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Objective: The objective of this study was to evaluate the clinical significance of ultrasonography (US) for screening for thyroid gland diseases when surveying the cervical lymph nodes to detect metastasis in subjects with oral squamous cell carcinoma (SCC)., Methods: The detection rates and characteristics of abnormal thyroid findings detected by US in 301 subjects with oral SCC were analyzed. Subjects with abnormal findings were referred to thyroid specialists and the diagnoses and treatments from these specialists were noted. The ratio of subjects who consulted a thyroid specialist after indications of thyroid gland abnormalities to analyze subject compliance was also examined. Follow-up examinations were regularly conducted to assess any changes in the thyroid gland., Results: Of the 301 subjects with oral SCC, 91 had abnormal thyroid gland findings on US. As subject age increased, the rate of detection of abnormal thyroid gland findings on US significantly increased. The rate of detection of abnormal findings in women by US was significantly higher than that in men, but the male-to-female ratio was lower compared with that in previous reports. It was demonstrated that oral SCC in the floor of the mouth was associated with the highest prevalence of abnormal findings in the thyroid gland (40%), followed by oral SCC of the maxillary gingiva (39%). Of the 91 subjects with abnormal findings, 10 showed enlargement in the size of the lesion on follow-up examination with US. Eleven subjects with no abnormal findings on initial examination showed abnormal findings on follow-up examination., Conclusion: The results suggest that subjects with oral SCC have a relatively high rate of abnormal findings in the thyroid gland that can be detected by US. Scans that include the thyroid gland should be performed when surveying cervical lymph nodes for metastasis during US examination. Particular attention should be paid to thyroid gland-related diseases in older men who have oral cancer and to thyroid gland abnormalities if patients had oral SCC in the floor of the mouth or of the maxillary gingiva. It is recommended that follow-up US examinations be regularly performed in cases of oral SCC., (Copyright 2010 Mosby, Inc. All rights reserved.)

Although genomic copy number aberrations (CNAs) of gastric carcinoma at the advanced stage have already been extensively characterized by array comparative genomic hybridization (array CGH) analysis, those of gastric carcinoma in situ (CIS) are still poorly understood. Furthermore, no reports have demonstrated correlations between CNAs and histopathological features of gastric adenoma. In this study, we investigated CNAs of 20 gastric CISs (Vienna category 4.2) and 20 adenomas including seven low-grade adenomas (LGA; Vienna category 3) and 13 high-grade adenomas (HGA; Vienna category 4.1), using oligonucleotide-based array CGH. The most frequent aberrations in CIS were gains at 8q (85%) and 20q (50%), and losses at 5q (50%) and 17p (50%), suggesting that these CNAs are involved in the development of CIS. We found that the pattern of CNAs in HGA was quite different from that in LGA. The most frequent CNAs in HGA were gains at 8q (62%) and 7pq (54%), whereas those in LGA were gain at 7q21.3-q22.1 (57%) and loss at 5q (43%). Interestingly, gains at 8q and 7pq, both of which occurred most frequently in HGA, were not detected in any cases of LGA. Of note, 8q gain was detected most frequently in both HGA and CIS but was undetected in LGA. Since HGA is believed to have a higher risk of progression to invasive carcinoma than LGA, these data suggest that 8q gain is important for the malignant transformation of gastric adenoma., (Copyright (c) 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)

Infectious arthritis of the temporomandibular joint (TMJ) is rare, and previous reports have identified malocclusion resulting from condylar deformity and displacement of the condyle as one of the clinical characteristics of the disease. Here we report the case of a 33-year-old man with chronic infectious arthritis of the TMJ without malocclusion associated with osteomyelitis of the right mandible. Based on radiological findings of more prominent inflammation at the TMJ than in other regions and on the observed efficacy of antibiotic administration, we made a diagnosis of suppurative arthritis of the TMJ. Based on our empirical experience, including the present case, we speculate that refusal to cooperate with medical care may be a factor in the development of infectious arthritis of the TMJ.

Purpose: To evaluate the clinical significance of dynamic magnetic resonance (MR) sialographic images in prognostic evaluation of saline solution irrigation of the parotid gland for the treatment of xerostomia., Materials and Methods: Morphologic findings and functional parameters were evaluated by use of dynamic MR sialography before saline solution irrigation of the parotid gland for the treatment of xerostomia in 17 patients. In addition, the MR sialographic data before the saline solution irrigation treatment in patients with improvement of salivary secretion and the sensation of dry mouth after irrigation treatment were compared with data in patients without improvement., Results: The maximum changing ratio in the group of patients with improvement after treatment was significantly higher (P = .042) than that in the group of patients without improvement. In addition, high correlations were found between the changing ratio and improvement on the visual analog scale for dry mouth sensation after treatment (Pearson r = 0.63, P = .001) and improvement of salivary flow rate (Pearson r = 0.77, P = .001). Moreover, in 12 patients with improvement of salivary flow rate after the saline solution irrigation treatment, the maximum changing ratio before the saline solution irrigation treatment was over 1.2. However, no significant differences in other parameters, including the detectable ductal area, were found between the group of patients with improvement after treatment and the group without improvement., Conclusions: Our study suggests that dynamic MR sialography might be useful for the prognostic evaluation of saline solution irrigation of the parotid gland for the treatment of xerostomia., (2010 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Purpose: This study attempted to assess the value of the RAPIRUN test for the diagnosis of Helicobacter pylori infection in the Vietnamese population., Methods: We recruited 148 Vietnamese patients undergoing upper gastrointestinal endoscopy during which five gastric biopsies were taken; blood and urine samples were collected from each patient. Helicobacter pylori infection status was determined by a combination of three different methods, including culture, immunohistochemistry, and serum ELISA. RAPIRUN tests were performed using urine samples., Results: The sensitivity, specificity, and accuracy of the RAPIRUN test in these Vietnamese patients were 79.5, 90.7, and 84.5%, respectively., Conclusions: The RAPIRUN test is useful for the diagnosis of H. pylori infection in the Vietnamese population, showing high specificity, acceptable sensitivity, non-invasiveness, convenience, and rapidity.

