bluuebunny/crossref_metadata_2025 huggingface dataset:
Laminin‐5‐enriched extracellular matrix accelerates angiogenesis and neovascularization in association with ePTFE
Authors: Kidd Kameha R. , Williams Stuart K.
Published: March 2004

The performance of biomedical implant devices is often limited by inappropriate tissue responses associated with synthetic materials used in device construction. Adverse healing responses, in particular the lack of an extensive vascular supply in the peri‐implant tissue, are believed to lead to the ultimate failure of many of these medical devices. Accelerated formation of new blood vessels in the peri‐implant tissue and within porous polymeric implants is hypothesized to improve the performance of such biomedical implant devices. The current study evaluated the use of cell‐mediated, extracellular matrix modification of expanded polytetrafluoroethylene (ePTFE) to increase vessel growth in peri‐implant tissue and within the pores of the implants. Discs of ePTFE were modified through cell‐mediated matrix deposition using epithelial and endothelial cell lines with variable deposition of collagen types, fibronectin, and laminin types. Cell matrix‐modified discs, Matrigel‐coated discs, and nonmodified discs were implanted in both the adipose and subcutaneous tissues of the rat. Following a 5‐week implant period, samples were removed and evaluated histologically and morphometrically for the presence of blood vessels in the peri‐implant tissue and within the pores of the polymer as well as for the presence of activated macrophages and monocytes. A significantly increased presence of activated macrophages and monocytes was associated only with the samples modified with the matrix from a human microvessel endothelial cell line. Increased vessel density was identified in association with those ePTFE samples modified with either the 804‐G, HaCaT, or II‐4 cell matrices, all of which have extracellular matrices enriched in the protein laminin‐5. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 69A: 294–304, 2004
Fibroblast response to a controlled nanoenvironment produced by colloidal lithography
Authors: Dalby Matthew J. , Riehle Mathis O. , Sutherland Duncan S. , Agheli Hossein , Curtis Adam S.G.
Published: March 2004

It is thought that by understanding how cells respond to topography, that better tissue engineering may be achievable. An important consideration in the cellular environment is topography. The effects of microtopography have been well documented, but the effects of nanotopography are less well known. Previously, methods of nanofabrication have been costly and time‐consuming, but research by engineers, physicists, and chemists is starting to allow the production of nanostructures using low‐cost techniques. In this report, nanotopography is specifically considered. Controlled patterns of 160 nm high nanocolumns were produced for in vitro cell culture using colloidal lithography. By studying cell adhesion with time and cytoskeletal (actin, tubulin, and vimentin) maturity, insight has been gained as to how fibroblasts adhere to these nanofeatures. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 69A: 314–322, 2004
Long‐term regeneration of the rat sciatic nerve through a biodegradable poly(DL‐lactide‐ϵ‐caprolactone) nerve guide: Tissue reactions with focus on collagen III/IV reformation
Authors: Jansen Koen , Meek Marcel F. , van der Werff John F. A. , van Wachem Pauline B. , van Luyn Marja J. A.
Published: March 2004

Long‐term studies on nerve‐guide regeneration are scarce. Therefore, in rats, long‐term (16 months) sciatic nerve regeneration through poly(DL‐lactide‐ϵ‐caprolactone) [poly(DLLA‐ϵ‐CL)] nerve guides was studied and compared with the nonoperated control side. Poly(DLLA‐ϵ‐CL) degradation and possible long‐term foreign body reaction against poly(DLLA‐ϵ‐CL) nerve guides, as well as the distribution of both collagen type III and IV were studied. In vivo poly(DLLA‐ϵ‐CL) studies have been performed before but not for such long time points; also, a detailed analysis of collagen III/IV has not been presented before. The results demonstrate that biodegradable poly(DLLA‐ϵ‐CL) nerve guides yield good nerve regeneration and collagen III/IV deposition relative to the anatomy of the control side. Regenerated nerve showed almost similar collagen type III/IV distribution patterns as compared with the nonoperated control side, although the delineation of matrix was clearer in the control side. The relative amount of collagen III and IV immunostaining in nerve cross‐sections did not, however, differ between the control nerve tissue and the operated side after 16 months. After 16 months of implantation, however, some very small fragments of biomaterial could still be found on the edge of the epineurium of the regenerated nerve, indicating remnants of a secondary foreign body reaction. The biomaterial fragments and foreign body reaction did not influence the nerve regeneration process after 16 months. Biodegradable poly(DLLA‐ϵ‐CL) nerve guides are useful for long‐term bridging of short peripheral nerve gaps. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 69A: 334–341, 2004
Comparison of environmental scanning electron microscopy with high vacuum scanning electron microscopy as applied to the assessment of cell morphology
Authors: McKinlay Karen J. , Allison Francis J. , Scotchford Colin A. , Grant David M. , Oliver James M. , King John R. , Wood John V. , Brown Paul D.
Published: March 2004

The efficacy of conventional high vacuum scanning electron microscopy (SEM), environmental SEM (ESEM), and confocal laser scanning microscopy techniques in the assessment of cell–material interactions is compared. Specific attention is given to the application of these techniques in the assessment of the early morphological response of human osteoblast‐like cells cultured on titanium dioxide. The processing of cells cultured for conventional high vacuum SEM leads to the loss of morphological features that are retained when using ESEM. The use of cytoskeletal labeling, viewed with confocal laser scanning microscopy, in conjunction with ESEM gives an indication of the changes to cell morphology as a consequence of incubation time in response to interactions at the biological/material interface. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 69A: 359–366, 2004
Bone formation using novel interconnected porous calcium hydroxyapatite ceramic hybridized with cultured marrow stromal stem cells derived from Green rat
Authors: Ito Yoshiyuki , Tanaka Nobuhiro , Fujimoto Yoshinori , Yasunaga Yuji , Ishida Osamu , Agung Muhammad , Ochi Mitsuo
Published: March 2004

