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Biomedical subjects

H Hanai

Publications and source records attributed to H Hanai.

At least 19 recordsLinked to original sources

Effect of genetic differences in omeprazole metabolism on cure rates for Helicobacter pylori infection and peptic ulcer.

BACKGROUND: Omeprazole is metabolized by S-mephenytoin 4'-hydroxylase (CYP2C19) in the liver. In persons with a poor-metabolizer genotype for CYP2C19, the therapeutic efficacy of omeprazole may be increased. OBJECTIVE: To investigate whether CYP2C19 genotype status is associated with cure rates for Helicobacterpylori infection and peptic ulcer achieved by using dual therapy with omeprazole and amoxicillin. DESIGN: Prospective cohort study. SETTING: University hospital and health service center in Hamamatsu, Japan. PATIENTS: 62 patients with peptic ulcer and H. pylori infection. INTERVENTION: Omeprazole and amoxicillin. MEASUREMENTS: CYP2C19 genotype status and cure rates for H. pylori infection and peptic ulcer. RESULTS: Cure rates for H. pylori infection were 28.6% (95% CI, 13.1% to 48.7%), 60% (CI, 38.6% to 83.0%), and 100% (CI, 66.4% to 100%) in the rapid-, intermediate-, and poor-metabolizer groups, respectively. Healing rates for both duodenal and gastric ulcer in the three groups were roughly parallel with cure rates for H. pylori infection. CONCLUSION: The results of the genotyping test for CYP2C19 seem to predict cure of H. pylori infection and peptic ulcer in patients who receive dual therapy with omeprazole and amoxicillin.

Adult

Pyoderma gangrenosum complicating ulcerative colitis: Successful treatment with methylprednisolone pulse therapy and cyclosporine.

A 32-year-old woman with ulcerative colitis had a relapsed of pyoderma gangrenosum during puerperium. Both the pyoderma gangrenosum and ulcerative colitis had been well controlled with oral prednisolone, but ulcerative colitis relapsed in pregnancy, and pyoderma gangrenosum relapsed in the puerperium. The pyoderma gangrenosum responded to methylprednisolone pulse therapy initially, but relapsed when prednisolone was tapered. A second trial of pulse therapy combined with cyclosporine resulted in complete remission of the pyoderma gangrenosum, and no recurrence was recognized after prednisolone was tapered. This is a very rare case of successful treatment with methylprednisolone pulse therapy combined with cyclosporine for pyoderma gangrenosum complicating ulcerative colitis.

Adult

Effect of Helicobacter pylori infection on gastric juice pH.

BACKGROUND: How Helicobacter pylori infection affects gastric acid secretion is still unclear. METHODS: Gastric juice pH, ammonia concentration in gastric juice, serum gastrin level, and grade of gastritis in accordance with the Sydney System were determined for patients with gastric ulcer (GU) and duodenal ulcer (DU) before and after treatment with lansoprazole and amoxicillin, and results were compared with those of H. pylori-negative controls. RESULTS: Scores for H. pylori density, atrophy, metaplasia, and activity of gastritis in the corpus were higher in patients with GU, especially those with proximally located GU, than in those with DU. Gastric juice pH was significantly higher in GU patients than in DU patients and controls. After H. pylori eradication, gastric juice pH and serum gastrin levels in both GU and DU patients were significantly decreased to control levels. In patients without eradication, no significant changes in these factors were observed. CONCLUSIONS: These findings suggest that H. pylori infection and gastritis in the corpus suppress acid secretion and increase gastric juice pH, resulting in hypergastrinemia, and that eradication of H. pylori normalizes acid secretion and serum gastrin levels.

2-Pyridinylmethylsulfinylbenzimidazoles

Analyses of mutation and loss of heterozygosity of coding sequences of the entire transforming growth factor beta type II receptor gene in sporadic human gastric cancer.