Various kinds of diseases may be found in the oral and maxillofacial regions and various modalities may be applied for their diagnosis, including intra-oral radiography, panoramic radiography, ultrasonography, computed tomography, magnetic resonance imaging, and nuclear medicine methods such as positron emission tomography. Of these modalities, ultrasound imaging is easy to use for the detection of noninvasive and soft tissue-related diseases. Doppler ultrasound images taken in the B-mode can provide vascular information associated with the morphology of soft tissues. Thus, ultrasound imaging plays an important role in confirming the diagnosis of many kinds of diseases in such oral and maxillofacial regions as the tongue, lymph nodes, salivary glands, and masticatory muscles. In the present article, we introduce three new applications of ultrasonography: guided fine-needle aspiration, measurement of tongue cancer thickness, and diagnosis of metastasis to cervical lymph nodes.

The determination of the cagA genotype is generally based on sequencing the variable 3' region of the cagA gene. In a previous study, we successfully generated an anti-East Asian CagA-specific antibody (anti-EAS Ab) immunoreactive only with the East Asian CagA and not with the Western CagA. In a small number of Japanese patients, anti-EAS Ab appeared to be a useful tool for phenotyping CagA immunohistochemically. The present study was conducted to validate the anti-EAS Ab immunohistochemistry method in a larger number of patients from Vietnam and Thailand. A total of 385 Vietnamese and Thais were recruited. Helicobacter pylori status was determined by a combination of three methods, including culture, histology, and immunohistochemistry with anti-H. pylori antibody. The sensitivity, specificity, and accuracy of the anti-EAS Ab immunohistochemistry method for the diagnosis of CagA phenotype were calculated based on the results of the cagA sequencing as the gold standard. The sensitivity, specificity, and accuracy of our immunohistochemistry method were 96.7%, 97.9%, and 97.1%, respectively. Moreover, anti-EAS Ab was not cross-reactive with noninfected gastric mucosa. In conclusion, immunohistochemistry with anti-EAS Ab appears to be a good method for determination of CagA phenotype.

Background and Aims: To investigate the utility of a new method of carrying out esophageal manometry using a narrow gauge manometry catheter via a transnasal endoscope., Methods: The Frequency Scale for the Symptoms of gastroesophageal reflux disease (GERD) (FSSG), a GERD-specific questionnaire, was given to 45 subjects. Subjects underwent transnasal endoscopy with three dry and three wet (3 mL water) swallows. Direct observations of the primary peristaltic wave and peristaltic pressure measurement were conducted simultaneously., Results: Endoscopic observation of lower esophageal motility associated with swallowing revealed dilatation of the esophageal lumen after swallowing, followed by contraction in association with the primary peristaltic wave. The peristaltic pressure was significantly lower with increased FSSG scores for dry swallows (r = -0.347, P = 0.0212), but no significant correlation was seen for wet swallows., Conclusions: The significant negative correlation between reflux symptoms and peristaltic pressure in dry swallows was thought to be that reduced pressure immediately rostral to the lower esophageal sphincter leads to decreased clearance following gastric acid reflux, playing a large part in the onset of symptoms.

Background: The incidence of gastric cancer differs among countries in Asia, and it has been suggested that virulence factors associated with Helicobacter pylori are partly responsible. The aim of this study was to investigate several genetic factors regarded as virulence or molecular epidemiologic markers in H. pylori isolates from Vietnamese subjects., Results: The cagA, vacA and cag right-end junction genotypes of 103 H. pylori strains from Vietnam (54 from Hanoi and 49 from Ho Chi Minh) were determined by PCR and sequencing. Three types of deletion in the region located upstream of the cagA Glu-Pro-Ile-Tyr-Ala (EPIYA) repeat region were identified: the 39-bp deletion type, the 18-bp deletion type, and the no-deletion type. The majority of strains studied (77%; 80/103) had the 18-bp deletion irrespective of geographical location in the country or clinical outcome. All of the 39-bp and 18-bp deletion-type strains possessed the East Asian type cagA repeat region. The type II cag right-end junction genotype was predominant (84%). The vacA m1 genotype was significantly more common in strains isolated in Hanoi, where the incidence of gastric cancer is higher, than in strains from Ho Chi Minh., Conclusion: Pre-EPIYA-region typing of the cagA gene could provide a new genetic marker of H. pylori genomic diversity. Our data support the hypothesis that vacA m1 is closely associated with gastric carcinogenesis.

Sitafloxacin showed MICs of less than or equal to 0.5 microg/ml against 105 isolates of Helicobacter pylori, including 44 isolates with mutations in the gyrA gene. The highest MICs for garenoxacin and levofloxacin were 8 and 64 times, respectively, higher than the highest MICs observed for sitafloxacin.

The (13)C-urea breath test (UBT) is widely used to examine the results of eradication therapy for Helicobacter pylori. We examined whether a stool antigen test can be used as efficiently as UBT. (i) Ninety-four patients infected with H. pylori underwent eradication therapy. Six or eight weeks after the completion of treatment, the results were evaluated by UBT and a stool antigen test (TPAg). In 77 out of 78 patients who had negative UBT results, the TPAg results were also negative. Among the 16 UBT-positive patients, 12 were also positive by TPAg. Agreement of UBT and TPAg was 94.7%. (ii) Twenty-two patients with peptic ulcers in the active stage also received eradication therapy followed by proton pump inhibitor (PPI) administration. TPAg and UBT were performed to examine the results of eradication therapy at the end of PPI administration and at least 7 days after its discontinuation. Of the 22 patients taking PPIs, TPAg evaluated the results of eradication therapy accurately in 21 patients. TPAg appears to be an accurate test for evaluating the results of H. pylori eradication therapy, and to be as efficient as (13)C-UBT. Use of the stool antigen test should be considered as an alternative, particularly in patients who have to take PPIs in order to avoid the risk of peptic ulcers.

We present a 43-year-old Japanese man with major pancreatic duct disruption caused by blunt pancreatic head damage. Computed tomography (CT) revealed pancreatic head injury, and endoscopic retrograde pancreatography showed pancreatic duct disruption at the injury site along with contrast media leakage. We placed a pancreatic stent for 3 months, after which closure of the pancreatic duct fistula was confirmed. CT on the 9th hospital day showed acute pancreatic fluid collections, but these had disappeared at the 3 month follow-up CT. The patient has remained asymptomatic at follow-up for 3 years.

