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D Shirasaka

Publications and source records attributed to D Shirasaka.

12 recordsLinked to original sources
PubMed2002

Variation in MT expression in early-stage depressed-type and polypoid-type colorectal tumours.

Metallothionein (MT) expression is observed in various carcinomas, but its role is not fully understood. To clarify the clinicopathological significance of MT, 87 colorectal adenomas and 128 early-stage carcinomas were immunohistochemically analysed for MT expression. The degree of MT immunostaining of a specimen was graded according to the proportion of MT-positive cells; negative (<5%) and positive (focally 5-50%, diffusely >50%). MT expression significantly decreased with tumour development. For carcinomas, MT-positivity was significantly associated with depth of invasion (T1 60% versus T2 33%; P<0.01), vascular involvement (positive 35% versus negative 61%; P<0.01) and morphology (polypoid 62% versus depressed 26%; P<0.01). Regarding MT-positive distribution, the diffuse-positive rate in MT-positive polypoid lesions was 28%, while MT-positive depressed lesions were all diffusely stained (P<0.01). In conclusion, our results suggested that decreasing MT expression is an early event in colorectal carcinogenesis and may reflect local invasion. Furthermore, MT-positive distribution may reflect genetic differences between the polypoid and depressed-type.

Adult↗
PubMed2001

Glut1 expression in T1 and T2 stage colorectal carcinomas: its relationship to clinicopathological features.

Glucose uptake is mediated by glucose transporter (Glut) proteins, which exhibit altered expression in a variety of malignant neoplasms. Glut1 expression is thought to be a potential marker for malignant transformation. The aim of the present study was to investigate the expression of Glut1 protein in colorectal adenomas, T1 and T2 stage carcinomas. Immunohistochemical detection of Glut1 protein was examined in 141 formalin-fixed and paraffin-embedded colorectal tumour specimens (57 adenomas, 84 carcinomas). The degree of Glut1 immunostaining of a specimen was graded according to the proportion of Glut1-positive cells in it; absent (positive cells are 0%), weakly positive (less than 10%), moderately positive (10-50%), and strongly positive (more than 50%). Glut1 expression was present in 18% of the adenomas with low-grade dysplasia, and in 63% of the adenomas with high-grade dysplasia. The positivity in such lesions was usually weak, but was moderate in 8% of the adenomas with high grade dysplasia. For the carcinomas, there were significant correlations between Glut1-positivity and depth of invasion (T1 45% versus T2 74%, P<0.01), histological differentiation (well 49% versus moderately to poorly 74%, P< 0.05) and morphological type (polypoid 42% versus depressed 73%, P< 0.05), if the cut-off value was set at 10% of cells. In conclusion, we clarified the relationship between Glut1 expression and clinicopathological features in T1 and T2 stage colorectal carcinomas, and our results suggested a high malignant potential of the depressed-type carcinoma.

Adenocarcinoma↗
PubMed2001

[Rapid urease test].

The rapid urease test is a simple, sensitive, and highly specific test that enables the endoscopist to diagnose Helicobacter pylori infection in the endoscopy room. Determination of the infection status of Helicobacter pylori by biopsies from the gastric body had a significantly higher sensitivity than antral biopsies. A false-negative reaction by rapid urease test occurred the use of antibiotics (correlates with clearance of the bacteria) and the use of proton pump inhibitor or a part of mucosal protective agents(correlates urease inhibitory effect) and in the case of non-urease producing Helicobacter pylori. The rapid urease test satisfactory overall sensitivity before eradication treatment. However, the sensitivity of these rapid urease tests was lower after eradication than before eradication.

Clinical Enzyme Tests↗
PubMed2000

Flat-elevated and depressed, subtypes of flat early colorectal cancers, should be distinguished by their pathological features.

