Fukunori Kinjo

Efficacy of agar-plate culture in detection of Strongyloides stercoralis infection.

Agar-plate culture of feces using a modified petri dish proved to be highly efficient in the detection of Strongyloides stercoralis infection. Furrows left by S. stercoralis on the agar plate were distinguished readily in size from those left by Necator americanus.

Association between Helicobacter pylori Virulence Factors and Gastroduodenal Diseases in Okinawa, Japan

ABSTRACT The incidence of gastric cancer in Okinawa is lowest in Japan. Some previous reports using small number of strains suggested that the high prevalence of Helicobacter pylori with Western-type cagA in Okinawa compared to other areas in Japan might contribute to the low incidence of gastric cancer. It has still not been confirmed why the prevalence of Western-type cagA strains is high in Okinawa. We examined the association between the virulence factors of H. pylori and gastroduodenal diseases in Okinawa. The genotypes of cagA and vacA of 337 H. pylori strains were determined by PCR and gene sequencing. The genealogy of these Western-type cagA strains in Okinawa was analyzed by multilocus sequence typing (MLST). Overall, 86.4% of the strains possessed cagA: 70.3% were East-Asian type and 16.0% were Western type. After adjustment by age and sex, the presence of East-Asian-type cagA/vacA s1m1 genotypes was significantly associated with gastric cancer compared to gastritis (odds ratio = 6.68, 95% confidence interval = 1.73 to 25.8). The structure of Western-type CagA in Okinawa was different from that of typical Western-type CagA found in Western countries. Intriguingly, MLST analysis revealed that the majority of Western-type cagA strains formed individual clusters but not hpEurope. Overall, low prevalence of gastric cancer in Okinawa may result from the high prevalence of non-East-Asian-type cagA strains. The origin of Western-type cagA strains in Okinawa may be different from those of Western countries.

Type 1 T helper cell predominance in granulomas of Crohn's disease

OBJECTIVE:The pathogenesis of Crohns disease (CD) is thought to be associated with production of several cytokines, especially type-1 cytokines. To elucidate the in situ cytokine profiles in CD, cytokine-containing cells were localized by immunohistochemistry, with special attention to noncaseating granulomas. The results were compared with those from studies of ulcerative colitis (UC).METHODS:We adopted the biotin-streptavidin-peroxidase method on frozen sections obtained at surgery from patients with CD or UC, and we immunohistochemically examined the expression of several cytokines (interferon-gamma, interleukin-2, -4, -10, and -12).RESULTS:In normal colonic tissue, expression of these cytokines was rare except for interleukin-4. In actively inflamed areas of CD, increased expression of all cytokines by mononuclear cells was observed. In contrast, granulomas in CD involved interferon-gamma+ lymphocytes and interleukin-12+ macrophage-lineage cells (epithelioid cells and multinucleated giant cells) but few interleukin-4+ or -10+ cells. Actively inflamed areas of UC also showed an increase in the number of cytokine-containing cells; however, quantitative analysis revealed that there was more expression of interferon-gamma and interleukin-12, and less of interleukin-10, in CD than in UC, indicating the presence of more type 1 T-helper cells in CD tissue than in UC.CONCLUSIONS:The findings of the present study suggest that granulomas of CD are coupled with type 1 T-helper responses; these responses may contribute to the pathogenesis of this disease.

Hepatitis delta virus genotype IIb predominates in an endemic area, Okinawa, Japan.

