bluuebunny/crossref_metadata_2025 huggingface dataset:
Granulosa Cell Apoptosis Induced by a Novel FSH Binding Inhibitory Peptide From Human Ovarian Follicular Fluid
Authors: Chitnis Swati S. , Navlakhe Rajshri M. , Shinde Gayatri C. , Barve Sharmila J. , D'Souza Serena , Mahale Smita D. , Nandedkar Tarala D.
Published: July 2008

Pituitary gonadotropins, follicle-stimulating hormone and luteinizing hormone, are the key regulators of ovarian folliculogenesis; these are known to be directly or indirectly modulated by many intraovarian factors. Our group has identified and studied one such novel peptide from human ovarian follicular fluid. Its partial N-terminal eight amino acid sequence has been deduced, referred to as octapeptide (OP). OP induces follicular atresia in mice and interferes with normal ovarian function in non-human primates, this action being similar to the native peptide. Thus, in this study, an attempt has been made to elucidate the mechanism of action of the synthetic OP by studying the pathway of follicular atresia in mouse ovary. Changes in granulosa cells were studied using various apoptotic markers by flow cytometry and immunohistochemistry. An increase in apoptotic cell population in atretic- and peptide-treated groups was observed compared with normal controls. Interestingly, both these groups exhibited differences in the apoptotic pathway. Results showed that the mitochondrial pathway was predominant in the atretic group, whereas the Fas-FasL pathway was predominant in the peptide-treated groups. The ultrastructural study also showed apoptotic changes in the OP-treated and atretic groups; the pattern of apoptosis differed at the subcellular level.
ΔFosB Mediates Epigenetic Desensitization of the c-fosGene After Chronic Amphetamine Exposure
Authors: Renthal William , Carle Tiffany L. , Maze Ian , Covington Herbert E. , Truong Hoang-Trang , Alibhai Imran , Kumar Arvind , Montgomery Rusty L. , Olson Eric N. , Nestler Eric J.
Published: July 2008

The molecular mechanisms underlying the transition from recreational drug use to chronic addiction remain poorly understood. One molecule implicated in this process is ΔFosB, a transcription factor that accumulates in striatum after repeated drug exposure and mediates sensitized behavioral responses to psychostimulants and other drugs of abuse. The downstream transcriptional mechanisms by which ΔFosB regulates drug-induced behaviors are incompletely understood. We reported previously the chromatin remodeling mechanisms by which ΔFosB activates the expression of certain genes; however, the mechanisms underlying ΔFosB-mediated gene repression remain unknown. Here, we identify c-fos, an immediate early gene rapidly induced in striatum after acute psychostimulant exposure, as a novel downstream target that is repressed chronically by ΔFosB. We show that accumulation of ΔFosB in striatum after chronic amphetamine treatment desensitizes c-fosmRNA induction to a subsequent drug dose. ΔFosB desensitizes c-fosexpression by recruiting histone deacetylase 1 (HDAC1) to the c-fosgene promoter, which, in turn, deacetylates surrounding histones and attenuates gene activity. Accordingly, local knock-out of HDAC1 in striatum abolishes amphetamine-induced desensitization of the c-fosgene. In concert, chronic amphetamine increases histone H3 methylation on the c-fospromoter, a chromatin modification also known to repress gene activity, as well as expression levels of the H3 histone methyltransferase, KMT1A (lysine methyltransferase 1A, formerly SUV39H1). This study reveals a novel epigenetic pathway through which ΔFosB mediates distinct transcriptional programs that may ultimately alter behavioral plasticity to chronic amphetamine exposure.
Pyramidal Tract Stimulation Restores Normal Corticospinal Tract Connections and Visuomotor Skill after Early Postnatal Motor Cortex Activity Blockade
Authors: Salimi Iran , Friel Kathleen M. , Martin John H.
Published: July 2008

Motor development depends on forming specific connections between the corticospinal tract (CST) and the spinal cord. Blocking CST activity in kittens during the critical period for establishing connections with spinal motor circuits results in permanent impairments in connectivity and function. The changes in connections are consistent with the hypothesis that the inactive tract is less competitive in developing spinal connections than the active tract. In this study, we tested the competition hypothesis by determining whether activating CST axons, after previous silencing during the critical period, abrogated development of aberrant corticospinal connections and motor impairments. In kittens, we inactivated motor cortex by muscimol infusion between postnatal weeks 5 and 7. Next, we electrically stimulated CST axons in the medullary pyramid 2.5 h daily, between weeks 7 and 10. In controls (n= 3), CST terminations were densest within the contralateral deeper, premotor, spinal layers. After previous inactivation (n= 3), CST terminations were densest within the dorsal, somatic sensory, layers. There were more ipsilateral terminations from the active tract. During visually guided locomotion, there was a movement endpoint impairment. Stimulation after inactivation (n= 6) resulted in significantly fewer terminations in the sensory layers and more in the premotor layers, and fewer ipsilateral connections from active cortex. Chronic stimulation reduced the current threshold for evoking contralateral movements by pyramidal stimulation, suggesting strengthening of connections. Importantly, stimulation significantly improved stepping accuracy. These findings show the importance of activity-dependent processes in specifying CST connections. They also provide a strategy for harnessing activity to rescue CST axons at risk of developing aberrant connections after CNS injury.
Functional Topography and Integration of the Contralateral and Ipsilateral Retinocollicular Projections ofEphrin-A−/−Mice
Authors: Haustead Daniel J. , Lukehurst Sherralee S. , Clutton Genevieve T. , Bartlett Carole A. , Dunlop Sarah A. , Arrese Catherine A. , Sherrard Rachel M. , Rodger Jennifer
Published: July 2008

