bluuebunny/crossref_metadata_2025 huggingface dataset:
Endothelial nitric oxide synthase regulates microvascular hyperpermeability in vivo
Authors: Hatakeyama Takuya , Pappas Peter J. , Hobson Robert W. , Boric Mauricio P. , Sessa William C. , Durán Walter N.
Published: May 2006

Nitric oxide (NO) is an important regulator of blood flow, but its role in permeability is still challenged. We tested in vivo the hypotheses that: (a) endothelial nitric oxide synthase (eNOS) is not essential for regulation of baseline permeability; (b) eNOS is essential for hyperpermeability responses in inflammation; and (c) molecular inhibition of eNOS with caveolin‐1 scaffolding domain (AP‐Cav) reduces eNOS‐regulated hyperpermeability. We used eNOS‐deficient (eNOS−/−) mice and their wild‐type control as experimental animals, platelet‐activating factor (PAF) at 10−7m as the test pro‐inflammatory agent, and integrated optical intensity (IOI) as an index of microvascular permeability. PAF increased permeability in wild‐type cremaster muscle from a baseline of 2.4 ± 2.2 to a peak net value of 84.4 ± 2.7 units, while the corresponding values in cremaster muscle of eNOS−/− mice were 1.0 ± 0.3 and 15.6 ± 7.7 units (P < 0.05). Similarly, PAF increased IOI in the mesentery of wild‐type mice but much less in the mesentery of eNOS−/− mice. PAF increased IOI to comparable values in the mesenteries of wild‐type mice and those lacking the gene for inducible NOS (iNOS). Administration of AP‐Cav blocked the microvascular hyperpermeability responses to 10−7m PAF. We conclude that: (1) baseline permeability does not depend on eNOS; (2) eNOS and NO are integral elements of the signalling pathway for the hyperpermeability response to PAF; (3) iNOS does not affect either baseline permeability or hyperpermeability responses to PAF; and (4) caveolin‐1 inhibits eNOS regulation of microvascular permeability in vivo. Our results establish eNOS as an important regulator of microvascular permeability in inflammation.
Muscle denervation promotes opening of the permeability transition pore and increases the expression of cyclophilin D
Authors: Csukly Kristina , Ascah Alexis , Matas Jimmy , Gardiner Phillip F. , Fontaine Eric , Burelle Yan
Published: May 2006

Loss of neural input to skeletal muscle fibres induces atrophy and degeneration with evidence of mitochondria‐mediated cell death. However, the effect of denervation on the permeability transition pore (PTP), a mitochondrial protein complex implicated in cell death, is uncertain. In the present study, the impact of 21 days of denervation on the sensitivity of the PTP to Ca2+‐induced opening was studied in isolated muscle mitochondria. Muscle denervation increased the sensitivity to Ca2+‐induced opening of the PTP, as indicated by a significant decrease in calcium retention capacity (CRC: 111 ± 12 versus 475 ± 33 nmol (mg protein)−1 for denervated and sham, respectively). This phenomenon was partly attributable to in vivo mitochondrial and whole muscle Ca2+ overload. Cyclosporin A, which inhibits PTP opening by binding to cyclophilin D (CypD), was significantly more potent in mitochondria from denervated muscle and restored CRC to the level observed in mitochondria from sham‐operated muscles. In contrast, the CypD independent inhibitor trifluoperazine was equally effective at inhibiting PTP opening in sham and denervated animals and did not correct the difference in CRC between groups. This phenomenon was associated with a significant increase in the content of the PTP regulating protein CypD relative to several mitochondrial marker proteins. Together, these results indicate that Ca2+ overload in vivo and an altered expression of CypD could predispose mitochondria to permeability transition in denervated muscles.
CO/FT
Regulatory Module Controls Timing of Flowering and Seasonal Growth Cessation in Trees
Authors: Böhlenius Henrik , Huang Tao , Charbonnel-Campaa Laurence , Brunner Amy M. , Jansson Stefan , Strauss Steven H. , Nilsson Ove
Published: May 2006

Forest trees display a perennial growth behavior characterized by a multiple-year delay in flowering and, in temperate regions, an annual cycling between growth and dormancy. We show here that the
CO/FT
regulatory module, which controls flowering time in response to variations in daylength in annual plants, controls flowering in aspen trees. Unexpectedly, however, it also controls the short-day–induced growth cessation and bud set occurring in the fall. This regulatory mechanism can explain the ecogenetic variation in a highly adaptive trait: the critical daylength for growth cessation displayed by aspen trees sampled across a latitudinal gradient spanning northern Europe.
Structure of the Eukaryotic Thiamine Pyrophosphate Riboswitch with Its Regulatory Ligand
Authors: Thore Stéphane , Leibundgut Marc , Ban Nenad
Published: May 2006

Riboswitches are untranslated regions of messenger RNA, which adopt alternate structures depending on the binding of specific metabolites. Such conformational switching regulates the expression of proteins involved in the biosynthesis of riboswitch substrates. Here, we present the 2.9 angstrom–resolution crystal structure of the eukaryotic
Arabidopsis thaliana
thiamine pyrophosphate (TPP)–specific riboswitch in complex with its natural ligand. The riboswitch specifically recognizes the TPP via conserved residues located within two highly distorted parallel “sensor” helices. The structure provides the basis for understanding the reorganization of the riboswitch fold upon TPP binding and explains the mechanism of resistance to the antibiotic pyrithiamine.
Leflunomide: a possible alternative for gangciclovir sensitive and resistant cytomegalovirus infections
Authors: Sudarsanam T D , Sahni R D , John G T
Published: May 2006

