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PubMed1987

Regression of cardiac hypertrophy after antihypertensive therapy with nifedipine and captopril.

The effects of two antihypertensive agents, nifedipine (N) and captopril (C), on left ventricular (LV) mass and volume were studied in 16 patients with essential hypertension (8 treated with N and 8 with C for 6 months) by means of a complete M-mode echocardiogram monitored by two-dimensional echocardiography. Both N and C induced a significant reduction in end-diastolic, but not systolic, posterior wall and septum thickness and an increase in end-diastolic volume, but not in end-systolic volume. A significant increase in the contribution of rapid filling together with a simultaneous reduction in the contribution of atrial systole to end diastolic volume were also observed. The reduction in LV wall thickness and mass after both C and N might be attributed to an improvement in diastolic function and to a reduction in wall tension, rather than to an effective regression of LV hypertrophy.

Adult↗
PubMed1989

[Orthodontic approach to temporomandibular arthrosis. A case report of medial displacement of the articular disk].

This clinical report presents orthodontic applications of double contrast arthrotomography and arthroscopy of the temporomandibular joint. We examined a case of mandibular shift with stomatognathic dysfunction using these techniques, and found medial displacement of the articular disk. Generally, displacement of the articular disk is examined only from sagittal section. However, this case indicates that frontal section of double contrast arthrotomography is necessary for the three dimensional understanding of the TMJ. Mandibular position with disk reduction was obtained by double contrast arthrogram, and medial displacement of the disk and malocclusion were treated by dynamic positioner. It is suggested that orthodontic treatment is an effective method both for treatment of internal derangement of the TMJ and also for the final reconstruction of occlusion.

Arthroscopy↗
PubMed1993

An antigenic polysaccharide from Campylobacter coli serotype O:30. Structure of a teichoic acid-like antigenic polysaccharide associated with the lipopolysaccharide.

A water-soluble antigenic polysaccharide of high M(r) associated with the lipopolysaccharide has been isolated from phenol-water extraction of cells of Campylobacter coli serotype O:30. The polysaccharide and oligosaccharide degradation products formed on O-dephosphorylation and by periodate oxidation followed by reduction have been investigated by one- and two-dimensional 1H, 13C, and 31P NMR. It is concluded that the antigenic polysaccharide has a teichoic acid-like structure with a poly-Ribitol phosphate, [5-Ribitol-1-P]n, backbone with side chains at O-2 of O-(6-deoxy-beta-D-talo-heptopyranosyl)-(1-->4)-(2-acetylamino-2-deoxy-beta-D- glucopyranosyl) units. The structure is unusual in Gram-negative bacteria and is unique in possessing 6-deoxy-D-talo-heptose as a constituent sugar. Evidence for the relationship of the antigenic polysaccharide to the lipopolysaccharide of low M(r) is discussed.

Campylobacter coli↗
PubMedDate not supplied

[A map of dyadic relations in the Giessen Test].

A series of random samples was carried out to validate a new model for diagnosing couple relationships using the Giessen test. The model delineates all theoretically possible types of couple relationships in the course of which individual scores can be compared simultaneously with standard scores. The interpretation is based on a two-dimensional diagram, which is to be understood as a reduction of a more complex structure.

Adult↗
PubMed1996

Alcohol and the heart: biochemical alterations.

A considerable amount of attention has focused on the cardiovascular events associated with ethanol consumption. The available evidence suggests that moderate ethanol consumption is associated with reduced risk of coronary heart disease, i.e., vessel events. In contrast, this review is primarily concerned with ethanol and heart muscle damage. Clinical features of the consequences of prolonged and excessive ethanol consumption encompass defects in myocardial contractility and derangement of cellular architecture, including disarray of the contractile elements. Although the incidence of heart muscle abnormalities in alcohol misusers is generally higher than previously considered, the mechanisms are only just being elucidated. This process has been facilitated by laboratory based studies in which animals receive either a single dose of ethanol (acute studies) or a continuous supply of ethanol in their daily diets (chronic studies). Results from these models show that acute ethanol dosage causes a marked decrease in the synthesis of contractile proteins. This occurs in the absence of overt mitochondrial abnormalities: ATP concentrations are generally unaffected. Paradoxically, the synthesis of mitochondrial proteins is reduced. Use of metabolic inhibitors suggests that the deleterious effects of acetaldehyde contribute to these reductions in protein synthesis. In chronic studies, ethanol causes a reduction in the amount of contractile proteins, and two dimensional protein profiling implicates selective loss of individual myocardial proteins. The differential activities of lysosomal proteases may contribute to this patterned response. However, in chronic ethanol feeding, adaptive mechanisms also become important, as the synthesis of the myofibrillary proteins increases. Overall, the mechanisms inherent in these biochemical responses may contribute to the genesis of a distinct disease entity, alcoholic heart muscle disease.

