bluuebunny/crossref_metadata_2025 huggingface dataset:
Hippocampal Estrogen Receptor-Alpha Splice Variant TADDI in the Human Brain in Aging and Alzheimer’s Disease
Authors: Ishunina T.A. , Swaab D.F.
Published: September 2008

Background/Aims: Estrogen receptor-α (ERα) splice variants are important for understanding estrogen effects on the brain and estrogen therapy pitfalls. We addressed the question whether a novel ERα splice variant TADDI is expressed at the protein level in the human brain and whether it changes in relation to aging and Alzheimer’s disease (AD). Methods: Immunoreactivity (-ir) for TADDI was assessed on postmortem human brain material from a total of 116 cases. Results: The highest levels of this splice form were found in the hypothalamic supraoptic nucleus (SON), pontine nuclei, medulla oblongata, gray matter of the spinal cord, the hippocampus, glomeruli of the cerebellum, the nucleus basalis of Meynert (NBM), and the tuberomamillary nucleus (TMN). TADDI-ir was mainly confined to the cytoplasm but was also determined in the nuclei of hippocampal neurons from young patients. In the hippocampus, the NBM, and the TMN, TADDI-ir was higher in postmenopausal women than in women ≤50 years old. In these brain areas and in the SON, it was diminished in AD women. In the NBM of AD men, TADDI-ir was enhanced. Conclusion: Aging- and AD-related changes in TADDI-ir show that it should be considered for the sensitivity of the neural tissue to estrogen therapy.
Inhibition of CD8+ T Lymphocytes Attenuates Respiratory Syncytial Virus-Enhanced Allergic Inflammation
Authors: Jiang Xiong-bin , Wang Zheng-dong , Zhu Yi , Zhang Xi-long , Cui Xue-Fan , Yao Kun , Yin Kai-sheng
Published: September 2008

Background: CD8+ T cells have an important role in the pathogenesis of respiratory virus-induced asthma exacerbations. However, the cellular mechanism of CD8+ T cells, linking viral respiratory infections to the development of airway inflammation, is not well defined. Objectives: To clarify the role of CD8+ T cells in the development of respiratory virus-induced asthma exacerbations. Methods: Using a murine model of prior ovalbumin exposure and subsequent respiratory syncytial virus infection, the airway responsiveness was assessed by barometric whole-body plethysmography. Airway eosinophils, lymphocytes, neutrophils as well as IFN-γ, IL-4, IL-5 and IL-13 in bronchoalveolar lavage fluid were measured by Diff-Quick staining and ELISA. The frequency of cytokine-producing CD8+ T lymphocytes in peribronchial lymph nodes was detected using 2-color immunofluorescence analysis. Histological examinations were carried out using hematoxylin and eosin and immunohistochemistry. Results: Anti-CD8 monoclonal antibody (1 mg/kg) clearly inhibited increases in airway responsiveness to acetylcholine and markedly reduced the number of eosinophils, neutrophils, lymphocytes as well as IL-4, IL-5 and IL-13 levels in bronchoalveolar lavage fluid. Furthermore, the antibody also attenuated airway inflammation and CD8+ T lymphocyte infiltration in lung tissue. Conclusions: These findings suggest that CD8+ T lymphocytes play a critical role for the development of respiratory syncytial virus-induced airway inflammation and airway hyperresponsiveness.
luxS-Based Quorum-Sensing Signaling Affects Biofilm Formation in Streptococcus mutans
Authors: Huang Z. , Meric G. , Liu Z. , Ma R. , Tang Z. , Lejeune P.
Published: September 2008

Background: Quorum sensing (QS) is a process by which bacteria communicate with diffusible chemical signaling molecules called autoinducers (AIs). The autoinducer-2 signal (AI-2) produced by the LuxS protein mediates interspecies communication among Gram-positive and Gram-negative bacteria. In this study, we report that luxS-dependent QS is involved in the formation of Streptococcus mutans biofilms. Methods: An S. mutans luxS mutant was constructed, and the differences in growth and biofilm formation were compared between the wild-type strain and the mutant strain. To quantificationally analyze the kinetic biofilm formation of the mutant strain, an assay of BioFilm Ring Test® was applied. Results: There is a small increase in the growth of the luxS mutant strain after the stationary phase, compared with the parent strain. However during the exponential period, there were no significant differences. Using the BioFilm Ring Test®, it was demonstrated that this luxS mutation was able to accelerate biofilm formation on a polystyrene surface during the mid-exponential growth phase. With 1% glucose treatment, even greater differences were observed between the mutant strain and its parental strain. Conclusion: These data suggest that a luxS-dependent signal may play an important role in the biofilm formation of S. mutans.
Chemokines in Vascular Dysfunction and Remodeling
Authors: Schober Andreas
Published: September 2008

Vascular remodeling stands for structural changes of the vessel wall in response to various noxious stimuli, which results in reorganization of the vessel wall architecture. Luminal narrowing because of neointima formation and constrictive remodeling leading to hypoperfusion is the most relevant clinical effect. Smooth muscle cell (SMC) accumulation, inflammatory cell recruitment, and endothelial regeneration are the critical parts in obstructive vascular remodeling. Chemokines and chemokine receptors have a great impact on initiating and progressing neointimal formation by controlling each step of the remodeling process. SDF-1α regulates vascular repair by CXCR4-dependent smooth muscle progenitor cell recruitment, which contributes to the maladaptive response to injury. The three distinct chemokine-chemokine receptor pairs MCP-1/CCR2, RANTES/CCR5, and Fractalkine/CX
3
CR1 direct lesional leukocyte infiltration. In addition MCP-1/CCR2 and Fractalkine/CX
3
CR1 increase neointimal SMC expansion. In contrast, KC/Gro-α supports endothelial recovery through CXCR2, which attenuates neointima formation. These findings highlight the importance to characterize specific functions of the chemokine network to enable therapeutic intervention.
Inhibition of CCR2 Ameliorates Insulin Resistance and Hepatic Steatosis in db/db Mice
Authors: Tamura Yukinori , Sugimoto Masayuki , Murayama Toshinori , Ueda Yukihiko , Kanamori Hiroshi , Ono Koh , Ariyasu Hiroyuki , Akamizu Takashi , Kita Toru , Yokode Masayuki , Arai Hidenori
Published: September 2008

