bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased Serum Inflammatory Markers in the Absence of Clinical and Skeletal Muscle Inflammation in Patients with Chronic Obstructive Pulmonary Disease
Authors: Piehl-Aulin Karin , Jones Ian , Lindvall Björn , Magnuson Anders , Abdel-Halim Samy M.
Published: March 2009

Background: Muscle wasting and cachexia are common occurrences in patients with chronic obstructive pulmonary disease (COPD). Objectives: The current study aimed to investigate markers of inflammation in the circulation and skeletal muscle that might be associated with development of muscle wasting. Methods: Three groups of patients with mild, moderate and severe COPD and matched healthy controls were recruited. Serum levels of C-reactive protein (CRP), high-sensitivity CRP (hs-CRP), IL-6, IL-8, TNF-α, cortisol, insulin-like growth factor 1 (IGF-1), leptin and ghrelin were analysed. Skeletal muscle inflammation was investigated microscopically using a panel of antibodies and standard staining for inflammatory cell infiltration. Results: All COPD patients were clinically stable, with no sign of inflammation and normal CRP values. Compared to controls, significantly increased hs-CRP levels were observed in all COPD patient groups. Significant rises in IL-6 levels were first observed in moderate COPD, while IL-8 levels were significantly elevated at the late severe stage. Circulating levels of TNF-α, cortisol, IGF-1, leptin and ghrelin were similar to control levels. No microscopic signs of skeletal muscle inflammation were observed. Conclusion: Our results identify hs-CRP as an early marker of inflammation that is significantly increased in the circulation even in mild COPD. Serum interleukin levels appear to be increased with disease progress. These changes were manifested in the absence of any clinical signs of disease exacerbation, evidence of skeletal muscle inflammation or hormonal changes.
The Combination of Dopa-Responsive Parkinsonian Syndrome and Motor Neuron Disease
Authors: Pinkhardt Elmar Hans , Sperfeld Anne-Dorte , Gdynia Hans-Jürgen , Ludolph Albert Christian , Kassubek Jan
Published: March 2009

Background: Idiopathic Parkinson’s syndrome (IPS) and motor neuron disorders (MND) are generally considered as distinct clinicopathological entities. However, cooccurrence of different neurodegenerative disorders is more frequent than would be expected. Therefore, there is an ongoing discussion whether some entities represent parts of a common spectrum. Objective and Methods: We describe clinical hallmarks and treatment options in a group of 8 patients who had combined features of both a dopa-responsive parkinsonian syndrome and MND. Results: All patients exhibited a typical clinical picture of IPS, and all were treated with levodopa or other dopaminergic drugs with good clinical response. The patients also showed clinical and electrophysiological signs of upper and/or lower motor neuron degeneration. Noticeably, in contrast to well-known distinct entities like the amyotrophic lateral sclerosis-parkinsonism/ dementia complex in southwest New Guinea, we did not observe any cognitive decline during the observation period except in 1 patient. Conclusion: This comorbidity of two neurodegenerative diseases supports the ongoing discussion of a pathophysiological and clinical overlap of disease processes. Due to the potent pharmacological options for the IPS symptoms in these overlap syndromes, these patients should be offered optimal symptomatic dopaminergic therapy.
Haplotype Analysis of the Engrailed-2 Gene in Young-Onset Parkinson’s Disease
Authors: Rissling Ida , Strauch Konstantin , Höft Christine , Oertel Wolfgang Hermann , Möller Jens Carsten
Published: March 2009

Background/Aims: Engrailed-2 is a homeobox transcription factor that is expressed in mesencephalic dopaminergic neurons from development to adulthood and probably plays an important role in the survival of these neurons. Methods: Here, we investigated six single-nucleotide polymorphisms (SNPs) in the promoter region (rs1345514) or transcribed part (rs3735653, rs6460013, rs1861972, rs2361689, and rs3808330) of the engrailed-2 gene, respectively, in 103 discordant pairs with young-onset Parkinson’s disease (YOPD). Results: The nominally significant p values in the single-marker and haplotype-based association analysis were suggestive of an association of SNP rs1345514 with YOPD. Conclusion: Altogether, our data suggest the possibility that variations of the engrailed-2 gene are implicated in the development of YOPD, although our results with respect to SNP rs1345514 should be verified in an independent sample.
Relationship between the Body Position-Specific Apnea-Hypopnea Index and Subjective Sleepiness
Authors: Tanaka Fujio , Nakano Hiroshi , Sudo Nobuyuki , Kubo Chiharu
Published: March 2009

