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Biomedical subjects

A V Nikolaev

Publications and source records attributed to A V Nikolaev.

At least 19 recordsLinked to original sources
PubMed2006

[Use of combined treatment of rectal cancer involving metastases to regional lymph nodes].

Use of combined pre- and intraoperative radiotherapy for rectal cancer involving metastases to regional lymph nodes failed to lower incidence of loco-regional recurrences or improve 5-year results, as compared with pre-operative radiotherapy alone. Besides, distant metastasis rates remained rather high (ca.30%). However, pre-operative radiotherapy plus local SHF-hyperthermia were followed by a significant drop in loco-regional recurrence incidence (to 2.3%), as compared with surgery alone and combined treatment using pre-operative hyper-fractionated-radiotherapy (TTD 25 Gy). Distant metastasis rates dropped to 25%. Also, 5-year survival increased significantly.

Dose Fractionation, Radiation↗
PubMed2005

Anisotropic packing and one-dimensional fluctuations of C60 molecules in carbon nanotubes.

The confinement of a C60 molecule encapsulated in a cylindrical nanotube depends on the tube radius. In small tubes with radius RT approximately < 7 A, a fivefold axis of the molecule coincides with the tube axis. The interaction between C60 molecules in the nanotube is then described by a O2-rotor model on a 1D liquid chain with coupling between orientational and displacive correlations. This coupling leads to chain contraction. The structure factor of the 1D liquid is derived. In tubes with a larger radius the molecular centers of mass are displaced off the tube axis. The distinction of two groups of peapods with on- and off-axis molecules suggests an explanation of the apparent splitting of Ag modes of C60 in nanotubes measured by resonant Raman scattering.

Journal Article↗
PubMed2005

Superexchange and electron correlations in alkali fullerides AC60, A=K, Rb, Cs.

Superexchange interactions in alkali fullerides AC(60) are derived for C(60) molecular ions separated by interstitial alkali-metal ions. We use a multiconfiguration approach which comprises the lowest molecular orbital states of the C(60) molecule and the excited s and d states of the alkali-metal atom A. Interactions are described by the valence bond (Heitler-London) method for a complex (C(60)-A-C(60))(-) with two valence electrons. The electronic charge transfer between the alkali-metal atom and a neighboring C(60) molecule is not complete. The occupation probability of excited d and s states of the alkali atom is not negligible. In correspondence with the relative positions of the C(60) molecules and A atoms in the polymer crystal, we consider 180 degrees and 90 degrees (angle) superexchange pathways. For the former case the ground state is found to be a spin singlet separated from a triplet at approximately 20 K. For T<20 K there appear strong spin correlations for the 180 degrees superexchange pathway. The results are related to spin lattice relaxation experiments on CsC(60) in the polymerized and in the quenched cubic phase.

Journal Article↗
PubMed2004

Valence electronic charge density of distorted C60- monomers in polymerized KC60 and RbC60.

We investigate the valence electronic charge density of the C(60) (-) monomers in (C(60) (-))(n) polymer chains in K- and RbC(60) by means of a nonorthogonal tight-binding formalism using experimental data on the positions of the carbon atoms. Various configurations of the C(60) cages are considered. Starting from the ideal icosahedral C(60) structure and moving to the realistic, experimentally determined spatial configuration of the C(60) cages in K- and RbC(60), we observe a systematic increase of the electric quadrupole moments on the C(60) (-) monomers. We also confirm the validity of factorizing the charge density of a C(60) (-) monomer into an angular and a radial part.

Journal Article↗
PubMed2001

An efficient and stereoselective synthesis of beta-D-Arap-(1-->2)-beta-D-Galp-(1-->3)-beta-D-Galp-(1-->4)-alpha-D-Manp, a tetrasaccharide fragment of Leishmania major lipophosphoglycan.

A tetrasaccharide fragment of Leishmania major lipophosphoglycan (which seems to be involved in a biological mechanism for the parasite transmission) has been synthesised using the thioglycoside, trichloroacetimidate and halide-exchange glycosylation procedures and step-wise chain elongation strategy.

Animals↗
PubMed2001

[Anatomic resection of spleen in experiment].

The study was carried out in 35 dogs. Basic surgical techniques developed experimentally for organ-saving operations on the spleen are presented. Methods of lobar and segmental resections of the spleen based on detailed study of variants of branching of splenic artery and vein are described. Angiography visualized sharply splenic arteries after lobar and segmental resections, including the stumps of transected arteries. Ultrasonic examination, performed before operation and in different terms after it (3-360 days), specified the size, shape echostructure and anatomic relationship of the spleen with adjacent organs before and after operation.

Anastomosis, Surgical↗
PubMed2000

Theory of distinct crystal structures of polymerized fullerides AC60, A = K, Rb, Cs: the specific role of alkalis.

The polymer phases of AC60 form distinct crystal structures characterized by the mutual orientations of the (C( -)(60))(n) chains. We show that the direct electric quadrupole interaction between chains always favors the orthorhombic structure Pmnn with alternating chain orientations. However, the specific quadrupolar polarizability of the alkali metal ions leads to an indirect interchain coupling which favors the monoclinic structure I2/m with equal chain orientations. The competition between direct and indirect interactions explains the structural difference between KC60 and RbC60, CsC60.

