PubMed Health⌕ Search

Biomedical subjects

R Batey

Publications and source records attributed to R Batey.

At least 19 recordsLinked to original sources
PubMed2003

Induction interferon and ribavirin for re-treatment of chronic hepatitis C patients unresponsive to interferon alone.

BACKGROUND: The optimal treatment for hepatitis C patients unresponsive to interferon is unclear. High-dose induction interferon may enhance early viral clearance, whilst ribavirin reduces relapse; in combination, they may improve sustained virological response rates. AIM: To compare the efficacy and safety of re-treatment with interferon induction, with or without ribavirin, in interferon non-responders. METHODS: We randomized 218 biochemical interferon non-responders to 10 MU interferon alpha 2b daily for 4 weeks, followed by 5 MU thrice weekly for 48 weeks plus ribavirin (II + R), or to the same interferon regimen plus placebo (II + P). All patients were viraemic at entry. RESULTS: The sustained virological response in the II + R group was 39%[95% confidence interval (CI), 30-48%], compared with 16% (95% CI, 9-23%) in the II + P group (P < 0.002). The study drug was discontinued for intolerable symptoms during induction in 9% of the II + R group and in 5% of the II + P group. By logistic regression, a sustained virological response was more likely following II + R treatment (odds ratio, 4.4; 95% CI, 2.1-9.7) and less likely in patients with genotype 1 or 4 (odds ratio, 0.16; 95% CI, 0.07-0.36). CONCLUSION: High-dose induction interferon plus ribavirin is well tolerated and effective for patients unresponsive to interferon alone.

Adolescent↗
PubMed2003

Intracerebral haemorrhage and hepatitis C treatment.

We report 3 episodes of intracerebral haemorrhage in a population of 1460 hepatitis C infected patients. We suggest the possibility of a link between HCV and its treatment and the occurrence of this serious complication.

Adult↗
PubMed2001

Shift of the gastric T-cell response in gastric carcinoma.

BACKGROUND AND AIMS: The etiology and pathophysiology of stomach carcinoma is complex, and the mechanism whereby H. pylori directly or indirectly induces carcinoma remains unclear. In this study, interleukin (IL)-8, IL-4 and interferon (IFN)-gamma were measured in the tissue culture supernatant of gastric organ cultures from subjects with chronic gastritis with or without H. pylori infection, and with or without gastric cancer and gastric dysplasia. RESULTS: Interleukin-8 levels were higher in cancer- and H. pylori-infected gastritis subjects than in H. pylori-negative subjects (12.95 +/- 3.16, 10.48 +/- 1.55 and 4.49 +/- 1.28 ng/mL, respectively). Elevated levels of IFN-gamma were detected in both H. pylori-infected and non-infected subjects with uncomplicated gastritis (72.23 +/- 19.0 and 34.61 +/- 5.30 pg/mL) and in non-infected dysplasia subjects (88 +/- 20.5 pg/mL). Background levels of IL-4 (< or = 9.4 pg/mL) in uncomplicated gastritis subjects and relatively high levels of IL-4 in dysplasia subjects (25.8 +/- 7.3 pg/mL) were detected. In contrast, trace amounts of IFN-gamma (16.01 +/- 0.35 pg/mL) and high levels of IL-4 (42.81 +/- 8.49 pg/mL) in gastric biopsy culture supernatants were found in cancer subjects. Mucosal IL-4 levels (but not IL-8 levels) correlated with infection and mucosal anti-H. pylori immunoglobulin G antibody. CONCLUSIONS: The significant differences between gastritis with and without cancer and dysplasia indicated a shift from a Th1 to a Th2 helper cell pattern of cytokine secretion. This study has identified a local mucosal defect in gastric cancer. The near absence of IFN-gamma production from the mucosa at the margins of the tumor may be a critical factor in promoting growth of neoplastic cells.

Adenocarcinoma↗
PubMed2001

Interleukin 2 modulates ion secretion and cell proliferation in cultured human small intestinal enterocytes.