Animals↗
PubMed1989

Dynamics of the multidomain fibrinolytic protein urokinase from two-dimensional NMR.

The recent demonstrations that thrombolytic therapy with plasminogen activators can result in substantial reductions in mortality from coronary thrombosis have generated considerable interest in the properties of fibrinolytic enzymes. Examination of the primary sequence of these proteins (which include tissue plasminogen activator, plasminogen, and urokinase) reveals that each is composed of a mosaic of domains which appear to be spatially distinct and connected by short peptide linkers. There is, however, little experimental information about the three-dimensional structure of any of the proteins, although several X-ray diffraction and NMR studies of isolated domains have been reported. Here we report two-dimensional NMR spectra of intact urokinase which are remarkably well resolved for a protein of this molecular weight. This effect is a consequence of substantial independent motion between individual domains of the protein, which overcomes the broadening effects anticipated for the slow overall tumbling rate of the intact molecule. As well as having significance for the physiological role of the protein, these results provide a direct means for the comparison of structural features determined for the isolated domains with those of the intact protein and may provide a basis for proposing or evaluating models for the overall structure of fibrinolytic proteins. Preliminary results with other proteins indicate that this approach may be generally applicable to other multidomain proteins of the fibrinolytic family.

Epidermal Growth Factor↗
PubMed2007

Two- and three-dimensional imaging of multicomponent systems using scanning thermal microscopy and localized thermomechanical analysis.

The aim of this study was to develop a novel approach to the spatial characterization of multicomponent samples, based on the emergent technique of microthermal analysis. More specifically, we present an assessment of the use of scanning thermal microscopy as a means of component mapping via thermal conductivity; we include a new statistical approach to data handling, which allows reduction of topographic effects. We also introduce a novel three-dimensional mapping technique based on localized thermomechanical analysis. Tablets of paracetamol and hyproxypropyl methylcellulose (HPMC) and 50:50 mixes of the two were prepared and the materials characterized in scanning and localized modes using a TA Instruments 2990 microthermal analyzer with a Thermomicroscopes Explorer AFM head and Wollaston wire thermal probe. L-TMA studies of the pure components indicated markedly differing thermal responses, with the paracetamol showing a sharp melting accompanied by a probe pull-in effect, while HPMC showed only thermal expansion over the temperature range studied. Thermal conductivity and topographic images indicated that two-dimensional differentiation between the components was possible in scanning mode. A means of delineating the relative contribution of the topographic and conductivity effects was developed based on a regression analysis of the thermal conductivity measurements on a set of terms representing the local surface curvature. The results of three-dimensional imaging using a grid of L-TMA measurements is presented. This technique utilized the distinct thermal responses of the two components to allow the probe to melt through the paracetamol down to the underlying HPMC. The advantages and limitations of this novel imaging method are discussed in the context of pharmaceutical and broader uses of the approach.

Journal Article↗
PubMed1981

Thrombin-induced proteolysis of human antithrombin III: an outstanding contribution of heparin.

