RESUMO
BACKGROUND: Systemic-to-pulmonary shunt is a palliative procedure used to decrease pulmonary blood flow in congenital heart diseases. Shunt stenosis or occlusion has been reported to be associated with mortality; therefore, the management of thrombotic complications remains a challenge for most congenital cardiovascular surgeons. Despite its importance, the optimal method for shunt anastomosis remains unclear. OBJECTIVE: The study investigates the clinical benefits of the punch-out technique over conventional methods in the anastomosis process of Systemic-to-pulmonary shunt, focusing on its potential to reduce shunt-related complications. METHODS: Anastomotic models were created by two different surgeons employing both traditional slit and innovative punch-out techniques. Computational tomography was performed to construct three-dimensional models for computational fluid dynamics (CFD) analysis. We assessed the flow pattern, helicity, magnitude of wall shear stress, and its gradient. RESULTS: The anastomotic flow area was larger in the model using the punch-out technique than in the slit model. In CFD simulation, we found that using the punch-out technique decreases the likelihood of establishing a high wall shear stress distribution around the anastomosis line in the model. CONCLUSION: The punch-out technique emerges as a promising method in SPS anastomosis, offering a reproducible and less skill-dependent alternative that potentially diminishes the risk of shunt occlusion, thereby enhancing patient outcomes.
RESUMO
BACKGROUND AND AIMS: Surgery for extensive thoracic aortic aneurysms is challenging. We aim to report our novel extended arch repair method, which we termed "parabronchial approach" for such disease. MATERIALS AND METHODS: The patient case data was extracted from hospital records. RESULTS: The patient was the case of a 31-year-old woman with Takayasu's arteritis who developed aortic dissection. She underwent extended arch repair via a simple sternotomy approach. The left pulmonary artery compression with a retractor arrowed us to obtain adequate working space. Postoperative computed tomography revealed a distal anastomosis site level was at the sixth thoracic vertebra. DISCUSSION AND CONCLUSION: This parabronchial approach could reduce the frequency of choosing a highly invasive approach and can be a potential minimally invasive approach in cases requiring extensive thoracic aortic aneurysm repair.
Assuntos
Aneurisma da Aorta Torácica , Dissecção Aórtica , Implante de Prótese Vascular , Adulto , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/cirurgia , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/cirurgia , Implante de Prótese Vascular/métodos , Feminino , Humanos , Esternotomia/métodosRESUMO
BACKGROUND AND AIMS: The clinical data of coronary artery disease in patients with double-chambered right ventricle are limited. We report an adult double-chambered right ventricle case with three-vessel coronary artery disease that was successfully treated with concomitant double-chambered right ventricle repair and coronary artery bypass grafting. MATERIALS AND METHODS: The patient case data was extracted from hospital records. RESULTS: The patient was the case of a 60-year-old man with a double-chambered right ventricle and three-vessel coronary artery disease. He underwent concomitant surgery comprising double-chambered right ventricle repair and coronary artery bypass grafting. Achieving cardiac arrest allowed us to obtain a good surgical view of the heavy and severely hypertrophied heart. Postoperative computed tomography revealed a feasible running course of the sequential graft, indicating that the path of the sequential graft should be clockwise (aorto-right coronary-left circumflex artery) in this unusual anatomical condition. DISCUSSION AND CONCLUSION: We report this rare disease combination and highlight the need for careful preoperative planning in such cases.
