Non-Helicobacter pylori helicobacters detected in the stomach of humans comprise several naturally occurring Helicobacter species in animals

Besides the well-known gastric pathogen Helicobacter pylori , other Helicobacter species with a spiral morphology have been detected in a minority of human patients who have undergone gastroscopy. The very fastidious nature of these non- Helicobacter pylori helicobacters (NHPH) makes their in vitro isolation difficult. These organisms have been designated ' Helicobacter heilmannii '. However, sequencing of several genes detected in NHPH-infected tissues has shown that the ' H. heilmannii ' group comprises at least five different Helicobacter species, all of them known to colonize the stomach of animals. Recent investigations have indicated that Helicobacter suis is the most prevalent NHPH species in human. This species has only recently been isolated in vitro from porcine stomach mucosa. Other NHPH that colonize the human stomach are Helicobacter felis, Helicobacter bizzozeronii, Helicobacter salomonis and ' Candidatus Helicobacter heilmannii'. In numerous case reports of human gastric NHPH infections, no substantial information is available about the species status of the infecting strain, making it difficult to link the species with certain pathologies. This review aims to clarify the complex nomenclature of NHPH species associated with human gastric disease and their possible animal origin. It is proposed to use the term 'gastric NHPH' to designate gastric spirals that are morphologically different from H. pylori when no identification is available at the species level. Species designations should be reserved for those situations in which the species is defined.     

Detection of non-pylori Helicobacter species in "Helicobacter heilmannii"-infected humans

BACKGROUND: A small proportion of patients suffering from chronic active gastritis are diagnosed with gastric Helicobacter species other than Helicobacter pylori. Circumstantial evidence has suggested that these bacteria, also referred to as "Helicobacter heilmannii"-like organisms (HHLO), may be transmitted through animals. The isolation of a Helicobacter bizzozeronii strain from a human patient confirmed this hypothesis. It was the aim of the present study to assess the presence of animal Helicobacter species and H. pylori in humans infected with HHLO, as diagnosed by histology. METHODS: Paraffin-embedded gastric biopsy specimens of 108 HHLO-infected patients (42 women and 66 men) from three clinical centers were screened for the presence of animal gastric Helicobacter species by polymerase chain reaction (PCR), using assays targeting the 16S rDNA region of the three known canine and feline helicobacters (H. bizzozeronii, H. salomonis and H. felis), "Candidatus H. suis", and "Candidatus H. bovis". In addition, the presence of H. pylori was evaluated by multiplex PCR analysis. RESULTS: In 63.4% of the stomachs (64/101) classification of the Helicobacter infection into the above mentioned groups was achieved. Non-pylori Helicobacter species commonly colonizing the stomachs of cats and dogs were found in 48.5% (49/101) of the patients. Fourteen (13.9%) samples tested positive for "Candidatus H. suis", and "Candidatus H. bovis" was demonstrated in 1 (0.9%) patient. The presence of H. pylori was established in 13 patients (12.9%). Eleven stomachs (10.9%) were infected with at least two different Helicobacter species. CONCLUSIONS: This study identifies animal Helicobacter species in the stomach of a large series of HHLO-infected patients, which may have clinical implications in a subset of patients with gastric disease.     

Characterization of Multiple Helicobacter bizzozeronii Isolates From a Finnish Patient With Severe Dyspeptic Symptoms and Chronic Active Gastritis

