bluuebunny/crossref_metadata_2025 huggingface dataset:
Allergy Immunotherapy as an Early Intervention in Patients with Child-Onset Atopic Asthma
Authors: Nagaya Hiroshi , Maren Stephen , Nagaya Naomi
Published: November 2005

Background: In patients with bronchial asthma an effective treatment is required at early stages of the disease to prevent irreversible structural changes of the airways. The objective of this study was to evaluate the beneficial effects of our routine immunotherapy as an early intervention on FEV1 in patients with child-onset atopic asthma. Methods: Beneficial effects of successful immunotherapy on FEV1 were analyzed retrospectively in 43 unselected patients who received our routine standard subcutaneous immunotherapy with periodic FEV1 measurements and became asymptomatic. Results: Although there was no significant correlation between the duration of asthma symptoms prior to immunotherapy and the changes in FEV1 before and after immunotherapy in 43 unselected patients, there was a significant inverse correlation between these two parameters in 23 patients whose asthma duration was less than 20 years. As the FEV1 increased after immunotherapy in all 14 patients whose asthma duration was less than 5 years, the 43 patients were divided into a group 1 including these 14 patients and a group 2 including 29 patients whose asthma duration was more than 5 years. The FEV1 decreased in 7 of the 29 asymptomatic patients in group 2. There was no difference in the initial FEV1 between the two groups, but the final FEV1 and the mean of the average increase in FEV1 per year by immunotherapy were significantly higher in group 1 than in group 2. Conclusions: Immunotherapy should be started as early as possible at the youngest age in order to increase a beneficial effect of successful immunotherapy on FEV1 improvement.
Excretory-Secretory Products Produced by Paragonimus westermani Differentially Regulate the Nitric Oxide Production and Viability of Microglial Cells
Authors: Jin Youngnam , Lee Jae-Chul , Choi In Young , Kim Eun A. , Shin Myeong Heon , Kim Won-Ki
Published: November 2005

Background:Tissue-invading helminth parasites secrete a large amount of cysteine proteases that may play critical roles in tissue invasion and immune modulation. However, roles of excretory-secretory products (ESP) secreted by Paragonimus westermani in the activation and death of microglial cells in brain are poorly understood. Objectives: In the present study, we investigated whether ESP could regulate microglial nitric oxide (NO) production and viability. Methods: The NO production and cell viability were assessed by respectively measuring the formation of nitrite and the release of lactate dehyrogenase. Results:At a low (0.2 µg/ml) concentration, ESP significantly stimulated NO production with no apparent cell injury or death in cultured microglial cells. However, at high (≧2 µg/ml) concentrations, ESP induced severe cell death. Inhibition of inducible NO synthase significantly reduced the NO productivity, but not cytotoxicity, of ESP. Similarly, inhibitors of the extracellular signal-regulated kinase, p38 and nuclear factor kappa B also blocked only the NO productivity of ESP. Interestingly, heat inactivation did not hamper the ability of ESP to stimulate microglial NO production. Similarly, pretreatment with thiol-crosslinking reagents dramatically reduced both proteolytic activity and cytotoxicity of ESP, but did not alter NO production in microglial cells. Interestingly, although cysteine protease competitive inhibitors and thiol-alkylating reagents markedly reduced the proteolytic activity of ESP, they did not influence the NO productivity and cytotoxicity of ESP. Conclusion: The present results indicate that the NO production and cytotoxicity by ESP may be differentially regulated via unknown mechanisms, not related with cysteine protease activity.
Sopoongsan Inhibits Mast Cell-Mediated Anaphylactic Reactions and Inflammatory Cytokine Secretion
Authors: Na Ho-Jeong , Jeong Hyun-Ja , Shin Hye-Young , Kim Nam-Song , Um Jae-Young , Hong Seung-Heon , Kim Hyung-Min
Published: November 2005

Background: Mast cells are key effector cells in the early-phase allergic inflammation and in diverse immunological and pathological processes. Sopoongsan (SPS), a traditional Korean medicine, has been used as therapeutics for allergic diseases such as atopic dermatitis (AD). The precise effect in experimental models of SPS, however, remains unknown. In this report, we investigated the effect of SPS on mast cell-mediated anaphylactic reactions and cytokine production in in vivo and in vitro murine models. Methods: Compound 48/80-induced histamine and ear swelling were measured with the various concentrations of SPS. The amount of dye was determined colorimetrically after antidinitrophenyl IgE antibody-induced passive cutaneous anaphylaxis reaction. Secretion of tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8) and IL-6 in supernatants from HMC-1 cells was measured by a sandwich enzyme-linked immunosorbent assay. The expression level of nuclear factor (NF)-ĸB/Rel A in the nucleus and the activation of mitogen-activated protein kinases (MAPKs) were examined by Western blot analysis. Results: SPS inhibited the degranulation and histamine release from the rat peritoneal mast cells activated by compound 48/80. Compound 48/80-induced ear swelling was significantly reduced. SPS also showed an inhibitory effect of passive cutaneous anaphylaxis reaction. Significantly reduced levels (p < 0.05) of TNF-α, IL-8 and IL-6 were observed in the human mast cell line with SPS and SPS components. In addition, SPS inhibited an increase of NF-ĸB and extracellular signal-regulated kinase 1/2 activity. Conclusions: These findings suggest that SPS has an inhibitory effect on atopic allergic reaction and this might be useful for the clinical application to treat allergic diseases such as AD.
Critical Appraisal and Review of the Rankin Scale and Its Derivatives
Authors: New Peter Wayne , Buchbinder Rachelle
Published: November 2005

