bluuebunny/crossref_metadata_2025 huggingface dataset:
Health-related quality of life is related to COPD disease severity
Authors: Ståhl Elisabeth , Lindberg Anne , Jansson Sven-Arne , Rönmark Eva , Svensson Klas , Andersson Fredrik , Löfdahl Claes-Göran , Lundbäck Bo
Published: September 2005

Background

The aim of this study was to evaluate the association between health-related quality of life (HRQL) and disease severity using lung function measures.

Methods

A survey was performed in subjects with COPD in Sweden. 168 subjects (70 women, mean age 64.3 years) completed the generic HRQL questionnaire, the Short Form 36 (SF-36), the disease-specific HRQL questionnaire; the St George's Respiratory Questionnaire (SGRQ), and the utility measure, the EQ-5D. The subjects were divided into four severity groups according to FEV1 per cent of predicted normal using two clinical guidelines: GOLD and BTS. Age, gender, smoking status and socio-economic group were regarded as confounders.

Results

The COPD severity grades affected the SGRQ Total scores, varying from 25 to 53 (GOLD p = 0.0005) and from 25 to 45 (BTS p = 0.0023). The scores for SF-36 Physical were significantly associated with COPD severity (GOLD p = 0.0059, BTS p = 0.032). No significant association were noticed for the SF-36, Mental Component Summary scores and COPD severity. Scores for EQ-5D VAS varied from 73 to 37 (GOLD I-IV p = 0.0001) and from 73 to 50 (BTS 0-III p = 0.0007). The SGRQ Total score was significant between age groups (p = 0.0047). No significant differences in HRQL with regard to gender, smoking status or socio-economic group were noticed.

Conclusion

The results show that HRQL in COPD deteriorates with disease severity and with age. These data show a relationship between HRQL and disease severity obtained by lung function.
Comparison of the uptake of health assessment items for Aboriginal and Torres Strait Islander people and other Australians: Implications for policy
Authors: Kelaher Margaret , Dunt David , Thomas David , Anderson Ian
Published: September 2005

Background

Health Assessment (HA) items were introduced in 1999 for Aboriginal and Torres Strait Islander people aged at least 55 years and all Australians aged over 75 years. In 2004 a new item was introduced for HAs among adult Aboriginal and Torres Strait Islander people aged 15–54 years. The new item has been applauded as a major policy innovation however this enthusiasm has been tempered with concern about potential barriers to its uptake. In this study we aim to determine whether there are disparities in uptake of HA items for Aboriginal and Torres Strait Islander people compared to other Australians.

Method

The analysis was based on Health Insurance Commission data. Indigenous status was ascertained based on the item number used. Logistic regression was used to compare uptake of HA items for older people among Aboriginal and Torres Strait Islander people compared to other Australians. Adjustments were made for dual eligibility. Uptake of the HA items for older people was compared to the uptake of the new item for Aboriginal and Torres Strait Islander people aged 15–44 years.

Results

Our analyses suggest a significant and persistent disparity in the uptake of items for older patients among Aboriginal and Torres Strait Islander people compared to other Australians. A similar disparity appears to exist in the uptake of the new adult Aboriginal and Torres Strait Islander HA item.

Conclusion

Further engagement of primary care providers and the community around the uptake of the new HA items may be required to ensure that the anticipated health benefits eventuate.
Radoslav K. Andjus (1926–2003)
Authors: STOJILKOVIC STANKO S. , ŽIVADINOVIĆ DRAGOSLAVA , HEGEDIŠ ALEKSANDAR , MARJANOVIĆ MARINA
Published: September 2005

Radoslav K. Andjus was a professor of physiology and biophysics at the University of Belgrade, Serbia, from 1953 to 1992. He was an elected member of the Serbian Academy of Sciences and Arts, the International Academy of Astronautics, and the Montenegrin Academy of Sciences and Arts. He published over 190 papers in domestic and international journals and three textbooks. The main field of his research was thermophysiology. He studied hypothermia, suspended animation and resuscitation, hibernation and biological rhythms, temperature adaptation and acclimation, and cryoprotection. Professor Andjus also contributed significantly to the fields of brain metabolism, endocrinology, electroretinography, as well as biophysical modeling and theoretical biology.
Equilibrium of Nucleotides in the Dogfish Brain
Authors: ANDJUS RADOSLAV K. , DŽAKULA ŽELJKO , MARJANOVIĆ MARINA
Published: September 2005

Abstract: In the past, the results of experiments on the time course of concentration changes of adenylates, phosphocreatine, and free creatine in muscle appeared compatible with an equilibrium hypothesis involving only the Lohmann and the myokinase reactions. Other reports, however, denied the applicability of the equilibrium hypothesis to the same tissue. The controversy may have been due to the high probability of experimental errors since time sampling was performed at second intervals. We presently test the hypothesis in the living brain of the small‐spotted dogfish shark (Scyliorhinus canicula), an animal‐model allowing for timing of sampling at hourly intervals. According to our earlier work, the dogfish shark can easily be resuscitated 8.2 h on average after being brought into the state of “suspended animation” at 0°C body temperature and exposed, out of water, to an atmosphere of nitrogen gas. To obtain a complete mathematical description of the time course of concentration changes of brain adenylates and phosphocreatine, we devised a kinetic model based on principles of classical multicompartmental analysis and biochemical kinetics. Model testing of the equilibrium hypothesis resulted in very good agreement between the hypothesis and our experimental data. Time‐course modeling, achieved by simultaneously fitting the time series of our data by the set of four equations constituting our model resulted in an excellent agreement between data points and the computed curves. Finally, modeling of the depletion profiles of brain energy status concerning three of its descriptors (energy charge, total adenylate, and primary energy stores expressed in high‐energy phosphate equivalents) allowed for a correlation to be established between energy status and the “revival time,” a valuable physiological descriptor of tolerance.
Mechanisms of Immediate Temperature Compensation: Experiments with Brain Synaptosomes from Rat and Ground Squirrel
Authors: MARJANOVIĆ MARINA , ŽIVADINOVIĆ DRAGOSLAVA , DŽAKULA ŽELJKO , ANDJUS RADOSLAV K.
Published: September 2005