Assuntos
Estenose Coronária , Comunicação Interventricular , Adulto , Ponte de Artéria Coronária , Estenose Coronária/diagnóstico por imagem , Estenose Coronária/cirurgia , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios XRESUMO
Dialysis patients are at increased risk of ischemic colitis and are likely to develop irreversible ischemic colitis. We report a rare case of ischemic colitis after the closure of a temporary ileostomy for low anterior resection(LAR)of rectal cancer in a dialysis patient. A 77-year-old man undergoing maintenance dialysis was diagnosed as having colorectal cancer with a type 2 tumor at the anastomosis site of high anterior resection performed for sigmoid colon cancer 14 years ago. After undergoing excision which included the anastomosis site of the previous operation, LAR with anastomosis in the transverse colon and rectum and temporary ileostomy were performed. Seven months later, closure of the temporary ileostomy was performed, which resulted in ileus and septic shock. Computed tomography(CT)revealed inflammation in the colon on the oral side of the anastomosis, which was diagnosed as ischemic colitis. Ischemic colitis did not improve with conservative treatment, and fever reoccurred at each maintenance dialysis session. Therefore, ileostomy was performed again, but multiple organ failure due to disseminated intravascular coagulopathy(DIC)progressed and he died. It is considered that Hartmann's operation should be selected for dialysis patients with serious underlying diseases, and if ischemic colitis is observed after closure of the stoma temporary colostomy in such patients, the lesion site of ischemic colitis should be excised promptly and colostomy should be performed again.
Assuntos
Colite Isquêmica , Neoplasias Retais , Idoso , Anastomose Cirúrgica , Colite Isquêmica/etiologia , Colite Isquêmica/cirurgia , Colostomia , Humanos , Ileostomia , Masculino , Complicações Pós-Operatórias/etiologia , Neoplasias Retais/cirurgia , Diálise RenalRESUMO
BACKGROUND & AIMS: Helicobacter pylori CagA-positive strain is associated with gastric adenocarcinoma. CagA is delivered into gastric epithelial cells, where it undergoes tyrosine phosphorylation at the EPIYA sites by Src family kinases (SFKs). Owing to homologous recombination within the 3'-region of the cagA gene, 4 distinct EPIYA sites, each of which is defined by surrounding sequences, are variably assembled in both number and order among CagA proteins from different clinical H pylori isolates. Tyrosine-phosphorylated CagA specifically binds and deregulates SHP-2 via the Western CagA-specific EPIYA-C or East Asian CagA-specific EPIYA-D site, and C-terminal Src kinase (Csk) via the EPIYA-A or EPIYA-B site. Here we investigated the influence of EPIYA-repeat polymorphism on the CagA activity. METHODS: A series of EPIYA-repeat variants of CagA were expressed in AGS gastric epithelial cells and the ability of individual CagA to bind SHP-2 or Csk was determined by the sequential immunoprecipitation and immunoblotting method. RESULTS: CagA proteins carrying multiple EPIYA-C or EPIYA-D sites bound and deregulated SHP-2 more strongly than those having a single EPIYA-C or EPIYA-D. Furthermore, the ability of CagA to bind Csk was correlated with the number of EPIYA-A and EPIYA-B sites. Because Csk inhibits SFK, CagA with greater Csk-binding activity more strongly inhibited Src-dependent CagA phosphorylation and more effectively attenuated induction of cell elongation caused by CagA-SHP-2 interaction. CONCLUSIONS: EPIYA-repeat polymorphism of CagA greatly influences the magnitude and duration of phosphorylation-dependent CagA activity, which may determine the potential of individual CagA as a bacterial virulence factor that directs gastric carcinogenesis.
