Kinetic mechanism of active site non-equivalence in transketolase

The two-step mechanism of coenzyme (TDP) binding to apotransketolase has been examined by kinetic modeling, and the rate and equilibrium constants for each binding step for two active sites have been determined. The dissociation constants for the primary fast binding step and the forward rate constants for the secondary slow binding step have been shown to be similar for two active sites. The backward rate constants for the secondary binding step are different for two active sites, providing the kinetic mechanism of their non-equivalence in TDP binding.     

Sensitivity of larvae of the malaria mosquito Anopheles messae with various inversion genotypes to the entomopathogenic bacteria Bacillus thuringiensis israelensis as a function of dose

The influence of the entomopathogenic bacterium Bacillus thuringiensis israelensis (Bti) on the chromosomal composition of a natural population of fourth instar larvae of the malaria mosquito (Anopheles messeae Fall.) was investigated. The two doses used in the experiment yielded different death rates. A dose of 6.17 micrograms Bti per 1 mg of host mass led to a death rate of 41.1 +/- 3.0%. The chromosomal composition of the population remained unchanged, but the proportion of XL11-2R11 females decreased, and the diversity of genotypes increased due to a slight increase in proportions of heterozygotes 2R01 and 3R01. A dose of 12.34 micrograms/mg caused a death rate of 71.9 +/- 2.7%. The percentages of chromosomal variants XL1(2), 2R1, 3R1, and 3L1, as well as heterozygotes 2R01 and 3R01, decreased, thereby lessening the diversity of inversion genotypes in the population. The pathogen-related mortality is considered a quantitative index of the selection strength.     

Pharmacological characterization of the receptors involved in the beta-adrenoceptor-mediated stimulation of the L-type Ca2+ current in frog ventricular myocytes

1. The whole-cell patch-clamp was used for studying the effects of various beta1- and beta2-adrenoceptor agonists and antagonists on the L-type Ca current (Ica) in frog ventricular myocytes. 2. Dose-response curves for the effects of isoprenaline (non selective beta-agonist), salbutamol (beta2-agonist), dobutamine (beta1-agonist) on ICa were obtained in the absence and presence of various concentrations of ICI 118551 (beta2-antagonist), metoprolol (beta1-antagonist) and xamoterol (partial beta1-agonist) to derive EC50 (i.e. the concentration of beta-agonist at which the response was 50% of the maximum) and Emax (the maximal response) values by use of a Michaelis equation. Schild regression analysis was performed to examine whether the antagonists were competitive and to determine the equilibrium dissociation constant (K(B)) for the antagonist-receptor complex. 3. Isoprenaline increased ICa with an EC50 of 20.0 nM and an Emax of 597%. ICI 118551 and metoprolol competitively antagonized the effect of isoprenaline with a K(B) of 3.80 nM and 207 nM, respectively. 4. Salbutamol increased ICa with an EC50 of 290 nM and an Emax of 512%. ICI 118551 and metoprolol competitively antagonized the effect of salbutamol with a K(B) of 1.77 nM and 456 nM, respectively. 5. Dobutamine increased ICa with an EC50 of 2.40 microM and an Emax of 265%. ICI 118551 and metoprolol competitively antagonized the effect of dobutamine with a K(B) of 2.84 nM and 609 nM, respectively. 6. Xamoterol had no stimulating effect on ICa. However, xamoterol competitively antagonized the stimulating effects of isoprenaline, salbutamol and dobutamine on ICa with a K(B) of 58-64 nM. 7. We conclude that a single population of receptors is involved in the beta-adrenoceptor-mediated regulation of ICa in frog ventricular myocytes. The pharmacological pattern of the response of ICa to the different beta-adrenoceptor agonists and antagonists tested suggests that these receptors are of the beta2-subtype.     

The development of chronic kidney failure in spontaneously hypertensive rats

Normotensive Wistar and spontaneously hypertensiverten Okamoto rats with relatively low blood pressure were compared with regard to the development of chronic renal failure after subtotal renal ablation. Structural and biochemical studies revealed that Okamoto rats had more intensive glomerular sclerosis and higher degrees of chronic renal failure than Wistar rats.     

Determination of both mechanical and electronic shifts in cone beam SPECT

The difference between the displacement of the centre of rotation (mechanical shift, MS) and the electronic centring misalignment (electronic shift, ES) in cone beam SPECT is evaluated. A method is proposed to determine both MS and ES using the centroid of a projected point source sampled over 360 degrees and the Marquardt non-linear fitting algorithm. Both shifts are characterized by two orthogonal components. This method is verified using Monte Carlo simulated point source data with different combinations of mechanical and electronic shifts. Both shifts can be determined correctly. We have also applied the proposed method to our cone beam SPECT system to determine both shifts as well as the focal length. The determined ES parameters are then used to correct the projections and the MS parameters are incorporated into a reconstruction algorithm. The point source images are reconstructed and the image resolutions with and without the shift corrections are measured. The experimental results demonstrate that the image resolution is improved after shift corrections. The experimental results also indicate that the shift parameters determined in the same experiment with the point source located at different places are consistent but change from time to time, suggesting that calibration of the system is needed on a periodic basis.     

Bilateral lobar transplantation utilizing living related donors

As the recipient list for patients requiring lung transplantation continues to increase, cadaveric donor lung availability has remained static. Our experience with utilizing lobes from living related donors for bilateral pulmonary transplantation in 20 patients has yielded a 75% survival at 1 year follow-up. Morbidity and mortality have been predominately due to infection. Rejection episodes have been mild and unilateral and have responded to augmented corticosteroids. Pulmonary function tests in the recipients tend to improve steadily during the first year postoperatively, and the patients have excellent functional capacity. There have been no significant complications in the donors. On the basis of our clinical experience, we have found that bilateral lobar transplantation utilizing living related donors has resulted in organ availability that can be lifesaving in critically ill patients and can provide a good alternative in certain noncritical, deteriorating patients.     

Plasma cell tumour in a renal transplant recipient

We report the occurrence of a plasma cell tumour in an immunosuppressed renal allograft recipient. The lesion showed polyclonal proliferation of plasma cells with equal staining for kappa and lambda chains. Purely cutaneous plasma cell tumours are uncommon, few cases having been reported in immunosuppressed patients.