A bioinformatics approach revealed the transcription factors of Helicobacter pylori pathogenic genes and their regulatory network nodes

BACKGROUND: Helicobacter pylori is a chronic pathogenic bacteria that causes gastric mucosal damage through various host-related and pathogen-related factors. Thus, a single gene research cannot fully explain its pathogenicity. PURPOSE OF STUDY: It is necessary to establish a Helicobacter pylori pathogenic gene transcription factor regulatory network (TFRN) and study its central nodes. RESULTS: The expression data of Helicobacter pylori pathogenic genes were obtained through GEO Datasets of NCBI. The genes were screened using linear model-empirical Bayesian statistics in R language Limma package combined with the conventional t-test; the results identified 1231 differentially expressed genes. The functional analysis (gene ontology-analysis) and signal pathway analysis (pathway-analysis) of differentially expressed genes were performed using the DAVID and KEGG databases, respectively. The pathogenic gene regulatory network was constructed by integrating transcriptional regulatory element database (TRED); the disease-related analysis of the pathogenic genes was conducted using the DAVID annotation tool. Five pathogenic genes (Nos2, Il5, Colla1, Tnf, and Nfkb1) and their transcription factors (Jun, Cebpa, Egrl, Ppara, and Il6) were found to suppress the host immune function and enhance the pathogenicity of Helicobacter pylori by regulating the host immune system. CONCLUSIONS: This effect was largely mediated via three signaling pathways: Tnf pathway, PI3K Akt pathway, and Jak­STAT pathway. The pathogenicity of Helicobacter pylori is closely related to the body's immune and inflammatory system. A better understanding of the correlation of the pathogenic factors with the host immune and inflammatory factors may help to determine the precise pathogenic mechanism of H. pylori infection.

Infecção pelo Helicobacter pylori e perfil imunológico em pacientes com diferentes doenças gastroduodenais / Helicobacter pylori infection and immune profile of patients with different gastroduodenal diseases

ABSTRACT BACKGROUND: The association between infection with Helicobacter pylori and different gastroduodenal diseases is related to bacterial, host and environmental factors. Studies have demonstrated an association between the genetic diversity of H. pylori, especially in the vacA and cagA genes, and the development of digestive diseases such as peptic ulcer and gastric cancer. In addition, the nature of the host inflammatory response may explain these different manifestations of infection caused by this microorganism. In this respect, host factors that regulate the immune and inflammatory responses involving the functional interaction of H. pylori infection with different components of the immune system, particularly T cells, in gastroduodenal diseases still need further investigation. OBJECTIVE: To characterize the immune response, including immunity induced by infection with H. pylori, especially virulent strains (vacA alleles and cagA gene), by analyzing the cytokine profile and T-cell population present in gastroduodenal diseases in a Brazilian population. METHODS: In a prospective study, gastric biopsies were collected from 554 patients with different gastroduodenal diseases for histological analysis and for the determination of bacterial genotype and cytokine production (IL-4, IL-10, IFN-γ and IL-12) by ELISA. RESULTS: The predominant genotype of the H. pylori strains isolated from the patients studied was s1m1cagA+, which was more common among patients with gastric ulcer, duodenal ulcer and gastric cancer. A significant association was observed between the s1m1cagA+ genotype and a higher degree of inflammation, higher neutrophil activity and the development of intestinal metaplasia. The gastric concentrations of IFN-γ and IL-12 were significantly higher in patients infected with H. pylori than in uninfected individuals. Higher levels of these cytokines were detected in patients with gastric ulcer and cancer, while the levels of IL-4 and IL-10 in the gastric mucosa were lower in these patients. In addition, IFN-γ and IL-12 concentrations in gastric biopsies were higher in patients infected with the virulent s1m1cagA+ genotype. In contrast, IL-4 and IL-10 levels were higher in tissue infected with s2m2cagA in gastric biopsies. CONCLUSION: Our study shows that the interaction between the type of infectious strain and the Th1 immune response can influence and perpetuate gastric inflammation, and thus contributes to the development of the different clinical manifestations of H. pylori infection.

