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Ken Haruma

Publications and source records attributed to Ken Haruma.

At least 19 recordsLinked to original sources
PubMed2006

Uptake of microparticles into the epithelium of human nasopharyngeal lymphoid tissue.

The M cells of nasopharyngeal lymphoid tissue (NALT) have been considered to play an important role for vaccine delivery systems in humans. A number of investigations have reported particle uptake data in NALT of rodents. However, there have been no reports indicating any involvement of the nasopharyngeal lymphoid tissue in human vaccination. In the present study, we investigated whether the epithelium of human adenoid tissues might incorporate fluorescent microparticles using electron and fluorescent microscopy. The dissected adenoid tissues were incubated with various sizes and concentrations of fluorescent microparticles for 120 min at 37 degrees C. Furthermore, the effect of surface coatings of microparticles with cations on the uptake into the epithelium of adenoid tissues was investigated. Transmission electron microscopy revealed that microparticles were taken up by the M cells of human nasopharyngeal lymphoid tissues. The NALT-M cells showed greater uptake of the smallest particles, 0.2 microm in diameter, than those of 0.5, 1.0, or 2.0 microm diameter. It was also revealed that surface coatings with poly-L: -lysin or chitosan resulted in efficient uptake into the NALT. These results indicate that nasal administration of antigenic microparticles, which were coated with cationic materials, probably leads to a useful method of transnasal vaccination against respiratory and intestinal infections in humans.

Adenoids↗
PubMed2006

Histological risk markers for non-cardia early gastric cancer. Pattern of mucin expression and gastric cancer.

There are limited data regarding the prognostic value of the pattern of mucin expression in IM. To examine the role of the type of IM and pattern of mucin expression in IM as histological risk markers of gastric cancer, 80 patients with a history of endoscopic mucosal resection (EMR) for early gastric cancer and 80 sex and age-matched controls were studied. Serum levels of pepsinogen (PG) were measured by RIA, and MUC2, MUC5AC and MUC6 were evaluated immunohistochemically. There is a significant association between types of IM and atrophic scores or PG levels. The most incomplete IM (type II and III) preserving gastric mucin is the gastric and intestinal mixed (GI) type, whereas the complete type is the intestinal (I) type especially in the corpus lesser curve. Gastric cancer was most significantly associated with incomplete IM in the corpus lesser curve (OR=6.4; 95% CI, 2.0-21, p=0.002). Asynchronous multiple lesions were associated with incomplete IM in the corpus greater curve (OR=4.8; 95% CI, 1.4-16, p=0.01). Classification of IM obtained using fixed-point biopsy samples may enhance the ability of surveillance programs to detect patients at increased risk of gastric cancer.

Aged↗
PubMed2006

Helicobacter pylori infection is the major risk factor for gastric inflammation in the cardia.

We attempted to clarify the pathogenesis of gastric inflammation in the cardia. Eighty Japanese participated in this study. Biopsy specimens of the gastric antrum, corpus, and cardia (1 cm from the squamocolumnar junction) were obtained, and histological gastritis was evaluated. Cardiac inflammation was also evaluated using magnifying gastroscopy. We examined Helicobacter pylori infection, gastric juice pH/bile acid (BA), serum pepsinogen and gastrin levels, gastroesophageal reflux disease (GERD), and habitual smoking and assessed the relations between these factors and cardiac inflammation. The prevalence of H. pylori infection was statistically higher in patients with cardiac inflammation than in those without inflammation (P < 0.05). The relationship was also demonstrated by magnifying gastroscopy. Cardiac inflammation was linked to low acid output but not linked to the BA concentration or habitual smoking. Cardiac inflammation was more pronounced in patients without GERD. These results suggest that H. pylori is a major risk factor for cardiac inflammation in the Japanese.

Adult↗
PubMed2006

Development of a novel method to detect Helicobacter pylori cagA genotype from paraffin-embedded materials: comparison between patients with duodenal ulcer and gastric cancer in young Japanese.

