bluuebunny/crossref_metadata_2025 huggingface dataset:
Spontaneous Electrical Activity and Structural Plasticity in the Mature Cerebellar Cortex
Authors: MORANDO LAURA , CESA ROBERTA , HARVEY ROBIN J. , STRATA PIERGIORGIO
Published: September 2005

Abstract: The Purkinje cell of the cerebellar cortex presents two distinct dendritic domains: a distal one, with spiny branchlets and a high density of spines innervated by many parallel fibers, and a proximal one, with a few clusters of spines innervated by a single climbing fiber terminal arbor. In adult rats, after 7 days of blocked electrical activity by the administration of TTX into the cerebellar parenchyma, the proximal dendritic domain of the Purkinje cell shows a remarkable growth of new spines that are innervated by parallel fibers. At the same time, the climbing fiber terminal arbor tends to become atrophic. In contrast, in the branchlets, spine density remains unmodified. These changes are reversible when TTX is removed. TTX treatment also leads to a decrease in spine size both in the branchlets and in the new spines of the proximal dendritic compartment. Spontaneous electrical activity should therefore be regarded not simply as noise, but as a significant signal for maintaining the typical profile of afferent innervation of the Purkinje cell and for preventing spines from shrinking.
Interaction between Microglia and Oligodendrocyte Cell Progenitors Involves Golli Proteins
Authors: FILIPOVIĆ RADMILA , ZEČEVIĆ NADA
Published: September 2005

Abstract: Multiple sclerosis (MS) is an autoimmune and chronic inflammatory disease characterized by plaques, areas of destroyed myelin sheaths in the CNS, which results in multiple disabilities for patients. In addition to demyelinated plaques, pathophysiological studies have shown “shadow plaques” that represent areas of partial remyelination. New myelin can be made by oligodendrocytes (OLs) generated from oligodendrocyte progenitor cells (OPCs) that pre‐exist in the demyelinated area or recruited from surrounding areas. To successfully repopulate the demyelinated area, OPCs have to proliferate, migrate, and differentiate into mature OLs capable of forming myelin. Identifying factors that influence remyelination is a current topic in developmental neurobiology. Previously, we showed that Golli proteins, which have a broad distribution in the nervous and immune systems, are present both in OPCs and activated microglia around MS lesions. We hypothesized that in response to inflammation, Golli proteins may promote proliferation of OPCs through microglial cells. To test this, we established neonatal mouse brain slice and cell cultures and used lipopolysaccharide (LPS) to induce inflammation. In LPS‐treated brain slices, Golli proteins displayed increased expression in the cortical subventricular zone. Furthermore, Golli proteins were demonstrated only in the conditioned medium from LPS‐treated microglial cell cultures (LPS‐MCM), and were absent in either conditioned medium from LPS‐treated astrocytes or control media. Finally, proliferation of purified OPCs was promoted with LPS‐MCM or Golli proteins, but not with LPS alone. In summary, these results demonstrate that activated microglia are beneficial for proliferation of OPCs and suggest possible involvement of Golli proteins as one of mediators in this process.
Exploring Motor Cortical Plasticity Using Transcranial Magnetic Stimulation in Humans
Authors: ILIĆ TIHOMIR V. , ZIEMANN ULF
Published: September 2005

Abstract: It is generally accepted that functional properties of the motor cortex in adult humans can be altered through behavioral or pharmacological manipulations, as well as in some pathological conditions. The ability and capacity of adult human cortex to undergo any adaptive or reorganizational changes is referred to as plasticity. Much of the evidence concerning motor cortical plasticity have been derived from studies using the non‐invasive technique of transcranial magnetic stimulation (TMS). TMS has proven to be a suitable tool to explore representational plasticity and to interact with neuronal activity in settings of induction protocols either alone or coupled with altered sensory inputs. Furthermore, plastic changes induced by motor learning protocols have attracted particular interest because of their relevance in functional recovery. Recent studies support the view that learning in human motor cortex occurs through long‐term potentiation (LTP)‐like mechanisms. Purposeful modulation of motor cortical plastic changes by manipulative TMS protocols may offer useful rehabilitative strategies in patients with chronic motor deficits.
Short‐Term Facilitation and Depression in the Cerebellum: Some Observations on Wild‐Type and Mutant Rodents Deficient in the Extracellular Matrix Molecule Tenascin C
Authors: ANDJUS PAVLE R. , BAJIĆ ALEKSANDAR , ZHU LAN , SCHACHNER MELITTA , STRATA PIERGIORGIO
Published: September 2005

Abstract: Short‐term plasticity was studied on synapses to Purkinje cells (PC): paired‐pulse facilitation in parallel fibers (PF) and paired‐pulse depression in climbing fibers (CF). Both phenomena relate to synaptic strength. These forms of short‐term plasticity were tested on cerebellar slices in rat by early postnatal synchronous stimulation of olivary neurons (i.e. CFs) with harmaline and by inhibition of a metabotropic glutamate receptor (mGluR) as well as in mice that were deficient in the extracellular matrix glycoprotein tenascin‐C. Harmaline stimulation delayed the developmental competition between CF inputs and maintained multiple innervation. Paired‐pulse depression of the CF‐PC synapse after harmaline treatment was more expressed. However, paired‐pulse facilitation in PF‐PC synapses remained unchanged. Electrophysiological responses of postsynaptic mGluR1 in CF‐PC synapses could be obtained only with AMPA receptors blocked and glutamate uptake impaired. The mGluR1‐specific antagonist CPCCOEt suppressed the CF‐mGluR EPSC in some PCs and potentiated it in other PCs. CF paired‐pulse depression was not changed with CPCCOEt, thus excluding a presynaptic effect. The postsynaptic effect was underlined by CPCCOEt‐induced rise in amplitude of EPSC and by a prolongation of its decay time. Tenascins are extracellular matrix glycoproteins that may restrict the regenerative capacity of the nervous tissue. Testing short‐term presynaptic plasticity in tenascin‐C‐deficient mice showed that CF paired‐pulse depression was less expressed while PF paired‐pulse facilitation was augmented except in a group of cells where there was even depression. The results underline differences in forms of short‐term plasticity with regard to susceptibility to diverse modulatory factors.
Direction Selectivity in the Goldfish Tectum Revisited
Authors: MAXIMOV VADIM , MAXIMOVA ELENA , MAXIMOV PAUL
Published: September 2005