RESUMO CONTEXTO: A associação da infecção por Helicobacter pylori com diferentes doenças gastroduodenais pode estar associada a fatores bacterianos, do hospedeiro e do ambiente. Nesse contexto, estudos têm demonstrado que a diversidade genética do H. pylori, sobretudo nos genes vacA e cagA, está associada ao desenvolvimento de doenças gastroduodenais como a úlcera péptica e o câncer gástrico. Além disso, a natureza da resposta inflamatória do hospedeiro pode explicar essas diferentes manifestações da infecção por esse microrganismo. Portanto, fatores do hospedeiro que regulam as respostas imunológica e inflamatória, envolvendo a interação funcional da infecção por H. pylori com diferentes membros do compartimento imunológico, especialmente respostas imunes de células T nas doenças gastroduodenais, ainda precisam ser melhor estudados. OBJETIVO: Caracterizar a resposta imune, incluindo imunidade induzida por infecção pelo H. pylori, especialmente com cepas virulentas de H. pylori (alelos vacA e gene cagA), através da análise do perfil de citocinas e da caracterização da população de células T presentes em doenças gastroduodenais em nossa população. MÉTODOS: Em um estudo prospectivo, foram coletadas biópsias gástricas de 554 pacientes portadores das diferentes doenças gastroduodenais. Nas amostras biológicas destes pacientes foi realizada a determinação do genótipo bacteriano e a detecção das citocinas IL-4, IL-10, INF-γ e IL-12 através do método Elisa. Foram obtidas biópsias gástricas para avaliação histológica. RESULTADOS: Observamos que o genótipo predominante nas cepas de H. pylori isoladas dos pacientes estudados foi s1m1cagA positivo, sendo mais frequentes entre os pacientes com úlcera gástrica, úlcera duodenal e câncer gástrico. Houve associação significativa das cepas com o genótipo s1m1cagA positivo com maior grau de inflamação, atividade neutrofílica e desenvolvimento de metaplasia intestinal. As concentrações gástricas de INF-γ e IL-12 foram significativamente mais elevadas em pacientes infectados pelo H. pylori do que nos não infectados. Foram detectados níveis mais elevados dessas citocinas nos portadores de úlcera e câncer gástrico, sendo que nesses pacientes foram observados níveis mais baixos de IL-4 e IL-10 na mucosa gástrica. Além disso, as concentrações de INF-γ e IL-12 em biópsias gástricas, foram mais elevadas nos pacientes portadores das cepas bacterianas virulentas s1m1cagA+. Contrariamente, os níveis de IL-4 e IL-10 foram maiores em tecido infectado por cepas s2m2cagA. Pacientes com maior grau de inflamação, de atividade neutrofílica e presença de metaplasia intestinal, apresentaram níveis mais elevados de INF-γ e IL-12 e uma concentração mais baixa de IL-4 e IL-10 nas biópsias gástricas. CONCLUSÃO: Nosso estudo demonstra que a interação entre o tipo de cepa infectante e resposta imunológica com perfil Th1, podem influenciar e perpetuar a inflamação gástrica contribuindo para o desenvolvimento de diferentes manifestações clínicas na infecção pelo H. pylori.

Avaliação de antígeno leucocitário humano classe I e II em pacientes pediátricos com gastrite e úlcera duodenal ativas e Helicobacter pylori positivo / Evaluation of human leukocyte antigen class i and ii antigens in helicobacter pylori-positive pediatric patients with active gastritis and duodenal ulcer

ABSTRACT BACKGROUND: As being the first bacteria determined to be carcinogenic, Helicobacter pylori (H. pylori) is a pathogen localized in the stomach in more than half of the world population. Some earlier studies have found a relation between tissue histocompatibility antigens and gastric cancers depending on the regions. OBJECTIVE: The present study aimed to determine the distribution of human leukocyte antigen (HLA) class I and class II antigens in H. pylori-positive pediatric patients with active gastritis and duodenal ulcer, excluding cancer cases, in our center. METHODS: The study included 40 patients diagnosed with H. pylori-positive active gastritis and duodenal ulcer and 100 controls consisting of healthy donor candidates. The HLA class I and class II antigens were studied in the isolated DNA samples using the polymerase chain reaction sequence-specific oligonucleotide probes. RESULTS: The frequency of HLA-B*51 antigen was significantly higher in the patient group than in the control group (40% vs 17%; P=0.003). There was no difference between the two groups in terms of the frequencies of HLA-A, HLA-C, HLA-DR, and HLA-DQ antigens. CONCLUSION: It was determined that HLA-B*51 plays a critical role in H. pylori infection.