Assuntos
Antígenos de Bactérias/fisiologia , Proteínas de Bactérias/fisiologia , Polimorfismo Genético , Sequências Repetitivas de Aminoácidos , Antígenos de Bactérias/classificação , Antígenos de Bactérias/genética , Antígenos de Bactérias/metabolismo , Proteínas de Bactérias/classificação , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Proteína Tirosina Quinase CSK , Linhagem Celular , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Fenótipo , Fosforilação , Proteína Tirosina Fosfatase não Receptora Tipo 11 , Proteínas Tirosina Fosfatases/antagonistas & inibidores , Proteínas Tirosina Fosfatases/metabolismo , Proteínas Tirosina Quinases/metabolismo , Tirosina/metabolismo , Quinases da Família src/metabolismoRESUMO
Helicobacter pylori vacuolating cytotoxin, VacA, induces vacuolation in mammalian cell lines. Sequence differences in the middle of VacA molecules define two families, termed m1VacA and m2VacA, which differ in cell specificity. Similar to m1VacA, m2VacA is activated by acid or alkali, which enhances its binding to cells. Immunoprecipitation experiments showed that, in AZ-521 cells, activated m2VacA, similar to m1VacA, binds to two receptor-like protein tyrosine phosphatases, RPTPalpha and RPTPbeta suggesting that activated m2VacA as well as m1VacA may contribute to gastrointestinal disease following H. pylori infection. G401 cells express RPTPalpha, not RPTPbeta, and responded to both m1VacA and m2VacA. HeLa cells likewise expressed RPTPalpha, not RPTPbeta, but, in contrast to other cell lines, responded poorly to m2VacA. m1VacA associated with RPTPalpha of HeLa cells to an extent similar to that in other toxin-sensitive cells, whereas activated m2VacA bound HeLa cell RPTPalpha less well, consistent with its low vacuolating activity against these cells. The molecular mass of RPTPalpha from HeLa cells is less than that of the protein from G401 cells, although their extracellular amino acid sequences are virtually identical, with only two amino acid differences noted. Different post-translational modifications of RPTPalpha in HeLa cells may be responsible for the reduced susceptibility to m2VacA.
Assuntos
Proteínas de Bactérias/metabolismo , Helicobacter pylori/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Proteínas Tirosina Fosfatases/metabolismo , Receptores de Superfície Celular/metabolismo , Vacúolos/ultraestrutura , Adenocarcinoma , Aderência Bacteriana , Proteínas de Bactérias/farmacologia , Linhagem Celular Tumoral , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Imunoprecipitação , Isoformas de Proteínas/metabolismo , Processamento de Proteína Pós-Traducional , Proteínas Tirosina Fosfatases Classe 4 Semelhantes a Receptores , Proteínas Tirosina Fosfatases Classe 5 Semelhantes a Receptores , Neoplasias Gástricas , Vacúolos/efeitos dos fármacosRESUMO
Colonization of the stomach mucosa by Helicobacter pylori is a major cause of acute and chronic gastric pathologies in humans. Several H. pylori virulence genes that may play a role in its pathogenicity have been identified. The most important determinants are vacA and cagA in the cag pathogenicity island (cagPAI) genes. In the present study, to consider the association of molecular genetics between vacA and the cagPAI regarding clinical outcome, we selected H. pylori strains with various genotypes of vacA in Japan and sequenced full-length vacA, cagA, and cagE genes. Sequencing of vacA and cagA genes revealed variable size, whereas the cagE gene was well conserved among strains. Each of the phylogenetic trees based on the deduced amino acid sequences of VacA, CagA, and CagE indicated that all three proteins were divided into two major groups, a Western group and an East Asian group, and the distributions of isolates exhibited similar patterns among the three proteins. The strains with s2 and s1a/m1a vacA genotypes and the Western-type 3' region cagA genotype were classified into the Western group, and the strains with the s1c/m1b vacA genotype and the East Asian-type 3' cagA genotype were included in the East Asian group. In addition, the prevalence of infection with the Western group strain was significantly higher in patients with peptic ulcer (90.0%, 9/10) than in patients with chronic gastritis (22.7%, 5/22) (chi2 = 12.64, P = 0.00057). These data suggest that the molecular genetics of vacA and cagPAI are associated and that the Western group with vacA and cagPAI genes is associated with peptic ulcer disease.
