bluuebunny/crossref_metadata_2025 huggingface dataset:
2-Hydroxyoleic acid affects cardiomyocyte [Ca2+]itransient and contractility in a region-dependent manner
Authors: Borchert Gudrun H. , Giggey Mike , Kolar Frantisek , Wong Tak Ming , Backx Peter H. , Escriba Pablo V.
Published: February 2008

Monounsaturated fatty acids such as oleic acid are cardioprotective, modify the physicochemical properties of cardiomyocyte membranes, and affect the electrical stability of these cells by regulating the conductance of ion channels. We have designed a nonhydrolysable oleic acid derivative, 2-hydroxyoleic acid (2-OHOA), which regulates membrane lipid structure and cell signaling, resulting in beneficial cardiovascular effects. We previously demonstrated that 2-OHOA induces PKA activation and PKCα translocation to the membrane; both pathways are thought to regulate transient outward K+current ( Ito) depending on the stimulus and the species used. This study was designed to investigate the effect of 2-OHOA on isolated cardiomyocytes. We examined the dose- and time-dependent effect of 2-OHOA on cytosolic Ca2+concentration ([Ca2+]i) transient and contraction of myocytes isolated from different parts of the rat ventricular myocardium. Although this drug had no effect on [Ca2+]itransient and cell shortening in myocytes isolated from the septum, it increased (up to 95%) [Ca2+]itransient and cell shortening in subpopulations of myocytes from the right and left ventricles. The pattern of the effects of 2-OHOA was similar to that observed following the application of the Itoblocker 4-aminopyridine, suggesting that the drug may act on this channel. Unlike the effect of 2-OHOA on [Ca2+]itransient and cell shortening, PKCα translocation to membranes was not region specific. Thus 2-OHOA-induced effects on [Ca2+]itransients and cell shortening are likely related to reductions in Itofunction, but PKCα translocation does not seem to play a role. The present results indicate that 2-OHOA selectively increases myocyte inotropic responsiveness, which could underlie its beneficial cardiovascular effects.
Effect of diazoxide on flavoprotein oxidation and reactive oxygen species generation during ischemia-reperfusion: a study on Langendorff-perfused rat hearts using optic fibers
Authors: Pasdois Philippe , Beauvoit Bertrand , Tariosse Liliane , Vinassa Béatrice , Bonoron-Adèle Simone , Santos Pierre Dos
Published: February 2008

This study analyzed the oxidant generation during ischemia-reperfusion protocols of Langendorff-perfused rat hearts, preconditioned with a mitochondrial ATP-sensitive potassium channel (mitoKATP) opener (i.e., diazoxide). The autofluorescence of mitochondrial flavoproteins, and that of the total NAD(P)H pool on the one hand and the fluorescence of dyes sensitive to H2O2or O2•−[i.e., the dihydrodichlorofluoroscein (H2DCF) and dihydroethidine (DHE), respectively] on the other, were noninvasively measured at the surface of the left ventricular wall by means of optic fibers. Isolated perfused rat hearts were subjected to an ischemia-reperfusion protocol. Opening mitoKATPwith diazoxide (100 μM) 1) improved the recovery of the rate-pressure product after reperfusion (72 ± 2 vs. 16.8 ± 2.5% of baseline value in control group, P < 0.01), and 2) attenuated the oxidant generation during both ischemic (−46 ± 5% H2DCF oxidation and −40 ± 3% DHE oxidation vs. control group, P < 0.01) and reperfusion (−26 ± 2% H2DCF oxidation and −23 ± 2% DHE oxidation vs. control group, P < 0.01) periods. All of these effects were abolished by coperfusion of 5-hydroxydecanoic acid (500 μM), a mitoKATPblocker. During the preconditioning phase, diazoxide induced a transient, reversible, and 5-hydroxydecanoic acid-sensitive flavoprotein and H2DCF (but not DHE) oxidation. In conclusion, the diazoxide-mediated cardioprotection is supported by a moderate H2O2production during the preconditioning phase and a strong decrease in oxidant generation during the subsequent ischemic and reperfusion phases.
Distinct Functions of Natural ADAM-15 Cytoplasmic Domain Variants in Human Mammary Carcinoma
Authors: Zhong Julia L. , Poghosyan Zaruhi , Pennington Caroline J. , Scott Xanthe , Handsley Madeleine M. , Warn Alba , Gavrilovic Jelena , Honert Katja , Krüger Achim , Span Paul N. , Sweep Fred C.G.J. , Edwards Dylan R.
Published: February 2008