RESUMO CONTEXTO: Determinada como sendo a primeira bactéria cancerígena, o Helicobacter pylori (H. pylori) é um patógeno localizado no estômago em mais da metade da população mundial. Alguns estudos anteriores têm encontrado uma relação entre câncer gástrico e antígenos de histocompatibilidade de tecido dependendo das regiões. OBJETIVO: O presente estudo teve como objetivo determinar a distribuição em nosso centro do antígeno leucocitário humano (HLA) de classe I e antígenos classe II em pacientes pediátricos H. pylori-positivos com gastrite e úlcera duodenal ativas, excluindo casos de câncer. MÉTODOS: O estudo incluiu 40 pacientes H. pylori-positivos diagnosticados com gastrite e úlcera duodenal ativas e 100 controles consistindo de candidatos doadores saudáveis. Foram estudadas nas amostras de DNA isoladas o antígeno leucocitário humano classe I e antígenos classe II, utilizando-se as cadeias de sequência específica de polimerase do oligonucleotideo. RESULTADOS: A frequência do antígeno HLA - B * 51 foi significativamente maior no grupo de pacientes do que no grupo controle (40% vs 17%; P=0,003). Não houve diferença entre os dois grupos em termos das frequências dos antígenos HLA-A, HLA-DR, HLA-DQ e HLA-C. CONCLUSÃO: Determinou-se que o HLA - B * 51 desempenha um papel crítico na infecção pelo H. pylori.

Immune Response and the Tumor Microenvironment: How They Communicate to Regulate Gastric Cancer

Gastric cancer is the second most common cause of cancer-related death in the world. A growing body of evidence indicates that inflammation is closely associated with the initiation, progression, and metastasis of many tumors, including those of gastric cancer. In addition, approximately 60% of the world's population is colonized by Helicobacter pylori, which accounts for more than 50% of gastric cancers. While the role of inflammation in intestinal and colonic cancers is relatively well defined, its role in stomach neoplasia is still unclear because of the limited access of pathogens to the acidic environment and the technical difficulties isolating and characterizing immune cells in the stomach, especially in animal models. In this review, we will provide recent updates addressing how inflammation is involved in gastric malignancies, and what immune characteristics regulate the pathogenesis of stomach cancer. Also, we will discuss potential therapeutics that target the immune system for the efficient treatment of gastric cancer.

Rastreio de síndrome poliglandular autoimune em uma população de pacientes com diabetes melito tipo 1 / Screening for autoimmune polyglandular syndrome in a cohort of patients with type 1 diabetes mellitus

OBJETIVO: Caracterizar uma população de pacientes com diabetes melito tipo 1 (DMT1) relativamente à presença de outras entidades autoimunes que permitam estabelecer o diagnóstico de síndrome poliglandular autoimune (SPGA). SUJEITOS E MÉTODOS: Incluímos 151 pacientes com DMT1. Analisamos os seguintes parâmetros clínicos: gênero, idade atual, duração da doença, antecedentes pessoais de patologia autoimune e antecedentes familiares de diabetes melito. Submetemos cada doente a um estudo laboratorial com o objetivo de detectar a presença de marcadores imunológicos para a tireoidite, insuficiência adrenocortical, gastrite e doença celíaca, e eventual disfunção associada. RESULTADOS: Coorte com 51,7% homens, idade média atual de 33,4 ± 13 anos e duração da doença de 14,4 ± 9,6 anos. Antecedentes pessoais de autoimunidade presentes em 2% da amostra e história familiar de diabetes melito em 31,1%. A frequência de marcadores imunológicos foi de 24% para a tireoidite, 9,4% para a insuficiência adrenocortical, 17,2% para a gastrite e 2% para a doença celíaca. Foi diagnosticada SPGA em 25,2% dos pacientes. O risco de SPGA e tireoidite autoimune foi superior em mulheres. A duração da doença correlacionou-se diretamente com a presença de autoanticorpos gástricos e inversamente com a positividade dos anticorpos anti-ilhota, antiglutamato descarboxilase e antitirosina fosfatase. Constatou-se a existência de uma associação entre os marcadores imunológicos da tireoidite e gastrite, bem como entre a doença celíaca e insuficiência adrenocortical. CONCLUSÃO: Atendendo à frequência e ao prognóstico inerente à SPGA, a necessidade de realizar rastreio em pacientes com DMT1 é enfatizada. O diagnóstico atempado de outras doenças autoimunes permitirá individualizar o tratamento e seguimento do doente.

