At magnetic resonance (MR) imaging and multidetector computed tomography (CT), artifacts arising from metallic orthopedic hardware are an obstacle to obtaining optimal images. Although various techniques for reducing such artifacts have been developed and corroborated by previous researchers, a new era of more powerful MR imaging and multidetector CT modalities has renewed the importance of a systematic consideration of methods for artifact reduction. Knowledge of the factors that contribute to artifacts, of related theories, and of artifact reduction techniques has become mandatory for radiologists. Factors that affect artifacts on MR images include the composition of the metallic hardware, the orientation of the hardware in relation to the direction of the main magnetic field, the strength of the magnetic field, the pulse sequence type, and other MR imaging parameters (mainly voxel size, which is determined by the field of view, image matrix, section thickness, and echo train length). At multidetector CT, the factors that affect artifacts include the composition of the hardware, orientation of the hardware, acquisition parameters (peak voltage, tube charge, collimation, and acquired section thickness), and reconstruction parameters (reconstructed section thickness, reconstruction algorithm used, and whether an extended CT scale was used). A comparison of images obtained with different hardware and different acquisition and reconstruction parameters facilitates an understanding of methods for reducing or overcoming artifacts related to metallic implants.
Piscidin 1 (Pis-1) is a novel cytotoxic peptide with a cationic alpha-helical structure that was isolated from the mast cells of hybrid striped bass [Silphaduang, U., and Noga, E. J. (2001) Nature 414, 268-269]. Pis-1 is not selective for bacterial versus mammalian cells. In the present study, to develop novel antibiotic peptides with selectivity for bacterial cells, we examined the effect of substituting two glycine residues, Gly8 and Gly13, with Ala or Pro on this peptide's structure and biological activities. The bacterial cell selectivity of the peptides decreased in the following order: Gly-->Pro analogues > Gly-->Pro/Ala analogues > Pis-1 > Gly-->Ala analogues. The antimicrobial and hemolytic activities and abilities to permeabilize the model phospholipid membranes were higher for Pis-1 with Gly or Pro at position 8 than for its counterparts with either Gly or Pro at position 13. We determined the tertiary structure of Pis-1 and its analogues in the presence of SDS micelles by NMR spectroscopy. We found that Pis-1 has an alpha-helical structure from Phe2 to Thr21. Also, Pis-1 AA (Gly8, Gly13-->Ala8, Ala13) with higher antibacterial and hemolytic activity than Pis-1 has a stable alpha-helical structure from Phe2 to Thr21. Pis-1 PG (Gly-->Pro8) with bacterial cell selectivity has a hinge structure at Pro8, which provides flexibility in piscidin, followed by a three-turn helix from Val10 to Gly22 in the C-terminal region. Taken together, our results demonstrate that the conformational flexibility provided by introduction of a Pro at position 8, coupled with the primary anchoring of phenylalanines and histidines in the N-terminus to the cell membrane and the optimal length of the C-terminal amphipathic alpha-helix, are the critical factors that confer antibacterial activity and bacterial cell selectivity to Pis-1 PG. Pis-1 PG may be a good candidate for the development of a new drug with potent antibacterial activity but without cytotoxicity.
Two-component signal transduction systems, commonly found in prokaryotes, typically regulate cellular functions in response to environmental conditions through a phosphorylation-dependent process. A new type of response regulator, hp1043 (HP-RR) from Helicobacter pylori, has been recently identified. HP-RR is essential for cell growth and does not require the well known phosphorelay scheme. Unphosphorylated HP-RR binds specifically to its own promoter (P 1043 ) and autoregulates the promoter of the tlpB gene (P tlpB ). We have determined the structure of HP-RR by NMR and x-ray crystallography, revealing a symmetrical dimer with two functional domains. The molecular topology resembles that of the OmpR/PhoB subfamily, however, the symmetrical dimer is stable even in the unphosphorylated state. The dimer interface, formed by three secondary structure elements (␣4-5-␣5), resembles that of the active, phosphorylated forms of ArcA and PhoB. Several conserved residues of the HP-RR dimeric interface deviate from the OmpR/PhoB subfamily, although there are similar salt bridges and hydrophobic patches within the interface. Our findings reveal how a new type of response regulator protein could function as a cell growth-associated regulator in the absence of post-translational modification.
