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Biomedical subjects

A A Fedorov

Publications and source records attributed to A A Fedorov.

At least 19 recordsLinked to original sources
PubMed2006

A common system of sparsely-branched projection (reticular) NADPH-diaphorase neurons in formations of densely-branched cells in the human forebrain.

Morphometric studies of human forebrain formations composed of densely branched cells - the entorhinal cortex, the basolateral amygdala, the nucleus accumbens, the striatum, and the dorsal thalamus - were performed using nine parameters, with statistical analysis of the resulting data; measurements addressed the major projection-type densely branched and sparsely branched reticular neurons (scattered reticular and marginal reticular cells of the dorsal thalamus) stained by the Golgi method and with NADPH-diaphorase. Scattered reticular cells in the various formations showed no differences in any of the nine measures, while there were significant differences (in 5-7 measures, apart from one comparison, where there were differences in two measures) in their major projection-type densely branched cells. Scattered reticular and main projection-type densely branched neurons in each formation differed in terms of 7-9 measures. In endbrain formations, scattered reticular neurons contained NADPH-diaphorase; in the dorsal thalamus, only intermediate marginal reticular neurons were NADPH-diaphorase-positive. Thus, these human formations contained a common system of ancient integrative NADPH-diaphorase-containing reticular cells. Our results, along with published data, show these to be projection-type cells with projections to layers V and VI of the neocortex, which suggests that they have modulatory influences on its descending systems.

Adult↗
PubMed2004

Effect of Noolit, a novel lithium preparation, on electrophysiological activity of rat cerebral cortex.

The effects of lithium carbonate and Noolit, a novel lithium enterosorbent, on electrophysiological activity of cerebral cortex in rats were compared. Both agents potentiated the theta-, alpha-, and beta-rhythms and modified the response to rhythmic flash stimulation from potentiation to inhibition of cerebral rhythms. Moreover, these drugs increased dispersion of all rhythms. By contrast to lithium carbonate, the effect of Noolit was milder and developed more slowly.

Alpha Rhythm↗
PubMed2004

Neurons of the basal ganglia of the human brain (striatum and basolateral amygdala) expressing the enzyme NADPH-d.

Types of NADPH-d+ neurons (Vincent et al., 1983) were identified in the striatum and basolateral nuclei of the amygdala; striocortical neurons were detected in the striatum using the DiI marker (Belichenko and Dahlström, 1995). NADPH-d+ cells were numerous. Staining of these cells and all their processes, along with our previous studies of the neurons in these formations in the human brain using the Golgi method, allowed us to identify their shapes and identify them as sparsely or extensively branched cells. The main efferent neurons of the striatum and basolateral amygdala (extensively branched medium spiny cells and bushy spiny cells respectively) and their extensively branched interneurons did not contain NADPH-d. Efferent NADPH-d+ neurons included reticular, sparsely branched cells with long dendrites, which were the most numerous cells in both formations, as well as occasional large multipolar branched neurons; the striatum also contained numerous sparsely branched short-dendrite cells (a neuron type most represented in the brainstem and especially the reticular formation). Projections of reticular cells from the striatum to the cortex were demonstrated. NADPH-d+ interneurons were sparsely branched: in the striatum, these were slender, long-dendrite, bipolar cells (numerous), ordinary bipolar cells, twisted and large dendrite-poor cells; the amygdala contained the same bipolar cells along with radial neurons. Thus, NADPH-d+ neurons in these formations were more ancient, i.e., structurally less complex, cell types.

Adult↗
PubMed2003

[Experimental and morphological as well as physical and chemical interaction of laser radiation of a close infrared range with the fibrous eye membrane].

Experimental-and-morphological as well as physical-and-chemical changes occurring in the eye fibrous coat tissues, i.e. the cornea and sclera, at non-ablation impact of fiber laser radiation (Er-glass) with a wavelength of 1.56 mcm were analyzed. Necrobiotic or necrotic changes occur in the tissues with regard for laser radiation capacity and impact duration; subsequently, the regenerative process involving a retraction of the sclera and a flattening of the cornea takes place in the end. When the cornea is heated by fiber laser radiation with a minimally possible intensity (up to 0.3 Wt), a temporary weakening is observed in the corneal rigidity. Should it be accompanied by a simultaneous occurrence of retraction forces coming from the sclera (at its coagulation), it can be used to change, in the clinical controllable mode, the corneal curvature radius.

