bluuebunny/crossref_metadata_2025_split huggingface dataset:
The molecular basis of celiac disease
Authors: Koning Frits 
Published: September 2003

AbstractCeliac disease is caused by inflammatory, gluten specific T cell responses in the small intestine. Invariably such responses are HLA‐DQ2 or HLA‐DQ8 restricted, providing an explanation for the strong association between celiac disease and these HLA‐class II alleles. It is now clear that some native gluten sequences can bind to HLA‐DQ2/8 and induce T cell responses. In addition, modification of gluten peptides by the enzyme tissue transglutaminase results in high affinity HLA‐DQ2/8 binding peptides that can induce T cell responses. Thus, gluten molecules contain a large number of immunogenic peptides and this is likely to play an important role in the breaking of oral tolerance to gluten. Copyright © 2003 John Wiley & Sons, Ltd.
Targeting with scFv: immune modulation by complement receptor specific constructs
Authors: Molnár Eszter , Prechl József , Isaák Andrea , Erdei Anna 
Published: September 2003

AbstractThe fate of a microbe in the host is determined by various molecules of the innate immune system, which recognize the microbe and enhance its interaction with antigen presenting cells. This ‘natural targeting’ phenomenon, however, does not function when antigens with limited immunogenicity enter the host. Peptide vaccines, for instance, require adjuvants to induce immune responses. As a surrogate for the natural targeting mechanisms, antibodies against selected receptors of antigen presenting cells, conjugated with the peptides, could be used as targeting devices. Here we review various antibody‐mediated antigen‐targeting strategies, paying special attention to complement receptor‐mediated targeting. We also describe and summarize our method of single‐chain antibody‐mediated targeting of viral epitopes to complement receptor type two and discuss the perspectives of single‐chain antibody‐mediated antigen targeting. Copyright © 2003 John Wiley & Sons, Ltd.
Destination ‘Lysosome’: a target organelle for tumour cell killing?
Authors: Castino Roberta , Démoz Marina , Isidoro Ciro 
Published: September 2003

AbstractLysosomes and lysosome‐related organelles constitute a system of acid compartments that interconnect the inside of the cell with the extracellular environment via endocytosis, phagocytosis and exocytosis. In recent decades it has been recognized that lysosomes are not just wastebaskets for disposal of unused cellular constituents, but that they are involved in several cellular processes such as post‐translational maturation of proteins, degradation of receptors and extracellular release of active enzymes. By complementing the autophagic process, lysosomes actively contribute to the maintenance of cellular homeostasis. Proteolysis by lysosomal cathepsins has been shown to mediate the death signal of cytotoxic drugs and cytokines, as well as the activation of pro‐survival factors. Secreted lysosomal cathepsins have been shown to degrade protein components of the extracellular matrix, thus contributing actively to its re‐modelling in physiological and pathological processes. The malfunction of lysosomes can, therefore, impact on cell behaviour and fate. Here we review the role of lysosomal hydrolases in several aspects of the malignant phenotype including loss of cell growth control, altered regulation of cell death, acquisition of chemoresistance and of metastatic potential. Based on these observations, the lysosome is proposed as a potential target organelle for the chemotherapy of tumours. We will also present some recent data concerning the technologies for delivering chemotherapeutic drugs to the endosomal–lysosomal compartment and the strategies to improve their efficacy. Copyright © 2003 John Wiley & Sons, Ltd.
Targeting dendritic cells for priming cellular immune responses
Authors: Gogolák Péter , Réthi Bence , Hajas György , Rajnavölgyi Éva 
Published: September 2003