Background:  Helicobacter pylori is the primary cause of gastritis and peptic ulceration in humans. In a minority of patients with upper gastrointestinal symptoms, long tightly coiled spiral bacteria, provisionally named " Helicobacter heilmannii, " are observed in gastric biopsies. These bacteria are extremely fastidious and only one previous study has succeeded in obtaining an isolate in vitro.
Materials and Methods:  We used two different selective media to isolate " H. heilmannii " from the gastric mucosa of a Finnish patient presenting with severe dyspeptic symptoms. The isolates were characterized by testing for urease and catalase activity, by using light and electron microscopy, and by sequencing of the partial 16S rRNA and ureAB genes. Single-enzyme amplified fragment length polymorphism (sAFLP) was used to analyze the genetic diversity among the isolates.
Results:  We obtained 15 isolates from different gastric biopsies prior and three after unsuccessful treatment of the patient. The isolates were identified as Helicobacter bizzozeronii . Eradication therapy was unsuccessful most probably due to high level of resistance to metronidazole. Persistent colonization by the same H. bizzozeronii clone was confirmed by sAFLP, however, small differences between the profiles suggested long-term colonization of the patient.
Conclusions:  Helicobacter bizzozeronii remains the only " H. heilmannii " species isolated from human gastric mucosa although it has been an infrequent observation among " H. heilmannii "-infected patients in PCR-based screening studies. The relevance of H. bizzozeronii and other potentially zoonotic gastric Helicobacter spp. in human disease remains to be determined.     

Distinction of gastric Helicobacter spp. in humans and domestic pets by scanning electron microscopy

Background. A number of different Helicobacter spp. can colonize the stomach of humans and domestic pets. Difficulties encountered with primary isolation of these spiral microorganisms and their unusual inertia with respect to biochemical reactions still represent considerable obstacles to their characterization with classic tools. In addition, the high degree of similarity in the 16S rRNA sequence hampers differentiation of Helicobacter spp. using routine molecular biological assays.
Materials and Methods. Samples from experimentally monoinfected mice, of naturally infected hosts, and of cultured strains were examined by scanning electron microscopy (SEM). In parallel, all samples were analyzed by molecular techniques to ascertain the Helicobacter spp. involved.
Results. Using the mouse samples as a reference, microorganisms found in naturally infected hosts were identified by SEM as belonging to H. pylori , H. felis , or a group consisting of H. bizzozeronii and H. heilmannii. A further spiral microorganism with unique morphology was found in a dog that was positive for H. salomonis , but the organism could not be recovered from experimentally infected mice. In culture, most Helicobacter strains lost their ultrastructural characteristics.
Conclusions. When gastric Helicobacter spp. were collected from their natural habitat and examined by SEM, relevant differences could be detected between H. felis , H. bizzozeronii and H. heilmannii , and H. salomonis , respectively. SEM, therefore, seems to be a useful auxillary tool for the distinction of various gastric Helicobacter spp. as based on their ultrastructure.     

Development of a microelectronic chip array for high-throughput genotyping of Helicobacter species and screening for antimicrobial resistance

A microelectronic array assay was developed to specifically genotype Helicobacter pylori versus Helicobacter heilmannii and to determine antimicrobial resistance. Helicobacter 16S rRNA and 23S rRNA genes were specifically generated with Helicobacter genus-specific primers, respectively. The single-nucleotide polymorphisms (SNPs) in 16S rRNA, 268T specific in the H. pylori sequence, and 263A specific in H. heilmannii were used as molecular markers for identification of H. pylori and H. heilmannii, respectively. A triple-base-pair resistant mutation, AGA965-967TTC in 16S rRNA, is known to be responsible for H. pylori tetracycline resistance and was detected to identify resistant strains. H. pylori macrolide resistance was determined by the identification of 3 defined mutations in the 23S rRNA gene using the same method. The assay could be directly used to detect H. pylori in feces. The assay performs multiple determinations, including identification of Helicobacter species and antibiotic resistances, on the same microelectronic platform and is highly amenable to the development of other DNA-based assays.     

