bluuebunny/crossref_metadata_2025 huggingface dataset:
The rGel/BLyS fusion toxin specifically targets malignant B cells expressing the BLyS receptors BAFF-R, TACI, and BCMA
Authors: Lyu Mi-Ae , Cheung Lawrence H. , Hittelman Walter N. , Marks John W. , Aguiar Ricardo C.T. , Rosenblum Michael G.
Published: February 2007

B lymphocyte stimulator (BLyS) is crucial for B-cell survival, and the biological effects of BLyS are mediated by three cell surface receptors designated B cell–activating factor receptor (BAFF-R), transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI), and B-cell maturation antibody (BCMA). Increased expression of BLyS and its receptors has been identified in numerous B-cell malignancies. We generated a fusion toxin designated rGel/BLyS for receptor-mediated delivery of the recombinant gelonin (rGel) toxin to neoplastic B cells, and we characterized its activity against various B-cell tumor lines. Three mantle cell lymphoma (MCL) cell lines (JeKo-1, Mino, and SP53) and two diffuse large B-cell lymphoma (DLBCL) cell lines (SUDHL-6 and OCI-Ly3) expressing all three distinct BLyS receptors were found to be the most sensitive to the fusion toxin (IC50 = 2–5 pmol/L and 0.001–5 nmol/L for MCL and DLBCL, respectively). The rGel/BLyS fusion toxin showed specific binding to cells expressing BLyS receptors and rapid internalization of the rGel component into target cells. The cytotoxic effects of rGel/BLyS were inhibited by pretreatment with free BLyS or with soluble BAFF-R, TACI, and BCMA decoy receptors. This suggests that the cytotoxic effects of the fusion toxin are mediated through BLyS receptors. The rGel/BLyS fusion toxin inhibited MCL cell growth through induction of apoptosis associated with caspase-3 activation and poly (ADP-ribose) polymerase cleavage. Our results suggest that BLyS has the potential to serve as an excellent targeting ligand for the specific delivery of cytotoxic molecules to neoplastic B cells expressing the BLyS receptors, and that the rGel/BLyS fusion toxin may be an excellent candidate for the treatment of B-cell malignancies especially MCL and DLBCL. [Mol Cancer Ther 2007;6(2):460–70]
Endobronchial Capillary Hemangioma: Case Report and Review of the Literature
Authors: Rose Anthony S. , Mathur Praveen N.
Published: February 2007

A 66-year-old man with mitral stenosis on coumadin presents with hemoptysis caused by a capillary hemangioma of the proximal airways. Argon plasma coagulation was utilized to treat the lesions resulting in resolution of hemoptysis. Tracheobronchial capillary hemangiomas are rare in adults, but are easily discovered and treated with bronchoscopic intervention. The literature to date is reviewed pertaining to adult tracheobronchial capillary hemangiomas.
Reactive Oxygen Species Activate the HIF-1α Promoter Via a Functional NFκB Site
Authors: Bonello Steve , Zähringer Christian , BelAiba Rachida S. , Djordjevic Talija , Hess John , Michiels Carine , Kietzmann Thomas , Görlach Agnes
Published: February 2007

Objective—

Reactive oxygen species have been implicated as signaling molecules modulating the activity of redox-sensitive transcription factors such as nuclear factor kappa B (NF-κB). Recently, the transcription factor hypoxia-inducible factor-1 (HIF-1), known to mediate gene expression by hypoxia, has been found to be also activated by nonhypoxic factors in a redox-sensitive manner. We therefore aimed to elucidate the link between these 2 important redox-sensitive transcription factors.

Methods and Results—

In pulmonary artery smooth muscle cells, reactive oxygen species generated either by exogenous H
2
O
2
or by a NOX4-containing NADPH oxidase stimulated by thrombin activated or induced NF-κB and HIF-1α. The reactive oxygen species-mediated HIF-1α induction occurred on the transcriptional level and was dependent on NF-κB. Transfection experiments with wild-type or mutant HIF-1α promoter constructs revealed the presence of a yet unidentified NF-κB binding element. Gel shift analyses and chromatin immunoprecipitation verified binding of NF-κB to this site. Furthermore, reactive oxygen species enhanced expression of plasminogen activator inhibitor-1, which was prevented by dominant-negative IκB or mutation of the HIF-1 binding site within the plasminogen activator inhibitor-1 promoter.

Conclusion—

These findings show for the first time to our knowledge that reactive oxygen species directly link HIF-1α and NF-κB, implicating an important pathophysiological role of this novel pathway in disorders associated with elevated levels of reactive oxygen species.
Factor IXa Inhibitors as Novel Anticoagulants
Authors: Howard Emily L. , Becker Kristian C.D. , Rusconi Christopher P. , Becker Richard C.
Published: February 2007

Currently available anticoagulants are limited by modest therapeutic benefits, narrow clinical applications, increased bleeding risk, and drug-induced thrombophilia. Because factor IX plays a pivotal role in tissue factor (TF)–mediated thrombin generation, it may represent a promising target for drug development. Several methods of attenuating factor IX activity, including monoclonal antibodies, synthetic active site-blocked competitive inhibitors, oral inhibitors, and RNA aptamers, have undergone investigation. This review summarizes present knowledge of factor IX inhibitors with emphasis on biology, pharmacology, preclinical data, and early-phase clinical experience in humans.
Phenotypic Heterogeneity of the Endothelium
Authors: Aird William C.
Published: February 2007