Background and Purpose:Efforts to reduce stroke burden require accurate assessment of outcomes in order to compare treatments. The Rankin Scale and its derivatives, the Modified Rankin Scale and the Oxford Handicap Scale, taken together, are among the most common outcome measures that have been used in stroke research. The aim of this study was to perform a critical appraisal of the clinimetric properties of these scales. It was also planned to review the use of these scales in a selection of articles to illustrate concerns raised by the critical appraisal. Summary of Review: A literature search was performed using electronic databases to locate relevant articles about the reviewed scales. The scales were appraised using a structured format regarding the following properties: purpose, development, presentation, language, method of administration, content validity, face validity, feasibility, construct validity, reliability, responsiveness, and generalizability. There are concerns in each of the appraised areas regarding the clinimetric properties of these scales. Conclusion: Further work is needed to improve the clinimetric properties of the reviewed scales to ensure that they are more useful tools in determining the outcome of stroke. Alternatively, a newer global outcome scale with improved clinimetric properties may be a better option for future stroke research.
Ritonavir Impairs Lipoprotein Lipase–Mediated Lipolysis and Decreases Uptake of Fatty Acids in Adipose Tissue
Authors: den Boer Marion A.M. , Berbée Jimmy F.P. , Reiss Peter , van der Valk Marc , Voshol Peter J. , Kuipers Folkert , Havekes Louis M. , Rensen Patrick C.N. , Romijn Johannes A.
Published: November 2005

Objective—The use of the HIV protease inhibitor ritonavir (RTV) is frequently associated with hypertriglyceridemia and lipodystrophy. The aim of our study was to determine the mechanism underlying the observed hypertriglyceridemia.

Methods and Results—Feeding female APOE*3-Leiden transgenic mice a Western-type diet supplemented with RTV (35 mg/kg per day) for 2 weeks resulted in a 2-fold increase in fasting plasma triglyceride (TG) levels, which was specific for very low–density lipoprotein (VLDL). RTV did not change the hepatic VLDL-TG production. Instead, RTV did increase the postprandial TG response to an oral fat load (area under the curve, 25.5±12.1 versus 13.8±6.8 mmol/L per hour in controls;P<0.05). Likewise, RTV hampered the plasma clearance of intravenously injected glycerol tri[3H]oleate-labeled VLDL–like emulsion particles (half time, 19.3±10.5 versus 5.0±1.3 minutes in controls;P<0.05) associated with a decrease of 44% in plasma lipoprotein lipase activity. Accordingly, RTV decreased the uptake of TG-derived fatty acids (FAs) into adipose tissue, as well as the uptake of albumin-bound FA.

Conclusions—We conclude that RTV causes hypertriglyceridemia via decreased lipoprotein lipase–mediated clearance of VLDL-TG. In addition, RTV specifically impairs the uptake of FA in adipose tissue, which may contribute to the lipodystrophy that is frequently observed in HIV-infected subjects on antiretroviral therapy.
Endothelial Nitric Oxide Synthase Activation by Tumor Necrosis Factor α Through Neutral Sphingomyelinase 2, Sphingosine Kinase 1, and Sphingosine 1 Phosphate Receptors
Authors: De Palma Clara , Meacci Elisabetta , Perrotta Cristiana , Bruni Paola , Clementi Emilio
Published: November 2005

Objective—

Tumor necrosis factor α (TNF-α), a key proinflammatory cytokine acting on the endothelium, activates endothelial nitric oxide synthase (eNOS). We have examined the signaling pathway leading to this activation and its biological role in endothelium, which are still unknown.

Methods and Results—

In human endothelial cells, we found that eNOS activation by TNF-α is time dependent and requires activation of Akt, a known eNOS activator. eNOS activation was preceded by sequential activation of neutral-sphingomyelinase-2 (N-SMase2) and sphingosine-kinase-1 (SK1) and generation of sphingosine-1-phosphate (Sph1P). Inhibition of N-SMase2 inhibited Sph1P formation, whereas inhibition of SK1 did not affect N-SMase2 activation by TNF-α. Blockade of N-SMase2, SK1, or the Sph1P receptors S1P
1
and S1P
3
, either by silencing or pharmacological inhibitors, prevented eNOS activation. Thus, eNOS is activated by TNF-α via S1P receptors, activated by Sph1P generated through N-SMase2 and SK1 activation. We found that nitric oxide generated through this pathway has a biological role, because it inhibits the expression of E-selectin and the adhesion of dendritic cells to the endothelium stimulated by TNF-α.

Conclusions—

This study establishes a previously undescribed link among TNF-α, Sph1P, and eNOS in a same signaling pathway of biological relevance in the process of endothelial cell activation by TNF-α.
Ferumoxtran-10–Enhanced MRI of the Hypercholesterolemic Rabbit Aorta
Authors: Hyafil Fabien , Laissy Jean-Pierre , Mazighi Mikael , Tchétché Didier , Louedec Liliane , Adle-Biassette Homa , Chillon Sylvie , Henin Dominique , Jacob Marie-Paule , Letourneur Didier , Feldman Laurent J.
Published: November 2005

Objective—

Ferumoxtran-10 is an MRI contrast agent, which accumulates in macrophages and induces magnetic susceptibility artifacts (MSAs). We evaluated the ability of ferumoxtran-10–enhanced MRI to quantify focal macrophage infiltration in the aortic wall of hypercholesterolemic rabbits.

