Correlation between the rate of ethanol elimination and the psychophysiological characteristics of rats

Ethanol elimination from the blood of rats with different psychophysiological features was studied using gas chromatographic head-space analysis in the general complex of tests aimed at determination of ethanol consumption. The selection of animals with different levels of the initial alcohol motivation was performed according to modified Porsolt's method. It was shown that the initial level of predisposition to depression-like states is in a dose-dependent correlation with the high rate of ethanol elimination. This is suggested to be one of the genetic indications which promotes the formation of the initial alcohol motivation and the development of experimental alcoholism.     

Structural-functional aspects of the postischemic recovery of the hepatocyte endoplasmic network in rats

The experiments on rats have shown that total hepatic ischemia reduces the content of microsomal cytochromes P-450 and b5 and causes amidopyrine and aniline disturbances over a 2-3-week post-ischemic period. The analysis of hepatocyte ultrastructure has revealed the interdependence of structural and functional changes in endoplasmic reticulum during recovery period. The damage of monooxygenase inducibility correlated with stable decline in the number of fixed ribosomes in post-ischemic period.     

Glycogen debranching enzyme: purification, antibody characterization, and immunoblot analyses of type III glycogen storage disease.

Type III glycogen storage disease is caused by a deficiency of glycogen debranching-enzyme activity. Many patients with this disease have both liver and muscle involvement, whereas others have only liver involvement without clinical or laboratory evidence of myopathy. To improve our understanding of the molecular basis of the disease, debranching enzyme was purified 238-fold from porcine skeletal muscle. In sodium dodecyl sulfate-polyacrylamide gel electrophoresis the purified enzyme gave a single band with a relative molecular weight of 160,000 that migrated to the same position as purified rabbit-muscle debranching enzyme. Antiserum against porcine debranching enzyme was prepared in rabbit. The antiserum reacted against porcine debranching enzyme with a single precipitin line and demonstrated a reaction having complete identity to those of both the enzyme present in crude muscle and the enzyme present in liver extracts. Incubation of antiserum with purified porcine debranching enzyme inhibited almost all enzyme activity, whereas such treatment with preimmune serum had little effect. The antiserum also inhibited debranching-enzyme activity in crude liver extracts from both pigs and humans to the same extent as was observed in muscle. Immunoblot analysis probed with anti-porcine-muscle debranching-enzyme antiserum showed that the antiserum can detect debranching enzyme in both human muscle and human liver. The bands detected in human samples by the antiserum were the same size as the one detected in porcine muscle. Five patients with Type III and six patients with other types of glycogen storage disease were subjected to immunoblot analysis. Although anti-porcine antiserum detected specific bands in all liver and muscle samples from patients with other types of glycogen storage disease (Types I, II, and IX), the antiserum detected no cross-reactive material in any of the liver or muscle samples from patients with Type III glycogen storage disease. These data indicate (1) immunochemical similarity of debranching enzyme in liver and muscle and (2) that deficiency of debranching-enzyme activity in Type III glycogen storage disease is due to absence of debrancher protein in the patients that we studied.     

The main immunogenic region (MIR) of the nicotinic acetylcholine receptor and the anti-MIR antibodies

Myasthenia gravis (MG) is caused by autoantibodies against the nicotinic acetylcholine receptor (AChR) of the neuromuscular junction. The anti-AChR antibodies are heterogeneous. However, a small region on the extracellular part of the AChR alpha subunit, called the main immunogenic region (MIR), seems to be the major target of the anti-AChR antibodies, but not of the specific T-cells, in experimental animals and possibly in MG patients. The major loop of the overlapping epitopes for all testable anti-MIR monoclonal antibodies (MAbs) was localized within residues 67-76 (WNPADYGGIK for Torpedo and WNPDDYGGVK for human AChR) of the alpha subunit. The N-terminal half of alpha 67-76 is the most critical, Asn68 and Asp71 being indispensable for binding. Yet anti-MIR antibodies are functionally and structurally quite heterogeneous. Anti-MIR MAbs do not affect channel gating, but they are very potent in mediating acceleration of AChR degradation (antigenic modulation) in cell cultures and in transferring experimental MG in animals. Fab fragments of anti-MIR MAbs bound to the AChR prevent the majority of the MG patients' antibodies from binding to and causing loss of the AChR. Whether this inhibition means that most MG antibodies bind on the same small region or is a result of broad steric/allosteric effects is under current investigation.     

Has the adipokine profile an influence on the catch-up growth type in small for gestational age infants?

Journal of Physiology and Biochemistry - Infants born small for gestational age (SGA) are at increased risk of perinatal morbidity, persistent short stature, and metabolic alterations in later...     

Simulation of protein misfolding using a lattice model

The structure of the tightly bound complex of the globular myosin head with F-actin is the key to understanding important details of the mechanism of how the actin-myosin motor functions. The current notion on this complex is based on the docking of known atomic structures of constituent proteins into low-resolution electron-density maps. The atomic structure of the complex was refined by the molecular mechanics method, which consists in minimizing the energy of molecular interaction and which makes it possible to optimize not only the relative position of protein backbones as rigid bodies, but also the position of side chains on the protein interface. The structure calculated using ICM-Pro software, on the one hand, is close to the model obtained using electron microscopy; on the other hand, it ensures the best calculated interaction energy and accounts for the results of mutagenesis experiments. On the basis of the structure obtained, we can suggest the molecular mechanisms underlying the actin-activated release of ATP hydrolysis products from myosin and the decrease in the affinity of myosin for actin upon binding of nucleotides.