Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0013395 (dyspepsia)
 4,879 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously cloned 10 Helicobacter pylori antigen genes from a Chilean strain including: cytotoxin VacA, a truncated region of CagA (called A17), a species-specific protein (Ag26), urease subunits (UreA, UreB), a flagellin, (FlaB), heat shock proteins (HspA and HspB), an adhesin (HpaA) and a lipoprotein (Lpp20). Immunogenicity of these antigens was tested by immunoblot with sera of Chilean infected patients, revealing that HpaA, A17, HspB and VacA were more frequently recognized (86%, 82%, 68% and 68%, respectively). According to the clinical condition, it was determined that Lpp20 was preferentially recognized by sera from non-ulcer dyspepsia patients (80%), A17 and VacA by patients with duodenal ulcer (92% and 83% respectively), and HspB by patients with duodenal ulcer (83%) and gastric cancer (90%). An ELISA was developed with a purified mixture of A17 and VacA antigens to test the different groups of patients. It was found that sera from duodenal ulcer patients showed higher values than those from non-ulcer dyspepsia patients, but this difference was not significant (p<0.2). Moreover, sera from gastric cancer patients showed values lower than those from non-ulcer dyspepsia patients (p<0.019). These results indicate that, in the Chilean population, antibodies raised against VacA and A 7 are not markers either for duodenal ulcer or for gastric cancer.
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PMID:Serological response to Helicobacter pylori recombinant antigens in Chilean infected patients with duodenal ulcer, non-ulcer dyspepsia and gastric cancer. 1066 Jan 36

Helicobacter pylori (HP), undoubtedly, the most common world-wide infection plays an important role in pathogenesis of peptic ulcer. Proof for a causal role for HP in peptic ulcer rests in two major points; 1) the majority of ulcer patients are HP infected and the prevalence of this infection for both gastric ulcer (GU) and duodenal ulcer (DU) is much higher than for gender- and age-adjusted controls and 2) the cure of HP infection dramatically reduces ulcer recurrence. Conclusions regarding the mechanisms by which HP induces peptic ulcer are restricted mainly to studies observing the consequences of its eradication by antibiotics combined with gastric inhibitors or bismuth agents. Several specific virulence factors such as cytotoxin-associated gene A (CagA) and vacuolating cytotoxin A (VacA) as well as other noxious substances including ammonia, lipopolysaccharide (endotoxin), platelet activating factor (PAF), nitric oxide (NO) and others have been implicated in gastritis and were found to be significantly more frequent in gastric cancer than in gender- and age-matched controls, especially in younger generation. Chronic inflammation, atrophic gastritis, intestinal metaplasia, impaired defense mechanisms combined with hypergastrinemia, deficiency of vitamin C in the stomach , excessive oxygen metabolites and epithelial cell proliferation have been associated with gastric cancer. This multi-step pathway originally proposed by Correa and his colleagues, long before the HP was discovered in the stomach, leads to cancer but may be reversed by eradication of HP. This is, however, a controversial issue because gastric atrophy and intestinal metaplasia may be also caused by other factors such as bile reflux, dietary irritants, and autoimmunity. The implication of HP in MALT-lymphoma is based on the observations that eradication of HP in early stage of low-grade of this tumor leads to complete remission. The significance of HP in non-ulcer dyspepsia remains questionable and requires further studies.
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PMID:Helicobacter pylori associated gastric pathology. 1069 52

