bluuebunny/crossref_metadata_2025 huggingface dataset:
A Replication-Limited Recombinant
Mycobacterium bovis
BCG Vaccine against Tuberculosis Designed for Human Immunodeficiency Virus-Positive Persons Is Safer and More Efficacious than BCG
Authors: Tullius Michael V. , Harth Günter , Masleša-Galić Saša , Dillon Barbara J. , Horwitz Marcus A.
Published: August 2008

Tuberculosis is the leading cause of death in AIDS patients, yet the current tuberculosis vaccine,
Mycobacterium bovis
bacillus Calmette-Guérin (BCG), is contraindicated for immunocompromised individuals, including human immunodeficiency virus-positive persons, because it can cause disseminated disease; moreover, its efficacy is suboptimal. To address these problems, we have engineered BCG mutants that grow normally in vitro in the presence of a supplement, are preloadable with supplement to allow limited growth in vivo, and express the highly immunoprotective
Mycobacterium tuberculosis
30-kDa major secretory protein. The limited replication in vivo renders these vaccines safer than BCG in SCID mice yet is sufficient to induce potent cell-mediated and protective immunity in the outbred guinea pig model of pulmonary tuberculosis. In the case of one vaccine, rBCG(
mbtB
)30, protection was superior to that with BCG (0.3-log fewer CFU of
M. tuberculosis
in the lung [
P
< 0.04] and 0.6-log fewer CFU in the spleen [
P
= 0.001] in aerosol-challenged animals [means for three experiments]); hence, rBCG(
mbtB
)30 is the first live mycobacterial vaccine that is both more attenuated than BCG in the SCID mouse and more potent than BCG in the guinea pig. Our study demonstrates the feasibility of developing safer and more potent vaccines against tuberculosis. The novel approach of engineering a replication-limited vaccine expressing a recombinant immunoprotective antigen and preloading it with a required nutrient, such as iron, that is capable of being stored should be generally applicable to other live vaccine vectors targeting intracellular pathogens.
Escherichia coliO157:H7 Survives within Human Macrophages: Global Gene Expression Profile and Involvement of the Shiga Toxins
Authors: Poirier Katherine , Faucher Sébastien P. , Béland Maxime , Brousseau Roland , Gannon Victor , Martin Christine , Harel Josée , Daigle France
Published: August 2008

Escherichia coliO157:H7 is an important food-borne pathogen that specifically binds to the follicle-associated epithelium in the intestine, which rapidly brings this bacterial pathogen in contact with underlying human macrophages. Very little information is available about the interaction betweenE. coliO157:H7 and human macrophages. We evaluated the uptake and survival of strain EDL933 during infection of human macrophages. Surprisingly, EDL933 survived and multiplied in human macrophages at 24 h postinfection. The global gene expression profile of this pathogen during macrophage infection was determined. Inside human macrophages, upregulation ofE. coliO157:H7 genes carried on O islands (such aspagC, the genes for both of the Shiga toxins, and the two iron transport system operonsfitandchu) was observed. Genes involved in acid resistance and in the SOS response were upregulated. However, genes of the locus of enterocyte effacement or genes involved in peroxide resistance were not differentially expressed. Many genes with putative or unknown functions were upregulated inside human macrophages and may be newly discovered virulence factors. As the Shiga toxin genes were upregulated in macrophages, survival and cytotoxicity assays were performed with isogenic Shiga toxin mutants. The initial uptake of Shiga toxins mutants was higher than that of the wild type; however, the survival rates were significantly lower at 24 h postinfection. Thus, Shiga toxins are implicated in the interaction betweenE. coliO157:H7 and human macrophages. Understanding the molecular mechanisms used byE. colito survive within macrophages may help in the identification of targets for new therapeutic agents.
Role of NleH, a Type III Secreted Effector from Attaching and Effacing Pathogens, in Colonization of the Bovine, Ovine, and Murine Gut
Authors: Hemrajani Cordula , Marches Olivier , Wiles Siouxsie , Girard Francis , Dennis Alison , Dziva Francis , Best Angus , Phillips Alan D. , Berger Cedric N. , Mousnier Aurelie , Crepin Valerie F. , Kruidenier Laurens , Woodward Martin J. , Stevens Mark P. , La Ragione Roberto M. , MacDonald Thomas T. , Frankel Gad
Published: August 2008

The human pathogen enterohemorrhagic
Escherichia coli
(EHEC) O157:H7 colonizes human and animal gut via formation of attaching and effacing lesions. EHEC strains use a type III secretion system to translocate a battery of effector proteins into the mammalian host cell, which subvert diverse signal transduction pathways implicated in actin dynamics, phagocytosis, and innate immunity. The genomes of sequenced EHEC O157:H7 strains contain two copies of the effector protein gene
nleH
, which share 49% sequence similarity with the gene for the
Shigella
effector OspG, recently implicated in inhibition of migration of the transcriptional regulator NF-κB to the nucleus. In this study we investigated the role of NleH during EHEC O157:H7 infection of calves and lambs. We found that while EHEC Δ
nleH
colonized the bovine gut more efficiently than the wild-type strain, in lambs the wild-type strain exhibited a competitive advantage over the mutant during mixed infection. Using the mouse pathogen
Citrobacter rodentium
, which shares many virulence factors with EHEC O157:H7, including NleH, we observed that the wild-type strain exhibited a competitive advantage over the mutant during mixed infection. We found no measurable differences in T-cell infiltration or hyperplasia in colons of mice inoculated with the wild-type or the
nleH
mutant strain. Using NF-κB reporter mice carrying a transgene containing a luciferase reporter driven by three NF-κB response elements, we found that NleH causes an increase in NF-κB activity in the colonic mucosa. Consistent with this, we found that the
nleH
mutant triggered a significantly lower tumor necrosis factor alpha response than the wild-type strain.
Stoichiometry and Nutrition of Plant Growth in Natural Communities
Authors: Ågren Göran I.
Published: August 2008

