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Biomedical subjects

E V Smirnova

Publications and source records attributed to E V Smirnova.

At least 19 recordsLinked to original sources
PubMed2006

How can we block sympathetic overactivity? Effects of rilmenidine and atenolol in overweight hypertensive patients.

The aim of the present study was to evaluate effects of long-term treatment with rilmenidine compared with atenolol on lipid and glucose metabolism and cardiovascular remodelling in hypertension. In total, 37 patients with hypertension were randomised to rilmenidine 1-2 mg/day or atenolol 50-100 mg/day for 26 weeks. Standard oral glucose tolerance test with a parallel measurement of insulin and glucose levels was performed. The 'areas under the curve' (AUC) for insulin and glucose were calculated. Plasma lipids, left ventricular mass index (LVMI), and intima-media thickness (IMT) were measured. Brachial artery diameter during reactive hyperaemia was used to test endothelium-dependent vasodilatation (EDVD). Blood pressure reduction was equally achieved in both treatment arms. The fasting glucose level increased in the atenolol group from 4.8+/-0.6 to 5.2+/-0.7 mmol/l (P<0.01). The AUC of glucose in rilmenidine group decreased from 860+/-93 to 737+/-66 mmol/min/l (P<0.05), and in the atenolol group it increased from 937+/-86 to 989+/-88 mmol/min/l (P<0.05). Rilmenidine showed a positive effect on lipid levels, whereas in the atenolol group a significant decrease of high-density lipoprotein cholesterol was observed. Left ventricular mass index decreased with rilmenidine by 9.6% and by 6.9% with atenolol (P<0.05). Intima-media thickness significantly decreased in the rilmenidine group. Endothelium-dependent vasodilatation slightly increased on in the rilmenidine group, while on in the atenolol group it remained unchanged. Our data suggest that in hypertensive patients central inhibition of sympathetic drive can produce favourable effects on glucose and lipid metabolism compared with standard beta-blockade with a similar antihypertensive efficacy. Rilmenidine also provides beneficial effects on cardiovascular remodelling and altered endothelial function in hypertension.

Adult↗
PubMed2005

Cloning and molecular modeling of duodenase with respect to evolution of substrate specificity within mammalian serine proteases that have lost a conserved active-site disulfide bond.

Mammalian serine proteases such as the chromosome 14 (Homo sapiens, Mus musculus) located granzymes, chymases, cathepsin G, and related enzymes including duodenase collectively represent a special group within the chymotrypsin family which we refer to here as "granases". Enzymes of this group have lost the ancient active-site disulfide bond Cys191-Cys220 (bovine chymotrypsinogen A numbering) which is strongly conserved in classic serine proteases such as pancreatic, blood coagulation, and fibrinolysis proteases and others (granzymes A, M, K and leukocyte elastases). We sequenced the cDNA encoding bovine (Bos taurus) duodenase, a granase with unusual dual trypsin-like and chymotrypsin-like specificity. The sequence revealed a 17-residue signal peptide and two-residue (GlyLys) activation peptide typical for granases. Production of the mature enzyme is apparently accompanied by further proteolytic processing of the C-terminal pentapeptide extension of duodenase. Similar C-terminal processing is known for another dual-specific granase, human cathepsin G. Using phylogenetic analysis based on 39 granases we retraced the evolution of residues 189 and 226 crucial for serine protease primary specificity. The analysis revealed that while there is no obvious link between mutability of residue 189 and the appearance of novel catalytic properties in granases, the mutability of residue 226 evidently gives rise to different specificity subgroups within this enzyme group. The architecture of the extended substrate-binding site of granases and structural basis of duodenase dual specificity based on molecular dynamic method are discussed. We conclude that the marked selectivity of granases that is crucial to their role as regulatory proteases has evolved through the fine-tuning of specificity at three levels--primary, secondary, and conformational.

Amino Acid Sequence↗
PubMed2003

Graspases--a special group of serine proteases of the chymotrypsin family that has lost a conserved active site disulfide bond.