The search for newer more cost effective treatments for infectious diseases remains a challenge. Cytomegalovirus (CMV) infection, which is especially common in the immunosupressed, is an important challenge for treating physicians. Gangciclovir's cost is a major hurdle in developing countries. Leflunomide is cheaper and is easily given orally. It works by a novel mechanism inhibiting virion assembly. It also has immunosuppressive properties. It and has been shown to be effective in both gangciclovir sensitive as well as resistant cases of CMV infection. Given these considerations we believe that leflunomide is an exiting new drug for CMV infection. However, hepatotoxicity and teratogenicity are known side effects. The exact dose and duration of treatment for CMV infection, for secondary prophylaxis, and in situations of gangciclovir resistance need further study.
TOP QUARK MEASUREMENTS
Authors: JUSTE AURELIO
Published: May 2006

Ten years after its discovery at the Tevatron collider, we still know little about the top quark. Its large mass suggests it may play a key role in the mechanism of Electroweak Symmetry Breaking (EWSB), or open a window of sensitivity to new physics related to EWSB and preferentially coupled to it. To determine whether this is the case, precision measurements of top quark properties are necessary. The high statistics samples being collected by the Tevatron experiments during Run II start to incisively probe the top quark sector. This report summarizes the experimental status of the top quark, focusing in particular on the recent measurements from the Tevatron Run II.
HEAVY FLAVOR, QUARKONIUM PRODUCTION AND DECAY
Authors: SHEN XIAOYAN
Published: May 2006

Recent experimental results on quarkonium physics are reviewed. In particular, the new observed particles since last one or two years, such as X(1835), X(3872), X(3940), Y(3940) and Y(4260) are discussed, the latest data on double charmonium production, heavy hadron spectroscopy and quarkonia decays are presented.
Functional significance of differential eNOS translocation
Authors: Sánchez Fabiola A. , Savalia Nirav B. , Durán Ricardo G. , Lal Brajesh K. , Boric Mauricio P. , Durán Walter N.
Published: May 2006

Nitric oxide (NO) regulates flow and permeability. ACh and platelet-activating factor (PAF) lead to endothelial NO synthase (eNOS) phosphorylation and NO release. While ACh causes only vasodilation, PAF induces vasoconstriction and hyperpermeability. The key differential signaling mechanisms for discriminating between vasodilation and hyperpermeability are unknown. We tested the hypothesis that differential translocation may serve as a regulatory mechanism of eNOS to determine specific vascular responses. We used ECV-304 cells permanently transfected with eNOS-green fluorescent protein (ECVeNOS-GFP) and demonstrated that the agonists activate eNOS and reproduce their characteristic endothelial permeability effects in these cells. We evaluated eNOS localization by lipid raft analysis and immunofluorescence microscopy. After PAF and ACh, eNOS moves away from caveolae. eNOS distributes both in the plasma membrane and Golgi in control cells. ACh (10−5 M, 10−4 M) translocated eNOS preferentially to the trans-Golgi network (TGN) and PAF (10−7 M) preferentially to the cytosol. We suggest that PAF-induced eNOS translocation preferentially to cytosol reflects a differential signaling mechanism related to changes in permeability, whereas ACh-induced eNOS translocation to the TGN is related to vasodilation.
Prenatal and early postnatal dietary sodium restriction sensitizes the adult rat to amphetamines
Authors: McBride Shawna M. , Culver Bruce , Flynn Francis W.
Published: May 2006

Acute sodium deficiency sensitizes adult rats to psychomotor effects of amphetamine. This study determined whether prenatal and early life manipulation of dietary sodium sensitized adult offspring to psychomotor effects of amphetamine (1 or 3 mg/kg ip) in two strains of rats. Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) dams were fed chow containing low NaCl (0.12%; LN), normal NaCl (1%; NN), or high NaCl (4%; HN) throughout breeding, gestation, and lactation. Male offspring were maintained on the test diet for an additional 3 wk postweaning and then fed standard chow thereafter until testing began. Overall, blood pressure (BP), total fluid intake, salt preference, and adrenal gland weight were greater in SHR than in WKY. WKY LN offspring had greater water intake and adrenal gland weight than did WKY NN and HN offspring, whereas WKY HN offspring had increased BP, salt intake, and salt preference compared with other WKY offspring. SHR HN offspring also had increased BP compared with other SHR offspring; all other measures were similar for SHR offspring. The low-dose amphetamine increased locomotor and stereotypical behavior compared with baseline and saline injection in both WKY and SHR offspring. Dietary sodium history affected the rats' psychomotor response to the higher dose of amphetamine. Injections of 3 mg/kg amphetamine in both strains produced significantly more behavioral activity in the LN offspring than in NN and HN offspring. These results show that early life experience with low-sodium diets produce long-term changes in adult rats' behavioral responses to amphetamine.
Local heat produces a shear-mediated biphasic response in the thermoregulatory microcirculation of the Pallid bat wing
Authors: Widmer R. J. , Laurinec J. E. , Young M. F. , Laine G. A. , Quick C. M.
Published: May 2006