Mutations in the transforming growth factor beta type II receptor (TGFbetaRII) gene have been detected in several human cancer types exhibiting microsatellite instability. Using intron primers previously reported for examination of the entire coding region of the TGFbetaRII gene, 29 sporadic gastric cancers were screened with non-radioactive single strand conformation polymorphism and subsequent DNA sequencing analysis. Mutations of the TGFbetaRII gene were detected in three out of 29 tumors (10%). Two cases showed deletions in a polyadenine tract in both alleles and was positively associated with replication error. One case had an insertion of GA dinucleotide sequence in one allele. Mutations of the TGFbetaRII gene were restricted to exon 3 and other coding regions were not affected. Loss of heterozygosity was detected by analyzing a polymorphic site in intron 2. Three out of nine (33%) informative cases, which were all of intestinal type and advanced cases, showed loss of heterozygosity but neither TGFbetaRII mutation nor replication error was found in these cases. Immunoreactivity of TGFbetaRII in tumor tissues was reduced to a different extent in the gastric cancer with genetically abnormal transforming growth factor. Although the numbers studied are small, homozygous (A)10 deletion or loss of heterozygosity of TGFbetaRII is involved in tumorigenesis and progression of at least some part of sporadic gastric cancer.

Humans

Amount of Helicobacter pylori in gastric mucus during anti-H. pylori treatment.

Helicobacter pylori is present in infected patients not only on the gastric epithelial cell surface but also in gastric mucus. We developed a competitive polymerase chain reaction (cPCR) method for quantitative measurement of H. pylori in gastric mucus. The aim of this study was to determine the number of H. pylori in gastric mucus before and after anti-H. pylori treatment. Patients with duodenal ulcer were treated with lansoprazole alone (n = 11) or lansoprazole and amoxycillin (n = 12). The amount of H. pylori in gastric mucus was measured over time by a cPCR assay. Helicobacter pylori infection was also tested for using histology, culture, and the rapid urease test (RUT). Although most patients treated with lansoprazole alone had become H. pylori-negative by the end of treatment when tested by histology, RUT, and culture, a large number of H. pylori organisms were found in the gastric mucus at that time by cPCR. These patients returned to being H. pylori positive 1 to 12 months later on the basis of histology, RUT, and culture. However, cPCR results indicated eradication of H. pylori by the end of treatment in eight of the 12 patients treated with lansoprazole and amoxicillin, and these patients remained H. pylori negative on histology, RUT, culture, and cPCR 1 to 12 months later. Testing for H. pylori in gastric mucus is thus useful for precise determination of the success or failure of H. pylori eradication therapy.

2-Pyridinylmethylsulfinylbenzimidazoles

Transforming growth factor beta type II receptor (TGF beta RII) mutation in gastric lymphoma without mutator phenotype.

A new mutation in the serine-threonine kinase domain of the transforming growth factor beta type II receptor (TGF beta RII) was found in a case of diffuse, B cell non-Hodgkin's lymphoma of the stomach. A missense mutation (ACA to GCA, Thr to Ala) was detected in exon 5, and a wild type allele was also present. This is the first naturally occurring mutation in the kinase domain of this gene identified in human primary lymphoma. The replication error at three loci was negative, and the poly A tract of exon 3, which is frequently a target of mismatch repair genes, was intact. Malignant lymphoma of B cell origin in the stomach is an addition to an expanding catalogue of tumors with TGF beta RII alterations, and the biological sequelae of the change in the functional domain and the clinical characteristics of the patient in this study are intriguing.

Aged

Increased acylCoA-cholesterol ester acyltransferase activity in gallbladder mucosa in patients with gallbladder cholesterolosis.

OBJECTIVE: Although cholesterolosis of the human gallbladder is a relatively common disease, its etiology has not been fully understood. The aim of this study was to determine this etiology. METHODS: The lipid composition of the gallbladder mucosa and gallbladder bile and the enzyme activities (acylCoA-cholesterol ester acyltransferase [ACAT] and cholesterol ester hydrolase [CEH]) of the gallbladder mucosa were measured in control subjects, patients with cholesterolosis, and patients with cholesterol gallstone disease. RESULTS: Levels of cholesterol ester in gallbladder mucosa in patients with cholesterolosis (n = 12) were higher than those in control subjects (n = 8). With regard to the lipid content in gallbladder bile, no differences were found in concentrations of cholesterol, phospholipids, and bile acids among control subjects (n = 11), patients with cholesterolosis (n = 13), and those with cholesterol gallstone disease (n = 15). In gallbladder mucosa, ACAT activity was significantly higher in patients with cholesterolosis (n = 10) than in control subjects (n = 8), whereas CEH activity did not differ between the two groups. As a result, the ACAT/CEH activity ratio was higher in patients with cholesterolosis than in control subjects. CONCLUSIONS: It would be suggested that cholesterol ester synthesis of gallbladder mucosa might play an etiological role in the development of cholesterolosis.

Bile

[Telomere length and telomerase activity in intestinal metaplasia, adenoma and well differentiated adenocarcinoma of the stomach].

