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1.
Hand Surg Rehabil ; 41(1): 90-95, 2022 02.
Article in English | MEDLINE | ID: mdl-34763114

ABSTRACT

Magnetic resonance imaging (MRI) can evaluate nerve morphology in cubital tunnel syndrome (CuTS), but its value in predicting surgical outcome is unclear. The purpose of this study was to determine whether ulnar nerve morphology on MRI correlated with outcome after CuTS surgery. We reviewed 40 patients who had preoperative MRI and electrodiagnostic (EDX) examinations for CuTS and outcome evaluation 6 months and 2 years postoperatively. Using MRI, ulnar nerve cross-sectional area (UNCSA), changes in signal intensity, and any space-occupying lesion were evaluated. Other factors assessed were age, symptom duration and severity, type-2 diabetes and EDX parameters. Factors associated with unfavorable surgical outcome were identified. At 6 months postoperatively, 12 patients (30%) had excellent, 19 (47.5%) good, 8 (20%) fair and 1 (2.5%) poor results on modified Wilson-Krout criteria. On univariate analysis, unfavorable outcomes were associated with increased UNCSA, space-occupying lesion, and decreased motor nerve conduction velocity (mNCV), and on multivariate analysis with increased UNCSA 1 cm distal from the epicondyle only (model 1) or increased UNCSA 1 cm proximal from the epicondyle and decreased mNCV (model 2). At 2 years, 15 patients (37.5%) had excellent, 21 (52.5%) good, 3 (7.5%) fair and 1 (2.5%) poor results, and no factors correlated with unfavorable outcome. Increased UNCSA on MRI was associated with unfavorable outcome at 6 months but not at 2 years. This study suggests that morphologic ulnar nerve changes can predict delayed nerve recovery after surgery for CuTS.


Subject(s)
Cubital Tunnel Syndrome , Cubital Tunnel Syndrome/surgery , Humans , Magnetic Resonance Imaging , Ulnar Nerve/diagnostic imaging , Ulnar Nerve/surgery
2.
Clin Radiol ; 73(9): 835.e17-835.e25, 2018 09.
Article in English | MEDLINE | ID: mdl-29910017

ABSTRACT

AIM: To evaluate the prevalence, clinical relevance, and magnetic resonance imaging (MRI) features of extra-capsular ganglia at the gastrocnemius origin and to assess their association with internal derangement and osteoarthritis of the knee. MATERIALS AND METHODS: One hundred consecutive knee MRI examinations, obtained within a 6-month period from patients with no history of recent knee trauma, recent injections, inflammatory arthritis, infection, or tumours, were evaluated retrospectively for the presence of ganglia at the gastrocnemius origin. The lesions were divided into two groups: an intra-capsular and an extra-capsular group. Cyst morphology (size, shape, and internal septa), internal derangement of the knee (cartilage lesion, cruciate ligament injury, meniscal tear, and corner injury on MRI, and osteoarthritis of the knee on radiographs) were evaluated. The chi-square, Fisher's exact, and t-tests were used to compare the two groups, in addition to multivariate stepwise logistic regression analysis. RESULTS: Thirty-nine ganglia with an extra-capsular location were identified on 100 knee MRI (39 %). Rounded shape and internal septa were more common in the extra-capsular than in the intra-capsular group (p<0.001). Frequencies of high-grade cartilage, meniscal tear, and high-grade osteoarthritis significantly differed between the groups (p≤0.038). In multivariate analysis, the only significant association was between high-grade osteoarthritis and the extra-capsular group. CONCLUSION: Extra-capsular ganglia at the gastrocnemius origin were not uncommon on knee MRI and had features typical of ganglia found at other sites. High-grade osteoarthritis was significantly associated with extra-capsular ganglia.


Subject(s)
Ganglia/diagnostic imaging , Magnetic Resonance Imaging/methods , Muscle, Skeletal/diagnostic imaging , Osteoarthritis, Knee/diagnostic imaging , Adolescent , Adult , Aged , Female , Humans , Image Interpretation, Computer-Assisted , Male , Middle Aged , Retrospective Studies
3.
Clin Radiol ; 72(1): 96.e7-96.e14, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27639917

ABSTRACT

AIM: To evaluate the efficacy of facet joint injection (FJI) for patients with lumbar central canal stenosis (LCS) in comparison with epidural steroid injection (ESI) in the same individuals. MATERIAL AND METHODS: Two hundred and fifty-two patients who underwent both FJI and ESI for LCS between January 2014 and December 2014 were considered for enrolment in the study. A radiologist retrospectively conducted a chart review and recorded which injection was chosen as the third injection after sequential injections of FJI and ESI, and why clinicians chose the particular injection method. The response was measured via the use of a five-point satisfaction scale. RESULTS: Among 252 patients, only 73 patients were included in the study (the remaining patients did not fulfil the inclusion criteria). Out of 73 patients (mean age, 69.7 years; range, 49∼87 years), 50 patients had received a third injection, 33 patients (66%) underwent FJIs as a third injection. Out of 19 patients who had experienced an ineffective first ESI, 13 (68.4%) patients reported the second FJI as effective. Out of six patients for whom the first FJI had been ineffective, three (50%) patients reported the second ESI as effective. CONCLUSION: FJIs can be administered as an alternative to ESIs in cases of LCS.