Flat-type colorectal tumors have are being detected with increasing frequency. It has become clear that these flat lesions contain two subtypes; flat-elevated and depressed lesions. However, their clinicopathological features and roles in colorectal carcinogenesis remain obscure. We classified colorectal adenomas and submucosal invasive cancers into three types: polypoid, flat-elevated, and depressed types. A clinicopathological study of 2505 colorectal tumors (2407 adenomas, 98 submucosal invasive cancers) was then performed. Furthermore, 64 tumors (25 adenomas with high-grade dysplasia, 39 submucosal invasive cancers) from which DNA was extracted were examined for K-ras gene mutation. The percentages of each configuration in the resected materials were 62.0%, 36.4%, and 1.6% of the polypoid, flat-elevated, and depressed types, respectively. The rate of submucosal invasive cancer in the depressed type was always high regardless of size. In the polypoid and flat-elevated types, lesions of larger size showed higher rates of invasion. Analysis of submucosal invasive cancers revealed no adenomatous components in any of the depressed-type lesions; in the polypoid and flat-elevated types the frequencies of cancer with adenomatous components were 83.6% and 77.8%, respectively. The flat-elevated type was more frequently located (77.8%) in the proximal colon than the other types (polypoid type 16.4%, depressed type 25.0%). The incidence of K-ras gene mutation was 47.2%, 18.2%, and 0% in the polypoid, flat-elevated, and depressed types, respectively. These findings suggest that the flat-elevated and depressed types are similar in that they are both morphologically flat and have infrequent incidences of K-ras gene mutation, but these two lesions differ in their pathological features. Especially, depressed type lesions have a tendency to invade the submucosal layer even when they are small. Therefore one should always be aware of this type of lesion during colonoscopic examination.

Adenoma↗
PubMed2000

Analysis of Helicobacter pylori vacA gene and serum antibodies to VacA in Japan.

Vacuolating cytotoxin, VacA, is one of the most important pathogenetic factors produced by Helicobacter pylori. However, it is not clear whether the diversity in disease outcome may be ascribed to variations in strain and/or to the host responses to virulence factors. In this study, we analyzed the vacA middle region sequence among 65 Japanese isolates to clarify the variation in strain and assayed antibody titer to VacA by ELISA using purified VacA to evaluate the host response to cytotoxin. The nucleotide sequence identities compared among Japanese isolates were 92.8 +/- 3.56%, and compared to 88.3 +/- 2.89% in tox+ strains reported in GenBank. Positive correlation was found between the antibody titers and the severity of atrophic change of the stomach. In Japan the nucleotide sequences of the vacA middle region were highly homologous and genetically closer to tox+ strains. Antibody titers and host response to cytotoxin may be associated with atrophy of the stomach.

Adult↗
PubMed2000

Helicobacter pylori-negative peptic ulcer in Japan: which contributes most to peptic ulcer development, Helicobacter pylori, NSAIDS or stress?

Of 302 patients with peptic ulcer, 11 (3.6%) proved negative for Helicobacter pylori: 9 with gastric ulcer (GU) and 2 with duodenal ulcer (DU). Among these 11 H. pylori-negative patients with ulcers, two with GU were using non-steroidal anti-inflammatory drugs (NSAIDs) and one with GU was using a corticosteroid. The Hanshin-Awaji earthquake induced life-event stress that not only triggered but exacerbated GU, particularly in the elderly, resulting in a higher GU/DU ratio than the corresponding period of the previous year (3.07 vs. 1.88) in the devastated area. Furthermore, the seroprevalence of the infection and the odds ratio from the case-control study were similar to or even higher than that reported previously in patients with GUs unrelated to the earthquake. H. pylori and the use of NSAIDs are the major independent risk factors for peptic ulcers, although, H. pylori infection plays some role in the development of peptic ulcers under stressful conditions.

Adult↗
PubMed1999

Application of Bead-ELISA method to detect Helicobacter pylori VacA.

Helicobacter pylori is an etiological agent of gastritis, gastric ulcer and gastric cancer. In order to clarify the significance of vacuolating cytotoxin (VacA) for the pathogenesis of Helicobacter pylori infection, we established and applied the sandwich bead enzyme-linked immunosorbent assay (Bead-ELISA) for quantitative determination of VacA in the culture mediums of H. pylori and other species of Helicobacter. The minimum concentration of VacA in culture medium detected by Bead-ELISA was 25 pg VacA/ml and its sensitivity was found to be quite high compared to vacuolation assay and Western blot analysis, e.g. the minimum concentrations of VacA in culture medium required for detection by vacuolation assay and Western blotting were 11 ng/ml and 38 ng/ml, respectively. All the H. pylori strains used were found to produce VacA in the culture medium by Bead ELISA, even though some strains were negative by Western blot and vacuolation assay. The results obtained by Bead-ELISA was consistent with those by PCR amplification of a 785 bp vacA fragments. A toxin immunologically similar to VacA produced by other strains of Helicobacter such as H. muridarum (ATCC49282), H. mustelae (F10) and H. felis (ATCC49179) could not be detected by Bead-ELISA as well as Western Blot.

Animals↗
PubMed1999

[Characteristics of anti-microbial agents and its clinical choice for H. pylori treatment].

