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J Calam

Publications and source records attributed to J Calam.

At least 37 records · Page 2Linked to original sources
PubMed1998

The histamine H3 receptor agonist N alpha-methylhistamine produced by Helicobacter pylori does not alter somatostatin release from cultured rabbit fundic D-cells.

BACKGROUND: The mechanisms underlying the suppression of somatostatin dependent reflexes in Helicobacter pylori infection are not fully determined. The H pylori product N alpha-methylhistamine and inflammatory mediators such as tumour necrosis factor-alpha (TNF-alpha) may be responsible for the alterations in somatostatin release. AIMS: To examine the effect of N alpha-methylhistamine on somatostatin release from cultured somatostatin-secreting D-cells. METHODS: Rabbit fundic D-cells were obtained by collagenase-EDTA digestion and enriched by centrifugal elutriation and cultured for 40 hours. The effects of N alpha-methylhistamine on somatostatin release soon after stimulation (two hours) and after more prolonged exposure (24 hours) were assessed. RESULTS: N alpha-Methylhistamine (1 nM-1 microM) had no effect on basal or carbachol or adrenaline stimulated release over two hours. Similarly with prolonged exposure no effect on somatostatin cell content or release was identified. In contrast, TNF-alpha (24 hours) led to a dose dependent fall in both somatostatin content and release. CONCLUSIONS: N alpha-Methylhistamine had no direct inhibitory effects on D-cells, but TNF-alpha both significantly reduced the cellular content and inhibited release. Inflammatory cytokines, rather than N alpha-methylhistamine, are therefore likely to be responsible for directly inhibiting D-cell function in H pylori infection.

Animals↗
PubMed1998

Pathogenic mechanisms in Helicobacter pylori infection.

The likelihood of clinical disease is affected by the strain of Helicobacter pylori, and whether gastritis extends to the gastric corpus. Plentiful acid from a healthy corpus may cause duodenal ulcers while corpus gastritis and acid hyposecretion are associated with gastric cancer.

Genes, Bacterial↗
PubMed1997

Stimulation of IL-8 production in human gastric epithelial cells by Helicobacter pylori, IL-1beta and TNF-alpha requires tyrosine kinase activity, but not protein kinase C.

Production of interleukin 8 (IL-8) is believed to be important in the pathogenesis of the gastritis seen in Helicobacter pylori infection. The aim of this study was to investigate the roles of protein kinase A (PKA), protein kinase C (PKC), protein tyrosine kinase (PTK) and intracellular calcium in the induction of IL-8 production by gastric epithelial cells. AGS gastric epithelial cells were stimulated with H. pylori, tumour necrosis factor alpha or interleukin 1beta together with activators or inhibitors of the relevant kinases. IL-8 production was measured by enzyme-linked immunosorbent assay. Helicobacter pylori, tumour necrosis factor alpha and interleukin 1beta produced a dose-dependent increase in IL-8 production. The increase with all three was significantly reduced by the tyrosine kinase inhibitors herbimycin A and genistein. Activation of PKC by phorbol myristate acetate was also an effective stimulus to IL-8 production and this was blocked by PKC depletion or inhibitors. Protein kinase C inhibition did not reduce the stimulation produced by H. pylori or the cytokines. Stimulation of PKA with forskolin or dibutyryl cyclic adenosine monophosphate or inhibition with H89 had no effect on IL-8 production. The calcium ionophore A23187 was a weak, PKC dependent, stimulant of IL-8 production. The production of IL-8 in AGS cells is stimulated via tyrosine kinase and protein kinase C dependent pathways. Stimulation by H. pylori, tumour necrosis factor alpha and interleukin 1beta requires tyrosine kinase activity.

Calcium↗
PubMed1997

Effect of transforming growth factor alpha and interleukin 8 on somatostatin release from canine fundic D cells.

