P W Keeling

Publications (64)405.13 Total impact

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  Available from: wjgnet.com

  Article: Central serotonergic and noradrenergic receptors in functional dyspepsia.

  S O'Mahony, T G Dinan, P W Keeling, A S B Chua
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  ABSTRACT: Functional dyspepsia is a symptom complex characterised by upper abdominal discomfort or pain, early satiety, motor abnormalities, abdominal bloating and nausea in the absence of organic disease. The central nervous system plays an important role in the conducting and processing of visceral signals. Alterations in brain processing of pain, perception and affective responses may be key factors in the pathogenesis of functional dyspepsia. Central serotonergic and noradrenergic receptor systems are involved in the processing of motor, sensory and secretory activities of the gastrointestinal tract. Visceral hypersensitivity is currently regarded as the mechanism responsible for both motor alterations and abdominal pain in functional dyspepsia. Some studies suggest that there are alterations in central serotonergic and noradrenergic systems which may partially explain some of the symptoms of functional dyspepsia. Alterations in the autonomic nervous system may be implicated in the motor abnormalities and increases in visceral sensitivity in these patients. Noradrenaline is the main neurotransmitter in the sympathetic nervous system and again alterations in the functioning of this system may lead to changes in motor function. Functional dyspepsia causes considerable burden on the patient and society. The pathophysiology of functional dyspepsia is not fully understood but alterations in central processing by the serotonergic and noradrenergic systems may provide plausible explanations for at least some of the symptoms and offer possible treatment targets for the future.
  World Journal of Gastroenterology 06/2006; 12(17):2681-7. · 2.47 Impact Factor
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  Available from: Ross Mcmanus

  Article: A common p73 polymorphism is associated with a reduced incidence of oesophageal carcinoma.

  B M Ryan, R McManus, J S Daly, E Carton, P W Keeling, J V Reynolds, D Kelleher
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  ABSTRACT: The incidence of oesophageal adenocarcinoma is rising; to date, no susceptibility genes have been identified. p73, a novel p53 homologue, maps to chromosome 1p36, a region commonly deleted in oesophageal cancers. p73 shares some p53-like activity, but in addition, may also play a role in gastrointestinal epithelial inflammatory responses. A non-coding p73 polymorphism (denoted AT or GC) may be functionally significant. We investigated whether this polymorphism might play a role in the aetiopathogenesis of oesophageal cancer. This was a case-control, retrospective study. 84 cases of oesophageal cancer (25 squamous and 59 adenocarcinoma) and 152 normal population controls were genotyped for this polymorphism. Informative cases were examined for p73 LOH within the tumour. AT/AT homozygotes were significantly less prevalent in the oesophageal cancer population (1/84 = 1.2%) compared to controls (15/152 = 9.9%) (P < 0.02), corresponding to an odds ratio of 0.11 (95% C.I. 0.02-0.6, P < 0.02), or 9-fold reduced risk. Moreover, AT/AT homozygotes were significantly less frequent in the cancer population than would be expected under the Hardy-Weinberg hypothesis (P = 0.0099). LOH at the p73 locus was observed in 37.8% (14/37) of the AT/GC heterozygotes studied; in all cases there was loss of the AT allele. Our findings indicate that p73 AT/AT homozygotes appear to be protected against the development of oesophageal cancer. Clinically, this observation could have implications in aiding identification of high-risk Barrett's oesophagus patients.
  British Journal of Cancer 11/2001; 85(10):1499-503. · 5.04 Impact Factor
• Article: Impact of cortisol on buspirone stimulated prolactin release: a double-blind placebo-controlled study.

  T G Dinan, L V Scott, J Thakore, J Naesdal, P W Keeling
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  ABSTRACT: Buspirone is known to stimulate prolactin release. Clinical studies (e.g. in chronic fatigue syndrome) suggest that the response may be influenced by baseline cortisol levels. We conducted a double-blind placebo-controlled study to examine the relationship between the prolactin response to buspirone challenge and baseline cortisol level. Fifty healthy volunteers took part in the study. Buspirone was found to consistently elevate PRL levels above those seen following placebo administration. The PRL response as measured by area under the curve was highly correlated with the baseline cortisol level.
  Psychoneuroendocrinology 11/2001; 26(7):751-6. · 5.81 Impact Factor
• Article: A double-blind placebo-controlled study of buspirone-stimulated prolactin release in non-ulcer dyspepsia--are central serotoninergic responses enhanced?

