bluuebunny/crossref_metadata_2025 huggingface dataset:
Accelerated endothelial dysfunction in mild prediabetic insulin resistance: the early role of reactive oxygen species
Authors: Duncan Edward R. , Walker Simon J. , Ezzat Vivienne A. , Wheatcroft Stephen B. , Li Jian-Mei , Shah Ajay M. , Kearney Mark T.
Published: August 2007

Insulin resistance is well established as an independent risk factor for the development of type 2 diabetes and cardiovascular atherosclerosis. Most studies have examined atherogenesis in models of severe insulin resistance or diabetes. However, by the time of diagnosis, individuals with type 2 diabetes already demonstrate a significant atheroma burden. Furthermore, recent studies suggest that, even in adolescence, insulin resistance is a progressive disorder that increases cardiovascular risk. In the present report, we studied early mechanisms of reduction in the bioavailability of the antiatheroscerotic molecule nitric oxide (NO) in very mild insulin resistance. Mice with haploinsufficiency for the insulin receptor (IRKO) are a model of mild insulin resistance with preserved glycemic control. We previously demonstrated that 2-mo-old (Young) IRKO mice have preserved vasorelaxation responses to ACh. This remained the case at 4 mo of age. However, by 6 mo, despite no significant deterioration in glucose homeostasis (Adult), IRKO mice had marked blunting of ACh-mediated vasorelaxation [IRKO maximum contraction response (Emax) 66 ± 5% vs. wild type 87 ± 4%, P < 0.01]. Despite the endothelial dysfunction demonstrated, aortic endothelial nitric oxide synthase (eNOS) mRNA levels were similar in Adult IRKO and wild-type mice, and, interestingly, aortic eNOS protein levels were increased, suggesting a compensatory upregulation in the IRKO. We then examined the potential role of reactive oxygen species in mediating early endothelial dysfunction. The superoxide dismutase mimetic Mn(III)tetrakis(1-methyl-4-pyridyl) porphyrin pentachloride (MnTMPyP) restored ACh relaxation responses in the Adult IRKO (Emaxto ACh with MnTMPyP 85 ± 5%). Dihydroethidium fluorescence of aortas and isolated coronary microvascular endothelial cells confirmed a substantial increase in endothelium-derived reactive oxygen species in IRKO mice. These data demonstrate that mild insulin resistance is a potent substrate for accelerated endothelial dysfunction and support a role for endothelial cell superoxide production as a mechanism underlying the early reduction in NO bioavailability.
Basal insulin, glucagon, and growth hormone replacement
Authors: Breckenridge Suzanne M. , Raju Bharathi , Arbelaez Ana Maria , Patterson Bruce W. , Cooperberg Benjamin A. , Cryer Philip E.
Published: August 2007

Conclusions drawn from the pancreatic (or islet) clamp technique (suppression of endogenous insulin, glucagon, and growth hormone secretion with somatostatin and replacement of basal hormone levels by intravenous infusion) are critically dependent on the biological appropriateness of the selected doses of the replaced hormones. To assess the appropriateness of representative doses we infused saline alone, insulin (initially 0.20 mU·kg−1·min−1) alone, glucagon (1.0 ng·kg−1·min−1) alone, and growth hormone (3.0 ng·kg−1·min−1) alone intravenously for 4 h in 13 healthy individuals. That dose of insulin raised plasma insulin concentrations approximately threefold, suppressed glucose production, and drove plasma glucose concentrations down to subphysiological levels (65 ± 3 mg/dl, P < 0.0001 vs. saline), resulting in nearly complete suppression of insulin secretion ( P < 0.0001) and stimulation of glucagon ( P = 0.0059) and epinephrine ( P = 0.0009) secretion. An insulin dose of 0.15 mU·kg−1·min−1caused similar effects, but a dose of 0.10 mU·kg−1·min−1did not. The glucagon and growth hormone infusions did not alter plasma glucose levels or those of glucoregulatory factors. Thus, insulin “replacement” doses of 0.20 and even 0.15 mU·kg−1·min−1are excessive, and conclusions drawn from the pancreatic clamp technique using such doses may need to be reassessed.
Myostatin regulates glucose uptake in BeWo cells
Authors: Antony Nisha , Bass John J. , McMahon Christopher D. , Mitchell Murray D.
Published: August 2007

Myostatin is a member of the transforming growth factor (TGF)-β superfamily, known for its ability to inhibit muscle growth. It can also regulate metabolism and glucose uptake in a number of tissues. To determine the mechanism of myostatin's effect on glucose uptake, we evaluated its actions using choriocarcinoma cell lines that are widely used as models for placental cells. Protein and mRNA were determined using immunoblotting and RT-PCR/PCR, respectively. Glucose uptake was assessed by uptake of radiolabeled deoxyglucose in vitro. All choriocarcinoma cell lines tested i.e., BeWo, JEG, and Jar, are used as models of placental cells, and all expressed myostatin protein and mRNA. Treatment of BeWo cells with myostatin resulted in inhibition of glucose uptake in a concentration-dependent manner ( P < 0.01). At all concentrations tested, follistatin, a functional inhibitor of myostatin, completely blocked the inhibitory effect of myostatin (40 nM) on glucose uptake by BeWo cells (0.4 nM, P < 0.05). Follistatin treatment alone also increased glucose uptake (0.4 and 4 nM, P < 0.001; 40 nM, P < 0.05). Because BeWo cells proliferated and greater cell densities were achieved, glucose uptake declined irrespective of treatment. Myostatin treatment of BeWo cells did not alter the levels of myostatin receptor, ActRII A/B proteins. The levels of glucose transport proteins also remained unaltered in BeWo cells with myostatin treatment. This study has shown that myostatin specifically inhibits glucose uptake into BeWo cells, suggesting that locally produced myostatin may control glucose metabolism within the placenta.
Hepatic response to restoration of GLUT4 in skeletal muscle of GLUT4 null mice
Authors: Ranalletta Mollie , Du Xiu Quan , Seki Yoshinori , Glenn Alan S. , Kruse Michael , Fiallo Ariana , Estrada Irma , Tsao Tsu-Shuen , Stenbit Antine E. , Katz Ellen B. , Charron Maureen J.
Published: August 2007

