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Biomedical subjects

A A Lebedev

Publications and source records attributed to A A Lebedev.

At least 37 records · Page 2Linked to original sources
PubMed1998

Crystal structure of tryptophanase.

The X-ray structure of tryptophanase (Tnase) reveals the interactions responsible for binding of the pyridoxal 5'-phosphate (PLP) and atomic details of the K+ binding site essential for catalysis. The structure of holo Tnase from Proteus vulgaris (space group P2(1)2(1)2(1) with a = 115.0 A, b = 118.2 A, c = 153.7 A) has been determined at 2.1 A resolution by molecular replacement using tyrosine phenol-lyase (TPL) coordinates. The final model of Tnase, refined to an R-factor of 18.7%, (Rfree = 22.8%) suggests that the PLP-enzyme from observed in the structure is a ketoenamine. PLP is bound in a cleft formed by both the small and large domains of one subunit and the large domain of the adjacent subunit in the so-called "catalytic" dimer. The K+ cations are located on the interface of the subunits in the dimer. The structure of the catalytic dimer and mode of PLP binding in Tnase resemble those found in aspartate amino-transferase, TPL, omega-amino acid pyruvate aminotransferase, dialkylglycine decarboxylase (DGD), cystathionine beta-lyase and ornithine decarboxylase. No structural similarity has been detected between Tnase and the beta 2 dimer of tryptophan synthase which catalyses the same beta-replacement reaction. The single monovalent cation binding site of Tnase is similar to that of TPL, but differs from either of those in DGD.

Amino Acid Sequence↗
PubMed1997

[A comparative genetic analysis of the role of the brain dopaminergic systems in the regulation of behavioral elements in the "open field" test in DBA/2J and C57BL/6J mice].

The effects of intraperitoneal injections of sulpiride (10 mg/kg), bromocriptine (5 mg/kg), and alaptide (1 mg/kg) on the behavior of male C57BL/6J (C57BL) and DBA/2J (DBA) mice in the open-field test were studied. In this test, C57BL mice exhibited a significantly higher horizontal locomotor activity than DBA mice, whereas DBA mice moved in place substantially longer than C57BL mice. Dopaminergic agents had different effects on the open-field behavior in different mouse strains. Alaptide increased horizontal locomotor activity in DBA, but not in C57BL mice; all the three agents decreased the duration of movement in place in DBA but not in C57BL mice; bromocriptine suppressed vertical locomotor activity and the act of looking into holes in C57BL but not in DBA mice. Thus, interstrain differences in dopaminergic functions were demonstrated. The revealed strain-specific characteristics largely contribute to the determination of open-field behavior in the studied mouse strains.

Animals↗
PubMed1996

Structural characterization of extracellular ribonuclease of Bacillus polymyxa: amino acid sequence determination and spatial structure prediction.

The primary structure of extracellular Bacillus polymyxa ribonuclease (RNase Bpo) was established by mass spectroscopy analysis and automatic Edman degradation of the individual peptides obtained from protein digestion with Glu-specific protease V8. RNase Bpo consists of 111 amino acid residues, with a relative molecular weight of 12 607. RNase Bpo is a close structural homolog of RNases of B. amyloliquefaciens (RNase Ba) and B. intermedius (RNase Bi), the similarity of their primary structures being 68%. Molecular modelling of the structure of the complex of RNase Bpo with substrate analog d(CGAC) was performed and a spatial model based on the known crystal structure of RNase Ba complex with the corresponding nucleotide was constructed using the methods of interactive computer graphics and energy minimization. The differences in the primary and tertiary structures of the enzymes were analyzed in order to understand the substrate specificity of Bacillus RNases.

Amino Acid Sequence↗
PubMed1994

X-ray crystallographic studies of recombinant inorganic pyrophosphatase from Escherichia coli.

An E. coli inorganic pyrophosphatase overproducer and a method for a large-scale production of the homogeneous enzyme are described. The inorganic pyrophosphatase was crystallized in the form containing one subunit of a homohexameric molecule per asymmetric unit: space group R32, a = 110.4 A, c = 76.8 A. The electron density map to 2.5 A resolution phased with Eu- and Hg-derivatives (figure of merit, = 0.51) was improved by the solvent flattening procedure ( = 0.77). The course of the polypeptide chain and the secondary structure elements, intersubunit contacts and positions of the active sites were characterized. Homology with S. cerevisiae inorganic pyrophosphatase structure was found.

Binding Sites↗
PubMed1994

Crystallization and preliminary X-ray investigation of holotryptophanases from Escherichia coli and Proteus vulgaris.

Crystals of Proteus vulgaris holotryptophanase have been grown by the hanging-drop technique using polyethylene glycol 4000 as precipitant in the presence of monovalent cations K+ or Cs+. Orthorhombic crystals (P2(1)2(1)2(1)) grown with Cs+ have unit cell parameters a = 115.0 A, b = 118.2 A and c = 153.7 A and diffract to 1.8 A. There are four subunits of the tetrameric molecule in the asymmetric unit. Native data have been collected to 2.5 A resolution. The 3.4 A data were collected from tetragonal crystals of Escherichia coli holotryptophanase grown under conditions described by Kawata et al. (1991). The molecular replacement solution for this crystal form has been found using tyrosine phenol-lyase coordinates. The correct enantiomorph is P4(3)2(1)2. There are two subunits in the asymmetric unit.

Crystallization↗
PubMed1994

[The lateralized effects of the melanostatin analog alaptide in rats raised in isolation and in a community].

Effects of alaptide on self-stimulation of the lateral hypothalamus, rotation behaviour and learning ability were studied in rats growing either in social adaptation or in groups. The effects on self-stimulation were opposite in these rats. Alaptide facilitated the learning process in grouped rats and potentiated the indirect dophamine-mimetic action of amphetamine in isolated rats.