Stoichiometric relations in plants, with emphasis on C:N:P, are reviewed. Both theoretically and empirically it is found for whole plants as well as for different tissues that nitrogen concentrations increase slower than phosphorus concentrations. A lack of data prevents the establishment of relations between nitrogen and other elements. Optimal element ratios where elements are simultaneously limiting growth can be established. There is a considerable variability around these optimal ratios in observed values. Conclusions about the ecological significance of stoichiometric relations based on these observations may therefore be biased. The significance of this variability remains to be established.
Top Predators as Conservation Tools: Ecological Rationale, Assumptions, and Efficacy
Authors: Sergio Fabrizio , Caro Tim , Brown Danielle , Clucas Barbara , Hunter Jennifer , Ketchum James , McHugh Katherine , Hiraldo Fernando
Published: August 2008

We review the ecological rationale behind the potential compatibility between top predators and biodiversity conservation, and examine their effectiveness as surrogate species. Evidence suggests that top predators promote species richness or are spatio-temporally associated with it for six causative or noncausative reasons: resource facilitation, trophic cascades, dependence on ecosystem productivity, sensitivity to dysfunctions, selection of heterogeneous sites and links to multiple ecosystem components. Therefore, predator-centered conservation may deliver certain biodiversity goals. To this aim, predators have been employed in conservation as keystone, umbrella, sentinel, flagship, and indicator species. However, quantitative tests of their surrogate-efficacy have been astonishingly few. Evidence suggests they may function as structuring agents and biodiversity indicators in some ecosystems but not others, and that they perform poorly as umbrella species; more consensus exists for their efficacy as sentinel and flagship species. Conservation biologists need to use apex predators more cautiously, as part of wider, context-dependent mixed strategies.
X Chromosome Dosage Compensation: How Mammals Keep the Balance
Authors: Payer Bernhard , Lee Jeannie T.
Published: August 2008

The development of genetic sex determination and cytologically distinct sex chromosomes leads to the potential problem of gene dosage imbalances between autosomes and sex chromosomes and also between males and females. To circumvent these imbalances, mammals have developed an elaborate system of dosage compensation that includes both upregulation and repression of the X chromosome. Recent advances have provided insights into the evolutionary history of how both the imprinted and random forms of X chromosome inactivation have come about. Furthermore, our understanding of the epigenetic switch at the X-inactivation center and the molecular aspects of chromosome-wide silencing has greatly improved recently. Here, we review various facets of the ever-expanding field of mammalian dosage compensation and discuss its evolutionary, developmental, and mechanistic components.
Chemistry of Marine Ligands and Siderophores
Authors: Vraspir Julia M. , Butler Alison
Published: August 2008

Marine microorganisms are presented with unique challenges to obtain essential metal ions required to survive and thrive in the ocean. The production of organic ligands to complex transition metal ions is one strategy to both facilitate uptake of specific metals, such as iron, and to mitigate the potential toxic effects of other metal ions, such as copper. A number of important trace metal ions are complexed by organic ligands in seawater, including iron, cobalt, nickel, copper, zinc, and cadmium, thus defining the speciation of these metal ions in the ocean. In the case of iron, siderophores have been identified and structurally characterized. Siderophores are low molecular weight iron-binding ligands produced by marine bacteria. Although progress has been made toward the identity of in situ iron-binding ligands, few compounds have been identified that coordinate the other trace metals. Deciphering the chemical structures and production stimuli of naturally produced organic ligands and the organisms they come from is fundamental to understanding metal speciation and bioavailability. The current evidence for marine ligands, with an emphasis on siderophores, and discussion of the importance and implications of metal-binding ligands in controlling metal speciation and cycling within the world's oceans are presented.
Dopaminergic Suppression of Synaptic Transmission in the Lateral Entorhinal Cortex
Authors: Caruana Douglas A. , Chapman C. Andrew
Published: August 2008

Dopaminergic projections to the superficial layers of the lateral entorhinal cortex can modulate the strength of olfactory inputs to the region. We have found that low concentrations of dopamine facilitate field EPSPs in the entorhinal cortex, and that higher concentrations of dopamine suppress synaptic responses. Here, we have used whole-cell current clamp recordings from layer II neurons to determine the mechanisms of the suppression. Dopamine (10 to 50 μM) hyperpolarized membrane potential and reversibly suppressed the amplitude of EPSPs evoked by layer I stimulation. Both AMPA- and NMDA-mediated components were suppressed, and paired-pulse facilitation was also enhanced indicating that the suppression is mediated largely by reduced glutamate release. Blockade ofD2-like receptors greatly reduced the suppression of EPSPs. Dopamine also lowered input resistance, and reduced the number of action potentials evoked by depolarizing current steps. The drop in input resistance was mediated by activation ofD1-like receptors, and was prevented by blockingK+channels with TEA. The dopaminergic suppression of synaptic transmission is therefore mediated by aD2receptor-dependent reduction in transmitter release, and aD1receptor-dependent increase in aK+conductance. This suppression of EPSPs may dampen the strength of sensory inputs during periods of elevated mesocortical dopamine activity.
Significance of Periprocedural Myonecrosis on Outcomes After Percutaneous Coronary Intervention
Authors: Prasad Abhiram , Rihal Charanjit S. , Lennon Ryan J. , Singh Mandeep , Jaffe Allan S. , Holmes David R.
Published: August 2008

