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PubMed2006

Alterations in contractile protein composition and function in human atrial dilatation and atrial fibrillation.

The cellular mechanisms responsible for contractile dysfunction associated with atrial fibrillation (AF) are still poorly understood. Atrial fibrillation is often preceded by atrial dilatation. This study aimed to explain contractile alterations associated with AF and their relation to atrial dilatation, by studying the relationships between atrial dimensions, contractile protein composition, force production and Ca(2+)-sensitivity. Force development was determined in mechanically isolated single skinned cardiomyocytes from right atrial appendages from patients with sinus rhythm without (SR;n=9), or with atrial dilation (SR+AD;n=11) or atrial fibrillation (AF;n=16). Echocardiography showed that, compared to the SR group, mean right atrial dimensions were increased by 18% and 35% in the SR+AD and AF group, respectively (P<0.05). Protein composition was determined by 1- and 2-dimensional gel electrophoresis. Compared to the SR group, the AF group exhibited: a reduction in the kinetics of force redevelopment (K(tr)) in isolated atrial cardiomyocytes, enhanced protein expression of the slow myosin heavy chain isoform (beta-MHC), an increase in troponin T (TnT) phosphorylation and a marked increase (70%) of the cytoskeletal protein desmin. Significant correlations were observed between the right atrial major axis (RA(major)) and beta-MHC expression as well as the desmin/actin ratio. Our findings indicate that dilatation may influence cardiomyocyte stability through altered desmin expression, but that it does not predispose to the alterations in contractile function observed in AF.

Aged↗
PubMed2006

Dynamical structure of center-of-pressure trajectories in patients recovering from stroke.

In a recent study, De Haart et al. (Arch Phys Med Rehabil 85:886-895, 2004) investigated the recovery of balance in stroke patients using traditional analyses of center-of-pressure (COP) trajectories to assess the effects of health status, rehabilitation, and task conditions like standing with eyes open or closed and standing while performing a cognitive dual task. To unravel the underlying control processes, we reanalyzed these data in terms of stochastic dynamics using more advanced analyses. Dimensionality, local stability, regularity, and scaling behavior of COP trajectories were determined and compared with shuffled and phase-randomized surrogate data. The presence of long-range correlations discarded the possibility that the COP trajectories were purely random. Compared to the healthy controls, the COP trajectories of the stroke patients were characterized by increased dimensionality and instability, but greater regularity in the frontal plane. These findings were taken to imply that the stroke patients actively (i.e., cognitively) coped with the stroke-induced impairment of posture, as reflected in the increased regularity and decreased local stability, by recruiting additional control processes (i.e., more degrees of freedom) and/or by tightening the present control structure while releasing non-essential degrees of freedom from postural control. In the course of rehabilitation, dimensionality stayed fairly constant, whereas local stability increased and regularity decreased. The progressively less regular COP trajectories were interpreted to indicate a reduction of cognitive involvement in postural control as recovery from stroke progressed. Consistent with this interpretation, the dual task condition resulted in less regular COP trajectories of greater dimensionality, reflecting a task-related decrease of active, cognitive contributions to postural control. In comparison with conventional posturography, our results show a clear surplus value of dynamical measures in studying postural control.

Aged↗
PubMed2002

Change of left ventricular geometric pattern after 1 year of antihypertensive treatment: the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study.

