Enhancement of ectopic bone formation in mice with a deficit in Fas-mediated apoptosis

Bone formation is under the control of cytokines as well as growth factors such as bone morphogenetic proteins (BMP). This suggests the possibility that osteogenesis might be modulated by factors which also modulate the immune system. To test whether immune disorders in the host may influence bone formation, we studied BMP-induced bone formation in a C3H/HeJ strain of mice bearing a mutant gene, the lymphoproliferation gene (lpr) or the generalized lymphoproliferative disease gene (gld), both of which are known to be a Fas deletion mutant and a Fas ligand mutant, respectively, and to induce immune disorders via a deficit in Fas-mediated apoptosis. Crude BMP derived from bovine bone were injected into the muscular tissue in the femur of adult C3H/HeJ mice or C3H/HeJ mice bearing an lpr or gld gene. Quantitative analysis of the resulting ectopic bone formation by X-ray photography 2 weeks after injection revealed that the presence of either the lpr or gld gene caused a bone mass significantly larger in dimension than that seen in the wild type mice. Histological examination also revealed the different influence between these mutant genes on the level of bone formation exhibited by hyaline cartilage and bone trabeculae. Based on these results, we discussed the possible mechanisms of the enhanced ectopic bone formation under the deficit in Fas-mediated apoptosis.     

Time- and dose-dependent pharmacokinetics of L-754,394, an HIV protease inhibitor, in rats, dogs and monkeys

L-754,394 is a potent and specific inhibitor of the HIV-1 encoded protease that is essential for the maturation of the infectious virus. The drug exhibited dose-dependent kinetics in all species studied (rat, dog and monkey); the apparent clearance decreased when the dose was increased. However, the dose-dependency cannot be explained by Michaelis-Menten kinetics. L-754,394 in plasma declined log-linearly with time, but with an apparent half-life that increased with dose. The apparent terminal half-life of L-754,394 in rats increased from 20 min at 0.5 mg/kg i.v. to 118 min at 10 mg/kg i.v. Furthermore, L-754,394 exhibited time-dependent pharmacokinetics. After chronic i.v. doses for 7 days (1 mg/kg/dose/day), the apparent clearance of L-754,394 in rats decreased from 87 ml/min/kg after the first dose to 25 ml/min/kg after the last dose. Similar results were observed in dogs and monkeys. In vitro spectral studies indicated that approximately 40 to 60% of the content of cytochrome P-450 was inactivated when L-754,394 (10 microM) was incubated with rat, dog and monkey liver microsomes in the presence of NADPH. Little or no inactivation of cytochrome P-450 was observed when either NADPH or L-754,394 was omitted. In addition, L-754,394 selectively inhibited CYP 2C11-dependent testosterone 2 alpha- and 16 alpha-hydroxylase activity and CYP 3A1/2-dependent testosterone 6 beta-hydroxylase activity, but not CYP 2D1/2-dependent bufuralol 1'-hydroxylase activity nor CYP 1A2-dependent phenacetin O-deethylase activity in rat liver microsomes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Characteristics of muscular contraction caused by magnetic stimulation

Characteristics of muscular contraction induced by magnetic stimulation were studied using isolated gastrocnemius muscles of a frog. The figure-eight coil position was regarded as 0 degrees when the direction of induced current was parallel to the muscle fiber axis, and 90 degrees when the induced current was perpendicular to the muscle fiber axis. Muscular contraction readily occurred with lower outputs of magnetic stimulation at 0 degrees and 180 degrees, but it was weak at 90 degrees and 270 degrees. Magnetic stimulation did not directly induce muscular contraction but it acted on the synapses forming end plates to muscle cells, and muscular contraction occurred if the direction of the eddy current was parallel to the nerve which innervated the muscle cells.     

''Alice in Wonderland'' syndrome as a precursor of depressive disorder

The effect of a single dose of morphine (50 mg/kg) and ethanol (2 g/kg) on total magnesium content in blood serum, brain, heart, lung, kidney, liver, femoral muscle and spleen in mice was studied. Significant decrease of magnesium serum concentration was observed after morphine and ethanol administration but not after both drugs given simultaneously. Morphine caused the evident decrease of magnesium content in brain, lung, kidney and muscle, while it was elevated in heart and spleen and unchanged in liver. Ethanol produced significant decrease of magnesium content in heart, lung and kidney and it's increase in liver and spleen. Concomitant administration of both drugs was connected with the diminished amount of magnesium in heart, lung, kidney and muscle and led to the rising of magnesium content in spleen. It is concluded that even a single dose of investigated drugs is sufficient to produce promptly some risk of alterations in magnesium homeostasis.     

Bonding characteristics and diffusion barrier effect of the TiC phase formed at the bonding interface in an explosively welded titanium/high- carbon steel clad

Microstructural aspects and bonding characteristics of the explosively welded titanium/high-carbon steel clad of the as-welded and postannealed states were investigated. Amorphous and βTi phases were observed at the interface in the as-welded clad. These were considered to be the trace of melting and subsequently rapid solidification of thin layers along the contact surface of both the parent materials. The melting layer was considered to be responsible for the substantial bonding. The TiC layer was formed at the bonding interface by postannealing, which served as a barrier for diffusion of species across the interface and suppressed the formation of Fe-Ti intermetallic compounds. As a result, high bonding strength was preserved even after prolonged annealing at elevated temperatures.     

Characteristics of mutations in the p53 gene of oral squamous-cell carcinomas associated with betel-quid chewing in Sri Lanka

The PCR copy of the ribR gene of Bacillus subtilis was subcloned in Escherichia coli cells under the control of the phage T7 inducible promoter. The polypeptide of 26 kDa corresponding to the 690-bp gene is the product of the ribR gene. The protein encoded by the ribR gene is flavokinase, and the riboflavin-reduced form is the substrate for it.