OBJECTIVE: To characterize a cohort of patients with type 1 diabetes mellitus (T1DM) on the presence of other autoimmune disorders that could establish the diagnosis of autoimmune polyglandular syndrome (APS). SUBJECTS AND METHODS: We included 151 patients with T1DM. The following clinical parameters were analyzed: gender, current age, disease duration, previous history of autoimmune disorders, and familial history for diabetes mellitus. Each patient was analyzed to detect autoimmune markers of thyroiditis, adrenocortical insufficiency, gastritis, and celiac disease, as well as possible associated dysfunctions. RESULTS: A cohort with 51.7% males, average current age of 33.4 ± 13 years and disease duration of 14.4 ± 9.6 years was analyzed. Previous history of autoimmunity was found in 2%, and familial history for diabetes mellitus in 31.1% of the cohort. Frequency of autoimmune markers was 24% for thyroiditis, 9.4% for adrenocortical insufficiency, 17.2% for gastritis, and 2% for celiac disease. APS was diagnosed on 25.2% of the patients. APS and autoimmune thyroiditis risk was higher in females. Disease duration correlated directly with gastric autoantibodies, and inversely with positive islet cell, glutamic acid decarboxylase, and tyrosine phosphatase antibodies. We noticed a correlation between autoimmune markers for thyroiditis and gastritis, as well as between celiac disease and adrenocortical insufficiency. CONCLUSION: Considering APS prevalence and prognosis, the need for APS screening in patients with T1DM is emphasized. Early diagnosis of other autoimmune disorders will enable us to adjust each patient treatment and follow-up.

Relationship of IL-1 and TNF-α polymorphisms with Helicobacter pylori in gastric diseases in a Brazilian population

It is well known that the risk of development of gastric cancer (GC) in Helicobacter pylori-infected patients depends on several factors. Thus, the aim of this study was to investigate the effect of proinflammatory cytokine gene polymorphisms for IL-1β, IL-1RN and TNF-α on the development of GC in a Brazilian population. A total of 202 biopsies obtained from Brazilian patients with chronic gastritis and GC were included in the study. Infection with H. pylori cagA+ was determined by the polymerase chain reaction (PCR) as previously described. IL-1β, IL-1RN and TNF-α polymorphism genotyping was performed by restriction fragment length polymorphism PCR. Associations between gene polymorphisms, clinical diseases and virulence markers were evaluated using either the χ² test or the Fisher exact test. Our results demonstrated that the IL-1β -511 C/C and IL-1β -511 C/T alleles were associated with chronic gastritis in H. pylori-positive patients (P = 0.04 and P = 0.05, respectively) and the IL-1β -511 C/C genotype was associated with GC (P = 0.03). The frequency of IL-1RN alleles from patients with chronic gastritis and GC indicated that there was no difference between the genotypes of the groups studied. Similar results were found for TNF-α -308 gene polymorphisms. Our results indicate that the IL-1β -511 C/C and C/T gene polymorphisms are associated with chronic gastritis and GC development in H. pylori-infected individuals.