Objective—

Recently, adipose tissue inflammation induced by macrophage infiltration through MCP-1/C-C chemokine receptor-2 (CCR2) pathway is considered to play a role in the development of visceral obesity and insulin resistance. In the present study, to further examine the role of CCR2 in the development of obesity and type 2 diabetes, we studied the effect of pharmacological inhibition of CCR2 from the early stage of obesity in db/db mice.

Methods and Results—

Db/+m (lean control) and db/db mice were fed with a standard diet with or without 0.005% propagermanium, as a CCR2 inhibitor for 12 weeks from 6 weeks of age. Propagermanium treatment decreased body weight gain, visceral fat accumulation, and the size of adipocytes only in db/db mice. Further, propagermanium suppressed macrophage accumulation and inflammation in adipose tissue. Propagermanium treatment also ameliorated glucose tolerance and insulin sensitivity, and decreased hepatic triglyceride contents in db/db mice.

Conclusions—

Propagermanium improved obesity and related metabolic disorders, such as insulin resistance and hepatic steatosis by suppressing inflammation in adipose tissue. Our data indicate that inhibition of CCR2 could improve obesity and type 2 diabetes by interfering adipose tissue inflammation, and that propagermanium may be a beneficial drug for the treatment of the metabolic syndrome.
Bone Morphogenetic Proteins 2 and 4 Are Selectively Expressed by Late Outgrowth Endothelial Progenitor Cells and Promote Neoangiogenesis
Authors: Smadja David M. , Bièche Ivan , Silvestre Jean-Sébastien , Germain Stéphane , Cornet Adeline , Laurendeau Ingrid , Duong-Van-Huyen Jean-Paul , Emmerich Joseph , Vidaud Michel , Aiach Martine , Gaussem Pascale
Published: September 2008

Objective—

Endothelial progenitor cells are currently identified either by their surface antigen expression or by their generation of early colonies in culture (CFU-Hill). Another population, endothelial colony-forming cells (ECFCs), has strong vessel-forming capacity but is less well characterized. Given the potential usefulness of CFU-Hill and ECFCs as cell therapy products, their thorough characterization is of major importance.

Methods and Results—

CFU-Hill and ECFCs were expanded from human cord and adult blood. Bone morphogenetic proteins 2 and 4 (BMP2/4) were selectively expressed by ECFCs but not by CFU-Hill. The BMP pathway was involved in ECFC commitment and angiogenic potential in vitro. In vivo, BMP inhibition strongly reduced plug vascularization in bFGF-containing Matrigel plugs implanted in C57/Bl6 mice. Moreover, ECFC exposure to BMP increased their therapeutic potential in a nude mouse model of hindlimb ischemia. In amputation specimens from patients with critical leg ischemia who had received a local therapeutic injection of bone marrow mononuclear cells, newly formed vessels were strongly positive for BMP2/4, suggesting that endothelial cells involved in neovascularization have an ECFC-like phenotype.

Conclusion—

BMP2/4 are a marker of ECFCs and play a key role in ECFC commitment and outgrowth during neovascularization.
Deficiency and Inhibition of Cathepsin K Reduce Body Weight Gain and Increase Glucose Metabolism in Mice
Authors: Yang Min , Sun Jiusong , Zhang Tinghu , Liu Jian , Zhang Jie , Shi Michael A. , Darakhshan Froogh , Guerre-Millo Michèle , Clement Karine , Gelb Bruce D. , Dolgnov Gregory , Shi Guo-Ping
Published: September 2008

Objectives—

Previous studies demonstrated increased levels of cysteine proteases cathepsins in serum and adipose tissues from obese patients. We now provide evidence from a mouse model of obesity to suggest a direct participation of cathepsin K (CatK) in mouse body weight gain and glucose metabolism.

Methods and Results—

Using real-time polymerase chain reaction, we detected 12-fold increase in CatK transcripts after adipogenesis of human preadipocytes. Using an immunohistology analysis, we consistently observed high levels of CatK expression in adipose tissues from obese humans and mice. Selective inhibition of CatK activity blocked the lipid accumulation in human and mouse preadipocytes. In mice, CatK deficiency reduced significantly diet-induced body weight gain and serum glucose and insulin levels. Similar results were obtained in diet-induced and genetically created (
ob/ob
) obese mice after animals were treated with a CatK-selective inhibitor. Mechanistic study demonstrated a role for CatK in degrading fibronectin, a matrix protein that controls adipogenesis. Deficiency or inhibition of CatK leads to fibronectin accumulation in muscle and adipose tissues.

Conclusion—

This study demonstrates an essential role of CatK in adipogenesis and mouse body weight gain, possibly via degradation of fibronectin, thus suggesting a novel therapeutic strategy for the control of obesity by regulating CatK activity.
Pioglitazone Inhibits the Expression of Inflammatory Cytokines From Both Monocytes and Lymphocytes in Patients With Impaired Glucose Tolerance
Authors: Zhang Wei-Yang , Schwartz Eric A. , Permana Paska A. , Reaven Peter D.
Published: September 2008

Objective—

The current study determines whether pioglitazone (PIO) therapy reduces both monocyte and lymphocyte inflammatory activity and their ability to induce inflammation in other tissues.

