bluuebunny/crossref_metadata_2025 huggingface dataset:
Somatosensory Activity Relevant for Motor Output
Authors: Gandevia S.C.
Published: February 2007

Several aspects of the function of receptors which contribute to somatic sensations are reviewed. First, there is evidence for a role of large-diameter cutaneous afferents in the reflex regulation of precision movements by the hand. Second, large-diameter muscle afferents from the intrinsic muscles of the hand, probably from primary muscle spindle afferents, can evoke specifïc sensations of finger movement. Third, the variable relationship between discharges in human C fibers from the hand and the specifïc sensation of pain is investigated. Activity in large-diameter cutaneous afferents can probably modify this sensation. Finally, the properties of small-diameter afferent fibers innervating joints are shown to be consistent with a role in the reflex regulation of joint integrity.
Muscles and Their Neural Control
Authors: ten Bruggencate Gerrit
Published: February 2007

The session on ‘The Muscles and Their Neural Control’ comprised papers that covered an extremely broad field, ranging from single membrane channels to integration at the motor unit level. To start with the molecular mechanisms, slow noninactivating sodium channels were postulated to be the common denominator in a number of myopathies, their activation causing depolarization and thus muscle weakness. New ideas were presented regarding muscle insulin receptors as the main target for neurotrophic influences, as well as transmitter release at nonmammalian motor nerve terminals. Changes in muscle compliance seem to be involved in adaptation of spindle sensitivity and reflex activity. Also, data were presented in favor of a neurotoxic component in myotrophic lateral sclerosis. Analysis of stationary motor unit discharges can differentiate parkinsonian patients without tremor from normal controls. Long-term use-dependent factors that change muscle properties have considerable effects on the way in which contractile force is graded.
Enhancement of Voluntary Motor Function Following Spinal Cord Stimulation - Case Study
Authors: Barolat Giancarlo , Myklebust Joel B. , Wenninger William
Published: February 2007

One patient with an incomplete traumatic myelopathy underwent epidural spinal cord stimulation for the management of severe intractable spasms, which were abolished by the stimulation. After several months of stimulation, the patient regained some voluntary motor function in the lower extremities. Voluntary motor control of the Ieft quadriceps was present only when spinal cord stimulation was activated and stopped immediately after it was turned off. The effects could be consistently reproduced. EMG polygraphic recordings confirmed the results.
Reproducibility of Repeated Mountings of a Noninvasive CT/MRI Stereoadapter
Authors: Hariz Marwan I. , Eriksson Tommy
Published: February 2007

The reproducibility of a noninvasive computed tomography (CT)/magnetic resonance imaging stereoadapter was tested on 12 healthy volunteers. The adapter was easy to mount and detach without discomfort. Two repeated mountings of the adapter showed a good reproducibility in relation to the scalp. When extrapolated to a hypothetical target in the right thalamus, the mean differences between the two mountings were 0.07 mm in the lateral, 0.16 mm in the anteroposterior and 0.17 mm in the height coordinates. This high degree of reproducibility seems to permit a safe CT-guided functional stereotaxis, where the preoperative CT scanning can take place on one day and the surgery may be performed on any other suitable day.
Sensory Input Modifying Central Motor Actions
Authors: Henn V.
Published: February 2007

Motor output is often initiated by sensory stimuli and continuously monitored during execution by sensory input, except for the fastest movements. Recent experiments in animals explored the interaction between classical sensory and motor areas of the central nervous system during motor tasks. In man, evoked potentials can give an estimate of involvement of these structures. In analogy, nystagmus has been analyzed in primates, where a more complete description of the sensorimotor process is possible.
Managing the Toxic Waste Problem
Authors: Worthley John A. , Torkelson Richard
Published: February 2007

Toxic waste disposal is likely to be among the most serious and far-reaching problems of public policy and management for the rest of this century. This article presentsfindings on the nature of the problem drawn from a study of thefirst major toxic waste disaster, Love Canal. Based on these findings, the authors identify legislative, organizational, andfiscal dimensions that require policy research and development. Their conclude that a collaborative effort between public-and private-sector interests is essential in dealing with the challenge.
A Comparison of Methods for Nonparametric Estimation of Item Characteristic Curves for Binary Items
Authors: Lee Young-Sun
Published: February 2007

This study compares the performance of three nonparametric item characteristic curve (ICC) estimation procedures: isotonic regression, smoothed isotonic regression, and kernel smoothing. Smoothed isotonic regression, employed along with an appropriate kernel function, provides better estimates and also satisfies the assumption of strict monotonicity. As the number of items and the sample size increase, the kernel smoothing and smoothed isotonic regression ICC estimation procedures yield similar results across all conditions.
Global value, full value and societal costs: capturing the true cost of destroying marine ecosystems
Authors: Failler Pierre , Pan Haoran
Published: February 2007

English

World fisheries are characterized by ecological, economic and social costs which are not taken into account by current market mechanisms. However, the sustainability of ecosystems and fishing activities depends on their being taken into account in order to arrive at the most appropriate management decisions. The European research programme ECOST (Ecosystem, Society, Consilience and Precautionary Principle: Development of an Assessment Method of the Societal Cost for Best Fishing Practices and Efficient Public Policies) develops an integrative approach to the various costs generated by fishing activities. In doing so it seeks to develop a decision-making tool which can contribute to the success of the Plan of Implementation proposed at the Johannesburg summit.