BACKGROUND/AIM: cagA gene polymorphism of Helicobacter pylori contributes to clinical outcome of patients. We investigated the implication of the cagA polymorphism in young Japanese patients using paraffin-embedded sections. METHODS: We studied 71 young patients with gastric cancer or with duodenal ulcer. H. pylori infection was confirmed by sections with Giemsa staining and immunohistochemical staining and the degree of gastritis was evaluated. DNA was extracted from paraffin-embedded sections of 20 patients both from the gastric corpus and the antrum. A portion of cagA gene was amplified with polymerase chain reaction, followed by direct sequencing of the fragment. RESULTS: We established a novel method to determine the cagA subtype using paraffin-embedded sections. We found that all the samples possessed East-Asian type cagA both in the corpus and the antrum, not only in patients with gastric cancer but also with duodenal ulcer. Although the cagA gene sequence was completely identical between the gastric corpus and the antrum in all patients, the corpus gastritis was more prominent in patients with gastric cancer than those with duodenal ulcer. CONCLUSIONS: cagA polymorphism can be evaluated with the use of paraffin-embedded sections. The degree of corpus gastritis may not be regulated by cagA diversity only.

Adult↗
PubMed2006

Causal role of Helicobacter pylori infection and eradication therapy in gastric carcinogenesis.

Many epidemiological reports indicate that Helicobacter pylori (H pylori) infection plays an important role in gastric carcinogenesis. Several genetic and epigenetic alterations contribute to the initiation, promotion, and progression of the cancer cells in a multi-step manner. H pylori is known to induce chronic inflammation in the gastric mucosa. Its products, including superoxides, participate in the DNA damage followed by initiation, and the inflammation-derived cytokines and growth factors contribute to the promotion of gastric carcinogenesis. By eradicating H pylori, gastric inflammation can be cured; the therapy diminishes the levels not only of inflammatory cell infiltration, but also atrophy/intestinal metaplasia in part. A randomized controlled trial revealed that the eradication therapy diminished the gastric cancer prevalence in cases without pre-cancerous conditions. In addition, recent epidemiological studies from Japanese groups demonstrated that the development of gastric cancer, especially of the intestinal type, was decreased by successful eradication therapy, although these were designed in a non-randomized manner. However, it should be mentioned that endoscopic detection is the only way to evaluate the degree of gastric carcinogenesis. We have reported that the endoscopic and histological morphologies could be modified by eradication therapy and it might contribute to the prevalence of gastric cancer development. Considering the biological nature of cancer cell proliferation, it is considered that a sufficiently long-term follow-up would be essential to discuss the anticancer effect of eradication therapy.

Animals↗
PubMed2006

The pharmacodynamic effect of omeprazole 10 mg and 20 mg once daily in patients with nonerosive reflux disease in Japan.

BACKGROUND: To evaluate the pharmacodynamic effect, efficacy, and safety of omeprazole 10 mg and 20 mg once daily in patients with nonerosive reflux disease (NERD) in Japan. METHODS: A total of 37 patients were randomized to omeprazole 10 mg or omeprazole 20 mg once daily for 4 weeks. Eligible patients had a history of moderate-to-severe heartburn for 2 days or more per week during the last 1 month or longer prior to the study screening, grade M or grade N on Hoshihara's modification of the Los Angeles classification (i.e., no sign of mucosal break on esophagogastroduodenoscopy), and heartburn episodes for 2 days or more per week during the last week of the observation period while taking antacids. Ambulatory 24-h intraesophageal pH was monitored on the day before treatment and on the last day of treatment. The occurrence of a heartburn episode was recorded during pH monitoring. The primary endpoint was the change in the percentage of time with intraesophageal pH < 4 during the 24-h period before and after omeprazole treatment. RESULTS: Both omeprazole 10 mg and omeprazole 20 mg once daily reduced the percentage of time with intraesophageal pH < 4. The percentage reduction in time with intraesophageal pH < 4 after treatment with omeprazole was associated with a reduced number of heartburn episodes. Patients with grade M or grade N esophagus had similar pH profiles and NERD characteristics (e.g., pH holding time, symptom index) and comparable responses to omeprazole. No serious, drug-related adverse events were reported. CONCLUSIONS: Omeprazole 10 mg or 20 mg reduces the percentage of time with intraesophageal pH < 4, is efficacious, and is well tolerated in patients with NERD in Japan, regardless of the patient's endoscopic classification.

Adult↗
PubMed2006

Lower esophageal sphincter- and vagus-preserving proximal partial gastrectomy for early cancer of the gastric cardia.