Subject(s)
Injections, Epidural/methods , Low Back Pain/drug therapy , Spinal Stenosis/drug therapy , Steroids/administration & dosage , Zygapophyseal Joint/drug effects , Aged , Aged, 80 and over , Female , Humans , Injections, Intra-Articular/methods , Low Back Pain/diagnosis , Low Back Pain/etiology , Male , Middle Aged , Pregnancy , Radiography, Interventional/methods , Retrospective Studies , Spinal Stenosis/complications , Spinal Stenosis/diagnostic imaging , Treatment Outcome , Zygapophyseal Joint/diagnostic imaging
4.
Clin Radiol ; 71(4): 381-8, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26868864

ABSTRACT

AIM: To investigate the magnetic resonance imaging (MRI) findings of spinal arteriovenous fistulas (AVFs) to predict their locations and types. MATERIALS AND METHODS: Patients who underwent spinal angiography for suspected spinal AVF between April 2003 and April 2013 were enrolled. Spine MRI images were analysed by two radiologists in consensus focusing on the distribution patterns of flow void pial vessels (FVPVs): longitudinal distribution pattern along the spinal level (even or uneven, with description of the most crowded level in uneven cases) and axial distribution pattern in relation to the cord (ventral, dorsal, or co-dominance). Spinal angiography served as the reference standard for the locations and types of fistulas. RESULTS: Thirty-two patients (M:F=24:8, mean age, 53 years; range, 2-74 years) were included. There were 18 patients with spinal dural AVFs (SDAVFs), seven with perimedullary AVFs, four with epidural AVFs, and three diagnosed as normal. In 12 of 15 longitudinally uneven AVFs, the most crowded levels of FVPVs corresponded to the true fistulous levels within two-level differences. While dorsal dominance was predominant in SDAVFs (13/18), ventral dominance was predominant in perimedullary AVFs (5/7; p<0.01). CONCLUSION: Fistulous levels may be predicted to be within two levels of the most crowded levels of FVPVs. The dorsal dominance pattern of FVPVs favours SDAVFs, whereas ventral dominance suggests perimedullary AVFs.


Subject(s)
Arteriovenous Fistula/pathology , Central Nervous System Vascular Malformations/pathology , Magnetic Resonance Imaging , Adolescent , Adult , Aged , Child , Child, Preschool , Diagnosis, Differential , Female , Humans , Male , Middle Aged , Reproducibility of Results , Spinal Cord/pathology , Young Adult
5.
Chem Sci ; 6(9): 5284-5292, 2015 Sep 01.
Article in English | MEDLINE | ID: mdl-29449930

ABSTRACT

A methodology for controlling aggregation in highly active and isoselective indium catalysts for the ring opening polymerization of racemic lactide is reported. A series of racemic and enantiopure dinuclear indium ethoxide complexes bearing salen ligands [(ONNOR)InOEt]2 (R = Br, Me, admantyl, cumyl, t-Bu) were synthesized and fully characterized. Mononuclear analogues (ONNOR)InOCH2Pyr (R = Br, t-Bu, SiPh3) were synthesized by controlling aggregation with the use of chelating 2-pyridinemethoxide functionality. The nuclearity of metal complexes was confirmed using PGSE NMR spectroscopy. Detailed kinetic studies show a clear initiation period for these dinuclear catalysts, which is lacking in their mononuclear analogues. The polymerization behavior of analogous dinuclear and mononuclear compounds is identical and consistent with a mononuclear propagating species. The isotacticity of the resulting polymers was investigated using direct integration and peak deconvolution methodologies and the two were compared.

6.
Clin Radiol ; 69(4): e173-82, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24457018

ABSTRACT

AIM: To compare the diagnostic accuracies of three-dimensional (3D) isotropic magnetic resonance arthrography (MRA) using fat-suppressed proton density (PD) or volume interpolated breath-hold examination (VIBE) sequences with that of conventional MRA for the diagnosis of rotator cuff and labral lesions. MATERIALS AND METHODS: Eighty-six patients who underwent arthroscopic surgery were included. 3D isotropic sequences were performed in the axial plane using fat-suppressed PD (group A) in 53 patients and using VIBE (group B) in 33 patients. Reformatted images were obtained corresponding to conventional images, and evaluated for the presence of labral and rotator cuff lesions using conventional and 3D isotropic sequences. The diagnostic performances of each sequence were determined using arthroscopic findings as the standard. RESULTS: Good to excellent interobserver agreements were obtained for both 3D isotropic sequences for the evaluation of rotator cuff and labral lesions. Excellent agreement was found between two-dimensional (2D) and 3D isotropic MRA, except for supraspinatus tendon (SST) tears by both readers and for subscapularis tendon (SCT) tears by reader 2 in group B. 2D MRA and 3D isotropic sequences had high diagnostic performances for rotator and labral tears, and the difference between the two imaging methods was insignificant. CONCLUSIONS: The diagnostic performances of 3D isotropic VIBE and PD sequences were similar to those of 2D MRA.