The clinical use of cultured marrow stromal stem cells (MSCs) has recently attracted attention in the field of tissue engineering. For the clinical use of the MSCs, a prominent scaffold is needed. A scaffold hybridized with MSCs is transformed into a “bioactive bone substitute,” and this provides good osteoconduction. In this study, a novel calcium hydroxyapatite ceramic with an interconnected porous structure (IP‐CHA) was used as a scaffold. MSCs were harvested from Green rats containing Green Fluorescent Protein (GFP), and then these hybrids were implanted into the tibias of Sprague–Dawley rats. The purposes of this study were to examine the osteogenic ability of these hybrids without coculture, and to evaluate whether the resulting bone formation originated from the grafted MSCs or the recipient's cells. The hybridized group showed excellent bone formation compared with the IP‐CHA‐only implant group. Observation of the implanted MSCs revealed that they survived 8 weeks after surgery, and differentiated into osteoblast‐like cells, thus providing bone formation. This implantation of the MSCs/IP‐CHA composite provides excellent osteoconduction, and is expected to have extensive clinical applications. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 69A: 454–461, 2004
Is telomere erosion a mechanism of species extinction?
Authors: Stindl Reinhard
Published: March 2004

According to the fossil record, 99.9% of all species that have ever lived on Earth have disappeared. However, only about 4% died out during the five mass extinction events, whereas it seems that the majority of species vanished without any signs of significant earthbound or extraterrestrial physical threats. Clearly, biological extinction mechanisms are by far the most important, but they are subject to serious limitations concerning the worldwide disappearance of species. In view of that, species‐inherent mechanisms, which could lead to the worldwide destabilization of a population, might be worth reconsideration. Telomeres, the protective caps of chromosome ends, and the enzyme telomerase have been well preserved in plants and animals during evolution. In the absence of telomerase activity, telomeric DNA has been shown to shorten every time a cell divides. The concept of a mitotic clock based on the gradual erosion of telomeres is now generally accepted and has been confirmed in numerous plants and animals. Chromosomal rearrangements are the hallmarks of two completely different biological phenomena, cancer and speciation. In premalignant cells, gradual telomere erosion beyond a critical threshold is a well‐known inducer of chromosomal instability. The species clock hypothesis, as presented here, is based on the idea of a tiny loss of mean telomere length per generation. This mechanism would not rapidly endanger the survival of a particular species. Yet, after many thousands of generations, critically short telomeres could lead to the weakening and even the extinction of old species and would simultaneously create the unstable chromosomal environment that might result in the origination of new species. J. Exp. Zool. (Mol. Dev. Evol.) 302B: 111–120, 2004. © 2004 Wiley‐Liss, Inc.
Geographic variability in expression of the sex‐linked AAT–1 gene of the bell‐ring frog, Buergeria buergeri
Authors: Sumida Masayuki , Ohta Shigeru , Atsumi Shigeru , Fujii Tamotsu
Published: March 2004

Cytological observation and artificial crossing experiments were used to examine the geographic differences in the sex‐determining mechanism and mode of inheritance of the sex‐linked AAT–1 gene in the bell‐ring frog, Buergeria buergeri. The AAT–1 phenotypes were also examined by allozyme analysis using field‐caught females and males collected from 19 populations from the Honshu, Shikoku, and Kyushu islands of Japan, in order to comprehensively elucidate the geographic variability in the expression of the sex‐linked AAT–1 gene of B. buergeri. The results showed that the Aomori population of B. buergeri from the northern end of Honshu was female heterogametic in sex determination, that chromosome No. VII was a sex chromosome of the ZZ/ZW type, and that the sex‐linked AAT–1 gene was expressed on both the Z and W chromosomes. This mode of AAT–1 expression in the Aomori population was different from that in the Hiroshima population from western Honshu, in which the AAT–1 gene was expressed on the Z chromosome but not on the W chromosome. The results also showed that there was no differentiation among populations in the expression of the AAT–1 genes on the Z chromosome, whereas two populations, the Hiroshima and Aomori frogs, exhibited distinct modes of expression of the AAT–1 gene on the W chromosome. These two modes of expression may be widely distributed in western and eastern Japan, and coexist in the central part of Honshu. J. Exp. Zool. (Mol. Dev. Evol.) 302B: 182–194, 2004. © 2004 Wiley‐Liss, Inc.
Comparative genomic analysis of vertebrate Hox3 and Hox4 genes
Authors: Hadrys Thorsten , Prince Victoria , Hunter Michael , Baker Robert , Rinkwitz Silke
Published: March 2004

