bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis and secretion of molecules exhibiting the HL1 epitope during development of the hyaline layer of the asteroid pisaster ochraceus
Authors: Pang T. , Crawford B.J. , Maghsoodi B.
Published: November 2002

A complex ECM layer called the hyaline layer (HL) surrounds embryos and larvae of the starfish Pisaster ochraceus. When preserved by freeze substitution, the HL of a bipinnaria larva consists of six sublayers. From the plasmalemma outwards these are the intervillous layer (iv), the H3, H2, H1 sublayers that make up the supporting layer, a boundary layer (b) and the coarse outer meshwork (cm). HL development begins at fertilization when exocytosis of the cortical granules releases ECM into the perivitelline space and elevates the fertilization membrane. Over the course of early development the layers are added in a sequential manner and by hatching the embryo is surrounded by a thin HL containing most if not all of the layers. The layers thicken over the next few days. By the bipinnaria stage the larvae are surrounded by a thick six‐layered HL. HL1 is a monoclonal antibody that reacts against an epitope found in all regions of the HL of the bipinnaria larva except the H2 sublayer. Western blots show that it is present on several molecules during HL development. The number and pattern of the HL1‐labeled molecules change during development, suggesting that either new molecules are being produced or that some molecules are precursors of others. Light (immunofluorescence) and TEM (immunogold) studies using HL1 in the early stages of development show that HL1‐positive material is not present in the corticle granules and that it only begins to be manufactured and secreted in quantity in the blastula stage at 18–20 h. Following this it continues to be secreted at least as far as the bipinnaria stage. Molecules containing the HL1 antigen therefore do not appear to play a major role in early development of the HL but are necessary for later events. The results suggest that, like the sea urchin HL, the starfish HL undergoes a sequential organization of the different HL layers from ECM components, which are released into the perivitelline space. J. Morphol. 255:58–68, 2003. © 2002 Wiley‐Liss, Inc.
Caste morphology and development intermitogetonnr.planus(insecta, isoptera, rhinotermitidae)
Authors: Parmentier Dominique , Roisin Yves
Published: November 2002

The termite family Rhinotermitidae displays a wide diversity in its patterns of social organization in castes. The genusTermitogetonprobably branched off early in the evolution of this family. We studied the developmental pathways of a putative undescribed species from New Guinea,Termitogetonnrplanus. The development begins with two white inactive instars (larvae), the second of which possesses small wing buds. These are followed by a relatively homogenous group of active immature stages (pseudergates) among which a biometric study revealed the presence of four instars. The first of these instars possesses wing buds that regress at subsequent molts. The external morphology of older instars resembles that of higher termite workers. Older pseudergates can differentiate into presoldiers and then into soldiers, but they are also able to molt into a unique stage with long wing pads (nymph), preceding the imago. Colony maturity can be reached with about 103individuals. The sex ratio is near 1:1 in all castes except soldiers, among which females are more numerous than males. The caste pattern ofT.nr.planusis reminiscent of those of the Kalotermitidae and Termopsidae, and ofProrhinotermesamong the Rhinotermitidae. None of these taxa possess a true worker caste, permanently diverted from imaginal development: social tasks are done by unspecialized immatures that retain a full array of developmental options, including that of proceeding to the imago. The most remarkable trait ofT.nr.planusis the presence in all second‐instar individuals of wing buds that later regress to reappear in the single nymphal stage. We suggest that the traditional definitions of the terms larvae, nymphs, and pseudergates should be revised because they cannot be satisfactorily applied to the castes ofTermitogeton. J. Morphol. 255:69–79, 2003. © 2002 Wiley‐Liss, Inc.
Biflagellate spermatozoon of the poison‐dart frogsepipedobates femoralisandcolostethussp. (anura, dendrobatidae)
Authors: Aguiar– Odair , Garda Adrian A. , Lima Albertina P. , Colli Guarino R. , Báo Sônia N. , Recco‐Pimentel Shirlei M.
Published: November 2002

This study describes the spermatozoa of the dendrobatidsEpipedobates femoralisandColostethussp. using light and transmission electron microscopy. Both species possess a biflagellate spermatozoon, an unusual characteristic only previously reported in two anuran species belonging to the families Leptodactylidae and Racophoridae. The acrosomal complex of both species consists of a conical acrosomal vesicle and a subacrosomal cone, both of which cover the anterior portion of the nucleus, but to differing extents. In the midpiece, the centrioles are disposed parallel to each other and to the cell axis and give rise to two axonemes. Two paraxonemal rods were also seen entering the nuclear fossa. Both flagella are surrounded by a single mitochondrial collar. Each flagellum is formed by an axial fiber connected to the axoneme by an axial sheath; juxta‐axonemal fibers are absent. Our data seem to support thatEpipedobates femoralisshould be placed in a separate clade possibly related toColosthetusand that these two genera may not be monophyletic. J. Morphol. 255:114–121, 2003. © 2002 Wiley‐Liss, Inc.
Meiosis in the golden hamster: A confocal microscopy and flow cytometric analysis
Authors: Vigodner M. , Lewin L.M. , Shochat L. , Mittelman L. , Golan R.
Published: November 2002