Abstract: Glucose conversion by brain synaptosomes can be regarded as a special case of intrinsic kinetic properties of the enzyme substrate system. Temperature modulation of apparent Km for this process can be described with our kinetic model. Using experimental data and the kinetic model, the minimal Km value for glucose conversion in ground squirrel synaptosomes was found at the lower temperature (6.5°C), much lower than that for the rat (16.6°C). The inversion temperatures (Tmin) closely coincided with the lowest body temperatures from which the unassisted recovery from hypothermia was demonstrated in both species. This study indicated that thermal modulation of enzyme affinities may have an adaptive role in endotherms that is linked to their tolerance to hypothermia.
Some Components of Hibernation Rhythms
Authors: ŽIVADINOVIĆ DRAGOSLAVA , MARJANOVIĆ MARINA , ANDJUS RADOSLAV K.
Published: September 2005

Abstract: At low ambient temperatures some small mammals drastically reduce their body temperature and enter a state of dormancy known as hibernation. They exhibit endogenous rhythms of heterothermy/homeothermy and body mass fluctuations with the period close to one year. At high ambient temperature only body mass cycling is expressed for almost one year as well. The effect of temperature on circannual periods of some biological rhythms in different hibernators in free‐running conditions as well as the circaseptal character of the intrahibernation rhythm of periodic arousals are reviewed.
Photopic Vision in Eels: Evidences of Color Discrimination
Authors: DAMJANOVIĆ ILIJA , BYZOV ALEXEY L. , BOWMAKER JAMES K. , GAČIĆ ZORAN , UTINA IYA A. , MAXIMOVA ELENA M. , MIĆKOVIĆ BRANISLAV , ANDJUS RADOSLAV K.
Published: September 2005

Abstract: Several classes of second‐order retinal neurons have been studied electrophysiologically in European eel (Anguilla anguilla) from two different localities, Lake Seliger in Russia and the coastal waters of the Adriatic Sea in Montenegro. The majority of L‐horizontal cells (68 explored) had both rod and cone inputs, an uncommon phenomenon among teleosts. Pronounced color‐opponent properties, often taken as pointing to the capacity of color vision, were identified in one amacrine cell, apparently of the “blue/yellow” (or /blue/green”) type. Microspectrophotometric measurements revealed two different spectral classes of cones with absorption maxima at about 525 and 434 nm. The existence of green‐sensitive and blue‐sensitive cone units was thus revealed by both electrophysiological and microspectrophotometric techniques.
Imaging of Spiking and Subthreshold Activity of Mitral Cells with Voltage‐Sensitive Dyes
Authors: DJURIŠIĆ MAJA , ZEČEVIĆ DEJAN
Published: September 2005

Abstract: To obtain a more complete description of individual neurons, it is necessary to complement electrical measurements with technologies such as voltage imaging with intracellular dyes, which permit massive parallel recording from many sites on neuronal processes. Utilizing such an approach, we investigate the functional structure of the mitral cell, the principal output neuron in the rat olfactory bulb. These experiments were designed to determine the number, location, and the stability of spike trigger zones, the excitability of terminal dendritic branches, the pattern and nature of spike initiation and propagation in the primary dendrite, the basic characteristics of the evoked EPSPs at the site of origin (the glomerular tuft), and its attenuation along the primary dendrite. The images of spike trigger zones showed that an action potential can be initiated in three different compartments of the mitral cell: the soma‐axon region, the primary dendrite trunk, and the terminal dendritic tuft, which appears to be fully excitable. The amplitude of the EPSPs evoked by olfactory nerve stimulation was determined at the site of origin (glomerular tuft) and its attenuation was monitored optically along the entire length of the primary dendrite.
Neurite‐Myelin Interaction in the Control of Purkinje Axon Growth and Regeneration
Authors: GIANOLA SARA , ROSSI FERDINANDO
Published: September 2005

Abstract: The limited regenerative capability of adult central neurons results from an interplay between the intrinsic growth potential of injured nerve cells and environmental growth‐inhibitory signals, such as myelin‐associated molecules. These molecules, which are known to inhibit axonal regeneration, are expressed in the adult intact central nervous system, suggesting that they also exert a constitutive regulatory function on uninjured neurites. However, most of the mechanisms underlying this function of myelin‐associated factors are still unclear. To address this issue, we examined Purkinje cells, which show extremely poor regenerative capabilities. Such a weak intrinsic growth potential is attributed, at least in part, to inhibitory activity exerted by the myelin‐associated molecule Nogo‐A on growth‐associated gene expression and axon plasticity of adult Purkinje cells. Indeed, the regenerative potential of these neurons declines during postnatal development in parallel with myelin deposition. In addition, myelin‐associated factors regulate the development of the Purkinje axon intracortical plexus, contributing to the shaping of mature cerebellar connectivity. The action of environmental inhibitory factors can be partially counteracted by overexpression of neuronal growth‐associated molecules. In fact, following axotomy, transgenic Purkinje cells that overexpress GAP‐43 are able to sprout their axons into white matter and show a pronounced tendency to lose myelin. Altogether, these results suggest that the control exerted by myelin on Purkinje axon plasticity plays an important role in preventing aberrant growth and in stabilizing intracortical connectivity. Such a constitutive regulation may eventually hamper compensatory mechanisms set up by the same neurons in response to injury and thus determine their weak regenerative abilities.
Endocytosis‐Dominated Membrane Area Decrease Requires Rab5 Protein in Rat Melanotrophs
Authors: SEDEJ SIMON , RUPNIK MARJAN , ZOREC ROBERT
Published: September 2005