Methods and Results—

Monocyte and lymphocyte cytokine gene and protein expression of interleukin (IL)-6 were first shown to be greater in subjects with impaired glucose tolerance (IGT) than in subjects with normal glucose tolerance. Sixty-six IGT subjects were then randomized to 4,5 months of placebo or PIO therapy. After receiving PIO, subjects had lower triglycerides and higher HDL cholesterol (
P
<0.05) than did subjects receiving placebo. Monocyte gene and protein expression of IL-1β, IL-6, and IL-8 (and IL-2, IL-6 and IL-8 from lymphocytes) was significantly lower after PIO therapy in the resting state, as well as after lipopolysaccharide (LPS) stimulation (
P
<0.05 for all). Moreover, IL-6, IL-8, and MCP-1 gene expression were decreased by nearly 50% in human adipocytes exposed to conditioned media from monocytes or lymphocytes from PIO treated subjects.

Conclusion—

These results demonstrate that PIO therapy in IGT can reduce proinflammatory gene and protein expression from both monocytes and lymphocytes. This intervention also reduces the inflammatory cross-talk between these immune cells and adipose tissue, which could in turn contribute to the metabolic improvements resulting from PIO therapy.
Athsq1
Is an Atherosclerosis Modifier Locus With Dramatic Effects on Lesion Area and Prominent Accumulation of Versican
Authors: Seidelmann Sara Bretschger , Kuo Chaoling , Pleskac Nick , Molina Jennifer , Sayers Scott , Li Rong , Zhou Jing , Johnson Pamela , Braun Kathleen , Chan Christina , Teupser Daniel , Breslow Jan L. , Wight Thomas N. , Tall Alan R. , Welch Carrie L.
Published: September 2008

Objective—

Susceptibility to atherosclerosis is genetically complex, and modifier genes that do not operate via traditional risk factors are largely unknown. A mouse genetics approach can simplify the genetic analysis and provide tools for mechanistic studies.

Methods and Results—

We previously identified atherosclerosis susceptibility QTL (
Athsq1
) on chromosome 4 acting independently of systemic risk factors. We now report confirmation of this locus in congenic strains carrying the MOLF-derived susceptibility allele in the C57BL/6J-
Ldlr
−/−
genetic background. Homozygous congenic mice exhibited up to 4.5-fold greater lesion area compared to noncongenic littermates (
P
<0.0001). Analysis of extracellular matrix composition revealed prominent accumulation of versican, a presumed proatherogenic matrix component abundant in human lesions but almost absent in the widely-used C57BL/6 murine atherosclerosis model. The results of a bone marrow transplantation experiment suggested that both accelerated lesion development and versican accumulation are mediated, at least in part, by macrophages. Interestingly, comparative mapping revealed that the
Athsq1
congenic interval contains the mouse region homologous to a widely-replicated CHD locus on human chromosome 9p21.

Conclusion—

These studies confirm the proatherogenic activity of a novel gene(s) in the MOLF-derived
Athsq1
locus and provide in vivo evidence for a causative role of versican in lesion development.
Mechanisms Underlying Erythrocyte and Endothelial Nitrite Reduction to Nitric Oxide in Hypoxia
Authors: Webb Andrew J. , Milsom Alexandra B. , Rathod Krishnaraj S. , Chu Wai Lum , Qureshi Shehla , Lovell Matthew J. , Lecomte Florence M.J. , Perrett David , Raimondo Carmelo , Khoshbin Espeed , Ahmed Zubair , Uppal Rakesh , Benjamin Nigel , Hobbs Adrian J. , Ahluwalia Amrita
Published: September 2008

Reduction of nitrite (NO2−) provides a major source of nitric oxide (NO) in the circulation, especially in hypoxemic conditions. Our previous studies suggest that xanthine oxidoreductase (XOR) is an important nitrite reductase in the heart and kidney. Herein, we have demonstrated that conversion of nitrite to NO by blood vessels and RBCs was enhanced in the presence of the XOR substrate xanthine (10 μmol/L) and attenuated by the XOR inhibitor allopurinol (100 μmol/L) in acidic and hypoxic conditions only. Whereas endothelial nitric oxide synthase (eNOS) inhibition had no effect on vascular nitrite reductase activity, in RBCs L-NAME, L-NMMA, andl-arginine inhibited nitrite-derived NO production by >50% (P<0.01) at pH 7.4 and 6.8 under hypoxic conditions. Western blot and immunohistochemical analysis of RBC membranes confirmed the presence of eNOS and abundant XOR on whole RBCs. Thus, XOR and eNOS are ideally situated on the membranes of RBCs and blood vessels to generate intravascular vasodilator NO from nitrite during ischemic episodes. In addition to the proposed role of deoxyhemoglobin, our findings suggest that the nitrite reductase activity within the circulation, under hypoxic conditions (at physiological pH), is mediated by eNOS; however, as acidosis develops, a substantial role for XOR becomes evident.
Pathophysiological Levels of Soluble P-Selectin Mediate Adhesion of Leukocytes to the Endothelium Through Mac-1 Activation
Authors: Woollard Kevin J. , Suhartoyo Andreas , Harris Emma E. , Eisenhardt Steffen U. , Jackson Shaun P. , Peter Karlheinz , Dart Anthony M. , Hickey Michael J. , Chin-Dusting Jaye P.F.
Published: September 2008