In this study, confocal microscopy and flow‐cytometry were utilized to follow meiosis in hamster spermatogenesis. Confocal microscopy was used as an analytical tool to observe spermatocytes inside the tubules following meiotic progression consecutively at defined spermatogenic stages. To study spermatocyte differentiation, the structure of the synaptonemal complex was studied in detail at various stages of hamster spermatogenesis using the antibody against SC3 (the protein of axial/lateral element). The synaptonemal complex was observed from the leptotene stage until the first meiotic division with maximal staining in mid‐pachytene spermatocytes, suggesting a role for SC3 at this postrecombinational stage. In addition, 3‐dimensional (3D) images of synaptonemal complex were observed, providing information about spatial distribution of the chromosomes within the nuclei of spermatocytes at different stages of meiosis. Changes in spermatocyte sizes and DNA condensation allowed assessment of meiosis by flow cytometry. Changes in chromatin condensation at different stages of hamster meiosis were followed, revealing decondensation from early to late pachytene stages. The analysis also allowed a comparing of chromatin status of mitotic and meiotic chromosomes, confirming the less compact structure of the latter, possibly connected to increased transcriptional activity during meiosis. Mol. Reprod. Dev. 64: 86–95, 2003. © 2003 Wiley‐Liss, Inc.
Real‐time autoshimming for echo planar timecourse imaging
Authors: Ward Heidi A. , Riederer Stephen J. , Jack Clifford R.
Published: November 2002

Head motion within an applied magnetic field alters the effective shim within the brain, causing geometric distortions in echo planar imaging (EPI). Even if subtle, change in shim can lead to artifactual signal changes in timecourse EPI acquisitions, which are typically performed for functional MRI (fMRI) or diffusion tensor imaging. Magnetic field maps acquired before and after head motions of clinically realistic magnitude indicate that motion‐induced changes in magnetic field may cause translations exceeding 3 mm in the phase‐encoding direction of the EPI images. The field maps also demonstrate a trend toward linear variations in shim changes as a function of position within the head, suggesting that a real‐time, first‐order correction may compensate for motion‐induced changes in magnetic field. This article presents a navigator pulse sequence and processing method, termed a “shim NAV,” for real‐time detection of linear shim changes, and a shim‐compensated EPI pulse sequence for dynamic correction of linear shim changes. In vivo and phantom experiments demonstrate the detection accuracy of shim NAVs in the presence of applied gradient shims. Phantom experiments demonstrate reduction of geometric distortion and image artifact using shim‐compensated EPI in the presence of applied gradient shims. In vivo experiments with intentional interimage subject motion demonstrate improved alignment of timecourse EPI images when using the shim NAV‐detected values to update the shim‐compensated EPI acquisition in real time. Magn Reson Med 48:771–780, 2002. © 2002 Wiley‐Liss, Inc.
Inductively coupled stent antennas in MRI
Authors: Quick Harald H. , Kuehl Hilmar , Kaiser Gernot , Bosk Silke , Debatin Jörg F. , Ladd Mark E.
Published: November 2002

The development of intimal hyperplasia following stent deployment can lead to narrowing or even occlusion of the stent lumen. The underlying mechanisms leading to neointimal proliferation within stents remain largely unknown. Long‐term evaluation of stent patency requires a noninvasive means for assessing the stent lumen. MR angiography (MRA) has shown potential to provide noninvasive assessment of the vascular system. However, a detailed assessment of the stent lumen with MRI is often hampered by material‐dependent susceptibility artifacts, as well as by radiofrequency (RF) eddy currents generated inside the electrically conducting stent mesh. In this study, stent prototypes were designed to act as active resonant structures at the Larmor frequency of the MR system. Employing the principle of inductive coupling, the B1 fields of the stents were coupled to that of an outside surface coil. The stents thus acted as local RF signal amplifiers. Various stent designs were investigated regarding their coupling to an external coil, signal homogeneity, and suitability for mechanical expansion for implantation purposes. The dependency of flip angle amplification on the quality factor Q of the stents was systematically investigated. Phantom experiments revealed signal amplification in all stent prototypes. Signal enhancement inside and close to the surface of the stents enabled their localization with high contrast in MR images. In vivo imaging experiments in the iliac, renal, and splenic arteries of two pigs confirmed the in vitro findings. Wireless active visualization of stents allows for detailed analysis of the stent lumen with high contrast and spatial resolution. The proposed method could thus provide a powerful diagnostic means for the noninvasive long‐term follow‐up of stent patency, thereby enhancing our understanding of the mechanisms of restenosis. Magn Reson Med 48:781–790, 2002. © 2002 Wiley‐Liss, Inc.
Optimization of signal behavior in the transition to driven equilibrium in steady‐state free precession sequences
Authors: Hennig Juergen , Speck Oliver , Scheffler Klaus
Published: November 2002

A new technique to avoid the initial signal fluctuations in steady‐state free precession (SSFP)‐sequences, such as trueFISP, FIESTA, and refocused FFE, is presented. The “transition into driven equilibrium” (TIDE) sequence uses modified flip angles over the initialization phase of a SSFP experiment, which not only avoids image artifacts but also improves the signal‐to‐noise ratio (SNR) and contrast behavior compared to conventional approaches. TIDE is demonstrated to be robust against variations of T1 and T2, and leads to a monotonous signal evolution for off‐resonance spins. The basic principles can also be applied repetitively to optimize continuous 3D acquisitions. Magn Reson Med 48:801–809, 2002. © 2002 Wiley‐Liss, Inc.
Variable‐density adaptive imaging for high‐resolution coronary artery MRI
Authors: Sussman Marshall S. , Stainsby Jeffrey A. , Robert Normand , Merchant Naeem , Wright Graham A.
Published: November 2002

