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Locally delivered rhTGF-beta2 enhances bone ingrowth and bone regeneration at local and remote sites of skeletal injury.

The purposes of the present study were to determine if recombinant human transforming growth factor-beta-2 (rhTGF-beta2) enhances bone ingrowth into porous-coated implants and bone regeneration in gaps between the implant and surrounding host bone. The implants were placed bilaterally for four weeks in the proximal humeri of skeletally mature, adult male dogs in the presence of a 3-mm gap. In three treatment groups of animals, the test implant was treated with hydroxyapatite/tricalcium phosphate (HA/TCP) and rhTGF-beta2 in buffer at a dose per implant of 1.2 microg (n = 6), 12 microg (n = 7), or 120 microg (n = 7) and placed in the left humerus. In these same animals, an internal control implant treated only with HA/TCP and buffer was placed in the right humerus. In a non-TGF-beta treated external control group of animals (n = 7), one implant was treated with HA/TCP while the contralateral implant was not treated with the ceramic. In vitro analyses showed that approximately 15%, of the applied dose was released within 120 h with most of the release occurring in the first 24 h. The TGF-beta treated implants had significantly more bone ingrowth than the controls with the greatest effect in the 12 microg/implant group (a 2.2-fold increase over the paired internal control (P = 0.004) and a 4-fold increase over the external control (P < 0.001)). The TGF-beta treated implants had significantly more bone formation in the gap than the controls with the greatest effect in the 12 and 120 microg groups (1.8-fold increases over the paired internal controls (P = 0.003 and P = 0.012, respectively) and 2.8-fold increases over the external controls (P < 0.001 and P = 0.001, respectively)). Compared to the external controls, the internal control implants tended to have more bone ingrowth (1.9-fold increase, P = 0.066) and had significantly more bone formation in the gap (1.7-fold increase. P = 0.008). Thus, application of rhTGF-beta2 to a porous-coated implant-stimulated local bone ingrowth and gap healing in a weakly dose-dependent manner and stimulated bone regeneration in the 3-mm gap surrounding the contralateral control implant, a site remote from the local treatment with the growth factor.

Animals↗

Systematic study of nuclear Overhauser effects vis-à-vis local helical parameters, sugar puckers, and glycosidic torsions in B DNA: insensitivity of NOE to local transitions in B DNA oligonucleotides due to internal structural compensations.

A method has been developed to solve structures of DNA oligomers in solution from the experimental NOE data. The method is a combination of two approaches: (1) full matrix NOESY simulations and (2) conformational calculations of DNA double helix based on generalized helical parameters. The process of the refinement of a solution structure does not involve NMR-derived interproton distance constraints; rather it consists of a direct fitting of a structure to the experimental NOE data, a weighted sum of energy, and R factor being under minimization. A helical parameters-based generation of DNA forms makes it possible to organize the search for the optimal structure more effectively, systematically varying starting conformations. The method has been used to calculate a structure for the self-complementary DNA hexamer GGATCC, which is consistent with the available experimental data. The structure belongs to the B family of forms, although the local structural heterogeneity is very strong. Sugar puckers vary from O4'-exo to C3'-exo; helical steps are open with different magnitudes toward the minor groove. Next, we have addressed the question of how uniquely the structure is defined by the existing NMR data. Different structural parameters have been systematically varied, and their effect on individual NOE's and the R factor has been studied. Two energetically conjugated parameters, sugar puckers and glycosidic angles, can be determined very reliably, because of the strong dependences of the intraresidue H6/H8 to H2'/H2''/H3' NOE's. In contrast, the local helical conformation of DNA and the geometry of base pairs proved to be underdetermined by the existing NOE information, because the effect of any helical parameter on interproton distances can be compensated by the concerted changes in other parameters.

Base Composition↗

Local base dynamics and local structural features in RNA and DNA duplexes.

Local base motion and local structural base information are derived with a simple motional model from site specifically spin-labeled polyribo- and polydeoxyribonucleotides. The model was developed earlier for some nucleic acids and has now been applied to analyze 22 different nucleic acid systems. We conclude that the base motion of the spin-labeled nucleotide in single-stranded RNA, DNA, or non-base-paired bases in duplexes is of the order of 1 ns and that its base mobility decreases by about a factor of 4 upon base pairing. Also, the tether motion of the probe is slower in an RNA than in a DNA duplex.

DNA↗

Topographical localization of peroxisomal acyl-CoA ligases: differential localization of palmitoyl-CoA and lignoceroyl-CoA ligases.