Purpose: The 2005 ACG guidelines for the management of dyspepsia recommend eradication and proton pump inhibitors for patients who are H. pylori-positive and-negative, respectively. To establish Japanese guidelines for dyspepsia, we evaluated H. pylori status and endoscopic findings among outpatients with dyspepsia., Methods: The status of H. pylori in dyspeptic patients was determined by measuring urinary levels of anti-H. pylori antibody (RAPIRAN). We then compared the endoscopic findings between H. pylori-positive and -negative patients., Results: The prevalence of H. pylori among 258 dyspeptic patients was 47.8%, and increased with age (11.1% at age 10-19 years; >50% at age >50 years). The prevalence of H. pylori in each age-group tended to be lower among male than female dyspeptic patients. Endoscopy (n = 138) showed that H. pylori-negative patients rarely had peptic ulcers or gastric cancer, and 84.7% had no endoscopic findings, which was significantly higher when compared to H. pylori-positive patients (67.3%) (p = 0.029)., Conclusions: Over half of the dyspeptic Japanese patients examined were negative for H. pylori. Patients who are H. pylori-positive should undergo endoscopy to rule out gastric malignancy, peptic ulcers and other diseases.

A recent meta-analysis by Huang et al. clarified that Helicobacter pylori infection and nonsteroidal antiinflammatory drugs (NSAIDs) are important factors for peptic ulcer. The results showed that the risk for ulcer in NSAID(+)/H. pylori(+) patients was 61.1 fold higher when compared with NSAID(-)/H. pylori(-) patients. Some gastric ulcers detected in patients on NSAID therapy may actually be caused by H. pylori, but it is difficult to differentiate NSAID-induced gastric ulcer from H. pylori-induced gastric ulcer. Several studies have investigated the effects of H. pylori eradication on ulcer healing. One study reported that H. pylori eradication actually lowered the healing rate of gastric ulcers. Because there have been no studies finding that H. pylori eradication facilitates healing, H. pylori eradication is not recommended for NSAID users. Concerning the efficacy of H. pylori eradication in the prevention of NSAID-induced gastric ulcer, a meta-analysis concluded that among all patients on NSAID therapy, H. pylori eradication lowered the prevalence of ulcer, which was particularly marked in NSAID-naïve patients. When compared with those of proton pump inhibitors (PPIs), the preventative effects of H. pylori eradication were inferior. In Japan, national health insurance does not cover procedures that prevent or lower the risk for NSAID-induced ulcer. When administering NSAID to patients with risk factors, it is desirable to administer antiulcer agents.

The guidelines on the management of Helicobacter pylori were updated at the European Helicobacter study group third Maastricht consensus conference in March 2005. Especially, this conference emphasis on the management of non ulcer dyspepsia, GERD, and the patients who use non steroidal anti-inflammatory drug. Eradication of H. pylori is recommended in patients with peptic ulcer, low grade MALT lymphoma, atrophic gastritis, unexplained iron deficiency anemia, chronic idiopathic thrombocytopenic purpura and first degree relatives of patients with gastric cancer. H. pylori eradication is less effective than proton pomp inhibitor(PPI) treatment in preventing ulcer recurrence in long term NSAIDs users. This meeting also emphasized on the relationship between H. pylori and gastric cancer. The guideline concluded that H. pylori eradication has the potential to reduce the risk of gastric cancer development. Japanese guideline in 2003 does not mention the effect of eradication for prevention of gastric cancer. The H. pylori eradication and new strategy should be desirable for global strategy of gastric cancer prevention.

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 (alpha-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 alpha-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 alpha-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.

Goals: We compared the eradication results of retreatment of eradication with proton pump inhibitor (PPI) plus amoxicillin and metronidazole for patients with Helicobacter pylori infection not eradicated by initial treatment with PPI plus amoxicillin and clarithromycin., Background: In Japan, the guideline proposes that the use of metronidazole in a triple therapy containing PPI, PPI plus amoxicillin and metronidazole is desirable in retreatment. However, there are no reports comparing various retreatment using different PPIs., Methods: After initial treatment failure with a PPI plus amoxicillin and clarithromycin, 169 patients were randomized to a PPI (rabeprazole, lansoprazole, or omeprazole) plus amoxicillin and metronidazole given b.i.d. for 7 days., Results: Pretreatment susceptibility testing showed a high level of clarithromycin resistance (78%). The over all eradication rates were similar with the 3 PPIs, 91.1% range 90.1 to 91.4 with intention-to-treat analysis. The presence of metronidazole resistance reduced the eradication rate by approximately 40% (from 96.6% to 57.1%, P<0.05)., Conclusions: In Japan, the combination of a PPI plus amoxicillin and metronidazole provide excellent eradication rates after initial treatment failure with a PPI plus amoxicillin and clarithromycin. The results with metronidazole resistant strains are less satisfactory and pretreatment susceptibility testing may become needed if the prevalence of metronidazole resistant H. pylori increase.

To investigate the genes related to the biosynthesis or accumulation of tetrodotoxin (TTX) in pufferfish, mRNA expression patterns in the liver from pufferfish, akamefugu Takifugu chrysops and kusafugu Takifugu niphobles, were compared by mRNA arbitrarily primed reverse transcription-polymerase chain reaction (RAP RT-PCR) with fish bearing different concentrations of TTX and its derivatives. RAP RT-PCR provided a 383 bp cDNA fragment and its transcripts were higher in toxic than non-toxic pufferfish liver. Its deduced amino acid sequence was similar to those of fibrinogen-like proteins reported for other vertebrates. Northern blot analysis and rapid amplification of cDNA ends (RACE) revealed that the cDNA fragment of 383 bp was composed of at least three fibrinogen-like protein (flp) genes, flp-1, flp-2 and flp-3. Relative mRNA levels of flp-1, flp-2 and flp-3 showed a linear correlation with toxicity of the liver for two pufferfish species.

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 (alpha-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.