Hepatitis delta virus (HDV) infection is relatively common in the Miyako Islands, Okinawa, Japan, where the infection has been reported to be associated with low pathogenicity. HDV RNA extracted from each of 6 patients with HDV‐related chronic liver disease living in the islands was amplified by reverse transcription‐polymerase chain reaction and examined genetically to determine the HDV genotype. All isolates from the 6 patients were classified as genotype II by the neighbor‐joining method. However, these isolates had relatively low homology (75–81%) to the HDV genotype II isolate reported from Japan, and showed relatively high identity (83–95%) to the novel genotype II isolate (HDV genotype IIb) recently reported from Taiwan. Phylogenetic analysis showed that the 6 isolates form a novel group within HDV genotype II. Furthermore, there was notable variation in sequence among the 6 isolates compared with the relatively close clustering of HDV isolates within limited areas (e.g., United States, Archangelos, Turkey, Albania, Peru). HDV genotype II in the Miyako Islands is therefore unique, and HDV infection may have been introduced at a relatively early time in this area. J. Med. Virol. 58:366–372, 1999.

Comparison of endoscopic findings with symptom assessment systems (FSSG and QUEST) for gastroesophageal reflux disease in Japanese centres

Background and Aim:  We compared endoscopic findings of the frequency scale for the symptoms of gastroesophageal reflux disease (FSSG), a written questionnaire developed in Japan, to that for the questionnaire for the diagnosis of reflux esophagitis (QUEST) for the diagnosis of reflux esophagitis.

Histologic and immunohistochemical analyses of α-fetoprotein--producing cancer of the stomach.

Background and Aim:As the histogenesis and development of &agr;-fetoprotein–producing gastric cancer (AFPGC) have not yet been elucidated, we analyzed the histologic and immunologic relationship between the histologic type of the mucosal lesion considered to be the primary lesion, and that of its invasive lesion, in 36 cases of AFPGC. Patients and Methods:We reviewed 23 AFPGCs with mucosal lesions (1 mucosal and 22 submucosal or deeper invasive tumors) among 36 AFPGCs that had been resected endoscopically or surgically between 1970 and 2005. AFPGC was defined as a tumor showing immunohistochemical positivity for either &agr;-fetoprotein (AFP) or glypican-3. Histologic types were divided into hepatoid (HPT), enteroblastic (ENT), yolk sac tumor, and common (COM) adenocarcinoma type. The tumor phenotypes were classified into gastric, gastrointestinal, and intestinal types on the basis of immunohistochemical analysis. Results:Among the histologic types of mucosal lesions, the COM and ENT mixed type was observed in 65.2% of cases (15/23 patients), COM alone in 26.1% (6/23), and ENT alone in 8.7% (2/23) of cases. Among the invasive lesions, 16 cases (72.7%) were HPT. Both AFP and glypican-3 were positive in 60.9% (14/23) of mucosal lesions and in 90.9% (20/22) of invasive lesions. With regard to phenotypic expression, 82.6% (19/23) of mucosal lesions were the intestinal type, compared with 95.5% (21/22) of invasive lesions. Conclusions:These findings suggest that many cases of AFPGC develop as COM or ENT in the mucosa, which differentiate into ENT and HPT during the process of tumor invasion and proliferation, acquiring AFP production ability.

Oral Spherical Adsorptive Carbon for the Treatment of Intractable Anal Fistulas in Crohn's Disease: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial

OBJECTIVES:Anal fistulas are common in individuals with Crohns disease (CD). We sought to evaluate the efficacy of oral spherical adsorptive carbon (AST-120) (Kremezin®; Kureha Corporation, Tokyo, Japan) for the treatment of intractable anal fistulas in patients with CD.METHODS:In this multicenter, randomized, double-blind, placebo-controlled trial, patients with CD and at least one active anal fistula under treatment were assigned to receive either AST-120 or placebo for 8 wk. Improvement was defined as a reduction of 50% or more from baseline in the number of draining fistulas observed at both 4 and 8 wk. Remission was defined by closure of all draining fistulas at both 4 and 8 wk. The Perianal Disease Activity Index (PDAI) and Crohns Disease Activity Index (CDAI) were also assessed.RESULTS:In total, 62 patients were randomized, of whom 57 received AST-120 (N = 27) or placebo (N = 30). The improvement rate in the AST-120 group (37.0%) was significantly greater than that in the placebo group (10.0%) (P= 0.025). The corresponding remission rates were 29.6% and 6.7%, respectively (P= 0.035). PDAI significantly improved at both 4 and 8 wk with AST-120, compared to placebo (P= 0.004 and P= 0.005, respectively). CDAI was also significantly improved at both 4 and 8 wk in the AST-120 group, compared to the placebo group (P= 0.007 and P= 0.001, respectively). AST-120 treatment was well tolerated and no life-threatening adverse events were observed.CONCLUSION:AST-120 is useful for the control of intractable anal fistulas in CD patients.