Variable‐density (VD) spiral k‐space acquisitions are used to acquire high‐resolution (0.78 mm), motion‐compensated images of the coronary arteries. Unlike conventional methods, information for motion compensation is obtained directly from the coronary anatomy itself. Specifically, periods of minimal coronary distortion are identified by applying the correlation coefficient template matching algorithm to real‐time images generated from the inner, high‐density portions of the VD spirals. Combining the data associated with these images together, high‐resolution, motion‐compensated coronary images are generated. Because coronary motion is visualized directly, the need for cardiac‐triggering, breath‐holding, and navigator echoes is eliminated. The motion compensation capability of the technique is determined by the inner‐spiral spatial and temporal resolution. Results indicate that the best performance is achieved using inner‐spiral images with high spatial resolution (1.6–2.9 mm), even though temporal resolution (four to six independent frames per second) suffers as a result. Image quality within the template region in healthy volunteers was found to be comparable to that achieved with cardiac‐triggered breath‐hold scans, although extended acquisition times of around 5 min were needed to overcome reduced SNR efficiency. Magn Reson Med 48:753–764, 2002. © 2002 Wiley‐Liss, Inc.
In vivo 3D MRI staining of mouse brain after subcutaneous application of MnCl2
Authors: Watanabe Takashi , Natt Oliver , Boretius Susann , Frahm Jens , Michaelis Thomas
Published: November 2002

Follow‐up T1‐weighted 3D gradient‐echo MRI (2.35 T) of murine brain in vivo (N = 5) at 120 μm isotropic resolution revealed spatially distinct signal increases 6–48 hr after subcutaneous application of MnCl2 (20 mg/kg). The effects result from a shortening of the water proton T1 relaxation time due to the presence of unchelated paramagnetic Mn2+ ions, which access the brain by systemic circulation and crossing of the blood–brain barrier (BBB). A pronounced Mn2+‐induced signal enhancement was first seen in structures without a BBB, such as the choroid plexus, pituitary gland, and pineal gland. Within 24 hr after administration, Mn2+ contrast highlighted the olfactory bulb, inferior colliculi, cerebellum, and the CA3 subfield of the hippocampus. The affinity of Mn2+ to various brain systems suggests the neuronal uptake of Mn2+ ions from the extracellular space and subsequent axonal transport. Thus, at least part of the Mn2+ contrast reflects a functional brain response of behaving animals, for example, in the olfactory system. In vivo MRI staining of the brain by systemic administration of MnCl2 may contribute to phenotyping mutant mice with morphologic and functional alterations of the central nervous system. Magn Reson Med 48:852–859, 2002. © 2002 Wiley‐Liss, Inc.
Single‐breathhold 3D‐trueFISP cine cardiac imaging
Authors: Jung Bernd A. , Hennig Jürgen , Scheffler Klaus
Published: November 2002

Cardiac MRI function measurements are typically based on multiple breathhold 2D sequences to acquire images of the entire heart. In the present study, the feasibility of a cine 3D TrueFISP technique in which several complete volumetric measurements may be obtained during a single breathhold is demonstrated. In contrast to 3D FLASH, the TrueFISP sequence offers an excellent contrast between the myocardium and the intraventricular cavity without the use of contrast agent. An ECG‐gated 3D cine TrueFISP sequence was implemented with a repetition time of 2.4–2.8 ms, which allows imaging of the complete heart within a single breathhold throughout 20–46 heartbeats with a 3D frame rate of 8–13 volumes per cardiac cycle and a spatial resolution of about 1.5 × 3.5 × 3.5 mm3. Breathhold volumetric cine imaging with the 3D TrueFISP technique holds promise for rapid and accurate evaluation of the cardiac regional wall motion and the calculation of cardiac volume and ejection fraction. Magn Reson Med 48:921–925, 2002. © 2002 Wiley‐Liss, Inc.
Homogeneous preparation encoding (HoPE) in multislice imaging
Authors: Fautz Hans‐Peter , Scheffler Klaus , Hennig Jürgen
Published: November 2002

Fast magnetization preparation techniques acquire a series of echoes after a single magnetization preparation. If these echoes are acquired from different slices using a multislice technique the change in the preparation state of the echoes due to relaxation effects leads to different contrast modification for each slice. Encoding different preparation states along the phase‐encoding direction of each slice instead of acquiring each slice in a different preparation state is introduced as a general concept to obtain images of identical contrast and point‐spread function. This can be realized either by cycling the slice excitation order several times over the total number of repetitions or by moving the point of time at which the preparation is applied within each repetition. One possible application of this method is chemical shift selective fat saturation imaging. A homogeneous fat suppression across a multislice volume could be achieved using a FLASH sequence at a repetition time of TR = 145 ms, including a single fat saturation preparation. Conventional fat saturated spin‐echo imaging at any TR can be accelerated significantly by reducing the number of applied preparations per repetition. A further application of the homogeneous preparation encoding (HoPE) method is described that encodes the spatial self‐saturation of the multislice excitation order homogeneously in all slices. Only a reduced number of slices of the total volume are excited in each repetition and the slice excitation order is continuously moved along the imaging volume. This method is applied for time of flight (TOF) imaging. Using a TONE‐like series of flip angles for the slice excitations of each repetition homogeneous TOF images can be obtained on the basis of a multislice acquisition. Magn Reson Med 48:745–752, 2002. © 2002 Wiley‐Liss, Inc.
GABAergic mechanisms of heroin‐induced brain activation assessed with functional MRI
Authors: Xi Zheng‐Xiong , Wu Gaohong , Stein Elliot A. , Li Shi‐Jiang
Published: November 2002