Plasma soluble P-selectin (sP-selectin) levels are increased in pathologies associated with atherosclerosis, including peripheral arterial occlusive disease (PAOD). However, the role of sP-selectin in regulating leukocyte–endothelial adhesion is unclear. The aim of this study was to assess the ability of exogenous and endogenous sP-selectin to induce leukocyte responses that promote their adhesion to various forms of endothelium. In flow chamber assays, sP-selectin dose-dependently increased neutrophil adhesion to resting human iliac artery endothelial cells. Similarly, sP-selectin induced neutrophil adhesion to the endothelial surface of murine aortae and human radial venous segments in ex vivo flow chamber experiments. Using intravital microscopy to examine postcapillary venules in the mouse cremaster muscle, in vivo administration of sP-selectin was also found to significantly increase leukocyte rolling and adhesion in unstimulated postcapillary venules. Using a Mac-1–specific antibody and P-selectin knockout mouse, it was demonstrated that this finding was dependent on a contribution of Mac-1 to leukocyte rolling and endothelial P-selectin expression. This was confirmed in an ex vivo perfusion model using viable mouse aorta and human radial vessels. In contrast, with tumor necrosis factor-α–activated endothelial cells and intact endothelium, where neutrophil adhesion was already elevated, sP-selectin failed to further increase adhesion. Plasma samples from PAOD patients containing pathologically elevated concentrations of sP-selectin also increased neutrophil adhesion to the endothelium in a sP-selectin–dependent manner, as demonstrated by immunodepletion of sP-selectin. These studies demonstrate that raised plasma sP-selectin may influence the early progression of vascular disease by promoting leukocyte adhesion to the endothelium in PAOD, through Mac-1–mediated rolling and dependent on endothelial P-selectin expression.
Thrombospondin-1 Deficiency Accelerates Atherosclerotic Plaque Maturation in
ApoE
−/−
Mice
Authors: Moura Rute , Tjwa Marc , Vandervoort Petra , Van kerckhoven Soetkin , Holvoet Paul , Hoylaerts Marc F.
Published: September 2008

Thrombospondin (TSP)1 is implicated in various inflammatory processes, but its role in atherosclerotic plaque formation and progression is unclear. Therefore, the development of atherosclerosis was compared in
ApoE
−/−
and
Tsp1
−/−
ApoE
−/−
mice kept on a normocholesterolemic diet. At 6 months, morphometric analysis of the aortic root of both mouse genotypes showed comparable lesion areas. Even when plaque burden increased ≈5-fold in
ApoE
−/−
and 10-fold in
Tsp1
−/−
ApoE
−/−
mice, during the subsequent 3 months, total plaque areas were comparable at 9 months. In contrast, plaque composition differed substantially between genotypes: smooth muscle cell areas, mostly located in the fibrous cap of
ApoE
−/−
plaques, both at 6 and 9 months, were 3-fold smaller in
Tsp1
−/−
ApoE
−/−
plaques, which, in addition, were also more fibrotic. Moreover, inflammation by macrophages was twice as high in
Tsp1
−/−
ApoE
−/−
plaques. This correlated with a 30-fold elevated incidence of elastic lamina degradation, with matrix metalloproteinase-9 accumulation, underneath plaques and manifestation of ectasia, exclusively in
Tsp1
−/−
ApoE
−/−
mice. At 9 months, the necrotic core was 1.4-fold larger and 4-fold higher numbers of undigested disintegrated apoptotic cells were found in
Tsp1
−/−
ApoE
−/−
plaques. Phagocytosis of platelets by cultured
Tsp1
−/−
macrophages revealed the instrumental role of TSP1 in phagocytosis, corroborating the defective intraplaque phagocytosis of apoptotic cells. Hence, the altered smooth muscle cell phenotype in
Tsp1
−/−
ApoE
−/−
mice has limited quantitative impact on atherosclerosis, but defective TSP1-mediated phagocytosis enhanced plaque necrotic core formation, accelerating inflammation and macrophage-induced elastin degradation by metalloproteinases, speeding up plaque maturation and vessel wall degeneration.
The PPARα/p16
INK4a
Pathway Inhibits Vascular Smooth Muscle Cell Proliferation by Repressing Cell Cycle–Dependent Telomerase Activation
Authors: Gizard Florence , Nomiyama Takashi , Zhao Yue , Findeisen Hannes M. , Heywood Elizabeth B. , Jones Karrie L. , Staels Bart , Bruemmer Dennis
Published: September 2008

Peroxisome proliferator-activated receptor (PPAR)α, the molecular target for fibrates used to treat dyslipidemia, exerts pleiotropic effects on vascular cells. In vascular smooth muscle cells (VSMCs), we have previously demonstrated that PPARα activation suppresses G
1
→S cell cycle progression by targeting the cyclin-dependent kinase inhibitor p16
INK4a
(p16). In the present study, we demonstrate that this inhibition of VSMC proliferation by PPARα is mediated through a p16-dependent suppression of telomerase activity, which has been implicated in key cellular functions including proliferation. PPARα activation inhibited mitogen-induced telomerase activity by repressing the catalytic subunit telomerase reverse transcriptase (TERT) through negative cross-talk with an E2F-1–dependent
trans
-activation of the TERT promoter. This
trans
-repression involved the recruitment of the retinoblastoma (RB) family proteins p107 and p130 to the TERT promoter resulting in impaired E2F-1 binding, an effect that was dependent on p16. The inhibition of cell proliferation by PPARα activation was lost in VSMCs following TERT overexpression or knockdown, pointing to a key role of telomerase as a target for the antiproliferative effects of PPARα. Finally, we demonstrate that PPARα agonists suppress telomerase activation during the proliferative response following vascular injury, indicating that these findings are applicable in vivo. In concert, these results demonstrate that the antiproliferative effects of PPARα in VSMCs depend on the suppression of telomerase activity by targeting the p16/RB/E2F transcriptional cascade.
Determination of Wall Tension in Cerebral Artery Aneurysms by Numerical Simulation
Authors: Isaksen Jørgen Gjernes , Bazilevs Yuri , Kvamsdal Trond , Zhang Yongjie , Kaspersen Jon H. , Waterloo Knut , Romner Bertil , Ingebrigtsen Tor
Published: September 2008