AbstractThe cardinal role of dendritic cells (DC) in priming adaptive immunity and in orchestrating immune responses against all classes of pathogens and also against tumors is well established. Their unique potential both to maintain self‐tolerance and to initiate protective immune responses against foreign and/or dangerous structures is based on the functional diversity and flexibility of these cells. Tissue DC lining antigenic portals such as mucosal surfaces and the skin are specialized to take up a wide array of compounds including proteins, lipids, carbohydrates, glycoproteins, glycolipids and oligonucleotides, particles carrying such structures and apoptotic or necrotic cells. This process is facilitated by specialized receptors with high endocytic capacity, which provides potential targets for delivering designed molecules. The best route for targeting B‐ and/or T cell epitopes, however, is still the subject of intense investigation. Immature DC, which reside in various tissues, can be activated by pathogens, stress and inflammation or modified metabolic products, which induce mobilization of cells to draining lymph nodes where they act as highly potent professional antigen presenting cells. This is brought about by the ability to present their accumulated intracellular content for both CD4+ helper (Th) and CD8+ cytotoxic/cytolytic T lymphocytes (Tc/CTL). Engulfed proteins are processed intracellularly and their peptide fragments are transported to the cell surface in the context of major histocompatibility complex encoded class I and II molecules for presentation to Th cells and CTLs, respectively. The T cell priming capacity of DC, however, depends not only on antigen presentation but also on other features of DC.Human monocyte‐derived DC provide an excellent tool to study the internalizing, antigen‐presenting and T cell‐activating functions of DC at their immature and activated differentiation states. These biological activities of DC, however, are highly dependent on their migratory potential from the peripheral non‐lymphoid tissues to the lymph nodes, on the expression of adhesion molecules, which support the interaction of DC with T lymphocytes, and the cytokines secreted by DC, which polarize immune responses to Th1‐mediated cellular or Th2‐mediated antibody responses. These results altogether demonstrate that monocyte‐derived DC are useful candidates for in vitro or in vivo targeting of antigens to induce efficient adaptive immune responses against pathogens and also against tumors. Copyright © 2003 John Wiley & Sons, Ltd.
Passive tracking exploiting local signal conservation: The white marker phenomenon
Authors: Seppenwoolde Jan‐Henry , Viergever Max A. , Bakker Chris J.G. 
Published: September 2003

AbstractThis article presents a novel approach to passive tracking of paramagnetic markers during endovascular interventions, exploiting positive contrast of the markers to their background, so‐called “white marker tracking.” The positive contrast results from dephasing of the background signal with a slice gradient, while near the marker the signal is conserved because a dipole field induced by the marker compensates the dephasing gradient. Theoretical investigation shows that a local gradient induced by the local dipole field will nearly always cancel the dephasing gradient somewhere, regardless of marker composition, gradient strength, orientation, and acquisition parameters. The actual appearance of the white marker is determined by the marker strength, echo‐time, slice thickness, and gradient strength, as shown both theoretically and experimentally. The novel concept is demonstrated by tracking experiments in a flow phantom and in pig models and is shown to allow reliable and robust depiction of paramagnetic markers with positive contrast and significant suppression of the background signal. Magn Reson Med 50:784–790, 2003. © 2003 Wiley‐Liss, Inc.
Impact of intravascular signal on quantitative measures of cerebral oxygen extraction and blood volume under normo‐ and hypercapnic conditions using an asymmetric spin echo approach
Authors: An Hongyu , Lin Weili 
Published: September 2003

AbstractAn asymmetric spin echo (ASE) single shot echo planar imaging (EPI) sequence is proposed for obtaining quantitative estimates of R2′, cerebral venous blood volume fraction (vCBV), and oxygen extraction fraction (OEF) noninvasively in normal volunteers. The impact of the presence of intravascular signal on the estimates of vCBV and OEF were examined in five subjects with different levels of flow attenuation. A significant reduction in the estimates of vCBV and a small increase in the measurements of OEF were observed in the presence of flow suppression gradients. In addition, mild hypercapnia was induced in normal subjects (n = 4). R2′, vCBV, and OEF were measured under both normocapnia and experimentally induced hypercapnia. In agreement with the well‐documented cerebral vascular responses to hypercapnia, estimates of R2′ and OEF decrease, while measures of vCBV increase during hypercapnia. Magn Reson Med 50:708–716, 2003. © 2003 Wiley‐Liss, Inc.
Sources of plasma glucose by automated bayesian analysis of 2H NMR spectra
Authors: Merritt Matthew , Bretthorst G. Larry , Burgess Shawn C. , Sherry A. Dean , Malloy Craig R. 
Published: September 2003