Subject(s)
Arthrography , Image Processing, Computer-Assisted , Imaging, Three-Dimensional , Magnetic Resonance Imaging , Protons , Rotator Cuff/pathology , Shoulder Joint/pathology , Adolescent , Adult , Aged , Contrast Media , Female , Gadolinium DTPA , Humans , Image Processing, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Male , Middle Aged , Radionuclide Imaging , Rotator Cuff/diagnostic imaging , Rotator Cuff Injuries , Sensitivity and Specificity , Shoulder Injuries , Shoulder Joint/diagnostic imaging
7.
Rapid Commun Mass Spectrom ; 23(14): 2221-32, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19530149

ABSTRACT

Response factors were determined for twelve GXG peptides (where G stands for glycine and X is any of alanine [A], arginine [R], asparagine [N], aspartic acid [D], glycine [G], histidine [H], leucine [L], lysine [K], phenylalanine [F], serine [S], tyrosine [Y], valine [V]) by electrospray ionization mass spectrometry (ESI-MS). The response factors were measured using a novel flow injection method. This new method is based on the Gaussian distribution of analyte concentration resulting from band-broadening dispersion experienced by the analyte upon passage through an extended volume of PEEK tubing. This method removes the need for preparing a discrete series of standard solutions to assess concentration-dependent response. Relative response factors were calculated for each peptide with reference to GGG. The observed trends in the relative response factors were correlated with several analyte physicochemical parameters, chosen based on current understanding of ion release from charged droplets during the ESI process. These include analyte properties: nonpolar surface area; polar surface area; gas-phase basicity; proton affinity; and Log D. Multivariate statistical analysis using multiple linear regression, decision tree, and support vector regression models were investigated to assess their potential for predicting ESI response based on the analyte properties. The support vector regression model was more versatile and produced the least predictive error following 12-fold cross-validation. The effect of variation in solution pH on the relative response factors is highlighted, as evidenced by the different predictive models obtained for peptide response at two pH values (pH = 6.0 and 9.0). The relationship between physicochemical parameters and associated ionization efficiencies for GXG tripeptides is discussed based on the equilibrium partitioning model.


Subject(s)
Peptides/chemistry , Spectrometry, Mass, Electrospray Ionization/methods , Flow Injection Analysis , Hydrogen-Ion Concentration , Models, Chemical , Multivariate Analysis
8.
Am J Physiol Renal Physiol ; 296(6): F1530-6, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19357178

ABSTRACT

In this paper, we describe our design for a new electrohydraulic (EH) pump-driven renal perfusion pressure (RPP)-regulatory system capable of implementing precise and rapid RPP regulation in experimental animals. Without this automated system, RPP is manually controlled via a blood pressure clamp, and the imprecision in this method leads to compromised RPP data. This motivated us to develop an EH pump-driven closed-loop blood pressure regulatory system based on flow-mediated occlusion using the vascular occlusive cuff technique. A closed-loop servo-controller system based on a proportional plus integral (PI) controller was designed using the dynamic feedback RPP signal from animals. In vivo performance was evaluated via flow-mediated RPP occlusion, maintenance, and release responses during baseline and ANG II-infused conditions. A step change of -30 mmHg, referenced to normal RPP, was applied to Sprague-Dawley rats with the proposed system to assess the performance of the PI controller. The PI's performance was compared against manual control of blood pressure clamp to regulate RPP. Rapid RPP occlusion (within 3 s) and a release time of approximately 0.3 s were obtained for the PI controller for both baseline and ANG II infusion conditions, in which the former condition was significantly better than manual control. We concluded that the proposed EH RPP-regulatory system could fulfill in vivo needs to study various pressure-flow relationships in diverse fields of physiology, in particular, studying the dynamics of the renal autoregulatory mechanisms.


Subject(s)
Blood Pressure/physiology , Kidney/blood supply , Animals , Kidney Function Tests , Male , Nonlinear Dynamics , Pulsatile Flow , Rats , Rats, Sprague-Dawley , Software
9.
Acta Radiol ; 45(4): 440-5, 2004 Jul.
Article in English | MEDLINE | ID: mdl-15323398

ABSTRACT

PURPOSE: To evaluate the risk factors related to the development of new fractures in adjacent vertebrae after vertebroplasty. MATERIAL AND METHODS: The study was conducted on 106 patients in whom 212 vertebroplasties were performed during a period of 3 years. Evaluations of the five vertebrae superior and inferior to the treated vertebra were performed. Consequently, 913 vertebrae were evaluated and the fracture-free interval of the vertebral body adjacent to the treated vertebra was calculated. Survival analysis was performed using the Kaplan-Meier method and Cox proportional hazards regression analysis. RESULTS: Seventy-two (7.9%) new fractures were revealed. The Kaplan-Meier estimate of the 1-year fracture-free rate was 93.1%. The mean fracture-free interval was 32 months (95% CI, 32 to approximately 33 months). The greater degree of height restoration of the treated vertebra, the location of the adjacent vertebra in the TL junction, and the shorter distance between the treated and the adjacent vertebra increased the risk of new vertebral fractures. CONCLUSION: Thoracolumbar junction, shorter distance from the treated vertebrae, and greater degree of height restoration of the cemented vertebrae may increase the fracture risk of vertebrae adjacent to cement vertebrae after vertebroplasty.