We analyzed telomere length and telomerase activity in intestinal metaplasia (IM), adenoma, and cancer of the stomach and studied the stages at which the cells acquire telomerase activity in carcinogenesis and also the correlation between telomerase activity and telomere length. Telomerase activity was detected in 15%, 45%, 89% of IM, adenomas, and cancers. Telomere lengths shortened as normal mucosa changed into IM and more into adenoma. Gastric cancers showed a broad range of telomeric length. The shortest telomere length was found among gastric adenomas. These results suggest that telomerase is expressed during early phase of gastric carcinogenesis but the activity at that stage is not strong enough to fully restore the reduced telomeric DNA.

Adenocarcinoma

Adenoma of the common human bile duct in Gardner's syndrome may cause relapsing acute pancreatitis.

Familial adenomatous polyposis of the colon, or Gardner's syndrome, is often accompanied by adenomas of the stomach and duodenum. We experienced a rare case of Gardner's syndrome, with adenomas of the common bile duct, in a patient who presented with relapsing acute pancreatitis. Our findings indicate that adenoma in the common bile duct or pancreatic duct should be considered as a possible etiology when patients with familial polyposis or Gardner's syndrome present with pancreatitis, particularly relapsing acute pancreatitis.

Adenoma

Expression of muscarinic receptor subtypes in rat gastric smooth muscle: effect of M3 selective antagonist on gastric motility and emptying.

Expression of muscarinic receptor subtypes in rat gastric smooth muscle was examined with reverse transcriptase-polymerase chain reaction (RT-PCR). Under the condition for detecting the messages of m1-m4 subtypes in brain, atrium, and gastric mucosa, only the fragments of m2 and m3 subtypes were amplified with RNA prepared from rat gastric smooth muscles. Furthermore, the amplified fragments were digested by restriction enzymes, reconfirming that the predicted size products of m2 and m3 contain the partial DNA sequences of m2 and m3 subtypes, respectively. We measured gastric motility in rats with a pressure transducer system under the continuous venous infusion of the muscarinic antagonists atropine and butylscopolamine (nonselective), AF-DX 116 (M2), zamifenacine (M3), and glucagon. Heart rate was monitored simultaneously in the tail. Gastric motility was inhibited in the presence of glucagon and zamifenacine without alteration of heart rate, whereas there was no inhibition in the presence of AF-DX 116 even after the augmentation of heart rate was observed. Gastric emptying was also suppressed in the presence of zamifenacine, which had an effect comparable with that of atropine, butylscopolamine, and glucagon. These results indicate that the activation of the M3 subtype in gastric smooth muscle causes its contraction, and the M3 selective antagonist could be a potentially useful drug without an adverse effect on the heart for radiological and endoscopic examination in the upper gastrointestinal tract.

Animals

Telomere length and telomerase activity in carcinogenesis of the stomach.

Telomerase activity is generally absent in primary cell cultures and normal tissues. Telomerase is known to be induced upon immortalization or malignant transformation of human cells. In the present study, we analyzed both telomere length and telomerase activity in biopsy samples from mucosa undergoing metaplasia, adenoma and cancer of the stomach. We attempted to estimate the correlation between telomerase activity and telomere length in these tissues. Telomerase activity was estimated using the telomeric repeat amplification protocol and telomere length by Southern blot analysis. Extracts were defined as telomerase-negative when the signals were less intense than those for 10(2) KATO-III cells (positive control). We detected telomerase activity in 15%, 45% and 89% of the examined cases of intestinal metaplasia, adenoma and gastric cancer respectively. However, telomere length in the gastric mucosa became reduced as the mucosa underwent metaplasia and developed into adenoma. Gastric cancers showed a broad range of telomere length among cases. However, gastric adenomas showed the shortest telomere length. These results suggest that telomerase is expressed during the early phase (intestinal metaplasia through adenoma) of gastric carcinogenesis, although the activity at that stage is not high enough to fully restore the reduced telomeric DNA.

Adenoma

Study of transmission routes of Helicobacter pylori in relation to seroprevalence of hepatitis A virus.

The seroprevalence of Helicobacter pylori in a group of 1,043 healthy Japanese people was compared with that of hepatitis A virus (HAV), which was used as a marker of fecal-oral exposure. No statistically significant relationship was observed between seropositivity for HAV and that for H. pylori. Therefore, the fecal-oral spread of H. pylori is of limited relevance in Japan.

Helicobacter Infections