Products obtained in reaction of excess antithrombin III (AT III) with human alpha-thrombin and heparin were found to contain markedly less of residual AT III than products of similar reactions without heparin. The increased utilization of AT III was primarily due to limited proteolysis of a portion of unbound inhibitor, associated with the release of a 50 000-dalton protein fragment. Thrombin-induced release of this fragment was promoted by polydispersed heparin preparation and, to a variable degree, by all heparin fractions obtained in gel filtration. The optimum amount of heparin required to facilitate AT III proteolysis was of 5 microgram/ml (0.8 u/ml). Excessive reduction of the residual inhibitory activity and changes in two-dimensional immunoelectrophoresis suggested that AT III in plasma is also subjected to nonproductive proteolysis and formation of a modified AT III derivative following addition of thrombin and heparin. These data indicate that the effect of heparin on AT III is more complex than generally recognized. On the one hand, heparin interacting with AT III and thrombin contributes to a rapid binding and neutralization of the enzyme; on the other, heparin facilitates proteolytic degradation of unbound inhibitor even in the presence of small quantities of thrombin accounting for excessive reduction of the overall inhibitory potential of AT III.

Antithrombin III↗
PubMed2004

Noise reduction in MR angiography with nonlinear anisotropic filtering.

PURPOSE: To evaluate three-dimensional nonlinear anisotropic filtering in suppressing image noise in high spatial resolution magnetic resonance angiograms (MRA) acquired with hybrid undersampled projection reconstruction and phase contrast vastly undersampled isotropic projection reconstruction (PC-VIPR). MATERIALS AND METHODS: Three-dimensional nonlinear anisotropic filtering was quantitatively analyzed and evaluated through the measurement of contrast to noise ratio (CNR) in PC-VIPR images and contrast enhanced peripheral MRA images. To filter MRA images with ultra-high spatial resolution and poor CNR, a spatial frequency dependent nonlinear anisotropic filtering algorithm was proposed that uses two-step processing to filter the whole spatial frequency data. RESULTS: Three-dimensional nonlinear anisotropic filtering was shown to be effective in suppressing noise and improving CNR in MRA with isotropic spatial resolution. Higher CNR was achieved using spatial frequency dependent nonlinear anisotropic filtering. A typical CNR gain of between 50-100% was shown in our studies. CONCLUSION: Three-dimensional nonlinear anisotropic filtering significantly improved CNR in MRA images with isotropic spatial resolution. Spatial frequency dependent nonlinear anisotropic filtering further improved CNR for MRA images with ultra-high spatial resolution and low CNR.

Anisotropy↗
PubMed1980

Effects of the reduction and S-carbamidomethylation on the conformation, activity and heparin-binding capacity of human antithrombin III.

Antithrombin III has been shown to contain three disulphide bridges. They can be broken by reduction under non-denaturing conditions. The completely reduced and S-carbamidomethylated protein is devoid of thrombin-inhibiting activity and does not bind heparin. However, the immunological reactivity as determined by electroimmunoassay is almost unchanged, indicating that no large conformational changes occur upon cleavage of the disulphide bonds. This is also supported by the observation that the reduced and S-carbamidomethylated protein has the same fluorescence properties as the native protein dichroic spectrum of the native protein shows a pronounced pattern in the near-ultraviolet region, indicating restricted rotation of the aromatic amino acid side chains. This is drastically changed by the reduction and carbamidomethylation. The character of the far-ultraviolet circular dichroic spectrum is similar in the native and reduced S-carbamidomethylated protein. The reduction and S-carbamidomethylation of antithrombin III induces some local changes in the tertiary structure affecting the inhibitor activity, heparin binding and near-ultraviolet circular dichroic spectrum, but do not seem to induce any substantial general conformation change.

2,2'-Dipyridyl↗
PubMed1984

Computer aided evaluation of two-dimensional NMR spectra of proteins.

A computer program for the automatic evaluation of two-dimensional NMR spectra of peptides and proteins has been developed. The used strategy is described, the advantages and limits of this approach are discussed. The program was successfully tested on a COSY-spectrum of the neuropeptide Glp-Pro-Pro-Gly-Gly-Ser-Lys-Val-Ile-Leu-Phe from hydra, resulting in a drastic reduction of the time needed for the evaluation of two-dimensional NMR data.

Amino Acid Sequence↗
PubMed2005

Functional significance of Glu-77 and Tyr-137 within the active site of isoaspartyl dipeptidase.