PURPOSE: Proximal gastrectomy and lymph node dissection are often performed for T1 cancer of the gastric cardia; however, direct esophagogastrostomy is frequently complicated by reflux esophagitis. We describe a simple technique for preventing esophageal reflux and discuss its results. METHODS: This technique is indicated for T1 cancer of the gastric cardia without lymphadenopathy. Partial resection, including the lesion, is performed, preserving the vagus nerve and lower esophageal sphincter (LES). Lymph node dissection is done around the left gastric, celiac, and splenic arteries. The esophagus is then anastomosed to the anterior wall in the center of the remnant stomach. RESULTS: We evaluated the results of this procedure in eight patients. X-ray films showed no esophageal reflux in either the supine or the right decubitus position. None of the patients complained of reflux or other dyscrasic symptoms, and none had any feeling of microgastria. One patient had some localized erosion near the anastomosis. CONCLUSIONS: This simple and safe technique does not result in post-gastrectomy syndrome or microgastria, and the risk of leaving cancer cells is minimal.

Aged↗
PubMed2006

Real-time visualization and quantitation of canine gastric mucosal blood flow by contrast-enhanced ultrasonography.

OBJECTIVE: Contrast-enhanced ultrasonography has become a method of choice for evaluating gastric blood flow, but intermittent scanning techniques can sometimes distort the results. Low-mechanical index imaging using Definity as the injected contrast material has been advocated for real-time evaluation of microperfusion in other organs. We investigated the reliability of low-mechanical index imaging using Definity in the evaluation of gastric mucosal blood flow. MATERIAL AND METHODS: Under general anesthesia, 10 beagle dogs weighing 9-10 kg underwent real-time harmonic imaging under low acoustic power (mechanical index = 0.2) after intravenous contrast injection using Definity (60 mg/kg). Laser Doppler flow measurement was also performed to evaluate gastric mucosal blood flow. After administration of a diclofenac sodium suppository, low-mechanical index imaging and laser Doppler flowmetry were repeated. RESULTS: Real-time visualization of gastric mucosal blood flow was successful in all dogs undergoing low-mechanical index imaging with Definity. Quantitative assessment of gastric mucosal blood flow was successful in eight dogs. After diclofenac sodium administration, gastric mucosal blood flow measured by both laser Doppler flowmetry and contrast ultrasonography decreased in seven of eight dogs; in the other dog, gastric mucosal blood flow increased slightly. A strong positive correlation was evident between blood flow measured by laser Doppler flowmetry and low-mechanical index imaging (r=0.777, p<0.005). CONCLUSIONS: Low-mechanical index imaging with Definity is a non-invasive way to evaluate gastric mucosal blood flow in real-time, high-resolutional images, which may have additional important gastrointestinal tract applications.

Animals↗
PubMed2006

Blockade of tumor necrosis factor-alpha-converting enzyme improves experimental small intestinal damage by decreasing matrix metalloproteinase-3 production in rats.

OBJECTIVE: Tumor necrosis factor (TNF)-alpha-converting enzyme (TACE), which has been purified, regulates maturity of TNF-alpha. Matrix metalloproteinases (MMPs) play a key role in various inflammatory conditions. The incidence of intestinal damage has increased, but the mechanism and treatment have not been well understood. The purpose of this study was to investigate the roles of TACE and MMP in indomethacin (Indo)-induced intestinal damage as well as the therapeutic effects of TACE inhibitor and selective MMP inhibitor (sMMPi) on this intestinal damage in rats. MATERIAL AND METHODS: In the first experiment, serial changes in intestinal ulcers and the production of MMP were investigated. In the second experiment, we assessed the effect of three TACE and/or MMP inhibitors and the production of TNF-alpha, TACE, MMP-3, -9 and tissue inhibitor of MMP (TIMP)-1. The rats were divided into five groups: a control group, and four groups that received Indo alone, Indo plus TACE inhibitor (GM6001), Indo plus a selective MMP-3 inhibitor and Indo plus an MMP-9/13 inhibitor, respectively. RESULTS: MMP-3 was overexpressed at 24 h after Indo administration, when intestinal injury was most prominent macroscopically and microscopically. GM6001 significantly decreased ulcer severity and suppressed MMP-3 in a dose-dependent fashion. The selective MMP-3 inhibitor dose-dependently ameliorated intestinal damage to the same degree as GM6001, but the MMP-9 inhibitor had no effect on the injury. CONCLUSIONS: MMP-3 inhibition ameliorates intestinal damage without apparently affecting either TNF-alpha or TACE production and the dose-response curve suggests that the beneficial effect of the so-called TACE inhibitor is actually mainly mediated via MMP-3 inhibition rather than TNF-alpha inhibition.

