bluuebunny/crossref_metadata_2025 huggingface dataset:
New Insights in the Treatment by Levofloxacin
Authors: File Jr. Thomas M.
Published: August 2004

Levofloxacin is widely regarded as one of the most important fluoroquinolones available today. It possesses excellent activity against a wide range of important pathogens, including those resistant to many other antimicrobials. While rates of resistance to other previously useful antimicrobial classes has grown, levofloxacin has maintained its efficacy, with generally very low rates of resistance around the world. It is indicated for a wide range of infections including community-acquired respiratory infections in adults, particularly community-acquired pneumonia (CAP), acute bacterial exacerbations of chronic bronchitis (AECB), and acute sinusitis. In addition, it is recommended for infections of skin and soft tissue, and the urinary tract. With postmarketing surveillance data available for the last decade, levofloxacin possesses an unparalleled database to demonstrate its clinical efficacy and safety. Remarkably, levofloxacin continues to expand its list of indications. The development of a new high-dose 750-mg schedule has the potential to decrease the duration of treatment as well as reduce the emergence of resistance.
Challenges in Addressing Community Concerns Regarding Clusters of Multiple Sclerosis and Potential Environmental Exposures
Authors: Williamson Dhelia M. , Henry Judy P.
Published: August 2004

Citizens living around hazardous waste sites in the USA have expressed concern to public health officials at the local, state and federal level about a perceived high prevalence of multiple sclerosis (MS) in their communities. Many believe the occurrence of the disease is directly linked to exposure to chemical agents from the nearby hazardous waste site. Although the public’s concern regarding these clusters should be addressed, epidemiologists have long known that evaluating perceived clusters is rarely fruitful for identifying an etiologic agent. In order to adequately address concerns regarding clusters of MS, as well as examining the role of environmental exposures and genetic susceptibility in the causal mechanism of disease, several activities need to be conducted including characterizing the occurrence of disease, developing a standardized case definition and establishing partnerships to develop innovative research techniques. Only with collaboration across disciplines and lessons learned from past research will we be able to effectively guide research efforts directed at determining the etiology of this disease.
Creation of a Bilingual Spanish-English Version of the Questionnaire for Verifying Stroke-Free Status
Authors: Castillo Pablo R. , Brott Thomas G. , Alvarez Salvador , Meschia James F.
Published: August 2004

Spanish-language versions of standardized questionnaires are important for facilitating inclusion of Hispanic populations in epidemiologic, genetic, and clinical studies. We aimed at producing a culturally adapted Spanish translation of the Questionnaire for Verifying Stroke-free Status (QVSS), an instrument used to screen for cerebrovascular end points and to ensure that subjects serving as controls in studies on stroke are indeed stroke free. Five professional translators and ten bilingual physicians independently translated the English-language version of the QVSS into Spanish. Blinded back-translation confirmed conceptual equivalence of the original English-language and final Spanish-language versions.
Regional Differences in Incidence Rates, Outcome Predictors and Survival of Stroke
Authors: Óváry Csaba , Suzuki Kazuo , Nagy Zoltán
Published: August 2004

The aim of our study was to compare subtype-specific incidence rates, case-fatality rates and outcome predictors in different geographical areas, and decide what drives the variations. Analyzing standardized, prospective stroke registers in the Akita Prefecture, Japan, and in Hungary with catchment areas of more than 1.2 and 1.5 million during the same 18 months, we assumed population and ethnic variations in subtype-specific incidence rates, indicating higher risk of ischemic stroke in Hungary and higher risk of hemorrhagic stroke in Japan. The determinants of 28-day case-fatality rates, at least in part, also varied in different populations. However, survival from stroke was mainly influenced by stroke management.
Protection against Acoustic Trauma by Forward and Backward Sound Conditioning
Authors: Niu Xianzhi , Tahera Yeasmin , Canlon Barbara
Published: August 2004

The purpose of the present study was to determine if short-term sound conditioning provides protection when delivered either before (forward sound conditioning) or after (backward sound conditioning) a traumatic exposure in the guinea pig. Two different sound conditioning paradigms were studied (1 kHz, 81 dB SPL, 24 h; 6.3 kHz, 78 dB SPL, 24 h). The 1-kHz forward sound conditioning paradigm (81 dB SPL, 24 h) protected distortion product otoacoustic emissions (DPOAEs) against a short-duration acoustic trauma (2.7 kHz, 103 dB SPL, 5 min) compared to the group exposed to the acoustic trauma alone. The 1-kHz forward sound conditioning paradigm (81 dB SPL, 24 h) also protected both the auditory brainstem response (ABR) thresholds and DPOAEs against a longer-duration acoustic trauma (2.7 kHz, 103 dB SPL, 30 min). The group exposed to the acoustic trauma alone showed ABR threshold shifts between 15 and 24 dB, and DPOAE amplitude shifts between 11 and 24 dB, while the group with 1-kHz forward sound conditioning showed statistically significant protection at all ABR frequencies and at all DPOAE frequencies. The 1-kHz backward sound conditioning paradigm protected against acoustic trauma (2.7 kHz, 103 dB SPL, 30 min). The ABR thresholds were protected at 1, 2 and 4 kHz, and DPOAEs at all frequencies (except 8 kHz) when compared to the group exposed only to the acoustic trauma. The 6.3-kHz forward sound conditioning paradigm protected against acoustic trauma (5.5 kHz, 109 dB SPL, 30 min) at 6.3, 8 and 10 kHz. The 6.3-kHz backward sound conditioning paradigm showed no protection against acoustic trauma at any DPOAE frequency. Taken together, these findings are important for understanding how the auditory system can be modulated by acoustic stimulation and highlights the importance of the acoustic environment during the recovery process of the auditory system.
The Role of the FcεRI β-Chain in Allergic Diseases
Authors: Kraft Stefan , Rana Shalini , Jouvin Marie-Hélène , Kinet Jean-Pierre
Published: August 2004