Abstract: Responses of direction‐selective (DS) ganglion cells (GCs) were recorded extracellularly from their axon terminals in the superficial layer of the tectum opticum (TO) of immobilized goldfish, Carassius auratus gibelio (Bloch). Directional tuning curves were measured with contrast edges moving in 12 or more different directions across the receptive field (RF). All directional tuning curves had cardioid‐like appearance, their acceptance angles amounted to somewhat more than 180°. According to their preferred directions DS GCs proved to comprise three distinct groups, each group containing DS GCs of ON and OFF subtypes approximately in equal quantity. Thus, this gives six physiological types of DS GCs in total. The preferred direction of a DS GC does not depend to some extent on a value of contrast, speed, size, and form of the stimuli. Coincidence in number of preferred directions with number of semicircular canals implies that DS GCs projecting to tectum are involved in some multimodal sensory integration in postural, locomotor, and oculomotor control in the three‐dimensional aquatic world. DS neurons of the TO itself respond independently of the sign of stimulus contrast, have enormous receptive fields, and seem likely to collect signals from the retinal DS units of both ON and OFF subtypes with the same preferred direction.
Quantitative Methods of Analysis of Footprinting Diagrams for the Complexes Formed by a Ligand with a DNA Fragment of Known Sequence
Authors: NECHIPURENKO YURII D. , JOVANOVIĆ BOŠKO , RIABOKON VADIM F. , GURSKY GEORGII V.
Published: September 2005

Abstract: The regulation of gene expression is based on the interaction of DNA with different ligands. A model of adsorption was considered that can be applied to the quantitative analysis of footprinting diagrams for the complexes formed by a ligand with a DNA fragment of known structure. This model allows the probabilities of ligand binding to DNA sites with a known sequence to be calculated and the variance of probabilities of ligand binding with a specified binding site to be estimated. The model was used for quantitative analysis of diagrams of DNAse footprinting for the complexes of the dimeric analogue of the antitumor antibiotic netropsin. Experimental and theoretically calculated profiles of distribution of netropsin bound on DNA are in good agreement with one another.
New Insights into the Structural Organization of the Plant Polymer Lignin
Authors: RADOTIĆ KSENIJA , MIĆIĆ MIODRAG , JEREMIĆ MILORAD
Published: September 2005

Abstract: The organizational features of lignin structure and the mechanism of its synthesis have significant implications for the response of the plant to stress. It was unknown whether the enzymic formation of lignin in the cell wall is an uncontrolled process or finely regulated in time and space. In vitro scanning tunneling microscopy (STM), atomic force microscopies (AFM), near‐field scanning optical microscopy (NSOM). and the novel environmental scanning electron microscopy (ESEM) imaging studies of the lignin model compounds have directly shown its highly ordered structure and elucidated its modular and fractal organization. Direct evidence was presented for the existence of strong intermolecular forces responsible for holding lignin globules together in highly ordered structures. Fractal analysis was applied as a theoretical approach, to show regularity and modular organization of lignin. Surface chemistry studies of the lignin monolayer reveal intrinsic properties that may be a key to osmotic pressure and cell size control mechanism in the higher plant cells. The obtained data contribute to the explanation of the mechanisms of cell wall synthesis in vivo.
Correlated ATP‐Induced Changes in Membrane Area and Membrane Conductance in Single Rat Adipocytes
Authors: CHOWDHURY HELENA H. , GRILC SONJA , ZOREC ROBERT
Published: September 2005

Abstract: In the past few years it has been shown that, like many other non‐neuroendocrine cells, adipocytes possess a mechanism for triggered exocytosis. Endocytosis and exocytosis affect the plasma membrane surface area, which can be directly monitored with electrophysiological patch‐clamp techniques by measuring membrane capacitance, a parameter linearly related to the plasma membrane area. In this study we used the whole‐cell mode of the patch‐clamp technique to measure changes in membrane capacitance to monitor the effect of extracellular adenosine triphosphate (ATP) on the dynamics of membrane area changes in single adipocytes. Experimental evidence shows that extracellular application of ATP (100 μM) increases membrane capacitance for 30 ± 2%. In controls a significantly smaller increase of 3 ± 2% was measured, which is due to a slow exocytic‐endocytic membrane cycling rate of 0/3%/min. We found that ATP induces a transient increase in membrane current, temporally associated with the peak rate in membrane capacitance increase. These results show directly the presence of ATP‐induced increase in membrane area correlated to the increase in membrane current in single adipocytes.
Downregulation of Glial Scarring after Brain Injury: The Effect of Purine Nucleoside Analogue Ribavirin
Authors: PEKOVIĆ SANJA , FILIPOVIĆ RADMILA , ŠUBAŠIĆ SANJA , LAVRNJA IRENA , STOJKOV DANIJELA , NEDELJKOVIĆ NADEŽDA , RAKIĆ LJUBISAV , STOJILJKOVIĆ MIRJANA
Published: September 2005

