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Biomedical subjects

O S Brusov

Publications and source records attributed to O S Brusov.

At least 19 recordsLinked to original sources
PubMed2005

[Structure of peripheral blood platelets surface in patients with amyotrophic lateral sclerosis and multiple sclerosis].

Using scanning electronic microscopy of peripheral blood platelets in 32 patients with amyotrophic lateral sclerosis (ALS) and 6 patients with multiple sclerosis (MS), platelets activation, emerging in pseudopodiums formation, aggregation and lysis, was found. Platelets activation was more pronounced in ALS than in MS. It was most markedly seen for quantitative evaluation of the above traits. The features of platelet activation found in the study support the evidence for considering ALS as a systemic disorder being characterized by a broad spectrum of alterations of biological processes.

Amyotrophic Lateral Sclerosis↗
PubMed2005

[Parameters of platelet serotonin system in patients with schizophrenia treated with olanzapine: a search for the serotonergic predictors of therapeutic efficacy].

Fifty-nine patients, 21 women and 38 men, with ICD-10 diagnosis of schizophrenia (F20.0), attack-like type, were treated with olanzapine during 28 weeks (8-weeks of acute and 20-weeks of maintenance therapy). Evaluation of clinical symptoms measured by the Positive and Negative Syndromes scale (PANSS) revealed that female patients responded better to therapy as compared to male ones, with PANSS total, PANSS negative and PANSS general psychopathological scores being significantly reduced (p < 0.006) in females after 1 week of the treatment and in males--after 2 weeks. In the female group, a reduction of PANSS total score by 50% in the acute stage of treatment qualified as a very good response was observed in 7 (33%) patients and in the male group--in 1 (2.7%). The between-groups difference was highly significant (p = 0.002). When examined for a rate of 3H-serotonin uptake into platelets, density of sites of 3H-imipramine binding on the whole platelets, platelet serotonin level and levels of high- also low-molecular weight forms of platelet immunoreactive serotonin transporter protein, a significant decrease of the platelet serotonin level, comparing to controls, was detected in the female group before treatment. During the treatment, this parameter gradually increased up to control level. Other parameters did not change significantly for 28-weeks of therapy and did not differ from the control values. There were positive correlations between the levels of platelet serotonin before treatment and subsequent reduction of the PANSS total and positive subscale scores in the female group. In responders with a very good treatment-related response, the serotonin level in the platelets before treatment was higher compared to the values in resistant patients: 5.4 +/- 2.5 and 2.7 +/- 1.3 nmol/10(9) cells, respectively. Relative risk (RR) of unfavorable treatment outcome in patients with initially reduced levels of platelet serotonin was approximately twice lower (RR = 1.83; Cl 95% 1.1-34.9) than that in patients with normal or elevated levels of platelet serotonin. The results suggest that selection of patients with initial higher level of platelet serotonin before olanzapine treatment can reduce the risk of non-responding to therapy by 36%.

Adult↗
PubMed2004

Analysis of serotonin transporter in human platelets by immunoblotting using site-specific antibodies.

We have produced a panel of site-specific antibodies recognizing different regions of the human serotonin transporter (SERT). This panel included: 1) monoclonal antibodies 23C5 (mAbs 23C5) to the C-terminal region (amino acid residues 597-630); 2) polyclonal antibodies (pAbs) to the N-terminal region (amino acid residues 69-83); 3) pAbs to the region (amino acid residues 86-100) in the beginning of the first transmembrane domain (TMD). The antibodies were produced using recombinant proteins and synthetic peptides (containing certain sequences of SERT) as antigens. These antibodies were purified by affinity chromatography, conjugated to horseradish peroxidase (HRP), and used for immunoblotting analysis of SERT in extracts of human platelets. Sodium dodecyl sulfate extracts were prepared under conditions preventing non-specific proteolytic degradation of the proteins. In platelet extracts, all antibodies were able to detect the 67 kD protein, apparently corresponding to full-length SERT molecule (its theoretical mass is about 70 kD). These antibodies also detected several polypeptides of smaller size (56, 37, 35, 32, 22, and 14 kD), apparently corresponding to N-terminal, C-terminal, and non-terminal SERT fragments. Specificity of immunostaining was confirmed by preincubation of HRP-labeled anti-SERT antibodies with excess of corresponding antigen, which resulted in disappearance of protein band staining. It is suggested that SERT undergoes a programmed proteolytic cleavage (processing) resulting in formation of several SERT-derived polypeptides of smaller size. It is possible that one of the cleaved SERT species is required for serotonin transport activity. Possible sites for specific proteolysis may be located in the region near TMD1 and in the intracellular loop between TMD4 and TMD5.