Methods and Results—

Six weeks after a double-balloon injury of the infrarenal aorta, 12 hypercholesterolemic rabbits underwent MRI of the aorta before (first MRI) and after (second MRI) intravenous injection of ferumoxtran-10 (n=10) or saline (n=2). A third MRI was performed 5 days later to detect ferumoxtran-10–induced MSA in the aortic wall. Aortas were subsequently processed for histology, immunohistochemistry, and gelatin zymography studies. Injured aortas displayed a macrophage-rich neointima with high-matrix metalloproteinase 2 and 9 activities. Iron stain of injured aortas showed massive accumulation of ferumoxtran-10 in neointimal macrophages. Five days after the injection of ferumoxtran-10, MSAs were detected only in the injured aortas by in vivo MRI and were quantified indirectly using the percentage reduction of luminal area attributable to the extension of these MSAs in the aortic lumen. This parameter correlated with macrophage infiltration on corresponding aortic cross-sections (
r
=0.82;
P
<0.05).

Conclusion—

Ferumoxtran-10–enhanced MRI allows quantitative assessment of macrophage infiltration induced by balloon angioplasty in the aorta of hypercholesterolemic rabbits.
Migration and Growth Are Attenuated in Vascular Smooth Muscle Cells With Type VIII Collagen-Null Alleles
Authors: Adiguzel Eser , Hou Guangpei , Mulholland Diane , Hopfer Ulrike , Fukai Naomi , Olsen Bjorn , Bendeck Michelle
Published: November 2005

Objective—Type VIII collagen is upregulated after vascular injury and in atherosclerosis. However, the role of type VIII collagen endogenously expressed by smooth muscle cells (SMCs) and in the context of the vascular matrix microenvironment, which is rich in type I collagen, is not known. To address this, we have compared aortic SMCs from wild-type (WT) mice to SMCs from type VIII collagen-deficient (KO) mice when plated on type I collagen.

Methods and Results—Type VIII collagen was upregulated after wounding of WT SMCs. KO SMCs exhibited greater adhesion to type I collagen than WT SMCs (optical density [OD595]=0.458±0.044 versus 0.193±0.071). By contrast, the WT SMCs spread more (389±75% versus 108±14% increase in cell area), migrated further (total distance 80.6±6.2 μm versus 64.2±4.4 μm), and exhibited increased [3H]-thymidine uptake (160 000±22 300 versus 63 100±12 100 counts per minute) when compared with KO SMCs. Gelatin zymograms showed that WT SMCs expressed latent matrix metalloproteinase 2, whereas KO SMCs did not. Addition of exogenous type VIII collagen returned levels of KO SMC adhesion (OD595=0.316±0.038), migration (79.5±5.8 μm), and latent matrix metalloproteinase 2 expression to levels comparable to WT SMCs.

Conclusions—This study suggests that SMCs can modify the matrix microenvironment by producing type VIII collagen, using it to overlay type I collagen, and generating a substrate favorable for migration.
What Is So Special About Apolipoprotein AI in Reverse Cholesterol Transport?
Authors: Curtiss Linda K. , Valenta David T. , Hime Neil J. , Rye Kerry-Anne
Published: November 2005

An initial step in reverse cholesterol transport is the movement of unesterified cholesterol from peripheral cells to high-density lipoproteins (HDLs). This transfer usually occurs in extracellular spaces, such as the subendothelial space of a vessel wall, and is promoted by the interaction of lipid-free or lipid-poor apolipoprotein (apo)AI with ATP binding cassette A1 cellular transporters on macrophages (MΦ). Because HDL does not interact with MΦ ATP binding cassette A1 and apoAI is not synthesized by macrophages, this apoAI must be generated from spherical HDL. In this brief review, we propose that spherical apoAI is derived from HDL by remodeling events that are accomplished by proteins secreted by cholesteryl ester–loaded foam cells, including the lipid transfer proteins, phospholipid transfer protein, and cholesteryl ester transfer protein, and the triglyceride hydrolases hepatic lipase and lipoprotein lipase.
Ca
2+
/Calmodulin–Dependent Protein Kinase Modulates Cardiac Ryanodine Receptor Phosphorylation and Sarcoplasmic Reticulum Ca
2+
Leak in Heart Failure
Authors: Ai Xun , Curran Jerry W. , Shannon Thomas R. , Bers Donald M. , Pogwizd Steven M.
Published: November 2005

Abnormal release of Ca from sarcoplasmic reticulum (SR) via the cardiac ryanodine receptor (RyR2) may contribute to contractile dysfunction and arrhythmogenesis in heart failure (HF). We previously demonstrated decreased Ca transient amplitude and SR Ca load associated with increased Na/Ca exchanger expression and enhanced diastolic SR Ca leak in an arrhythmogenic rabbit model of nonischemic HF. Here we assessed expression and phosphorylation status of key Ca handling proteins and measured SR Ca leak in control and HF rabbit myocytes. With HF, expression of RyR2 and FK-506 binding protein 12.6 (FKBP12.6) were reduced, whereas inositol trisphosphate receptor (type 2) and Ca/calmodulin–dependent protein kinase II (CaMKII) expression were increased 50% to 100%. The RyR2 complex included more CaMKII (which was more activated) but less calmodulin, FKBP12.6, and phosphatases 1 and 2A. The RyR2 was more highly phosphorylated by both protein kinase A (PKA) and CaMKII. Total phospholamban phosphorylation was unaltered, although it was reduced at the PKA site and increased at the CaMKII site. SR Ca leak in intact HF myocytes (which is higher than in control) was reduced by inhibition of CaMKII but was unaltered by PKA inhibition. CaMKII inhibition also increased SR Ca content in HF myocytes. Our results suggest that CaMKII-dependent phosphorylation of RyR2 is involved in enhanced SR diastolic Ca leak and reduced SR Ca load in HF, and may thus contribute to arrhythmias and contractile dysfunction in HF.
Restoration of Cardiac Progenitor Cells After Myocardial Infarction by Self-Proliferation and Selective Homing of Bone Marrow–Derived Stem Cells
Authors: Mouquet Frédéric , Pfister Otmar , Jain Mohit , Oikonomopoulos Angelos , Ngoy Soeun , Summer Ross , Fine Alan , Liao Ronglih
Published: November 2005