Heroin has been hypothesized to activate opiate receptors and inhibit γ‐aminobutyric acid (GABA) release from inhibitory GABAergic interneurons which, in turn, activates dopamine projection cells. Since the distal sites and consequences of this disinhibition are not well understood on a systems level, heroin‐induced brain activity was measured using functional MRI (fMRI) in rats. A significant blood oxygen level‐dependent (BOLD) signal increase was seen in cortical regions, including prefrontal cortex, cingulate, and olfactory cortex following acute heroin administration. In contrast, a significant signal decrease was seen in several subcortical areas, including the caudate and putamen, nucleus accumbens, thalamus, and hypothalamus. Pretreatment of γ‐vinyl GABA (GVG), an irreversible GABA transaminase inhibitor, significantly attenuated the heroin‐induced BOLD signal changes. Pretreatment of naloxone, an opiate μ receptor antagonist, eliminated the heroin‐induced BOLD signal changes and posttreatment of naloxone reversed the heroin‐induced BOLD signal changes. It is suggested that the heroin‐induced negative and positive BOLD changes are due to direct inhibitory and indirect disinhibitory mechanisms of GABAergic activities. Administration of GVG altered these mechanisms and further suggested that involvement of the opiate's pharmacological actions can, at least in part, be mediated by inhibiting brain GABA release. Magn Reson Med 48:838–843, 2002. © 2002 Wiley‐Liss, Inc.
Real‐time quantification of T changes using multiecho planar imaging and numerical methods
Authors: Hagberg G.E. , Indovina I. , Sanes J.N. , Posse S.
Published: November 2002

Conventional approaches to quantify whole brain T maps use nonlinear regression with intensive computational requirements that therefore likely limit quantitative T mapping for real‐time applications. To overcome these limitations an alternative method, NumART (NUMerical Algorithm for Real‐time T mapping) that directly calculates T by a linear combination of images obtained at three or more different echo times was developed. NumART, linear least‐squares, and nonlinear regression techniques were applied to multiecho planar images of the human brain and to simulated data. Although NumART may overestimate T, it yields comparable values to regression techniques in cortical and subcortical areas, with only moderate deviations for echo spacings between 18 and 40 ms. NumART, like linear regression, requires 2% of the computational time needed for nonlinear regression and compares favorably with linear regression due to its higher precision. The use of NumART for continuous on‐line T mapping in real time fMRI studies is shown. Magn Reson Med 48:877–882, 2002. © 2002 Wiley‐Liss, Inc.
Fast phase‐contrast velocity measurement in the steady state
Authors: Overall William R. , Nishimura Dwight G. , Hu Bob S.
Published: November 2002

A new method of encoding flow velocity as image phase in a refocused steady‐state free precession (SSFP) sequence, called steady‐state phase contrast (SSPC), can be used to generate velocity images rapidly while retaining high signal. Magnitude images with refocused‐SSFP contrast are simultaneously acquired. This technique is compared with the standard method of RF‐spoiled phase contrast (PC), and is found to have more than double the phase‐signal to phase‐noise ratio (PNR) when compared with standard PC at reasonable repetition intervals (TRs). As TR decreases, this advantage increases exponentially, facilitating rapid scans with high PNR efficiency. Rapid switching between the two necessary steady states can be accomplished by the insertion of a single TR interval with no flow‐encoding gradient. The technique is implemented in a 2DFT sequence and validated in a phantom study. Preliminary results indicate that further TR reduction may be necessary for high‐quality cardiac images; however, images in more stationary structures, such as the descending aorta and carotid bifurcation, exhibit good signal‐to‐noise ratio (SNR) and PNR. Comparisons with standard‐PC images verify the PNR advantage predicted by theory. Magn Reson Med 48:890–898, 2002. © 2002 Wiley‐Liss, Inc.
Sensitivity‐encoded single‐shot spiral imaging for reduced susceptibility artifacts in BOLD fMRI
Authors: Weiger Markus , Pruessmann Klaas P. , Österbauer Robert , Börnert Peter , Boesiger Peter , Jezzard Peter
Published: November 2002

Sensitivity encoding (SENSE) with iterative image reconstruction was used to shorten the readout duration in single‐shot spiral imaging by a factor of 2. This enabled susceptibility‐related blurring and signal loss artifacts to be reduced and spatial resolution to be improved. As a beneficial side effect, the gradient duty cycle was also reduced. The spiral SENSE technique was applied to functional MRI (fMRI) with blood oxygen level‐dependent (BOLD) contrast and compared to a conventional spiral acquisition. Stimulation experiments were performed in seven volunteers using motor, visual, and taste paradigms. The signal‐to‐noise ratio (SNR) and signal‐to‐fluctuation‐noise ratio (SFNR) of the SENSE acquisitions were reduced by 20% and 13%, respectively, with respect to the longer readout. The overall activation detected was comparable to that of the conventional spiral acquisition, even though difficulties in reproducing the stimulation response hampered the evaluation. In some cases, the application of SENSE enabled recovery of activation in regions affected by signal loss due to field inhomogeneity. Magn Reson Med 48:860–866, 2002. © 2002 Wiley‐Liss, Inc.
Functional hepatocyte cation compartmentation demonstrated with 133Cs NMR
Authors: Wellard R.M. , Adam W.R.
Published: November 2002

