European Journal of NeurologyVolume 23, Issue 12 p. e76-e77 Letter to the Editor Minocycline-induced human herpesvirus 6 encephalomyelitis with drastically disseminated contrast-enhanced lesions K. Shinoda, K. Shinoda Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, JapanSearch for more papers by this authorT. Iwata, T. Iwata Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, JapanSearch for more papers by this authorY. Nakamura, Y. Nakamura Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, JapanSearch for more papers by this authorK. Masaki, K. Masaki Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, JapanSearch for more papers by this authorT. Matsushita, T. Matsushita Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, JapanSearch for more papers by this authorR. Yamasaki, R. Yamasaki Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, JapanSearch for more papers by this authorJ.-I. Kira, Corresponding Author J.-I. Kira kira@neuro.med.kyushu-u.ac.jp Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, JapanCorrespondence: J.-I. Kira, Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan (tel.: +81 92 642 5340; fax: +81 92 642 5352; e-mail: kira@neuro.med.kyushu-u.ac.jp).Search for more papers by this author K. Shinoda, K. Shinoda Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, JapanSearch for more papers by this authorT. Iwata, T. Iwata Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, JapanSearch for more papers by this authorY. Nakamura, Y. Nakamura Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, JapanSearch for more papers by this authorK. Masaki, K. Masaki Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, JapanSearch for more papers by this authorT. Matsushita, T. Matsushita Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, JapanSearch for more papers by this authorR. Yamasaki, R. Yamasaki Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, JapanSearch for more papers by this authorJ.-I. Kira, Corresponding Author J.-I. Kira kira@neuro.med.kyushu-u.ac.jp Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, JapanCorrespondence: J.-I. Kira, Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan (tel.: +81 92 642 5340; fax: +81 92 642 5352; e-mail: kira@neuro.med.kyushu-u.ac.jp).Search for more papers by this author First published: 24 November 2016 https://doi.org/10.1111/ene.13190Citations: 1Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume23, Issue12December 2016Pages e76-e77 RelatedInformation

症例は70代女性．下腹部違和感のため当院を受診した．下痢の訴えはなかった．胃食道逆流症のため3ヵ月前からランソプラゾールを継続内服していた．腹部CTでS状結腸の壁肥厚を認めた．腹部超音波検査ではS状結腸の軽度の壁肥厚を認めた．粘膜下層のエコーレベルはやや低下し，粘膜層や固有筋層との境界は不明瞭だった．大腸内腔と粘膜面の境界エコーが明瞭に同定できた．大腸内視鏡ではS状結腸に約5 cmにわたる縦走潰瘍を認めた．潰瘍は浅く，潰瘍周囲に軽度の粘膜浮腫を認めたが，その他の粘膜には異常を認めなかった．潰瘍近傍の粘膜からの生検で，上皮直下のcollagen bandの沈着，粘膜固有層内の慢性炎症細胞浸潤を認め，collagenous colitisと診断した．ランソプラゾールの中止により症状の消失を認め，腹部超音波検査を再検したところ，S状結腸の壁肥厚は消失していた．

BACKGROUND:Helicobacter pylori infection produces progressive mucosal damage that may eventually result in gastric cancer. We studied the changes that occurred in the presence and severity of atrophic gastritis and the prevalence of H. pylori infection that occurred coincident with improvements in economic and hygienic conditions in Japan since World War II. MATERIALS AND METHODS:The prevalence of H. pylori infection and histologic grades of gastric damage were retrospectively evaluated using gastric biopsy specimens obtained over a 40-year period. Gastric atrophy and intestinal metaplasia were scored using the updated Sydney classification system. RESULTS:The prevalence of H. pylori and severity of atrophy were examined in 1381 patients including 289 patients examined in the 1970s (158 men; mean age, 44.9 years), 787 in the 1990s (430 men; 44.2 years), and 305 in the 2010s (163 men; 53.2 years). Overall, the prevalence of H. pylori infection decreased significantly from 74.7% (1970s) to 53% (1990s) and 35.1% (2010s) (p < .01). The prevalence of atrophy in the antrum and corpus was significantly lower in the 2010s (33, 19%, respectively) compared to those evaluated in either the 1970s (98, 82%) (p < .001) or 1990s (80, 67%) (p < .001). The severity of atrophy and intestinal metaplasia also declined remarkably among those with H. pylori infection. CONCLUSIONS:There has been a progressive and rapid decline in the prevalence of H. pylori infection as well a fall in the rate of progression of gastric atrophy among H. pylori-infected Japanese coincident with the westernization and improvements in economic and hygienic conditions in Japan since World War II.