French

Les pêcheries mondiales sont caractérisées par des coûts écologiques, économiques et sociaux qui ne sont pas pris en compte par les mécanismes de marchés actuels. Or la pérennité des écosystèmes et des activités de pêche dépend de leur prise en compte afin de prendre les décisions d'aménagement les plus appropriées. Le programme de recherche européen en coopération ECOST (Ecosystèmes, société, consilience et principe de précaution: développement d'une méthode d'évaluation des coûts sociétaux pour parvenir à des pratiques de pêche et des politiques publiques durables) développe une approche intégrative des différents coûts engendrés par les activités de pêche ainsi que les politiques publiques. Il tend de la sorte à développer un outil d'aide à la décision pouvant contribuer à la réussite du plan d'implémentation du sommet de Johannesbourg.
Managing Membership Decline in a Hostile Environment: The Case of the Print Unions in the Czech Republic, Slovakia and Hungary
Authors: Gennard John
Published: February 2007

This article examines printing trade unions in the Czech Republic, Slovakia and Hungary. Since 1990 they have been under major pressure from financial difficulties resulting from a dramatic fall in membership. This, in turn, stemmed from the hostile environment of privatization, corporate mergers and acquisitions, technological change and anti-trade union policies on the part of some employers. To reduce costs and ensure institutional survival, and potentially revival, the leaderships of the three unions have implemented strategies to redefine union objectives, the means of their achievement and the procedures of union democracy. Modernization is, however, constrained by their unions' decision-making structures, cultures, resources and their own ideologies.
Activation of the STAT1 signalling pathway in lupus nephritis in MRL/lpr mice
Authors: Dong J , Wang Q-X , Zhou C-Y , Ma X-F , Zhang Y-C
Published: February 2007

Interferons (IFNs), type I (α/β) and type II γ, comprise a family of multifunctional cytokines with antiviral, antiproliferative and immunomodulating properties. Both type I and type II IFNs have been heavily implicated in the pathogenesis of systemic lupus erythematosus (SLE). The biological effects of IFNs are mediated through the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway in which both IFN-α/β and IFN-γ activate the transcription factor STAT1. However, little is known about the pathogenic significance of STAT1 in SLE. At this point, we examined the expression and activation of STAT1 in the kidney of MRL/ lpr mice with lupus nephritis (LN) by immunohistochemistry, Western botting and real time quantitative RT-PCR. Increased levels of total STAT1 protein and its activated/phosphorylated form were detected in kidney samples from MRL /lpr mice with LN as compared to those from control mice. Phosphorylated STAT1 was predominantly detected in glomeruli cells. Gene expression of the STAT induced feedback inhibitors suppressor of cytokine signalling-1 (SOCS-1) and SOCS-3 was also enhanced in MRL /lpr mice. In MRL/ lpr mesangial cells, both IFN-α and IFN-γ rapidly induced the phosphorylation of STAT1 in vitro. Our results demonstrate that expression and activation of STAT1 are significantly increased in murine lupus nephritis, and indicate that STAT1 signalling pathway may play an important role in the pathogenesis of kidney inflammation.
Chloroquine treatment reduces the number of cutaneous HLA-DR+ and CD1a+ cells in patients with systemic lupus erythematosus
Authors: Wozniacka A , Lesiak A , Narbutt J , Kobos J , Pavel S , Sysa-Jedrzejowska A
Published: February 2007

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can be exacerbated by exposure to ultraviolet radiation (UVR). The number and phenotype of antigen presenting cells in the skin play a role in cutaneous immune response generation. Although antimalarials are widely used in SLE treatment, their mode of action is not completely elucidated. The aim of our study was to determine the effect of chloroquine treatment on HLA-DR+ and CD1a+ cell number in locally irradiated (three minimal erythema doses of UVB) and normal appearing skin in SLE patients and healthy subjects. A significantly higher number of HLA-DR+ and CD1a+ cells were found in both locations in SLE patients compared with controls. Following three months of daily chloroquine treatment (250 mg), the HLA-DR+ and CD1a+ cell counts were significantly reduced in both irradiated and unirradiated sites of SLE patients, although still higher than in controls. Chloroquine treatment reduces the number of antigen presenting cells in the skin of SLE patients, and this effect may explain the antimalarials beneficial immunoregulatory and anti-inflammatory properties.
Derridada
Authors: Weiss Richard M.
Published: February 2007

Acknowledging that deconstruction had failed to catch on as a research method among management scholars, Weitzner argues for reconsidering Derrida's potential contributions to management scholarship—this time as an ethicist, whose core idea is that the hallmark of an ethical decision is that it is not amenable to rational decision processes. Illustrating the Derridean style of academic debate, he responds to criticisms of Derrida's ethical position as amoral by noting Derrida's declaration that such critics were not serious and by declaring that “in fact” their critique is incorrect. His demonstration of the value of Derrida's views consists of the contention that they are not inconsistent with some existing perspectives. This article argues that the Derridean view errs in portraying ethical decisions as necessarily noninstrumental and nonrational and contrasts it with Weber's view that noninstrumental action may nevertheless be rational. The very divergent practical implications of these opposing perspectives are examined.
Semantic, Executive, and Visuospatial Abilities in Mathematical Reasoning of Referred College Students
Authors: Cirino Paul T. , Morris Mary K. , Morris Robin D.
Published: February 2007