Background: It is well known that the sleeping position influences the rate of apnea-hypopnea events; however, whether events in one position may have more influence on daytime sleepiness than events in another position has not been thoroughly investigated. Objectives: We retrospectively examined the relationship between the body position-specific apnea-hypopnea index (AHI) and daily sleepiness. Methods: We assessed the sleeping body position, the body position-specific AHI and the Epworth Sleepiness Scale (ESS) in a total of 699 patients who were referred for suspected obstructive sleep apnea-hypopnea syndrome (OSAHS) and underwent diagnostic polysomnography. Results: For all subjects, only the lateral position-specific AHI (L-AHI) showed a weak but significant correlation with the ESS (r = 0.102; p < 0.05). For mild-to-moderate OSAHS patients, there was no correlation between the ESS and the AHI at any position. For severe OSAHS patients, the ESS showed a closer correlation with the L-AHI (r = 0.266; p < 0.001) than with the supine position-specific AHI (S-AHI; r = 0.141; p < 0.05). In a subgroup analysis, divided into positional and non-positional severe OSAHS patients, the correlation coefficients also identified a link between the L-AHI and the ESS. Finally, a multiple linear regression analysis indicated that the ESS was better explained by the L-AHI than by the S-AHI in severe OSAHS patients. Conclusion: The L-AHI is considered to have a stronger influence on daytime sleepiness than the S-AHI in Japanese patients with severe OSAHS.
Proprotein Convertase Subtilisin Kexin Type 9 Null Mice Are Protected From Postprandial Triglyceridemia
Authors: Le May Cédric , Kourimate Sanae , Langhi Cédric , Chétiveaux Maud , Jarry Anne , Comera Christine , Collet Xavier , Kuipers Folkert , Krempf Michel , Cariou Bertrand , Costet Philippe
Published: March 2009

Objectives—

Proprotein convertase subtilisin kexin type 9 (PCSK9) is a natural inhibitor of the low-density lipoprotein receptor, and its deficiency in humans results in low plasma LDL-cholesterol and protection against cardiovascular disease. We explored whether PCSK9 expression impacts postprandial triglyceridemia, another important cardiovascular risk factor.

Methods and Results—

Real-time PCR and confocal microscopy were used to show that PCSK9 is expressed throughout the entire small intestine and in human enterocytes. On olive oil gavage, PCSK9-deficient mice showed a dramatically decreased postprandial triglyceridemia compared with their wild-type littermates. Lymph analysis revealed that intestinal TG output is not quantitatively modified by PCSK9 deletion. However, PCSK9
−/−
mice present with a significant reduction of lymphatic apoB secretion compared to PCSK9
+/+
mice. Modulating PCSK9 expression in polarized CaCo-2 cells confirmed the relationship between PCSK9 and apoB secretion; PCSK9
−/−
mice consistently secrete larger TG-rich lipoprotein than wild-type littermates. Finally, kinetic studies showed that PCSK9-deficient mice have an increased ability to clear chylomicrons compared to wild-type littermates.

Conclusion—

These findings indicate that in addition to its effect on LDL-cholesterol, PCSK9 deficiency might protect against cardiovascular disease by reducing postprandial triglyceridemia.
G Protein–Coupled Receptors as Potential Drug Targets for Lymphangiogenesis and Lymphatic Vascular Diseases
Authors: Dunworth William P. , Caron Kathleen M.
Published: March 2009

Absrtract—

G protein–coupled receptors (GPCRs) are widely expressed cell surface receptors that have been successfully exploited for the treatment of a variety of human diseases. Recent studies in genetically engineered mouse models have led to the identification of several GPCRs important for lymphatic vascular development and function. The adrenomedullin receptor, which consists of an oligomer between calcitonin receptor-like receptor and receptor activity modifying protein 2, is required for normal lymphatic vascular development and regulates lymphatic capillary permeability in mice. Numerous studies also suggest that lysophospholipid receptors are involved in the development of lymphatic vessels and lymphatic endothelial cell permeability. Given our current lack of pharmacological targets for the treatment of lymphatic vascular diseases like lymphedema, the continued identification and study of GPCRs in lymphatic endothelial cells may eventually lead to major breakthroughs and new pharmacological strategies for the treatment of lymphedema.
Inferior Vena Cava Ligation Rapidly Induces Tissue Factor Expression and Venous Thrombosis in Rats
Authors: Zhou Ji , May Linda , Liao Peng , Gross Peter L. , Weitz Jeffrey I.
Published: March 2009

Objective—

Although stasis is important in the pathogenesis of deep vein thrombosis (DVT), how it contributes to thrombogenesis is largely unknown. To gain mechanistic insight, we used a rat model of inferior vena cava (IVC) ligation.

Methods and Results—

Rats were subjected to IVC ligation for 15 to 60 minutes. Ligation resulted in rapid IVC dilatation and by 60 minutes, thrombi were detected in all rats. Small thrombi were detected in the IVC of most rats after 15 minutes of ligation. Thrombi were rich in fibrin, contained aggregated platelets as well as trapped leukocytes and red cells, and most originated at sites of localized endothelial denudation. Immunohistochemical analysis revealed tissue factor (TF)-expressing leukocytes within the thrombi and adherent to the vessel wall. Despite a largely intact vessel wall, endothelial cells also stained for TF. The expression of TF colocalized with that of protein disulfide isomerase (PDI), an enzyme implicated in TF decryption.

Conclusions—

These findings suggest that the rapid development of DVT after IVC ligation reflects a combination of stasis-induced vein wall injury and enhanced TF expression in endothelial cells and leukocytes. Because TF expression occurs so soon after ligation, new synthesis is unlikely. Instead, stasis-induced venous dilatation with or without exposure of subendothelial TF, may be responsible for vessel wall TF expression. Colocalization of TF and PDI raises the possibility that PDI-mediated TF decryption plays a role in the pathogenesis of DVT.
A 30-Year Perspective (1975–2005) Into the Changing Landscape of Patients Hospitalized With Initial Acute Myocardial Infarction
Authors: Floyd Kevin C. , Yarzebski Jorge , Spencer Frederick A. , Lessard Darleen , Dalen James E. , Alpert Joseph S. , Gore Joel M. , Goldberg Robert J.
Published: March 2009

Background—

The effects of lifestyle changes and evolving treatment practices on coronary disease incidence rates, demographic and clinical profile, and the short-term outcomes of patients hospitalized with acute myocardial infarction have not been well characterized. The purpose of this study was to examine multidecade-long trends (1975–2005) in the incidence rates, demographic and clinical characteristics, treatment practices, and hospital outcomes of patients hospitalized with an initial acute myocardial infarction from a population-based perspective.

