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Biomedical subjects

A Ivanov

Publications and source records attributed to A Ivanov.

At least 19 recordsLinked to original sources
PubMed2001

Resonant spin excitation in an overdoped high temperature superconductor.

An inelastic neutron scattering study of overdoped Bi(2)Sr(2)CaCu(2)O(8+delta) ( T(c) = 83 K) has revealed a resonant spin excitation in the superconducting state. The mode energy is E(res) = 38.0 meV, significantly lower than in optimally doped Bi(2)Sr(2)CaCu(2)O(8+delta) ( T(c) = 91 K, E(res) = 42.4 meV). This observation, which indicates a constant ratio E(res)/k(B)T(c) approximately 5.4, helps resolve a long-standing controversy about the origin of the resonant spin excitation in high temperature superconductors.

Journal Article↗
PubMed2001

Establishment and functional characterization of an in vitro model of the blood-brain barrier, comprising a co-culture of brain capillary endothelial cells and astrocytes.

OBJECTIVE: The aim was to establish a flexible, abundantly available, reproducible and functionally characterized in vitro model of the blood-brain barrier (BBB). METHODS: In a first step, bovine brain capillaries and newborn rat astrocytes were isolated. Subsequently, a co-culture of primary brain capillary endothelial cells (BCEC) on semi-permeable filter inserts, with astrocytes on the bottom of the filter was established. The cell material was characterized on the basis of specific cell-type properties and (functional expression of) specific BBB properties. RESULTS: BCEC displayed: (1) characteristic endothelial cell morphology; (2) expression of endothelial cell markers (i.e., CD51, CD62P, CD71 and cadherin 5); (3) marginal F-actin localization; (4) tight junction formation between the cells; (5) expression of gamma-glutamyl-transpeptidase (gamma-GTP); (6) expression of P-glycoprotein (Pgp); (7) functional transendothelial transferrin transport and uptake; (8) restriction of paracellular transport; and (9) high transendothelial electrical resistance (TEER). Astrocytes displayed characteristic astrocyte morphology and expressed glial fibrillary acidic protein (GFAP). Co-culture with astrocytes increased TEER and decreased paracellular transport. In addition, expression of the glucocorticoid receptor (GR) was demonstrated in the endothelial cells of the BBB, while no expression of the mineralocorticoid receptor (MR) was found. CONCLUSIONS: A high quality and mass-production in vitro BBB model was established in which experiments with physiological (e.g., regulation of BBB permeability), pharmacological (e.g., pharmacokinetics and pharmacodynamics) and pathophysiological (e.g., disease influence on BBB permeability) objectives can be reproducibly performed.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Local opiate withdrawal in locus coeruleus neurons in vitro.

Noradrenergic neurons of the brain nucleus locus coeruleus (LC) become hyperactive during opiate withdrawal. It has been uncertain to what extent such hyperactivity reflects changes in intrinsic properties of these cells. The effects of withdrawal from chronic morphine on the activity of LC neurons were studied using intracellular recordings in rat brain slices. LC neurons in slices from chronically morphine-treated rats exhibited more than twice the frequency of spontaneous action potentials after naloxone compared with LC neurons from control rats. However, after naloxone treatment, the resting membrane potential (MP) of LC neurons from dependent rats was not significantly different from that in control rats. Neither resting MP nor spontaneous discharge rate (SDR) was altered by naloxone in LC neurons from control rats. Neither kynurenic acid nor a cocktail of glutamate and GABA antagonists (6-cyano-7-nitroquinoxalene-2,3-dione + 2-amino-5-phosphonopentanoic acid + bicuculline) blocked the hyperactivity of LC neurons precipitated by naloxone in slices from morphine-dependent rats. The effects of ouabain on MP and SDR were similar in LC neurons from control and morphine-dependent rats. These results indicate that an adaptive change in glutamatergic or GABAergic synaptic mechanisms or altered Na/K pump activity does not underlie the withdrawal-induced activation of LC neurons in vitro. Specific inhibitors of protein kinase A [Rp-cAMPS or N-(2-[p-bromocinnamylamino]ethyl)-5-isoquinolinesulfonamide (H-89)] partially suppressed the withdrawal hyperactivity of LC neurons, and activators of cAMP (forskolin) or protein kinase A (Sp-cAMPS) increased the discharge rate of LC neurons from control rats. These results suggest that upregulation of cAMP-dependent protein kinase A during chronic morphine treatment is involved in the withdrawal-induced hyperactivity of LC neurons.

2-Amino-5-phosphonovalerate↗
PubMed2000

Changes in p53 expression in mouse fibroblasts can modify motility and extracellular matrix organization.