Numerous epidemiological studies demonstrated the association between Helicobacter pylori (H. pylori) infection and gastric cancer but the mechanism of the involvement of H. pylori in gastric cancerogenesis remains virtually unknown. This study was designed to determine the seropositivity of H. pylori and cytotoxin associated gene A (CagA), serum gastrin and gastric lumen gastrin levels under basal conditions and following stimulation with histamine in gastric cancer patients and controls. 100 gastric cancer patients aging from 21 to 60 years and 300 gender- and age-adjusted controls hospitalized with non-ulcer dyspepsia (NUD) entered this study. 13C-Urea Breath Test (UBT), serum immunoglobulin (IgG) antibodies to H. pylori and CagA were used to assess the H. pylori infection and serum levels of IL-1beta, IL-8 and TNFalpha were measured by enzyme-linked immunosorbent assay (ELISA) to evaluate the degree of gastric inflammation by H. pylori . Gastrin-17 mRNA and gastrin receptors (CCK(B)) mRNA expression in gastric mucosal samples taken by biopsy from the macroscopically intact fundic and antral mucosa as well as from the gastric tumor was determined using RT-PCR. The overall H. pylori seropositivity in gastric cancer patients at age 21-60 years was about 92%, compared, respectively, to 68%, in controls. A summary odds ratio (OR) for gastric cancer in H. pylori infected patients was about 5.0 . The H. pylori CagA seropositivity in gastric cancer patients was about 58.5% compared to 32.4% in controls, giving the summary OR for gastric cancer in CagA positive patients about 8.0. The prevalence of H. pylori- and H. pylori CagA-seropositivity was significantly higher in cancers than in controls, irrespective of the histology of gastric tumor (intestinal, diffuse or mixed type). Median IL-1beta and IL-8 reached significantly higher values in gastric cancer patients (9.31 and 30.8 pg/ml) than in controls (0.21 and 3.12, respectively). In contrast, median serum gastrin in cancers (as total group) was several folds higher (62.6 pM) than in controls (19.3 pM). Also median luminal gastrin concentration in gastric cancer patients was many folds higher (310 pM) than in controls (20 pM). This study shows for the first time that cancer patients are capable of releasing large amounts of gastrin into the gastric lumen to increase luminal hormone concentration to the level that was recently reported to stimulate the growth of H. pylori. There was no any correlation between plasma gastrin levels and gastric luminal concentration of gastrin suggesting that: 1) luminal gastrin originates from different source than plasma hormone, most probably from the cancer cells, 2) cancer cells are capable of expressing gastrin and releasing it mainly into the gastric juice and 3) the gastric cancer cells are equipped with gastrin-specific (CCK(B)) receptor so they exhibit the self-growth promoting activity in autocrine fashion. This notion is supported by direct detection of gastrin mRNA and gastrin receptor (CCK(B)-receptors) mRNA using RT-PCR in cancer tissue. To our knowledge this is the first study showing an important role of gastrin as self-stimulant of cancer cells in patients infected with H. pylori. Basal and histamine maximally stimulated acid outputs were significantly lower in gastric cancer patients than in controls despite of enhanced gastrin release, particularly in cancer patients and this might reflect the mucosal inflammatory changes (increased serum levels of proinflammtory interleukins - IL-1beta and IL-8), that are known to increase gastrin release. We conclude that: 1) H. pylori infected patients, particularly those showing CagA-seropositivity, are at greatly increased risk of development of gastric cancer, 2) H. pylori-infected cancer patients produce significantly more IL-1beta and IL-8 that might reflect an H. (ABSTRACT TRUNCATED)
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PMID:Role of gastrin in gastric cancerogenesis in Helicobacter pylori infected humans. 1069 65

Previously we demonstrated an inverse relation between cancer of the gastrointestinal tract and glutathione S-transferase activity of the gastrointestinal mucosa. Chronic infection with H. pylori has been associated with an increased risk of gastric cancer. The aim of this study was to investigate the levels of glutathione and glutathione S-transferase activity in H. pylori-infected and noninfected antral mucosa. Glutathione and glutathione S-transferases were measured in antral biopsies of patients with nonulcer dyspepsia without H. pylori infection (A), with prior H. pylori infection who became H. pylori negative after eradication therapy (B) and with proven H. pylori infection (C). Glutathione concentration and glutathione S-transferase activity in group A were 31.0 (range 6.0-59.6) nmol/mg protein and 810 (range 165-1312) nmol/min/mg protein, in group B 27.0 (range 5.0-53.8) nmol/mg protein and 745 (range 403-1199) nmol/min/mg protein, and in group C 18.5 (range 1.6-55.8) nmol/mg protein and 572 (range 144-1047) nmol/min/mg protein, respectively. The glutathione and glutathione S-transferase values were significantly lower in patients infected with H. pylori than in patients who were H. pylori negative.
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PMID:Antral glutathione concentration and glutathione S-transferase activity in patients with and without Helicobacter pylori. 1074 43

In-depth meetings of the XIth International Workshop on Gastroduodenal Pathology and Helicobacter pylori led to the presentation and discussion of extensive new data on H. pylori and its diseases. The mode of transmission of H. pylori remains unclear, and it remains unknown why only a small proportion of infected individuals develop duodenal or gastric ulcer disease and even fewer develop gastric cancer. The role of H. pylori eradication in persons with uninvestigated dyspepsia remains controversial. New clinical trials of H. pylori treatment show symptom relief and improvement in the quality of life of persons with functional dyspepsia, especially in those with ulcer-like or reflux-like dyspepsia. Clearly the move is toward symptom-based management of persons with dyspepsia, with fewer endoscopies being needed in the otherwise healthy young dyspeptic patients. It remains controversial whether eradicating H. pylori in duodenal ulcer or functional dyspepsia increases the risk of subsequent development of gastroesophageal reflux disease. The one-week proton pump inhibitor-based triple regimens remain the gold standard of H. pylori therapy, but some of the ranitidine bismuth citrate plus two antibiotic regimens also achieve an 80% H. pylori eradication rate on an intention-to-treat basis. While the urea breath test remains the noninvasive test of choice, interesting new data are available on the use of stool antigen testing to diagnose H. pylori infection. The number of H pylori-associated gastroduodenal diseases grows to include possible liver, vascular, immune and skin conditions.
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PMID:From bench to bedside to bug: an update of clinically relevant advances in the care of persons with Helicobacter pylori- associated diseases. 1075 16