Amino Acid Sequence↗
PubMed2003

[Association of homozygosity for short allele (S) of heavy neurofilament subunit gene with motor neuron disease and oxidative stress development].

We analyzed distribution of heavy neurofilament (NF-H) gene S/L-polymorphic variants in 51 patients with idiopathic motor neuron disease (MND) vs control group and in relation to superoxide dismutases (SODs) activity and thiobarbituric acid reactive substances (TBARS) level in cerebrospinal fluid (CSF), erythrocytes and blood serum. We found that individuals with homozygosity for NF-H gene short allele (S/S-genotype carriers) in MND group predominate significantly over those in control one (p < 0.001). We revealed significant increase of oxidative markers in CSF and blood serum in MDN patients vs controls (p < 0.05), but not in patients with spondylogenic myelopathy, conforming non-specific role of oxidative stress in MND pathogenesis. There were no differences between TBARS level in CSF and serum in relation to the rate of MND progression, suggesting that oxidative stress does not influence the MND course. We showed normal SOD-1 activity in erythrocytes and CSF of MND patients that argued for the absence of these antioxidant enzymes deficiency in MND without SOD-1 gene mutations. We found significant association between homozygosity for short allele (S) and increased TBARS level in CSF (p < 0.02). These findings specify the role of NF-H with lower molecular weight in MND pathogenesis and make expedient antioxidants administration to MND patients homozygous for S-allele of NF-H gene.

Alleles↗
PubMed2003

[Peculiarities of sporadic motor neuron disease associated with D90A and G12R mutations in Russian population].

Fifty-one blood samples of Russian patients with sporadic motor neuron disease were examined for mutations in Cu/Zn superoxide dismutase (SOD-1) gene. One female patient with amyotrophic lateral sclerosis (ALS) was heterozygous for G12R mutation. This patient suffered from ALS with cervical cord onset, pyramidal variant and fast progression. Mutation was also detected in her healthy son. Earlier, such mutation was described in 5 Italian patients with slow progressive ALS. Also, D90A SOD-1 gene associated haplotypes of the female ALS patients previously examined by the authors have been analyzed. A homozygous female patient with ALS was characterized by typical lumbar onset and extremely slow progression, as well as a female patient with heterozygous mutation and moderate progression carried so-called "Scandinavian" haplotype. To our knowledge, it is the first report on the finding of the haplotype considered as a "protective" one in the subjects heterozygous for D90A mutation with clinical symptoms of ALS. Mechanisms of "protective" influence of this haplotype on ALS course are not yet elucidated. Our finding suggests that the presence of "Scandinavian" haplotype does not completely protect from the disease development in patients exposed to other more pathogenic causative factors. This assumption is in line with modern conceptions on motor neuron disease as a complicated multifactor disorder.

Aged↗
PubMed2001

[Levels and molecular heterogeneity of serotonin transporter protein in platelets of patients with different mental diseases: a comparative analysis with the use of monoclonal and polyclonal antibodies].

Polyclonal (PAb) and monoclonal (MAb) antibodies to CT2-epitope of the C-terminal fragment of serotonin transporter (SERT) protein were used to study the levels and molecular heterogeneity of platelet SERT in healthy donors and patients with affective (AD) and somatoform (SD) disorders, schizoaffective disorder (SAD) and schizophrenia. SERT was found to exist as high molecular wight (HMW) and low molecular weight (LMW) forms separated after electrophoresis. The levels of HMW and LMW forms of SERT were significantly, decreased in mentally ill patients as compared to healthy individuals. Unlike PAb, horse radish peroxidase (HRP)-conjugated MAbs were more sensitive and specific to SERT and could detect the LMW form of SERT as a duplet protein form with MW about 40 and 43 kDa. The MAb to CT2 C-terminal fragment of SERT conjugated with HRP is considered to be a new valuable tool for further investigation of SERT expression, properties, and posttranslation modification in the controls and in patients with different psychopathology.