Endothelial cells, which form the inner cellular lining of blood vessels and lymphatics, display remarkable heterogeneity in structure and function. This is the second of a 2-part review on the phenotypic heterogeneity of blood vessel endothelial cells. The first part discusses the scope, the underlying mechanisms, and the diagnostic and therapeutic implications of phenotypic heterogeneity. Here, these principles are applied to an understanding of organ-specific phenotypes in representative vascular beds including arteries and veins, heart, lung, liver, and kidney. The goal is to underscore the importance of site-specific properties of the endothelium in mediating homeostasis and focal vascular pathology, while at the same time emphasizing the value of approaching the endothelium as an integrated system.
Activation of Extracellular Signal-Regulated Kinase 5 Reduces Cardiac Apoptosis and Dysfunction via Inhibition of a Phosphodiesterase 3A/Inducible cAMP Early Repressor Feedback Loop
Authors: Yan Chen , Ding Bo , Shishido Tetsuro , Woo Chang-Hoon , Itoh Seigo , Jeon Kye-Im , Liu Weimin , Xu Haodong , McClain Carolyn , Molina Carlos A. , Blaxall Burns C. , Abe Jun-ichi
Published: February 2007

Substantial evidence suggests that the progressive loss of cardiomyocytes caused by apoptosis significantly contributes to the development of heart failure. β-Adrenergic receptor activation and subsequent persistent phosphodiesterase 3A (PDE3A) downregulation and concomitant inducible cAMP early repressor (ICER) upregulation (PDE3A/ICER feedback loop) has been proposed to play a key role in the pathogenesis of cardiomyocyte apoptosis. In contrast, insulin-like growth factor-1 can activate cell survival pathways, providing protection against cell death and restoring muscle function. In this study, we found that insulin-like growth factor-1 activates extracellular signal-regulated kinase 5 (ERK5) and inhibits PDE3A/ICER feedback loop. Insulin-like growth factor-1 normalized isoproterenol-mediated PDE3A downregulation and ICER upregulation via ERK5/MEF2 activation, and also inhibited isoproterenol-induced myocyte apoptosis. To determine the physiological relevance of ERK5 activation in regulating PDE3A/ICER feedback loop, we investigated the PDE3A/ICER expression and cardiomyocyte apoptosis in transgenic mice with cardiac specific expression of a constitutively active form of mitogen-activated protein (MAP)/extracellular signal-regulated protein kinase (ERK) kinase 5α (MEK5α) (CA-MEK5α-Tg). In wild-type mice, pressure overload- or doxorubicin-induced significant reduction of PDE3A expression and subsequent ICER induction. Cardiac specific expression of CA-MEK5α rescued pressure overload- or doxorubicin-mediated PDE3A downregulation and ICER upregulation and inhibited myocyte apoptosis as well as subsequent cardiac dysfunction in vivo. These data suggest that preventing the feedback loop of PDE3A/ICER by ERK5 activation could inhibit progression of myocyte apoptosis as well as cardiac dysfunction. These data suggest a new therapeutic paradigm for end stage of heart failure by inhibiting the PDE3A/ICER feedback loop via activating ERK5.
Regulation of Endothelial Cell Cycle by Laminar Versus Oscillatory Flow
Authors: Guo Deliang , Chien Shu , Shyy John Y.-J.
Published: February 2007

Steady laminar flow in the straight parts of the arterial tree is atheroprotective, whereas disturbed flow with oscillation in branch points and the aortic root are athero-prone, in part, because of the distinct roles of the flow patterns in regulating the cell cycle of vascular endothelial cells (ECs). To elucidate the molecular basis underlying the endothelial cell cycle regulated by distinct flow patterns, we conducted flow-channel experiments to investigate the effects of laminar versus oscillatory flows on activation of AMP-activated protein kinase (AMPK) and Akt in ECs. Laminar flow caused a transient activation of both AMPK and Akt, but oscillatory flow activated only Akt, with AMPK being maintained at its basal level. Constitutively active and dominant-negative mutants of AMPK and Akt were used to elucidate further the positive effect of Akt and negative role of AMPK in mediating mTOR (mammalian target of rapamycin) and its target p70S6 kinase (S6K) in response to laminar and oscillatory flows. Measurements of phosphorylation of mTOR Ser2448 and S6K Thr389 showed that AMPK, by counteracting Akt under laminar flow, resulted in a transient activation of S6K. Under oscillatory flow, because of the lack of AMPK activation to effect negative regulation, S6K was activated in a sustained manner. As a functional consequence, AMPK activation attenuated cell cycle progression in response to both laminar and oscillatory flows. In contrast, AMPK inhibition promoted EC cycle progression by decreasing the cell population in the G
0
/G
1
phase and increasing it in the S+G
2
/M phase. In vivo, phosphorylation of the promitotic S6K in mouse thoracic aorta was much less than that in mouse aortic root. In contrast, AMPK phosphorylation was higher in the thoracic aorta. These results provide a molecular mechanism by which laminar versus oscillatory flow regulates the endothelial cell cycle.
Decompressive Hemicraniectomy for the Treatment of Intractable Intracranial Hypertension After Aneurysmal Subarachnoid Hemorrhage
Authors: Schirmer Clemens M. , Hoit Daniel A. , Malek Adel M.
Published: February 2007

Background and Purpose—

Decompressive hemicraniectomy and duroplasty (DHCD) can improve survival in patients with severe cerebral edema. We present our clinical experience with DHCD for the treatment of refractory elevated intracranial pressure (ICP) in patients with aneurysmal subarachnoid hemorrhage (aSAH).