Topographically ordered projections are established by molecular guidance cues and refined by neuronal activity. Retinal input to a primary visual center, the superior colliculus (SC), is bilateral with a dense contralateral projection and a sparse ipsilateral one. Both projections are topographically organized, but in opposing anterior–posterior orientations. This arrangement provides functionally coherent input to each colliculus from the binocular visual field, supporting visual function. When guidance cues involved in contralateral topography (ephrin-As) are absent, crossed retinal ganglion cell (RGC) axons form inappropriate terminations within the SC. However, the organization of the ipsilateral projection relative to the abnormal contralateral input remains unknown, as does the functional capacity of both projections. We show here that inephrin-A−/−mice, the SC contains an expanded, diffuse ipsilateral projection. Electrophysiological recording demonstrated that topography of visually evoked responses recorded from the contralateral superior colliculus ofephrin-A−/−mice displayed similar functional disorder in all genotypes, contrasting with their different degrees of anatomical disorder. In contrast, ipsilateral responses were retinotopic inephrin-A2−/−but disorganized inephrin-A2/A5−/−mice. The lack of integration of binocular input resulted in specific visual deficits, which could be reversed by occlusion of one eye. The discrepancy between anatomical and functional topography in both the ipsilateral and contralateral projections implies suppression of inappropriately located terminals. Moreover, the misalignment of ipsilateral and contralateral visual information inephrin-A2/A5−/−mice suggests a role for ephrin-As in integrating convergent visual inputs.
Effect of Stimulus Intensity on the Spike–Local Field Potential Relationship in the Secondary Somatosensory Cortex
Authors: Ray Supratim , Hsiao Steven S. , Crone Nathan E. , Franaszczuk Piotr J. , Niebur Ernst
Published: July 2008

Neuronal oscillations in the gamma frequency range have been reported in many cortical areas, but the role they play in cortical processing remains unclear. We tested a recently proposed hypothesis that the intensity of sensory input is coded in the timing of action potentials relative to the phase of gamma oscillations, thus converting amplitude information to a temporal code. We recorded spikes and local field potential (LFP) from secondary somatosensory (SII) cortex in awake monkeys while presenting a vibratory stimulus at different amplitudes. We developed a novel technique based on matching pursuit to study the interaction between the highly transient gamma oscillations and spikes with high time–frequency resolution. We found that spikes were weakly coupled to LFP oscillations in the gamma frequency range (40–80 Hz), and strongly coupled to oscillations in higher gamma frequencies. However, the phase relationship of neither low-gamma nor high-gamma oscillations changed with stimulus intensity, even with a 10-fold increase. We conclude that, in SII, gamma oscillations are synchronized with spikes, but their phase does not vary with stimulus intensity. Furthermore, high-gamma oscillations (>60 Hz) appear to be closely linked to the occurrence of action potentials, suggesting that LFP high-gamma power could be a sensitive index of the population firing rate near the microelectrode.
Distinct Roles for Two Histamine Receptors (hclAandhclB) at theDrosophilaPhotoreceptor Synapse
Authors: Pantazis Antonios , Segaran Ashvina , Liu Che-Hsiung , Nikolaev Anton , Rister Jens , Thum Andreas S. , Roeder Thomas , Semenov Eugene , Juusola Mikko , Hardie Roger C.
Published: July 2008

Histamine (HA) is the photoreceptor neurotransmitter in arthropods, directly gating chloride channels on large monopolar cells (LMCs), postsynaptic to photoreceptors in the lamina. Two histamine-gated channel genes that could contribute to this channel inDrosophilaarehclA(also known asort) andhclB(also known ashisCl1), both encoding novel members of the Cys-loop receptor superfamily.DrosophilaS2 cells transfected with these genes expressed both homomeric and heteromeric histamine-gated chloride channels. The electrophysiological properties of these channels were compared with those from isolatedDrosophilaLMCs. HCLA homomers had nearly identical HA sensitivity to the native receptors (EC50= 25 μm). Single-channel analysis revealed further close similarity in terms of single-channel kinetics and subconductance states (∼25, 40, and 60 pS, the latter strongly voltage dependent). In contrast, HCLB homomers and heteromeric receptors were more sensitive to HA (EC50= 14 and 1.2 μm, respectively), with much smaller single-channel conductances (∼4 pS). Null mutations ofhclA(ortUS6096) abolished the synaptic transients in the electroretinograms (ERGs). Surprisingly, the ERG “on” transients inhclBmutants transients were approximately twofold enhanced, whereas intracellular recordings from their LMCs revealed altered responses with slower kinetics. However, HCLB expression within the lamina, assessed by both a GFP (green fluorescent protein) reporter gene strategy and mRNA tagging, was exclusively localized to the glia cells, whereas HCLA expression was confirmed in the LMCs. Our results suggest that the native receptor at the LMC synapse is an HCLA homomer, whereas HCLB signaling via the lamina glia plays a previously unrecognized role in shaping the LMC postsynaptic response.
Interactions between Medial Temporal Lobe, Prefrontal Cortex, and Inferior Temporal Regions during Visual Working Memory: A Combined Intracranial EEG and Functional Magnetic Resonance Imaging Study
Authors: Axmacher Nikolai , Schmitz Daniel P. , Wagner Tobias , Elger Christian E. , Fell Juergen
Published: July 2008

