhosis and alcoholic liver disease, plasma glutathione levels were significantly decreased compared with those in controls. Of importance is the fact that the plasma levels increased after recovery in patients with acute viral hepatitis and after abstinence from alcohol intake in patients with alcoholic liver disease. Determination of plasma glutathione may be valuable in the evaluation of liver disease, particularly in acute viral hepatitis and alcoholic liver disease in which the hepatic content of glutathione is suggested to be decreased. Such patients may be susceptible to oxidative stress and radical‐related hepatic injury.
Effects of vaso‐active agents on hepatic function and blood gases in patients with cirrhosis: A study of vasopressin and nitroglycerin
Authors: IWAO TADASHI , TOYONAGA ATSUSHI , SUMINO MICHIHIRO , TAKAGI KOHSUKE , OHO KAZUHIKO , OHKUBO KAZUNORI , INOUE RINTAROH , TANIKAWA KYUICHI
Published: March 2008

The effects of vaso‐active agents on hepatic function and splanchnic oxygenation were studied in 17 patients with cirrhosis and portal hypertension. Eight patients received vasopressin (0.3 iu/min) and nine patients received nitroglycerin (50 μg/min). Both drugs caused a significant reduction in the portal venous pressure gradient. Vasopressin infusion significantly decreased intrinsic clearance of indocyanine green (‐23%, P<0.01). This may be due to a decreased hepatic perfusion (‐28%, P<0.01) and portal venous oxygenation (‐15% in portal venous oxygen tension, P<0.05). In contrast, no changes in hepatic perfusion and portal venous oxygenation were observed after nitroglycerin infusion. Nitroglycerin did not decrease intrinsic clearance of indocyanine green. These results suggest that vasodilators, rather than vasoconstrictors, might be welcome in the treatment of patients with cirrhosis and portal hypertension.
Contrasting effects of butyrate on the expression of phenotypic markers of differentiation in neoplastic and non‐neoplastic colonic epithelial cells in vitro
Authors: GIBSON PETER R. , MOELLER INGRID , KAGELARI OURANIA , FOLINO MARISA , YOUNG GRAEME P.
Published: March 2008

The in vitro effect of butyrate on expression of differentiation markers in colonic epithelial cells was assessed in the colon cancer cell line, LIM1215 and in epithelial cells isolated from a surgically resected histologically normal colon. Markers used to assess cell differentiation were: net glycoprotein synthesis ([3H]‐glucosamine uptake) expressed relative to net protein synthesis ([14C]‐leucine uptake), and the expression of the brush border glycoproteins (alkaline phosphatase and carcino‐embryonic antigen) in cell homogenates calculated relative to cellular protein content. In response to 24 h exposure to 1 mmol/L butyrate, all markers significantly increased in LIM1215 cells whereas they all significantly decreased in isolated colonic epithelial cells under identical culture conditions. Similar effects were seen at butyrate concentrations of up to 4 mmol/L. Butyrate suppressed proliferation of LIM1215 cells but had no consistent effect on [3H]‐thymidine uptake by, or DNA content of, normal epithelial cells. Additional experiments found no evidence of a toxic effect of butyrate at those concentrations nor of an alteration of cell responsiveness to butyrate due to the isolation process itself. In contrast to its differentiative effect on neoplastic cells, butyrate reduces the expression of phenotypic markers of differentiation in vitro in colonic epithelial cells from non‐neoplastic mucosa.
The effect of chilli ingestion on gastrointestinal mucosal proliferation and azoxymethane‐induced cancer in the rat
Authors: KANG J. Y. , ALEXANDER B. , BARKER F. , MAN W. K. , WILLIAMSON R. C. N.
Published: March 2008