Background and Purpose—

Cerebral artery aneurysms rupture when wall tension exceeds the strength of the wall tissue. At present, risk-assessment of unruptured aneurysms does not include evaluation of the lesions shape, yet clinical experience suggests that this is of importance. We aimed to develop a computational model for simulation of fluid-structure interaction in cerebral aneurysms based on patient specific lesion geometry, with special emphasis on wall tension.

Methods—

An advanced isogeometric fluid-structure analysis model incorporating flexible aneurysm wall based on patient specific computed tomography angiogram images was developed. Variables used in the simulation model were retrieved from a literature review.

Results—

The simulation results exposed areas of high wall tension and wall displacement located where aneurysms usually rupture.

Conclusion—

We suggest that analyzing wall tension and wall displacement in cerebral aneurysms by numeric simulation could be developed into a novel method for individualized prediction of rupture risk.
Recurrent Stroke and Massive Right-to-Left Shunt
Authors: Serena Joaquín , Marti-Fàbregas Joan , Santamarina Estevo , Rodríguez Juan Jesús , Perez-Ayuso María Jesús , Masjuan Jaime , Segura Tomás , Gállego Jaime , Dávalos Antonio
Published: September 2008

Background and Purpose—

Few studies have prospectively examined the risk of recurrent stroke associated with patent foramen ovale. We present the results of the Spanish right-to-left shunt (RLSh) multicenter study.

Methods—

Four hundred eighty-six patients with cryptogenic stoke were included at 17 participating hospitals. Patients were examined by contrast transcranial Doppler methods at baseline. The magnitude of RLSh was quantified during the Valsalva maneuver. Transthoracic and/or transesophageal echocardiography, computed tomography scan, or magnetic resonance imaging was performed. Functional outcome and stroke recurrence were evaluated at 3 months and yearly thereafter. The independent relation between RLSh magnitude and stroke recurrence was analyzed by logistic-regression analysis in the whole group and in the younger subgroup (<55 years).

Results—

Massive RLSh was detected in 200 patients (41.2%). The mean follow-up was 729±411 days. Stroke recurrence was low (5.8%, n=28) and similar in patients with massive RLSh, with nonmassive RLSh, and with no RLSh, in both the younger group (3.4% vs 2.3% vs 4.5%, respectively;
P
=0.75) and in the whole population (5.0% vs 6.2% vs 6.3%, respectively;
P
=0.58). Regression analysis found no association between massive RLSh and recurrent stroke in either group (in the whole population, odds ratio=0.94; 95% CI, 0.36 to 2.40;
P
=0.89; in the younger population, odds ratio=0.93; 95% CI, 0.18 to 4.91;
P
=0.93). These results were similar when concurrent atrial septal aneurysm and massive RLSh were analyzed and when antithrombotic treatment and concomitant stroke risk factors were included.

Conclusions—

These results suggest that neither massive RLSh nor massive RLSh with concurrent atrial septal aneurysm is an independent risk factor for recurrent stroke, in either the general or younger stroke populations.
Mercantile Networks, Port Cities, and “Pirate” States: Conflict and Competition in the Indian Ocean World of Trade before the Sixteenth Century
Authors: Margariti Roxani Eleni
Published: September 2008

The prevailing image of the Indian Ocean world of trade before the arrival of western Europeans and Ottomans in the region in the sixteenth century is one of a generally peaceful, conflict-free realm dominated by cosmopolitan traders who moved easily across boundaries of geography, ethnicity, language, and religion. This paper modifies this picture by examining the evidence for conflict and competition between pre-modern maritime polities in the western end of the Indian Ocean. In the fifth/eleventh and sixth/twelfth centuries maritime polities on the islands of Kish in the Persian Gulf and Dahlak in the Red Sea antagonized Aden's supremacy as the region's most frequented entrepot. In the subsequent three centuries, the Ayyubids and Rasulids of Yemen also strove to control maritime routes and networks.L'historiographie en vigueur de l'Océan Indien à l'époque précédant la venue des Ottomans et des Européens au XVIème siècle, décrit une aire commerciale généralement paisible parcourue aisément par des négociants cosmopolites par-delà les obstacles géographiques, ethniques, religieux et linguistiques. Cette contribution modifie cette image par un examen des témoignages des Vème/XIème et VIème/XIIe siècles qui attestent les conflits et rivalités des cités portuaires de Kish en la Golfe de Perse, de Dahlak en la Mer Rouge contestant la suprématie d'Aden, l'entrepôt le plus fréquenté. Durant les trois siècles suivants, les Ayyûbides et Rasûlides du Yémen s'efforcèrent également de contrôler les routes et réseaux maritimes.
The Nature and Role of Phenomenological Psychology in Alfred Schutz
Authors: Embree Lester
Published: September 2008