It is a fundamental question whether the medial temporal lobe (MTL) supports only long-term memory encoding, or contributes to working memory (WM) processes as well. Recent data suggest that the MTL is activated whenever multiple items or item features are being maintained in WM. This may rely on interactions between the MTL or the prefrontal cortex (PFC) and content-specific areas in the inferior temporal (IT) cortex. Here, we investigated the neural mechanism through which the MTL, PFC, and IT cortex interact during WM maintenance. First, we quantified phase synchronization of intracranial EEG data in epilepsy patients with electrodes in both regions. Second, we used directional coupling analysis to study whether oscillatory activity in the IT cortex drives the MTL or vice versa. Finally, we investigated functional connectivity in functional magnetic resonance imaging data of healthy subjects with seeds in the MTL and PFC. With increasing load, EEG phase synchronization between the IT cortex and anterior parahippocampal gyrus and within the MTL increased. Coupling was bidirectional in all load conditions, but changed toward an increased top-down (anterior parahippocampal gyrus → IT) coupling in the high gamma range (51–75 Hz) with increasing load. Functional connectivity between the MTL seed and the visual association cortex increased with load, but activity within the MTL and the PFC correlated with fewer voxels, suggesting that more specific neural networks were engaged. These data indicate that WM for multiple items depends on an increased strength of top-down control of activity within the IT cortex by the MTL.
Step Training Reinforces Specific Spinal Locomotor Circuitry in Adult Spinal Rats
Authors: Ichiyama Ronaldo M. , Courtine Grégoire , Gerasimenko Yury P. , Yang Grace J. , van den Brand Rubia , Lavrov Igor A. , Zhong Hui , Roy Roland R. , Edgerton V. Reggie
Published: July 2008

Locomotor training improves function after a spinal cord injury both in experimental and clinical settings. The activity-dependent mechanisms underlying such improvement, however, are sparsely understood. Adult rats received a complete spinal cord transection (T9), and epidural stimulation (ES) electrodes were secured to the dura matter at L2. EMG electrodes were implanted bilaterally in selected muscles. Using a servo-controlled body weight support system for bipedal stepping, five rats were trained 7 d/week for 6 weeks (30 min/d) under quipazine (0.3 mg/kg) and ES (L2; 40 Hz). Nontrained rats were handled as trained rats but did not receive quipazine or ES. At the end of the experiment, a subset of rats was used for c-fosimmunohistochemistry. Three trained and three nontrained rats stepped for 1 h (ES; no quipazine) and were returned to their cages for 1 h before intracardiac perfusion. All rats could step with ES and quipazine administration. The trained rats had higher and longer steps, narrower base of support at stance, and lower variability in EMG parameters than nontrained rats, and these properties approached that of noninjured controls. After 1 h of stepping, the number of FOS+ neurons was significantly lower in trained than nontrained rats throughout the extent of the lumbosacral segments. These results suggest that training reinforces the efficacy of specific sensorimotor pathways, resulting in a more selective and stable network of neurons that controls locomotion.
Different CA1 and CA3 Representations of Novel Routes in a Shortcut Situation
Authors: Alvernhe Alice , Van Cauter Tiffany , Save Etienne , Poucet Bruno
Published: July 2008

Place cells are hippocampal neurons whose discharge is strongly related to a rat's location in its environment. The existence of place cells has led to the proposal that they are part of an integrated neural system dedicated to spatial navigation. To further understand the relationships between place cell firing and spatial problem solving, we examined the discharge of CA1 and CA3 place cells as rats were exposed to a shortcut in a runway maze. On specific sessions, a wall section of the maze was removed so as to open a shorter novel route within the otherwise familiar maze. We found that the discharge of both CA1 and CA3 cells was strongly affected in the vicinity of the shortcut region but was much less affected farther away. In addition, CA3 fields away from the shortcut were more altered than CA1 fields. Thus, place cell firing appears to reflect more than just the animal's spatial location and may provide additional information about possible motions, or routes, within the environment. This kinematic representation appears to be spatially more extended in CA3 than in CA1, suggesting interesting computational differences between the two subregions.
Self-Limited Hyperexcitability: Functional Effect of a Familial Hemiplegic Migraine Mutation of the Nav1.1 (SCN1A) Na+Channel
Authors: Cestèle Sandrine , Scalmani Paolo , Rusconi Raffaella , Terragni Benedetta , Franceschetti Silvana , Mantegazza Massimo
Published: July 2008

Familial hemiplegic migraine (FHM) is an autosomal dominant inherited subtype of severe migraine with aura. Mutations causing FHM (type 3) have been identified inSCN1A, the gene encoding neuronal voltage-gated Nav1.1 Na+channel α subunit, but functional studies have been done using the cardiac Nav1.5 isoform, and the observed effects were similar to those of some epileptogenic mutations. We studied the FHM mutation Q1489K by transfecting tsA-201 cells and cultured neurons with human Nav1.1. We show that the mutation has effects on the gating properties of the channel that can be consistent with both hyperexcitability and hypoexcitability. Simulation of neuronal firing and long depolarizing pulses mimicking promigraine conditions revealed that the effect of the mutation is a gain of function consistent with increased neuronal firing. However, during high-frequency discharges and long depolarizations, the effect became a loss of function. Recordings of firing of transfected neurons showed higher firing frequency at the beginning of long discharges. This self-limited capacity to induce neuronal hyperexcitability may be a specific characteristic of migraine mutations, able to both trigger the cascade of events that leads to migraine and counteract the development of extreme hyperexcitability typical of epileptic seizures. Thus, we found a possible difference in the functional effects of FHM and familial epilepsy mutations of Nav1.1.
Chronic Psychoemotional Stress Impairs Cannabinoid-Receptor-Mediated Control of GABA Transmission in the Striatum
Authors: Rossi Silvia , De Chiara Valentina , Musella Alessandra , Kusayanagi Hajime , Mataluni Giorgia , Bernardi Giorgio , Usiello Alessandro , Centonze Diego
Published: July 2008

