We present herein the first complete genome sequence of a thermophilic Bacillus-related species, Geobacillus kaustophilus HTA426, which is composed of a 3.54 Mb chromosome and a 47.9 kb plasmid, along with a comparative analysis with five other mesophilic bacillar genomes. Upon orthologous grouping of the six bacillar sequenced genomes, it was found that 1257 common orthologous groups composed of 1308 genes (37%) are shared by all the bacilli, whereas 839 genes (24%) in the G.kaustophilus genome were found to be unique to that species. We were able to find the first prokaryotic sperm protamine P1 homolog, polyamine synthase, polyamine ABC transporter and RNA methylase in the 839 unique genes; these may contribute to thermophily by stabilizing the nucleic acids. Contrasting results were obtained from the principal component analysis (PCA) of the amino acid composition and synonymous codon usage for highlighting the thermophilic signature of the G.kaustophilus genome. Only in the PCA of the amino acid composition were the Bacillus-related species located near, but were distinguishable from, the borderline distinguishing thermophiles from mesophiles on the second principal axis. Further analysis revealed some asymmetric amino acid substitutions between the thermophiles and the mesophiles, which are possibly associated with the thermoadaptation of the organism.
An endoscopic tube‐tip type urease sensor was developed for the purpose of on‐site detection of Helicobacter pylori (H. pylori) using a pH‐sensitive field effect transistor (pH‐FET). The sensor is composed of an endoscopic‐tube connected to a feed pump with a urea solution and a pH‐FET attached to a sensor holder at the open end of the tube. The urease activity on the gastric wall can be measured by bringing the sensor into contact with the gastric wall just after replacing gastric juice with the urea solution. The presence of H. pylori causes a pH change in the urea solution inside the sensor holder in 20 seconds due to the strong urease activity of this bacterial species. After measurement, the sensor is detached from the wall, and washed with urea solution by turning on the urea pump. A measurement at one site is completed within 30 seconds. Repetition of the procedure makes multi‐site measurements possible. In preliminary evaluations, it was found that clinical sensitivity and specificity were 89% and 86%, respectively, using standard bacteriological testing results as a reference.
AmBisome, a liposomal formulation of amphotericin B (CAS 1397-89-3, L-AMB), shows different pharmacokinetics from the conventional formulation, amphotericin B deoxycholate (D-AMB). To characterize the clearance process of L-AMB, the form in which it exists in rat plasma, pharmacokinetics in hepatic or renal failure rats, cellular distribution in rat liver, and placental and milk transfer in rat were investigated. Furthermore, to predict the drug-drug interaction, in vitro metabolism of amphotericin B (AMB) by rat, dog and human liver S9 fraction, and effects of L-AMB on drug-metabolizing enzyme systems were investigated. L-AMB was found to exist stably as a liposomal form in rat plasma without any notable transfer to milk or fetus in rats. After administration to hepatic failure rats, the CLtot of AMB decreased to 1/4 and the Vdss decreased to 1/8 compared with the control rat case. In contrast, after administration to renal failure rats, plasma AUC of AMB did not significantly change compared with sham-operated rats. These data suggest that hepatic clearance is the main determinant of the CLtot for L-AMB. In rat liver, L-AMB was distributed mainly to non-parenchymal cells. In the in vitro metabolism study using liver S9 fraction, no metabolite peaks were observed. After repeated administration of L-AMB to rats, there was no change in parameters related to the drug-metabolising enzyme system in liver microsomes. These data demonstrate that clinically significant metabolism-based drug interaction with L-AMB should be less likely.
A rapid diagnostic system for Helicobacter pylori (H. pylori) was developed based on an urease analyser using a pH‐sensitive field effect transistor (pH‐FET). The system is composed of a solid‐phase capillary‐tube and a pH‐measuring cell. The solid‐phase tube, with an inner diameter 0.55 mm and coated with a monoclonal antibody against H. pylori's urease, was used to selectively capture the urease in endoscopically collected gastric mucus. The urease activity on the inner surface of the solid‐phase tube was measured by coupling it with ph‐FET in a pH measuring cell containing urea solution. Before immuno reaction in the solid‐phase, gastric mucus was diluted with a phosphate buffered saline containing 1% n‐octylglucoside, which was effective for accelerating the release of active urease from H. pylori's cells suspended in the sample solution. As a result of preliminary evaluations, it was found that the clinical sensitivity and specificity were 100 and 86%, respectively, using a bacteriological test as a reference.
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