bluuebunny/crossref_metadata_2025 huggingface dataset:
Managing the economy, managing the people: Britain c.1931–701
Authors: TOMLINSON JIM
Published: July 2005

The rise and consolidation of national economic management is one of the key themes of British economic and political history in the middle decades of the twentieth century. This article seeks to complement the existing substantial literature focused upon elite economic policy‐making processes with an analysis of how that economic management has been accompanied by persistent government attempts to develop and popularize new understandings of 'the economy'. In this way, governments were involved in a profound shift in their relationship with the wider society, as they sought to shape the beliefs and behaviour of producers, consumers, and the public in general. The article attempts to link the elite discourse of national economic management to the attempts to shape popular understandings about the economy, and the (problematic) impact of these understandings on behaviour. The particular focus is on the 1960s, when these attempts reached some kind of culmination.
Microvascular angioadaptation after endurance training with l‐arginine supplementation in rat heart and hindleg muscles
Authors: Suzuki Junichi
Published: July 2005

This study was designed to examine whether dietary l‐arginine supplementation modulates exercise‐induced angiogenesis and vascular endothelial growth factor (VEGF) expression in female Wistar rats. Exercise training (running) lasted for 6 weeks at 25 m min−1 on a 20% gradient for 10–60 min day−1. Rats in the l‐arginine‐treated groups drank water containing 4%l‐arginine. Histochemical identification of capillary profiles showed that training with l‐arginine significantly increased the capillary/fibre (C/F) ratio in the subendocardium of the left ventricle, whereas training alone did not. Because of a significantly higher fibre cross‐sectional area, a concomitant, but not significant, decrease in capillary density was also observed. In the hindleg muscles, training with l‐arginine significantly increased the C:F ratio, although the degree of change was the same as that observed after training alone. Western blot analysis showed that training with l‐arginine significantly increased VEGF protein expression by 1.7‐fold in the left ventricle, while the increase with training alone was insignificant. In the soleus muscle, although VEGF protein expression was elevated insignificantly after training (2.8‐fold), training with l‐arginine significantly increased the protein levels (3.8‐fold). Tissue endothelial nitric oxide synthase protein levels did not changed after either training or l‐arginine treatment. The present results suggest that l‐arginine supplementation causes additional effects on exercise‐induced angiogenesis in the rat heart by promoting VEGF expression.
Physiological and morphological development of the rat cerebellar Purkinje cell
Authors: McKay Bruce E. , Turner Ray W.
Published: July 2005

Cerebellar Purkinje cells integrate multimodal afferent inputs and, as the only projection neurones of the cerebellar cortex, are key to the coordination of a variety of motor‐ and learning‐related behaviours. In the neonatal rat the cerebellum is undeveloped, but over the first few postnatal weeks both the structure of the cerebellum and cerebellar‐dependent behaviours mature rapidly. Maturation of Purkinje cell physiology is expected to contribute significantly to the development of cerebellar output. However, the ontogeny of the electrophysiological properties of the Purkinje cell and its relationship to maturation of cell morphology is incompletely understood. To address this problem we performed a detailed in vitro electrophysiological analysis of the spontaneous and intracellularly evoked intrinsic properties of Purkinje cells obtained from postnatal rats (P0 to P90) using whole‐cell patch clamp recordings. Cells were filled with neurobiotin to enable subsequent morphological comparisons. Three stages of physiological and structural development were identified. During the early postnatal period (P0 to ∼P9) Purkinje cells were characterized by an immature pattern of Na+‐spike discharge, and possessed only short multipolar dendrites. This was followed by a period of rapid maturation (from ∼P12 to ∼P18), consisting of changes in Na+‐spike discharge, emergence of repetitive bursts of Na+ spikes terminated by Ca2+ spikes (Ca2+–Na+ bursts), generation of the trimodal pattern, and a significant expansion of the dendritic tree. During the final stage (> P18 to P90) there were minor refinements of cell output and a plateau in dendritic area. Our results reveal a rapid transition of the Purkinje cell from morphological and physiological immaturity to adult characteristics over a short developmental window, with a close correspondence between changes in cell output and dendritic growth. The development of Purkinje cell intrinsic electrophysiological properties further matches the time course of other measures of cerebellar structural and functional maturation.
Defining electrical communication in skeletal muscle resistance arteries: a computational approach
Authors: Diep Hai K. , Vigmond Edward J. , Segal Steven S. , Welsh Donald G.
Published: July 2005

Vascular cells communicate electrically to coordinate their activity and control tissue blood flow. To foster a quantitative understanding of this fundamental process, we developed a computational model that was structured to mimic a skeletal muscle resistance artery. Each endothelial cell and smooth muscle cell in our virtual artery was treated as the electrical equivalent of a capacitor coupled in parallel with a non‐linear resistor representing ionic conductance; intercellular gap junctions were represented by ohmic resistors. Simulations revealed that the vessel wall is not a syncytium in which electrical stimuli spread equally to all constitutive cells. Indeed, electrical signals spread in a differential manner among and between endothelial cells and smooth muscle cells according to the initial stimulus. The predictions of our model agree with physiological data from the feed artery of the hamster retractor muscle. Cell orientation and coupling resistance were the principal factors that enable electrical signals to spread differentially along and between the two cell types. Our computational observations also illustrated how gap junctional coupling enables the vessel wall to filter and transform transient electrical events into sustained voltage responses. Functionally, differential electrical communication would permit discrete regions of smooth muscle activity to locally regulate blood flow and the endothelium to coordinate regional changes in tissue perfusion.
Modulating parameters of excitability during and after transcranial direct current stimulation of the human motor cortex
Authors: Nitsche Michael A. , Seeber Antje , Frommann Kai , Klein Cornelia Carmen , Rochford Christian , Nitsche Maren S. , Fricke Kristina , Liebetanz David , Lang Nicolas , Antal Andrea , Paulus Walter , Tergau Frithjof
Published: July 2005