Semantic retrieval (SR) and executive-procedural (EP), but not visuospatial (VS) skills, have been found to be uniquely predictive of mathematical calculation skills in a sample of clinically referred college students. This study set out to cross-validate these results in an independent sample of clinically referred college students (N = 337) as well as extend them by examination of the contributions of these cognitive domains to math reasoning skills. Results indicate that these cognitive domains were able to predict 30% of the variance in calculation skills and 50% of the variance in math reasoning; however, in both cases, only the domains of semantic retrieval and visuospatial skill contributed uniquely. Differences between studies, and the lack of unique contribution of the EP domain to either type of math skill, may be due to measurement and sampling differences, the degree of shared relations among domains, and the choice of measures that represent the EP domain. Implications and future directions are explored.
Does Negative Mood Influence Self-Report Assessment of Individual and Relational Measures? An Experimental Analysis
Authors: Heene Els , De Raedt Rudi , Buysse Ann , Van Oost Paulette
Published: February 2007

The present study was designed to test the influence of negative mood on the self-report of individual and relational correlates of depression and marital distress. The authors applied a combined experimental mood induction procedure, based on music, autobiographical recall, and environmental manipulation. Results showed that the mood manipulation was effective, and the depressed Mood Induction Procedure (MIP) and neutral MIP groups did not differ in their self-rated measures of the above-mentioned variables. In conclusion, the authors argue that these measures are generally insensitive to depressed mood, providing an important contribution to this literature.
Malingering in Toxic Exposure
Authors: Greve Kevin W. , Springer Steven , Bianchini Kevin J. , Black F. William , Heinly Matthew T. , Love Jeffrey M. , Swift Douglas A. , Ciota Megan A.
Published: February 2007

This study examined the sensitivity and false-positive error rate of reliable digit span (RDS) and the WAIS-III Digit Span (DS) scaled score in persons alleging toxic exposure and determined whether error rates differed from published rates in traumatic brain injury (TBI) and chronic pain (CP). Data were obtained from the files of 123 persons referred for neuropsychological evaluation related to alleged exposure to environmental and industrial substances. Malingering status was determined using the criteria of Slick, Sherman, and Iverson (1999). The sensitivity and specificity of RDS and DS in toxic exposure are consistent with those observed in TBI and CP. These findings support the use of these malingering indicators in cases of alleged toxic exposure and suggest that the classification accuracy data of indicators derived from studies of TBI patients may also be validly applied to cases of alleged toxic exposure.
Materialism, Perceived Financial Problems, and Marital Satisfaction
Authors: Dean Lukas R. , Carroll Jason S. , Yang Chongming
Published: February 2007

Although scholars and counselors have long acknowledged a link between financial problems and marital outcomes, little research has examined how materialistic attitudes may affect these associations. This article examines a conceptual model linking spousal materialism, perceived financial problems, and marital satisfaction. Group comparison and structural equation modeling analyses were run with a nationally representative sample of 600 married couples. Analyses confirmed that higher levels of spousal materialism are associated with increased perceptions of financial problems, which in turn are negatively associated with levels of marital satisfaction. Analyses also found that materialistic attitudes have a stronger impact on spouses' perceptions of financial problems than do levels of couple income. These findings support the notion that materialism contributes to how couples define and react to financial problems in their relationship and that these factors indirectly and directly affect general levels of marital satisfaction. Implications for research and intervention are discussed.
Welcome to Ruth's World
Authors: Evans Kevin D.
Published: February 2007

This autoethnography deals with the reflexive nature of conducting ethnography with an elderly woman in an assisted living facility. As the interview progresses, the author, graduate student, and participant are united in a shared memory that transcends the research process. This tale is provided as a means to demonstrate the multilevel horizons that can surface through a shared memory and how that can influence the researcher. The hope is to move further out and also evoke within the reader a shared memory. This article also reveals some of the effects of catalytic validity directed at the researcher.
Strategic ambiguity as a discourse practice: the role of keywords in the discourse on ‘sustainable’ biotechnology
Authors: Leitch Shirley , Davenport Sally
Published: February 2007

In this article we examined the ways in which strategic ambiguity (Eisenberg, 1984) in the use of keywords (Williams, 1976/1983) served an enabling function within a discourse marked by conflict and ideological divisions. Our analysis focused on the intertextual relationships between five documents intended by the government to guide the development of biotechnology in New Zealand. Through our analysis we identified ‘sustainability’ as a keyword and three major roles for the deployment of the discourse strategy of strategic ambiguity in the use of this keyword. First, strategic ambiguity lent an internal and intertextual coherence to the texts (albeit superficial). Second, it allowed multiple perspectives and objectives to co-exist. Third, strategic ambiguity facilitated the participation of discourse actors who subscribed to ideologies that were more or less incommensurable.
Impact on respiratory tract infections of heptavalent pneumococcal conjugate vaccine administered at 3, 5 and 11 months of age
Authors: Esposito Susanna , Lizioli Alessandro , Lastrico Annalisa , Begliatti Enrica , Rognoni Alessandro , Tagliabue Claudia , Cesati Laura , Carreri Vittorio , Principi Nicola
Published: February 2007

Background

Medical and public health importance of pneumococcal infections justifies the implementation of measures capable of reducing their incidence and severity, and explains why the recently marketed heptavalent pneumococcal conjugate vaccine (PCV-7) has been widely studied by pediatricians. This study was designed to evaluate the impact of PCV-7 administered at 3, 5 and 11 months of age on respiratory tract infections in very young children.