Correlation between serum transaminase activity and virus load among patients with chronic liver disease type B

Newly developed hepatitis B virus (HBV)-DNA quantitative assays, transcription-mediated amplification and hybridization protection assay (TMA-HPA) and branched-DNA assay were clinically evaluated. The subjects consisted of 160 chronic HBV carriers; 48 were hepatitis Be antigen (HBeAg)-positive, whereas 109 were anti-HBe-positive (three were both negative). All subjects with HBeAg, except one, showed high HBV-DNA replication levels (>/=10(5.8) copies/ml). In HBeAg negative subjects, there was a strong correlation between the serum HBV-DNA and alanine aminotransferase (ALT) levels; ALT level was usually normal if the samples tested showed an HBV-DNA level less than 10(5)/ml, whereas, the majority of the sera with an HBV-DNA concentration greater than 10(7)copies/ml showed elevation in serum ALT level. An intermediate range of HBV-DNA level (10(5)-10(7) copies/ml) was associated with variable ALT activity. In conclusion, a serum HBV-DNA level associated with ALT elevation was lower in patients with type B chronic liver disease negative for HBeAg compared with their HBeAg-positive counterparts. There was usually no or mild liver disease activity when patients with chronic HBV infection have serum HBV-DNA levels less than 10(5)copies/ml.

Esophagitis dissecans superficialis and autoimmune bullous dermatoses: A review

Esophagitis dissecans superficialis (EDS) is a rare and severe endoscopic finding characterized by sloughing of large fragments of esophageal mucosal lining. Although EDS has been reported in association with serious illnesses and certain medications, the pathophysiological association of autoimmune bullous dermatoses with EDS has gained remarkable attention. Among these dermatoses, pemphigus vulgaris and pemphigoid frequently present with various types of esophageal involvement including EDS. We review the pathophysiology and clinical features of this involvement with the presentation of our experiences. The importance of endoscopic evaluation of this entity is discussed.

NF-κB activation by Helicobacter pylori requires Akt-mediated phosphorylation of p65

BackgroundThe inflammatory response in Helicobacter pylori-infected gastric tissue is mediated by cag pathogenicity island (PAI)-dependent activation of nuclear factor-κB (NF-κB). Phosphatidylinositol 3-kinase (PI3K)/Akt signaling is known to play a role in NF-κB activation, but little information is available on the relationship between H. pylori and PI3K/Akt signaling in gastric epithelial cells. We examined whether H. pylori activates Akt in gastric epithelial cells, the role of cag PAI in this process and the role of Akt in regulating H. pylori-induced NF-κB activation.ResultsPhosphorylated Akt was detected in epithelial cells of H. pylori-positive gastric tissues. Although Akt was activated in MKN45 and AGS cells by coculture with cag PAI-positive H. pylori strains, a cag PAI-negative mutant showed no activation of Akt. H. pylori also induced p65 phosphorylation. PI3K inhibitor suppressed H. pylori-induced p65 phosphorylation and NF-κB transactivation, as well as interleukin-8 expression. Furthermore, transfection with a dominant-negative Akt inhibited H. pylori-induced NF-κB transactivation. Transfection with small interference RNAs for p65 and Akt also inhibited H. pylori-induced interleukin-8 expression.ConclusionThe results suggest that cag PAI-positive H. pylori activates Akt in gastric epithelial cells and this may contribute to H. pylori-mediated NF-κB activation associated with mucosal inflammation and carcinogenesis.