We used a comparative genomic approach to identify putative cis‐acting regulatory sequences of the zebrafish hoxb3a and hoxb4a genes. We aligned genomic sequences spanning the clustered Hoxb1 to Hoxb5 genes from pufferfish, mice, and humans with the zebrafish hoxba and hoxbb cluster sequences. We identified multiple blocks of conserved sequences in non‐coding regions within and surrounding the Hoxb3/b4 gene locus; a subset of these blocks are conserved in the zebrafish hoxbb cluster, despite loss of hoxb3/b4 genes. Overall, we find that the architecture of the Hoxb3/b4 loci and of the conserved sequence elements is very similar in teleosts and mammals. Our analyses also revealed two alternative transcripts of the zebrafish hoxb3a gene and an exon sequence unusually located 10 kb upstream of adjacent hoxb4a; an equivalent murine Hoxb3 exon has not yet been confirmed. We show that many of the Hoxb3/b4 conserved non‐coding sequences correlate with functional neural enhancers previously described in the mouse. Further, within the conserved non‐coding sequences we have identified binding sites for transcription factors, including Kreisler/Valentino, Krox20, Hox, and Pbx, some of which had not been previously described for the mouse. Finally, we demonstrate that the regulatory sequences of zebrafish hoxa3a are divergent with respect to the mouse ortholog Hoxa3, or the paralog hoxb3a. Despite limited conservation of regulatory sequences, zebrafish hoxa3a and hoxb3a genes share very similar expression profiles. J. Exp. Zool. (Mol. Dev. Evol.) 302B: 147–164, 2004. © 2004 Wiley‐Liss, Inc.
It's “juxta” potassium channel!
Authors: Rasband Matthew N.
Published: March 2004

Neuronal excitability depends on the appropriate expression and localization of ion channels. Juxtaparanodal Kv1 channels have been used as a model to study the role of neuroglial interactions in regulating the expression and localization of channels in myelinated axons. Recent advances in our understanding of the composition of juxtaparanodal Kv1 channel protein complexes as well as the cellular and molecular mechanisms underlying their localization at juxtaparanodes are discussed. © 2004 Wiley‐Liss, Inc.
Systemic administration of N‐acetylcysteine protects dopaminergic neurons against 6‐hydroxydopamine‐induced degeneration
Authors: Muñoz Ana M. , Rey Pablo , Soto‐Otero Ramon , Guerra Maria J. , Labandeira‐Garcia Jose L.
Published: March 2004

The results of several in vitro studies have shown that cysteine prodrugs, particularly N‐acetylcysteine, are effective antioxidants that increase the survival of dopaminergic neurons. N‐acetylcysteine can be systemically administered to deliver cysteine to the brain and is of potential use for providing neuroprotection in the treatment of Parkinson's disease. However, it has also been reported that an excess of cysteine may induce neurotoxicity. In the present study, we injected adult rats intrastriatally with 2.5 μl of 6‐hydroxydopamine (7.5 μg) and N‐acetylcysteine (240 mM) or cysteine (240 mM) or intraventricularly with 6‐hydroxydopamine (200 μg) and subcutaneously with N‐acetylcysteine (10 and 100 mg/kg). We studied the effects of these compounds on both the nigrostriatal dopaminergic terminals and the surrounding striatal tissue. The tissue was stained with fluoro‐jade (a marker of neuronal degeneration) and processed by immunohistochemistry to detect tyrosine hydroxylase, neuronal and glial markers, and the stress protein heme‐oxygenase‐1. After intrastriatal injection, both cysteine and N‐acetylcysteine had clear neuroprotective effects on the striatal dopaminergic terminals, but also led to neuronal degeneration (as revealed by fluoro‐jade staining) and astroglial and microglial activation, as well as intense induction of heme‐oxygenase‐1 in astrocytes and microglial cells. Subcutaneous administration of N‐acetylcysteine also induced significant reduction of the dopaminergic lesion (about 30% reduction). However, we did not observe appreciable N‐acetylcysteine‐induced fluoro‐jade labeling in striatal neurons or any of the above‐mentioned changes in striatal glial cells. The results suggest that low doses of cysteine prodrugs may be useful neuroprotectors in the treatment of Parkinson's disease. © 2004 Wiley‐Liss, Inc.
Best practices: Choosing the right methods for evaluation
Authors: Hannum Kelly
Published: March 2004

When evaluating leadership development it is best to use multiple methods, but which methods should be
chosen? Several factors can guide you.
Corrosion behavior of steel in Chengdao offshore oil exploitation area
Authors: Li Y. , Hou B. , Li H. , Zhang J.
Published: March 2004

From September 1992 to September 1995, the corrosion behavior of three marine steels was studied in Chengdao offshore area by means of individually and electro‐connectedly hanging plates in order to provide data for anticorrosion design of oil‐exploitation structures there.

The variation trend of corrosion rate with exposure time showed that the variation curves and degrees of three steels were generally identical and had nothing to do with the exposure time. The whole change trend of corrosion rates in three years showed that the corrosion rates of 20# steel were nearly identical in different positions, each of which was a little lower than that of 16 Mn steel specimens in corresponding positions, also was lower than that of A3 steel specimens in tidal zone and immersion zone. Although 20# steel corroded rapidly at first, its corrosion rate has a decreasing trend in the long‐term service. Therefore, 20# steel is feasible to be applied for a long time in various marine zones, especially nearby the low tidal line and immersion zone. The results of A3 steel, 16 Mn steel and 20# steel by means of electrically connected hanging plate in three years indicated that the corrosion of the steel specimens in the splash zone was the most severe as the result of dry‐wet cycle and macrocell effect. Specimens in the other positions corroded mildly, and that in tidal zone corroded most slowly. The corrosion rate of 20# steel was the highest among the three steels in the test, and the corrosion rates of A3 steel and 16 Mn steel were identical on the whole. When the specimens were hanged electro‐connectedly, the macrocell effect generally tended to increase with exposure time. The highest corrosion rate of A3 steel in the splash zone in the three years was about 0.278 mm/a, while that of 16 Mn steel was about 0.321 mm/a, and that of 20# steel was 0.330 mm/a or so. In contrast, the corrosion rate of the steels in the tidal zone was the lowest in three years, which were 0.052 mm/a (A3 steel), 0.048 mm/a (16 Mn steel) and 0.040 mm/a (20# steel).
The influence of Metal Dusting on gas reactions
Authors: Kempen A. T. W. , van Wortel J. C.
Published: March 2004