Established risk factors for gastric cancer include a diet high in nitrate or nitrite and low in vitamin C and the presence of achlorhydria or hypochlorhydria. The aim of this study was to investigate the relationship between intragastric nitrite concentration and atrophic change of the stomach or gastric carcinogenesis in Japanese Helicobacter pylori-infected patients. Gastric juice pH, nitrite, and total vitamin C concentrations in gastric juice, serum pepsinogen I and II concentrations, and specific Helicobacter pylori antibody were analyzed. Intragastric total vitamin C concentration was decreased by Helicobacter pylori infection of the gastric mucosa and with progression of the atrophic grade. There was a significant positive correlation between atrophic grade and intragastric nitrite concentration. In conclusion, the levels of nitrite in gastric juice play a causal role in the development of cancer in Helicobacter pylori-associated atrophic gastric mucosa.

This study investigated whether the serum nitrite concentration reflects Helicobacter pylori-induced inflammation and atrophic changes of gastric mucosa. Ninety-seven patients underwent biopsy of both antrum and fundus. Samples were analyzed by the rapid urease test and histopathological examination according to the updated Sydney system. Fasting serum samples from each subject were analyzed for specific IgG Helicobacter pylori antibodies, pepsinogen I and II concentrations, and NO2−/NO3− content. Eleven patients had H. pylori eradicated with proton pump-based triple therapy. There was a strong positive correlation between the Helicobacter pylori density in the gastric mucosa and the serum nitrite concentration, but a negative correlation existed between the atrophic grade of the gastric mucosa and both serum nitrite concentration and Helicobacter pylori density in the gastric mucosa. Serum nitrite concentrations decreased significantly after successful eradication of Helicobacter pylori. Therefore, serum nitrite concentration may be a useful marker for oxidative DNA damage and apoptosis associated with Helicobacter pylori infection.

Recent advances of videoendoscopy have enabled the early detection of invasive colorectal carcinoma.The AIM of this study is to clarify the characteristics and cancer management of submucosal colorectal carcinoma smaller than 10mm in diameter.METHODS : We performed clinicopathologic analysis of 66 cases of submucosal colorectal carcinoma smaller than 10mm (small sm-ca) in comparison with 407 cases larger than 10mm (large sm-ca) experienced during same period.All lesions were finally resected surgically and confirmed histopathologically if lymph node metastasis occurred or not.RESULTS : Prevalence of small sm-ca was 14% {66/473) of all sm-ca, Prevalence of superficially depressed type in small sm-ca (26/66; 39%) was significantly (p<0.01)higher than that of large sm-ca (711407; 17%).There was no significant difference in prevalence of massive invasive lesions between small sm-ca and large sm-ca.Prevalence of lymph node metastasis in each size of submucosal carcinoma was 8 (12%) of 66 small sm-ca and 40 (10%) of 407 large sm-ca, respectively (NS).Among small smca, 11 cases <5mm showed no lymph node metastasis.Cases of 6 to 9mm showed lymph node metastasis in 8 (15%) of 55 cases.CONCLUSION : Small sm-ca, which includes a significantly more cases of superficially depressed type, showed metastatic potential as same as large sm-ca.However, of them, submucosal carcinoma -<5mm can be cured by complete endoscopic resection alone, because cases <5mm showed no lymph node metastasis.

Recent advances of videoendoscopy have enabled the early detection of invasive colorectal carcinoma.The AIM of this study is to clarify the characteristics and cancer management of submucosal colorectal carcinoma smaller than 10mm in diameter.METHODS : We performed clinicopathologic analysis of 66 cases of submucosal colorectal carcinoma smaller than 10mm (small sm-ca) in comparison with 407 cases larger than 10mm (large sm-ca) experienced during same period.All lesions were finally resected surgically and confirmed histopathologically if lymph node metastasis occurred or not.RESULTS : Prevalence of small sm-ca was 14% {66/473) of all sm-ca, Prevalence of superficially depressed type in small sm-ca (26/66; 39%) was significantly (p<0.01)higher than that of large sm-ca (711407; 17%).There was no significant difference in prevalence of massive invasive lesions between small sm-ca and large sm-ca.Prevalence of lymph node metastasis in each size of submucosal carcinoma was 8 (12%) of 66 small sm-ca and 40 (10%) of 407 large sm-ca, respectively (NS).Among small smca, 11 cases <5mm showed no lymph node metastasis.Cases of 6 to 9mm showed lymph node metastasis in 8 (15%) of 55 cases.CONCLUSION : Small sm-ca, which includes a significantly more cases of superficially depressed type, showed metastatic potential as same as large sm-ca.However, of them, submucosal carcinoma -<5mm can be cured by complete endoscopic resection alone, because cases <5mm showed no lymph node metastasis.

