The genetic heterogeneity of hereditary human diseases]

The paper deals with the probability regularities of mutations arising in the same locus (or nucleotide) in human populations. It is shown that in a population of constant size the number of such recurrent mutations tends to an equilibrium value. It is demonstrated that dynamics of this number of recurrent mutations depends on the population structure essentially. This phenomenon is illustrated by comparing non-subdivided and hierarchy populations of the same size.     

Biochemical heterogeneity of mitochondria]

Rat liver mitochondria were fractionated on the basis of their sedimentation coefficients in the gradient of ficoll. The fractions ("heavy", "middle" and "light" mitochondria) were heterogeneous with regard to the content of protein, DNA, cytochrome a + a3 and respiratory activity. Heterogeneity of mitochondria did not result from the damage or microsomal and lysosomal contamination. The biosynthesis of DNA, RNA and proteins in the different fractions of mitochondria was studied. In vivo incorporation of radioactive precursor into RNA was highest in the fractions of "middle" mitochondria, whereas in vitro the "heavy" mitochondria showed maximum activity in the synthesis of RNA. In vitro DNA synthes was maximum in the fractions of "heavy" mitochondria, protein synthesis in "heavy" and "light" mitochondria. Activity of the synthesis of RNA, DNA and proteins in vitro depends on the content of DNA and cytochrome a + a3 in the different fractions of mitochondria. It is supposed that heterogeneity of mitochondria may be connected with their biogenesis.     

Lateral heterogeneity of bacterial membranes]

Isolated membranes of M. lysodeikticus were rapidly frozen and disrupted in a Hughes press. After disruption the fragments were centrifuged at 144000 g for 1 hour and part of the supernatant just above the pellet was subjected to isopycnic centrifugation in a continuous sucrose density gradient. It was found that the material tested was a mixture of fragments differing in their buoyant densities. These fragments also differed in their protein/lipid ratios, cytochrome content and dehydrogenase activities calculated per protein and lipid as well as in proportion of the respiratory chain enzymes. The results obtained are indicative of lateral heterogeneity of the bacterial membrane and the existence of areas in the membrane having high concentration of the respiratory chain enzymes. The latter may suggest that the system of substrate oxidation is segregated in the membrane. It is assumed that there exists in the membrane an exchange of components between different electron-transporting chains operated due to their lateral diffusion.     

Conformation and stability of streptokinases from nephritogenic and nonnephritogenic strains of streptococci

Conformation and stability of three Sks from Streptococcus equisimilis strain H46A, Streptococcus pyogenes strain A374, and Streptococcus pyogenes strain AT27 were compared by limited proteolysis, CD, and fluorescence measurements and by DSC. The general similarity of the peptide CD spectra in the spectral region 185 to 260 nm indicates the same type of folding for the three proteins. Fluorescence and aromatic CD spectra are consistent with a predominant surface localization of the aromatic amino acids and a low rigidity of their surroundings. A major difference among the three Sks is shown by deconvolution of their excessive heat capacity functions. Deconvolution reveals two energetic folding units in Sk H46A but three energetic folding units in Sk A374 and Sk AT27. Digestion of the Sks with trypsin indicates a reduced sensitivity of the C-terminal region of Sk A374 and Sk AT27 in comparison to Sk H46A. This suggests that amino acids of the C-terminal region participate in the formation of the third folding unit of Sk A374 and Sk AT27. Proteins 27:26–35 © 1997 Wiley-Liss, Inc.     

Morphologic and biochemical heterogeneity of lysosomes]

By means of isopycnic centrifugation in the continuous density gradient of sucrose two subfractions of lysosomes were isolated from rat liver homogenates: a "light" one (with the floating density p=1.13) and a "heavy" one (p=1.24). Electron microscopic, enzymatic and electron microscope enzymatic analysis of the isolated subfractions showed that the "light" subfraction consisted mainly of newly-formed primary lysosomes, while the "heavy" one was presented by secondary lysosomes. Parallel biochemical investigations demonstrated a considerable enzymatic heterogeneity of the two lysosomal subfractions: the "light" subfraction was characterized by a high specific activity of acid DNase, acid RNase and beta-galactosidase, and by almost total absence of beta-glucosidase activity, while the "heavy" one was characterized by a high specific activity of beta-glucosidase, beta-glucuronidase and beta-N-acetylglucosaminidase. Possible causes of enzyme heterogeneity of rat liver lysosomes are discussed.     

Enzymatic heterogeneity of the rat myocardium]

The histoenzymatic method was applied to the study of distribution of the activity of the redox enzymes in the myocardium of the ventricles in rats; distribution of the activity of lactic and malic dehydrogenase and of alpha-glycerophosphate proved to be the most manifest near the apex of the heart and was expressed in the presence of "spotty" areas of increased activity against the general homogeneous background of formazan deposits. The activity of mitochondrial upsilon-glycerophoric dehydrogenase was seen in all the portions of the ventricles and was characterized by an uneven distribution in the sarcoplasm with increase in the direction from the interdisc to the nucleus. Unevenness of distribution of the beta-oxybutyric dehydrogenase activity was detected in some of the animals and was pronounced in all the portions of the myocardium. The intensity of the reaction in detection of succinic dehydrogenase, NAD- and NADP-diaphorases varied but insignificantly.     