Weak transcranial direct current stimulation (tDCS) of the human motor cortex results in excitability shifts which occur during and after stimulation. These excitability shifts are polarity‐specific with anodal tDCS enhancing excitability, and cathodal reducing it. To explore the origin of this excitability modulation in more detail, we measured the input–output curve and motor thresholds as global parameters of cortico‐spinal excitability, and determined intracortical inhibition and facilitation, as well as facilitatory indirect wave (I‐wave) interactions. Measurements were performed during short‐term tDCS, which elicits no after‐effects, and during other tDCS protocols which do elicit short‐ and long‐lasting after‐effects. Resting and active motor thresholds remained stable during and after tDCS. The slope of the input–output curve was increased by anodal tDCS and decreased by cathodal tDCS. Anodal tDCS of the primary motor cortex reduced intracortical inhibition and enhanced facilitation after tDCS but not during tDCS. Cathodal tDCS reduced facilitation during, and additionally increased inhibition after its administration. During tDCS, I‐wave facilitation was not influenced but, for the after‐effects, anodal tDCS increased I‐wave facilitation, while cathodal tDCS had only minor effects. These results suggest that the effect of tDCS on cortico‐spinal excitability during a short period of stimulation (which does not induce after‐effects) primarily depends on subthreshold resting membrane potential changes, which are able to modulate the input‐output curve, but not motor thresholds. In contrast, the after‐effects of tDCS are due to shifts in intracortical inhibition and facilitation, and at least partly also to facilitatory I‐wave interaction, which is controlled by synaptic activity.
Virtual head rotation reveals a process of route reconstruction from human vestibular signals
Authors: Day Brian L. , Fitzpatrick Richard C.
Published: July 2005

The vestibular organs can feed perceptual processes that build a picture of our route as we move about in the world. However, raw vestibular signals do not define the path taken because, during travel, the head can undergo accelerations unrelated to the route and also be orientated in any direction to vary the signal. This study investigated the computational process by which the brain transforms raw vestibular signals for the purpose of route reconstruction. We electrically stimulated the vestibular nerves of human subjects to evoke a virtual head rotation fixed in skull co‐ordinates and measure its perceptual effect. The virtual head rotation caused subjects to perceive an illusory whole‐body rotation that was a cyclic function of head‐pitch angle. They perceived whole‐body yaw rotation in one direction with the head pitched forwards, the opposite direction with the head pitched backwards, and no rotation with the head in an intermediate position. A model based on vector operations and the anatomy and firing properties of semicircular canals precisely predicted these perceptions. In effect, a neural process computes the vector dot product between the craniocentric vestibular vector of head rotation and the gravitational unit vector. This computation yields the signal of body rotation in the horizontal plane that feeds our perception of the route travelled.
MODIFIED BETHE–WEIZSÄCKER MASS FORMULA WITH ISOTONIC SHIFT AND NEW DRIPLINES
Authors: CHOWDHURY P. ROY , SAMANTA C. , BASU D. N.
Published: July 2005

Nuclear masses are calculated using the modified Bethe–Weizsäcker mass formula in which the isotonic shifts have been incorporated. The results are compared with the improved liquid drop model with isotonic shift. Mass excesses predicted by this method compares well with the microscopic–macroscopic model while being much more simple. The neutron and proton drip lines have been predicted using this modified Bethe–Weizsäcker mass formula with isotonic shifts.
TOPOLOGICAL MASS IN SEVEN DIMENSIONS AND DUALITIES IN FOUR DIMENSIONS
Authors: BETANCOURT M. , KHOUDEIR A.
Published: July 2005

The massive topologically and self-dual theories in seven dimensions are considered. The local duality between these theories is established and the dimensional reduction leads to different dualities for massive antisymmetric fields in four dimensions.
LITTLE HIGGS MODELS FOR NON-UNIVERSALITY FERMION
Authors: CHAI YAN , YIN FURONG
Published: July 2005

We introduce the fermion non-universality into the little Higgs models SU (5)/ SO (5), SU (6)/ Sp (6) and study the phenomenology of the new models. We find that if we change the transform property of the observed fermions under the extended [ SU (2)× U (1)]2, the cancellation of the one-loop quadratically divergent correction to the Higgs mass arising from gauge bosons will not be changed, whereas the phenomenology at W-pole, Z-pole and low q2 will be changed.
PRIMORDIAL BLACK HOLES, HAWKING RADIATION AND THE EARLY UNIVERSE
Authors: FRAMPTON PAUL H. , KEPHART THOMAS W.
Published: July 2005

The 511 keV gamma emission from the galactic core may originate from a high concentration (~ 1022) of primordial black holes (PBHs) in the core, each of whose Hawking radiation includes ~ 1021 positrons per second. The PBHs we consider are taken as near the lightest with longevity greater than the age of the universe (mass ~ 1012 kg ; Schwarzschild radius ~ 1 fm ). These PBHs contribute only a small fraction of cold dark matter, Ω PBH ~ 10-8. This speculative hypothesis, if confirmed implies the simultaneous discovery of Hawking radiation and an early universe phase transition.
CLUSTER SIZE DEPENDENCE ON RELATIVISTIC CHARGED PARTICLE MULTIPLICITY IN NUCLEUS–NUCLEUS COLLISIONS
Authors: AHMAD N. , KHAN M. M. , AHMAD SHAKEEL , ZAFAR M. , IRFAN M.
Published: July 2005

