In a search for Helicobacter species in the intestinal mucosae of 42 patients with ulcerative col... more In a search for Helicobacter species in the intestinal mucosae of 42 patients with ulcerative colitis (UC) and 74 without UC, only H. pylori was found. Although the bacterium was detected in UC patients by culture (7.1%) and nested PCR (19.0%), its presence was not associated with the disease ( P = 0.13).
Although Helicobacter heilmannii infection is less common than H. pylori infection in humans, it ... more Although Helicobacter heilmannii infection is less common than H. pylori infection in humans, it is considered to be of medical importance because of its association with gastritis, gastric ulcer, carcinoma, and mucosa-associated lymphoid tissue lymphoma of the stomach. However, there have been no studies evaluating the role of the Th cell response in H. heilmannii gastric infection. We evaluated the participation of pro-inflammatory and anti-inflammatory cytokines, IFN-γ and IL-4, in H. heilmannii gastric infection in genetically IFN-γ-or IL-4-deficient mice. The serum IFN-γ and IL-4 concentrations were determined by ELISA. The gastric polymorphonuclear infiltrate was higher (P = 0.007) in H. heilmannii-positive than in H. heilmanniinegative wild-type (WT) C57BL/6 mice, whereas no significant inflammation was demonstrable in the stomach of H. heilmannii-positive IFN-γ-/-C57BL/6 mice. The degree of gastric inflammatory cells, especially in oxyntic mucosa, was also higher (P = 0.007) in infected IL-4-/than in WT BALB/c mice. Serum IFN-γ levels were significantly higher in IL-4-/than in WT BALB/c mice, independently of H. heilmannii-positive or-negative status. Although no difference in serum IFN-γ levels was seen between H. heilmannii-positive (11.3 ± 3.07 pg/mL, mean ± SD) and-negative (11.07 ± 3.5 pg/mL) WT BALB/c mice, in the group of IL-4-/animals, the serum concentration of IFN-γ was significantly higher in the infected ones (38.16 ± 10.5 pg/ mL, P = 0.04). In contrast, serum IL-4 levels were significantly decreased in H. heilmannii-positive (N = 10) WT BALB/c animals compared to the negative (N = 10) animals. In conclusion, H. heilmannii infection induces a predominantly Th1 immune response, with IFN-γ playing a central role in gastric inflammation.
The histamine concentration of the oxyntic mucosa was determined in Helicobacter pylori-positive ... more The histamine concentration of the oxyntic mucosa was determined in Helicobacter pylori-positive patients with duodenal ulcer before and after antimicrobial therapy and in H. pylori-negative subjects. Determination of serum gastrin was also performed in duodenal ulcer patients before and after H. pylori eradication. The histamine content of the oxyntic mucosa was lower in patients with duodenal ulcer than in H. pylori-negative subjects, but it increased after H. pylori eradication. Conversely, in patients in whom therapy failed to eradicate the microorganism, the histamine content remained unchanged. Serum gastrin levels fell after microorganism eradication, and the percentage of this fall was correlated with the percentage of increase in gastric histamine. In conclusion, our findings suggest that abnormalities of histamine store present in duodenal ulcer patients might be a feature of H. pylori infection.
Skip to Content. If you are seeing this message, you may be experiencing temporary network proble... more Skip to Content. If you are seeing this message, you may be experiencing temporary network problems. Please wait a few minutes and refresh the page. If the problem persists, you may wish to report it to your local Network Manager. ...
Brazilian Journal of Medical and Biological Research
1. The accuracy of an indirect immunofluorescence (IIF) test for the serodiagnosis of Helicobacte... more 1. The accuracy of an indirect immunofluorescence (IIF) test for the serodiagnosis of Helicobacter pylori infection was evaluated in adult patients and compared with culture, preformed urease test and smears stained with carbolfuchsin. 2. We studied 80 consecutive patients submitted to gastroduodenoscopy (17 of whom were found to have duodenal ulcer) plus 57 patients with duodenal ulcer. 3. H. pylori was identified by microbiological methods in 65 of the 80 consecutive patients and in all 57 patients with duodenal ulcer. 4. Among the 74 patients with duodenal ulcer, 71 presented antibody titers > or = 1:20 and 46 of the 48 H. pylori-positive patients without duodenal ulcer presented antibody titers > or = 1:20. 5. Thirteen of the 15 H. pylori-negative patients presented antibody titers < or = 1:10. 6. The sensitivity, specificity and positive predictive value of the IIF test were 95.9%, 88.8% and 98.4%, respectively. 7. The seroprevalence of H. pylori in 380 asymptomatic Br...
International journal of systematic bacteriology, 1996
A new Helicobacter species that colonizes the colonic mucosa of Wistar and Holtzman rats was isol... more A new Helicobacter species that colonizes the colonic mucosa of Wistar and Holtzman rats was isolated and characterized. This bacterium was gram negative, its cells were rod shaped with pointed ends, and its protoplasmic cylinder was entwined with periplasmic fibers. It was catalase and oxidase positive, rapidly hydrolyzed urea, and was susceptible to metronidazole and resistant to cephalothin and nalidixic acid. The new organism was microaerophilic and grew at 42 degrees C, a feature that differentiates it from two other murine intestine colonizers, Helicobacter hepaticus and Helicobacter muridarum. On the basis of 16S rRNA sequence analysis data, the new organism was identified as a Helicobacter species that is most closely related to H. hepaticus. This bacterium is named Helicobacter trogontum. The type strain is strain LRB 8581 (= ATCC 700114).