Abstract: Eukaryotic cells internalize extracellular macromolecules by endocytosis and it was shown that Rab5 protein is required for this process. While it is clear that endocytosis consists of vesicle fission from the plasma membrane, the role of Rab5 protein in the plasma membrane surface area changes is still unclear. Here we studied whether Rab5 is required for membrane surface area changes in rat melanotrophs—cells deriving from the pituitary pars intermedia. The presence of this protein in melanotrophs was probed by immunocytochemistry and its putative role in membrane area dynamics was monitored electrophysiologically with membrane capacitance measurements as this parameter directly reflects changes in membrane surface area. We found that Rab5 protein exists in melanotrophs. At [Ca2+]i < 3 μM, endocytosis‐dominated membrane capacitance decrease was found to be blocked by microinjection of specific Rab5 antibody. At high [Ca2+]i, Rab5 antibody did not affect the steady‐state increase in membrane capacitance, while it elevated the rate of membrane capacitance increase, which is consistent with an inhibition of endocytosis.
Effects of Extracellular Calcium on fASIC1 Currents
Authors: TODOROVIĆ NATAŠA , ĆORIĆ TATJANA , ZHANG PING , CANESSA CECILIA
Published: September 2005

Abstract: Fish ASIC1 (fASIC1) cloned from Opsanus tau, unlike the rat ASICs, requires Ca2+ in the extracellular preconditioning solution (pH 7.4) to be activated. Here we show that fASIC1 is interacting with Ca2+ in the same way as mammalian ASICs: extracellular Ca2+ is increasing the proportion of channels available for activation by stabilizing the closed state of the channel; in the activation process Ca2+ is released; H+ compete for the binding site of Ca2+ making the gating mechanism both Ca2+ and H+ dependent; H+ stabilizes the desensitized state; Ca2+ blocks the fASIC1 channel; and the affinity of the block is also modulated by H+. The “Ca2+ activation requirement” of fASIC1 reflects its greater affinity for steady‐state desensitization by H+ compared to mammalian ASIC1.
Role of Calcium in Exocytosis Induced by Hypotonic Swelling
Authors: FEDOROVICH SERGEI V. , WASEEM TATYANA V. , LAVRUKEVICH TATYANA V. , KONEV SERGEI V.
Published: September 2005

Abstract: We studied the influence of Ca2+ on exocytosis induced by hypotonic shock using the fluorescent dyes acridine orange FM1‐43 and FM2‐10. It was shown using acridine orange that lowering osmolarity to 230 mOsm/L induces exocytosis both in calcium‐containing and calcium‐free media. By contrast, we were able to demonstrate calcium dependence of exocytosis using styryl dyes. Lowering osmolarity leads to an increase of neurotransmitter release in a calcium‐independent manner. Thus, our data suggest that hypotonic swelling induces calcium‐independent exocytosis. Calcium influx mediated by stretch channels is able to switch mode of exocytosis from “kiss and run” to full fusion.
Determinants of Low EPSP Attenuation in Primary Dendrites of Mitral Cells: Modeling Study
Authors: POPOVIĆ MARKO , DJURIŠIĆ MAJA , ZEČEVIĆ DEJAN
Published: September 2005

Abstract: Efficiency of synaptic potential propagation through neurons depends mainly on their membrane properties and intracellular resistivity. We use a morphologically realistic compartmental model of a mitral cell and data obtained from whole‐cell patch‐clamp and voltage‐imaging experiments to explore passive parameter space in which reported low EPSP attenuation is observed.
Allosteric Modulation of the Nicotinic Acetylcholine Receptor by Physostigmine
Authors: SVOBODOVÁ LUCIE , KRUŠEK JAN , HENDRYCH TOMÁŠ , VYSKOCIL FRANTIŠEK
Published: September 2005

Abstract: The action of physostigmine on mouse muscle nicotinic acetylcholine receptor expressed in the COS‐7 cell line was studied by the patch‐clamp technique. Physostigmine accelerated, by allosteric modulation, the rate of desensitization of whole cell currents induced by acetylcholine and decreased the maximal amplitude in concentration‐dependent manner.
Mitochondrial Superoxide Production and MnSOD Activity after Exposure to Agonist and Antagonists of Ionotropic Glutamate Receptors in Hippocampus
Authors: RADENOVIĆ LIDIJA , SELAKOVIĆ VESNA , KARTELIJA GORDANA
Published: September 2005

Abstract: Competitive glutamate receptor antagonists APV and CNQX were injected with kainate unilaterally into CA3 region of the rat hippocampus. They both expressed sufficient neuroprotection in the sense of decreasing superoxide production and increasing MnSOD levels, but with differential effect in mechanisms and time dynamics. Our findings suggest that NMDA and AMPA/kainate receptors are differentially involved in superoxide production, and they also impose different neuroprotective effects on the induction of MnSOD activity in hippocampus.
CuZn Superoxide Dismutase in the Hippocampus and Brain Cortex of Rats Exposed to Various Stress Conditions
Authors: FILIPOVIĆ DRAGANA , RADOJČIĆ MARIJA B.
Published: September 2005

