Biochemical polymorphism of the growth hormone system proteins and its manifestations in human prostate cells.

The basic mechanisms are considered that are responsible for producing biochemical polymorphism of human proteins realized at three basic levels: the structures of genome and genes; the transcription and maturation of transcripts; the postsynthetic formation of functionally active protein products of gene expression. The data on biochemical polymorphism of growth hormone (GH) and some other proteins that are directly or indirectly necessary for its functioning and support this polymorphism by polylocus, polyallelism, alternative splicing, and various postsynthetic modifications are analyzed. The role of polymorphic proteins of the GH system is discussed in formation of a variety of oligomeric molecular structures of this system (multicomponent transport complexes, receptors, and endocellular protein ensembles involved in the regulation of gene expression).

[A study of the single nucleotide polymorphism in seven genes (GHR, IGFBP3, IGFR1, IRS1, FMN1, ANXA2, TaGLN) in ethnic Russians and in patients with prostate cancer].

Using the RT-PCR method for allele discrimination, we examined nine known SNPs in seven genes (GHR, IGFBP3, IGFR1, IRS1, FMN1, ANXA2, TaGLN) in ethnic Russians and in patients with prostate cancer (PC). For Russian population data on genotype distribution in studied SNPs was obtained. It was revealed that six of nine analyzed sites in examined locus were polymorphic.

[NP-detecting DNA technologies: solving problems of applied biochemistry].

Heterozygosity of CANP3, ACTN3, and GHR genes in specialized collections was studied using state-of-the-art DNA technologies for DNA analysis. A new dinucleotide deletion (AC) at the beginning of exon 21 was identified in five individuals with heterozygous CANP3 gene. Analysis of polymorphism (SNP1747 C-->T) of ACTN3 gene demonstrated a positive association of allele C with a high muscular performance.

[Human myoblast culture as muscle stem cells in medical and biological studies].

The method for obtaining human myoblast culture has been modified to consider the specific histological localization of the satellite cells as well as their growth properties; the cultivation conditions have been selected to grow up to 150000 cells/cm2. At high densities, the cells remain mononuclear and preserve their typical myoblast morphology as well as the capacity for fusion and the formation of myotubes. By contrast to fibroblasts, up to 80% of the cells in the myoblast culture were positive in the acid phosphatase test, which indicates their stem nature.

[Clinical polymorphism, genetic heterogeneity and primary myopathy pathogenesis problems].

The peculiarities of clinic picture of primary myopathies with general gene defects, in particular differences in disease debut, dystrophy severity and degree of diverse muscle group's involvement in the dystrophic process, were analyzed. An attention was drawn specially to the cases of similar and identical mutations, including family cases, which gave rise to dramatically different pathological phenotypes. This information, along with the Becker muscular dystrophy cases (with deletions of DMD gene), describing the patients, aged 55 to 60 years, who maintained a certain movement activity, allow to revise an absolutely severe prognosis of primary myopathies and to stimulate primary myopathy pathogenesis studies.

[Dystrophin gene expression in patients with Duchenne muscular dystrophy after myoblast transplantation].

Based on originally designed technique of myoblast cultivation and in accordance with the approved by the Russian Ministry of Health "one muscle treatment" protocol of myoblast transplantation to the Duchenne muscular dystrophy patients, the first in Russia clinical trial of this gene correction method was carried out. Immonologically related myoblast cultures (30 to 90 million cells per patient) were injected after all preliminary procedures into tibialis anterior muscles of four boys selected from a group of volunteer recipients (Duchenne muscular dystrophy patients) based on the analysis of a number of surface antigens in donor-recipient pairs. The condition of the patients remained satisfactory during the whole period of post-transplantation follow-up (from 6 months to 1.

[Polymorphism of exon 4 in the CANP-3 gene in patients with primary myopathies].

The structures of the gene for calpain (CANP-3) and of the DMD gene were analyzed in patients with primary myopathies [limb-girdle muscular distrophy (LGMD) and Duchenne-Becker myodystrophy (DBM)] from various regions of Russia. Via amplification of DNA isolated from the peripheral blood lymphocytes of 74 patients, extended deletions were found in 18 out of 55 patients with DBM. In none of the 19 patients with LGMD, were extended deletions in the CANP-3 gene found.

High incidence of 550delA mutation of CAPN3 in LGMD2 patients from Russia.

Autosomal recessive limb gird muscular dystrophy (LGMD2) is a clinically and genetically heterogeneous group of diseases that are characterized by progressive atrophy and weakness of the proximal limb muscles. At least eight genetic loci leading to LGMD2 are recognized. The proportion of particular gene involved in producing different forms of LGMD2 shows a marked geographical variation.

[The use of low doses of prednisolone for the treatment of patients with Duchenne-Becker myodystrophy].

A special program for long-term application of low-dose prednisolone treatment in Duchenne-Becker muscular dystrophy with complex control of the patients' state was developed. Three-month cycles of prednisolone treatment alternated with three-month cycles of placebo during the year. Each patient received 0.

[A databank on Russian families with hereditary neuromuscular diseases].

The information about 5 thousands Russian families with hereditary neuromuscular disorders (HNMD) was collected by means of both different genetic epidemiological methods and authors' own observations. On the basis of this material a computer database MYODYS in Excel 5.0 format was created, which included information about 30 different signs concerning 1920 families from 70 regions of Russia.

[The dystrophin gene structure in patients with Duchenne myodystrophy].

The study was performed of the alterations within 17 exons and promoter region of dystrophin gene by means of multiplex DNA amplification in boys of Slavonic population with clinical diagnosis of muscular Duchenne's dystrophy. The dystrophin gene's deletions were found in different exons of 11 boys from 33 examined families, that is in 33% of the families. In 8 cases the deletions were clustered near a central part of dystrophin gene.

