bluuebunny/crossref_metadata_2025 huggingface dataset:
Ventriculocystostomy and endoscopic third ventriculostomy/shunt placement in the management of hydrocephalus secondary to giant retrocerebellar cysts in infancy
Authors: King James A. J. , Auguste Kurtis I. , Halliday William , Drake James M. , Kulkarni Abhaya V.
Published: April 2010

Hydrocephalus secondary to giant retrocerebellar cysts in infancy is a challenging condition and many treatment options exist. The authors report on 3 consecutive cases involving infants under the age of 6 months treated successfully with ventriculocystostomy in combination with direct hydrocephalus treatment (endoscopic third ventriculostomy or shunt placement). They describe the operative procedure, the surgical morbidity, and outcome in each case and review the literature regarding surgical approaches to this condition.
The parallel use of endoscopic fenestration and a cystoperitoneal shunt with programmable valve to treat arachnoid cysts: experience and hypothesis
Authors: Mottolese Carmine , Szathmari Alexandru , Simon Emile , Ginguene Carole , Ricci-Franchi Anne-Claire , Hermier Marc
Published: April 2010

Object

The authors share their experience of the treatment of arachnoid cysts with endoscopic fenestration and cystoperitoneal shunt placement during the same operation. The importance of this strategy is related to the fact that the shunt can induce the collapse of the cyst and that the endoscopic fenestration could make it possible to remove the shunt, avoiding the phenomenon of shunt dependence.

Methods

Between 1996 and 2005, 35 patients with an arachnoid cyst were treated using endoscopic fenestration and placement of a programmable shunt. The patients' ages (70% boys and 30% girls) ranged from 2 months to 16 years. These patients were reviewed with MR imaging and clinical examination. The cyst volumes and clinical examinations were evaluated.

Results

No serious complications were reported; the cyst disappeared in 60% of the cases, and in 54% of the cases it was possible to remove the shunt without shunt dependence.

Conclusions

In the authors' view, this strategy seems easy, does not take longer than a simple shunt surgery or an endoscopic cystostomy alone, and can be useful for treatment of arachnoid cysts in all locations.
Microencephaloceles: another dual pathology of intractable temporal lobe epilepsy in childhood
Authors: Aquilina Kristian , Clarke Dave F. , Wheless James W. , Boop Frederick A.
Published: April 2010

Temporal lobe encephaloceles can be associated with temporal lobe epilepsy. The authors report on the case of an adolescent with multiple microencephaloceles, in the anterolateral middle fossa floor, identified at surgery (temporal lobectomy) for intractable partial-onset seizures of temporal origin. Magnetic resonance imaging revealed only hippocampal atrophy. Subdural electrodes demonstrated ictal activity arising primarily from the anterior and lateral temporal lobe, close to the microencephaloceles, spreading to the anterior and posterior mesial structures. Pathological examination revealed diffuse temporal gliosis involving the hippocampus, together with microdysgenesis of the amygdala. The literature on epilepsy secondary to encephaloceles is reviewed and the contribution of the microencephaloceles to the seizure disorder in this patient is discussed.
Longitudinal comparison of pre- and postoperative diffusion tensor imaging parameters in young children with hydrocephalus
Authors: Air Ellen L. , Yuan Weihong , Holland Scott K. , Jones Blaise V. , Bierbrauer Karin , Altaye Mekibib , Mangano Francesco T.
Published: April 2010

Object

The goal in this study was to compare the integrity of white matter before and after ventriculoperitoneal (VP) shunt insertion by evaluating the anisotropic diffusion properties with the aid of diffusion tensor (DT) imaging in young children with hydrocephalus.

Methods

The authors retrospectively identified 10 children with hydrocephalus who underwent both pre- and postoperative DT imaging studies. The DT imaging parameters (fractional anisotropy [FA], mean diffusivity, axial diffusivity, and radial diffusivity) were computed and compared longitudinally in the splenium and genu of the corpus callosum (gCC) and in the anterior and posterior limbs of the internal capsule (PLIC). The patients' values on DT imaging at the pre- and postshunt stages were compared with the corresponding age-matched controls as well as with a large cohort of healthy children in the database.

Results

In the gCC, 7 of 10 children had abnormally low preoperative FA values, 6 of which normalized postoperatively. All 3 of the 10 children who had normal preoperative FA values had normal FA values postoperatively as well. In the PLIC, 7 of 10 children had abnormally high FA values, 6 of which normalized postoperatively, whereas the other one had abnormally low postoperative FA. Of the remaining 3 children, 2 had abnormally low preoperative FA values in the PLIC; this normalized in 1 patient after surgery. The other child had a normal preoperative FA value that became abnormally low postoperatively. When comparing the presurgery frequency of abnormally low, normal, and abnormally high FA values to those postsurgery, there was a statistically significant longitudinal difference in both gCC (p = 0.02) and PLIC (p = 0.002).