Gas composition analysis measurements have been performed in the outlet gas stream of a laboratory metal dusting test furnace in order to study the influence of metal dusting on gas reactions. This analysis has shown that carbon deposition is associated with metal dusting, i.e. the material most severely attacked by metal dusting, catalyses the formation of carbon to the largest extent. Also, metal dusting has not been seen to influence the methanation reactions. A kinetic model has been used to interpret the obtained data with respect to the catalytic activity of several high temperature materials showing that the catalytic activity of the material can vary by orders of magnitude for different reactions.
Stress corrosion cracking behaviour of Al‐Li alloy 8090‐T8171 plate exposed to various synthetic environments
Authors: Braun R.
Published: March 2004

The stress corrosion cracking (SCC) behaviour of 8090‐T8171 plate material was investigated in short transverse direction performing constant load tests and constant extension rate tests under permanent immersion conditions. At an applied stress of 100 MPa, smooth round tensile specimens were exposed to synthetic environments containing chlorides and various nonhalide anions. Environment‐induced cracking was not observed in aqueous solutions of 0.6 M NaCl, LiCl, NH4Cl, or MgCl2. In 0.6 M NaCl solutions containing 0.06 M Na2SO4 or Na3PO4, the SCC behaviour of 8090‐T8171 plate was similar to that observed in pure 0.6 M NaCl solution. Sodium chloride solutions with additions of nitrate, hydrogen carbonate, or carbonate promoted stress corrosion cracking. Threshold stresses below 100 MPa were obtained from constant load tests using the latter environments. When sodium sulfite or sodium hydrogen phosphate was added, values being 100 MPa or slightly higher were determined. Lithium and ammonium present as cations in mixed salt electrolytes accelerated SCC failure. Lithium chloride solutions containing nitrate, hydrogen carbonate, carbonate, or sulfite were highly conducive to stress corrosion cracking. Very low SCC resistance was found for alloy 8090‐T8171 exposed to synthetic environments with additions of ammonium salts. Constant extension rate tests were carried out using notched tensile specimens. Displacement rates were in the range 2 × 10−6 − 2 × 10−5 mms−1. Aqueous 0.6 M NaCl solutions with additions of 0.06 M NH4HCO3, (NH4)2SO4, or Li2CO3 promoted environment‐induced cracking with 8090‐T8171 plate, as indicated by severe degradation of notch strength. The constant extension rate testing technique did not indicate SCC susceptibility using sodium chloride solutions containing sodium sulfate or lithium sulfate. For specimens exposed to substitute ocean water a slight degradation of notch strength was found at the lowest displacement rate applied.
Effect of Co and W on the corrosion behaviour of 1% Cr steel in flowing synthetic seawater
Authors: Choi Yoon‐Seak , Shim Jae‐Joo , Kim Jung‐Gu
Published: March 2004

The aqueous corrosion characteristics of 1% Cr‐steel alloyed with small amounts of Co and W in synthetic seawater was studied by using immersion weight‐loss tests, electrochemical corrosion tests (potentiodynamic tests and electrochemical impedance spectroscopy (EIS) measurements) and analytical techniques. 1% Cr steels containing Co or W from 0.2 to 0.4 wt.% showed higher corrosion resistance than the 1% Cr steel in the immersion and potentiodynamic tests. EIS measurements showed that the Nyquist plot presented one time constant. Furthermore, the Co‐ and W‐bearing steels present higher Rp values than the 1% Cr steel through all the test period. The better corrosion resistance of the Co‐and W‐bearing steels is attributed to the protectiveness of the surface layer. The corrosion products were examined using electron probe microanalysis (EPMA) and X‐ray photoelectron spectroscopy (XPS). The results of EPMA indicated that Cr was concentrated in the inner region of the rust layer, while Co and W were distributed all over the rust layer. XPS results showed that Co existed as a trivalent oxide in the rust layer and W in the rust appeared in the form of a WO4 compound. These compounds act as a factor for corrosion resistance in aqueous solutions.
Hochfeste Stangen aus NiCr23Mo16Al – Einfluss der Kaltverfestigung auf die mechanischen Eigenschaften und das Korrosionsverhalten
Authors: Brill U.
Published: March 2004

Bei hohen Anforderungen an die mechanischen Eigenschaften in Kombination mit besonders korrosiven Umgebungsbedingungen werden häufig kaltverfestigte NiCrMo‐Legierungen eingesetzt.

In dieser Arbeit wurde der Einfluss einer durch Ziehen eingebrachten Kaltverformung bis zu 42% auf die mechanischen Eigenschaften und das Korrosionsverhalten der Legierung NiCr23Mo16Al untersucht.

Bei den bei 20°C, 204°C und 371°C durchgeführten Zugversuchen wies die 0,2%‐Streckgrenze bis zur maximalen Kaltverformung von 42% eine lineare Steigerung auf. Bei allen Kaltverfestigungsgraden und allen Prüftemperaturen wurden im Zugversuch mindestens 16% Bruchdehnung erreicht. Auch die Kerbschlagarbeit lag selbst bei Prüftemperaturen bis zu − 40°C bei ca. 200 J.

Die nach ASTM G 28 A/B und G 48 C/D durchgeführten Korrosionsuntersuchungen weisen bei 42% Kaltverformung keine Verschlechterung des Korrosionsverhaltens gegenüber dem lösungsgeglühten Ausgangszustand auf. Lediglich zwischen ca. 15–30% Kaltverformung deutet sich ein geringfügig ungünstigeres Verhalten an, dass durch eine starke Gefügeinhomogenität und als Folge davon als Lokalelementbildung zwischen stark verformtem Rand und unverformter Mitte erklärt wird.