BACKGROUND: Patients with hypertension have different types of left ventricular (LV) geometry, but the impact of blood pressure (BP) reduction on LV geometry change during antihypertensive treatment remains unclear. METHODS: Two-dimensional and M-mode echocardiograms were recorded at baseline in 853 unmedicated patients with stage II to III hypertension and LV hypertrophy determined by electrocardiography (Cornell voltage duration > or =2440 mV x ms or modified Sokolow-Lyon criteria: SV1 + RV5/RV6 >38 mV) after 14 days of placebo treatment. Follow-up echocardiography was done after 1 year of blinded treatment with either losartan or atenolol, in some cases supplemented with thiazide and calcium antagonist to reach target a BP of 140/90 mm Hg. RESULTS: Baseline systolic/diastolic BP were reduced from 174 +/- 20/95 +/- 11 to 151 +/- 19/84 +/- 11 mm Hg. LV mass was reduced from 234 +/- 56 to 207 +/- 51 g and relative wall thickness from 0.41 +/- 0.07 to 0.38 +/- 0.06 (all P <.001). Prevalence of concentric LV hypertrophy decreased from 24% to 6%, eccentric LV hypertrophy from 46% to 37%, and concentric LV remodeling from 10% to 6%; normal geometry increased from 20% to 51%. A shift toward lower LV mass and relative wall thickness was found, as approximately 73% of those with concentric LV remodeling at baseline shifted to normal geometric pattern, whereas only 7% of those with normal pattern at baseline shifted to concentric LV remodeling. Of patients with concentric LV hypertrophy at baseline, 34% shifted to eccentric LV hypertrophy, whereas only 3% with eccentric LV hypertrophy at baseline had concentric LV hypertrophy. Furthermore, multiple regression analysis showed that Doppler stroke volume reduction was a significant correlate of LV mass reduction (beta = 0.108, P <.001) independent of BP, heart rate change, and assigned drug treatment. CONCLUSIONS: Antihypertensive treatment reduces LV mass and decreases the prevalence of LV hypertrophy and concentric LV remodeling. Additional control of Doppler stroke volume potentiates the effect of BP reduction on LV mass regression independent of the BP reduction per se.

Aged↗
PubMed1995

A computer simulation study of normal and abnormal hip joint contact pressure.

The contact pressure on 112 normal hip joints and 66 acetabular dysplastic hip joints was analysed using a three-dimensional rigid body spring model. Geometric models were made from conventional anteroposterior radiographs, with the assumption that the acetabular surface was spherical. In normal hips, the distribution of contact pressure was almost even over the joint surface, and the maximum contact pressure was relatively low. However, in a dysplastic hip joint, the pressure was concentrated on the anterolateral edge of the acetabulum and increased enormously not only with the reduction in lateral coverage but also with the reduction in the anterior coverage of the acetabulum. This result indicates that a three-dimensional analysis is indispensable for estimating the mechanical effect on acetabular cartilage.

Acetabulum↗
PubMed1997

Prostate volumes and organ movement defined by serial computerized tomographic scans during three-dimensional conformal radiotherapy.

The aim of this study was to assess changes in prostate volumes and organ movement during a course of external beam irradiation using serial computerized tomographic (CT) scans and three-dimensional treatment planning software. Ten consenting prostate cancer patients underwent repeat CT scans at biweekly intervals during the course of external beam irradiation. The spacing of 5 mm was used because this spacing mimics our clinical treatment approach. Prostate locations were determined by merging CT images using bony anatomy and comparing the differences in the prostate volumes, the edges (anterior, posterior, superior, inferior, and lateral) and centers of the prostate (EoP and CoP, respectively). Compared to the 10 initial treatment planning CT scans, the prostate volume determined by the repeat CT scans tended to be smaller (approximately 14%, P < 0.001). The prostate volumes determined by repeat CT scans tended to be stable with a mean volume of 86% (S.D. = 18%) of the initial CT. When assessed by changes in the EoP, superior movements appeared to be the most common source for concern for adequate coverage of the prostate, while inferior movement was not seen. When assessed by changes in CoP, movement of > or = 3 mm was noted in 47% of the studies in the superior direction, with the average displacement being approximately 2.0 mm. In this study, the prostate volume tended to be smaller 2 weeks after the start of radiotherapy. Moreover, the prostate volumes defined by the serial CT scans were less reproducible than expected. Superior displacement of the prostate is the most common and significant type of displacement, while inferior movement is least frequent when patients are simulated with their rectums empty. Because of the magnitude of daily setup errors, organ movement, and problems with reproducibility in target definition, additional field edge reductions do not appear to be warranted during the delivery of three-dimensional conformal radiotherapy. Efforts should be directed at improving our ability to reduce organ movement and accurately targeting the prostate.