Conclusions

In this first longitudinal DT imaging study of young children with hydrocephalus, DT imaging anisotropy yielded abnormal results in several white matter regions of the brain, and trended toward normalization following VP shunt placement.
Amaurosis in infancy due to craniopharyngioma: a not-exceptional but often misdiagnosed symptom
Authors: Feletti Alberto , Marton Elisabetta , Mazzucco Grazia Marina , Fang Shanna , Longatti Pierluigi
Published: April 2010

Since children may not be able to complain of progressive reduction in optic acuity, visual assessment in infancy may present practical difficulties. The authors report a case of craniopharyngioma, which led a young child to early blindness before the correct diagnosis could be made. Similar to other reported cases, the authors found that surgery did not substantially modify the preoperative visual deficit. They conclude that minimal improvement in visual acuity can be expected despite successful microsurgical removal of the tumor.
Magnetic resonance imaging–graded hypothalamic compression in surgically treated adult craniopharyngiomas determining postoperative obesity
Authors: Van Gompel Jamie J. , Nippoldt Todd B. , Higgins Dominique M. , Meyer Fredric B.
Published: April 2010

Object

Obesity as a consequence of management of pediatric craniopharyngioma is a well-described phenomenon related to the degree of hypothalamic involvement. However, weight change and obesity have not been analyzed in adult patients. Therefore, the purpose of this study was 1) to evaluate the pattern of postoperative weight gain related to preoperative body mass index (BMI), 2) determine if postoperative weight gain is an issue in adult patients, and 3) develop an objective MR imaging grading system to predict risk of postoperative weight gain and obesity in adults treated for craniopharyngioma.

Methods

The authors retrospectively screened 296 patients with known craniopharyngioma for the following inclusion criteria: pathologically confirmed craniopharyngioma, index surgery at the authors' institution, and operative weight and height recorded with at least 3 months of follow-up including body weight measurement. Patients aged 18 years or younger were excluded, yielding 28 cases for analysis. Cases of craniopharyngiomas were compared with age- and sex-matched controls (pituitary adenoma patients) to evaluate the pattern and significance of perioperative weight changes.

Results

Mean age was 46 ± 17 years at surgery, and 64% of the patients were male. Complete resection was achieved in 71% of cases. There was no correlation of preoperative BMI and postoperative weight gain testing in a linear model. Sixty-one percent and 46% of patients had postoperative weight gains greater than 4 and 9%, respectively.

Comparing craniopharyngioma patients (cases) to age- and sex-matched controls, the preoperative BMIs were similar (p = 0.93) between cases (mean 28.9 [95% CI 30.9–26.9]) and controls (mean 29.3 [95% CI 31.9–26.7]). However, there was a trend to a greater mean postoperative weight change (percentage) in cases (10.1%) than in controls (5.6%) (p = 0.24). Hypothalamic T2 signal change and irregular contrast enhancement correlated and predicted higher-grade hypothalamic involvement. Furthermore, they can be used to objectively grade hypothalamic involvement as the authors propose. Progressive hypothalamic involvement correlated with larger postoperative weight gains (p = 0.022); however, hypothalamic involvement did not correlate with preoperative BMI (p = 0.5).

Conclusions

Postoperative weight gain in adult patients undergoing surgery for craniopharyngioma is a significant problem and correlates with hypothalamic involvement, as it does in pediatric patients. Finally, objective MR imaging criteria can be used to predict risk of postoperative weight gain and aid in grading of hypothalamic involvement.
Early outcomes of endoscopic transsphenoidal surgery for adult craniopharyngiomas
Authors: Jane John A. , Kiehna Erin , Payne Spencer C. , Early Stephen V. , Laws Edward R.
Published: April 2010

Object

Although the transsphenoidal approach for subdiaphragmatic craniopharyngiomas has been performed for many years, there are few reports describing the role of the endoscopic transsphenoidal technique for suprasellar craniopharyngiomas. The purpose of this study was to report the outcomes of the endoscopic transsphenoidal approach for adults with craniopharyngiomas in whom the goal was gross-total resection.

Methods

Twelve patients were identified who were older than 18 years at the time of their pure endoscopic transsphenoidal surgery. Their medical records and imaging studies were retrospectively reviewed.

Results

Gross-total resection was achieved in 42% of cases when assessed by intraoperative impression alone and in 75% when assessed by the first postoperative MR imaging study. However, 83% of patients achieved at least a 95% resection when assessed by both intraoperative impression and the first postoperative MR imaging study. Permanent diabetes insipidus occurred postoperatively in 44% of patients. Six (67%) of 9 patients who had a functioning hypothalamic-pituitary axis preoperatively developed panhypopituitarism after surgery. Visual improvement or normalization occurred in 78% of patients with preoperative visual deficits. Although no patient experienced a postoperative CSF leak, 1 patient was treated for meningitis.

Conclusions

The authors have achieved a high rate of radical resection and symptomatic improvement with the endoscopic transsphenoidal technique for both subdiaphragmatic (sellar/suprasellar) and supradiaphragmatic (suprasellar) craniopharyngiomas. However, this is also associated with a high incidence of new endocrinopathy. Endoscopic assessment of tumor resection may be more sensitive for residual tumor than the first postoperative MR imaging study.
Craniopharyngioma Clinical Status Scale: a standardized metric of preoperative function and posttreatment outcome
Authors: Elliott Robert E. , Sands Stephen A. , Strom Russell G. , Wisoff Jeffrey H.
Published: April 2010

Object

Controversy persists concerning the optimal treatment of craniopharyngiomas in children, and no standard outcome metric exists for comparison across treatment modalities, nor is there one that adequately reflects the multisystem dysfunction that may arise.