AIMS: To determine if interleukin 2 (IL-2) alters epithelial transport and barrier function in cultured human small intestinal enterocytes. METHODS: Confluent monolayers of small intestinal cells derived from duodenal biopsies were treated with IL-2 0.2-50 U/ml for 24 hours prior to study. Transport measurements were performed under short circuited conditions in Ussing chambers, with and without the secretagogues forskolin and 3-isobutyl-1-methyl xanthine (IBMX). Serosal to mucosal flux of 3[H] mannitol (permeability) and 3[H] thymidine uptake (proliferation) were measured. IL-2 receptor and cystic fibrosis transmembrane conductance regulator (CFTR) mRNA were identified using reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: IL-2 did not alter baseline electrical parameters but caused a significant increase in cAMP dependent chloride secretion. The effect was mediated by the IL-2 receptor and paralleled a rapid increase in tyrosine phosphorylation, janus kinase 1, and signal transducers and activators of transcription (STATs) 1, 3, and 5. IL-2 significantly increased proliferation but at a lower dose than observed for enhanced secretion but did not alter permeability. IL-2 receptor beta and gammac chains and CFTR mRNA were identified by RT-PCR. CONCLUSIONS: IL-2 treatment enhances cAMP stimulated chloride secretion and cellular proliferation in a human small intestinal cell line expressing a functional IL-2 receptor.

Analysis of Variance↗
PubMed2000

Circulating T-cell response to Helicobacter pylori infection in chronic gastritis.

BACKGROUND: Helicobacter pylori elicits a specific humoral and cellular immune response. There is increasing evidence that the type of T-cell response contributes to clinical outcome in H. pylori infection. MATERIALS AND METHODS: The host response to H. pylori infection in 34 subjects with chronic gastritis was examined in terms of T-cell proliferation and cytokine production in whole-blood cultures stimulated or unstimulated with H. pylori acid-glycine extract antigens (AGE). RESULTS: The proliferative response in whole-blood cultures was similar for both H. pylori-positive and -negative subjects stimulated with H. pylori AGE. While an increase in interferon-gamma (IFN-gamma) production was observed from both H. pylori-positive and -negative subjects with gastritis, significantly higher levels of IFN-gamma were detected in the former when stimulated with H. pylori AGE. In contrast, interleukin 4 (IL-4) was undetectable regardless of antigen stimulation. However, if an in situ IL-4 antibody capture assay was used, antigen-independent production of IL-4 was detected, but there was no difference between H. pylori-positive and -negative subjects with gastritis. After eradication of H. pylori, antigen-induced production of IL-4 was increased, with no decrease in the levels of secretion of IFN-gamma. IL-4 production was dependent on CD4+ T cells, as addition of anti-CD4 but not anti-CD8 mouse monoclonal antibody or matched IgG isotype to the whole-blood culture inhibited the production of IL-4. CONCLUSION: The results suggest that a shift toward a balanced Th1-Th2 response due to an increase in antigen-induced IL-4 production from CD4+ T cells follows eradication. We suggest that the downregulation of mucosal inflammation consequent on reduction in antigen levels or removal of downregulation after eradication of H. pylori contributes to this shift in cytokine balance.

Adult↗
PubMed2000

Non-urease producing Helicobacter pylori in chronic gastritis.

BACKGROUND: Helicobacter pylori infection is the commonest cause of gastritis. Different patterns of immune response to H. pylori infection and characteristics of bacteria are considered to contribute to clinical outcomes. AIM: To determine characteristics of the host H. pylori relationship in subjects with non-ulcer dyspepsia and a histological diagnosis of gastritis. METHODS: Thirty-five subjects with chronic gastritis undergoing endoscopy (mean age 53 years, range 24-82, 14 male and 21 female) were studied, none of whom was on nonsteroidal anti-inflammatory drugs or antibiotics. H. pylori infection was determined by rapid urease test (CLOtest), culture, antibody and RT-PCR for Ure C, Cag A and 26 kDa gene and histology. Cytokine production of mucosal IL-6 and IL-8 were measured by ELISA. RESULTS: Fifteen subjects were positive by CLOtest and/or bacterial culture. In these subjects histology showed numerous helical forms of H. pylori (Group I). Nine subjects were negative by CLOtest, bacterial culture, and mRNA for urease C fragment, but positive by PCR for the 26 kDa protein encoding gene. Histology in these subjects showed the presence of either coccoid forms (four), or scant helical forms (two), or mixed coccoid/helical forms (three) (Group II). Eleven subjects were negative by all methods of detection (Group III). IgG and IgA antibody levels in serum (p<0.05) and gastric tissue culture supernatant (p<0.001) were significantly higher in Group I than those in Group II or III. There were significant differences in the IgG serum and IgA supernatant antibody levels (p<0.01 and p<0.05) when Group II was compared to Group III. Supernatant IL-6 levels were significantly higher in Group I (p<0.01) than those from Groups II and III. IL-8 levels were higher in Group I (p<0.01) and Group II (p<0.05) when compared to Group III. CONCLUSIONS: 'H. pylori-negative' gastritis can be associated with a non-urease producing form of H. pylori, with a reduction in both local and systemic antibody levels and mucosal pro-inflammatory cytokines.