Subject(s)
Lumbar Vertebrae/pathology , Spinal Fractures/etiology , Thoracic Vertebrae/pathology , Adult , Aged , Aged, 80 and over , Bone Cements/therapeutic use , Disease-Free Survival , Female , Follow-Up Studies , Fractures, Spontaneous/surgery , Humans , Lumbar Vertebrae/surgery , Male , Middle Aged , Osteoporosis/surgery , Polymethyl Methacrylate/therapeutic use , Proportional Hazards Models , Retrospective Studies , Risk Factors , Spinal Fractures/surgery , Survival Analysis , Thoracic Vertebrae/surgery
10.
Int Angiol ; 23(4): 355-67, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15767981

ABSTRACT

AIM: Various non- to less-invasive tests have been recently introduced in the management of congenital vascular malformations (CVM) and have become essential for the initial diagnostic work-up, largely replacing the traditional role of invasive tests. Whole body blood pool scintigraphy (WBBPS) was initially adopted as a supplementary test to reinforce other well-established essential diagnostic tests, and has been used extensively together in our Clinic, for years. We have evaluated WBBPS retrospectively for the diagnosis of venous malformation (VM) and arterio-venous malformation (AVM), and also for a further possible role for the interim assessment of treatment results during multistaged embolo/sclerotherapy. METHODS: Of 123 VMs and 48 AVMs selected for various treatments, 80 patients (66 VMs and 14 AVMs) were reviewed. The reliability of WBBPS as an initial diagnostic tool for VMs and AVM was assessed first by comparing its findings with matching MRI and/or duplex scan findings. These 80 patients underwent embolo/sclerotherapy with absolute ethanol mostly for VM, and N-butyl cyanoacrylate for AVM. A total of 251 sessions were performed either as a primary treatment independently or in conjunction with surgical treatment preoperatively. Thirty-six patients were available in terms of the subsequent review of the treatment results, to compare their 72 post-therapy WBBPS findings with matching duplex scan and MRI findings. The WBBPS assessment of treatment response was based on the percentage reduction of abnormal blood pooling over the region of interest (ROI) from baseline (initial) value. Treatment response was also qualitatively and semi-quantitatively assessed according to the degree of abnormal blood pool reduction. RESULTS: Of the 80 CVM (66 VM and 14 AVM) patients, 61 of 66 WBBPS findings of VM on initial diagnosis were confirmed as true-positive. Twelve of 14 AVMs were also confirmed as WBBPS true-positive findings. The sensitivity of WBBPS for the initial diagnosis was 93.8% (61/65) for VM and 92.3% (12/13) for AVM. The positive predictive value was 98.4% (61/62) for VM and 92.3% (12/13) for AVM. Of 72 post-therapy WBBPS performed for follow-up assessment of the results of treatment on 36 patients, 52 WBBPS showed positive findings qualitatively and/or quantitatively, the remaining 20 were negative. Fifty-one of the 52 WBBPS-positive findings were true-positive and 18 of the 20 were true-negative. Hence, WBBPS for follow-up assessment showed a sensitivity of 96% (51/53); a specificity of 95% (18/19); a positive predictive value of 98% (51/52); and a negative predictive value of 90% (18/20). CONCLUSIONS: Contemporary management of CVMs can be improved by using WBBPS, which is a less expensive, simple, and safe non-invasive test, especially for venous and arterio-venous malformations. WBBPS is a cost-effective and practical test with dependable accuracy for the assessment of treatment results, especially for interim measurements during multistage embolo/sclerotherapy.


Subject(s)
Arteries/abnormalities , Arteriovenous Fistula/diagnostic imaging , Arteriovenous Fistula/therapy , Gated Blood-Pool Imaging/methods , Veins/abnormalities , Adolescent , Adult , Embolization, Therapeutic/methods , Female , Follow-Up Studies , Humans , Male , Predictive Value of Tests , Retrospective Studies , Sclerotherapy/methods , Sensitivity and Specificity
11.
Skeletal Radiol ; 31(11): 631-6, 2002 Nov.
Article in English | MEDLINE | ID: mdl-12395274