Methods

The authors retrospectively analyzed the records of 86 consecutive children who underwent a uniform treatment paradigm of attempted radical resection performed by a single surgeon. Excluding 3 perioperative deaths and 3 patients with inadequate follow-up, 80 children (34 girls and 46 boys; mean age 9.56 years; mean follow-up 9.6 years) composed the study group (53 primary and 27 previously treated/recurrent tumors). Building on existing classification schemes proposed by De Vile for hypothalamic dysfunction and Wen for overall functional outcome, the authors devised a more nuanced classification system (Craniopharyngioma Clinical Status Scale [CCSS]) that assesses outcome across 5 axes, including neurological examination, visual status, pituitary function, hypothalamic dysfunction, and educational/occupational status at last follow-up (there is a 4-tiered grading scale in each domain, with increasing values reflecting greater dysfunction).

Results

There was a significant increase in pituitary dysfunction following treatment—consistent with the high rates of diabetes insipidus and hypopituitarism common to the surgical management of craniopharyngiomas—and less dramatic deterioration in hypothalamic function or cognitive domains. Significant improvement in vision was also demonstrated, with no significant overall change in neurological status. Preoperative CCSS scores predicted postoperative outcome better than clinical characteristics like patient age, sex, tumor size, and the location or presence of hydrocephalus.

Conclusions

Preoperative CCSS scores predicted outcome with higher accuracy than clinical or imaging characteristics. In lieu of randomized trials, the CCSS may provide a useful outcome assessment tool for comparison across treatment paradigms and surgical approaches. Long-term follow-up is critical to the analysis of outcomes of craniopharyngioma treatment, given the often-delayed sequelae of all therapies and the high recurrence rates of these tumors.
The role of radiosurgery in the treatment of craniopharyngiomas
Authors: Veeravagu Anand , Lee Marco , Jiang Bowen , Chang Steven D.
Published: April 2010

The treatment of craniopharyngiomas is composed of an intricate balance of multiple modalities. Resection and radiotherapy have been combined to synergistically control tumor growth while preventing undue harm to crucial neurovascular structures. Although a craniopharyngioma is a benign lesion pathologically, it may induce severe neurological injury due to its location and rate of growth. More recently, the advent of targeted, fractionated radiotherapy has allowed for more aggressive tumor control while reducing the necessity for large resections. Initial studies have demonstrated significant tumor control in patients who are treated with resection combined with radiation therapy, versus surgery alone, with a lower rate of treatment-associated neurological deficits. In this review, a detailed account of the current studies evaluating the role of stereotactic radiosurgery in the management of craniopharyngiomas is presented. The authors also provide a short account of their experience to aid in defining the role of CyberKnife radiosurgery.
Prophecy, Power and Propriety: The Encounter of Solomon and the Queen of Sheba
Authors: Elias Jamal J.
Published: April 2010

The encounter of Solomon with the Queen of Sheba stands out as one of the more noteworthy stories related in the Qur'an. Among the distinguishing characteristics of the majority of Qur'anic pericopes of pre-Islamic prophetic figures are the apparent disjointedness of the references, the absence of sustained narrative, and allusions to characters and events that do not appear in the Qur'anic text itself. The story of the Queen of Sheba is elliptical and terse to the point that often one is not clear which of the principal characters in the story – God, Solomon, the Queen of Sheba, or some fourth party – is speaking. I argue that these Qur'anic references are fully comprehensible only if one is familiar with the narrative from some other source, which strongly suggests that it is intended for an audience that already knew the story of the encounter between Solomon and the queen. Through a study of the Qur'anic account as it has been explained and embellished by key historians and exegetes, I will attempt to show how early Islamic writers saw in this epic meeting themes and underlying messages regarding religious and temporal authority which go beyond the obvious details of a tale laced with sexual innuendo, and that their discussion of these themes provides a degree of understanding of the very nature of gender and authority in Islamic society; furthermore, the story of the Queen of Sheba is best seen primarily not as a story about the queen but as an important episode underlining Solomon's prophetic status.
Calligraphy, Colour and Light in the Blue Qur'an
Authors: George Alain
Published: April 2010

The Blue Qur'an is one of the most mesmerising manuscripts produced in Islam. Today, the most commonly held view is that this manuscript was produced for the early Fāṭimid court, before the conquest of Egypt in 358/969. However, in recent years our knowledge of early Qur'anic manuscripts, their calligraphy and the illumination that adorns their pages has greatly progressed. In the first part of this article, I will argue that the Blue Qur'an is in fact much earlier than has hitherto been recognised and dates to the early ʿAbbāsid period. This will be the occasion to posit some elements of chronology for early Qur'anic scripts. Once this new framework has been set for the manuscript, I will move on to explore the origin of its colour scheme, and its different layers of meaning; between the practical, the temporal and the spiritual.
Entropy-Related Extremum Principles for Model Reduction of Dissipative Dynamical Systems
Authors: Lebiedz Dirk
Published: April 2010

Chemical kinetic systems are modeled by dissipative ordinary differential equations involving multiple time scales. These lead to a phase flow generating anisotropic volume contraction. Kinetic model reduction methods generally exploit time scale separation into fast and slow modes, which leads to the occurrence of low-dimensional slow invariant manifolds. The aim of this paper is to review and discuss a computational optimization approach for the numerical approximation of slow attracting manifolds based on entropy-related and geometric extremum principles for reaction trajectories.
Current and Emerging Detoxification Therapies for Critical Care
Authors: Howell Brett A. , Chauhan Anuj
Published: April 2010