Dependence of cluster size on relativistic charged particle multiplicity is examined by analyzing experimental data involving 530 and 283 interactions with nh≥0 caused by 4.5 A and 14.5 A GeV/c28 Si –beams in nuclear emulsion. The results reveal that the maximum number of charged particles constituting a cluster is four for the collisions having ns≥10, where ns is the number of relativistic charged particles produced in interactions with relative velocity β≥0.7. However, this number is found to be three for the interactions having ns≤9. Results also show that the cluster size is essentially insensitive to the projectile energy.
ENTRANCE CHANNEL EFFECTS ON THE ISOSPIN FRACTIONATION AT INTERMEDIATE ENERGY HEAVY ION COLLISIONS
Authors: LIU JIAN-YE , XING YONG ZHONG , LIU HANG , GUO WEN-JUN , LEE XI GUO
Published: July 2005

We investigate the dependence of isospin fractionation degree on the entrance channel condition, which includes the impact parameter, the beam energy, the mass and the neutron–proton ratio of the colliding system as well as quantifying the gas phase and the liquid phase by using the isospin dependent quantum molecular dynamics model. We found that the isospin fractionation degree increases markedly with the enhancements of the neutron–proton ratio of system and the beam energy; however, it decreases with increasing system mass as well as slowly increases with the enhancement of the impact parameter. In particular, the property for the sensitive dependence of isospin fractionation degree on the symmetry potential and its weak dependence on the in-medium nucleon–nucleon cross-section is preserved for all the neutron-rich systems and all the impact parameters in the relative lower beam energy region. In this case, the isospin fractionation degree for all the neutron-rich systems can be directly compared with the experimental data to extract the information on the symmetry potential in the relative lower beam energy region.
QUANTUM-INFORMATION CONTENT OF FRACTIONAL OCCUPATION PROBABILITIES IN NUCLEI
Authors: CHATZISAVVAS K. CH. , PANOS C. P.
Published: July 2005

Three measures of the information content of a probability distribution are briefly reviewed. They are applied to fractional occupation probabilities in light nuclei, taking into account short-range correlations. The effect of short-range correlations is to increase the information entropy (or disorder) of nuclei, comparing with the independent particle model. It is also indicated that the information entropy can serve as a sensitive index of order and short-range correlations in nuclei. It is concluded that increasing Z, the information entropy increases, i.e. the disorder of the nucleus increases for all measures of information considered in the present work.
Instrumentation Aspects of Animal PET
Authors: Tai Yuan-Chuan , Laforest Richard
Published: July 2005

▪ Abstract  Biological research has been accelerated by the development of noninvasive imaging techniques and by use of genetically engineered mice to model human diseases and normal development. Because these mice can be expensive, noninvasive imaging techniques, such as high-resolution positron emission tomography (PET), that permit longitudinal studies of the same animals are very attractive. Such studies reduce the number of animals used, reduce intersubject variability, and improve the accuracy of biological models. PET provides quantitative measurements of the spatiotemporal distribution of radiotracers and is an extremely powerful tool in using molecular imaging to study biology, to monitor disease intervention, and to establish pharmacokinetics for new drugs. The design of animal PET scanners has improved significantly in the past decade and can provide adequate image resolution and sensitivity to study transgenic mice. This article reviews the fundamental and technical challenges of small-animal PET imaging, with a particular focus on the latest developments and future directions of detector technologies and system design.
DNA Mechanics
Authors: Benham Craig J. , Mielke Steven P.
Published: July 2005

▪ Abstract  We review the history of DNA mechanics and its analysis. We evaluate several methods to analyze the structures of superhelical DNA molecules, each predicated on the assumption that DNA can be modeled with reasonable accuracy as an extended, linearly elastic polymer. Three main approaches are considered: mechanical equilibrium methods, which seek to compute minimum energy conformations of topologically constrained molecules; statistical mechanical methods, which seek to compute the Boltzmann distribution of equilibrium conformations that arise in a finite temperature environment; and dynamic methods, which seek to compute deterministic trajectories of the helix axis by solving equations of motion. When these methods include forces of self-contact, which prevent strand passage and preserve the topological constraint, each predicts plectonemically interwound structures. On the other hand, the extent to which these mechanical methods reliably predict energetic and thermodynamic properties of superhelical molecules is limited, in part because of their inability to account explicitly for interactions involving solvent. Monte Carlo methods predict the entropy associated with supercoiling to be negative, in conflict with a body of experimental evidence that finds it is large and positive, as would be the case if superhelical deformations significantly disrupt the ordering of ambient solvent molecules. This suggests that the large-scale conformational properties predicted by elastomechanical models are not the only ones determining the energetics and thermodynamics of supercoiling. Moreover, because all such models that preserve the topological constraint correctly predict plectonemic interwinding, despite these and other limitations, this constraint evidently dominates energetic and thermodynamic factors in determining supercoil geometry. Therefore, agreement between predicted structures and structures obtained experimentally, for example, by electron microscopy, does not in itself provide evidence for the correctness or completeness of any given model of DNA mechanics.
LAW FACTS
Authors: Stinchcombe Arthur L.
Published: July 2005