  T G Dinan, N Mahmud, O Rathore, J Thakore, L V Scott, E Carr, J Naesdal, C A O'Morain, P W Keeling
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  ABSTRACT: Dyspepsia is a common symptom for which an organic cause is found in only 40% of patients. When no cause is apparent and the dyspepsia is considered to be idiopathic, a diagnosis of non-ulcer dyspepsia is made. The pathophysiology of non-ulcer dyspepsia is poorly understood and numerous theories have been put forward, including a theory of enhanced central serotoninergic receptor sensitivity. To determine the sensitivity of serotonin receptors in non-ulcer dyspepsia. Using a randomized, double-blind, placebo-controlled design, we compared buspirone (a serotonin type 1a partial agonist)-stimulated prolactin release in 50 patients and 59 healthy comparison subjects. Buspirone, 30 mg, or matching placebo was administered on two separate occasions and prolactin release over 180 min was monitored. Patients and healthy subjects received both treatments in random order, 1 week apart. Overall, patients with non-ulcer dyspepsia had greater prolactin release in response to the buspirone challenge than the healthy comparison subjects, with differences most significant at 90 min following the challenge. Enhancement occurred in patients both with and without Helicobacter pylori infection. Female subjects, both patients and healthy volunteers, showed a greater response to buspirone than male subjects, and the augmentation of response observed in male and female patients was greater in females. Patients with non-ulcer dyspepsia have enhanced central serotoninergic responses and such responses are independent of H. pylori infection. Blockade of such receptors might be an appropriate therapeutic strategy.
  Alimentary Pharmacology & Therapeutics 11/2001; 15(10):1613-8. · 3.77 Impact Factor
• Article: Potential impact of magnetic resonance cholangiopancreatography on endoscopic retrograde cholangiopancreatography workload and complication rate in patients referred because of abdominal pain.

  R J Farrell, N Noonan, N Mahmud, M M Morrin, D Kelleher, P W Keeling
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  ABSTRACT: Endoscopic retrograde cholangiopancreatography (ERCP) has a significant mortality, morbidity, and failed cannulation rate. Magnetic resonance cholangiopancreatography (MRCP) is a safer, noninvasive method of imaging the pancreaticobiliary tree. A substantial number of patients are referred for ERCP because of abdominal pain, a high proportion of whom have normal ducts or pathology not requiring interventional ERCP. The aim was to assess the potential impact of MRCP on overall ERCP workload and patient outcome if MRCP were the primary investigation in patients referred for ERCP because of abdominal pain. 1758 consecutive ERCPs performed in 1148 patients over a 3-year period in a single tertiary referral center in the pre-MRCP era were reviewed. Cannulation failure, ERCP findings, need for follow-up ERCP and all 30-day major complication rates were analyzed with regard to clinical indications. The overall workload comprised 1108 (63 %) successful initial ERCPs, 188 (11 %) failed cannulation attempts and 462 (26 %) follow-up ERCPs. Of the patients, 299 (27 %) had normal ERCP findings, 331 (30 %) had choledocholithiasis and 246 (22 %) had strictures. lf MRCP had been used as the primary imaging investigation in the 451 patients (39 %) referred for ERCP because of abdominal pain, we estimate that 197 patients (44 %) would have avoided ERCP, and the overall ERCP workload would have been reduced by 13 %. Initial MRCP in suspected gallstone pancreatitis and certain miscellaneous groups, it was estimated, would have further decreased ERCP workload by 9 %. Four of 40 major ERCP-related complications (3.5 %) and one of four ERCP-related deaths (0.35 %) would potentially have been avoided. Initial MRCP in patients referred with abdominal pain would potentially have avoided ERCP in 44 % of cases, reduced ERCP workload by 13 % and significantly reduced patient morbidity and mortality. The relatively small reduction in ERCP workload among these patients reflects the fact that over half of them had probable sphincter dysfunction, a significant proportion of whom might have benefited from biliary manometry and/or endoscopic intervention despite a normal MRCP. Furthermore, a small number of patients with calculi and subtle biliary and pancreatic strictures would be missed by this approach.
  Endoscopy 09/2001; 33(8):668-75. · 5.21 Impact Factor
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  Available from: James J Farrell