Computer Simulation↗
PubMed2005

Three-dimensional isotropic contrast-enhanced MR angiography of the carotid artery using sensitivity-encoding and random elliptic centric k-space filling: technique optimization.

We present a study that helped optimize a three-dimensional isotropic contrast-enhanced MR angiographic (CE-MRA) technique, using sensitivity encoding (SENSE) and random elliptic centric k-space filling. Two-dimensional gradient-echo sequence (TR/TE/flip angle 3.4/0.97/40 degrees ) was used to generate time-intensity curves in porcine carotid arteries for a fixed dose of Gd-DTPA (0.02 mmol/kg) at the following intravenous injection rates: 0.1, 0.3, 0.5, 1.0, 1.5, 2.0, and 3.0 ml/s. The time of contrast arrival and time to peak were recorded. Based on the time-intensity curves, three-dimensional high-resolution isotropic (1 mm3) CE-MRA sequence (TR/TE/flip angle: 4.9/2.4/30 degrees ), using SENSE (reduction factor of 2) and random elliptic centric k-space filling, was initiated twice for each of the above injection rates: first at the time of contrast arrival and second at the time of peak contrast. The three-dimensional CE-MRA images were analyzed for artifacts, signal-to-noise ratio, and venous contamination. For the three-dimensional CE-MRA acquisitions that were initiated at the time of contrast arrival, there was a gradual improvement in signal-to-noise ratio (SNR) in the carotid arteries with increasing injection rate. The same trend was not observed for the acquisitions that were initiated at the time of peak contrast. SENSE combined with random elliptic k-space acquisition in CE-MRA allows for higher SNR with fewer ringing artifacts at faster contrast injection rates.

Animals↗
PubMed1999

Volumetric reduction of a choroid plexus carcinoma using preoperative chemotherapy.

We report for the first time a measured volumetric reduction of a choroid plexus carcinoma utilizing preoperative chemotherapy. Histologically proven choroid plexus carcinoma was diagnosed in a fifteen month old female. She was treated with three courses of chemotherapy including etoposide (VP16), cyclophosphamide, vincristine, and cisplatin. Computer-assisted three dimensional reconstruction of the tumor volume was performed prior to and after three courses of chemotherapy. An overall reduction of 29.5% of tumor volume was accomplished preoperatively. Staged surgical procedures resulted in a complete resection of her lesion and she has remained disease-free for 31 months. A volumetric measurement as a response to preoperative chemotherapy may prove valuable in determining future optimal treatment regimens for choroid plexus carcinoma of childhood.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Conformational change of adrenodoxin induced by reduction of iron-sulfur cluster. Proton nuclear magnetic resonance study.

Bovine adrenodoxin in the reduced form has been measured by one- and two-dimensional 1H NMR spectroscopy. By comparing the spectrum of reduced adrenodoxin with that of the oxidized protein, resonances have been assigned for the aromatic residues. The spin-lattice relaxation time for the resonances due to histidine residues was found to depend on the reduction state of adrenodoxin. The distance from the paramagnetic center is calculated by using the Solomone-Bloembergen equation. The resonances from Tyr-82 and Ala-81 show large chemical shift changes upon reduction of adrenodoxin. The conformational change of adrenodoxin manifested by chemical shift difference between reduced and oxidized forms is found in the sequence around Tyr-82 and Ala-81. Modification with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide at Glu-74, Asp-79, and Asp-86 inhibited the interaction with both adrenodoxin reductase and cytochrome P-450scc (Lambeth, D. J., Geren, L. M., and Millett, F. (1984) J. Biol. Chem. 259, 10025-10029; Geren, L. M., O'Brien, P., Stonehuerner, J., and Millett, F. (1984) J. Biol. Chem. 259, 2155-2160). Thus, the sequence of these amino acids was assigned to the interaction site with the redox partners. The present 1H NMR investigation of adrenodoxin demonstrates that a conformational change upon reduction of the iron-sulfur cluster occurs in the sequence of negatively charged amino acids that is a putative site for interaction with redox partners. This could offer the structural basis of the electron transfer mechanism in which adrenodoxin functions as a mobile electron carrier.