Background—

Myonecrosis after percutaneous coronary intervention (PCI) has been correlated with a worse prognosis, but controversy exists about the clinical significance and potential mechanisms for the association. The aim of this study was to evaluate the relative impact of preprocedural and postprocedural cardiac troponin T (cTnT) levels on survival rate after PCI.

Methods and Results—

We evaluated 5487 patients from the Mayo Clinic registry who required nonemergency PCI, and we examined the relationship between periprocedural cTnT levels, with the 99th percentile cutoff value used for normal (<0.01 ng/mL), and outcomes. The patients were divided into 3 groups: normal preprocedural and postprocedural cTnT levels (no myonecrosis), normal preprocedural but elevated postprocedural cTnT levels (PCI-related myonecrosis), and abnormal preprocedural cTnT. The 30-day death rates were 0.1%, 0.6%, and 2.3%, respectively, in the 3 groups. In a multivariable model, an abnormal pre-PCI cTnT level (hazard ratio 9.66 [2.30–40.57];
P
=0.002), and PCI-related myonecrosis (4.71 [1.02–21.83];
P
=0.048) were independent predictors of 30-day mortality. Over a median follow-up of 28 months, an abnormal pre-PCI cTnT level (hazard ratio 1.79 [1.35–2.39];
P
<0.001) independently predicted death, but the occurrence of PCI-related myonecrosis did not. A postprocedural elevation in creatine kinase MB fraction was not an independent predictor of long-term risk of death (0.912 [0.70–1.19];
P
=0.5).

Conclusions—

A preprocedural cTnT level >0.01 is a powerful independent predictor of prognosis after PCI and is of greater prognostic significance than the postprocedural biomarker levels. PCI-related myonecrosis occurs frequently and predicts short-term but not long-term risk of death.
Lack of Association Between Large Angiographic Late Loss and Low Risk of In-Stent Thrombus
Authors: Takano Masamichi , Yamamoto Masanori , Murakami Daisuke , Inami Shigenobu , Okamatsu Kentaro , Seimiya Koji , Ohba Takayoshi , Seino Yoshihiko , Mizuno Kyoichi
Published: August 2008

Background—

It recently has been hypothesized that a larger late loss may have a protective role against stent thrombosis. The relationship between angiographic late loss and the presence of thrombus based on angioscopic findings within paclitaxel-eluting stents (PES) and sirolimus-eluting stents (SES) was investigated in this study.

Methods and Results—

Prospective 6-month follow-up angiographic and angioscopic examinations were performed on 18 patients for PES and on 20 patients for SES. Late loss was measured by quantitative coronary angiography. Angioscopic neointimal stent coverage (NSC) grade was classified as follows: 0=uncovered struts without neointima, 1=visible struts through thin neointima, and 2=no visible struts. In each patient, maximum NSC, minimum NSC, and the existence of thrombus were evaluated. Late loss and maximum NSC were greater in PES than in SES (0.38�0.43 versus 0.10�0.23 mm;
P
=0.02 and
P
=0.0004, respectively). Late loss was correlated with maximum NSC (grade 0, 0.06�0.01 mm; grade 1, 0.10�0.05 mm; and grade 2, 0.48�0.46 mm), whereas there was no correlation between late loss and minimum NSC. The prevalence of patients with uncovered struts did not differ (44% of PES, 40% of SES;
P
=0.78). In-stent thrombus was found more frequently in PES than in SES (72% versus 40%,
P
=0.046) despite no occurrence of stent thrombosis. Only within PES were thrombi found in the segments of NSC grade 2 associated with large late loss.

Conclusion—

The present study suggests that angiographic large late loss was not associated with a low risk of in-stent thrombus.
Aortic Wall Injury as a Complication of Neonatal Aortic Valvuloplasty
Authors: Brown David W. , Chong Erin C. , Gauvreau Kimberlee , Keane John F. , Lock James E. , Marshall Audrey C.
Published: August 2008

Background—

Transcatheter balloon aortic valvuloplasty for critical aortic stenosis in neonates is routinely performed without recognized complication. Aortic wall injury has rarely been observed after balloon aortic valvuloplasty, although the incidence of this complication is unstudied. We reviewed single-center data to determine the incidence of aortic injury during balloon aortic valvuloplasty and to identify risk factors.

Methods and Results—

This retrospective study included all patients <2 months of age who underwent balloon aortic valvuloplasty at our institution from 1985 to 2007. We defined aortic wall injury as an intimal flap, dissection, or vessel rupture as diagnosed by angiography, echocardiography, or direct surgical or postmortem inspection. Primary imaging data were reviewed, as were all procedural and pathology reports, to identify cases of aortic wall injury. Patient and procedural variables were analyzed. Of 187 procedures performed, 28 procedures resulted in aortic wall injury (15%). Injury was recognized at the time of the procedure in only 16 cases (57%). Intimal flaps occurred most commonly in the distal ascending aorta (n=13), most often involving the greater curvature. In multivariate analysis, severe ventricular dysfunction at the time of the procedure (odds ratio, 2.8;
P
=0.02), greater number of balloon dilation attempts per procedure (odds ratio, 1.5;
P
=0.005), and novice interventional staff (odds ratio, 2.5;
P
=0.05) were associated with aortic injury. Incidence of injury was not different in the recent era compared with earlier experience.