Journal Article↗
PubMed2000

Characterization of the elongating alpha-D-mannosyl phosphate transferase from three species of Leishmania using synthetic acceptor substrate analogues.

Leishmania express lipophosphoglycans and proteophosphoglycans that contain Galbeta1-4Manalpha1-P phosphosaccharide repeat structures assembled by the sequential addition of Manalpha1-P and betaGal. The synthetic acceptor substrate Galbeta1-4Manalpha1-P-decenyl and a series of analogues were used to probe Leishmania alpha-D-mannosyl phosphate transferase activity. We show that the activity detected with Galbeta1-4Manalpha1-P-decenyl is the elongating alpha-D-mannosyl phosphate transferase associated with lipophosphoglycan biosynthesis (eMPT(LPG)). Differences in the apparent K(m) values for the donor and acceptor substrates were found using L. major, L. mexicana, and L. donovani promastigote membranes, but total activity correlated with the number of lipophosphoglycan repeats. Further comparisons showed that lesion-derived L. mexicana amastigotes, that do not express lipophosphoglycan, lack eMPT(LPG) and that nondividing L. major metacyclic promastigotes contain 5-fold less eMPT(LPG) activity than dividing procyclic promastigotes. The fine specificity of promastigote eMPT(LPG) activity was determined using 24 synthetic analogues of Galbeta1-4Manalpha1-P-decenyl. The three species gave similar results: the negative charge of the phosphodiester and the C-6 hydroxyl of the alphaMan residue are essential for substrate recognition, the latter most likely acting as a hydrogen bond acceptor. The C-6' hydroxyl of the betaGal residue is required for substrate recognition as well as for catalysis. The rate of Manalpha1-P transfer declines with increasing acceptor substrate chain length. The presence of a monosaccharide substituent at the C-3 position of the terminal betaGal residue abrogates Man-P transfer, showing that chain elongation must precede side chain modification during lipophosphoglycan biosynthesis. In contrast, substitution of the penultimate phosphosaccharide repeat does not abrogate transfer but is slightly stimulatory in L. mexicana and inhibitory in L. major.

Amino Acid Sequence↗
PubMed2000

C-reactive protein binds to phosphorylated carbohydrates.

C-reactive protein (CRP) is a major acute phase protein in man. In order to more fully understand the physiological role of this serum protein, we have demonstrated high avidity binding for a defined chemically synthesized carbo-hydrate ligand which represents the repeating disaccharide of lipophosphoglycan, the major surface glycoconjugate of the unicellular parasite Leishmania donovani. Increasing the number of phosphorylated disaccharides in a molecule from one up to seven did not increase the avidity for CRP, however increasing this to 10 potential CRP binding sites did. In order to define the important features of this complex and variable structure for CRP binding we competed CRP binding to whole Leishmania parasites with amino, sulfated, phosphorylated, and unsubstituted monosaccharides, of which only phosphorylated monosaccharides were able to inhibit. Both the carbohydrate and the position of phosphorylation influenced the avidity for CRP. Synthetic oligosaccharides and phospho-oligosaccharides of various lengths and conformations were used to define the structural requirements for CRP recognition. The optimum structure for recognition of a single phosphate group was between two monosaccharide pyranose rings, and within a linear rather than a cyclic molecule. This stresses the importance of the interaction of the CRP binding site with both the carbohydrate and the phosphate group. CRP function may be mediated via the recognition of large arrays of phosphorylated carbohydrates as are characteristic of the surface of microorganisms.

C-Reactive Protein↗
PubMed1999

Extracellular signal-related kinase (ERK) and p38 mitogen-activated protein (MAP) kinases differentially regulate the lipopolysaccharide-mediated induction of inducible nitric oxide synthase and IL-12 in macrophages: Leishmania phosphoglycans subvert macrophage IL-12 production by targeting ERK MAP kinase.

Macrophage activation by cytokines or microbial products such as LPS results in the induction and release of several key immune effector molecules including NO and IL-12. These have been shown to play crucial roles in the development of immunity to intracellular pathogens such as Leishmania. The molecular mechanisms underlying the induction of these effector molecules are not fully understood. We now show that the extracellular signal-related kinase (ERK) and p38 mitogen-activated protein (MAP) kinases play differential roles in the regulation of LPS-stimulated inducible NO synthase and IL-12 gene expression. In macrophages, LPS stimulates the simultaneous activation of all three classes of MAP kinases, ERK, c-jun N-terminal kinase, and p38, albeit with differential activation kinetics. However, studies using inhibitors selective for ERK (PD98059) and p38 (SB203580) show that while p38 plays an essential role in the induction of inducible NO synthase, ERK MAP kinases play only a minor role in promoting NO generation. In contrast, while p38 promotes induction of IL-12 (p40) mRNA, ERK activation suppresses LPS-mediated IL-12 transcription. The biological relevance of these regulatory signals is demonstrated by our finding that Leishmania lipophosphoglycans, which promote parasite survival, act by stimulating ERK MAP kinase to inhibit macrophage IL-12 production. Thus, as ERK and p38 MAP kinases differentially regulate the induction of the macrophage effector molecules, inducible NO synthase and IL-12, these kinases are potential targets not only for the development of novel strategies to combat intracellular pathogens but also for therapeutic immunomodulation.