Of the three main races of Singapore, Malays and Indians are less susceptible to gastric and colorectal carcinoma and peptic ulcer when compared with Chinese. Racial differences in dietary habits include a smaller amount of chilli consumed by the Chinese when compared with the other two races. Chilli may be expected to accelerate gastrointestinal transit and hence to inhibit colonic carcinogenesis, while its active ingredient capsaicin protects against experimental gastric mucosal injury. The effect of chilli consumption was studied in relation to: (i) gastrointestinal crypt cell production rate and nucleic acid content as indices of mucosal proliferation, which is related to the risk of development of gastrointestinal cancer and peptic ulcer; and (ii) azoxymethane‐induced intestinal cancer. Sprague‐Dawley rats (n= 102) received either standard powdered chow or chow supplemented with 100 or 200 mg of chilli powder daily for 1, 18 or 24 weeks. Gastric, small‐bowel and colonic crypt cell production rates were studied at all three time periods, while mucosal DNA, RNA and protein contents were measured at 1 and 24 weeks. While crypt cell production rates were unaffected by chilli ingestion, mucosal contents of nucleic acid and protein were mostly increased in chilli‐fed animals compared to controls, especially in the colon at 24 weeks. A further 99 rats received subcutaneous injections of either azoxymethane 15 mg/kg/week x 6 or sterile water and were randomized to the same three dietary groups for 26 weeks. The number, size and location of benign and malignant duodenal and colonic tumours were unaffected by chilli intake. Chilli therefore had no effect on mucosal proliferation, although a moderate effect on mucosal mass was seen. It did not alter intestinal carcinogenesis.
Hepatitis C virus infection in chronic liver disease and hepatocellular carcinoma in Saudi Arabia
Authors: KARAWI MOHAMED ALI AL , SHARIQ SOHAIL , MOHAMED ABDEL RAHMAN EL SHIEKH , SAEED AWAD A. , AHMED ABDUL MUTAAL MOHAMED
Published: March 2008

The prevalence of antibody to hepatitis C virus (HCV) was determined in 139 patients with chronic liver disease (CLD) and 42 patients with hepatocellular carcinoma (HCC) during one year at the Riyadh Military Hospital, Saudi Arabia. The anti‐HCV was detected in 36 of 96 (37.5%) HBsAg‐negative patients with chronic liver disease and six of 43 (13.9%) HBsAg‐positive patients with chronic liver disease. In addition, 11 (42.3%) HBsAg‐negative hepatocellular carcinoma patients and two of 16 (12.5%) HBsAg‐positive hepatocellular patients had antibody to HCV. The anti‐HCV prevalence was 1.5% in 4818 healthy blood donors and 1% in 385 antenatal patients. The overall HCV seropositivity of 30.4% in 181 liver disease patients (CLD and HCC) in Saudi Arabia is lower than that reported from European countries.
Loss of heterozygosity on chromosome 16 in hepatocellular carcinoma
Authors: SAKAI KAGARI , NAGAHARA HIKARU , ABE KOHJI , OBATA HIROSHI
Published: March 2008

In order to understand the molecular genetics of human hepatocellular carcinoma (HCC) a common chromosomal abnormality in HCC was examined using restriction fragment length polymorphism (RFLP) analysis. Sixty‐eight HCC specimens were examined for loss of heterozygosity at 11 different chromosomal arms including 1p, 5p, 11p, 11q, 13q, 14q, 15q, 16p, 16q, 18q, and 19q. Losses were not detected on chromosome 1, 5, 14, 15 or 19, and the frequencies of losses were low (11–19%) for chromosomes 11, 13 and 18. In contrast, loss of heterozygosity was frequently observed for three different loci on chromosome 16, the HBA locus at 16p 13.3 (22%), the MT2 locus at 16q21–22.1 (15%) and the HP locus at 16q22.1–22.2 (39%). There was no remarkable difference in the frequencies of loss of heterozygosity at these loci among HBV related HCC, HCV related HCC and neither virus (NBNC) related HCC.

Thus, the results indicate that at least three different genetic abnormalities in chromosome 16 are commonly observed in various HCC, and that this chromosome may have some important role(s) in recessive genetic changes which generate this tumour.
Complications of hepatolithiasis
Authors: FAN S. T. , WONG J.
Published: March 2008

Hepatolithiasis or intrahepatic stone is associated with a variety of complications of which biliary sepsis is one. Left untreated, infection results in formation of micro‐abscesses, portal thrombophlebitis and fistulation into adjacent structures. With repeated infection, biliary strictures and severe destruction of liver parenchyma occur. Biliary cirrhosis, portal hypertension and bleeding varices are the terminal manifestations. Early recognition and proper treatment are essential for the prevention of severe complications and functional deterioration.
Brush border hydrolases in normal and neoplastic colonic epithelium
Authors: YOUNG G. P. , MACRAE F. A. , GIBSON P. R. , ALEXEYEFF M. , WHITEHEAD R. H.
Published: March 2008