The study aimed to examine the serum serological response among H. pylori-infected patients with various upper gastrointestinal diagnoses; to ascertain whether it could be predictive to the diagnostic outcome of dyspepsia. One hundred seventy H. pylori-infected patients with dyspeptic symptoms but without previous treatment were enrolled, including those with duodenal ulcer disease (N = 47), gastric ulcer (N = 23), nonulcer dyspepsia (N = 60), gastric cancer (N = 34), and MALToma (N = 6). Sera from dyspeptic patients without H. pylori infection (N = 33) were used as controls. During endoscopy, gastric biopsies were taken for CLO-test, histology, and culture for the detection of H. pylori infection, defined by a positive culture or positive results of both CLO-test and histology. Total H. pylori IgG antibody was tested by an ELISA method. Antibody responses to specific H. pylori proteins were tested by a western blotting system. Of patients with H. pylori-infected gastroduodenal diseases, 76.5%, 42.9%, 23.6%, 46.7%, 84.1%, 76.5%, 82.9%, and 32.4% on average, showed responses to the 116-kDa (CagA), 89-kDa (VacA), 60-kDa, 45-kDa, 35-kDa, 30-kDa, 26.5-kDa, and 19.5-kDa H. pylori-specific proteins, respectively. A significant association was found between the serological response to 19.5-kDa and 26.5-kDa proteins and malignant outcome of H. pylori infection (P<0.02). Among patients without malignancy, the absence of a band at 19.5 kDa was statistically associated with the presence of an ulcer (P<0.05). The presence of serum antibody against CagA is not different between patients with ulcer and with malignancy in clinical diagnosis. The serum test for detecting antibodies against lower-molecular-weight proteins of H. pylori, such as those of 19.5 and 26.5 kDa, could be useful to identify H. pylori-infected patients at risk of peptic ulcer or malignancy.
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PMID:Serologic response to lower-molecular-weight proteins of H. pylori is related to clinical outcome of H. pylori infection in Taiwan. 1075 50

Our knowledge of Helicobacter pylori infection is now changing the way in which we investigate patients presenting with dyspepsia, with noninvasive H. pylori testing replacing endoscopy. Non-invasive H. pylori testing has been shown to be useful in predicting the underlying diagnosis in patients presenting with dyspepsia. Several studies have shown that 20-50% of dyspeptic patients with a positive H. pylori test will have evidence of underlying ulcer disease or duodenitis. In contrast, less than 5% of dyspeptic patients with a negative H. pylori test will have evidence of ulcer disease and in these subjects, the likeliest diagnosis is gastroesophageal reflux disease. This has led to many groups recommending that noninvasive H. pylori testing should be used in place of endoscopy, with all those testing positive being given anti-H. pylori therapy and those testing negative being treated symptomatically. One concern about nonendoscopic management of dyspeptic patients is the possibility of missing underlying malignancy but studies have shown that in western countries this is rare in patients less than 55 years of age presenting with dyspepsia in the absence of sinister symptoms. There is increasing evidence supporting eradication of H. pylori infection in dyspeptic patients without ulcer disease. Meta-analysis of four prospective randomized trials indicates that such treatment is superior to placebo in about 10% of subjects. H. pylori-positive dyspeptic patients are also recognized to have an increased risk of developing ulcer disease in the future which will be removed by treating the infection. Another justification for eradicating the infection in the absence of ulcer disease is the fact that H. pylori infection is now proven to be a risk factor for gastric cancer. Prospective randomized studies comparing endoscopy with noninvasive H. pylori testing in the management of dyspeptic patients indicate that managing dyspepsia by noninvasive H. pylori testing is at least as effective as endoscopic-based management in producing symptomatic resolution and saves a substantial number of endoscopic procedures. There is therefore now substantial evidence indicating that noninvasive H. pylori testing should be used in place of endoscopy to determine the management of younger dyspeptic patients without sinister symptoms and who are not taking nonsteroidal anti-inflammatory drugs.
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PMID:Should non-invasive Helicobacter pylori testing replace endoscopy in investigation of dyspepsia? 1082 49