  Article: Increased incidence of non-Hodgkin's lymphoma in inflammatory bowel disease patients on immunosuppressive therapy but overall risk is low.

  R J Farrell, Y Ang, P Kileen, D S O'Briain, D Kelleher, P W Keeling, D G Weir
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  ABSTRACT: There is concern that the incidence of non-Hodgkin's lymphoma (NHL) will rise with increasing use of immunosuppressive therapy. Our aim was to determine the risk of NHL in a large cohort of patients with inflammatory bowel disease (IBD), and to study the association between IBD, NHL, and immunosuppressive therapy. We studied 782 IBD patients (238 of whom received immunosuppressive therapy) who attended our medical centre between 1990 and 1999 (median follow up 8.0 years). Standardised incidence ratios (SIRs) and 95% confidence intervals (CI) were calculated. Expected cases were derived from 1995 age and sex specific incidence rates recorded by the National Cancer Registry of Ireland. There were four cases of NHL in our IBD cohort (SIR 31.2; 95% CI 2.0-85; p=0.0001), all of whom had received immunosuppressive therapy: azathioprine (n=2), methotrexate (n=1), and methotrexate and cyclosporin (n=1). Our immunosuppressive group had a significantly (59 times) higher risk of NHL compared with that expected in the general population (p=0.0001). Three cases were intestinal NHL and one was mesenteric. Mean age at NHL diagnosis was 49 years, mean duration of IBD at the time of NHL diagnosis was 3.1 years, and mean duration between initiation of immunosuppressive therapy and diagnosis of NHL was 20 months. Although underlying IBD may be a causal factor in the development of intestinal NHL, our experience suggests that immunosuppressive drugs can significantly increase the risk of NHL in IBD. This must be weighed against the improved quality of life and clinical benefit immunosuppressive therapy provides for IBD patients.
  Gut 11/2000; 47(4):514-9. · 10.11 Impact Factor
• Article: Randomized comparison of unfractionated heparin with corticosteroids in severe active inflammatory bowel disease.

  Y S Ang, N Mahmud, B White, M Byrne, A Kelly, M Lawler, G S McDonald, O P Smith, P W Keeling
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  ABSTRACT: Heparin therapy may be effective in steroid resistant inflammatory bowel disease. A randomized pilot study, to compare unfractionated heparin as a first-line therapy with corticosteroids in colonic inflammatory bowel disease. Twenty patients with severe inflammatory bowel disease (ulcerative colitis, n=17; Crohn's colitis, n=3) were randomized to either intravenous heparin for 5 days, followed by subcutaneous heparin for 5 weeks (n=8), or high-dose intravenous hydrocortisone for 5 days followed by oral prednisolone 40 mg daily, reducing by 5 mg per day each week (n=12). After 5 days, non-responders in each treatment group were commenced on combination therapy. Response to therapy was monitored by: clinical disease activity (ulcerative colitis: Truelove and Witt Index; Crohn's colitis: Harvey and Bradshaw Index), stool frequency, serum C-reactive protein and alpha1 acid glycoprotein, endoscopic and histopathological grading. The response rates were similar in both treatment groups: clinical activity index (heparin vs. steroid; 75% vs. 67%; P=0.23), stool frequency (75% vs. 67%; P=0.61), endoscopic (75% vs. 67%; P=0.4) and histopathological grading (63% vs. 50%; P=0.67). Both treatments were well-tolerated with no serious adverse events. Heparin as a first line therapy is as effective as corticosteroids in the treatment of colonic inflammatory bowel disease. Large multicentre randomized comparative studies are required to determine the role of heparin in the management of inflammatory bowel disease.
  Alimentary Pharmacology & Therapeutics 09/2000; 14(8):1015-22. · 3.77 Impact Factor
• Article: Serum mutant K-ras in the colorectal adenoma-to-carcinoma sequence. Implications for diagnosis, postoperative follow-up, and early detection of recurrent disease.