Conclusions—

Aortic wall injury, specifically creation of an intimal flap, is an underrecognized complication of neonatal balloon aortic valvuloplasty, occurring in 15% of cases even in the recent era. Only severe ventricular dysfunction, greater number of balloon dilations, and novice staff were associated with injury. The clinical sequelae of aortic wall injury remain incompletely understood.
Incidence and Prognostic Implication of Unrecognized Myocardial Scar Characterized by Cardiac Magnetic Resonance in Diabetic Patients Without Clinical Evidence of Myocardial Infarction
Authors: Kwong Raymond Y. , Sattar Hamid , Wu Henry , Vorobiof Gabriel , Gandla Vijay , Steel Kevin , Siu Samuel , Brown Kenneth A.
Published: August 2008

Background—

Silent myocardial infarctions (MIs) are prevalent among diabetic patients and inflict significant morbidity and mortality. Although late gadolinium enhancement (LGE) imaging by cardiac magnetic resonance (CMR) can provide sensitive characterization of myocardial scar, its prognostic significance in diabetic patients without any clinical evidence of MI is unknown.

Methods and Results—

We performed clinically indicated CMR imaging in 187 diabetic patients who were grouped by the absence (study group, n=109) or presence (control group, n=78) of clinical evidence of MI (clinical history of MI or Q waves on ECG). CMR imaging and follow-up were successful in 107 study patients (98%) and 74 control patients (95%). Cox regression analyses were performed to associate LGE with major adverse cardiovascular events (MACE), including death, acute MI, new congestive heart failure or unstable angina, stroke, and significant ventricular arrhythmias. LGE by CMR was present in 30 of 107 study patients (28%). At a median follow-up of 17 months, 38 of 107 patients (36%) experienced MACE, which included 18 deaths. Presence of LGE was associated with a >3-fold hazards increase for MACE and for death (hazard ratio, 3.71 and 3.61;
P
<0.001 and
P
=0.007, respectively). Adjusted to a model that combines patient age, sex, ST or T changes on ECG, and left ventricular end-systolic volume index, LGE maintained a >4-fold hazards increase for MACE (adjusted hazard ratio, 4.13; 95% confidence interval, 1.74 to 9.79;
P
=0.001). In addition, LGE provided significant prognostic value with MACE and with death adjusted to a diabetic-specific risk model for 5-year events. The presence of LGE was the strongest multivariable predictor of MACE and death by stepwise selection in the study patients.

Conclusions—

CMR imaging can characterize occult myocardial scar consistent with MI in diabetic patients without clinical evidence of MI. This imaging finding demonstrates strong association with MACE and mortality hazards that is incremental to clinical, ECG, and left ventricular function combined.
Dynamic Mechanism for Initiation of Ventricular Fibrillation In Vivo
Authors: Gelzer Anna R.M. , Koller Marcus L. , Otani Niels F. , Fox Jeffrey J. , Enyeart Michael W. , Hooker Giles J. , Riccio Mark L. , Bartoli Carlo R. , Gilmour Robert F.
Published: August 2008

Background—

Dynamically induced heterogeneities of repolarization may lead to wave-front destabilizations and initiation of ventricular fibrillation (VF). In a computer modeling study, we demonstrated that specific sequences of premature stimuli maximized dynamically induced spatial dispersion of refractoriness and predisposed the heart to the development of conduction block. The purpose of this study was to determine whether the computer model results pertained to the initiation of VF in dogs in vivo.

Methods and Results—

Monophasic action potentials were recorded from right and left ventricular endocardium in anesthetized beagle dogs (n=11) in vivo. Restitution of action potential duration and conduction time and the effective refractory period after delivery of the basic stimulus (S
1
) and each of 3 premature stimuli (S
2
, S
3
, S
4
) were determined at baseline and during verapamil infusion. The effective refractory period data were used to determine the interstimulus intervals for a sequence of 4 premature stimuli (S
2
S
3
S
4
S
5
=CL
VF
) for which the computer model predicted maximal spatial dispersion of refractoriness. Delivery of CL
VF
was associated with discordant action potential duration alternans and induction of VF in all dogs. Verapamil decreased spatial dispersion of refractoriness by reducing action potential duration and conduction time restitution in a dose-dependent fashion, effects that were associated with reduced inducibility of VF with CL
VF
.

Conclusion—

Maximizing dynamically induced spatial dispersion of repolarization appears to be an effective method for inducing VF. Reducing spatial dispersion of refractoriness by modulating restitution parameters can have an antifibrillatory effect in vivo.
Drug-Eluting Versus Bare Metal Stents in Patients With ST-Segment–Elevation Myocardial Infarction
Authors: Kelbæk Henning , Thuesen Leif , Helqvist Steffen , Clemmensen Peter , Kløvgaard Lene , Kaltoft Anne , Andersen Bente , Thuesen Helle , Engstrøm Thomas , Bøtker Hans E. , Saunamäki Kari , Krusell Lars R. , Jørgensen Erik , Hansen Hans-Henrik T. , Christiansen Evald H. , Ravkilde Jan , Køber Lars , Kofoed Klaus F. , Terkelsen Christian J. , Lassen Jens F.
Published: August 2008

Background—

Implantation of drug-eluting stents (DES) limits the rate of coronary restenosis in most patients with coronary artery disease, but data are scarce with regard to their use in patients with ST-segment–elevation myocardial infarction and in connection with distal protection of the microvascular perfusion during primary percutaneous coronary intervention.