Animals↗
PubMed1999

Regulation of the miniature plasma membrane Ca(2+) channel I(min) by inositol 1,4,5-trisphosphate receptors.

I(min) is a plasma membrane-located, Ca(2+)-selective channel that is activated by store depletion and regulated by inositol 1,4, 5-trisphosphate (IP(3)). In the present work we examined the coupling between I(min) and IP(3) receptors in excised plasma membrane patches from A431 cells. I(min) was recorded in cell-attached mode and the patches were excised into medium containing IP(3). In about 50% of experiments excision caused the loss of activation of I(min) by IP(3.) In the remaining patches activation of I(min) by IP(3) was lost upon extensive washes of the patch surface. The ability of IP(3) to activate I(min) was restored by treating the patches with rat cerebellar microsomes reach in IP(3) receptors but not by control forebrain microsomes. The re-activated I(min) had the same kinetic properties as I(min) when it is activated by Ca(2+)-mobilizing agonists in intact cells and by IP(3) in excised plasma membrane patches and it was inhibited by the I(crac) inhibitor SKF95365. We propose that I(min) is a form of I(crac) and is gated by IP(3) receptors.

Animals↗
PubMed1999

Regulation of macrophage IL-12 synthesis by Leishmania phosphoglycans.

It is now generally accepted that IFN-gamma, secreted by Th1 cells, is the most potent cytokine leading to macrophage activation and host resistance against infection with the intracellular protozoan parasite Leishmania. It is also established that IL-12 is a critical cytokine involved in the differentiation and expansion of Th1 cells. Therefore, the ability of Leishmania parasites to actively suppress IL-12 production by host macrophages may be an important strategy for parasite survival. Here we report that a major parasite cell surface molecule, phosphoglycan (PG), of Leishmania could selectively inhibit the synthesis of IL-12(p40, p70) by activated murine macrophages. Furthermore, synthetic PG (sPG) was able to inhibit IL-12 release in a dose-dependent manner. Inhibition was dependent on the galactose(beta1-4)mannose(alpha1)-PO4 repeating units and not the glycophosphoinositol lipid anchor of lipophosphoglycan. At the concentration used, sPG had no effect on the release of TNF-alpha or IL-6 in activated macrophages. The inhibition of IL-12(p40) production was at the transcriptional level, but was not mediated through NF kappaB inhibition. These data demonstrate that PG may be an important molecule for the establishment and survival of the parasite in permissive hosts.

Animals↗
PubMed1999

The preparation of neoglycoconjugates containing inter-saccharide phosphodiester linkages as potential anti-Leishmania vaccines.

The Leishmania express complex glycoconjugates containing phosphosaccharide repeat units at all stages of their life-cycle. One of these molecules, lipophosphoglycan (LPG) has been suggested to be a vaccine candidate. To assess the immunological properties of Leishmania phosphosaccharides, we have prepared neoglycoproteins and neoglycolipids containing synthetic Leishmania phosphosaccharide repeats. The coupling procedure uses the dec-9-enyl spacer of previously synthesised phosphosaccharides for linkage to protein and phospholipid. This alkene moiety is converted by ozonolysis to an aldehyde which is then attached to protein and phospholipid amino groups by reductive amination. The procedure produces neoglycoconjugates in good yield and without compromising the labile phosphodiester linkages within the phosphosaccharide chains.

Animals↗
PubMed1999

[Preoperative thermoradiotherapy in the combined treatment of rectal tumors is the inferior ampullar segmentŏ].

Data on the examination of 260 radically-treated patients with rectal tumors in the inferior ampullar segment are presented. 107 patients received surgery alone, another 75--preoperative radiotherapy, while still another 78--preoperative thermoradiotherapy. Combined treatment of stage III tumors significantly reduced recurrence incidence and was followed by significant increase in recurrence-free survival rates. In cases of tumor disseminated to the regional lymph nodes, recurrence-free survival was observed after preoperative thermoradiation only.

Adult↗
PubMed1998

[K+]out accelerates inactivation of Shal-channels responsible for A-current in rat CA1 neurons.

Somato-dendritic subthreshold transient potassium current [I(SA)] was measured in acutely isolated rat hippocampal CA1 pyramidal neurons. The inactivation of this current was insensitive to externally applied H2O2 (20 mM) which causes cysteine oxidation. This result suggests that Shal-channels not Shaker Kv1.4 channels underlie the somato-dendritic I(SA) in rat CA1 pyramidal neurons. The kinetics of the I(SA) inactivation was measured at various [K+]out. Increase in [K+]out leads to acceleration of Shal-channel inactivation. Thus, the shift in [K+]out from 1 to 50 mM results in decreased inactivation time constant from 37 to 19 ms. This effect of [K+]out on the I(SA) is opposite to the previously described action of [K+]out on the inactivation of Shaker K+ channels.

Animals↗