Receptores tipo Toll, patogénesis y respuesta inmune a Helicobacter pylori / Toll-like receptors, pathogenesis and immune response to Helicobacter pylori

Helicobacter pylori coloniza el epitelio gástrico y la mayoría de las personas infectadas es asintomática, de 10 al 20 por ciento desarrolla gastritis atrófica, úlcera péptica, y menos de 3 por ciento genera cáncer gástrico. Estas patologías están determinadas por la relación entre los factores de virulencia de la bacteria y los factores del hospedero como predisposición genética y respuesta inmune. La inmunidad innata, representada principalmente por los receptores tipo Toll y tipo Nod, reconocen a sus ligandos específicos y activan factores de transcripción como NF-kB, AP-1, CREB-1, induciendo la producción de citocinas inflamatorias como IL-8, IL-12, IL-6, IL-1β, IL-18 y TNF-α, e IL-10. La inflamación crónica favorece los cambios de morfología gástrica, evita la apoptosis y favorece la angiogénesis, ocasionando lesiones neoplásicas y cáncer. El objetivo de esta revisión es analizar los mecanismos propuestos a la fecha de la respuesta inmune innata y adaptativa, involucrados en la infección por H. pylori, y se puntualiza en los mecanismos de eliminación o persistencia de la infección.

Helicobacter pylori colonize the gastric epithelial, most infected people are asymptomatic, 10 to 20 percent develop atrophic gastritis, peptic ulcer and less than 3 percent gastric cancer. These diseases are determined by the relationship between virulence factors of bacteria, host factors such as, genetic predisposition, and immune response. The innate immune response mainly represented by Toll-like receptors and Nod-like receptors that recognize their specific ligands, activate transcription factors as NF-kB, AP-1, CREB-1, inducing production of inflammatory cytokines such as IL -8, IL-12, IL-6, IL-1β, IL-18, TNF-α and IL-10. Chronic inflammation promotes gastric morphological changes, prevents apoptosis and allows angiogenesis generating neoplasic lesions and cancer. The aim of this review is to analyze the mechanisms proposed to date of the innate and adaptative immune response involved in H. pylori infection; remarking the mechanisms related in the elimination or persistence.

Colonization by Helicobacter pylori of leprosy patients in Spain: immunomodulation to low molecular weight antigens of H. pylori

We studied the prevalence of Helicobacter pylori in patients with leprosy and the effects of co-infection on the immune response to Helicobacter antigens in the polar groups of leprosy (lepromatous and tuberculoid). We showed that there is no difference in the prevalence of H. pylori in patients with leprosy as compared to a non-leprosy population. We also demonstrated that the immune response to low molecular weight H. pylori antigens (35, 26 and 19 kDa) differs in patients with lepromatous as compared to those with tuberculoid leprosy. In lepromatous leprosy, we show that there is a higher prevalence of the 35 and 26 kDa antigens, but a lower prevalence of the 19 kDa antigen. These immunological results are consistent with previous histopathological studies illustrating a more severe gastrointestinal inflammation in lepromatous patients; importantly, a response to the 35 kDa antigen is recognized as a marker for the development of ulcerative disease.

Evaluación de la respuesta de inmunoglobulina a secretora anti-helicobacter pylori en saliva de pacientes con gastritis crónica / Evaluation of the response to secretory immunoglobulin anti-helicobacter pylori in saliva from patients with chronic gastritis

Helicobacter pylori ha sido implicado como el principal agente asociado a la patogénesis de gastritis crónica, úlcera péptica y neoplasias gástricas en humanos. El microorganismo ha sido detectado en placa dental, saliva y heces. En el presente estudio se determinó la respuesta immune de Ig A secretora anti- H.pylori en la saliva de 39 pacientes con dispepsia y en 20 sujetos sanos. Se tomaron biopsias gástricas de cada paciente para estudio histopatológico, prueba de ureasa, cultivo microbiológico y Reacción en Cadena de la Polimerasa (RCP), así como 5 ml de saliva no estimulada. Las muestras fueron obtenidas previo a la endoscopia. Los niveles de anticuerpos específicos de IgA secretora-Anti H.pylori fueron determinados por ensayo inmunoabsorbente ELISA. El antígeno utilizado fué preparado por sonicación de 5 cepas de H. pylori aislados de pacientes con úlceras duodenales. H. pylori fue detectado en 24/39 (62 por ciento) de los pacientes, todos con gastritis crónica. Los pacientes sintomáticos infectados con H.pylori presentaron niveles significativamente mayores de IgA secretora en saliva (0,2862 ± 0,144), que los pacientes del grupo control (0,1511 ± 0,069) (p>0005). Nuestros resultados indican que existe una correlación entre la presencia de H. pylori en la mucosa gástrica de pacientes con enfermedad de las vías digestivas superiors y la presencia de IgA secretora anti-H.pylori en saliva. Este ensayo a nivel de saliva representa una prueba rápida, no invasiva que puede ser utilizado en estudios epidemiológicos sobre todo en pacientes pediátricos

