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1.
J Bacteriol ; 183(5): 1645-54, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11160095

ABSTRACT

Bacterial spores are protected from the environment by a proteinaceous coat and a layer of specialized peptidoglycan called the cortex. In Bacillus subtilis, the attachment of the coat to the spore surface and the synthesis of the cortex both depend on the spore protein SpoIVA. To identify functionally important amino acids of SpoIVA, we generated and characterized strains bearing random point mutations of spoIVA that result in defects in coat and cortex formation. One mutant resembles the null mutant, as sporulating cells of this strain lack the cortex and the coat forms a swirl in the surrounding cytoplasm instead of a shell around the spore. We identified a second class of six mutants with a partial defect in spore assembly. In sporulating cells of these strains, we frequently observed swirls of mislocalized coat in addition to a coat surrounding the spore, in the same cell. Using immunofluorescence microscopy, we found that in two of these mutants, SpoIVA fails to localize to the spore, whereas in the remaining strains, localization is largely normal. These mutations identify amino acids involved in targeting of SpoIVA to the spore and in attachment of the coat. We also isolated a large set of mutants producing spores that are unable to maintain the dehydrated state. Analysis of one mutant in this class suggests that spores of this strain accumulate reduced levels of peptidoglycan with an altered structure.


Subject(s)
Bacillus subtilis/physiology , Bacterial Proteins/chemistry , Bacterial Proteins/metabolism , Sigma Factor , Transcription Factors , Alleles , Amino Acid Sequence , Bacillus subtilis/chemistry , Bacillus subtilis/genetics , Bacterial Proteins/genetics , Blotting, Western , Peptidoglycan/metabolism , Point Mutation , Spores, Bacterial/chemistry , Spores, Bacterial/metabolism , Structure-Activity Relationship
2.
Aliment Pharmacol Ther ; 12(5): 447-51, 1998 May.
Article in English | MEDLINE | ID: mdl-9663724

ABSTRACT

BACKGROUND: No clinical study has been performed to-date to evaluate the efficacy of the dual therapy of ranitidine bismuth citrate (RBC) plus clarithromycin (C) 500 mg b.d. given for 7 days for the eradication of H. pylori. AIM: To assess the eradication rates achieved by treatment with RBC 400 mg b.d. for 28 days combined with clarithromycin 500 mg b.d. for 7 days in H. pylori-positive duodenal ulcer patients. METHODS: One hundred and twelve H. pylori-positive patients with endoscopically proven active duodenal ulcer were included in a multicentre, open, randomized trial. H. pylori infection was initially detected by CLO-test and histology on antral and corpus biopsies, and by 13C-urea breath test (UBT). Patients were included if at least two of the tests were positive for H. pylori infection. Patients were randomized to receive RBC 400 mg b.d. for 4 weeks combined with clarithromycin 500 mg b.d. for the first 7 days (Group A) or 14 days (Group B). A second endoscopy was performed at least 28 days after the end of therapy for the assessment of ulcer healing and H. pylori infection. Eradication was assumed if all the tests (CLO-test, histology and UBT) were negative for H. pylori. RESULTS: Fifty patients in Group A and 55 in Group B were assessed for H. pylori eradication and ulcer healing. The eradication rates according to intention-to-treat analysis were 75% in Group A and 80% in Group B. Considering only those patients with evaluable data at least 28 days after the end of therapy, H. pylori eradication was achieved in 84% and 82% in Group A and B, respectively. No statistically significant difference in eradication was found between the two groups by Mantel-Haenszel test. Only one patient, in Group A, was withdrawn because of adverse events (epigastric pain and pruritus).


Subject(s)
Anti-Bacterial Agents/therapeutic use , Anti-Ulcer Agents/therapeutic use , Bismuth/therapeutic use , Clarithromycin/therapeutic use , Duodenal Ulcer/drug therapy , Helicobacter Infections/drug therapy , Helicobacter pylori , Ranitidine/analogs & derivatives , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/adverse effects , Anti-Ulcer Agents/administration & dosage , Anti-Ulcer Agents/adverse effects , Bismuth/administration & dosage , Bismuth/adverse effects , Clarithromycin/administration & dosage , Clarithromycin/adverse effects , Drug Therapy, Combination , Duodenal Ulcer/microbiology , Female , Helicobacter Infections/microbiology , Humans , Male , Middle Aged , Ranitidine/administration & dosage , Ranitidine/adverse effects , Ranitidine/therapeutic use
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