Although several recent studies have reported that curing Helicobacter pylori (H. pylori) may result in the development of reflux esophagitis (RE), the mechanisms leading to this complication are unknown. One by product of H. pylori infection is ammonia, which serves as an acid neutralizer. The aim of this study was to clarify whether ammonia, which is produced during H. pylori infection, has a protective effect on the esophagus. Eight-week-old male Sprague-Dawley rats were fasted for 24 hrs. Under anesthesia, both the pylorus and limiting ridge were simultaneously ligated. One hour postligation, 0.3 ml of saline or ammonia at various concentrations was administered intragastrically by gastric intubation. Three hours after ligation, the animals were killed, the esophagus and stomach were removed, and the length of esophageal hemorrhagic erosions was measured. The incidence of RE was 100% (7/7) in the control group, 71% (5/7) in the low-ammonia group, 29% (2/7) in the middle-ammonia group, and 14% (1/7) in the high-ammonia group. The severity of lesions decreased in correspondence to increases in ammonia concentration. The development of RE was significantly inhibited by ammonia in a dose-dependent manner. This study indicates that ammonia protects against development of RE. A decreased amount of ammonia in the stomach might be related to the development of RE after H. pylori eradication therapy.

BACKGROUND: Histological examination using biopsy specimens is common method to evaluate histological gastritis but invasive and localized.The aim of this study is to investigate the diagnostic potential of histological gastritis using magnifying endoscope.In addition, we tried to investi-

BACKGROUND: Histological examination using biopsy specimens is common method to evaluate histological gastritis but invasive and localized.The aim of this study is to investigate the diagnostic potential of histological gastritis using magnifying endoscope.In addition, we tried to investi-

B-cell monoclonality has been reported not only in gastric lymphoma, but also in 1.3–21% of Helicobacter pylori-associated chronic gastritis (Hp-CG) cases. The aim of this study was to determine the significance of B-cell monoclonality in Hp-CG. We examined 134 gastric biopsy specimens from 99 patients with Hp-CG. The density of Hp, polymorphonuclear neutrophil activity, chronic inflammation, glandular atrophy, and intestinal metaplasia (IM) were scored according to the updated Sydney System. B-cell monoclonality was analyzed for immunoglobulin heavy chain gene rearrangement using polymerase chain reaction amplification. B-cell monoclonality was detected in 6% of informative samples. B-cell monoclonality was found in 18% of the samples from Hp-CG patients with marked glandular atrophy but in none of the samples from Hp-CG patients with none to moderate glandular atrophy. Monoclonality was also detected in 20% of the samples from Hp-CG patients with marked IM, in 11% of the samples from Hp-CG patients with moderate IM, and in none of the samples from Hp-CG patients without IM. Therefore, B-cell monoclonality was significantly more frequent in Hp-CG patients with marked glandular atrophy than in Hp-CG patients with none to moderate atrophy. It was also more significantly frequent in Hp-CG patients with moderate or marked IM than in Hp-CG patients without IM (P<0.05). Of 35 Hp-CG patients, 26 (74%) had identical B-cell populations in the antrum and the corpus, and all were polyclonal. The remaining nine (26%) Hp-CG patients had B-cell populations that differed in the antrum and the corpus. Four of the nine (44%) showed monoclonal B-cell populations in at least one gastric biopsy specimen. There were no patients with monoclonal B-cell populations in both the antrum and the corpus. These data suggest that glandular atrophy and IM in gastric biopsy specimens may be markers for gastric mucosa-associated lymphoid tissue (MALT) lymphomagenesis and that multiple gastric biopsy specimens from both the antrum and the corpus may be needed to assess the risk of gastric MALT lymphoma.

BACKGROUND: Histological examination using biopsy specimens is common method to evaluate histological gastritis but invasive and localized.The aim of this study is to investigate the diagnostic potential of histological gastritis using magnifying endoscope.In addition, we tried to investi-

Recent studies have shown that Helicobacter pylori infection is etiologically and experimentally associated with gastric carcinoma. However, the role of H. pylori in carcinogenesis has not been clarified. H. pylori infection leads to sustained production of the reactive nitrogen species that cause DNA damage. We discuss hypotheses related to possible mechanisms of action of H. pylori in human gastric carcinogenesis and tumor progression, especially the role of reactive nitrogen species and inflammatory cytokines. Immunohistochemical analysis revealed that the expression of inducible nitric oxide synthase (iNOS) and nitrotyrosine in the gastric mucosa was significantly higher in H. pylori-positive subjects than in H. pylori-negative subjects. Among the H. pylori-positive patients, the expression of iNOS and nitrotyrosine in the gastric mucosa was significantly higher in those who developed gastric carcinoma than in the controls. H. pylori with cagA gene induces inflammatory cytokines, including interleukin (IL)-1, IL-6, IL-8, and tumor necrosis factor (TNF). IL-1 and TNF may cause overexpression of iNOS and nitrotyrosine in gastric mucosa, and IL-8 may promote tumor growth through its angiogenic activity.