Adult↗
PubMed2000

[The degradation of glycoproteins with lithium borohydride. Isolation and analysis of O-glycopeptides with reduced C-terminal amino acid residue].

By the example of fetuin and a blood-group-specific mucin from porcine stomach, we showed that, under conditions of reductive degradation of glycoproteins with LiBH4-LiOH in 70% aqueous tert-butyl alcohol, the reduction and cleavage of amide bonds occur much faster than the simultaneous beta-elimination of carbohydrate chains O-linked with Ser and Thr residues of the peptide chain. The major degradation products containing the O-linked glycans are the O-glycosylated derivatives of 2-aminopropane-1,3-diol and 2-aminobutane-1,3-diol (the products of reduction of glycosylated Ser and Thr) and the glycopeptides containing 2-4 amino acid residues with reduced C-terminal amino acid. Seventeen homogeneous O-glycopeptides were isolated from the fetuin degradation products by ion-exchange and reversed-phase HPLC. Their structures were determined by MALDI-TOF mass spectrometry and by analyses for amino acids, amino alcohols, and carbohydrates. The application of the reaction for characterization of O-glycans and localization of O-glycosylation sites in O- and N,O-glycoproteins is discussed.

Animals↗
PubMed2000

[Specific aspects of thrombocyte system of serotonin in patients with different manifestations of schizoaffective psychosis].

45 women with different manifestations of schizoaffective psychosis (SAP) were examined. The diagnosis corresponded to ICD-10 (F25). According to the classification elaborated in Mental Health Research Centre of Russian Academy of Medical Sciences, groups of patients were identified with different variants of the psychoses course: a nuclear SAP type; a borderline SAP variation with phasic-recurrent course; SAP with progredient variation (schizoaffective variation of schizophrenia). The patients were examined both during the attack and remission. A rate of serotonine uptake (Vmax) in blood platelets, a specific imipramine binding (Bmax) and the level of serotonin in blood platelets were evaluated. It was found that dynamics of both Vmax and the level of serotonin in different SAP types were different, that was related to clinical and biological SAP heterogeneity. A tendency to decreasing of serotonin system functional activity was found in progredient SAP variations, especially during the remission, which was of low quality in these cases. On the contrary, in the borderline variations the indices of the decreased function of serotonin system corresponded well to those of acute psychosis. In nuclear type--a type with the most favourable course of psychosis--any significant changes weren't revealed as compared with the normal parameters.

Acute Disease↗
PubMed1999

[The status of serotonin protein -- a serotonin transporter in thrombocytes in patients with somatoform disorders].

The role of serotonin transporter (SERT) protein in the development of somatoform disorders (SD) was investigated. An association study was performed in terms of the evaluation of the level of SERT immunoreactive (IR-SERT) protein using site-specific antibodies directed at SERT C-terminus fragment, poorly conserved among the other cotransporters. The level of the anxious symptomatology was also estimated in the patients with SD. 22 patients, who met DSM-IV criteria for somatoform disorders, and 32 normals were examined. In platelets from normals, IR-SERT protein migrated as a difuse band between 68 and 105 kDa, and a major sharper band at 43 kDa. Almost complete disappearance of platelet 43 kDa IR-SERT protein band was observed in most of the patients with SD. These findings permitted to suggest a possibility of either biosynthetic or processing abnormality of SERTs in the affected population, that might reflect a dysfunction of serotonin neurotransmission in CNS of the patients with SD.

Adult↗
PubMed1998

[The indices of the thrombocyte serotonin system and of the nerve growth factor system in children with hereditary disorders of neuropsychic development].

Indices of both platelet serotoninergic system and the system of nerve growth factor (NGF) were examined in children with neurofibromatosis (15 patients), polygenic oligophrenia (24 patients) and Rett's syndrome (14 ones). There was an increase of both the level of blood serum autoantibodies (aAB) to NGF and the value of specific binding of 3H-imipramine (Bmax) in platelets of patients with oligophrenia. For this group of patients a significant negative correlation exists between the rate of platelet uptake of serotonin (Vmax value) and the degree of mental retardation (r = -0.425, p < 0.03). Decrease of both Vmax and activity of platelet NGF receptors was revealed in patients with neurofibromatosis. In such patients there was positive correlation between sensitivity of platelet NGF receptors to NGF (during their stimulation by test dose of purified NGF) and the degree of mental retardation (r = 0.697, p < 0.04). In patients with Rett's syndrome a significant increase of activity of platelet NGF receptors to NGF was observed. The conclusion was made on the existence of some general mechanism of intellectual defect development. Autoimmune processes considered to be such mechanism.