The heterogeneity of collection strains of Yersinia pseudotuberculosis and their molecular biological properties]

The capacity of Y. pseudotuberculosis strains for disassociation with the appearance of S- and P-forms has been studied. Strains 852 and 9547 show high stability in S-forms, their conversion into R-forms occurring at 40-42 degrees C. Strain 6953 shows pronounced polymorphism and instability of its associations at different growth temperatures. Strain 9532 exists in S- and R-forms which retain their stability during numerous subculturings at different growth temperatures and prolonged storage. This strain has plasmids of 130, 72.2, 5.7 kb. All plasmids are retained in S- and R-forms, i. e. the dissociation of the strain is not accompanied by the loss of plasmids. The conversion of the strain from the S-form into the R-form leads to changes in the structure of lipopolysaccharide and the composition of low-molecular (less than 23 kD) proteins in the outer and inner membranes. In tests on guinea pigs the LD50 of the R-form of the strain is tenfold greater than that of its S-form. The dissociants of strain 9532 are transformed by plasmid DNA with equal efficiency and equally inherit them without selective pressure.     

Plasmid heterogeneity in populations of Yersinia pestis strains]

Yersinia pestis strains with the typical plasmid patterns were shown to have the heterogenic populations. Heterogeneity is increased by cultivation passages in artificial nutrient media and is manifested in plasmid elimination within several clones, plasmid integration into the chromosome, appearance of auxiliary plasmids or the ones with increased molecular masses. Passages of strains in experimental animals result in populations homogeneity with the typical plasmid patterns within all clones tested. The clones having changed the plasmid content and selected from heterogenic populations pertain their properties when cultivated in nutrient media and passaged in experimental animals.     

Structure of scorpion hemocyanin: heterogeneity of its sub-units]

Six dissociation products isolated from the Androctonus australis scorpion haemocyanin are studied through analytical ultracentrifugation and acrylamide-SDS electrophoresis: the results show that one of these fractions exists as a dimer and that the five others are monomers. A genetical study shows that two subunits at least can undergo mutations.     

Characterization of the basis of lipoprotein [a] lysine-binding heterogeneity

Although elevated plasma concentrations of lipoprotein [a] (Lp[a]) are considered to be a risk factor for atherosclerosis, the mechanisms by which Lp[a] mediates its pathogenic effects have not been conclusively determined. The apolipoprotein [a] (apo[a]) component of Lp[a] confers unique structural properties to this lipoprotein, including the ability to bind to lysine residues in biological substrates. It has been shown, however, that only a fraction of plasma Lp[a] (Lp[a]-Lys(+)) binds to lysine-Sepharose in vitro. The nature of the non-lysine-binding Lp[a] fraction in plasma (Lp[a]-Lys(-)) is currently unknown. In the present study, the Lp[a]-Lys(+) fraction was determined in the plasma of six unrelated individuals; the Lp[a]-Lys(+) fraction in these plasma samples ranged from approximately 37 to approximately 48%. Interestingly, purification of the Lp[a] by density gradient ultracentrifugation followed by gel filtration and ion-exchange chromatography resulted in progressive increases in the Lp[a]-Lys(+) fraction. Addition of either purified low density lipoprotein (LDL) or fibronectin to the purified Lp[a] at a 1:1 molar ratio reduced the Lp[a]-Lys(+) fraction (maximal decrease of 34 and 20%, respectively) whereas addition of both fibronectin and LDL to the purified Lp[a] resulted in a further decrease (45% maximally) in this fraction. Similar results were obtained by using a recombinant expression system for apo[a]: addition of a 4-fold molar excess of either LDL or fibronectin to conditioned medium containing metabolically labeled recombinant apo[a] reduced the Lys(+) fraction by 49 and 23%, respectively.Taken together, our data suggest that the lysine-binding heterogeneity of plasma Lp[a] is not primarily an intrinsic property of the lipoprotein, but rather results in large part from its ability to noncovalently associate with abundant plasma components such as LDL and fibronectin. These interactions appear to mask the lysine-binding site in apo[a] kringle IV type 10, which mediates the interaction of Lp[a] with lysine-Sepharose. The contribution of these interactions to the function of Lp[a] in vivo remains to be investigated.     

Functional heterogeneity of lateral geniculate body neurons in the rabbit]

Background and evoked activity of LGB units was studied on immobilized and anaesthetized rabbits. Two groups of projection units were revealed, differing by the level of background activity, latencies and mean frequency of discharges in responses to single photic flashes and to electrical stimulation of the optic nerve. It is assumed that these groups of units belong to the slowly and rapidly conducting paths of sensory information transmission in the visual projection system.