ABSTRACT

OBJECTIVE: The aim of this study was to evaluate the imaging features of ischial bursitis with an emphasis on ultrasonography (US). DESIGN AND PATIENTS: Our study included 31 patients with a painful mass or tenderness in their buttock who underwent US (n=27), CT (n=1), or MR imaging (n=4). A needle aspiration (n=6) or a bursal excision (n=5) was performed in those patients who had no clinical improvement in spite of the conservative treatment. Evaluation included lesion location, size, wall of the bursae, and intrinsic characteristics on US, CT and MR imaging. RESULTS: Ischial bursitis was superficial to the ischial tuberosity in all patients (n=31). The lesion ranged from 1.5 cm to 7 cm (average 3.8 cm) in diameter. The bursal wall was identifiable in 25 cases (81%). Internal septa and mural nodules were seen in 12 (39%) and 17 cases (55%), respectively. Sonography showed that fluid within the bursa was hypoechoic (59%), hyperechoic (26%), or of mixed echogenicity (15%). The bursae were compressible by the transducer. Power Doppler examination (n=7) showed hypervascularity of the bursal wall. All lesions imaged with contrast-enhanced CT and MR imaging had an enhancing thin wall and mural nodule. CONCLUSIONS: Ischial bursitis, superficial to the ischial tuberosity, can be clearly demonstrated on sonography and appears as a thin-walled cystic lesion, with or without internal septa and mural nodules.


Subject(s)
Bursitis/diagnosis , Ischium , Adult , Aged , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Tomography, X-Ray Computed , Ultrasonography, Doppler
12.
Acta Radiol ; 43(1): 96-100, 2002 Jan.
Article in English | MEDLINE | ID: mdl-11972470

ABSTRACT

PURPOSE: To assess whether a single three-dimensional double-echo steady state (3D-DESS) sequence can produce equivalent results when compared to a 3D free induction with steady precession (3D-FISP) sequence for the evaluation of the neural foraminal diameter and structures. MATERIAL AND METHODS: Five phantoms were imaged on CT with 3-mm axial slices followed by reformatted axial 3D-DESS and 3D-FISP sequences. In addition, 3D-DESS and 3D-FISP sequences of 20 healthy subjects were compared with regard to image quality, differentiation between vertebrae and discs, differentiation between discs and neural foramina, and differentiation between vertebrae and neural foramina. RESULTS: Compared with CT, 3D-DESS and 3D-FISP sequences consistently underestimated the diameters of the neural foramina. The mean difference values for the 3D-DESS was 12.8%, compared to 9.5% for the 3D-FISP sequence. Concerning the in vivo studies, the 3D-DESS sequence was superior but not statistical significant to the 3D-FISP sequence with regard to image quality, differentiation between vertebrae and discs, differentiation between discs and neural formina, and identification of the nerve roots. CONCLUSION: The 3D-DESS sequence is moderately accurate in the evaluation of the neural foraminal size. Compared to the 3D-FISP sequence, the 3D-DESS sequence is compatible concerning the image quality, differentiation between the cervical vertebrae and discs, and between the discs and neural foramina.


Subject(s)
Cervical Vertebrae/diagnostic imaging , Cervical Vertebrae/pathology , Imaging, Three-Dimensional , Magnetic Resonance Imaging , Spinal Nerve Roots/diagnostic imaging , Spinal Nerve Roots/pathology , Tomography, X-Ray Computed , Adult , Cervical Vertebrae/innervation , Female , Humans , Intervertebral Disc/diagnostic imaging , Intervertebral Disc/innervation , Intervertebral Disc/pathology , Male , Middle Aged , Phantoms, Imaging , Reference Values , Sensitivity and Specificity
13.
J Pept Res ; 58(2): 151-8, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11532074

ABSTRACT

We examined the functional role of glycine at position 4 in the potent glucagon antagonist [desHis(1), Glu(9)]glucagon amide, by substituting the L- and D-enantiomers of alanine and leucine for Gly(4) in this antagonist. The methyl and isobutyl side-chain substituents were introduced to evaluate the preference shown by the glucagon receptor, if any, for the orientation of the N-terminal residues. The L-amino acids demonstrated only slightly better receptor recognition than the D-enantiomers. These results suggest that the Gly(4) residue in glucagon antagonists may be exposed to the outside of the receptor. The enhanced binding affinities of analogs 1 and 3 compared with the parent antagonist, [desHis(1), Glu(9)]glucagon amide, may have resulted from the strengthened hydrophobic patch in the N-terminal region and/or the increased propensity for a helical conformation due to the replacement of alanine and leucine for glycine. Thus, as a result of the increased receptor binding affinities, antagonist activities of analogs 1-4 were increased 10-fold compared with the parent antagonist, [desHis(1), Glu(9)]glucagon amide. These potent glucagon antagonists have among the highest pA(2) values of any glucagon analogs reported to date.