▪ Abstract  This review article is not dedicated to a subject matter of research. Instead it outlines various kinds of facts commonly used to analyze the relations of law and society. To illustrate, it gives examples of eight distinct kinds of facts on how action departs from relevant laws on the books: actions in crusades; actions following deep norms when coordination norms are in conflict with them; police culture undermining legal citizen protection; corruption; legal pluralism as in colonies; crucial missing facts on behavior deliberately left out of the law of contract and similar laws to create flexibility; and disagreements between public opinion and the law. Each of these and more are then analyzed in terms of what is distinctive about them and of the kind of law and society theories they bear on.
Current Status and Future Directions in Couple Therapy
Authors: Snyder Douglas K. , Castellani Angela M. , Whisman Mark A.
Published: July 2005

Couple therapy research affirms that various approaches to couple treatment produce statistically and clinically significant improvement for a substantial proportion of couples in reducing overall relationship distress. Recent studies have extended these findings in indicating the effectiveness of couple-based interventions for a broad range of coexisting emotional, behavioral, or physical health problems in one or both partners. In contrast to these encouraging results, research also indicates that a sizeable percentage of couples fail to achieve significant gains from couple therapy or show significant deterioration afterward. Research on processes of change and predictors of treatment outcome in couple therapy provides preliminary evidence regarding factors potentially contributing to variable treatment response. The chapter concludes with 12 recommendations regarding future directions in couple therapy research and clinical training.
Apical ammonium inhibition of cAMP-stimulated secretion in T84 cells is bicarbonate dependent
Authors: Worrell Roger T. , Best Alison , Crawford Oscar R. , Xu Jie , Soleimani Manoocher , Matthews Jeffrey B.
Published: July 2005

Normal human colonic luminal (NH4+) concentration ([NH4+]) ranges from ∼10 to 100 mM. However, the nature of the effects of NH4+ on transport, as well as NH4+ transport itself, in colonic epithelium is poorly understood. We elucidate here the effects of apical NH4+ on cAMP-stimulated Cl− secretion in colonic T84 cells. In HEPES-buffered solutions, 10 mM apical NH4+ had no significant effect on cAMP-stimulated current. In contrast, 10 mM apical NH4+ reduced current within 5 min to 61 ± 4% in the presence of 25 mM HCO3−. Current inhibition was not simply due to an increase in extracellular K+-like cations, in that the current magnitude was 95 ± 5% with 10 mM apical K+ and 46 ± 3% with 10 mM apical NH4+ relative to that with 5 mM apical K+. We previously demonstrated that inhibition of Cl− secretion by basolateral NH4+ occurs in HCO3−-free conditions and exhibits anomalous mole fraction behavior. In contrast, apical NH4+ inhibition of current in HCO3− buffer did not show anomalous mole fraction behavior and followed the absolute [NH4+] in K+-NH4+ mixtures, where K+ concentration + [NH4+] = 10 mM. The apical NH4+ inhibitory effect was not prevented by 100 μM methazolamide, suggesting no role for apical carbonic anhydrase. However, apical NH4+ inhibition of current was prevented by 10 min of pretreatment of the apical surface with 500 μM DIDS, 100 μM 4,4′-dinitrostilbene-2,2′-disulfonic acid (DNDS), or 25 μM niflumic acid, suggesting a role for NH4+ action through an apical anion exchanger. mRNA and protein for the apical anion exchangers SLC26A3 [downregulated in adenoma (DRA)] and SLC26A6 [putative anion transporter (PAT1)] were detected in T84 cells by RT-PCR and Northern and Western blots. DRA and PAT1 appear to associate with CFTR in the apical membrane. We conclude that the HCO3− dependence of apical NH4+ inhibition of secretion is due to the action of NH4+ on an apical anion exchanger.
Inhibition of lymphocyte apoptosis by pancreatic stellate cells: impact of interleukin-15
Authors: Sparmann Gisela , Glass Änne , Brock Peter , Jaster Robert , Koczan Dirk , Thiesen Hans-Jürgen , Liebe Stefan , Emmrich Jörg
Published: July 2005

There is growing evidence that pancreatic stellate cells (PSCs) produce cytokines and take part in the regulation of inflammatory processes in the pancreas. IL-15 inhibits apoptosis of various cell populations. This study was performed to investigate whether PSCs produce IL-15 and thereby can affect lymphocytes. Primary PSCs were isolated from the rat pancreas using density gradient centrifugation. mRNA expression of IL-15 was demonstrated by RT-PCR, and IL-15 protein was analyzed by immunoblotting. Lymphocytes obtained from rat mesenterial lymph nodes were cocultured with in vitro activated PSCs. Apoptosis has been quantified by the binding of annexin V-FITC with a flow cytometer. Proliferation was monitored using [3H]thymidine incorporation. PSCs express two splice variants of IL-15. The protein was detectable only in cell lysates but not in the cell culture supernatant. Cocultivation of lymphocytes with PSCs and IL-15 inhibited spontaneous lymphocyte apoptosis, and this effect was reduced by an anti-IL-15 antibody. Lymphocytes induced vice versa the proliferation and collagen production of PSCs. The inhibition of spontaneous lymphocyte apoptosis in cocultures with PSCs was at least partially mediated by cell-bound IL-15. This effect and the stimulation of PSCs by lymphocytes may lead to a circulus vitiosus, resulting in the persistence of inflammatory processes and the development of fibrosis during chronic pancreatitis.
Augmented responses to ozone in obese carboxypeptidase E-deficient mice
Authors: Johnston Richard A. , Theman Todd A. , Shore Stephanie A.
Published: July 2005

