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Biomedical subjects

M Settles

Publications and source records attributed to M Settles.

12 recordsLinked to original sources
PubMed2005

Detection of hepatocellular carcinoma: comparison of Gd-DTPA- and ferumoxides-enhanced MR imaging.

The aim was to compare the diagnostic performance of dynamic Gd-DTPA- and ferumoxides-enhanced MRI for hepatocellular carcinoma (HCC). Twenty-five patients with chronic hepatitis or liver cirrhosis underwent both dynamic gadopentetate- and ferumoxides-enhanced MRI studies of the liver for HCC detection on the same day. MR data of both studies were retrospectively and independently analyzed. Two observers determined in consensus the grade of diffuse fibrotic liver changes (mild, moderate or severe) and the number of focal lesions. HCCs were confirmed by histology (n=22) and/or follow-up studies for at least six months (n=64). Differences in results obtained from both MR data sets were tested for significance with the McNemar's test (p<0.05). Ferumoxides-enhanced MR images detected 84 of 99 hepatic lesions, including 82 of 86 HCCs and 2 false positive, nonmalignant lesions, while Gd-DTPA-enhanced MR images detected 92 of 99 hepatic lesions, including 81 of 86 HCCs and 11 false positive, nonmalignant lesions. Sensitivity of MRI for detection of HCCs was not significantly different between ferumoxides-enhanced (95.3%; p>0.05) and Gd-DTPA-enhanced scans (94.2%). Gd-DTPA- and ferumoxides-enhanced MRI perform equally well for HCC detection. The majority of small hypervascular hepatic lesions, detected on dynamic Gd-DTPA-enhanced MRI but not on ferumoxides-enhanced MRI, represent no HCCs.

Adult↗
PubMed2005

Evaluation of reconstructed orbital wall fractures: high-resolution MRI using a microscopy surface coil versus 16-slice MSCT.

We evaluated high-resolution magnetic resonance imaging (MR) using a 47-mm microscopy surface coil in comparison to 16-slice multislice CT (MSCT) for postsurgical imaging of reconstructed orbital walls. Twenty-five patients with 27 internal orbital wall fractures were imaged prospectively after reconstruction with resorbable polydioxanone sulfate (PDS) sheets. Coronal high-quality T1- and T2-weighted MR images were obtained with an in-plane resolution of 350 microm within a measure time of 6-7 min for each sequence. Nineteen symptomatic patients underwent MSCT as the current gold standard. In MRI the PDS foil appears in T1- and T2-weighted images as a thin, low-signal-intensity linear structure. In CT it appears hyperdense in comparison to soft tissue and slightly hypodense in comparison to cortical bone. PDS foils could be clearly depicted in 20 out of 25 patients (80%) with MRI and in 13 out of 19 patients (68%) with MSCT. An inadequate foil position or size could be diagnosed in eight patients with MRI and in only three patients with MSCT. In ten symptomatic patients secondary surgery could be avoided because of regular MRI findings except mild hematoma and muscle edema. High-resolution MRI of the orbit using a 47-mm microscopy coil is a promising method to accurately demonstrate normal and pathologic conditions in symptomatic patients after orbital wall reconstruction with PDS foils.

Adolescent↗
PubMed2001

The quantification of DeltaR2(*) under brain activation: dependence on relaxation rate at rest and significance threshold.

Transverse relaxation rates R2(*) were measured in subjects performing a motor task using a segmented EPI double gradient echo sequence (TE = 23/70 ms) with five different voxel sizes between 1.8 mm(3) and 41.7 mm(3). An analysis of the errors involved in the calculation of the change of the transverse relaxation rate--DeltaR2(*) and of the consequences of defining an arbitrary threshold of statistical significance in the data analysis was performed. Correlations between the magnitude of the BOLD effect and the significance level on one hand and between the transverse relaxation time at rest and its change under activation on the other, both referenced in the literature, can be understood as a consequence of this procedure. Analysing histograms of parameter changes rather than average values alone allows for an estimate of the contribution of false positive voxels. Furthermore, while the averaged signal change increases in proportion to the selection threshold the histograms of activated voxels remain insensitive to the latter.

Adult↗
PubMed2001

[Virtual endoscopy of the urinary tract from T(2)-weighted and gadolinium-enhanced T(1)-weighted MR urographic images].

