Tumour necrosis factor-alpha promoter polymorphisms in primary biliary cirrhosis.

Background/aims: The incidence of primary biliary cirrhosis (PBC) is increased in the close relatives of patients, suggesting that genetic factors play a role in disease susceptibility. Decreased in vitro production of tumour necrosis factor (TNF)-alpha has been reported in PBC patients, suggesting a potential aetiological role for this cytokine. The aim of this study was to examine two biallelic polymorphisms in the promoter region of the TNF-alpha gene, which may play a role in the control of TNF-alpha secretion, as candidate susceptibility loci in PBC.

Helicobacter pylori in vivo causes structural changes in the adherent gastric mucus layer but barrier thickness is not compromised.

Background: It has been proposed that a pathogenic effect of Helicobacter pylori is a weakening of the protective mucus barrier; however, this remains controversial.

Aims: To clarify the effects of H pylori infection on the mucus gel barrier in vivo.

Methods: Mucus gel polymeric structure and the thickness of the adherent mucus barrier were measured in endoscopic biopsy samples in subjects with and without H pylori infection.

Enhanced immune responses and resistance against infection in aged mice conferred by Flu-ISCOMs vaccine correlate with up-regulation of costimulatory molecule CD86.

Ageing is associated with a decline in immune function and our primary objective is to 'reverse' age-related decline in protective immune responses to vaccination by formulating vaccines in appropriate delivery systems. In this paper, we demonstrate that influenza vaccine formulated as ISCOMs is highly immunogenic and confers protection in aged mice, when compared to current influenza vaccine. The enhanced protection conferred by Flu-ISCOMs in aged mice correlates with the up-regulation of co-stimulatory molecule, CD86 (B7.

The RsaI polymorphism of CYP2E1 and susceptibility to alcoholic liver disease in Caucasians: effect on age of presentation and dependence on alcohol dehydrogenase genotype.

Twin studies in Caucasians suggest that susceptibility to alcoholic liver disease is, in part, genetically determined. Because most of the deleterious effects of alcohol are caused by its metabolism, attention has focused upon genes encoding ethanol metabolizing enzymes. Caucasians are polymorphic at only two of these gene loci--cytochrome P450 2E1 (CYP2E1) and alcohol dehydrogenase 3 (ADH3).

Protection against respiratory syncytial virus infection by DNA immunization.

Respiratory syncytial virus (RSV) remains a major cause of morbidity and mortality in infants and the elderly and is a continuing challenge for vaccine development. A murine T helper cell (Th) type 2 response associates with enhanced lung pathology, which has been observed in past infant trials using formalin-inactivated RSV vaccine. In this study, we have engineered an optimized plasmid DNA vector expressing the RSV fusion (F) protein (DNA-F).

Omeprazole, ranitidine, and cimetidine have no effect on peak blood ethanol concentrations, first pass metabolism or area under the time-ethanol curve under 'real-life' drinking conditions.

Background: Considerable controversy persists over the influence of H2-receptor antagonists on the first pass clearance of ethanol. The majority of previously published studies have studied the effects of the drugs on low-dose ethanol in the fasting state. We elected to study the possible interaction under simulated real-life conditions.

Enhanced antibody and cytokine responses to influenza viral antigens in perforin-deficient mice.

Cytotoxic T lymphocytes (CTL) lyse virus-infected target cells by secreting the pore-forming effector molecule, perforin. Perforin-mediated cell death appears to be a major mechanism in viral clearance but its role in regulating immune responses in vivo is unclear. In this report, we show that following immunization with influenza viral antigens, perforin-deficient mice generated about 100-fold greater serum antibody responses than wild-type mice.

Is the SF-36 suitable for assessing health status of older stroke patients?

Introduction: The Medical Outcomes Study short form 36 health survey (SF-36) is being increasingly used and recommended as a suitable measure of subjective health status. However, it is unlikely that any measure will be appropriate for all groups. We wished to determine the suitability of the SF-36 for assessing quality of life in older stroke patients.

Role of mitochondrial DNA mutations in human aging: implications for the central nervous system and muscle.

It has been proposed that one mechanism for nerve and muscle dysfunction with age involves the mitochondria. Mitochondria contain the only DNA outside the nucleus in mammalian cells. Mitochondrial DNA (mtDNA) has a high mutation rate, and low levels of pathogenic mutations have been found in tissues from elderly subjects.