Adult↗
PubMed2000

Effects of CH-100, a chinese herbal medicine, on acute concanavalin A-mediated hepatitis in control and alcohol-fed rats.

BACKGROUND: Administration of concanavalin A (Con A) leads to acute hepatitis that involves T-cell activation and inflammatory mediator production in mice and rats. We examined the role of CH-100, a Chinese herbal medicine previously trialed in human hepatitis C, in the prevention of Con A-related, T-cell-mediated, acute liver injury in rats. METHODS: Female Wistar rats were fed 40% ethanol, 2% sucrose, or isocaloric sucrose for 8 weeks. At the same time, these animals were fed either the Chinese herbal medicine CH-100 (4 tablets/kg body weight/ day) or placebo in chow daily. Blood from the tail vein was collected for endotoxin (lipopolysaccharide) assay at 0, 4, and 8 weeks of ethanol consumption. Twenty-four hours after injection of Con A (20 mg/kg body weight) or phosphate-buffered saline, blood from the tail vein was collected for alanine aminotransferase and tumor necrosis factor (TNF)-alpha assays. Liver-associated CD4+ T cells were isolated from liver perfusates and then cultured with Con A (5 microg/ml) at 37 degrees C for 24 hr. Supernatants were harvested for TNF-alpha assay. The proportion of CD4+ T cells in blood and liver perfusates was measured. Liver samples were collected for histopathological analysis. RESULTS: Lipopolysaccharide levels were significantly reduced in CH-100-treated ethanol-fed rats compared with placebo-treated rats. After Con A injection, alanine aminotransferase levels were lower at 12 and 24 hr in herb-treated rats compared with placebo-treated rats. Furthermore, serum TNF-alpha levels were lower in ethanol-fed rats on herbal treatment. A significant decrease in TNF-alpha production by liver-associated CD4+ T cells in culture was observed in CH-100-treated ethanol-fed rats. CH-100 treatment was associated with a decreased percentage of CD4+ cells in both blood and liver perfusate in all groups. Herb-treated rats displayed markedly less hepatic necrosis and a reduced CD4+ T-cell infiltrate in portal areas than did placebo-fed rats. CONCLUSIONS: The results demonstrate that CH-100 modified the T-cell response to Con A injection. The effect was more marked in ethanol-fed rats, which suggests a possible role for CH-100 in treating alcoholic liver disease.

Alanine Transaminase↗
PubMed1999

Coccoid forms of Helicobacter pylori can be viable.

Controversy exists as to whether the coccoid form of Helicobacter pylori can exist in a viable form. Conversion of helical to coccoid morphology occurs in culture over several days. In this study, the morphology was correlated with parameters of genetic integrity in the reference NCTC 11637 strain over 21 days of culture. The capacity to regrow colonies of helical form was demonstrated from a culture where the coccoid form constituted up to 95% and negligible urease activity could be detected. Urease enzyme activity and its mRNA decreased between day 0 and 10 while 26 kD mRNA and 16S rRNA were expressed unchanged for up to 14 and 21 days of culture, respectively. Expression of mRNA for the Cag A gene behaved in a similar fashion to that of urease. No evidence of DNA fragmentation was detected. These data suggest that a viable form of non-urease producing H. pylori exists after short to intermediate culture and that some if not all of these viable bacteria have coccoid morphology.

Antigens, Bacterial↗
PubMed1999

Ethanol-altered liver-associated T cells mediate liver injury in rats administered Concanavalin A (Con A) or lipopolysaccharide (LPS).