Methods and Results—

Residents of the Worcester, Mass, metropolitan area (median age, 37 years; 89% white) hospitalized with an initial acute myocardial infarction (n=8898) at all greater-Worcester medical centers during 15 annual periods between 1975 and 2005 comprised the sample of interest. The incidence rates of initial acute myocardial infarction were lower in 2005 (209 of 100 000 population) than in 1975 (277 of 100 000), although these trends varied inconsistently over time. Patients hospitalized during the most recent study years were significantly older (mean age, 64 years in 1975; 71 years in 2005), more likely to be women (38% in 1975; 48% in 2005), and have a greater prevalence of comorbidities. Hospitalized patients were increasingly more likely to receive effective cardiac medications and coronary interventional procedures for the period under investigation. Hospital survival rates improved significantly over time (81% survived in 1975; 91% survived in 2005), although varying trends were observed in the occurrence of clinically important complications.

Conclusions—

The results of this community-wide investigation provide insight into the changing magnitude, characteristics, management practices, and outcomes of patients hospitalized with a first myocardial infarction.
Use of Oseltamivir After Influenza Infection Is Associated With Reduced Incidence of Recurrent Adverse Cardiovascular Outcomes Among Military Health System Beneficiaries With Prior Cardiovascular Diseases
Authors: Casscells S. Ward , Granger Elder , Kress Amii M. , Linton Andrea , Madjid Mohammad , Cottrell Linda
Published: March 2009

Background—

Influenza infection has been associated with increased risk of adverse cardiac and cerebral vascular outcomes. Oseltamivir, a treatment for influenza, has been shown to decrease the severity of an influenza episode, but few data exist regarding its potentially protective effect against recurrent vascular outcomes among influenza patients with a history of vascular disease.

Methods and Results—

Electronic healthcare service and pharmacy records for 37 482 TRICARE beneficiaries, aged 18 and older, with a coded history of cardiovascular (CV) disease and a subsequent diagnosis of influenza from October 1, 2003, through September 30, 2007, were examined. Subjects were grouped according to whether they had filled a prescription for oseltamivir within 2 days of their influenza diagnosis. The incidence of recurrent CV events within 30 days after the influenza diagnosis among oseltavmivir-treated and untreated subjects was 8.5% and 21.2%, respectively (
P
<0.005). Subject age was a persistent and significant contributor to the likelihood of recurrent CV outcomes. After controlling for the differences in demographics among treated and untreated cohorts using a propensity-scored logistic regression model, a statistically significant protective effect was associated with oseltamivir treatment (odds ratio, 0.417; 95% CI, 0.349 to 0.498).

Conclusions—

Our findings suggests that oseltamivir treatment for influenza is associated with significant decrease in the risk of recurrent CV events in subjects with a history of CV disease. These findings merit confirmation in further prospective and controlled studies. Meanwhile, in patients with CV disease, strict adherence with current practice guidelines for prevention and treatment of influenza is recommended.
Perioperative Complications After Vascular Surgery Are Predicted by the Revised Cardiac Risk Index But Are Not Reduced in High-Risk Subsets With Preoperative Revascularization
Authors: Garcia Santiago , Moritz Thomas E. , Goldman Steven , Littooy Fred , Pierpont Gordon , Larsen Greg C. , Reda Domenic J. , Ward Herbert B. , McFalls Edward O.
Published: March 2009

Background—

The Revised Cardiac Risk Index (RCRI) is useful for risk stratifying patients before noncardiac operations. Among patients with documented coronary artery disease who undergo vascular surgery, it is unclear whether preoperative revascularization reduces postoperative cardiac complications in high-risk subsets defined by the RCRI.

Methods and Results—

The Coronary Artery Revascularization Prophylaxis Trial was a randomized, controlled trial that tested the long-term benefit of a preoperative coronary artery revascularization before elective vascular surgery. Using preoperative baseline characteristics to determine the RCRI, we tested the benefit of preoperative revascularization on death and nonfatal myocardial infarction in patients with multiple risks. Among 462 patients undergoing vascular surgery, there were 72 complications (15.6%) within 30 days postsurgery, including 15 deaths (3.2%) and 57 nonfatal myocardial infarctions (12.3%). The postoperative risk of death and nonfatal myocardial infarction after surgery increased according to the RCRI (odds ratio, 1.73; 95% CI, 1.26 to 2.38;
P
<0.001), with a rate of 1.6% in patients with no risk that increased to 23.4% in patients with ≥3 risks. Preoperative revascularization had no influence on the incidence of complications in any risk subset (odds ratio, 0.86; 95% CI, 0.50 to 1.49;
P
=0.60). Among those individuals with ≥2 risks who also demonstrated ischemia on a preoperative stress-imaging test (N=146), the incidence of events was 23% in patients with and without preoperative revascularization (
P
=0.95).