Adamalysins [a disintegrin and metalloproteinase (ADAM)] are a family of cell surface transmembrane proteins that have broad biological functions encompassing proteolysis, adhesion, and cell signal regulation. We previously showed that the cytoplasmic domain of ADAM-15 interacts with Src family protein tyrosine kinases and the adaptor protein growth factor receptor binding protein 2 (Grb2). In the present study, we have cloned and characterized four alternatively spliced forms of ADAM-15, which differ only in their cytoplasmic domains. We show that the four ADAM-15 variants were differentially expressed in human mammary carcinoma tissues compared with normal breast. The expression of the individual isoforms did not correlate with age, menopausal status, tumor size or grade, nodal status, Nottingham Prognostic Index, or steroid hormone receptor status. However, higher levels of two isoforms (ADAM-15A and ADAM-5B) were associated with poorer relapse-free survival in node-negative patients, whereas elevated ADAM-15C correlated with better relapse-free survival in node-positive, but not in node-negative, patients. The expression of ADAM-15A and ADAM-15B variants in MDA-MB-435 cells had differential effects on cell morphology, with adhesion, migration, and invasion enhanced by expression of ADAM-15A, whereas ADAM-15B led to reduced adhesion. Using glutathione S-transferase pull-down assays, we showed that the cytoplasmic domains of ADAM-15A, ADAM-15B, and ADAM-15C show equivalent abilities to interact with extracellular signal-regulated kinase and the adaptor molecules Grb2 and Tks5/Fish, but associate in an isoform-specific fashion with Nck and the Src and Brk tyrosine kinases. These data indicate that selective expression of ADAM-15 variants in breast cancers could play an important role in determining tumor aggressiveness by interplay with intracellular signaling pathways. (Mol Cancer Res 2008;6(3):383–94)
Dilation-Dependent Activation of Platelets and Prothrombin in Human Thoracic Ascending Aortic Aneurysm
Authors: Touat Ziad , Lepage Laurent , Ollivier Véronique , Nataf Patrick , Hvass Ulrich , Labreuche Julien , Jandrot-Perrus Martine , Michel Jean-Baptiste , Jondeau Guillaume
Published: February 2008

Objectives—

The purpose of this study was to investigate whether thoracic ascending aortic aneurysm (TAAA) induces platelet activation as mural thrombus participates in aortic dilatation in abdominal aortic aneurysm and TAAA are associated with rheological factors favoring coagulation activation.

Methods and Results—

We studied the relation between coagulation activation and aortic diameter in Marfan patients (MFS) with various aortic diameters (n=52). We then studied patients presenting large aneurysms associated with bicuspid aortic valve (BAV) and degenerative form. Lastly, we used immunochemistry and biochemistry to investigate prothrombin/thrombin retention within the aortic wall. Microparticles, sGPV, tissue factor, and TAT complexes were increased in plasma from MFS with large aneurysms (≥45 mm) compared to MFS with limited aortic dilatation (<45 mm). Similar elevations were observed in all patients with large aortic aneurysms, regardless of the etiology, the site of maximal aortic dilation, associated valvulopathy, risk factors, or treatments. P-selectin and platelet-bound fibrinogen were also increased, demonstrating platelet activation in large aneurysms. Significant increase in sCD146 plasma concentration suggested alteration of endothelium.

Conclusions—

Platelet activation occurs in patients with large aneurysms of the ascending aorta, is dependent on aortic dilation, and is associated with thrombin generation, part of which appears to be retained in mucoid degeneration areas.
In Vivo Platelet–Endothelial Cell Interactions in Response to Major Histocompatibility Complex Alloantibody
Authors: Morrell Craig N. , Murata Kazunori , Swaim Anne Marie , Mason Emily , Martin Tanika V. , Thompson Laura E. , Ballard Mathew , Fox-Talbot Karen , Wasowska Barbara , Baldwin William M.
Published: February 2008

Platelets recruit leukocytes and mediate interactions between leukocytes and endothelial cells. Most studies examining this important platelet immune function have focused on the development of atherosclerosis, but similar mechanisms may contribute to acute and chronic vascular lesions in transplants. Platelets have been described as markers of transplant rejection, but little investigation has critically examined a role for platelets in transplant vasculopathy and, in particular, alloantibody-mediated transplant rejection. We now demonstrate using a skin transplant model that alloantibody indirectly induces platelet activation and rolling in vivo. Repeated IgG2a alloantibody injections result in sustained platelet–endothelial interactions and vascular pathology, including von Willebrand factor release, small platelet thrombi, and complement deposition. Maintenance of continued platelet–endothelial interactions are dependent on complement activation. Furthermore, we demonstrate that platelets recruit leukocytes to sites of alloantibody deposition and sustain leukocyte–endothelial cell interactions in vivo. Taken together, our model demonstrates an important role for platelets in alloantibody induced transplant rejection.
Industry-Sponsored Medical Education — In the Quest for Professional Integrity and Legal Certainty
Authors: Buchner Benedikt
Published: February 2008

Industry-sponsored medical education is a much disputed issue. So far, there has been no regulatory framework which provides clear and definite rules as to whether and under what circumstances the sponsorship of medical education is acceptable. State regulation does not exist, or confines itself to a very general principle. Professional regulation, even though applied frequently, is rather vague and indefinite, raising the general question as to whether self-regulation is the right approach at all. Certainly, self-regulation by industry cannot and should not replace other regulatory approaches. Ultimately, advertising law in general and the European Directive 2001/83/EC specifically, might be a good starting point in providing legal certainty and ensuring the independence of medical education. Swiss advertising law illustrates how the principles of the European Directive could be implemented clearly and unambiguously.
The Influence of the Rulings of the Constitutional Court on the Development of Health Law in Lithuania
Authors: Birmontienė Toma
Published: February 2008