Tissue-specific progenitor cells contribute to local cellular regeneration and maintain organ function. Recently, we have determined that cardiac side-population (CSP) cells represent a distinct cardiac progenitor cell population, capable of in vitro differentiation into functional cardiomyocytes. The response of endogenous CSP to myocardial injury, however, and the cellular mechanisms that maintain this cardiac progenitor cell pool in vivo remain unknown. In this report we demonstrate that local progenitor cell proliferation maintains CSP under physiologic conditions, with little contribution from extracardiac stem cell sources. Following myocardial infarction in adult mice, however, CSP cells are acutely depleted, both within the infarct and noninfarct areas. CSP pools are subsequently reconstituted to baseline levels within 7 days after myocardial infarction, through both proliferation of resident CSP cells, as well as through homing of bone marrow–derived stem cells (BMC) to specific areas of myocardial injury and immunophenotypic conversion of BMC to adopt a CSP phenotype. We, therefore, conclude that following myocardial injury, cardiac progenitor cell populations are acutely depleted and are reconstituted to normal levels by both self-proliferation and selective homing of BMC. Understanding and enhancing such processes hold enormous potential for therapeutic myocardial regeneration.
Detection of Thrombus in Acute Ischemic Stroke
Authors: Kim Eung Yeop , Lee Seung-Koo , Kim Dong Joon , Suh Sang-Hyun , Kim Jinna , Heo Ji Hoe , Kim Dong Ik
Published: November 2005

Background and Purpose—

Previous studies on the hyperdense middle cerebral artery (MCA) sign were conducted using ≥5-mm thickness noncontrast-computed tomography (NCT). The purpose of this study was to compare thin-section NCT with 5-mm NCT in the detection of thrombus in acute ischemic stroke.

Methods—

Enrolled were consecutive 51 patients with acute infarction in the anterior or MCA territory. All patients underwent both 5-mm NCT and either 1.25- or 1-mm thin-section helical NCT within 6 hours of symptom onset. Patients were assigned to either the single or multisegmental occlusion group, depending on the thrombus extent on thin-section NCT. Thin-section NCT and 5-mm NCT were compared in the detection of thrombi.

Results—

Thrombi were identified in 45 patients (88%) on thin-section NCT and 16 on 5-mm NCT (31%;
P
<0.001). No occlusion was seen in 6 patients. Both sensitivity and specificity of thin-section NCT in detection of thrombus were 100%.

Conclusions—

Acute thrombus can be detected with higher sensitivity on thin-section NCT than on 5-mm NCT, and its extent is more accurately determined on thin-section NCT.
Fibrinogen Is Associated With an Increased Risk of Alzheimer Disease and Vascular Dementia
Authors: van Oijen Marieke , Witteman Jacqueline C. , Hofman Albert , Koudstaal Peter J. , Breteler Monique M.B.
Published: November 2005

Background and Purpose—

Vascular and inflammatory factors may play an important role in the pathogenesis of dementia. Studies reported an association between plasma levels of inflammation markers and the risk of dementia. Both fibrinogen and C-reactive protein are considered inflammatory markers. Fibrinogen also has important hemostatic properties. We investigated the association of fibrinogen and C-reactive protein with dementia.

Methods—

The study was based on the prospective population-based Rotterdam Study. Fibrinogen was measured in a random sample of 2835 persons. High-sensitivity C-reactive protein was measured in the total cohort of 6713 persons. We identified 395 incident dementia cases during follow-up (mean, 5.7 years). We estimated the associations of fibrinogen and C-reactive protein with dementia using Cox proportional hazard models.

Results—

Persons with higher levels of fibrinogen had an increased risk of dementia. The hazard ratio for dementia per SD increase of fibrinogen was 1.26 (95% CI, 1.11 to 1.44), adjusted for age and gender, and 1.30 (95% CI, 1.13 to 1.50) after additional adjustment for cardiovascular factors and stroke. For Alzheimer disease, the adjusted hazard ratio was 1.25 (95% CI, 1.04 to 1.49), and for vascular dementia it was 1.76 (95% CI, 1.34 to 2.30). High levels of C-reactive protein were not associated with an increased risk of dementia.

Conclusions—

High fibrinogen levels were associated with an increased risk of both Alzheimer disease and vascular dementia, but levels of C-reactive protein were not. This suggests that the increased risk of dementia associated with fibrinogen is because of the hemostatic rather than the inflammatory properties of fibrinogen.
Conversion of Ischemic Brain Tissue Into Infarction Increases With Age
Authors: Ay Hakan , Koroshetz Walter J. , Vangel Mark , Benner Thomas , Melinosky Christopher , Zhu Mingwang , Menezes Nina , Lopez Chloe J. , Sorensen A. Gregory
Published: November 2005

Background and Purpose—

Brain regions normal on diffusion-weighted imaging (DWI) but abnormal on mean transit time (MTT) maps represent tissue at risk of infarction, yet the fate of these regions is quite variable. The imperfect correlation between tissue outcome and initial imaging parameters suggests that each patient’s brain may have different susceptibility to ischemic stress. We hypothesize that age is a marker for tissue susceptibility to ischemia and thus plays a role in determining tissue outcome in human stroke.