Transactions of the Royal Society of Tropical Medicine and Hygiene, 1999
We studied, prospectively, seroconversion for Helicobacter pylori in adults from a developing cou... more We studied, prospectively, seroconversion for Helicobacter pylori in adults from a developing country and investigated risk factors for the acquisition of the microorganism in this population. A group of 213 volunteers of low socioeconomic level from a district in the metropolitan area of Belo Horizonte, south-east Brazil was evaluated. Anti-H. pylori IgG antibodies were measured by ELISA using Cobas Core anti-H. pylori EIA (Roche) in serum samples collected in 1992 and in 1997. The subjects were interviewed and sociodemographic data were collected. A total of 174 (81.7%) subjects presented anti-H. pylori antibodies on the occasion of the first visit. During 56 months of follow-up, 2 of 39 seronegative adults converted to seropositive with an annual infection rate of 1.1%, and 2 of 174 seropositive subjects reverted to seronegative (0.2%/year). The prevalence of infection increased significantly with age and an inverse association was observed between prevalence of infection and educational level. In conclusion, the results of the present study demonstrate that in a developing country there is a low but continuous risk of H. pylori infection in adulthood.
The density of antral gastrin (G)- and somatostatin (D)-immunoreactive cells and the contents of ... more The density of antral gastrin (G)- and somatostatin (D)-immunoreactive cells and the contents of antral gastrin and somatostatin were investigated in endoscopic antral biopsy specimens from patients with duodenal ulcer before and after eradication of Helicobacter pylori. After H. pylori eradication both antral somatostatin concentration (p = 0.0002) and antral D-cell density (p = 0.01) increased significantly. Conversely, although the number of G-cells was unchanged, antral (p = 0.0002) and serum (p = 0.001) gastrin contents decreased significantly. The number of oxyntic D-cells did not change significantly. These results strongly suggest that the hypergastrinaemia observed in H. pylori-positive patients may be due to a deficiency in antral somatostatin, which normally inhibits the synthesis and release of gastrin.
Helicobacter pylori infection is mainly acquired in childhood, and polymorphisms in the host gene... more Helicobacter pylori infection is mainly acquired in childhood, and polymorphisms in the host genes coding for Toll-like receptors (TLRs) may influence the innate and adaptive immune response to the infection, affecting the susceptibility to H. pylori or the disease outcomes. Our aim was to investigate whether TLR4, TLR2, and TLR5 polymorphisms were associated with H. pylori susceptibility and risk for duodenal ulcer in children. Gastric biopsy specimens were obtained at endoscopy for evaluation of H. pylori status, TLR4, TLR2 and TLR5 polymorphisms from 486 children (254 H. pylori-negative and 232 H. pylori-positive: 72 with and 160 without duodenal ulcer). cagA status of H. pylori infection was investigated by PCR. The levels of gastric cytokines were detected by ELISA. H. pylori-positivity or duodenal ulcer were not associated with TLR2, TLR4 or TLR5 polymorphisms. Otherwise, the presence of TLR4 polymorphic allele was associated with infection by cagA-positive strains and with increased gastric levels of interleukin-8 and interleukin-10. TLR4 polymorphism might ultimately contribute to more severe consequences of the infection in adulthood since it was associated with susceptibility to cagA-positive H. pylori infection early in life.
The ultrastructural features of a helical-shaped bacterium occurring in the stomach of pigs, with... more The ultrastructural features of a helical-shaped bacterium occurring in the stomach of pigs, within the mucus on the mucosal surface of antral pits, were examined. The bacterial cell had three to eight spiral turns, flattened and truncated ends and was approximately 4.0 pm long and 0.6 pm wide. In some sections, up to six flagella, about 22 nm in diameter, were seen arising from each pole. The cytoplasm contained sparse, irregular granules, numerous ribosomes and large single-layered membrane-bound granules. In the flagella insertion area, there was a highly electrondense component, the "polar membrane". This microorganism differed from similar bacteria described in cats, dogs and monkeys, and may cause inflammation in the antral mucosa of pigs similar to Helicobacter pylori infection in man. Furthermore, it was morphologically similar to the spiral microorganism distinct from H. pylori which has been described recently in human antral mucosa from patients with gastritis and may be of potential significance as a pathogen in man. The name "Gastrospirillum suis" is proposed for this bacterium.