Subject(s)
Glucagon/analogs & derivatives , Glucagon/antagonists & inhibitors , Glycine/metabolism , Adenylyl Cyclases/metabolism , Animals , Binding, Competitive , Cell Membrane/metabolism , Chromatography, High Pressure Liquid , Chromatography, Thin Layer , Dose-Response Relationship, Drug , Glucagon/chemical synthesis , Glucagon/metabolism , Glucagon/pharmacology , Inhibitory Concentration 50 , Liver/cytology , Liver/drug effects , Liver/metabolism , Male , Protein Binding/drug effects , Rats , Rats, Sprague-Dawley , Structure-Activity Relationship
14.
J Med Chem ; 44(19): 3109-16, 2001 Sep 13.
Article in English | MEDLINE | ID: mdl-11543679

ABSTRACT

In search for the bioactive conformation of glucagon, "positional cyclization scanning" was used to determine secondary structures of glucagon required for maximal interaction with the glucagon receptor. Because glucagon is flexible in nature, its bioactive conformation is not known except for an amphiphilic helical conformation at the C-terminal region. To understand the conformational requirement for the N-terminal region that appears to be essential for signal transduction, a series of glucagon analogues conformationally constrained by disulfide or lactam bridges have been designed and synthesized. The conformational restrictions via disulfide bridges between cysteine i and cysteine i + 5, or lactam bridges between lysine i and glutamic acid i + 4, were applied to induce and stabilize certain corresponding secondary structures. The results from the binding assays showed that all the cyclic analogues with disulfide bridges bound to the receptor with significantly reduced binding affinities compared to their linear counterparts. On the contrary, glucagon analogues containing lactam bridges, in particular, c[Lys(5), Glu(9)]glucagon amide (10) and c[Lys(17), Glu(21)]glucagon amide (14), demonstrated more than 7-fold increased receptor binding affinities than native glucagon. These results suggest that the bioactive conformation of glucagon may adopt a helical conformation at the N-terminal region as well as the C-terminal region, which was not evident from earlier biophysical studies of glucagon.


Subject(s)
Glucagon/analogs & derivatives , Glucagon/chemistry , Adenylyl Cyclases/metabolism , Amino Acid Sequence , Cell Membrane/drug effects , Cell Membrane/metabolism , Circular Dichroism , Disulfides/chemical synthesis , Disulfides/chemistry , Disulfides/pharmacology , Glucagon/chemical synthesis , Glucagon/pharmacology , In Vitro Techniques , Lactams/chemical synthesis , Lactams/chemistry , Lactams/pharmacology , Liver/ultrastructure , Molecular Sequence Data , Protein Binding , Protein Structure, Secondary , Radioligand Assay , Spectrometry, Mass, Electrospray Ionization , Structure-Activity Relationship
15.
Spine (Phila Pa 1976) ; 26(13): E287-93, 2001 Jul 01.
Article in English | MEDLINE | ID: mdl-11458168

ABSTRACT

STUDY DESIGN: In vivo flexion-extension and axial rotation magnetic resonance imaging (MRI) studies of the cervical spine were performed inside a positioning device. OBJECTIVE: To determine the functional changes of neuroforaminal size that occur during flexion-extension and axial rotation of the cervical spine in healthy persons. SUMMARY OF BACKGROUND DATA: Kinematic MRI studies of the cervical spine were performed to obtain detailed information about the functional changes that occur in neuroforaminal size during flexion-extention and axial rotation. The results were compared with published data of in vitro functional flexion-extension and axial rotation studies of the cervical spine. METHODS: Inside a positioning device, the cervical spines of 30 healthy persons were examined in a whole-body magnetic resonance scanner from 40 degrees of flexion to 30 degrees of extension at nine different angle positions. In addition, axial rotation was performed at neutral position (0 degrees ) and at 20 degrees and 40 degrees of axial rotation to both sides. The images were analyzed with respect to the neuroforaminal size at each position using a reformatted 3D-FISP sequence. RESULTS: At flexion, widening of the neuroforaminal size of up to 31% (compared with neutral position, 0 degrees ) was observed. Conversely, at extension a decrease in the size of the neuroforamen of up to 20% was recognized. At 20 degrees and 40 degrees of ipsilateral rotation of the head, a reduction in the neuroforaminal size of up to 15% and 23%, respectively, compared with the neutral position was noted. In contrast, a widening of the foraminal size was recognized on the contralateral side of 9% and 20% at 20 degrees and 40 degrees rotation. Statistically significant differences (p <== 0.05) were found in the neuroforaminal size between different degrees of flexion and extension and in addition for axial rotation compared to neutral position (0 degrees ). CONCLUSION: Compared with the results of previous biomechanical studies of human cadaver cervical spines, kinematic MRI provides additional noninvasive data concerning the physiological changes of the neuroforaminal size during flexion-extension and axial rotation in healthy individuals.


Subject(s)
Cervical Vertebrae/physiology , Magnetic Resonance Imaging , Movement , Neck Pain/etiology , Adult , Biomechanical Phenomena , Female , Humans , Male , Pliability , Posture , Reference Values
16.
Int J Cancer ; 93(2): 262-8, 2001 Jul 15.
Article in English | MEDLINE | ID: mdl-11410875