Abstract: The CuZn superoxide dismutase (CuZnSOD) protein expression in hippocampus and brain cortex of Wistar male rats exposed to acute, chronic, or combined stress was followed by Western immunoblotting. The CuZnSOD was significantly induced by acute stressors but not by chronic or combined stress conditions. As CuZnSOD expression is regulated by stress steroids, the lack of SOD upregulation under chronic stress and its moderate upregulation in combined stress may lead to inefficient ROS defense and increased oxidative damage of brain tissues under the stress conditions.
Antioxidant Enzyme Activity in Rat Hippocampus after Chronic and Acute Stress Exposure
Authors: STOJILJKOVIĆ VESNA , TODOROVIĆ ANA , KASAPOVIĆ JELENA , PEJIĆ SNEŽANA , PAJOVIĆ SNEŽANA B.
Published: September 2005

Abstract: Chronic exposure to stress alters the prooxidant‐antioxidant balance, which might lead to the development of various human pathological states. In order to explain the role of antioxidant response in stress‐induced injury, we examined the effects of two types of acute stress, as well as combined effects of chronic and acute stress on manganese‐superoxide dismutase, copper, zinc‐superoxide dismutase, and catalase activities in rat brain hippocampus. Our results show that chronic stress induces an increase in oxidative enzyme activities and that adaptation to chronic stress might alter hippocampal antioxidant mechanisms' response to acute stress.
Detecting Long‐Range Correlations in Time Series of Dorsal Horn Neuron Discharges
Authors: BLESIĆ SUZANA , STRATIMIROVIĆ DJORDJE , MILOŠEVIĆ SAVA , LJUBISAVLJEVIĆ MILOŠ
Published: September 2005

Abstract: We have studied the discharge dynamics of dorsal horn neurons by applying the detrended fluctuation analysis and the wavelet transform technique. We have adopted that the neuronal discharge dynamics is manifested by the random time series of interspike intervals. In all cases studied, we found two different power‐law type behaviors across interspike intervals enumeration scale, that are separated by crossover regions (which implies existence of two different types of neuronal noise). Our results reveal that complex neuronal dynamics may change in the presence of external stimulation, manifested by changing of the noise characteristics that appear before crossover.
Combination of Nucleoside Analogues Tiazofurin and Ribavirin Downregulates Experimental Autoimmune Encephalomyelitis
Authors: LAVRNJA IRENA , STOJKOV DANIJELA , PEKOVIĆ SANJA , ŠUBAŠIĆ SANJA , MOSTARICA‐STOJKOVIĆ MARIJA , STOŠIC‐GRUJIČIĆ STANISLAVA , NEDELJKOVIĆ NADEŽDA , MEDIĆ‐MIJAČEVIĆ LJUBICA , RAKIĆ LJUBISAV , STOJILJKOVIĆ MIRJANA
Published: September 2005

Abstract: The effect of combined treatment with ribavirin and tiazofurin on the development of experimental autoimmune encephalomyelitis, the best characterized animal model for human autoimmune disease multiple sclerosis, was investigated. The disease was induced in highly susceptible Dark Agouti rats with spinal cord homogenate in complete Freund's adjuvant. Although ribavirin or tiazofurin alone reduced the clinical and histopathological signs of experimental autoimmune encephalomyelitis, the combination of drugs achieved the same effect with significantly lower doses.
MAPK Activation in Cerebellar Basket Cell Terminals after Harmaline Treatment
Authors: MILAŠIN JELENA , BUFFO ANNALISA , CARULLI DANIELA , ANDJUS PAVLE , STRATA PIERGIORGIO
Published: September 2005

Abstract: The mitogen‐activated protein kinases (MAPKs) are a family of signal transduction mediators that regulate a number of cellular activities, including cell growth and proliferation, differentiation and survival, via phosphorylation (activation) of protein kinases. MAPKs are also recruited during synaptic plasticity and remodeling. In the present study we used Western blotting and immunohistochemistry to examine the effects of harmaline administration on the phosphorylation state of three MAPKs: the extracellular signal‐regulated kinase (ERK1/2), c‐Jun‐N‐terminal kinase/stress‐activated protein kinase (JNK/SAPK), and p38 MAPK. Harmaline is a tremorigenic drug known to induce enhanced and rhythmic firing of the inferior olive. In rats, synchronous activity of the inferior olive cells induced by harmaline administered for four days from postnatal day 9 to 12 resulted in prolonged maintenance of polyinnervation of Purkinje cells by climbing fibers (axons of olivary cells). Immunohistochemistry showed small but sustained cytoplasmic positivity to phospho‐ERK in Purkinje cells and a strong signal for phospho‐ERK in the “pinceaux,” terminals of the interneuronal basket cells onto Purkinje cells. A similar pattern was observed for/JNK/SAPK, while no changes in p38 were noticed. Thus, it was revealed that the activation of two members of the MAPK family in these inhibitory presynaptic terminals is also one consequence of synchronous olivary input to Purkinje cells known to affect developmental plasticity.
Spectral Sensitivity of Direction‐Selective Ganglion Cells in the Fish Retina
Authors: MAXIMOVA ELENA , GOVARDOVSKI VICTOR , MAXIMOV PAUL , MAXIMOV VADIM
Published: September 2005