Aim: To investigate the mutation of p53 immunohistochemically in non-tumorous gastric mucosa with H pylori infection before and after H pylori eradication therapy., Methods: 53 subjects (36 male, 17 female, mean age +/- SEM, 57.1 +/- 12.1) undergoing endoscopic examination were included in this study. 42 of 53 patients were H pylori-positive, and 11 were H pylori-negative. All H pylori-positive patients had successful eradication therapy. Biopsy specimens were taken from five points of the stomach, as recommended by the updated Sydney system. Immunohistochemical studies were performed by using primary antibodies against p53 (DO-7 and PAb240)., Results: p53 (DO-7 and PAb240) immunoreactivity was shown in the neck region of the gastric pits, however, quite a few cells were found to be immunopositive for p53 (PAb240) in the H pylori-infected gastric mucosa. The proportion of patients immunopositive for p53 (PAb240) was significantly reduced 6 mo after eradication [28/42 (66.7%) to 6/42 (14.3%)] (P < 0.05), while the biopsies taken from H pylori-negative patients showed no immunoreactivity for p53 (PAb240). p53 (PAb240)-positive patients were divided into two groups by the number of positive cells detected: one with more than six positive cells per 10 gastric pits (group A, n = 12), and the other with less than five positive cells per 10 gastric pits (group B, n = 30). Atrophy scores in group A were significant higher than those in group B at the greater curvature of the antrum (group A: 2.00 +/- 0.14 vs group B: 1.40 +/- 0.15, P = 0.012), the lesser curvature of the corpus (group A: 2.00 +/- 0.21 vs group B: 1.07 +/- 0.23, P = 0.017), and the greater curvature of the corpus (group A: 1.20 +/- 0.30 vs group B: 0.47 +/- 0.21, P = 0.031). Group A showed significant higher intestinal metaplasia scores than group B only at the lesser curvature of the antrum (group A: 2.10 +/- 0.41 vs group B: 1.12 +/- 0.29, P = 0.035)., Conclusion: H pylori-associated chronic gastritis expressed the mutant-type p53, which was significantly associated with more severe atrophic and metaplastic changes. H pylori eradication led to a significant reduction in the expression of the mutant-type p53. It is considered that H pylori-infected chronic gastritis is associated with a genetic instability that leads to gastric carcinogenesis, and H pylori eradication may prevent gastric cancer.

In the years that followed the issuance in 2000 of the Guidelines for the Management of Helicobacter pylori Infection in Japan by the Japanese Society for Helicobacter Research (JSHR), a number of major issues arose, including the emergence of H. pylori strains resistant to clarithromycin as part of primary eradication therapy, and this led to the Guidelines being revised by the JSHR in 2003. While the JSHR aimed in the 2000 Guidelines to prepare clinicians for the task ahead in view of H. pylori eradication therapy becoming available, the JSHR went a step further in the 2003 Guidelines to include more evidence-based recommendations to address clinical and institutional challenges and issues of interest in the management of H. pylori infection in Japan. Thus, a number of diseases were upgraded to either class A or B indications for H. pylori eradication, including mucosa-associated lymphoid tissue lymphoma (class A), and after endoscopic mucosal resection for early gastric cancer, atrophic gastritis, and gastric hyperplastic polyp (all class B), with further diseases such as extragastric disease also included as class C indications requiring further examination. Concern was expressed over reliance on a single diagnostic test for H. pylori infection, which is in place due to institutional constraints. Metronidazole was also recommended for use in the place of clarithromycin as part of a second-line eradication regimen in light of increasing clarithromycin resistance, although metronidazole remains to be approved for health insurance coverage. Finally, areas requiring further clinical research and endeavors, including establishment of second-line eradication therapy, were also proposed in the 2003 Guidelines to point the way for the future.

Background: Proton pump inhibitor-amoxicillin-metronidazole is recommended as second-line Helicobacter pylori therapy in Japan. The authors assessed the efficacy and safety of second-line eradication using the H2-receptor antagonist famotidine as a substitute for proton pump inhibitor., Materials and Methods: Sixty-one patients who failed in first-line H. pylori eradication using proton pump inhibitor-clarithromycin-amoxicillin were randomly assigned to either second-line therapy including metronidazole: a 7-day course of lansoprazole 30 mg, amoxicillin 750 mg, and metronidazole 250 mg, b.i.d. (lansoprazole group); or a 7-day course of famotidine 40 mg, amoxicillin 750 mg, and metronidazole 250 mg, b.i.d. (famotidine group). Eradication was assessed for each group at least 4 weeks after completing eradication therapy. Drug susceptibility test was performed using 57 strains in pretreatment to clarithromycin, metronidazole, and amoxicillin., Results: Prior to second-line H. pylori eradication, the rate of resistance to clarithromycin was high at 84% (48/57). Similarly, resistance to metronidazole was low at 5.3% (3/57); however, no amoxicillin-resistant strains were found. The eradication rates for both lansoprazole and famotidine treatment groups were high at 97% (29/30) and 94% (29/31), respectively., Conclusions: Famotidine treatment including metronidazole-amoxicillin as second-line therapy provided a high eradication rate similar to lansoprazole therapy. Famotidine is therefore expected to serve as a useful H. pylori eradication regimen in patients with proton pump inhibitor allergy, an economic benefit in terms of reduced health-care costs is also anticipated.

Seasonal variation of bivalve toxicity was monitored in association with the abundance of the toxic dinoflagellate Pyrodinium bahamense var. compressum in Masinloc Bay, Luzon Island. Among 7 species of bivalve, 6 species became toxic during a bloom of the dinoflagellate. However, remarkable difference in the toxicity was observed among the species. The toxicity of thorny oyster Spondylus squamosus was the highest among the species, showing more than 30 times that of safety consumption level after the peak bloom of the dinoflagellate, while other bivalve species showed much lower toxicity. The toxicity of thorny oyster decreased under absence of the dinoflagellate, but this species maintained a considerably high toxicity throughout a year. Similar trend was observed in penshell Atrina vexillum in a small scale, indicating that these species in the bay are not safe for human consumption almost throughout a year. The toxicity of green mussel Perna viridis increased to significant level during a bloom, but it decreased rapidly when the dinoflagellate disappeared. Toxin analysis of cultured and natural cells showed typical toxin profile of the dinoflagellate. Toxin profile of all the bivalve species reflected the characteristic toxin profile of the dinoflagellate.