Helicobacter pylori has been implicated as the major acquired factor in the pathogenesis of chronic gastritis, peptic ulcer disease, and gastric neoplasia in humans. The microorganism has been detected in dental plaque, saliva and feces. In this study, we investigated the salivary anti H. pylori immunoglubulin A (IgA) immune response in 39 dyspeptic patients and 20 healthy volunteers. Gastric antrum biopsies were taken for histological examination, urease test, culture and polymerase chain reaction (PCR). Five mililiters of unstimulated saliva were obtained from all subjects before the endoscopy. The levels of specific antibodies in saliva were determined by ELISA test. The soluble antigen material for immunoenzymatic assay was prepared by sonication of five H. pylori strains isolated from duodenal ulcer patients. H. pylori was detected in antral samples from 24/39 (62 percent) patients, all of whom had chronic gastritis. Symptomatic patients infected with H. pylori showed levels significantly higher of secretory Ig A in saliva ( 0.2862 ± 0.144) than asymptomatic patients. (0.1511 ± 0.069) (p>0.005). Our results indicate that there is a correlation between the presence of H. pylori in gastric mucosa of symptomatic patients and the occurrence of secretory Ig A antibodies against H. pylori in saliva. Saliva testing is a rapid, noninvasive test that may have a role in epidemiological studies and in screening dyspeptic patients, specially in pediatric populations

The histopathology of chronic gastritis.

Chronic gastritis is a multifactorial disorder thought to be influenced by bacterial and host genetic factors. Histopathological examination is the mainstay of diagnosis, however features like the presence of Helicobacter pylori are difficult to evaluate on biopsy. We evaluated 120 gastric antral biopsies using the revised Sydney system. The density of the inflammatory infiltrate, H pylori and mast cells were evaluated. It was seen that the presence of H pylori is strongly associated with an acute and a chronic inflammatory infiltrate. The presence of neutrophils on biopsy is strongly associated with the presence of H pylori and with the density and the grade of the chronic inflammatory infiltrate. The chronic inflammatory response is an intermediary between the acute inflammatory process and glandular atrophy. The lymphocytic infiltrate is also a precursor lesion of the lymphoid follicles. The presence of mast cells does not appear to be related to any of the other inflammatory parameters. The presence of one feature is a strong indicator for the presence of other inflammatory features.

The Role of Gastric Acid in the H. pylori-induced Gastritis in Mouse / 대한소화기학회지

BACKGROUND/AIMS: This study was designed to investigate the role of gastric acid in the extent of H. pylori-induced gastritis. METHODS: Twenty eight mice were innoculated with live H. pylori. They were allocated into four groups. Mice in group I received no treatment, group II mice were treated with sham injection, group III received 125microgram/kg body weight of pentagastrin, while group IV received 250microgram/kg body weight of pentagastrin subcutaneously three times a week. After 7 months, the mucosal pH, H. pylori density, neutrophils and monocytes infiltration, and the degree of atrophy were assessed in the stomach. RESULTS: In the gastric body, the densities of H. pylori were not different among groups. The degree of neutrophil infiltration was significantly lower in group IV compared to other groups (p<0.05). The degree of monocyte infiltration was also significantly lower in group IV than group III (p<0.05). In the gastric antrum, there was no significant difference of the H. pylori density, neutrophil and monocyte infiltration, and degree of atrophy among the groups. The mice with the gastric mucosal pH lower than mean of 3.2 had significant lower level of H. pylori density (1.4 vs. 2.4, p=0.04), and infiltration of neutrophils (0.9 vs. 2.3, p=0.018), and monocytes (1.2 vs. 1.8; p=0.011) than the those with mucosal pH above 3.2 in the body of stomach. CONCLUSIONS: Gastric acid plays a role in suppressing the proximal propagation of H. pylori-induced gastritis to the body of stomach.