Adrenodoxin↗
PubMed1992

Measurement of efflux from G1-phase in a growth factor dependent cell line.

In order to test a mathematical model of G1/S-phase transition, the proliferative response of the murine myeloid interleukin 3 (IL-3) dependent cell line NFS-78 to graded reduction of IL-3 levels was measured. Exponentially growing cells were exposed to bromodeoxyuridine (BUdR), which replaces thymidine (TdR) in the DNA double strands during DNA synthesis. After incubation periods ranging from 3 to 36 h the cells were fixed and stained with a fluorescence dye mixture of Hoechst 33258 and ethidium bromide (EB) and subsequently analyzed in a two-parametrical flow cytometer. The BUdR-quenched TdR-specific Hoechst 33258 fluorescence of each cell provides information on the cell cycle location at the start of incubation and on whether or not a cell has divided. The DNA-specific EB fluorescence provides information on the actual cell cycle location at the end of the incubation period. From the 2-dimensional fluorescence distributions the efflux from G1-phase was calculated. Upon IL-3 reduction the cells showed accumulation in the G1-phase along with a reduction in the progression rate through the other phases of the cell cycle. By staining with the vital dye Hoechst 33342 as well as with propidium iodide (PI) it was further possible to show that cell death after IL-3 withdrawal occurred in all phases of the cell cycle.

Animals↗
PubMed1994

Quantitative and 3-dimensional analysis of Langerhans cells in basal cell carcinoma. A comparative study using light microscopy and confocal laser scanning microscopy.

We have analysed Langerhans cells (LCs) in basal cell carcinoma (BCC) and in healthy skin in 15 patients, using three different techniques: light microscopic examination of horizontal sheets, and of 6-micron-thick vertical skin sections, and confocal laser scanning microscopy (CLSM) of 25-micron-thick vertical sections. The use of CLSM enables both a quantitative and a three-dimensional (3-D) analysis of the cells in the same tissue volume. A statistically significant reduction in the relative volume of epidermal CD1a reactivity confined to tumour areas was found with CLSM. This difference was confirmed when the number of LCs in horizontal sheets were counted. In contrast, no significant reduction in epidermal CD1a+ cells was found in thin vertical sections. This is probably due to the smaller tissue sample examined, and to variations in the number of CD1a+ cells, with less cells directly overlying the tumour nests. The ratio of CD1a-expressing cells in the epidermis/dermis was significantly reduced in BCCs, compared with healthy looking skin. Few LCs were observed in tumour nests, but they were numerous in the surrounding stroma of the dermis. Three-dimensional reconstructions of CD1a+ cells in BCC revealed striking morphological changes; they had a reduced number of dendrites, and these were often short and had few branches. The results demonstrate that CLSM is a suitable technique for quantitative and morphological analysis of CD1a-expressing cells in the skin. We suggest that the alterations in LC numbers, distribution and morphology in BCC most probably are secondary to changes in the local environment.

Adult↗
PubMed2001

Bony orbital development after early enucleation in humans.

AIM: To analyse the extent of bony orbital volume reduction after enucleation in humans. METHODS: Volumetric studies on bony orbital volumes based on three dimensional reconstructions acquired from high resolution computed tomograph (CT) scans were performed in 29 patients with acquired anophthalmia and four patients before enucleation (controls). Eight patients (follow up 25-52 years) were enucleated in childhood aged between 0.4 and 8 years (group I), 21 in adulthood aged between 15 and 53 years. Fifteen of these patients (group IIa) had long standing anophthalmia (follow up 7-53 years), six patients (group IIb) were enucleated 9 months to 4 years before CT. RESULTS: Bony orbital volumes were reduced in all patients with long standing anophthalmia. The median percentage reduction in enucleated orbits was 7.0% in group I, 3.8% in group IIa, and 1.9% in group IIb. In patients with long standing anophthalmia (I and IIa) the reductions were statistically significantly different (p <0.01) from zero. There was some evidence of a correlation between orbital volume reduction and age at enucleation (rho = 0.36, p = 0.09, Spearman rank correlation coefficient) and a statistically significant correlation between volume reduction and time interval since enucleation (rho = -0.5, p = 0.003). Clinically none of the patients showed significant facial asymmetry. CONCLUSIONS: These data provide strong evidence that enucleation both in children and adults is associated with a reduction of bony orbital volume and that this decrease in volume is associated with increasing time. However, the reduction is smaller than generally assumed and does not cause obvious facial asymmetry. It is more related to the time interval since enucleation than the age at enucleation, which makes a mechanism of volume adaptation more likely than just retardation of growth.