PURPOSE: To determine the diagnostic performance of T(2)-weighted (T2w) and gadolinium-enhanced T(1)-weighted (T1w-Gd-enhanced) MR urographic images for virtual endoscopy of the urinary tract. MATERIALS AND METHODS: 36 patients underwent MR urography at 1.5 T. In each patient a T2w (3D-TSE, respiration-triggered) and a T1w-Gd-enhanced sequence (T1-FFE, breathhold) were acquired. Data reconstruction was performed as maximum intensity projection (MIP) and virtual endoscopy (VE). RESULTS: Combined analysis of MIP and VE delineated 32 of 36 pathologies; 86 % (19/22) of intraluminal pathologies could be depicted by VE and 15 % (3/22) by MIP (p </= 0.01). For the assessment of the renal pelvis, MIP was superior to VE in 55 % (39/71). Concerning the ureter, MIP was equal in 52 % (37/71) and superior to VE in 45 % (32/71). For virtual ureterorenoscopy both data sets were comparable in their diagnostic performance. T2w data sets were superior for virtual cystoscopy because no contrast medium is required in cases of renal failure and sedimentation artifacts can be avoided. CONCLUSION: For the depiction of the upper urinary tract, MIP is in most cases equally good or superior to VE. However, virtual endoscopy of the urinary tract, especially virtual cystoscopy, is a useful tool for the depiction of intraluminal pathology.

Adult↗
PubMed2001

Observation of the swallowing process by application of videofluoroscopy and real-time magnetic resonance imaging-consequences for retronasal aroma stimulation.

The process of eating and drinking was observed in vivo by application of videofluoroscopy, a dynamic X-ray technique, as well as real-time magnetic resonance imaging. The study was aimed at elucidating the timing and performance of the physiological organs involved in mastication and swallowing, mainly the tongue, the pharynx and the soft palate (velum palatinum). It was shown for the first time that effective physiological barriers do exist during food consumption that are capable of retaining volatiles such as helium within the oral cavity. These barriers allow the access of odorants to the nasal cavity only at certain times during the eating process. Their effectiveness is related to the texture of the food as well as the amount of food material present in the oral cavity and, thereby, directly influences retronasal aroma perception.

Adult↗
PubMed1998

Solvent composition and viscosity effects on the kinetics of CO binding to horse myoglobin.

Ligand binding to myoglobin in aqueous solution involves two kinetic components, one extramolecular and one intramolecular, which have been interpreted in terms of two sequential kinetic barriers. In mixed solvents and sub-zero temperatures, the outer barrier increases and the inner barrier splits into several components, giving rise to fast intramolecular recombination. The nature of these barriers and their relation to structural relaxation are examined using the effect of solvent composition and viscosity on the kinetics of CO binding to horse myoglobin in 60% ethylene glycol/water, 75% and 90% glycerol/water, 80% and 92% sucrose/water solutions. Measurements of the corresponding solvent structural relaxation rates by frequency resolved calorimetry allow us to discriminate between solvent composition and viscosity-related effects. The outer kinetic barrier controlling ligand entry and release depends on the viscosity consistent with Kramers-Stokes law of activated escape in the presence of friction. At high cosolvent concentration, we observe deviations from Stokes law, implying a smaller microviscosity at the protein-solvent interface as compared to the bulk. The inner barrier and its coupling to structural relaxation appears to be independent of viscosity but changes with solvent composition. As a possible explanation, we discuss the role of distal water molecules in the formation of the effective inner barrier. At low temperatures, this barrier has a distributed height, depending only slightly on the nature of the cosolvent and temperature at low cosolvent concentrations. In contrast, myoglobin embedded in a sucrose glass (92% sucrose/water) exhibits a temperature-dependent and bimodal enthalpy distribution. This result demonstrates that the exchange between protonation states of His64, A0 left and right arrow A1, can take place in the glass and at temperatures as low as 80 K.

Animals↗
PubMed1993

Structural relaxation and nonexponential kinetics of CO-binding to horse myoglobin. Multiple flash photolysis experiments.