Expression of GLUT4 in fast-twitch skeletal muscle fibers of GLUT4 null mice (G4-MO) normalized glucose uptake in muscle and restored peripheral insulin sensitivity. GLUT4 null mice exhibit altered carbohydrate and lipid metabolism in liver and skeletal muscle. To test the hypothesis that increased glucose utilization by G4-MO muscle would normalize the changes seen in the GLUT4 null liver, serum metabolites and hepatic metabolism were compared in control, GLUT4 null, and G4-MO mice. The fed serum glucose and triglyceride levels of G4-MO mice were similar to those of control mice. In addition, the alternations in liver metabolism seen in GLUT4 nulls including increased GLUT2 expression and fatty acid synthesis accompanied by an increase in the oxidative arm of the pentose phosphate pathway were absent in G4-MO mice. The transgene used for GLUT4 restoration in muscle was specific for fast-twitch muscle fibers. The mitochondria hypertrophy/hyperplasia in all GLUT4 null skeletal muscles was absent in transgene-positive extensor digitorum longus muscle but present in transgene-negative soleus muscle of G4-MO mice. Results of this study suggest that the level of muscle GLUT4 expression influences mitochondrial biogenesis. These studies also demonstrate that the type and amount of substrate that muscle takes up and metabolizes, determined in part by GLUT4 expression levels, play a major role in directing hepatic carbohydrate and lipid metabolism.
Calcium-Dependent Fast Depolarizing Afterpotentials in Vasopressin Neurons in the Rat Supraoptic Nucleus
Authors: Teruyama Ryoichi , Armstrong William E.
Published: August 2007

Oxytocin (OT) and vasopressin (VP) synthesizing magnocellular cells (MNCs) in the supraoptic nucleus (SON) display distinct firing patterns during the physiological demands for these hormones. Depolarizing afterpotentials (DAPs) in these neurons are involved in controlling phasic bursting in VP neurons. Our whole cell recordings demonstrated a Cs+-resistant fast DAP (fDAP; decay tau = ∼200 ms), which has not been previously reported, in addition to the well-known Cs+-sensitive slower DAP (sDAP; decay tau = ∼2 s). Immunoidentification of recorded neurons revealed that all VP neurons, but only 20% of OT neurons, expressed the fDAP. The activation of the fDAP required influx of Ca2+ through voltage-gated Ca2+ channels as it was strongly suppressed in Ca2+-free extracellular solution or by bath application of Cd2+. Additionally, the current underlying the fDAP ( IfDAP) is a Ca2+-activated current rather than a Ca2+ current per se as it was abolished by strongly buffering intracellular Ca2+ with BAPTA. The I-V relationship of the IfDAP was linear at potentials less than −60 mV but showed pronounced outward rectification near −50 mV. IfDAP is sensitive to changes in extracellular Na+ and K+ but not Cl−. A blocker of Ca2+-activated nonselective cation (CAN) currents, flufenamic acid, blocked the fDAP, suggesting the involvement of a CAN current in the generation of fDAP in VP neurons. We speculate that the two DAPs have different roles in generating after burst discharges and could play important roles in determining the distinct firing properties of VP neurons in the SON neurons.
Altered microRNA expression in human heart disease
Authors: Ikeda Sadakatsu , Kong Sek Won , Lu Jun , Bisping Egbert , Zhang Hao , Allen Paul D. , Golub Todd R. , Pieske Burkert , Pu William T.
Published: August 2007

MicroRNAs are recently discovered regulators of gene expression and are becoming increasingly recognized as important regulators of heart function. Genome-wide profiling of microRNAs in human heart failure has not been reported previously. We measured expression of 428 microRNAs in 67 human left ventricular samples belonging to control ( n = 10), ischemic cardiomyopathy (ICM, n = 19), dilated cardiomyopathy (DCM, n = 25), or aortic stenosis (AS, n = 13) diagnostic groups. miRNA expression between disease and control groups was compared by ANOVA with Dunnett's post hoc test. We controlled for multiple testing by estimating the false discovery rate. Out of 428 microRNAs measured, 87 were confidently detected; 43 were differentially expressed in at least one disease group. In supervised clustering, microRNA expression profiles correctly grouped samples by their clinical diagnosis, indicating that microRNA expression profiles are distinct between diagnostic groups. This was further supported by class prediction approaches, in which the class (control, ICM, DCM, AS) predicted by a microRNA-based classifier matched the clinical diagnosis 69% of the time ( P < 0.001). These data show that expression of many microRNAs is altered in heart disease and that different types of heart disease are associated with distinct changes in microRNA expression. These data will guide further studies of the contribution of microRNAs to heart disease pathogenesis.
Assessment of Aortic Valve Area in Aortic Stenosis Using Cardiac Magnetic Resonance Tomography: Comparison with Echocardiography
Authors: Malyar Nasser M. , Schlosser Thomas , Barkhausen Jörg , Gutersohn Achim , Buck Thomas , Bartel Thomas , Erbel Raimund
Published: August 2007