Investigators report that local heat causes an increase in skin blood flow consisting of two phases. The first is solely sensory neural, and the second is nitric oxide mediated. We hypothesize that mechanisms behind these two phases are causally linked by shear stress. Because microvascular blood flow, endothelial shear stress, and vessel diameters cannot be measured in humans, bat wing arterioles (26.6 ± 0.3, 42.0 ± 0.4, and 58.7 ± 2.2 μm) were visualized noninvasively on a transparent heat plate via intravital microscopy. Increasing plate temperature from 25 to 37°C increased flow in all three arterial sizes (137.1 ± 0.3, 251.9 ± 0.5, and 184.3 ± 0.6%) in a biphasic manner. With heat, diameter increased in large arterioles ( n = 6) by 8.7 ± 0.03% within 6 min, medium arterioles ( n = 8) by 19.7 ± 0.5% within 4 min, and small arterioles ( n = 8) by 31.6 ± 2.2% in the first minute. Lidocaine (0.2 ml, 2% wt/vol) and NG-nitro-l-arginine methyl ester (0.2 ml, 1% wt/vol) were applied topically to arterioles (∼40 μm) to block sensory nerves, modulate shear stress, and block nitric oxide generation. Local heat caused only a 10.4 ± 5.5% increase in diameter with neural blockade ( n = 8) and only a 7.5 ± 4.1% increase in diameter when flow was reduced ( n = 8), both significantly lower than control ( P < 0.001). Diameter and flow increases were significantly reduced with NG-nitro-l-arginine methyl ester application ( P < 0.05). Our novel thermoregulatory animal model illustrates 1) regulation of shear stress, 2) a nonneural component of the first phase, and 3) a shear-mediated second phase. The time course of dilation suggests that early dilation of small arterioles increases flow and enhances second-phase dilation of the large arterioles.
Modulation of upper airway muscle activities by bronchopulmonary afferents
Authors: Bailey E. Fiona , Fregosi Ralph F.
Published: May 2006

Here we review the influence of bronchopulmonary receptors (slowly and rapidly adapting pulmonary stretch receptors, and pulmonary/bronchial C-fiber receptors) on respiratory-related motor output to upper airway muscles acting on the larynx, tongue, and hyoid arch. Review of the literature shows that all muscles in all three regions are profoundly inhibited by lung inflation, which excites slowly adapting pulmonary stretch receptors. This widespread coactivation includes the recruitment of muscles that have opposing mechanical actions, suggesting that the stiffness of upper airway muscles is highly regulated. A profound lack of information on the modulation of upper airway muscles by rapidly adapting receptors and bronchopulmonary C-fiber receptors prohibits formulation of a conclusive opinion as to their actions and underscores an urgent need for new studies in this area. The preponderance of the data support the view that discharge arising in slowly adapting pulmonary stretch receptors plays an important role in the initiation of the widespread and highly coordinated recruitment of laryngeal, tongue, and hyoid muscles during airway obstruction.
Sensory-mechanical relationships during high-intensity, constant-work-rate exercise in COPD
Authors: O’Donnell Denis E. , Hamilton Alan L. , Webb Katherine A.
Published: May 2006

During constant-work-rate exercise in chronic obstructive pulmonary disease, dyspnea increases steeply once inspiratory reserve volume (IRV) falls to a critical level that prevents further expansion of tidal volume (Vt). We studied the effects of this mechanical restriction on the quality and intensity of exertional dyspnea and examined the impact of an anticholinergic bronchodilator. In a randomized, double-blind, crossover study, 18 patients with chronic obstructive pulmonary disease (forced expiratory volume in 1 s = 40 ± 3%predicted; mean ± SE) inhaled tiotropium 18 μg or placebo once daily for 7–10 days each. Pulmonary function tests and symptom-limited cycle exercise at 75% of each patient’s maximal work capacity were performed 2 h after dosing. Dyspnea intensity (Borg scale), operating lung volumes, breathing pattern, and esophageal pressure ( n = 11) were measured during exercise. Dynamic hyperinflation reached its maximal value early in exercise and was associated with only mild increases in dyspnea intensity and the effort-displacement ratio, which is defined as the ratio between tidal swings of esophageal pressure (expressed relative to maximum inspiratory pressure) and Vt (expressed relative to predicted vital capacity). After a minimal IRV of 0.5 ± 0.1 liter was reached, both dyspnea and the effort-displacement ratio rose steeply until an intolerable level was reached. Tiotropium did not alter dyspnea-IRV relationships, but the increase in resting and exercise inspiratory capacity was associated with an improved effort-displacement ratio throughout exercise. Once a critically low IRV was reached during exercise, dyspnea rose with the disparity between respiratory effort and the Vt response. Changes in dyspnea intensity after tiotropium were positively correlated with changes in this index of neuromechanical coupling.
Evaluation of Indocyanine Green Toxicity to Rat Retinas
Authors: Sato Yumi , Tomita Hiroshi , Sugano Eriko , Isago Hitomi , Yoshida Madoka , Tamai Makoto
Published: May 2006

Purpose: To investigate the toxicity of indocyanine green (ICG) on retinal cells using cultured retinal pigment epithelium (RPE) cells and the effects of intravitreous injection of ICG into rat eyes. Methods: Cultured RPE cells were exposed to various concentrations of ICG for 2 min, a viability assay was performed 1 day after exposure. For an in vivo study, 5 µl of ICG (5 or 25 mg/ml) were injected into the vitreous cavity of rat eyes, which were examined 1, 3 and 7 days after the injection by histological and glutamine synthetase (GS) immunohistological evaluation. Results: Viabilities of RPE cells were decreased dependent on the ICG dose. In the histological evaluation, we observed differences of effects of ICG between the central retinal area and the peripheral area. ICG injection caused degeneration of all retinal layers in the central retinal area. GS immunoreactivities decreased by ICG injection, which corresponded to an area of severe destruction. Conclusion: A high concentration of ICG may cause toxic effects on retinal cells. Mueller cell dysfunction may play some role in the retinal toxicity caused by ICG.
Changes in Expression of N-Methyl-D-Aspartate Receptor Subunits Occur Early in the R6/2 Mouse Model of Huntington’s Disease
Authors: Ali Noore J. , Levine Michael S.
Published: May 2006