Methods and Results—

We randomly assigned 626 patients referred within 12 hours from symptom onset of an ST-elevation myocardial infarction to have a DES or a bare metal stent implanted in the infarct-related lesion with or without distal protection during primary percutaneous coronary intervention. Quantitative coronary angiography was performed during the index treatment and 8 months later. The primary end point was loss of the lumen diameter in the infarct-related lesion induced by neointimal proliferation. Patients were comparable with regard to baseline demographic and angiographic characteristics. The mean late lumen loss was significantly lower in patients treated with a DES (0.06 mm; SD, 0.66 mm) than in patients who had a bare metal stent implanted (0.47 mm; SD, 0.69 mm;
P
<0.001). The rate of the composite end point of cardiac death, recurrent myocardial infarction, and target lesion revascularization was 8.6% in the DES group versus 14.4% in the bare metal stent group (
P
=0.03). Cardiac death occurred in 4.2% and 1.6% of the patients (
P
=0.09) and stent thrombosis occurred in 2.0% and 2.6% (
P
=0.72), respectively.

Conclusion—

Implantation of DES improves the angiographic outcome and need for repeat revascularization without increasing the short-term risk of stent thrombosis but has a tendency to increase cardiac death in patients with ST-segment–elevation myocardial infarction.
Restorative Effect of Atrial Natriuretic Peptide or Chronic Neutral Endopeptidase Inhibition on Blunted Cardiopulmonary Vagal Reflexes in Aged Rats
Authors: Thomas Colleen J. , McAllen Robin M. , Salo Lauren M. , Woods Robyn L.
Published: August 2008

Arterial baroreflex function diminishes with age, but whether cardiopulmonary vagal reflexes are similarly altered with physiological aging has not been fully elucidated. In this study, predominantly cardiac high pressure mechanoreceptor-activated (ramp baroreflex) and cardiopulmonary chemoreceptor-activated (von Bezold-Jarisch reflex) vagal reflexes in conscious, instrumented rats were impaired by 30% to 40% (P<0.05) in 24-month-old (n=12) compared with 6-month-old rats (n=12). To determine whether this is a restorable deficit, the influence of atrial natriuretic peptide (ANP), either by infusion or blockade of its breakdown, was studied. ANP infusion was previously shown to enhance Bezold-Jarisch reflex and ramp baroreflex bradycardia in young adult rats. The present study confirmed that vagal reflex augmentation by ANP (50 pmol/kg per minute) also occurs in old rats (increased by 60±18% (Bezold-Jarisch reflex) and 91±15% (ramp baroreflex;P<0.05). Direct vagal stimulation in anesthetized animals showed that the target for ANP was not the cardiac vagus itself in old rats (n=7), although in young rats only, we confirmed the published finding that ANP enhances vagal bradycardia (by 58±14%, n=7). Neutral endopeptidase 24.11 degrades ANP and several other peptides. The neutral endopeptidase inhibitor candoxatrilat (5 mg/kg per day IV for 7 to 9 days) restored vagal reflex bradycardia in old rats (n=6) to levels similar to those in young neutral endopeptidase inhibitor-treated rats (n=6). Impaired cardiopulmonary vagal reflex control of heart rate is thus a feature of normal aging, and this deficit may be ameliorated by either ANP infusion or chronic neutral endopeptidase inhibition.
Effect of Olmesartan on Tissue Expression Balance Between Angiotensin II Receptor and Its Inhibitory Binding Molecule
Authors: Shigenaga Atsu-ichiro , Tamura Kouichi , Wakui Hiromichi , Masuda Shin-ichiro , Azuma Koichi , Tsurumi-Ikeya Yuko , Ozawa Motoko , Mogi Masaki , Matsuda Miyuki , Uchino Kazuaki , Kimura Kazuo , Horiuchi Masatsugu , Umemura Satoshi
Published: August 2008

We previously cloned a novel molecule interacting with angiotensin II (Ang II) type 1 receptor protein (ATRAP) and showed it to be an endogenous inhibitor of Ang II type 1 receptor signaling in cardiovascular cells. In this study, we tested a hypothesis that the balance of tissue expression of ATRAP and Ang II type 1 receptor is regulated in a tissue-specific manner during the development of hypertension and related cardiac hypertrophy. Concomitant with blood pressure increase and cardiac hypertrophy in spontaneously hypertensive rats, there was a constitutive decrease in the ratio of cardiac expression of ATRAP to Ang II type 1 receptor. However, treatment with olmesartan, an Ang II type 1 receptor–specific antagonist, either at a depressor or subdepressor dose, recovered the suppressed cardiac ATRAP to Ang II type 1 receptor ratio, which was accompanied by a decrease in Ang II type 1 receptor density, an inhibition of p38 mitogen-activated protein kinase activity, and a regression of cardiac hypertrophy. Furthermore, Ang II stimulation suppressed the ATRAP to Ang II type 1 receptor ratio with hypertrophic responses in both the cardiomyocytes and rat hearts. These findings show a tissue-specific regulatory balancing of the expression of ATRAP and Ang II type 1 receptor during the development of hypertension and cardiac remodeling and further suggest that the upregulation of the tissue ATRAP to Ang II type 1 receptor ratio may be one of the therapeutic benefits of olmesartan beyond its blood pressure-lowering effect.
Music for the Jilted Generation: Open-Source Public Diplomacy
Authors: Fisher Ali
Published: August 2008