We found that peroxisomal lignoceroyl-CoA ligase, like palmitoyl-CoA ligase, is present in the peroxisomal membrane whereas the peroxisomal beta-oxidation enzyme system is localized in the matrix. To further define the role of peroxisomal acyl-CoA ligases (membrane component) in providing acyl-CoA for peroxisomal beta-oxidation, we examined the transverse topographical localization of enzymatic sites of palmitoyl-CoA and lignoceroyl-CoA ligases in the peroxisomal membranes. The disruption of peroxisomes by various techniques resulted in the release of a "latent" pool of lignoceroyl-CoA ligase activity while palmitoyl-CoA ligase activity remained the same. Proteolytic enzyme treatment inhibited palmitoyl-CoA ligase activity in intact peroxisomes but had no effect on lignoceroyl-CoA ligase activity. Lignoceroyl-CoA ligase activity was inhibited only if peroxisomes were disrupted with detergent before trypsin treatment. Antibodies to palmitoyl-CoA ligase and to peroxisomal membrane proteins (PMP) inhibited palmitoyl-CoA ligase in intact peroxisomes, and no pool of "latent" activity appeared when antibody-treated peroxisomes were disrupted with detergent. On the other hand, disruption of PMP antibody-treated peroxisomes with detergent resulted in the appearance of a "latent" pool of lignoceroyl-CoA ligase activity. These results demonstrate that the enzymatic site of palmitoyl-CoA ligase is on the cytoplasmic surface whereas that for lignoceroyl-CoA ligase is on the luminal surface of peroxisomal membranes. This implies that palmitoyl-CoA is synthesized on the cytoplasmic surface and is then transferred to the matrix through the peroxisomal membrane for beta-oxidation in the matrix.(ABSTRACT TRUNCATED AT 250 WORDS)

Acyl Coenzyme A↗

Evaluation of a double-tracer autoradiographic technique for the measurement of both local cerebral glucose metabolism and local cerebral blood flow.

A solvent washout technique is evaluated that could be used to remove one 14C tracer after a combined autoradiographic CMRglu and CBF study using [14C]2-deoxyglucose (2DG) and [14C]iodoantipyrine (IAP). The technique permits the simultaneous measurement of local CBF and local CMRglu in the same animal without the use of the short-lived tracers of iodine, 123I and 131I, for iodoantipyrine labeling. This report shows that brain tissue sections did not retain 14C from [14C]2DG when chloroform was used as the washout solvent. Chloroform washing removes nearly all the 14C from [14C]IAP. For this study, careful attention was given to the control, prewash measurement of 14C concentration.

Animals↗

Localization of epitopes for monoclonal antibodies to urokinase-type plasminogen activator: relationship between epitope localization and effects of antibodies on molecular interactions of the enzyme.

We localized the epitopes for several murine mAbs to human urokinase-type plasminogen activator (uPA) by Ala scanning mutagenesis and related the localization to the effects of the mAbs on the molecular interactions of uPA. Several antibodies against the serine proteinase domain (SPD) were found to have overlapping epitopes composed of variable combinations of Arg178, Arg179, His180, Arg181, Tyr209, Lys211, and Asp214 in the so-called 37-loop and 60-loop, located near the active site and taking part in the binding of uPA to plasminogen activator inhibitor-1 (PAI-1). Besides inhibiting uPA-catalysed plasminogen activation, all antibodies to SPD strongly delayed the binding of uPA to PAI-1, decreasing the second-order rate constant 15- to 6500-fold. There was no correlation between the relative effects of the 37-loop and 60-loop substitutions on the second-order rate constant and on the binding of the antibodies, indicating that the antibodies did not delay complex formation by blocking residues of specific importance for the uPA-PAI-1 reaction, but rather by steric hindrance of the access of PAI-1 to the active site. The affinity of the SPD antibodies for the uPA-PAI-1 complex was only slightly lower than that for free uPA, indicating that the 37-loop and 60-loop are exposed in the complex. The epitopes for two antibodies to the kringle included Arg108, Arg109, and Arg110. The ability of these antibodies to block the binding of uPA to polyanions correlated with a reduced uPA-polyanion affinity after substitution of the three Arg residues.

Animals↗

Complications of treatment with local field external beam radiotherapy for localized prostate cancer.