BACKGROUND: Recent work from our laboratory implicates T cells in the pathogenesis of alcoholic liver disease. We have studied the role of liver-associated T cells in acute hepatitis produced in control rats administered Concanavalin A (Con A) after adoptive transfer of T cells from alcohol-consuming animals. METHODS: Liver-associated T cells from ethanol-consuming rats were transferred via tail vein to nonethanol-consuming rats. They then received Con A (20 mg/kg body weight) intravenously. This produced a severe hepatitis. Serum was collected for the assay of alanine aminotransferase (ALT) and cytokines. RESULTS: Hepatic necrosis was accompanied by an increase in plasma levels of ALT, interleukin-6, and tumor necrosis factor-alpha. These increases correlated with increased production of interleukin-6 and tumor necrosis factor-alpha in culture of liver-associated T cells stimulated or unstimulated with Con A. Immunohistology staining showed increased infiltration of inflammatory cells comprised of neutrophils and mononuclear cells, which included greater numbers of CD4+ T cells in the portal tract areas and around the central vein. Focal and lobular necrosis was seen with inflammatory cells in the necrotic area. Hepatocytes isolated from the liver showed increased apoptosis compared with rats that received liver-associated T cells from nonethanol-consuming rats. Injection of endotoxin LPS, in the same model, was associated with less hepatocyte injury indicating a distinct role for T cells as opposed to Kupffer cells in this model of liver disease. CONCLUSIONS: Chronic ethanol consumption induces a lesion in a pool of liver-associated T cells which can mediate liver injury after polyclonal mitogen activation.

Alanine Transaminase↗
PubMed1998

IL-6, IFN-gamma and TNF-alpha production by liver-associated T cells and acute liver injury in rats administered concanavalin A.

The relationship between the development of acute hepatitis and the production of TNF-alpha IFN-gamma and IL-6 by liver-associated T lymphocytes following intravenous injection of concanavalin A (Con A) was studied in rats. Following a single injection of Con A, there was a dose and time-dependent correlation in the serum levels of serum alanine aminotransferase (ALT), IL-6, IFN-gamma and TNF-alpha. These increases correlated with an increase in the numbers of CD4+, CD8+ and CD25+ T cells in blood and CD4+ and CD25+ T cells in the liver perfusate, but not with CD8+ T cells in liver perfusate. Increased levels of IL-6, IFN-gamma and TNF-alpha were constitutively produced by liver-associated CD4+ T cells when cultured. In Con A-stimulated cultures, liver-associated CD4+ T cells secreted increasing levels of TNF-alpha in a time-dependent manner following Con A injection, but TNF-alpha production by peripheral blood lymphocytes was transient with peak levels detected at 1 h which then declined over 24 h. Histological examination of the liver revealed fatty change, hepatocyte degeneration and necrosis, with an associated cell infiltrate of neutrophils and CD4+ T cells both in the portal areas and around the central veins. These results support the hypothesis that Con A-induced liver damage is mediated by CD4+ T cells acting within the liver, at least in part through the secretion of TNF-alpha, IFN-gamma and IL-6.

Alanine Transaminase↗
PubMed1998

Decreased tumor necrosis factor-alpha and interleukin-1alpha production from intrahepatic mononuclear cells in chronic ethanol consumption and upregulation by endotoxin.

The relationship between the changes in liver pathology and the production of interleukin (IL)-1alpha, IL-6, and tumor necrosis factor-alpha (TNF-alpha) by intrahepatic mononuclear cells was studied in rats fed alcohol and subsequently exposed to lipopolysaccharide (LPS). Rats were fed 40% ethanol in drinking water, whereas control rats were provided with a chow diet with isocaloric or 2% sucrose drinking solutions for up to 20 weeks. Decreased IL-1alpha and TNF-alpha production in 24-hr culture supernatants of mononuclear cells isolated from liver perfusate was detected while IL-6 remained unchanged over 20 weeks. When animals were injected with LPS (1.0 microg/kg body weight), there was a 5-fold rise in ALT levels in the ethanol-fed group, but not in control groups. Increased IL-6 and TNF-alpha levels in the serum and supernatant of cultured intrahepatic mononuclear cells stimulated with or without LPS or concanavalin A was observed. There was a correlation between levels of ALT and TNF-alpha, but not IL-6. T cells and Kupffer cells were the major source of TNF-alpha in culture supernatants of hepatic perfusate mononuclear cells from ethanol-consuming rats injected LPS. In addition, pathological liver injury was evident, which suggests a pathogenic role for TNF-alpha in alcohol-induced liver disease.