Conclusions—

The risk of death and nonfatal myocardial infarction is accurately predicted by the RCRI in patients undergoing vascular surgery but is not reduced in any high-risk subset of the RCRI with preoperative coronary artery revascularization.
Ciliary Polycystin-2 Is a Mechanosensitive Calcium Channel Involved in Nitric Oxide Signaling Cascades
Authors: AbouAlaiwi Wissam A. , Takahashi Maki , Mell Blair R. , Jones Thomas J. , Ratnam Shobha , Kolb Robert J. , Nauli Surya M.
Published: March 2009

Cardiovascular complications such as hypertension are a continuous concern in patients with autosomal dominant polycystic kidney disease (ADPKD). The
PKD2
encoding for polycystin-2 is mutated in ≈15% of ADPKD patients. Here, we show that polycystin-2 is localized to the cilia of mouse and human vascular endothelial cells. We demonstrate that the normal expression level and localization of polycystin-2 to cilia is required for the endothelial cilia to sense fluid shear stress through a complex biochemical cascade, involving calcium, calmodulin, Akt/PKB, and protein kinase C. In response to fluid shear stress, mouse endothelial cells with knockdown or knockout of
Pkd2
lose the ability to generate nitric oxide (NO). Consistent with mouse data, endothelial cells generated from ADPKD patients do not show polycystin-2 in the cilia and are unable to sense fluid flow. In the isolated artery, we further show that ciliary polycystin-2 responds specifically to shear stress and not to mechanical stretch, a pressurized biomechanical force that involves purinergic receptor activation. We propose a new role for polycystin-2 in transmitting extracellular shear stress to intracellular NO biosynthesis. Thus, aberrant expression or localization of polycystin-2 to cilia could promote high blood pressure because of inability to synthesize NO in response to an increase in shear stress (blood flow).
Calcium-Mediated Dual-Mode Regulation of Cardiac Sodium Channel Gating
Authors: Biswas Subrata , DiSilvestre Deborah , Tian Yanli , Halperin Victoria L. , Tomaselli Gordon F.
Published: March 2009

Intracellular Ca
2+
([Ca
2+
]
i
) can trigger dual-mode regulation of the voltage gated cardiac sodium channel (Na
V
1.5). The channel components of the Ca
2+
regulatory system are the calmodulin (CaM)-binding IQ motif and the Ca
2+
sensing EF hand–like (EFL) motif in the carboxyl terminus of the channel. Mutations in either motif have been associated with arrhythmogenic changes in expressed Na
V
1.5 currents. Increases in [Ca
2+
]
i
shift the steady-state inactivation of Na
V
1.5 in the depolarizing direction and slow entry into inactivated states. Mutation of the EFL (Na
V
1.5
4X
) shifts inactivation in the hyperpolarizing direction compared with the wild-type channel and eliminates the Ca
2+
sensitivity of inactivation gating. Modulation of the steady-state availability of Na
V
1.5 by [Ca
2+
]
i
is more pronounced after the truncation of the carboxyl terminus proximal to the IQ motif (Na
V
1.5
Δ1885
), which retains the EFL. Mutating the EFL (Na
V
1.5
4X
) unmasks CaM-mediated regulation of the kinetics and voltage dependence of inactivation. This latent CaM modulation of inactivation is eliminated by mutation of the IQ motif (Na
V
1.5
4X-IQ/AA
). The LQT3 EFL mutant channel Na
V
1.5
D1790G
exhibits Ca
2+
insensitivity and unmasking of CaM regulation of inactivation gating. The enhanced effect of CaM on Na
V
1.5
4X
gating is associated with significantly greater fluorescence resonance energy transfer between enhanced cyan fluorescent protein–CaM and Na
V
1.5
4X
channels than is observed with wild-type Na
V
1.5. Unlike other isoforms of the Na channel, the IQ-CaM interaction in the carboxyl terminus of Na
V
1.5 is latent under physiological conditions but may become manifest in the presence of disease causing mutations in the CT of Na
V
1.5 (particularly in the EFL), contributing to the production of potentially lethal ventricular arrhythmias.
Proposed Criteria for Metabolic Syndrome in Japanese Based on Prospective Evidence
Authors: Doi Yasufumi , Ninomiya Toshiharu , Hata Jun , Yonemoto Koji , Arima Hisatomi , Kubo Michiaki , Tanizaki Yumihiro , Iwase Masanori , Iida Mitsuo , Kiyohara Yutaka
Published: March 2009

Background and Purpose—

The current criteria of metabolic syndrome (MetS) are not based on evidence derived from prospective studies on cardiovascular disease (CVD).

Methods—

In a 14-year follow-up study of 2452 community-dwelling Japanese individuals aged ≥40 years, we examined which of the MetS criteria are most predictive for the development of CVD. During the follow-up, 246 first-ever CVD events occurred.

Results—

An optimal cutoff point of waist circumference for predicting CVD was 90 cm in men (age-adjusted hazard ratio=1.81; 95% CI, 1.19 to 2.74;
P
=0.005) and 80 cm in women (age-adjusted hazard ratio=1.46; 95% CI, 0.99 to 2.16;
P
=0.05). A comparison of MetS criteria showed that the modified Japanese criteria using this cutoff point instead of the original definition were the strongest predictor of CVD events in both sexes (men: age-adjusted hazard ratio=2.58; 95% CI, 1.65 to 4.02;
P
<0.001; women: age-adjusted hazard ratio=2.39; 95% CI, 1.65 to 3.48;
P
<0.001). These observations remained robust even after adjustment for other confounding factors. According to this criteria set, only in the presence of central obesity, the hazard ratios for future CVD increased significantly as the number of MetS components increased, and a significant relationship was identified from 2 or more MetS components compared with individuals who had no MetS component.