A leading hypothesis of the cause of neuronal death in Huntington’s disease (HD) is excitotoxicity, in which subpopulations of striatal neurons are hypersensitive to glutamate release due to changes in postsynaptic N-methyl-D-aspartate receptors (NMDARs). In the present study we used RT-PCR methods on single cells and tissue to compare the expression of NMDAR subunits, NR1, NR2A and NR2B, in the striatum of R6/2 transgenic mice with their wild-type (WT) littermates at three different age groups corresponding to different symptomatic milestones (19–25 days showing no overt evidence of abnormal behavior, 38–45 days at the onset of the overt phenotype and 78–90 days displaying the full behavioral phenotype). Single-cell RT-PCR studies also examined neurons for the expression of substance P and enkephalin to define different subpopulations of medium-sized projection neurons of the striatum. The results showed a significant decrease in the percentage of cells expressing NR2A at all ages examined. The decrease in expression was not associated with any significant change in expression of NR1 or NR2B. Cells that did not express NR2A contained both enkephalin and substance P, but proportionately more cells containing enkephalin displayed decreases in NR2A. Semi-quantitative RT-PCR studies on striatal tissue in the oldest age group confirmed the significant decrease in NR2A and also showed a decrease in NR2B. These results support the hypothesis that changes in the composition of postsynaptic NMDARs occur in the R6/2 model of HD and this effect occurs early in the expression of the phenotype.
Plasma Homocysteine and Risk of Coexisting Silent Brain Infarction in Alzheimer’s Disease
Authors: Matsui Toshifumi , Nemoto Miyako , Maruyama Masahiro , Yuzuriha Takefumi , Yao Hiroshi , Tanji Haruko , Ootsuki Mari , Tomita Naoki , Matsushita Sachio , Higuchi Susumu , Yoshida Yo-ichi , Seki Takashi , Iwasaki Koh , Furukawa Katsutoshi , Arai Hiroyuki
Published: May 2006

Background: Cerebrovascular disease is common in Alzheimer’s disease (AD). Elevated plasma homocysteine (pHcy) levels are reported to be associated with an increased risk of poor cognition and dementia. Objective: To determine whether high pHcy levels are associated with an increased risk of coexisting silent brain infarctions (SBIs) in AD. Methods: Study population comprising 143 outpatients with clinical diagnosis of probable AD (73.3 ± 7.0 years) were classified into 2 groups according to the presence or absence of SBIs on magnetic resonance imaging. Results: SBIs were noted in 32.9% (47/143) of the AD patients. The pHcy levels in the AD with SBIs (14.0 ± 4.5 µmol/l) were significant ly elevated compared with the AD without SBIs (11.7 ± 4.7 µmol/l, p = 0.007). After adjusting for age and gender, high pHcy (>12.4 µmol/l), but not hypertension, was associated with an increased risk of developing SBIs in AD (OR = 4.61, 95% CI = 1.74–12.2, p = 0.002). However, age at onset, cognitive function, cerebrospinal tau or amyloid β-peptide1–42 levels were not significantly correlated with pHcy levels in AD. Conclusion: SBIs commonly coexist with AD, and may be a unique vascular condition in which homocysteine plays an important role. Homocysteine-lowering therapy rather than antihypertensive medication might be an appropriate strategy to prevent stroke associated with AD.
Segregation Analysis of a Complex Quantitative Trait: Approaches for Identifying Influential Data Points
Authors: Igo Jr. Robert P. , Chapman Nicola H. , Wijsman Ellen M.
Published: May 2006

Background/Aims: Complex traits pose a particular challenge to standard methods for segregation analysis (SA), and for such traits it is difficult to assess the ability of complex SA (CSA) to approximate the true mode of inheritance. Here we use an oligogenic Bayesian Markov chain Monte Carlo method for SA (OSA) to verify results from a single-locus likelihood-based CSA for data on a quantitative measure of reading ability. Methods: We compared the profile likelihood from CSA, maximized over the trait allele frequency, to the posterior distribution of genotype effects from OSA to explore differences in the overall parameter estimates from SA on the original phenotype data and the same data Winsorized to reduce the potential influence of three outlying data points. Results: Bayesian OSA revealed two modes of inheritance, one of which coincided with the QTL model from CSA. Winsorizing abolished the model originally estimated by CSA; both CSA and OSA identified only the second OSA model. Conclusion: Differences between the results from the two methods alerted us to the presence of influential data points, and identified the QTL model best supported by the data. Thus, the Bayesian OSA proved a valuable tool for assessing and verifying inheritance models from CSA.
Quality of Life after Treatment for Laryngeal Carcinomas
Authors: Olthoff A. , Steuer-Vogt M.K. , Licht K. , Sauer-Goenen M. , Werner C. , Ambrosch P.
Published: May 2006