Toxicity resulting from prescription drugs such as tricyclic antidepressants and cardioactive steroids, as well as drugs of abuse and exposure to environmental chemicals, represents a major need for detoxification treatments. Particles and colloids, antibody fragments (Fab), and indirect treatment methods such as macroemulsions, are currently being developed or employed as detoxification therapies. Colloids, particles, and protein fragments typically mitigate toxicity by binding to the toxin and reducing its concentration in vital organs. Indirect methods such as macroemulsions and sodium bicarbonate act directly on the affected organs, rather than the toxin. In this review, key design parameters (i.e. binding affinity, biocompatibility, pharmacokinetics) are discussed for each type of detoxification treatment. In addition, some of the latest research in each area is reviewed.
Anticancer Effect and Structure-Activity Analysis of Marine Products Isolated from Metabolites of Mangrove Fungi in the South China Sea
Authors: Tao Li-yang , Zhang Jian-ye , Liang Yong-ju , Chen Li-ming , Zheng Li-sheng , Wang Fang , Mi Yan-jun , She Zhi-gang , To Kenneth Kin Wah , Lin Yong-cheng , Fu Li-wu
Published: April 2010

Marine-derived fungi provide plenty of structurally unique and biologically active secondary metabolites. We screened 87 marine products from mangrove fungi in the South China Sea for anticancer activity by MTT assay. 14% of the compounds (11/86) exhibited a potent activity against cancer in vitro. Importantly, some compounds such as compounds 78 and 81 appeared to be promising for treating cancer patients with multidrug resistance, which should encourage more efforts to isolate promising candidates for further development as clinically useful chemotherapeutic drugs. Furthermore, DNA intercalation was not involved in their anticancer activities, as determined by DNA binding assay. On the other hand, the structure-activity analysis indicated that the hydroxyl group was important for their cytotoxic activity and that bulky functional groups such as phenyl rings could result in a loss of biological activity, which will direct the further development of marine product-based derivatives.
Multi-Camera Sensor System for 3D Segmentation and Localization of Multiple Mobile Robots
Authors: Losada Cristina , Mazo Manuel , Palazuelos Sira , Pizarro Daniel , Marrón Marta
Published: April 2010

This paper presents a method for obtaining the motion segmentation and 3D localization of multiple mobile robots in an intelligent space using a multi-camera sensor system. The set of calibrated and synchronized cameras are placed in fixed positions within the environment (intelligent space). The proposed algorithm for motion segmentation and 3D localization is based on the minimization of an objective function. This function includes information from all the cameras, and it does not rely on previous knowledge or invasive landmarks on board the robots. The proposed objective function depends on three groups of variables: the segmentation boundaries, the motion parameters and the depth. For the objective function minimization, we use a greedy iterative algorithm with three steps that, after initialization of segmentation boundaries and depth, are repeated until convergence.
GFZ Wireless Seismic Array (GFZ-WISE), a Wireless Mesh Network of Seismic Sensors: New Perspectives for Seismic Noise Array Investigations and Site Monitoring
Authors: Picozzi Matteo , Milkereit Claus , Parolai Stefano , Jaeckel Karl-Heinz , Veit Ingo , Fischer Joachim , Zschau Jochen
Published: April 2010

Over the last few years, the analysis of seismic noise recorded by two dimensional arrays has been confirmed to be capable of deriving the subsoil shear-wave velocity structure down to several hundred meters depth. In fact, using just a few minutes of seismic noise recordings and combining this with the well known horizontal-to-vertical method, it has also been shown that it is possible to investigate the average one dimensional velocity structure below an array of stations in urban areas with a sufficient resolution to depths that would be prohibitive with active source array surveys, while in addition reducing the number of boreholes required to be drilled for site-effect analysis. However, the high cost of standard seismological instrumentation limits the number of sensors generally available for two-dimensional array measurements (i.e., of the order of 10), limiting the resolution in the estimated shear-wave velocity profiles. Therefore, new themes in site-effect estimation research by two-dimensional arrays involve the development and application of low-cost instrumentation, which potentially allows the performance of dense-array measurements, and the development of dedicated signal-analysis procedures for rapid and robust estimation of shear-wave velocity profiles. In this work, we present novel low-cost wireless instrumentation for dense two-dimensional ambient seismic noise array measurements that allows the real–time analysis of the surface-wavefield and the rapid estimation of the local shear-wave velocity structure for site response studies. We first introduce the general philosophy of the new system, as well as the hardware and software that forms the novel instrument, which we have tested in laboratory and field studies.
Designing the Future
Authors: De Zeeuw Friso , Franzen Agnes , Aalbers Kristel , Van Hal Anke , Dulski Birgit
Published: April 2010

The Netherlands has a tradition in public spatial planning and design. In the past 20 years, we have seen an increasing role for the market in this field, and more recently, growing attention for sustainability. Sustainability has become an economic factor. Not only at the building level, but also on the level of large-scale area development projects. More and more local governments have high ambitions for sustainable development. Increasingly, during project development, buildings are developed on a sustainable basis. Most of the time, the focus in this approach is on energy. However, sustainability also comprises social aspects. Energy measures have a direct relation to an economic factor such as investment costs, and payback time can be calculated. The economic aspects of social sustainability are more complex. Therefore, for all sustainability development projects, especially in large-scale projects planned over a longer period, it is necessary to make presumptions, which are less reliable as the planning period is extended. For future larger-scale developments, experience in the Netherlands points to two design approaches: ‘backcasting’, or using a growth model (or a combination of these two). The power of design is the ability to imagine possible scenarios for the future. The layer approach helps to integrate sustainability into public spatial planning. And more specifically, Urban Design Management (UDM) supports an integrative and collaborative approach also on the operational level of a project in which public and market partners work together. This article outlines how design, based on these approaches, can contribute to sustainable development based on the ‘new playing field’, where spatial problems should be solved in networks. Dutch projects in Almere (Benoordenhout) and Rijswijk are used to illustrate this approach.
Fluctuating Asymmetry and Steroid Hormones: A Review
Authors: Benderlioglu Zeynep
Published: April 2010