Assuntos
Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Helicobacter pylori/genética , Úlcera Péptica/microbiologia , Sequência de Aminoácidos , Sequência de Bases , Variação Genética , Humanos , Dados de Sequência Molecular , FilogeniaRESUMO
The CagA protein is one of the virulence factors of Helicobacter pylori, and two major subtypes of CagA have been observed, the Western and East Asian type. CagA is injected from the bacteria into gastric epithelial cells, undergoes tyrosine phosphorylation, and binds to Src homology 2 domain-containing protein-tyrosine phosphatase SHP-2. The East Asian type CagA binds to SHP-2 more strongly than the Western type CagA. Here, we tried to distinguish the CagA type by highly sensitive real-time PCR with the objective of establishing a system to detect H. pylori and CagA subtypes from gastric biopsies. We designed primers and probe sets for Western or East Asian-cagA at Western-specific or East Asian-specific sequence regions, respectively, and H. pylori 16S rRNA. We could detect the H. pylori 16S rRNA gene, Western and East Asian-cagA gene from DNA of gastric biopsies. The sensitivity and specificity for H. pylori infection was 100% in this system. In Thai patients, 87.8% (36/41) were cagA-positive; 26.8% (11/41) were Western-cagA positive and 53.7% (22/41) were East Asian-cagA positive, while 7.3% (3/41) reacted with both types of cagA. These results suggest that this real-time PCR system provides a highly sensitive assessment of CagA type as a new diagnostic tool for the pathogenicity of H. pylori infection.
Assuntos
Antígenos de Bactérias/isolamento & purificação , Proteínas de Bactérias/isolamento & purificação , Mucosa Gástrica/microbiologia , Genes Bacterianos , Infecções por Helicobacter/diagnóstico , Helicobacter pylori/isolamento & purificação , Reação em Cadeia da Polimerase/métodos , Adulto , Idoso , Sequência de Aminoácidos , Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Sequência de Bases , Biópsia , Feminino , Infecções por Helicobacter/microbiologia , Helicobacter pylori/genética , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Polimorfismo Genético , RNA Bacteriano/análise , RNA Ribossômico 16S/análise , Sensibilidade e Especificidade , TailândiaRESUMO
Mongolian gerbils are an ideal animal model to explore the role of H. pylori on cancer development. However, there have been no established adenocarcinoma cell lines from this model animal. In the present study, we have established cancer cell lines from a primary gastric cancer tissue of a Mongolian gerbil. The derived cells could be stably attached with H. pylori, revealed under a scanning electron microscope, and easily transplanted to the nude mice. Rapid phosphorylation of IkappaB, Erk1/2, and AKT of these cells was observed by Interleukin-1 beta stimulation, and luciferase reporter gene assay on transcriptional activation of Nuclear Factor kappa B after challenging with either H. pylori NCTC11637 or its isogenic cagE-knockout mutant, H. pylori revealed the cagE-dependent NF-kappaB transcriptional activation. The newly established cancer cell lines from the in vivo gastric carcinogenesis model animal, the Mongolian gerbil, can be used to develop effective therapeutic strategies against gastric cancer, especially in exploring the effect of H. pylori, and thus might greatly contribute to gastric cancer prevention and treatment in humans.
Assuntos
Modelos Animais de Doenças , Infecções por Helicobacter/complicações , Helicobacter pylori/patogenicidade , NF-kappa B/biossíntese , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/patologia , Animais , Regulação da Expressão Gênica , Gerbillinae , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , NF-kappa B/genética , Invasividade Neoplásica , Neoplasias Gástricas/veterinária , Células Tumorais CultivadasRESUMO
The severity of Helicobacter pylori-related disease is correlated with the presence of a cag pathogenicity island (PAI). Genetic diversity within the cag PAI may have a modifying effect on the pathogenic potential of the infecting strain. We analyzed the complete cag PAI sequences of 11 representative Japanese strains according to their vacA genotypes and clinical effects and examined the relationship between the diversity of the cag PAI and clinical features. The cag PAI genes were divided into two major groups, a Western and a Japanese group, by phylogenetic analysis based on the entire cag PAI sequences. The predominant Japanese strains formed a Japanese cluster which was different from the cluster formed by Western strains. The diversity of the cag PAI was associated with the vacA and cagA genotypes. All strains with the s1c vacA genotype were in the Japanese cluster. In addition, all strains with the East Asian-type cagA genotype were also in the Japanese cluster. Patients infected with the Japanese-cluster strain had high-grade gastric mucosal atrophy. These results suggest that a distinct diversity of the cag PAI of H. pylori is present among Japanese strains and that this diversity may be involved in the development of atrophic gastritis and may increase the risk for gastric cancer.