Methods—

DHCD was performed in 16 patients (11 female; median age, 49.5 years) with aSAH (11 Hunt-Hess grade 4 to 5) for sustained ICP >250 mm H
2
O refractory to maximal medical treatment and cerebrospinal fluid drainage at a median of 2 days from admission. Half of the patients were treated with endovascular coiling and the other half with surgical clipping.

Results—

DHCD (mean flap size, 8536 mm
2
) reduced ICP from 350±157 to 147±124 mm H
2
O. Eleven patients survived (69%), and at latest follow-up (median, 450 days), 7 (64%) had a modified Rankin score of 0 to 3 and 4 (36%) a score of 4 to 5. Peak herniated brain volume was inversely associated with good outcome (
P
<0.005). Early craniectomy performed within 48 hours after the aSAH was associated with better outcome: 6 of 8 patients had good outcomes (75%) compared with 1 of 8 patients in whom late decompression was performed (
P
<0.01). Midline shift, Hunt-Hess grade, presence of hemorrhage, hematoma volume, craniectomy area, peak ICP, and relative ICP reduction were not associated with outcome in this patient population.

Conclusions—

DHCD is a useful adjunct modality for management of refractory intracranial hypertension in patients with high-grade aSAH, even in the absence of large intraparenchymal hemorrhage. In our series, long-term outcome was better in patients who underwent early intervention.
Preconditioning Suppresses Inflammation in Neonatal Hypoxic Ischemia Via Akt Activation
Authors: Yin Wei , Signore Armando P. , Iwai Masanori , Cao Guodong , Gao Yanqin , Johnnides Michael J. , Hickey Robert W. , Chen Jun
Published: February 2007

Background and Purpose—

Hypoxic preconditioning (PC) confers robust neuroprotection against neonatal hypoxic-ischemic brain injury (H-I), yet the underlying mechanism is poorly understood. In the adult brain, neuronal survival after ischemia is associated with the activation of the phosphatidylinositol 3-kinase (PI3-K)/Akt signaling pathway. Suppression of inflammation is a newly identified direct consequence of PI3-K/Akt signaling. We therefore investigated whether PI3-K/Akt suppresses inflammation and contributes to PC-induced neuroprotection.

Methods—

Postnatal day 7 rats were exposed for 3 hours to either ambient air or 8% oxygen, which induces hypoxic PC. H-I was produced 24 hours later by unilateral carotid artery ligation followed by 2.5 hours of hypoxia. Animals were euthanized 0 to 24 hours later for detecting Akt and glycogen synthetase kinase-3β phosphorylation (p-Akt, p-GSK-3β), 24 hours later for assessing cytokine expression and inflammatory markers, and 7 days later for measuring brain tissue loss. In addition, LY294002 was injected intracerebroventricularly to inhibit PI3-K/Akt.

Results—

Brains with H-I without PC showed delayed but sustained reduction in p-Akt. PC restored the levels of p-Akt and the Akt substrate GSK-3β, reduced proinflammatory markers (NF-κB, COX-2, CD68, myeloperoxidase, and microglial activation), and markedly ameliorated H-I-induced brain tissue loss. Inhibition of PI3-K/Akt using LY294002 attenuated PC neuroprotection and promoted the expression of NF-κB, COX-2, and CD68. Proteomic microarray analysis revealed that PC inhibited expression of proinflammatory cytokines induced by H-I or a dose of lipopolysaccharide that resulted in minimal tissue damage.

Conclusions—

Suppression of inflammatory responses may contribute to PC neuroprotection against neonatal H-I brain injury. This effect is mediated in part via upregulating PI3-K/Akt activity.
Autonomous Underwater Vehicle Measurements of Surface Wave Decay and Directional Spectra in the Marginal Sea Ice Zone*
Authors: Hayes Daniel R. , Jenkins Adrian , McPhail Stephen
Published: February 2007

In March 2003 several autonomous underwater vehicle (AUV) missions were carried out under sea ice in the western Bellingshausen Sea. Data from the upward-looking acoustic Doppler current profiler (ADCP) on the “Autosub” AUV indicate a strongly oscillating horizontal velocity of the ice due to ocean swell. Swell period, height, direction, and directional spread have been computed every 800 m from the ice edge to 10 km inward for three missions. Exponential, period-dependent attenuation of waves propagating through sea ice was observed. Mean period increased with distance from the ice edge. The wave field refracted during propagation. The directional wave spread does not seem to relate to distance from the ice edge, although higher frequencies tended to be more spread. If suitably deployed, an ordinary ADCP may be used with this technique to study both scalar and directional properties of waves in open or ice-covered water.
An Exchange Window for the Injection of Antarctic Intermediate Water into the South Pacific
Authors: Iudicone Daniele , Rodgers Keith B. , Schopp Richard , Madec Gurvan
Published: February 2007