Fluctuating asymmetry (FA) represents random, minor deviations from perfect symmetry in paired traits. Because the development of the left and right sides of a paired trait is presumably controlled by an identical set of genetic instructions, these small imperfections are considered to reflect genetic and environmental perturbations experienced during ontogeny. The current paper aims to identify possible neuroendocrine mechanisms, namely the actions of steroid hormones that may impact the development of asymmetrical characters as a response to various stressors. In doing so, it provides a review of the published studies on the influences of glucocorticoids, androgens, and estrogens on FA and concomitant changes in other health and fitness indicators. It follows the premise that hormonal measures may provide direct, non-invasive indicators of how individuals cope with adverse life conditions, strengthening the associations between FA and health, fitness, and behavior.
Broken Time Translation Symmetry as a Model for Quantum State Reduction
Authors: Van Wezel Jasper
Published: April 2010

The symmetries that govern the laws of nature can be spontaneously broken, enabling the occurrence of ordered states. Crystals arise from the breaking of translation symmetry, magnets from broken spin rotation symmetry and massive particles break a phase rotation symmetry. Time translation symmetry can be spontaneously broken in exactly the same way. The order associated with this form of spontaneous symmetry breaking is characterised by the emergence of quantum state reduction: systems which spontaneously break time translation symmetry act as ideal measurement machines. In this review the breaking of time translation symmetry is first compared to that of other symmetries such as spatial translations and rotations. It is then discussed how broken time translation symmetry gives rise to the process of quantum state reduction and how it generates a pointer basis, Born’s rule, etc. After a comparison between this model and alternative approaches to the problem of quantum state reduction, the experimental implications and possible tests of broken time translation symmetry in realistic experimental settings are discussed.
Cell–Cell Interaction Promotes Rat Marrow Stromal Cell Differentiation into Endothelial Cell via Activation of TACE/TNF-α Signaling
Authors: Xu Jian , Liu Xinfeng , Chen Jieli , Zacharek Alex , Cui Xu , Savant-Bhonsale Smita , Chopp Michael , Liu Zhenguo
Published: April 2010

Marrow stromal cells (MSCs) are capable of differentiating into various cell types including endothelial cells. Microenvironment is important in cell fate determination. Tumor necrosis factor-α converting enzyme (TACE), a well-characterized “sheddase,” participates in the differentiation process of multiple lineages by the proteolytic release of membrane-bound proteins such as tumor necrosis factor-α (TNF-α). We investigated the endothelial differentiation of MSCs under two coculture conditions: 1) direct MSCs-rat brain microvascular endothelial cells (rBMECs) contact coculture; and 2) indirect coculture of MSCs and rBMECs. Also, we examined the role of TACE/TNF-α signaling in the process of differentiation under direct coculture condition. We found that endothelial differentiation of MSCs was substantially enhanced in MSCs-rBMECs direct contact coculture, but not in indirect transwell coculture condition. Transcript levels of TACE and TNF-α as well as TACE protein expression were significantly upregulated in direct, but not in indirect, coculture condition. Addition of human recombinant TACE promoted gene expression of endothelial specific markers including vWF, CD31, VE-cadherin, Flk-1, and Flt-1 in the differentiating MSCs. Furthermore, inhibition of TACE with TAPI-2 or inhibition of TNF-α with Etanercept attenuated endothelial differentiation of MSCs in the direct coculture condition. We demonstrated for the first time that direct MSCs-rBMECs interaction stimulated the endothelial differentiation of MSCs via TACE/TNFα signaling.
Both CD133+Cells and Monocytes Provide Significant Improvement for Hindlimb Ischemia, Although They do not Transdifferentiate Into Endothelial Cells
Authors: Sanchez-Guijo Fermin M. , Oterino Enrique , Barbado Maria-Victoria , Carrancio Soraya , Lopez-Holgado Natalia , Muntion Sandra , Hernandez-Campo Pilar , Sanchez-Abarca Luis-Ignacio , Perez-Simon Jose A. , Miguel Jesús F. San , Briñon Jesús G. , Del Cañizo Maria-Consuelo
Published: April 2010