Amphetamine↗
PubMed1994

[The dopaminergic and serotoninergic components of the self-stimulation reaction of the lateral hypothalamus in rats with disruption of the medial prefrontal cortex].

Amphetamine (1 mg/kg) promoted a pedal self-stimulation of lateral hypothalamus of Wistar rats in the Skinner box. An unipolar lesion of medical prefrontal cortex with kainic acid 10-14 days prior to an experiment did not prevent the facilitating effect of amphetamine on self-stimulation, though the levels of hypothalamic noradrenaline and dopamine are 43% and 4.5-fold decreased respectively, the hypothalamic serotonin concentration not changing. Lysergic acid diethylamid (10 mkg/kg) did not influence on self-stimulation response in rats with damaged medial prefrontal cortex, but after preliminary administration prevented the stimulating effect of amphetamine on self-stimulation of lateral hypothalamus. The data are discussed from the point of view of a hypothesis that the phenomenon obtained is associated with the presence of a hypothalamic autoregulatory dopaminergic system providing the realization of self-stimulation. However, it does not exclude that the modulating influence of medial prefrontal cortex on lateral hypothalamus is connected with not only dopaminergic but with serotoninergic axons too.

Amphetamine↗
PubMed1992

[Attention and associative memory in patients with sequelae of ischemic stroke].

To study social and adaptation potentialities of 56 patients with a history of ischemic brain stroke, they were examined for attention and associative memory (AM). Use was made of neuropsychological techniques and phonooscillography of latent conditions of AM. The patients manifested deceleration and instability of all the time parameters of the process of attention (tempo, rate, quality, productivity, accuracy), its depletion (in hemispheric foci) and instability (in stem derangement), as well as a decrease of the level of active attention and of the capability of its switching over (especially in pathology of the left cerebral hemisphere). This evidences restricted potentialities of postinsult patients in adaptation. Examination of AM revealed not only a decline of the scope and deceleration of the time processes of its organization but also showed the dominant hemisphere to play an essential part in the retention (memory scope) and extraction (latent period) of mnemonic associations.

Attention↗
PubMed1992

[Treatment of patients with neurocirculatory asthenia by intermittent hypobaric hypoxia].

Rheoencephalography and electroencephalography were employed during 25 days of hypobarotherapy of 62 patients suffering from vegetovascular dystonia with different types of brain +blood circulation. The efficacy of the treatment with the aid of periodic hypobaric hypoxia turned out inconclusive which was specified by the initial status of vegetative regulation of the vascular tone and initial dyscirculatory arteriovenous alterations determining in many respects specific features of cerebrovascular reactions. The positive response to intermittent hypoxia seen in the majority of patients allows recommending the given treatment schedule for hemodynamic disorders in patients suffering from vegetovascular dystonia with different types of brain +blood circulation.

Adolescent↗
PubMed1991

[Factor analysis of the coagulative-rheological properties of blood and plasma and cerebral and general hemodynamics in patients with the initial forms of cerebrovascular insufficiency].

Coagulation and rheological, cerebrovascular and total hemodynamic factors were studied and compared in patients with the initial manifestations of brain blood supply insufficiency (IMBBSI) associated with vegetovascular dystonia, essential hypertension and atherosclerosis by means of factor analysis. Interrelations between the parameters under study appeared multiple in nature, possessing a high capacity for differentiation between those conditions. As IMBBSI progressed, namely from vegetovascular dystonia to the hypertonic and atherosclerotic disease forms, there was a rise in the rate of the prognostically unfavourable ++inter-systemic relations between hemostasis and hemodynamics attesting to a certain risk of cerebral ischemias.

Adolescent↗
PubMed1991

[Diagnosis and prognosis of lesions of the nervous system in newborn infants in cases of maternal threatened abortion].

A study was made of the status of the central nervous system in 91 neonates born to mothers with a history of threatened abortion. Using consecutive Wald's analysis the role was estimated of the clinical characteristics of pregnancy and delivery, and of the content of hormones (estriol, estradiol, progesterone, testosterone) as well as of cyclic adenosine-3,5-monophosphate, detected in the future mother over pregnancy, in the genesis of neurological disorders in the child.

Abortion, Threatened↗
PubMed1990

[Therapeutic effect of antiaggregants in patients with neurocirculatory asthenia with the initial signs of cerebral ischemia].

Therapeutic effect of antiaggregation drugs in patients with vasoautomomic dystonia with initial signs of insufficient blood supply to the brain. In 43 patients with vasoautonomic dystonia and initial manifestations fo cerebral circulation insufficiency, the effects of aggregation-inhibiting drugs (dipyrodamol, metindol, stugeron, prodectin) on blood coagulation and rheology, platelet aggregation and general hemodynamics were studied. Antiaggregation drugs were shown to be the tools of choice which could be administered with due account of baseline hemostasis and the type of cerebral hemocirculation, and of their selective action on the carotid and vertebrobasilar cerebral vessels.

Adolescent↗
PubMed1989

[Determination of the professional work capacity of patients with initial manifestations of cerebral circulatory insufficiency].

In 45 patients with initial signs of cerebral circulation insufficiency involved professionally in work demanding high attention levels, the deceleration and instability of all time parameters of attention (rate, quality, productivity, precision) was detected with its exhaustiveness increased, active attention levels and switch-over capabilities decreased. This suggested the instability and reduced mobility of nervous processes with restricted capability of adaptation to mental loading. This approach can yield clinical criteria of professional rehabilitation potentialities of these patients.

Adult↗