The high affinity receptor for IgE, FcΕRI, is a multimeric surface receptor that is expressed exclusively as a tetramer on rodent cells, but exists as a tetramer or trimer on human cells. The tetrameric form is expressed on effector cells of allergic responses such as mast cells and basophils and is composed of an IgE-binding α-subunit, a β-subunit and a γ-subunit dimer. Complexes lacking the β-subunit are found on human antigen-presenting cells. On mast cells and basophils, FcΕRI is essential for IgE-mediated acute allergic reactions. Crosslinking of FcΕRI by IgE and multivalent antigen induces a signaling cascade that culminates in the release of preformed mediators and the synthesis of lipid mediators and cytokines. The β-subunit functions as an amplifier of FcΕRI expression and signaling. As a consequence, strongly enhanced mast cell effector functions and in vivo allergic reactions can be observed in the presence of FcΕRIβ. In contrast, a truncated β-isoform (βT) that is produced by alternative splicing acts as an inhibitor of FcΕRI surface expression. Thus, by producing two proteins with antagonistic functions, the FcΕRIβ gene could serve as a potent regulator of allergic responses. In addition, the genomic region encompassing the β-chain has been linked to atopy and a number of polymorphisms within the FcΕRIβ gene are associated with various atopic diseases. It remains to be elucidated how these polymorphisms might affect the allergic phenotype. These functions of the β-chain together with the described genetic linkages to atopy make it a candidate for a role in the pathophysiology of allergic diseases.
Association of Gender and Age with Erythropoietin Resistance in Hemodialysis Patients: Role of Menstrual Status
Authors: Di Iorio Biagio R. , Stellato Davide , de Santo Natale G. , Cirillo Massimo
Published: August 2004

Background: Female gender is associated with high erythropoietin (EPO) resistance in end-stage renal disease. The aim of our study was to investigate the roles of age and menstrual status in this relationship. Methods: Cross-sectional analysis of registry data for 3,224 hemodialysis adults treated with EPO. Data collection included gender, age, weight, height, dialytic age, hemoglobin, EPO dose, and, for women with ages 25–44 only, also information on menstrual status and iron homeostasis. EPO resistance index (ERI) was calculated as EPO dose per kilogram BW/hemoglobin. Results: Men and women had not significantly different hemoglobin and significantly different EPO dose per kilogram weight (women vs. men, +18.2%, p < 0.001). Thus, ERI was higher in women than in men (+19.5%, p < 0.001). The gender-associated difference in ERI linearly decreased along age groups: +30.9% for ages 25–44, +23.2% for ages 45–64, and +14.2% for ages 65–84 (p < 0.05 for interaction between age and gender-associated difference in ERI). Within the subgroup of women with ages 25–44, women with menses in comparison to women without had 44.6% higher ERI (p < 0.01) due to combination of lower hemoglobin (p < 0.05) with higher EPO dose (p < 0.001). Women with menses had also lower serum iron, transferrin saturation, and serum ferritin (p < 0.001). Conclusion: The gender-associated difference in ERI is lower with increasing patients’ age. The large difference between young men and women is due to women with menses who have iron deficiency more frequently than women without periods.
The Claustrum Is Not Missing from All Monotreme Brains
Authors: Ashwell Ken W. S. , Hardman Craig , Paxinos George
Published: August 2004

Many authors have reported that the claustrum, which comprises the insular claustrum and the endopiriform nucleus, is missing from the monotreme forebrain. We used Nissl and myelin staining in conjunction with enzyme histochemistry for acetylcholinesterase and immunohistochemistry for parvalbumin, calbindin, calretinin and tyrosine hydroxylase to examine the brains of two monotremes, the short-beaked echidna (Tachyglossus aculeatus) and the platypus (Ornithorhynchus anatinus). We found that although the insular claustrum is a small structure in the echidna brain, it is nevertheless clearly present as loosely clustered neurons embedded in the white matter ventrolateral to the putamen and deep to the piriform and entorhinal cortices. Neurons in this region share the chemical features of the adjacent cortex (presence of a similar proportion of parvalbumin immunoreactive neurons and minimal activity for acetylcholinesterase and tyrosine hydroxylase), unlike the adjacent putamen and ventral pallidum. A putative endopiriform nucleus can be identified in the interior of the piriform lobe of the echidna as calretinin immunoreactive neurons embedded within the white matter. The situation is much less clear in the platypus, but our data suggest that there may be an insular claustrum deep to frontal cortex, separated from layer VI by only a thin layer of white matter. We could not identify an endopiriform nucleus in our platypus material. Our findings indicate that presence of the claustrum cannot be considered a feature confined to therian mammals and lend weight to arguments that this structure was present in the ancestral mammalian brain.
Reduced Attention Shift in Response to Auditory Changes in Subjects with Tinnitus
Authors: Cuny Caroline , Norena Arnaud , El Massioui Farid , Chéry-Croze Sylviane
Published: August 2004