We performed this analysis to document the rate and severity of complications both during and after local field irradiation for localized prostate cancer and to assess the influence of three-dimensional conformal radiation therapy (3DCRT) on these complications. Bowel, urinary and cutaneous toxicities were noted in all patients treated with primary radiotherapy (RT) for prostate cancer using Radiation Therapy Oncology Group/European Organization for Research on Treatment of Cancer scores. Evaluations were performed weekly during RT, 6 weeks after RT and 3 monthly thereafter. Data on 111 were analysed. We also compared the complications of conventional and 3DCRT. The serious complication rates identified in this study compare favourably with those reported in the literature. Only 3.6%, 0.8% and 0% had acute grade 3 or 4 urinary, bowel or skin reactions respectively. Only two patients had chronic grade 3 or 4 urinary complications. Thus far no patients have developed chronic bowel or skin complications greater than grade 2. Despite dose escalation from 66 Gy to 70 Gy (with 3DCRT), there was a trend towards reduced toxicity when 3DCRT was compared with conventional radiation. RT is a well-tolerated treatment for early stage carcinoma of the prostate and our complication rates are compatible with international experiences. Further follow-up is required to determine the efficacy of treatment, the incidence of impotence and the final number of late complications.

Adenocarcinoma↗

Evaluation of total choline from in-vivo volume localized proton MR spectroscopy and its response to neoadjuvant chemotherapy in locally advanced breast cancer.

Results of the proton magnetic resonance spectroscopy carried out on normal, benign breast disease and locally advanced breast cancer patients are presented. The in-vivo MR spectra of malignant breast tissue of patients (n = 67) suffering from infiltrating ductal carcinoma are dominated by the water resonance, while the spectra of the unaffected contralateral breast tissue of these patients are mainly dominated by resonance arising from lipids which is similar to the spectra of normal breast tissue obtained from volunteers (controls, n = 16). In addition to the water and lipid peaks, in majority of the patients (approximately 80%) the water suppressed spectra showed a resonance at 3.2 ppm due to choline containing compounds (TCho) before treatment. In patients receiving neoadjuvant chemotherapy, absence/reduction in choline was observed in 89% of the patients. TCho was also observed in 2 of 14 benign lesions. The sensitivity and specificity of in-vivo MRS in detecting TCho in malignant tumours was 78% and 86%, respectively. Observation of TCho before treatment and its disappearance (or reduction) after treatment may be a useful indicator of response of locally advanced breast cancer to neoadjuvant chemotherapy.

Adult↗

The complex of recombinant human insulin-like growth factor-I (rhIGF-I) and its binding protein-5 (IGFBP-5) induces local bone formation in murine calvariae and in rat cortical bone after local or systemic administration.

The influence of recombinant human insulin-like growth factor-I (rhIGF-I), its binding protein-5 (IGFBP-5) or their equimolar complexes on calvarial osteogenesis was investigated by quantitative radiography and histomorphometry after local administration to adult mice or mature rats. The systemic effects of these proteins were investigated in aged Sprague-Dawley rats with regard to their ability to prevent or restore bone mass in ovariectomy induced osteopenia as assessed by radiography, dual-energy X-ray absorptiometry (DEXA) analyses, peripheral computerized tomography (pQCT) and mineral analyses after daily s.c. administration for 3 or 8 weeks following a bone depletion period of 8 weeks. Bone mass of murine calvariae was significantly increased in a dose-dependent manner by the complex 7 days after discontinuation of local administration for 19 days in mice, whereas IGF-I alone expressed only weak effects. IGFBP-5 alone was ineffective in this respect. In the same model, only the complex had a weak osteogenetic potential in 7 week or 5 month old rats. Systemic long-term treatment with the complex of rhIGF-I/IGFBP-5 (2.0/7.6 mg/kg/day, s.c.) for 8 weeks resulted in significantly increased cortical thickness, area and mineral density in femoral midshaft or tibial metaphysis suggesting periosteal bone formation. This was obviously related to increased muscle strength since these effects were parallelled by increased body weight. No effect on trabecular bone occurred as demonstrated by site-specific analyses (vertebrae, proximal tibia) using DEXA, pQCT and radiography. This selective action of rhIGF-I/IGFBP-5 on periosteal bone formation is unique for an IGFBP. Femoral ash and calcium content, both corrected for tissue volume, increased slightly. However, when the increase in cortical thickness and bone mass was corrected for bone size, the effects are nearly abolished, suggesting an additional effect of bone growth. This potential deserves further evaluation in order to differentiate between effects on cortical bone via muscle strength and lack of efficacy on trabecular bone balance.

Age Factors↗

Localization of superficial cerebral lesions using a magnetic resonance imaging-guided localizer.