Animals↗
PubMed1998

Altered T-lymphocyte responsiveness to polyclonal cell activators is responsible for liver cell necrosis in alcohol-fed rats.

The role of T-cell activation in alcoholic liver disease was investigated in rats fed alcohol and subsequently exposed to concanavalin A (Con A). Following Con A injection (20 mg/kg body weight), greater increases in liver-to-body weight ratio and ALT levels were observed at 12 and 24 hr in rats fed ethanol, compared with control rats fed sucrose. Furthermore, increases in serum interleukin-6 and tumor necrosis factor-alpha levels were noted in ethanol-fed rats, with maximal levels detected at 4 hr declining thereafter, but remaining above control levels at 24 hr. Analysis of T-cell subpopulations showed an increased percentage of CD4+, CD5+, and CD8+ T cells in blood from all groups, but not in liver perfusate. In contrast, a significant increase in the percentage of activated CD25+ T cells was detected in both blood and liver perfusate from rats fed ethanol even 24 hr after Con A injection. When CD4+ and CD8+ T cells from liver perfusate were cultured in the absence or presence of Con A, an increase in interleukin-6 and tumor necrosis factor-alpha production in supernatants was observed in ethanol-fed rats. In cultures stimulated with Con A, a 2- to 8-fold increase in cytokine production was detected, with intrahepatic CD4+ T cells being the major source. Immunohistological analysis revealed infiltration of CD4+ T cells around portal vein and central vein areas associated with fatty liver and severe hepatic necrosis. The results suggest that alcohol consumption induced a dysregulated T-cell population that mediated hepatic necrosis following polyclonal activation with Con A.

Animals↗
PubMed1996

Immunologic, functional, and morphological characterization of three new human small intestinal epithelial cell lines.

BACKGROUND & AIMS: Epithelial cell cultures can be used for the study of epithelial cell biology, although human small intestinal cultures have not been available to date. The aim of this study was to characterize three cell lines derived from normal human duodenum. METHODS: Cells were cultured from tissue fragments obtained from endoscopic biopsy specimens and characterized with respect to morphology and cytokine gene expression and for the presence of vectorial transport. RESULTS: All cell lines grew as polarized continuous monolayers and were mostly cuboidal in shape but were not immortalized. Cells showed junctional complexes and sparse microvilli. All cell lines showed cytokeratins and mucin antigen but not chromagranin and messenger RNA for epidermal growth factor, interleukin 6, and vascular cell adhesion molecule 1. Disaccharidase activities were low and correlated with the low proportion of cells (1%-10%), showing positive immunocytochemistry for sucrase. Monolayer resistance varied from 30 to 200 ohms. One monolayer (BN) consistently showed secretion in response to forskolin (10 micromol/L), which could b inhibited by chloride-free buffer and apical addition of the chloride channel blocker diphenylamine decarboxylate. No monolayer had evidence of glucose transport. CONCLUSIONS: These three nonimmortalized lines show morphological, phenotypic, and transport characteristics of crypt-like intestinal epithelial cells. The pattern of messenger RNA expression suggests a growth-promoting and immunomodulatory role.

Aged↗
PubMed1996

Complications and outcome of percutaneous endoscopic gastrostomy in different patient groups.