A current idea about the persistence of tinnitus is that fixation of this phantom auditory perception in the central auditory system may be influenced by attention to it. The present study investigated the mechanisms of involuntary attention and analysed performance in categorising sounds in tinnitus, simulated-tinnitus and control subjects. The sounds were presented in one ear and were preceded by presentation of frequent and deviant stimuli in the other ear. The results showed classical attention capture by deviant stimuli. In addition, the unilateral tinnitus subjects responded more accurately in the tinnitus ear than in the non-tinnitus ear. In contrast, the ‘simulated-tinnitus’ group showed no difference in the results between the ear where the tinnitus simulation was presented and the opposite ear. These findings suggest a difficulty in attention directing when the attention location coincides with the tinnitus ear and provides evidence for an attention focus on the tinnitus ear.
Regulation of Plasma High-Density Lipoprotein Levels by the ABCA1 Transporter and the Emerging Role of High-Density Lipoprotein in the Treatment of Cardiovascular Disease
Authors: Brewer H. Bryan , Remaley Alan T. , Neufeld Edward B. , Basso Federica , Joyce Charles
Published: August 2004

High-density lipoproteins (HDL) protect against cardiovascular disease. HDL removes and transports excess cholesterol from peripheral cells to the liver for removal from the body. HDL also protects low-density lipoproteins (LDL) from oxidation and inhibits expression of adhesion molecules in endothelial cells, preventing monocyte movement into the vessel wall. The ABCA1 transporter regulates intracellular cholesterol levels in the liver and in peripheral cells by effluxing excess cholesterol to lipid-poor apoA-I to form nascent HDL, which is converted to mature α-HDL by esterification of cholesterol to cholesteryl esters (CE) by lecithin cholesterol acyltransferase. The hepatic ABCA1 transporter and apoA-I are major determinants of levels of plasma α-HDL cholesterol as well as poorly lipidated apoA-I, which interact with ABCA1 transporters on peripheral cells in the process of reverse cholesterol transport. Cholesterol in HDL is transported directly back to the liver by HDL or after transfer of CE by the cholesteryl ester transfer protein (CETP) by the apoB lipoproteins. Current approaches to increasing HDL to determine the efficacy of HDL in reducing atherosclerosis involve acute HDL therapy with infusions of apoA-I or apoA-I mimetic peptides and chronic long-term therapy with selective agents to increase HDL, including CETP inhibitors.
Hemodynamic Regulation of CD34
+
Cell Localization and Differentiation in Experimental Aneurysms
Authors: Sho Eiketsu , Sho Mien , Nanjo Hiroshi , Kawamura Koichi , Masuda Hirotake , Dalman Ronald L.
Published: August 2004

Objectives—

Bone marrow-derived vascular progenitor cells (CD34
+
) are present in human and animal models of abdominal aortic aneurysm (AAA) disease. These preterminally differentiated cells may modulate disease resistance. We examined the influence of variable hemodynamic conditions on progenitor cell localization and differentiation in experimental AAAs.

Methods and Results—

Murine AAAs were created via porcine pancreatic elastase (PPE) infusion. AAA blood flow was increased by aortocaval fistula (ACF) formation (HF-AAA), decreased via left iliac ligation (LF-AAA), or left unchanged (NF-AAA). ACF creation increased flow by 1700%, whereas iliac ligation decreased flow 79% compared with baseline (0.6±0.1 mL/min). Wall shear stress (WSS) increased or decreased accordingly, and remained elevated (9.2±2.0 dynes/cm
2
) in HF-AAA 14 days after PPE infusion. CD34
+
cells were identified throughout the aortic wall in all flow conditions. Seven days after PPE infusion, HF-AAAs had more CD34
+
cells than LF-AAA (187±10 versus 155±7 CD34
+
cells/cross sectional,
P
<0.05), more medial smooth muscle cells, fewer infiltrative macrophages, and a smaller diameter than LF-AAA. LF-AAAs also contained more adventitial capillaries (CD34
+
capillaries 181±12 versus 89±32/cross-sectional area in HF-AAA,
P
<0.05). The total progenitor cell/capillary index (CD34
+
capillary plus CD31
+
capillary/cross sectional area) was higher in LF-AAA (282±31 versus 129±47,
P
<0.05). Vascular endothelial (VEGF) and platelet-derived growth factor (PDGF) expression varied directly with capillary density between groups. Increased granulocyte-macrophage colony-stimulating factor (GM-CSF) expression was also present in LF-AAAs.

Conclusions—

Hemodynamic conditions influence CD34
+
cell localization and differentiation in experimental AAA. Adventitial capillary angiogenesis may augment inflammation and disease progression. Modulating cell lineage differentiation of mature progenitor cells may represent a novel therapeutic strategy to maintain medial cellularity and extracellular matrix integrity in AAA disease.
Oxidized Low-Density Lipoproteins Stimulate Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) Release by Coronary Smooth Muscle Cells
Authors: Haug Cornelia , Lenz Christina , Díaz Fredy , Bachem Max G.
Published: August 2004

Objective—Matrix metalloproteinases (MMPs) seem to play a prominent role in atherogenesis. Extracellular MMP inducer (EMMPRIN), a cell surface glycoprotein which stimulates MMP synthesis, has recently been detected in human atheroma. We have investigated the influence of oxidized low-density lipoproteins (oxLDLs) on EMMPRIN expression in human coronary artery smooth muscle cells (HCA-SMCs).

Methods and Results—OxLDL induced a significant increase of EMMPRIN release into HCA-SMC supernatants and a concomitant decrease of cell-associated EMMPRIN. These effects were antagonized by antioxidants as well as by EDTA and the MMP inhibitor GM6001. Western blot analysis demonstrated that MMP-1 and MMP-2 induce the cleavage of the extracellular domain from cell-associated EMMPRIN. MMP-1 and MMP-2 synthesis was upregulated by oxLDL, and, in addition, we have shown that soluble EMMPRIN, isolated from macrophage supernatants, increased MMP-1 and MMP-2 synthesis in HCA-SMC.