Bei den in 1 M NaCl aufgenommenen Stromdichte‐Potential‐Kurven nach ASTM G 61/98 konnte kein Einfluss der Kaltverformung auf das elektrochemische Verhalten nachgewiesen werden.
On Ethylene Polymerisation with Aluminium and Scandium Complexes: DFT and Post‐HF Calculations
Authors: Meier Robert J. , Koglin Eckhard
Published: March 2004

Summary: The performance of Density Functional Theory (DFT) methods in predicting ethylene polymerisation and/or oligomerisation activity in selected aluminium and scandium based complexes was studied using both DFT and post‐Hartree‐Fock CCSD(T) calculations. Whereas previous reports have drawn attention to the underestimation of the barrier for the β‐hydrogen termination process for a few aluminium based species, we found that the same holds for the corresponding scandium complexes. New, however, is the observation that apart from underestimating the energy barrier connected to β‐hydrogen termination, the insertion of ethylene is also severely underestimated by the DFT methods applied compared to post‐Hartree‐Fock calculations up to the CCSD(T) level.

Structure of the diketiminate complex referred to in the text.

image

Structure of the diketiminate complex referred to in the text.
Chromosome 17p13.2 transfer reverts transformation phenotypes and fas‐mediated apoptosis in breast epithelial cells
Authors: Lareef Mohamed H. , Tahin Quivo , Song Joon , Russo Irma H. , Mihaila Dana , Slater Carolyn M. , Balsara Binaifer , Testa Joseph R. , Broccoli Dominique , Grobelny Jennifer V. , Mor Gil , Cuthbert Andrew , Russo Jose
Published: March 2004

Transformation of the human breast epithelial cells (HBEC) MCF‐10F with the carcinogen benz(a)pyrene (BP) into BP1‐E cells resulted in the loss of the chromosome 17 p13.2 locus (D17S796 marker) and formation of colonies in agar‐methocel (colony efficiency (CE)), loss of ductulogenic capacity in collagen matrix, and resistance to anti‐Fas monoclonal antibody (Mab)‐induced apoptosis. For testing the role of that specific region of chromosome 17 in the expression of transformation phenotypes, we transferred chromosome 17 from mouse fibroblast donors to BP1‐E cells. Chromosome 11 was used as negative control. After G418 selection, nine clones each were randomly selected from BP1‐E‐11neo and BP1‐E‐17neo hybrids, respectively, and tested for the presence of the donor chromosomes by fluorescent in situ hybridization and polymerase chain reaction‐based restriction fragment length polymorphism (PCR‐RFLP) analyses. Sensitivity to Fas Mab–induced apoptosis and evaluation of transformation phenotype expression were tested in MCF‐10F, BP1‐E, and nine BP1‐E‐11neo and BP1‐E‐17neo clones each. Six BP1‐E‐17neo clones exhibited a reversion of transformation phenotypes and a dose dependent sensitivity to Fas Mab‐induced apoptosis, behaving similarly to MCF‐10F cells. All BP1‐E‐11neo, and three BP1‐E‐17neo cell clones, like BP1‐E cells, retained a high CE, loss of ductulogenic capacity, and were resistant to all Fas Mab doses tested. Genomic analysis revealed that those six BP1‐E‐17neo clones that were Fas‐sensitive and reverted their transformed phenotypes had retained the 17p13.2 (D17S796 marker) region, whereas it was absent in all resistant clones, indicating that the expression of transformation phenotypes and the sensitivity of the cells to Fas‐mediated apoptosis were under the control of genes located in this region. © 2004 Wiley‐Liss, Inc.
Measurement of aroma compound self‐diffusion in food models by DOSY
Authors: Gostan Thierry , Moreau Céline , Juteau Alexandre , Guichard Elisabeth , Delsuc Marc‐André
Published: March 2004

Self‐diffusion measurement of solutes in polymer gels has been investigated using pulsed gradient spin echo NMR spectroscopy. However, few data are available on the self‐diffusion of small solutes in natural polysaccharide polymers used as thickeners in the food industry. Since aroma diffusion in food matrices could have an impact on flavor release, this is an interesting and economic challenge. Diffusion ordered spectroscopy (DOSY) resolves diffusion data for each component in complex mixtures. We used DOSY with the inverse Laplace transform approach with the maximum entropy algorithm to investigate diffusion of two aroma compounds, ethyl butanoate and linalool, in an ι‐carrageenan matrix as the food model. We showed that the self‐diffusion coefficient values of small molecules in a polysaccharide matrix could be easily extracted using this method. We then investigated the impact of the gelling state of ι‐carrageenan matrices on the self‐diffusion of ethyl butanoate. Copyright © 2004 John Wiley & Sons, Ltd.
Exploring lung function with hyperpolarized 129Xe nuclear magnetic resonance
Authors: Ruppert Kai , Mata Jaime F. , Brookeman James R. , Hagspiel Klaus D. , Mugler John P.
Published: March 2004

