Analysis of the N-Acetyltransferase 2 Gene Polymorphism in the Patients with Chronic Obstructive Pulmonary Disease and in Populations of the Volga–Ural Region

Restriction fragment-length polymorphism of the gene coding for N-acetyltransferase 2 (NAT2) was typed in populations of the Volga–Ural region (Bashkirs, Tatars, Chuvashes, Udmurts, and Russians) as well as in patients with chronic obstructive pulmonary disease (COPD) and in healthy individuals. Rapid and slow acetylator phenotypes were determined based on the presence or absence of the KpnI, TaqI, and BamHI restriction endonuclease recognition sites. The proportion of slow acetylators in the populations examined varied from 40.00% in Bashkirs to 64.15% in Chuvashes with statistically significant difference between these two ethnic groups (² = 5.7; P = 0.02). Overall, in the Volga–Ural populations slow acetylators represented 56.25% of the subjects examined. This value was similar to those presented in other studies of Caucasoid populations. In the COPD patients a statistically significant decrease of the slow acetylator frequency to 48.28% compared to healthy individuals (62.18%) was observed (² = 4.60; P = 0.036). The data obtained suggest a possible association between the drug resistance in the COPD patients with the rapid acetylator phenotype, which can lead to the development of the chronic form of the disease.     

Different amyloid aggregation of smooth muscles titin in vitro

A comparative study of amyloid properties of the aggregates of smooth muscle titin (SMT) from chicken gizzard was carried out. These aggregates were formed in two solutions: 0.15 M glycine-KOH, pH 7.2–7.4 (SMT(Gly)) and 0.2 M KCl, 10 mM imidazole, pH 7.0 (SMT(KCl)). Electron microscopy data showed that SMT aggregates has an amorphous structure in both cases. The results of atomic-force microscopy demonstrated slight differences in morphology in two types of aggregates. The SMT(Gly) aggregates were represented as branching chains, composed of spherical aggregates approximately 300–500 nm in diameter and up to 35 nm in height. The SMT(KCl) aggregates formed sponge-like structures with strands of 8–10 nm in height. Structural analysis of SMT aggregates by X-ray diffraction revealed the presence of cross-β-sheet structure in the samples under study. In the presence of SMT(Gly) aggregates, thioflavine T fluorescence intensity was higher (~3-fold times) compared with that in the presence of SMT(KCl) aggregates. Congo red-stained SMT(Gly) aggregates had yellow to apple-green birefringence under polarized light, which was not observed for SMT(KCl) aggregates. Dynamic light scattering data showed the similar rate of aggregation for both types of aggregates, though SMT(KCl) aggregates were able to partially disaggregate under increased ionic strength of the solution. The ability of SMT to aggregation followed by disaggregation may be functionally significant in the cell.     

On the Peculiarities of the Aggregation of Multidomain Muscle Proteins

Biophysics - Abstract—The hypothesis that formed the basis of this work has been made on our studies that have shown that giant multi-domain muscle proteins of the titin family (titin...     

Complement System Activation by Amyloid Aggregates of Aβ(1-40) and Aβ(1-42) Peptides: Facts and Hypotheses

Biophysics - Abstract—Here, we consider the problem of the activation of the complement system by amyloid aggregates, in particular, amyloid fibrils of the Aβ(1-40) and Aβ(1-42)...     

Changes in Titin Structure during Its Aggregation

Molecular Biology - In this paper, the property of the muscle titin protein to form in vitro specific amyloid-like aggregates is discussed. The main difference from the known amyloid aggregates is...     

Cross-correlation analysis of background neuronal activity in guinea pig neocortical slices in vitro

Interaction between the background activity of adjoining neurons was investigated using simultaneous recording in surviving slices from the guinea pig sensory motor cortex by means of cross-correlation analysis. A numerical connection was found between the timing of successive discharges in sixteen of the twenty six neuronal pairs investigated. Significant discrepancies were observed in correlation tables, mainly in the range of time shifts of ±100 msec from zero point. These emerged as symmetrical or asymmetrical peaks of up to 150 msec in duration and negative shifts measuring up to 200 msec. More complex positive-negative cross-correlation patterns were also encountered. These findings may be compared with those obtained in the cortex of the intact brain. The subject of the contribution made by intrinsic cortical neuronal interaction and that of external afferents to firing correlation is discussed.Institute of Biological Physics, Academy of Sciences of the USSR, Pushchino, Moscow. Translated from Neirofiziologiya, Vol. 23, No. 4, pp. 392–399, July–August, 1991.     

Polymorphism of Xenobiotic Metabolism Genes in Petrochemical Workers

Genetic polymorphism of xenobiotic metabolizing enzymes responsible for individual susceptibility to different environmental factors was examined in a cohort of petrochemical workers occupationally exposed to adverse action of chemical compounds. Molecular genetic analysis of the I462V mutation in exon 7 of the CYP1A1gene demonstrated close similarity between the genotype and allele frequency distribution patterns in the industrial and control groups. No association between the CYP1A1polymorphic alleles and genotypes and the duration of service and concomitant diseases was observed. The odds ratio of the disease development in the workers carrying heterozygous CYP1A1 mutant allele was 2.2. Analysis of the GSTM1 gene polymorphism demonstrated a decrease in the frequency of the homozygous deletion carriers in the workers compared to the control group. There were no substantial differences between the industrial and control groups with respect to the frequencies of rapid and slow acetylator genotypes revealed at the analysis of the NAT2 gene polymorphism. However, considering the concomitant diseases, in the corresponding industrial subgroup a clear trend towards lower frequency of rapid acetylators was demonstrated. In addition, the odds ratio of the disease development for the workers with slow acetylator phenotype was 1.7.     

Amyloid properties of titin

This review considers data on structural and functional features of titin, on the role of this protein in determination of mechanical properties of sarcomeres, and on specific features of regulation of the stiffness and elasticity of its molecules, amyloid aggregation of this protein in vitro, and possibilities of formation of intramolecular amyloid structure in vivo. Molecular mechanisms are described of protection of titin against aggregation in muscle cells. Based on the data analysis, it is supposed that titin and the formed by it elastic filaments have features of amyloid.     

Molecular Genetic Analysis of the Interleukin 6 and Tumor Necrosis Factor α Gene Polymorphisms in Multiple Myeloma

The –174G C polymorphism of the interleukin 6 (IL-6) gene promoter and the –308G A polymorphism of the tumor necrosis factor (TNF) gene promoter were tested for association with multiple myeloma (MM) varying in severity. Of 69 patients, 19 had aggressive MM, 26 had benign MM, and 24 had unidentified MM. The control group (N = 102) matched the test group in age and sex composition. The two groups did not significantly differ in allele and genotype frequencies of the IL-6 and TNF genes. Genotype CC, which determines low-level expression of IL-6, occurred at a frequency of 0.35 in patients with low-progressing MM and was absent from patients with aggressive MM. The TNF gene showed no association with predisposition to MM or clinical variant of the disease. As for MM progression, genotype CC of the IL-6 gene was associated with milder clinical signs in patients from Bashkortostan.