Conclusion—Our data suggest that oxLDLs stimulate the release of soluble EMMPRIN, at least in part, by MMP-dependent shedding from the cell surface. Additionally, oxLDLs might induce a circular upregulation of matrix degradation because, in turn, soluble EMMPRIN stimulates MMP synthesis in HCA-SMC.
C-Reactive Protein-Induced In Vitro Vasorelaxation Is an Artefact Caused by the Presence of Sodium Azide in Commercial Preparations
Authors: van den Berg Carmen W. , Taylor Karolina E. , Lang Derek
Published: August 2004

Objective—

Although C-reactive protein (CRP) is increasingly recognized as an independent risk factor for acute myocardial events, recent evidence suggests that it can directly induce vasorelaxation. This study aimed to investigate the mechanism of this CRP-induced response.

Methods and Results—

Isometric tension recordings were used to measure endothelium-dependent and endothelium-independent vascular smooth muscle relaxation in isolated rabbit aortic rings. CRP generated in-house by genetic engineering and expressed in Chinese hamster ovary cells, CRP purified from ascites, and CRP obtained from commercial sources were assessed for vasorelaxing properties. Only the commercial CRP preparation induced vasorelaxation; more than half maximal relaxation was observed at 0.025 μg/mL and maximum relaxation attained at 0.25 μg/mL. Commercial CRP contains high levels of sodium azide, a well-known vasorelaxant. Removal of this agent by dialysis abolished the vasodilatory effect of commercial CRP. Sodium azide alone at concentrations equivalent to that present in the commercial CRP produced a near-identical relaxation pattern to the undialyzed commercial product.

Conclusions—

CRP has no vasorelaxant properties per se, and the reported vasorelaxant ability of CRP is an artifact caused by sodium azide present in commercial preparations of this agent.
High-Density Lipoproteins Retard the Progression of Atherosclerosis and Favorably Remodel Lesions Without Suppressing Indices of Inflammation or Oxidation
Authors: Choudhury Robin P. , Rong James X. , Trogan Eugene , Elmalem Valerie I. , Dansky Hayes M. , Breslow Jan L. , Witztum Joseph L. , Fallon John T. , Fisher Edward A.
Published: August 2004

Objective—Protective properties of high-density lipoproteins (HDL) may include reverse cholesterol transport and suppression of oxidation and inflammation. These were investigated in vivo, as were the effects of HDL on the characteristics of atherosclerotic lesions.

Methods and Results—Male apolipoprotein E knockout (apoE−/−) and apoE−/− mice expressing human apolipoprotein AI (hAI/apoE−/−) were studied up to 20 weeks after commencing a high-fat diet. Plasma HDL cholesterol was twice as high in hAI/apoE−/− mice. Over time, aortic root lesion area remained less in hAI/apoE−/− mice, although plaques became complex. In advanced lesions, plaque lipid was higher in apoE−/− mice, whereas plaque collagen and alpha actin were increased in hAI/apoE−/− mice. In nonlesional aorta, mRNA abundance for pro-inflammatory proteins (vascular cell adhesion molecule [VCAM]-1, intercellular adhesion molecule-1 [ICAM-1], monocyte chemoattractant protein-1 [MCP-1]) increased between 4 and 16 weeks in apoE−/− (but not wild-type) mice, and were not reduced by elevated HDL. Autoantibodies to malondialdehyde low-density lipoprotein (LDL) increased progressively in apoE−/− mice, with similar results in hAI/apoE−/− mice.

Conclusions—HDL retarded plaque size progression despite greatly elevated plasma cholesterol. This effect was over a wide range of lesion severity. Expression of hAI reduced plaque lipid and increased the proportion of plaque occupied by collagen and smooth muscle cells, but did not affect indicators of inflammation or LDL oxidation.
Human Endothelial Progenitor Cells Tolerate Oxidative Stress Due to Intrinsically High Expression of Manganese Superoxide Dismutase
Authors: He Tongrong , Peterson Timothy E. , Holmuhamedov Ekhson L. , Terzic Andre , Caplice Noel M. , Oberley Larry W. , Katusic Zvonimir S.
Published: August 2004

Objective—

Endothelial progenitor cells (EPCs) display a unique aptitude to promote angiogenesis and restore endothelial function of injured vessels. How progenitor cells can execute a regenerative program in the unfavorable environment of injury/inflammation-induced oxidative stress is poorly understood. We hypothesized that EPCs are resistant to oxidative stress and that this resistance is due to high expression and activity of antioxidant enzymes.

Methods and Results—

EPCs outgrown from human blood of healthy subjects demonstrated a marked resistance to cytotoxic effect of LY83583 (an

generator), tumor necrosis factor-α, and serum depletion. LY83583 inhibited in vitro tube formation by human umbilical vein endothelial cells (HUVECs) and human coronary artery endothelial cells (CAECs), but not by EPCs. Compared with HUVECs and CAECs, EPCs exhibited ≈3- to 4-fold higher expression and activity of manganese superoxide dismutase (MnSOD), but not copper zinc superoxide dismutase (CuZnSOD) or catalase. The antioxidant profile in EPCs was associated with preservation of the mitochondrial network when exposed to LY83583. Moreover, cytotoxic effects of LY83583 on CAECs and HUVECs were reversed by adenoviral overexpression of MnSOD.