With the use of polarization‐transfer pulse sequences and hyperpolarized 129Xe NMR, gas exchange in the lung can be measured quantitatively. However, harnessing the inherently high sensitivity of this technique as a tool for exploring lung function requires a fundamental understanding of the xenon gas‐exchange and diffusion processes in the lung, and how these may differ between healthy and pathological conditions. Toward this goal, we employed NMR spectroscopy and imaging techniques in animal models to investigate the dependence of the relative xenon gas exchange rate on the inflation level of the lung and the tissue density. The spectroscopic results indicate that gas exchange occurs on a time scale of milliseconds, with an average effective diffusion constant of about 3.3 × 10−6cm2/s in the lung parenchyma. Polarization‐transfer imaging pulse sequences, which were optimized based on the spectroscopic results, detected regionally increased gas‐exchange rates in the lung, indicative of increased tissue density secondary to gravitational compression. By exploiting the gas‐exchange process in the lung to encode physiologic parameters, these methods may be extended to noninvasive regional assessments of lung‐tissue density and the alveolar surface‐to‐volume ratio, and allow lung pathology to be detected at an earlier stage than is currently possible. Magn Reson Med 51:676–687, 2004. © 2004 Wiley‐Liss, Inc.
EPR oximetry in the beating heart: Myocardial oxygen consumption rate as an index of postischemic recovery
Authors: Ilangovan Govindasamy , Liebgott Thibaut , Kutala Vijay Kumar , Petryakov Sergey , Zweier Jay L. , Kuppusamy Periannan
Published: March 2004

Oxygen plays a critical role in the pathophysiology of myocardial injury during both ischemia and subsequent reperfusion (I/R). Thus, oxygen concentration is an important variable to measure during I/R. In the present work, electron paramagnetic resonance (EPR)‐based oximetry was used to measure the oxygen concentration during a series of I/R episodes and oxygenation levels were correlated with the contractile and hemodynamic functions of the heart. A custom‐developed electronically tunable surface coil resonator working at 1.1 GHz was used to determine tissue pO2 in the beating heart. Microcrystalline particulate of lithium phthalocyanine was used as an EPR oximetry probe. Isolated and perfused rat hearts were subjected to 1 or 3 hr durations of preischemic perfusion, followed by 15‐min I/R cycles. In hearts perfused for 3 hr prior to 15‐min I/R cycles, the myocardial pO2 decreased gradually on subsequent reperfusions of three successive I/R cycles. However, in hearts perfused for 1 hr there was almost 100% recovery of myocardial pO2 in all three I/R cycles. The extent of oxygenation recovered in each reperfusion cycle correlated with the recovery of hemodynamic and contractile function. The results also showed that the oxygen consumption rate of the heart at the end of each I/R episode decreased in direct proportion to the functional recovery. In summary, it was observed that the amount of myocardial oxygen consumption during I/R could provide a reliable index of functional impairment in the heart. Magn Reson Med 51:835–842, 2004. © 2004 Wiley‐Liss, Inc.
Novel pH‐sensitive paramagnetic liposomes with improved MR properties
Authors: Løkling Knut‐Egil , Skurtveit Roald , Bjørnerud Atle , Fossheim Sigrid L.
Published: March 2004

The use of paramagnetic pH‐sensitive liposomes was recently suggested as a new approach for monitoring pathologic changes in pH by MRI. Such liposomes must be stable in blood and selectively release the encapsulated paramagnetic agent when exposed to lower pH in the target tissue. In the present study, different liposomal systems were formulated and characterized by relaxometry, cryo‐transmission electron microscopy (cryo‐TEM), and MRI. The pH‐sensitive system dipalmitoylphosphatidylethanolamine/palmitic acid (DPPE/PA) liposomal GdDTPA‐BMA, which was previously shown to be unstable in blood, was modified to improve its stability. The incorporation of cholesterol into the DPPE/PA liposomes significantly increased their stability in blood, but the pH sensitivity was diminished. Polyethylene glycol (PEG)‐modified DPPE/PA liposomes were pH‐insensitive in buffer, and unstable in blood. However, exchanging PA with the double‐chained amphiphile dipalmitoylglycerosuccinate (DPSG) yielded liposomes with improved properties. DPPE/DPSG liposomal GdDTPA‐BMA was stable in blood at physiological pH, and displayed a marked pH sensitivity. The pH sensitivity was not diminished after preincubation in blood, contrary to what has been reported for analogues containing unsaturated lipids. The potential of this system for monitoring pH was demonstrated in an in vitro MRI phantom study. Magn Reson Med 51:688–696, 2004. © 2004 Wiley‐Liss, Inc.
Parallel excitation with an array of transmit coils
Authors: Zhu Yudong
Published: March 2004

Theoretical and experimental results are presented that establish the value of parallel excitation with a transmit coil array in accelerating excitation and managing RF power deposition. While a 2D or 3D excitation pulse can be used to induce a multidimensional transverse magnetization pattern for a variety of applications (e.g., a 2D localized pattern for accelerating spatial encoding during signal acquisition), it often involves the use of prolonged RF and gradient pulses. Given a parallel system that is composed of multiple transmit coils with corresponding RF pulse synthesizers and amplifiers, the results suggest that by exploiting the localization characteristics of the coils, an orchestrated play of shorter RF pulses can achieve desired excitation profiles faster without adding strains to gradients. A closed‐form design for accelerated multidimensional excitations is described for the small‐tip‐angle regime, and its suppression of interfering aliasing lobes from coarse excitation k‐space sampling is interpreted based on an analogy to sensitivity encoding (SENSE). With or without acceleration, the results also suggest that by taking advantage of the extra degrees of freedom inherent in a parallel system, parallel excitation provides better management of RF power deposition while facilitating the faithful production of desired excitation profiles. Sample accelerated and specific absorption rate (SAR)‐reduced excitation pulses were designed in this study, and evaluated in experiments. Magn Reson Med 51:775–784, 2004. © 2004 Wiley‐Liss, Inc.
3D DT‐MRI using a reduced‐FOV approach and saturation pulses
Authors: Wang Jiun‐Jie , Deichmann Ralf , Turner Robert , Ordidge Roger
Published: March 2004