The role of IFN-gamma and IL-4 in gastric mucosa inflammation associated with Helicobacter heilmannii type 1 infection

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-gamma and IL-4, in H. heilmannii gastric infection in genetically IFN-gamma- or IL-4-deficient mice. The serum IFN-gamma and IL-4 concentrations were determined by ELISA. The gastric polymorphonuclear infiltrate was higher (P = 0.007) in H. heilmannii-positive than in H. heilmannii-negative wild-type (WT) C57BL/6 mice, whereas no significant inflammation was demonstrable in the stomach of H. heilmannii-positive IFN-gamma-/- 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-gamma 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-gamma 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-g 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-gamma playing a central role in gastric inflammation.

The Effect of the Repeated Subcultures of Helicobacter pylori on Adhesion, Motility, Cytotoxicity, and Gastric Inflammation

In vitro subcultures of bacteria can lead to genetic and phenotypic changes. This study aimed at investigating the effect of repeated subcultures on the adhesion, motility, cytotoxicity, and gastric inflammation caused by Helicobacter pylori. H.pylori SS1 strain was subcultured 64 times on agar plates containing Brucella broth and 5% bovine calf serum. The adhesion, motility, cytotoxicity, and gastric inflammation produced in Mongolian gerbils were compared between the first and 64th subcultured strain. The adhesion rates, following 3 hr exposure of AGS cells to either the first strain or the 64th-transferred strain, were 21% and 12%, respectively. The motility of the 64th-transferred strain decreased significantly when compared to the 1st strain (9.1 mm vs. 15.1 mm). The cytotoxicity index tended to be higher in the first strain than in the 64th-transferred strain (73.7% vs. 69.2%). The initial infection rate on the gerbils showed no difference between the two strains. However, chronic gastric inflammation of the first strain-infected gerbils was somewhat more severe than that of the 64th-transferred strain-infected gerbils. Therefore, the use of repeatedly subcultured strains of H. pylori in virulence experiments can lead to different results from thoses of the original strain.

Lymphocitic astritis: a study of its frequency and review of the literature

Lymphocytic gastritis is currently recognized as a special type of chronic gastritis characterized by a large number of intraepithelial lymphocytes in antral or oxyntic mucosa. The frequency of lymphocytic gastritis rarely exceeds 5 per cent of the histologic diagnosis of gastric biopsies. This diagnosis can be easily made by intraepithelial lymphocyte counts in preparations stained with hematoxylin and eosin. Very little is known about the etiopathogeny, clinical significance and evoution of the disease. The objective of the present study was to investigate the frequency of lymphocytic gastritis in gastric mucosa biopsies from the antrum and body in patientes submitted to upper digestive endoscopy in Belo Horizonte, MG, Brazil. Histological sections of antral and oxyntic mucosa from 400 patients with no gastric ulcer or neoplasia of the gastrointestinal tract were analyzed retrospectively. The following lymphocyte numbers per 100 epithelial cells were obtained: 0 a 5 lymphocytes in 366 patients (91,5 per cent); 6 to 15 lymphocytes in 22 patients (5,5 per cent); 16 to 29 lymphocytes in eight patients (2.0 per cent), and 30 or more lymphocytes in four patients (1 per cent). Patients with 30 or more lymphocytes were considered to haver lymphocytic gastritis. Three of these four cases with lymphocytic gastritis presented an endoscopic diagnosis of enanthematous pangastritis, and one presented erosive pangastritis.