Imprint cytology of gastric mucosa biopsy--fast, simple and reliable method for detection of Helicobacter pylori infection

The aim of the study was to determine the value of gastric mucosa imprint cytology in the detection of Helicobacter pylori infection. A total of 182 biopsy specimens, from 182 randomly selected patients undergoing gastroscopy with gastric mucosa biopsy, were analyzed. Specimens were first submitted to slide imprinting and then formalin fixed for further routine histopathology. One-hundred and fifty-five specimens proved adequate for definitive comparison of the methods used for detection of Helicobacter pylori infection. Helicobacter pylori was detected by histopathology in 51 specimens and by cytology in 54 specimens. Agreement between the findings obtained by the two methods was recorded in 130 of 155 (83.1%) specimens. Positive cytology and negative histology findings were obtained in 14, and vice versa in 11 specimens. Gastric mucosa imprint cytology provides a useful method for the detection of Helicobacter pylori infection. The method is advantageous for being fast, simple and inexpensive. When the sample is obtained exclusively for confirmation of the presence of Helicobacter pylori infection, cytology reduces the time and cost of the procedure, at the same time providing data on morphological changes of gastric mucosa. Every finding suspect of malignant transformation of the mucosa can also be verified by histopathology because imprint manipulation causes no damage to the sample.     

Use of polymerase chain reaction and enzymatic cleavage in the identification of Helicobacter spp. in gastric mucosa of human beings from North Paraná, Brazil

Helicobacter pylori is the most common gastric bacteria of human beings. Animal-borne helicobacter have been associated with gastritis, ulceration, and gastric mucosa-associated lymphoid-tissue lymphoma in people. We attempted to identify the species of Helicobacter spp. that infect human beings in north Paran , Brazil. Samples of gastric mucosa from 38 dyspeptic patients were analyzed by optic microscopy on silver stained slides, polimerase chain reaction (PCR), and enzymatic cleavage. Genus and species-specific primers to H. pylori, H. heilmannii, H. felis, and consensual primers to H. bizzozeronii or H. salomonis were used. The PCR products were submitted to enzymatic cleavage by VspI (Helicobacter spp. product) and HinfI (species products) enzymes. Thirty-two out of 38 patients evaluated had 3.2 to 5 m long bacteria that resembled H. pylori in Warthin-Starry stained slides and were positive to the genus Helicobacter by PCR. In 30 of these patients the bacteria were identified as H. pylori. Two samples positive by silver stain were negative to all species tested by PCR. None of the 38 samples was positive to animal-origin helicobacter species. These results show that PCR and enzymatic restriction are practical methods to identify the species of helicobacters present in gastric mucosa of human beings. People in north Paran appear to be infected mostly with H. pylori.     

Culture of Helicobacter pylori: Effect of Preimmersion of Biopsy Forceps in Formalin

Background. Treatment of antibiotic-resistant Helicobacter pylori should be based on bacterial sensitivity testing that requires the ability to isolate the bacterium from gastric mucosal biopsies. The aim of this study was to determine whether the yield for detecting H. pylori infection by culture is reduced by immersion of biopsy forceps in formalin prior to obtaining the specimen.
Materials and Methods. Gastric antral mucosal biopsies (100 specimens) from 50 patients were obtained for culture of H. pylori. An antral biopsy was taken for culture, and with the same forceps a biopsy was taken for histological examination. The biopsy specimen was removed by shaking, whereas the forceps was immersed in 10% buffered formalin for the histological investigation. The forceps was then used without rinsing to obtain a second specimen for culture from an area adjacent to the first site. H. pylori status was determined by histological assessment with the Genta stain and a rapid urease test.
Results. Fifty patients with H. pylori infection documented by histological inquiry and positive rapid urease testing entered the study; 29 had duodenal ulcers, 5 had gastric ulcers, 1 had mucosal associated lymphoid tissue (MALT) lymphoma, and 15 were without ulcer disease. The results of culture both before and after immersion in formalin were identical. One patient had both cultures negative; the sensitivity of culture for detection of H. pylori infection was 98% (95% confidence interval =93%-100%).
Conclusion. Preimmersion of biopsy forceps in formalin does not adversely affect the ability to culture H. pylori.     