Effects of p53 expression on cell morphology and motility were studied using the derivatives of p53-null 10(1) mouse fibroblasts with tetracycline-regulated expression of exogenous human p53. Induction of p53 expression was accompanied by significant decrease in extracellular matrix (fibronectin) and reduction of matrix fibrils, diminution of the number and size of focal contacts, decrease of cell areas, establishment of more elongated cell shape and alterations of actin cytoskeleton (actin bundles became thinner, their number and size decreased). Expression of His175 and Gln22/ Ser23 p53 mutants caused no such effects. To study the influence of p53 expression on cell motility we used wound technique and videomicroscopy observation of single living cells. It was found that induction of p53 expression led to increase of lamellar activity of cell edge. However, in spite of enhanced lamellar activity p53-expressing cells migrated to shorter distance and filled the narrow wound in longer time as compared with their p53-null counterparts. Possible mechanisms of the influence of p53 expression on cell morphology and motility are discussed.

Actins↗
PubMed2000

Spin dynamics and orbital state in LaTiO3

A neutron scattering study of the Mott-Hubbard insulator LaTiO3 ( T(N) = 132 K) reveals a spin wave spectrum that is well described by a nearest-neighbor superexchange constant J = 15.5 meV and a small Dzyaloshinskii-Moriya interaction ( D = 1.1 meV). The nearly isotropic spin wave spectrum is surprising in view of the absence of a static Jahn-Teller distortion that could quench the orbital angular momentum, and it may indicate strong orbital fluctuations. A resonant x-ray scattering study has uncovered no evidence of orbital order in LaTiO3.

Journal Article↗
PubMed2000

Packing of the transmembrane helices of Na,K-ATPase: direct contact between beta-subunit and H8 segment of alpha-subunit revealed by oxidative cross-linking.

Spatial relationships among the transmembrane (TM) segments of alpha- and beta-subunits of the Na,K-ATPase molecule have been investigated using oxidative induction of disulfide bonds. The catalytic alpha-subunit contains 10 TM alpha-helices (H1-H10) with 9 Cys residues located within or close to the membrane moiety. There is one Cys residue in the single TM segment of beta-subunit (Hbeta). Previously, the cross-linking products containing the beta-subunit and two fragments of alpha-subunit (the N-terminal containing H1-H2 helices and the C-terminal containing H7-H10 helices) have been identified in experiments with membrane-bound or detergent-solubilized preparations of the membrane moiety of trypsin-digested Na,K-ATPase [Sarvazyan, N. A., Modyanov, N. N., and Askari, A. (1995) J. Biol. Chem. 270, 26528-26532 and Sarvazyan, N. A., Ivanov, A., Modyanov, N. N., and Askari, A. (1997) J. Biol. Chem. 272, 7855-7858]. Here, we have shown that Cu(2+)-phenanthroline treatment of digitonin-solubilized preparation provides the most efficient formation of intersubunit cross-linked product that is predominantly a dimer of beta-subunit and a 22-kDa C-terminal alpha-fragment containing H7-H10 helices. This cross-linked product was isolated and subjected to CNBr cleavage. The resulting fragments were electrophoretically separated and sequenced. A 17-kDa peptide composed of Ile853-Met942 alpha-fragment and Ala5-Met56 beta-fragment was identified as a product of intersubunit disulfide cross-link between Cys44 of Hbeta and either Cys911 or Cys930, located in H8. This provides the first direct experimental evidence of the juxtaposition of Hbeta and H8 within the Na,K-ATPase molecule. The second detected cross-linked product was composed of alpha-fragments Lys947-Met963 and Tyr974-Tyr1016 linked by induced disulfide bridge between Cys964 (H9) and Cys983 (H10). The spatial proximity of these Cys residues defines the mutual orientation of H9 and H10 helices of alpha-subunit.

Cross-Linking Reagents↗
PubMed2000

Persistence of well-defined collective excitations in a molten transition metal

Well-defined microscopic collective excitations are found in liquid Ni at 1763 K by means of inelastic neutron scattering. Such excitations are supported by the liquid despite an anharmonic character of its thermodynamic functions. Consideration of the detailed shape of the interionic pair potential provides a way to understand why atomic motions at microscopic scales behave in a way much closer to the alkali metals than to the liquefied rare gases.

Journal Article↗
PubMed2000

Quantum impurities and the neutron resonance peak in YBa2Cu3O7: Ni versus Zn.

The influence of magnetic (S=1) and nonmagnetic (S=0) impurities on the spin dynamics of an optimally doped high temperature superconductor is compared in YBa2(Cu0.97Ni0.03)3O7 (Tc=80 K) and YBa2(Cu0.99Zn0.01)3O7 (Tc=78 K). In the Ni-substituted system, the magnetic resonance peak (which is observed at Er approximately 40 meV in the pure system) shifts to lower energy with a preserved Er/Tc ratio while the shift is much smaller upon Zn substitution. By contrast Zn, but not Ni, restores significant spin fluctuations around 40 meV in the normal state. These observations are discussed in the light of models proposed for the magnetic resonance peak.