Recent advances of videoendoscopy have enabled the early detection of invasive colorectal carcinoma.The AIM of this study is to clarify the characteristics and cancer management of submucosal colorectal carcinoma smaller than 10mm in diameter.METHODS : We performed clinicopathologic analysis of 66 cases of submucosal colorectal carcinoma smaller than 10mm (small sm-ca) in comparison with 407 cases larger than 10mm (large sm-ca) experienced during same period.All lesions were finally resected surgically and confirmed histopathologically if lymph node metastasis occurred or not.RESULTS : Prevalence of small sm-ca was 14% {66/473) of all sm-ca, Prevalence of superficially depressed type in small sm-ca (26/66; 39%) was significantly (p<0.01)higher than that of large sm-ca (711407; 17%).There was no significant difference in prevalence of massive invasive lesions between small sm-ca and large sm-ca.Prevalence of lymph node metastasis in each size of submucosal carcinoma was 8 (12%) of 66 small sm-ca and 40 (10%) of 407 large sm-ca, respectively (NS).Among small smca, 11 cases <5mm showed no lymph node metastasis.Cases of 6 to 9mm showed lymph node metastasis in 8 (15%) of 55 cases.CONCLUSION : Small sm-ca, which includes a significantly more cases of superficially depressed type, showed metastatic potential as same as large sm-ca.However, of them, submucosal carcinoma -<5mm can be cured by complete endoscopic resection alone, because cases <5mm showed no lymph node metastasis.

The 13C-urea breath test (UBT) is considered to be the most accurate way of diagnosing Helicobacter pylori infection. Values are affected by H. pylori infection and by the severity of atrophic gastritis. Our objective was to determine the association of UBT values with gastric cancer, and to evaluate the risk of gastric cancer in terms of UBT values. Methods. Our study involved 413 consecutive patients who had undergone esophagogastroduodenal examination and the UBT test. Results. Of the 398 patients with positive UBT results, atrophy and intestinal metaplasia scores in both antrum and corpus were significantly higher in patients with gastric cancer than in those with gastritis, duodenal ulcer, and gastric ulcer. The UBT value related to gastric cancer (22.01 ± 1.89‰) was significantly lower than that for gastritis (35.19 ± 1.53‰; P < 0.01), duodenal ulcer (29.01 ± 1.97‰; P < 0.05), or gastric ulcer (30.79 ± 2.83‰; P < 0.05). When the UBT values were less than 20‰, increases in the risk of gastric cancer correlated with decreasing UBT values. Conclusions. These findings indicate that the UBT value related to gastric cancer is significantly lower than that for gastritis, duodenal ulcer, or gastric ulcer in H. pylori-positive patients. Low UBT values were associated with the risk of gastric cancer.

PURPOSE:The purpose of this study was to investigate the mechanism of the regulation of histamine synthesis in enterochromaffin-like cells, chemically and structurally, by treatment with omeprazole and pirenzepine.METHODS:The ultrastructures of enterochromaffin-like cells and parietal cells were examined in rats treated with oral omeprazole (20 mg/kg) or intraperitoneal pirenzepine (1 mg/kg) administration. Serum gastrin concentrations, mRNA levels of H+-K+-ATPase and histidine decarboxylase, and the fundic concentrations of somatostatin and histamine were determined.RESULTS:Pirenzepine treatment suppressed omeprazole-induced increases in serum gastrin levels and mRNA levels of H+-K+-ATPase and histidine decarboxylase. Pirenzepine also decreased omeprazole-induced increases of histamine concentration in fundic mucosa. Pirenzepine elevated somatostatin mRNA level, previously decreased by omeprazole treatment, in fundic mucosa. In the cytoplasm of enterochromaffin-like cells, omeprazole markedly reduced the numbers of vesicles and granules, but significantly increased their diameters, whereas pirenzepine treatment changed neither of these features. The densities and diameters of both vesicles and granules produced by treatment with omeprazole and pirenzepine were between those produced by treatment with omeprazole alone and pirenzepine alone.CONCLUSIONS:Omeprazole-induced hypergastrinemia and pirenzepine-induced somatostatin synthesis play important roles not only in histamine synthesis but also in ultrastructural changes in enterochromaffin-like cells.