BACKGROUND & AIMS: Helicobacter pylori infection in patients who have peptic ulcer disease is associated with altered regulation of gastric secretion, hypergastrinemia, and diminished somatostatin expression in gastric mucosa. Tumor necrosis factor (TNF)-alpha and interleukin (IL)-8 are the predominant cytokines produced in the gastric mucosa of patients with H. pylori infection. The aim of this study was to examine whether IL-8 and TNF-alpha could regulate somatostatin release from isolated canine gastric D cells. METHODS: Canine gastric D cells were isolated from fundic mucosa and enriched by centrifugal elutriation. Secretagogue-stimulated somatostatin release was measured by radioimmunoassay. RESULTS: TNF-alpha dose dependently increased somatostatin release after 2 hours of treatment. The stimulatory effect of TNF-alpha was additive to that of epinephrine but was unaffected by a maximal concentration of cholecystokinin. IL-8 did not alter basal or secretagogue (cholecystokinin, epinephrine)-mediated somatostatin release. The stimulatory effect of TNF-alpha (10 ng/mL) was potentiated by the addition of IL-8 (1 nmol/L), inhibited by octreotide and staurosporine, but unaffected by indomethacin. Pretreatment of D cells with TNF-alpha (10 ng/mL) for 24 hours abolished the subsequent stimulatory effect of this cytokine and secretagogues on somatostatin release. CONCLUSIONS: TNF-alpha was shown to regulate somatostatin release from cultured D cells in a divergent manner.

Animals↗
PubMed1997

How does Helicobacter pylori cause mucosal damage? Its effect on acid and gastrin physiology.

Helicobacter pylori infection increases gastric acid secretion in patients with duodenal ulcers but diminishes acid output in patients with gastric cancer and their relatives. Investigation of the basic mechanisms may show how H. pylori causes different diseases in different persons. Infection of the gastric antrum increases gastrin release. Certain cytokines released in H. pylori gastritis, such as tumor necrosis factor alpha and specific products of H. pylori, such as ammonia, release gastrin from G cells and might be responsible. The infection also diminishes mucosal expression of somatostatin. Exposure of canine D cells to tumor necrosis factor alpha in vitro reproduces this effect. These changes in gastrin and somatostatin increase acid secretion and lead to duodenal ulceration. But the acid response depends on the state of the gastric corpus mucosa. The net effect of corpus gastritis is to decrease acid secretion. Specific products of H. pylori inhibit parietal cells. Also, interleukin 1 beta, which is overexpressed in H. pylori gastritis, inhibits both parietal cells and histamine release from enterochromaffin-like cells. H. pylori also promotes gastric atrophy, leading to loss of parietal cells. Factors such as a high-salt diet and a lack of dietary antioxidants, which also increase corpus gastritis and atrophy, may protect against duodenal ulcers by decreasing acid output. However, the resulting increase of intragastric pH may predispose to gastric cancer by allowing other bacteria to persist and produce carcinogens in the stomach.

Animals↗
PubMed1997

The effect of gastrin-releasing peptide on gastrin and somatostatin messenger RNAs in humans infected with Helicobacter pylori.

BACKGROUND & AIMS: Gastrin-releasing peptide stimulates gastrin secretion but also inhibits its release via somatostatin. Exogenous gastrin-releasing peptide stimulates a greater increase in plasma gastrin concentrations in patients infected with Helicobacter pylori than in uninfected controls. Because this infection suppressed gastric mucosal somatostatin, we studied whether the increased gastrin response was a result of an abnormal response of the somatostatin cell. METHODS: Patients without dyspeptic ulcers received an infusion of either gastrin-releasing peptide or saline on separate occasions. Acid secretion was measured, and gastric biopsy specimens were taken for gastrin and somatostatin messenger RNA (mRNA) analysis and H. pylori diagnosis. RESULTS: In response to gastrin-releasing peptide, the increase in plasma gastrin concentrations in the infected patients was significantly higher than in the uninfected. Antral gastrin mRNA also increased significantly in the infected group but decreased significantly in the uninfected group. Basal somatostatin was lower in the infected group; gastrin-releasing peptide produced a significant increase in antral somatostatin mRNA concentration in infected, but not uninfected, patients. CONCLUSIONS: The somatostatin cell responds to gastrin-releasing peptide in H. pylori infection. Gastrin-releasing peptide normally inhibits gastrin mRNA expression, but inhibition is deficient in H. pylori infection, possibly because of low stimulated somatostatin levels.

Adult↗
PubMed1997

Effect of Helicobacter pylori products and recombinant cytokines on gastrin release from cultured canine G cells.