Assuntos
Helicobacter pylori/genética , Helicobacter pylori/patogenicidade , Antígenos de Bactérias/metabolismo , Proteínas de Bactérias/metabolismo , Helicobacter pylori/classificação , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Fosforilação , Filogenia , Transporte Proteico , Proteína Tirosina Fosfatase não Receptora Tipo 11 , Proteínas Tirosina Fosfatases/metabolismoRESUMO
We investigated the relationship between the diversity of Helicobacter pylori CagA protein and clinical outcome. The cagA gene was sequenced in 115 clinical isolates. The binding affinity of CagA to Src homology 2 domain-containing tyrosine phosphatase (SHP-2) was examined by in vitro infection. Two major CagA subtypes were observed--the East Asian and the Western type. The grades of inflammation, activity of gastritis, and atrophy were significantly higher in patients with gastritis infected with the East Asian CagA-positive strain than in patients with gastritis infected with cagA-negative or Western CagA-positive strains. All strains isolated from patients with gastric cancer were East Asian CagA positive. East Asian CagA exhibited stronger SHP-2-binding activity than did Western CagA. These findings suggest that infection with East Asian CagA-positive H. pylori is associated with atrophic gastritis and gastric cancer and that persistent active inflammation induced by the East Asian CagA-positive strain may play a role in the pathogenesis of disease.
Assuntos
Antígenos de Bactérias/metabolismo , Proteínas de Bactérias/metabolismo , Mucosa Gástrica/patologia , Helicobacter pylori/genética , Proteínas Tirosina Fosfatases/metabolismo , Neoplasias Gástricas/patologia , Estômago/patologia , Sequência de Aminoácidos , Sequência de Bases , Sítios de Ligação , Sequência Conservada , Primers do DNA , Gastrite/microbiologia , Gastrite/patologia , Variação Genética , Helicobacter pylori/isolamento & purificação , Humanos , Dados de Sequência Molecular , Alinhamento de Sequência , Neoplasias Gástricas/microbiologia , Domínios de Homologia de srcRESUMO
It has been reported that Helicobacter pylori infection with the type I strain, which expresses the VacA and CagA antigens, is associated with duodenal ulcer. We examined the diversity of vacA and cagA genes in 143 isolates obtained from patients with duodenal ulcer or chronic gastritis in East Asia (two different areas of Japan, Fukui and Okinawa, and also in Hangzhou, China) by polymerase chain reaction (PCR) and sequence analysis. Diversities of cagA and vacA genes were detected in East Asia. The prevalence of cagA-positive H. pylori was significantly different between Fukui and Okinawa (P=0.0032). The prevalence of Western type CagA was significantly higher in Okinawa than in Fukui (P<0.0001). However, there was no significant association between the genotype of cagA and clinical outcome. In Japan, the predominant vacA genotype was s1c/m1b. In contrast, in Hangzhou, the predominant vacA genotype was s1c/m2, and they were all East Asian CagA-positive. These findings suggest that a distinct distribution of the vacA and cagA genotypes is present in East Asia, regardless of clinical outcome.
Assuntos
Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Úlcera Duodenal/microbiologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/genética , Adulto , Alelos , Sequência de Bases , China , Ásia Oriental , Feminino , Genes Bacterianos , Variação Genética , Genótipo , Helicobacter pylori/patogenicidade , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Virulência/genéticaRESUMO
Recent experiments have indicated that CagA of Helicobacter pylori is injected into epithelial cells via the type IV secretion system and undergoes tyrosine phosphorylation in cells and that translocated CagA binds the SRC homology 2 domain-containing tyrosine phosphatase (SHP-2). We investigated these phenomena in in vivo human gastric mucosa. Tyrosine-phosphorylated CagA and CagA-coimmunoprecipitated SHP-2 were detected in gastric mucosa from H. pylori-positive patients with atrophic gastritis and in noncancerous tissues from H. pylori-positive patients with early gastric cancer. In contrast, CagA was not detected in gastric mucosa with either intestinal metaplasia or cancer. Our results provide the first evidence that CagA is translocated into the gastric epithelial cells, receives tyrosine phosphorylation, and binds SHP-2 in in vivo human gastric mucosa. Deregulation of SHP-2 by CagA may play a role in the acquisition of a cellular-transformed phenotype at a relatively early stage of multistep gastric carcinogenesis.