The localization of superficial cerebral lesions may be difficult even if they reach the surface of the cerebral cortex. Intraoperative ultrasound often fails to detect subcortical lesions. A localization device using multiplanar MR-imaging has been designed to project such lesions to the scalp. This device is a hood-shaped grid made of polyethylene tubing filled with paramagnetic contrast agent. In this hemispherical grid the tubes are arranged at a distance of 15 to 30 mm so that the MR-plane always slices perpendicular to the axis of the tubing and depicts a bright spot per tube. It is rapidly filled prior to each MR-examination, placed on the patient's head, and taped to his forehead to avoid unintentional displacement during and after the examination until the projection of the lesion is marked on the skin.

Brain Neoplasms↗

Local angular momentum-local impact parameter analysis: derivation and properties of the fundamental identity, with applications to the F+H2, H+D2, and Cl+HCl chemical reactions.

The technique of local angular momentum-local impact parameter (LAM-LIP) analysis has recently been shown to provide valuable dynamical information on the angular scattering of chemical reactions under semiclassical conditions. The LAM-LIP technique exploits a nearside-farside (NF) decomposition of the scattering amplitude, which is assumed to be a Legendre partial wave series. In this paper, we derive the "fundamental NF LAM identity," which relates the full LAM to the NF LAMs (there is a similar identity for the LIP case). Two derivations are presented. The first uses complex variable techniques, while the second exploits an analogy between the motion of the scattering amplitude in the Argand plane with changing angle and the classical mechanical motion of a particle in a plane with changing time. Alternative forms of the fundamental LAM-LIP identity are described, one of which gives rise to a CLAM-CLIP plot, where CLAM denotes (Cross section) x LAM and CLIP denotes (Cross section) x LIP. Applications of the NF LAM theory, together with CLAM plots, are reported for state-to-state transitions of the benchmark reactions F+H2-->FH+H, H+D2-->HD+D, and Cl+HCl-->ClH+Cl, using as input both numerical and parametrized scattering matrix elements. We use the fundamental LAM identity to explain the important empirical observation that a NF cross section analysis and a NF LAM analysis provide consistent (and complementary) information on the dynamics of chemical reactions.

Journal Article↗

Immunohistochemical localization of the D1 dopamine receptor in rat brain reveals its axonal transport, pre- and postsynaptic localization, and prevalence in the basal ganglia, limbic system, and thalamic reticular nucleus.

D1 dopamine receptor localization was examined by immunohistochemistry using a polyclonal anti-peptide antibody which (i) immunoprecipitated a protein fragment encoded by a D1 receptor cDNA and (ii) on Western blots of solubilized striatal and hippocampal membranes recognized two proteins of approximately 50 kDa and 75 kDa, corresponding to reported sizes of D1 receptor proteins. Immunoreactivity overlapped with dopamine-containing pathways, patterns of D1 receptor binding, and mRNA expression. Staining was concentrated in prefrontal, cingulate, parietal, piriform, entorhinal, and hippocampal cortical areas and subcortically in the basal ganglia, amygdala, septal area, substantia inominata, thalamus, hypothalamus, and neurohypophysis. Prominent labeling was seen in the thalamic reticular nucleus, a region known to integrate ascending basal forebrain inputs with thalamocortical and corticothalamic pathways and in fiber bundles interconnecting limbic areas. In striatal neuropil, staining appeared in spines (heads and necks), at postsynaptic sites in dendrites, and in axon terminals; in the pars reticulata of the substantia nigra, labeling was prevalent in myelinated and unmyelinated axons and dendrites. These data provide direct evidence for the regional and subcellular distribution of D1 receptor protein in the brain and for its pre- and postsynaptic localization in the basal ganglia. The prominent immunoreactivity seen in the limbic system and thalamic reticular nucleus supports an important role for this receptor subtype in mediating integrative processes involved with learning, memory, and cognition.

Animals↗

Interferon regulatory factor subcellular localization is determined by a bipartite nuclear localization signal in the DNA-binding domain and interaction with cytoplasmic retention factors.