Background: Cardiac magnetic resonance tomography (CMR) is a new imaging technique capable of imaging the aortic valve with high resolution. We assessed the aortic valve area (AVA) in patients with aortic stenosis (AS) using CMR and compared the results to those obtained by transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE). Methods: Forty-two patients (36% female, 71 ± 8 years) symptomatic for AS underwent TTE followed by TEE to determine the AVA; the continuity equation was used with TTE and the planimetry technique with TEE. In 26 of these patients, the AVA was additionally obtained by CMR planimetry. Results: The mean AVA derived by TTE, TEE and CMR were 0.74 ± 0.27, 0.87 ± 25 and 0.97 ± 0.30 cm2, respectively. The mean absolute differences in AVA were 0.13 ± 0.19 cm2 for TTE vs. TEE, 0.21 ± 0.25 cm2 for TTE vs. CMR and 0.05 ± 0.11 cm2 for CMR vs. TEE. Conclusion: There is a good agreement between CMR and the echocardiographic determination of the AVA. If multicenter, large-scale studies confirm these observations, CMR could serve as a noninvasive alternative to TTE/TEE for the assessment of AVA in AS.
Botulinum Toxin Therapy in the Ovalbumin-Sensitized Rat
Authors: Wen Wei-Dong , Yuan Fang , Wang Jian-Lin , Hou Yi-Ping
Published: August 2007

Objective: The aim of this study was to determine whether intranasal administration of botulinum toxin type A (BTX-A) could relieve the typical symptoms of allergic rhinitis (AR) and alter substance P (SP)- and vasoactive intestinal peptide (VIP)-immunoreactive (IR) expression in nasal mucosa of AR animals sensitized with ovalbumin (OVA). Methods: AR was induced by intraperitoneal injection of OVA followed by its repeated intranasal instillation in female Wistar rats. Some AR animals were intranasally treated with a cotton strip containing BTX-A (10 U per nostril) for 1 h. After BTX-A treatment, OVA was repeatedly instilled in AR and AR + BTX-A groups every 2 days for 10 days. Subsequently, nasal symptoms were evaluated, and nasal secretions collected. Finally, the nasal mucosae of all animals were prepared for histological and immunohistochemical assessment. Results: BTX-A administration alleviated typical AR symptoms including rhinorrhea, nasal itching and sneezing, and subsequent intranasal repeated challenge with OVA did not trigger AR symptoms. After BTX-A treatment, inflammatory histological characteristics within the nasal mucosa of AR animals were absent, but atrophy of serous glands was observed. BTX-A decreased dense SP-IR and VIP-IR cells and fibers within and beneath the epithelium, around blood vessels and close to serous glands in AR animals. Conclusion: Local BTX-A treatment is an effective method to reduce AR symptoms. BTX-A decreased the excessive SP-IR and VIP-IR expression induced by OVA. Therefore, BTX-A may affect the nasal mucosa via the suppression of neuropeptides, playing a major role in autonomous mucosal innervation in the pathophysiology of AR.
Constrictive Bronchiolitis after Treatment of Colon Cancer with 5-Fluorouracil
Authors: Valdivia-Arenas Martin A. , Soriano Andres O. , Arteaga Roque B.
Published: August 2007

Constrictive bronchiolitis (CB) is a rare disease with unclear etiology. We report a 37-year-old female with CB who developed progressive dyspnea and cough after completing a course of 5-fluorouracil (5-FU) for colon cancer. The patient had evidence of irreversible obstructive lung disease and lung biopsy showed typical findings of chronic inflammation, submucosal thickening and obliteration of bronchioles. To the best of our knowledge this is the first reported case of CB after treatment with 5-FU.
Establishment of a Single-Dose Irinotecan Model of Gastrointestinal Mucositis
Authors: Gibson Rachel J. , Bowen Joanne M. , Alvarez Enrique , Finnie John , Keefe Dorothy M.K.
Published: August 2007

Background: Irinotecan is a common cytotoxic agent used in advanced colorectal cancers. However, a major clinical problem with this cytotoxic is that it causes gastrointestinal mucositis manifest by severe diarrhoea. To date there is no established single dose of irinotecan in rats to enable determination of changes occurring following administration. Therefore, the primary aim of this study was to determine a single dose of irinotecan that induced reproducible gastrointestinal mucositis in DA rats. The secondary aim was to determine if the presence of tumour altered the development of mucositis. Methods: Eighty-eight rats were divided into two groups, 44 received tumours and 44 remained tumour naïve. These were randomized to receive a single dose of irinotecan at 150, 200, 250 or 300 mg/kg. Two control groups of rats received either no treatment or 2 doses of 150 mg/kg irinotecan, shown previously to induce reproducible gastrointestinal mucositis. Rats were monitored closely for incidence and severity of diarrhoea, and mortality, before being killed 48 and 144 h following treatment. Results: Rats administered 250 and 300 mg/kg of irinotecan all developed diarrhoea, and this was associated with high mortality rates (up to 100%). Necropsies revealed that many of these rats had duodenal perforations and fatty lysis consistent with peritonitis. The lower doses of 150 and 200 mg/kg irinotecan also caused diarrhoea, but were not associated with high mortality rates. Histopathological examination confirmed small and large intestinal damage in all rats that received irinotecan, regardless of dose. Tumour-bearing rats had worse diarrhoea and higher mortality compared to tumour-naïve rats. Conclusions: We find that a single dose of 200 mg/kg irinotecan causes reproducible gastrointestinal mucositis as measured by levels of diarrhoea, and small and large intestinal histology. Importantly this dose has a low mortality. The response to irinotecan is more pronounced in tumour-bearing rats.
The Effects of Statins on the Progression of Atherosclerotic Renovascular Disease
Authors: Cheung Ching M. , Patel Amit , Shaheen Nilam , Cain Sharon , Eddington Helen , Hegarty Janet , Middleton Rachel J. , Cowie Alistair , Mamtora Hari , Kalra Philip A.
Published: August 2007