  B M Ryan, R O McManus, J S Daly, P W Keeling, D G Weir, F Lefort, D Kelleher
  Annals of the New York Academy of Sciences 05/2000; 906:29-30. · 3.15 Impact Factor
• Article: High multidrug resistance (P-glycoprotein 170) expression in inflammatory bowel disease patients who fail medical therapy.

  R J Farrell, A Murphy, A Long, S Donnelly, A Cherikuri, D O'Toole, N Mahmud, P W Keeling, D G Weir, D Kelleher
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  ABSTRACT: The multidrug resistance (MDR) gene codes for a drug efflux pump P-glycoprotein 170 (Pgp-170) expressed on the surface of lymphocytes and intestinal epithelial cells. Inflammatory bowel disease (IBD) poorly responsive to medical therapy may relate to MDR expression because glucocorticoids are known Pgp-170 substrates. Using flow cytometry, we measured peripheral blood lymphocyte (PBL) MDR in 153 IBD patients and 50 healthy volunteers, and assessed the relationship between PBL, mucosal intraepithelial lymphocyte (IEL), and mucosal epithelial cell (EC) MDR expression in a further 20 IBD patients and 19 controls. Compared with controls, PBL MDR was significantly elevated in patients with Crohn's disease who required bowel resection for failed medical therapy (mean +/- SEM, 26.7 +/- 2.8 vs. 11.9 +/- 1.0; P <0.0001) and patients with ulcerative colitis who required proctocolectomy for failed medical therapy (20.3 +/- 2.5 vs. 11.9 +/- 1.0; P = 0.001). PBL MDR remained stable over time and was not influenced by disease activity or glucocorticoid therapy. Both PBL and mucosal MDR expression appeared independent of disease activity, and there was a significant correlation between PBL MDR expression and both IEL expression (r = 0.92; P < 0.0001) and EC expression (r = 0.54; P < 0.001). PBL and mucosal MDR expression may play an important role in determining the response of IBD patients to glucocorticoid therapy.
  Gastroenterology 03/2000; 118(2):279-88. · 11.68 Impact Factor
• Article: Heparin and inflammatory bowel disease.

  B White, Y S Ang, N Mahmud, P W Keeling, O P Smith
  The Lancet 10/1999; 354(9184):1122-3. · 38.28 Impact Factor
• Article: Extrapulmonary small cell gastric carcinoma. A case report and review of the literature.

  K J O'Byrne, A K Cherukuri, M I Khan, R J Farrell, P A Daly, E C Sweeney, P W Keeling
  Acta Oncologica 02/1997; 36(1):78-80. · 3.33 Impact Factor
• Article: Eating patterns in functional dyspepsia: a case control study.

  P Cuperus, P W Keeling, M J Gibney
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  ABSTRACT: To determine whether eating patterns differ between patients with endoscopically determined functional dyspepsia and non-dyspeptic controls. Case-control study (50 per group). A seven-day record of food consumption with time of food consumption was determined. Endoscopy clinic, St. James' Hospital and the Clinical Nutrition Laboratory at the Trinity College Medical School. Meal eating pattern and their temporal distribution; consumption of food categories and their temporal distribution; data for all subjects and for employed vs unemployed subjects. There was no evidence to suggest that the pattern of food and meal intake throughout the day was in any way influenced by endoscopically determined functional dyspepsia. The widely held belief that patients with functional dyspepsia eat differently to healthy controls to relieve or prevent symptoms of dyspepsia is not supported by these findings.
  European Journal of Clinical Nutrition 09/1996; 50(8):520-3. · 2.46 Impact Factor
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  Available from: Noirin Noonan

  Article: Endoscopic papillectomy: a novel approach to difficult cannulation.