Previous studies have suggested that abnormal expression of enzymes characteristic of the intestinal brush border might accompany colonic neoplasia and possibly facilitate identification of epithelium at risk of malignancy. To test this possibility, the distribution of the brush border enzymes sucrase‐isomaltase (SIM), maltase‐glucoamylase (MGA), aminopeptidase‐N (APN) and diaminopeptidylpeptidase‐IV (DPPIV) were studied by the immunoperoxidase method in biopsies from the rectum and caecum of normal subjects, and neoplastic and non‐neoplastic tissues from patients with adenoma or cancer. Brush border enzymes were detected by immunohistochemistry more frequently in the caecum than the rectum (P < 0.05) of normal subjects. Diaminopeptidylpeptidase‐IV and APN were present in highest concentration at the brush border of the most mature colonocytes on the luminal surface with less staining in the crypt, whereas SIM and MGA staining of the brush border was as prominent on crypt cells as surface cells. While all cancers expressed at least one enzyme, there was heterogeneity of staining within tumours and a tendency to lose polarity of enzyme expression in cells, sometimes with dense staining of the cytoplasm. Distally situated adenomas uncommonly expressed a brush border enzyme (25%) and the only enzyme expressed in them was SIM. These findings indicate that these brush border enzymes are not exclusively expressed in the small intestine; DPPIV and APN are markers of the normal mature colonocyte and should prove useful as markers of differentiation. However, the changes associated with neoplasia would not appear to be of clinically predictive value. The low expression in adenomas suggests a block in the differentiation process early in tumourigenesis, whereas the patchy re‐expression, accompanied by a loss of cellular polarity in cancers, suggests derepression of gene expression for these enzymes.
C‐reactive protein and lactate dehydrogenase isoenzymes in the assessment of the prognosis of acute pancreatitis
Authors: CHEN C‐C. , WANG S‐S. , CHAO Y. , LU C‐W. , LEE S‐D. , TSAI Y‐T. , LO K‐J.
Published: March 2008

The value of serum C‐reactive protein, lactate dehydrogenase isoenzymes and erythrocyte sedimentation rate in predicting the outcome of acute pancreatitis was evaluated for 57 episodes in 54 patients. Serum C‐reactive protein levels on day 2, 4 and 7 after admission were significantly higher in 19 episodes of severe attacks than in 38 episodes of mild attacks (13.71±9.68, 9.00±7.54, 6.02±3.83 vs 4.78±3.91, 3.30±3.61, 1.43±2.08 mg/dL; P < 0.0001, P < 0.005, P < 0.0001, respectively). The sensitivity, specificity and accuracy of predicting a severe attack were 94, 76 and 82% using C‐reactive protein ≥ 8 mg/dL on day 2; 67, 92 and 84% using C‐reactive protein ≥ 5 mg/dL on day 7; and 59, 76 and 70% using Ranson's criteria ≥ 3. Increases in LDH‐4 and LDH‐5 isoenzymes were found in both groups, with LDH‐4 being slightly higher in severe attacks than in mild attacks. There was no significant difference of erythrocyte sedimentation rate between both groups. When compared with Ranson's criteria, lactate dehydrogenase isoenzymes and erythrocyte sedimentation rate, C‐reactive protein is more valuable in the early assessment of the severity of acute pancreatitis.
A review of postgastrectomy bone disease
Authors: TOVEY F. I. , HALL M. L. , ELL P. J. , HOBSLEY M.
Published: March 2008

Postgastrectomy bone disease was a term devised to describe the metabolic disorders of bone which may follow a gastrectomy operation. Although the use of this operation has declined drastically in recent years, this metabolic bone disorder is still with us and may escape and confuse the unwary. These disorders may take the form of osteomalacia, osteoporosis in excess of normal ageing, or a combination of both. For screening purposes, regular estimations of plasma alkaline phosphatase levels identify patients who may be developing osteomalacia which can then be treated with calcium and vitamin D supplements. Numerically, osteoporosis in excess of ageing is a bigger problem and its prevention and treatment is at present unsatisfactory. Screening procedures for osteoporosis are reviewed, including the more recent methods of bone mineral density assessment. Osteopenia or demineralization occurs in both osteomalacia and osteoporosis therefore osteomalacia must be excluded before attributing any loss to osteoporosis. The present situation with regards to the prevention and treatment of osteoporosis is also reviewed.
Quantitative immunohistochemical analysis of lymphocyte subsets in alcoholic liver disease
Authors: SAKAI YOSHINORI , IZUMI NAMIKI , MARUMO FUMIAKI , SATO CHIFUMI
Published: March 2008