This study utilized the large intrinsic chemical shift range of 133Cs, a potassium congener, in an NMR study of intracellular cation distribution. It demonstrates two distinct intracellular environments in isolated perfused hepatocytes from cesium‐fed rats, evident as compartments with different 133Cs chemical shifts and containing different proportions of total detected cesium. The chemical shifts of the two intracellular compartments were 2.44 ± 0.07 and 1.21 ± 0.18 ppm, relative to the cesium signal from the perfusate. The observation of two distinct intracellular cesium signals suggests slow exchange on an NMR chemical shift time‐scale (k exchange > 0.02 s). The area of the high‐frequency component represented 62 ± 10% (N = 12) of the total intracellular cesium signal. Manipulation of the intracellular environment using anoxia with aglycemia or digitonin produced changes in the distribution between the two intracellular compartments, showing their dynamic nature. Changes measured in association with metabolic manipulation suggest cytoplasm and mitochondria as the origin of the high and low‐frequency intracellular peaks, respectively. Magn Reson Med 48:810–818, 2002. © 2002 Wiley‐Liss, Inc.
Method to correct for the effects of limited spatial resolution in phase‐contrast flow MRI measurements
Authors: Lagerstrand K.M , Lehmann H. , Starck G. , Vikhoff‐Baaz B. , Ekholm S. , Forssell‐Aronsson E.
Published: November 2002

Phase‐contrast (PC) magnetic resonance imaging (MRI) flow measurements suffer from the effect of the point spread function (PSF) due to the limited sampling of k‐space. The PSF, which in this case is a sinc function, deforms the flow profile and forms a ringing pattern around the vessel. In this work, an empirical method is presented that corrects for errors due to the deformation of the flow profile. The ringing pattern is used to obtain a well‐defined vessel segmentation, which after correction provides more accurate vessel radius and volume flow rate (VFR). The correction method was developed from phantom measurements at constant flow and applied on phantom measurements at moderately pulsatile flow. After correction, the error of the estimated tube radius and the VFR was less than 10% and 5%, respectively. Corresponding errors without correction overestimated the radius by 60% and the VFR by 35%. Preliminary results indicate that the method is also valid in vivo. The variation in the estimated radius and VFR for different spatial resolution decreased when the method was applied. The presented method gives a more accurate estimation of the radius and VFR in vessels of the size of a few pixels without prior knowledge about the true vessel radius. Magn Reson Med 48:883–889, 2002. © 2002 Wiley‐Liss, Inc.
Myocardial viability imaging using Gd‐DTPA: Physiological modeling of infarcted myocardium, and impact on injection strategy and imaging time
Authors: Moran G.R. , Thornhill R.E. , Sykes J. , Prato F.S.
Published: November 2002

Results of simulations are shown which illustrate how the concentration‐time curves of an extravascular extracellular (EVEC) contrast agent, such as Gd‐DTPA, vary in myocardial tissue. The simulations show that the variable permeability of dead myocytes within a recent myocardial infarction will significantly alter delayed enhancement patterns following a bolus injection, invariably reducing the sensitivity of this technique for the detection of permanently damaged tissue. It is further predicted that if the bolus injection is followed by a suitably selected constant infusion, the infarct size and infarct volume of distribution may be more accurately determined, even though the degree of enhancement of an infarcted region (with normal flow) above normal tissue is slightly higher for the bolus technique within the first 30 min following the injection. The degree of enhancement of an infarcted region (with normal flow) above normal tissue was comparable between the two techniques at the point in the constant infusion at which the volume of contrast injected was the same as in the bolus case, i.e., at approximately 30 min after the bolus injection. The constant infusion approach became superior thereafter as overall tissue concentrations became greater in both normal and infarcted tissue, and these concentrations remained more stable with the constant infusion approach. Preliminary experimental results in a canine model of infarction/reperfusion illustrated a delayed wash‐in of contrast agent in infarcted tissue, which may be explained by a physiological model in which dead myocytes in infarcted myocardium have non‐infinite permeability. Magn Reson Med 48:791–800, 2002. © 2002 Wiley‐Liss, Inc.
MR angiography with a new rapid‐clearance blood pool agent: Initial experience in rabbits
Authors: Ruehm Stefan G. , Christina Heidi , Violas Xavier , Corot Claire , Debatin Jörg F.
Published: November 2002

The purpose of this study was to assess a new Gd‐based macromolecular intravascular contrast agent (P792, Vistarem®; Laboratoire Guerbet, Aulnay sous Bois, France) for MR angiography (MRA). P792 is a macrocyclic gadolinium compound based on a gadoterate meglumine structure substituted by hydrophilic arms. In vitro imaging of phantoms containing varying concentrations of P792 and gadoterate meglumine (Gd‐DOTA) was performed. In rabbits (N = 5), arterial concentrations for P792 and Gd‐DOTA were determined, and in vivo 3D MRA was performed. For gadolinium concentrations ranging from 200 to 3000 μmol/l, in vitro imaging showed higher SNR values for P792 compared to Gd‐DOTA. Determination of arterial Gd concentration showed comparable bolus phase curves for P792 and Gd‐DOTA. With P792, higher concentrations were obtained due to a restricted diffusion into the interstitial space. P792 allowed acquisition of high‐quality MR angiograms. Image quality was rated as superior for P792 in the post‐bolus phase images. In conclusion, P792 appears to be well suited for high‐quality first‐pass and equilibrium‐phase MRA. The intravascular properties lead to an excellent signal in the vasculature, with limited background enhancement. Since the agent is rapidly renally excreted, it should be well suited for perfusion and permeability imaging. Magn Reson Med 48:844–851, 2002. © 2002 Wiley‐Liss, Inc.
T1‐insensitive flow suppression using quadruple inversion‐recovery
Authors: Yarnykh Vasily L. , Yuan Chun
Published: November 2002