The development of new technology has spawned different ideas and new approaches to engaging with people around the world. One such development is the ability to approach public diplomacy based on the methodology employed in the production of open-source software. This approach provides the means to engage with communities of other concerned actors, communicatae through human voices, place emphasis on understanding lessons from previous initiatives, and vitally engage on the bases of the interests of those communities. Ideas can no longer be seen as owned by a country; mass communication provides the means to see beyond national claims of unity. Recognizing this and embracing the means to engage with communities that are defined by ideology rather than physical borders provides the potential to render public diplomacy initiatives more relevant to the target audience and ultimately more influential.
The Emergence of International Public Opinion and the Origins of Public Diplomacy in Japan in the Inter-War Period
Authors: Akami Tomoko
Published: August 2008

This article argues that what we now call public diplomacy emerged in the mid- to late 1930s in the case of Japan. It questions the notion that public diplomacy is new in contrast to 'traditional' diplomacy. It also questions the conventional understanding of Japan's diplomatic isolationism of the 1930s. The article argues that as a result of greater mass political participation, the idea of 'international public opinion' emerged as a new norm in inter-war international politics. States increasingly regarded news and cultural activities as crucial resources of their soft power for winning this international public opinion. Responding to technological developments in communications, they developed a more systematic approach to propaganda in order to utilize these resources in mainstream foreign policy. Even in the age of the socalled rise of nationalism and diplomatic isolationism, Japan could neither afford not to respond to other states' actions nor to ignore international public opinion. In the diplomatic crises of the 1930s, Japan began to coordinate news and cultural propaganda activities, and integrated them into a broader propaganda scheme. Here we see the origin of what is now called public diplomacy. This modern and internationalist thinking then prepared the institutional base for wartime propaganda.
Indian Pulp Fiction in English: A Preliminary Overview from Dutt to Dé
Authors: Khair Tabish
Published: August 2008

This article provides an overview of the long history of Indian pulp fiction in English, offering a tentative definition of the genre by identifying both qualitative and quantitative markers. Beginning with nineteenth-century romances, such as Toru Dutt's Bianca, K. K. Lahiri's Roshinara and K. Chakravarti's Sarata and Hingana, it moves forward to a consideration of twentieth-century pulp forms, including detective fiction, science fiction and fantasy fiction. It includes a more detailed account of the rise of Shoba Dé, discussing her work in relation to the phenomenon of Indian film and gossip magazines like Stardust, and of the fiction of Sujata Massey, “the creator of the Rei Shimura mysteries”. It argues that while Dé's work expresses the half-realized social and cultural issues of urban and metropolitan India, Massey's fiction is self-consciously topical within a cosmopolitan scenario.
A Tale of Two Novels: Developing a Devolved Approach to Black British Writing
Authors: Fowler Corinne
Published: August 2008

In October 2000, Penguin launched Zadie Smith's novel White Teeth. In the same month, Headline Review released a novel by Joe Pemberton. It was called Forever and Ever Amen. This article traces the differing fortunes of these two British novels and seeks to understand why Forever and Ever Amen, which was also a critical success, came nowhere near the sales or popular acclaim of White Teeth. It examines the commercial and (multi)cultural logic by which novels are coded as worthy of national and international readerships by corporate publishers and high street retail outlets. Emphasizing the significance of many black British novels that emerge from non-metropolitan glocalities, the author calls for a sustained focus by literary scholarship on the discomforting links between the political and literary economy. Most particularly, novels such as Pemberton's invite popular and critical engagement with what James Procter has described as “devolved” diasporic cultures throughout Britain.
Daljit Nagra, Faber Poet: Burdens of Representation and Anxieties of Influence
Authors: Gunning Dave
Published: August 2008

This article examines Daljit Nagra's recent poetry collection Look We Have Coming to Dover! in relation to the idea of the burden of representation placed upon minority writers. While Nagra has been lionized as “the voice of British Asian poetry”, his verse actually serves to question the homogenization of diverse individuals and communities implied within such labelling. The collection consists of a mix of confessional poetry and dramatic monologues, and is marked by repeated quotation from and parody of the English poetic tradition as well as a linguistic inventiveness in portraying the voices of British Punjabis: the article suggests that each of these aspects can be seen as part of Nagra's attempt to engage with his anxieties of influence. Crucially, these anxieties must be understood not only in the Bloomian sense of the writer's relation to tradition, but also as formed by the discursive expectations of a society structured by racialization.
Terms of Hospitality: Abdulrazak Gurnah's By the Sea
Authors: Farrier David
Published: August 2008