Methods—

Sixty patients with acute ischemic stroke and a region of DWI/MTT mismatch that was >20% of the DWI volume were included. All patients were scanned twice, within 12 hours of symptom onset and on day 5 or later. The percentage mismatch lost (PML) was calculated as percentage of initial DWI/MTT mismatch volume that was infarcted on the follow-up MRI. The statistical analysis explored relationships among the covariates age, Trial of Org 10172 in Acute Stroke Treatment (TOAST) subtypes, time-to-MRI, and initial DWI, MTT volume, mean arterial blood pressure and blood glucose level at admission, and previous history of hypertension and diabetes mellitus.

Results—

Univariate comparisons showed that age (
P
=0.003), hypertension (
P
=0.009), and diabetes mellitus (
P
=0.0002) were significantly associated with PML. Regression analyses showed age to be a significant covariate (
P
=0.02). The regression model predicted a change in PML of ≈0.65% per year. The adjusted proportion of variance (
R
2
) in PML that could be explained by age alone was 14%.

Conclusion—

Age-dependent increase in conversion of ischemic tissue into infarction suggests that age is a biological marker for the variability in tissue outcome in acute human stroke.
Facilitation of Sensory and Motor Recovery by Thermal Intervention for the Hemiplegic Upper Limb in Acute Stroke Patients
Authors: Chen Jia-Ching , Liang Chung-Chao , Shaw Fu-Zen
Published: November 2005

Background and Purpose—

Thermal stimulation (TS) is commonly used in orthopedic rehabilitation, but the role of TS in the facilitation of sensorimotor recovery in hemiplegic patients remains unknown. This study addressed the issue of TS intervention in the facilitation of functional outcomes.

Methods—

Forty-six stroke survivors were randomly assigned to standard rehabilitation treatment and standard treatment plus TS (30 minutes daily for 6 weeks). Twenty-nine patients completed the experiment. Six measures, including Brunnstrom stage, modified motor assessment scale, grasping strength, angles of wrist extension and flexion, sensation by monofilament, and muscle tone by modified Ashworth scale, were performed weekly to evaluate sensory and motor functional outcomes.

Results—

The performance of Brunnstrom stage and wrist extension and sensation were improved significantly after TS intervention. Recovery rates of 6 measures after TS were significantly higher than those of the control, except for grasping. Similar muscle tones were found in both groups.

Conclusion—

TS on the paretic hand significantly enhances the recovery of several aspects of sensory and motor functions in hemiplegic stroke patients.
Metalloporphyrin-Based Superoxide Dismutase Mimic Attenuates the Nuclear Translocation of Apoptosis-Inducing Factor and the Subsequent DNA Fragmentation After Permanent Focal Cerebral Ischemia in Mice
Authors: Lee Byung I. , Chan Pak H. , Kim Gyung W.
Published: November 2005

Background and Purpose—

Recently, apoptosis- inducing factor (AIF), a mitochondrial proapoptotic protein, and its nuclear translocation have been reported in caspase-independent neuronal apoptosis. In this study, we investigated the contribution of reactive oxygen species (ROS) to the nuclear translocation of AIF and the subsequent DNA fragmentation after permanent focal cerebral ischemia (pFCI) using manganese tetrakis (4-benzoic acid) porphyrin (MnTBAP), which mimics mitochondrial superoxide dismutase.

Method—

Adult male ICR mice were subjected to pFCI by intraluminal suture blockade of the middle cerebral artery. Immunohistochemistry and Western blot analysis were performed. Large-scale DNA fragmentation was evaluated by pulse field gel electrophoresis, and apoptotic cell death was quantified. MnTBAP was injected into the ventricle to determine whether the removal of ROS contributes to AIF translocation and the subsequent DNA fragmentation.

Results—

Western blot analysis showed that the nuclear translocation of AIF occurred as early as 2 hours after pFCI. AIF translocation was not blocked by a pan-caspase inhibitor. MnTBAP-treated mice had attenuated AIF translocation and blocked large-scale DNA fragmentation. Caspase-3 activity was similarly inhibited between the pan-caspase inhibitor– and MnTBAP-treated mice, but the amount of apoptosis-associated DNA fragmentation in the MnTBAP-treated mice was less than in the pan-caspase inhibitor–treated mice (
P
<0.001).

Conclusion—

These results suggest that the MnTBAP, a mitochondrial O
2
−
scavenger, may attenuate the caspase-independent nuclear translocation of AIF after pFCI and subsequent apoptosis-associated DNA fragmentation.
Constrictor and Dilator Effects of Angiotensin II on Cerebral Arterioles
Authors: Vincent Jean-Martin , Kwan Yiu Wa , Lung Chan Siu , Perrin-Sarrado Caroline , Atkinson Jeffrey , Chillon Jean-Marc
Published: November 2005

Background and Purpose—

In light of the equivocal data on the cerebral vasoconstrictor and vasodilator actions of angiotensin II (Ang II) and the potential clinical importance of this, we investigated the effects of Ang II on rat pial arterioles.

Methods—

We determined the effect of Ang I (3.10
−6
mol/L) in the absence and presence of the converting enzyme inhibitor, captopril (10
−5
mol/L) in cerebral arterioles of male Wistar rats (open-skull preparation), and those of Ang II (3.10
−12
to 3.10
−6
mol/L) in the absence and presence of the Ang II receptor (AT
1
) antagonist, telmisartan (10
−5
mol/L) or the AT
2
antagonist, PD123319 (10
−5
mol/L). We examined the effect of PD123319 (10
−5
mol/L) and the Ca
2+
-activated K
+
(BK
Ca
) channel blocker, tetraethylammonium (10
−4
mol/L) on the Ang II responses in the presence of telmisartan (10
−5
mol/L).

