ABSTRACT
The ligand binding domain of the human vitamin D receptor (VDR) was modeled based on the crystal structure of the retinoic acid receptor. The ligand binding pocket of our VDR model is spacious at the helix 11 site and confined at the beta-turn site. The ligand 1alpha, 25-dihydroxyvitamin D(3) was assumed to be anchored in the ligand binding pocket with its side chain heading to helix 11 (site 2) and the A-ring toward the beta-turn (site 1). Three residues forming hydrogen bonds with the functionally important 1alpha- and 25-hydroxyl groups of 1alpha,25-dihydroxyvitamin D(3) were identified and confirmed by mutational analysis: the 1alpha-hydroxyl group is forming pincer-type hydrogen bonds with S237 and R274 and the 25-hydroxyl group is interacting with H397. Docking potential for various ligands to the VDR model was examined, and the results are in good agreement with our previous three-dimensional structure-function theory.
Subject(s)
Receptors, Calcitriol/chemistry , Amino Acid Sequence , Animals , COS Cells , Calcitriol/chemistry , Computer Simulation , Humans , Hydrogen Bonding , Ligands , Models, Molecular , Molecular Sequence Data , Mutation , Protein Binding/genetics , Protein Structure, Secondary , Receptors, Calcitriol/genetics , Receptors, Retinoic Acid/chemistry , Sequence Alignment , Structure-Activity Relationship , Transcription, GeneticABSTRACT
The various biological activities of side-chain mobility restricted analogs, four diastereomers at C(20) and C(22) of 22-methyl-1alpha,25-dihydroxyvitamin D3, were evaluated. The relationship between structure and the various activities of the analogs was discussed in terms of the active space region concept that we previously suggested.
Subject(s)
Calcitriol/chemistry , Calcitriol/pharmacology , Animals , Biological Transport , Bone and Bones/drug effects , Bone and Bones/metabolism , Calcium/metabolism , Cell Differentiation/drug effects , Cell Division/drug effects , Humans , Intestinal Mucosa/metabolism , Intestines/drug effects , Keratinocytes/cytology , Keratinocytes/drug effects , Models, Molecular , Molecular Structure , Rats , Stereoisomerism , Structure-Activity Relationship , Tumor Cells, CulturedABSTRACT
The combination therapy of lansoprazol (LPZ), amoxycillin (AMPC), and clarythromycin (CAM) (LAC regimen) is one of the most effective eradication regimen of Helicobacter pylori (HP) positive ulcer patients, but the optimal treatment period of this therapy is still pending. The aim of this study was to assess the optimal treatment period of this regimen. One hundred and six patients who diagnosed as HP positive gastric and duodenal ulcer since August 1996 were randomized to one-week treatment group (group 1) or to two-weeks treatment group (group 2): LPZ 30 mg once daily, AMPC 1500 mg twice daily, CAM 800 mg twice daily. Both group received four weeks LPZ treatment (30 mg once daily) following the each combination therapy. The eradication rate of HP was 82.1% (43/56) in group 1 and 85.7% (36/42) in group 2. There was no statistical significant difference between two groups (p = 0.636). Although both treatment regimen was very useful for eradicating HP in the HP positive ulcer patients, one week LAC regimen would be better choice judging from the cost benefit.
Subject(s)
Anti-Ulcer Agents/administration & dosage , Helicobacter Infections/drug therapy , Helicobacter pylori , Peptic Ulcer/drug therapy , 2-Pyridinylmethylsulfinylbenzimidazoles , Amoxicillin/administration & dosage , Clarithromycin/administration & dosage , Drug Administration Schedule , Drug Evaluation , Drug Therapy, Combination/administration & dosage , Helicobacter Infections/microbiology , Humans , Lansoprazole , Omeprazole/administration & dosage , Omeprazole/analogs & derivatives , Peptic Ulcer/microbiology , Proton Pump Inhibitors , Recurrence , Treatment OutcomeABSTRACT
The hemothorax due to rupture of arteriovenous fistula is very rare and only 6 cases of this complication have been reported in Japanese literature. 44-year-old male complained of chest pain and dyspnea. A chest roentgenogram revealed right pleural effusion and an abnormal pulmonary shadow. By further examination including pulmonary angiography, the rupture of pulmonary arteriovenous fistula into right pleural cavity was diagnosed. Partial resection of the right lung containing arteriovenous fistula was successfully performed and postoperative course was uneventful.
Subject(s)
Arteriovenous Fistula/surgery , Hemothorax/etiology , Pulmonary Artery/abnormalities , Pulmonary Veins/abnormalities , Adult , Arteriovenous Fistula/complications , Humans , Male , Pleura , Rupture, SpontaneousABSTRACT
A 68-year-old male underwent the right completion pneumonectomy with combined resection of pericardium, diaphragm and chest wall. Three months later, he was diagnosed as a bronchial fistula with bloody sputum and decreasing of right pleural effusion level on chest X-ray film. The conservative therapy with pleural drainage and endoscopic practice with fibrin matrix was failed to close a fistula and pyothorax was developed. Therefore, surgical treatment with simple omentopexy without thoracoplasty and/or muscle transposition was performed onto fistula and SILASTIC sheet used for the repair of diaphragm at initial operation was left in the thoracic cavity. Although pleural fluid remained the contamination with bacteria for one month postsurgically, infection did not develop and fistula closed successfully. Moreover, infection did not prolong in the presence of artificial SILASTIC sheet followed by simple omentopexy. Omentopexy may be very useful for the treatment of bronchial fistula with the presence of infection.