  R J Farrell, M I Khan, N Noonan, K O'Byrne, P W Keeling
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  ABSTRACT: Selective cannulation of the biliary and pancreatic ducts is considered to be the most difficult and rate limiting aspect of diagnostic endoscopic retrograde cholangiopancreatography (ERCP). A novel technique for difficult cannulation is described and its potential role in relieving malignant duodenal obstruction secondary to ampullary carcinoma. A diagnostic endoscopic papillectomy was performed in 10 patients in whom previous attempts at cannulation had failed. Five patients had exophytic ampullary carcinomas, one had carcinoma of the head of pancreas, two had an oedematous ampulla secondary to low common bile duct stones, while two had protuberant ampullae with ectopic orifices. The technique entails snaring the ampulla flush with the duodenal wall using a polypectomy snare and in a similar fashion to polypectomy removing the ensnared ampulla with diathermy using a coagulation current. The underlying exposed ducts can then be cannulated while the ensnared ampulla can be retrieved to aid histological diagnosis. Successful cannulation was achieved in all 10 cases with significant haemorrhage in one patient (10%). Four of the snared ampullary carcinomas (80%) were retrieved enabling a histological diagnosis to be made. This study demonstrates the potential role for endoscopic papillectomy as a means of cannulation in difficult circumstances, however larger comparative studies are required.
  Gut 08/1996; 39(1):36-8. · 10.11 Impact Factor
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  Available from: tcd.ie

  Article: Expression of CD44 and its variants on gastric epithelial cells of patients with Helicobacter pylori colonisation.

  X Fan, A Long, M Goggins, P W Keeling, D Kelleher
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  ABSTRACT: Studies have suggested that expression of the adhesion molecule CD44 may be of prognostic importance in gastric cancer. In addition, there is strong evidence that Helicobacter pylori has a role in gastric cancer. To determine the expression of CD44 and its variants (v6, v9) and HLA class II molecules on human gastric epithelial cell and intraepithelial lymphocytes in patients with and without H pylori infection. Eighteen patients (seven men and 11 women) attending for endoscopic evaluation because of upper gastrointestinal symptoms were included. An additional 10 patients (five men and five women) were analysed for CD44 variant expression). Biopsy specimens were taken from the gastric antrum during endoscopy. Gastric epithelial cells and intraepithelial lymphocytes were examined by two colour flow cytometry and compared in patients with and without H pylori infection. Expression of CD44 and its variants (CD44 v9) was increased in epithelial cells but not in intraepithelial lymphocytes. Both epithelial cells and intraepithelial lymphocytes expressed higher levels of HLA class II molecules (DR and DP), possibly as a result of local cytokine production. Furthermore, results showed upregulation of CD44 on a gastric epithelial cell line (AGS) by cytokines and peripheral blood mononuclear cell supernatant. These data suggest that H pylori, either directly or through a local inflammatory response, is responsible for increased expression of CD44 and its variant CD44 v9. These data are of potential importance in relation to increased expression of CD44 and CD44 v9 on gastric carcinoma.
  Gut 05/1996; 38(4):507-12. · 10.11 Impact Factor
• Article: Carcinoma of the ampulla of Vater: a tumour with a poor prognosis?