The objective of this study was to evaluate the impact of different surgical treatments as well as of radiotherapy for laryngeal carcinomas on health-related quality of life (QL). In a prospective, randomized multicenter study (five university hospitals in Germany), a total of 146 patients with laryngeal carcinomas (UICC stages: I–IV) underwent different surgical treatments (32 total laryngectomies, 81 CO2 laser microsurgical partial laryngectomies, 33 open partial laryngectomies). Postoperative radiotherapy was performed in 44 patients. QL data were obtained by using the EORTC QLQ-C30 questionnaire (developed by the European Organization for Research and Treatment of Cancer). Impaired QL data were seen after total laryngectomy and after radiotherapy. Radiotherapy seemed to have more impact on QL than surgical treatment. Global QL was not affected by any treatment. In general, the QL data were not as discriminating as presumed. To evaluate coping abilities, objective measures (voice, swallowing, breathing) should be obtained for comparison in further investigations.
Sodium Lauryl Sulfate-Induced Irritation in the Human Face: Regional and Age-Related Differences
Authors: Marrakchi S. , Maibach H.I.
Published: May 2006

The particular sensitivity of the human face to care products prompted us to study irritation induced by sodium lauryl sulfate (SLS) in its various regions. We examined regional and age-related differences, correlating basal transepidermal water loss (TEWL) and capacitance to SLS irritation. SLS (2% aq.) was applied under occlusion for 1 h to the forehead, cheek, nose, nasolabial and perioral areas, chin, neck and forearm to two groups of subjects – one with 10 subjects with an average age of 25.2 ± 4.7 years and another with 10 subjects with an average age of 73.7 ± 3.9 years. TEWL was measured before and 1 h and 23 h after patch removal. Baseline stratum corneum hydration was also measured. Irritation was assessed by the changes in TEWL (δTEWL = TEWL after patch removal – basal TEWL) after corrections to the control. In the younger group, all areas of the face and the neck reacted to SLS, whereas the forearm did not. In the older group, the nose, perioral area and forearm did not react. In both age groups, some significant differences between the regions of the face were detected. The younger group showed higher changes in TEWL than the older group in all the areas studied, but only in the chin and nasolabial area were the differences statistically significant. Significant correlations were found between basal TEWL and δTEWL in 5 of the 7 areas which reacted to SLS. Baseline TEWL is one parameter that correlates with the susceptibility of the face to this irritant.
Chronobiology: Biological Clocks and Rhythms of the Skin
Authors: Mehling A. , Fluhr J.W.
Published: May 2006

The cyclicity of time affects virtually all aspects of our being and is the basis of the underlying rhythmicity which is typical of our lives. To ‘tell time’, most living organisms use internal timing mechanisms known as ‘biological clocks’. These ‘clocks’ coordinate our physiological and behavioral functions and interactions with our environment. One of the strongest influences on rhythmicity is the solar day. The study of these temporal rhythms in biological systems has been coined chronobiology. With the present article we aim to give an overview on chronobiology. Examples of chronobiological effects on skin will be described. Particular emphasis will be placed on circadian rhythms (including rhythms that take place within a 24-hour period, including so-called infradian and/or diurnal rhythms) but also on seasonal variations (circaannual rhythms).
Yield of Sputum Microbiological Examination in Patients Hospitalized for Exacerbations of Chronic Obstructive Pulmonary Disease with Purulent Sputum
Authors: Roche N. , Kouassi B. , Rabbat A. , Mounedji A. , Lorut C. , Huchon G.
Published: May 2006

Background: Whether sputum microbiological examination should be performed systematically in hospitalized patients with chronic obstructive pulmonary disease (COPD) exacerbations remains unclear. Objectives: To assess the yield of sputum microbiological examination in COPD patients hospitalized in a medical ward for an acute exacerbation with purulent sputum. Methods: Two hundred consecutive exacerbations in 118 patients were studied. Patients underwent sputum microbiological examination on admission and baseline lung function tests and CT scans were recorded. Factors associated with positive culture were analyzed. Results: Sputum culture was positive (≧107 CFU/ml) in 59% of samples, Haemophilus influenzae and Streptococcus pneumoniae being the most frequent pathogens. Factors associated with positive culture were bronchiectasis, long-term oxygen therapy and low FEV1. Pseudomonas spp. were found in 8.5% of all patients, who all had a FEV1 <50% of predicted and were older. Only 25% of sputum samples satisfied all quality criteria. Sputum culture was positive in a high proportion of these samples (80.5%), but also in one half of samples with >25 leukocytes but >10 epithelial cells per field. Microbiological results induced a change in antibiotic therapy in 43.9% of cases with both quality criteria but also in 25.2% of cases with only one quality criterion. Finally, a predominant aspect after Gram stain was found in all positive samples. Conclusions: These data suggest that sputum microbiological examination with direct examination and leukocyte count should be performed routinely in patients hospitalized for COPD exacerbations with purulent sputum, especially when FEV1 is less than 50% predicted and in patients with bronchiectasis.
The Tramadol Metabolite, O-Desmethyl Tramadol, Inhibits 5-Hydroxytryptamine Type 2C Receptors Expressed in Xenopus Oocytes
Authors: Horishita Takafumi , Minami Kouichiro , Uezono Yasuhito , Shiraishi Munehiro , Ogata Junichi , Okamoto Takashi , Shigematsu Akio
Published: May 2006