A new flow suppression method has been proposed for the acquisition of blood‐suppressed (black‐blood) images in combination with administration of a positive contrast agent. The technique employs the quadruple inversion‐recovery (QIR) preparative pulse sequence, which consists of two double‐inversion modules followed by two delays. Within each double inversion, a nonselective RF pulse is immediately followed by a slice‐selective one. The time intervals of the sequence can be calculated using an algorithm based on minimization of the variation of a signal equation over an entire range of T1 occurring in blood before and after contrast administration. QIR is highly insensitive to variations of T1, providing efficient suppression of a flow signal with T1 in a range of 200–1200 ms. The technique utilizes identical scan parameters for pre‐ and postcontrast acquisition, and thus allows reliable quantitative interpretation of contrast enhancement (CE). The clinical application of QIR was demonstrated in high‐resolution, contrast‐enhanced, black‐blood imaging of atherosclerotic plzzaque. Magn Reson Med 48:899–905, 2002. © 2002 Wiley‐Liss, Inc.
Observation and identification of metabolites emerging during postmortem decomposition of brain tissue by means of in situ1H‐magnetic resonance spectroscopy
Authors: Ith Michael , Bigler Peter , Scheurer Eva , Kreis Roland , Hofmann Lucie , Dirnhofer Richard , Boesch Chris
Published: November 2002

Postmortem decomposition of brain tissue was investigated by1H‐magnetic resonance spectroscopy (MRS) in a sheep head model and selected human cases. Aiming at the eventual estimation of postmortem intervals in forensic medicine, this study focuses on the characterization and identification of newly observed metabolites. In situ single‐voxel1H‐MRS at 1.5 T was complemented by multidimensional homo‐ and heteronuclear high‐resolution NMR spectroscopy of an extract of sheep brain tissue. The inclusion of spectra of model solutions in the program LC Model confirmed the assignments in situ. The first postmortem phase was characterized mainly by changes in the concentrations of metabolites usually observed in vivo and by the appearance of previously reported decay products. About 3 days postmortem, new metabolites, including free trimethylammonium, propionate, butyrate, and iso‐butyrate, started to appear in situ. Since the observed metabolites and the time course is comparable in sheep and human brain tissue, the model system seems to be appropriate. Magn Reson Med 48:915–920, 2002. © 2002 Wiley‐Liss, Inc.
Real‐time changes in 1H and 31P NMR spectra of malignant human mammary epithelial cells during treatment with the anti‐inflammatory agent indomethacin
Authors: Glunde Kristine , Ackerstaff Ellen , Natarajan Kshama , Artemov Dmitri , Bhujwalla Zaver M.
Published: November 2002

Choline metabolites in malignant human mammary epithelial cells (HMECs) are significantly altered compared to normal HMECs. 1H NMR studies of cell extracts have shown that treatment of malignant HMECs with a nonsteroidal anti‐inflammatory agent, indomethacin, results in a distribution of choline compounds more typical of nonmalignant HMECs. To follow the time course of these changes, in this study real‐time monitoring of choline compounds of malignant MDA‐MB‐231 cells was performed during treatment with indomethacin. The contribution of changes in intra‐ and extracellular pH to changes in choline compounds was also examined. Changes in water‐soluble choline phospholipid metabolites, such as phosphocholine (PC), glycerophosphocholine (GPC), and total choline, as well as intracellular pH, were monitored by 31P and diffusion‐weighted 1H NMR spectroscopy of living cells using an NMR‐compatible perfusion system. An accumulation of GPC and a decrease of PC, resulting in an increased [GPC]/[PC] ratio, were detected within 2 hr of treatment with 200 μM indomethacin. Since a decreased [GPC]/[PC] ratio is associated with increased malignancy, these data demonstrate that nonspecific cyclooxygenase inhibition by indomethacin alters the choline metabolite profile of malignant cells towards a less malignant phenotype. These changes were not related to alterations of intra‐ or extracellular pH. Magn Reson Med 48:819–825, 2002. © 2002 Wiley‐Liss, Inc.
Separating changes in the intra‐ and extracellular water apparent diffusion coefficient following focal cerebral ischemia in the rat brain
Authors: Silva Matthew D. , Omae Tsuyoshi , Helmer Karl G. , Li Fuhai , Fisher Marc , Sotak Christopher H.
Published: November 2002

Selective intracellular (IC) and extracellular (EC) brain water apparent diffusion coefficient (ADC) values were measured in normal and ischemic rat brain. Selective T1‐relaxation enhancement of the EC water, using intracerebroventricular (ICV) infusion of an NMR contrast reagent (CR), was used to separate the IC and EC signal contributions. In the CR‐infused, normal brain (n = 4), T1 = 235 ± 10 ms and T2 = 46 ± 2 ms for IC water (85%) and T1 = 48 ± 8 ms and T2 = 6 ± 2 ms for EC water (15%). Volume‐localized ADCz (z‐gradient axis) values were 0.90 ± 0.02 (EC+IC), 0.81 ± 0.05 (IC), 0.51 ± 0.02 (EC+IC), and 0.53 ± 0.07 (IC), for normal, CR‐infused, ischemic, and ischemic/CR‐infused groups, respectively (ADC values are ×10‐3 mm2/s; n = 5 for each group). Imaging ADCz values were 0.81 ± 0.03 (EC+IC), 0.75 ± 0.05 (IC), 0.51 ± 0.04 (EC+IC), and 0.52 ± 0.05 (IC), respectively, for the same groups. Imaging ADCav (average diffusivity) values for the same groups were 0.70 ± 0.05 (EC+IC), 0.69 ± 0.06 (IC), 0.45 ± 0.06 (EC+IC), and 0.44 ± 0.06 (IC), respectively. These results suggest that the IC water ADC determines the overall water ADC value in normal and ischemic rat brain. Magn Reson Med 48:826–837, 2002. © 2002 Wiley‐Liss, Inc.
Optimization of static field homogeneity in human brain using diamagnetic passive shims
Authors: Wilson James L. , Jenkinson Mark , Jezzard Peter
Published: November 2002