This article seeks to relate asylum issues to postcolonial studies. In the current immigration climate hospitality is an increasingly conditional provision; refugees are reclassified as asylum seekers, conditional presences dependent on the discretion of the host. Following Derrida's investigation of hospitable relationships, I examine how the reception of the asylum seeker is made conditional, through a reading of the relationship between an asylum seeker, Saleh Omar, and his various hosts in Abdulrazak Gurnah's novel By the Sea (2001). I argue that the increasingly fractured legal terminology of asylum represents a deliberate strategy of exclusion, and read the encounter between host and guest as a contest to define hospitality as either conditional or unconditional. I also consider Derrida's assertion that this contest is always interrupted by the urgent need to make a decision and how this interruption can represent a postcolonial inversion of the neo-colonial relationship of host and guest.
Interpersonal Perceptions and Metaperceptions
Authors: Cooper Mick
Published: August 2008

This article aims to systematize and develop humanistic practice by considering the implications of adopting an experiential stance to working within the “interexperiential” realm: the interface between one person's experiences and those of another. Psychological theory and research are used to develop an understanding of how people perceive, and misperceive, others' experiences, and implications for practice are discussed, particularly the need to encourage clients to test out their assumptions about others' experiences and to communicate more transparently their own. The article then focuses on the issue of “metaperceptions”— how one person perceives another person as perceiving him or her and his or her experiences—and again argues that people often make significant errors in their judgments. Implications for practice are discussed, with a particular emphasis on using appropriate self-disclosure to deliberately challenge clients' metaperceptual errors. In the conclusion, the proposed interexperiential practices are presented as specific process—experiential tasks.
Why Humanistic Psychology Lost Its Power and Influence in American Psychology
Authors: Elkins David N.
Published: August 2008

Why did humanistic psychology lose its power and influence in American psychology? Previous answers have focused on the historical shortcomings of the humanistic movement, a perspective that essentially “blames the victim.” In contrast, this article suggests that two outside forces—mainstream American psychology and conservative forces in the larger culture—also played a role in undermining the humanistic vision. The article concludes that humanistic psychology lost its power and influence, in large measure, because it is inherently incompatible with the basic assumptions and values of contemporary mainstream psychology and with the conservative ideologies that have increasingly gained power in American culture since the 1960s. Implications of this analysis for the future of the humanistic movement are presented.
Pharmacokinetics of Efavirenz When Co‐administered With Rifampin in TB/HIV Co‐infected Patients: Pharmacogenetic Effect ofCYP2B6Variation
Authors: Kwara Awewura , Lartey Margaret , Sagoe Kwamena W. , Xexemeku Fafa , Kenu Ernest , Oliver‐Commey Joseph , Boima Vincent , Sagoe Augustine , Boamah Isaac , Greenblatt David J. , Court Michael H.
Published: August 2008

The goal of this study was to determine the effect ofCYP2B6genetic variation on the steady‐state pharmacokinetics of efavirenz (600 mg/d) in TB/HIV co‐infected patients receiving concomitant rifampin, a potentCYPinducer. In the 26 patients studied,CYP2B6c.516GG, GT, and TT genotype frequencies were 0.27, 0.50, and 0.23, respectively. Mean plasma efavirenz area under the curve was significantly higher in patients withCYP2B6c.516TT than in those with GT (107 vs 27.6 μg·h/mL,P< .0001) or GG genotype (107 vs 23.0 μg·h/mL,P< .0001). Apparent oral clearance (CL/F) was significantly lower in patients withCYP2B6c.516TT than in those with GT genotype (2.1 vs 8.4 mL/min/kg,P< 0.0001) and GG genotype (2.1 vs 9.9 mL/min/kg,P< .0001). No differences in efavirenz exposure or CL/F existed between patients withCYP2B6c.516GT and GG genotypes. Our results indicate thatCYP2B6c.516TT genotype can be used to identify efavirenz poor metabolizers in patients co‐treated with rifampin.
Deconstructing the Turkish Military's Popularity
Authors: Sarigil Zeki
Published: August 2008

Why is the military so popular in Turkish society? By using World Values Survey data, this study explores the impact of several political, social, and personal factors on societal confidence in the military. Empirical results indicate that there is a significant variance in confidence in the military across certain political groups. Although the military's popularity is high among nationalists, it is rather limited among pro-Islamic and pro-Kurdish groups. Interestingly, however, religion cuts both ways in the formation of confidence in the military. Pro-Islamic groups do not have much confidence in the strictly secular military, but being a devout Muslim does not reduce the military's popularity. Another interesting finding is that trust in civilians and support for democracy do not necessarily reduce military's popularity. A brief discussion of some implications of these findings for the civil—military relations and prospects for the consolidation of democracy in the Turkish Republic is also provided.
Effects of stretching and heat treatment on hamstring extensibility in children with severe mental retardation and hypertonia
Authors: Lee Glory PS , Ng Gabriel YF
Published: August 2008

Objectives: To examine the effect of heat and duration of stretching on the extensibility of hamstring muscles and their electromyographic responses to passive stretch in children with hypertonia and severe mental retardation.

Design: Randomized cross-over trial.

Setting: Developmental disability unit in a local hospital.

Participants: Twenty-nine subjects (9 females) with ages ranged from 4 to 13 years with spastic and/or dystonic hypertonia and hamstring tightness.

Interventions: Subjects received four treatment sessions in random order with each consisting of five repetitions of stretching: (A) 10-second stretching, (B) 30-second stretching, (C) hot pack followed by 10-second stretching, and (D) hot pack followed by 30-second stretching. Each treatment session comprised five repetitions of stretch and successive treatments were separated by at least 24 hours.

Main outcome measures: The distance between greater trochanter and lateral malleolus and hamstring electromyographic (EMG) activity during passive knee extension stretching.