Synergism of Helicobacter pylori infection and stress on the augmentation of gastric mucosal damage and its prevention with alpha-tocopherol

Despite evidence that Helicobacter pylori (H. pylori) infection is closely associated with stress in gastric ulcer patients, the underlying mechanism why ulcer recurrence after stress is augmented especially in patients with H. pylori remains unknown. In this study, we found that oxidative stress played a critical role in the augmented mucosal damage provoked by water immersion restraint stress (WIRS) in H. pylori infection and that an antioxidant, alpha-tocopherol, could ameliorate the aggravation of stress-associated gastric mucosal damage. Two hundred forty SD rats were divided into two groups according to H. pylori inoculation, and after 24 weeks of H. pylori infection, the water immersion restraint stress was imposed for 30, 120, or 480 min, respectively. To evaluate the therapeutic effects of an antioxidant, alpha-tocopherol was administrated 40 mg/kg daily prior to imposing WIRS. Remarkably increased hemorrhagic lesions and bleeding indexes were noted in the H. pylori-infected group with statistical significance (P < 0.05) compared to the noninfected group at the same duration of WIRS. Significantly higher oxidative stress documented by iNOS, lipid peroxides, and GSH level was detected in gastric homogenates of the H. pylori-infected group. Proteomic analysis using 2-dimensional electrophoresis showed a decrease of HSP27 and other chaperone proteins. alpha-Tocopherol pretreatment significantly prevented the gastric mucosal damage, caused by WIRS in the presence of H. pylori. alpha-Tocopherol induced HSP27 expression, which was well correlated with downregulation of iNOS mRNA. Conclusively, the presence of H. pylori caused significant deterioration of stress-induced gastric mucosal lesions through increased oxidative stress and thus antioxidant treatment such as alpha-tocopherol protected the gastric injuries.     

Involvement of endothelin-1 in up-regulation of gastric mucosal inflammatory responses to Helicobacter pylori lipopolysaccharide

In this study, we investigated gastric mucosal inflammatory responses during Helicobacter pylori lipopolysaccharide-induced gastritis by analyzing the interplay between mucosal expression of endothelin-1 (ET-1), interleukin-4 (IL-4) and tumor necrosis factor-alpha (TNF-alpha). The assays conducted 4 days after intragastric dose of H. pylori lipopolysaccharide demonstrated a pattern of acute mucosal reaction characterized by the inflammatory infiltration of the lamina propria, hyperemia, and epithelial hemorrhage. This was accompanied by a 3.1-fold increase in the mucosal expression of ET-1 and a 9-fold enhancement in TNF-alpha, while the level of IL-4 showed a 20.8% decline. The results implicate ET-1 in gastric mucosal responses to H. pylori, and suggest that an increase in its level, combined with a loss of compensatory action by IL-4, may be responsible for the induction of TNF-alpha and triggering apoptotic events that exacerbate the inflammatory process.     

Eicosanoid synthesis and Helicobacter pylori associated gastritis: increase in leukotriene C4 generation associated with H. pylori colonization.

The importance of pro-inflammatory leukotriene C4 in Helicobacter pylori (H. pylori) associated gastritis in man is unknown. Fresh gastric biopsy specimens from 28 dyspeptic patients were obtained: 10 showed normal antral histology with no evidence of H. pylori, the remaining 18 patients exhibited histological gastritis and were H. pylori positive as assessed by histology, culture and urease test. Twelve of these 18 patients received 240 mg twice daily colloidal bismuth subcitrate for four weeks before re-endoscopy. Gastric biopsies from H. pylori positive patients were incubated under basal and Ca(2+)-ionophore mediated conditions: Radioimmunoassay analysis of the supernatant showed basal release of prostaglandin E2 and leukotriene C4 was slightly but not significantly elevated in H. pylori positive mucosa. However in H. pylori positive mucosa there was an 85% increase in leukotriene C4 synthesis when biopsies were incubated with ionophore, compared to only 13% increase in H. pylori negative mucosa (p less than 0.02). After eradication of H. pylori by colloidal bismuth subcitrate, there was a clearance of inflammatory cell infiltrate as assessed by histology and a significant reduction in ionophore-mediated leukotriene C4 formation compared with before treatment (p less than 0.02). These results suggest that H. pylori gastritis is associated with increased capacity to generate leukotriene C4, which may amplify the damaging effects of the bacteria on gastric mucosa.     