Methods

A total of 1,571 healthy infants (910 males) aged 75–105 days (median 82 days) were enrolled in this prospective cohort trial to receive a hexavalent vaccine (DTaP/IPV/HBV/Hib) and PCV-7 (n = 819) or the hexavalent vaccine alone (n = 752) at 3, 5 and 11 months of age. Morbidity was recorded for the 24 months following the second dose by monthly telephone interviews conducted by investigators blinded to the study treatment assignment using standardised questionnaires. During these interviews, the caregivers and the children's pediatricians were questioned about illnesses and the use of antibiotics since the previous telephone call. All of the data were analysed using SAS Windows v.12.

Results

Among the 1,555 subjects (98.9%) who completed the study, analysis of the data by the periods of follow-up demonstrated that radiologically confirmed community-acquired pneumonia (CAP) was significantly less frequent in the PCV-7 group during the follow-up as a whole and during the last period of follow-up. Moreover, there were statistically significant between-group differences in the incidence of acute otitis media (AOM) in each half-year period of follow-up except the first, with significantly lower number of episodes in children receiving PCV-7 than in controls. Furthermore, the antibiotic prescription data showed that the probability of receiving an antibiotic course was significantly lower in the PCV-7 group than in the control group.

Conclusion

Our findings show the effectiveness of the simplified PCV-7 schedule (three doses administered at 3, 5 and 11–12 months of age) in the prevention of CAP and AOM, diseases in which Streptococcus pneumoniae plays a major etiological role. A further benefit is that the use of PCV-7 reduces the number of antibiotic prescriptions. All of these advantages may also be important from an economic point of view.
Apical ballooning syndrome complicated by acute severe mitral regurgitation with left ventricular outflow obstruction – Case report
Authors: Chandrasegaram Manju D , Celermajer David S , Wilson Michael K
Published: February 2007

Background

Apical ballooning syndrome (or Takotsubo cardiomyopathy) is a syndrome of transient left ventricular apical ballooning. Although first described in Japanese patients, it is now well reported in the Caucasian population. The syndrome mimicks an acute myocardial infarction but is characterised by the absence of obstructive coronary disease. We describe a serious and poorly understood complication of Takotsubo cardiomyopathy.

Case Presentation

We present the case of a 65 year-old lady referred to us from a rural hospital where she was treated with thrombolytic therapy for a presumed acute anterior myocardial infarction. Four hours after thrombolysis she developed acute pulmonary oedema and a new systolic murmur. It was presumed she had acute mitral regurgitation secondary to a ruptured papillary muscle, ischaemic dysfunction or an acute ventricular septal defect.

Echocardiogram revealed severe mitral regurgitation, left ventricular apical ballooning, and systolic anterior motion of the mitral valve with significant left ventricular outflow tract gradient (60–70 mmHg). Coronary angiography revealed no obstructive coronary lesions.

She had an intra-aortic balloon pump inserted with no improvement in her parlous haemodynamic state. We elected to replace her mitral valve to correct the outflow tract gradient and mitral regurgitation. Intra-operatively the mitral valve was mildly myxomatous but there were no structural abnormalities. She had a mechanical mitral valve replacement with a 29 mm St Jude valve. Post-operatively, her left ventricular outflow obstruction resolved and ventricular function returned to normal over the subsequent 10 days. She recovered well.

Conclusion

This case represents a serious and poorly understood association of Takotsubo cardiomyopathy with acute pulmonary oedema, severe mitral regurgitaton and systolic anterior motion of the mitral valve with significant left ventricular outflow tract obstruction. The sequence of our patient's presentation suggests that the apical ballooning caused geometric alterations in her left ventricle that in turn led to acute and severe mitral regurgitation, systolic anterior motion of the mitral valve and left ventricular outflow tract obstruction. The left ventricular outflow tract obstruction and mitral regurgitation were corrected by mechanical mitral valve replacement. We describe a variant of Takotsubo cardiomyopathy with acute mitral regurgitation, systolic anterior motion of the mitral valve leaflet and left ventricular outflow tract obstruction of a dynamic nature.
Non-invasive MR imaging of inflammation in a patient with both asymptomatic carotid atheroma and an abdominal aortic aneurysm: a case report
Authors: Howarth Simon PS , Tang Tjun Y , Graves Martin J , U-King-Im Jean-Marie , Li Zhi-Yong , Walsh Stewart R , Gaunt Michael E , Gillard Jonathan H
Published: February 2007

Inflammation is a recognized risk factor for the vulnerable atherosclerotic plaque.

USPIO-enhanced MRI imaging is a promising non-invasive method to identify high-risk atheromatous plaque inflammation in vivo in humans, in which areas of focal signal loss on MR images have been shown to correspond to the location of activated macrophages, typically at the shoulder regions of the plaque. This is the first report in humans describing simultaneous USPIO uptake within atheroma in two different arterial territories and again emphasises that atherosclerosis is a truly systemic disease. With further work, USPIO-enhanced MR imaging may be useful in identifying inflamed vulnerable atheromatous plaques in vivo, so refining patient selection for intervention and allowing appropriate early aggressive pharmacotherapy to prevent plaque rupture.
Rapid, accurate, computational discovery of Rho-independent transcription terminators illuminates their relationship to DNA uptake
Authors: Kingsford Carleton L , Ayanbule Kunmi , Salzberg Steven L
Published: February 2007

Background

In many prokaryotes, transcription of DNA to RNA is terminated by a thymine-rich stretch of DNA following a hairpin loop. Detecting such Rho-independent transcription terminators can shed light on the organization of bacterial genomes and can improve genome annotation. Previous computational methods to predict Rho-independent terminators have been slow or limited in the organisms they consider.