  R J Farrell, N Noonan, I M Khan, M Goggins, D P Kelleher, P W Keeling
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  ABSTRACT: To assess the overall prognosis of patients with ampullary carcinomas and evaluate the presentation, diagnosis, pathology and management of these potentially highly curable tumours, attempting to relate these factors to overall survival. Forty patients with ampullary carcinoma were reviewed. Age, Sex, nature and duration of history, laboratory information at admission, results of diagnostic radiology, endoscopic retrograde cholangiopancreatograms and pathological findings were considered. Both curative and palliative management strategies were reviewed. The overall median survival was 19 months. The median duration of history was 5.9 +/- 5.4. weeks, with no significant difference in survival between patients with short and those with long histories (P = 0.46). Twenty nine (73%) patients were potentially resectable, but only 15 (37%) underwent potentially curative surgery. The difference in survival between the Whipple's (13) and the endoscopically stented (20 ) groups was not significant (p = 0.08). The Whipple's group were significantly younger than the stented group (P = 0.001) and had a significant operative morbidity, re-operation rate (38%) and post-operative mortality (15%). Only five of 13 patients were alive following Whipple's treatment after a mean follow-up of 18.9 months. Sphincterotomy before Whipple's treatment improved survival significantly (P = 0.04); absence of jaundice, exophytic macroscopic appearance, well-differentiated tumours and early stage were also associated with good survival. Endoscopic retrograde cholangiopancreatography has a high diagnostic yield and a low associated morbidity and mortality, with endoscopic papillectomy aiding cannulation while effective palliation was provided through stenting, endoscopic papillectomy and laser debulking of obstructing tumours. Little benefit was obtained from chemoradiotherapy. Despite the potential for curative resection in patients with ampullary carcinoma, the majority of such patients are unsuitable for curative surgery on grounds of age, general health status or advanced disease; since only 37% of patients undergo potentially curative surgery the condition has a poor prognosis.
  European Journal of Gastroenterology & Hepatology 03/1996; 8(2):139-44. · 1.76 Impact Factor
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  Available from: nih.gov

  Article: Helicobacter pylori increases proliferation of gastric epithelial cells.

  X G Fan, D Kelleher, X J Fan, H X Xia, P W Keeling
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  ABSTRACT: The direct and indirect effects of helicobacter pylori on cell kinetics of gastric epithelial cell line AGS were investigated by flow cytometric analysis of Ki-67 positive cells and by MTT assay. Flow cytometric analysis of Ki-67 positivity permits detection of cells that are in S-phase, whereas the MTT assay is a colometric measure of the number of viable cells. In the absence of added stimulants, 23.06 (4.88)% mean (SD) of AGS cells were Ki-67 positive. When cells were preincubated in the presence of H pylori, there was a significant increase in Ki-67 positivity (66.20 (7.89)%, p < 0.001). This increase was not seen in cells cultured in the presence of Campylobacter jejuni (24.63 (8.11)% or Escherichia coli (21.66 (9.78)%). Pre-incubation of AGS cells with supernatants from both H pylori and mitogen activated peripheral blood lymphocytes also increased the per cent of cells that were Ki-67 positive (72.93 (8.68) and 69.96 (12.35)%; p, 0.001) respectively. Similar results were also found in MTT assay. These data show that both H pylori directly and the immune/inflammatory response to H pylori indirectly can influence the rate of epithelial cell proliferation, suggesting this bacterium may be an initiating step in gastric carcinogenesis and an important co-carcinogenic factor in H pylori positive subjects.
  Gut 01/1996; 38(1):19-22. · 10.11 Impact Factor
• Article: Up-regulation of CD44 and ICAM-1 expression on gastric epithelial cells by H. pylori.

  X G Fan, X J Fan, H X Xia, P W Keeling, D Kelleher
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  ABSTRACT: Interaction between lymphocytes and epithelial cells may play a key role in Helicobacter pylori (H. pylori)-associated gastric mucosal inflammation. This interaction process is at least partially mediated by various cell adhesion molecules. The aims of the present study were to assess using flow cytometric analysis whether H. pylori directly or supernatants from H. pylori-activated peripheral blood mononuclear cells (PBMC) can affect the expression of adhesion molecules on the gastric epithelial cell line AGS in vitro. The results showed that resting AGS cells expressed CD44 and ICAM-1. Co-culture of AGS with H. pylori or cytokine-rich supernatants from H. pylori-activated PBMC resulted in up-regulation of expression of CD44 and ICAM-1 on AGS cells. These data suggest that H. pylori directly and indirectly through inflammatory cytokines may contribute to alternations in adhesion molecule expression on gastric epithelial cells. This may be of pathological significance in H. pylori-associated gastric mucosal inflammation and carcinogenesis.
  Apmis 11/1995; 103(10):744-8. · 1.99 Impact Factor
• Article: Effect of IL-4 on peripheral blood lymphocyte proliferation: implication in immunopathogenesis of H. pylori infection.

