Mucins are highly glycosylated molecules with glycans predominately O-linked to serine and threonine residues present in large tandem repeat (TR) regions.The mucin MUC5AC protects stomach, gallbladder, and bronchial epithelium from chemical and physical damage.Studies published to date have only shown partial eDNA sequences of both mouse and human MUC5AC and the genomic organization is unknown at this time.Aim: To determine the sequence and structure of the mouse MucSAC gene.Methods: Muc5AC was initially isolated by screening a mouse gastric eDNA library with anti-deglycosylated gastric mucin antibody, resulting in identification of a eDNA containing a 48 bp TR region encoding for 16 amino acids that is rich in threonine and serine.This was then used as a probe to isolate eDNA and genomic clones of Muc5AC.eDNA sequences were extended by 3' and 5' RACE techniques.Overlapping clones have been identified and sequenced.Results: One set of eDNA clones was isolated by using a fragment of genomic DNA that is 5' of the TR region.A total of 1.7 kb of unique 5' sequence has been determined.Sequence analysis shows a 73% homology to a partial human gastric mucin eDNA (HGM1) and 71% to the human MUC2 within the D3 domain, named by its homology to the D3 domain of von Willibrand factor (vWF).Analysis of upstream genomic sequences has revealed a region that is 76% homologous to the D2 domain ofMUC2.A second set of eDNA clones isolated represent 2.1 kb of unique sequence 3' of the TR region which demonstrate an 88% and 73% homology to the rat and human MUC5AC 3' ends respectively.All three sequences have homology to the D4 domain of vWF.D4 domains are located in the 3' end of MUC2 and MUC5B but not MUC6.Contiguous genomic clones have been isolated that span 36 kb of the gene.The 3' region downstream of the TR (including introns and exons) encompasses 6.1 kb.The 3' region contains numerous introns which is similar to the organization of MUC5B but not that of MUC6.The TR region of Muc5AC is less than 2.3 kb which is relatively small compared to other secretory mucins.Using PCR analysis the TR region has been shown to be interrupted by at least one cysteinerich domain.Analysis by partial digestion with the restriction enzyme AluI has indicated that there are about 40 repeated sequences.Conclusions: The structure of the mouse Muc5AC gene is very similar to the MUC2 secretory mucin.They share D2 and D3 domains 5' of the TR region and D4 domains 3' of the TR region.The structure suggests that both mucins likely participate in end-to-end disulfide-liked polymer formation.
BACKGROUND:Helicobacter pylori eradication is accomplished using a wide array of drugs combined in a multitude of dosage schedules. The aim of the present study was to define the best 14-day eradication schedule using a PPI plus either two antibiotics or one antibiotic and bismuth. MATERIAL AND METHODS:For this study, 367 subjects (198 males, 169 females, age 22-87 years) with document H. pylori infection of the stomach were recruited from out-patients of the Gastroenterology Department of the Venezia Hospital. In all patients, H. pylori infection was identified by histology and the CLO-test. Patients were treated as follows: 1) PPI (P) plus clarithromycin (C) 250 mg plus amoxicillin (A) 1000 mg bid (P + C + A); 2) P plus C plus bismuth subcitrate (B) 120 mg qid (P + C + B); 3) P plus C plus tinidazole (T) 500 mg bid (P + C + T); and 4) P plus A plus T bid (P + A + T). After two months, an upper gastrointestinal endoscopy was repeated for end point histological evaluation and the CLO- test. Positivity of one of the two methods was considered sufficient to define H. pylori as "not eradicated". STATISTICS:Chi-squared test and Fisher exact test. RESULTS:Thirty-three subjects dropped out (six due to adverse events). P + C + B was proven significantly less effective than P + C + A, P + C + T and P + A + T, eradication rates being, respectively, 75.0%, 90.5%, 87.6%, 92.0%, (p = .005, per protocol analysis). CONCLUSIONS:All PPI-based triple therapies tested in this study were effective in curing H. pylori infection; however, P + C + B resulted in rates too low (< 85%) to be recommended. P + C + A and P + A + T resulted in the high cure rates and thus may be considered the treatment of choice.
An open, prospective, randomized, 6-month, clinical trial was performed on 198 patients with healed duodenal ulcers (DUs) to compare three omeprazole schedules for the prevention of ulcer relapse-20 mg daily (group 1), 20 mg every other day (group 2), and 40 mg on Saturday and Sunday (group 3). Patients were followed up at 3-month intervals; endoscopy and laboratory screening (including basal serum gastrin measurement) were performed at baseline, after 6 months, and in the event of any symptomatic relapse. One-way analysis of variance, the chi-square test, and Student's t test on paired data were used for statistical analysis of the study data. Per protocol analysis (PPa) and a more restrictive analysis (Ra) considering all dropouts as treatment failures were also used. Patients were randomly assigned to one of three treatment groups: 67 to group 1, 69 to group 2, and 62 to group 3. Thirty-two patients dropped out of the study, 14 in group 1, 3 in group 2, and 15 in group 3. Confirmed ulcer relapse rates were 3.8% in group 1, 19.7% in group 2, and 23.4% in group 3 (PPa, P < 0.01). Pa rates were 23.9%, 23.2%, and 41.9%, respectively (P < 0.03). No severe side effects were recorded. Over a 6-month period, omeprazole 20 mg daily appeared to be the most effective maintenance treatment for healed DU. All three omeprazole schedules were well tolerated.