Results

We describe TransTermHP, a new computational method to rapidly and accurately detect Rho-independent transcription terminators. We predict the locations of terminators in 343 prokaryotic genomes, representing the largest collection of predictions available. In Bacillus subtilis, we can detect 93% of known terminators with a false positive rate of just 6%, comparable to the best-known methods. Outside the Firmicutes division, we find that Rho-independent termination plays a large role in the Neisseria and Vibrio genera, the Pasteurellaceae (including the Haemophilus genus) and several other species. In Neisseria and Pasteurellaceae, terminator hairpins are frequently formed by closely spaced, complementary instances of exogenous DNA uptake signal sequences. We quantify the propensity for terminators to include these sequences. In the process, we provide the first discussion of potential uptake signals in Haemophilus ducreyi and Mannheimia succiniciproducens, and we discuss the preference for a particular configuration of uptake signal sequences within terminators.

Conclusion

Our new fast and accurate method for detecting transcription terminators has allowed us to identify and analyze terminators in many new genomes and to identify DNA uptake signal sequences in several species where they have not been previously reported. Our software and predictions are freely available.
Contrasting effects of FLIPL overexpression in human T cells on activation-induced cell death and cytokine production
Authors: Charo Jehad , Robbins Paul F
Published: February 2007

There have been disparate findings about the role of FLIP in the survival of mouse T cells and human tumor cell lines. The role of cellular FLIP in human T cell activation and function needs to be clarified further. To study this role, we have overexpressed long transcript FLIP (FLIPL) in primary T cells, including self-antigen-reactive, melanoma-specific T cells. We found that FLIPL overexpression protects human T cells from activation-induced cell death and enhances their prolifertive capacity but suppresses the ability of these cells to produce the proinflammatory cytokines IL-2 and IFN-γ in response to CD3 or antigen-specific stimulation. The multiple effects of FLIPL indicate that this protein may influence T cell responses to antigenic stimulation.
Variation in Institutional Review Board Responses to a Standard, Observational, Pediatric Research Protocol
Authors: Mansbach Jonathan , Acholonu Uchechi , Clark Sunday , Camargo Carlos A.
Published: February 2007

Background:
Multicenter studies are becoming more common, and variability in local institutional review board (IRB) assessments can be problematic.

Objective:
To investigate the variability of IRB responses to a multicenter observational study of children presenting to emergency departments.

Methods:
The authors collected the original IRB applications, subsequent correspondence, and a survey assessing submission timing and response and the nature of IRB queries. The study was conducted as part of the Emergency Medicine Network http://www.emnet‐usa.org

Results:
Of 37 sites initiating the IRB process, 34 (92%) participated in this IRB‐approved study. Institutional review boards returned initial applications in a median of 19 days (IQR, 11–34 d), and 91% considered the protocol to be minimal risk. Of 34 submissions, 13 required no changes, 18 received conditional approvals, and 3 were deferred. The median time from initial submission to final approval was 42 days (IQR, 27–61 d). Seven sites did not participate in patient recruitment: two had institutional issues, one obtained IRB approval too late for participation, and four sites (12%) reported that IRB hurdles contributed to their lack of participation. Nonetheless, 68% of sites that recruited patients reported that the overall experience made them more likely to participate in future multicenter research.

Conclusions:
There was substantial variation in IRB assessment of a standard protocol in this study. The burden of the application process contributed to some investigators not participating, but the majority of investigators remain enthusiastic about multicenter research. A national IRB may streamline the review process and facilitate multicenter clinical research.
Differential Gene Expression Patterns and Interaction Networks in BCR-ABL–Positive and –Negative Adult Acute Lymphoblastic Leukemias
Authors: Juric Dejan , Lacayo Norman J. , Ramsey Meghan C. , Racevskis Janis , Wiernik Peter H. , Rowe Jacob M. , Goldstone Anthony H. , O'Dwyer Peter J. , Paietta Elisabeth , Sikic Branimir I.
Published: February 2007

Purpose

To identify gene expression patterns and interaction networks related to BCR-ABL status and clinical outcome in adults with acute lymphoblastic leukemia (ALL).

Patients and Methods

DNA microarrays were used to profile a set of 54 adult ALL specimens from the Medical Research Council UKALL XII/Eastern Cooperative Oncology Group E2993 trial (21 p185BCR-ABL–positive, 16 p210BCR-ABL–positive and 17 BCR-ABL–negative specimens).

Results

Using supervised and unsupervised analysis tools, we detected significant transcriptomic changes in BCR-ABL–positive versus –negative specimens, and assessed their validity in an independent cohort of 128 adult ALL specimens. This set of 271 differentially expressed genes (including GAB1, CIITA, XBP1, CD83, SERPINB9, PTP4A3, NOV, LOX, CTNND1, BAALC, and RAB21) is enriched for genes involved in cell death, cellular growth and proliferation, and hematologic system development and function. Network analysis demonstrated complex interaction patterns of these genes, and identified FYN and IL15 as the hubs of the top-scoring network. Within the BCR-ABL–positive subgroups, we identified genes overexpressed (PILRB, STS-1, SPRY1) or underexpressed (TSPAN16, ADAMTSL4) in p185BCR-ABL–positive ALL relative to p210BCR-ABL–positive ALL. Finally, we constructed a gene expression- and interaction-based outcome predictor consisting of 27 genes (including GRB2, GAB1, GLI1, IRS1, RUNX2, and SPP1), which correlated with overall survival in BCR-ABL–positive adult ALL (P = .0001), independent of age (P = .25) and WBC count at presentation (P = .003).