ADAM Proteins↗
PubMed2006

Aged garlic extract has potential suppressive effect on colorectal adenomas in humans.

Epidemiological and animal studies suggest AGE and its organosulfur constituents, such as S-allylcysteine and S-allylmercaptocysteine have anticarcinogenic effects. To confirm these effects in humans, a preliminary double-blind, randomized clinical trial using high-dose AGE (AGE 2.4 mL/d) as an active treatment and low-dose AGE (AGE 0.16 mL/d) as a control was performed on patients with colorectal adenomas-precancerous lesions of the large bowel. The study enrolled 51 patients who were diagnosed as carrying colorectal adenomas. The patients were randomly assigned to the two groups after adenomas larger than 5 mm in diameter were removed by polypectomy. The number and size of adenomas right before intake (0 mo) and at 6 and 12 mo after intake were measured using colonoscopy. Thirty-seven patients (19 in the active group, 18 in the control group) completed the study and were evaluated for the efficacy of AGE. The number of adenomas increased linearly in the control group from the beginning (the baseline), but AGE significantly suppressed both the size and number of colon adenomas in patients after 12 mo of high-dose treatment (P=0.04). The results suggest AGE suppresses progression of colorectal adenomas in humans. It appears that AGE has multiple pathways to reduce cancer incidence and suppress its growth and proliferation.

Adenoma↗
PubMed2006

The effect of Helicobacter pylori eradication therapy on gastric ulcer healing after endoscopic mucosal resection.

BACKGROUND AND AIM: It remains unclear whether Helicobacter pylori eradication therapy accelerates the healing of acute gastric ulcer after endoscopic mucosal resection (EMR) of gastric tumor. We examined the effect of H. pylori eradication therapy on ulcer healing after EMR. METHODS: Twenty-six patients who underwent successful H. pylori eradication therapy before EMR were followed prospectively. Patients underwent endoscopic examination 1 or 2 months after EMR, during which the ulcer status and reduction rate were assessed. The effect of H. pylori eradication on the quality of ulcer healing was also evaluated. Six patients in whom eradication therapy failed and 26 patients who underwent EMR without eradication therapy served as control subjects. RESULTS: Endoscopically, 18 (75%) of 24 ulcers in the eradication group were at the healing stage 1 month after EMR. The ulcer reduction rates were 85.0 +/- 2.6% and 96. 9 +/- 1.1% at 1 and 2 months after EMR, respectively. Ulcer stage and reduction rate did not differ significantly between the eradication group and control group. However, we frequently observed a better quality of ulcer healing in the eradication group than in the control groups (P < 0.01). CONCLUSION: H. pylori eradication therapy does not accelerate ulcer healing after EMR but may improve the quality of ulcer healing of gastric ulcer after EMR.

Aged↗
PubMed2006

A pilot study to evaluate a new combination therapy for gastric ulcer: Helicobacter pylori eradication therapy followed by gastroprotective treatment with rebamipide.

BACKGROUND AND AIM: Controversies remain over the need for antiulcer treatment following 1-week eradication triple therapy for Helicobacter pylori-positive peptic ulcers. The usefulness of combination therapy for gastric ulcers in Japanese patients, which consists of H. pylori eradication followed by gastroprotective therapy with rebamipide, was therefore evaluated. METHODS: The study was conducted in 52 H. pylori-positive patients with an endoscopically-proven open gastric ulcer. All patients received 1-week triple therapy (lansoprazole, amoxicillin and clarithromycin) followed by 7-week rebamipide therapy. After completion of the combination therapy, all patients underwent evaluation of ulcer healing by endoscopy, gastric ulcer symptoms and H. pylori eradication by rapid urease test and (13)C-urea breath test. RESULTS: The ulcer healing rates were 85.7% (36/42) at 8 weeks, 83.3% (30/36) in eradicated patients and 100% (6/6) in non-eradicated patients. The overall gastrointestinal symptom-free rate improved from 19.0% at baseline to 88.1% at 8 weeks. H. pylori was effectively eradicated in 85.7% (36/42) of patients. CONCLUSIONS: The results suggested that the combination therapy for open gastric ulcer was safe, well-tolerated and effective. However, data from a double-blind placebo-controlled study is necessary to confirm these findings.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2006

Endoscopic characteristics and Helicobacter pylori infection in NSAID-associated gastric ulcer.

