tetracycline and Metaplasia

Tissue-specific transgene expression using tetracycline (tet)-regulated promoter/operator elements has been used to revolutionize our understanding of cellular and molecular processes. However, because most tet-regulated mouse strains use promoters of genes expressed in multiple tissues, to achieve exclusive expression in an organ of interest is often impossible. Indeed, in the extreme case, unwanted transgene expression in other organ systems causes lethality and precludes the study of the transgene in the actual organ of interest. Here, we describe a novel approach to activating tet-inducible transgene expression solely in the airway by administering aerosolized doxycycline. By optimizing the dose and duration of aerosolized doxycycline exposure in mice possessing a ubiquitously expressed Rosa26 promoter-driven reverse tet-controlled transcriptional activator (rtTA) element, we induce transgene expression exclusively in the airways. We detect no changes in the cellular composition or proliferative behavior of airway cells. We used this newly developed method to achieve airway basal stem cell-specific transgene expression using a cytokeratin 5 (also known as keratin 5)-driven rtTA driver line to induce Notch pathway activation. We observed a more robust mucous metaplasia phenotype than in mice receiving doxycycline systemically. In addition, unwanted phenotypes outside of the lung that were evident when doxycycline was received systemically were now absent. Thus, our approach allows for rapid and efficient airway-specific transgene expression. After the careful strain by strain titration of the dose and timing of doxycycline inhalation, a suite of preexisting transgenic mice can now be used to study airway biology specifically in cases where transient transgene expression is sufficient to induce a phenotype.

Topics: Aerosols; Animals; Doxycycline; Gene Expression; Keratin-5; Metaplasia; Mice; Mice, Transgenic; Organ Specificity; Phenotype; Promoter Regions, Genetic; Receptors, Notch; Respiratory System; RNA, Untranslated; Signal Transduction; Tetracycline; Trans-Activators; Transgenes

Since the Korean College of Helicobacter and Upper Gastrointestinal Research has first developed the guideline for the diagnosis and treatment of Helicobacter pylori infection in 1998, the revised guideline was proposed in 2009 by the same group. Although the revised guideline was made by comprehensive review of previous articles and consensus of authoritative expert opinions, the evidence-based developmental process was not applied in the revision of the guideline. This new guideline has been revised especially in terms of changes in the indication and treatment of H. pylori infection in Korea, and developed by the adaptation process as evidence-based method; 6 guidelines were retrieved by systematic review and the Appraisal of Guidelines for Research and Evaluation (AGREE) II process, 21 statements were made with grading system and revised by modified Delphi method. After revision, 11 statements for the indication of test and treatment, 4 statements for the diagnosis and 4 statements for the treatment have been developed, respectively. The revised guideline has been reviewed by external experts before the official endorsement, and will be disseminated for usual clinical practice in Korea. Also, the scheduled update and revision of the guideline will be made periodically.

Topics: Amoxicillin; Anti-Bacterial Agents; Aspirin; Bismuth; Breath Tests; Clarithromycin; Gastroesophageal Reflux; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Lymphoma, B-Cell, Marginal Zone; Metaplasia; Metronidazole; Peptic Ulcer; Proton Pump Inhibitors; Republic of Korea; Stomach Neoplasms; Tetracycline

Helicobacter pylori is associated with B-type gastritis, duodenal ulcer disease, and possibly gastric carcinoma. The object of this study was to assess the effect of eradication of H. pylori infection on gastric epithelial cell proliferation.. Gastric epithelial cell proliferation was assessed in 22 H. pylori-positive duodenal ulcer patients before and 6 weeks after 'triple therapy' with bismuth, tetracycline and metronidazole. Cell proliferation was studied either by immunostaining for the proliferating cell nuclear antigen (PCNA) or by a microdissection technique.. Eradication was successful in 10 of the 22 H. pylori-positive patients. Treatment with 'triple therapy' resulted in a significant fall in the rate of gastric epithelial cell proliferation; this effect was seen in both the gastric body and antrum. There was a significant correlation between the number of PCNA-labelled cells and the histological grade of activity (neutrophil inflammation) (r = 0.49, P = 0.02); the same correlation was found for the number of mitoses per gland (r = 0.5, P = 0.02). There was no significant difference in the treatment effect for eradicated or non-eradicated patients or either the body or antrum. Six patients, who had at least one antral biopsy that showed evidence of focal intestinal metaplasia, had a higher rate of cell proliferation.. The reduction in epithelial cell proliferation in the body and antrum after triple therapy is independent of successful eradication of H. pylori, and it may be due to an anti-inflammatory effect of triple therapy.

Topics: Adult; Aged; Bismuth; Cell Division; Drug Therapy, Combination; Duodenal Ulcer; Female; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Humans; Longitudinal Studies; Male; Metaplasia; Metronidazole; Middle Aged; Nuclear Proteins; Proliferating Cell Nuclear Antigen; Pyloric Antrum; Tetracycline

Topics: Absorption; Animals; Body Height; Body Weight; Bone Development; Bone Diseases, Developmental; Bone Resorption; Brain; Cattle; Cerebrospinal Fluid; Choroid Plexus; Cisterna Magna; Diet; Dura Mater; Fluoresceins; Histocytochemistry; Intracranial Pressure; Lumbar Vertebrae; Male; Metacarpus; Metaplasia; Methods; Organ Size; Parotid Gland; Perfusion; Pineal Gland; Pituitary Gland; Skull; Tetracycline; Vitamin A; Vitamin A Deficiency