Purpose: This study examined the possible relationship between peptic ulcer recurrence and the presence or absence of maintenance therapy with an H(2)-receptor antagonist performed until evaluation of Helicobacter pylori eradication., Methods: The subjects were 483 patients with peptic ulcer (281 gastric ulcer and 202 duodenal ulcer) who were diagnosed as H. pylori positive. After receiving eradication therapy for H. pylori, patients were allocated at random to one of three different maintenance therapies: control group (no maintenance therapy), H(2)-receptor antagonist half-dose group, and H(2)-receptor antagonist full-dose group. The maintenance therapy was performed for 4 weeks until evaluation of H. pylori eradication., Results: Among the 25 patients with a recurrent ulcer, 18 patients (72%) had a recurrence at the time of or before evaluation of H. pylori eradication. In the control group, the rate of ulcer recurrence occurring before evaluation of H. pylori eradication was 10.5% (14/133). This rate was significantly higher than those in the H(2)-receptor antagonist half-dose group (2.9%, 4/136) and the full-dose group (0%, 0/135)., Conclusion: The results of this study suggest that maintenance therapy with an H(2)-receptor antagonist performed after eradication therapy until evaluation of H. pylori eradication is likely to greatly reduce the ulcer recurrence rate without affecting evaluation of H. pylori eradication.

There appears to be the strong association between Helicobacter pylori (H pylori) and gastric cancer. We reviewed the latest evidences about the effects of H pylori infection on gastric carcinogenesis, classified into epidemiology, dynamics of gastric mucosal changes, DNA damages, virulence factors, host factors, and source of gastric malignancy. Through the considerable progress made in research into virulence factors resulting from differences between H pylori strains, such as cagA positivity, as well as into host factors, such as gene polymorphisms, a diverse spectrum of H pylori-associated diseases, including gastric cancer, is beginning to lend itself to elucidation. The impact of the novel hypothesis advanced by Houghton et al proposing bone-marrow derived stem cells (BMDC) as a potential source of gastric malignancy on evolving research remains to be seen with interest. Further progress in research into H pylori eradication as a viable prophylaxis of gastric cancer, as well as into the mechanisms of gastric carcinogenesis, is to be eagerly awaited for the current year and beyond.

Background: Widespread use of eradication therapy for Helicobacter pylori has increased the prevalence of clarithromycin-resistant strains. The purpose of the present paper was to measure the in vitro antibacterial activity of minocycline against H. pylori, and study the effectiveness of minocycline-based first- and second-line eradication therapies., Methods: For first-line therapy, 79 patients were randomly assigned to the treatment with rabeprazole, amoxicillin, and clarithromycin or with rabeprazole, amoxicillin, and minocycline. For second-line therapy, 88 patients were tested for sensitivity to metronidazole: 67 patients with metronidazole-sensitive strains received a 7-day course of rabeprazole, minocycline, and metronidazole; the remaining 21 patients were given a 7-day course of rabeprazole, minocycline, and faropenem., Results: There was virtually no resistance to minocycline among the strains tested. The eradication rate of H. pylori infection in first-line therapy was significantly lower for minocycline-containing regimen (38.5%, 15/39) than for clarithromycin-containing regimen (82.5%, 33/40; P < 0.01). For second-line therapy, a high eradication rate against metronidazole-sensitive strains was obtained with rabeprazole, minocycline and metronidazole (85%, 57/67)., Conclusions: A combination of rabeprazole, minocycline, and metronidazole is safe and effective for second-line therapy of H. pylori infection. Because this regimen can be administered to patients with penicillin allergy and patients who suffer adverse reactions to amoxicillin, such as diarrhea and other digestive symptoms, it should be considered useful for second- and third-line eradication therapy.

In order to obtain more detailed information on the distribution of domoic acid-producing Nitzschia in Asian waters, Nitzschia-like diatoms were isolated primarily from the Philippines and established in culture for analysis by HPLC with fluorescence detection. Out of 58 isolates, 35 Nitzschia-like diatoms from the estuary areas of San Pedro Bay, Tacloban City and Manila Bay showed significant levels of domoic acid production (1.3-5.6pg/cell). These were identified as Nitzschia navis-varingica. Two isolates from the same locality did not produce domoic acid. Of the 21 isolates from Bulacan Estuary, Manila Bay, none produced domoic acid. They did, however, produce two substances that seemed to be domoic acid derivatives. One of the strains was mass cultured and the substances were extracted, purified and analyzed by LC-MS/MS, proton and (13)C NMR, and UV spectra. The produced substances were determined as isodomoic acids A and B. This is the first report of a diatom that produces isodomoic acids A and B as major toxin components.

Although various animal models have been developed to clarify gastric carcinogenesis, apparent mechanism of gastric cancer was not clarified in recent years. Since the recognition of the pathogenicity of Helicobacter pylori (H pylori), several animal models with H pylori infection have been developed to confirm the association between H pylori and gastric cancer. Nonhuman primate and rodent models were suitable for this study. Japanese monkey model revealed atrophic gastritis and p53 mutation after long-term infection of H pylori. Mongolian gerbil model showed the development of gastric carcinoma with H pylori infection alone, as well as with combination of chemical carcinogens, such as N-methyl-N-nitrosourea and N-methyl-N-nitro-N'-nitrosoguanidine. The histopathological changes of these animal models after H pylori inoculation are closely similar to those in human beings with H pylori infection. Eradication therapy attenuated the development of gastric cancer in H pylori-infected Mongolian gerbil. Although several features of animal models differ from those seen in human beings, these experimental models provide a starting point for further studies to clarify the mechanism of gastric carcinogenesis as a result of H pylori infection and assist the planning of eradication therapy to prevent gastric carcinoma.

Persistent Helicobacter pylori infection contributes towards the development of chronic gastritis. To clarify the changes in chronic gastritis as a precursor of gastric cancer secondary to H. pylori eradication is an important issue, as it has significant implications for reducing the risk of gastric cancer. Studies published to date, however, are far from consistent with regard to the morphologic changes reported following H. pylori eradication. Of these, some papers reported improvement in gastric atrophy or intestinal metaplasia, versus others reporting no improvement, with the majority of papers published after 2000 reporting improvement in these end points. The inconsistent results concerning the impact of H. pylori eradication on gastric atrophy could be due to the inconsistency of the diagnostic criteria employed for evaluation of the morphology, confounded by the difficulties involved in evaluating atrophic changes in the gastric mucosa. While adherence to the Updated Sydney System available for evaluation of gastritis is primarily required worldwide to ensure consistency in evaluating gastritis, long-term research into the morphologic changes associated with H. pylori eradication is also required to explore strategies for the prevention of gastric cancer with H. pylori eradication.