Abstract: The weak regenerative capacity of self‐repair after injury to the adult brain is caused by the formation of glial scar due to reactive astrogliosis. In the present study the beginning of reactive astrogliosis in the adult, as shown immunocytochemically by upregulation of glial fibrillary acidic protein (GFAP) and vimentin, was seen two days after the left sensorimotor cortex lesion, being maximal during the first two weeks and declining by 30 days after the lesion. This was accompanied by intensive glial scarring. Conversely, after the neonatal lesion a lack of gliotic scar was seen until 30 days postsurgery, although the pattern of GFAP and vimentin expression during recovery period was the same. The aim of the study was to define an appropriate therapeutic intervention that could modulate astrocyte proliferation and diminish glial scar formation after adult brain lesion. For this purpose the effects of an antiproliferative agent, the purine nucleoside analogue ribavirin was examined. It was shown that daily injection of ribavirin for 5 and 10 days considerably decreased the number of reactive astrocytes, while slight GFAP labeling was restricted to the lesion site. Obtained results show that ribavirin treatment downregulates the process of reactive astrogliosis after adult brain injury, and thus may be a useful approach for improving neurological recovery from brain damage.
31P NMR Spectroscopy and Polarographic Combined Study of Erythrocytes Treated with 5‐Fluorouracil: Cardiotoxicity‐Related Changes in ATP, 2,3‐BPG, and O2 Metabolism
Authors: SPASOJEVIĆ IVAN , ZAKRZEWSKA JOANNA , BAČIĆ GORAN G.
Published: September 2005

Abstract: Antineoplastic drug 5‐fluorouracil (5‐FU) frequently shows cardiotoxic effects, the mechanism of which has not yet been elucidated. The objective of the present study was to explore effects of 5‐FU on metabolism of ATP, 2,3‐BPG, and oxygen in erythrocytes and to relate these to the phenomenon of 5‐FU cardiotoxicity. We determined that 5‐FU induced rapid increase in O2 consumption, which led to drastic changes in the metabolism of phosphate compounds in erythrocytes. Decrease in pO2 provoked increase in production of 2,3‐BPG and subsequent deoxygenation of oxyHb to deoxyHb. However, the most important effect of 5‐FU on erythrocytes is severe decrease in the level of ATP. This could lead to a number of irreversible changes in erythrocyte structure and functioning, such as echinocytosis, increase in membrane fluidity, and non‐functioning of membrane ion pumps. All these changes affect normal functioning of erythrocytes, leading to difficulties in oxygen transport and insufficient supply of oxygen to the heart, and pointing to the importance of studying the effects of antineoplastic drugs on intracellular metabolism of erythrocytes.
Estradiol Affects Calcium Transport across Mitochondrial Membrane in Different Brain Regions
Authors: PETROVIĆ SNJEŽANA , DEMAJO MIROSLAV , HORVAT ANICA
Published: September 2005

Abstract: The in vitro effect of estradiol on flux of Ca2+ in the synaptosomal mitochondria from nucleus caudatus and hippocampus of chronically ovariectomized female rats was examined. No effect of estradiol on Ca2+ influx through ruthenium red‐sensitive channels was found. Estradiol, at a concentration of 0.05‐5 nmol/L for nucleus caudatus and 0.5‐5 nmol/L for the hippocampus, decreased Na‐dependent Ca2+ efflux about 25%.
Electrophysiological Effect of β‐N‐Methylamino‐L‐Alanine on Retzius Nerve Cells of the Leech Haemopis sanguisuga
Authors: NEDELJKOV VLADIMIR , LOPIČIĆ SRDJAN , PAVLOVIĆ DRAGAN , ČEMERIKIĆ DUŠAN
Published: September 2005

Abstract: We investigated the effect of β‐N‐methylamino‐L‐alanine (L‐BMAA) on input membrane resistance of leech Retzius nerve cells and the effect of the same substance on the membrane potential in the presence of 20 mM bicarbonate. Results of our experiments show that L‐BMAA significantly reduces input membrane resistance on our model. This leads to the conclusion that L‐BMAA depolarizes the cell by increasing membrane permeability and conductance. The effect of L‐BMAA in 20 mM bicarbonate is significantly higher than in standard Ringer solution. These results indicate that bicarbonate increases the excitatory effect of L‐BMAA in our model.
Effects of Cooling on the Response of the Snail Bursting Neuron to Acetylcholine
Authors: NEDELJKOVIĆ MIODRAG , KARTELIJA GORDANA , RADENOVIĆ LIDIJA
Published: September 2005

Abstract: The Br‐type neuron of the snail Helix pomatia, involved in neuronal regulation of various homeostatic and adaptive mechanisms, represents an interesting model for studying effects of temperature change on neuronal activity of poikilotherms. Acetylcholine induces a transient, inward dose‐dependent current in the identified Br neuron. In the work presented, we analyzed the effects of cooling on the acetylcholine‐induced inward current. The amplitude of acetylcholine‐induced inward current was markedly decreased after cooling, and the speed of the decay of acetylcholine response was decreased.
Effects of Some Heavy Metals on the Action Potentials of an Identified Helix pomatia Photosensitive Neuron
Authors: KARTELIJA GORDANA , RADENOVIĆ LIDIJA , TODOROVIĆ NATAŠA , NEDELJKOVIĆ MIODRAG
Published: September 2005

Abstract: In the photosensitive MB neuron in the left parietal ganglion of Helix pomatia, the onset of light prolongs significantly (by about 40%) the duration of the action potential. The broadening of the action potential after the onset of light was found to be due to its calcium component and could not be induced after blocking Ca2+ channels by Cd2+ and Pb2+ and in absence of Ca2+ in medium. The blocking effect of both compounds was reversible. It was found that CdCl2 exhibited a more intense blocking effect than PbCl2.
Differences in Antioxidative Response of Rat Hippocampus and Cortex after Exposure to Clinical Dose of γ‐Rays
Authors: TODOROVIĆ ANA , KASAPOVIĆ JELENA , PEJIĆ SNEŽANA , STOJILJKOVIĆ VESNA , PAJOVIĆ SNEŽANA B.
Published: September 2005