This article highlights some recent developments in the constitutional doctrine of the right to health care in Lithuania, and more in particular the impact of the decisions of the Constitutional Court of Lithuania on the development of health law. The right to health care, enshrined in the Constitution, is both an obligation of the state and an individual right. The Constitutional Court has developed a doctrine of the right to health care, as well a doctrine of certain other constitutional social rights, which is based on the understanding of the close interrelation between the different constitutional rights, the principle of indivisibility and equal importance of these rights, and the presumption of justiciability of social rights. The analysis is based on the jurisprudence of the Constitutional Court. Two cases on the disputes of the legal regulation concerning the pharmaceutical activities are presented in more detail.
Competing Values in World Culture and the Emergence of Middle Ground
Authors: Song Eun young
Published: February 2008

This paper, focusing on a Botswanan case of Community-Based Natural Resource Management (CBNRM), illustrates how globalized norms in seeming competition nonetheless reveal a potential middle ground. In Botswana there have been conflicts between regimes of environmentalism and indigenous cultural rights. Environmental protectionism has been based on a concept of “pristine nature” which does not allow for human interaction. Thus, the more protected areas are designated, the more indigenous peoples' lands are claimed as nature reserves. This forces local peoples to abandon cultural practices such as hunting animals and gathering wild plants. In contrast, impelled by the ascention of human rights issues, advocacy groups for the unorganized fourth world and indigenous communities have been struggling to protect indigenous people's cultural rights, thereby giving prominence to human rights issues. NGO advocates for indigenous peoples as well as professionals involved with indigenous groups have found that indigenous people's practices are in fact not harmful to the ecosystem. Rather, their ethno-biological knowledge and customary activities contribute to balancing the local ecosystem. This means that conflicting guidelines can be harmonized in “buffer zones” around protected areas, and the buffering program that has resulted, that by CBNRM, has been widely accepted in Botswana and is likely applicable to other countries in which we find similar value competition.
Painting, Law and Professions, II: Paris Visual Academie and French Law
Authors: Sciulli David
Published: February 2008

Aside from English law being cited as pioneering the first professionalism project, French law is also frequently treated as an exemplar of early professionalism. We challenge this consensus by demonstrating that the Academie Royale de Peinture et de Sculpture of Paris preceded along a professionalism project centuries in advance of French law. Using this comparison, we also provide alternative explanations for questions and issues which remain troubling in the literature of French law.
Changes of Government Policies Towards Mission Education in Colonial Kenya and Their Effects on the Missions: The Case of the Gospel Missionary Society
Authors: Wamagatta Evanson
Published: February 2008

Before the First World War, the provision and management of African education was almost entirely in the hands of the missionaries. After the war, the government enacted a series of laws that were designed to improve the quality of education. However, the new policies placed a heavy financial burden on the missions, which found it difficult to function without government grants. This paper analyzes the effects of government education policies on the fluctuating fortunes of the Gospel Missionary Society (GMS). It shows that, although the GMS was not opposed to the grants, its small size and faith basis made it impossible to meet the government's conditions for receiving the grants. The government's pressure and the mission's inability to implement the policies eventually forced the GMS to withdraw from the mission field altogether, and that is why there are today no schools or churches associated with it in Kenya. The paper is based on secondary sources and primary materials obtained from the Kenya National Archives (KNA) and the GMS's and other missionary societies' archives.
Caring for the Patient and the Family in the Last Hours of Life
Authors: Kehl Karen A.
Published: February 2008

Recognition of the signs and symptoms that are common in the final hours of life and a basic understanding of how to manage these signs and symptoms are important to helping the patient and family experience a good death in the home setting. The most common signs and symptoms, including pain, dyspnea, and terminal restlessness or delirium, and their management are discussed. Also addressed are other signs and symptoms, such as cardiovascular signs and symptoms including cold extremities, mottling, and changes in vital signs; respiratory signs and symptoms such as changes in breathing pattern, noisy breathing, and mandibular breathing; and neurological signs and symptoms such as disorientation, sensory changes, and semicomatose state. Changes in metabolism such as fatigue, surge of energy, and increased temperature are presented, along with decreased intake, excretion, and communication changes.
Cognitive Barriers in the Scenario Development Process
Authors: Bradfield Ronald M.
Published: February 2008

The literature on scenario planning can be neatly divided into two broad categories: (a) anecdotal, practitioner oriented articles that describe how scenario planning has been undertaken in organizations, its espoused benefits, and experienced-based advice on how to construct scenarios and (b) articles that are more academic and analytical in that they attempt to provide a theoretical underpinning for scenarios based on a small body of empirical studies of related topics. It is this second category, the empirical studies of related topics that this article focuses on, in particular, research findings from the cognitive psychology domain in terms of how knowledge is organized and activated in the human mind, cognitive simplification processes, and inductive versus deductive thinking. A research project focusing on the scenario development process is described and the preliminary findings related to the impact of these cognitive phenomena in terms of learning barriers in the development process is discussed.
Constitutive activation of distinct BCR-signaling pathways in a subset of CLL patients: a molecular signature of anergy
Authors: Muzio Marta , Apollonio Benedetta , Scielzo Cristina , Frenquelli Michela , Vandoni Irene , Boussiotis Vassiliki , Caligaris-Cappio Federico , Ghia Paolo
Published: February 2008