Diffusion tensor imaging (DTI) can provide vital insights into brain connectivity, and may become an important tool for the diagnosis and treatment of neurological disease. However, DTI's intrinsic low signal‐to‐noise ratio (SNR) and vulnerability to ghosting artifacts can result in poor image quality with low spatial resolution, which limits its clinical applications. In this study, a new double‐shot EPI sequence (half‐FOV EPI) with high spatial resolution was developed. This method enables DT measurements to be obtained with high isotropic spatial resolution and whole‐brain coverage. To avoid ghosting artifacts, the data are combined in image space rather than in k‐space. Magn Reson Med 51:853–857, 2004. © 2004 Wiley‐Liss, Inc.
Correction for partial volume errors in MR heart perfusion imaging
Authors: Köstler Herbert , Ritter Christian , Reiss‐Zimmermann Martin , Beer Meinrad , Hahn Dietbert , Sandstede Jörn
Published: March 2004

Myocardial MR first‐pass perfusion time courses are contaminated by signals from the ventricles (spillover) as a consequence of partial volume effects and motion. An early increase in the signal intensity from the myocardium is an indicator of contamination. This contamination leads to under‐ or overestimation of perfusion, depending on the amount of contamination. In this work a simple method for contamination correction is proposed: curves proportional to the signal intensity time courses in the ventricles are subtracted from the signal intensity time courses in the myocardium to minimize the variance of signal before the arrival of the contrast medium in the myocardium. The proposed correction is easy to apply, removes the contamination, and leads to more precise perfusion values. Magn Reson Med 51:848–852, 2004. © 2004 Wiley‐Liss, Inc.
Improved combination of spiral‐in/out images for BOLD fMRI
Authors: Glover Gary H. , Thomason Moriah E.
Published: March 2004

Acquisitions with the spiral‐in/out technique result in two separate image timeseries obtained during the spiral‐in and spiral‐out trajectory. In uniform brain regions the two components have comparable signal and BOLD contrast and can be averaged, but in regions compromised by susceptibility effects where both signal and noise can differ in the two images other combination methods may be more effective. Here, several weighting schemes are compared for signal and activation contrast recovery in whole brain and prefrontal cortex using verbal working memory (seven subjects) and breathholding tasks (six subjects) scanned at 3 T. It was found that a statistically weighted combination based on activation maps derived separately from the spiral‐in and spiral‐out images provides activation volumes with increases of 33–59% over second‐choice signal‐weighted combination and 100–200% increases over spiral‐out acquisition alone, and that simple averaging is inferior to signal‐weighted combination. Magn Reson Med 51:863–868, 2004. © 2004 Wiley‐Liss, Inc.
Semiautomatic segmentation and stenosis quantification of 3D contrast‐enhanced MR angiograms of the internal carotid artery
Authors: van Bemmel Cornelis M. , Viergever Max A. , Niessen Wiro J.
Published: March 2004

A technique is presented for the segmentation and quantification of stenosed internal carotid arteries (ICAs) in 3D contrast‐enhanced MR angiography (CE‐MRA). Segmentation with sub‐pixel accuracy of the ICA is achieved via level‐set techniques in which the central axis serves as the initialization. The central axis is determined between two user‐defined points, and minimal user interaction is required. For quantification, the cross‐sectional area is measured in the stenosis and at a reference segment in planes perpendicular to the central axis. The technique was applied to 20 ICAs. The variation in measurements obtained by this method in comparison with manual observations was 8.7%, which is smaller than the interobserver variability among three experts (11.0%). Magn Reson Med 51:753–760, 2004. © 2004 Wiley‐Liss, Inc.
Efficient method for calculating kinetic parameters using T1‐weighted dynamic contrast‐enhanced magnetic resonance imaging
Authors: Murase Kenya
Published: March 2004

It has become increasingly important to quantitatively estimate tissue physiological parameters such as perfusion, capillary permeability, and the volume of extravascular‐extracellular space (EES) using T1‐weighted dynamic contrast‐enhanced MRI (DCE‐MRI). A linear equation was derived by integrating the differential equation describing the kinetic behavior of contrast agent (CA) in tissue, from which K1 (rate constant for the transfer of CA from plasma to EES), k2 (rate constant for the transfer from EES to plasma), and Vp (plasma volume) can be easily obtained by the linear least‐squares (LLSQ) method. The usefulness of this method was investigated by means of computer simulations, in comparison with the nonlinear least‐squares (NLSQ) method. The new method calculated the above parameters faster than the NLSQ method by a factor of approximately 6, and estimated them more accurately than the NLSQ method at a signal‐to‐noise ratio (SNR) of < ∼10. This method will be useful for generating functional images of K1, k2, and Vp from DCE‐MRI data. Magn Reson Med 51:858–862, 2004. © 2004 Wiley‐Liss, Inc.
Quantitative assessment of uptake and distribution of iron oxide particles (NC100150) in human melanoma xenografts by contrast‐enhanced MRI
Authors: Graff Bjørn A. , Vangberg Lars , Rofstad Einar K.
Published: March 2004