Background/Aims: The aim was to examine the influence of statin therapy on the natural history of atherosclerotic renal artery stenosis (RAS). Methods: Our hospital atherosclerotic renovascular disease (ARVD) database was analysed for patients who underwent repeat renal angiography during clinical follow-up. Patients with ≧1 RAS lesion and ≧4 months between baseline and repeat renal angiography were analysed. 79 patients were included. Baseline renal arterial anatomy was classified as normal, ≤50% RAS, >50% RAS or renal artery occlusion. Results: Mean follow-up time between angiograms was 27.8 ± 22.3 (4.0–101.9) months. Progression of RAS occurred in 28 (23%) vessels, regression in 14 (12%) and no significant change in 79 (65%). Multivariate regression analysis showed that baseline proteinuria >0.6 g/day increased the risk of progressive disease (relative risk, RR, 3.8; 95% confidence interval, CI, 1.2–12.1), treatment with statin reduced the risk of progression (RR 0.28; 95% CI 0.10–0.77). 14 renal arteries from 12 patients showed RAS regression with a greater proportion on statin [statin treatment 10 (83%) versus no statin treatment 2 (17%), p = 0.001]. Change in estimated glomerular filtration rate (eGFR) per year was not different between statin- and no-statin-treated groups. Conclusions: Progression or development of RAS was significantly less likely to occur with statin therapy. ΔeGFR did not correlate with progression of RAS, reflecting the importance of intrarenal injury in the aetiology of renal dysfunction. Our results suggest statin therapy can alter the natural history of ARVD.
Cadherins, RhoA, and Rac1 Are Differentially Required for Stretch-Mediated Proliferation in Endothelial Versus Smooth Muscle Cells
Authors: Liu Wendy F. , Nelson Celeste M. , Tan John L. , Chen Christopher S.
Published: August 2007

Abnormal mechanical forces can trigger aberrant proliferation of endothelial and smooth muscle cells, as observed in the progression of vascular diseases such as atherosclerosis. It has been previously shown that cells can sense physical forces such as stretch through adhesions to the extracellular matrix. Here, we set out to examine whether cell–cell adhesions are also involved in transducing mechanical stretch into a proliferative response. We found that both endothelial and smooth muscle cells exhibited an increase in proliferation in response to stretch. Using micropatterning to isolate the role of cell–cell adhesion from cell–extracellular matrix adhesion, we demonstrate that endothelial cells required cell–cell contact and vascular endothelial cadherin engagement to transduce stretch into proliferative signals. In contrast, smooth muscle cells responded to stretch without contact to neighboring cells. We further show that stretch stimulated Rac1 activity in endothelial cells, whereas RhoA was activated by stretch in smooth muscle cells. Blocking Rac1 signaling by pharmacological or adenoviral reagents abrogated the proliferative response to stretch in endothelial cells but not in smooth muscle cells. Conversely, blocking RhoA completely inhibited the proliferative response in smooth muscle cells but not in endothelial cells. Together, these data suggest that vascular endothelial cadherin has an important role in mechanotransduction and that endothelial and smooth muscle cells use different mechanisms to respond to stretch.
Machines, Faces, Neurons: Towards an Ethics of Dance
Authors: Lepecki André
Published: August 2007

The final installment of a continuing series on choreography considering the mutual interrogation of philosophy and dance, the articles propose a tentative ethics of dance as a “practical philosophy” under the influence of Gilles Deleuze read through specific choreographic practices. Gerald Siegmund describes his private experience of Boris Charmatz's choreographic machine as a metaphor for the entrapment of theatre and as generative of new bodily subjectivities. Introducing anthropological applications of cognitive science to the particular strategies of choreographers working in Brazil, Christine Greiner argues for a political conception of self through dance. Examining the kinetics of the face in RoseAnne Spradlin's Survive Cycle, Victoria Anderson Davies meditates on the relationship of facial expression to language, to consciousness, and to movement.
Transforming Geographies and Reconfigured Spaces: South Africa's National Arts Festival
Authors: Larlham Daniel
Published: August 2007

Janelle Reinelt explores playwright Howard Brenton's return to Britain's national stages after almost a decade's absence, discussing recent productions that address the fraught relationship between religious belief and human conduct. Joshua Chambers-Letson contemplates the queer politics of failure in regard to Nao Bustamante's Hero, which challenges the value of “normality” via the possibility of a communal being-in-failure for queers, people of color, and other nonnormative subjects. Engaging South Africa's 2006 National Arts Festival, Daniel Larlham addresses the country's national transformations through its changing artistic landscape, newly opened to a variety of imaginative, discursive, and affective spaces in which a communal historical consciousness might develop.
Causing More Trouble Out There: Mark Russell on P.S. 122
Authors: Kurkjian Beth
Published: August 2007