Adolescent↗
PubMed1996

[A clinico-biological study of the thrombocyte serotonin-transport complex in therapeutically resistant patients with endogenous depression undergoing combined treatment].

The platelet parameters of the functional status of the serotonin-reuptake complex were studied in drug-resistant depressive patients given various regimens of complex therapy or selective serotonin re-uptake inhibitors (fluvoxamine and fluoxetine). The most persistent and marked clinical effect was seen in electroconvulsive therapy and it was due to the normalization of the serotonin-reuptake system.

Adult↗
PubMed1995

[The thrombocytic serotoninergic markers of the efficacy of electroconvulsive therapy in endogenous depressions].

The changes of main platelet serotonergic parameters (maximal velocity of 3H-serotonin uptake, Vmax; and density of (3)3H-imipramine binding sites, Bmax) were followed up in 25 endogenously depressed patients before and after electroconvulsive therapy (ECT). It was found a marked decrease in the velocity of 3H-serotonin uptake into platelets (Vmax) from patients before ECT (especially in non-responder group) and the significant increase of Vmax- and Bmax-values after the course of ECT in responders but not in resistant patients (non-responders). The increase of Vmax- and Bmax-values in responders was evidence of the rise of the functional activity serotonin system after treatment. The results evidence about the significance of serotonergic-mechanisms in the therapeutic efficacy of ECT.

Adult↗
PubMed1995

[Thrombocytic serotoninergic markers in therapy-resistant patients with endogenous depression undergoing alpha-tocopherol treatment].

The main platelet serotoninergic parameters (maximal velosity of 3H-serotonin uptake, Vmax and density of 3H-imipramine binding sites, Bmax) were measured in 17 therapy-resistant endogenously depressed patients before and after combined treatment (antidepressants and alpha-tocopherol). It was found a significant decrease of Vmax-, Vmax/Bmax- values and the increase of Bmax- values in patients before treatment. A beneficial effect of the combined therapy was found in 47% of patients. However, it was not followed by the changes of main platelet serotoninergic parameters in patients after treatment in spite of the obtained clinical improvement. There were not also observed the significant differences of measured biochemical parameters between responders and non-responders. These findings suggest that the beneficial clinical effect of the combined antidepressive therapy with alpha-tocopherol does not involve serotoninergic mechanisms.

Adult↗
PubMed1992

[Nerve growth factor and the state of serotoninergic system in endogenous depression and mental retardation].

Platelet parameters of the serotonin system were studied in patients with endogenous depressions and children with late documented phenylketonuria (PKU) before and after antidepressive therapy. There was a significant decrease in the rate of back platelet uptake of 3H-serotonin and an increase in the sensitivity of serotonin receptors to serotonin in the patients before therapy and normalization of these parameters after therapy. The normalization correlated with clinical improvement in patients with endogenous depression. The course therapy with L-DOPA and the antidepressant azaphen resulted in a substantial mental improvement in children with PKU. There was a significant reduction in the ability of platelets from the patients in question to react by releasing 3H-serotonin in response to nerve growth factor stimulation of cells in vitro.

Adolescent↗
PubMed1992

[The characteristics of thrombocyte morphological structure in patients with endogenous depression during antidepressant therapy].

The study of platelets surface in patients with endogenous depressions made before the beginning of therapy, 1-3 days later and during the first days of clinical recovery with scanning electron microscopy showed that the platelets of patients who had not received antidepressants were activated. More marked activation took place after long-term therapy in the form of platelets with distinct pseudopodia, which were 2-3 times longer than cells body and with inclination to form large aggregations. This cell type is also characterized by formation of a new type of rod platelets. It is suggested that antidepressants accumulation takes place on cell membrane during long-term therapy that causes selective or general increase of membranes permeability, cytotoxicity.

Adolescent↗