The intratumor heterogeneity in uptake of iron oxide particles (NC100150) in human melanoma xenografts was studied by MRI and the uptake was related to the blood volume fraction, BV, and the permeability surface area product, PS, in an attempt to identify transport barriers limiting the delivery of large macromolecular therapeutic agents to tumors. Dynamic MRI was performed by using spoiled gradient recalled sequences and the extravascular uptake of NC100150, BV, and PS were calculated for each tumor voxel by using a two‐compartment tissue model. The uptake of NC100150 and BV were low in the tumor center and increased gradually towards the tumor periphery, whereas there was no radial gradient in PS. Significant correlations were found between the voxel values of the parameters. Thus, PS was inversely correlated to BV, and this correlation was stronger in the center than in the periphery of the tumors. The uptake of NC100150 was positively correlated to PS and this correlation was strong in the tumor periphery, where the blood perfusion is high, and weak in the tumor center, where the blood perfusion is low. In contrast, the uptake of NC100150 was not correlated to BV in any tumor region. These observations suggest that the extravascular uptake of NC100150 was limited primarily by the microvascular permeability in the tumor periphery and primarily by the blood perfusion in the tumor center. Magn Reson Med 51:727–735, 2004. © 2004 Wiley‐Liss, Inc.
View‐ordering in radial fast spin‐echo imaging
Authors: Theilmann Rebecca J. , Gmitro Arthur F. , Altbach Maria I. , Trouard Theodore P.
Published: March 2004

Radial MRI sequences are frequently used to obtain images with reduced sensitivity to motion. To decrease imaging time, multiple spin‐echo acquisitions can be incorporated into radial sequences. In this case, different radial lines of Fourier data have different TE times and the resulting images can contain streaking artifacts due to T2 decay. The streaking is not only dependent on the T2 of the object and the timing of the data acquisition, but also on the order in which radial lines are collected (view order). The view ordering can easily be controlled to minimize artifacts due to T2 decay as well as motion. Four view‐ordering techniques are presented and evaluated for the radial FSE sequence. Magn Reson Med 51:768–774, 2004. © 2004 Wiley‐Liss, Inc.
The effect of gradient sampling schemes on measures derived from diffusion tensor MRI: A Monte Carlo study†
Authors: Jones Derek K.
Published: March 2004

There are conflicting opinions in the literature as to whether it is more beneficial to use a large number of gradient sampling orientations in diffusion tensor MRI (DT‐MRI) experiments than to use a smaller number of carefully chosen orientations. In this study, Monte Carlo simulations were used to study the effect of using different gradient sampling schemes on estimates of tensor‐derived quantities assuming a b‐value of 1000 smm–2. The study focused in particular on the effect that the number of unique gradient orientations has on uncertainty in estimates of tensor‐orientation, and on estimates of the trace and anisotropy of the diffusion tensor. The results challenge the recently proposed notion that a set of six icosahedrally‐arranged orientations is optimal for DT‐MRI. It is shown that at least 20 unique sampling orientations are necessary for a robust estimation of anisotropy, whereas at least 30 unique sampling orientations are required for a robust estimation of tensor‐orientation and mean diffusivity. Finally, the performance of sampling schemes that use low numbers of sampling orientations, but make efficient use of available gradient power, are compared to less efficient schemes with larger numbers of sampling orientations, and the relevant scenarios in which each type of scheme should be used are discussed. Magn Reson Med 51:807–815, 2004. Published 2004 Wiley‐Liss, Inc.
Resolution‐insensitive velocity and flow rate measurement in low‐background phase‐contrast MRA
Authors: van der Weide Remko , Viergever Max A. , Bakker Chris J. G.
Published: March 2004

Magnetic resonance (MR) phase‐contrast (PC) flow measurements are degraded by partial volume errors when the spatial resolution is low, in particular when a large difference in signal magnitude exists between the fluid and the surrounding material. The latter is often the case in phantom studies and may be encountered when flow is measured in prosthetic vessel segments (such as shunts, grafts, and bypasses) and in contrast‐enhanced blood. This paper presents a new method that is designed to measure flow in vessels of circular cross‐section with Poiseuille flow and negligible background signal arising from static material around the lumen. The method calculates the average flow velocity directly from the original complex image data by integrating the signal in oppositely velocity‐sensitized PC images. The radius is calculated from the summed signal modulus. The method allows accurate and resolution‐insensitive measurements of the average flow velocity to be obtained in both cross‐sectional and in‐plane acquisitions. It is not critical to any of the assumed conditions. The validity and capabilities of the proposed technique are demonstrated by in vitro experiments. Magn Reson Med 51:785–793, 2004. © 2004 Wiley‐Liss, Inc.
MRI assessment of neuropathology in a transgenic mouse model of Alzheimer's disease
Authors: Helpern Joseph A. , Lee Sang‐Pil , Falangola Maria F. , Dyakin Victor V. , Bogart Adam , Ardekani Babak , Duff Karen , Branch Craig , Wisniewski Thomas , de Leon Mony J. , Wolf Oliver , O'Shea Jacqueline , Nixon Ralph A.
Published: March 2004

The cerebral deposition of amyloid β‐peptide, a central event in Alzheimer's disease (AD) pathogenesis, begins several years before the onset of clinical symptoms. Noninvasive detection of AD pathology at this initial stage would facilitate intervention and enhance treatment success. In this study, high‐field MRI was used to detect changes in regional brain MR relaxation times in three types of mice: 1) transgenic mice (PS/APP) carrying both mutant genes for amyloid precursor protein (APP) and presenilin (PS), which have high levels and clear accumulation of β‐amyloid in several brain regions, starting from 10 weeks of age; 2) transgenic mice (PS) carrying only a mutant gene for presenilin (PS), which show subtly elevated levels of Aβ‐peptide without β‐amyloid deposition; and 3) nontransgenic (NTg) littermates as controls. The transverse relaxation time T2, an intrinsic MR parameter thought to reflect impaired cell physiology, was significantly reduced in the hippocampus, cingulate, and retrosplenial cortex, but not the corpus callosum, of PS‐APP mice compared to NTg. No differences in T1 values or proton density were detected between any groups of mice. These results indicate that T2 may be a sensitive marker of abnormalities in this transgenic mouse model of AD. Magn Reson Med 51:794–798, 2004. © 2004 Wiley‐Liss, Inc.