For 21 years, Mark Russell served as the Artistic Director of Performance Space 122 , the New York institution hailed as the mecca of downtown experimental art. Russell looks back on the nascent years of P.S. 122 , discussing his desire to “serve” the experimental performance community, often navigating the “ecology” on the artists' behalf and helping to further their careers. Artists' profiles, images by photographer Dona Ann McAdams, and Russell's short reflection on both the new direction of P.S. 122 and his own life give a multidimensional look at this East Village landmark and the impresario who put it on the artistic map of New York City.
Linear Coding of Voice Onset Time
Authors: Frye Richard E. , Fisher Janet McGraw , Coty Alexis , Zarella Melissa , Liederman Jacqueline , Halgren Eric
Published: August 2007

Voice onset time (VOT) provides an important auditory cue for recognizing spoken consonant-vowel syllables. Although changes in the neuromagnetic response to consonant-vowel syllables with different VOT have been examined, such experiments have only manipulated VOT with respect to voicing. We utilized the characteristics of a previously developed asymmetric VOT continuum [Liederman, J., Frye, R. E., McGraw Fisher, J., Greenwood, K., & Alexander, R. A temporally dynamic contextual effect that disrupts voice onset time discrimination of rapidly successive stimuli. Psychonomic Bulletin and Review, 12, 380–386, 2005] to determine if changes in the prominent M100 neuromagnetic response were linearly modulated by VOT. Eight right-handed, English-speaking, normally developing participants performed a VOT discrimination task during a whole-head neuromagnetic recording. The M100 was identified in the gradiometers overlying the right and left temporal cortices and single dipoles were fit to each M100 waveform. A repeated measures analysis of variance with post hoc contrast test for linear trend was used to determine whether characteristics of the M100 were linearly modulated by VOT. The morphology of the M100 gradiometer waveform and the peak latency of the dipole waveform were linearly modulated by VOT. This modulation was much greater in the left, as compared to the right, hemisphere. The M100 dipole moved in a linear fashion as VOT increased in both hemispheres, but along different axes in each hemisphere. This study suggests that VOT may linearly modulate characteristics of the M100, predominately in the left hemisphere, and suggests that the VOT of consonant-vowel syllables, instead of, or in addition to, voicing, should be examined in future experiments.
Masking Disrupts Reentrant Processing in Human Visual Cortex
Authors: Fahrenfort J. J. , Scholte H. S. , Lamme V. A. F.
Published: August 2007

In masking, a stimulus is rendered invisible through the presentation of a second stimulus shortly after the first. Over the years, authors have typically explained masking by postulating some early disruption process. In these feedforward-type explanations, the mask somehow “catches up” with the target stimulus, disrupting its processing either through lateral or interchannel inhibition. However, studies from recent years indicate that visual perception—and most notably visual awareness itself—may depend strongly on cortico-cortical feedback connections from higher to lower visual areas. This has led some researchers to propose that masking derives its effectiveness from selectively interrupting these reentrant processes. In this experiment, we used electroencephalogram measurements to determine what happens in the human visual cortex during detection of a texture-defined square under nonmasked (seen) and masked (unseen) conditions. Electro-encephalogram derivatives that are typically associated with reentrant processing turn out to be absent in the masked condition. Moreover, extrastriate visual areas are still activated early on by both seen and unseen stimuli, as shown by scalp surface Laplacian current source-density maps. This conclusively shows that feedforward processing is preserved, even when subject performance is at chance as determined by objective measures. From these results, we conclude that masking derives its effectiveness, at least partly, from disrupting reentrant processing, thereby interfering with the neural mechanisms of figure-ground segmentation and visual awareness itself.
Open Access Series of Imaging Studies (OASIS): Cross-sectional MRI Data in Young, Middle Aged, Nondemented, and Demented Older Adults
Authors: Marcus Daniel S. , Wang Tracy H. , Parker Jamie , Csernansky John G. , Morris John C. , Buckner Randy L.
Published: August 2007

The Open Access Series of Imaging Studies is a series of magnetic resonance imaging data sets that is publicly available for study and analysis. The initial data set consists of a cross-sectional collection of 416 subjects aged 18 to 96 years. One hundred of the included subjects older than 60 years have been clinically diagnosed with very mild to moderate Alzheimer's disease. The subjects are all right-handed and include both men and women. For each subject, three or four individual T1-weighted magnetic resonance imaging scans obtained in single imaging sessions are included. Multiple within-session acquisitions provide extremely high contrast-to-noise ratio, making the data amenable to a wide range of analytic approaches including automated computational analysis. Additionally, a reliability data set is included containing 20 subjects without dementia imaged on a subsequent visit within 90 days of their initial session. Automated calculation of whole-brain volume and estimated total intracranial volume are presented to demonstrate use of the data for measuring differences associated with normal aging and Alzheimer's disease.
Social Regulation of Affective Experience of Humor
Authors: Goel Vinod , Dolan Raymond J.
Published: August 2007