Abstract: Ionizing radiation increases intracellular production of reactive oxygen species, which can damage cell structure and function. The brain is particularly vulnerable to oxidative injury, and in an area‐dependent manner. In order to elucidate differences in enzymatic antioxidative response of rat hippocampus and cortex, we measured activities of CuZnSOD, MnSOD, and CAT in those two brain regions, isolated 1 h and 24 h after exposure to 2 Gy of γ‐rays. Our results indicate that lower MnSOD activities and inducibility, found in the hippocampus, are probably some of the main reasons for the particularly great oxidative vulnerability of this brain region.
The Effects of Exposure to Extremely Low‐Frequency Magnetic Field and Amphetamine on the Reduced Glutathione in the Brain
Authors: JELENKOVIĆ ANKICA , JANAĆ BRANKA , PEŠIĆ VESNA , JOVANOVIĆ MARINA D. , VASILJEVIĆ IVANA , PROLIĆ ZLATKO
Published: September 2005

Abstract:Continuous exposure to extremely low‐frequency magnetic field (ELF‐MF, 50 Hz, 0.5 mT) alone and combined with D‐amphetamine (1.5/mg/kg) affected the reduced glutathione content in brain regions of rats. Compared to sham‐exposed rats, the glutathione content in the forebrain cortex of the ELF‐MF‐exposed rats decreased (P< 0.001), but this reverted after giving amphetamine upon ELF‐MF exposure. In this group, the glutathione content was increased in the brain stem and cerebellum (P< 0.05compared to the sham‐exposed, ELM‐MF‐exposed, and amphetamine‐treated groups). It is suggested that biogenic monoamines are involved in the reduced glutathione changes observed. The changes are not uniform in the brain regions examined.
The Effect of Extremely Low‐Frequency Magnetic Field on Motor Activity of Rats in the Open Field
Authors: PROLIĆ ZLATKO , JANAĆ BRANKA , PEŠIĆ VESNA , JELENKOVIĆ ANKICA
Published: September 2005

Abstract: Exposure to extremely low‐frequency magnetic field (ELF‐MF, 50 Hz, 0.5 mT) for seven days did not change spontaneous motor activity of rats in the open field compared to sham‐exposed animals. Pre‐exposure to ELF‐MF decreased locomotor and stereotypic activity induced by amphetamine (1.5 mg/kg body weight) and accordingly increased the resting time compared to sham‐exposed and amphetamine‐treated rats. Vertical activity (rearing) of these two groups was similar. Our results indicate that ELF‐MF has different effects on some parameters of amphetamine‐induced motor activity, probably due to brain region‐specific effects on catecholaminergic systems responsible for movement control.
Different Effects of Adenosine A1 Agonist Ribavirin on Amphetamine‐Induced Total Locomotor and Stereotypic Activities in Rats
Authors: JANAĆ BRANKA , PEŠIĆ VESNA , PEKOVIĆ SANJA , RAKIĆ LJUBISAV , STOJILJKOVIĆ MIRJANA
Published: September 2005

Abstract: Pretreatment with a single dose of ribavirin (10, 20, and 30 mg/kg b.w. i.p.) decreased amphetamine (1.5 mg/kg b.w. i.p.)‐induced total locomotor activity (distance traveled) compared to amphetamine alone, but the most significant effect was observed with 30 mg/kg dose. In contrast, total stereotypic activities (such as sniffing, self‐grooming, licking, and head weaving) of these animals were unchanged. These findings demonstrate the ability of ribavirin to modulate in a different way central regulation of locomotor and stereotypic activities that in the future could have a practical application in target therapy of some movement disorders.
Simulation of the Neuronal Interactions and Connection of Neuronal Activity with Changes of Heart Rhythm and Myocardial Electrophysiological Properties
Authors: PRUDNIKAU HEORHI A.
Published: September 2005

Abstract: The purpose was to create the software for analysis of temporal relationship between spike trains of several neurons and connection of neuronal activity with changes of heart rhythm and some electrocardiogram parameters. The designed software represents an integrated estimation of the cross‐correlograms and cardiac‐cycle triggered correlograms combination. It permits the study of the nonrandom temporal relationship between spike trains of neurons using experimental data and the estimation of the roles of one neuron and a group of them and the role of their discharges patterns in changes of heart rhythm and electrophysiological properties of the myocardium.
Estimation of Parameter kmaxin Fractal Analysis of Rat Brain Activity
Authors: SPASIĆ SLADJANA , KALAUZI ALEKSANDAR , ĆULIĆ MILKA , GRBIĆ GORDANA , MARTAĆ LJILJANA
Published: September 2005

Abstract:We recorded electrocortical activity in anesthetized rats and constructed kmaxnew self‐similar time series, applying Higuchi's algorithm. The aim of this study was to estimate value of the parameter kmaxin order to obtain fractal dimension values as an optimum measure of biosignal change. After our analysis, electrocortical activity recordings resulted in a family of curves f(kmax). Three regions could be distinguished 2 ≤ kmax< 8, with a U‐shape; 8 ≤ kmax≤ 30, with a steeper quasilinear increase; and kmax≥ 30, with a smaller slope quasilinear increase. We suggest the optimum region for kmax: 8 < kmax< 18, specifically kmax= 8.
A Theoretical Study of Hypothalamo‐Pituitary‐Adrenocortical Axis Dynamics
Authors: SAVIĆ DANKA , JELIĆ SMILJANA
Published: September 2005