BACKGROUND AND AIM: Helicobacter pylori infection and non-steroidal anti-inflammatory drugs (NSAIDs) are deeply involved in the etiology of gastric ulcers. The aim of our study was to clarify the endoscopic characteristics and H. pylori infection status of NSAID-associated gastric ulcers. METHODS: The study group comprised 50 patients (23 men, 27 women; mean age 66.5 years) with NSAID-associated gastric ulcers and 100 sex- and age-matched patients with gastric ulcer associated with other factors (control group). Ulcer morphology, size and number of lesions, onset site and incidence of hemorrhagic ulcers were investigated endoscopically in both groups. H. pylori infection was diagnosed by serology, histology and (13)C-urea breath test. RESULTS: Multiple lesions (68% vs 20%, P<0.001), occurrence in the antrum (56% vs 6%, P<0.001), and hemorrhagic ulcer (34% vs 4%, P<0.001) were significantly more prevalent in patients with NSAID-associated gastric ulcers than in patients with non-NSAID-associated gastric ulcer. The H. pylori infection rate was significantly lower in NSAID-associated gastric ulcer patients than in non-NSAID-associated gastric ulcer patients (48% vs 96%, P<0.001). In the NSAID-associated gastric ulcer group, the prevalence of H. pylori infection was significantly lower in patients with ulcers in the antrum than in those with ulcers in the angulus or corpus (25% vs 77.3%, P<0.001). CONCLUSIONS: In contrast to non-NSAID-associated gastric ulcers, NSAID-associated gastric ulcers frequently occur in the antrum with bleeding. The rate of H. pylori infection in NSAID-associated gastric ulcers is significantly lower than that in non-NSAID-associated gastric ulcers.

Adult↗
PubMed2006

Evaluation of endoscopic and histological findings in Helicobacter pylori-positive Japanese young adults.

BACKGROUND AND AIM: Many studies have shown that Helicobacter pylori infection is associated with chronic gastritis, peptic ulcers and gastric carcinoma in adults. However, little is known about these associations in the younger population. The aim of this study was to clarify endoscopic and histological findings in H. pylori-positive young adults. METHODS: Two hundred consecutive outpatients younger than 29 years old undergoing esophago-gastroduodenal endoscopy at four hospitals between 2001 and 2002 were eligible for this study. At endoscopy, three biopsy specimens were obtained from the mid-antrum, the angulus and the mid-corpus. Endoscopic and histological interpretations were based on the updated Sydney System. H. pylori infection was determined by histology and serology. RESULTS: The rates of H. pylori infection were 1.2% (1/86) in normal, 95.8% (46/48) in gastritis, 97.8% (45/46) in duodenal ulcers, 100% (17/17) in gastric ulcers, and 100% (3/3) in gastric carcinomas. Endoscopic findings in 112 H. pylori-positive patients were 25 normal (22.3%), 38 atrophy (33.9%), 18 erosion (16.1%), and 31 nodularity (27.7%). Histological findings of H. pylori-positive patients in the anturm revealed mononuclear cell and neutrophil infiltration in 100%, and atrophy in 27.7%. Histological findings of H. pylori-positive patients in the corpus revealed mononuclear cell infiltration in 75%, neutrophil infiltration in 60.7%, and atrophy in 28.6%. CONCLUSIONS: The study shows that H. pylori infection is strongly associated with chronic gastritis and peptic ulcers, and that histological corpus gastritis was found with high frequency in Japanese young adults.

Adult↗
PubMed2006

Surface structure of antral gastric mucosa represents the status of histologic gastritis: fundamental evidence for the evaluation of antral gastritis by magnifying endoscopy.