The geminate recombination kinetics of CO-myoglobin strongly deviates from single exponential behavior in contrast to what is expected for unimolecular reactions (1). At low temperatures, this result was attributed to slowly exchanging conformational states which differ substantially in barrier height for ligand binding. Above 160 K the kinetics apparently slow down with temperature increase. Agmon and Hopfield (2) explain this result in terms of structural relaxation perpendicular to the reaction coordinate, which enhances the activation energy. In their model, structural relaxation homogenizes the kinetic response. Recently, Steinbach et al. (3) proposed a relaxation model which conserves the kinetic inhomogeneity. Below we test these conjectures by single and multiple excitation experiments. This method allows for discrimination between parallel (inhomogeneous) and sequential (homogeneous) kinetic schemes. The kinetic anomaly above 160 K is shown to result from a homogeneous, structurally relaxed intermediate. However a second anomaly is found above 210 K concerning the inhomogeneous phase which may indicate either a shift in activation energy or entropy.

Animals↗
PubMed1992

Solvent damping of internal processes in myoglobin studied by specific heat spectroscopy and flash photolysis.

We address the question of dynamic coupling between protein and solvent by comparing the enthalpy relaxation of the solvent (75% v/v glycerol-water) to internal ligand binding in myoglobin. When the solvent relaxation is slow compared to intramolecular events we observe decoupling of protein motions from the solvent. In the opposite limit there is a significant contribution of the solvent to internal friction. The solvent enhances the apparent activation energy of transitions in myoglobin. This result is discussed in terms of a generalized Kramer's law involving a dynamic friction coefficient.

Animals↗
PubMed1990

Human immunodeficiency virus type 1-infected individuals make autoantibodies that bind to CD43 on normal thymic lymphocytes.

Sera from human immunodeficiency virus type 1 (HIV-1)-infected and -noninfected individuals were screened for antibodies that could bind to native T cell differentiation antigens. Antibodies that could immunoprecipitate CD43 (sialophorin, leukosialin) from a T cell lymphoma line were detected in sera from 27% of patients, and antibodies that could bind specifically to transfected cells expressing CD43 were detected in 47% of patients. The anti-CD43 antibodies were related to HIV-1 infection in that no patients with other chronic viral infections or systemic lupus erythematosus contained such antibodies in their sera. The anti-CD43 autoantibodies bound to a partially sialylated form of CD43 expressed by normal human thymocytes, but not by normal, circulating T lymphocytes. However, the determinant(s) recognized by the anti-CD43 autoantibodies was present on a large proportion of circulating T lymphocytes, but masked from antibody recognition by sialic acid residues. These results demonstrate that HIV-1 infection is specifically associated with the production of autoantibodies that bind to a native T cell surface antigen.

Antigens, CD↗
PubMed1990

Surface immunoglobulin-positive T lymphocytes in HIV-1 infection: relationship to CD4+ lymphocyte depletion.

T lymphocytes bound to autologous immunoglobulin (surface Ig + T cells) and serum antibodies that bind to allogeneic lymphocytes have been detected in HIV-1-infected individuals, but their significance in the immunopathogenesis of HIV-1 infection is uncertain. We tested peripheral blood from HIV-1-infected individuals to determine if surface Ig+ T cells are specific for HIV-1 infection and are associated with CD4+ lymphocyte depletion. The majority of HIV-1-infected individuals contained substantial numbers of circulating surface Ig+ T cells. The presence of such cells was restricted to seropositive individuals and not related to risk factors associated with the acquisition of HIV-1 infection. Autologous immunoglobulin was detected on both CD4+ and CD8+ cells in all patients tested. Most individuals with surface Ig+ T lymphocytes also had serum anti-T-lymphocyte antibodies. The presence of surface Ig+ T lymphocytes correlated significantly with lower absolute CD4+ lymphocyte counts only in asymptomatic, HIV-1-infected individuals.

Antigens, CD↗
PubMed1990

Percolation model of ionic channel dynamics.

The nonexponential closed-time distributions observed for ionic channels have been explained recently by quasi-one-dimensional models of structural diffusion (Millhauser, G. L., E. E. Salpeter, and R. E. Oswald. 1988. Proc. Natl. Acad. Sci. USA. 85: 1503-1507; Condat, C. A., and J. Jäckle. 1989. Biophys. J. 55: 915-925; Levitt, D. G. 1989. Biophys. J. 55: 489-498). We generalize this treatment by allowing for more complex trajectories using percolation theory. We assume that the gating transition depends on marginally connected conformational states leading to the observed spread in time scales.

Computer Simulation↗