Conclusions—

Our findings suggest that the optimal cutoff point of waist circumference is 90 cm in men and 80 cm in women and that the modified Japanese criteria of MetS with this cutoff point as an essential component better predict CVD in the general Japanese population.
Prior Statin Use, Intracranial Hemorrhage, and Outcome After Intra-Arterial Thrombolysis for Acute Ischemic Stroke
Authors: Meier Niklaus , Nedeltchev Krassen , Brekenfeld Caspar , Galimanis Aekaterini , Fischer Urs , Findling Oliver , Remonda Luca , Schroth Gerhard , Mattle Heinrich P. , Arnold Marcel
Published: March 2009

Background and Purpose—

There are only limited data on whether prior statin use and/or cholesterol levels are associated with intracranial hemorrhage (ICH) and outcome after intra-arterial thrombolysis. The purpose of this study was to evaluate the association of statin pretreatment and cholesterol levels with the overall frequency of ICH, the frequency of symptomatic ICH, and clinical outcome at 3 months.

Methods—

We analyzed 311 consecutive patients (mean age, 63 years; 43% women) who received intra-arterial thrombolysis.

Results—

Statin pretreatment was present in 18%. The frequency of any ICH was 20.6% and of symptomatic ICH 4.8%. Patients with any ICH were more often taking statins (30% versus 15%,
P
=0.005), more often had atrial fibrillation (45% versus 30%,
P
=0.016), had more severe strokes (mean National Institute of Health Stroke Scale score 16.5 versus 14.7,
P
=0.022), and less often good collaterals (16% versus 24%,
P
=0.001). Patients with symptomatic ICH were more often taking statins (40% versus 15%,
P
=0.009) and had less often good collaterals (0% versus 24%,
P
<0.001). Any ICH or symptomatic ICH were not associated with cholesterol levels. After multivariate analysis, the frequency of any ICH remained independently associated with previous statin use (OR, 3.1; 95% CI, 1.53 to 6.39;
P
=0.004), atrial fibrillation (OR, 2.5; CI, 1.35 to 4.75;
P
=0.004), National Institutes of Health Stroke Scale score (OR, 1.1; CI, 1.00 to 1.10;
P
=0.037), and worse collaterals (OR, 1.7; CI, 1.19 to 2.42;
P
=0.004). There was no association of outcome with prior statin use, total cholesterol level, or low-density lipoprotein cholesterol level.

Conclusion—

Prior statin use, but not cholesterol levels on admission, is associated with a higher frequency of any ICH after intra-arterial thrombolysis without impact on outcome.
Temporal and Spatial Dynamics of Cerebral Immune Cell Accumulation in Stroke
Authors: Gelderblom Mathias , Leypoldt Frank , Steinbach Karin , Behrens Doerthe , Choe Chi-Un , Siler Dominic A. , Arumugam Thiruma V. , Orthey Ellen , Gerloff Christian , Tolosa Eva , Magnus Tim
Published: March 2009

Background and Purpose—

Ischemic stroke leads to significant morbidity and mortality in the Western world. Early reperfusion strategies remain the treatment of choice but can initiate and augment an inflammatory response causing secondary brain damage. The understanding of postischemic inflammation is very limited. The objectives of this study were to define the temporal and spatial infiltration of immune cell populations and their activation patterns in a murine cerebral ischemia–reperfusion injury model.

Methods—

Transient middle cerebral artery occlusion was induced for 1 hour followed by 12-hour to 7-day reperfusion in C57/BL6 mice. Immunohistochemistry and flow cytometry were used to quantify the infiltrating immune cell subsets.

Results—

Accumulation of microglia and infiltration of the ischemic hemisphere by macrophages, lymphocytes, and dendritic cells (DCs) preceded the neutrophilic influx. DCs were found to increase 20-fold and constituted a substantial proportion of infiltrating cells. DCs exhibited a significant upregulation of major histocompatibility complex II and major histocompatibility complex II high-expressing DCs were found 100 times more abundant than in sham conditions. Upregulation of the costimulatory molecule CD80 was observed in DCs and microglial cells but did not further increase in major histocompatibility complex II high-expressing DCs. No lymphocyte activation was observed. Additionally, regulatory immune cells (natural killer T-cells, CD4
−
/CD8
−
T lymphocytes) cumulated in the ischemic hemisphere.

