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The objective of this study was to evaluate the real-world safety and effectiveness of adalimumab with methotrexate (MTX) in disease-modifying antirheumatic drug (DMARD)- and biologic-naïve Japanese patients with rheumatoid arthritis (RA) at risk of progressive structural joint damage. This multicenter, prospective, observational, postmarketing surveillance study was conducted between February 2013 and April 2015 at 84 centers in Japan. Patients with RA at risk of progressive structural joint damage were enrolled and initiated treatment with adalimumab and MTX. Adverse events were recorded up to week 28. Effectiveness/disease activity was assessed using the Disease Activity Score based on a 28-joint count with erythrocyte sedimentation rate and C-reactive protein (DAS28-4ESR and DAS28-4CRP), Clinical Disease Activity Index, and Simplified Disease Activity Index at 0, 4, 12, and 24 weeks. DAS28-4CRP response was evaluated in the low-dose (<8 mg/week) and high-dose (≥8 mg to ≤16 mg/week) MTX groups at week 24. One hundred fifty-seven of 163 patients comprised the safety cohort: mean (SD) age, 56.5 (13.9) years; females, 65.6%; rheumatoid factor positive, 73.2%; anti-cyclic citrullinated peptide antibody positive, 66.9%; bone erosions, 51.6%; mean disease duration, 9.5 months. The majority of patients (≥80%) had moderate or high disease activity at baseline, and ≥50% with available data achieved remission or low disease activity at week 24 (DAS28-4CRP <3.2). Five serious adverse drug reactions occurred in four patients, including pyelonephritis, Pneumocystis jirovecipneumonia, interstitial lung disease, pleurisy, and pericarditis; the outcomes were either recovered or recovering. Significant improvements/reductions in disease activity over 24 weeks were noted in all effectiveness measures (P< 0.0001). Most of the population achieved DAS28-4CRP remission (<2.6) at week 24 regardless of the MTX dose. Adalimumab in combination with MTX could be a beneficial treatment option for DMARD- and biologic-naïve Japanese patients with RA at risk of progressive structural joint damage. Funding: AbbVie GK and Eisai. Trial Registration: ClinicalTrials.gov identifier, NCT01783730.

In order to reduce the risk of vaginal recurrence, we have chosen total laparoscopic modified radical hysterectomy instead of extrafascial hysterectomy in the treatment of endometrial cancer. The aim of this study was to assess the safety of this method.

Multielements in a typical Japanese diet certified reference material prepared at the National Institute for Environmental Studies (NIES) of Japan, in collaboration with the National Institute of Radiological Sciences (NIRS) of Japan were determined by instrumental neutron activation analysis (INAA). Five samples (ca. 510–1000 mg) and comparative standards were irradiated for a short time (10 s) at a thermal neutron flux of 1.5 × 1012n cm–2s–1(pneumatic transfer) and for a long time (6 h) at a thermal neutron flux of 3.7 × 1012n cm–2s–1(central thimble) in the Rikkyo University Research Reactor (TRIGA Mark-II, 100 kW). The irradiated samples were measured by conventional γ-ray spectrometry using a coaxial Ge detector, and by anti-coincidence and coincidence γ-ray spectrometry with a coaxial Ge detector and a welltype NaI(Tl) detector. The concentrations of 38 elements were determined by these methods.

Using an oligonucleotide probe designed on the basis of the N-terminal amino acid sequence of purified rat aldosterone synthase cytochrome P-450 [(1989) J. Biol. Chem. 264 10935] we have isolated from rat adrenal cDNA library a 2687 base pair cDNA that encodes a protein of 500 amino acid residues. The deduced amino acid sequence contained the regions well conserved among all cytochrome P-450s sequenced to date, and also a portion (residues 25–44) which was identical to the N-terminal peptide sequence of rat aldosterone synthase cytochrome P-450. These results indicate that the cDNA encodes a precursor form of rat aldosterone synthase cytochrome P-450.

Using an oligonucleotide probe designed on the basis of the N‐terminal amino acid sequence of purified rat aldosterone synthase cytochrome P‐450 [(1989) J. Biol. Chem. 264 10935] we have isolated from rat adrenal cDNA library a 2687 base pair cDNA that encodes a protein of 500 amino acid residues. The deduced amino acid sequence contained the regions well conserved among all cytochrome P‐450s sequenced to date, and also a portion (residues 25–44) which was identical to the N‐terminal peptide sequence of rat aldosterone synthase cytochrome P‐450. These results indicate that the cDNA encodes a precursor form of rat aldosterone synthase cytochrome P‐450.

The effects of omeprazole, a proton pump inhibitor, on gastric secretion and gastric or duodenal ulcers or erosions in rats were studied. Omeprazole, given intraduodenally, dose-dependently inhibited the gastric secretion (volume, acid and pepsin output) of pylorus-ligated rats. The antisecretory activity of omeprazole at 100 mg/kg persisted for 14 hr after treatment. Acutely induced gastric ulcers or erosions such as Shay ulcers, water-immersion stress-, indomethacin-, aspirin-, or prednisolone-induced erosions were all markedly inhibited by oral or intraduodenal administration of 10–100 mg/kg of omeprazole. The development of duodenal ulcers and gastric erosions caused by mepirizole was also potently inhibited by omeprazole at 3–10 mg/kg given orally. Repeated administration of omeprazole, 200 mg/kg/day in two divided doses for 14 days, significantly accelerated the spontaneous healing of acetic acid-induced gastric ulcers. The mechanism by which omeprazole inhibits the development of acute ulcers and accelerates healing of preexisting ulcers appears to be mainly due to its potent and longlasting antisecretory activity. The antisecretory and antiulcer activities of omeprazole are equal to or exceed those of cimetidine, both in the maximum inhibitory response and ED50 values.