Abstract To investigate the role of lymphocytes frequently observed in the parenchyma of alcoholic liver disease (ALD), lymphocytes infiltrating into the liver were stained immunohistochemically with monoclonal antibodies (MoAb) and were quantitatively assessed by a morphometric analysis in 17 patients with ALD and, for comparison in five patients with chronic active hepatitis B (B‐CAH). In patients with alcoholic hepatitis, the number of CD8+ lymphocytes in the hepatic lobule was similar to that in patients with B‐CAH but was significantly greater than that in alcoholics with hepatic fibrosis (HF). The CD4/CD8 ratio in the hepatic lobule was low in both alcoholic hepatitis and B‐CAH compared with that of alcoholic patients with HF. When Mallory bodies (MB) and lymphocytes were simultaneously stained with a specific antibody against MB and MoAb, respectively, only CD3+ and CD8+ lymphocytes were found to have a close contact with MB. These results suggest that in alcoholic hepatitis, hepatocyte necrosis may be partly mediated by immunological mechanisms involving cytotoxic T cells infiltrating into the hepatic lobule.
Verrucous carcinoma of the oesophagus and achalasia
Authors: ROACH ELIOT , BARR GAVIN
Published: March 2008

Abstract A 67 year old male caucasian clerical worker with a background of long‐standing gastro‐oesophageal reflux‐like dyspepsia and brochiectasis presented to a tertiary hospital gastroenterology unit with a recent onset of dysphagia. An initial diagnosis of achalasia was made and within 1 year an established verrucous carcinoma of the upper oesophagus had developed. The tumour was inoperable due to tracheal invasion and therefore palliative treatment was given. The patient developed a tracheo‐oesophageal fistula and died of pneumonia. Thus, verrucous squamous cell carcinoma of the oesophagus can occur with achalasia.
The role of luminal factors in prostaglandin protection against ethanol‐induced gastric mucosal injury
Authors: MALCONTENTI‐WILSON C. , ANDREWS F. J. , SILEN W. , O'BRIEN P. E.
Published: March 2008

Prostaglandins (PG) protect the gastric mucosa against damage by several irritants, but the mechanisms remain unclear. A standard rat model of gastric injury induced by 50% ethanol was used to test the hypothesis that PG protection occurs either by increasing luminal fluid volume and hence diluting the irritant, or by production of protective factors within this fluid. Quantitative histology was used to asssess microscopic mucosal damage. The increase in luminal fluid volume in prostaglandin E2 (PGE2)‐treated animals was measured, and the ability of this increased fluid to protect saline‐treated animals via dilution of the irritant was assessed. The transfer of protection by exchange of luminal fluid from PG to non‐PG treated animals was also tested. Results showed that PGE2 induced a specific increase in luminal fluid volume of 45.6%. When given together with ethanol treatment the extra fluid volume was not protective. Removal of luminal fluid after PG and before ethanol treatment did not abolish protection and no protective factor was transferred with the luminal fluid. In conclusion, this study has shown that neither dilution of ethanol by accumulation of luminal fluid nor the presence of luminal factors is responsible for PG protection.
Tumour suppressor genes and colorectal neoplasia
Authors: KOOREY DAVID J. , McCAUGHAN GEOFFREY W.
Published: March 2008

Two distinct gene classes have been implicated in colorectal carcinogenesis. Tumour promoter genes (oncogenes, dominant oncogenes) produce an excessive positive stimulus to cell proliferation. The ras family of oncogenes are an example. Acquired mutations of the c‐k‐ras gene are commonly found in colonic adenomas and carcinomas. Tumour suppressor genes (anti‐oncogenes, recessive oncogenes) normally constrain or regulate cell proliferation. Loss of this function through gene deletion or mutation is oncogenic. Inherited tumour suppressor gene mutations have now been identified in several of the familial cancer syndromes. Acquired tumour suppressor gene mutations are found in both sporadic and hereditary cancers. Together with the tumour promoter genes they provide the genetic basis for the cellular changes occurring during carcinogenesis. The retinoblastoma gene was the first human tumour suppressor gene to be characterized and exemplifies the class. More recently, linkage studies in the hereditary cancer syndromes and the detection of specific deletions in sporadic tumours have helped to identify several new tumour suppressor genes. At least four of these (MCC, APC, p53 and DCC) apparently contribute to sporadic colorectal carcinogenesis. Germ line APC mutations produce the inherited colorectal cancer syndrome familial adenomatous polyposis (FAP). Detection of these mutations using linked markers has already found clinical application in the screening of families with this disease. In the future, genetic diagnosis of hereditary non‐polyposis colorectal cancer (HNPCC) and the recognition of those genetically susceptible to sporadic colorectal cancer may become possible. At the same time, as our understanding of the genes involved improves, new avenues for treatment and prevention of colorectal cancer may emerge.