These preliminary studies demonstrate that static field inhomogeneity in the human inferior frontal cortex (IFC) is significantly diminished through placement of a small amount of strongly diamagnetic material in the roof of the mouth. As a result, susceptibility‐related image artifacts in this region, as observed in blood oxygen level dependent (BOLD) functional MRI (fMRI), are considerably decreased without compromising the spatial or temporal resolution of the study. Simulations of the static field utilizing perturbation theory are shown, which support the experimental results. The limitations and possible future developments of the technique are described. The application of diamagnetic passive shimming on other regions of the brain is also discussed. Routine use of the proposed method within fMRI studies is practicable through subject‐specific optimization of the technique utilizing the simulation algorithm. Magn Reson Med 48:906–914, 2002. © 2002 Wiley‐Liss, Inc.
Evidence that both fast and slow water ADC components arise from intracellular space
Authors: Sehy Jonathan V. , Ackerman Joseph J.H. , Neil Jeffrey J.
Published: November 2002

Evaluation of water diffusion in the brain has revealed both fast‐ and slow‐diffusing water populations. It has been suggested that these populations represent extra‐ and intracellular water, respectively. We have identified and characterized both populations in the intracellular space of the Xenopus oocyte. We have also determined their T1 and T2 relaxation properties. The fast and slow intracellular populations have diffusion coefficients of 1.06 ± 0.05 μm2/ms and 0.16 ± 0.02 μm2/ms, respectively, with the fast fraction representing 89% ± 1% of the total water signal. These values are quite similar to those for total water in brain and are observed in the absence of signal from the perfusate (extracellular) water population. Volumetric swelling (16% ± 4%) of the oocyte in hypoosmotic media increased the diffusion coefficients of both intracellular populations (fast = 1.27 ± 0.03 μm2/ms, slow = 0.22 ± 0.02 μm2/ms), but did not change their relative signal fractions. This phenomenon runs counter to the effects observed in brain injury, following which the apparent diffusion coefficient (ADC) decreases 30–50%. The results presented herein suggest that this ADC decrease in brain occurs despite cell swelling, which by itself would be expected to induce an increase in intracellular diffusion coefficients. Magn Reson Med 48:765–770, 2002. © 2002 Wiley‐Liss, Inc.
A load cluster management system using SNMP and web
Authors: Kim Myung‐Sup , Choi Mi‐Joung , Hong James W.
Published: November 2002

Clustered servers for Internet service is a popular solution to cope with the explosive increase in client requests. The high probability of service failure in cluster servers make the cluster management system necessary to provide high availability and convenient administrator control. In this paper, we present the design and implementation of a load cluster management system (LCMS) based on SNMP and Web technology. Our LCMS implementation has been deployed on a commercial ultra‐dense server. Copyright © 2002 John Wiley & Sons, Ltd.
Transparent bridging support for Bluetooth–IP service interworking
Authors: Chen Jiann‐Liang , Yen Ka‐Chin
Published: November 2002

A PC‐based transparent gateway for interconnecting Bluetooth Piconets and IP local area networks (LAN) was designed in our research. The essential function of this designed Bluetooth‐IP gateway is to achieve a seamless integration among home appliances, networking elements and multi‐systems using the address resolution protocol (ARP) and connection management scheme. The key techniques developed, as well as the performance analysis in terms of queue length, loss rate, throughput and transmission delay are explored in this research. The results allow us to determine the value of the optimal command and infer the maximum queue length requirements such that the service quality is kept at an acceptance level. Copyright © 2002 John Wiley & Sons, Ltd.
Construct validity of the adjustment scales for children and adolescents and the preschool and kindergarten behavior scales: Convergent and divergent evidence
Authors: Canivez Gary L. , Rains Jaime D.
Published: November 2002

Construct validity (convergent and divergent) of the Adjustment Scales for Children and Adolescents (ASCA; McDermott, Marston, & Stott, 1993) and the Preschool and Kindergarten Behavior Scales (PKBS; Merrell, 1994a) is presented. Regular classroom teachers (n = 38) randomly selected 5‐ and 6‐year‐old children (N = 123) and rated them on the ASCA and PKBS in counterbalanced order. Convergent evidence of construct validity was observed for the PKBS Externalizing Problems scale and the ASCA Overactivity syndrome. Divergent evidence of construct validity was provided for the PKBS Externalizing Problems scale and ASCA Underactivity syndrome. Convergent and divergent evidence of construct validity for the PKBS Internalizing Problems scale and ASCA Overactivity and Underactivity syndromes was mixed. Results were identical to those of Canivez and Bordenkircher (2002). © 2002 Wiley Periodicals, Inc. Psychol Schs 39: 621–633, 2002.
Modularity, strategic flexibility, and firm performance: a study of the home appliance industry
Authors: Worren Nicolay , Moore Karl , Cardona Pablo
Published: November 2002

Recent theorizing has proposed that modular product and process architectures are key enablers of strategic flexibility. We formulated an integrative conceptual model encompassing antecedents, contributing factors, and outcomes of modularity. We then tested this model on data from managers in U.S. and U.K. home appliance companies using structural equations modeling. The results indicate a positive relationship between modular product architectures and performance, with product model variety as a mediating variable. The results also highlight linkages between perceptions of market context and the use of modular products architectures, and between complementary organizational capabilities and firm performance. Copyright © 2002 John Wiley & Sons, Ltd.
Return predictability in African stock markets
Authors: Appiah‐Kusi Joe , Menyah Kojo
Published: November 2002