Abstract: In color matching experiments with extracellular recordings from axon terminals of ganglion cells in the tectum opticum of immobilized goldfish, direction‐selective ganglion cells were shown to be color‐blind. Their spectral sensitivity is determined by a high positive input from the long wavelength‐sensitive cones and weak opponent input from other cone types.
Effects of Metal Ions on Plasma Membrane Mg2+‐ATPase in Rat Uterus and Ovaries
Authors: MILOŠEVIĆ MAJA , PETROVIĆ SNJEŽANA , DEMAJO MIROSLAV , HORVAT ANICA
Published: September 2005

Abstract: The in vitro effects of cadmium and mercury were investigated on the Mg2+‐ATPase activity of plasma membranes from the rat ovary and uterus. ATP hydrolyzing activities were significant and dose‐dependent‐inhibited in both plasma membrane preparations by both metals. According to the IC50 and apparent Ki, Cd2+ was most potent in the ovary, while Hg2+ was most potent in the uterus. In ovaries and uterus, Cd2+ inhibits competitively, while Hg2+ inhibits noncompetitively in both organs. The observed inhibition was a consequence of direct action of the chosen metal ions on the enzyme protein and by decreasing ATP hydrolysis, Hg2+ and Cd2+ may affect mammalian fertility.
Numerically Simulated pH‐Induced Reactivation of Catalytic Activity of Horseradish Peroxidase
Authors: POPOVIĆ‐BIJELIĆ ANA , BIJELIĆ GORAN , KOLAR‐ANIĆ LJILJANA , VUKOJEVIĆ VLADANA
Published: September 2005

Abstract: A model mechanism that accounts for the experimentally observed pH‐dependent enhancement of enzymatic activity of horseradish peroxidase through the catalase‐like pathway is proposed. Predictions of the model are tested against a number of experimental results to confirm that kinetic constants used in the numerical simulation are correctly chosen and that the model can be used to emulate the reaction between horseradish peroxidase and hydrogen peroxide in a wide range of conditions.
Detection of Oxygen‐Centered Radicals Using EPR Spin‐Trap DEPMPO: The Effect of Oxygen
Authors: MOJOVIĆ MILOŠ , VULETIĆ MIRJANA , BAČIĆ GORAN G.
Published: September 2005

Abstract: Studies of the ability of the EPR spin trap DEPMPO to detect both superoxide and hydroxyl radicals produced by systems in vitro and in vivo are presented. Experiments using free radical‐generating systems confirmed the suitability of the EPR spin trapping technique but also revealed the existence of an undesirable conversion of DEPMPO/OOH into DEPMPO/OH adducts. The rate of conversion decreases with oxygenation, and the production of oxygen‐centered radicals increases. However, this property of DEPMPO does not have a significant influence on its ability to independently detect radicals produced by plant plasma membranes. Since the adduct conversion appears to be rather slow compared to radical generation, we conclude that the DEPMPO spin‐trap can be efficiently used for detection of oxygen‐centered radicals produced by systems in vivo, as demonstrated for isolated plasma membranes.
Gibberellic Acid Nitrite Stimulates Germination of Two Species of Light‐Requiring Seeds via the Nitric Oxide Pathway
Authors: JOVANOVIĆ VLADAN , GIBA ZLATKO , DJOKOVIĆ DEJAN , MILOSAVLJEVIĆ SLOBODAN , GRUBIŠIĆ DRAGOLJUB , KONJEVIĆ RADOMIR
Published: September 2005

Abstract: We used two species of light‐requiring seeds, Paulownia tomentosa, which have absolute light requirement (no germination in darkness), and Stellaria media seeds, which germinate in darkness to a certain extent because of presence of preformed active phytochrome, to obtain results strongly suggesting that gibberellic acid nitrite stimulates seed germination via its capability as a functional NO donor. Exogenous application of gibberellic acid nitrite stimulates gibberellin‐insensitive Stellaria media seed germination in darkness as do a wide variety of NO donors. Pure gibberellic acid could replace the light requirement of P. tomentosa seeds, thus enabling them to germinate in darkness. Gibberellic acid nitrite did not have this effect. A stimulative effect from gibberellic acid nitrite could be detected only after exposure of these seeds to short, 10 min, pulse of red light. Taken together, these results suggest that gibberellic activity of gibberellic acid nitrite is lost after nitrosation but, regarding to the presence of −O‐NO moiety in the molecule, gibberellic acid nitrite shares stimulative properties in seed germination with other compounds with NO‐releasing properties.
Fluorescent Properties of Spinach Leaf Plasma Membranes and Chloroplast Envelopes
Authors: CVETIĆ TIJANA , VUČINIĆ ŽELJKO
Published: September 2005

Abstract: Plasma membranes and chloroplast envelopes were isolated from green spinach leaves, and emission and excitation spectra recorded in aqueous solution at 25°C. Chloroplast envelopes excited by 420 nm showed strong emission peaks at 635 and 680 nm that came from chlorophyll precursors present only in these membranes. Upon UV excitation, both plasma membranes and chloroplast envelopes exhibited emission peak at 420 nm originating from pterins and 520 nm due to flavins. Oxidation of the membranes increased both the emission and excitation fluorescence intensity.
Mycorrhiza Formation Enhances Adaptive Response of Hybrid Poplar to Drought
Authors: MARJANOVIĆ ŽAKLINA , UWE NEHLS , HAMPP RUEDIGER
Published: September 2005