BACKGROUND: Recent studies have demonstrated the diagnostic potential of magnifying endoscopy in cases of histologic gastritis. The aim of the present study was to clarify whether the mucosal surface structure reflects the degree of histologic gastritis below the surface. METHODS: Gastric biopsy specimens were obtained from 1018 Japanese patients and were stained with hematoxylin and eosin. In 863 sections examined, gastritis was graded by means of the updated Sydney system, and the surface structure was classified as one of four types: flat, irregular, papillary, or non-structured. In addition, 103 patients underwent gastric examination by magnifying gastroscopy. RESULTS: The surface structure of most biopsy sections with normal mucosa and no Helicobacter pylori infection was classified as the flat type. Grades of histological gastritis were statistically lower in flat-type sections than in other types. Histologic gastritis was found in 91% of sections with a non-flat surface structure. Helicobacter pylori infection was confirmed in 96% of these cases. Most biopsy sections in patients with abnormal magnifying endoscopy features were of the non-flat type and showed histologic gastritis. CONCLUSIONS: The surface structure of the gastric mucosa reflects the status of histologic gastritis. Magnifying gastroscopy could be a useful non-invasive method of diagnosing histologic gastritis.

Female↗
PubMed2006

[Ultrasonographic assessment of sigmoid colon in patients with irritable bowel syndrome].

UNLABELLED: Although the pathophysiological factors may play a role in the pathogenesis of irritable bowel syndrome (IBS), the function of sigmoid colon has been reported as a major pathogenesis of IBS. Our objective was to evaluate motility patterns of sigmoid colon by using ultrasonography(US) in patients with IBS compared to healthy volunteers (HV). SUBIECTS AND METHODS: US examination of sigmoid colon was performed in 69 patients with IBS and 69 HV with 3.75 MHz curved array scanner and 7.5 MHz linear array scanner. The US probe was positioned longitudinally to permit simultaneous visualization of sigmoid colon crossing over the iliopsoas. We classified 3 types of fasting sigmoid colon, spastic type, empty type, and normal type, according to the US findings. Four IBS patients with diarrhea, 4 with constipation and 4 HV were given the liquid test meal (200ml, 400kcal). The frequency of segmental contractions (contractions without propagation) and propulsion were evaluated by US in the same fashion for 30 minutes before and for 60 minutes after investigation. RESULTS: Sixty-two percent of IBS showed spastic type and 65% of HV showed normal type. IBS patients accounted for 80 % of spastic type (IBS vs spastic type of US findings: Sensitivity 62%, Specificity 91%). The changes of frequency of segmental contractions were smaller in IBS patients with constipation. The changes of frequency of propulsion were larger in IBS patients with diarrhea. CONCLUSION: Ultrasonographic assessment of sigmoid colon may provide a better understanding of the pathogenesis of IBS.

Colon, Sigmoid↗
PubMed2005

A classification system of echogenicity for gastrointestinal neoplasms.

BACKGROUND AND AIMS: To confirm the utility of a newly-devised endoscopic ultrasonography (EUS) echogenicity classification system, which is based on the normal five-layer structure of the gastrointestinal wall, for the differential diagnosis of gastrointestinal neoplasms. METHODS: A total of 275 patients with gastrointestinal disease detected by endoscopy, 53 with submucosal tumor (22 esophageal, 27 gastric, and 4 duodenal), 208 with cancer (58 esophageal, 150 gastric), and 14 with gastric malignant lymphoma, were examined. In each case, we performed standard EUS with 7.5, 12, or 20 MHz to evaluate the echogenicity of the lesion. Echogenicity was classified into seven levels that is based on the echogenicity of the normal five-layer structure of the gastrointestinal wall. The levels are stratified from anechoic (level 0) to hyperechoic (level 6), muscularis propria and deep mucosa being referred to as level 2 and level 4, respectively. Level 6 was equivalent to or higher than the echogenicity of submucosa. RESULTS: EUS findings revealed several distinct echogenicities among the diseases. In submucosal tumor, levels 0, 2, and 6 were observed only in patients with cyst, myogenic tumor, and lipoma, respectively. In malignancies, levels 0, 5, and 6 were not observed in this study. The echo level of malignant lymphoma was markedly lower than that of epithelial cancer. CONCLUSION: Our classification system of echogenicity can be a useful method in the differential diagnosis of gastrointestinal neoplasms.

Adult↗