Stimulation through the B-cell antigen receptor (BCR) is believed to be involved in the natural history of chronic lymphocytic leukemia (CLL). Some cases respond to the in vitro cross-linking of surface immunoglobulin (sIg) with effective activation. In contrast, the remaining cases do not respond to such stimulation, thereby resembling B cells anergized after antigen encounter in vivo. However the biochemical differences between the 2 groups are ill defined, and in humans the term B-cell anergy lacks a molecular definition. We examined the expression and activation of key molecules involved in signaling pathways originating from the BCR, and we report that a proportion of CLL patients (a) expresses constitutively phosphorylated extracellular signal-regulated kinase (ERK)1/2 in the absence of AKT activation; (b) displays constitutive phosphorylation of MEK1/2 and increased nuclear factor of activated T cells (NF-AT) transactivation; and (c) is characterized by cellular unresponsiveness to sIg ligation. This molecular profile recapitulates the signaling pattern of anergic murine B cells. Our data indicate that constitutive activation of mitogen activated protein (MAP) kinase signaling pathway along with NF-AT transactivation in the absence of AKT activation may also represent the molecular signature of anergic human B lymphocytes. CLL cases with this signature may be taken as a human model of anergic B cells aberrantly expanded.
Targeting Bcl-2 family members with the BH3 mimetic AT-101 markedly enhances the therapeutic effects of chemotherapeutic agents in in vitro and in vivo models of B-cell lymphoma
Authors: Paoluzzi Luca , Gonen Mithat , Gardner Jeffrey R. , Mastrella Jill , Yang Dajun , Holmlund Jon , Sorensen Mel , Leopold Lance , Manova Katia , Marcucci Guido , Heaney Mark L. , O'Connor Owen A.
Published: February 2008

Overexpression of antiapoptotic members of the Bcl-2 family are observed in approximately 80% of B-cell lymphomas, contributing to intrinsic and acquired drug resistance. Nullifying antiapoptotic function can potentially overcome this in-trinsic and acquired drug resistance. AT-101 is a BH3 mimetic known to be a potent inhibitor of antiapoptotic Bcl-2 family members including Bcl-2, Bcl-XL, and Mcl-1. In vitro, AT-101 exhibits concentration- and time-dependent cytotoxicity against lymphoma and multiple myeloma cell lines, enhancing the activity of cytotoxic agents. The IC50 for AT-101 is between 1 and 10 μM for a diverse panel of B-cell lymphomas. AT-101 was synergistic with carfilzomib (C), etoposide (E), doxorubicin (D), and 4-hydroxycyclophosphamide (4-HC) in mantle cell lymphoma (MCL) lines. In a transformed large B-cell lymphoma line (RL), AT-101 was synergistic when sequentially combined with 4-HC, but not when both drugs were added simultaneously. AT-101 also induced potent mitochondrial membrane depolarization (ΔΨm) and apoptosis when combined with carfilzomib, but not with bortezomib in MCL. In severe combined immunodeficient (SCID) beige mouse models of drug-resistant B-cell lymphoma, 35 mg/kg per day of AT-101 was safe and efficacious. The addition of AT-101 to cyclophosphamide (Cy) and rituximab (R) in a schedule-dependent manner enhanced the efficacy of the conventional therapy.
Multi-Axis Sinusoidal Whole-Body Vibrations: Part II — Relationship between Vibration Total Value and Discomfort Varies between Vibration Axes
Authors: Dickey James P. , Eger Tammy R. , Oliver Michele L. , Boileau Paul-Emile , Trick Lana M. , Edwards A. Michelle
Published: February 2008

The influence of vibration duration and the amount of rest between successive vibrations was addressed in Part I of this study. The relationship between discomfort and Vibration Total Value for different axes of vibration is assessed in Part II. Ten subjects were exposed to repeated single axis, planar, and 6 degree of freedom multi-axial vibrations. We observed statistically significant differences in discomfort between the different axes of vibration for similar ranges of Vibration Total Values. In particular. we observed that discomfort reports for vibrations in the Z axis and XY plane were less than discomfort reports associated with XZ plane and 6 df vibrations when the same range of Vibration Total Values were compared. Furthermore, single axis vertical vibrations were typically associated with less discomfort than multi-axis vibrations when similar ranges of Vibration Total Values were compared. This finding infers that the frequency weighting scheme presented in ISO 2631–1 does not achieve inter-axis equivalence and indicates that a more comprehensive study of multi-axis vibration is required to suggest changes to the ISO 2631–1 weighting factors.
Anti-Windup Using Switch for SISO System
Authors: Kosaka Manabu , Uda Hiroshi
Published: February 2008

In this paper, we propose a new anti-windup method with a clear procedure of initialization to avoid vibrations and overshoots in spite of saturation of the control input. This method is based on a single-input single-output 2 degree of freedom model matching control system and by using a switch, a saturated control input and an output are respectively used for updating a reference output and a feedforward input instead of a control input and a reference output; these are not affected by input saturation. By this means, even if the control input is saturated, the state of the reference model corresponds with that of the control object and at the moment the updated control input is not saturated, the output immediately corresponds with the reference output. Furthermore, a procedure to initialize the reference model by which vibrations and overshoots do not occur even if the control input is saturated, is given. This method is suitable for systems in which vibrations and overshoots are taboo, such as tool machines.