A retrospective study of percutaneous endoscopic gastrostomy (PEG) was performed to evaluate the complications of PEG and determine the role of prophylactic antibiotics in preventing early wound infection and to evaluate the outcome of patients in different groups (neurological disease, head injury, AIDS). Percutaneous endoscopic gastrostomy was performed on 50 patients between March 1991 and November 1993 and the survey was completed in July 1994. The average time to PEG placement post-cerebrovascular accident or head injury was 5 weeks. No deaths were attributable to the procedure. Four of 50 (8%) patients died in the first 30 days (early mortality). Wound infection (early eight, late five) was the most common complication: two of 13 patients receiving prophylactic antibiotics and six of 37 not receiving antibiotics had early wound infection. At completion of follow-up 19 of 26 patients with neurological disease had died (median survival = 370 days), three resumed oral feeding and four continued PEG feeding. All head injury patients (n = 6) were alive and had resumed oral feeding; five returned home. All AIDS patients (n = 7) died within 12 months (median survival = 138 days), although improved nutritional state was found after gastrostomy feeding. In conclusion, PEG placement is a useful procedure to assist feeding in multiple patient groups. Wound infection is a common but not life threatening complication. The need for prophylactic antibiotics to prevent early wound infection has not been proven. The 5 week delay in PEG insertion may contribute to lower early mortality. The 100% survival rate in head injury patients may reflect their young age and absence of underlying medical illness. In AIDS patients, improved nutritional state is not known to translate into better quality of life or prolonged survival.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Ethanol-related liver injury in the rat: a model of steatosis, inflammation and pericentral fibrosis.

BACKGROUND/AIMS: While several animal models exist for the study of ethanol heptotoxicity, they are limited in their applicability. This paper describes a relatively simple rat model of alcohol-related liver injury. METHODS: Ethanol was supplied in the drinking water in a concentration of 40% v/v for up to 29 weeks. Animals are concurrently supplied a chow diet which provides adequate protein and choline for normal growth. Total fat intake is low (7% of consumed calories). RESULTS: Histological changes of steatosis, inflammation, hepatocyte necrosis and pericentral sclerosis were evident in ethanol-treated rat livers. Littermate controls with and without pair-feeding had normal livers. Electron microscopy revealed abnormal mitochondria and a marked proliferation of smooth endoplasmic reticulum in livers of animals fed ethanol. Biochemical analysis revealed that levels of hepatic-free choline were similar in treated and pair-fed control rats. There was an expected increase in the activity of the microsomal enzyme cytochrome P450 2E1 in ethanol-fed rats. CONCLUSIONS: The model provides a convenient method for the production of alcoholic liver injury, and it may be useful for the study of the pathogenesis of ethanol-related liver disease.

Alcohol Drinking↗
PubMed1994

GM-CSF, IL-1 alpha, IL-1 beta, IL-6, IL-8, IL-10, ICAM-1 and VCAM-1 gene expression and cytokine production in human duodenal fibroblasts stimulated with lipopolysaccharide, IL-1 alpha and TNF-alpha.

The role of mucosal fibroblasts in intestinal inflammatory reactions is not known. In this study, we demonstrate that fibroblasts grown from histologically normal human duodenal biopsy tissues expressed mRNA genes for granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-1 alpha, IL-1 beta, IL-6, IL-8, IL-10, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) when stimulated with lipopolysaccharide (LPS) or IL-1 alpha. The increased mRNA expression of GM-CSF, IL-1 alpha, IL-1 beta, IL-6 and IL-8 in response to IL-1 alpha and LPS stimulation was time- and dose-dependent. In contrast, IL-10 was weakly expressed when fibroblasts were stimulated with LPS, IL-1 alpha or tumour necrosis factor-alpha (TNF-alpha), but the expression was enhanced in the presence of cycloheximide combined with optimal concentrations of LPS, IL-1 alpha or TNF-alpha, IL-1 alpha was a more potent stimulator than LPS for GM-CSF, IL-6, IL-8 and IL-10 expression, but not for IL-1 alpha and IL-1 beta. Increased GM-CSF, IL-6 and IL-8 gene expression was associated with the production of cytokine proteins in culture supernatant, but IL-1 alpha and IL-1 beta remained undetectable. Dexamethasone suppressed both gene expression and protein production of GM-CSF, IL-6 and IL-8 when fibroblasts were exposed to IL-1 alpha. TNF-alpha stimulated the release of GM-CSF, IL-6 and IL-8 and, combined with IL-1 alpha, cytokine production was enhanced synergistically. Finally, both LPS and IL-1 alpha up-regulated ICAM-1 and VCAM-1 gene expression. These findings implicate duodenal fibroblasts in the initiation and/or regulation of intestinal inflammation.

Adult↗