A novel method of protein analysis for prediction of biological function: application to tumor toxins

Informational spectra method was applied to the analysis of lymphotoxin and tumor necrosis factor. The correlation between the information contained in primary structure of these tumor toxins and some oncogen transforming proteins was established. This correlation implies the possibility of a competitive action between these two groups of proteins. "Hot spots" positions in the primary structure of lymphotoxin and tumor necrosis factor for the functional "up" and "down" mutations were predicted.     

An antioxidant prevents and reverses calcium-induced uncoupling of rat liver mitochondria

Accumulation of Ca2+ by rat liver mitochondria in the presence of inorganic phosphate results in spontaneous activation of respiration accompanied by a progressive loss of the accumulated cation. The lipid peroxidation inhibitor, ionol, completely prevents and reverses the Ca2+/phosphate-induced loss of accumulated Ca2+ and restores the respiration to state 4 level without having any effect on the rate of Ca2+ accumulation and respiration in the presence of an uncoupler. No correlation between the ionol-dependent loss of Ca2+ and the formation of malonic dialdehyde in mitochondria was found. The measurements of delta psi across the inner mitochondrial membrane during a progressive loss of Ca2+ suggest that the Ca2+/phosphate-induced "uncoupling" is mainly due to the appearance of electrogenic fluxes (but not Ca2+ cycling) which is under control of some products of initial steps of lipid peroxidation.     

Role of protein kinase C in regulating smooth muscle electrical and contractile activity: the effect of phorbol ester

The effects of protein kinase C activation by 12-O-tetra-decanoyl-phorbol-13-acetate (TPA) on the functions of guinea-pig smooth muscle taenia coli have been studied, using double-sucrose-gap method. A 15-20-min treatment of the muscle with 2 X 10(-8) M TPA caused a progressing inhibition of spontaneous electrical activity and mechanical tension, suppression of post-hyperpolarizing electrical and contractile "off-responses", a decrease in the number of action potentials during superthreshold membrane depolarization, depression of electrical and mechanical responses induced by acetylcholine, histamine, bradykinin mediators. The treatment of pre-depolarized (140 mM kappa+) muscle with 2.10(-8) TPA has led to a considerable reduction in contractile responses induced by the above mediators. The results obtained indicate that protein kinase C is capable of regulating both voltage-sensitive and receptor-operated ionic channels in smooth muscle cells.     

Effect of dibunol and isoptin on the creatine kinase and myoglobin content of the blood serum in dogs undergoing postischemic coronary reperfusion

The effect of an antioxidant dibunol and calcium antagonist verapamil on postperfusion release of myoglobin (Mb) and MB-creatine kinase (MB-CK) has been assessed in 30 dogs with experimental coronary occlusive myocardial infarction. It has been shown that reperfusion after 3-hour ischemia does not only accelerate the release of intracellular proteins, but also leads to pronounced myoglobinemia and blood enzymes. In postischemic blood flow recovery with combined dibunol and verapamil preliminary injections, an almost threefold decrease in MB-CK and Mb blood content, as compared to "reperfusion" indexes, was observed by the 10th minute of reperfusion.     

Calculation of the stability of mini-duplexes of DNA in an electrolyte solution using a molecular mechanics method in approximating a statistical model of the environment

Approximation of the statistical model of environment (SME) to estimate the energy of the macromolecule in electrolyte solution has been developed and used for calculating the conformational energy of nucleic acids by means of the molecular mechanics method. Calculation of base pairs opening delta Hcalop enthalpies and enthalpies of DNA miniduplexes dissociation delta Hcaldis were performed for 10 types of diduplexes. The approximation SME enable to perform calculations of the absolute base-dependent values of delta Hcalop which coincide in the range of 1 kcal/mol with the experimental base-dependent values of the helix-coil transition enthalpies. Values of dissociation enthalpies delta Hcalop greater than delta Hcaldis for all miniduplexes, the difference of delta Hcalop--delta Hcaldis determine the base-dependent energy of the helix-coil boundary. The values of activation barriers for the strands dissociation delta H d not equal to congruent to 8 kcal/mol and association delta H not equal to as congruent to 4 kcal/mol were obtained for GG/CC and AA/TT duplexes. It is concluded that the approximation SME enables to increase substantially the accuracy of the calculations of the macromolecule conformational rearrangement enthalpies in the electrolytes solution.     

The response of murine intestinal crypts to short-range promethium-147 beta irradiation: deductions concerning clonogenic cell numbers and positions

An exteriorized loop of mouse intestine was exposed to 147Pm low-energy electrons, where the dose rate decreased by a factor of 5 from the base of the crypt to the top of the proliferative zone. A crypt survival curve was obtained, expressed in terms of exposure time. The shape of the curve was interpreted in terms of survival parameters for colony-forming cells (clonogens) derived using 137Cs gamma rays and the depth-dose curve measured for 147Pm electrons. It is concluded that the shape of the crypt survival curve using 147Pm electrons is inconsistent with the notion of either the presence of a large number of clonogens or a small number near the top of the proliferative zone. A computer fitting procedure showed that the best agreement between predicted and observed curves was achieved with 2.7 +/- 0.5 clonogens at cell position 5.6 +/- 0.6, in the putative stem-cell zone.     

Potassium cyanate modification of the toxic and mutagenic effects of gamma radiation and benzo(a)pyrene

In experiments with CHO-AT3-2 cell culture, a study was made of the effect of potassium cyanate (KNCO) on the effect of gamma radiation and benzo(a)pyrene (BP) by the following tests: cell viability, induction of cells with micronuclei and fragmented nuclei and mutations by thymidine kinase (TK) and Na+/K+-ATPase loci. Some tests have revealed the increase in the effect of gamma radiation and BP produced by potassium cyanate. It is suggested that the sensitizing effects are related to repair system inhibition and/or changes in the cell chromatin structure produced by KNCO.     

The dosage thresholds for disordered physical work capacity in mice and rats following irradiation

Physical efficiency of mice and rats at early times following irradiation with doses of 35 to 200 Gy was estimated by the muscle endurance and motor coordination indices. A threshold nature of the effects was exhibited at high doses. For instance, as large as 40 Gy was the dose threshold at which stability in the accomplishment of the known operations was impaired; at 70-100 Gy, the accomplishment decreased down to 50% of the initial level, by the 2nd hour after irradiation, with the subsequent partial restoration; 200 Gy was the threshold dose at which the disturbances were irreversible. These values were also similar to those of the threshold doses at which clinical picture of the affection was changed.     

A standardized x-ray examination of mandibular fractures

Proceeding from an x-ray examination of 143 patients with mandibular fractures, the most informative methods and projections as well as the order of their use with account of the site of a fracture, were determined. The most informative method in all fracture sites was orthopantomography; panoramic roentgenography was indicated only in fractures of the frontal part. If panoramic tomography cannot be done, roentgenography or electroroentgenography in the frontal-nasal projection is recommended. If panoramic roentgenography cannot be done, extraoral roentgenography is indicated in the diagnosis of fractures of the frontal part of the mandible.     

A decrease in the level of unscheduled DNA synthesis in preparations of irradiated rat hepatocyte nuclei under the effect of polyamines

The results obtained show the possibility of polyamine (spermine and spermidine) utilization to stabilize the nuclear chromatin and to protect it against nuclease degradation in the course of isolation of liver cell nuclei. Besides, the inhibition of the unscheduled DNA synthesis induced by nuclease incision and by gamma- or UV-radiation was demonstrated in the presence of polyamines.