The effectiveness of the proposed method is verified by numerical simulation.
Sri Lanka in 2007: Military Successes, but at Humanitarian and Economic Costs
Authors: Wickramasinghe Nira
Published: February 2008

The year 2007 saw a successful military campaign that led to the “liberation” of the Eastern Province by government security forces. The country's high economic growth rate continued despite the war, but inflation and the cost of living also rose significantly. The regime's human rights record came under serious scrutiny.
Vietnam in 2007: A Profile in Economic and Socio-Political Dynamism
Authors: Han Vo X.
Published: February 2008

The year 2007 witnessed a continuation of a five-year dynamic momentum evident on several fronts, notably a fast-growing economy and a vivid sociopolitical landscape, coupled with an active diplomacy. People's standard of living has improved and a sense of confidence and hope in a better future has permeated the populace. Viet Nam's scorecard on the diplomatic front continued to show impressive gains. Yet, momentum can be sustained only if limitations in institutions, education, and infrastructure can be addressed effectively.
Organisms, Machines, and Thunderstorms: A History of Self-Organization, Part One
Authors: Keller Evelyn Fox
Published: February 2008

Over the last quarter century, the term "self-organization" has acquired a currency that, notwithstanding its long history, has been taken to signal a paradigm shift, and perhaps even a scientific revolution, introducing a new Weltanschauungin fields as diverse as mathematics, physics, biology, ecology, cybernetics, economics, sociology, and engineering. But there is a prehistory to this revolution, as to the term itself, with at least two earlier episodes in which the same term was used to signal two other, quite different revolutions. In this paper, I review the pre-history of "self-organization," starting with Immanuel Kant, who first introduced the term, and then turn to the dramatic reframing of the concept by mid-twentieth century engineers. In a subsequent paper, I will review the more recent history of this concept when the term was once again reframed, this time by physicists. My aim will be to situate this latest incarnation of "self-organization" against the backdrop of earlier discussions.
Plants and Pigeonholes: Classification as a Practice in American Ecology
Authors: Kohler Robert E.
Published: February 2008

Between the 1890s and the 1930s field ecologists in the United States (and elsewhere) looked to classification to make their fledgling science an exacting and respectable one. Taking plant taxonomy as their model, ecologists expected that more comprehensive empirical knowledge of vegetation types would produce robust systems of classifications, as it did with species taxonomy. In the event, however, scaled-up data-gathering in the field led ecologists to conclude that vegetation types were not natural units, as species are. Most ecologists then abandoned classification for agendas borrowed from causal sciences such as chemistry or physiology. This cycle of expectation and despair is examined in the practical fieldwork of four ecologists: Henry Cowles, Frederic Clements, Henry Gleason, and Arthur Vestal. Their experiences reveal how perceptions of categories depend on the density and geographical scope of data. Cycles of optimism and disillusionment probably characterize all the classifying sciences in the modern period: because in the "Age of Progress" all sciences sought to advance by expanding and perfecting their empirical base. Comparative study of collecting and classifying practices across the sciences is in order.
Ultrasound‐guided periarticular injections of the sacroiliac region in horses: A cadaveric study
Authors: COUSTY M. , ROSSIER Y. , DAVID F.
Published: February 2008

Reasons for performing study: The traditional techniques for injection of the sacroiliac (SI) region are based on external landmarks. Because of the depth of the SI joint and pathological modifications, SI injections are sometimes challenging in horses.

Hypothesis: An ultrasound‐guided technique would allow placement of the needle without depending on external landmarks.

Methods: Fourteen pelvic specimens were isolated from mature horses. A 20 cm bent spinal needle was positioned with ultrasonographic guidance under both iliac wings aiming for SI joints using 5 approaches: cranial, craniomedial, medial and 2 caudal approaches. The length of needle inserted was recorded and 2 ml of latex injected. The distance from latex to the closest sacral articular margin, the contact between latex and the SI interosseous ligament or the contact with the neurovascular structures emerging from the greater sciatic foramen were recorded at the time of dissection.

Results: Latex was identified under the iliac wing in all injections but one. The distance from the latex to the closest sacral articular margin was significantly shorter (P = 0.02) for the 2 caudal approaches compared to the cranial, craniomedial and medial approaches. Contact between latex and the SI interosseous ligament was significantly more frequent (P = 0.01) with the cranial, craniomedial and medial approaches (38/73) compared to the caudal approaches (1/24). Contact between latex and the neurovascular structures was significantly less frequent (P = 0.005) for the cranial and craniomedial approaches (0/47) compared to the medial and caudal approaches (8/60). Four erratic injections were encountered.

Conclusions: Ultrasonographic guidance allowed the needle to engage under the iliac wing without being dependent on external landmarks. The caudal approaches allowed deposition of liquid extremely close to the SI joint although retroperitoneal injections occurred.