BACKGROUND & AIMS: The pathophysiology of hypergastrinemia in Helicobacter pylori infection is undefined, but the infected antrum shows a marked inflammatory response with local production of cytokines. Hypergastrinemia and inflammatory infiltrate clear with successful eradication. The aim of this study was to examine whether the cytokines tumor necrosis factor alpha or interleukin 8 (IL-8), which are produced in the gastric mucosa of patients with H. pylori-induced peptic disease or H. pylori products, can stimulate gastrin release from isolated cultured canine G cells. METHODS: Canine G cells were isolated by collagenase digestion, enriched by centrifugal elutriation, incubated with cytokines, bacterial components, or both, and gastrin release was measured by radioimmunoassay. RESULTS: IL-8 (1 and 10 nmol/L) stimulated gastrin release by 34% +/- 13% and 43% +/- 23% (P < 0.05) above basal, respectively. H. pylori sonicates, water extract preparations, and lipopolysaccharide had no stimulatory actions, but the sonicates from two of four strains potentiated the effects of IL-8, leading to maximal gastrin release of 230% +/- 130% and 232% +/- 33% above basal, respectively (P < 0.05). CONCLUSIONS: IL-8 stimulated gastrin release from isolated G cells, and the effect was potentiated by H. pylori products. The interaction of cytokines and H. pylori may contribute to the hypergastrinemia seen in vivo.

Animals↗
PubMed1997

Helicobacter pylori stimulates granulocyte-macrophage colony-stimulating factor (GM-CSF) production from cultured antral biopsies and a human gastric epithelial cell line.

OBJECTIVE: To examine the regulation of granulocyte-macrophage colony-stimulating factor (GM-CSF) production by gastric epithelial cells in Helicobacter pylori infection. DESIGN: The effect of H. pylori infection on gastric GM-CSF production was assessed using short-term culture of antral biopsies. The mechanism of GM-CSF induction was investigated using a gastric epithelial cancer cell line. METHODS: Production of GM-CSF was assessed by enzyme-linked immunosorbent assay. The mechanism of stimulation of GM-CSF production was examined by co-culture of AGS carcinoma cells with H. pylori and specific stimulants and inhibitors. RESULTS: Biopsies from H. pylori-negative patients in the basal state did not produce GM-CSF. However, over 24 h in the presence of the active phorbol ester, phorbol myristate acetate (PMA), significant release of GM-CSF was seen. H. pylori-positive biopsies produced significantly more GM-CSF in both the unstimulated and PMA-stimulated state than H. pylori-negative biopsies. Constitutive release of GM-CSF from cultured human gastric AGS cells could be significantly enhanced by co-culture with live H. pylori or the addition of interleukin-1 beta, tumour necrosis factor alpha and PMA, but not by exposure to forskolin. The protein kinase C inhibitor staurosporine abolished the stimulatory effect of PMA on AGS cells, whereas the protein-tyrosine kinase inhibitor herbimycin A prevented the stimulation of GM-CSF production seen with H. pylori and both cytokines. CONCLUSION: H. pylori enhances GM-CSF production by gastric epithelia. H. pylori appears to stimulate gastric epithelial cells directly to produce GM-CSF and this stimulation involves a tyrosine kinase dependent step. Induction of GM-CSF may play a role in the initiation and perpetuation of gastric inflammation in H. pylori infection.

Adenocarcinoma↗
PubMed1997

Helicobacter pylori infection and tumour necrosis factor-alpha increase gastrin release from human gastric antral fragments.

OBJECTIVES: To investigate the mechanism of the hypergastrinaemia associated with Helicobacter pylori infection by examining the effect of H. pylori infection and the cytokine tumour necrosis factor-alpha (TNF-alpha) on gastrin release from human antral fragments. DESIGN: In-vitro experimental study. METHODS: Human antral biopsy fragments were cultured for 6 h with and without TNF-alpha (20 ng/ml) and the gastrin released over the following 2-h stimulation period measured by radioimmunoassay. The integrity of the paracrine feedback loop inhibiting gastrin release was tested by concurrent administration of cholecystokinin (CCK). RESULTS: H. pylori-positive fragments were associated with significantly greater bombesin-stimulated gastrin release (increased by 40%, P < 0.05) and less inhibition produced by CCK administration (decreased by 55%, P < 0.05), than H. pylori-negative fragments. TNF-alpha treatment of H. pylori-negative fragments significantly enhanced bombesin-stimulated gastrin release (by 82%, P < 0.01) and diminished inhibitory feedback by CCK (by 53%, P < 0.05). CONCLUSION: H. pylori infection is associated with enhanced gastrin release from human antrum and TNF-alpha produces a similar effect. Proinflammatory cytokines generated in the antrum in response to the infection are likely to play a significant role in the hypergastrinaemia of H. pylori infection.