Detection of Helicobacter species DNA by quantitative PCR in the gastrointestinal tract of healthy individuals and of patients with inflammatory bowel disease

In many animal species different intestinal Helicobacter species have been described and a few species are associated with intestinal infection. In humans, the only member of the Helicobacter family which is well described in literature is Helicobacter pylori. No other Helicobacter-associated diseases have definitely been shown in humans. We developed a sensitive quantitative PCR to investigate whether Helicobacter species DNA can be detected in the human gastrointestinal tract. We tested gastric biopsies (including biopsies from H. pylori positive persons), intestinal mucosal biopsies and fecal samples from healthy persons, and intestinal mucosal biopsies from patients with inflammatory bowel disease (IBD) for the presence of Helicobacter species. All gastric biopsies, positive for H. pylori by culture, were also positive in our newly developed PCR. No Helicobacter species were found in the mucosal biopsies from patients with IBD (n = 50) nor from healthy controls (n = 25). All fecal samples were negative. Our study suggests that Helicobacter species, other than H. pylori, are not present in the normal human gastrointestinal flora and our results do not support a role of Helicobacter species in IBD.     

Effect of probiotics and triple eradication therapy on the cyclooxygenase (COX)-2 expression, apoptosis, and functional gastric mucosal impairment in Helicobacter pylori-infected Mongolian gerbils

BACKGROUND: Helicobacter pylori infection in Mongolian gerbils is an established experimental model of gastric carcinogenesis that mimics H. pylori-positive patients developing gastric ulcer and gastric cancer, but the effect of probiotic therapy on functional aspects of this infection remains unknown. METHODS: We compared the effects of intragastric inoculation of gerbils with H. pylori strain (cagA+ vacA+, 5 x 10(6) colony forming units/ml) with or without triple therapy including omeprazole, amoxicillin, and tinidazol or probiotic bacteria Lacidofil. Histology of glandular mucosa, the viable H. pylori, and density of H. pylori colonization were evaluated. The gastric blood flow was measured by H2-gas clearance method; the plasma gastrin and gastric luminal somatostatin were determined by RIA and expression of cyclooxygenase (COX)-2 and apoptotic Bax and Bcl-2 proteins were evaluated by Western blot. RESULTS: The gastric H. pylori infection was detected in all animals by histology and H. pylori culture. Basal gastric acid was significantly reduced in H. pylori-infected animals but not in those with triple therapy or Lacidofil. Early lesions were seen already 4 weeks upon H. pylori inoculation and consisted of chronic gastritis and glandular atypia associated with typical regenerative hyperplasia and increased mitotic activity and formation of apoptotic bodies. The H. pylori infection was accompanied by the fall in gastric blood flow, the marked increase in plasma gastrin, the significant fall in gastric somatostatin levels and Bcl-2 protein expression, and the rise in expression of COX-2 and Bax proteins. These mucosal changes were counteracted by the triple therapy and Lacidofil. CONCLUSIONS: H. pylori infection in gerbils, associated with regenerative hyperplasia of glandular structure, results in the suppression of gastric secretion, overexpression of COX-2, and enhancement in apoptosis and impairment of both, gastric blood flow and gastrin-somatostatin link that were reversed by anti-H. pylori triple therapy and attenuated by probiotics.     

Gastric mucosal changes induced by long term infection with Helicobacter pylori in Mongolian gerbils: effects of bacteria eradication.