  X G Fan, J Yakoob, X J Fan, P W Keeling
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  ABSTRACT: Interleukin (IL) 4 is a type 2 cytokine which has a negative immunoregulatory role in human infection. IL-4 suppresses the production of interferon-gamma and enhances IL-10 synthesis. However, the effect of IL-4 on proliferative response of lymphocytes remains to be elucidated. We have previously reported an increase in production of IL-4 in subjects with Helicobacter pylori (H. pylori) infection. To evaluate whether the increased IL-4 is responsible for the down-regulation of immune responses in H. pylori infection, we observed the proliferative response of peripheral blood lymphocytes (PBL) co-cultured with phythaemagglutinin (PHA) or H. pylori in the presence and absence of added IL-4. As we have previously shown, PHA and H. pylori may increase PBL proliferation (P < 0.001). An increase in PBL proliferation was observed when PBL were co-cultured with PHA (P < 0.001) or H. pylori (P < 0.001) in the presence of IL-4 compared to that in the absence of IL-4. The optimal dose of IL-4 to give maximal lymphocyte proliferation is 50 pg/ml for the PHA-stimulated group or 100 pg/ml for the H. pylori-stimulated group. The data suggest that the increased IL-4 does not directly contribute to suppressed lymphocyte proliferation in H. pylori infection. Further studies will be required to determine the role of IL-4 in other aspects of down-regulation of immune responses in H. pylori infection.
  Immunology Letters 11/1995; 48(1):45-8. · 2.53 Impact Factor
• Article: Adhesion molecule expression on gastric intra-epithelial lymphocytes of patients with Helicobacter pylori infection.

  X Fan, A Long, P W Keeling, D Kelleher
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  ABSTRACT: To examine the expression of adhesion molecules on gastric intra-epithelial lymphocytes (IELs) from patients infected with Helicobacter pylori. The expression of adhesion molecules and T-cell activation markers by gastric IELs from patients with gastritis or duodenal ulceration was examined using two-colour flow cytometry. Ten of the patients were H. pylori positive and eight were H. pylori negative. Expression of lymphocyte function-associated antigen-1 (LFA-1) on IELs was significantly lower (P < 0.05) in patients with H. pylori infection than in patients negative for H. pylori. There were no significant differences in the expression on IELs of intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), human mucosal lymphocyte (antigen)-1 (HML-1), very late antigen-4 (VLA-4) or CD43 between H. pylori-positive and H. pylori-negative individuals. In addition, the transferrin receptor, a maker associated with proliferation and activation, was found on a small population of IELs from H. pylori-positive individuals. A reduction in the expression of LFA-1 has previously been reported on activation of IELs. The finding of reduced LFA-1 expression and increased transferrin receptor expression on IELs from H. pylori-positive individuals suggests that activation of these cells is associated with H. pylori infection.
  European Journal of Gastroenterology & Hepatology 06/1995; 7(6):541-6. · 1.76 Impact Factor
• Article: Helicobacter pylori-induced lipid peroxidation in peripheral blood lymphocytes.

  X G Fan, J Yakoob, A Chua, X J Fan, P W Keeling
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  ABSTRACT: Several lines of evidence implicate Helicobacter pylori infection in the pathogenesis of gastritis and peptic ulceration. To investigate whether H. pylori can cause lipid peroxidation in lymphocytes in vitro and to look for experimental evidence of lipid peroxidation induced by H. pylori, the lipid peroxide (LPO) level in peripheral blood lymphocytes was measured using the thiobarbituric acid fluorescence method. In the absence of added H. pylori, the LPO level in lymphocytes was 0.133 +/- 0.033 nmol/10(6) cells, and in the co-culture of H. pylori with peripheral blood mononuclear cells 0.340 +/- 0.097 nmol/10(6) cells. A significant difference was found between the two groups (p < 0.001). Antioxidants, either superoxide dismutase or catalase, could inhibit LPO production in lymphocytes. The present data provide further evidence that H. pylori can induce lipid peroxidation, which may be responsible for the pathogenesis of H. pylori-associated mucosal damage.
  Apmis 05/1995; 103(4):316-9. · 1.99 Impact Factor