[Effect of cyclosporin on various metabolic processes in fungi].

Sensitivity of the representatives of Aspergillus and Piricularia to various concentrations of cyclosporine (in the submerged culture) was studied for choosing the test object for the subcellular investigation of the mechanism of the cyclosporine antifungal action. Changes in the main physiological and biochemical parameters of the fungal cells under the action of cyclosporine in concentrations of 10 to 80 micrograms per 1 ml of the medium were characterized. Low concentrations of cyclosporine (10 to 20 micrograms/ml) did not inhibit the growth of Aspergillus niger but induced stimulation of the growth processes.

[Dynamics of the content of glycolysis enzymes in Streptomyces rimosus as it relates to the problem of regulation of oxytetracycline biosynthesis].

The activities of the key glycolytic enzymes i.e. hexokinase, phosphofructokinase, pyruvate kinase and lactate dehydrogenase were detected and investigated in 3 strains of Streptomyces rimosus differing in the level of the oxytetracycline production.

[Activity of glycolysis enzymes in cyclosporine-producing Tolypocladium sp].

Enzymes of various glycolysis stages, i.e. hexokinase, phosphofructokinase, pyruvate kinase and lactate dehydrogenase, were detected in cyclosporine-producing organisms belonging to Tolypocladium.

[Cloning in Escherichia coli of a mitochondrial DNA fragment from Acremonium chrysogenum containing a region responsible for DNA replication].

A bireplicone plasmid pSU901,4.6 kb in length, was constructed on the basis of plasmid pUC19 and the pstIB fragment, 1.9 kb in length, from mitochondrial DNA of A.

[High-molecular polyphosphates and pyrophosphate in cyclosporin- producing Tolypocladium sp. and their role in the processes of growth and antibiotic synthesis].

The contents of high-energy phosphorous compounds, i.e. three fractions of polyphosphates, pyrophosphate, and ATP were determined in isogenic strains of Tolypocladium sp.

[Isolation and characteristics of mitochondrial DNA from Acremonium chrysogenum].

Circular mDNAs 26.85 and 26.94 kb in length were isolated from two isogenic strains of A.

[Pathways of the synthesis of glutamic acid by cephalosporin C-producing Acremonium chrysogenum].

There were observed two pathways of glutamic acid formation in two strains of Acremonium chrysogenum differing in the production levels of cephalosporin C. The pathway involving glutamate dehydrogenase is known. The other pathway involved amination catalyzed by glutamine synthetase.

[The protoplasts of Acremonium chrysogenum. Biochemical and morphological studies].

A procedure for preparing stable A. chrysogenum protoplasts capable of 60 per cent regeneration was developed. Two morphogenetic types of the regeneration were detected.

[Valinomycin biosynthesis and the dynamics of the content of macroergic phosphorus compounds in Streptomyces cyaneofuscatus].

The pattern of accumulation and consumption of macroergic phosphoric compounds such as polyphosphates, pyrophosphate and ATP in the mycelium of the valinomycin-producing organism was studied. The content of high polymeric polyphosphates in the high productive strain A of S. cyaneofuscatus was much lower than that in the isogenic low productive strain B, which was indicative of their participation in providing bioenergetics of antibiotic production.

[Metabolic characteristics of polyphosphates and other macroergic phosphorus compounds in relation to the degree of penicillin production and growth conditions of Penicillium chrysogenum].

Metabolism of macroergic phosphorus compounds was studied in high- and low-productive isogenic strains of Penicillium chrysogenum. It was shown that the levels of the high-polymer polyphosphates (fractions PP1, PP2 and PP3) in the strain intensively producing penicillin were 2-3 times higher than those in the low-productive strain by the 2nd day of the fermentation process (the period of penicillin production). The levels of pyrophosphate and ATP in the mycelium during the fermentation process did not significantly differ in the strains.

[Possible role of the respiratory system of Fusidium coccineum in regulating fusidic acid biosynthesis].

The respiration system was studied in three strains of the fungus Fusidium coccineum differing in their capability to synthesize fusidic acid. In all of the three strains, the system of oxidative phoshorylation predominated in supplying the cells with energy. In the strains with low and zero activities, the terminal oxidation of reduced equivalents occurred mainly via the respiration chain with cytochrome oxidase as a terminal component.

[Photoreduction of bacteriophenophytin b in the primary light reaction of Rhodopseudomonas viridis chromatophores].

Photoconversions of the reaction center pigments in chromatophores of nonsulfur purple bacteria Rhodopseudomonas viridis have been studied as a function of redox potential of medium (Eh). It has been shown that at a decrease in the Eh values from +400 mV to--100 divided by--600 mV a photo-induced accumulation of P980+ (oxidized primary electron donor in R. viridis) is replaced by the photoaccumulation of a reduced pigment complex P800 (bleaching of bacteriopheophytin b absorption bands at 545 and 800 nm, a development of broad bands at 680 and 430 nm and a blue shift of the bacteriochlorophyll band at 830 nm).

Photooxidation of P-960 and photoreduction of P-800 (bacteriopheophytin b-800) in reaction centers from Rhodopseudomonas viridis.

The light excitation of P-960 results in the oxidation of P-960 and the reduction of P-800 (bacteriophytin b-800) in the reaction centers from Rhodopseudomonas viridis. A negative 847 nm band of the circular dichroism psectrum disappears under P-960 photooxidation, while a positive 827 nm band disappears under P-800 photoreduction. Exciton interaction of the pigment molecules in the reaction center is discussed.