AbstractSources of blood glucose can be determined after oral ingestion of 2H2O followed by isolation of plasma glucose and measurement of the relative 2H enrichments in select positions within the glucose molecule. Typically, 2H enrichments are obtained by mass spectrometry but 2H NMR offers an alternative. Here it is demonstrated that the entire analysis may be automated by Bayesian analysis of a 2H free induction decay signal of monoacetone glucose to obtain a direct readout of the relative contributions of glycogenolysis, glycerol, and phosphoenol pyruvate to plasma glucose production. Furthermore, Markov Chain Monte Carlo (MCMC) simulations of the posterior probability density provide uncertainties in all metabolic parameters from a single patient, thereby allowing comparisons in glucose metabolism from one individual to another. The combined MCMC Bayesian methodology is operationally simple and requires little intervention from the operator. Magn Reson Med 50:659–663, 2003. © 2003 Wiley‐Liss, Inc.
Statistical model for diffusion attenuated MR signal
Authors: Yablonskiy Dmitriy A. , Bretthorst G. Larry , Ackerman Joseph J.H. 
Published: September 2003

AbstractA general statistical model that can describe a rather large number of experimental results related to the structure of the diffusion‐attenuated MR signal in biological systems is introduced. The theoretical framework relies on a phenomenological model that introduces a distribution function for tissue apparent diffusion coefficients (ADC). It is shown that at least two parameters—the position of distribution maxima (ADC) and the distribution width (σ)—are needed to describe the MR signal in most regions of a human brain. A substantial distribution width, on the order of 36% of the ADC, was found for practically all brain regions examined. This method of modeling the MR diffusion measurement allows determination of an intrinsic tissue‐specific ADC for a given diffusion time independent of the strength of diffusion sensitizing gradients. The model accounts for the previously found biexponential behavior of the diffusion‐attenuated MR signal in CNS. Magn Reson Med 50:664–669, 2003. © 2003 Wiley‐Liss, Inc.
Magnetic resonance measurement of tetramethylammonium diffusion in rat brain: Comparison of magnetic resonance and ionophoresis in vivo diffusion measurements
Authors: Kroenke Christopher D. , Ackerman Joseph J.H. , Neil Jeffrey J. 
Published: September 2003

AbstractMagnetic resonance (MR) and ionophoresis are two experimental methods that provide measurements of molecular diffusion in living tissue. Typical experimental settings yield MR studies that are sensitive to mean molecular displacements of ∼5 μm, and ionophoresis experiments to displacements of ≥100 μm. An assessment of the correspondence between the methods is hampered by the fact that no common probe molecule has been used. One of the most frequently utilized probe molecules in ionophoresis measurements is the tetramethylammonium (TMA) ion. In the current work the diffusion properties of TMA were studied in rat brain in vivo with localized1H MR spectroscopy (MRS). Standard treatment of the MR data yielded a 3.6‐fold lower apparent diffusion coefficient (ADC) compared to ionophoresis. To explore the source of this discrepancy, a separate data processing scheme was applied to the MR data to monitor individual elapsed displacement‐distance subpopulations of TMA molecules. This analysis revealed a dependence of the ADC estimation on a given subpopulation's elapsed displacement distance. The MR‐derived ADC approached the ionophoresis‐derived value as the elapsed displacement distance increased to 15 μm. These observations demonstrate that MR and ionophoresis studies provide complementary information, and that ADC estimates obtained from the two techniques are sensitive to different biophysical determinants. Magn Reson Med 50:717–726, 2003. © 2003 Wiley‐Liss, Inc.
Scalar couplings as pH probes in compartmentalized biological systems: 31P NMR of phosphite
Authors: Eykyn Thomas R. , Kuchel Philip W. 
Published: September 2003

AbstractThe use of scalar couplings in nuclear magnetic resonance (NMR) spectra was investigated as a possible tool for the measurement of pH in different compartments of biological systems. The proposed method is attractive because no internal reference is required, unlike more widely used chemical shift titrations. The phosphite anion is shown to be ideal for the measurement of pH in the physiological range. In isotonic solution, the divalent anion PHO has a one‐bond 1JPH of 568.1 Hz, increasing to 620.7 Hz for the monovalent anion PH(OH)O, with a measured pKa of 6.19. The technique was applied to the measurement of pH in a suspension of human erythrocytes. The 31P spectra of these species give well‐resolved doublets for the intra‐ and extracellular spaces, and can be used to measure the pH difference across the cell membrane with errors on the order of about 0.01 pH units in the range of pH 5–7. Variations in erythrocyte pH due to metabolic changes are clearly observed. Magn Reson Med 50:693–696, 2003. © 2003 Wiley‐Liss, Inc.
Characterization of continuously distributed cortical water diffusion rates with a stretched‐exponential model
Authors: Bennett Kevin M. , Schmainda Kathleen M. , Bennett (Tong) Raoqiong , Rowe Daniel B. , Lu Hanbing , Hyde James S. 
Published: September 2003