To address a number of questions regarding the experimental use of bone marrow (BM) stem cells in hindlimb ischemia, including which is the best cell type (e.g., purified hematopoietic stem cell or monocytes), the best route of delivery [intramuscular (IM) or intravenous (IV)], and the mechanism of action (transdifferentiation or paracrine effects), we have compared the neovascularization capacities of CD133+stem cells and monocytes (CD11b+) from the BM of Tie2-GFP mice either via IV or IM in a murine severe hindlimb ischemia model. To test the effect of cytokine administration, an extra group received BM conditioned medium. Peripheral blood flow as well as capillary density and GPF-positivity detection in ischemic muscles was evaluated 7, 14, and 21 days postinjection. In addition, CD133+and CD11b+cells from transgenic animals were cultured in vitro with angiogenic media for 7, 14, and 21 days to assess GFP expression. In all four cell-treated groups, blood flow and capillary density significantly recovered compared with the mice that received no cells or conditioned medium. There were no differences with respect to cell types or administration routes, with the exception of a faster flow recovery in the CD133+-treated cell group. We did not find GFP+cells in the ischemic muscles and there was no GFP expression after in vitro proangiogenic culture. Our study shows that both purified CD133+stem cells and myeloid mononuclear cells, either IM or IV administered, have similar neoangiogenic ability. Nevertheless, transdifferentiation into endothelial cells is not the mechanism responsible for their beneficial effect.
Controlled Release of Neurotrophin-3 and Platelet-Derived Growth Factor from Fibrin Scaffolds Containing Neural Progenitor Cells Enhances Survival and Differentiation into Neurons in a Subacute Model of SCI
Authors: Johnson Philip J. , Tatara Alexander , Shiu Alicia , Sakiyama-Elbert Shelly E.
Published: April 2010

A consistent problem with stem/neural progenitor cell transplantation following spinal cord injury (SCI) is poor cell survival and uncontrolled differentiation following transplantation. The current study evaluated the feasibility of enhancing embryonic stem cell-derived neural progenitor cell (ESNPC) viability and directing their differentiation into neurons and oligodendrocytes by embedding the ESNPCs in fibrin scaffolds containing growth factors (GF) and a heparin-binding delivery system (HBDS) in a subacute rat model of SCI. Mouse ESNPCs were generated from mouse embryonic stem cells (ESCs) using a 4–/4+ retinoic acid (RA) induction protocol. The ESNPCs were then transplanted as embryoid bodies (EBs, 70% neural progenitor cells) into the subacute model of SCI. ESNPCs (10 EBs per animal) were implanted directly into the SCI lesion, encapsulated in fibrin scaffolds, encapsulated in fibrin scaffolds containing the HBDS, neurotrophin-3 (NT-3), and platelet-derived growth factor (PDGF), or encapsulated in fibrin scaffolds with NT-3 and PDGF with no HBDS. We report here that the combination of the NT-3, PDGF, and fibrin scaffold (with or without HBDS) enhanced the total number of ESNPCs present in the spinal cord lesion 2 weeks after injury. In addition, the inclusion of the HBDS with growth factor resulted in an increase in the number of ESNPC-derived NeuN-positive neurons. These results demonstrate the ability of fibrin scaffolds and the controlled release of growth factors to enhance the survival and differentiation of neural progenitor cells following transplantation into a SCI model.
Large-Scale Comparison of Liberase HI and Collagenase NB1 Utilized for Human Islet Isolation
Authors: Brandhorst H. , Friberg A. , Nilsson B. , Andersson H. H. , Felldin M. , Foss A. , Salmela K. , Tibell A. , Tufveson G. , Korsgren O. , Brandhorst D.
Published: April 2010

For more than a decade Liberase HI was commonly used as the standard enzyme blend for clinical human islet isolation until enforced replacement by collagenase NB1 (NB1). This change resulted initially in a reduction in islet isolation outcome and transplant activities worldwide. This retrospective study was initiated to compare the efficiency of NB1 premium grade with Liberase in 197 human islet isolations. All pancreata were processed between January 2006 and June 2008 utilizing the same procedures for isolation and quality assessment except the administration of preselected lots of either Liberase ( n = 101) or NB1 ( n = 96). Utilizing Liberase, significantly more digested tissue and purified islet yield was produced compared to NB1. In contrast, the use of NB1 was associated with significantly higher purity and glucose stimulation index during dynamic perifusion. The expression of proinflammatory markers was almost identical except tissue factor expression, which was higher after utilization of Liberase. No difference was found in the percentage of pancreata fulfilling the criteria for clinical islet transplantation. The results suggest that Liberase is more efficient for pancreas dissociation than collagenase NB1 but seems to be more harmful to exocrine cells and islet tissue.
Nonalbumin Proteinuria in Islet Transplant Recipients
Authors: Leitão Cristiane B. , Froud Tatiana , Cure Pablo , Tharavanij Thipaporn , Pileggi Antonello , Ricordi Camillo , Alejandro Rodolfo
Published: April 2010

The aim of this study was to evaluate the importance of nonalbumin-predominant proteinuria on kidney function (KF) after islet transplantation (ITx). Twenty-four-hour proteinuria and albuminuria were available in 27 recipients. KF was assessed by serum creatinine and estimated glomerular filtration rate (eGFR) was calculated by Modification of Diet in Renal Disease formula. Correlations between eGFR and albuminuria ( r = −0.422, p < 0.001) were higher than with proteinuria ( r = −0.223, p < 0.001; p = 0.006 for comparison between correlations). Nineteen (70%) subjects had proteinuria ≥ 300 mg/24 h during the follow-up. Subjects were divided into three groups according to urinary protein excretion patterns: no proteinuria ( n = 8), nonalbumin-predominant ( n = 8), and albumin-predominant ( n = 11) proteinuria. Proteinuria ≥ 500 mg/24 h was observed only among patients with albumin-predominant proteinuria (64%; p = 0.002) and these patients had the lowest eGFR means post-ITx (no proteinuria: 84.2 ± 16.4 vs. nonalbumin: 69.1 ± 13.8 vs. albumin-predominant proteinuria: 65.5 ± 16.6 ml/min/1.73 m2, p = 0.044 for first vs. last group). In conclusion, high frequency of proteinuria was observed after ITx. However, it seems to be milder and have less impact on KF when albumin is not the major source of proteinuria. Prospective evaluation of proteinuria, including tubular function markers, should be performed to elucidate the mechanisms of kidney damage in this population.
A First Semimanual Device for Clinical Intramuscular Repetitive Cell Injections
Authors: Richard Pierre-Luc , Gosselin Clément , Laliberté Thierry , Paradis Martin , Goulet Marlyne , Tremblay Jacques P. , Skuk Daniel
Published: April 2010