Results—

Ang II-induced dose-dependent constriction with a maximum decrease of −20.1±1.0% at 10
−6
mol/L. Captopril significantly decreased Ang I-induced vasoconstriction (−4.0±0.9 versus −21.3±2.5%; n=4). Telmisartan reversed Ang II-induced vasoconstriction (9.5±2.5 versus −20.1±1% at 10
−6
mol/L; n=5). PD123319 significantly increased Ang II-induced vasoconstriction (−12.9±0.8 versus −10.2±0.4% at 10
−6
mol/L; n=5). PD123319 abolished (−2.6±0.7 versus 9.3±1.1% at 10
−6
mol/L; n=5) whereas tetraethylammonium reversed (−12.1±1.6 versus 9.9±1.0% at 10
−6
mol/L; n=4) Ang II-induced vasodilatation in the presence of telmisartan.

Conclusion—

Angiotensin is converted locally into Ang II; the overall effect of Ang II is vasoconstrictor following stimulation of the AT
1
receptor, but a vasodilator response can be evoked following stimulation of the AT
2
receptor and activation of BK
Ca
.
Polyamine Oxidase and Acrolein as Novel Biochemical Markers for Diagnosis of Cerebral Stroke
Authors: Tomitori Hideyuki , Usui Teruyoshi , Saeki Naokatsu , Ueda Shiro , Kase Hiroshi , Nishimura Kazuhiro , Kashiwagi Keiko , Igarashi Kazuei
Published: November 2005

Background and Purpose—

We found previously that plasma levels of acrolein (CH
2
=CHCHO) and spermine oxidase (SMO) were well correlated with the degree of severity of chronic renal failure. The aim of this study was to test whether the levels of these 2 markers and of acetylpolyamine oxidase (AcPAO) were increased in the plasma of stroke patients.

Methods—

The activity of AcPAO and SMO and the level of protein-conjugated acrolein in plasma of the stroke patients and normal subjects were measured by high-performance liquid chromatography and ELISA, respectively. Focal infarcts were estimated by MRI or computed tomography (CT).

Results—

The levels of AcPAO, SMO, and acrolein were significantly increased in the plasma of stroke patients. The size of stroke was nearly parallel with the multiplied value of acrolein and total polyamine oxidase (AcPAO plus SMO). After the onset of stroke, an increase in AcPAO first occurred, followed by increased levels of SMO and finally acrolein. In 1 case, an increase in AcPAO and SMO preceded focal damage as detected by MRI or CT. Furthermore, stroke was confirmed by MRI in a number of mildly symptomatic patients (11 cases) who had increased levels of total polyamine oxidase and acrolein. Among apparently normal subjects (8 cases) who had high values of acrolein×total polyamine oxidase, stroke was found in 4 cases by MRI.

Conclusions—

The results indicate that increased levels of AcPAO, SMO, and acrolein are good markers of stroke.
Hemodynamic Evaluation of Embolic Trajectory in an Arterial Bifurcation
Authors: Bushi Doron , Grad Ygael , Einav Shmuel , Yodfat Ofer , Nishri Boaz , Tanne David
Published: November 2005

Background and Purpose—

Despite the importance of embolism as a major cause of brain infarction, little is known about the hemodynamic factors governing the path large emboli tend to follow. Our aim was to test in vitro, whether hemodynamic parameters other than flow ratios between bifurcation branches may affect the distribution of embolic particles in a Y-shaped bifurcation model, used as an analogue to an arterial bifurcation.

Methods—

In vitro experiments were conducted using suspensions of sphere-shaped particles (0.6, 1.6, and 3.2 mm) in water-glycerin mixture, using steady and pulsatile laminar flow regimes in a Y-shaped bifurcation model (identical branching angles [θ
1
=θ
2
=45
o
] with one daughter branch diameter wider than the other [D
1
=6 mm, D
2
=4 mm]; average Reynolds number 500).

Results—

Experiments using naturally buoyant particles under steady flow conditions and four outlet-flow ratios revealed that small (0.6 mm) and mid-sized (1.6 mm) particles entered into either the narrower or wider bifurcation daughter branch nonpreferentially, proportionally to the flow ratios. Large particles (3.2 mm), however, preferentially entered the wider daughter branch. Moreover, as the flow ratio increases this phenomenon was augmented. Further experiments revealed that the preference of the wider daughter branch for high particle-to-branch diameter-ratios further increases under pulsatile flow and by the density ratio between particles and fluid.

Conclusion—

Particles’ distribution in a bifurcation is affected, beyond its outlets-flow-ratios, by the particle-to-branch diameter-ratio. The tendency of large particles to preferentially enter the wider bifurcation branch, beyond the flow ratio, is augmented under pulsatile flow conditions and is affected by particle-to-fluid density-ratio. These findings may have important implications for understanding the hemodynamic mechanisms underlying the trajectory of large emboli.
Evaluation of Probation Case Management (PCM) for Drug-Involved Women Offenders
Authors: Chan Monica , Guydish Joseph , Prem Rosemary , Jessup Martha A. , Cervantes Armando , Bostrom Alan
Published: November 2005