Modulation of the biological functions of galectin-3 by matrix metalloproteinases.

Galectin-3 is an important intracellular and extracellular lectin which is presumed to interact with extracellular matrix proteins and cell surface glycoproteins in normal and pathophysiological conditions. The exact physiological role of the protein is presently not known. We have previously demonstrated that recombinant human galectin-3 is a novel substrate for metalloproteinases, particularly MMP-2 and MMP-9.

Autoimmune hepatitis in older patients.

Aim: autoimmune hepatitis (AIH) is thought to present rarely in old people. The aims of the present study were to (i) review individuals diagnosed clinically as having AIH presenting over or under 65 years of age at Freeman Hospital, Newcastle, from 1979 to 1993 and (ii) compare diagnostic and histological scores, treatment and outcome, and hence provide a useful profile of the disease in older patients.

Methods: 310 individuals with a histological diagnosis of chronic hepatitis were identified, and review of the medical notes of 286 revealed 54 with a diagnosis of AIH.

A strategy for rational design of fully synthetic glycopeptide conjugate vaccines.

The present study describes a strategy to rationally design fully synthetic glycopeptide conjugate vaccines. Glycopeptide immunogens were constructed by coupling synthetic oligosaccharides comprising repeating units of synthetic 3-beta-D-ribose-(1-1)-D-ribitol-5-phosphate (sPRP) to synthetic peptides containing potent T-helper cell determinants and B-cell epitopes of the Haemophilus influenzae type b (Hib) outer membrane proteins (OMPs) P1, P2, and P6. Rabbit immunogenicity studies revealed that some of these fully synthetic glycoconjugates were capable of eliciting high titers of both anti-PRP and anti-OMP immunoglobulin G antibodies.

Transjugular intrahepatic portosystemic shunt: a limited role in refractory ascites.

Objective: To evaluate the role of the transjugular intrahepatic portosystemic shunt (TIPS) in the management of patients with refractory ascites.

Design: A retrospective study of 25 consecutive patients for whom refractory ascites was the primary indication for TIPS insertion.

Setting: Regional liver unit at Freeman Hospital, Newcastle upon Tyne, UK.

A multicentre randomised trial comparing octreotide and injection sclerotherapy in the management and outcome of acute variceal haemorrhage.

Background: Few studies have compared vasoactive drugs with endoscopic sclerotherapy in the control of acute variceal haemorrhage. Octreotide is widely used for this purpose, but its value remains undetermined.

Aims: To compare octreotide with endoscopic sclerotherapy for acute variceal haemorrhage.

Hepatocellular carcinoma in primary biliary cirrhosis and its impact on outcomes.

In this study we have determined the incidence of hepatocellular carcinoma (HCC) development in primary biliary cirrhosis (PBC) and its effects on patient survival. Six hundred and sixty seven patients with liver histology compatible with or diagnostic of PBC were seen over a 20-year period. Two hundred and seventy three patients who had stage III or IV disease on their last biopsy and who had been followed up for at least 1 year following that biopsy (total follow-up with advanced disease 2,010 patient years) were identified (243 female, 30 male).

Mitochondrial involvement in the ageing process. Facts and controversies.

Mitochondria are believed to be involved in human ageing. Whilst it is clear that various mitochondrial DNA mutations do accumulate in human tissues with age, whether or not they interfere with respiratory chain function is uncertain. We question the results of previous studies which have measured respiratory chain function in human skeletal muscle with age.

Incidence and prevalence of primary biliary cirrhosis in the city of Newcastle upon Tyne, England.

Objective: To describe the incidence and prevalence of primary biliary cirrhosis in an urban population between 1987 and 1994, using stringent inclusion criteria and a well-defined study area and population.

Design: Descriptive study based on a case register compiled by a retrospective and prospective case-finding exercise and examination of case notes.

Setting: The city of Newcastle upon Tyne.

Effect of lipid modification on the physicochemical, structural, antigenic and immunoprotective properties of Haemophilus influenzae outer membrane protein P6.

The outer membrane lipoprotein, P6 of Haemophilus influenzae was studied to determine the importance of the native palmitoyl moiety on its physicochemical and immunological properties. A recombinant P6 (rP6) molecule devoid of lipidation signal sequence was expressed in Escherichia coli and its properties were compared to those of the palmitylated protein purified from H. influenzae.