Isoaspartyl dipeptidase (IAD) is a binuclear metalloenzyme and a member of the amidohydrolase superfamily. This enzyme catalyzes the hydrolytic cleavage of beta-aspartyl dipeptides. The pH-rate profiles for the hydrolysis of beta-Asp-Leu indicates that catalysis is dependent on the ionization of two groups; one that ionizes at a pH approximately 6 and the other approximately 9. The group that must be ionized for catalysis is directly dependent on the identity of the metal ion bound to the active site. This result is consistent with the ionization of the hydroxide that bridges the two divalent cations. In addition to the residues that interact directly with the divalent cations there are two other residues that are highly conserved and found within the active site: Glu-77 and Tyr-137. Mutation of Tyr-137 to phenylalanine reduced the rate of catalysis by three orders of magnitude. The three dimensional X-ray structure of the Y137F mutant did not show any significant conformation changes relative to the three dimensional structure of the wild-type enzyme. The positioning of the side-chain phenolic group of Tyr-137 in the active site of IAD is consistent with the stabilization of the tetrahedral adduct concomitant with nucleophilic attack by the hydroxide that bridges the two divalent cations. Mutation of Glu-77 resulted in the reduction of catalytic activity by five orders of magnitude. The three dimensional structure of the E77Q mutant did not show any significant conformational changes in the mutant relative to the three dimensional structure of the wild-type enzyme. The positioning of the side-chain carboxylate of Glu-77 is consistent with the formation of an ion pair interaction with the free alpha-amino group of the substrate.

Binding Sites↗
PubMed1995

Role of disulfide linkages in structure and activity of proteinase inhibitor from horsegram (Dolichos biflorus).

Proteinase inhibitor isolated from horsegram (Dolichos biflorus or Macrotyloma uniflorum) inhibited specifically the enzymes trypsin and chymotrypsin. The inhibitor contained seven disulfide linkages and was free from thiol groups. The inhibitor is resistant to denaturation by urea, guanidine hydrochloride or sodium dodecyl sulfate. Reduction of the inhibitor with dithiothreitol abolished both trypsin and chymotrypsin inhibitory activities. The kinetic plots of the reduction as followed by activity and loss in structure as reflected in the 257 nm CD band could be superposed; loss in the activity paralleled the loss in structure. The kinetics of the reduction process was complex; reduction of the inhibitor was slow and depended on the concentration of DTT. Reduction of the disulfide linkages with DTT affected the tertiary structure significantly and secondary structure was not affected considerably. Fluorescence quenching by acrylamide and potassium iodide suggested the unfolding of the molecule due to reduction. Thus, disulfide linkages play a predominant role in maintaining the three-dimensional structure of the inhibitor.

Disulfides↗
PubMed2003

Brosilow-Ziff model for the CO-NO surface reaction on disordered two- and three-dimensional substrates.

The Brosilow-Ziff model, which for a uniform lattice shows superficial poisoning by the "checkerboard mechanism" for simplified Langmuir-Hinshelwood kinetics of the reduction reaction of NO by CO, has been studied in the case of various disordered substrates: two-dimensional (2D) incipient percolation cluster, backbone, and diffusion-limited aggregate (2D) fractals, together with a deterministic fractal and a statistical substrate, both three-dimensional. Some additional effects such as diffusion, nearest-next-neighbor sites, and desorption are also considered. The systems were found to be nonreactive and pseudoreactive in all the cases which showed the checkerboard mechanism. Otherwise, a reactive zone (window) related directly to the geometric structure of the substrate is seen.

Journal Article↗
PubMed1996

Response characteristics of a low-dimensional model neuron.

It is shown that a low-dimensional model neuron with a response time constant smaller than the membrane time constant closely reproduces the activity and excitability behavior of a detailed conductance-based model of Hodgkin-Huxley type. The fast response of the activity variable also makes it possible to reduce the model to a one-dimensional model, in particular for typical conditions. As an example, the reduction to a single-variable model from a multivariable conductance-based model of a neocortical pyramidal cell with somatic input is demonstrated. The conditions for avoiding a spurious damped oscillatory response to a constant input are derived, and it is shown that a limit-cycle response cannot occur. The capability of the low-dimensional model to approximate higher-dimensional models accurately makes it useful for describing complex dynamics of nets of interconnected neurons. The simplicity of the model facilitates analytic studies, elucidations of neurocomputational mechanisms, and applications to large-scale systems.