Helicobacter trogontum is a micro-aerophilic urease-positive bacterium that has recently been iso... more Helicobacter trogontum is a micro-aerophilic urease-positive bacterium that has recently been isolated from the intestinal mucosa of rats. The purpose of this investigation was to study the ultrastructural details of this microorganism in both pure culture and in the gastrointestinal tract of germ-free mice infected with H. trogontum. The microorganism was a fusiform to slightly spiral gram-negative cell, 4-6pm long and 0.6-0.7pm wide, with four to seven bipolar sheathed flagella. The cytoplasm presented several irregular and also globular granules. On each side of the polar regions of the cells, there was a highly electron-dense band, the 'polar membrane'. Coccoidal forms were seen in old cultures. H. trogontum showed several ultrastructural characteristics of the Helicobacter genus and much resemblance to H. rappini and H. bilis. H. trogontum mainly colonised the large bowel of the gnotobiotic mice where it could be seen in the lumen and also inside the enterocytes. Vacuolation of the ileal epithelial cells, loss of microvilli and pronounced desquamation of the enterocytes of the caecum were observed in the bowel colonised by the bacterium. These observations raise the possibility that H. trogontum could cause some harm to the host at least in particular circumstances such as when it colonises the gastrointestinal tract of a germ-free host.
To establish an experimental model to study gastric spiral non-cultivable bacteria, 30 4-week-old... more To establish an experimental model to study gastric spiral non-cultivable bacteria, 30 4-week-old female CFW (LOB) mice were inoculated with porcine gastric mucus containing " Gastrospirillum suis" and 25 mice were inoculated with mucus without " G. suis". Mice were examined 3,7, 14,21,28 and 60 days after inoculation. Fragments from the membranous, oxyntic and antral gastric mucosa and from the duodenal mucosa were obtained for histological and microbiological analysis. Tightly spiralled bacteria were seen in smears and in histological sections of the antral and oxyntic mucosa from all G. suis-infected mice. The pre-formed urease test also gave positive results in both tissues. In control mice, no tightly spiralled bacteria were seen. By 7 days after inoculation, the test animals had developed an inflammatory infiltrate of mononuclear cells, some neutrophils and a few eosinophils, mainly in the lower third of the antral and oxyntic mucosa, which persisted for the remainder of the observation period. This model can assist in the understanding of several clinical, pathological and immunological aspects of infection with spiral gastric bacteria, particularly those associated with non-cultivable spiral bacteria.
To evaluate a possible association between infection with cag A-positive strains and gastric carc... more To evaluate a possible association between infection with cag A-positive strains and gastric carcinoma increased risk we studied 119 Helicobacter pylori-positive patients with gastric carcinoma and 119 matched controls. The presence of cag A gene was investigated by PCR in H. pylori isolates and in gastric biopsy specimens. A significant association was found between cag A-positive status and distal gastric carcinoma for both the intestinal and diffuse types of tumor for both males and females. On the other hand, no association was observed between cag A-positive status and proximal gastric carcinoma.
Background: The detection of the putative disease-specific Helicobacter pylori marker duodenal ul... more Background: The detection of the putative disease-specific Helicobacter pylori marker duodenal ulcer promoting gene A (dupA) is currently based on PCR detection of jhp0917 and jhp0918 that form the gene. However, mutations that lead to premature stop codons that split off the dupA leading to truncated products cannot be evaluated by PCR. Methods: We directly sequence the complete dupA of 75 dupA-positive strains of H. pylori isolated from patients with gastritis (n = 26), duodenal ulcer (n = 29), and gastric carcinoma (n = 20), to search for frame-shifting mutations that lead to stop codon. Results: Thirty-four strains had single nucleotide mutations in dupA that lead to premature stop codon creating smaller products than the predicted 1839 bp product and, for this reason, were considered as dupA-negative. Intact dupA was more frequently observed in strains isolated from duodenal ulcer patients (65.5%) than in patients with gastritis only (46.2%) or with gastric carcinoma (50%). In logistic analysis, the presence of the intact dupA independently associated with duodenal ulcer (OR = 5.06; 95% CI = 1.22-20.96, p = .02). Conclusion: We propose the primer walking methodology as a simple technique to sequence the gene. When we considered as dupA-positive only those strains that carry dupA gene without premature stop codons, the gene was associated with duodenal ulcer and, therefore, can be used as a marker for this disease in our population.