AbstractExperience with diffusion‐weighted imaging (DWI) shows that signal attenuation is consistent with a multicompartmental theory of water diffusion in the brain. The source of this so‐called nonexponential behavior is a topic of debate, because the cerebral cortex contains considerable microscopic heterogeneity and is therefore difficult to model. To account for this heterogeneity and understand its implications for current models of diffusion, a stretched‐exponential function was developed to describe diffusion‐related signal decay as a continuous distribution of sources decaying at different rates, with no assumptions made about the number of participating sources. DWI experiments were performed using a spin‐echo diffusion‐weighted pulse sequence with b‐values of 500–6500 s/mm2 in six rats. Signal attenuation curves were fit to a stretched‐exponential function, and 20% of the voxels were better fit to the stretched‐exponential model than to a biexponential model, even though the latter model had one more adjustable parameter. Based on the calculated intravoxel heterogeneity measure, the cerebral cortex contains considerable heterogeneity in diffusion. The use of a distributed diffusion coefficient (DDC) is suggested to measure mean intravoxel diffusion rates in the presence of such heterogeneity. Magn Reson Med 50:727–734, 2003. © 2003 Wiley‐Liss, Inc.
Generalized reconstruction of phase contrast MRI: Analysis and correction of the effect of gradient field distortions
Authors: Markl M. , Bammer R. , Alley M.T. , Elkins C.J. , Draney M.T. , Barnett A. , Moseley M.E. , Glover G.H. , Pelc N.J. 
Published: September 2003

AbstractTo characterize gradient field nonuniformity and its effect on velocity encoding in phase contrast (PC) MRI, a generalized model that describes this phenomenon and enables the accurate reconstruction of velocities is presented. In addition to considerable geometric distortions, inhomogeneous gradient fields can introduce deviations from the nominal gradient strength and orientation, and therefore spatially‐dependent first gradient moments. Resulting errors in the measured phase shifts used for velocity encoding can therefore cause significant deviations in velocity quantification. The true magnitude and direction of the underlying velocities can be recovered from the phase difference images by a generalized PC velocity reconstruction, which requires the acquisition of full three‐directional velocity information. The generalized reconstruction of velocities is applied using a matrix formalism that includes relative gradient field deviations derived from a theoretical model of local gradient field nonuniformity. In addition, an approximate solution for the correction of one‐directional velocity encoding is given. Depending on the spatial location of the velocity measurements, errors in velocity magnitude can be as high as 60%, while errors in the velocity encoding direction can be up to 45°. Results of phantom measurements demonstrate that effects of gradient field nonuniformity on PC‐MRI can be corrected with the proposed method. Magn Reson Med 50:791–801, 2003. Published 2003 Wiley‐Liss, Inc.
Comparison of dendrimer‐based macromolecular contrast agents for dynamic micro‐magnetic resonance lymphangiography
Authors: Kobayashi Hisataka , Kawamoto Satomi , Choyke Peter L. , Sato Noriko , Knopp Michael V. , Star Robert A. , Waldmann Thomas A. , Tagaya Yutaka , Brechbiel Martin W. 
Published: September 2003

AbstractFew methods are currently available to visualize the entire lymphatic system. A method known as micro‐magnetic resonance lymphangiography (MRL), which employs a dendrimer‐based MRI contrast agent (PAMAM‐G8) and a clinical‐grade 1.5T MRI instrument, was recently developed for use in mice. In the present study, three dendrimer‐based MRI contrast agents (PAMAM‐G8, DAB‐G5, and PAMAM‐G4) with different pharmacokinetic characteristics were compared to determine the best reagent to visualize the lymphatic system under physiological or pathological conditions. In addition, two established MRI contrast agents (Gadomer‐17 and Gd‐[DTPA]‐dimeglumine (Magnevist)) were used as control agents. In experiments with mice, most of the deep lymphatic system was visualized by micro‐MRL with all agents except Gd‐[DTPA]‐dimeglumine. PAMAM‐G8 was best for visualizing lymphatic vessels, whereas DAB‐G5 was better for visualizing lymph nodes. PAMAM‐G4 was intermediate in character between PAMAM‐G8 and DAB‐G5, except in exhibiting a low background signal (especially in the liver). The lymphatic system was not clearly visualized with Gd‐[DTPA]‐dimeglumine; however, the lymph nodes were visualized with Gadomer‐17, although not as well as with dendrimer‐based agents. In conclusion, DAB‐G5 and PAMAM‐G4 can be used to identify lymph nodes and lymphatic vessels, respectively. Their rapid excretion makes these compounds potentially attractive for human use. Magn Reson Med 50:758–766, 2003. Published 2003 Wiley‐Liss, Inc.
RINGLET motion correction for 3D MRI acquired with the elliptical centric view order
Authors: Bernstein Matt A. , Shu Yunhong , Elliott Andrew M. 
Published: September 2003