Antarctic Intermediate Water (AAIW) occupies the intermediate horizon of most of the world oceans. Formed in the Southern Ocean, it is characterized by a relative salinity minimum. With a new, denser in situ National Oceanographic Data Center dataset, the authors have reanalyzed the export characteristics of AAIW from the Southern Ocean into the South Pacific Ocean. These new data show that part of the AAIW is exported from the subpolar frontal region by the large-scale circulation through an exchange window of 10° width situated east of 90°W in the southeast corner of the Pacific basin. This suggests the origin of this water to be in the Antarctic Circumpolar Current. A set of numerical modeling experiments has been used to reproduce these observed features and to demonstrate that the dynamics of the exchange window is controlled by the basin-scale meridional pressure gradient. The exchange of AAIW between the Southern and Pacific Oceans must therefore be understood in the context of the large basin-scale dynamical balance rather than simply local effects.
Ecclesiastes Gone ‘Sideways’
Authors: Middlemas Jill
Published: February 2007

In the light of modern day attention to happiness as a personal and societal goal, this paper explores how this theme has been presented in the movie Sideways as well as in the biblical book ‘Ecclesiastes’. Although the outlook of the two clearly overlaps, the biblical perspective tempers the modern view.
Origen’s Doctrine of Creation
Authors: Bostock Gerald
Published: February 2007

Origen’s concept of the Logos can bridge the gulf between creation and redemption. Through the Logos, this world, formed instantaneously and characterized by the variability of matter, is linked with the eternal Wisdom. Origen sees creation as the imposing of order on chaos, with humanity a microcosm reflecting the macrocosm.
The World Polity and Deforestation
Authors: Shandra John M.
Published: February 2007

Over the past decade, there has been a growth in international organizations concerned with environmental matters. These organizations include international non-governmental organizations (INGOs), inter-governmental organizations (IGOs), and treaties. This article presents cross-national models examining the effects of these variables on deforestation. In doing so, I use data for up to 73 nations to examine the determinants of deforestation from 1990 to 2000. I fi nd substantial support for world polity hypotheses that all these organizations reduce deforestation. I also fi nd support for world system arguments that economic dependency relationships based upon commodity concentration increase deforestation. Finally, I fi nd that economic growth decreases deforestation and population growth increases deforestation. I conclude with some brief policy recommendations and directions for future research.
The Effects of Primary Sector Foreign Investment on Carbon Dioxide Emissions from Agriculture Production in Less-Developed Countries, 1980-99
Authors: Jorgenson Andrew K.
Published: February 2007

This research helps to increase our collective understanding of the complex interrelationships between foreign investment dependence and environmental degradation. Panel regresssion analyses of 35 less developed countries from 1980 to 1999 are conducted to test the hypothesis that foreign direct investment in the primary sector increases carbon dioxide emissions from agriculture production. Results confi rm the hypothesis, providing support for the theory of foreign capital dependence. Level of agriculture production and the use of tractors are also found to increase the growth of carbon dioxide emissions from this primary sector activity. Conversely, nations more likely to ratify international environmental treaties exhibit suppressed growth in emissions. These fi ndings underscore the need for social scientists to investigate the environmental impacts of both the level and transnational organization of production in different sectors as well as the overall use of relevant machinery and the environmental commitments of nation-states.
When do children generalize the plural to novel nouns?
Authors: Zapf Jennifer A. , Smith Linda B.
Published: February 2007

Despite the theoretical importance of the processes of generalization to the development of morphological rules, not much is known about the basic developmental trend or the relevant processes. The present study seeks to answer the question: at what age are children able to generalize the plural to new nouns. In a six-week longitudinal study, children aged 17.5 to 28 months participated in a spontaneous production task in which they were either provided with the singular form of common and novel nouns and asked to generate the plural form, or given the plural form of those nouns and asked to generate the singular form. The results suggest that very young children do generalize the plural to novel forms. The data also strongly suggest that, long before a truly productive regular plural is evident, very young learners of English know that there is a singular and plural form, and they know how they are related.
Adapting the Diabetes Prevention Program Lifestyle Intervention for Delivery in the Community
Authors: Ackermann Ronald T. , Marrero David G.
Published: February 2007

The Diabetes Prevention Program (DPP) demonstrated that a structured diet and physical activity intervention that achieves and maintains modest weight loss for over-weight adults with impaired glucose tolerance can significantly reduce the development of diabetes. Although tens of millions of American adults could benefit from access to the DPP lifestyle intervention, there currently is no available model for nationwide dissemination of this highly beneficial and cost-effective approach to diabetes prevention. In this article, the authors describe the evolution of adaptations to improve DPP lifestyle intervention implementation and dissemination by a strong community partner, the YMCA. They also provide information about early field research and an ongoing clinical trial that will provide information about the feasibility and effectiveness of applying this new model on a national scale.
Outcome of Conservative Management of Athletic Chronic Groin Injury Diagnosed as Pubic Bone Stress Injury
Authors: Verrall Geoffrey M. , Slavotinek John P. , Fon Gerald T. , Barnes Peter G.
Published: February 2007

Background

Little data exist on the results of treatment for sports-related chronic groin injury.

Hypothesis

Sports-related chronic groin injury treated with a conservative (rest) program results in a satisfactory outcome.

Study Design

Case series; Level of evidence, 4.

Methods

Professional Australian male football players, at the end of the playing season, had their groin injury diagnosed using specific clinical and magnetic resonance imaging (MRI) criteria. Those assessed as having a non-hip-related cause for their chronic groin injury were treated principally by 12 weeks of complete rest from active weightbearing activities. Response to treatment was assessed at different stages of rehabilitation by recording the number of athletes who had returned to playing football and the number of athletes without symptoms.