Conclusion—

This study provides a detailed analysis of the temporal dynamics of immune cell accumulation in a rodent stroke model. The peculiar activation pattern and massive increase of antigen-presenting cells in temporal conjunction with regulatory cells might provide additional insight into poststroke immune regulation.
Beyond Hemispheric Dominance: Brain Regions Underlying the Joint Lateralization of Language and Arithmetic to the Left Hemisphere
Authors: Pinel Philippe , Dehaene Stanislas
Published: March 2009

Language and arithmetic are both lateralized to the left hemisphere in the majority of right-handed adults. Yet, does this similar lateralization reflect a single overall constraint of brain organization, such an overall “dominance” of the left hemisphere for all linguistic and symbolic operations? Is it related to the lateralization of specific cerebral subregions? Or is it merely coincidental? To shed light on this issue, we performed a “colateralization analysis” over 209 healthy subjects: We investigated whether normal variations in the degree of left hemispheric asymmetry in areas involved in sentence listening and reading are mirrored in the asymmetry of areas involved in mental arithmetic. Within the language network, a region-of-interest analysis disclosed partially dissociated patterns of lateralization, inconsistent with an overall “dominance” model. Only two of these areas presented a lateralization during sentence listening and reading which correlated strongly with the lateralization of two regions active during calculation. Specifically, the profile of asymmetry in the posterior superior temporal sulcus during sentence processing covaried with the asymmetry of calculation-induced activation in the intraparietal sulcus, and a similar colateralization linked the middle frontal gyrus with the superior posterior parietal lobule. Given recent neuroimaging results suggesting a late emergence of hemispheric asymmetries for symbolic arithmetic during childhood, we speculate that these colateralizations might constitute developmental traces of how the acquisition of linguistic symbols affects the cerebral organization of the arithmetic network.
Cross-cultural Reading the Mind in the Eyes: An fMRI Investigation
Authors: Adams Reginald B. , Rule Nicholas O. , Franklin Robert G. , Wang Elsie , Stevenson Michael T. , Yoshikawa Sakiko , Nomura Mitsue , Sato Wataru , Kveraga Kestutis , Ambady Nalini
Published: March 2009

The ability to infer others' thoughts, intentions, and feelings is regarded as uniquely human. Over the last few decades, this remarkable ability has captivated the attention of philosophers, primatologists, clinical and developmental psychologists, anthropologists, social psychologists, and cognitive neuroscientists. Most would agree that the capacity to reason about others' mental states is innately prepared, essential for successful human social interaction. Whether this ability is culturally tuned, however, remains entirely uncharted on both the behavioral and neural levels. Here we provide the first behavioral and neural evidence for an intracultural advantage (better performance for same- vs. other-culture) in mental state decoding in a sample of native Japanese and white American participants. We examined the neural correlates of this intracultural advantage using fMRI, revealing greater bilateral posterior superior temporal sulci recruitment during same- versus other-culture mental state decoding in both cultural groups. These findings offer preliminary support for cultural consistency in the neurological architecture subserving high-level mental state reasoning, as well as its differential recruitment based on cultural group membership.
The Neural Basis of Perceptual Category Learning in Human Infants
Authors: Grossmann Tobias , Gliga Teodora , Johnson Mark H. , Mareschal Denis
Published: March 2009

We measured looking times and ERPs to examine the cognitive and brain bases of perceptual category learning in 6-month-old infants. In Experiment 1, we showed that categorization and exemplar discrimination rely on different cortical processes. Specifically, the repetition of individual exemplars resulted in differential cortical processing at posterior channels at an early stage during object processing (100–300 msec), whereas discriminating among members of different categories was reflected in ERP differences over anterior cortical regions occurring later in time (300–500 msec) than the repetition effects. In Experiment 2, replicating the findings of Study 1, we found that infants engage the same cortical processes to categorize visual objects into basic-level categories, regardless of whether a basic (bird vs. fish) or global level is crossed (birds vs. cars). This pattern of findings is consistent with perceptual accounts of infant categorization [Quinn, P. C., & Eimas, P. D. Perceptual organization and categorization in young infants. In C. Rovee-Collier & L. P. Lipsitt (Eds.), Advances in infancy research ( pp. 1–36). Norwood, NJ: Ablex, 1996] and accords with recent adult neural-level models of perceptual categorization.
In Search of Recollection and Familiarity Signals in the Hippocampus
Authors: Wais Peter E. , Squire Larry R. , Wixted John T.
Published: March 2009

fMRI studies of recognition memory have often been interpreted to mean that the hippocampus selectively subserves recollection and that adjacent regions selectively subserve familiarity. Yet, many of these studies have confounded recollection and familiarity with strong and weak memories. In a source memory experiment, we compared correct source judgments (which reflect recollection) and incorrect source judgments (often thought to reflect familiarity) while equating for old–new memory strength by including only high-confidence hits in the analysis. Hippocampal activity associated with both correct source judgments and incorrect source judgments exceeded the activity associated with forgotten items and did so to a similar extent. Further, hippocampal activity was greater for high-confidence old decisions relative to forgotten items even when source decisions were at chance. These results identify a recollection signal in the hippocampus and may identify a familiarity signal as well. Similar results were obtained in the parahippocampal gyrus. Unlike in the medial temporal lobe, activation in prefrontal cortex increased differentially in association with source recollection.
High-resolution fMRI of Content-sensitive Subsequent Memory Responses in Human Medial Temporal Lobe
Authors: Preston Alison R. , Bornstein Aaron M. , Hutchinson J. Benjamin , Gaare Meghan E. , Glover Gary H. , Wagner Anthony D.
Published: March 2009