The essay reviews how phenomenological psychology can draw on Edmund Husserl's transcendental phenomenology in order to clarify the foundations of the cultural sciences and then explicates the theory of this psychology implicit in Schutz's oeuvre.Max Weber has shown that all phenomena of the socio-cultural world originate in social interaction and can be referred to it. According to him, it is the central task of sociology to understand the meaning which the actor bestows on his action (the “subjective meaning” in his terminology). But what is action, what is meaning, and how is the understanding of such meaning by a fellow-man possible, be he a partner of the social interaction, or merely an observer in everyday life, or a social scientist? I submit that any attempt to answer these questions leads immediately to questions with which Husserl was concerned and which he has to a certain extent solved. (Schutz, 1962, p. 145)
Relationship between Aortic Atherosclerosis and Dental Loss in an Inner-City Population
Authors: Castillo Ricardo , Fields Aurora , Qureshi Ghazanfar , Salciccioli Louis , Kassotis John , Lazar Jason M.
Published: September 2008

Prior studies have suggested an association between atherosclerosis and periodontal disease, both of which are more prevalent in certain minority and economically disadvantaged groups. Few studies have addressed the relationship between cardiovascular disease and dentition among ethnically diverse populations. We studied 131 subjects (60% females, age 59 ± 15 years) who were referred for clinically indicated transesophageal echocardiography. Dental loss was more severe in patients with hypertension ( P < .001), diabetes ( P = .05), coronary artery disease ( P = .04), and calcium channel blocker use ( P = .04). On univariate analysis, maximal aortic intima—media thickness (MAIMT) was significantly correlated with dental loss ( r = .40; P < .001). Age was correlated with MAIMT ( R = .41; P < .001) and with dental loss ( r = .57; P < .001). On multivariate analysis, dental loss ( P = .03) and history of coronary artery disease ( P = .04) were independent predictors of MAIMT ( R 2 = .44). In this inner-city predominantly African American population, atherosclerosis and dental loss are age dependent and are interrelated independent of age.
Aadamkhor Haseena (The Man-Eating Beauty) and the	anthropology of a moment
Authors: Singh Bhrigupati
Published: September 2008

In this article I trace certain related trajectories: the emergence and possible disappearance of the cinematic form of the soft-porn ‘morning show’; the waxing and waning arrangements of certain spaces in the city of Delhi, in particular cinema halls in Old Delhi; and lives enmeshed in this unstable itinerant matrix of cinema and the city. In confronting these situations of permanent mobility, we are led to the conceptual issue of time. Do the hands of a clock describe units of experience? Does time privilege movement or rest? How do we understand time in terms of both materiality and subjectivity? How do cinematic affects relate to durational experience? I address these questions by setting out the anthropology of a ‘moment’ as a way of understanding durational experience. The moment is conceptualised in two distinct but related forms: as a chronograph (that tracks trajectories of movement and matter) and as a crystal (that follows varying states of mind). Understanding the issue of time as a philosophical problem through the writings of Gilles Deleuze, I also consider what kind of relationship exists, or might exist, between anthropology and philosophy.
Narrative absence
Authors: Kaur Ravinder
Published: September 2008

The core of symbolic communities, like the community of Partition migrants, is formed through the discursive ownership of historical experiences—for instance, the loss of human lives, personal property and dismemberment of national territory; followed by the restoration of that loss through examples of successful refugee resettlement and national self-assertion. Within the master narrative of Partition migration history, however, the experiences of forced movement and resettlement suffered by the ‘Untouchables’ are obscured. Popular accounts of violence, forced movement and suffering are largely built around the narratives produced by upper caste and upper middle-class migrants and exclude the experiences of Untouchable migrants. This narrative absence becomes a gauge of both the discursive and physical exclusion of ‘Untouchable'refugees from the legitimate community of Partition migrants. Such a meta-version of Partition history constitutes the realm of the normal, outside which ‘Untouchable’ narratives exist as an aberration in the theme of modern citizen-making in post-colonial India. In this article, I examine these ‘aberrations’ to provide an alternate reading that helps us challenge the master narrative of Partition migration history.
A tale of two wards: political participation and the urban poor in Dhaka city
Authors: Banks Nicola
Published: September 2008

This paper investigates the extent of political participation of the urban poor in Dhaka, identifying the actors with whom the urban poor interact for problem solving and gaining access to services. Through a comparison of the different experiences of “active” and “non-active” poor residents across two wards, the research identifies barriers to effective political participation; it then considers how opportunities for participation can be advanced. The experience of the Coalition for the Urban Poor's (CUP) Basti Basheer Odhikar Surakha Committee (BOSC) illustrates how collective mobilization of the poor has been successful in incorporating the urban poor into municipal governance. However, alongside its successes, the research investigates constraints to such initiatives in terms of securing national commitment to urban poverty reduction.
With and beyond the state — co-production as a route to political influence, power and transformation for grassroots organizations
Authors: Mitlin Diana
Published: September 2008

This paper reviews the use of co-production — with state and citizens working together — as a grassroots strategy to secure political influence and access resources and services. To date, the literature on social movements has concentrated on more explicitly political strategies used by such movements to contest for power and influence. Co-production, when considered, is viewed as a strategy used by citizens and the state to extend access to basic services with relatively little consideration given to its wider political ramifications. However, co-production is used increasingly by grassroots organizations and federations as part of an explicit political strategy. This paper examines the use of co-productive strategies by citizen groups and social movement organizations to enable individual members and their associations to secure effective relations with state institutions that address both immediate basic needs and enable them to negotiate for greater benefits.
Budget sheets and buy-in: financing community-based waste management in Siem Reap, Cambodia
Authors: Parizeau Kate , Maclaren Virginia , Chanthy Lay
Published: September 2008