Journal Article↗
PubMed2000

Hypocretin/orexin depolarizes and decreases potassium conductance in locus coeruleus neurons.

Recent studies demonstrated that noradrenergic locus coeruleus (LC) neurons are a particularly strong target of the novel neuropeptide, hypocretin (orexin). The present study sought to elucidate the action of hypocretin-B (HCRT) on LC neurons recorded intracellularly in rat brain slices. Bath (1.0 microM) or local puff application (50-100 microM in pipette) of HCRT depolarized LC neurons in rat brain slices and increased their spontaneous discharge rate. Depolarization evoked by HCRT was persistent in the presence of tetrodotoxin (TTX, 1 microM) and Co2+ (1 mM), indicating that HCRT directly activated LC neurons, and that its effect on the postsynaptic cell was not due to activation of TTX-sensitive sodium channels or Co2+-sensitive calcium channels. The apparent input resistance was significantly increased in the majority of LC neurons during the HCRT-evoked depolarization. Moreover, the HCRT-evoked depolarization was decreased in amplitude with hyperpolarization of membrane. The present results indicate that decreased potassium conductance is involved in the effect of HCRT on LC neurons.

Animals↗
PubMed2000

The spin excitation spectrum in superconducting YBa(2)Cu(3)O(6.85)

A comprehensive inelastic neutron scattering study of magnetic excitations in the near optimally doped high-temperature superconductor YBa(2)Cu(3)O(6.85) is presented. The spin correlations in the normal state are commensurate with the crystal lattice, and the intensity is peaked around the wave vector characterizing the antiferromagnetic state of the insulating precursor, YBa(2)Cu(3)O(6). Profound modifications of the spin excitation spectrum appear abruptly below the superconducting transition temperature T(c), where a commensurate resonant mode and a set of weaker incommensurate peaks develop. The data are consistent with models that are based on an underlying two-dimensional Fermi surface, predicting a continuous, downward dispersion relation connecting the resonant mode and the incommensurate excitations. The magnetic incommensurability in the YBa(2)Cu(3)O(6+)(x) system is thus not simply related to that of another high-temperature superconductor, La(2-)(x)Sr(x)CuO(4), where incommensurate peaks persist well above T(c). The temperature-dependent incommensurability is difficult to reconcile with interpretations based on charge stripe formation in YBa(2)Cu(3)O(6+x) near optimum doping.

Journal Article↗
PubMed2000

Arrest in metaphase and anatomy of mitotic catastrophe: mild heat shock in two human osteosarcoma cell lines.

The exits from metaphase arrest and anatomy of mitotic catastrophe were studied in two human osteosarcoma cell lines, nontumorigenic HOS TE85 and its chemically transformed strain MNNG-HOS, applying mild genotoxic damage by heat shock at 41.8 degrees C for 24 h. Under these conditions, both cell lines doubled or tripled their mitotic index entering arrest in metaphase. On return to 37 degrees C, the arrest was either released or ended in apoptosis. The transformed strain showed a greater capacity to arrest in metaphase as well as a greater probability of developing the third pathway: to restitute this arrest in polyploid interphase. This, in turn, either entered an 'endocycle' or, following a delay, apoptosis. Thus, arrest in metaphase was a cross-point of the mitotic cycle, apoptosis, and endocycle. Mitotic catastrophe can morphologically manifest combinations of elements of these three processes.

Anaphase↗
PubMed2000

[Risk of drug-induced acute pancreatitis following propofol anesthesia used in abdominal operations].

The postoperative pancreatitis is a well-known complication. More than eighty-five drugs have been reported to have induced postoperative pancreatitis. Twenty-five cases of Propofol-induced pancreatitis have been reported till now. The relation of pancreatitis to Propofol (Diprivan; Zeneca; London, UK) is considered as a possible one, but has been proved. The goal of the authors is to reveal the plasma lipid and amylase level dynamics in patients after Propofol anaesthesia. The clinicians have to consider this possible relation, because of the growing use of Propofol recently.

Abdomen↗
PubMed1999

Hypocretin (orexin) activation and synaptic innervation of the locus coeruleus noradrenergic system.