Cornea↗
PubMed2002

[Neurons of the human basal ganglia (striatum and basolateral amygdala) expressing the enzyme NADPH-d].

In human striatum and basolateral amygdala NADPH-d+ neurons were revealed (after Vincent et al., 1983); and in striatum strio-cortical neurons were also revealed using DiI marker (after Dahtstrom and Belichenko, 1995). The NADPH-d+ neurons were numerous in both formations. Staining of NADPH-d+ neurons with their processes, and our previous study of striatal and amygdalar human neurons by Golgi method made it possible to identify the species of neurons with their assessment as sparsely or densely branched. The main efferent neurons of striatum and basolateral amygdala (densely branched medium spiny and bushy spiny, respectively) and their densely branched interneurons were not marked. Efferent NADPH-d+ neurons included the most numerous ones in both formations. A projection of reticular striatal neurons to cortex was also shown. The NADPH-d+ interneurons belonged to sparsely branched forms. In striatum they included slender-dendritic and long-dendritic bipolars (numerous), ordinary bipolars, twisted and large poor-dendritic cells; in amygdala--the same bipolars and radial cells. Thus, the NADPH-d positive cells in the formations under study were represented by more "ancient" or less structurally complex cell forms.

Adult↗
PubMed2001

Structural basis for co-stimulation by the human CTLA-4/B7-2 complex.

Regulation of T-cell activity is dependent on antigen-independent co-stimulatory signals provided by the disulphide-linked homodimeric T-cell surface receptors, CD28 and CTLA-4 (ref. 1). Engagement of CD28 with B7-1 and B7-2 ligands on antigen-presenting cells (APCs) provides a stimulatory signal for T-cell activation, whereas subsequent engagement of CTLA-4 with these same ligands results in attenuation of the response. Given their central function in immune modulation, CTLA-4- and CD28-associated signalling pathways are primary therapeutic targets for preventing autoimmune disease, graft versus host disease, graft rejection and promoting tumour immunity. However, little is known about the cell-surface organization of these receptor/ligand complexes and the structural basis for signal transduction. Here we report the 3.2-A resolution structure of the complex between the disulphide-linked homodimer of human CTLA-4 and the receptor-binding domain of human B7-2. The unusual dimerization properties of both CTLA-4 and B7-2 place their respective ligand-binding sites distal to the dimer interface in each molecule and promote the formation of an alternating arrangement of bivalent CTLA-4 and B7-2 dimers that extends throughout the crystal. Direct observation of this CTLA-4/B7-2 network provides a model for the periodic organization of these molecules within the immunological synapse and suggests a distinct mechanism for signalling by dimeric cell-surface receptors.

Abatacept↗
PubMed1999

Morphological study of the entorhinal cortex, hippocampal formation, and basal ganglia in Rett syndrome patients.

Entorhinal cortex (EC), fascia dentata (FD), hippocampus (HP), and basal ganglia (BG) were studied in Rett syndrome (RS) cases and compared with control brains and an autism case. Kluver-Barrera and Golgi methods were used. In RS most of the areas of EC, HP, and FD showed severe cell hypochromia. In the EC all cells of layer II and most in layer III were in a state of total chromatolysis or were "ghost" cells, but the cells of layers V and VI were preserved and moderately hyperchromic. In FD and HP the majority of the granular cells and cells of CA3 and CA4 fields were severely hypochromic, whereas in the CA1 field most cells were normal or slightly hypercaryochromic. In BG mostly mild or moderate aberration from normal cell structure was observed: in striatum, mild hypercaryochromia of small neurons and more expressive hyperchromia of large neurons were found; and in pallidum, mild or moderate hypercaryochromia to severe hyperchromia in pallidum internum was found. Degeneration of thick myelinated fibers was evident in pallidum. Large striatal and pallidal neurons showed signs of constructive changes in Golgi slices. These data allow the determination of the cause of the main symptoms of RS. The motor disorders, including specific stereotyped movements, could be related to the enhanced activity of BG cells due to their deafferentation from the side of the neocortex and to supposed hyperactivity of the EC-striatal pathway; the mental retardation and epileptic seizures could be due to FD-HP involvement.

Adolescent↗
PubMed1999

Structure of EVH1, a novel proline-rich ligand-binding module involved in cytoskeletal dynamics and neural function.