Helicobacter pylori infection has been reported to induce various mucosal changes, including gastric adenocarcinoma, in Mongolian gerbils 62 weeks after inoculation. Using Mongolian gerbils, this study examined whether or not eradication of the bacteria with drugs at specified times after infection prevents the development of mucosal changes. After orally inoculating with H. pylori (TN2GF4, vacA- and cagA-positive), the animals were killed 18 months later. Four or 8 months after H. pylori inoculation, eradication was performed by concurrent treatment with omeprazole+clarithromycin. Immediately after treatment ended, in both the 5 and 9 month groups, it was verified that H. pylori was completely eradicated. Autopsy performed 18 months after H. pylori inoculation revealed gastric hyperplastic polyps with erosive lesions and ulcers that were grossly visible in the non-treated control group. In addition, atrophic gastritis, intestinal metaplasia, carcinoids, and adenocarcinomas were histologically observed in the animals. In animals eradicated after 4 months and autopsied after 18 months, however, such mucosal changes were not observed. In contrast, intestinal metaplasia and mucosal atrophy was observed in animals eradicated after 8 months and autopsied after 18 months. It was concluded that early eradication of H. pylori infection with drug therapy can prevent severe gastric mucosal changes, to include adenocarcinomas, in Mongolian gerbils.     

L-lactic acid secreted from gastric mucosal cells enhances growth of Helicobacter pylori

BACKGROUND: Helicobacter pylori mainly inhabit the mucus layer in the gastric mucosa. However, mechanisms involving H. pylori colonization and proliferation in gastric mucosa are not well established. This study focuses on elucidating the role of gastric mucosal cells on growth of H. pylori. MATERIALS AND METHODS: H. pylori was co-cultured with the murine gastric surface mucosal cells (GSM06), and the growth of H. pylori on the cells was assessed by enumerating the colony-forming units (CFU). The H. pylori growth factor in the culture media conditioned by GSM06 cell was purified by HPLC, and the chemical structure of the growth factor was identified by analyses of (1)H- and (13)C-NMR spectra. RESULTS: A marked increase in the number of CFU of H. pylori was observed in the GSM06 cells. The enhanced H. pylori growth was also observed when indirectly incubated with GSM06 cells through semi-permeable membrane. In addition, culture media conditioned by GSM06 cell stimulated H. pylori growth approximately one thousand-fold. By bioassay-guided purification, the H. pylori growth factor was isolated from the conditioned medium of GSM06 cells and identified as L-lactic acid. The H. pylori growth-enhancing activity under microaerobic condition was well correlated with L-lactic acid concentrations in the conditioned media. CONCLUSIONS: This study demonstrates that L-lactic acid secreted by gastric mucosal cells enhances the growth of H. pylori, and this L-lactic acid-dependent growth of H. pylori may be important to the long-term colonization of H. pylori in the stomach.     

Role of mast cells as a trigger of inflammation in Helicobacter pylori infection.

Helicobacter pylori (H. pylori) induces severe inflammation and plays a key role in gastric mucosal diseases. In general, mast cells have been believed to play an important role in inflammation. Although mast cells were detected in the gastric mucosa, the role of mast cells in the gastric mucosal inflammation caused by H. pylori is still unclear. Therefore, we examined the effects of H. pylori water extract on the degranulation of mast cells to clarify the role of these cells in gastric mucosal inflammation induced by H. pylori. Mast cells prepared from rat abdominal cavity were incubated with H. pylori for 30 min. The protein concentrations of H. pylori water extract used in this study were 0.5-3 mg/ml. The degranulation of mast cells were monitored morphologically by phase contrast microscopy equipped with time-lapse video recording system and biochemically by measuring histamine and beta-hexosaminidase. H. pylori water extract induced the degranulation of mast cells dose-dependently. The identical experiment was performed without extracellular calcium, and no significant degranulation was found. The data indicates that the degranulation of mast cells by H. pylori water extract depend on extracellular calcium. The present results indicate that H. pylori might be involved in the gastric mucosal inflammation as a trigger of mast cell degranulation for releasing chemical mediators.     

Helicobacter pylori and apoptosis.

In an attempt to understand the diverse effects of infection with Helicobacter pylori on epithelial mucosal mass and consequent clinical outcome, the relationship between H. pylori infection and gastric epithelial cellular turnover has been investigated. Our results indicate that H. pylori increases epithelial cell proliferation and apoptosis in vivo, but that infection with bacteria of the cagA genotype leads to relatively more proliferation than apoptosis. This review explores the causes of the induction of apoptosis in gastric epithelial cells by H. pylori and the consequences of alterations in apoptosis to the maintenance of gastric mucosal homeostasis.     