The element of surprise, a necessary condition for the experience of humor, often derives from the fact that the alternative interpretation/resolution offered by the punch line of a joke is physically or socially forbidden. Children's humor typifies violation of physical norms, whereas adult humor typically pushes the boundaries of social norms. Excess norm violation, to the point of offending, can attenuate the experience of humor/mirth. To examine the neural basis of regulation of affective experience of humor by social norms, we scanned 16 normal subjects while they viewed a series of cartoons that varied in funniness and social acceptability. Behavioral results indicated two separate groups of subjects, those who found the cartoons less offensive and those who found them more offensive. In the group that found the jokes more offensive, there was a negative correlation between funniness and social inappropriateness. In this group, the corresponding Humor by Social inappropriateness interaction during functional magnetic resonance imaging revealed enhanced activation in the right hippocampus along with relative deactivation in the ventral medial prefrontal cortex (VMPFC). By contrast, the Funniness by Social appropriateness interaction resulted in activation in the VMPFC and relative deactivation in the right hippocampus. These results suggest that the regulation of humor by social norms involves reciprocal response patterns between VMPFC and hippocampus regions implicated in contextual regulation of behavior and memory, respectively.
Presidential Conditional Agenda Setting in the Former Communist Countries
Authors: Tsebelis George , Rizova Tatiana P.
Published: August 2007

Nine out of 27 presidents in the former communist world have the power to amend vetoed legislation. These presidential powers in the former Soviet Bloc have not been given adequate attention in the comparative politics literature. The authors analyze veto procedures in the excommunist region (27 countries) and argue that amendatory veto power enhances presidential powers in legislative decision making. The findings are particularly important in light of the fact that one of the goals of constitutional design in the former communist world was to curtail rather than boost presidential authority.
Participatory Learning in Introductory Economics
Authors: Kramer Brent
Published: August 2007

It is a major challenge to find ways to incorporate the principles of popular education into teaching economics. Students have significant experience of the economic system they live under, and some have heard of (or even studied) other models as well. The author has experimented with tapping into students' experiences and creativity in a group process to evoke alternative economic models in an attempt to undermine the assumption that modern industrial capitalism is the best system possible.
Intermediate Maple Syrup Urine Disease: Neuroimaging Observations in 3 Patients From South India
Authors: Bindu P.S. , Shehanaz K.E. , Christopher Rita , Pal Pramod K. , Ravishankar S.
Published: August 2007

Maple syrup urine disease is a disorder of branched-chain keto acid metabolism. Three children were diagnosed with the intermediate form of maple syrup urine disease during routine evaluation of mental retardation. Clinical features were characterized by mental retardation, seizures, autistic features, and movement disorder in the form of dystonia. High-performance liquid chromatography of the urine and serum revealed elevated levels of branched-chain amino acids, suggesting a diagnosis of maple syrup urine disease. Magnetic resonance imaging showed diffuse hyperintense signals in the white matter along with involvement of the thalami and globus pallidus. Magnetic resonance imaging in the intermediate form showed myelination in the posterior limb of the internal capsule, in contrast to the classic form of the disease. Knowledge about the neuroimaging findings of this rare disease will help to narrow down the differential diagnosis when evaluating children with unexplained mental retardation and seizures.
Congenital Cervical Spinal Cord Lesions: Pathogenesis, Management, and Outcome
Authors: Govender Rajeshree , Wieselthaler Nicky A. , Ramanjam Veruschka , Ndondo Alvin , Wilmshurst Jo M.
Published: August 2007

Three patients (2 boys) presented with nontraumatic congenital lesions of the spinal cord resulting in paralysis and contractures of their upper limbs from birth. Limited improvement occurred in all. Two survived. One patient required ventilation support after birth; his upper limbs had lower motor neuron flaccid paralysis, and his lower limbs evolved to pyramidal tract impairment. He died at 9 months of age with an intercurrent chest infection. The other 2 patients had lower motor neuron pathology in their upper limbs and normal lower limb function. One of these patients attained ambulation. All 3 patients retained normal higher mental function. Neuroimaging of the spinal cord from the most affected patient demonstrated atrophy of the cervical and high thoracic regions (C4-T3). Spinal neuroimaging results from the less affected patient were normal. Multidisciplinary management assisted these children to reach their full potential in a resource-poor setting. The etiology of focal pathology to the cervical region in these infants with congenital nontraumatic insults remains undefined, similar to the few cases in the literature. The diverse pathogeneses are hypothesized and the literature reviewed.
Exercise Capacity in a Child With McArdle Disease
Authors: Pérez Margarita , Maté-Muñoz José L. , Foster Carl , Rubio Juan C. , Andreu Antoni L. , Martín Miguel A. , Arenas Joaquín , Lucia Alejandro
Published: August 2007

We report the exercise capacity of an 8-year-old boy with clinical, histological, biochemical, and genetic evidence of McArdle disease. The patient presented with severe myalgia, proteinuria, hematuria, pyrexia, and elevated creatine kinase after swimming. After pre-exercise ingestion of sucrose, he performed treadmill exercise to symptom limitation. His peak oxygen uptake (18.8 mL/kg/min) and ventilatory threshold (16.0 mL/kg/min) were reduced by 40% and 20% compared with healthy age-matched and gender-matched controls. The results suggest that exercise capacity is reduced early in life in patients with McArdle disease and suggest the need for prophylactic exercise training (following pre-exercise feeding to prevent rhabdomyolysis) to minimize deconditioning.
Epilepsy in Children in Navarre, Spain: Epileptic Seizure Types and Epileptic Syndromes
Authors: Durá-Travé Teodoro , Yoldi-Petri María Eugenia , Gallinas-Victoriano Fidel
Published: August 2007