The essential role of the medial temporal lobe (MTL) in long-term memory for individual events is well established, yet important questions remain regarding the mnemonic functions of the component structures that constitute the region. Within the hippocampus, recent functional neuroimaging findings suggest that formation of new memories depends on the dentate gyrus and the CA3 field, whereas the contribution of the subiculum may be limited to retrieval. During encoding, it has been further hypothesized that structures within MTL cortex contribute to encoding in a content-sensitive manner, whereas hippocampal structures may contribute to encoding in a more domain-general manner. In the current experiment, high-resolution fMRI techniques were utilized to assess novelty and subsequent memory effects in MTL subregions for two classes of stimuli—faces and scenes. During scanning, participants performed an incidental encoding (target detection) task with novel and repeated faces and scenes. Subsequent recognition memory was indexed for the novel stimuli encountered during scanning. Analyses revealed voxels sensitive to both novel faces and novel scenes in all MTL regions. However, similar percentages of voxels were sensitive to novel faces and scenes in perirhinal cortex, entorhinal cortex, and a combined region comprising the dentate gyrus, CA2, and CA3, whereas parahippocampal cortex, CA1, and subiculum demonstrated greater sensitivity to novel scene stimuli. Paralleling these findings, subsequent memory effects in perirhinal cortex were observed for both faces and scenes, with the magnitude of encoding activation being related to later memory strength, as indexed by a graded response tracking recognition confidence, whereas subsequent memory effects were scene-selective in parahippocampal cortex. Within the hippocampus, encoding activation in the subiculum correlated with subsequent memory for both stimulus classes, with the magnitude of encoding activation varying in a graded manner with later memory strength. Collectively, these findings suggest a gradient of content sensitivity from posterior (parahippocampal) to anterior (perirhinal) MTL cortex, with MTL cortical regions differentially contributing to successful encoding based on event content. In contrast to recent suggestions, the present data further indicate that the subiculum may contribute to successful encoding irrespective of event content.
Interest, Leverage and Public Opinion in Mediation
Authors: William Zartman I.
Published: March 2009

Saadia Touval’s important contributions to the study of mediation included an emphasis on the interests and motivations of mediators, hitherto often assumed to be pure or non-existent. As a result, legitimacy is usually considered to be inherent in the selfless mediator, although in internal affairs, mediation is illegitimate meddling. At the same time, much of the work on mediation either exaggerates or underestimates the nature of leverage. Public opinion also has an important but ambiguous relation to mediation. Interests, public opinion and leverage were topics where Touval helped to establish a more realistic appreciation, as illustrated in this second commemorative issue of International Negotiation.
Kiwis Against Possums: A Critical Analysis of Anti-Possum Rhetoric in Aotearoa New Zealand
Authors: Potts Annie
Published: March 2009

The history of brushtail possums in New Zealand is bleak. The colonists who forcibly transported possums from their native Australia to New Zealand in the nineteenth century valued them as economic assets, quickly establishing a profitable fur industry. Over the past 80 or so years, however, New Zealand has increasingly scapegoated possums for the unanticipated negative impact their presence has had on the native environment and wildlife. Now this marsupial—blamed and despised—suffers the most miserable of reputations and is extensively targeted as the nation's number one pest. This paper examines anti-possum rhetoric in New Zealand, identifying the operation of several distinct—yet related—discourses negatively situating the possum as (a) an unwanted foreign invader and a threat to what makes New Zealand unique; (b) the subject of revenge and punishment (ergo the deserving recipient of exploitation and commodification); and (c) recognizably “cute, but...” merely a pest and therefore unworthy of compassion. This paper argues that the demonization of possums in New Zealand is overdetermined, extreme, and unhelpfully entangled in notions of patriotism and nationalism.
Thinking Across Species Boundaries: General Sociality and Embodied Meaning
Authors: Dillard-Wright David
Published: March 2009

Denying special traits like the use of language to nonhuman animals has often been a basis for the creation of a stand-alone human sphere, apart from and above the animal world and the environmental milieu. Merleau-Ponty's phenomenology shows that human communication arises from the semiosis in the extra-human world and is not self-contained. Given many recent insights in scientific studies of nonhuman animals, only a few of which are cited here, it becomes impossible to say that animals are mute, reactive entities. They too share many of the same features of communication with human beings. That said, articulating an interspecies ethic of sympathy or concern must take into account species and individual differences.
Growth Effects of FDI: Is Greenfield Greener?
Authors: Nanda Nitya
Published: March 2009

Based on conventional wisdom, Greenfield foreign investment is more beneficial to host countries as compared to the FDI that comes through the merger and acquisition route. However, the current economic thinking has been dominated by the argument that such a distinction is meaningless, though there has not been any concrete evidence to the contrary. Given this context, this study tries to assess the impact of both types of FDI on the growth rates of host countries. The study looks into the theoretical possibilities, conducts an econometric analysis, and as a result, finds that not only is the merger and acquisition-related FDI less beneficial, compared to Greenfield investment, it may also have an adverse impact on growth.
Diplomatic Mediation as an Independent Variable
Authors: Steiner Barry H.
Published: March 2009

Successful third-party diplomatic mediation illustrates diplomacy as a causative, independent element in world politics. This article asks how mediators forge agreement between force-prone, deadlocked parties in intractable diplomatic conflict, and why some such conflicts are more difficult to mediate than others. It compares three interstate and three intrastate mediation cases, each probed as a deviant episode, and tests the conventional view that intrastate conflict presents the more difficult mediation challenge. Confirming that intrastate conflict is more difficult to mediate than its interstate counterpart, the study narrows and refines the sources of the added difficulty.
Religion and Mediation: The Role of Faith-Based Actors in International Conflict Resolution
Authors: Bercovitch Jacob , Ayse Kadayifci-Orellana S.
Published: March 2009