Free radicals (FRs) play an important role in the pathogenesis of gastroduodenal mucosal inflammation, peptic ulcer disease, and probably even gastric cancer. Various micronutrients protect the gastric mucosa by scavenging FRs. Only limited data is available regarding the concentration of micronutrients in the gastric mucosa in patients with gastritis and peptic ulcer disease. Our aim was to analyze micronutrient antioxidant concentrations in the antral mucosa in patients with gastritis and gastric ulcer and to determine the influence of Helicobacter pylori infection on gastric mucosal antioxidants in patients with gastritis and gastric ulcer. Patients who underwent upper endoscopy for evaluation of dyspepsia were included in the study. Ascorbic acid, alpha-tocopherol, alpha-carotene, beta-carotene, total carotenoids, lutein, cryptoxanthin, and lycopene levels were measured in the sera and antral mucosal biopsies in these patients. The diagnosis of H. pylori was confirmed by histology, urease test (CLO) and serology. Patients with negative endoscopic findings and normal histology and no H. pylori infection served as controls. In patients with gastritis, alpha-tocopherol levels were reduced in serum and mucosa irrespective of H. pylori status, whereas carotenoids and ascorbic acid levels were similar to controls. However, in patients with gastric ulcer, serum and mucosal levels of all micronutrient antioxidants were markedly decreased compared with both controls and patients with gastritis. The degree of depletion of antioxidants was similar in patients with either H. pylori-induced or nonsteroidal antiinflammatory drug (NSAID)-induced ulcers. Patients with gastric ulcer have very low gastric antioxidant concentrations compared to patients with gastritis and normal mucosa. This depletion in antioxidants seems to be a nonspecific response and was not related to H. pylori infection.
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PMID:Micronutrient antioxidants in gastric mucosa and serum in patients with gastritis and gastric ulcer: does Helicobacter pylori infection affect the mucosal levels? 1115 82

Discrepancies among reports from different geographical regions worldwide on the association between the presence of cagA and peptic ulcer disease prompted this study on the predictive value of the cagA gene in Helicobacter pylori-associated gastroduodenal diseases in the Singapore population. H. pylori strains were obtained from 169 patients with a peptic ulcer, 83 with non-ulcer dyspepsia, and nine with gastric cancer. The presence of the cagA gene was evaluated by polymerase chain reaction (PCR). The expected 400 bp PCR product coding for the cagA gene was present in 232/261 (89%) H. pylori isolates. Of these, 151/169 (89%) strains from patients with peptic ulcer, 73/83 (88%) strains from patients with non-ulcer dyspepsia and 8/9 (89%) strains from cancer patients were positive for the cagA gene. There was no statistically significant difference between the prevalence of cagA-positive strains from patients with distinct clinical outcomes (p > 0.05). The prevalence of cagA-positive strains in the Singapore population is high regardless of clinical disease status. The results suggest that the cagA gene is not a universal virulence marker of H. pylori.
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PMID:The status of the cagA gene does not predict Helicobacter pylori-associated peptic ulcer disease in Singapore. 1088 1

Helicobacter pylori is a recognized cause of a variety of gastroduodenal pathology. The high prevalence of both H pylori infection and related diseases within the community warrants its consideration as a public health care issue. The availability of reliable and safe noninvasive diagnostic techniques coupled with the development of effective and tolerable treatments has enabled primary health care personnel to manage this infection actively. The role of the primary care physician in the future management of H pylori infection is thus of central importance. The wealth of evidence produced by over 15 years of research into H pylori has expanded the list of disease associations and treatment benefits as well as elucidated the pathophysiological mechanisms involved. As a result, there has been a growing need to harmonize this information with clinical practice and to provide direction for the appropriate management by both specialists and general practitioners. Several national guidelines have been produced. The areas relating to H pylori infection that they considered and their recommendations vary. In 1994, the National Institutes of Health produced globally accepted recommendations for the management of H pylori-related peptic ulceration. The broader role of H pylori as a gastroduodenal pathogen and a public health care issue was not addressed. Recently, European and Canadian consensus guidelines have been published that identified overall management issues, including the role of primary and specialist care, and considered the appropriateness of employing eradication therapy for the spectrum of conditions in which H pylori has a direct or indirect association based on the available information. These guidelines, while in agreement regarding many issues, differ considerably in their recommendations for primary health care and regarding central issues such as the management of dyspepsia and gastric cancer. Some variations may reflect differing health care structures as well as the prevalence of both infection and associated diseases. However, the interpretation of evidence produced by recent research contributes to their conflicting statements.
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PMID:Consensus guidelines: agreement and debate surrounding the optimal management of Helicobacter pylori infection. 1088 32


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