We reported previously that mice obese as a result of leptin deficiency ( ob/ ob) have enhanced ozone (O3)-induced airway hyperresponsiveness (AHR) and inflammation compared with wild-type (C57BL/6) controls. To determine whether this increased response to O3 was independent of the modality of obesity, we examined O3-induced AHR and inflammation in Cpe fat mice. These mice are obese as a consequence of a mutation in the gene encoding carboxypeptidase E (Cpe), an enzyme important in processing prohormones and proneuropeptides involved in satiety and energy expenditure. Airway responsiveness to intravenous methacholine, measured by forced oscillation, was increased in Cpe fat vs. wild-type mice after air exposure. In addition, compared with air exposure, airway responsiveness was increased 24 h after O3 exposure (2 ppm for 3 h) in Cpe fat but not in wild-type mice. Compared with air-exposed controls, O3 exposure increased bronchoalveolar lavage fluid (BALF) protein, IL-6, KC, MIP-2, MCP-1, and soluble TNF receptors (sTNFR1 and sTNFR2) as well as BALF neutrophils. With the exception of sTNFR1 and sTNFR2, all of these outcome indicators were greater in Cpe fat vs. wild-type mice. Serum sTNFR1, sTNFR2, MCP-1, leptin, and blood leukocytes were elevated in Cpe fat compared with wild-type mice even in the absence of O3 exposure, similar to the chronic systemic inflammation observed in human obesity. These results indicate that increased O3-induced AHR and inflammation are consistent features of obese mice, regardless of the modality of obesity. These results also suggest that chronic systemic inflammation may enhance airway responses to O3 in obese mice.
Effect of histamine and cimetidine on retinal and choroidal blood flow in humans
Authors: Resch Hemma , Zawinka Claudia , Lung Solveig , Weigert Günther , Schmetterer Leopold , Garhöfer Gerhard
Published: July 2005

Intravenous administration of histamine causes an increase in choroidal blood flow and retinal vessel diameter in healthy subjects. The mechanism underlying this effect remains to be elucidated. In the present study, we hypothesized that H2 receptor blockade alters hemodynamic effects of histamine in the choroid and retina. Eighteen healthy male nonsmoking volunteers were included in this randomized, double-masked, placebo-controlled two-way crossover study. Histamine (0.32 μg·kg−1·min−1 over 30 min) was infused intravenously in the absence (NaCl as placebo) or presence of the H2 blocker cimetidine (2.3 mg/min over 50 min). Ocular hemodynamic parameters, blood pressure, and intraocular pressure were measured before drug administration, after infusion of cimetidine or placebo, and after coinfusion of histamine. Subfoveal choroidal blood flow and fundus pulsation amplitude were measured with laser-Doppler flowmetry and laser interferometry, respectively. Retinal arterial and venous diameters were measured with a retinal vessel analyzer. Retinal blood velocity was assessed with bidirectional laser-Doppler velocimetry. Histamine increased subfoveal choroidal blood flow (+14 ± 15%, P < 0.001), fundus pulsation amplitude (+11 ± 5%, P < 0.001), retinal venous diameter (+3.0 ± 3.6%, P = 0.002), and retinal arterial diameter (+2.8 ± 4.2%, P < 0.01) but did not change retinal blood velocity. The H2 antagonist cimetidine had no significant effect on ocular hemodynamic parameters. In addition, cimetidine did not modify effects of histamine on choroidal blood flow, fundus pulsation amplitude, retinal venous diameter, and retinal arterial diameter compared with placebo. The present data confirm that histamine increases choroidal blood flow and retinal vessel diameters in healthy subjects. This ocular vasodilator effect of histamine is, however, not altered by administration of an H2 blocker. Whether the increase in blood flow is mediated via H1 receptors or other hitherto unidentified mechanisms remains to be elucidated.
Ontogeny and nutritional programming of adiposity in sheep: potential role of glucocorticoid action and uncoupling protein-2
Authors: Gnanalingham Muhuntha G. , Mostyn Alison , Symonds Michael E. , Stephenson Terence
Published: July 2005

Increased glucocorticoid action and adipose tissue inflammation contribute to excess adiposity. These adaptations may be enhanced in offspring exposed to nutrient restriction (NR) in utero, thereby increasing their susceptibility to later obesity. We therefore determined the developmental ontogeny of glucocorticoid receptor (GR), 11β-hydroxysteroid dehydrogenase (11βHSD) types 1 and 2, and uncoupling protein (UCP)-2 mRNA in perirenal adipose tissue between late gestation and 6 mo after birth in the sheep, as well as the effect of maternal NR targeted between early to mid (28–80 days, term ∼147 days)- or late (110–147 days) gestation. GR and 11βHSD1 mRNA increased with fat mass and were all maximal within the 6-mo observation period. 11βHSD2 mRNA abundance demonstrated a converse decline, whereas UCP2 peaked at 30 days. GR and 11βHSD1 mRNA abundance were strongly correlated with total and relative perirenal adipose tissue weight, and UCP2 was strongly correlated with GR and 11βHSD1 mRNA. Early- to midgestational NR increased GR, 11βHSD1, and UCP2 mRNA, but decreased 11βHSD2 mRNA abundance, an adaptation reversed with late-gestational NR. We conclude that the continual rise in glucocorticoid action and fat mass after birth may underlie the development of later obesity. The magnitude of this adaptation is partly dependent on maternal food intake through pregnancy.
Light induces c-fos and per1 expression in the suprachiasmatic nucleus of arrhythmic hamsters
Authors: Barakat Monique T. , O’Hara Bruce F. , Cao Vinh H. , Heller H. Craig , Ruby Norman F.
Published: July 2005