Conclusion

We identified prominent molecular features of BCR-ABL–positive adult ALL, which may be useful for developing novel therapeutic targets and prognostic markers in this disease.
Phase I Study of Intraventricular Administration of Rituximab in Patients With Recurrent CNS and Intraocular Lymphoma
Authors: Rubenstein James L. , Fridlyand Jane , Abrey Lauren , Shen Arthur , Karch Jon , Wang Endi , Issa Samar , Damon Lloyd , Prados Michael , McDermott Michael , O'Brien Joan , Haqq Chris , Shuman Marc
Published: February 2007

Purpose

We previously determined that intravenous administration of rituximab results in limited penetration of this agent into the leptomeningeal space. Systemic rituximab does not reduce the risk of CNS relapse or dissemination in patients with large cell lymphoma. We therefore conducted a phase I dose-escalation study of intrathecal rituximab monotherapy in patients with recurrent CNS non-Hodgkin's lymphoma (NHL).

Patients and Methods

The protocol planned nine injections of rituximab (10 mg, 25 mg, or 50 mg dose levels) through an Ommaya reservoir over 5 weeks. The safety profile of intraventricular rituximab was defined in 10 patients.

Results

The maximum tolerated dose was determined to be 25 mg and rapid craniospinal axis distribution was demonstrated. Cytologic responses were detected in six patients; four patients exhibited complete response. Two patients experienced improvement in intraocular NHL and one exhibited resolution of parenchymal NHL. High RNA levels of Pim-2 and FoxP1 in meningeal lymphoma cells were associated with disease refractory to rituximab monotherapy.

Conclusion

These results suggest that intrathecal rituximab (10 to 25 mg) is feasible and effective in NHL involving the CNS.
T-cell-receptor-dependent actin regulatory mechanisms
Authors: Huang Yanping , Burkhardt Janis K.
Published: February 2007

Following stimulation, T cells undergo marked changes in actin architecture that are required for productive immune responses. T-cell-receptor-dependent reorganization of the actin cytoskeleton is necessary for the formation of the immunological synapse at the T-cell–antigen-presenting-cell contact site and the distal pole complex at the opposite face of the T cell. Convergence of specific signaling molecules within these two plasma membrane domains facilitates downstream signaling events leading to full T-cell activation. Recent studies have identified many of the relevant actin-regulatory proteins, and significant progress has been made in our understanding of how these proteins choreograph molecular movements associated with T-cell activation. Proteins such as WASp, WAVE2, HS1 and cofilin direct the formation of a cortical actin scaffold at the immune synapse, while actin-binding proteins such as ezrin and moesin direct binding of signaling molecules to actin filaments within the distal pole complex.
BMP-9 signals via ALK1 and inhibits bFGF-induced endothelial cell proliferation and VEGF-stimulated angiogenesis
Authors: Scharpfenecker Marion , van Dinther M. , Liu Zhen , van Bezooijen R.L. , Zhao Qinghai , Pukac Laurie , Löwik Clemens W. G. M. , ten Dijke P.
Published: February 2007

Genetic studies in mice and humans have shown that the transforming growth factor-β (TGF-β) type-I receptor activin receptor-like kinase 1 (ALK1) and its co-receptor endoglin play an important role in vascular development and angiogenesis. Here, we demonstrate that ALK1 is a signalling receptor for bone morphogenetic protein-9 (BMP-9) in endothelial cells (ECs). BMP-9 bound with high affinity to ALK1 and endoglin, and weakly to the type-I receptor ALK2 and to the BMP type-II receptor (BMPR-II) and activin type-II receptor (ActR-II) in transfected COS cells. Binding of BMP-9 to ALK2 was greatly facilitated when BMPR-II or ActR-II were co-expressed. Whereas BMP-9 predominantly bound to ALK1 and BMPR-II in ECs, it bound to ALK2 and BMPR-II in myoblasts. In addition, we observed binding of BMP-9 to ALK1 and endoglin in glioblastoma cells. BMP-9 activated Smad1 and/or Smad5, and induced ID1 protein and endoglin mRNA expression in ECs. Furthermore, BMP-9 was found to inhibit basic fibroblast growth factor (bFGF)-stimulated proliferation and migration of bovine aortic ECs (BAECs) and to block vascular endothelial growth factor (VEGF)-induced angiogenesis. Taken together, these results suggest that BMP-9 is a physiological ALK1 ligand that plays an important role in the regulation of angiogenesis.
Simple Relational Contracts to Motivate Capacity Investment: Price Only vs. Price and Quantity
Authors: Taylor Terry A. , Plambeck Erica L.
Published: February 2007