Exposure to stressful events has a myriad of consequences in animals and in humans, and triggers synaptic adaptations in many brain areas. Stress might also alter cannabinoid-receptor-mediated transmission in the brain, but no physiological study has addressed this issue so far. In the present study, we found that social defeat stress, induced in mice by exposure to aggression, altered cannabinoid CB1-receptor-mediated control of synaptic transmission in the striatum. In fact, the presynaptic inhibition of GABAergic IPSCs induced by the cannabinoid CB1receptor agonist HU210 [(6aR)-trans-3-(1,1-dimethylheptyl)-6a,7,10,10a-tetrahydro-1-hydroxy-6,6-dimethyl-6H-dibenzo[b,d]pyran-9-methanol] was reduced after a single stressful episode and fully abolished after 3 and 7 d of stress exposure. Repeated psychoemotional stress also impaired the sensitivity of GABA synapses to endocannabinoids mobilized by group I metabotropic glutamate receptor stimulation, whereas the cannabinoid CB1-mediated control of glutamate transmission was unaffected by repeated exposure to an aggressor. Corticosteroids released in response to the activation of the hypothalamic–pituitary–adrenal axis played a major role in the synaptic defects observed in stressed animals, because these alterations were fully prevented by pharmacological blockade of glucocorticoid receptors and were mimicked by corticosterone injections. The recovery of stress-induced synaptic defects was favored when stressed mice were given access to a running wheel or to sucrose consumption, which function as potent natural rewards. A similar rescuing effect was obtained by a single injection of cocaine, a psychostimulant with strong rewarding properties. Targeting cannabinoid CB1receptors or endocannabinoid metabolism might be a valuable option to treat stress-associated neuropsychiatric conditions.
Did the Middle Ages Believe in Their Miracles?
Authors: Justice Steven
Published: July 2008

For all the proud accomplishments of its last decades, the study of premodern Christianity continues to bruise its shins against the problem of "belief." New categorical explanations of religious belief repeatedly and inadvertently prove identical with old explanations; more oddly, so do categorical refusals to explain it. The fallacy lies in thinking that belief can be categorically identified in the first place. But recognition of the fallacy does not leave us stymied. A short theoretical discussion of St. Thomas Aquinas and a longer reading of the Life of Christina of Markyate suggest how belief may be historically discussed without being unhistorically cartooned.
Taboo: Time and Belief in Exotica
Authors: Ford Phil
Published: July 2008

In the 1950s, exotica was a genre of pop music that specialized in depicting imaginary exotic paradises and conventionalized natives. By the late 1960s, exotica pop had disappeared, but its tropes of temporal and spatial disjuncture persisted, structuring the music, visual art, and social theory of the utopian counterculture. While 1950s and 1960s kinds of exotica differ in their preferred imaginary destinations, both raise the question of what intermediate shades between belief and disbelief are demanded by aestheticized representations of human life. This essay theorizes exotica as a mode of representation governed by a peculiar mode of reception—one of willed credulity enabled by submission to its spectacle. What exotica demands is what intellectuals are least likely to give, though, and the peculiar pleasures of exotica spectacle are denigrated or rendered invisible in the hermeneutic regime.
The Invention of Criminal Blasphemy: Rex v. Taylor (1676)
Authors: Visconsi Elliott
Published: July 2008

This article provides an account of the emergence of the common law jurisdiction over blasphemy, arguing that the blasphemy laws first developed in Rex v. Taylor had an explicitly secular purpose. Instead of understanding this crucial decision as an emblem of the early modern fusion of church and state, this article reads Sir Matthew Hale's axiom that "Christianity is parcel of the laws of England" as a step toward the emergence of an English civil religion.
Undescended testes in children: the paediatric urologist's point of view
Authors: Mouriquand Pierre D E
Published: July 2008

Undescended testes (UDT) are found in 1% boys at the age of 1-year old, 3% of full-term male infants and 33% in premature babies at birth. Spontaneous descent is possible until 6 months of age. The two main phases of descent of the testis during gestation are described, as well as the possible aetiologies, the consequences of an abnormal migration, and the main locations of UDTs. Clinical examination is essential and should be done in optimal conditions. Laparoscopic exploration is the only valuable complementary investigation in the case of non-palpable UDT.
Isn’t the heart the source of energy for blood circulation? „The heart doesn’t know the basic laws of physics”
Authors: Papp Lajos
Published: July 2008

Az egyetemes orvostudomány évszázadok óta a szívet tartja a vérkeringés központi szervének, a keringés egyedüli energiaforrásaként a szívfunkciót jelöli meg, kiemelten kezelve a szívbillentyűk szerepét. A jelenleg általánosan elfogadott paradigma: a keringési rendszerben az áramlást fenntartó erő a működő szív által létrehozott nyomásgradiens. Súlyos, kombinált szívbillentyű-betegségekben a billentyűfunkciók gyakorlatilag megszűnnek. A szív űrtereiben és a nagyerekben mért nyomásértékek alapján a vérkeringésnek az ellentétes irányba – a magasabb nyomású hely felől az alacsonyabb nyomású felé – kellene irányulnia. Tény, hogy a véráramlás ilyen esetekben sem a főartériák (aorta, arteria pulmonalis) felől a vénás rendszer felé irányul: billentyűfunkciók nélkül – és látszólag a fizika alaptörvényeivel szemben – megtartja eredeti irányát, amiből joggal feltételezhetjük, hogy nem a szívizomzat munkája adja a vérkeringés energiaforrását. A szívnek a vérkeringés fenntartásában elengedhetetlen funkciója van; pulzust generál. A szív elsődlegesen pulzusgenerátor, és nem nyomásgenerátor.
The characteristics of nurses’ and caregivers’ behaviour in different clinical settings with special attention to burnout syndrome
Authors: Pálfiné Szabó Ilona
Published: July 2008