Based on availability of case management services, drug-involved women offenders entered either a probation case management (PCM) intervention(n = 65) or standard probation(n = 44). Participants were placed in the case management condition until all slots were filled, then placed in standard probation until case management slots opened. Participants were interviewed at program entry and at 6- and 12-month follow-up using measures of substance abuse, psychiatric symptoms, and social support. Results showed modest change over time in both conditions, but PCM did not result in more services or treatment, or better outcomes than standard probation. These findings are discussed in the context of study limitations and in the context of state initiatives like those in Arizona and California designed to apply treatment as an alternative to incarceration.
Which Substance and What Community? Differences in Juvenile Disposition Severity
Authors: Terry-McElrath Yvonne M. , McBride Duane C. , Ruel Erin , Harwood Eileen M. , Vanderwaal Curtis J. , Chaloupka Frank J.
Published: November 2005

There is a need in the literature for research describing disposition severity differences between specific drug and alcohol law violations within the context of community characteristics. We conducted an exploratory study of prosecutor-reported juvenile disposition severity by both specific drug charge and community context using a national sample of prosecutors from communities surrounding schools participating in the nationally representative Monitoring the Future survey. Results indicated (a) strong within- and between-substance disposition severity variance as well as (b) evidence for differential effects of both prosecutor case load and community characteristics, including community income, ethnicity, and region.
Preaching and practising ‘flexibility’: Implications for theories of subjectivity at work
Authors: Whittle Andrea
Published: November 2005

This article explores the relationship between discourse and subjectivity in organizations with reference to an ethnographic study of UK management consultants. The article reveals the contradiction, criticism, cynicism and ambivalence involved in their role as preachers and practitioners of flexible work. These findings question the assumption that management consultants are evangelists that are identified with the discourses they sell. However, I also argue that the dis-identification and contradiction I observed did not in fact disrupt or disturb the production and promotion of their flexible working discourse. I suggest that the consultants constructed pragmatic, instrumental and dramaturgical selves in order to manage the tension between being preacher and practitioner. I conclude by suggesting that cynicism, ambivalence and contradiction constitute important but neglected features of work and organization.
Bringing humility to leadership: Antecedents and consequences of leader humility
Authors: Morris J. Andrew , Brotheridge Céleste M. , Urbanski John C.
Published: November 2005

As noted by McGill and Slocum (1998), effective leadership tends to operate as a contingency theory. The romanticized notion of celebrity CEOs that has been lionized in the popular business press has its place in the leadership pantheon, but, like any other approach to leadership, has limitations in its application. In particular, as discussed by Collins (2001a), sustained organizational functioning is more likely to be the result of the celebrity’s antithesis, a person possessing a blend of humility and strong personal will. This article draws from a diversity of sources in order to explore this potential nexus between humility and leadership. It offers a precise conceptualization of the concept of humility, identifies traits that are predictors of humility as well as the specific leadership behaviors that are likely to be the outcomes of high levels of humility.
Early Socialization Contexts and Social Experiences of Infants in Rural and Urban Gujarat, India
Authors: Abels Monika , Keller Heidi , Mohite Prerna , Mankodi Hina , Shastri Jigisha , Bhargava Shruti , Jasrai Sucheta , Lakhani Aruna
Published: November 2005

In this study, the early social experiences of infants from a rural, traditionally agricultural community are compared with those of urban infants of the same region. Using spot observations, infants'daily social experiences were assessed when they were about 3 months of age. Based on overarching sociocultural orientations, the authors expected rural and urban caregivers to provide their infants with the same amount of body contact, kissing, and body stimulation. Based on different educational profiles of the caregivers, less eyetoeye contact, exclusive attention, and object stimulation by rural compared to urban caregivers were expected. Differences between mothers and other caregivers in their interaction with the infant and during distress and nondistress waking states of the infant were explored. The results confirmed their expectations partially. Urban infants experienced more eye-to-eye contact and more exclusive attention but also more body contact. There were no differences in kissing, body stimulation, and object stimulation.
Help on the Line
Authors: Wetta-Hall Ruth , Berg-Copas Gina M. , Dismuke S. Edwards
Published: November 2005

Telephone triage programs have been shown to be cost-effective and favorably utilized by insured populations. However, there are 45 million Americans who are uninsured and who do not have access to telephone nursing. A telephone triage service was piloted for local uninsured residents. Within the 17-month trial period, 320 calls were received, representing 207 clients. This study reports on the results of the telephone survey with a cross-sectional sample of uninsured triage patrons (N = 80). One half reported they would have sought other medical care if the telephone triage service had not been available. Most callers (98%) believed that their health care concern was understood. Moreover, 98% agreed with the advice given, and 90% reported following up on the advice given. Overall satisfaction by the uninsured population with the telephone-based nurse triage service was positive and appears to be an effective and acceptable tool by those uninsured individuals who utilized its services.
Effects of repeated doses of caffeine on mood and performance of alert and fatigued volunteers
Authors: Smith Andrew , Sutherland David , Christopher Gary
Published: November 2005