Results

Twenty-seven athletes were considered to have chronic groin injury. Clinical and MRI (pubic bone marrow edema N = 26 [96%]), hyperintense line N = 25 [93%]) criteria suggested a pubic bone stress injury as diagnosis for the chronic groin injury. Eighty-nine percent of athletes returned to sport in the subsequent playing season, with 100% having returned by the second playing season after diagnosis. Forty-one percent of the athletes were without symptoms at the commencement of the following playing season, rising to 67% by the end of that playing season.

Conclusions

Conservative management of athletic chronic groin injury resulted in an excellent outcome when assessed by the return to sport criterion. However, the results were only satisfactory if the criterion of ongoing symptoms after treatment was used. More research is needed to compare the efficacy of all treatments that are used in this troublesome condition.
Arthroscopic Repair of Type II Superior Labral Anterior Posterior Lesions with and without Acromioplasty
Authors: Coleman Struan H. , Cohen David B. , Drakos Mark C. , Allen Answorth A. , Williams Riley J. , O'Brien Stephen J. , Altchek David W. , Warren Russell F.
Published: February 2007

Background

The treatment of type II superior labral anterior posterior (SLAP) lesions remains controversial. Many surgeons are reluctant to combine a SLAP repair with an acromioplasty for fear of postoperative shoulder stiffness and a poor clinical outcome.

Hypothesis

A SLAP repair and an acromioplasty done concomitantly may yield acceptable outcomes.

Study Design

Case series; Level of evidence, 4.

Methods

We compared the clinical results of 50 patients who had either an isolated type II SLAP repair (SLAP group, 34 patients) or a combined type II SLAP repair and acromioplasty (combined group, 16 patients). Patients were excluded for full-thickness rotator cuff tears or instability. All patients were evaluated with the L'Insalata Functional Shoulder Rating Questionnaire, with the American Shoulder and Elbow Surgeons (ASES) questionnaire, and by subjective evaluation.

Results

At an average of 3.4 years postoperatively, the L'Insalata and ASES scores were similar for the 2 groups: 87.1 and 85.8 for the SLAP group and 85.1 and 86.5 for the combined group, respectively (P > .05). Subjectively, only 65% of the patients in the SLAP group reported a “good” or “excellent” satisfaction with the surgery, compared with an 81% “good” or “excellent” satisfaction rating among the patients in the combined group. Seven patients (21%) in the SLAP group had postoperative clinical impingement, compared with no patients (0%) in the combined group (P < .03).

Conclusions

According to our data, these 2 procedures done concomitantly may yield acceptable outcomes. Our findings indicated that a combined type II SLAP repair and acromioplasty had no negative effect clinically and, furthermore, appeared to prevent residual clinical impingement.
Interobserver Agreement in the Classification of Rotator Cuff Tears
Authors:   Multicenter Orthopaedic Outcomes Network-Shoulder (MOON Shoulder Group), Kuhn John E. , Dunn Warren R. , Ma Benjamin , Wright Rick W. , Jones Grant , Spencer Edwin E. , Wolf Brian , Safran Marc , Spindler Kurt P. , McCarty Eric , Kelly Brian , Holloway Brian
Published: February 2007

Background

Six classification systems have been proposed for describing rotator cuff tears designed to help understand their natural history and make treatment decisions.

Purpose

To assess the interobserver variation for these classification systems and identify the method with the best interob-server agreement.

Study Design

Cohort study (diagnosis); Level of evidence, 2.

Methods

Six rotator cuff tear classification systems were identified in a literature search. The components of these systems included partial-thickness rotator cuff tears and classification by size, shape, configuration, number of tendons involved, and by extent, topography, and nature of the biceps. Twelve fellowship-trained orthopaedic surgeons who each perform at least 30 rotator cuff repairs per year reviewed arthroscopy videos from 30 patients with a random assortment of rotator cuff tears and classified them by the 6 classification systems. Interobserver variation was determined by a kappa analysis.

Results

Interobserver agreement was high when distinguishing between full-thickness and partial-thickness tears (0.95, [UNKNOWN]=0.85). The investigators agreed on the side (articular vs bursal) of involvement for partial-thickness tears (observed agreement 0.92, [UNKNOWN]= 0.85) but could not agree when classifying the depth of the partial-thickness tear (observed agreement 0.49, [UNKNOWN]= 0.19). The best agreement for full-thickness tears was seen when the tear was classified by topography (degree of retraction) in the frontal plane (observed agreement 0.70, [UNKNOWN]= 0.54).