Abstract: Does the hypothalamo‐pituitary‐adrenocortical (HPA) axis itself generate oscillations? The affirmative answer to this question is commonly assumed, because a regular daily rhythm of its hormones is observed. We offer another plausible explanation of the origin of this pattern: HPA just responds to an external pacemaker. A qualitative mathematical model is constructed wherein all the terms in the equations are physicochemically interpretable. Linear stability analysis shows that this system does not generate oscillations. Computer simulation yields oscillations that are the system's response to an external pulsing activator, implying that the observed pattern does not have to be an intrinsic property of this system.
Receptive‐Field Structure of Direction‐Selective Ganglion Cells Projecting to the Goldfish Tectum
Authors: GOLOVKIN MICHAEL , GORBUNOV VADIM , MAXIMOVA ELENA , MAXIMOV VADIM
Published: September 2005

Abstract: The receptive field of a direction‐selective unit of any type consists of an excitatory center 3°‐5° in size, a near inhibitory surround and a far surround upon which illumination exerts an influence for both spontaneous activity and specific cell response.
Influence of Photic Environment on the Form of the Fish Electroretinographic Off‐Response
Authors: GAČIĆ ZORAN , DAMJANOVIĆ ILIJA , KONJEVIĆ DJORDJE , BAJIĆ ALEKSANDAR , MILOŠEVIĆ MILENA , ANDJUS PAVLE R. , MIĆKOVIĆ BRANISLAV , ANDJUS RADOSLAV K.
Published: September 2005

Abstract: Scotopic electroretinogram of dogfish shark (Scylliorhinus canicula) and eel (Anguilla anguilla) is characterized by a negative off‐response, changing in sign under photopic condition. It increased under the effect of increased background illumination, but its amplitude never exceeded that of the b‐wave. On the other hand, dark‐adapted electroretinograms of two perch‐like species, perch (Perca fluviatilis) and painted comber (Serranus scriba), exhibited a positive off‐wave, exceeding the b‐wave amplitude under bright photopic conditions.
Apoptosis of Peripheral Human Blood Lymphocytes Induced by Physical‐Chemical Influences and Generation of Reactive Oxygen Species
Authors: TAMASHEVSKI A.EXANDER , SLOBOZHANINA EKATERINA , SERGIENKO TATIANA , BAKKUN A.EXANDRA , TARAS IRINA , MEDVED IRINA , SVIRNOVSKI A.CADI
Published: September 2005

Abstract: The sensitivity of peripheral blood lymphocytes of healthy people (blood donors) to induced apoptotic processes and reactive oxygen species production under physical‐chemical influences was evaluated in vitro.
Study of the pH‐Dependent Conformational Changes in α1‐Acid Glycoprotein Using FRET
Authors: MIKHAILOV ALEXEI S.
Published: September 2005

Abstract: We studied pH‐dependent conformational changes in α1‐acid glycoprotein using both binding of cationic fluorescent probe Quinaldine Red with protein molecule and changes in distance between tryptophan from binding site of the protein and Calcofluor White on glycan surface using FRET. Our data show that the binding site of the protein has undergone a conformational change at pH 9.0. At this pH. the binding site forms a more hydrophobic region and tryptophan residues from the binding site move to the center of the protein core.
Nonenzymatic Reaction of Dihydroxyacetone with Hydrogen Peroxide Enhanced via a Fenton Reaction
Authors: MAKSIMOVIĆ VUK , MOJOVIĆ MILOŠ , NEUMANN GÜNTER , VUČINIĆ ŽELJKO
Published: September 2005

Abstract: An analysis of the reaction of dihydroxyacetone with hydrogen peroxide was performed using HPLC with electrochemical and spectrophotometric detection and EPR spectroscopy of the reactants and products. Glycolate production in such a reaction has been documented, and the glycolate yield analyzed at different pH values. The participation of hydroxyl free radical is shown with DEPMPO spin trap. Two types of mechanisms are proposed, one at higher pH values and pronounced participation of free radicals (enhanced by the presence of metal ions and Fenton reaction) and the other at lower pH values, with decreased free radical production and lower glycolate yield.
The Effect of Anoxia on PolyP Content of Phycomyces blakesleeanus Mycelium Studied by 31P NMR Spectroscopy
Authors: ZAKRZEWSKA JOANNA , ŽIŽIĆ MILAN , ŽIVIĆ MIROSLAV
Published: September 2005

Abstract: The effect of anoxia and the respiratory chain inhibitors azide and cyanide on the polyphosphate content of Phycomyces was studied by in vivo31P NMR spectroscopy. Anoxia was manifested by a decrease of core polyphosphates (PPi) and increase of intracellular inorganic phosphate (Pi) signal. Normalized changes in PPi/Pi ratio between control and nitrogen‐purged mycelia suggest that the sensitivity to anoxia differs with growth phases. Azide acts in the same way as anoxia, by decreasing the PPi/Pi ratio, while cyanide causes an increase of the PPi/Pi ratio.
Ca2+ and H+ Ion Fluxes near the Surface of Gravitropically Stimulated Phycomyces Sporangiophore
Authors: ŽIVANOVIĆ BRANKA
Published: September 2005

Abstract: The single‐celled fungus Phycomyces blakesleeanus forms vertically oriented sporangiophores from hyphae, which display a negative gravitropic response. Longitudinal growth and gravitropic bending of these sporangiophores were measured with noninvasive H+ and Ca2+ ion‐selective microelectrode measurements. The directions of H+ and Ca2+ fluxes, recorded at different locations of sporangiophores, were opposite when the sporangiophores were kept in vertical position. Ca2+ fluxes were in most experiments positive (efflux), while H+ fluxes were negative (influx). The direction of ion fluxes depended on developmental stage of sporangiophores and changed with gravistimulation.
A New Model System for Investigation of Ionic Channels in Filamentous Fungi: Evidence for Existence of Two K+‐Permeable Ionic Channels in Phycomyces blakesleeanus
Authors: ŽIVIĆ MIROSLAV , POPOVIĆ MARKO , ŽIVANOVIĆ BRANKA , VUČINIĆ ŽELJKO
Published: September 2005