A szerző szeretné felhívni a figyelmet a választott téma aktualitására, annak személyi és intézményi hatására. A kiégés patomechanizmusában a munkahelyi stressz fontos szerepet játszik. Az ápolók jelentős munkahelyi stresszterheltségnek vannak kitéve, így a kiégés előfordulása körükben várhatóan magas. A jelen vizsgálat célja, hogy képet adjon a magyar ápolók helyzetéről, mentálhigiénés állapotáról, a kiégési szindróma fokáról és mértékéről adott ellátási szituációkban. A kutatás módszere: önkitöltős, anonim kérdőív volt, amely rákérdezett a vizsgált minta szociodemográfiai adataira; felhasznált három standardizált kérdőívet, amely a kiégés mértékét, a fizikai és pszichés kimerültséget, valamint a diszfunkcionális attitűdöket mérte.
Eredmények:
A kérdőíves felmérés 805 fővel történt, amelyben elemzésre kerültek a segítő kapcsolatok sajátos körülményei, a munkahelyi jellemzők közül a kiégés fokának és a kórházi osztály ellátási formájának kapcsolódási pontjai. Az intenzív osztályokon dolgozó 374 ápolóból 9,4% ki van égve, míg az aktív osztályon dolgozók esetében ez az arány 155 főből 0,6% volt. A kutatás eredményei szerint befolyásoló tényezőként hat még a jelenségre az ápolók által a főállásukon túl végzett melléktevékenység ténye, valamint az erkölcsi és anyagi megbecsülés hiánya is. A vizsgált populáció 33,9%-a, 273 fő veszélyben van a kiégés mértékét illetően, 5,5%-a, 44 fő a kiégettség állapotában van, és 0,9%-a, 7 fő gyógyításra szorul. A tanulmány bizonyos személyiségfaktorok (diszfunkcionális attitűdök) befolyásoló szerepét feltételezte a burnout kialakulásában. Az összehasonlítások alapján a burnout jelenség és a diszfunkcionális attitűdök összefüggése is beigazolódott.
Következtetés:
A vizsgálat eredményei alapján megállapítható, hogy a vizsgált populációban a szociodemográfiai faktorok nem befolyásolják a kiégés kialakulását. Meghatározó a munkahelyi tényezők között az ápoltak betegségének súlyossági foka, valamint az intenzív osztályon elszenvedett állandó stressz mértéke.
The role of the Medical Scientific Council’s Forensic Committee in the consent judgments regarding private insurance companies
Authors: Horváth János
Published: July 2008

A korábbi években az igazságügyi orvosszakértői vélemények szakmai felülbírálatát, a szakvélemények közötti ellentmondások feloldását az Egészségügyi Tudományos Tanács Igazságügyi Bizottsága látta el. A jelen dolgozat az üzleti biztosítók ellen indított kártérítési perekben készített felülvélemények, valamint a jogerős bírósági ítéletek kapcsolatát elemzi.
Célkitűzés:
A szerző értékeli az Igazságügyi Bizottság felülvéleményeinek perben elfoglalt szerepét, jelentőségét.
Eredmények:
A bíróság a vizsgált ügyek mintegy kétharmadában a felülvéleményeket pozitívan értékelte, és az adott szakkérdésre adott testületi válaszokat beépítette ítéletébe. Előfordult, hogy a bíró az orvosszakértői véleményekben használt alapvető orvosszakmai, orvosszakértői fogalmakat félreértette. Az igazságügyi orvostan szakorvosa, a társadalombiztosító szakértője és az üzleti biztosító bizalmi orvosa esetenként különböző fogalmakat használt, így az ítéletekben a szakértői fogalmak keveredtek.
Következtetések:
A szerző új módszertani levél létrehozását javasolja, amely a kártérítést érintő egyes jelentősebb orvosszakértői fogalmakat, ismereteket közérthetően definiálja, a mindennapi gyakorlathoz igazítva megmagyarázza annak érdekében, hogy a különböző szakterületen tevékenykedő szakértők és a jogalkalmazók közös nyelven beszélhessenek.
Molecular analysis of multifocal papillary thyroid carcinoma
Authors: Lin Xiaoqi , Finkelstein Sydney D , Zhu Bing , Silverman Jan F
Published: July 2008

Papillary thyroid carcinoma (PTC) frequently presents as a multifocal process. To study the importance of separating independent primary (IP) from intrathyroid metastatic (ITM) PTC, we examined 19 molecular markers on 42 separate tumors from 18 multifocal PTC cases. In 12 of 18 (66.7%) cases, including 6 of 12 (50%) papillary microcarcinoma cases, the same or similar profile of loss of heterozygosities (LOH) and v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutation was demonstrated, indicating that they were from the same primary and represented ITM. Different profiles of LOHs and BRAF mutation were detected in separate tumors of 6 of 18 cases, indicating that they represented IP. Patients with ITM, including papillary microcarcinoma, had significantly increased lymph node metastasis. The frequencies of LOHs of 17q21, 17p13, 10q23, and 22q13 were higher in tumors with lymph node metastasis, suggesting that these LOHs may be important in increased lymph node metastasis. LOH of 9p21 was found at the highest frequency in PTC (53.8%), followed by 1p36 (46.2%), 10q23 (34.6%), and 22q13 (34.6%). Papillary microcarcinoma had acquired similar genomic mutations as conventional PTC, but higher frequencies of mutations of BRAF, 1p36, 18q, and 22q13 were found in the larger PTC, suggesting that they might play a role in the aggressiveness of PTC. Different profiles of mutations were observed in conventional, follicular variants, and diffuse sclerosing variant of PTC, which might influence the different morphological appearances and clinical courses. In conclusion, molecular analysis can separate multifocal IP PTC from ITM PTC, and may be more important than tumor size in predicting lymph node metastasis, aggressiveness, and prognosis of PTC.
Congestion charging in Dublin
Authors: Rogers M. , Eagney C.
Published: July 2008