Piscidin 1 (Pis-1) is a novel cytotoxic peptide with a cationic alpha-helical structure isolated from the mast cells of hybrid striped bass. In our previous study, we showed that Pis-1[PG] with a substitution of Pro(8) for Gly(8) in Pis-1 had higher bacterial cell selectivity than Pis-1. We designed peptoid residue-substituted peptide, Pis-1[NkG], in which Gly(8) of Pis-1 was replaced with Nlys (Lys peptoid residue). Pis-1[NkG] had higher antibacterial activity and lower cytotoxicity against mammalian cells than Pis-1 and Pis-1[PG]. We determined the tertiary structure of Pis-1[PG] and Pis-1[NkG] in the presence of DPC micelles by NMR spectroscopy. Both peptides had a three-turn helix in the C-terminal region and a bent structure in the center. Pis-1[PG] has a rigid bent structure at Pro(8) whereas Pis-1[NkG] existed as a dynamic equilibrium of two conformers with a flexible hinge structure at Nlys(8). Depolarization of the membrane potential of Staphylococcus aureus and confocal laser-scanning microscopy study revealed that Pis-1[NkG] effectively penetrated the bacterial cell membrane and accumulated in the cytoplasm, whereas Pis-1[PG] did not penetrate the membrane but remained outside or on the cell surface. Introduction of a lysine peptoid at position 8 of Pis-1 provided conformational flexibility and increased the positive charge at the hinge region; both factors facilitated penetration of the bacterial cell membrane and conferred bacterial cell selectivity on Pis-1[NkG].
The diagnosis of nerve entrapment and compressive neuropathy has been traditionally based on the clinical and electrodiagnostic examinations. As a result of improvements in the magnetic resonance (MR) imaging modality, it plays not only a fundamental role in the detection of space-occupying lesions, but also a compensatory role in clinically and electrodiagnostically inconclusive cases. Although ultrasound has undergone further development in the past decades and shows high resolution capabilities, it has inherent limitations due to its operator dependency. We review the course of normal peripheral nerves, as well as various clinical demonstrations and pathological features of compressed and entrapped nerves in the upper extremities on MR imaging, according to the nerves involved. The common sites of nerve entrapment of the upper extremity are as follows: the brachial plexus of the thoracic outlet; axillary nerve of the quadrilateral space; radial nerve of the radial tunnel; ulnar nerve of the cubital tunnel and Guyon's canal; median nerve of the pronator syndrome, anterior interosseous nerve syndrome, and carpal tunnel syndrome. Although MR imaging can depict the peripheral nerves in the extremities effectively, radiologists should be familiar with nerve pathways, common sites of nerve compression, and common space-occupying lesions resulting in nerve compression in MR imaging.
Vascular endothelial growth factor (VEGF), which has neurotrophic and neuroprotective effects in addition to its major role in angiogenesis, interacts with Aβ and accumulates in the senile plaques of Alzheimer's disease (AD) patients' brains. It is known that Aβ binds to the heparin-binding domain (HBD) of the 165-amino acid VEGF variant, VEGF(165). In this study, we showed that triamterene (Trm) inhibits VEGF--Aβ interaction without affecting other biological activities of VEGF or Aβ. We investigated the importance of structural and dynamic features of HBD for its molecular-recognition processes. The binding model of HBD and Trm was constructed based on measurements of chemical shift changes and docking study. The results showed that the loop region (S11-L17) and F18 at the beginning of the first β-sheet in the HBD constitute the inhibitor binding site. The N1 atom of pteridine ring of Trm forms hydrogen bonding with backbone amide proton of R13, and the phenyl ring took part in a hydrophobic interaction with the aromatic ring of F18. To investigate the functional importance of the inherent structural flexibility of the HBD in VEGF, the dynamic properties of free HBD and HBD--Trm complex were assessed by measuring spin relaxation rates, and the backbone dynamics were investigated by model-free analysis. The residues in the disordered loop region of the N-terminus exhibited conformational exchanges in free HBD, and flexibility of this loop region decreased dramatically upon binding to Trm, suggesting that Aβ as well as inhibitor may recognize these unique dynamic features of the HBD. Furthermore, C-terminal residues continued to exhibit slow conformational motions, even in the HBD--Trm complex, implying that these motions at the C-terminus of the HBD might be important for interactions with heparin molecules. The flexibility of HBD demonstrated here should be essential for VEGF function and interaction with other protein partners.
Purpose : We wanted to determine the diagnostic accuracy of 16-slice MDCT arthrography (CTA) for glenoid labral and rotator cuff tears of the shoulder. Materials and Methods: We enrolled forty-five patients who underwent arthroscopy after CTA for pain or instability of the shoulder joint. The CTA images were analyzed for the existence, sites and types of glenoid labral tears and the presence and severity of rotator cuff tears. We determined the sensitivity, specificity and accuracy of CTA for detecting glenoid labral and rotator cuff tears on the basis of the arthroscopy findings. Results: At arthroscopy, there were 33 SLAP lesions (9 type I, 23 type II and 1 type III), 6 Bankart lesions and 31 rotator cuff lesions (21 supraspinatus, 9 infraspinatus and 1 subscapularis). On CTA, the sensitivity, specificity and accuracy for detecting 24 SLAP lesions, excluding the type I lesions, were 83%, 100% and 91%, the total rotator cuff tears were 90%, 100% and 98%, the full thickness supraspinatus tendon tears were 100%, 94% and 96%, and the partial thickness supraspinatus tendon tears were 29%, 100% and 89%, respectively. Conclusion: 16-slice MDCT arthrography has high accuracy for the diagnosis of abnormality of the glenoid labrum or rotator cuff tears and it can be a useful alternative to MRI or US.
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