Conclusion

With the exception of distinguishing partial-thickness from full-thickness rotator cuff tears and identifying the side (articular vs bursal) of involvement with partial-thickness tears, currently described rotator cuff classification systems have little interobserver agreement among experienced shoulder surgeons. Researchers should consider describing full-thickness rotator cuff tears by topography (degree of retraction) in the frontal plane.
The Development and Use of the Healthy School Indicator Tool (HSIT)
Authors: Andrews Jac J. W. , Conte Richard
Published: February 2007

This article describes the development and use of a norm-referenced instrument called the Healthy School Indicator Tool (HSIT) that was designed to assist educational professionals monitor their progress in addressing critical health issues in schools. Factor analyses of two administrations of the survey indicated a stable factor structure. In terms of reliability, both split-half and Cronbach’s alpha analyses revealed adequate reliability of factors. In terms of validity, the survey appears to adequately cover critical school health issues and is able to discriminate schools that have been involved in comprehensive school health programs for varying amounts of time.
An Initial Investigation of the Impact of Self-Regulation and Emotionality on Behavior Problems in Children With ADHD
Authors: Crundwell R. Marc A.
Published: February 2007

Children with attention-deficit hyperactivity disorder (ADHD) are reported to have more difficulties with self-regulation and emotional regulation. Current ADHD models suggest a primary deficit in behavioral inhibition causes secondary deficits in executive functions, impacting on emotional regulation. This study examined the relationship of regulation and emotionality on behavior problems in children with ADHD and the relationship between ADHD symptoms and emotional regulation and emotionality. Mothers of 32 male children between the ages of 6 and 11 diagnosed as ADHD combined type or predominantly hyperactive-impulsive type completed questionnaires assessing self-control and emotionality. Results indicated that ADHD boys who showed greater emotionality in terms of anger/frustration and less self-control and inhibition were rated as having more behavioral difficulties. Children with symptoms of hyperactivity and impulsivity were rated as lower in self-control and inhibition and higher in emotionality. Results of the study are discussed with respect to current theoretical models of ADHD.
Recommended Best Practices for the Early Identification and Diagnosis of Children with Specific Learning Disabilities in Ontario
Authors: Harrison Allyson G.
Published: February 2007

Despite the importance of early intervention for most disorders to minimize potential deleterious lifetime effects for the individuals concerned, there is currently no universally accepted protocol for the early screening, identification, and assessment of specific learning disabilities, and no consistent age at which initial diagnosis occurs. In Ontario, as well as in other jurisdictions, the distinction between key terms, such as identification and diagnosis, for the sake of service provision and funding in the school system is often not clearly understood. This article presents a rationale and recommended best practice procedures for the screening, identification, and diagnosis of specific learning disabilities in Ontario for children aged 4 to 8 years. A clarification of key terms, challenges to diagnostic accuracy, and implications of recommended improvements to current practice are articulated.
Community Resilience Impact on Child and Youth Health Outcomes
Authors: Mykota David B. , Muhajarine Nazeem
Published: February 2007

In this study the authors investigated community resilience from the perspectives of well-defined, geographically bounded neighbourhoods and in relation to factors within them that may mediate, either positively or negatively, child and youth health outcomes. Three socially contrasting neighbourhoods with heterogeneous child health outcomes were selected for study. Within each neighbourhood, adults and 13- to 18-year-old youth were recruited for focus group interviews; in addition, key informants from the educational sector were included in the study. The results provide empirical support to a conceptual model of community resilience that integrates structural and process-related dualisms as well as risk and protective factors for child health. While presenting an integrated model of community resilience, the authors acknowledge the need for studies that further illuminate specific contributions of community and individual factors and their mechanisms in producing child and youth health outcomes.
Analysis of Shaft-Loaded Membrane Delamination Using Stationary Principles
Authors: Majidi Carmel , Groff Richard E. , Fearing Ron S.
Published: February 2007

The following analysis investigates the delamination of an elastic membrane which on one side adheres to a smooth substrate while the other side is attached to a rigid cylindrical shaft. When the shaft is pulled perpendicularly from the substrate, this system is equivalent to the blister test of Malyshev and Salganik ( International Journal of Fracture Mechanics, 1, 114 (1965)) and a solution is derived using the principle of minimum potential energy. Delamination can also be caused by rotating the shaft, which may be induced by a shear load and/or moment applied to the free end. For this more complicated system, an approximate solution is obtained from upper and lower bounds on strain energy that are derived from stationary principles with restricted deformation and stress fields, respectively. Beyond their applicability to blister tests, these results are relevant to the emerging study of biologically-inspired adhesives, as membranes constitute a critical attachment structure for a variety of wall-clinging organisms.
Magnetizable and Polarizable Elastic Materials
Authors: Ericksen J.L.
Published: February 2007

In research on materials, it is not unusual for workers to be unaware of good ideas and results produced long ago, and I will discuss a case in point. When workers became acquainted with radiation pressure, it stimulated them to consider the possibility that electromagnetic fields could not only exert forces on matter, but that matter could exert forces on fields, extending ideas of action and reaction to combinations of these. I will present a formulation of these ideas and a similar one about energies, then use them to formulate a theory of materials that can be magnetized and polarized, one that can be compared with various theories of this kind in the literature. There are important differences between the theory presented here and most of the others. So, this provides food for thought as to what should be taken as bases for formulating such theories.
On the Theory of Viscoelastic Mixtures and Stability
Authors: Ieşan D. , Nappa L.
Published: February 2007

A theory is developed for binary mixtures of viscoelastic materials. The basic equations of a nonlinear theory of heat conducting viscoelastic mixtures are derived in Lagrangian description. The individual components of the mixture are modeled as Kelvin—Voigt viscoelastic materials. A nonlinear constitutive relation which generalizes Darcy's law is derived. The linearized version of the theory is established. In the present theory the diffusive force depends on relative displacement and relative velocity. Stability results are presented in the context of materials which are non-conductor of heat.
Magnetostriction of a Hard Ferromagnetic and Elastic Thin-Film Structure
Authors: Nobili Andrea , Tarantino Angelo Marcello
Published: February 2007