Conclusions—

Human EPCs are resistant to oxidative stress. High intrinsic expression of MnSOD is a critical mechanism protecting EPCs against oxidative stress.
Chemokines
Authors: Weber Christian , Schober Andreas , Zernecke Alma
Published: August 2004

Understanding the increasingly complex role of chemokines in various manifestations of atherosclerotic vascular disease and the apparent redundancy in their expression requires improved concepts defining the specialization and cooperation of chemokines in regulating the recruitment of mononuclear cells to vascular lesions. In an attempt to elaborate such models, this review highlights recent insights into the functional role of chemokines in mediating distinct steps during the atherogenic recruitment of monocytes and T cells obtained in genetically deficient mice and in suitable models. A particular focus is placed on the contribution of platelet chemokines deposited on endothelium for monocyte arrest, on differences in the involvement of chemokines between recruitment to native lesions and to neointimal lesions after arterial injury, and on closely related functions of macrophage migration inhibitory factor, a cytokine with considerable structural homology to chemokines. As an evolving aspect of atherosclerotic vascular disease, a role of chemokines, foremost stromal cell-derived factor-1α, in the recruitment of mononuclear progenitors of vascular cells during neointimal hyperplasia, endothelial recovery, and angiogenesis is discussed. The functional diversity and pleiotropy of chemokines in and beyond mononuclear cell recruitment awaits further elucidation to enable therapeutic targeting of atherogenesis by context-specific blockade of nonoverlapping chemokine receptor pairs.
Inhibition of Rho-Kinase Leads to Rapid Activation of Phosphatidylinositol 3-Kinase/Protein Kinase Akt and Cardiovascular Protection
Authors: Wolfrum Sebastian , Dendorfer Andreas , Rikitake Yoshiyuki , Stalker Timothy J. , Gong Yulan , Scalia Rosario , Dominiak Peter , Liao James K.
Published: August 2004

Objective—

Rho-Kinase activity is increased in cardiovascular diseases and in patients with cardiovascular risk factors. However, it is not known whether inhibition of Rho-kinase could lead to cardiovascular protection and, if so, by what mechanism.

Methods and Results—

In human endothelial cells, the Rho-kinase inhibitor, hydroxyfasudil (HF) (1 to 100 μmol/L), increased Akt serine-473 phosphorylation within 15 minutes, leading to a 2.2-fold and 4.0-fold increase in Akt kinase activity and nitric oxide (NO) release, respectively. Activation of Akt and eNOS by HF was completely blocked by the phosphatidylinositol 3-kinase (PI3-kinase) inhibitor, LY294002 (10 μmol/L). To determine the physiological relevance of this pathway, we used 2 models of ischemia-reperfusion (I/R) injury. Acute administration of fasudil (10 mg/kg, intraperitoneal, 1 hour before ischemia) decreased leukocyte recruitment and adhesion to the mesenteric endothelium after I/R injury in wild-type but not eNOS
−/−
mice. Similarly, treatment with fasudil decreased myocardial infarct size by 38% in rats subjected to transient coronary artery occlusion. Cotreatment with 2 PI3-kinase inhibitors, wortmannin and LY294002, or the eNOS inhibitor,
l
-NAME, blocked the cardiovascular protective effects of fasudil.

Conclusions—

Inhibition of Rho-kinase leads to the activation of the PI3-kinase/Akt/eNOS pathway and cardiovascular protection. These findings suggest that Rho-kinase may play an important role in mediating the inflammatory response to I/R injury.
Bone Marrow–Derived Cells for Enhancing Collateral Development
Authors: Kinnaird Tim , Stabile Eugenio , Burnett Mary Susan , Epstein Stephen E.
Published: August 2004

Initial animal studies of single angiogenic agents, such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), generated enthusiasm for the concept that these agents might enhance collateral development and thereby provide alternative therapies for patients with vascular disease not amenable to traditional revascularization. The enthusiasm, apparently justified by the subsequent results of small nonrandomized phase-I clinical trials, was then tempered by the subsequent disappointing results of randomized clinical trials. In light of these disappointing results, investigators have pursued alternative strategies in an attempt to improve tissue perfusion. One such strategy is the utilization of bone marrow-derived cell therapy. This review discusses mechanistic pathways mediating the effects of such cell therapy, summarizes the animal and early clinical experience, and speculates on the potential of genetic manipulation of bone marrow-derived cells in an attempt to further enhance their potency.
Phosphorylation Regulates Id3 Function in Vascular Smooth Muscle Cells
Authors: Forrest Scott T. , Taylor Angela M. , Sarembock Ian J. , Perlegas Demetra , McNamara Coleen A.
Published: August 2004

Understanding the mechanisms that regulate cell cycle progression in vascular smooth muscle cells (VSMCs) is key to understanding and modulating vascular lesion formation. Results of the present study provide the first evidence that phosphorylation of the helix-loop-helix factor Id3 in VSMCs occurs in vitro and in vivo and provides a regulatory switch controlling Id3-induced regulation of p21
Cip1
and VSMC growth.
Vascular Reactivity in Heart Failure
Authors: Karim Syed M. , Rhee Albert Y. , Given Allison M. , Faulx Michael D. , Hoit Brian D. , Brozovich Frank V.
Published: August 2004