The transduction of type I interferon signals to the nucleus relies on activation of a protein complex, ISGF3, involving two signal transducers and activators of transcription (STAT) proteins, STAT1 and STAT2, and the interferon (IFN) regulatory factor (IRF) protein, p48/ISGF3gamma. The STAT subunits are cytoplasmically localized in unstimulated cells and rapidly translocate to the nucleus of IFN-stimulated cells, but the p48/ISGF3gamma protein is found in both the nucleus and the cytoplasm, regardless of IFN stimulation. Here, we demonstrate that p48 is efficiently and constitutively targeted to the nucleus. Analysis of the subcellular distribution of green fluorescent protein-p48 fragments indicates that p48 contains a bipartite nuclear retention signal within its amino-terminal DNA-binding domain. This signal is preserved in two other IRF proteins involved in immune responses, ICSBP and IRF4. Mutations to clustered basic residues within amino acids 50-100 of p48 or IRF4 disrupt their nuclear accumulation, and DNA-binding ability is not required for nuclear targeting. This is the only example of a nuclear localization signal for any ISGF3 component and assigns a second function to the IRF DNA-binding domain. We also demonstrate that the nuclear distribution of p48 is dramatically altered by coexpression of the STAT2 protein, indicating that STAT2 forms a cytoplasmic complex with p48, overriding the intrinsic p48 nuclear targeting. Retention by STAT2 may serve to regulate the activity of free p48 and/or guarantee that cytoplasmic pools of preassociated STAT2:p48 are available for rapid activation of the IFN response. These findings suggest that analogous mechanisms may exist for regulating the distribution of other IRF proteins.

3T3 Cells↗

The nuclear localization signal of lymphoid enhancer factor-1 is recognized by two differentially expressed Srp1-nuclear localization sequence receptor proteins.

Proteins are directed to the nucleus by their nuclear localization sequences (NLSs) in a multistep process. The first step, which is to dock the NLS-containing protein to the nuclear pore, is carried out in part by a recently identified NLS receptor named Srp1/importin-alpha. Using the high mobility group (HMG) DNA binding domain of human lymphoid enhancer factor-1 (hLEF-1) as bait in a yeast two-hybrid screen, we have identified two different mouse Srp1 proteins (pendulin/importin-alpha and mSrp1) that each bind to a 9-amino acid sequence in hLEF-1 called the B box. We show that the B box of hLEF-1, a region essential for high affinity DNA binding, is also necessary and sufficient for nuclear localization, lending support to the model that NLSs can function both in nuclear transport and DNA binding. Pendulin and mSrp1 are the mouse homologues of hRch1/hSrp1alpha/importin-alpha and hSrp1/karyopherin alpha/NPI-1, respectively, and show considerable sequence divergence from each other. We find a surprising and significant difference in the expression pattern of pendulin and mSrp1 mRNA, suggesting that these two Srp1 proteins are distinguishable in function as well as sequence.

Amino Acid Sequence↗

Strikingly different localization of galectin-3 and galectin-4 in human colon adenocarcinoma T84 cells. Galectin-4 is localized at sites of cell adhesion.

Two beta-galactoside-binding proteins were found to be prominently expressed in the human colon adenocarcinoma T84 cell line. Cloning and sequencing of one, a 36-kDa protein, identified it as the human homolog of galectin-4, a protein containing two carbohydrate binding domains and previously found only in the epithelial cells of the rat and porcine alimentary tract. The other, a 29-kDa protein, is galectin-3, containing a single carbohydrate binding domain, previously found in a number of different cell types including human intestinal epithelium. Despite the marked similarities in the carbohydrate binding domains of these two galectins, their cellular distribution patterns are strikingly different and vary with cellular conditions. In confluent T84 cells, galectin-4 is mostly cytosolic and concentrated at the basal membrane, whereas galectin-3 tends to be concentrated in large granular inclusions mostly at the apical membrane. In subconfluent T84 cells, each galectin is distributed to specific domains of lamellipodia, with galectin-4 concentrated in the leading edge and galectin-3 more proximally. Such different localization of galectins-4 and -3 within T84 cells implies different targeting mechanisms, ligands, and functions. The localization of galectin-4 suggests a role in cell adhesion which is also supported by the ability of immobilized recombinant galectin-4 to stimulate adhesion of T84 cells.

Adenocarcinoma↗

Differences in eNOS activity because of subcellular localization are dictated by phosphorylation state rather than the local calcium environment.