Assuntos
Antígenos de Bactérias , Proteínas de Bactérias/metabolismo , Células Epiteliais/metabolismo , Mucosa Gástrica/metabolismo , Helicobacter pylori/metabolismo , Proteínas Tirosina Fosfatases/metabolismo , Gastrite Atrófica/enzimologia , Gastrite Atrófica/etiologia , Gastrite Atrófica/microbiologia , Gastrite Atrófica/patologia , Infecções por Helicobacter/enzimologia , Infecções por Helicobacter/metabolismo , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Helicobacter pylori/patogenicidade , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Fosforilação , Ligação Proteica , Transporte Proteico , Proteína Tirosina Fosfatase não Receptora Tipo 11 , Neoplasias Gástricas/enzimologia , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/patologiaRESUMO
Genetic diversity within the cag pathogenicity island (PAI) of Helicobacter pylori may have a modifying effect on the pathogenic potential of the infecting strain. The genetic structure of the cag PAI was examined in Japanese isolates. The composition and nucleotide sequences of the cag PAI were quite similar among strains; however, diversity between 2 cag genes (virB10 and cagA) was observed. The variety in the number of repetition of the 5-amino acid sequence R1 (EPIYA) in the 3' region of the cagA gene was identified. The frequencies of the genotypes that contained >4 R1 sequences were significantly higher in atrophic gastritis-causing strains than in duodenal ulcer-causing strains. One-third of strains with >4 R1 sequences were gastric cancer-causing strains. Although the cag PAI is conserved in H. pylori isolates in Japan, H. pylori infection with the cagA genotype with >4 R1 sequences may correlate with the pathogenesis of atrophic gastritis and gastric cancer.
Assuntos
Antígenos de Bactérias , Proteínas de Bactérias/genética , Gastrite Atrófica/microbiologia , Variação Genética , Infecções por Helicobacter/complicações , Helicobacter pylori/patogenicidade , Neoplasias Gástricas/microbiologia , Sequência de Aminoácidos , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Progressão da Doença , Feminino , Gastroenteropatias/microbiologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/genética , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Alinhamento de Sequência , Análise de Sequência de DNA , VirulênciaRESUMO
Helicobacter pylori is a causative agent of gastritis and peptic ulcer. cagA(+) H. pylori strains are more virulent than cagA(-) strains and are associated with gastric carcinoma. The cagA gene product, CagA, is injected by the bacterium into gastric epithelial cells and subsequently undergoes tyrosine phosphorylation. The phosphorylated CagA specifically binds SHP-2 phosphatase, activates the phosphatase activity, and thereby induces morphological transformation of cells. CagA proteins of most Western H. pylori isolates have a 34-amino acid sequence that variably repeats among different strains. Here, we show that the repeat sequence contains a tyrosine phosphorylation site. CagA proteins having more repeats were found to undergo greater tyrosine phosphorylation, to exhibit increased SHP-2 binding, and to induce greater morphological changes. In contrast, predominant CagA proteins specified by H. pylori strains isolated in East Asia, where gastric carcinoma is prevalent, had a distinct tyrosine phosphorylation sequence at the region corresponding to the repeat sequence of Western CagA. This East Asian-specific sequence conferred stronger SHP-2 binding and morphologically transforming activities to Western CagA. Finally, a critical amino acid residue that determines SHP-2 binding activity among different CagA proteins was identified. Our results indicate that the potential of individual CagA to perturb host-cell functions is determined by the degree of SHP-2 binding activity, which depends in turn on the number and sequences of tyrosine phosphorylation sites. The presence of distinctly structured CagA proteins in Western and East Asian H. pylori isolates may underlie the strikingly different incidences of gastric carcinoma in these two geographic areas.