Congestive heart failure (CHF) is a clinical syndrome, which is the result of systolic or diastolic ventricular dysfunction. During CHF, vascular tone is regulated by the interplay of neurohormonal mechanisms and endothelial-dependent factors and is characterized by both central and peripheral vasoconstriction as well as a resistance to nitric oxide (NO)–mediated vasodilatation. At the molecular level, vascular tone depends on the level of regulatory myosin light chain phosphorylation, which is determined by the relative activities of myosin light chain kinase and myosin light chain phosphatase (MLCP). The MLCP is a trimeric enzyme with a catalytic, a 20-kDa and a myosin targeting (MYPT1) subunit. Alternative splicing of a 3′ exon produces leucine zipper positive and negative (LZ
+/−
) MYPT1 isoforms. Expression of a LZ
+
MYPT1 has been suggested to be required for NO-mediated smooth muscle relaxation. Thus, we hypothesized that the resistance to NO-mediated vasodilatation in CHF could be attributable to a change in the relative expression of LZ
+/−
MYPT1 isoforms. To test this hypothesis, left coronary artery ligation was used to induce CHF in rats, and both the dose response relationship of relaxation to 8-Br-cGMP in skinned smooth muscle and the relative expression of LZ
+/−
MYPT1 isoforms were determined. In control animals, the expression of the LZ
+
MYPT1 isoform predominated in both the aorta and iliac artery. In CHF rats, LVEF was reduced to 30±5% and there was a significant decrease in both the sensitivity to 8-Br-cGMP and expression of the LZ
+
MYPT1 isoform. These results indicate that CHF is associated with a decrease in the relative expression of the LZ
+
MYPT1 isoform and the sensitivity to 8-Br-cGMP–mediated smooth muscle relaxation. The data suggest that the resistance to NO-mediated relaxation observed during CHF lies at least in part at the level of the smooth muscle and is a consequence of the decrease in the expression of the LZ
+
MYPT1 isoform.
Microplasmin Reduces Ischemic Brain Damage and Improves Neurological Function in a Rat Stroke Model Monitored With MRI
Authors: Suzuki Yasuhiro , Chen Feng , Ni Yicheng , Marchal Guy , Collen Desire , Nagai Nobuo
Published: August 2004

Background and Purpose—

Microplasmin (μPli), a derivative of plasmin lacking the 5 “kringle” domains, was studied in a rat thrombotic stroke model with MRI monitoring.

Methods—

Brain ischemia was induced by middle cerebral artery (MCA) occlusion with photochemically induced thrombosis. Brain tissue damage was assessed at 1 hour and 24 hours after MCA occlusion by MRI and 2,3,5-triphenyl tetrazolium chloride (TTC) staining. Neurological symptoms were scored at 24 hours. Animals with insufficient evidence of significant jeopardized brain tissue on perfusion-weighted imaging (PWI) at 1 hour were excluded before randomization. Included animals were randomized (blinded) to controls (solvent), 7.5 or 10 mg/kg μPli, administered as an intravenous bolus 90 minutes after MCA occlusion (n=8 per dose group).

Results—

μPli treatment reduced cerebral damage measured by TTC staining at 24 hours, from 250±69 mm
3
(mean±SD) in controls to 150±30 and 170±62 mm
3
with 7.5 and 10 mg/kg μPli, respectively; it reduced the expansion of the PWI positive area between 1 and 24 hours, and it reduced neurological deficits from a Bederson score of 7 (6 to 9) in controls to 4.5 (3 to 8) and 4 (3 to 6), with 7.5 and 10 mg/kg μPli, respectively (median and range
P
<0.05 for each dose versus controls for all parameters).

Conclusions—

Bolus intravenous μPli given 90 minutes after thrombotic MCA occlusion in rats reduces cerebral ischemic damage and improves neurological dysfunction, suggesting that μPli could be beneficial in ischemic stroke patients.
Remodeling of Saccular Cerebral Artery Aneurysm Wall Is Associated With Rupture
Authors: Frösen Juhana , Piippo Anna , Paetau Anders , Kangasniemi Marko , Niemelä Mika , Hernesniemi Juha , Jääskeläinen Juha
Published: August 2004

Background and Purpose—

The cellular mechanisms of degeneration and repair preceding rupture of the saccular cerebral artery aneurysm wall need to be elucidated for rational design of growth factor or drug-releasing endovascular devices.

Methods—

Patient records, preoperative vascular imaging studies, and the snap-frozen fundi resected after microsurgical clipping from 66 aneurysms were studied. Immunostainings for markers of smooth muscle cell (SMC) phenotype, proliferation, and inflammatory cell subtypes and TUNEL reaction were performed.

Results—

Unruptured (24) and ruptured (42) aneurysms had similar dimensions (median diameter in unruptured 6 mm; median in ruptured 7 mm;
P
=0.308). We identified 4 basic types of aneurysm wall that associated with rupture: (1) endothelialized wall with linearly organized SMCs (17/66; 42% ruptured), (2) thickened wall with disorganized SMCs (20/66; 55% ruptured), (3) hypocellular wall with either myointimal hyperplasia or organizing luminal thrombosis (14/66; 64% ruptured), and (4) an extremely thin thrombosis-lined hypocellular wall (15/66; 100% ruptured). Apoptosis, de-endothelialization, luminal thrombosis, SMC proliferation, and T-cell and macrophage infiltration associated with rupture. Furthermore, macrophage infiltration associated with SMC proliferation, and both were increased in ruptured aneurysms resected <12 hours from rupture, suggesting that these were not just reactive changes.

Conclusions—

Before rupture, the wall of saccular cerebral artery aneurysm undergoes morphological changes associated with remodeling of the aneurysm wall. Some of these changes, like SMC proliferation and macrophage infiltration, likely reflect ongoing repair attempts that could be enhanced with pharmacological therapy.
Venous Thromboembolism After Acute Ischemic Stroke
Authors: Kelly J. , Rudd A. , Lewis R.R. , Coshall C. , Moody A. , Hunt B.J.
Published: August 2004

Background and Purpose—

We prospectively evaluated the prevalence and clinical risk factors for venous thromboembolism (VTE) after acute ischemic stroke using magnetic resonance direct thrombus imaging, a highly accurate noninvasive technique that directly visualizes thrombus.