Nitric oxide (NO) produced in the endothelium via the enzyme endothelial nitric-oxide synthase (eNOS) is an important vasoactive compound. Wild-type (WT) eNOS is localized to the plasma membrane and perinuclear/Golgi region by virtue of N-terminal myristoylation and palmitoylation. Acylation-deficient mutants (G2AeNOS) remain cytosolic and release less NO in response to Ca2+-elevating agonists; a disparity that we hypothesized was attributed to the greater distance between G2AeNOS and plasma membrane Ca2+ influx channels. The reduced activity of G2AeNOS versus WT was reversed upon disruption of cellular integrity with detergents or sonication. NO production from both constructs relied almost exclusively on the influx of extracellular Ca2+, and elevating intracellular Ca2+ to saturating levels with 10 microM ionomycin in the presence of 10 mM extracellular Ca2+ equalized NO production. To identify the contribution of calcium to the differences in activity between these enzymes, we created Ca2+/CaM-independent eNOS mutants by deleting the two putative autoinhibitory domains of eNOS. There was no difference in NO production between WT and G2A-targeted Ca2+-independent eNOS, suggesting that Ca2+ was the factor responsible. When eNOS constructs were fused in-frame to the bioluminescent probe aequorin, membrane-bound probes were exposed to higher [Ca2+] in unstimulated cells but upon ionomycin stimulation, the probes experienced equal amounts of Ca2+. The WT and G2A enzymes displayed significant differences in the phosphorylation state of Ser617, Ser635, and Ser1179, and mutating all three sites to alanine or restoring phosphorylation with the phosphatase inhibitor calyculin abolished the differences in activity. We therefore conclude that the disparity in NO production between WTeNOS and G2AeNOS is not caused by different localized [Ca2+] upon stimulation with ionomycin, but rather differences in phosphorylation state between the two constructs.

Animals↗

Differential localization of VE- and N-cadherins in human endothelial cells: VE-cadherin competes with N-cadherin for junctional localization.

The two major cadherins of endothelial cells are neural (N)-cadherin and vascular endothelial (VE)- cadherin. Despite similar level of protein expression only VE-cadherin is located at cell-cell contacts, whereas N-cadherin is distributed over the whole cell membrane. Cotransfection of VE-cadherin and N-cadherin in CHO cells resulted in the same distribution as that observed in endothelial cells indicating that the behavior of the two cadherins was not cell specific but related to their structural characteristics. Similar amounts of alpha- and beta-catenins and plakoglobin were associated to VE- and N-cadherins, whereas p120 was higher in the VE-cadherin complex. The presence of VE-cadherin did not affect N-cadherin homotypic adhesive properties or its capacity to localize at junctions when cotransfectants were cocultured with cells transfected with N-cadherin only. To define the molecular domain responsible for the VE-cadherin-dominant activity we prepared a chimeric construct formed by VE-cadherin extracellular region linked to N-cadherin intracellular domain. The chimera lost the capacity to exclude N-cadherin from junctions indicating that the extracellular domain of VE-cadherin alone is not sufficient for the preferential localization of the molecule at the junctions. A truncated mutant of VE-cadherin retaining the full extracellular domain and a short cytoplasmic tail (Arg621-Pro702) lacking the catenin-binding region was able to exclude N-cadherin from junctions. This indicates that the Arg621-Pro702 sequence in the VE-cadherin cytoplasmic tail is required for N-cadherin exclusion from junctions. Competition between cadherins for their clustering at intercellular junctions in the same cell has never been described before. We speculate that, in the endothelium, VE- and N-cadherin play different roles; whereas VE-cadherin mostly promotes the homotypic interaction between endothelial cells, N-cadherin may be responsible for the anchorage of the endothelium to other surrounding cell types expressing N-cadherin such as vascular smooth muscle cells or pericytes.

Animals↗

Quantification of signal selection efficiency, extra volume suppression and contamination for ISIS, STEAM and PRESS localized 1H NMR spectroscopy using an EEC localization test object.

The three most widely used single-volume NMR localization techniques (ISIS, STEAM and PRESS) are assessed quantitatively for 1H spectroscopy using an EEC localization test object. Signal selection efficiency, suppression of outer volume signals and contamination are measured on a 1.5 T whole-body Siemens GBS1 system. The ISIS signal selection efficiency (volume of interest (VOI), 1-125 cm3) ranged from 90% to 95%, with T1 relaxation during the sequence shown to account for the observed 5-10% signal loss. Contamination for ISIS was found to be higher for smaller VOIS and ranged from approximately 45% (VOI = 1 cm3) to approximately 9% (VOI = 125 cm3). For PRESS, contamination ranged from 7% to 12% and it was between 3% and 8% for STEAM. However, the maximum signal selection efficiency for the latter two techniques (echo time, 270 ms) was relatively low (10-17%), and limited by T2 losses and the non-rectangular slice profiles of sinc pulses.

Humans↗