See editorial on page 244. cation, nutrition, stress, gastric acidity, and hormonal and seasonal ... more See editorial on page 244. cation, nutrition, stress, gastric acidity, and hormonal and seasonal changes, their etiology remains un-Background & Aims: Swine present spontaneously pepknown. 2,7 Similarly, the answer to the peptic ulcer questic ulcer in the gastric pars esophagea and are fretion in humans was largely unknown until the spiral quently colonized by a spiral bacterium that is of the bacterium Helicobacter pylori was accepted as being the same species as Helicobacter heilmannii type 1. This major predisposing factor in the pathogenesis of the organism is also observed in the gastric mucosa of disease. Inasmuch as we have shown previously that patients with gastric symptoms and who present with swine can harbor in their stomachs the spiral bacterium gastritis at histology. The aim of this study was to Gastrospirillum suis, 8,9 it seems justified to assume that, investigate the association between the presence of in analogy with human ulcer disease, this bacterium H. heilmannii type 1 and lesions of the pars esophagea. could be involved in the pathogenesis of the gastric Methods: H. heilmannii type 1 infection was investigated by mouse inoculation, urease test, and carbolpeptic ulcer of swine. Furthermore, it was shown refuchsin stain in 20 stomachs with ulcer, 30 stomachs cently that a tightly spiral bacterium, morphologically with preulcer lesions, and 20 stomachs with a macrosimilar to G. suis, was more frequently observed in hisscopically normal pars esophagea. Results: The microtological sections of gastric mucosa from swine with organism was more frequently found in the stomachs ulcer than in those sections from animals without any with ulcer (100%) and in those with preulcer lesions lesions of the pars esophagea. 10 The relevance of this (90%) than in stomachs with macroscopically normal subject is increased by the fact that this organism is pars esophagea (35%). Histological alterations were also a human pathogen candidate because it was shown observed in the pars esophagea and in the glandular recently by 16S ribosomal RNA sequencing that it beregions of bacterium-positive stomachs. Conclusions:
Brazilian Journal of Medical and Biological Research, 1998
ABSTRACT We evaluated the accuracy of a 2nd generation ELISA to detect Helicobacter pylori infect... more ABSTRACT We evaluated the accuracy of a 2nd generation ELISA to detect Helicobacter pylori infection in adults from a developing country in view of variations in sensitivity and specificity reported for different populations. We studied 97 non-consecutive patients who underwent endoscopy for evaluation of dispeptic symptoms. The presence of H. pylori was determined in antral biopsy specimens by culture, by the preformed urease test and in carbolfuchsin-stained smears. Patients were considered to be H. pylori positive if at least two of the three tests presented a positive result or if the culture was positive, and negative if the three tests were negative. Sixty-five adults (31 with peptic ulcer) were H. pylori positive and 32 adults were H. pylori negative. Antibodies were detected by Cobas Core anti-H. pylori EIA in 62 of 65 H. pylori-positive adults and in none of the negative adults. The sensitivity, specificity and positive and negative predictive values of the test were 95.4, 100, 100 and 91.4%, respectively. The Cobas Core anti-H. pylori EIA presented high sensitivity and specificity when employed for a population in Brazil, permitting the use of the test both to confirm the clinical diagnosis and to perform epidemiologic surveys.
Brazilian Journal of Medical and Biological Research, 2006
Although Helicobacter heilmannii infection is less common than H. pylori infection in humans, it ... more Although Helicobacter heilmannii infection is less common than H. pylori infection in humans, it is considered to be of medical importance because of its association with gastritis, gastric ulcer, carcinoma, and mucosa-associated lymphoid tissue lymphoma of the stomach. However, there have been no studies evaluating the role of the Th cell response in H. heilmannii gastric infection. We evaluated the participation of pro-inflammatory and anti-inflammatory cytokines, IFN-γ and IL-4, in H. heilmannii gastric infection in genetically IFN-γ-or IL-4-deficient mice. The serum IFN-γ and IL-4 concentrations were determined by ELISA. The gastric polymorphonuclear infiltrate was higher (P = 0.007) in H. heilmannii-positive than in H. heilmanniinegative wild-type (WT) C57BL/6 mice, whereas no significant inflammation was demonstrable in the stomach of H. heilmannii-positive IFN-γ-/-C57BL/6 mice. The degree of gastric inflammatory cells, especially in oxyntic mucosa, was also higher (P = 0.007) in infected IL-4-/than in WT BALB/c mice. Serum IFN-γ levels were significantly higher in IL-4-/than in WT BALB/c mice, independently of H. heilmannii-positive or-negative status. Although no difference in serum IFN-γ levels was seen between H. heilmannii-positive (11.3 ± 3.07 pg/mL, mean ± SD) and-negative (11.07 ± 3.5 pg/mL) WT BALB/c mice, in the group of IL-4-/animals, the serum concentration of IFN-γ was significantly higher in the infected ones (38.16 ± 10.5 pg/ mL, P = 0.04). In contrast, serum IL-4 levels were significantly decreased in H. heilmannii-positive (N = 10) WT BALB/c animals compared to the negative (N = 10) animals. In conclusion, H. heilmannii infection induces a predominantly Th1 immune response, with IFN-γ playing a central role in gastric inflammation.
Brazilian Journal of Medical and Biological Research, 2003
We infected NIH germ-free female mice with Helicobacter trogontum, a recently described intestina... more We infected NIH germ-free female mice with Helicobacter trogontum, a recently described intestinal bacterium of rats, in order to study the lesions it induced in the liver of this host. Fifteen mice were challenged with a single dose of H. trogontum (test group) and killed 6, 12 and 18 months after inoculation (5 animals/group). Nine animals were challenged with 0.85% saline alone (control group) and killed at the same times. Fragments from the liver, cecum and colon were obtained for microbiologic and histologic examination. Stool samples were also collected. H. trogontum was detected in the cecum, colon and/or stool samples of all test mice. As expected, the bacterium was not isolated from any specimen obtained from the control animals. On the other hand, although we could not cultivate the bacterium from the liver, 13 test animals (86.7%) presented histological changes in this organ. The 6-month group presented infiltration of mononuclear and polymorphonuclear cells in the hepatic parenchyma and the two other groups presented foci of mononuclear cells. The results suggest that H. trogontum can elicit a hepatic inflammatory response in mice since the only difference between control and test animals was the presence of H. trogontum in the latter. This result, together with the growing number of related reports in the literature, reinforces the possible role of Helicobacter infection in the pathogenesis of hepatobiliary diseases.