Background: Although Helicobacter pylori has been regarded as a pathogen of gastric cancer, the mechanism by which H. pylori is involved in gastric carcinogenesis remains unknown. To clarify the role of H. pylori in carcinogenesis, the expression of tumor suppressor p53 and its regulator multiple double minute 2 (MDM2) in gastric mucosa were examined before and after H. pylori eradication., Methods: Biopsy specimens were obtained from 31 patients with H. pylori-infected gastric mucosa. Endoscopic biopsies were repeated 6 months after successful eradication. In addition, biopsy specimens from 12 patients with non-infected gastric mucosa were obtained. Immunohistochemical analysis was performed on the specimens using primary antibodies specific for p53 and MDM2., Results: Six months after H. pylori eradication, labeling indices for p53 were significantly reduced in the gastric corpus (2.3-fold; P < 0.01), and in the gastric antrum (2.0-fold; P < 0.01). Similarly, labeling indices for MDM2 were significantly reduced in the corpus (1.7-fold; P < 0.01), and in the antrum (3.5-fold; P < 0.01). In the non-infected group, labeling indices for p53 and MDM2 in the gastric mucosa were significantly lower (P < 0.01) than those of the H. pylori-infected group., Conclusion: A significant increase is shown in p53 and MDM2 expression in H. pylori-infected gastric mucosa as compared to normal gastric mucosa; but successful eradication of H. pylori dramatically reduced the p53 and MDM2 levels. Therefore, H. pylori infection may be associated with alteration of cell proliferation and apoptosis.

Background: Two main pathogenic factors, bile reflux and Helicobacter pylori infection, have been identified in the remnant stomach, but it is still unclear which factor is important in the pathogenesis of gastritis in the remnant stomach after distal gastrectomy., Methods: In 184 patients who had had distal gastrectomy performed using the Billroth-I procedure (B-I; n-106), Billroth-II procedure (B-II; n-36), and jejunal interposition (J-I; n-42) we examined the severity of remnant gastritis endoscopically and carried out examinations for H. pylori infection and histological examination., Results: The endoscopic severity of remnant gastritis was grade 1 or more in 101 of the 106 B-I patients (95.3%) and in all 36 B-II patients (100%). But, of the 42 J-I patients, the grade was 0 in 33 (78.6%). The endoscopic severity of remnant gastritis was significantly milder for J-I than for B-I (P < 0.001) and B-II (P < 0.001). H. pylori infection was confirmed in 59 of the 106 B-I patients (55.6%), 21 of the 36 B-II patients (58.3%), and 32 of the 42 J-I patients (76.1%). The rate of H. pylori infection was higher for J-I patients than for B-I (P < 0.05), but not for B-II patients (P = 0.1495). The severity of chronic and active inflammatory cellular infiltration tended to be inverse proportional relation with the endoscopic severity of the remnant gastritis. Furthermore, the histological inflammation and activity scores of H. pylori-positive patients were higher than those of H. pylori-negative patients, without regard to the endoscopic grade of gastritis., Conclusions: Reconstruction techniques play an important role in the prevention of bile reflux, and we found that endoscopically more severe remnant gastritis was associated with a lower rate of H. pylori infection and with a lower degree of inflammatory cellular infiltration.

It has been documented that sucralfate, a basic aluminum salt, enhances the efficacies of antibiotics against Helicobacter pylori, resulting in eradication rates comparable to those associated with the use of proton pump inhibitors. However, its mechanism of action remains unclear. The aim of the present study was to investigate sucralfate's ability to complement antibiotic treatment of H. pylori infection in vivo. Four weeks following induced H. pylori infection, clarithromycin (CAM) and amoxicillin (AMPC) were administered orally to C57BL/6 mice for 5 days, both with and without sucralfate or lansoprazole. When sucralfate was concurrently given with CAM and AMPC at the maximum noninhibitory doses for the treatment of H. pylori infection, the bacterial clearance rates were comparable to those achieved by treatment with lansoprazole plus those antibiotics. The results of pharmacokinetic studies showed that lansoprazole delayed gastric clearance and accelerated the absorption of CAM, whereas sucralfate suppressed both gastric clearance and absorption. AMPC was undetectable in all samples. Scanning electron microscopy with a microscope to which a energy dispersive spectrometer was attached revealed that aluminum-containing aggregated substances coated the mucosa surrounding H. pylori in mice receiving sucralfate plus antibiotics, whereas the gastric surface and pits where H. pylori had attached were clearly visible in mice receiving lansoprazole plus antibiotics. The addition of sucralfate to the antibiotic suspension resulted in a more viscous mixture that bound to the H. pylori-infected mucosa and that inhibited the loss of CAM bioavailability in the acidic environment. Sucralfate delays gastric clearance of CAM and physically captures H. pylori through the creation of an adherent mucus, which leads to bacterial clearance.

Helicobacter pylori is considered to have a close association with gastric cancer. Many epidemiological studies have shown a strong association between chronic H. pylori infection and subsequent development of gastric carcinoma in humans. To clarify this link more clearly, it is necessary to use this bacterium in experimental studies to develop gastric carcinoma in suitable experimental animals. Persistent H. pylori infection was seen in the Japanese monkey model, and has recently been achieved in the Mongolian gerbil model. In these models, the sequential histopathological changes in the gastric mucosa are very similar to those in humans. The Japanese monkey model showed advances in atrophic change and p53 point mutations in the gastric mucosa during long-term observation. The Mongolian gerbil model demonstrated that H. pylori infection enhances gastric carcinogenesis in combination with known carcinogens such as N-methyl-N-nitrosourea (MNU) and N-methyl-N-nitro-N'-nitrosoguanidine (MNNG), and also showed that H. pylori infection alone can result in the development of gastric carcinoma. These important results provide a starting point for further studies to clarify the mechanism of gastric carcinogenesis as a result of H. pylori infection and assist in the planning of eradication therapy to prevent gastric carcinoma.

