Background-Prostaglandin endoperoxide synthase/cyclooxygenase (COX) is the key enzyme in gastric mucosal protection and repair but its cellular localisation in the human stomach is still unclear. Aims-To investigate immunohistochemically the cellular distribution of COX-1 and COX-2 proteins in the human stomach with or without gastritis or ulceration. Patients and methods-Tissues were obtained by surgical resection of gastric ulcers associated with perforation (n=9) or by biopsy from Helicobacter pylori positive patients with gastric ulcers (n=45) and H pylori negative healthy subjects (n=15). COX expression was detected by semiquantitative reverse transcriptionpolymerase chain reaction (RT-PCR), western blotting, and light and electron microscopic immunohistochemistry. Results-COX-2 mRNA and protein were detected in gastric ulcer tissues but not in intact gastric mucosa. COX-1 mRNA and protein were detected in the intact mucosa. COX-2 immunostaining was exclusively localised in macrophages and fibroblasts between necrotic and granulation tissues of the ulcer bed. The percentage of COX-2 expressing cells was significantly higher in open than in closed ulcers, and in gastritis than in gastric mucosa without H pylori infection. COX-1 immunoreactivity localised in lamina propria mesenchymal cells was similar in various stages of ulcer disease and in intact gastric mucosa. Electron microscopic immunohistochemistry revealed both COX-1 and COX-2 on the luminal surfaces of the endoplasmic reticulum and nuclear envelope of macrophages and fibroblasts. Conclusions-Our results showed that COX-2 protein was induced in macrophages and fibroblasts in gastric ulcers and H pylori related gastritis, suggesting its involvement in the tissue repair process. (Gut 2000;46:782-789)

We previously reported a mouse monoclonal antibody (MAb), termed L2, specific for Helicobacter pylori urease strongly inhibited its enzymatic activity. Here, to gain insight into how this antibody affects urease activity, the epitope that was recognized by the antibody was determined. By screening a panel of overlapping synthetic peptides covering the entire sequence of the two subunits (UreA and UreB), we identified a stretch of UreB-derived 19 amino acid (aa) residues (UB-33; aa 321 to 339, CHHLDKSIKEDVQFADSRI) that was specifically recognized by the L2 antibody. Further sequential amino acid deletion of the 19-mer peptide from either end allowed us to determine the minimal epitope as 8 amino acid residues (F8; SIKEDVQF) for L2 reactivity. This epitope appears to lie exactly on a short sequence which formed a flap over the active site of urease, suggesting that binding of the L2 antibody sterically inhibits access of urea, the substrate of urease. Finally, immunization of rabbits with either the 19-mer peptide or the 8-mer minimal epitope resulted in generation of antiurease antibodies that were capable of inhibiting the enzymatic activity. Since urease is critical for virulence of H. pylori, antigenic peptides that induce production of antibodies to inhibit its enzymatic activity may potentially be a useful tool as a vaccine for prevention and treatment of H. pylori infection.

The effect of meal volume and fat content on gastroesophageal reflux was investigated in 20 asymptomatic healthy subjects. In each subject, intraesophageal pH monitoring was performed during a 3-hr postprandial period (PP) in the same position (supine or upright) on two successive days. On day 1, 500-ml low- and high-fat meals were ingested and, on day 2, an 800-ml low-fat meal was ingested. The acid exposure time was assessed as the percentage of time with a pH < 4.0. The acid exposure time in subjects in the upright position was significantly longer in the 800-ml group than in the 500-ml group for the entire PP (2.7 +/- 1.5%; mean +/- SE, 0.7 +/- 0.4%; P < 0.05). Of subjects in the supine position, the high-fat group showed significantly longer acid exposure time than the low-fat group both for the entire PP (7.6 +/- 3.0%, 0.7 +/- 0.5%; p < 0.05) and for the second hour (P < 0.05). We have demonstrated that differences in the meal volume and fat content influence gastroesophageal reflux in healthy asymptomatic subjects and that this influence varies with the position.

BackgroundOrthopedic surgeries of lower extremities such as total knee arthroplasty (TKA), total hip arthroplasty (THA), and hip fracture surgery (HFS) are widely considered to carry a high risk of developing deep venous thrombosis (DVT) and pulmonary thromboembolism (PTE). Growing attention to epidemiological studies using a healthcare database led us to quantify the risks using a Japanese database to reveal recent medical care for such events.MethodsThe study comprised 36,947 patients who had undergone orthopedic surgeries of the lower extremities and whose medical information from April 2008 to September 2013 was available. The source population of the database was derived from 100 acute-care hospitals with Diagnosis Procedure Combination. The events were defined by diagnosis, medication, imaging, and laboratory tests.ResultsA breakdown of patients who underwent orthopedic surgeries by type of surgery showed 13.6% for TKA, 10.4% for THA, 56.8% for HFS, 1.5% for rupture of Achilles tendon, and 18.0% for simple fracture of lower extremities. The incidence for DVT, PTE, and bleeding events by type of surgery was 1.3, 0.2, and 1.0% for TKA; 0.9, 0.2, and 1.1% for THA; and 0.4, 0.1, and 1.8% for HFS, respectively. The population for risk factor analysis consisted of patients with similar background factors who underwent TKA, THA, or HFS. The statistically significant risk factors for PTE analyzed by the backward elimination procedure in a multivariate model were female sex, history of venous thromboembolism (VTE), thrombophilia, and varicose veins of lower extremity.ConclusionsThe incidence of DVT, PTE, and bleeding events and the risk factors for DVT and PTE in patients by type of orthopedic surgeries of lower extremities found in our study are considered to be rational as they reflect evidence from real-world cases.Trial registrationUniversity Hospital Medical Information Network Clinical Trials Registry UMIN000012667 Electronic supplementary materialThe online version of this article (doi:10.1186/s13018-017-0549-4) contains supplementary material, which is available to authorized users.

(Gut 1998;43:168-175)