Results: Two-way ANOVA showed a larger increase in hamstring extensibility in conditions C and D (1.3 ± 1.1 cm) than conditions A and B (0.7 ± 0.9 cm) (P<0.001). For the EMG recordings, conditions B and D (-25.1 ± 58.4μV) had greater decrease than conditions A and C (-3.5 ± 36.6 μV) (P= 0.039).

Conclusions: Heat application to the hamstrings before stretching could result in greater increase in extensibility than stretching alone in children with hypertonia and severe mental retardation. Stretching could promote relaxation of the hamstring muscles regardless of prior heat treatment. Stretching sustained for 30 seconds led to greater relaxation than that for 10 seconds.
Staying connected: re-establishing social relationships following vision loss
Authors: Wang Shu-Wen , Boerner Kathrin
Published: August 2008

Objective: To examine the nature of relationship-related challenges experienced by adults with vision impairment, as well as the strategies employed to deal with them.

Design: Cross-sectional qualitative study.

Setting: Vision rehabilitation agency.

Subjects: Fifty-eight young, middle-aged and older adults with vision impairment.

Method: Telephone and in-person interviews included an open-ended question about how having a vision impairment has changed relationships. Interviews were coded using a qualitative analytical approach.

Results: Participants' responses fell into two categories: difficulty in social situations was due either to other people's lack of understanding and/or one's own lack of visual cues. Responses were either to readjust one's behaviour to maintain relationships or to let relationships go or turn sour. Within these two directions, participants reported specific strategies. For readjusting one's behaviour, participants mentioned explaining themselves more and being more assertive, relying on other senses for information, 'faking' it through interactions, and being more selective about who they interacted with. For letting relationships go, participants reported either withdrawing and making fewer initiatives to socialize, or getting angry and telling people off.

Conclusions: Study findings suggest that re-establishing relationships following vision loss is a multifaceted experience in which individuals employ different strategies. These need to be further researched, given their importance to individuals dealing with vision impairment.
'We're just sick people, nothing else': ... factors contributing to elderly stroke patients' satisfaction with rehabilitation
Authors: Mangset Margrete , Tor Erling Dahl  , Førde Reidun , Wyller Torgeir Bruun
Published: August 2008

Objective: To identify factors contributing to elderly stroke patients' satisfaction with rehabilitation following stroke.

Design: Qualitative study using semi-structured interviews.

Setting: Interviews conducted in two phases, once in a stroke rehabilitation unit and once after hospital discharge.

Subjects: Twelve elderly stroke patients (seven women and five men, aged 60—87 years).

Results: One main category: 'To be treated with respect and dignity' was identified as a core factor contributing to patients' satisfaction with the rehabilitation services. This main factor was divided into five subcategories: (1) Being treated with humanity, (2) Being acknowledged as individuals, (3) Having their autonomy respected, (4) Having confidence and trust in professionals, (5) Dialogue and exchange of information. The statements covered a continuum from satisfaction via indifference to dissatisfaction. Expressions of satisfaction emerged mainly as general statements while expressions of dissatisfaction described situations in greater detail. Satisfaction was merely connected to daily care experiences and fulfilment of basic needs. Trust in providers and being dignified seemed more closely associated with satisfaction than being involved in treatment decisions. The findings demonstrate how the quality of patient—professional interaction influences patients' satisfaction with stroke rehabilitation.

Conclusion: To be treated with respect and dignity seems to be a core element influencing vulnerable elderly stroke patients' satisfaction with rehabilitation. A merely functional definition of the success of rehabilitation should be expanded into an approach encompassing patients' perceptions and personal preferences. The meaning of dignity for elderly stroke patients in the rehabilitation setting should be further clarified and given practical substance.
Comparison of two extracorporeal shock wave therapy techniques for the treatment of painful subcalcaneal spur. A randomized controlled study
Authors: Tornese Davide , Mattei Enrico , Lucchesi Giampaolo , Bandi Marco , Ricci Gabriele , Melegati Gianluca
Published: August 2008

Objective: To describe and compare two extracorporeal shock wave therapy techniques for the treatment of painful subcalcaneal spur.

Design: Random assignment to two groups of treatment with two and eight months follow-up.

Setting: The data were collected in outpatients.

Subjects: Forty-five subjects with a history of at least six months of heel pain were studied.

Interventions: Each subject received a three-session ultrasound-guided extracorporeal shock wave therapy (performed weekly). Perpendicular technique was used in group A (n=22, mean age 59.3 ± 12 years) and tangential technique was used in group B (n= 23, mean age 58.8 ± 12.3 years).

Main outcome measures: Mayo Clinical Scoring System was used to evaluate each subject before the treatment and at two and eight months follow-up.

Results: Mayo Clinical Scoring System pretreatment scores were homogeneous between the groups (group A 55.2 ±18.7; group B 53.5 ± 20; P>0.05). In both groups there was a significant (P<0.05) increase in the Mayo Clinical Scoring System score at two months (group A 83.9 ± 13.7; group B 80 ± 15,8) and eight months (group A 90 ± 10.5; group B 90.2 ±8.7) follow-up. No significant differences were obtained comparing the Mayo Clinical Scoring System scores of the two groups at two and eight months follow-up.

Conclusions: There was no difference between the two techniques of using extracorporeal shock wave therapy. The tangential technique was found to be better tolerated as regards treatment-induced pain, allowing higher energy dosages to be used.