AbstractA new rigid‐body motion correction algorithm is described that is compatible with 3D image sets acquired with the elliptical centric (EC) view order. With this view order, an annular ring of k‐space data is acquired in the ky‐kz plane during any short time interval. Images for tracking motion can be reconstructed in the yz‐plane from any ring of the acquisition data. In these tracking images, a point source (such as an external marker) shows a characteristic bull's‐eye pattern that permits motion monitoring and correction. The true position of the point object is located at the center of the bull's‐eye pattern. Cross correlation can be performed to automatically track the positions of markers reconstructed from adjacent rings of k‐space. To increase the marker signal, the markers are encased in inductively coupled RF coils. Rigid‐body motion in the yz‐plane is calculated directly with the Euclidean group for rotation and translation, and corrected by rotating and applying phase shifts to any corrupted rings of data. In the current work we present a theoretical analysis of this method, as well as results of volunteer and controlled phantom experiments that demonstrate its initial feasibility. Although the EC view order has mainly been used for MR angiography (MRA), it can also be used for most 3D acquisitions. Magn Reson Med 50:802–812, 2003. © 2003 Wiley‐Liss, Inc.
Imaging the fate of implanted bone marrow stromal cells labeled with superparamagnetic nanoparticles
Authors: Jendelová Pavla , Herynek Vít , DeCroos Jane , Glogarová Kateřina , Andersson Benita , Hájek Milan , Syková Eva 
Published: September 2003

AbstractBone marrow stromal cells (MSCs) are pluripotent progenitor cells that have the capacity to migrate toward lesions and induce or facilitate site‐dependent differentiation in response to environmental signals. In animals with a cortical photochemical lesion, the fate of rat MSCs colabeled with magnetic iron‐oxide nanoparticles (Endorem®) and bromodeoxyuridine (BrdU) was studied. MSCs were either grafted intracerebrally into the contralateral hemisphere of adult rat brain or injected intravenously. In vivo MRI was used to track their fate; Prussian blue staining and transmission electron microscopy (TEM) confirmed the presence of iron‐oxide nanoparticles inside the cells. During the first week posttransplantation, the transplanted cells migrated to the lesion site and populated the border zone of the damaged cortical tissue. The implanted cells were visible on MR images as a hypointense area at the injection site and in the lesion. The hypointense signal persisted for more than 50 days. The presence of BrdU‐positive and iron‐containing cells was confirmed by subsequent histological staining. Three to 4 weeks after injection, <3% of MSCs around the lesion expressed the neuronal marker NeuN. Our study demonstrates that a commercially available contrast agent can be used as a marker for the long‐term noninvasive MR tracking of implanted cells. Magn Reson Med 50:767–776, 2003. © 2003 Wiley‐Liss, Inc.
Effects of barrier‐induced nuclear spin magnetization inhomogeneities on diffusion‐attenuated MR signal
Authors: Sukstanskii A.L. , Ackerman J.J.H. , Yablonskiy D.A. 
Published: September 2003

AbstractThe spatial distribution of the transverse nuclear spin magnetization, appearing in a single compartment with impermeable boundaries in a Stejskal‐Tanner gradient pulse MR experiment, is analyzed in detail. At short diffusion times the presence of diffusion‐restrictive barriers (membranes) reduces effective diffusivity near the membranes and leads to an inhomogeneous spin magnetization distribution (the edge‐enhancement effect). In this case, the signal reveals a quasi‐two‐compartment behavior and can be empirically modeled remarkably well by a biexponential function. The current results provide a framework for interpreting experimental MR data on various phenoma, including water diffusion in giant axons, metabolite diffusion in the brain, and hyperpolarized gas diffusion in lung airways. Magn Reson Med 50:735–742, 2003. © 2003 Wiley‐Liss, Inc.