Locomotor activity rhythms in a significant proportion of Siberian hamsters ( Phodopus sungorus sungorus) become arrhythmic after the light-dark (LD) cycle is phase-delayed by 5 h. Arrhythmia is apparent within a few days and persists indefinitely despite the presence of the photocycle. The failure of arrhythmic hamsters to regain rhythms while housed in the LD cycle, as well as the lack of any masking of activity, suggested that the circadian system of these animals had become insensitive to light. We tested this hypothesis by examining light-induced gene expression in the suprachiasmatic nucleus (SCN). Several weeks after the phase delay, arrhythmic and reentrained hamsters were housed in constant darkness (DD) for 24 h and administered a 30-min light pulse 2 h after predicted dark onset because light induces c- fos and per1 genes at this time in entrained animals. Brains were then removed, and tissue sections containing the SCN were processed for in situ hybridization and probed with c- fos and per1 mRNA probes made from Siberian hamster cDNA. Contrary to our prediction, light pulses induced robust expression of both c- fos and per1 in all reentrained and arrhythmic hamsters. A separate group of animals held in DD for 10 days after the light pulse remained arrhythmic. Thus, even though the SCN of these animals responded to light, neither the LD cycle nor DD restored rhythms, as it does in other species made arrhythmic by constant light (LL). These results suggest that different mechanisms underlie arrhythmicity induced by LL or by a phase delay of the LD cycle. Whereas LL induces arrhythmicity by desynchronizing SCN neurons, phase delay-induced arrhythmicity may be due to a loss of circadian rhythms at the level of individual SCN neurons.
Subcellular responses of p53 and Id2 in fast and slow skeletal muscle in response to stretch-induced overload
Authors: Siu Parco M. , Alway Stephen E.
Published: July 2005

Tumor suppressor p53 and inhibitor of DNA-binding/differentiation Id2 were examined after 7 or 21 days of wing weighting in fast patagialis (PAT) and slow anterior latissimus dorsi (ALD) wing muscles of young adult and old Japanese quails. The contralateral wing served as the intra-animal control. Seven days of loading increased PAT and ALD muscle weight by 28 and 96%, respectively, in young birds. PAT and ALD muscle weight was 49 and 179% greater, respectively, than control muscles after 21 days of loading in young birds. In aged birds, no PAT or ALD hypertrophy was found after 7 days of loading; however, PAT and ALD muscle weight increased by 29 and 102%, respectively, after 21 days of loading. Id2 protein in the nuclear muscle fraction increased in both PAT and ALD muscles from young adult and old birds that were loaded for 7 days and in ALD muscles after 21 days of loading relative to contralateral control muscles. Nuclear p53 protein was greater in 7- or 21-day loaded PAT and ALD muscles relative to control muscles in both age groups. Cytosolic Id2 and p53 protein contents were not changed in loaded PAT or ALD muscles relative to control muscles at any time point. These data suggest that nuclear, but not cytosolic, Id2 and p53 are responsive to stretch-induced muscle overload. Moreover, the attenuated ability of the aged skeletal muscle to achieve hypertrophy does not appear to be explained by the subcellular changes in Id2 and p53 content with overload.
Acute and chronic cardiovascular effects of intermittent hypoxia in C57BL/6J mice
Authors: Campen M. J. , Shimoda L. A. , O’Donnell C. P.
Published: July 2005

We investigated the effects of 1) acute hypoxia and 2) 5 wk of chronic intermittent hypoxia (IH) on the systemic and pulmonary circulations of C57BL/6J mice. Mice were chronically instrumented with either femoral artery or right ventricular catheters. In response to acute hypoxia (4 min of 10% O2; n = 6), systemic arterial blood pressure fell ( P < 0.005) from 107.7 ± 2.5 to 84.7 ± 6.5 mmHg, whereas right ventricular pressure increased ( P < 0.005) from 11.7 ± 0.8 to 14.9 ± 1.3 mmHg. Another cohort of mice was then exposed to IH for 5 wk (O2 nadir = 5%, 60-s cycles, 12 h/day) and then implanted with catheters. In response to 5 wk of chronic IH, mice ( n = 8) increased systemic blood pressure by 7.5 mmHg, left ventricle + septum weight by 32.2 ± 7.5 × 10−2 g/100 g body wt ( P < 0.015), and right ventricle weight by 19.3 ± 3.2 × 10−2 g/100 g body wt ( P < 0.001), resulting in a 14% increase in the right ventricle/left ventricle + septum weight ( P < 0.005). We conclude that in C57BL/6J mice 1) acute hypoxia causes opposite effects on the pulmonary and systemic circulations, leading to preferential loading of the right heart; and 2) chronic IH in mice results in mild to moderate systemic and pulmonary hypertension, with resultant left- and right-sided ventricular hypertrophy.
Nasoalveolar Cysts: Review of 3 Cases
Authors: Erkan Alper Nabi , Yilmazer Cüneyt , Yilmaz İsmail , Bolat Filiz Aka
Published: July 2005

Nasoalveolar cysts, also known as nasolabial cysts or Klestadt’s cysts, are rare, nonodontogenic, soft-tissue lesions that arise during development of the maxilla. They occur lateral to the midline in the region of the maxillary lip and alar base. In this case report clinical features and treatment options of three patients with nasoalveolar cysts are discussed.
The Lowest Effective Intensity of Prophylactic Anticoagulation for Patients with Atrial Fibrillation
Authors: Cheung Chun-ming , Tsoi Tak-hong , Huang Chen-ya
Published: July 2005