Adolescent↗
PubMed2000

Kinetic characterization of Desulfovibrio gigas hydrogenase upon selective chemical modification of amino acid groups as a tool for structure-function relationships.

The effect of amino acid residues modification of Desulfovibrio gigas hydrogenase on different activity assays is reported. The first method consisted in the modification of glutamic and aspartic acid residues of the enzyme with ethylenediamine in order to change the polarity of certain regions of the protein surface. The second method consisted in the modification of histidine residues with a Ru complex in order to change the acid-base properties of the histidine residues. The implication of these modifications in the enzyme kinetics has been studied by measuring in parallel the activities of para/ortho hydrogen conversion, deuterium/hydrogen exchange and dyes reduction with hydrogen. Our experimental data support some hypothesis based on the three-dimensional structure of this enzyme: (a) electrostactic interactions between the hydrogenase and the redox partner play an essential role in the kinetics; (b) the histidine ligand and the surrounding acidic residues of the distal [4Fe4S] cluster form the recognition site of the redox partner of the hydrogenase; and (c) histidine residues are involved in the hydron transfer pathway of the hydrogenase.

Amino Acids↗
PubMed1980

Optoelectric (Selspot) gait measurement in two- and three-dimensional space--a preliminary report.

Traditional studies of human movement by photographic methods require tedious, error-prone, and expensive data reduction. Various optoelectronic methods have been designed. A commercially available system, SELSPOT, purchased for the Cleveland VAMC Motion Study Laboratory, is described. Sequentially pulsed light-emitting-diode targets on the subject are observed, with data fed into a computer for combination with force plate data (Cohen, Orin, and Marsolais, Technical Note, BPR 10-33). Calibration methods, errors, and practical difficulties are described. Though problems remain after revisions (see progress reports in BPR), it is believed that SELSPOT offers potential for clinically useful real-time acquisition and analysis of three-dimensional data.

Biomechanical Phenomena↗
PubMed1989

Interferon gamma inhibits both proliferation and expression of differentiation-specific alpha-smooth muscle actin in arterial smooth muscle cells.

Differentiation of muscle cells is characterized morphologically by the acquisition of contractile filaments and characteristic shape changes, and on the molecular level by induction of the expression of several genes, including those for the muscle-specific alpha-actin isoforms. IFN-gamma is an inhibitor of proliferation for several cells, including vascular smooth muscle, and is also an inducer of differentiated properties for several hematopoietic cells. We have therefore investigated whether IFN-gamma affects the expression of alpha-smooth muscle actin in cultured arterial smooth muscle cells. Cells exposed to IFN-gamma show a reduction of alpha-smooth muscle actin-containing stress fibers, as detected by immunofluorescence. The effect was observed in all phases of the cell cycle, and was caused by a reduction of the synthesis of alpha-smooth muscle actin protein as revealed by two-dimensional electrophoretic analysis of actin isoforms. RNA hybridization using a cRNA probe that hybridizes to all actin mRNAs showed that IFN-gamma-treated cells have a reduced content of the 1.7-kb mRNA that codes for alpha-smooth muscle actin, and to a lesser extent, also of the 2.1-kb mRNA encoding the beta and gamma-cytoplasmic actins. The reduction of alpha-smooth muscle actin mRNA was confirmed using an alpha-smooth muscle actin-specific cRNA probe. The reduction of alpha-smooth muscle actin mRNA occurs within 12 h, and is dependent on protein synthesis, since cycloheximide treatment reversed the effect. The inhibition of this mRNA species was dose dependent, and detectable by RNA hybridization at a dose of 50 U/ml IFN-gamma. These results suggest that the differentiation of arterial smooth muscle cells is not necessarily coupled to an inhibition of cellular proliferation. Instead, IFN-gamma may regulate the expression of several genes that control both proliferation and expression of differentiation markers.