In this paper, the magnetostriction of a thin film ferromagnetic and elastic structure is investigated. The structure is composed of an elastic layer confined between two perfectly bonded thin ferromagnetic layers in a plane strain setting. The ferromagnetic layers are saturated insulators and their magnetization is assumed at every stage parallel to the relevant layer's axis (latent microstructure). The structure is studied within the theory of magneto-elastic interaction and focus is set on reducing the problem to a manageable one-dimensional form. This is accomplished employing the Euler—Bernoulli kinematics in conjunction with Maxwell equations. Once the model is stated, a system of coupled nonlinear integro-differential equations is obtained in the deformation components. Integral terms spring from the non-local character of the magnetic interaction. Some features of the solution are pointed out through an asymptotic analysis. The system is solved through the spectral method and a collocation technique, employing Gaussian quadrature at a second grid to assess the magnetic field and an iterative solver for nonlinear systems. Plots of the deformed configuration, of the internal action and of the layers's interaction are given. A parametric analysis brings out the role of some dimensionless quantities. Finally, solutions are compared with experimental results on Nickel magnetostriction.
Stress Distribution Around a Crack in Anti-Plane Micropolar Elasticity
Authors: Shmoylova E. , Potapenko S.
Published: February 2007

In this paper we formulate the boundary value problem of anti-plane micropolar elasticity for a domain containing a crack in Sobolev spaces and prove the existence and continuous dependence on the data of the corresponding weak solutions. We consider the cases of both finite and infinite domain and find the solutions in terms of modified single layer and modified double layer integral potentials with distributional densities.
Intravenous immunoglobulins contain naturally occurring antibodies that mimic antineutrophil cytoplasmic antibodies and activate neutrophils in a TNFα-dependent and Fc-receptor–independent way
Authors: Jarius Sven , Eichhorn Peter , Albert Michael H. , Wagenpfeil Stefan , Wick Manfred , Belohradsky Bernd H. , Hohlfeld Reinhard , Jenne Dieter E. , Voltz Raymond
Published: February 2007

Intravenous immunoglobulin (IVIg) preparations are increasingly used for therapy of several neuroimmunologic diseases. IVIg therapy is considered safe, although serious side effects like aseptic meningitis, cerebral vasospasm, or ischemic encephalopathy have been reported. These side effects are frequently associated with neutrophilic pleocytosis in the cerebrospinal fluid (CSF), suggesting a neutrophil-mediated mechanism. To elucidate the potential role of neutrophil activation, we analyzed IVIg preparations from 5 different commercial sources for the presence of antineutrophil cytoplasmic antibody (ANCA)–like immunoglobulins against ethanol-fixed peripheral-blood neutrophils, purified human antigens, and a panel of human and nonhuman tissues. All IVIg batches tested (n = 13) contained atypical ANCAs (IgG titer up to 1:2048, IgA up to 1:512). Moreover, all preparations were capable of inducing hydrogen peroxide production in TNFα-primed human neutrophils, with a significant correlation (P < .005) between atypical ANCA titers in IVIg preparations and neutrophil activation. Fc-mediated binding and activation was ruled out by the use of IVIg-F(ab′)2 fragments. Our findings strongly suggest that in vivo activation of TNFα-primed neutrophils by atypical ANCAs of IVIg may contribute to the side effects of IVIg therapy and for the first time demonstrate that the activation of neutrophil granulocytes by IVIg occurs in an Fc receptor (FcR)–independent, hence antigen-dependent, way.
Mapping helper T-cell epitopes on platelet membrane glycoprotein IIIa in chronic autoimmune thrombocytopenic purpura
Authors: Sukati Hosea , Watson Henry G. , Urbaniak Stanislaw J. , Barker Robert N.
Published: February 2007

Chronic autoimmune thrombocytopenic purpura (AITP) is associated with autoantibodies specific for platelet membrane components, often including glycoprotein GPIIIa. T helper (Th) cells reactive with GPIIIa, which are capable of driving the autoantibody response, are activated in AITP, and the aim here was to map the epitopes that they recognize. Peripheral blood mononuclear cells (PBMCs) were obtained from 31 patients with AITP and 30 control donors and stimulated with a panel of 86 overlapping synthetic 15-mer peptides spanning the complete sequence of GPIIIa. One or more peptides elicited recall proliferation by PBMCs from 28 of the patients, and, typically, multiple sequences were stimulatory. In contrast, responses in healthy control donors were rare (chi-square test = 115.967; P ≤ .001). It was confirmed that the proliferating PBMCs from patients were cells of the CD3+CD4+ helper phenotype that were MHC class II restricted. Despite variation between different cases of AITP, particular sequences were commonly recognized with PBMCs from 24 patients (77%) responding to 1 or more of the 4 most dominant peptides. Mapping such dominant autoreactive helper epitopes is the first step in the development of new approaches to the treatment of AITP, based on the use of peptides to tolerize Th cells specific for platelet glycoproteins.
Effective asparagine depletion with pegylated asparaginase results in improved outcomes in adult acute lymphoblastic leukemia: Cancer and Leukemia Group B Study 9511
Authors: Wetzler Meir , Sanford Ben L. , Kurtzberg Joanne , DeOliveira Divino , Frankel Stanley R. , Powell Bayard L. , Kolitz Jonathan E. , Bloomfield Clara D. , Larson Richard A.
Published: February 2007