Data for children 1 month to 15 years of age at the time of diagnosis of epilepsy were recorded from the children's hospital “Virgen del Camino” in Pamplona (Spain) from January to December 2005. International League Against Epilepsy criteria were used for diagnoses. A total of 365 children were recruited into the study. Mean age at diagnosis was 5.97 years, and time of follow-up was 4.6 years. Etiology was idiopathic in 166 (45.5%), cryptogenic in 106 (29.0%), and symptomatic in 93 (25.5%). Focal seizures were seen in 52.9% of the patients, generalized epilepsy in 43.5%, and 3.6% were not determined. In infants, West syndrome (34.1%) and focal symptomatic seizures (24.4%) were the most prevalent syndromes. In early childhood, the main syndromes were cryptogenic focal epilepsies (17.7%) and Doose syndrome (12.8%). In school-aged children, benign epilepsies (27.3%) and absences (24.5%) were prevalent. In adolescents, cryptogenic focal epilepsies (26.6%) and benign epilepsies (23.4%).
Brain Structure in Prenatal Stroke: Quantitative Magnetic Resonance Imaging (MRI) Analysis
Authors: Bava Sunita , Archibald Sarah L. , Trauner Doris A.
Published: August 2007

Neonatal stroke outcome studies demonstrate variable findings of either relatively spared intellectual function or persistent impairments. Volumetric measurement of the brain can provide more precise data on lesion—cognition outcomes. We studied 7 children with unilateral focal lesions from prenatal stroke. Whole-brain magnetic resonance imaging scans were analyzed to produce volumes of cortical gray matter, total white matter, cerebrospinal fluid, lesion, and lesion constricted fluid, and we ascertained the relationship of morphometric variables to intellectual and clinical outcome. Children with cystic encephalomalacia plus atrophy had poorer outcomes than children with atrophy or gliosis alone. These children also demonstrated the largest lesion size, smallest gray matter volume, and greatest proportion of hyperintense white matter in the affected hemisphere. Findings suggest that the type and size of the lesion, in addition to the integrity of white matter and residual cortex, may be better predictors of intellectual functioning than either of these indices alone.
Temporal Lobe Epilepsy in Childhood: Comprehensive Neuropsychological Assessment
Authors: Guimarães Catarina A. , Li Li M. , Rzezak Patrícia , Fuentes Daniel , Franzon Renata C. , Augusta Montenegro Maria , Cendes Fernando , Thomé-Souza Sigride , Valente Kette , Guerreiro Marilisa M.
Published: August 2007

The neuropsychological features of children with temporal lobe epilepsy are not yet well defined. The aim of this study was to identify the neuropsychological deficits in children with temporal lobe epilepsy. We evaluated 25 patients and compared them with 25 normal children. All children underwent a comprehensive neuropsychological assessment. We found a significant difference in favor of the control group in the following measures: IQ; forward digit; Trail Making Test for Children B; Wisconsin Card Sorting Test; block design; Boston naming test, verbal fluency; and Wide Range Assessment of Memory and Learning verbal learning, visual learning, verbal memory, visual memory, delayed recall of verbal learning, delayed recall of stories, and recognition of stories. Our findings show that children with temporal lobe epilepsy present with several neuropsychological deficits, despite normal IQ. These findings point to a dysfunction of cerebral areas other than temporal lobe, particularly the frontal lobes.
Lack of Evidence for Association Between D2S124 and D2S111 Polymorphisms of the SCN2A Gene and Idiopathic Generalized Epilepsy With Generalized Tonic—Clonic Seizures
Authors: Volzone Anna , Rizzo Renata , Gagliano Antonella , Palmarino Mariella , Lucarelli Paola , Arpino Carla , Curatolo Paolo
Published: August 2007

Idiopathic generalized epilepsy syndromes are generally considered as brain channelopathies due to alteration of several genes. The aim of our study was to compare the distribution of D2S124 and D2S111 genetic polymorphisms of the SCN2A gene between cases with a specific idiopathic generalized epilepsy subtype (with generalized tonic—clonic seizures) and healthy controls. Allele frequencies of both the D2S111 and the D2S124 polymorphisms were not significantly different between cases and control. Further studies are needed to investigate if possible polymorphic variants of SCN2A gene may influence seizures susceptibility of idiopathic generalized epilepsy with tonic—clonic seizures.
To Get Her Heart in Hand
Authors: Staller Karen M.
Published: August 2007

In this study, the author examines a small set of words uttered by a female adolescent sexual abuse survivor and an experienced male social worker practitioner. She speaks of the burden She carries in Her heart. He speaks about His responsibility to retrieve objective stories from sexually abused children, knowing He holds their hearts in His hands. Analysis focused on the words and metaphors used in the passages. Woven together, the two create a picture of the treacherous path of disclosure in a world of disbelieving adults and the responsibility of social work professionals to shoulder the burden of that passage. Implications for social work practice are considered.
Blood Is Thicker Than Water
Authors: Athens Lonnie
Published: August 2007

Pop, the Greek-immigrant owner of the Manchester Café, fires his counter-man, “Pete the Greek,” for getting into too many altercations with customers. To appease some of his long-time patrons, Pop, then, decides to hire Linwood Lots, a local native, as Pete's replacement. Pete and Irene, Pop's daughter, get married and, later, have a son, Pop's first grandchild. After catching Linwood drinking wine filched from the café's wine stock, Pop fires Linwood and immediately rehires Pete. Pop's action ignites a bitter rivalry between Linwood and Pete that is charged with ethnic hatred.
Researching Inequality Through Interpretive Collaborations
Authors: Dodson Lisa , Piatelli Deborah , Schmalzbauer Leah
Published: August 2007