Method—102 unselected patients with AIS receiving standard prophylaxis with aspirin and graded compression stockings (GCS) were sequentially recruited, underwent regular clinical assessments, and were screened for VTE.

Results—

The prevalence of all VTE, proximal deep vein thrombosis (PDVT), and pulmonary embolism (PE) after 21 days were 40%, 18%, and 12%, increasing to 63%, 30%, and 20% in patients with Barthel indices (BI) of ≤9 2 days after stroke (BI-2≤9). Clinical deep vein thrombosis and PE occurred in 3% and 5% overall; half these events were overlooked by the attending team. The true incidence of clinical events is probably higher because the natural history of subclinical PDVT was modified by screening and anticoagulation. BI-2≤9 or nonambulatory status 2 days after stroke were the clinical factors most strongly associated with subsequent VTE on univariate analysis. Odds ratios for any VTE and PDVT for BI-2≤9 versus >9 were 8.3 (95% CI, 2.7 to 25.2) and 8.1 (95% CI, 1.7 to 38.3) on multivariable analysis.

Conclusion—

BI ≤9 or nonambulatory status around the time of admission identifies a subgroup of acute ischemic stroke patients at very high risk for VTE in whom the current strategy of thromboprophylaxis may be inadequate. Future thromboprophylactic studies should focus on the patients at high risk defined in this study.
Intracranial Clot Lysis With Intravenous Microbubbles and Transcranial Ultrasound in Swine
Authors: Culp William C. , Porter Thomas R. , Lowery John , Xie Feng , Roberson Paula K. , Marky Louis
Published: August 2004

Background and Purpose—

Destruction of microbubbles by transcutaneous low-frequency ultrasound (LFUS) has been used to lyse adjacent clot and recanalize acutely thrombosed vessels. LFUS with intraarterial microbubbles has been shown to lyse cerebral clot rapidly in pigs without thrombolytic drugs. We hypothesized that intravenous platelet-targeted microbubbles with LFUS may be a rapid noninvasive technique to recanalize thrombosed intracerebral vessels.

Methods—

After angiography, 0.5 cc of autogenous thrombus was injected into 1 ascending pharyngeal artery of a pig, occluding it and the rete mirabile. These vessels connect the carotid to the internal carotid and are the main cerebral blood supply. Saline control or intravenous decafluorobutane-sonicated dextrose albumin microbubbles tagged with a subtherapeutic quantity of glycoprotein 2b/3a receptor inhibitor eptifibatide (75 U/kg plus 12 cc of microbubbles administered over 21 minutes), or eptifibatide control, was given with transcutaneous temporal LFUS (1 MHz at 2.0 W/cm
2
) for 24 minutes. Angiography followed with scoring of declotting and flow. The same protocol was repeated on the contralateral side with the other test fluid so each animal received a saline control and either tagged microbubble or eptifibatide alone.

Results—

Fifteen pigs completed the protocol with a mean clot age of 4.6 hours. Using tagged microbubbles, 6 of 8 achieved success compared with 0 of 7 receiving eptifibatide alone (
P
=0.007) and 1 of 15 receiving saline alone (
P
=0.02).

Conclusions—

Intravenous platelet-targeted microbubbles combined with transcranial LFUS can rapidly open acute intracranial thrombotic occlusions. Further development for ischemic stroke therapy is justified.
Interdisciplinary Collaboration in Digital Media Arts: A Psychological Perspective on the Production Process
Authors: Steinheider Brigitte , Legrady George
Published: August 2004

The complexity of digital media technologies requires artists to form teams of specialized experts integrating their contributions. Studies on interdisciplinary collaborations in organizational and scientific research-and-development teams have revealed that three processes—communication, coordination and knowledge-sharing—significantly influence their efficiency and effectiveness. This model was applied to an international and interdisciplinary digital media art production team to analyze the effects of team members' geographical dispersion, differing nationalities and heterogeneity of disciplines. The results are in accordance with previous studies of teams in corporate and scientific settings but also reveal differences between artistic and industrial product development processes.
Artistic Experiments on Telematic Nets: Recent Experiments in Multi-User Virtual Environments in Brazil
Authors: Prado Gilbertto
Published: August 2004

The author explores the transformation and derivations in the field of artistic experimentation on the Net. The article examines the accomplishments artists have made with the “new poetics” of the dynamic universe of telematic art, expressed in contemporary artistic production. The text introduces five distinctive projects in multi-user virtual environments that were recently produced in Brazil and then places the projects within the more general context of art on the Net.
Feel-in-Touch!: Imagination through Vibration: A Utopia of Vibro-Acoustic Technology, Puppetry and Multimedia Art
Authors: Özcan Oguzhan
Published: August 2004

This article introduces a conceptual design for an interactive artwork called Feel-in-Touch! Its aim is to improve the use of imagination in artworks using abstract images in the formats of interactive media and vibro-tactile aids. New technologies can visually realize every surrealistic narration we can imagine, but these technologies limit our perceptions by presenting only one way of imagining, instead of multiple alternatives. This restricts creative thinking. Working from the above assumption, this article explores how to increase the degree of imagination in an interactive artwork. The author discusses problems of the imagination in art and interactive media and summarizes current research on vibro-tactile and vibroacoustic applications. He then outlines Feel-in-Touch! and discusses the outputs of this conceptual design.
Reseau/Resonance: Connective Processes and Artistic Practice
Authors: Broeckmann Andreas
Published: August 2004