Bombesin↗
PubMed1997

Effect of N alpha-methyl-histamine on acid secretion in isolated cultured rabbit parietal cells: implications for Helicobacter pylori associated gastritis and gastric physiology.

BACKGROUND: Helicobacter pylori has been shown to produce the unusual metabolite N alpha-methyl-histamine. This compound is known to be a potent agonist at inhibitory histamine H3 receptors. There is increasing evidence implicating this receptor in the control of gastric acid secretion but the mechanism for this remains to be clarified. AIMS: To investigate the effect of N alpha-methyl-histamine on the acid secretory activity of parietal cells and to determine the mechanism for such effects, thus helping to determine the role of this compound in the pathophysiology of H pylori infection. METHODS: Rabbit parietal cells were isolated and enriched by collagenase-EDTA digestion and centrifugal elutriation. Following culture on Matrigel coated plates, acid secretion was assessed by 14C aminopyrine accumulation. RESULTS: N alpha-methyl-histamine (100 microM) was as potent as histamine (100 microM) in stimulating acid secretion. This effect was reversed by ranitidine indicating it was mediated via the H2 receptor. N alpha-methyl-histamine potentiated the effects of both carbachol (increased by 280%) and gastrin (by 350%) (p < 0.01). N alpha-methyl-histamine had no inhibitory actions on forskolin or carbachol stimulated acid secretion suggesting that there is not an inhibitory H3 receptor located directly on the parietal cell. CONCLUSIONS: Bacterially produced N alpha-methyl-histamine directly stimulates acid secretion by parietal cells and this may contribute to the increased acid secretion that contributes to duodenal ulceration.

Aminopyrine↗
PubMed1997

Effects of a panel of dietary lectins on cholecystokinin release in rats.

We previously showed that soybean lectin (SBL) releases cholecystokinin (CCK) and have now asked whether other dietary lectins have this effect and if extracellular calcium is involved. Lectins and vehicle were first infused into the duodenum of anesthetized rats. The CCK response to vehicle was 3.1 +/- 0.6 pmol/l (P < 0.05 vs. basal). SBL and peanut lectin (PNL) (84 microg/ml) significantly increased plasma CCK concentrations from 2.0 +/- 0.4 pmol/l to a maximum of 8.4 +/- 0.5 pmol/l (P < 0.01 vs. vehicle, mean +/- SE) and from 1.9 +/- 0.5 to 7.0 +/- 0.6 pmol/l (P < 0.05 vs. vehicle, mean +/- SE), respectively. Wheat germ lectin (WGL) (840 microg) also increased plasma CCK levels from 1.5 +/- 0.3 pmol/l to a maximum of 9.7 +/- 1.3 pmol/l (P < 0.05 vs. vehicle, mean +/- SE). Corresponding increases in pancreatic protein output occurred. Broad bean lectin (BBL) had no effect on either parameter. Dose-dependent responses were seen with SBL, PNL, and WGL (1, 10, and 100 microg/ml) in perifused rat intestinal cells. These responses were abolished in calcium-free medium and in the presence of the competing sugars of the lectins. Therefore, SBL, PNL, and WGL, which bind to motifs including N-acetyl-D-galactosamine, galactose, and N-acetylglucosamine, respectively, released CCK, but BBL, which binds to mannose and glucose, did not. Ingestion of lectins may have major CCK-mediated effects on gastrointestinal function and growth.

Animals↗
PubMed1997

Cytoplasmic antineutrophil cytoplasmic antibody-positive vasculitis associated with ulcerative colitis.