Intramuscular cell transplantation in humans requires so far meticulous repetitive cell injections. Performed percutaneously with syringes operated manually, the procedure is very time consuming and requires a lot of concentration to deliver the cells exactly in the required region. This becomes impractical and inaccurate for large volumes of muscle. In order to accelerate this task, to render it more precise, and to perform injections more reproducible in large volumes of muscle, we developed a specific semimanual device for intramuscular repetitive cell injections. Our prototype delivers very small quantities of cell suspension, homogeneously throughout several needles, from a container in the device. It was designed in order to deliver the cells as best as possible only in a given subcutaneous region (in our case, skeletal muscles accessible from the surface), avoiding wasting in skin and hypodermis. The device was tested in monkeys by performing intramuscular allotransplantations of β-galactosidase-labeled myoblasts. During transplantations, it was more ergonomic and considerably faster than manually operated syringes, facilitating the cell graft in whole limb muscles. Biopsies of the myoblast-injected muscles 1 month later showed abundant β-galactosidase-positive myofibers with homogeneous distribution through the biopsy sections. This is the first device specifically designed for the needs of intramuscular cell transplantation in a clinical context.
Treatment of Acute HCV Infection in HIV-Positive Patients: Experience from a Multicentre European Cohort
Authors: Vogel Martin , Dominguez Stéphanie , Bhagani Sanjay , Azwa Alex , Page Emma , Guiguet Marguerite , Valantin Marc-Antoine , Katlama Christine , Rockstroh Jürgen K , Nelson Mark
Published: April 2010

Background

Early treatment of acute HCV infection has been shown to improve virological response rates in HIV-positive patients; however, details on when and how to best treat acute HCV infection remain unclear at present.

Methods

In this European multicentre cohort study, HIV-positive patients with acute HCV infection were offered immediate or delayed anti-HCV therapy, pegylated interferon or pegylated interferon plus ribavirin combination therapy for 24 or 48 weeks, depending on the local protocol. The main outcome measure was the rate of sustained virological response (SVR).

Results

A total of 150 HIV-infected men with acute HCV were enrolled between 2001 and 2006, 111 of whom received anti-HCV therapy. The predominant HCV genotype was type 1 and was present in 71 (64%) patients. Patients were treated with pegylated interferon ( n=14) or pegylated interferon plus ribavirin ( n=97), with a median duration of treatment of 25 weeks. SVR was obtained in 62% (95% confidence interval 52–71) of patients. There was no difference in SVR by genotype, CD4+ T-cell count, HIV RNA, HCV RNA, alanine amino-transferase levels or use of ribavirin. Negative HCV RNA at weeks 4 and 12 were strong predictors of SVR.

Conclusions

High rates of SVR (62%) were obtained in HIV-coinfected patients with acute HCV infection undergoing early anti-HCV treatment using pegylated interferon alone or in combination with ribavirin. Treatment response at weeks 4 and 12 might be of help to further guide treatment duration. Urgent prospective studies are needed to further determine the optimal treatment regimen and the duration of therapy.
Effect of the HIV protease inhibitor amprenavir on the growth and differentiation of primary gingival epithelium
Authors: Israr Mohd , Mitchell Danielle , Alam Samina , Dinello Donald , Kishel Joseph J , Meyers Craig
Published: April 2010

Background

HIV-positive patients taking antiretroviral drugs, including protease inhibitors, have shown a significant increase in the development of oral complications; these complications are a major health issue for affected patients. The effect of these drugs on oral epithelium growth and differentiation is presently unknown. In this study, we explore for the first time the effect of the HIV protease inhibitor amprenavir on gingival epithelium growth and differentiation.

Methods

Organotypic (raft) cultures of gingival keratinocytes were established and the raft cultures treated with a range of amprenavir concentrations. Haematoxylin and eosin staining was performed to examine the effect of amprenavir on gingival epithelium growth and stratification. The raft cultures were also immunohistochemically analysed to determine the effect of amprenavir on the expression of key differentiation and proliferation markers, including cytokeratins, proliferating cell nuclear antigen (PCNA) and cyclin A.

Results

Amprenavir severely inhibited the growth of gingival epithelium when the drug was present throughout the growth period of the tissue. When the drug was added at day 8, amprenavir treatment altered the proliferation and differentiation of gingival keratinocytes. Expression of the cytokeratins 5, 14, 6 and 10, PCNA and cyclin A was increased; their expression pattern was also altered over time in treated rafts. Biochemically, the tissue exhibited characteristics of increased proliferation in the suprabasal layers of amprenavir-treated tissue.