ABSTRACT

We demonstrated the induction of cell death in a hepatoma cell line by IFN-gamma and its possible mechanism. Among the 2 hepatitis B virus (HBV)-associated hepatoma cell lines, SNU-354 and SNU-368, IFN-gamma induced cell death and increased caspase-3 activity in SNU-368 but not in SNU-354. IFN-gamma induced several changes in the mRNA expression level of apoptosis-regulating genes, e.g., increased expression of Fas, caspase-1 and TNF-related apoptosis-inducing ligand (TRAIL). In particular, IFN-gamma potently increased the mRNA expression of TRAIL in both cell lines. However, it did not change the mRNA expression level of death-mediating TRAIL receptors, e.g., DR4 and DR5, which were constitutively expressed in both cell lines. In contrast, the decoy receptor DcR1 was expressed in SNU-354 but not in SNU-368, and its expression level in SNU-354 was increased by IFN-gamma. Another decoy receptor, DcR2, was constitutively expressed in both cell lines; however, its expression level in SNU-368 was decreased by IFN-gamma. In addition, exogenous recombinant TRAIL reduced viability in SNU-368, but not in SNU-354, cells. From these findings, we speculated that TRAIL up-regulation and the subsequent TRAIL-mediated apoptosis serve as a mechanism of IFN-gamma-induced cell death in SNU-368. To confirm this hypothesis, we demonstrated that soluble DR4-Fc fusion protein, a TRAIL pathway inhibitor, inhibited IFN-gamma-induced cell death in SNU-368. Our results demonstrated that IFN-gamma acts as an inducer of cell death through TRAIL-mediated apoptosis.


Subject(s)
Apoptosis , Interferon-gamma/pharmacology , Membrane Glycoproteins/metabolism , Receptors, Tumor Necrosis Factor/metabolism , Tumor Necrosis Factor-alpha/metabolism , Apoptosis Regulatory Proteins , Carcinoma, Hepatocellular/pathology , Caspase 1/genetics , Caspase 1/metabolism , Caspase 3 , Caspases/metabolism , Cell Survival/drug effects , Enzyme Activation , Fas Ligand Protein , Humans , Immunoglobulin Fc Fragments/genetics , Liver Neoplasms/pathology , Membrane Glycoproteins/genetics , RNA, Messenger/metabolism , Receptors, TNF-Related Apoptosis-Inducing Ligand , Receptors, Tumor Necrosis Factor/genetics , Recombinant Proteins/pharmacology , TNF-Related Apoptosis-Inducing Ligand , Tumor Cells, Cultured , Tumor Necrosis Factor-alpha/genetics , fas Receptor/genetics , fas Receptor/metabolism
17.
J Med Chem ; 44(9): 1372-9, 2001 Apr 26.
Article in English | MEDLINE | ID: mdl-11311060

ABSTRACT

In pursuit of truncated glucagon analogues that can interact with the glucagon receptor with substantial binding affinity, 23 truncated glucagon analogues have been designed and synthesized. These truncated analogues consist of several fragments of glucagon with 11 or 12 amino acid residues (1-4), conformationally constrained analogues containing the sequence of the middle region of glucagon (5-15), and truncated analogues containing the sequence of the C-terminal region (16-23). Biological assays of these analogues showed that the truncated glucagon analogues with the sequence of the C-terminal region possess significantly better binding affinity compared to the truncated analogues with the sequence of the middle region, and these analogues (17-23) demonstrated potent antagonistic activity (pA(2) values between 6.5 and 7.5). On the basis of these results, it can be suggested that glucagon interacts with its receptor with two hydrophobic patches located in the middle and the C-terminal regions of glucagon, and both hydrophobic patches are necessary for significant receptor recognition. These two hydrophobic binding motifs, located in two different regions of glucagon, appear to be the reason why the earlier attempts to obtain truncated analogues with good binding affinity did not result in any success. Long peptide hormones such as glucagon seem to require more than one binding pocket on the receptors for maximal interaction.


Subject(s)
Glucagon/antagonists & inhibitors , Glucagon/chemistry , Peptide Fragments/chemistry , Adenylyl Cyclases/metabolism , Animals , Cell Membrane/metabolism , Combinatorial Chemistry Techniques , In Vitro Techniques , Liver/ultrastructure , Male , Peptide Fragments/pharmacology , Rats , Rats, Sprague-Dawley , Structure-Activity Relationship
18.
Radiology ; 218(3): 848-53, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11230666

ABSTRACT

PURPOSE: To assess magnetic resonance (MR) imaging features in differentiating tuberculous arthritis from pyogenic arthritis. MATERIALS AND METHODS: Findings in 29 patients with tuberculous arthritis were compared with those of 13 patients with pyogenic arthritis. Bone erosion, marrow signal intensity, synovial lesion signal intensity, boundaries (smooth or irregular) for extraarticular extension of infection, and abscess rim enhancement (thin and smooth or thick and irregular) were analyzed. RESULTS: Bone erosion was more common in patients with tuberculous arthritis (24 [83%] of 29) than in those with pyogenic arthritis (six [46%] of 13) (P =.026), while subchondral marrow signal intensity abnormality was seen more frequently in patients with pyogenic arthritis (12 [92%] of 13) than in those with tuberculous arthritis (17 [59%] of 29) (P =.036). On T2-weighted images, there was no significant difference between the synovial lesion signal intensities of tuberculous arthritis and pyogenic arthritis. Lesions in 16 (70%) of 23 patients with tuberculous arthritis and two (17%) of 12 patients with pyogenic arthritis had smooth extraarticular boundaries, while those in seven (30%) of 23 patients with tuberculous arthritis and 10 (83%) of 12 patients with pyogenic arthritis had irregular boundaries (P =.005). Tuberculous abscesses (16 [100%] of 16) had thin and smooth rim enhancement, while most pyogenic abscesses (five [71%] of seven) had thick and irregular rims (P =.001). CONCLUSION: MR imaging of bone abnormalities, extraarticular lesions, and associated abscesses provides useful information in the differentiation of tuberculous arthritis and pyogenic arthritis.