In a search for Helicobacter species in the intestinal mucosae of 42 patients with ulcerative col... more In a search for Helicobacter species in the intestinal mucosae of 42 patients with ulcerative colitis (UC) and 74 without UC, only H. pylori was found. Although the bacterium was detected in UC patients by culture (7.1%) and nested PCR (19.0%), its presence was not associated with the disease ( P = 0.13).
Although Helicobacter heilmannii infection is less common than H. pylori infection in humans, it ... more Although Helicobacter heilmannii infection is less common than H. pylori infection in humans, it is considered to be of medical importance because of its association with gastritis, gastric ulcer, carcinoma, and mucosa-associated lymphoid tissue lymphoma of the stomach. However, there have been no studies evaluating the role of the Th cell response in H. heilmannii gastric infection. We evaluated the participation of pro-inflammatory and anti-inflammatory cytokines, IFN-γ and IL-4, in H. heilmannii gastric infection in genetically IFN-γ-or IL-4-deficient mice. The serum IFN-γ and IL-4 concentrations were determined by ELISA. The gastric polymorphonuclear infiltrate was higher (P = 0.007) in H. heilmannii-positive than in H. heilmanniinegative wild-type (WT) C57BL/6 mice, whereas no significant inflammation was demonstrable in the stomach of H. heilmannii-positive IFN-γ-/-C57BL/6 mice. The degree of gastric inflammatory cells, especially in oxyntic mucosa, was also higher (P = 0.007) in infected IL-4-/than in WT BALB/c mice. Serum IFN-γ levels were significantly higher in IL-4-/than in WT BALB/c mice, independently of H. heilmannii-positive or-negative status. Although no difference in serum IFN-γ levels was seen between H. heilmannii-positive (11.3 ± 3.07 pg/mL, mean ± SD) and-negative (11.07 ± 3.5 pg/mL) WT BALB/c mice, in the group of IL-4-/animals, the serum concentration of IFN-γ was significantly higher in the infected ones (38.16 ± 10.5 pg/ mL, P = 0.04). In contrast, serum IL-4 levels were significantly decreased in H. heilmannii-positive (N = 10) WT BALB/c animals compared to the negative (N = 10) animals. In conclusion, H. heilmannii infection induces a predominantly Th1 immune response, with IFN-γ playing a central role in gastric inflammation.
The histamine concentration of the oxyntic mucosa was determined in Helicobacter pylori-positive ... more The histamine concentration of the oxyntic mucosa was determined in Helicobacter pylori-positive patients with duodenal ulcer before and after antimicrobial therapy and in H. pylori-negative subjects. Determination of serum gastrin was also performed in duodenal ulcer patients before and after H. pylori eradication. The histamine content of the oxyntic mucosa was lower in patients with duodenal ulcer than in H. pylori-negative subjects, but it increased after H. pylori eradication. Conversely, in patients in whom therapy failed to eradicate the microorganism, the histamine content remained unchanged. Serum gastrin levels fell after microorganism eradication, and the percentage of this fall was correlated with the percentage of increase in gastric histamine. In conclusion, our findings suggest that abnormalities of histamine store present in duodenal ulcer patients might be a feature of H. pylori infection.
Skip to Content. If you are seeing this message, you may be experiencing temporary network proble... more Skip to Content. If you are seeing this message, you may be experiencing temporary network problems. Please wait a few minutes and refresh the page. If the problem persists, you may wish to report it to your local Network Manager. ...
Brazilian Journal of Medical and Biological Research
1. The accuracy of an indirect immunofluorescence (IIF) test for the serodiagnosis of Helicobacte... more 1. The accuracy of an indirect immunofluorescence (IIF) test for the serodiagnosis of Helicobacter pylori infection was evaluated in adult patients and compared with culture, preformed urease test and smears stained with carbolfuchsin. 2. We studied 80 consecutive patients submitted to gastroduodenoscopy (17 of whom were found to have duodenal ulcer) plus 57 patients with duodenal ulcer. 3. H. pylori was identified by microbiological methods in 65 of the 80 consecutive patients and in all 57 patients with duodenal ulcer. 4. Among the 74 patients with duodenal ulcer, 71 presented antibody titers > or = 1:20 and 46 of the 48 H. pylori-positive patients without duodenal ulcer presented antibody titers > or = 1:20. 5. Thirteen of the 15 H. pylori-negative patients presented antibody titers < or = 1:10. 6. The sensitivity, specificity and positive predictive value of the IIF test were 95.9%, 88.8% and 98.4%, respectively. 7. The seroprevalence of H. pylori in 380 asymptomatic Br...
International journal of systematic bacteriology, 1996
A new Helicobacter species that colonizes the colonic mucosa of Wistar and Holtzman rats was isol... more A new Helicobacter species that colonizes the colonic mucosa of Wistar and Holtzman rats was isolated and characterized. This bacterium was gram negative, its cells were rod shaped with pointed ends, and its protoplasmic cylinder was entwined with periplasmic fibers. It was catalase and oxidase positive, rapidly hydrolyzed urea, and was susceptible to metronidazole and resistant to cephalothin and nalidixic acid. The new organism was microaerophilic and grew at 42 degrees C, a feature that differentiates it from two other murine intestine colonizers, Helicobacter hepaticus and Helicobacter muridarum. On the basis of 16S rRNA sequence analysis data, the new organism was identified as a Helicobacter species that is most closely related to H. hepaticus. This bacterium is named Helicobacter trogontum. The type strain is strain LRB 8581 (= ATCC 700114).