Eradication of Helicobacter pylori (H. pylori) is now established as main treatment of upper-gastrointestinal diseases. Resistance to H. pylori and acid condition in the stomach were important factors which influenced H. pylori eradication. Recolonized H. pylori strains will be easily resistant to metronidazole and clarithromycin, whereas almost all of H. pylori strains are sensitive to amoxicillin. On the other hand, amoxicillin targets cell wall biosynthesis and clarithromycin inhibits protein synthesis of Helicobacter pylori mainly in the growth phase which induced high intragastric pH condition, however, metronidazole targets DNA and, therefore, is independent of the stationary or growth phase distribution. To established a optimal regimen for Helicobacter pylori treatment, several factors included them should be account according to the parmacokinetical standings.

Anti-Bacterial Agents↗
PubMed1999

HLA-DQB1 locus and the development of atrophic gastritis with Helicobacter pylori infection.

Helicobacter pylori is known to be involved in digestive diseases such as peptic ulcer, atrophic gastritis, and gastric cancer. It is supposed that the incidence of these digestive diseases associated with H. pylori is influenced by the strain diversity of H. pylori, factors involving the host or environment, and the duration of infection. In this study, we directed our attention to HLA, a host factor, and investigated the relation between HLA-DQB1 genotype of H. pylori-infected patients and the development of atrophic gastritis. HLA-DQB1 genotyping was performed by the polymerase chain reaction-restriction fragment length polymorphism method on 122 H. pylori-infected patients with atrophic gastritis and 28 uninfected Japanese controls. Infected patients with developed atrophic gastritis were classified as the open type and those with undeveloped atrophic gastritis as the closed type. To estimate the grade of atrophic gastritis reliably, histological and serological evaluations were also undertaken. The allele frequency of DQB1*0401 was significantly higher in the open-type group compared to either the closed-type or the uninfected group. These results suggest that immunogenic factors play an important role in the development of atrophic gastritis in H. pylori-infected patients, and that DQB1*0401 is a useful marker for determining susceptibility to this disease.

Adolescent↗
PubMed1999

Sufficient effect of 1-week omeprazole and amoxicillin dual treatment for Helicobacter pylori eradication in cytochrome P450 2C19 poor metabolizers.

Omeprazole is widely used for the treatment of Helicobacter pylori infection. It is metabolized by cytochrome P450 2C19 enzyme (CYP2C19) in the liver. Because this enzyme exhibits a genetic polymorphism, patients with low metabolic activity (poor metabolizers) may be exposed to higher concentrations of this drug than are patients who are extensive metabolizers. Eighty-six patients with cultured H. pylori-positive gastritis or peptic ulcers who completed the treatment and assessment of anti-H. pylori therapy were analyzed for CYP2C19 genotyping using a polymerase chain reaction-restriction fragment length polymorphism method [the wild-type or two mutant genes (ml in exon 5 and m2 in exon 4), or both]. Patients were classified into three groups according to the H. pylori eradication regimen: group I (n = 21; omeprazole 40mg/ day and amoxicillin 2000mg/day for 1 week); group II (n = 21; group I regimen plus sucralfate 4000mg/day, for 1 week); group III (n = 44; group I regimen plus clarithromycin 800mg/day, for 1 week). The combination of two mutant alleles (ml/ml, ml/m2, m2/m2-poor metabolizers) was observed in 13 of 86 patients (15%), and all poor metabolizer patients achieved H. pylori eradication regardless of their treatment regimens. In addition, the eradication rates of the poor metabolizers were significantly higher than those of other genotypes who carry homozygous or heterozygous normal allele (extensive metabolizers) in group I or groups I and II combined. CYP2C19 genotyping can provide a new strategy to choose an optimal regimen, and this genotyping is especially useful for Japanese, as the frequency of poor metabolizers is five times greater than that found among Caucasians.

Amoxicillin↗
PubMed1996

Acute gastric anisakiasis: 28 cases during the last 10 years.

Anisakiasis is a disease which occurs following eating raw fish infected with anisakis larvae. Many cases have been reported from Japan and from other countries with increasing opportunities of eating raw fish such as "sushi" and "sashimi." We have reviewed 28 patients with acute gastric anisakiasis during the last 10 years from November 1984 to October 1994. This disease has rarely been detected in persons over 60 years of age and in patients with gastric surgery. Therefore it is postulated that gastric acid secretion influences the activities of anisakis larvae. An alkaline gastric pH could interfere with the toxicity of anisakis larvae.

Adult↗