Clinical relevance: Each approach has advantages/drawbacks that could be favoured for selected purposes, but additional work is required to evaluate them on clinical cases.
Use of ultrasonography to detect pulmonary lesions in Thoroughbred foals in Argentina
Authors: Cortez J. , Aguilar J. J. , Lagioia M. , Fernandez R. , Losinno L.
Published: February 2008

Rhodococcus equi is an important cause of pulmonary disease in foals often related to economic losses and death. A study was performed on a Thoroughbred farm (Buenos Aires Province, Argentina) where this disease was enzootic causing 1–2% of foal deaths every year. One hundred foals were monitored by thoracic ultrasonography at ages 1–5 months to detect pulmonary lesions in order to initiate an early treatment. This strategy allowed reducing the number of foal deaths almost totally. In our experience, thoracic ultrasonography was proved to be very efficient in detection of early cases of pneumonia on a farm with high density of horses and intensive management.
Coxsackievirus B4 infection of murine foetal thymus organ cultures
Authors: Brilot Fabienne , Jaïdane Hela , Geenen Vincent , Hober Didier
Published: February 2008

The infection of foetal thymus with coxsackievirus B4 (CV‐B4) E2 has been studied ex vivo by using CD‐1 mice on foetal day 14, as a ready source of organs for experimentation to investigate the hypothesis of the role of thymic viral infections in the pathogenesis of type 1 diabetes. The replication of CV‐B4 E2 in murine foetal thymus organ cultures has been demonstrated by evaluating the levels of positive‐ and negative‐stranded viral RNA in cells by using a real‐time quantitative RT‐PCR method and by determining titres of infectious viral particles in culture supernatants for 7 days post‐infection (p.i.). Staining of tissue sections with an anti‐cytokeratin antibody and haematoxylin–eosin showed that CV‐B4 infection had no visible effect on cell survival and organ integrity. Cell counts in mock‐ and virus‐infected foetal thymus organ cultures increased from day 1 through day 7, and live cell numbers were comparable in both conditions as shown by Trypan blue exclusion test and 7‐amino‐actinomycin D staining of thymocytes. Compared with controls on day 7 p.i., cytofluorometric analyses on cells from CV‐B4 E2‐infected foetal thymus organ cultures displayed a marked increase in the percentage of the most immature CD3−CD4−CD8− thymocytes, and a decrease in the percentage of immature CD3−CD4+CD8+ cells, together with an increase in the percentage of mature CD3+CD4+ and CD3+CD8+ cells. These data show that CV‐B4 E2 disturbs T‐cell maturation and differentiation processes in infected murine foetal thymus organ cultures and provide evidence of a suitable system to investigate the effect of viruses in T‐cell differentiation. J. Med. Virol. 80:659–666, 2008. © 2008 Wiley‐Liss, Inc.
Overcoming resistance to existing therapies in HIV‐infected patients: The role of new antiretroviral drugs
Authors: Perno Carlo‐Federico , Moyle Graeme , Tsoukas Chris , Ratanasuwan Winai , Gatell Jose , Schechter Mauro
Published: February 2008

Resistance to available antiretroviral (ARV) agents is of increasing concern, and development of novel agents that address this problem has been identified as a major public health priority. As ARV resistance becomes more prevalent with extended use of existing agents, individuals with HIV infection resistant to all three traditional classes of ARVs, nucleoside reverse transcriptase inhibitors (NRTIs), non‐nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs), find themselves increasingly limited with regard to effective treatment options. The need for tolerable new drug regimens that effectively suppress viral replication while being simple to adhere to is increasingly pressing. This article reviews the epidemiology of antiretroviral drug resistance, the factors that contribute to the emergence of resistance, and presents data that support the need for early detection of resistance and maximal virologic suppression in order to delay treatment failure and reduce mortality. Healthcare providers are encouraged to optimize therapy through the use of new agents from existing drug classes, which can minimize cross‐resistance, as well as agents with novel mechanisms of action, in order to realize the potential for greater viral containment and to forestall development of resistance mutations. This article evaluates several emerging therapies that are in late‐stage clinical development and promise to expand treatment options for highly treatment‐experienced patients with the goal of improving outcomes for HIV‐infected individuals whose options for sustained antiviral efficacy are increasingly limited. J. Med. Virol. 80:565–576, 2008. © 2008 Wiley‐Liss, Inc.
Incidence of respiratory viruses among travelers with a febrile syndrome returning from tropical and subtropical areas
Authors: Camps M. , Vilella A. , Marcos M.A. , Letang E. , Muñoz J. , Salvadó E. , González A. , Gascón J. , Jiménez de Anta M.T. , Pumarola T.
Published: February 2008

Fifty million people are estimated to travel from industrial countries to the tropics annually. In spite of exhaustive studies and widely different diagnosis among returned patients, some cases of febrile illnesses remain without an etiological diagnosis, suggesting that these cases could be due to viral respiratory tract infections. From August 2005 to October 2006, 118 febrile patients without a specific diagnosis in their first visit at the Center for International Health of the Hospital Clínic of Barcelona were included. In all of them, in order to study respiratory viruses, a nasopharyngeal swab was collected. Clinical and radiological features and epidemiological data, as well as other samples for microbiologic studies, were also collected during consultation. Based on the physician's judgment at the time of consultation, patients were classified into four groups: respiratory symptoms (62%), febrile syndrome with nonspecific symptoms (24%), digestive symptoms (10%), and patients presenting both respiratory and digestive symptoms (4%). A pathogen microorganism was detected in 61 patients (52%). Respiratory viruses were detected in 44 out of 118 (37%) travelers included in the study, representing 56% of the patients with respiratory symptoms. The most frequently viruses detected were influenza virus (38%), rhinovirus (23%), adenovirus (9%), and respiratory syncytial virus (9%). Respiratory viruses have been shown to play an important role in imported fever. In light of the fact that international tourism is an increasing phenomenon, new strategies to prevent the spread of respiratory viruses should be considered, specially for influenza when a vaccine is available. J. Med. Virol. 80:711–715, 2008. © 2008 Wiley‐Liss, Inc.
Quantitation of human herpes virus 6 genome in children with acute lymphoblastic leukemia
Authors: Seror Elisa , Coquerel Bérénice , Gautheret‐Dejean Agnès , Ballerini Paola , Landman‐Parker Judith , Leverger Guy , Schneider Pascale , Vannier Jean‐Pierre
Published: February 2008