Transactions of the Royal Society of Tropical Medicine and Hygiene, 1999
We studied, prospectively, seroconversion for Helicobacter pylori in adults from a developing cou... more We studied, prospectively, seroconversion for Helicobacter pylori in adults from a developing country and investigated risk factors for the acquisition of the microorganism in this population. A group of 213 volunteers of low socioeconomic level from a district in the metropolitan area of Belo Horizonte, south-east Brazil was evaluated. Anti-H. pylori IgG antibodies were measured by ELISA using Cobas Core anti-H. pylori EIA (Roche) in serum samples collected in 1992 and in 1997. The subjects were interviewed and sociodemographic data were collected. A total of 174 (81.7%) subjects presented anti-H. pylori antibodies on the occasion of the first visit. During 56 months of follow-up, 2 of 39 seronegative adults converted to seropositive with an annual infection rate of 1.1%, and 2 of 174 seropositive subjects reverted to seronegative (0.2%/year). The prevalence of infection increased significantly with age and an inverse association was observed between prevalence of infection and educational level. In conclusion, the results of the present study demonstrate that in a developing country there is a low but continuous risk of H. pylori infection in adulthood.
The density of antral gastrin (G)- and somatostatin (D)-immunoreactive cells and the contents of ... more The density of antral gastrin (G)- and somatostatin (D)-immunoreactive cells and the contents of antral gastrin and somatostatin were investigated in endoscopic antral biopsy specimens from patients with duodenal ulcer before and after eradication of Helicobacter pylori. After H. pylori eradication both antral somatostatin concentration (p = 0.0002) and antral D-cell density (p = 0.01) increased significantly. Conversely, although the number of G-cells was unchanged, antral (p = 0.0002) and serum (p = 0.001) gastrin contents decreased significantly. The number of oxyntic D-cells did not change significantly. These results strongly suggest that the hypergastrinaemia observed in H. pylori-positive patients may be due to a deficiency in antral somatostatin, which normally inhibits the synthesis and release of gastrin.
Helicobacter pylori infection is mainly acquired in childhood, and polymorphisms in the host gene... more Helicobacter pylori infection is mainly acquired in childhood, and polymorphisms in the host genes coding for Toll-like receptors (TLRs) may influence the innate and adaptive immune response to the infection, affecting the susceptibility to H. pylori or the disease outcomes. Our aim was to investigate whether TLR4, TLR2, and TLR5 polymorphisms were associated with H. pylori susceptibility and risk for duodenal ulcer in children. Gastric biopsy specimens were obtained at endoscopy for evaluation of H. pylori status, TLR4, TLR2 and TLR5 polymorphisms from 486 children (254 H. pylori-negative and 232 H. pylori-positive: 72 with and 160 without duodenal ulcer). cagA status of H. pylori infection was investigated by PCR. The levels of gastric cytokines were detected by ELISA. H. pylori-positivity or duodenal ulcer were not associated with TLR2, TLR4 or TLR5 polymorphisms. Otherwise, the presence of TLR4 polymorphic allele was associated with infection by cagA-positive strains and with increased gastric levels of interleukin-8 and interleukin-10. TLR4 polymorphism might ultimately contribute to more severe consequences of the infection in adulthood since it was associated with susceptibility to cagA-positive H. pylori infection early in life.
The ultrastructural features of a helical-shaped bacterium occurring in the stomach of pigs, with... more The ultrastructural features of a helical-shaped bacterium occurring in the stomach of pigs, within the mucus on the mucosal surface of antral pits, were examined. The bacterial cell had three to eight spiral turns, flattened and truncated ends and was approximately 4.0 pm long and 0.6 pm wide. In some sections, up to six flagella, about 22 nm in diameter, were seen arising from each pole. The cytoplasm contained sparse, irregular granules, numerous ribosomes and large single-layered membrane-bound granules. In the flagella insertion area, there was a highly electrondense component, the "polar membrane". This microorganism differed from similar bacteria described in cats, dogs and monkeys, and may cause inflammation in the antral mucosa of pigs similar to Helicobacter pylori infection in man. Furthermore, it was morphologically similar to the spiral microorganism distinct from H. pylori which has been described recently in human antral mucosa from patients with gastritis and may be of potential significance as a pathogen in man. The name "Gastrospirillum suis" is proposed for this bacterium.