The Ena-VASP homology (EVH1) domain is a protein interaction module found in several proteins that are involved in transducing migratory and morphological signals into cytoskeletal reorganization. EVH1 specifically recognizes proline-rich sequences in its binding partners and directs the localization and formation of multicomponent assemblies involved in actin-based motile processes and neural development. The structure of the complex between an EVH1 domain and the target peptide sequence EFPPPPT identifies the interactions responsible for recognition and distinguishes it from other proline-rich binding modules, including SH3 and WW domains. Surprisingly, the EVH1 domain has structural similarity to pleckstrin homology (PH), phosphotyrosine-binding (PTB) and ran-binding (RanBD) domains.

Amino Acid Sequence↗
PubMed1999

Profilin binds proline-rich ligands in two distinct amide backbone orientations.

The actin regulatory protein profilin is targeted to specific cellular regions through interactions with highly proline-rich motifs embedded within its binding partners. New X-ray crystallographic results demonstrate that profilin, like SH3 domains, can bind proline-rich ligands in two distinct amide backbone orientations. By further analogy with SH3 domains, these data suggest that non-proline residues in profilin ligands may dictate the polarity and register of binding, and the detailed organization of the assemblies involving profilin. This degeneracy may be a general feature of modules that bind proline-rich ligands, including WW and EVH1 domains, and has implications for the assembly and activity of macromolecular complexes involved in signaling and the regulation of the actin cytoskeleton.

Amino Acid Sequence↗
PubMed1998

Expression, crystallization and preliminary X-ray analysis of ligand-free human glutathione S-transferase M2-2.

Human glutathione-S-transferase M2-2 (hGSTM2-2) was expressed in Escherichia coli and purified by GSH-affinity chromatography. The recombinant enzyme and the protein isolated from human tissue were indistinguishable based on physicochemical, enzymatic and immunological criteria. The catalytically active dimeric hGSTM2-2 was crystallized without GSH or other active-site ligands in two crystal forms. Diffraction from form A crystals extends to 2.5 A and is consistent with the space group P21 (a = 53.9, b = 81.5, c = 55.6 A, beta = 109.26 A) with two monomers in the asymmetric unit. Diffraction from form B crystals extends to 3 A and is consistent with a space group P212121 (a = 57.2, b = 80.7, c = 225.9 A) with two dimers in the asymmetric unit. This is the first report of ligand-free mu-class GST crystals, and a comparison with liganded complexes will provide insight into the structural consequences of substrate binding which are thought to be important for catalysis.

Crystallization↗
PubMed1998

Crystal packing induces a conformational change in profilin-I from Acanthamoeba castellanii.

Profilin-I from Acanthamoeba castellanii is a 13-kDa protein that binds actin and poly-l-proline. The native protein has been crystallized in two different but closely related forms. The second form proved more amenable to three-dimensional structural determination using heavy-atom isomorphous methods to obtain crystallographic phase information. We used the second crystal structure as a test molecule in the molecular replacement procedure to determine the structure of the first crystal form of profilin-I. More residues participate in crystal lattice contacts in the first crystal form than in the second. The two crystal forms differ significantly in the C-terminal helix that interacts with actin and in the loop preceding this helix. Coordinates of some main chain atoms here differ by about 1.0 A, and side chain atoms differ by more than 2.0 A.

Acanthamoeba↗
PubMed1997

Essential functions and actin-binding surfaces of yeast cofilin revealed by systematic mutagenesis.

Cofilin stimulates actin filament turnover in vivo. The phenotypes of twenty yeast cofilin mutants generated by systematic mutagenesis were determined. Ten grew as well as the wild type and showed no cytoskeleton defects, seven were recessive-lethal and three were conditional-lethal and caused severe actin organization defects. Biochemical characterization of interactions between nine mutant yeast cofilins and yeast actin provided evidence that F-actin binding and depolymerization are essential cofilin functions. Locating the mutated residues on the yeast cofilin molecular structure allowed several important conclusions to be drawn. First, residues required for actin monomer binding are proximal to each other. Secondly, additional residues are required for interactions with actin filaments; these residues might bind an adjacent subunit in the actin filament. Thirdly, despite striking structural similarity, cofilin interacts with actin in a different manner from gelsolin segment-1. Fourthly, a previously unrecognized cofilin function or interaction is suggested by identification of spatially proximal residues important for cofilin function in vivo, but not for actin interactions in vitro. Finally, mutation of the cofilin N-terminus suggests that its sequence is conserved because of its critical role in actin interactions, not because it is sometimes a target for protein kinases.