In this report we propose a new approach to classification of serine proteases of the chymotrypsin family. Comparative structure-function analysis has revealed two main groups of proteases: a group of trypsin-like enzymes and graspases (granule-associated proteases). The most important structural peculiarity of graspases is the absence of conservative "active site" disulfide bond Cys191-Cys220. The residue at position 226 in the S1-subsite of graspases is responsible for substrate specificity, whereas the residue crucial for specificity in classical serine proteases is located at position 189. We distinguish three types of graspases on the base of their substrate specificity: 1) chymozymes prefer uncharged substrates and contain an uncharged residue at position 226; 2) duozymes possess dual trypsin-like and chymotrypsin-like specificity and contain Asp or Glu at 226; 3) aspartases hydrolyze Asp-containing substrates and contain Arg residue at 226. The correctness of the proposed classification was confirmed by phylogenic analysis.

Amino Acid Sequence↗
PubMed2003

[Preparation no-shpa forte for the treatment of renal colic].

In 24 patients there was studied up the preparation Nospa-forte efficacy in renal colic occurrence due to presence of calculus in ureter, basing on analysis of the pain syndrome dynamic, the heart rhythm changes, the central and systemic hemodynamics indexes, renal function and urinanalysis. There was established efficacy of the preparation in the pain syndrome removal, the blood circulation hyperdynamics reduction, the vegetative nervous system state optimization and the heart rhythm stabilization. It is expedient to use Nospa-forte in the treatment of various visceral pain.

Adult↗
PubMed2001

A new trick for an old dog: TraY binding to a homopurine-homopyrimidine run attenuates DNA replication.

The effects of the d(GA)(n).d(TC)(n) repeat on plasmid replication in Escherichia coli cells were analyzed using electrophoretic analysis of replication intermediates. This repeat appeared to stall the replication fork progression in E. coli strains carrying F' episomes. The potency of replication stalling increased with the repeat's length but did not depend on its orientation relative to the replication origin, or transcription through the repeat. Treatment of E. coli cells with the protein synthesis inhibitor chloramphenicol abolished replication blockage, indicating that protein binding might be responsible for the repeat-caused replication blockage. Concordantly, dimethylsulfate footprinting in vivo revealed methylation protection of all guanine residues within the d(GA)(n).d(TC)(n). Gel retardation assays with crude cell extracts confirmed the presence of a d(GA)(n).d(TC)(n) -binding activity in F', but not F(-), strains. Further, strains cured from the F' episome lost this activity, while F(-) strains that acquired the F' factor via conjugation, acquired d(GA)(n).d(TC)(n)-binding activity as well. Thus, this d(GA)(n).d(TC)(n)-binding protein is encoded by the F' factor. Purification of this protein by affinity chromatography revealed a single polypeptide with an apparent molecular mass of 15.2 kDa. Microsequencing of its two tryptic peptides revealed two perfect matches with the TraY protein, which is encoded by the F factor. Overexpression of an individual TraY protein in the F(-) E. coli strain conveyed d(GA)(n).d(TC)(n)-binding activity in vitro and replication stalling at d(GA)(n).d(TC)(n) repeats in vivo. We conclude that TraY binding to a homopurine-homopyrimidine repeat is responsible for stalling DNA replication. Biological applications of this phenomenon are discussed.

Amino Acid Sequence↗
PubMed2001

[Secondary tumors in Hodgkin's disease patients].

A study is presented of second malignancies detected after treatment for Hodgkin's disease in 942 patients treated at the Institute's Clinic (1973-1993). Solid tumors were diagnosed, generally, during long complete remission, both after chemoradiation or radiotherapy (2.2 and 1.3%, respectively, p > 0.1). Yet, second tumor incidence tended to increase after combination treatment. Intestinal tumors were the most frequent. Tumors did not arise necessarily at sites which had been irradiated. Total doses absorbed by involved organs varied from 4-7 to 24-44 Gy, thus implying that absolute values of such doses did not correlate directly with risk of solid tumor development; the same was true for size of exposure fields. Dose distribution in time is of particular interest: there were no tumors among those treated with accelerated multifractionated irradiation. If radiotherapy procedures are improved and individual schedules of fractionated irradiation are used, the probability of solid tumor incidence, which, after radiotherapy of Hodgkin's disease, is not very high, can be still lowered.

Adult↗
PubMed2000

[The endogenous differentiation factor of the HL-60 cells shows a nuclease activity].