As Dublin, Ireland becomes more congested, the option of imposing a charge for access to central Dublin at peak times has become a realistic option. This paper outlines, in brief, the history of Dublin transportation planning that has led to this point, lists the alternative number of demand management tools which potentially could be used to limit demand for private car travel to the city centre with the implementation of a congestion charge being an option which would be particularly applicable to Dublin city. Estimates of the willingness of road users in Dublin to pay such a charge are put forward. The Dublin Transportation Office's Transportation Model is used to quantify the effect of different congestion charges on car usage into Dublin city centre at peak times. Effective implementation of such a measure is only seen as taking place within the context of improved public transport services within central Dublin.
Optical compensation for two stereoscopic distortions
Authors: Grebenyuk Konstantin A. , Petrov Vladimir V.
Published: July 2008

Abstract— A stereoscopic display configuration for presenting stereoscopic images without keystone and depth‐plane‐curvature distortions is proposed. The main idea of the proposed configuration is to perform optical compensation for these distortions by presenting left and right perspective images at two intersecting screens. The possibility of such distortion elimination was proven by two independent ways: analytically and graphically.
High‐efficacy plasma‐display designs achieving 5 lm/W
Authors: Akiyama Toshiyuki , Yamada Takashi , Noguchi Yasuyuki , Shinohe Koji , Kitagawa Masatoshi , Shinoda Tsutae
Published: July 2008

Abstract— Under high‐Xe‐content conditions, the luminous characteristics were evaluated for the sustaining electrode width and the sustaining pulse cycle. It was recognized that the proper designs for them in a high‐Xe‐content gas mixture make it possible to obtain high luminous efficacy. In this research, it was found that narrower electrodes can gain higher luminous efficacy in high‐Xe‐content conditions. The dependency of the luminous characteristics on the electrode width was analyzed and the differences of discharge phenomena from low‐Xe‐content conditions, which explain the dependency on the electrode width, were recognized. In an 8‐in. test panel, 5.2 lm/W of the maximum white efficacy was obtained. The found phenomenon that narrower electrodes are more advantageous for the luminous efficacy is favorable in high‐definition PDPs.
Analysis of amphetamines illegally produced in Serbia
Authors: Nevescanin Marina , Banovic-Stevic Sonja , Petrovic Slobodan , Vajs Vlatka
Published: July 2008

Forensic practice in the Republic of Serbia faced the illegal production of amphetamine for the first time in 2003. This paper presents the results of the chemical characterization of 32 batches of amphetamine samples from three separate cases, for the purpose of identification of the active components and additives. Through the profiling of impurities of all samples, using gas chromatography/mass spectrometry (GC/MS), 30 compounds associated with amphetamine were identified. The results of the analysis of powder tartrate, sulfate and phosphate salts of amphetamine, as well as variously formulated tablets are presented in this study. The analyses showed that the amphetamines were synthesized by the Leuckart method in all cases. .
Diurnal Variation of Human Sweet Taste Recognition Thresholds Is Correlated With Plasma Leptin Levels
Authors: Nakamura Yuki , Sanematsu Keisuke , Ohta Rie , Shirosaki Shinya , Koyano Kiyoshi , Nonaka Kazuaki , Shigemura Noriatsu , Ninomiya Yuzo
Published: July 2008

OBJECTIVE—It has recently been proposed that the peripheral taste organ is one of the targets for leptin. In lean mice, leptin selectively suppresses gustatory neural and behavioral responses to sweet compounds without affecting responses to other taste stimuli, whereas obese diabetic db/db mice with defects in leptin receptor lack this leptin suppression on sweet taste. Here, we further examined potential links between leptin and sweet taste in humans.

RESEARCH DESIGN AND METHODS—A total of 91 nonobese subjects were used to determine recognition thresholds using a standard stair-case methodology for various taste stimuli. Plasma leptin levels were determined by an enzyme-linked immunosorbent assay at several timepoints during the day under normal and restricted-meal conditions.

RESULTS—The recognition thresholds for sweet compounds exhibited a diurnal variation from 0800 to 2200 h that parallels variation for leptin levels, with the lowest thresholds in the morning and the highest thresholds at night. This diurnal variation is sweet-taste selective—it was not observed in thresholds for other taste stimuli (NaCl, citric acid, quinine, and mono-sodium glutamate). The diurnal variation for sweet thresholds in the normal feeding condition (three meals) was independent of meal timing and thereby blood glucose levels. Furthermore, when leptin levels were phase-shifted following imposition of one or two meals per day, the diurnal variation of thresholds for sweet taste shifted in parallel.

CONCLUSIONS—This synchronization of diurnal variation in leptin levels and sweet taste recognition thresholds suggests a mechanistic connection between these two variables in humans.
Alterations in MicroRNA Expression Contribute to Fatty Acid–Induced Pancreatic β-Cell Dysfunction
Authors: Lovis Pascal , Roggli Elodie , Laybutt D. Ross , Gattesco Sonia , Yang Jiang-Yan , Widmann Christian , Abderrahmani Amar , Regazzi Romano
Published: July 2008

OBJECTIVE—Visceral obesity and elevated plasma free fatty acids are predisposing factors for type 2 diabetes. Chronic exposure to these lipids is detrimental for pancreatic β-cells, resulting in reduced insulin content, defective insulin secretion, and apoptosis. We investigated the involvement in this phenomenon of microRNAs (miRNAs), a class of noncoding RNAs regulating gene expression by sequence-specific inhibition of mRNA translation.

RESEARCH DESIGN AND METHODS—We analyzed miRNA expression in insulin-secreting cell lines or pancreatic islets exposed to palmitate for 3 days and in islets from diabetic db/db mice. We studied the signaling pathways triggering the changes in miRNA expression and determined the impact of the miRNAs affected by palmitate on insulin secretion and apoptosis.