Helicobacter trogontum is a micro-aerophilic urease-positive bacterium that has recently been iso... more Helicobacter trogontum is a micro-aerophilic urease-positive bacterium that has recently been isolated from the intestinal mucosa of rats. The purpose of this investigation was to study the ultrastructural details of this microorganism in both pure culture and in the gastrointestinal tract of germ-free mice infected with H. trogontum. The microorganism was a fusiform to slightly spiral gram-negative cell, 4-6pm long and 0.6-0.7pm wide, with four to seven bipolar sheathed flagella. The cytoplasm presented several irregular and also globular granules. On each side of the polar regions of the cells, there was a highly electron-dense band, the 'polar membrane'. Coccoidal forms were seen in old cultures. H. trogontum showed several ultrastructural characteristics of the Helicobacter genus and much resemblance to H. rappini and H. bilis. H. trogontum mainly colonised the large bowel of the gnotobiotic mice where it could be seen in the lumen and also inside the enterocytes. Vacuolation of the ileal epithelial cells, loss of microvilli and pronounced desquamation of the enterocytes of the caecum were observed in the bowel colonised by the bacterium. These observations raise the possibility that H. trogontum could cause some harm to the host at least in particular circumstances such as when it colonises the gastrointestinal tract of a germ-free host.
To establish an experimental model to study gastric spiral non-cultivable bacteria, 30 4-week-old... more To establish an experimental model to study gastric spiral non-cultivable bacteria, 30 4-week-old female CFW (LOB) mice were inoculated with porcine gastric mucus containing " Gastrospirillum suis" and 25 mice were inoculated with mucus without " G. suis". Mice were examined 3,7, 14,21,28 and 60 days after inoculation. Fragments from the membranous, oxyntic and antral gastric mucosa and from the duodenal mucosa were obtained for histological and microbiological analysis. Tightly spiralled bacteria were seen in smears and in histological sections of the antral and oxyntic mucosa from all G. suis-infected mice. The pre-formed urease test also gave positive results in both tissues. In control mice, no tightly spiralled bacteria were seen. By 7 days after inoculation, the test animals had developed an inflammatory infiltrate of mononuclear cells, some neutrophils and a few eosinophils, mainly in the lower third of the antral and oxyntic mucosa, which persisted for the remainder of the observation period. This model can assist in the understanding of several clinical, pathological and immunological aspects of infection with spiral gastric bacteria, particularly those associated with non-cultivable spiral bacteria.
To evaluate a possible association between infection with cag A-positive strains and gastric carc... more To evaluate a possible association between infection with cag A-positive strains and gastric carcinoma increased risk we studied 119 Helicobacter pylori-positive patients with gastric carcinoma and 119 matched controls. The presence of cag A gene was investigated by PCR in H. pylori isolates and in gastric biopsy specimens. A significant association was found between cag A-positive status and distal gastric carcinoma for both the intestinal and diffuse types of tumor for both males and females. On the other hand, no association was observed between cag A-positive status and proximal gastric carcinoma.
Background: The detection of the putative disease-specific Helicobacter pylori marker duodenal ul... more Background: The detection of the putative disease-specific Helicobacter pylori marker duodenal ulcer promoting gene A (dupA) is currently based on PCR detection of jhp0917 and jhp0918 that form the gene. However, mutations that lead to premature stop codons that split off the dupA leading to truncated products cannot be evaluated by PCR. Methods: We directly sequence the complete dupA of 75 dupA-positive strains of H. pylori isolated from patients with gastritis (n = 26), duodenal ulcer (n = 29), and gastric carcinoma (n = 20), to search for frame-shifting mutations that lead to stop codon. Results: Thirty-four strains had single nucleotide mutations in dupA that lead to premature stop codon creating smaller products than the predicted 1839 bp product and, for this reason, were considered as dupA-negative. Intact dupA was more frequently observed in strains isolated from duodenal ulcer patients (65.5%) than in patients with gastritis only (46.2%) or with gastric carcinoma (50%). In logistic analysis, the presence of the intact dupA independently associated with duodenal ulcer (OR = 5.06; 95% CI = 1.22-20.96, p = .02). Conclusion: We propose the primer walking methodology as a simple technique to sequence the gene. When we considered as dupA-positive only those strains that carry dupA gene without premature stop codons, the gene was associated with duodenal ulcer and, therefore, can be used as a marker for this disease in our population.