Researchers committed to feminist participatory research must grapple with power and vulnerability—both those of other people as well as their own. In this article, the authors argue that in the current context of sharp economic disparity, political polarization, and global conflict, researchers must undertake collaborative and even risk-taking social inquiry in order to learn about alternative lives. The authors highlight the importance of using a feminist participatory methodology with a focus on the interpretive process. Drawing on field research, they explore an innovative approach to analyzing meaning through interpretive focus groups as “safer space.” The following questions are raised: Is there an ethical way to inquire into habits of life that are intentionally kept hidden? And even if individual confidentiality is ensured, what about collective confidentiality and the obligations that researchers have in a context of increasing inequality?
Development of a New Psychosocial Treatment for Adult ADHD
Authors: Solanto Mary V. , Marks David J. , Mitchell Katherine J. , Wasserstein Jeanette , Kofman Michele D.
Published: August 2007

Objective: The purpose of this study was to assess the effectiveness of a new manualized group Meta-Cognitive Therapy (MCT) for adults with ADHD that extends the principles and practices of cognitive-behavioral therapy to the development of executive self-management skills. Method: Thirty adults diagnosed with ADHD completed an 8- or 12-week program designed to target impairments in time management, organization, and planning skills. Treatment efficacy was measured using pre- and posttreatment self-report standardized measures (CAARS-S:L & Brown ADD Scales). Results: General linear modeling revealed a robust significant posttreatment decline on the CAARS DSM-IV Inattentive symptom scale ( p < .001) as well as improvement on the Brown ADD Scales ( p < .001). Conclusion: The findings indicate that participants in the MCT program showed marked improvement with respect to core ADHD symptoms of inattention, as well as executive functioning skills, suggesting that this program has promise as a treatment for meta-cognitive deficits in adults with ADHD. (J. of Att. Dis. 2008; 11(6) 728-736)
Caspase-cleaved HPK1 induces CD95L-independent activation-induced cell death in T and B lymphocytes
Authors: Brenner Dirk , Golks Alexander , Becker Mareike , Müller Wolfgang , Frey Christian R. , Novak Rostislav , Melamed Doron , Kiefer Friedemann , Krammer Peter H. , Arnold Rüdiger
Published: August 2007

Life and death of peripheral lymphocytes is strictly controlled to maintain physiologic levels of T and B cells. Activation-induced cell death (AICD) is one mechanism to delete superfluous lymphocytes by restimulation of their immunoreceptors and it depends partially on the CD95/CD95L system. Recently, we have shown that hematopoietic progenitor kinase 1 (HPK1) determines T-cell fate. While full-length HPK1 is essential for NF-κB activation in T cells, the C-terminal fragment of HPK1, HPK1-C, suppresses NF-κB and sensitizes toward AICD by a yet undefined cell death pathway. Here we show that upon IL-2–driven expansion of primary T cells, HPK1 is converted to HPK1-C by a caspase-3 activity below the threshold of apoptosis induction. HPK1-C se-lectively blocks induction of NF-κB–dependent antiapoptotic Bcl-2 family members but not of the proapoptotic Bcl-2 family member Bim. Interestingly, T and B lymphocytes from HPK1-C transgenic mice undergo AICD independently of the CD95/CD95L system but involving caspase-9. Knock down of HPK1/HPK1-C or Bim by small interfering RNA shows that CD95L-dependent and HPK1/HPK1-C–dependent cell death pathways complement each other in AICD of primary T cells. Our results define HPK1-C as a suppressor of antiapoptotic Bcl-2 proteins and provide a molecular basis for our understanding of CD95L-independent AICD of lymphocytes.
Improve protective efficacy of a TB DNA-HSP65 vaccine by BCG priming
Authors: Gonçalves Eduardo DC , Bonato Vânia Luiza D , da Fonseca Denise M , Soares Edson G , Brandão Izaíra T , Soares Ana Paula M , Silva Célio L
Published: August 2007

Vaccines are considered by many to be one of the most successful medical interventions against infectious diseases. But many significant obstacles remain, such as optimizing DNA vaccines for use in humans or large animals. The amount of doses, route and easiness of administration are also important points to consider in the design of new DNA vaccines. Heterologous prime-boost regimens probably represent the best hope for an improved DNA vaccine strategy. In this study, we have shown that heterologous prime-boost vaccination against tuberculosis (TB) using intranasal BCG priming/DNA-HSP65 boosting (BCGin/DNA) provided significantly greater protection than that afforded by a single subcutaneous or intranasal dose of BCG. In addition, BCGin/DNA immunization was also more efficient in controlling bacterial loads than were the other prime-boost schedules evaluated or three doses of DNA-HSP65 as a naked DNA. The single dose of DNA-HSP65 booster enhanced the immunogenicity of a single subcutaneous BCG vaccination, as evidenced by the significantly higher serum levels of anti-Hsp65 IgG2a Th1-induced antibodies, as well as by the significantly greater production of IFN-γ by antigen-specific spleen cells. The BCG prime/DNA-HSP65 booster was also associated with better preservation of lung parenchyma.

The improvement of the protective effect of BCG vaccine mediated by a DNA-HSP65 booster suggests that our strategy may hold promise as a safe and effective vaccine against TB.