Purpose: Tramadol is widely used clinically as an analgesic, yet the mechanism by which it produces antinociception remains unclear. O-Desmethyl tramadol, the main metabolite of tramadol, is a more potent analgesic than tramadol. We reported previously that tramadol inhibits the 5-hydroxytryptamine (5-HT) type 2C receptor (5-HT2CR), a G-protein-coupled receptor that is expressed widely within brain and that mediates several effects of 5-HT, including nociception, feeding, and locomotion. The effects of O-desmethyl tramadol on 5-HT2CR have not been studied. In this study, we investigated the effect of O-desmethyl tramadol on 5-HT2CR expressed in Xenopus oocytes. Methods: We examined the effect of O-desmethyl tramadol on 5-HT2CR using the Xenopus oocyte expression system. Furthermore, we investigated the effects of O-desmethyl tramadol on the binding of [3H]5-HT by 5-HT2CR. Results: O-Desmethyl tramadol, at pharmacologically relevant concentrations, inhibited 5-HT-evoked Ca2+-activated Cl– currents in oocytes that expressed 5-HT2CR. The inhibitory effect of O-desmethyl tramadol on 5-HT2CR was overcome at higher concentrations of 5-HT. Bisindolylmaleimide I (GF109203X), a protein kinase C inhibitor, increased 5-HT-evoked currents but had little effect on the inhibition of 5-HT-evoked currents by O-desmethyl tramadol. O-Desmethyl tramadol inhibited the specific binding of [3H]5-HT by 5-HT2CR expressed in oocytes. O-Desmethyl tramadol altered the apparent dissociation constant for binding of [3H]5-HT by 5-HT2CR without changing maximum binding, which indicated competitive inhibition. Conclusion: These results suggest that O-desmethyl tramadol inhibits 5-HT2CR, which provides further insight into the pharmacological properties of tramadol and O-desmethyl tramadol.
Evidence for a Functional Role of Endothelial Transient Receptor Potential V4 in Shear Stress–Induced Vasodilatation
Authors: Köhler Ralf , Heyken Willm-Thomas , Heinau Philipp , Schubert Rudolf , Si Han , Kacik Michael , Busch Christoph , Grgic Ivica , Maier Tanja , Hoyer Joachim
Published: May 2006

Objective—

Ca
2+
-influx through transient receptor potential (TRP) channels was proposed to be important in endothelial function, although the precise role of specific TRP channels is unknown. Here, we investigated the role of the putatively mechanosensitive TRPV4 channel in the mechanisms of endothelium-dependent vasodilatation.

Methods and Results—

Expression and function of TRPV4 was investigated in rat carotid artery endothelial cells (RCAECs) by using in situ patch-clamp techniques, single-cell RT-PCR, Ca
2+
measurements, and pressure myography in carotid artery (CA) and
Arteria gracilis
. In RCAECs in situ, TRPV4 currents were activated by the selective TRPV4 opener 4α-phorbol-12,13-didecanoate (4αPDD), arachidonic acid, moderate warmth, and mechanically by hypotonic cell swelling. Single-cell RT-PCR in endothelial cells demonstrated mRNA expression of TRPV4. In FURA-2 Ca
2+
measurements, 4αPDD increased [Ca
2+
]
i
by &140 nmol/L above basal levels. In pressure myograph experiments in CAs and
A gracilis
, 4αPDD caused robust endothelium-dependent and strictly endothelium-dependent vasodilatations by &80% (K
D
0.3 μmol/L), which were suppressed by the TRPV4 blocker ruthenium red (RuR). Shear stress–induced vasodilatation was similarly blocked by RuR and also by the phospholipase A
2
inhibitor arachidonyl trifluoromethyl ketone (AACOCF
3
). 4αPDD produced endothelium-derived hyperpolarizing factor (EDHF)–type responses in
A gracilis
but not in rat carotid artery. Shear stress did not produce EDHF-type vasodilatation in either vessel type.

Conclusions—

Ca
2+
entry through endothelial TRPV4 channels triggers NO- and EDHF-dependent vasodilatation. Moreover, TRPV4 appears to be mechanistically important in endothelial mechanosensing of shear stress.
Atheroprotective Potential of Macrophage-Derived Phospholipid Transfer Protein in Low-Density Lipoprotein Receptor-Deficient Mice Is Overcome by Apolipoprotein AI Overexpression
Authors: Valenta David T. , Ogier Nicolas , Bradshaw Gary , Black Audrey S. , Bonnet David J. , Lagrost Laurent , Curtiss Linda K. , Desrumaux Catherine M.
Published: May 2006

Objective—

Using bone marrow transplantation, we assessed the impact of macrophage-derived phospholipid transfer protein (PLTP) on lesion development in hypercholesterolemic mice that expressed either normal levels of mouse apolipoprotein AI (apoAI) or elevated levels of only human apoAI.

Methods and Results—

Bone marrow transplantations were performed in low-density lipoprotein receptor-deficient mice (LDLr−/−) that expressed either normal levels of mouse apoAI (
ms
apoAI) or high levels of only human apoAI (
ms
apoAI−/−, LDLr−/−,
hu
apoAITg). Mice were lethally irradiated, reconstituted with either PLTP-expressing or PLTP-deficient bone marrow cells, and fed a high-fat diet over 16 weeks. Macrophage PLTP deficiency increased atherosclerosis in LDLr−/− mice with minimal changes in total plasma cholesterol levels. In contrast, the extent of atherosclerosis in
ms
apoAI−/−, LDLr−/−,
hu
apoAITg mice was not significantly different between groups that had received PLTP−/− or PLTP+/+ bone marrow. In vitro studies indicated that PLTP deficiency led to a significant decrease in α-tocopherol content and increased oxidative stress in bone marrow cells.