Abstract: Mycorrhized and nonmycorrhized plants of hybrid poplar (Populus tremula L. ×Populus tremuloides Mich) were cultivated in petri dishes until the amount of water became limiting (detected by a decrease of photosynthetic yield). RNA was isolated from both main and fine roots and used for analysis of water channel (aquaporin) gene expression by semiquantitative RT‐PCR. For three of five investigated aquaporin genes, expression did not differ between mycorrhized and nonmycorrhized plants. However, expression of the two other aquaporin genes was more pronounced in fine roots of mycorrhized plants, indicating that the root‐fungus symbiosis may improve the water transport capacity under conditions of reduced water availability.
Biophysical Scenario of Giant Gel Formation in the Northern Adriatic Sea
Authors: SVETLIČIĆ VESNA , ŽUTIĆ VERA , ZIMMERMANN AMELA HOZIĆ
Published: September 2005

Abstract: The macroscopic gel phase (mucilage) appears episodically in the northern Adriatic Sea covering tens of square kilometers of sea surface. Current views leave no doubt on phytoplankton production as a proximal source of polymers constituting the gel network, but the mechanism leading to its rapid production remains unknown. We introduced electrochemical sensing of marine microparticles and atomic force microscopy to image supramolecular organization of marine gel network. Our biophysical scenario of mucilage event features self‐organization of biopolymers into microparticles (“marine vesicles”) that under specific conditions transform to giant gel by a fast vesicle‐to‐gel transition.
Genetics of Myeloid Malignancies: Pathogenetic and Clinical Implications
Authors: Fröhling Stefan , Scholl Claudia , Gilliland D. Gary , Levine Ross L.
Published: September 2005

Myeloid malignancies are clonal disorders that are characterized by acquired somatic mutation in hematopoietic progenitors. Recent advances in our understanding of the genetic basis of myeloid malignancies have provided important insights into the pathogenesis of acute myeloid leukemia (AML) and myeloproliferative diseases (MPD) and have led to the development of novel therapeutic approaches. In this review, we describe our current state of understanding of the genetic basis of AML and MPD, with a specific focus on pathogenetic and therapeutic significance. Specific examples discussed include RAS mutations, KIT mutations, FLT3 mutations, and core binding factor rearrangements in AML, and JAK2 mutations in polycythemia vera, essential thrombocytosis, and chronic idiopathic myelofibrosis.
Targeting Histones and Proteasomes: New Strategies for the Treatment of Lymphoma
Authors: O'Connor Owen A.
Published: September 2005

Our ever-increasing understanding of cancer cell biology has begun to provide a variety of new, and potentially drugable targets for the treatment of many forms of cancer. Nowhere else is this more apparent than in the treatment of the lymphomas. A rapidly emerging experience in gene expression profiling has begun to suggest that we can define different subtypes of lymphoma on the basis of unique molecular signatures. These signatures can define important signaling pathways that may help account for the biology of different subsets of lymphoma, and are teaching us that the lymphomas are truly a heterogeneous set of diseases. What remains equally as interesting is the idea that empiric observations of novel targeted drugs in select subtypes of lymphoma can teach us much about the biology of different lymphomas. A priori assumptions about the anticipated activity of novel targeted agents in select subtypes of lymphoma have been turned upside down. Two pathways that have emerged recently as potentially important targets for new agents in lymphoma include the ubiquitin proteasome pathway and the biochemical reactions that control histone acetylation. New classes of drugs that affect these targets, such as bortezomib, depsipeptide, suberoylanilide hydroxamic acid, and a host of other compounds, though affecting a unique target in the cell, are associated with a remarkable panoply of different downstream biologic effects. In this article, we will review some of the prevailing theories about how these novel targeted drugs affect lymphoma biology, and how these compounds are changing the face of lymphoma therapy.
State-of-the-Art Therapeutics: Diffuse Large B-Cell Lymphoma
Authors: Coiffier Bertrand
Published: September 2005

This article is a review of the improvement in the treatment of patients with diffuse large B-cell lymphoma made during the last 10 years. Patients with diffuse large B-cell lymphoma now have a better outcome with longer survival because of two major developments: (1) increasing the dose of active drugs with shortening the time between cycles, resulting in dose-dense and/or dose-intense regimens; and (2) combining rituximab with chemotherapy. Both strategies were associated with higher response rates, lower relapse rates, longer event-free survival, longer time to progression, and longer overall survival, particularly in patients without adverse prognostic parameters. A combination of dose-dense, dose-intense regimens plus rituximab is currently being tested for poor-risk patients with diffuse large B-cell lymphoma. However, much work has to be done for patients with high-risk lymphoma. It may come with a better definition of genetic abnormalities specifically associated with refractoriness to chemotherapy.
State-of-the-Art Therapeutics: Marginal-Zone Lymphoma
Authors: Bertoni Francesco , Zucca Emanuele
Published: September 2005

Marginal-zone lymphomas comprise the mucosa-associated lymphoid tissue (MALT) type (extranodal marginal-zone lymphoma [EMZL]), the nodal marginal zone B-cell lymphoma (NMZL) and the splenic MZL (SMZL). EMZL is relatively common, whereas the remaining two entities are relatively rare disorders. EMZL, especially in its gastric localization, is the most studied MZL, and there are many data both on the underlying genetic lesions and on the role of infectious agents. These data have determined unique approach among all other lymphoma subtypes: the possibility of treating a subset of patients with antibiotics alone as first line of treatment. Indeed, there is compelling evidence that histologic regressions can be achieved in most gastric MALT lymphomas by eradicating Helicobacter pylori infection. However, molecular follow-up studies showed the persistence of the malignant clone in half of the cases in histologic remission after antibiotic treatment and transient, either histologic or molecular, relapses have been reported, too. Hence, a careful long-term follow-up is mandatory after antibiotic treatment. Radiotherapy, chemotherapy, anti-CD20 monoclonal antibodies are effective alternative therapies. The precise role of surgical resection should be redefined in view of the encouraging results of conservative approaches. Differently from EMZL, both SMLZ and NMZL often present with disseminated disease at diagnosis. The therapeutic approach comprises splenectomy, for SMZL, and chemotherapy, but with no consensus about the best treatment. This review addresses the current knowledge on the clinical features and therapeutic approaches for the individual MZLs.
Gene Expression Profiling in Acute Myeloid Leukemia
Authors: Bullinger Lars , Valk Peter J.M.
Published: September 2005