Abstract: A technique was developed to obtain viable cytoplasmic droplets, enabling the formation of a gigaohm seal. Such cytoplasmic droplets can be used for characterization of plasma membrane ion channels from filamentous fungi by patch‐clamp technique. Two K+ ionic channels are characterized with a conductance of 43 pS and 74 pS.
Changes in Chenopodium rubrum Seeds with Aging
Authors: MITROVIĆ ALEKSANDRA , DUČIĆ TANJA , LIRIĆ‐RAJLIĆ IVANA , RADOTIĆ KSENIJA , ŽIVANOVIĆ BRANKA
Published: September 2005

Abstract: We studied antioxidative system, germination, growth, and flowering in vitro in Chenopodium rubrum seeds of different ages. Peroxidase, superoxide dismutase, and catalase activity, as well as glutathione status, were determined in 2.5‐h imbibed seeds. Germination was tested under controlled conditions. Growth and flowering of plants were tested in vitro. The enzyme activities and glutathione content were higher in younger seeds. Germination declines with seed age. Plants derived from older seeds were smaller, and flowering percentage was lower compared to plants derived from younger seeds. Gibberellic acid reduced the difference in growth and flowering between plants derived from seeds different in age.
The Mutual Effect of Extracellular Ca2+, Abscisic Acid, and pH on the Rate of Stomatal Closure
Authors: PROKIĆ LJILJANA , JOVANOVIĆ ZORICA , STIKIĆ RADMILA , VUČINIĆ ŽELJKO
Published: September 2005

Abstract: An analysis of the rate of stomatal closure in epidermal strips of Commelina communis L. induced by different calcium concentrations (10 nM to 1 mM) demonstrated a biphasic dependency, the initial process of closure being more calcium dependent. This dependency was more evident at pH 7 than pH 5 of the bathing medium. Addition of low concentrations of abscisic acid (10 nM) induced a broadening of the Ca2 dependency, while 10 μM abscisic acid increased the rate of stomatal closure in the whole Ca2+ range and to a large extent abolished the calcium‐induced effects. Such results indicate an interaction of external protons, Ca2+, and abscisic acid, and possible competition for the membrane associated binding sites of the mechanism(s) responsible for the regulation of stomatal closure.
Genetic Code: An Alternative Model of Translation
Authors: DAMJANOVIĆ ZVONIMIR M. , RAKOČEVIĆ MILOJE M.
Published: September 2005

Abstract: Our earlier studies of translation have led us to a specific numeric coding of nucleotides (A = 0, C = 1, G = 2, and U = 3)—that is, a quaternary numeric system; to ordering of digrams and codons (read right to left: .yx and Z.yx) as ordinal numbers from 000 to 111; and to seek hypothetic transformation of mRNA to 20 canonic amino acids. In this work, we show that amino acids match the ordinal number—that is, follow as transforms of their respective digrams and/or mRNA‐codons. Sixteen digrams and their respective amino acids appear as a parallel (discrete) array. A first approximation of translation in this view is demonstrated by a “twisted” spiral on the side of “phantom” codons and by ordering amino acids in the form of a cross on the other side, whereby the transformation of digrams and/or phantom codons to amino acids appears to be one‐to‐one! Classification of canonical amino acids derived from our dynamic model clarifies physicochemical criteria, such as purinity, pyrimidinity, and particularly codon rules. The system implies both the rules of Siemion and Siemion and of Davidov, as well as balances of atomic and nucleon numbers within groups of amino acids. Formalization in this system offers the possibility of extrapolating backward to the initial organization of heredity.
Novel Immune-Based Treatment Strategies for Chronic Lymphocytic Leukemia
Authors: Wierda William G. , Kipps Thomas J. , Keating Michael J.
Published: September 2005

Immune-based treatments represent a new group of therapeutic strategies for patients with cancer, including chronic lymphocytic leukemia (CLL), that employ immune effector mechanisms. Among these strategies is passive immunotherapy with monoclonal antibody, alone or in combination with chemotherapy. Active immunotherapy strategies currently under development include vaccines, administration of expanded and activated T cells, and allogeneic stem cell transplantation. These immune-based strategies represent new treatments with potentially complementary mechanisms of action to standard therapies and signify major advances in treatments for patients with CLL.
New Targeted Approaches in Chronic Myeloid Leukemia
Authors: Cortes Jorge , Kantarjian Hagop
Published: September 2005

The treatment of chronic myeloid leukemia has changed dramatically in the last few years. Stem-cell transplantation and the use of interferon alfa had already offered the possibility of complete and durable cytogenetic responses, improving the survival over that expected with conventional chemotherapy. The introduction of imatinib mesylate has started the era of molecular therapy with remarkable results including complete cytogenetic responses in up to 90% of patients and major molecular responses in most. However, some patients, particularly those treated in the advanced stages, may develop resistance to imatinib. Thus there has been interest in developing new agents that would not only help patients for whom imatinib is ineffective or intolerable, but that could also be combined with the intention of eliminating all evidence of disease. Several approaches are being pursued. These include new and more potent tyrosine kinase inhibitors that may not be affected by the most common mutations seen in the clinic. Some of these agents also inhibit Src-related kinases that may play a role in the development of resistance to imatinib. Other agents are directed at downstream or alternative pathways in leukemic cells, exploring potential synergy with imatinib. Another approach is to pursue an immune modulation that might eliminate small amounts of residual disease. Many of these agents are already showing promising results in the clinic. This manuscript reviews some of these agents, particularly those for which clinical data are already available.
Molecular Pathogenesis of Mucosa-Associated Lymphoid Tissue Lymphoma
Authors: Farinha Pedro , Gascoyne Randy D.
Published: September 2005

Extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) type occur in a number of anatomic sites, but share overlapping morphologic and immunophenotypic features. Helicobacter pylori infection has been identified as an etiologic factor in gastric MALT lymphoma, and a growing list of other infectious organisms have recently been shown to be associated with MALT lymphomas at other anatomic sites. Although cause and effect has not been established for most of these infectious agents, our understanding of the biology has significantly improved, in part through the application of standard cytogenetic analyses. The common karyotypic alterations that characterize MALT lymphomas include the trisomies 3 and 18, the translocations t(11;18)(q21;q21), t(1;14)(p22;q32), t(14;18)(q32;q21), t(3;14)(q27;q32), and the recently described t(3;14)(p14.1;q32). This apparent complexity of cytogenetic alterations that have now been implicated in the pathogenesis of extranodal MALT lymphoma serves as a paradigm for molecular cross talk in neoplastic disease. Recent data have shown that at least three of the disparate translocations affect a common signaling mechanism, and thus unify all three under a common pathogenesis, resulting in the constitutive activation of the nuclear factor kappa B (NF-κB) pathway. It may be that the new MALT-related translocation involving the FOXP1 gene and other as yet undiscovered translocations may all have in common increased NF-κB signaling.
Pathogenesis of Mantle-Cell Lymphoma: All Oncogenic Roads Lead to Dysregulation of Cell Cycle and DNA Damage Response Pathways
Authors: Fernàndez Veronica , Hartmann Elena , Ott German , Campo Elias , Rosenwald Andreas
Published: September 2005

Mantle-cell lymphoma (MCL) is a well-defined subtype of B-cell non-Hodgkin's lymphomas (B-NHL), accounts for approximately 6% of all lymphoid neoplasms, and has a median survival of 3 to 4 years. The genetic hallmark of MCL is the chromosomal translocation t(11;14)(q13;q32) that leads to deregulation and upregulation of Cyclin D1, an important regulator of the G1 phase of the cell cycle. This genetic event is present in virtually all cases of MCL, whereas additional genetic alterations that occur in subsets of MCL have been described. Most of these alterations appear to disturb the cell cycle machinery/interfere with the cellular response to DNA damage, thus making MCL a paradigm for cell cycle and DNA damage response dysregulation in cancer in general. In particular, Cyclin D1 upregulation, genomic amplification of the cyclin-dependent kinase (CDK) -4, deletions of the CDK inhibitor p16INK4a and overexpression of BMI-1, a transcriptional repressor of the p16INK4a locus, are associated with dysregulation of the cell cycle machinery in MCL. The DNA damage response pathway is affected by frequent alterations of the ataxia-telangiectasia mutated (ATM) kinase as well as occasional inactivation of checkpoint kinase (CHK)-1 and CHK2 that are kinases that act downstream of ATM in response to detection of DNA damage. Moreover, p53 is frequently targeted by alterations in MCL. A recent gene expression profiling study defined the proliferation signature, a quantitative measure of gene expression of proliferation-associated genes as the strongest survival predictor available to date allowing the definition of prognostic MCL subgroups that differ in median survival by more than 5 years.
Molecular Genetics of Acute Lymphoblastic Leukemia
Authors: Armstrong Scott A. , Look A. Thomas
Published: September 2005

From its beginnings two decades ago with the analysis of chromosomal translocation breakpoints, research into the molecular pathogenesis of acute lymphoblastic leukemia (ALL) has now progressed to the large-scale resequencing of candidate oncogenes and tumor suppressor genes in the genomes of ALL cases blocked at various developmental stages within the B- and T-cell lineages. In this review, we summarize the findings of these investigations and highlight how this information is being integrated into multistep mutagenesis cascades that impact specific signal transduction pathways and synergistically lead to leukemic transformation. Because of these advances, fueled by improved technology for mutational analysis and the development of small-molecule drugs and monoclonal antibodies, the future is bright for a new generation of targeted therapies. Best illustrated by the successful introduction of imatinib mesylate, these new treatments will interfere with disordered molecular pathways specific for the leukemic cells, and thus should exhibit much less toxicity and fewer long-term adverse effects than currently available therapeutic modalities.
Immunotherapy for Non-Hodgkin's Lymphoma: Monoclonal Antibodies and Vaccines
Authors: Maloney David G.
Published: September 2005

Advances in the development of monoclonal antibodies have led to new agents rapidly incorporated into standard lymphoma therapy. The characteristics of the target antigen and the properties of the antibody including interaction with the host immune system have been found to correlate with outcome. Antibodies targeting the CD20 antigen on B cells have been most widely used, led by the chimeric antibody rituximab, now used in nearly all types of B-cell non-Hodgkin's lymphoma (NHL). New antibodies targeting CD20 with augmented complement or Fc receptor binding are now being evaluated and will eventually have to be compared with rituximab. Challenges to these new antibodies include the nearly universal use of rituximab early in NHL therapy, and its increasing use as maintenance therapy. It is not clear what the activity of these antibodies will be in rituximab-refractory patients. New antibodies targeting antigens such as CD40 and CD80 are also being tested alone and in combination with rituximab. Vaccine trials using patient-specific immunization with immunoglobulin idiotype (Ig-Id present on the surface of most B-cell NHL) isolated by molecular rescue or by cell hybridization techniques are also nearing completion. These approaches attempt to actively induce specific humoral or cellular immune responses to the Ig-Id by attaching the protein to a carrier protein and the use of an immunologic adjuvant such as granulocyte macrophage colony-stimulating factor. Prior rituximab appears to delay humoral responses to the idiotype but may still allow cellular responses. The incorporation of all these approaches into optimal NHL therapy remains a challenge.
Treatment Strategies in Follicular Lymphomas: Current Status and Future Perspectives
Authors: Hiddemann Wolfgang , Buske Christian , Dreyling Martin , Weigert Oliver , Lenz Georg , Forstpointner Roswitha , Nickenig Christina , Unterhalt Michael
Published: September 2005