Because of long lead times associated with product development and building capacity, a supplier must initiate investment in capacity when the product development effort is ongoing. Because the product is ill defined at this point in time, the buyer is unable to commit to the future terms of trade through a court-enforceable contract. Instead, to provide incentives for capacity investment, the buyer informally promises future terms of trade. The prospect of future interaction creates an incentive for the buyer to pay the supplier as promised. We characterize optimal price-only and price-and-quantity promises and compare their performance. If the production cost is low and either the capacity cost is low or the discount factor is high, then the buyer should promise to purchase a specific quantity rather than simply promise to pay a per unit price; otherwise, the buyer should simply promise to pay a specified unit price.
A Newsvendor’s Procurement Problem when Suppliers Are Unreliable
Authors: Dada Maqbool , Petruzzi Nicholas C. , Schwarz Leroy B.
Published: February 2007

We consider the problem of a newsvendor that is served by multiple suppliers, where any given supplier is defined to be either perfectly reliable or unreliable. By perfectly reliable we mean a supplier that delivers an amount identically equal to the amount desired, as is the case in the most basic variant of the newsvendor problem. By unreliable, we mean a supplier that with some probability delivers an amount strictly less than the amount desired. Our results indicate the following effects of unreliability: From the perspective of the newsvendor, the aggregate quantity ordered is higher than otherwise would be ordered if the newsvendor’s suppliers were completely reliable. From the perspective of end customers, however, the service level provided is lower than otherwise would be provided if the newsvendor’s suppliers were completely reliable. From the perspective of the suppliers, although reliability affects how much is ordered from a selected supplier, cost generally takes precedence over reliability when it comes to selecting suppliers in the first place. Even perfect reliability is no guarantee for qualification since, in an optimal solution, a given supplier will be selected only if all less-expensive suppliers are selected, regardless of the given supplier’s reliability level. Nevertheless, the relative size of a selected supplier’s order depends on its reliability.
Antibodies to citrullinated peptides: a significant step forward in the early diagnosis of rheumatoid arthritis
Authors: Bizzaro Nicola
Published: February 2007

The early diagnosis of rheumatoid arthritis (RA) has become a priority owing to the availability of effective disease-modifying agents that can improve patient wellbeing and influence the clinical outcome. However, this represents a real challenge, as no clinical, radiological or immunological features are pathognomonic at the time of presentation. For this reason, development of the anti-cyclic citrullinated peptide (CCP) antibody assay, a highly disease-specific serological marker for RA, has been a great step forward for the rheumatologist and the clinical laboratory. Over recent years, this test has increased in popularity and many studies have been performed. This review briefly considers the most recent data on the diagnostic accuracy of the CCP test, the genetic background that predisposes to antibody production, the diagnostic, prognostic and predictive values, and the clinical use of the assay in patients with RA.

Clin Chem Lab Med 2007;45:150–7.
Lipid transfer protein activities in subjects with impaired glucose tolerance
Authors: Julius Ulrich , Jauhiainen Matti , Ehnholm Christian , Pietzsch Jens
Published: February 2007

Clin Chem Lab Med 2007;45:237–43.
Quantification of relative changes in specific mRNAs from frozen whole blood – methodological considerations and clinical implications
Authors: Øvstebø Reidun , Lande Knut , Kierulf Peter , Haug Kari Bente Foss
Published: February 2007

Clin Chem Lab Med 2007;45:171–6.
Cardiac natriuretic peptides after myocardial infarction: relationship with infarct size, left ventricular function and remodelling assessed by 99mTc-sestamibi gated-single photon emission tomography
Authors: Ceriani Luca , Giovanella Luca
Published: February 2007

: The aim of the study was to investigate the potential relationship between A-type (atrial) and B-type (brain) natriuretic peptides (ANP, BNP) and infarct size (IS), left ventricular (LV) function and remodelling as assessed by 99m technetium-hexakis-2-methoxy-isobutyl-isonitrile (99mTc-sestamibi) gated-single photon emission tomography (G-SPET).

: Plasma concentrations of ANP and BNP in peripheral blood were measured in 54 patients with coronary artery disease (CAD) and previous myocardial infarction (MI). Of these, 25 subjects had a recent (<2 weeks) and 29 subjects an old (>6 months) MI. IS, left ventricular ejection fraction (LVEF) and end diastolic (EDV), end systolic (ESV) and stroke volume (SV) were quantitatively calculated from at-rest G-SPET.

: In either univariate or multivariate regression analysis that included IS and the other G-SPET derived parameters as co-variables, both BNP and ANP showed a significant association with IS (BNP p<0.002; ANP p<0.01). No significant relationship was found between the two peptides and LVEF, EDV or ESV values. BNP, but not ANP concentrations, were significantly higher in patients with antero-septal vs. infero-lateral (p=0.01) and recent vs. old MI (p=0.003). In these two subgroups, univariate and multivariate analyses confirmed the correlation between BNP and IS, whereas ANP demonstrated a relationship with IS only in subjects with recent MI. CAD extent had no influence on BNP and ANP levels.

: The present study showed a positive correlation between BNP and the perfusion defect measured by 99mTc-sestamibi G-SPET in patients with previous MI. Consequently, BNP may reflect the functional significance of myocardial damage and may be considered of prognostic value. ANP was also related to scintigraphic defects in the early phase after MI, but not in the chronic phase, confirming that ANP is a less sensitive marker of LV remodelling, depending also on atrial load conditions and dilatation. These preliminary data based on a small group of subjects need to be confirmed by prospective longitudinal studies involving larger populations.