Conclusions—

Our observations suggest an atheroprotective role of macrophage-derived PLTP in mice with normal apoAI plasma levels. The atheroprotective properties of macrophage-derived PLTP were not observable in the presence of elevated plasma concentrations of apoAI.
Syndecan-4 Clustering Induces Cell Migration in a PDZ-Dependent Manner
Authors: Tkachenko Eugene , Elfenbein Arye , Tirziu Daniela , Simons Michael
Published: May 2006

Cell migration is a dynamic process involving formation of a leading edge in the direction of migration and adhesion points from which tension is generated to move the cell body forward. At the same time, disassembly of adhesion points occurs at the back of the cell, a region known as the trailing edge. Syndecan-4 (S4) is a transmembrane proteoglycan thought to be involved in the formation of focal adhesions. Recent studies have shown that its cytoplasmic domain can engage in signal transduction, making S4 a bona fide receptor. Here, we show that ligand clustering of cell surface S4 on endothelial cells initiates a signaling cascade that results in activation of Rac1, induction of cell polarization, and stimulation of cell migration that depends on S4 interaction with its PDZ-binding partner. Expression of an S4 mutant lacking its PDZ-binding region (S4-PDZ
−
) leads to decreased cell motility and a failure to form a trailing edge. On clustering S4, but not S4-PDZ
−
, targets activated Rac1 to the leading edge of live cells. Cells lacking synectin, a PDZ domain containing protein that interacts with S4, fail to migrate in response to S4 clustering. Both S4-PDZ
−
–expressing and synectin
−/−
endothelial cells exhibit elevated basal levels of Rac1. Thus, our data suggest that S4 promotes endothelial cell migration in response to ligand binding by activating Rac1 and localizing it to the leading edge, and that these processes are dependent on its PDZ-binding domain interaction with synectin.
A Sphingosine-1–Phosphate-Activated Calcium Channel Controlling Vascular Smooth Muscle Cell Motility
Authors: Xu Shang-Zhong , Muraki Katsuhiko , Zeng Fanning , Li Jing , Sukumar Piruthivi , Shah Samir , Dedman Alexandra M. , Flemming Philippa K. , McHugh Damian , Naylor Jacqueline , Cheong Alex , Bateson Alan N. , Munsch Christopher M. , Porter Karen E. , Beech David J.
Published: May 2006

In a screen of potential lipid regulators of transient receptor potential (TRP) channels, we identified sphingosine-1–phosphate (S1P) as an activator of TRPC5. We explored the relevance to vascular biology because S1P is a key cardiovascular signaling molecule. TRPC5 is expressed in smooth muscle cells of human vein along with TRPC1, which forms a complex with TRPC5. Importantly, S1P also activates the TRPC5–TRPC1 heteromultimeric channel. Because TRPC channels are linked to neuronal growth cone extension, we considered a related concept for smooth muscle. We find S1P stimulates smooth muscle cell motility, and that this is inhibited by E3-targeted anti-TRPC5 antibody. Ion permeation involving TRPC5 is crucial because S1P-evoked motility is also suppressed by the channel blocker 2-aminoethoxydiphenyl borate or a TRPC5 ion-pore mutant. S1P acts on TRPC5 via two mechanisms, one extracellular and one intracellular, consistent with its bipolar signaling functions. The extracellular effect appears to have a primary role in S1P-evoked cell motility. The data suggest S1P sensing by TRPC5 calcium channel is a mechanism contributing to vascular smooth muscle adaptation.
Drafting Community: Understanding the Fate of Conscription
Authors: Leander Anna
Published: May 2006

Discussion about the fate of conscription has focused on whether structural trends are undermining its viability. This article takes another point of departure, arguing that the fate of conscription will be determined by its legitimacy as a social institution. This legitimacy is now under question because conventional myths legitimating the institution no longer function. The fate of conscription depends on whether the institution can be re-enchanted. With reference to the French abandoning conscription and the Swedes reforming it, the article shows that (paradoxically) the re-enchantment of conscription is less likely if the conventional myths are well articulated, central to politics, and hence in a position to overshadow discussions and capture political imagination (as in France). Inversely, conscription is more readily re-enchanted when conventional myths are less central and well articulated (as in Sweden).
Security Ethics and the Modern Military: The Case of the Israel Defense Forces
Authors: Sucharov Mira
Published: May 2006

The rise to the fore of realist ontologies in international relations has meant that ethical issues have been associated more with evaluation than explanation. Yet ignoring the constitutive role of morality and ethics in structuring security policy choices leaves us without a complete understanding of the causes and consequences of international behavior. Accordingly, this article seeks to transplant the role of ethics from the realm of evaluative to empirical theory by introducing the idea of a security ethic, referring to the state’s—and by extension the military’s—normative attitudes toward the use of organized violence, including under what circumstances it is ethically permissible to use force at all, and the manner in which force can be justly employed in a given military operation. The article develops this framework by reference to the historical security outlook of the Israel Defense Forces.
What Costs Will Democracies Bear? A Review of Popular Theories of Casualty Aversion
Authors: Smith Hugh
Published: May 2006

Can democracies any longer tolerate casualties? The question has important implications for national decision-making and for international politics. This article examines how and why governments take casualties into account in decisions about military commitments—the casualty factor. This is a phenomenon that goes beyond the normal military desire to reduce losses. The article explores the wide range of popular theories put forward to explain why the casualty factor appears to have become casualty aversion or even casualty phobia in democratic nations. Explanations are classified under four headings: national interest, strategic calculus, internal politics, and long-term social change. Each type of explanation has strengths and weaknesses. Finally, an assessment is made of the overall influence of casualty aversion in democratic decision-making.
Volunteering for Risk: The Culture of the Turkish Armed Forces
Authors: Varoglu A. Kadir , Bicaksiz Adnan
Published: May 2006