Over the last decades, significant advances have been made in the knowledge and treatment of acute myeloid leukemia (AML). The WHO has recognized this new information by incorporating into its classification morphologic, immunophenotypic, genetic, and clinical features in an attempt to define biologically and clinically relevant entities. Nevertheless, well-defined cytogenetic subgroups exhibit considerable heterogeneity, and in many AML subtypes the pathogenic event is still not known. A classification system based on the underlying molecular pathogenetic abnormalities would be ideal, but such detailed knowledge is not yet available. Novel approaches in genomics, such as surveying the expression levels of thousands of genes in parallel using DNA microarray technology, open possibilities to further refine the studies on AML. Today, gene expression profiling in AML is becoming well established and has already been proven to be valuable in diagnosing different cytogenetic subtypes, discovering novel AML subclasses, and predicting clinical outcome. Recently, gene expression profiling studies in AML showed a remarkable level of concordance in findings, which may ultimately lead to an increasingly refined molecular taxonomy. While many challenges remain to be overcome, a combination of gene expression profiling with other microarray-based applications, high-throughput mutational analyses and proteomic approaches will not only significantly contribute to the classification and therapeutic decision making of AML, but also give important insights into the true pathobiologic nature of this type of leukemia.
Molecular Pathogenesis of Follicular Lymphoma: A Cross Talk of Genetic and Immunologic Factors
Authors: de Jong Daphne
Published: September 2005

Follicular lymphoma (FL) is the second most frequent type of non-Hodgkin's lymphoma in adults. The disease is characterized by an indolent course with frequent relapses. Ultimately, resistance to chemotherapy or transformation to a more aggressive phase of the disease in the form of diffuse large B-cell lymphoma develops, and patients die as a result of their disease. Median survival is 8 to 10 years. The range is very wide, however, with patients surviving for more than 15 years and 10% to 15% of the patients who run a rapidly fatal course and die within 3 years after diagnosis. The translocation t(14;18) is the basic molecular defect in FL and results in protection from apoptosis by aberrant overexpression of bcl-2 protein. Accumulation of genomic alterations and clonal selection account for subsequent progression and transformation. Recently, the role of the immunologic microenvironment of FL in determining clinical behavior and prognosis has been substantiated. Combined genetic and immunologic data may now support a model for the development of FL as a disease of functional B cells in which specific molecular alterations infer intrinsic growth properties of the tumor cells as well as dictate a specific functional cross talk with the immunologic regulatory network resulting in extrinsic growth support. These insights may lead to improvement of risk stratification, but most importantly will provide tools for developing new targets and strategies for treatment.
Peptide YY3–36 and Glucagon-Like Peptide-17–36 Inhibit Food Intake Additively
Authors: Neary Nicola M. , Small Caroline J. , Druce Maralyn R. , Park Adrian J. , Ellis Sandra M. , Semjonous Nina M. , Dakin Catherine L. , Filipsson Karin , Wang Fang , Kent Aysha S. , Frost Gary S. , Ghatei Mohammad A. , Bloom Stephen R.
Published: September 2005

Peptide YY (PYY) and glucagon like peptide (GLP)-1 are cosecreted from intestinal L cells, and plasma levels of both hormones rise after a meal. Peripheral administration of PYY3–36 and GLP-17–36 inhibit food intake when administered alone. However, their combined effects on appetite are unknown. We studied the effects of peripheral coadministration of PYY3–36 with GLP-17–36 in rodents and man. Whereas high-dose PYY3–36 (100 nmol/kg) and high-dose GLP-17–36 (100 nmol/kg) inhibited feeding individually, their combination led to significantly greater feeding inhibition. Additive inhibition of feeding was also observed in the genetic obese models, ob/ob and db/db mice. At low doses of PYY3–36 (1 nmol/kg) and GLP-17–36 (10 nmol/kg), which alone had no effect on food intake, coadministration led to significant reduction in food intake. To investigate potential mechanisms, c-fos immunoreactivity was quantified in the hypothalamus and brain stem. In the hypothalamic arcuate nucleus, no changes were observed after low-dose PYY3–36 or GLP-17–36 individually, but there were significantly more fos-positive neurons after coadministration. In contrast, there was no evidence of additive fos-stimulation in the brain stem. Finally, we coadministered PYY3–36 and GLP-17–36 in man. Ten lean fasted volunteers received 120-min infusions of saline, GLP-17–36 (0.4 pmol/kg·min), PYY3–36 (0.4 pmol/kg·min), and PYY3–36 (0.4 pmol/kg·min) + GLP-17–36 (0.4 pmol/kg·min) on four separate days. Energy intake from a buffet meal after combined PYY3–36 + GLP-17–36 treatment was reduced by 27% and was significantly lower than that after either treatment alone. Thus, PYY3–36 and GLP-17–36, cosecreted after a meal, may inhibit food intake additively.
Regulatory Roles of Bone Morphogenetic Proteins and Glucocorticoids in Catecholamine Production by Rat Pheochromocytoma Cells
Authors: Kano Yoshihiro , Otsuka Fumio , Takeda Masaya , Suzuki Jiro , Inagaki Kenichi , Miyoshi Tomoko , Miyamoto Manabu , Otani Hiroyuki , Ogura Toshio , Makino Hirofumi
Published: September 2005