Action Potentials↗
PubMed1984

Improvement in left ventricular diastolic function during intravenous and oral diltiazem therapy in patients with hypertrophic cardiomyopathy: an echocardiographic study.

M-mode echocardiography was used to evaluate the acute effect of intravenously administered diltiazem, 10 mg, and the chronic effects of oral diltiazem, 180 mg/day, and propranolol, 60 to 120 mg/day, administered for 2 weeks on left ventricular (LV) systolic and diastolic function in 13 patients with hypertrophic cardiomyopathy. Intravenous injection of diltiazem reduced isovolumic relaxation time from 114 +/- 26 to 99 +/- 21 ms (p less than 0.01) and the time to peak rate of LV dimensional lengthening from 166 +/- 17 to 133 +/- 10 ms (p less than 0.01), without significant changes of LV dimensions or fractional shortening. No significant changes were observed in LV dimensions or fractional shortening, but a significant increase in peak rate of LV dimensional lengthening (from 4.1 +/- 1.5 to 4.8 +/- 1.6/s, p less than 0.05) and a reduction in isovolumic relaxation time (from 105 +/- 26 to 77 +/- 23 ms, p less than 0.01) and the time to peak rate of LV dimensional lengthening (from 156 +/- 23 to 124 +/- 20 ms, p less than 0.01) occurred during the oral administration of diltiazem. In contrast, propranolol caused no significant changes in these values. Thus, diltiazem improves LV relaxation and diastolic filling without altering LV systolic function in patients with hypertrophic cardiomyopathy.

Administration, Oral↗
PubMed1979

Effect of alkylation on the physical properties of simian virus 40 T-antigen species.

We analyzed large and small species of T-antigen by immunoprecipitation and two-dimensional gel electrophoresis. The T-antigen species were subjected to electrophoresis either directly or after reduction and alkylation with N-ethylmaleimide. Treatment with N-ethylmaleimide improved the resolution of large-T by two-dimensional gel electrophoresis and was a requirement for the resolution of small-t antigen on two dimensional gels. Large-T did not form a discrete protein spot, but rather formed a streak from approximately pH 6.5 to 6.9 on isoelectric focusing gels. Small-t formed a sharp protein spot at approximately pH 7.2 when subjected to electrophoresis under non-equilibrium conditions which extended the pH gradient to include proteins with basic isoelectric points. Treatment with N-ethylmaleimide decreased the mobility of the T-antigen species during sodium dodecyl sulfate gel electrophoresis. We suggest that the apparent increase in molecular weight was due to the association of N-ethylmaleimide with cysteine-rich regions of these proteins. Viable deletion mutants of simian virus 40 which do not induce the synthesis of small-t but product small-t-related polypeptides were used to localize the cysteine-rich region of small-t to between 0.54 and 0.59 on the genetic map of simian virus 40.

Alkylation↗
PubMedDate not supplied

Two dimensional prolate spheroidal wave functions for MRI.

The tradeoff between spatial and temporal resolution is often used to increase data acquisition speed for dynamic MR imaging. Reduction of the k-space sampling area, however, leads to stronger partial volume and truncation effects. A two dimensional prolate spheroidal wave function (2D-PSWF) method is developed to address these problems. Utilizing prior knowledge of a given region of interest (ROI) and the spatial resolution requirement as constraints, this method tailors the k-space sampling area with a matching 2D-PSWF filter so that optimal signal concentration and minimal truncation artifacts are achieved. The k-space sampling area is reduced because the shape and size of the sampling area match the resolution posed by the non-rectangular shape of a convex ROI. The 2D-PSWF method offers an efficient way for spatial and temporal tradeoff with minimal penalty due to truncation, and thus, it promises a wide range of applications in MRI research.

Adult↗