This paper details some of the difficulties in financing a community-based waste management (CBWM) project for the collection of waste in Siem Reap, Cambodia. It presents a series of financing scenarios based on several potential logistical arrangements. The financial variables investigated include labour costs and honorariums, collection fees, charges for secondary collection, land and equipment costs, and educational programmes. The case study illustrates how the loss of a political champion and a lack of cooperation by a private waste collection company derailed the financing of a CBWM project despite the presence of other favourable conditions for its success. The waste collection company's participation was fundamental to ensuring the affordability of secondary waste collection, and this one financial element greatly affected the feasibility of the entire system. The paper concludes that without buy-in and financial cooperation from all stakeholders, the best laid plans for CBWM (and the accompanying budget sheets) are rendered irrelevant.
Bridging local institutions and civil society in Latin America: can city-to-city cooperation make a difference?
Authors: Bontenbal Marike , Van Lindert Paul
Published: September 2008

In order to improve the quality of urban governance in cities in the South, it is believed that local institutions and citizens should be brought together more closely. To bridge the gap, there is a need both for citizen participation to have a stronger role in collective decision making and for institutional strengthening, to make local governments more responsive to community needs. This paper explores the role that North—South city-to-city cooperation can play as an instrument for meeting those needs. The outcome of two partnerships between cities in Nicaragua and Peru and their sister cities in the Netherlands is discussed in terms of the resulting support to urban governance. The case studies reveal that while city-to-city cooperation has a particular potential to strengthen local governments, their administrations, service delivery performance and levels of responsiveness, the outcome with regard to encouraging citizenship and citizen participation in urban decision making and development planning has been more modest.
Cities' contribution to global warming: notes on the allocation of greenhouse gas emissions
Authors: Satterthwaite David
Published: September 2008

This paper suggests that the contribution of cities to global anthropogenic greenhouse gas emissions is often overstated. Many sources suggest that cities are responsible for 75—80 per cent of all such emissions. But as statistics drawn from the IPCC's Fourth Assessment show, this considerably understates the contributions from agriculture and deforestation and from heavy industries, fossil-fuelled power stations and high-consumption households that are not located in cities. It is likely that, worldwide, less than half of all anthropogenic greenhouse gas emissions are generated within city boundaries. However, if greenhouse gas emissions from power stations and industries are assigned to the location of the person or institution who consumes them (rather than where they are produced), cities would account for a higher proportion of total emissions. But it would be misleading to attribute this to “cities” in general, since these emissions would be heavily concentrated in cities in high-income nations and they should be ascribed to the individuals and institutions whose consumption generates them, not to the places where they are located.
Towards action on social determinants for health equity in urban settings
Authors: Kjellstrom Tord , Mercado Susan
Published: September 2008

More than half of the global population now live in urban settings. Urbanization can and should be beneficial for health. In general, nations with high life expectancies and low infant mortality rates are those where city governments address the key social determinants of health. Better housing and living conditions, access to safe water and good sanitation, efficient waste management systems, safer working environments and neighbourhoods, food security and access to services such as education, health, welfare, public transportation and child care are examples of social determinants of health that can be addressed through good urban governance. Failure of governance in today's cities has resulted in the growth of informal settlements and slums that constitute unhealthy living and working environments for one billion people. A credible health agenda is one that benefits all people in cities, especially the urban poor who live in informal settlements. International agreements calling for urgent action to reduce poverty, such as the Millennium Development Goals, can only be met through national strategies that include both urban and rural commitments and involve local governments and the poor themselves. Health inequalities in urban areas need to be addressed in countries at all income levels. Urban development and town planning are key to creating supportive social and physical environments for health and health equity. Achieving healthy urbanization in all countries is a shared global responsibility. Eliminating deprived urban living conditions will require resources — aid, loans, private investments — from more affluent countries in the order of US$ 200 billion per year, no more than 20 per cent of the annual increase in GDP in high-income countries. Creating global political support for a sustained and well-funded effort for social, economic and health equity is one of the greatest challenges of this generation.
The CD34-like protein PODXL and α6-integrin (CD49f) identify early progenitor MSCs with increased clonogenicity and migration to infarcted heart in mice
Authors: Lee Ryang Hwa , Seo Min Jeong , Pulin Andrey A. , Gregory Carl A. , Ylostalo Joni , Prockop Darwin J.
Published: September 2008

We screened for surface proteins expressed only by the early progenitor cells present in low-passage, low-density cultures of the adult stem/progenitor cells from bone marrow referred to as mesenchymal stem cells or multipotent stromal cells (MSCs). Six proteins were identified that were selectively expressed in the early progenitors: podocalyxin-like protein (PODXL), α6-integrin (CD49f), α4-integrin (CD49d), c-Met, CXCR4, and CX3CR1. All were previously shown to be involved in cell trafficking or tumor progression. Antibodies to CD49f and PODXL, a sialomucin in the CD34 family, were the most robust for FACScan assays. PODXLhi/CD49fhi MSCs were more clonogenic and differentiated more efficiently than PODXLlo/CD49flo cells. Inhibition of expression of PODXL with RNA interference caused aggregation of the cells. Furthermore, PODXLhi/CD49fhi MSCs were less prone to produce lethal pulmonary emboli, and larger numbers were recovered in heart and kidney after intravenous infusion into mice with myocardial infarcts.
Defective Notch activation in microenvironment leads to myeloproliferative disease
Authors: Kim Young-Woong , Koo Bon-Kyoung , Jeong Hyun-Woo , Yoon Mi-Jeong , Song Ran , Shin Juhee , Jeong Dae-Chul , Kim Sun-Hee , Kong Young-Yun
Published: September 2008