Objective: To verify whether cefixime is suitable for the treatment of Helicobacter pylori infection in monotherapy. Design: Prospective, two-centre study with open randomization in two antisecretory treatment schedules. Patients: Duodenal ulcer patients with an endoscopically documented active lesion. Intervention: All patients received antisecretory treatment (either ranitidine 300 mg twice daily or ranitidine 300 mg three times daily) for 31 days (3 weeks+/-10 days) plus cefixime 400 mg four times daily during the fast 10 days. Histology, rapid urease test and culture were used to diagnose H. pylori infection. An upper gastrointestinal endoscopy was performed at the beginning of the study, 31-35 days after starting treatment and 1 month after stopping treatment. Results: Of the 26 patients who joined the study, five were test to follow-up, the ulcer lesion was found unhealed in six out of 21 patients at the end of the therapy and three out of 21 patients were found to be free of H. pylori. One month later, two out of these th ree patients remained free of infection. Ten adverse events were registered, mainly diarrhoea (seven cases). Conclusions: Cefixime is not suitable as monotherapy for H. pylori eradication.
Contractor's risk management capability (RMC) reflects the sophistication of contractor's understanding of risk portfolio and how to manage those risks. This paper aims to develop a RMC assessment model for subway project contractors and to assess the current overall RMC of subway project contractors in mainland China. To achieve the objectives, a questionnaire survey was conducted and data were collected from 58 respondents. The empirical research findings showed that the overall RMC of subway project contractors can be regarded as between “low” and “medium”. In addition, currently in subway projects' area, contactor's risk analysis capability is relatively more mature than other capabilities. However, contractors' risk management attitude is relatively less mature than other capabilities. Assessing the current RMC of subway project contractors can be used to identify the priority or weakest areas needed for improvement.
This multicenter, prospective, randomized, open, long-term study compared the efficacy of sucralfate (1 g twice daily) versus ranitidine (150 mg once daily) versus no therapy in patients with gastric ulcer. The results at the end of the first of a scheduled 3-year follow-up are reported. Two hundred ninety patients with healed GU entered the 3-year, open study. Ninety patients were randomly assigned to receive sucralfate, 105 to receive ranitidine, and 95 to receive no treatment. The three groups proved well matched in terms of standard clinical data. Fifty patients were withdrawn from the study during the first year; a gastric neoplasm was diagnosed in four patients. At months 3, 6, and 12 of therapy, the remission rates were, respectively, 94.8%, 86.2%, and 79.6% with sucralfate; 98.9%, 91.6%, and 82.5% with ranitidine; and 89.3%, 80.7%, and 66.9% with no treatment. Sucralfate was as effective as ranitidine (P = NS), and both drugs produced higher cumulative remission rates than no treatment (P < 0.06 and P < 0.01, respectively). We conclude that 1 g of sucralfate twice daily was as effective as 150 mg of ranitidine once daily in maintaining GU remission for 1 year; both treatments led to a better outcome than no treatment.
UNLABELLED Helicobacter pylori (Hp) is connected with active/chronic gastritis, gastric gastric and duodenal ulcer. It is not known whether exogenous factors are involved in Hp infection. The aim of this prospective study, performed on 286 consecutive subjects undergoing upper gastrointestinal endoscopy, was to evaluate the influence of smoking and alcohol consumption on Hp infection. For each patient the following parameters were taken into account: sex, age, smoking (no, < 10, > 10 cig/day) and alcohol (no, < 40, > 40 g ethanol/day) intake, antiulcer therapy (no, H2-blockers, omeprazole, sucralfate), presence of gastric or duodenal ulcer (DU). At least two biopsies from both the antrum and the corpus were obtained for histological examination; the gastritis was classified and scored according to the Sydney system. STATISTICS chi-squared test (corrected), Fisher's exact test. RESULTS 43 pts had Hp (27M, 16F; age 57.8 yrs, range 23-91), 47 Hp ++ (25M, 22F; age 61.1, range 19-86), 81 Hp + (48H, 33F; age 56, range 16-84), 115 Hp- (75M, 40F; age 57.8, range 19-84). Hp infection was found to be significantly correlated with presence of ulcer symptoms, gastritis, lymphoid follicles and, among DU patients, with active DU. The other parameters considered did not influence Hp infection. In conclusion smoking habits and alcohol consumption do not affect Hp infection of the stomach.
This multicenter, prospective, randomized, open, long-term study compares sucralfate (2 g daily) with ranitidine (150 mg daily) and no treatment in gastric ulcer (GU). We report the results of the second year of a scheduled 3-year follow-up, the outcome of the 1 st year has been reported earlier. The 24-month follow-up was completed by 142 patients who were continuously either treated with the drug randomly assigned at the beginning of the study or left untreated (i.e. 32 patients took 150 mg ranitidine at bedtime, 29 took 1 g sucralfate twice daily and 81 were left untreated, 23 of whom came from the ranitidine group, 19 from the sucralfate group and 39 from the untreated group). Seven patients dropped out and 26 subjects relapsed (5 under ranitidine, 4 under sucralfate and 17 untreated cases). Ranitidine versus previous ranitidine, sucralfate versus previous sucralfate and each one versus no treatment showed comparable relapse rates. An additional study, using Cox's models, showed that three variables have a significant correlation with relapse during the 1 st year of follow-up: therapy carried out (p = 0.0025), symptoms (p = 0.0047) and family history of ulcer (p = 0.0392). In conclusion, both ranitidine 150 mg and sucralfate 2 g proved effective in reducing GU relapse as compared with no treatment, an effect which does not seem to persist during the 2nd year of therapy, when the 'no treatment' option may be taken into account.