Antigenic diversity and serotypes of Helicobacter pylori associated with peptic ulcer diseases

OBJECTIVES: Clinical presentation of Helicobacter pylori (H. pylori) infection has marked variation mainly due to the strain diversity and host susceptibility. Although H. pylori is identified as a major risk factor for gastric and duodenal ulcers, the ulcerogenic or pathogenic strain has not been documented yet. The objective of this study was to investigate antigenic types of the ulcerogenic strain of H. pylori. METHODS: The sera of 64 patients were tested by Western blot using Helicoblot 2.0 for six major anti-H. pylori antibodies, together with CLO test and histological examination of gastric biopsy tissues. Thirty-five, nine and 20 patients had duodenal ulcer, gastric ulcer and chronic active gastritis, respectively. The antigenic types of H. pylori were analyzed in 54 patients with positive H. pylori infection. In this study, H. pylori was divided into four serotypes according to the presence and absence of CagA and VagA: type I; CagA (+) and VacA(+), type Ia: CagA (+) and VacA(-), type Ib: CagA(-) and VacA(+), and type II: CagA(-) and VacA(-). RESULTS: There was no difference in the number of bands for six antigens: 3.2 +/- 1.4, 3.0 +/- 1.2 and 3.1 +/- 1.4 in 35 duodenal ulcer, 7 gastric ulcer and 12 chronic gastritis, respectively. The band with 119 kDa was 90.7%, which was the most common band with the order of 35, 30, 26.5, 89 and 19.5 kDa. Type I, la and Ib were positive in 22.2, 42.6 and 27.8%, respectively, which were significantly higher than type II (p < 0.05). There was no difference in the positive rates of four urease subtypes between the four serotypes.

Host tissue reaction to Gnathostoma malaysiae (Nematoda: Gnathostomidae) in Rattus surifer Miller.

The occurrence of adult Gnathostoma malaysiae in Rattus surifer and R. tiomanicus in Malaysia has been reported but there are no known reports on the host tissue reactions. This paper reports on the gross pathology caused by G. malaysiae in a red spiny forest rat, R. surifer and the tissue reactions caused. A tumor-like growth was located on the mid-stomach wall in a female rat captured in Gunung Bachock, Kelantan, Malaysia. This growth consisted of four tunnel-like structures containing sanguinopurulent fluid and leukocytes and this structure led into a central canal. The tissue surrounding the tumor was greatly inflamed and there was localized gastritis. The tunnel-like structure was surrounded by dense fibrotic tissue. The stomach wall was devoid of superficial epithelium and smooth muscle but mucinous glands were present. The midregion of the fibrotic scar contained eggs of G. malaysiae which had evoked a strong tissue reaction and were surrounded by pus. Blood vessels were empty, dilated and had undergone vasculitis and thrombosis.

La gastritis linfocítica / Lymphocytic gastritis

Se presenta una revisión de 100 biopsias endoscópicas consecutivas de patología gástrica inflamatoria, encontrándose 4 casos de Gastritis Linfocitaria que se caracteriza por la infiltración de linfocitos intraepiteliales de epitelio superficial y foveolar de la mucosa gástrica, mientras que el infiltrado inflamatorio del corion es moderado. Se comenta la relación estrecha entre las características histológicas de ésta y el aspecto endoscópico de la llamada "Gastritis varioliforme". Em 2 de 4 casos clasificados como Gastritis Linfocitaria se identificaron organismos de tipo Campylobacter pylori. Se comenta brevemente la literatura mencionado la hipótesis de la probable participación del Campylobacter pylori en la patogenia de esta entidad

Respuesta de anticuerpos IgG en pacientes colonizados por helicobacter pylori / Antibodies to helicobacter pylori in colonized patients with gastric symptoms and in asymptomatic groups

The IgG antibody response specific to Helicobacter pylori was evaluated through ELISA in a group of 92 gastric patients colonized by this bacteria. 74 had gastritis and 19 gastroduodenal ulcer. Three control groups were studied in a similary way: normal adult volunteers (n=17), adults with E coli or S typhi bacteremia (n=30) and normal infants (n = 30). IgG antibody response to H pylori was demonstrated in 98% of colonized patients and 0% of infants. Asymptomatic individuals and those with bacteremia had high rates of antibody response (76 and 90% respectively), although this rate and also the titers of antibody response were significantly lower than that of colonized patients (p < 0.05). ELISA reactive sera from colonized patients and asymptomatic individuals evidenced a similar antibody pattern when tested by blotting. This profile was absent in non reactive sera, including those with high antibody titers to C jejuni. The presence of specific IgG antibodies to H pylory in the majority of colonized gastric patients and asymptomatic adults suggest that this infection is very common in our population