Acute lymphoblastic leukemia is the main type of leukemia in children. An infectious etiology has been suspected and the role of the Human herpesvirus‐6 (HHV‐6) has been suggested. Several studies have tried to establish a link between HHV‐6 infections and hematological malignancies, with discordant results. The potential role of HHV‐6 in the pathogenesis of pediatric acute lymphoblastic leukemia was investigated. HHV‐6 genome copy number was measured by quantitative real‐time PCR (RQ‐PCR) in bone marrow or peripheral blood samples obtained from 36 children (median age = 4 years) with B acute lymphoblastic leukemia (n = 31) and T acute lymphoblastic leukemia (n = 5) at diagnosis and during complete remission. Positive samples were further characterized to define viral variant, A or B. A total of 24.7% of samples were positive for HHV‐6 genome: 13.9% were leukemia samples and 34.1% were complete remission samples. Viral load was low with values lower at diagnosis (median viral copy number = 22.9) than at complete remission (median copy number = 60.1). Among the 17 patients with positive samples, 15 were typed as B‐variant whereas 2 could not be typed. These results argue against a role of HHV6 infection in the development of pediatric acute lymphoblastic leukemia. They also suggest that HHV‐6 may infect latently bone marrow progenitors but seems not able to infect leukemic cells, raising again the question of the mechanism of virus fusion and entry. This observation shows that a reactivation may be observed during complete remission supporting the possibility of virus reactivation in immunocompromised hosts. J. Med. Virol. 80:689–693, 2008. © 2008 Wiley‐Liss, Inc.
Molecular typing and epidemiology of non‐polio enteroviruses isolated from Yunnan Province, the People's Republic of China
Authors: Bingjun Tian , Yoshida Hiromu , Yan Wu , Lin Lu , Tsuji Takao , Shimizu Hiroyuki , Miyamura Tatsuo
Published: February 2008

This report presents an overview of human enteroviruses in Yunnan Province, the People's Republic of China. A total of 210 non‐polioviruses isolated under acute flaccid paralysis (AFP) surveillance during a total study period of 5 years—1997 to 2000 and 2004—were examined. Of the 210 non‐poliovirus isolates, 12 adenoviruses were serologically identified, and the remaining 198 isolates were used for molecular typing. The viral genomes of 195 non‐polio enteroviruses (NPEVs) on VP1 partial region of virus capsid were translated to the corresponding amino acid sequences; these were compared with those of prototype strains. Based on molecular typing, 5 isolates were classified into 5 serotypes of the human enterovirus A species, 158 isolates, into 35 serotypes of the human enterovirus B species; and 32 isolates, into 6 serotypes of the human enterovirus C species. Viruses belonging to the human enterovirus D species were not isolated. Thus, under AFP surveillance, the human enterovirus B species accounted for 75.2% of the 210 isolates, and it was considered the predominant species. This was followed by human enterovirus C (12.2%), adenovirus (5.7%), and human enterovirus A (2.4%). Further, molecular analysis suggested that several serotypes of human enteroviruses B and C that exhibited genetic polymorphism were indigenous. Molecular typing methods may aid in understanding the epidemiology of NPEVs in Yunnan Province. J. Med. Virol. 80:670–679, 2008. © 2008 Wiley‐Liss, Inc.
Possible molecular mechanism of the relationship between NS5B polymorphisms and early clearance of hepatitis C virus during interferon plus ribavirin treatment
Authors: Nakamura Mitsuyasu , Saito Hidetsugu , Ikeda Masanori , Tada Shinichiro , Kumagai Naoki , Kato Nobuyuki , Shimotohno Kunitada , Hibi Toshifumi
Published: February 2008

We previously reported the relationship between viral polymerase polymorphisms and the initial decline in viral load induced by interferon‐α and ribavirin therapy in genotype 1b‐related chronic hepatitis C patients. The presence of E124K and I85V of NS5B was closely associated with viral clearance at 8 weeks of treatment. The aim of this study was to investigate the mechanisms by which this polymorphism of NS5B protein affects early viral clearance. We used a replicon system derived from strain O, genotype 1b virus. Three mutants (V85I), (K124E), and (V85I/K124E) were introduced to the replicon. OR6c, a derivative of HuH7 cells, was transfected with the replicon including a luciferase reporter gene. Luciferase activities were measured 72 hr post‐transfection. All three mutants showed higher luciferase activity than that of the wild type, and the V85I mutant showed the highest activity. This result was also confirmed by neomycin gene‐containing replicons with same mutations. All replicons were down‐regulated by ribavirin, but the level of reduction in the V85I mutant was the lowest. Our results suggested that this mutation at least partly contributes to resistance to early viral clearance during interferon and ribavirin combination therapy. J. Med. Virol. 80:632–639, 2008. © 2008 Wiley‐Liss, Inc.
Molecular epidemiological analysis of a nosocomial outbreak of respiratory syncytial virus associated pneumonia in a kangaroo mother care unit in South Africa
Authors: Visser Adele , Delport Suzanne , Venter Marietjie
Published: February 2008