Background: A relationship between Helicobacter pylori infection and idiopathic thrombocytopenic purpura (ITP) has previously been reported. We determined the prevalence of H pylori infection in Japanese patients with chronic ITP and the effect of its eradication on platelet count., Methods: The study population comprised 53 Japanese adults with chronic ITP and a platelet count of less than 100 x 10(3)/ micro L. A (13)C-urea breath test was performed to determine H pylori infection status. Those patients who were H pylori positive gave written informed consent and received eradication therapy. The effect of H pylori eradication on platelet count was evaluated up to 6 months after therapy. Clinical parameters were compared between responders to the therapy (increase in platelet count) and nonresponders, as well as between H pylori-positive and -negative patients., Results: Of the 53 patients with chronic ITP in the study, 39 (74%) were H pylori positive. Of the 32 infected patients who received treatment, H pylori was successfully eradicated in 27 patients (84%). In 10 (37%) of these patients, this resulted in a favorable platelet response. A partial response was seen in 5 additional patients (19%). A significant (P<.001) increase in platelet count was demonstrated in patients in whom H pylori was successfully eradicated but not in patients who were unsuccessfully treated or in untreated patients. Current corticosteroid therapy was reported more often in nonresponders than in responders., Conclusion: Eradication of H pylori may prove effective in increasing platelet count in H pylori-positive patients with chronic ITP.

The widespread use of eradication therapy for Helicobacter pylori has lead to an increase in antibiotic-resistant strains and the problem of retreatment in cases of eradication failure. Retreatment in cases of eradication failure has achieved relatively good results with regimens containing bismuth compounds and tetracyclines in the world, but consensus has not been reached in Japan and each institution has its own policy. An triple therapy consisted of proton pump inhibitor, amoxicillin and metronidazole has been reported to show a good cure rate as a second line therapy in Japan, but metronidazole has not been approved by the Japanese regulatory authority for use against bacterial infections, including H. pylori, despite its worldwide use as an antimicrobial agent in H. pylori eradication regimens.

Background: In Prader-Willi syndrome (PrWS), marked obesity is the most serious and common complication, contributing significantly to morbidity and mortality. Because of the associated psychosocial difficulties, bariatric surgery appears to be the only effective treatment., Case Report: A 30-year-old man with PrWS weighing 108 kg (BMI 50 kg/m2), underwent Roux-en-Y gastric bypass (RYGBP). 3 months before the RYGBP, he weighed 146 kg (BMI 68.5), partly because of heart failure. 18 months after RYGBP, he weighed 92.4 kg (BMI 43.3), with no postoperative complications. Moreover, he showed considerable increase in serum HDL-cholesterol levels with reciprocal reduction in LDL-cholesterol after the surgery., Conclusion: RYGBP resulted in satisfactory weight loss and improvement in serum lipid profile in a Japanese morbidly obese patient with PrWS.

Background: Reinfection of Helicobacter pylori after eradication is rare in developed countries but most often occurs within 1 year. In the present study, we attempted to differentiate between reinfection and recrudescence of H. pylori strains between 6 months and 6 years after successful eradication in Japan, a country with a high prevalence of H. pylori infection., Materials and Methods: After successful eradication of H. pylori, 274 patients were followed up by endoscopy and urea breath test. In recurrent patients, H. pylori strains isolated initially and after recurrence were compared using PCR-based restriction fragment length polymorphism (RFLP) analysis., Results: Recurrence of H. pylori occurred in 15 of 274 patients (5.5%) at 6 months after eradication and the annual recurrence rate was 2.0% per patient year (between 1 and 6 years). PCR-based RFLP analysis of H. pylori strains isolated initially and after recurrence showed that 62.5% (at 6 months) and 100% (after 1 years) of bacteria were of different strains., Conclusion: Reinfection of H. pylori was not as rare at 6 months after eradication as reported previously, and up to 6 years after eradication, the annual reinfection rate is 2.0% per patient year in Japan.

Background: The (13)C-urea breath test (UBT) is a simple breath test for the diagnosis of Helicobacter pylori infection, but several factors have been reported to affect the results of this test. In this study, the effects of the antiulcer drugs used in Japan on the results of UBT were determined., Methods: The subjects of the study were 64 adult volunteers who tested positive for H. pylori infection by the serum antibody method. Eight classes of anti-ulcer drugs used in Japan were administered at their usual doses to these subjects: lansoprazole, a proton pump inhibitor (PPI); nizatidine, an H(2)-receptor antagonist (H(2)RA); and polaprezinc, ecabet sodium, rebamipide, teprenone, cetraxate hydrochloride, and sucralfate, all mucoprotective agents. The study drugs were randomized for administration to the subjects, and each of the drugs was administered for 14 consecutive days. The UBT was performed on days 0, 14, and 21., Results: The mean Delta(13)C per thousand in the lansoprazole group was significantly decreased on day 14, to below 10 per thousand, in 4 of 16 subjects, and in 1 of the 4 subjects, the test result was negative, with the Delta(13)C per thousand falling to 1.7 per thousand. The value returned to baseline 1 week after the discontinuation of lansoprazole. The other drugs administered had no significant effect on the result of the UBT, except that the mean Delta(13)C per thousand showed a tendency to decrease after the administration of ecabet sodium and rebamipide., Conclusions: Administration of a PPI may produce a false-negative UBT result, while other anti-ulcer drugs, for the most part, have little effect on the result of the UBT when used alone. The (13)C-urea breath test (UBT) is a simple test for the diagnosis of Helicobacter pylori infection, but several factors have been reported to affect the results of this test. In this study, the effects of the anti-ulcer drugs used in Japan on the results of the UBT were determined.

Many epidemiological studies have shown a strong association between chronic Helicobacter pylori infection and subsequent development of gastric carcinoma in humans. To confirm this link more clearly, it is necessary to use this bacterium in experimental studies to develop gastric carcinoma in suitable experimental animals. Persistent H. pylori infection has recently been achieved in the Japanese Monkeys and Mongolian gerbil models, with results demonstrating that the sequential histopathological changes in the gastric mucosa are closely mimic the gastric mucosal changes caused by H. pylori infection in humans. Gastric mucosa infected with H. pylori exhibited significantly higher gastritis score, reduction in glandular height, increase in the number of Ki-67 positive cells and over expression of p53 protein and p53 gene mutation in the Japanese Monkey Model. In the Mongolian gerbil model, H. pylori infection enhances gastric carcinogenesis in combination with known carcinogens such as MNU and MNNG, and also demonstrated that H. pylori infection alone can result in the development of gastric carcinoma. However, diagnostic criteria of gastric carcinoma in animal models remain in the great discussion. These important results provide a starting point for further studies to clarify the mechanism of gastric carcinogenesis as a result of H. pylori infection and assist the planning of eradication therapy to prevent gastric carcinoma.