Clin Chem Lab Med 2007;45:226–31.
Amniotic fibronectin fragmentation and expression of its domains, sialyl and fucosyl glycotopes associated with pregnancy complicated by intrauterine infection
Authors: Hirnle Lidia , Kątnik-Prastowska Iwona
Published: February 2007

: The presence of fibronectin fragments has been observed in some inflammatory diseases and is believed to reflect tissue breakdown. In this study, possible fibronectin fragmentation and alterations in its domain and sialyl and fucosyl glycotope expressions were analyzed in amniotic fluids in relation to intrauterine infection.

: Samples of amniotic fluid were taken from normal pregnancies and pregnancies (28 and 42 weeks) complicated by intrauterine infection. Fibronectin fragmentation was analyzed by immunoblotting. The expression of cellular, fibrin, C-terminal and EDA fibronectin domains, as well as α2,3- and α2,6-linked sialic acids, and α1,6-, α1,3- and α1,2-linked fucoses, was determined by ELISA, using domain-specific monoclonal antibodies and specific lectins, respectively.

: Amniotic fibronectin immunoblots from pregnancies with intrauterine infection revealed three groups of results. In group 1, with the native fibronectin band, and in group 2 with bands of native fibronectin and several fibronectin fragments, only higher α1,6-linked fucose expression was observed. In the infection group 3, characterized by profound fragmentation of fibronectin, lower expression of all fibronectin domains analyzed and of α1,6-linked sialic acid and α1,2-linked fucose was found.

: Amniotic fibronectin status was found to be associated with pregnancy complicated by intrauterine infection. Such alterations could have a potential diagnostic value in the prevention of or intervention in fetal intrauterine infection.

Clin Chem Lab Med 2007;45:208–14.
Determination of the hepatitis C virus subtype: comparison of sequencing and reverse hybridization assays
Authors: Stelzl Evelyn , Meer Carola van der , Gouw Remko , Beld Marcel , Grahovac Maja , Marth Egon , Kessler Harald H.
Published: February 2007

Hepatitis C virus (HCV) genotyping and accurate subtyping is becoming increasingly relevant to epidemiological studies, clinical management, pathogenicity, and vaccine development.

The TRUGENE

All amplified samples from among the members of a HCV genotyping proficiency program panel that contained a single HCV genotype were subtyped correctly using all three HCV genotyping assays. With the TRUGENE

The two new methods show advantages over the routinely used TRUGENE

Clin Chem Lab Med 2007;45:167–70.
Prostataspezifisches Antigen: Bedeutung für die Diagnostik des Prostatakarzinoms bei geriatrischen Patienten / Prostate-specific antigen: significance for the diagnosis of prostate cancer in geriatric patients
Authors: Stachon Axel
Published: February 2007

Bei Männern der westlichen Welt ist das Prostatakarzinom die häufigste maligne Erkrankung. Für die frühzeitige Erkennung eines, möglichst noch auf das Organ begrenzten, bösartigen Wachstums der Prostata wird unter anderem die Bestimmung des prostataspezifischen Antigens (PSA) herangezogen. Sowohl benignes hyperplastisches als auch malignes Prostatagewebe sezernieren vermehrt PSA. Das führt, neben dem alterskorrelierenden Anstieg der PSA-Konzentration, zu einer geringen Spezifität der Gesamt-PSA-Bestimmung. Serielle PSA-Messungen, die Bestimmung von freiem oder komplexiertem PSA sowie die Berücksichtigung von klinischen Daten stellen diagnostische Strategien dar, um die Trennschärfe zwischen benigner Prostatahyperplasie und Prostatakarzinom zu erhöhen. Für aussagekräftige Messergebnisse sind neben den präanalytischen Bedingungen und den patientenspezifischen Einflussgrößen die Methodenwahl sowie die weitere Probenbehandlung von Bedeutung.
Schilddrüsenfunktion und -dysfunktion im Alter / Thyroid function and dysfunction in the elderly
Authors: Weissel Michael
Published: February 2007

Die vorliegende Übersichtsarbeit gibt den momentanen Stand des Wissens über die Funktion und Dysfunktion der Schilddrüse im Alter wieder. Nach Besprechung der Epidemiologie und der Abhängigkeit der Funktionsstörungen von der Jodversorgung der Bevölkerung werden die physiologischen – also beim Gesunden auftretenden – Veränderungen des Schilddrüsen-Hypophysenregelkreises besprochen. Den Hauptteil der Arbeit stellt die Besprechung der Klinik, Labordiagnose und Therapie von Funktionsstörungen der Schilddrüse im Alter dar. Es wird auf die altersbedingte Symptomarmut und die daraus resultierende Schwierigkeit der klinischen Diagnose hingewiesen. Bei der Labordiagnose wird besonders auf die Interpretationsmöglichkeiten pathologischer Thyreotropin (TSH) Werte und ihrer therapeutischen und diagnostischen Konsequenzen beim alten Menschen eingegangen. Abschließend werden die Besonderheiten der Therapie vor allem der subklinischen Funktionsstörungen der Schilddrüse im Alter besprochen. Besonders hingewiesen wird darauf, dass latente Hypothyreosen beim betagten Patienten auf Grund des kardialen Risikos einer iatrogen induzierten Überfunktion nur im Einzelfall behandelt werden sollen. Es wird hervorgehoben, dass regelmäßige Laborkontrollen besonders beim alten Menschen unnötige Therapien vermeiden können.