RESULTS—Prolonged exposure of the β-cell line MIN6B1 and pancreatic islets to palmitate causes a time- and dose-dependent increase of miR34a and miR146. Elevated levels of these miRNAs are also observed in islets of diabetic db/db mice. miR34a rise is linked to activation of p53 and results in sensitization to apoptosis and impaired nutrient-induced secretion. The latter effect is associated with inhibition of the expression of vesicle-associated membrane protein 2, a key player in β-cell exocytosis. Higher miR146 levels do not affect the capacity to release insulin but contribute to increased apoptosis. Treatment with oligonucleotides that block miR34a or miR146 activity partially protects palmitate-treated cells from apoptosis but is insufficient to restore normal secretion.

CONCLUSIONS—Our findings suggest that at least part of the detrimental effects of palmitate on β-cells is caused by alterations in the level of specific miRNAs.
Cerebral Blood Flow and Cerebral Edema in Rats With Diabetic Ketoacidosis
Authors: Yuen Natalie , Anderson Steven E. , Glaser Nicole , Tancredi Daniel J. , O'Donnell Martha E.
Published: July 2008

OBJECTIVE— Cerebral edema (CE) is a potentially life-threatening complication of diabetic ketoacidosis (DKA) in children. Osmotic fluctuations during DKA treatment have been considered responsible, but recent data instead suggest that cerebral hypoperfusion may be involved and that activation of cerebral ion transporters may occur. Diminished cerebral blood flow (CBF) during DKA, however, has not been previously demonstrated. We investigated CBF and edema formation in a rat model of DKA and determined the effects of bumetanide, an inhibitor of Na-K-Cl cotransport.

RESEARCH DESIGN AND METHODS— Juvenile rats with streptozotocin-induced DKA were treated with intravenous saline and insulin, similar to human treatment protocols. CBF was determined by magnetic resonance (MR) perfusion–weighted imaging before and during treatment, and CE was assessed by determining apparent diffusion coefficients (ADCs) using MR diffusion–weighted imaging.

RESULTS— CBF was significantly reduced in DKA and was responsive to alterations in pCO2. ADC values were reduced, consistent with cell swelling. The reduction in ADCs correlated with dehydration, as reflected in blood urea nitrogen concentrations. Bumetanide caused a rapid rise in ADCs of DKA rats without significantly changing CBF, while saline/insulin caused a rapid rise in CBF and a gradual rise in ADCs. DKA rats treated with bumetanide plus saline/insulin showed a trend toward more rapid rise in cortical ADCs and a larger rise in striatal CBF than those observed with saline/insulin alone.

CONCLUSIONS— These data demonstrate that CE in DKA is accompanied by cerebral hypoperfusion before treatment and suggest that blocking Na-K-Cl cotransport may reduce cerebral cell swelling.
Elevated Toll-Like Receptor 4 Expression and Signaling in Muscle From Insulin-Resistant Subjects
Authors: Reyna Sara M. , Ghosh Sangeeta , Tantiwong Puntip , Meka C.S. Reddy , Eagan Phyllis , Jenkinson Christopher P. , Cersosimo Eugenio , DeFronzo Ralph A. , Coletta Dawn K. , Sriwijitkamol Apiradee , Musi Nicolas
Published: July 2008

OBJECTIVE— Tall-like receptor (TLR)4 has been implicated in the pathogenesis of free fatty acid (FFA)-induced insulin resistance by activating inflammatory pathways, including inhibitor of κB (IκB)/nuclear factor κB (NFκB). However, it is not known whether insulin-resistant subjects have abnormal TLR4 signaling. We examined whether insulin-resistant subjects have abnormal TLR4 expression and TLR4-driven (IκB/NFκB) signaling in skeletal muscle.

RESEARCH DESIGN AND METHODS— TLR4 gene expression and protein content were measured in muscle biopsies in 7 lean, 8 obese, and 14 type 2 diabetic subjects. A primary human myotube culture system was used to examine whether FFAs stimulate IκB/NFκB via TLR4 and whether FFAs increase TLR4 expression/content in muscle.

RESULTS— Obese and type 2 diabetic subjects had significantly elevated TLR4 gene expression and protein content in muscle. TLR4 muscle protein content correlated with the severity of insulin resistance. Obese and type 2 diabetic subjects also had lower IκBα content, an indication of elevated IκB/NFκB signaling. The increase in TLR4 and NFκB signaling was accompanied by elevated expression of the NFκB-regulated genes interleukin (IL)-6 and superoxide dismutase (SOD)2. In primary human myotubes, acute palmitate treatment stimulated IκB/NFκB, and blockade of TLR4 prevented the ability of palmitate to stimulate the IκB/NFκB pathway. Increased TLR4 content and gene expression observed in muscle from insulin-resistant subjects were reproduced by treating myotubes from lean, normal-glucose-tolerant subjects with palmitate. Palmitate also increased IL-6 and SOD2 gene expression, and this effect was prevented by inhibiting NFκB.

CONCLUSIONS— Abnormal TLR4 expression and signaling, possibly caused by elevated plasma FFA levels, may contribute to the pathogenesis of insulin resistance in humans.
G/T Substitution in Intron 1 of the UNC13B Gene Is Associated With Increased Risk of Nephropathy in Patients With Type 1 Diabetes
Authors: Trégouet David-Alexandre , Groop Per-Henrik , McGinn Steven , Forsblom Carol , Hadjadj Samy , Marre Michel , Parving Hans-Henrik , Tarnow Lise , Telgmann Ralph , Godefroy Tiphaine , Nicaud Viviane , Rousseau Rachel , Parkkonen Maikki , Hoverfält Anna , Gut Ivo , Heath Simon , Matsuda Fumihiko , Cox Roger , Kazeem Gbenga , Farrall Martin , Gauguier Dominique , Brand-Herrmann Stefan-Martin , Cambien François , Lathrop Mark , Vionnet Nathalie ,   for the EURAGEDIC Consortium
Published: July 2008

OBJECTIVE— Genetic and environmental factors modulate the susceptibility to diabetic nephropathy, as initiating and/or progression factors. The objective of the European Rational Approach for the Genetics of Diabetic Complications (EURAGEDIC) study is to identify nephropathy susceptibility genes. We report molecular genetic studies for 127 candidate genes for nephropathy.