We here report a new physiological system that governs catecholamine synthesis involving bone morphogenetic proteins (BMPs) and activin in the rat pheochromocytoma cell line, PC12. BMP type I receptors, including activin receptor-like kinase-2 (ALK-2) (also referred to as ActRIA) and ALK-3 (BMPRIA), both type II receptors, ActRII and BMPRII, as well as the ligands BMP-2, -4, and -7 and inhibin/activin subunits were expressed in PC12 cells. PC12 cells predominantly secrete dopamine, whereas noradrenaline and adrenaline production is negligible. BMP-2, -4, -6, and -7 and activin A each suppressed dopamine and cAMP synthesis in a dose-dependent fashion. The BMP ligands also decreased 3,4-dihydroxyphenylalanine decarboxylase mRNA expression, whereas activin suppressed tyrosine hydroxylase expression. BMPs induced both Smad1/5/8 phosphorylation and Tlx2-Luc activation, whereas activin stimulated 3TP-Luc activity and p38 MAPK phosphorylation. ERK signaling was not affected by BMPs or activin. Dexamethasone enhanced catecholamine synthesis, accompanying increases in tyrosine hydroxylase and 3,4-dihydroxyphenylalanine decarboxylase transcription without cAMP accumulation. In the presence of dexamethasone, BMPs and activin failed to reduce dopamine as well as cAMP production. In addition, dexamethasone modulated mitotic suppression of PC12 induced by BMPs in a ligand-dependent manner. Furthermore, intracellular BMP signaling was markedly suppressed by dexamethasone treatment and the expression of ALK-2, ALK-3, and BMPRII was significantly inhibited by dexamethasone. Collectively, the endogenous BMP/activin system plays a key role in the regulation of catecholamine production. Controlling activity of the BMP system may be critical for glucocorticoid-induced catecholamine synthesis by adrenomedullar cells.
Low Doses of Dexamethasone Can Produce a Hypocorticosteroid State in the Brain
Authors: Karssen A. M. , Meijer O. C. , Berry A. , Sanjuan Piñol R. , de Kloet E. R.
Published: September 2005

The synthetic glucocorticoid dexamethasone (dex) blocks stress-induced hypothalamic-pituitary-adrenal (HPA) activation primarily at the level of the anterior pituitary because multidrug resistance P-glycoprotein hampers its penetration in the brain. Here, we tested the hypothesis that central components of the HPA axis would escape dex suppression under conditions of potent peripheral glucocorticoid action. We subchronically treated rats with low or high doses of dex. The animals were subjected on the last day of treatment for 30 min to a restraint stressor after which central and peripheral markers of HPA axis activity were measured. Basal and stress-induced corticosterone secretion, body weight gain, adrenal and thymus weight, as well as proopiomelanocortin mRNA in the anterior pituitary were reduced in a dose-dependent manner by dex administered either 5 d sc or 3 wk orally. In the brain, the highest dose dex suppressed CRH mRNA and CRH heteronuclear RNA in the paraventricular nucleus (PVN). However, in the peripherally active low-dose range of dex CRH mRNA and heteronuclear RNA showed resistance to suppression, and CRH mRNA expression in the PVN was in fact enhanced under the long-term treatment condition. In the PVN, c-fos mRNA was suppressed by the highest dose of dex, but this effect showed a degree of resistance after long-term oral treatment. c-fos mRNA responses in the anterior pituitary followed those in PVN and reflect central drive of the HPA axis even if corticosterone responses are strongly reduced. The results support the concept that low doses of dex can create a hypocorticoid state in the brain.
The Human Estrogen Receptor-α Isoform hERα46 Antagonizes the Proliferative Influence of hERα66 in MCF7 Breast Cancer Cells
Authors: Penot Graziella , Le Péron Christine , Mérot Yohann , Grimaud-Fanouillère Eva , Ferrière François , Boujrad Noureddine , Kah Olivier , Saligaut Christian , Ducouret Bernadette , Métivier Raphaël , Flouriot Gilles
Published: September 2005

The expression of two human estrogen receptor-α (hERα) isoforms has been characterized within estrogen receptor-α-positive breast cancer cell lines such as MCF7: the full-length hERα66 and the N terminally deleted hERα46, which is devoid of activation function (AF)-1. Although hERα66 is known to mediate the mitogenic effects that estrogens have on MCF7 cells, the exact function of hERα46 in these cells remains undefined. Here we show that, during MCF7 cell growth, hERα46 is mainly expressed in the nucleus at relatively low levels, whereas hERα66 accumulates in the nucleus. When cells reach confluence, the situation reverses, with hERα46 accumulating within the nucleus. Although hERα46 expression remains rather stable during an estrogen-induced cell cycle, its overexpression in proliferating MCF7 cells provokes a cell-cycle arrest in G0/G1 phases. To gain further details on the influence of hERα46 on cell growth, we used PC12 estrogen receptor-α-negative cell line, in which stable transfection of hERα66 but not hERα46 allows estrogens to behave as mitogens. We next demonstrate that, in MCF7 cells, overexpression of hERα46 inhibits the hERα66-mediated estrogenic induction of all AF-1-sensitive reporters: c-fos and cyclin D1 as well as estrogen-responsive element-driven reporters. Our data indicate that this inhibition occurs likely through functional competitions between both isoforms. In summary, hERα46 antagonizes the proliferative action of hERα66 in MCF7 cells in part by inhibiting hERα66 AF-1 activity.