Actin Cytoskeleton↗
PubMed1999

Diagnostic change and personality stability following functional restoration treatment in chronic low back pain patients.

This study examined personality pathology in a group of patients with chronic low back pain (CLBP) using both diagnostic interviews and dimensional self-report instruments. A group of CLBP patients (N = 125) was assessed before functional restoration treatment and compared with a matched normal comparison group (N = 75). The CLBP group evidenced broad personality pathology in all assessment modes pretreatment relative to the normal comparison sample. In addition, two subsamples of CLBP patients (n = 49 and n = 56) were assessed after treatment. Reductions in personality pathology between pre- and posttreatment assessments were more pronounced for diagnostic interview than dimensional self-report assessments. These results are discussed in the context of personality assessment and CLBP.

Adolescent↗
PubMed2005

Reduction of the concentration difference of proteins in biological liquids using a library of combinatorial ligands.

The discovery of polypeptides and proteins with relevance to a particular biological state is complicated by their vast number and concentration range in most biological mixtures. Depletion methodologies are frequently used to remove the most abundant species; however, this removal not only fails significantly to enrich trace proteins, it may also nonspecifically deplete them due to their interactions with the removed high-abundance proteins. Here we report a simple-to-use methodology that reduces the protein concentration range of a complex mixture like whole serum through the simultaneous dilution of high-abundance proteins and the concentration of low-abundance proteins. This methodology utilizes solid-phase ligand libraries of immense diversity, generated by "split, couple, recombine" combinatorial chemistry, that are used for affinity-based binding to the proteins of a given mixture. With a controlled sample-to-ligand ratio it is possible to modulate the relative concentration of proteins such that many peptides or proteins that are undetectable by classical analytical methods become easily accessible. The reduction in the dynamic range of unfractionated serum is specifically described along with treatment of other proteomes such as extracts from Escherichia coli, chicken egg white and cell culture supernatant. Mono- and bi-dimensional electrophoresis (1-DE and 2-DE respectively) and surface-enhanced laser desorption/ionization-mass spectrometry (SELDI-TOF-MS) technology demonstrate the reduction in protein concentration range. Combining this approach with additional fractionation methods further increased the number of detectable species.

Adsorption↗
PubMed2004

Feature reduction and morphological processing for hyperspectral image data.

An automatic target detection system that uses hyperspectral (HS) imagery is proposed. HS images contain both spatial and spectral response information that provides detailed descriptions of an object. These new, to our knowledge, sensor data are useful in automatic target recognition applications. To provide discrimination information from the HS images and to select features that generalize well, we describe a new, to our knowledge, high-dimensional generalized discriminant feature-extraction algorithm and compare its performance with that of other feature-reduction methods for two HS target detection applications (mine and vehicle detection) by using a nearest-neighbor classifier. We also advance an approach to simultaneously optimize both spatial and spectral responses.

Journal Article↗
PubMed2002

The origin of ultrasound-induced friction reduction in microscopic mechanical contacts.

We present a study of the origin of ultrasound-induced friction reduction in microscopic mechanical contacts. The effect of friction reduction caused by Rayleigh-type surface acoustic waves (SAWs) is demonstrated for propagating and two-dimensional, standing wave fields using lateral force microscopy (LFM). It is shown that with increasing wave amplitude, friction is completely suppressed. To detect and distinguish between the effect of lateral and vertical surface oscillation components on the cantilever movement, we employed multimode scanning acoustic force microscopy (SAFM). We found that the friction reduction effect is only due to the vertical oscillation component. Because this effect does not appear for purely in-plane polarized Love waves, we concluded that the mechanical diode effect is most probably responsible for the SAW-induced lubrication. This explanation is also supported by vertical and longitudinal SAFM measurements, which show that, in areas where friction is completely suppressed, low frequency vertical cantilever oscillations can still be observed, whereas lateral or torsional oscillations are no longer excited.

Acoustics↗