Subject(s)
Arthritis, Infectious/diagnosis , Magnetic Resonance Imaging , Tuberculosis, Osteoarticular/diagnosis , Abscess/diagnosis , Adolescent , Adult , Aged , Diagnosis, Differential , Female , Humans , Male , Middle Aged , Suppuration
19.
Acta Radiol ; 41(5): 492-7, 2000 Sep.
Article in English | MEDLINE | ID: mdl-11016774

ABSTRACT

OBJECTIVE: To compare the sensitivity of conventional MR sequences, MR arthrography, and CT arthrography for the detection of cartilage lesions of the patella in cadavers. MATERIAL AND METHODS: Cartilage lesions in 10 cadaveric specimens were evaluated by MR imaging, including T1-weighted, proton density-weighted and T2-weighted sequences, and fat-suppressed spoiled gradient recalled acquisition in the steady state (SPGR), MR arthrography including T1-weighted and SPGR sequences, and double-contrast CT arthrography including conventional and subtracted images. The sensitivities with regard to detection of lesions were compared to results from morphologic and histologic investigations of sectioned specimens. RESULTS: Twenty-one lesions were detected morphologically. For the detection of these lesions, sensitivities were as follows: T1-weighted images 33.3%; proton density-weighted images 85.7%; T2-weighted images 85.7%; SPGR images 80.9%; MR arthrography with T1-SE sequences 57.1%; MR arthrography with SPGR sequence 90.5%; and CT arthrography, both regular and subtracted images 85.7%. CONCLUSION: For noninvasive techniques, T2-weighted images revealed the highest sensitivity for the detection of patellar cartilage lesions, which was surpassed only by MR arthrography using the SPGR sequence. CT arthrography delineated surface irregularities but failed to demonstrate intrachondral lesions.


Subject(s)
Cartilage/pathology , Magnetic Resonance Imaging , Patella/pathology , Tomography, X-Ray Computed , Aged , Aged, 80 and over , Arthrography , Cadaver , Cartilage/diagnostic imaging , Cartilage Diseases/diagnosis , Cartilage Diseases/diagnostic imaging , Contrast Media , False Negative Reactions , Female , Humans , Image Processing, Computer-Assisted/methods , Knee Joint/diagnostic imaging , Knee Joint/pathology , Magnetic Resonance Imaging/methods , Male , Middle Aged , Patella/diagnostic imaging , Prospective Studies , Sensitivity and Specificity , Subtraction Technique
20.
Skeletal Radiol ; 29(4): 217-23, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10855470

ABSTRACT

OBJECTIVE: To define the possible mechanism of posture-dependent symptoms of spinal stenosis by measuring the effect of low back posture on morphologic changes of the intervertebral discs and spinal canal in healthy young people. DESIGN: Twenty healthy young volunteers underwent magnetic resonance imaging while supine with their spine in neutral, flexed, extended, and right and left rotational positions. The axial MR images at the middle of the intervertebral discs of L3-4 and L4-5 were analyzed to measure the difference in the size and shape of the intervertebral discs and spinal canal in each posture. RESULTS: Extension or rotation decreased the sagittal diameters and cross-sectional areas of the dural sac and spinal canal and increased the thickness of the ligamentum flavum, whereas flexion had the opposite effects. The gap between the convex posterior disc margin and the anterior margin of the facet joint on each side, represented as the subarticular sagittal diameter, increased with flexion and decreased with extension or rotation. The direction of rotation did not result in asymmetry of the subarticular sagittal diameter, but right rotation caused thickening of the right ligamentum flavum, and vice versa. The shape and dimensions of the disc did not change significantly according to the positions of the low back. CONCLUSIONS: With extension or rotation, the thickness of the ligamentum flavum increased and the posterior margin of the intervertebral disc was approximated to the facet joint without any change in shape and size of the disc. These phenomena result in a decrease in the size of the spinal canal and dural sac in extension or rotation postures in young healthy people without disc degeneration, and may explain the posture-dependent symptom of spinal stenosis.


Subject(s)
Lumbar Vertebrae/anatomy & histology , Lumbar Vertebrae/physiology , Adult , Analysis of Variance , Female , Humans , Intervertebral Disc/anatomy & histology , Intervertebral Disc/physiology , Ligamentum Flavum/anatomy & histology , Ligamentum Flavum/physiology , Magnetic Resonance Imaging , Male , Rotation , Spinal Canal/anatomy & histology , Spinal Canal/physiology , Spinal Stenosis/diagnosis , Supine Position/physiology
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