RESEARCH DESIGN AND METHODS— Polymorphisms were identified through sequencing of promoter, exon, and flanking intron gene regions and a database search. A total of 344 nonredundant SNPs and nonsynonymous variants were tested for association with diabetic nephropathy (persistent albuminuria ≥300 mg/24 h) in a large type 1 diabetes case/control (1,176/1,323) study from three European populations.

RESULTS— Only one SNP, rs2281999, located in the UNC13B gene, was significantly associated with nephropathy after correction for multiple testing. Analyses of 21 additional markers fully characterizing the haplotypic variability of the UNC13B gene showed consistent association of SNP rs13293564 (G/T) located in intron 1 of the gene with nephropathy in the three populations. The odds ratio (OR) for nephropathy associated with the TT genotype was 1.68 (95% CI 1.29–2.19) (P = 1.0 × 10−4). This association was replicated in an independent population of 412 case subjects and 614 control subjects (combined OR of 1.63 [95% CI 1.30–2.05], P = 2.3 × 10−5).

CONCLUSIONS— We identified a polymorphism in the UNC13B gene associated with nephropathy. UNC13B mediates apopotosis in glomerular cells in the presence of hyperglycemia, an event occurring early in the development of nephropathy. We propose that this polymorphism could be a marker for the initiation of nephropathy. However, further studies are needed to clarify the role of UNC13B in nephropathy.
Brain Glucagon-Like Peptide-1 Regulates Arterial Blood Flow, Heart Rate, and Insulin Sensitivity
Authors: Cabou Cendrine , Campistron Gérard , Marsollier Nicolas , Leloup Corinne , Cruciani-Guglielmacci Celine , Pénicaud Luc , Drucker Daniel J. , Magnan Christophe , Burcelin Rémy
Published: July 2008

OBJECTIVE— To ascertain the importance and mechanisms underlying the role of brain glucagon-like peptide (GLP)-1 in the control of metabolic and cardiovascular function. GLP-1 is a gut hormone secreted in response to oral glucose absorption that regulates glucose metabolism and cardiovascular function. GLP-1 is also produced in the brain, where its contribution to central regulation of metabolic and cardiovascular homeostasis remains incompletely understood.

RESEARCH DESIGN AND METHODS— Awake free-moving mice were infused with the GLP-1 receptor agonist exendin-4 (Ex4) into the lateral ventricle of the brain in the basal state or during hyperinsulinemic eu-/hyperglycemic clamps. Arterial femoral blood flow, whole-body insulin-stimulated glucose utilization, and heart rates were continuously recorded.

RESULTS— A continuous 3-h brain infusion of Ex4 decreased femoral arterial blood flow and whole-body glucose utilization in the awake free-moving mouse clamped in a hyperinsulinemic-hyperglycemic condition, only demonstrating that this effect was strictly glucose dependent. However, the heart rate remained unchanged. The metabolic and vascular effects of Ex4 were markedly attenuated by central infusion of the GLP-1 receptor (GLP-1R) antagonist exendin-9 (Ex9) and totally abolished in GLP-1 receptor knockout mice. A correlation was observed between the metabolic rate and the vascular flow in control and Ex4-infused mice, which disappeared in Ex9 and GLP-1R knockout mice. Moreover, hypothalamic nitric oxide synthase activity and the concentration of reactive oxygen species (ROS) were also reduced in a GLP-1R–dependent manner, whereas the glutathione antioxidant capacity was increased. Central GLP-1 activated vagus nerve activity, and complementation with ROS donor dose-dependently reversed the effect of brain GLP-1 signaling on peripheral blood flow.

CONCLUSIONS— Our data demonstrate that central GLP-1 signaling is an essential component of circuits integrating cardiovascular and metabolic responses to hyperglycemia.
Integrin-Associated Protein Association With Src Homology 2 Domain Containing Tyrosine Phosphatase Substrate 1 Regulates IGF-I Signaling In Vivo
Authors: Maile Laura A. , Capps Byron E. , Miller Emily C. , Aday Ariel W. , Clemmons David R.
Published: July 2008

OBJECTIVE—Smooth muscle cell (SMC) maintained in medium containing normal levels of glucose do not proliferate in response to IGF-I, whereas cells maintained in medium containing 25 mmol/l glucose can respond. The aim of this study was to determine whether signaling events that have been shown to be required for stimulation of SMC growth were regulated by glucose concentrations in vivo.

RESEARCH DESIGN AND METHODS—We compared IGF-I–stimulated signaling events and growth in the aortic smooth muscle cells from normal and hyperglycemic mice.

RESULTS—We determined that, in mice, hyperglycemia was associated with an increase in formation of the integrin-associated protein (IAP)/Src homology 2 domaine containing tyrosine phosphatase substrate 1 (SHPS-1) complex. There was a corresponding increase in Shc recruitment to SHPS-1 and Shc phosphorylation in response to IGF-I. There was also an increase in mitogen-activated protein kinase activation and SMC proliferation. The increase in IAP association with SHPS-1 in hyperglycemia appeared to be due to the protection of IAP from cleavage that occurred during exposure to normal glucose. In addition, we demonstrated that the protease responsible for IAP cleavage was matrix metalloprotease-2. An anti-IAP antibody that disrupted the IAP–SHPS-1 association resulted in complete inhibition of IGF-I–stimulated proliferation.

CONCLUSIONS—Taken together, our results support a model in which hyperglycemia is associated with a reduction in IAP cleavage, thus allowing the formation of the IAP–SHPS-1 signaling complex that is required for IGF-I–stimulated proliferation of SMC.