Background: Stroke prevention trials in patients with atrial fibrillation (AF) mainly studied the use of warfarin in Caucasians, and the international normalized ratio (INR) was targeted in the range of 2–4. The result may not necessarily be applicable to other ethnic groups. This study aimed to determine the optimal intensity of anticoagulation for stroke prevention in Chinese patients. Methods:  We performed a retrospective study on all Chinese patients with AF taking warfarin for stroke prevention in our hospital from January 1, 2000, to June 30, 2002. Patients with a mechanical heart valve were excluded. We systematically studied their indication of using warfarin, duration of therapy and all INR results. Only those patients whose indications of using warfarin were consistent with the ACC/AHA/ESC Executive Summary were included. Thrombo-embolic episodes, sudden death, major bleeding, intracranial haemorrhage and the INR at the time of the event were recorded. The INR range was divided into six categories: <1.5, 1.5–1.9, 2.0–2.5, 2.6–3.0, 3.1–3.5, >3.5. The number of events was recorded for each category, and this formed the numerator. The denominator was the summation of time each patient stayed in each category of INR. The event rate was then calculated for each INR category. Results: 555 patients were included in the analysis, they constituted 893 patient-years. The INR was kept below 2.6 in 84.9% of the time and between 1.5 and 1.9 in 35% of the time. The overall event rate in our patients was 6.0%, of which 3.9% were due to thrombo-embolic events and 2.1% were due to serious bleeding. The overall event rate was lowest in the INR range from 1.5 to 1.9. which is not significantly different from that of INR 2.0–2.5 and 2.6–3.0. The overall event rate was 3.6% in INR 1.5–3.0 which was significantly lower than 15.1% in INR <1.5 and 20.5% in INR >3.0 (p < 0.01). Conclusions: Our retrospective cohort showed that a lower INR range of 1.5–3.0 was safe and effective for stroke prevention in Chinese patients treated in a single hospital.
Link between Platelet Activity and Outcomes after an Ischemic Stroke
Authors: Yip Hon-Kan , Liou Chia-Wei , Chang Hsueh-Wen , Lan Min-Yu , Liu Josef S. , Chen Mien-Cheng
Published: July 2005

Background: Platelets play an important role in atherosclerosis and thromboembolic events. We examined the relationship between platelet activity and outcomes after an ischemic stroke. Methods: Using flow cytometry, we serially measured the fractions of circulating platelet activity (CD62p expression) after an ischemic stroke in early (<48 h), recent (day 7), convalescent (day 21) and chronic (day 90) phases in 92 consecutive patients with an ischemic stroke. Patients were classified into high (CD62p expression >3.16%) and low (CD62p expression ≤3.16%) platelet activity groups according to the median value of CD62p expression in the early phase of a stroke. Results: The composite end point – death, recurrent stroke and severe neurological impairment (alive in care), defined as a score of >13 on the National Institutes of Health Stroke Scale – within the first 30 days and at an interval of 8.2 ± 1.5 months of follow-up was determined for each group. In the first 30 days, the composite end point occurred in 37.0% of patients in the high platelet activity group as compared with 6.5% in the low platelet activity group (p = 0.0004). At a mean follow-up of 8.2 ± 1.5 months, the composite end point occurred in 36.6% of patients in the high platelet activity group as compared with 10.9% in the low platelet activity group (p = 0.0044). Multiple stepwise logistic regression analysis displayed that high platelet activity (p = 0.011), age (p = 0.013) and the presence of coronary artery disease (p = 0.021) were independently associated with adverse outcomes at the intermediate-term follow-up. Conclusions: Results of this study showed that high platelet activity is strongly associated with adverse clinical outcomes after an early ischemic stroke.
Oestrogen Replacement in vivo Rescues the Dysfunction of Pituitary Somatotropes in Ovariectomised Aromatase Knockout Mice
Authors: Yan Ming , Jones Margaret E.E. , Hernandez Maria , Liu Dongling , Simpson Evan R. , Chen Chen
Published: July 2005

The mechanism of regulation of growth hormone (GH) secretion by oestrogens and androgens is still controversial. Available data on the action of oestrogens on GH expression and secretion in somatotropes is poorly understood. We previously reported that the aromatase knockout (ArKO) mouse with oestrogen deficiency and excessive androgen levels had dysfunctional somatotropes. In order to clarify the influence of androgen and oestrogen, we investigated the in vivo treatment of ovariectomised (OVX) ArKO mice with exogenous oestradiol (E2) on the mRNA expression of GH, GH-secretagogue receptor (GHS-R), GH-releasing hormone receptor (GHRH-R), pituitary-specific transcription factor (Pit-1), and somatostatin receptors (sst1–5) in pituitary glands. Circulating plasma GH levels were also evaluated. The results showed that ArKO/OVX mice have a low expression of pituitary GH, GHRH-R, GHS-R and Pit-1, and significantly reduced GH levels. Treatment of female ArKO/OVX (E2-deficient without excessive androgen) mice with E2 for 21 days enhanced expression of pituitary GHRH-R and Pit-1 to 151 and 168%, respectively, of that in mice without treatment. E2 treatment increased GH expression and plasma levels in ArKO/OVX mice to levels comparable with those in wild-type female mice. We conclude therefore that long-term E2 replacement rescues the dysfunction of somatotropes in ArKO/OVX mice through increases in expression of GH, GHRH-R, and Pit-1 in the pituitary somatotropes, whereas the level of androgen in this oestrogen-deficient female mouse does not significantly influence the function of somatotropes.
Absorption of Quercetin and Rutin in Rat Small Intestine
Authors: Carbonaro Marina , Grant George
Published: July 2005