This paper models weekly index returns adjusted for thin trading as a nonlinear autoregressive process with conditional heteroscedasticity to investigate the weak‐form pricing efficiency of 11 African stock markets. Specifically, the use of the EGARCH‐M model allows us to capture how conditional volatility affects the pricing process without imposing undue restrictions on the parameters of the conditional variance equation. On the basis of such a robust model, we are able to reject the evidence in prior studies that the Nigerian stock market is weak‐form efficient. On the other hand, we confirm extant results that the markets in Egypt, Kenya, and Zimbabwe are efficient while that of South Africa is not weak‐form efficient. We also generate new results, which point to the efficiency of the stock markets in Mauritius and Morocco, while the markets in Botswana, Ghana, Ivory Coast, and Swaziland are not consistent with weak‐form efficiency.
Increased frequency of cytochrome P450 2D6 poor metabolizers among patients with metoprolol‐associated adverse effects
Authors: Wuttke Henrike , Rau Thomas , Heide Roland , Bergmann Klaus , Böhm Michael , Weil Joachim , Werner Dierk , Eschenhagen Thomas
Published: November 2002

Objective

The CYP2D6 genotype is a major determinant of interindividual differences in metoprolol plasma clearance. Cytochrome P450 2D6 (CYP2D6) poor metabolizers exhibit 3‐ to 10‐fold higher plasma concentrations after administration of metoprolol than extensive metabolizers. However, the impact of the CYP2D6 genotype on the occurrence of adverse effects of metoprolol remains controversial. This study addressed whether the incidence of poor metabolizers was higher in patients with metoprolol‐associated adverse effects than in the German population at large.

Methods

Approximately 1200 German physicians were asked to report on patients who had experienced pronounced adverse effects in association with administration of metoprolol. CYP2D6 genotypes were determined with a combination of allele‐specific polymerase chain reaction and polymerase chain reaction‐restriction fragment length polymorphism. The adverse effects, consisting of symptoms related to β‐adrenergic receptor blockade and nonspecific symptoms, were recorded by use of a standardized questionnaire.

Results

Twenty‐four patients were included in the study. Nine patients had 2 null alleles (poor metabolizer genotype; 38%); the remaining 15 had either 1 null allele (n = 7) or no null alleles (n = 8). Therefore the occurrences of poor metabolizer genotypes in the study population were 4.9‐ and 5.2‐fold more frequent, respectively, than that found in unselected members of the German population in two large studies (P < .0001; χ2 test).

Conclusions

These data showed that CYP2D6 poor metabolizers had a 5‐fold higher risk for development of adverse effects during metoprolol treatment than patients who were not poor metabolizers. Because the absolute risk of adverse effects of metoprolol is unknown, the clinical relevance of the CYP2D6 genotype for metoprolol therapy has to be determined in a prospective manner.

Clinical Pharmacology & Therapeutics (2002) 72, 429–437; doi: 10.1067/mcp.2002.127111
Ribavirin dosing in chronic hepatitis C: Application of population pharmacokinetic‐pharmacodynamic models
Authors: Jen Juif , Laughlin Mark , Chung Carol , Heft Samuel , Affrime Melton B. , Gupta Samir K. , Glue Paul , Hajian Gerald
Published: November 2002

Background

Combination therapy of ribavirin with interferon alfa‐2b and pegylated interferon alfa‐2b is currently approved for the treatment of chronic hepatitis C. Approved ribavirin dosages vary from a fixed dosage of 800 mg/d to as much as 1200 mg/d on the basis of body weight.

Objective

Our objective was to evaluate ribavirin dosing strategies by comparison of their relative efficacy and toxicity profiles.

Methods

Three models were developed on the basis of data collected from a large phase III trial. A population pharmacokinetic model was used to describe the ribavirin dose‐concentration relationship and the influence of covariates. Logistic regression models were developed for both sustained virologic response and hematologic toxicity. Ribavirin concentration was an important explanatory variable for both response and toxicity. Simulations of these models were developed for different ribavirin doses to obtain efficacy and toxicity profiles across the various dosing strategies. These strategies included a fixed 800‐mg/d dose, empiric weight‐adjusted doses (ie, 1000 mg/d for patients who weighed ≤75 kg and 1200 mg/d for patients who weighed >75 kg [1000/1200 mg/d on the basis of body weights ≤75/>75 kg] and 800 mg/d for patients who weighed <65 kg, 1000 mg/d for patients who weighed from 65 to 85 kg, and 1200 mg/d for patients who weighed >85 kg [800/1000/1200 mg/d on the basis of body weights <65/65‐85/>85 kg]), a dose of 13 mg/kg per day, and other per‐body weight doses between 9 and 16 mg/kg per day.

Results

Simulation results showed that both efficacy and toxicity increased as the milligrams‐per‐kilogram dose of ribavirin increased. The body weight‐based 800/1000/1200‐mg/d dose had overall response and toxicity rates that were 6.3% and 2.5% higher than those of the fixed 800‐mg/d dose. In particular, patients with genotype‐1 disease had a 7.4% increase in response rate. There were no differences in response and toxicity rates between the 800/1000/1200‐mg/d and 13‐mg/kg per day dose groups.

Conclusions

This simulation suggests that ribavirin dosage (in combination with pegylated interferon alfa‐2b) for patients with chronic hepatitis C should be based on body weight.

Clinical Pharmacology & Therapeutics (2002) 72, 349–361; doi: 10.1067/mcp.2002.127112