PURPOSE: Recently, endoscopic mucosal resection has been performed commonly for colorectal tumors. However, incomplete endoscopic mucosal resection produces a residual tumor that grows rapidly. The aim of this study was to clarify the characteristics of the residual tumor using the nude mouse model. METHODS: Human colon cancer cells (colo201 or colo320DM) were implanted subcutaneous into nude mice. We then removed more than one-half of the tumor with an electrocautery snare or a surgical knife, and compared the tumor growth rate with that of control tumors. Before and after resection, we examined the Ki-67 labeling index of the tumors with an immunohistochemical assay and mRNA expression for epidermal growth factor receptor, vascular endothelial growth factor, and transforming growth factor alpha. RESULTS: Residual tumors showed a higher growth rate in tumor volume than control tumors using both methods (electrocautery snare and surgical knife). Colo201 groups showed a higher total volume change per day than colo320DM groups after resection. Furthermore, these tumors also showed a higher Ki-67 labeling index, and a stronger epidermal growth factor receptor and transforming growth factor alpha mRNA expression than primary and control tumors in the colo201 implanted groups. There was no significant difference in vascular endothelial growth factor mRNA expression between groups implanted with colo201 or colo320DM. CONCLUSION: Our results suggest that residual tumors caused by incomplete endoscopic mucosal resection may have a higher growth potential than the tumors before resection.

Aim: Recent developments in molecular biology have been revealed the pathogenesis of esophageal cancer, and disorder of cell cycle regulation and cell-cell adhesion contributes to the carcinogenesis in various cancers.In this study, we examined the expression of cell cycle regulatory proteins and adhesinon molecules, and clarify their roles of pathogenesis in esophageal cancer.Methods: Forty patients with squamous cell carcinoma (SCC) who underwent esophagectomy at Dokkyo University School of Medicine froml987 to 1999, were selected.We studied them about cell cycle regulatory proteins and adhesinon molecules immunohistochemically by the LSAB metod (DAKO)_ Using antibodies were PCNA (PCID, DAKO), cyclinDI(DCS-6, DAKO) , p27 (k25027, Transduction Lab), E-cadherin (CI9220,Transduction Lab), DF3IMUCI(TFB).Results: PCNA-labeling index (positive cell counts/WOO tumor cells, %) of dysplasia and mucosal carcinoma was lower than that of invasive portion.Comparing the lesions with lymph node metastasis (M +) and the lesions without metastasis (M-), the incidence of (M +) was higher than that of (M-) about the overexpression of cyclinD 1, and the incidence of (M +) was lower than that of (M-) about the overexpression of p27.DF3IMUCI expressed in the most of SCC and no DF3IMUCI expressed in the normal epithelium, the incidence of (M +) was higher than that of (M-) about the overexpression of DF3/ MUC!.Most of (M +) showed no expression or abnomal expression (cytoplasmic) of E-cadherin, especially, at the invasive front.Conclusion: We concluded that disorder of the cell cycle control and dysfunction of the adhesion molecule was related to the pathogenesis of the esophageal cancer, and cyclinDI, p27, E-cadherin, DF3IMUCI may be useful marker for the prediction of lymph node metastasis of esophageal SCC.

BACKGROUND:We investigated the effects of rabeprazole compared with those of omeprazole on enterochromaffin-like cells and parietal cells in rats.METHODS:Rabeprazole or omeprazole was administered for 7 days by intraperitoneal injection (100 mg/kg or 20mg/kg once a day) and the serum gastrin concentration, the antral density of G cells and D cells, fundic histamine content, fundic H+, K+-ATPase mRNA level, and parietal cell morphology were determined.RESULTS:Both rabeprazole and omeprazole inhibited gastric acid secretion and increased the intragastric pH to over 6.5, as well as causing a marked increase in the serum gastrin concentration. The serum gastrin level was lower with rabeprazole treatment than with omeprazole treatment at both doses. Also, the antral G-cell density was higher with omeprazole than with rabeprazole, while the increase in both the histamine content and the H+, K-ATPase mRNA level in the fundic mucosa was higher with omeprazole treatment at both doses, with the difference being significant at 100 mg/kg. Ultrastructural examination indicated that the stimulation of parietal cells by omeprazole was stronger than that by rabeprazole.CONCLUSIONS:Rabeprazole treatment does not drive enterochromaffin-like cells and parietal cells as strongly as omeprazole treatment despite its potent acid suppressive effect, suggesting that it represents a new generation of proton pump inhibitors.