This article discusses the impact of casualty risks on recruitment for the Turkish Armed Forces. The issue is treated in the context of Turkey as a martial society, for which the embeddedness of military service is a prime example. There is ample experience with military casualties in recent history: in Korea, in Cyprus, during a number of peacekeeping missions, and especially during operations in southeast Turkey over the last two decades. For this latter case, statistical data are analyzed not only vis-à-vis the recruitment of professionals and the behavior of those already serving, but also in relation to the attitudes of conscripts. All in all, the culture of the Turkish Armed Forces is characterized by a low degree of risk aversion rooted in strong civil-military relations. While conscription remains as a symbol of the latter, this sets limits for the trend toward professionalization.
Coups and Conflict in West Africa, 1955-2004
Authors: McGowan Patrick J.
Published: May 2006

From independence through 2004, the sixteen West African states have experienced forty-four successful military-led coups, forty-three often-bloody failed coups, at least eighty-two coup plots, seven civil wars, and many other forms of political conflict. This two-part article seeks answers to the question, what has gone wrong inWest Africa? Part I uses world-systems and rational-choice analyses to provide theoretical answers involving macro structures and micro leadership behavior. Structural peripherality and poor leadership result in underdevelopment and state weakness, the major structural causes of West African instability. Empirical evidence demonstratesWest Africa's peripheral role in the world-economy, the high risks associated with political leadership in the region, andWest Africa's critical socioeconomic situation. Part II, appearing in the January 2006 issue, will examine new data on coups and conflict inWest Africa and speculate on what can be done to improve the situation.
Reflexivity and Researching the Military
Authors: Higate Paul , Cameron Ailsa
Published: May 2006

While the concept of reflexivity has been used extensively across the social sciences over many decades, its impact on studies of the military has remained marginal. Reasons for this go to the heart of the dominant epistemological foundations of a military sociology that implicitly assumes that researcher bias can be neutralized by adhering to the traditional positivist model of sociological research. In this article, the authors argue that there is much to be gained by reflecting on the process of doing research, and “writing in” the authors where appropriate, particularly within the context of research on the military. In appraising the quality of research projects, it is helpful to know more about the motivations of researchers (especially given that many are veterans), theways in which access to the military sample were negotiated, and the criteria placed upon researchers and their projects by military funders. Overall, the authors argue that the paucity of material focused on the process of researching the military represents a significant limitation that is in need of further consideration.
What Do the Soldiers Say?
Authors: Griffith James
Published: May 2006

Doctrinally, the U.S. Army determines the readiness of company-sized and battalionsized units by assessing them in four areas: personnel, equipment on hand, equipment serviceability, and training to meet mission-essential tasks. Surprisingly, these assessments do not include factors identified in surveys, personal interviews, and observational accounts of soldiers regarding what prepares them for combat and contributes to their combat effectiveness. Among the more prominent of these factors are the quality of small (primary) group relationships and the competencies of unit leaders. The present study considers these factors in addition to doctrinal readiness assessments. Soldier perceptions combined with doctrinal assessments (1) more readily differentiated the readiness of units; (2) were associated with independently derived soldier perceptions of fellow soldiers, leaders, and equipment being prepared for combat operations; and (3) implied interventions to improve specific unit activities.
“Civilianization” in Greece versus “Demilitarization” in Turkey
Authors: Duman Özkan , Tsarouhas Dimitris
Published: May 2006

The civil-military-relations literature has long concentrated on domestic factors in explaining the relationship between civilians and the military. This article concentrates on the effect of an external actor, the European Union (EU), on civil-military relations in Greece and Turkey. The main findings reveal that the two countries shared similar characteristics until the mid-1970s. However, their path of civil-military relations diverged considerably as soon as Greece’s EU membership prospect became tangible. While in the Greek case, “civilianization” took place, Turkey had witnessed a mere “demilitarization” of its regime. However, the article also shows how EU membership paves the way for the improvement of civil-military relations in the Turkish case.
Gun Possession among Massachusetts Batterer Intervention Program Enrollees
Authors: Rothman Emily F. , Johnson Renee M. , Hemenway David
Published: May 2006

Batterers with access to firearms present a serious lethal threat to their partners. The purpose of this exploratory study is to estimate the prevalence of and risk markers for gun possession among Massachusetts men enrolled in batterer intervention programs. The authors found that 1.8% of the men reported having a gun in or around their home. Those most likely to report having a gun were White, earned $25,000 or more per year, had served in the military, engaged in problem gambling, and had attempted homicide or threatened their partner with a firearm. Recommendations for strengthening relevant gun laws both within and outside of Massachusetts are discussed.
Disarming Batterers Through Restraining Orders
Authors: Seave Paul L.
Published: May 2006

Laws that prohibit persons under a domestic violence restraining order from purchasing or possessing a firearm are a primary way to keep guns out of the hands of batterers. In July 2005, the California Attorney General's Task Force on the Local Criminal Justice Response to Domestic Violence issued a report called Keeping the Promise: Victim Safety and Batterer Accountability. The report focused, in part, on the extent to which California's domestic violence restraining order system succeeds in disarming batterers. Restraining orders are the principal means by which the criminal justice system can accomplish this objective. The Task Force found that criminal justice agencies and the courts performed poorly in this area. The report strongly recommended that a more strategic, collaborative use of laws already on the books could significantly improve performance, without much additional expense. What follows is a summary of those finding and recommendations.