Evaluation of brushing cytology in the diagnosis of Helicobacter pylori gastritis

OBJECTIVE: To evaluate clinical utility of rapid urease test (RUT), brash cytology and histology for detecting Helicobacter pylori. STUDY DESIGN: Brush cytology materials were obtained from the antrum of the stomach in 109 patients who suffered from dyspepsia and were candidates for endoscopy. RUT and histology with hematoxylin-eosin staining were performed. Infection status was established by observation of typical HP in cytology or biopsy. RESULTS: A total of 78% ofpatients were diagnosed as positivefor HP organisms using brush cytology; 66% had histologic results positive for HP and 59% for RUT. Observation of typical organism by cytology or histology was the gold standard; 3 tests results were compared. Sensitivity of brush cytology (95%) was higher than that of histology (80.5%) and RUT (72%). CONCLUSION: Gastric brushing cytology provides a sensitive, inexpensive, accurate and easy technique for rapid detection of HP infection. When additional information on severity of mucosal damage or presence of cell atypias is not necessary, histologic examination can be omitted; a cost-effective strategy for assessing HP status might consist of taking antral biopsies, the former for RUT, and performing brush cytology slides, which should be stained and examined only when the RUT result is negative.     

Presence of Thrombin-Activatable Fibrinolysis Inhibitor in Helicobacter pylori-Associated Gastroduodenal Disease

Thrombin-activatable fibrinolysis inhibitor (TAFI) plays a role in the regulation of coagulation and inflammation. In addition to inhibiting the fibrinolytic system, TAFI may also regulate the bradykinin and complement systems. We hypothesized that TAFI also plays a role in defense mechanisms of the gastric mucosa during Helicobacter pylori infection. This study comprised 65 patients with gastroduodenal disorders: 41 patients with H. pylori infection, 13 without, and 11 patients with cured H. pylori infection. The gastric intramucosal concentrations of TAFI were measured by enzyme immunoassay. The gastric levels of TAFI and plasminogen activator inhibitor-1 were significantly increased in patients with H. pylori compared to those without infection or cured H. pylori . The presence of TAFI was detected in gastric mucosal epithelial cells. The concentration of TAFI was correlated with the degree of gastric mucosal atrophy, inflammation, and disease activity. These results show that TAFI is present in the gastric mucosa and that it may play a role in the pathogenesis of H. pylori infection-associated gastroduodenal disorders.     

幽门螺杆菌感染促进胃炎儿童胃粘膜细胞的增殖

本研究旨在探讨幽门螺杆菌感染对小儿慢性胃炎患者细胞增殖的影响,使用内镜检查消化不良患者的上消化道症状,使用改良的Giemsa染色检测胃粘膜活组织中幽门螺杆菌,用苏木精/曙红和改良的吉姆萨染色活组织,并通过光学显微镜研究染色后胃粘膜样品组织病理学变化,RT-PCR检测各组胃粘膜细胞中调控细胞凋亡的Bcl-2、Bcl-xl、Bax和PCNA的mRNA表达,提取胃粘膜细胞蛋白质,利用蛋白质免疫印迹分析蛋白质浓度。组织化学染色结果表明,与对照相比,患有胃炎和幽门杆菌感染后的胃炎患者胃粘膜细胞明显增加,且幽门螺杆菌感染后细胞增殖更显著(p<0.05);幽门螺杆菌感染后Bcl-2和Bcl-xl,PCNA在患者体内表达显著上调(p<0.05),而细胞促凋亡因子Bax基因在胃炎患者感染幽门螺杆菌后被显著下调(p<0.05),蛋白免疫印迹分析Bcl-2,Bcl-xl,Bax和PCNA蛋白表达趋势与基因表达一致,说明结果可靠。幽门螺杆菌感染会显著提高慢性胃炎儿童患者胃粘膜细胞的增殖。