See editorial on page 244. cation, nutrition, stress, gastric acidity, and hormonal and seasonal ... more See editorial on page 244. cation, nutrition, stress, gastric acidity, and hormonal and seasonal changes, their etiology remains un-Background & Aims: Swine present spontaneously pepknown. 2,7 Similarly, the answer to the peptic ulcer questic ulcer in the gastric pars esophagea and are fretion in humans was largely unknown until the spiral quently colonized by a spiral bacterium that is of the bacterium Helicobacter pylori was accepted as being the same species as Helicobacter heilmannii type 1. This major predisposing factor in the pathogenesis of the organism is also observed in the gastric mucosa of disease. Inasmuch as we have shown previously that patients with gastric symptoms and who present with swine can harbor in their stomachs the spiral bacterium gastritis at histology. The aim of this study was to Gastrospirillum suis, 8,9 it seems justified to assume that, investigate the association between the presence of in analogy with human ulcer disease, this bacterium H. heilmannii type 1 and lesions of the pars esophagea. could be involved in the pathogenesis of the gastric Methods: H. heilmannii type 1 infection was investigated by mouse inoculation, urease test, and carbolpeptic ulcer of swine. Furthermore, it was shown refuchsin stain in 20 stomachs with ulcer, 30 stomachs cently that a tightly spiral bacterium, morphologically with preulcer lesions, and 20 stomachs with a macrosimilar to G. suis, was more frequently observed in hisscopically normal pars esophagea. Results: The microtological sections of gastric mucosa from swine with organism was more frequently found in the stomachs ulcer than in those sections from animals without any with ulcer (100%) and in those with preulcer lesions lesions of the pars esophagea. 10 The relevance of this (90%) than in stomachs with macroscopically normal subject is increased by the fact that this organism is pars esophagea (35%). Histological alterations were also a human pathogen candidate because it was shown observed in the pars esophagea and in the glandular recently by 16S ribosomal RNA sequencing that it beregions of bacterium-positive stomachs. Conclusions:
Brazilian Journal of Medical and Biological Research, 1998
ABSTRACT We evaluated the accuracy of a 2nd generation ELISA to detect Helicobacter pylori infect... more ABSTRACT We evaluated the accuracy of a 2nd generation ELISA to detect Helicobacter pylori infection in adults from a developing country in view of variations in sensitivity and specificity reported for different populations. We studied 97 non-consecutive patients who underwent endoscopy for evaluation of dispeptic symptoms. The presence of H. pylori was determined in antral biopsy specimens by culture, by the preformed urease test and in carbolfuchsin-stained smears. Patients were considered to be H. pylori positive if at least two of the three tests presented a positive result or if the culture was positive, and negative if the three tests were negative. Sixty-five adults (31 with peptic ulcer) were H. pylori positive and 32 adults were H. pylori negative. Antibodies were detected by Cobas Core anti-H. pylori EIA in 62 of 65 H. pylori-positive adults and in none of the negative adults. The sensitivity, specificity and positive and negative predictive values of the test were 95.4, 100, 100 and 91.4%, respectively. The Cobas Core anti-H. pylori EIA presented high sensitivity and specificity when employed for a population in Brazil, permitting the use of the test both to confirm the clinical diagnosis and to perform epidemiologic surveys.
Brazilian Journal of Medical and Biological Research, 2006
Although Helicobacter heilmannii infection is less common than H. pylori infection in humans, it ... more Although Helicobacter heilmannii infection is less common than H. pylori infection in humans, it is considered to be of medical importance because of its association with gastritis, gastric ulcer, carcinoma, and mucosa-associated lymphoid tissue lymphoma of the stomach. However, there have been no studies evaluating the role of the Th cell response in H. heilmannii gastric infection. We evaluated the participation of pro-inflammatory and anti-inflammatory cytokines, IFN-γ and IL-4, in H. heilmannii gastric infection in genetically IFN-γ-or IL-4-deficient mice. The serum IFN-γ and IL-4 concentrations were determined by ELISA. The gastric polymorphonuclear infiltrate was higher (P = 0.007) in H. heilmannii-positive than in H. heilmanniinegative wild-type (WT) C57BL/6 mice, whereas no significant inflammation was demonstrable in the stomach of H. heilmannii-positive IFN-γ-/-C57BL/6 mice. The degree of gastric inflammatory cells, especially in oxyntic mucosa, was also higher (P = 0.007) in infected IL-4-/than in WT BALB/c mice. Serum IFN-γ levels were significantly higher in IL-4-/than in WT BALB/c mice, independently of H. heilmannii-positive or-negative status. Although no difference in serum IFN-γ levels was seen between H. heilmannii-positive (11.3 ± 3.07 pg/mL, mean ± SD) and-negative (11.07 ± 3.5 pg/mL) WT BALB/c mice, in the group of IL-4-/animals, the serum concentration of IFN-γ was significantly higher in the infected ones (38.16 ± 10.5 pg/ mL, P = 0.04). In contrast, serum IL-4 levels were significantly decreased in H. heilmannii-positive (N = 10) WT BALB/c animals compared to the negative (N = 10) animals. In conclusion, H. heilmannii infection induces a predominantly Th1 immune response, with IFN-γ playing a central role in gastric inflammation.
Brazilian Journal of Medical and Biological Research, 2003
We infected NIH germ-free female mice with Helicobacter trogontum, a recently described intestina... more We infected NIH germ-free female mice with Helicobacter trogontum, a recently described intestinal bacterium of rats, in order to study the lesions it induced in the liver of this host. Fifteen mice were challenged with a single dose of H. trogontum (test group) and killed 6, 12 and 18 months after inoculation (5 animals/group). Nine animals were challenged with 0.85% saline alone (control group) and killed at the same times. Fragments from the liver, cecum and colon were obtained for microbiologic and histologic examination. Stool samples were also collected. H. trogontum was detected in the cecum, colon and/or stool samples of all test mice. As expected, the bacterium was not isolated from any specimen obtained from the control animals. On the other hand, although we could not cultivate the bacterium from the liver, 13 test animals (86.7%) presented histological changes in this organ. The 6-month group presented infiltration of mononuclear and polymorphonuclear cells in the hepatic parenchyma and the two other groups presented foci of mononuclear cells. The results suggest that H. trogontum can elicit a hepatic inflammatory response in mice since the only difference between control and test animals was the presence of H. trogontum in the latter. This result, together with the growing number of related reports in the literature, reinforces the possible role of Helicobacter infection in the pathogenesis of hepatobiliary diseases.
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Papers by Silvia Moura