Religion has often been thought of as playing a crucial role in generating conflicts, particularly internal ones. While it may often be a source of conflict, its role in the overall peace process has all too often been overlooked. In this paper we emphasize the importance of religion and religious actors in the process of mediation. We examine the general conditions that facilitate mediation in international relations and assess how much these hold true in the case of faith-based mediation. We find that aspects such as legitimacy and leverage have a major impact on the success or failure of mediation. We examine how these factors manifest themselves in the case of religious mediators, and we show that legitimacy and leverage are still crucial to successful mediation but have a very different meaning and content in the case of religious actors. We explore the consequences of these differences and explain how religious mediation may work best in tandem with the more traditional forms of mediation.
Conceptual Quandaries about Genetic Data — A Comparative Perspective
Authors: Krajewska Atina
Published: March 2009

Recently, several regulatory initiatives have been taken by the Council of Europe, OECD and national legislators to regulate different aspects of human genetics. However, the latest research findings and the emergence of systems biology call this approach into question as they constitute a substantial change in natural science and philosophy. This article argues that law should take this paradigm shift into consideration and that it is not possible to perceive genetic data as exceptional and suitable for special protection. Instead, norms should be designed around notions such as ‘biological’ and ‘predictive’ data.
Semantic, Pedantic or Paradigm Shift? Recruitment, Retention and Property in Modern Population Biobanking
Authors: Harmon Shawn H.E.
Published: March 2009

Evolving uses of human biological material, including their collection and retention in biobanks and their distribution to diverse projects, are sites of great tension from the human rights perspective. In the medical-legal setting, these rights are often protected and realised through consent practices. In the biobank setting, there endures a widely shared concern over consent, and the many divergent ways it is fashioned and deployed. This article reconsiders consent in the biobank setting, first, addressing the theoretical foundation of consent and its deployment in the broader medical context, second, examining the nature of biobanks and the uncomfortable position of consent therein, and finally, offering a means of approaching recruitment and retention in the biobank setting which is sensitive to originator interests, including human dignity, doing so within the rubric of a property model.
Biomedical Research and Human Research Subject Protection:
Authors: Stühlinger Verena , Fortwengel Gerhard , Thoeni Magdalena , Staudinger Roland
Published: March 2009

Biomedical research and international collaborations in biomedical research become more and more important — economically and politically, making harmonised legislation for human research subject protection indispensible. The European Convention on Human Rights and Biomedicine is the first binding contract under international law to protect human rights in the field of biomedical research. Almost 10 years after its entry into force neither Germany nor Austria have signed or ratified the Convention. Research involving incapacitated adults is one of the key issues in this context. This paper analyses the Convention and other European, US and international legislation, focusing on research involving incapacitated adults in “nontherapeutic” trials. It shows that a ban of “non-therapeutic” research involving incapacitated adults leads to an unjust exclusion of this patient group, leading to uncertainty and disadvantages in medical treatment.
Developments in International/European Health Law
Authors: Roscam Abbing Henriette D.C.
Published: March 2009

International (European) organizations have impact on health law. The most recent developments are: a revision of the world Medical’s Association Declaration of Helsinki, a proposal for a Directive (European Commission) on standards of quality and safety of human organs intended for transplantation, accompanied by a ten point action plan; a proposal (European Commission) for a Directive on the application of patients’ rights in cross-border health care; a proposal (European commission) for a Directive on information to the general public on medicinal products subject to medical prescription.
The No Impunity Policy in International Criminal Law: Justice versus Revenge
Authors: Matwijkiw Anja
Published: March 2009

In this article, the author examines the issue of justice versus revenge in the context of jus cogens crimes and fundamental moral and legal principles. Her objective is to provide a critical appraisal of M. Cherif Bassiouni's theory of punishment in the light of his general jurisprudence. The main question is whether there is a consistency problem. On the one hand, Bassiouni draws a distinction between justice and revenge. On the other hand, the distinction is not a dichotomy. This is to say that Bassiouni does not dogmatically prohibit revenge as a punitive measure in circumstances where jus cogens crimes have been committed and where there is no effective, independent and impartial judiciary, which can secure justice in terms of strict and legal accountability. Outlining the various premises for Bassiouni's so-called Mixed Model, the author shows that conclusions pertaining to consistency should not be interpreted simplistically.
Procedural Obligations Under the European Convention on Human Rights: Useful Guidelines for the Assessment of 'Unwillingness' and 'Inability' in the Context of the Complementarity Principle
Authors: Lyngdorf Sandra , van der Wilt Harmen
Published: March 2009

The authors are involved in a research project “Impact of International Courts on Domestic Criminal Procedures in mass atrocity cases” (DOMAC), uniting Hebrew University, University College London, Reykjavik University and the University of Amsterdam.
International War Crimes Tribunals and the Challenge of Outreach
Authors: Clark Janine Natalya
Published: March 2009

A significant challenge facing international war crimes tribunals is to reach out to and to communicate their work to the local populations concerned. The purpose of this article, therefore, is to analyze and to explore the Outreach programmes of three particular courts, namely the International Criminal Tribunal for the former Yugoslavia (ICTY), the Special Court for Sierra Leone (SCSL) and the International Criminal Court (ICC). It will argue that notwithstanding the important and creative Outreach work being undertaken by these courts, more resources must be invested in their Outreach sections if they are to achieve their ambitious objectives, not least the goal of contributing to peace.