Despite the great importance of nonhematopoietic cells constituting the microenvironment for normal hematopoiesis, the cellular interactions between nonhematopoietic cells themselves are largely unknown. Using the Cre-loxP system in mice to inactivate Mind bomb-1 (Mib1), an essential component for Notch ligand endocytosis, here we show that the development of an MPD is dependent on defective Notch activation in the microenvironment. Our 2 independent Mib1 conditional knockout (CKO) mouse lines each developed a myeloproliferative disease (MPD), with gradual accumulations of immature granulocytes. The mutant mice showed hepatosplenomegaly, anemia, granulocytosis, and leukocyte infiltration in multiple organs and finally died at approximately 20 weeks of age. We were surprised to find that the transplantation of wild-type bone marrow cells into the Mib1-null microenvironment resulted in a de novo MPD. Moreover, by introducing the constitutively active intracellular domain of Notch1 in the Mib1-null background, we show that active Notch1 expression in the Mib1-null microenvironment significantly suppressed the disease progression, suggesting that the MPD development in the Mib1 CKO mice is due to defective Notch activation in the nonhematopoietic cells. These findings demonstrate that normal hematopoiesis absolutely requires Notch activation through the Notch ligand-receptor interaction between microenvironmental cells themselves and shed light on the microenvironment that fosters hematopoietic disorders.
An L-selectin ligand distinct from P-selectin glycoprotein ligand-1 is expressed on endothelial cells and promotes neutrophil rolling in inflammation
Authors: Shigeta Akiko , Matsumoto Masanori , Tedder Thomas F. , Lowe John B. , Miyasaka Masayuki , Hirata Takako
Published: September 2008

Neutrophils recruited from the blood are key players in the innate immune response. Selectins play critical roles in neutrophil recruitment by mediating their tethering and rolling in inflamed venules. While the roles of P- and E-selectin in this process are well established, the mechanisms of L-selectin–mediated neutrophil recruitment remain elusive. One proposal is that tethering is mediated by L-selectin on flowing neutrophils interacting with P-selectin glycoprotein ligand-1 (PSGL-1) on adherent neutrophils. To clarify whether L-selectin–mediated neutrophil recruitment depends entirely on PSGL-1, we examined the impact of L-selectin deficiency in mice with a PSGL-1–deficient background. L-selectin and PSGL-1 double-knockout mice exhibited a higher increase in their peripheral blood neutrophil count and a worse defect in neutrophil recruitment into the inflamed peritoneum than PSGL-1–deficient mice. Intravital microscopy of inflamed cremaster muscle venules showed that L-selectindeficiency or antibody blockade of L-selectin reduced the residual leukocyte rolling in PSGL-1–deficient mice. Flow cytometric analyses showed that the endothelial cells from the cremaster muscle bound L-selectin in a PSGL-1–independent manner. These results provide evidence for the existence of an L-selectin ligand distinct from PSGL-1 in inflammation and indicate that such a ligand is expressed on endothelial cells, promoting neutrophil rolling in vivo.
Mll5 contributes to hematopoietic stem cell fitness and homeostasis
Authors: Zhang Yan , Wong Jasmine , Klinger Mark , Tran Mary T. , Shannon Kevin M. , Killeen Nigel
Published: September 2008

MLL5 is a novel trithorax group gene and a candidate tumor suppressor gene located within a 2.5-Mb interval of chromosome band 7q22 that frequently is deleted in human myeloid malignancy. Here we show that inactivation of the Mll5 gene in mice results in a 30% reduction in the average representation of hematopoietic stem cells and in functional impairment of long-term hematopoietic repopulation potential under competitive conditions. Bone marrow cells from Mll5-deficient mice were defective in spleen colony-forming assays, and the mutant mice showed enhanced susceptibility to 5-fluorouracil–induced myelosuppression. Heterozygous and homozygous Mll5 mutant mice did not spontaneously develop hematologic cancers, and loss of Mll5 did not alter the phenotype of a fatal myeloproliferative disorder induced by oncogenic Kras in vivo. Collectively, the data reveal an important role for Mll5 in HSC homeostasis and provide a basis for further studies to explore its role in leukemogenesis.
Aurora-A kinase: a novel target of cellular immunotherapy for leukemia
Authors: Ochi Toshiki , Fujiwara Hiroshi , Suemori Koichiro , Azuma Taichi , Yakushijin Yoshihiro , Hato Takaaki , Kuzushima Kiyotaka , Yasukawa Masaki
Published: September 2008

Aurora-A kinase (Aur-A) is a member of the serine/threonine kinase family that regulates the cell division process, and has recently been implicated in tumorigenesis. In this study, we identified an antigenic 9–amino-acid epitope (Aur-A207-215: YLILEYAPL) derived from Aur-A capable of generating leukemia-reactive cytotoxic T lymphocytes (CTLs) in the context of HLA-A*0201. The synthetic peptide of this epitope appeared to be capable of binding to HLA-A*2402 as well as HLA-A*0201 molecules. Leukemia cell lines and freshly isolated leukemia cells, particularly chronic myelogenous leukemia (CML) cells, appeared to express Aur-A abundantly. Aur-A–specific CTLs were able to lyse human leukemia cell lines and freshly isolated leukemia cells, but not normal cells, in an HLA-A*0201–restricted manner. Importantly, Aur-A–specific CTLs were able to lyse CD34+ CML progenitor cells but did not show any cytotoxicity against normal CD34+ hematopoietic stem cells. The tetramer assay revealed that the Aur-A207-215 epitope–specific CTL precursors are present in peripheral blood of HLA-A*0201–positive and HLA-A*2402–positive patients with leukemia, but not in healthy individuals. Our results indicate that cellular immunotherapy targeting Aur-A is a promising strategy for treatment of leukemia.