A structural homology between the endogenous differentiation factor of the HL-60 cell line of promyelocyte leukemia (HLDF) and several DNA/RNA-binding and DNA/RNA-hydrolyzing proteins was revealed, and expression of the hldf gene in prokaryotic systems was studied. On the basis of these experiments, the amino acid sequence of an 8-membered fragment of HLDF with potential nuclease activity was identified. The synthetic octapeptide RRWHRLKE was shown to be capable of the cleavage of RNA, linear DNA from phage lambda, and all forms of plasmid DNA. We established that treatment of the HL-60 cell culture with this peptide (10(-6) M) results in an increase in the number of apoptotic cells and suggested that HLDF is involved in processes of apoptosis.

Amino Acid Sequence↗
PubMed2000

Cloning and characterization of the human ribosomal protein S21 gene [.

A full-size functional gene encoding the human ribosomal protein S21 was cloned and characterized. Its nucleotide sequence, exon-intron organization, and transcription initiation site were determined. The gene comprises 1417 bp and is composed of six exons and five introns. Like most known genes of mammalian ribosomal proteins, it lacks the canonical TATA- and CAAT sequences in the promoter region and harbors potential binding sites for transcription factors both upstream and downstream the transcription initiation site. The first intron of the rpS21 gene is located in the 5'-untranslated region. The transcription initiation site is at a 53-bp distance from the ATG codon, and the initiation cytidine is surrounded by polypyrimidine tracts. The 5'-flanking region contains two repeats belonging to the Alu-S and Alu-J families.

Base Sequence↗
PubMed1997

[Nucleotide sequence of cDNA and organization of the gene for alpha-subunit of photoreceptor phosphodiesterase of cyclic GMP in human retinal cones].

Five clones were isolated from a human retina cDNA library whose cDNA inserts allowed reconstruction of the total sequence of the human clone cGMP phosphodiesterase alpha'-subunit cDNA comprising 3455 bp. The protein's deduced sequence contains 858 amino acids residues with molecular mass 99,169 Da. A substantial homology was revealed between the amino acid sequence of the human cones cGMP-phosphodiesterase alpha'-subunit and the corresponding sequences of alpha, beta, and alpha' subunits of visual cGMP-phosphodiesterase of bovine, murine, chicken and human retinas. Four recombinant bacteriophages were isolated from a genomic library whose inserts made it possible to reconstruct a 32-kb fragment of the human cones cGMP-phosphodiesterase alpha'-subunit gene. 5'-Flanking region of the gene and first 14 exons, encoding an N-terminal segment of the protein, along with the adjacent intron segments were sequenced.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1996

Human cone-specific cGMP phosphodiesterase alpha' subunit: complete cDNA sequence and gene arrangement.

Four independent phage clones containing the fragments of cone-specific cGMP phosphodiesterase (PDE) alpha' subunit (PDE-alpha') cDNA were isolated from the human cDNA library. The screening of the genomic library resulted in isolation of four independent phage clones with the fragments of human cone PDEalpha' gene including 5'-flanking region and exons ranged from 1 to 14 (overall 32 kilobases). Structural studies of the clones made it possible to establish the complete human cone PDEalpha' cDNA structure (3455 base pairs). The encoding polypeptide consists of 858 amino acid residues with a calculated molecular mass of 99169 Da. The deduced amino acid sequence displays high homology to the earlier analyzed catalytic alpha, beta and alpha' subunits of bovine, human, chicken and mouse photoreceptor PDEs.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1996

[Method of adaptometry in the evaluation of gastric secretory function in children under conditions of the North].

Some ways of evaluating the man-made environmental tension of populations are proposed. Using the parameters of gastric secretion, the authors made a comparative analysis of man-made environmental tension in various ethnic children populations when they had different recreation and diets in autumn and spring. To study the nature of adaptative changes, correlation adaptometry was chosen, which is currently the most accessible for processing and the most accurate in reflecting tension dynamics in the study groups. The findings indicate high man-made environmental tension of the digestive system in children from all ethnic groups. Moreover, dysadaptation was found in the children of newcomers and the North's nationalities on the European nutrition style.

Adaptation, Physiological↗