Although little progress has been made in the treatment of follicular lymphomas (FL) within the last few decades, several new therapeutic modalities have recently demonstrated promising activity. These include myeloablative therapy followed by autologous stem cell transplantation in younger patients in first remission revealing a significant prolongation of remission duration in three prospective randomized trials, whereas the impact on overall survival still needs to be determined. Adding the anti-CD20 antibody rituximab to conventional chemotherapy resulted in a significant increase in remission rate, remission duration and in two of four currently available prospective randomized studies even in a longer overall survival. A prolongation of remission duration was also seen when rituximab was administered as maintenance after cytoreductive therapy or by prolonged application as a single agent. Radioimmunotherapy (RIT) with radioisotopes coupled to monoclonal antibodies revealed encouraging data in several phase II studies. Prospective randomized studies are warranted, however, to define the impact of RIT on FL therapy. New therapeutic perspectives also emerge from increasing insights into the biology of the disease that unravel molecular targets for novel agents, some of which have entered clinical evaluation already.
Molecular Pathogenesis of Hodgkin's Lymphoma
Authors: Re Daniel , Küppers Ralf , Diehl Volker
Published: September 2005

According to the WHO classification, Hodgkin's lymphoma (HL) is subdivided into a classical variant and a nodular lymphocyte predominant variant which are characterized by the presence of Hodgkin's and Reed-Sternberg (H-RS) cells or lymphocytic and histiocytic (L&H) cells, respectively. This article reviews genetic characteristics and transcriptional changes of H-RS and L&H cells, including recent knowledge about transforming mechanisms and signaling pathways that contribute to the antiapoptotic phenotype displayed by H-RS and L&H cells. We also discuss major cellular and molecular mediators contributing to the establishment and maintenance of a reactive background in HL-affected tissues. We believe that an in-depth understanding of the pathogenesis of HL will eventually lead to the development of novel biologically based therapeutic strategies in the near future.
Current Treatment Approaches for Mantle-Cell Lymphoma
Authors: Witzig Thomas E.
Published: September 2005

Mantle-cell lymphoma (MCL) is now recognized as a distinct clinicopathologic subtype of B-cell non-Hodgkin's lymphoma. Patients with MCL are typically older adults with a male predominance and usually present with stage IV disease. The cells are characterized as CD20+ CD5+ CD23− with a t(11;14)(q13;q32) and cyclin D1 overexpression on immunohistochemistry. Response to chemotherapy usually results in a tumor response but unmaintained remissions are short and the median survival is 3 to 4 years. The treatment approach to newly diagnosed patients with MCL depends on the patient's eligibility for stem cell transplantation (SCT). Those who are eligible are usually treated with either rituximab-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) followed by SCT or rituximab-HyperCVAD (cyclophosphamide, vincristine, doxorubicin, decadron, cytarabine, and methotrexate) followed by observation. The purine nucleoside analogues also have activity as single agents and with rituximab. Unfortunately none of these approaches can definitively cure patients with MCL, and new agents are needed. Recent studies in patients with relapsed MCL have shown substantial antitumor activity of single-agent bortezomib, single-agent temsirolimus, and the combination of thalidomide and rituximab. Studies integrating these novel agents earlier in the disease course or in combination with each other will hopefully produce more durable responses with less toxicity.
Prostaglandin E2 Strongly Inhibits Human Osteoclast Formation
Authors: Take Ikuko , Kobayashi Yasuhiro , Yamamoto Yohei , Tsuboi Hideki , Ochi Takahiro , Uematsu Setsuko , Okafuji Norimasa , Kurihara Saburo , Udagawa Nobuyuki , Takahashi Naoyuki
Published: September 2005

Prostaglandin E2 (PGE2) enhances osteoclast formation in mouse macrophage cultures treated with receptor activator of nuclear factor-κB ligand (RANKL). The effects of PGE2 on human osteoclast formation were examined in cultures of CD14+ cells prepared from human peripheral blood mononuclear cells. CD14+ cells differentiated into osteoclasts in the presence of RANKL and macrophage colony-stimulating factor. CD14+ cells expressed EP2 and EP4, but not EP1 or EP3, whereas CD14+ cell-derived osteoclasts expressed none of the PGE2 receptors. PGE2 and PGE1 alcohol (an EP2/4 agonist) stimulated cAMP production in CD14+ cells. In contrast to mouse macrophage cultures, PGE2 and PGE1 alcohol inhibited RANKL-induced human osteoclast formation in CD14+ cell cultures. H-89 blocked the inhibitory effect of PGE2 on human osteoclast formation. These results suggest that the inhibitory effect of PGE2 on human osteoclast formation is mediated by EP2/EP4 signals. SaOS4/3 cells have been shown to support human osteoclast formation in cocultures with human peripheral blood mononuclear cells in response to PTH. PGE2 inhibited PTH-induced osteoclast formation in cocultures of SaOS4/3 cells and CD14+ cells. Conversely, NS398 (a cyclooxygenase 2 inhibitor) enhanced osteoclast formation induced by PTH in the cocultures. The conditioned medium of CD14+ cells pretreated with PGE2 inhibited RANKL-induced osteoclast formation not only in human CD14+ cell cultures, but also in mouse macrophage cultures. These results suggest that PGE2 inhibits human osteoclast formation through the production of an inhibitory factor(s) for osteoclastogenesis of osteoclast precursors.