CALGB 9511 used pegaspargase (PEG-ASP) in lieu of the native enzyme. The aim was to compare differences in overall survival (OS) and disease-free survival (DFS) between patients who did and did not achieve asparagine depletion, defined by enzyme levels greater than 0.03 U/mL plasma for 14 consecutive days after at least 1 of 4 planned PEG-ASP administrations. Samples were available from 85 eligible patients. On univariate analyses, the 22 patients who did not achieve asparagine depletion had inferior OS (P = .002; hazard ratio [HR] = 2.37; 95% CI = 1.38-4.09) and DFS (P = .012; HR = 2.21; 95% CI = 1.19-4.13). After adjusting for age, performance status, leukocyte count, and karyotype in a proportional hazards model, both the OS and DFS HRs decreased to 1.8 (P = .056; 95% CI = 1.0-3.2 and P = .084; 95% CI = 0.9-3.6, respectively). We conclude that effective asparagine depletion with PEG-ASP is feasible as part of an intensive multiagent therapeutic regimen in adult acute lymphoblastic leukemia and appears associated with improved outcomes.
Statins synergistically potentiate 7-hydroxystaurosporine (UCN-01) lethality in human leukemia and myeloma cells by disrupting Ras farnesylation and activation
Authors: Dai Yun , Khanna Payal , Chen Shuang , Pei Xin-Yan , Dent Paul , Grant Steven
Published: February 2007

Interactions between UCN-01 and HMG-CoA reductase inhibitors (ie, statins) have been examined in human leukemia and myeloma cells. Exposure of U937 and U266 cells to minimally toxic concentrations of UCN-01 and various statins (eg, lovastatin, simvastatin, or fluvastatin) dramatically increased mitochondrial dysfunction, caspase activation, and apoptosis. Comparable effects were observed in other leukemia and myeloma cell lines as well as in primary acute myeloid leukemia (AML) blasts but not in normal hematopoietic cells. Potentiation of UCN-01 lethality by lovastatin was associated with disruption of Ras prenylation and activation. These events were significantly attenuated by farnesyl pyrophosphate (FPP) but not by geranylgeranyl pyrophosphate (GGPP), implicating perturbations in farnesylation rather than geranylgeranylation in synergistic interactions. Coexposure to statins and UCN-01 resulted in inactivation of ERK1/2 and Akt, accompanied by JNK activation. U266 cells ectopically expressing JNK1-APF, a dominant negative JNK1 mutant, displayed significantly reduced susceptibility to lovastatin/UCN-01–mediated lethality. Moreover, transfection of U266 cells with constitutively activated H-Ras (Q61L) attenuated ERK1/2 inactivation and dramatically diminished the lethality of this regimen. Collectively, these findings indicate that HMG-CoA reductase inhibitors act through a Ras farnesylation-associated mechanism to induce signaling perturbations, particularly prevention of Ras and ERK1/2 activation, in UCN-01–treated cells, resulting in the synergistic induction of cell death.
Kringle 5 of human plasminogen, an angiogenesis inhibitor, induces both autophagy and apoptotic death in endothelial cells
Authors: Nguyen Tri Minh Bui , Subramanian Indira V. , Kelekar Ameeta , Ramakrishnan Sundaram
Published: February 2007

Inhibition of endothelial cell proliferation and angiogenesis is emerging as an important strategy in cancer therapeutics. Kringle 5 (K5) of human plasminogen is a potent angiogenesis inhibitor. Previous studies have shown K5 exposure promotes caspase activity and apoptosis in endothelial cells. Here we report that K5 treatment evokes an autophagic response in endothelial cells that is specific and initiated even in the absence of nutritional stress. Endothelial cells exposed to K5 up-regulated Beclin 1 levels within a few hours. Furthermore, progressively increasing amounts of antiapoptotic Bcl-2 were found to be complexed with Beclin 1, although total levels of Bcl-2 remained unchanged. Prolonged exposure to K5 ultimately led to apoptosis via mitochondrial membrane depolarization and caspase activation in endothelial cells. Knocking down Beclin 1 levels by RNA interference decreased K5 induced autophagy but accelerated K5-induced apoptosis. These studies suggest that interfering with the autophagic survival response can potentiate the antiangiogenic effects of Kringle 5 in endothelial cells.
How I treat patients with polycythemia vera
Authors: Finazzi Guido , Barbui Tiziano
Published: February 2007

The clinical course of polycythemia vera (PV) is marked by a high incidence of thrombotic complications; fibrotic and leukemic disease transformations are additional causes of morbidity and mortality. Major predictors of vascular events are increasing age and previous thrombosis; leukocytosis and high JAK2 V617F allele burden are currently being investigated for additional prognostic value in this regard. Myelosuppressive drugs can reduce the rate of thrombosis, but there is concern that their use raises the risk of transformation into acute leukemia. To tackle this dilemma, a risk-oriented management strategy is recommended. Low-risk patients should be treated with phlebotomy and low-dose aspirin. Cytotoxic therapy is indicated in high-risk patients, and the drug of choice is hydroxyurea because of its efficacy in preventing thrombosis and low leukemogenicity. Interferon-alpha should be reserved for selected categories of patients due to high cost and toxicity. The demonstration of JAK2 V617F mutation in the vast majority of PV patients opens the avenue for the development of promising new molecularly targeted drugs.