Cytotoxin‐associated antigen A (CagA) protein produced by Helicobacter pylori is proposed to be associated with the pathogenesis of gastric cancer as well as gastritis and gastroduodenal ulcer. It ...has been reported that the CagA of H. pylori widespread in East Asian countries, where the mortality rate due to gastric cancer is high, is structurally different from that in Western countries, where the gastric cancer mortality rate is relatively low. In this study, we generated an antibody, East Asian CagA‐specific antibody (α‐EAS Ab), which is specifically immunoreactive with East Asian CagA but not with Western CagA. The CagA was immunohistochemically detected at the surface of the gastric mucosa. Interestingly, positive immunoreactivity was also detected in the nucleus and cytoplasm of the infected gastric epithelium, suggesting that CagA may play some pathogenic role in both the nucleus and cytoplasm. Immunohistochemistry of 47 gastric biopsy specimens detected East Asian CagA‐positive H. pylori in 43 cases. In 46 of the 47 cases examined, the data obtained by immunohistochemistry were completely consistent with those obtained by sequencing of the cagA gene of the isolated strain, suggesting that our immunohistochemical method is reliable and useful for diagnosis of the cagA genotype. (Cancer Sci 2007; 98: 521–528)
The cytotoxin‐associated antigen A (CagA) of Helicobacter pylori prevalent in East Asian countries, where the mortality rate due to gastric cancer is high, has been reported to be structurally ...different from that in Western countries, where the gastric cancer mortality rate is relatively low. Based on the structural features of the EPIYA motifs located at the carboxyl terminal of the protein, CagA was subdivided into two types: East Asian CagA and Western CagA. A recent study suggested that immunohistochemistry with anti‐East Asian‐specific antibody (α‐EAS Ab), which was specifically immunoreactive with East Asian CagA but not with Western CagA, may be useful for diagnosis of the cagA genotype. To further evaluate the value of this diagnostic method in terms of sensitivity, specificity, and accuracy, 143 gastric biopsy specimens with α‐EAS Ab were analyzed on immunohistochemistry and compared with the sequencing of the cagA gene. It was found that diagnosis of the cagA genotype of H. pylori on immunohistochemistry using the α‐EAS Ab was highly sensitive (sensitivity 93.2%) and specific (specificity 72.7%), suggesting that immunohistochemical diagnosis of the cagA genotype is useful for diagnosis of the cagA genotype.
Neurotoxicity caused by nonfibrillar amyloid β (Aβ) oligomers in the brain is suggested to be associated with the onset of Alzheimer’s disease (AD). Elucidating the structural features of Aβ ...oligomers is critical for promoting drug discovery research for AD. One of the Aβ oligomers, known as Aβ*56, is a dodecamer that impairs memory when injected into healthy rats, suggesting that Aβ*56 may contribute to cognitive deficits in AD patients. Another dodecamer structure, formed by 20-residue peptide segments derived from the Aβ peptide (Aβ17–36), has been revealed by X-ray crystallography. The structure of the Aβ17–36 dodecamer is composed of trimer units and shows the oligomer antibody A11 reactivity, which are characteristic of Aβ*56, indicating that Aβ*56 and the Aβ17–36 dodecamer share a similar structure. However, the structure of the C-terminal regions (Aβ37–42) remains unclear. The C-terminal region, which is abundant in hydrophobic residues, is thought to play a key role in stabilizing the oligomer structure by forming a hydrophobic core. In this study, we employed dissipative particle dynamics, a coarse-grained simulation method with soft core potentials, utilizing the crystal structure information to unravel Aβ dodecamer structures with C-terminal regions. The simulation results were validated by the reported experimental data. Hence, an analysis of the simulation results can provide structural insights into Aβ oligomers. Our simulations revealed the stabilization mechanism of the dodecamer structure at the molecular level. We showed that C-terminal regions spontaneously form a hydrophobic core in the central cavity, contributing to stabilizing the dodecamer structure. Furthermore, four consecutive hydrophobic residues in the C-terminal region (i.e., Val39–Ala42) are important for core formation.
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