Respiratory syncytial virus (RSV) may cause severe lower respiratory tract disease in premature infants. Prolonged viral shedding has been reported in patients with underlying immunosuppressive disorders, such as human immunodeficiency virus 1 (HIV‐1) infection. During March to May 2006, 23 preterm pediatric patients developed nosocomial pneumonia in a district hospital in the Gauteng Province of South Africa due to RSV infection. The patients were identified using routine diagnostic testing. All had been admitted with their mothers to a Kangaroo Mother Care (KMC) ward from birth—a low care unit for the management of stable low birth weight infants. The HIV‐1 seroprevalence among the mothers to these infants was 52.6%, translating to a 52.6% perinatal exposure. A multiplex nested RT‐PCR was used to subtype RSV positive nasopharyngeal aspirates. Sequencing and phylogenetic analysis of part of the G‐protein gene was used for molecular epidemiological analysis of the outbreak. In total, 19 of the 23 RSV positive specimens could be PCR amplified and sequenced. The subtype A, GA5 genotype was identified in 14 specimens and the BA genotype, a new subtype B genotype not previously recognized in South Africa, in seven. One patient had an infection with both genotypes. Phylogenetic analysis demonstrated eight separate introductions. Two of the strains identified in this outbreak were identical to strains circulating in a general pediatric ward of this hospital during the preceding month. Inadequate infection control measures by health care providers and mothers to children in KMC units may increase potentially the risk of severe RSV infection in a population group with compounded risk factors. J. Med. Virol. 80:724–732, 2008. © 2008 Wiley‐Liss, Inc.
Improved detection of natural hepatitis B virus surface antigen (HBsAg) mutants by a new version of the VITROS® HBsAg assay
Authors: Echevarría José M. , Avellón Ana
Published: February 2008

The sensitivity of immunoassays for hepatitis B virus (HBV) surface antigen (HBsAg) detection may be hampered by the presence of mutants involving the major antigenic determinant of the protein. The performance of the VITROS® HBsAg Assay has been shown to be affected by mutations comprising amino acid changes at residues 143, 144, and 145 of the HBsAg molecule. Sixty‐seven serum samples from HBV carriers containing major populations of natural HBsAg mutants assayed previously by that assay were tested by the new VITROS® HBsAg ES Assay. Samples displayed either single or multiple amino acid substitutions between positions 112 and 145 of the HBsAg, including changes in relevant residues such as 118–120, 125–127, and 143–145. Testing of undiluted samples by the current assay gave rise to false negative results in two samples displaying the single substitutions 145A and 145R, and in one additional sample displaying a dual mutation 118A + 145A. Unusually weak reactivity (<25 S/CO units) was, in addition, recorded in samples containing mutants 143L (2 samples) and 115N + 120Q + 131K + 144A (1 sample). Testing samples at the 1/40 dilution by the modified assay did not produce, in contrast, false negative results, and reactivity below 25 S/CO units was recorded only in three cases. These results confirm that the capability of immunoassays to detect the presence of natural HBsAg mutants in clinical samples may be improved significantly by introducing changes in their design, and show that such improvement has been achieved successfully with the new VITROS® HBsAg ES Assay. J. Med. Virol. 80:598–602, 2008. © 2008 Wiley‐Liss, Inc.
Physiological Improvement to Enhance Escherichia coli Cell‐Surface Display via Reducing Extracytoplasmic Stress
Authors: Narayanan Niju , Chou C. Perry
Published: February 2008

Cell physiology was impaired when enhanced yellow fluorescence protein (EYFP) was displayed on the Escherichia coli cell surface, resulting in growth arrest and poor display performance. Coexpression of Skp, a periplasmic chaperone known to interact with several outer membrane proteins for their transport and insertion in the outer membrane, was demonstrated to be effective to restore cell physiology. When Skp was coexpressed with EYFP display, host cells became less sensitive to ethylenediaminetetraacetic acid and sodium dodecyl sulfate, implying that cell physiology was improved. Most importantly, the display performance was highly enhanced as a result of the increased specific fluorescence intensity without growth arrest. The results of transmission electron microscopy indicate that the density of surface‐displayed EYFP was highly increased upon Skp coexpression. Cells with EYFP display experienced extracytoplasmic stress, as reflected by the induced promoter activities of three stress‐responsive genes, degP, cpxP, and rpoH. The extracytoplasmic stress reflected by the degP promoter activity appears to be consistent with the cell physiology observed phenotypically under various culture conditions for cell‐surface display. Therefore, the PdegP:: lacZ allele was proposed to be a suitable “sensor” for monitoring the extracytoplasmic stress and cell physiology during the course of E. coli cell‐surface display.