ObjectiveTo date, no randomised trials have compared the efficacy of vonoprazan and amoxicillin dual therapy with other standard regimens for Helicobacter pylori treatment. This study aimed to investigate the efficacy of the 7-day vonoprazan and low-dose amoxicillin dual therapy as a first-line H. pylori treatment, and compared this with vonoprazan-based triple therapy.DesignThis prospective, randomised clinical trial was performed at seven Japanese institutions. Patients with H. pylori–positive culture test and naive to treatment were randomly assigned in a 1:1 ratio to either VA-dual therapy (vonoprazan 20 mg+amoxicillin 750 mg twice/day) or VAC-triple therapy (vonoprazan 20 mg+amoxicillin 750 mg+clarithromycin 200 mg twice/day) for 7 days, with stratification by age, sex, H. pylori antimicrobial resistance and institution. Eradication success was evaluated by 13C-urea breath test at least 4 weeks after treatment.ResultsBetween October 2018 and June 2019, 629 subjects were screened and 335 were randomised. The eradication rates of VA-dual and VAC-triple therapies were 84.5% and 89.2% (p=0.203) by intention-to-treat analysis, respectively, and 87.1% and 90.2% (p=0.372) by per-protocol analysis, respectively. VA-dual was non-inferior to VAC-triple in the per-protocol analysis. The eradication rates in strains resistant to clarithromycin for VA-dual were significantly higher than those for VAC-triple (92.3% vs 76.2%; p=0.048). The incidence of adverse events was equal between groups.ConclusionThe 7-day vonoprazan and low-dose amoxicillin dual therapy provided acceptable H. pylori eradication rates and a similar effect to vonoprazan-based triple therapy in regions with high clarithromycin resistance.Trial registration numberUMIN000034140.

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The aim of the present study was to quantify the density and affinity of human extrastriatal dopamine D2 receptors using positron emission tomography (PET). [(11)C]FLB-457, a high-affinity dopamine D2 receptor antagonist with various specific radioactivities (SA) was used. Eight healthy male subjects, age 20-35 yr, participated twice or three times at different SAs (1-279 GBq/ µmol), and serial dynamic scans were performed in the 3D data acquisition mode. The peak of the specific binding was not well defined with high SA due to the flatness of the curves after 60 min but was observed within the PET measurement. In the experiment with low SA, the peak came earlier than that with high SA. Scatchard analysis was performed using the maximal specific binding value (transient equilibrium) and the radioactivity in the cerebellum as free ligand concentration. The highest density was observed in the thalamus (2.3+/-0.6 pmol/ml), followed by the temporal cortex (1.5+/-0.5 pmol/ml), hippocampus (1.4+/-0.5 pmol/ml), parietal cortex (0.9+/-0.4 pmol/ml), frontal cortex (0.8+/-0.2 pmol/ml) and occipital cortex (0.7+/-0.3 pmol/ml). There was no significant difference in K(d) values in these six regions. The present results demonstrate that dopamine D2 receptor densities in the extrastriatal regions were only 2-8% of that in the striatum. Although the density of extrastriatal dopamine D2 receptor was low, significant regional differences were observed in the present study, as reported in postmortem studies.

Using a rice maturing seed pUC9 expression library, we isolated a cDNA clone corresponding to 10 kDa sulfurrich prolamin by immunoscreening. A longer cDNA clone was obtained from a λgtll library by plaque hybridization using this (32)P-labeled cDNA as a probe. A polypeptide sequence composed of 134 amino acids was deduced from the nucleotide sequence. A 24 amino acid signal peptide was assigned by computer calculation for the membrane spanning region and Edman sequencing of the purified mature polypeptide. Remarkably, 20% of methionine and 10% of cysteine were found in the mature polypeptide as well as high contents of glutamine, and hydrophobic amino acids. Part of the amino acid sequence was homologous with a conserved cysteine-rich region found in other plant prolamins. Two repeats of amino acid sequence were found in the polypeptide.

Background As a first‐line therapy for Helicobacter pylori, dual therapy with vonoprazan and amoxicillin (VA‐dual) provides an eradication rate similar to that of vonoprazan‐based triple therapy. As the factors associated with the eradication rate of H. pylori with VA‐dual are unknown,we investigated them in this study. Materials and Methods Overall, 163 patients diagnosed with H. pylori infection received VA‐dual (vonoprazan 20 mg twice daily and amoxicillin 750 mg twice daily for 7 d). The association between successful H. pylori eradication and the following patient clinical factors was analyzed: sex, age, height, weight, body surface area (BSA), body mass index (BMI), history of early gastric carcinoma and peptic ulcer, comorbidity of cirrhosis, alcohol consumption habit, smoking habit, common use of proton pump inhibitors, and concomitant use of drugs that are substratesof cytochrome P450 (CYP) 3A4. The association between post‐eradication adverse events and clinical factors was analyzed retrospectively. Results Successful H. pylori eradication was associated with a lower BSA (eradication rate: 90.8% in patients with BSA <1.723 vs. 79.6% in those with BSA ≥1.723; p = 0.045). The incidence of adverse events was higher in women than in men (adverse events: 40.0% in women vs. 19.4% in men; p = 0.004). Conclusions Successful H. pylori eradication with VA‐dual was associated with the small body size of patients. This therapy may have to be adjusted per body size.

Clozapine could occupy a high proportion of dopamine D(2) receptors. The time course of occupancy was relatively fast, with a half-life of several hours.

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Abstract Hereditary mixed polyposis syndrome (HMPS) is a rare autosomal dominant disorder characterized by a mixture of typical and/or atypical juvenile polyps, adenomas and hyperplastic polyps, resulting in an increased risk of colorectal cancer. In HMPS, four different germline BMPR1A variants from five unrelated families have been reported. This study is the first to report HMPS within a Japanese family. The proband underwent repeated colonoscopic polypectomies over a 5-year period, since the age of 67. Histological examination of these resected polyps revealed adenomas, juvenile-like polyps and hyperplastic changes. Genetic testing was conducted to identify the causative genes for hereditary gastrointestinal cancer syndromes, including BMPR1A. We detected a germline variant, c.72_73delGA, in BMPR1A. The proband’s elder brother, younger sister and nephew have also undergone repeated colonoscopic polypectomies at other clinics. His sister and nephew underwent genetic testing, and the same BMPR1A variant was identified.