The case of a man with poorly controlled ulcerative colitis, who developed a cytoplasmic antineutrophil cytoplasmic antibody-positive systemic vasculitis, causing small bowel infarction is reported. Antineutrophil cytoplasmic antibodies occur in 50-70% of patients with ulcerative colitis, but are usually of the perinuclear or atypical pattern; the cytoplasmic pattern seen in this case is indicative of systemic vasculitis. A variety of vasculitic diseases have been reported as occurring rarely with ulcerative colitis, but this report is the first description of a cytoplasmic antineutrophil cytoplasmic antibody-positive vasculitis with this association.

Adult↗
PubMed1997

Host mechanisms: are they the key to the various clinical outcomes of Helicobacter pylori infection?

It is unclear why Helicobacter pylori produces different diseases in different persons. High and low acid secretion rates probably contribute to duodenal ulceration and gastric carcinogenesis, respectively. Both of these changes seem to be corrected by eradicating Helicobacter pylori. We are therefore exploring the basic mechanisms and asking why patients react differently? Helicobacter pylori products and certain cytokines released in Helicobacter pylori gastritis release gastrin from G-cells but inhibit parietal cells. Also tumour necrosis factor alpha inhibits somatostatin-cells and interleukin 1 beta inhibits enterochromaffin-like cells. The net result is that antral gastritis tends to increase, whilst corpus gastritis tends to decrease acid secretion. Corpus atrophy further lowers acid through loss of parietal cells. Factors postulated to increase corpus gastritis include host genetics, early acquisition of Helicobacter pylori, more aggressive strains, poor general health and diets high in salt or lacking in antioxidant vitamins. Further research should address the interaction of bacterium, host and environment with a view to preventing the serious clinical outcomes.

Cytokines↗
PubMed1996

Reflux symptom relief with omeprazole in patients without unequivocal oesophagitis.

BACKGROUND: As many as 50% of patients with reflux symptoms have no endoscopic evidence of oesophagitis. This multicentre study was designed to assess symptom relief after omeprazole 20 mg once daily in patients with symptoms typical of gastro-oesophageal reflux disease but without endoscopic evidence of oesophagitis. METHODS: Patients (n = 209) were randomized in a double-blind study to receive either omeprazole 20 mg once daily (n = 98) or placebo (n = 111) for 4 weeks. Symptoms were assessed at clinic visits and using daily diary cards, with patient-completed questionnaires providing additional data on symptoms and on psychological disturbance. RESULTS: On completion, symptom relief favoured omeprazole: 57% of patients on omeprazole were free of heartburn (vs. 19% on placebo), 75% were free of regurgitation (47%) and 43% were completely asymptomatic (14%), each with P < 0.0001. Fewer patients in the omeprazole group required alginate/antacid relief medication (P < 0.05). Symptom relief (time to first heartburn-free day) was more rapid with omeprazole (2 vs. 5 days on placebo; P < 0.01). A greater reduction in anxiety occurred in the omeprazole group (P < 0.05). CONCLUSION: Omeprazole 20 mg once daily is effective in providing relief of the symptoms typical of gastro-oesophageal reflux disease in patients with essentially normal oesophageal mucosa.

Adult↗
PubMed1996

Tumour necrosis factor alpha stimulates gastrin release from canine and human antral G cells: possible mechanism of the Helicobacter pylori-gastrin link.

There is evidence that gastric Helicobacter pylori (Hp) infection promotes duodenal ulceration by releasing gastrin. We therefore asked how Hp releases gastrin. Tumour necrosis factor alpha (TNF-alpha) is up-regulated in Hp gastritis and stimulates hormone release from pituitary cells, so we tested its effect on primary cultures of canine antral G cells and human antral fragments. TNF-alpha pretreatment (100 ng mL-1) of canine G cells significantly increased both basal (by 89%: P < 0.01) and bombesin-stimulated (by 39% P < 0.05) gastrin release. A similar pattern of increase was seen following TNF-alpha (20 ng mL-1) pretreatment of human antral fragments: basal gastrin release was increased by 38% (P < 0.05) and bombesin-stimulated by 26% (P < 0.05). This effect persisted during immunoblockade with anti-somatostatin antibody S6. We propose that TNF-alpha provides the link between Hp infection and gastrin release and thus contributes to duodenal ulceration.

Animals↗