Actin Depolymerizing Factors↗
PubMed1997

The molecular basis for allergen cross-reactivity: crystal structure and IgE-epitope mapping of birch pollen profilin.

BACKGROUND: The profilins are a group of ubiquitous actin monomer binding proteins that are responsible for regulating the normal distribution of filamentous actin networks in eukaryotic cells. Profilins also bind polyphosphoinositides, which can disrupt the profilin-action complex, and proline-rich ligands which localize profilin to sites requiring extensive actin filament accumulation. Profilins represent cross-reactive allergens for almost 20 % of all pollen allergic patients. RESULTS: We report the X-ray crystal structure of birch pollen profilin (BPP) at 2.4 resolution. The major IgE-reactive epitopes have been mapped and were found to cluster on the N- and C-terminal alpha helices and a segment of the protein containing two strands of the beta sheet. The overall fold of this protein is similar to that of the mammalian and amoeba profilins, however, there is a significant change in the orientation of the N-terminal alpha helix in BPP. This change in orientation alters the topography of a hydrophobic patch on the surface of the molecule, which is thought to be involved in the binding of proline-rich ligands. CONCLUSIONS: Profilin has been identified as an important cross-reactive allergen for patients suffering from multivalent type I allergy. The prevalent epitopic areas are located in regions with conserved sequence and secondary structure and overlap the binding sites for natural profilin ligands, indicating that the native ligand-free profilin acts as the original cross-sensitizing agent. Structural homology indicates that the basic features of the G actin-profilin interaction are conserved in all eukaryotic organisms, but suggests that mechanistic differences in the binding of proline-rich ligands may exist. The structure of BPP provides a molecular basis for understanding allergen cross-reactivity.

Acanthamoeba↗
PubMed1997

Structure determination of yeast cofilin.

Cofilin, a ubiquitous 15,000 M(r) protein, plays a central role in regulating cytoskeletal dynamics. Cofilin binds to actin monomers and filaments, and has a pH-dependent actin severing activity. The structure will allow for a detailed analysis of cofilin function.

Actin Depolymerizing Factors↗
PubMed1996

Ionic interactions in crystalline bovine pancreatic ribonuclease A.

Isomorphous crystals (space group P3(2)21) of bovine pancreatic ribonuclease A (RNase A) were prepared at a pH of 5.5 in a series of high salt conditions, where both the nature of the ions and the ionic strength varied: 80% ammonium sulfate (mu = 12.5); 8 M sodium formate (mu = 8.0); 3 M NaCl, 30% ammonium sulfate (mu = 7.0); 3 M CsCl, 30% ammonium sulfate (mu = 7.0); and 2.5 M NaCl, 3.3 M sodium formate (mu = 5.8). These structures were independently refined to a resolution of 2.0 A or better with R-factors that range from 16.1% to 17.5%. A comparison of these six structures and the monoclinic crystal form of RNase A grown from alcohol shows that changes in ionic strength do not alter the secondary or tertiary structure and that there are no significant changes in intramolecular salt bridges. These findings support the notion that structures determined from crystals grown in high salt are representative of the overall structural and electrostatic features present under physiological conditions. While little effect was observed on the main chain conformation, several residues adopted different side chain conformations and altered hydrogen-bonding patterns, either as result of direct anion binding or more subtle indirect effects. Changes in the ionic composition of the mother liquor allowed for the occupancy of the active site with different anions. The direct observation of active site-bound chloride and formate anions supports the proposal that these species act as true competitive inhibitors of RNase A and not through nonspecific electrostatic effects. The identification of bound formate anions allowed for an experimental validation of computational-based functional group mapping techniques and suggests a useful modification to these approaches. Electrostatic surface potential calculations identify a nearly continuous band of positive potential, consistent with an extended binding site for polynucleotide ligands and substrates. The majority of these residues are not involved in salt bridges, which may facilitate binding to extended polynucleotide substrates. Selection of the appropriate solvent conditions results in an unoccupied active site, which will allow this crystal form to be used for the crystallographic study of productive ligand-binding modes.

Amino Acid Sequence↗