Background: Gastric carcinoids are strongly associated with chronic atrophic gastritis A, and it is suggested that hypergastrinemia plays a critical role in development of gastric carcinoids. Since Helicobacter pylori infection causes hypergastrinemia, it is held that H. pylori infection produces gastric carcinoids. We followed the histological changes of H. pylori-infected stomachs of Mongolian gerbils for a long time., Materials and Methods: Five-week-old-male Mongolian gerbils were infected with H. pylori ATCC 43504 with cagA gene, expressing vacuolating cytotoxin. Determination of the serum gastrin and histopathological examination of the stomach at 6, 12, 18, and 24 months after H. pylori inoculation was studied and compared with uninfected animals., Results: In infected animals, the gastric carcinomas appeared 18 and 24 months after infection. Endocrine cell dysplasias and carcinoids with marked atrophic gastritis of the oxyntic mucosa were observed in the infected animals 24 months after H. pylori inoculation. The serum gastrin level in the infected group increased from an average of 86.2 pg/ml at the beginning of the study to an average of 498 pg/ml and 989 pg/ml at 18 and 24 months after infection, respectively. These changes in the serum gastrin levels were significant compared with uninfected controls that showed no changes., Conclusions: H. pylori infection caused not only gastric carcinomas but also enterochromaffin-like cell tumors in Mongolian gerbils, due to hypergastrinemia. This model is thought to be useful to study the relationship between hypergastrinemia and gastric carcinoids.

Helicobacter pylori infection is recognized to be a pathogen of various gastroduodenal disease. Eradication therapy of H. pylori reduces the recurrence of gastro-duodenal ulcer, improves histological gastritis, and is suggested to act a certain role in protection against gastric carcinogenesis. Although, several studies show uncomfortable results arise after H. pylori infection was cured. These studies suggest that gastro-esophageal reflux disease (GERD) and gastro-duodenal erosion may increase after successful eradication of H. pylori. Recently, adenocarcinoma of the gastric cardia and esophagus increase in incidence. Reflux esophagitis and Barrett's esophagus are recognized as precancerous lesion of esophageal adenocarcinoma. It is uncertain the association of newly occurrence of GERD after H. pylori eradication and increase of esophageal adenocarcinoma. GERD may cause adenocarcinoma development, though long term observations is necessary after H. pylori eradication.

Background: Helicobacter pylori is accepted as a definite human gastric carcinogen from an epidemiological point of view despite insufficient experimental data. Although we previously showed that the number of p53 immunopositive cells in the atrophic gastric mucosa of H. pylori-infected Japanese monkeys gradually increased over time, data on p53 gene mutations were not obtained in that study. To obtain direct evidence of carcinogenesis associated with H. pylori infection, we investigated whether p53 gene mutations are present in the gastric mucosa of a nonhuman primate model susceptible to H. pylori., Materials and Methods: Using the DNA from gastric tissues obtained from six H. pylori-uninfected monkeys of different ages, nucleotide sequence of the wild-type p53 gene was determined by amplification of exons (Ex) 5, 6, 7 and 8 and sequencing. Gastric specimens obtained from eight Japanese monkeys that had been infected with H. pylori for different lengths of time (1.5-7.5 years), were analyzed for mutations in exons 5-8 of p53., Results: In the six H. pylori-uninfected monkeys, nucleotide sequences of p53 Ex 5-8 were completely common and no mutations were noted. However, among the monkeys that were infected with H. pylori over various periods of time, there was an accumulation of p53 nucleotide (amino acid) substitutions as the gastric atrophy score increased., Conclusions: We conclude that the appearance of p53 gene mutation may be closely associated with the degree of gastric mucosal atrophy, which depends on the duration of H. pylori infection. Searching for p53 gene mutations may be useful for studying the progression of gastric carcinogenesis associated with H. pylori.

A complete response was obtained by interferon (IFN) therapy for hepatitis C virus (HCV)-related advanced chronic hepatitis after curative treatment of initial and recurrent hepatocellular carcinoma (HCC). The patient is alive 73 months after diagnosis of initial HCC and is in a tumor-free state 53 months after diagnosis of the last HCC. This case suggest that it is possible to suppress recurrence and to prolong the life of patients with HCV-related advanced chronic hepatitis, if a complete response is obtained by means of IFN therapy after the curative treatment of the recurrent HCC.

Background: p53 gene mutations are believed to play a critical role in the development of gastric carcinoma. We examined the relation between Helicobacter pylori infection and p53 gene mutations of the gastric mucosa in human and animal models., Methods: To detect the original p53 DNA sequences of the Japanese monkey and Mongolian gerbil, the p53 genes of these animals were amplified using the nested polymerase chain reaction method with primers for the human p53 gene. Direct DNA sequencing of exons 5, 6, 7, and 8 of the p53 genes was performed by the dideoxy terminator method for gastric mucosa of humans, the Japanese monkey, and the Mongolian gerbil. The expression of p53 was examined immunohistochemically in a Japanese monkey model., Results: Mutations of the p53 gene were identified in 52.4% of human H. pylori-positive mucosa and in 100% of monkey H. pylori-positive mucosa. However, no mutations of the p53 gene were found in the H. pylori-positive gastric mucosa of Mongolian gerbils. There were no mutations in H. pylori-negative gastritis mucosa of humans, monkeys, or Mongolian gerbils. Nuclear staining of p53 was seen in the glandular cells of the H. pylori-infected mucosa of Japanese monkeys, especially in the neck region of the glands., Conclusions: These findings demonstrate that the H. pylori infection can induce p53 point mutations in humans and the Japanese monkey and appear to be involved in the pathway leading to dysplasia or carcinoma. However, our direct DNA sequencing method showed no p53 mutations in the Mongolian gerbil model at present. Further studies with this model are needed.