Conclusions

Our results suggest that amprenavir treatment deregulates the cell cycle/proliferation and differentiation pathways, resulting in abnormal epithelial repair and proliferation. Our system could be developed as a potential model for studying the effects of highly active antiretroviral therapy in vitro.
Representing Classes of Things and Properties in General in Conceptual Modelling
Authors: Shanks Graeme , Moody Daniel , Nuredini Jasmina , Tobin Daniel , Weber Ron
Published: April 2010

How classes of things and properties in general should be represented in conceptual models is a fundamental issue. For example, proponents of object-role modelling argue that no distinction should be made between the two constructs, whereas proponents of entity-relationship modelling argue the distinction is important but provide ambiguous guidelines about how the distinction should be made. In this paper, the authors use ontological theory and cognition theory to provide guidelines about how classification should be represented in conceptual models. The authors experimented to test whether clearly distinguishing between classes of things and properties in general enabled users of conceptual models to better understand a domain. They describe a cognitive processing study that examined whether clearly distinguishing between classes of things and properties in general impacts the cognitive behaviours of the users. The results support the use of ontologically sound representations of classes of things and properties in conceptual modelling.
A Trade Value Perspective on Ecommerce Research
Authors: King Ruth C. , Sen Ravi , D’Aubeterre Fergle , Sethi Vikram
Published: April 2010

The impact of web-based electronic commerce on the process of disintermediation and re-intermediation has been extensively studied. Two major limitations of the existing work are the focus on a single economic measure (i.e., transaction cost minimization) and the examination of channel-structure decisions from only a single perspective (the seller’s). This paper introduces transactional value theory in the context of channel-structure research and integrates it with transaction cost theory to generate a trade value framework. The trade value framework considers channel-structure decisions from the perspectives of both buyers and sellers and is used to analyze the impact of web-based e-commerce on intermediated channel-structures. The proposed framework suggests that intermediaries function best in a channel-structure if they can reduce trade-inhibiting factors and improve trade-enhancing factors. Intermediaries may also prosper if they deliver extraordinary value on one side of the trade value framework to the point that inhibiting factors on the other end of the trade can be overlooked. Intermediaries maximize the value of the trade for both the buyers and the sellers by trading through an intermediated channel-structure as opposed to trading directly.
Evolution of the Pentraxin Family: The New Entry PTX4
Authors: Martinez de la Torre Yeny , Fabbri Marco , Jaillon Sebastien , Bastone Antonio , Nebuloni Manuela , Vecchi Annunciata , Mantovani Alberto , Garlanda Cecilia
Published: April 2010

Pentraxins (PTXs) are a superfamily of multifunctional conserved proteins, some of which are components of the humoral arm of innate immunity and behave as functional ancestors of Abs. They are divided into short (C-reactive protein and serum amyloid P component) and long pentraxins (PTX3 and neuronal pentraxins). Based on a search for pentraxin domain-containing sequences in databases, a phylogenetic analysis of the pentraxin family from mammals to arthropods was conducted. This effort resulted in the identification of a new long pentraxin (PTX4) conserved from mammals to lower vertebrates, which clusters alone in phylogenetic analysis. The results indicated that the pentraxins consist of five clusters: short pentraxins, which can be found in chordate and arthropods; neuronal pentraxins; the prototypic long pentraxin PTX3, which originated very early at the divergence of the vertebrates; the Drosophila pentraxin-like protein B6; and the long pentraxin PTX4 discovered in this study. Conservation of flanking genes in mammalian evolution indicates maintenance of synteny. Analysis of PTX4, in silico and by transcript expression, shows that the gene is well conserved from mammals to lower vertebrates and has a unique pattern of mRNA expression. Thus, PTX4 is a new unique member of the pentraxin superfamily, conserved in evolution.
IL-17 Amplifies Human Contact Hypersensitivity by Licensing Hapten Nonspecific Th1 Cells to Kill Autologous Keratinocytes
Authors: Pennino Davide , Eyerich Kilian , Scarponi Claudia , Carbone Teresa , Eyerich Stefanie , Nasorri Francesca , Garcovich Simone , Traidl-Hoffmann Claudia , Albanesi Cristina , Cavani Andrea
Published: April 2010

Th17 is a newly identified lineage of effector T cells involved in autoimmunity and immune responses to pathogens. We demonstrate in this study the pathogenic role of IL-17–producing CD4+ T lymphocytes in allergic contact dermatitis (ACD) to skin-applied chemicals. IL-17+ T cells infiltrate ACD reactions and predominantly distribute at the site of heavy spongiosis. Skin IL-17+ T cells were functionally and phenotypically heterogeneous: although pure Th17 prevailed in ACD skin, hapten responsiveness was restricted to Th1/IL-17 (IFN-γ+IL-17+) and Th0/IL-17 (IFN-γ+IL-17+IL-4+) fractions, and to lesser extent Th2/IL-17 cells. In the IFN-γ–dominated ACD environment, IL-17–releasing T cells affect immune function of keratinocytes by promoting CXCL8, IL-6, and HBD-2 production. In addition, compared with Th1, supernatants from Th1/IL-17 T cells were much more efficient in inducing ICAM-1 expression on keratinocytes and keratinocyte–T cell adhesiveness in vitro. As a consequence, exposure to combined IFN-γ and IL-17 rendered keratinocytes susceptible to ICAM-1–dependent Ag nonspecific T cell killing. Thus, IL-17 efficiently amplifies the allergic reaction by rendering virtually all of the T lymphocytes recruited at the site of skin inflammation capable to directly contribute to tissue damage.