Most Internet art projects use the Net solely as a telematic and telecommunicative transmission medium that connects computers and servers and through which artists, performers and users exchange data, communicate and collaboratively create files and events. At the same time, however, some artists are exploring the electronic networks as specific socio-technical structures with their respective forms of social and machinic agency, in which people and machines interact in ways unique to this environment. The author discusses recent projects that use the Net as a performative space of social and aesthetic resonance in which notions of subjectivity, action and production are being articulated and reassessed. This text discusses the notion of “resonance” in order to think through these approaches to network-based art practices.
Art in the Space Age: Exploring the Relationship between Outer Space and Earth Space
Authors: Osaka Takuro
Published: August 2004

The author's interest in Space Art has taken several forms, including project proposals for the effective use of the International Space Station, research on the theme of the possibility of art in outer space, and conducting interviews with astronauts. He has also performed experiments in a micro-gravity environment generated by parabolic flight. This article provides an account of his plans and the results of these experiments.
Is Religion What We Want? Motivation and the Cultural Transmission of Religious Representations
Authors: Nichols Shaun
Published: August 2004

Many psychologists and philosophers have suggested that religious ideas emerge because they are motivationally attractive. This paper attempts to support a version of the motivational thesis by relying on religious creeds as a source of historical evidence. This simple source of evidence indicates that the cultural evolution of religious ideas is partly a function of the motivational attractiveness of the religious ideas.
A Cross-Cultural Developmental Analysis of Children's and Adults' Understanding of Illness in South Asia (India) and the United States
Authors: Raman Lakshmi , Gelman Susan
Published: August 2004

Forty-one Indian and American preschoolers, 48 first graders, 41 third graders, 43 fifth graders, and 48 college students were presented with vignettes that described symptoms of illnesses. Participants in both countries were presented with a biological, moral, psychological, and irrelevant choice for each of the illnesses. Results indicated that across all ages in both countries, the biological model was the most prominent. However, with increasing age Indian participants acknowledged significantly more moral and psychological causes than Americans. Participants' justifications revealed that Americans made explicit reference to germs whereas Indians primarily referred to contamination. This indicates that although the cultural backdrops between the two sets of populations are very different, there is a complex interaction of similarities and differences.
Speak before you Think: The Role of Language in Verb Concepts
Authors: Packiam Alloway Tracy , Corley Martin
Published: August 2004

This study investigates the role of language on verb concepts in a cross-linguistic environment. The inflectional morphology of verbs in Tamil is contrasted with Mandarin, a language that does not explicitly reflect tense changes in the same manner as Tamil and English. In the baseline condition in experiment 1, participants were required to rate the similarity of object picture pairs; and in the experimental condition, they were asked to rate the similarity of action picture pairs. In experiment 2, participants' similarity judgments and response latencies were recorded when they were presented with the object and action picture pairs. This allowed us to investigate the strength of linguistic influence when representing event concepts. Data from this study revealed a moderate influence of language on verb concepts in the target populations. There was a significant different in the response latencies of the Tamil and Chinese participants, although both language groups exhibited a similar response pattern in the action picture judgment task. This finding suggests that while both groups perceived the events similarly, language may be mediating their responses, resulting in longer response times for the Chinese participants. This could be because considering tense in Mandarin is not 'automatic' and requires extra work, possibly because it is not intrinsic to the verb.
Contradictions in Counter-Intuitive Beliefs and Naïve Dialecticism
Authors: Samson Alain
Published: August 2004

In an article aimed at complementing Boyer and Sperber's (relatively structural) views of counter-intuitive concepts and their robustness in the religious domain, Franks (2003) has recently drawn attention to the fact that the tolerance of such conflict or contradiction appears to be less domain-specific in some cultures, such as those found in East Asia. This paper follows up on this important point by highlighting the similarities and differences of the tolerance for contradictions evident in East Asian 'naïve dialecticism' and nonnatural religious representations. It is argued that, despite their dissimilarity with respect to the content represented, both types of tolerances may be structurally similar. Both could also be anchored in intuition, albeit in qualitatively different ways. Given the general tolerance of psychological contradiction among persons of East Asian cultures and the potential role of religion, the question whether there is a place for the study of 'tolerance of contradiction' in cross-cultural psychology and cognitive anthropology is raised.
Respondents in Asian Cultures (e.g., Chinese) are More Risk-Seeking and More Overconfident than Respondents in Other Cultures (e.g., in United States) but the Reciprocal Predictions are in Total Opposition: How and Why?
Authors: Li Shu , Fang Yongqing
Published: August 2004

Triggered by rather surprising findings that respondents in Asian cultures (e.g., Chinese) are more risk-seeking and more overconfident than respondents in other cultures (e.g., in United States) and that the reciprocal predictions are in total opposition, four experiments were designed to extend previous collective-culture oriented researches. Results revealed that (1) Singapore 21, which is a vision of Singapore in the 21st century and has highlighted the promotion of a collective culture, did not advocate greater risk-seeking but led to weaker overconfidence; (2) the knowledge of "financial help from social network" did not permit prediction of risk preference but the knowledge of "the value difference between possible outcomes" did; (3) the social network could be viewed not only as a positive "cushion" but also as a negative "burden" in both gain and loss domains of risky choices; (4) the predictions of the risk-as-value, risk-as-feelings and stereotype hypotheses were not consistent with the predicted risk preferences of others but the predictions of the economic-performance hypothesis were consistent with the predicted risk preferences as well as the predicted overconfidence of others. The implications for cross-cultural variations in overconfidence and for cross-cultural variations in risk-taking were discussed.