Background/Aims: Dietary antioxidant flavonoids, especially flavonols, are ubiquitous constituents of plant foods with potential health-promoting effects. However, the actual bioavailability of these compounds in vivo, especially in the prevalent glycosidic form, remains a controversial point in making an assessment of their biological importance. Thus, absorption of quercetin and rutin in the small intestine has been determined. Methods: The bioavailability of quercetin and rutin (quercetin-3-rutinoside) was assessed in vivo, with single-meal experiments with rats and by an in vitro method with ligated loops of rat small intestine. The amount of quercetin or rutin in the plasma of rats or in the lumen of each intestinal segment was assayed by maximum absorption in the UV/VIS optical spectrum as was the amount of compound that had crossed the gut wall into the incubation buffer. In addition, uptake of [14C]quercetin was tested in vitro. Results: Absorption of both quercetin and rutin from the small intestine of rat was evident. However, rutin appeared to be absorbed more slowly than quercetin. Experiments with [14C]quercetin showed that only 1.5% quercetin crossed the gut wall in vitro and more than half of the total quercetin was bound to the small intestinal tissue. Conclusions: Both quercetin and rutin can attach to and traverse the small intestine of the rat. Binding of flavonoids to the intestinal wall components may however greatly limit their absorption from the small intestine.
European Status of Resistance in Nosocomial Infections
Authors: Goossens Herman
Published: July 2005

Background: Surveillance studies are mandatory to carefully monitor changing trends in Europe. Methods: Surveys on antibiotic resistance conducted in European hospitals were reviewed. Data were obtained from own studies, through searches of Medlines, Pubmed, abstracts and posters presented at meetings, from the World Wide Web and from surveillance studies conducted by the pharmaceutical industry. Results: A high prevalence of MRSA was found in most European hospitals, except in northern Europe, and an increasing trend in non-intensive care unit patients was observed. In most European hospitals, the prevalence of infections caused by vancomycin-resistant enterococci remains very low and most outbreaks have occurred in at-risk wards. No major changes of resistance among Enterobacteriaceae were observed. Very few of the major antibiotics are now reliably effective for the treatment of severe nosocomial carbapenem-resistant Acinetobacter infections. Conclusions: Although antimicrobial resistance appears to be increasing all over Europe, it is difficult to accurately estimate the extent of this emerging problem. One of the main reasons for this can be attributed to the fact that the published susceptibility data are difficult to compare due to the different methods used, population bias, and clonal variation. Increasing antimicrobial resistance necessitates a critical appraisal of the remaining antibiotic treatment options.
Clinical Significance of Osteopontin in Esophageal Squamous Cell Carcinoma: Comparison with Common Tumor Markers
Authors: Shimada Yutaka , Watanabe Go , Kawamura Junichiro , Soma Toshiya , Okabe Michio , Ito Tetsuo , Inoue Harutaka , Kondo Masato , Mori Yukiko , Tanaka Eiji , Imamura Masayuki
Published: July 2005

Objective: Osteopontin (OPN) is a secreted integrin-binding glycophosphoprotein that may have a role in head and neck squamous cell carcinoma (SCC). To evaluate the clinical significance of OPN in esophageal squamous cell carcinoma (ESCC), we compared plasma OPN levels with those of common tumor markers. Methods: Preoperative plasma OPN levels were measured by enzyme immunoassay in 103 ESCC patients. Serum SCC antigen, Cyfra 21-1, and carcinoembryonic antigen (CEA) levels were also measured routinely at admission by radioimmunoassay. Results: Plasma OPN levels ranged from 82.8 to 1,980 ng/ml. High OPN level was associated with lymph node metastasis (p = 0.05), but not with tumor histology or depth of invasion. The overall survival of the patients with high OPN levels was worse than that of those with low OPN levels (p = 0.02). SCC antigen and Cyfra 21-1 levels were associated with the depth of tumor invasion, the tumor diameter, lymph node metastasis, and the overall survival, but CEA was not associated with these clinicopathological factors. Combined evaluation of OPN plus Cyfra 21-1 or OPN plus SCC antigen was useful as an independent prognostic indicator. Conclusion: Measurement of the plasma OPN level, as well as serum SCC antigen and Cyfra 21-1, may help to predict the progression of ESCC.
Hepatic and Cardiovascular Consequences of Familial Hypobetalipoproteinemia
Authors: Sankatsing Raaj R. , Fouchier Sigrid W. , de Haan Stefan , Hutten Barbara A. , de Groot Eric , Kastelein John J.P. , Stroes Erik S.G.
Published: July 2005

Objective—

Individuals with familial hypobetalipoproteinemia (FHBL) have been reported to be prone to fatty liver disease (FLD). Conversely, the profound reduction of low-density lipoprotein (LDL) cholesterol in this disorder might decrease cardiovascular risk. In the present study, we assessed hepatic steatosis as well as noninvasive surrogate markers for cardiovascular disease (CVD) in subjects with FHBL and in matched controls.

Methods and Results—

Hepatic steatosis was assessed by abdominal ultrasonography. Carotid intima-media thickness (IMT) and distal common carotid arterial wall stiffness as surrogate markers for CVD risk were measured using high-resolution B-mode ultrasonography. Whereas transaminase levels were only modestly elevated, both prevalence (54% versus 29%;
P
=0.01) and severity of steatosis were significantly higher in FHBL individuals compared with controls. Despite similar IMT measurements, arterial stiffness was significantly lower in FHBL (
P
=0.04) compared with controls. Additionally, the increase in arterial stiffness as seen in the presence of traditional risk factors was attenuated, suggesting that very low levels of apoB-containing lipoproteins can negate the adverse effects of other risk factors on the vasculature.

Conclusions—

FHBL is characterized by an increased prevalence and severity of fatty liver disease. The observed decreased level of arterial wall stiffness, most pronounced in the presence of nonlipid risk factors, is indicative of cardiovascular protection in these subjects.