Hypocretin has been identified as a regulator of metabolic and endocrine systems. Several brain regions involved in the central regulation of autonomic and endocrine processes or attention are targets of extensive hypocretin projections. The most dense arborization of hypocretin axons in the brainstem was detected in the locus coeruleus (LC). Multiple labeling immunocytochemistry revealed a massive synaptic innervation of catecholaminergic LC cells by hypocretin axon terminals in rats and monkeys. In both species, all tyrosine hydroxylase-immunopositive cells in the LC examined by electron microscopy were found to receive asymmetrical (excitatory) synaptic contacts from multiple axons containing hypocretin. In parallel electrophysiological studies with slices of rat brain, all LC cells showed excitatory responses to the hypocretin-2 peptide. Hypocretin-2 uniformly increased the frequency of action potentials in these cells, even in the presence of tetrodotoxin, indicating that receptors responding to hypocretin were expressed in LC neurons. Two mechanisms for the increased firing rate appeared to be a reduction in the slow component of the afterhyperpolarization (AHP) and a modest depolarization. Catecholamine systems in other parts of the brain, including those found in the medulla, zona incerta, substantia nigra or olfactory bulb, received significantly less hypocretin input. Comparative analysis of lateral hypothalamic input to the LC revealed that hypocretin-containing axon terminals were substantially more abundant than those containing melanin-concentrating hormone. The present results provide evidence for direct action of hypothalamic hypocretin cells on the LC noradrenergic system in rats and monkeys. Our observations suggest a signaling pathway via which signals acting on the lateral hypothalamus may influence the activity of the LC and thereby a variety of CNSfunctions related to noradrenergic innervation, including vigilance, attention, learning, and memory. Thus, the hypocretin innervation of the LC may serve to focus cognitive processes to compliment hypocretin-mediated activation of autonomic centers already described.

Action Potentials↗
PubMed1999

Excitatory amino acids and synaptic transmission in embryonic rat brainstem motoneurons in organotypic culture.

We used brainstem motoneurons recorded in organotypic slice co-cultures maintained for more than 18 days in vitro, together with multibarrel ionophoretic applications of glutamate receptor agonists and bath applications of specific blocking agents, to study the responses of rat brainstem motoneurons to glutamate receptor activation, and the contribution of these receptors to synaptic transmission. Differentiated brainstem motoneurons in vitro are depolarized by glutamate, N-methyl-d-aspartate (NMDA) and dl-alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) iontophoresis, and express NMDA, AMPA and also specific kainate receptors, as evidenced by (+/-)2-amino-5-phosphonovaleric acid (APV)- and (-)1-(4-aminophenyl)-3-methyl-carbamoyl-4-methyl-7, 8-methylenedioxy-3,4-dihydro-5H-2,3-benzo-diazepine [GYKI 53784 (LY303070)]-resistant depolarizations. Electrical stimulations applied to the dorsal part of the explant trigger excitatory synaptic potentials with latencies distributed in three regularly spaced groups. Excitatory postsynaptic potentials (EPSPs) in the earliest group have a similar latency and time course and correspond to monosynaptic activation. EPSPs in later groups have more scattered latencies and time courses and correspond to polysynaptic activation. Monosynaptic EPSPs are insensitive to the specific NMDA blocker APV, and are completely and reversibly suppressed by the non-competitive AMPA receptor antagonist GYKI 53784 (LY303070). Detailed analysis of the spontaneous excitatory synaptic activity shows that APV decreases the frequency of spontaneous EPSPs without modifying their shape or amplitude. We conclude that excitatory synapses on brainstem motoneurons in vitro are mainly activated through AMPA receptors (AMPA-Rs). NMDA receptors (NMDA-Rs) are present in the membrane, but are located either at extrasynaptic sites or silent synapses, and are not directly involved in synaptic transmission on motoneurons. On the contrary, NMDA receptors contribute to synaptic transmission within the premotor interneuronal network.

Animals↗
PubMed1999

Effect of mebendazole on human cystic echinococcosis: the role of dosage and treatment duration.

Fifty-three patients with single, multiple and/or multi-organ hydatid cysts were treated with mebendazole, in varying dosages (30-70 mg/kg.day) and over varying periods (6-24 months). Treatment failure was recorded if the mebendazole had no apparent effect on cyst morphology (monitored by radiology, ultrasonography and computed tomography) or only a parasitostatic effect (characterized by mixed and transitory, hypo- and hyper-echoic changes in the lesions). Cure was indicated by a parasitocidal effect (characterized by a totally echogenic picture, increased density of the cyst contents, reduction in the size or complete disappearance of the cysts, complete detachment of the endocysts and/or calcification of the cyst wall). Treatment failure was seen in about 40% of the patients and cure in about 38%; the other 23% had an intermediate result considered as an improvement. Cure rates increased both with dosage and duration, daily dosages of 60-70, 50 and 30-40 mg/kg curing 48%, 33% and 25%, respectively. The pre-treatment condition of any cysts should be taken into consideration when determining dosage and treatment duration.

Adolescent↗
PubMed1999

[Large-intestine perforations caused by primary colorectal cancer].

Twenty-seven cases of perforation, produced by primary colorectal carcinoma over the period 1993-1998, are described. The underlying causes of colorectal carcinoma complication and types of perforations observed are discussed. This is a report on personal experience with the therapeutic approach and operative management of this severest complication of colorectal carcinoma.

Colonic Diseases↗