Evidence for behavioural effects of caffeine is well documented in the literature. It is associated with increased subjective alertness, improved reaction time and enhanced encoding of new information. These effects are most prominent in low arousal situations. However, there is an ongoing debate as to whether such changes are in fact improvements or merely a reversal of the negative effects of a period of caffeine withdrawal (e.g. overnight abstinence). To avoid such a confound this study included multiple doses of caffeine which were administered under double-blind conditions to participants who had ingested their normal daily quota of caffeine. In the present study participants were fatigued by carrying out a prolonged testing schedule in the evening. Sixty volunteers, all regular caffeine consumers, took part in the study. They attended for three sessions on separate days. They were instructed to consume normal amounts of caffeinated beverages. Consumption was measured by a diary and saliva samples were taken and caffeine assays conducted. A baseline test session was carried out at 18.00h and following this a double blind placebo controlled caffeine challenge (1.5mg/kg) conducted. The test battery was repeated twice approximately 30 minutes after the caffeine challenge. Following this another drink was administered and the test battery repeated twice more. On one test session volunteers had placebo in both drinks, in another they had caffeine in both drinks and another caffeine in the first and placebo in the second. Order of conditions was balanced across subjects. The results showed that caffeine led to a more positive mood and improved performance on a number of tasks. Different effects of caffeine were seen depending on the person’s level of arousal. Linear effects of caffeine dose were also observed. This is evidence against the argument that behavioural changes due to caffeine are merely the reversal of negative effects of a long period of caffeine abstinence. The findings are discussed in relation to both noradrenergic and cholinergic neurotransmitter systems.
New trends in the cyber and street market of recreational drugs? The case of 2C-T-7 (‘Blue Mystic’)
Authors: Schifano Fabrizio , Deluca Paolo , Agosti Lisa , Martinotti Giovanni , Corkery John M. ,   The Psychonaut 2002 Research Group
Published: November 2005

2C-T-7 (‘Blue Mystic’), an illicit compound which shows similarities with MDMA and other designer drugs, has been only occasionally identified in the EU, but discussion on the Internet between experimenters has recently grown significantly. We aimed at collecting together in a review the available information on 2C-T-7, both at the cyber and at the street market level. 2C-T-7 was first synthesized in 1986; its desired effects include both a sense of empathy and of well-being. Hallucinations, nausea, anxiety, panic attacks and paranoid ideation are anecdotally reported. According to the different European sources here approached, the availability of 2C-T-7 at street level seems to be currently very low, although one death related to a mono-intoxication with 2C-T-7 has been documented in the USA. With respect to information on 2C-T-7 available online, due to both redundancy and relevance issues the initial identified sample of 360 was reduced to 118 websites. In 14 (11.9%) websites, the detailed description of the 2C-T-7 synthesis was given. Harm Reduction websites appeared significantly earlier in the search engines results’ list than Anti drugs ( p 0.006) websites. Five (4.2%) websites apparently offered 2C-T-7 for sale. The large body of knowledge available online seems to contrast with small numbers of seizures at street level; an exhaustive web mapping of drug-related issues may be of interest for the clinician. Projects aimed at designing more ‘attractive’ prevention websites should be planned and future studies should better assess the characteristics of those consumers who take advantage of the online information of hallucinogenic compounds.
Efficient Fair Division
Authors: Brams Steven J. , King Daniel L.
Published: November 2005

Two or more players rank a set of indivisible items from best to worst. An efficient allocation of items is characterized, which may satisfy such properties as maximin, Borda maximin, and envy-avoidance. Whereas the two maximin properties are in conflict with envy-avoidance, there is always an efficient allocation that does not ensure envy, but it may not be maximin or Borda maximin. Computer calculations show that maximin allocations lead to envy quite often, but Borda maximin allocations do so only rarely. Implications of the theoretical findings for real-world fair-division problems are discussed.
On the Front Line
Authors: Gerber Brian J. , Cohen David B. , Cannon Brian , Patterson Dennis , Stewart Kendra
Published: November 2005

Municipal governments’ efforts in preparing for possible terrorist events are critical to effective homeland security. Using data gathered from a nationwide sample of municipal officials, the authors identify determinants of homeland security preparedness in U.S. cities, across several attitudinal and behavioral indicators. The authors find that perceptions of terror threat vulnerability and response capacity are tied to factors such as city size and budgetary constraints. Perhaps more important, the authors show that administrative capacity demonstrates consistent explanatory power for both perceived policy commitment and specific preparedness actions. From these analyses, the authors outline several key policy implications for homeland security policy making.
Cities and Subcultures
Authors: Sharp Elaine B.
Published: November 2005

Recently there has been renewed attention to the concept of culture in analyses of urban politics. That resurgence has taken a different path from the religion-, race-, and ethnicity-dominated approach of classic formulations. Instead, a variety of scholars conceptualize and measure subculture based on trends at the heart of a postindustrial, cultural divide in the United States. Focusing on change in women’s social roles, greater prevalence of postsecondary education, increases in nontraditional household arrangements, the decline in traditional religious attachments, and the growing importance of “creative-class” occupations, writers have identified an emergent “unconventional” or “new political culture” that can be differentiated from a traditional or conventional subculture. This article presents a measurement validation study of this new approach that also shows the substantial correspondence between Census Bureau–based and survey-based measures of this new conceptualization.
An Approach to Parallel M × N Communication
Authors: Bertrand Felipe , Yuan Yongquan , Chiu Kenneth , Bramley Randall
Published: November 2005

High performance scientific applications are frequently multiphysics codes composed from single-physics programs, or have a functional decomposition based on physics as well as a domain decomposition for parallelism. In either case, dividing the application into independent components that can be developed and tested separately is useful. This requires a fast and efficient mechanism to share the large parallel data structures that are used in scientific applications. The “ M× Nproblem” is the transfer of data between two scientific parallel programs with different numbers of processes on each side. We present a solution to the M× Nproblem based on an I/O message passing interface (MPI). In this solution, the client application reads and writes data using the standard MPI I/O, but instead of going to hard drives the data are streamed in parallel between module programs working together on an integrated simulation. This approach builds on existing technology, emphasizes the easy migration of current applications, and simplifies the unit testing of the components while maintaining parallel high performance throughout the application. It also does not require a component to know how many processes another communicating component has.