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[The reaction of holo-, apo- and coenzyme of the peroxidase to heating (author's transl)].

The thermal reaction of the two components of the horseradish peroxidase--the apoenzyme and the prosthetic group--with that of the holoenzyme were compared. From this we conclude that the thermal inactivation of the peroxidase in aqueous solution is not caused by a change of the apoprotein alone, but rather by participation of the entire three-dimensional structure including the prosthetic group. Spectrophotometric studies of the inactivation process in the holoenzyme revealed that the absorbance of the Soret band changes parallely to a reduction of the enzyme activity during heating. Since it has been found that the Soret absorption increases again during storage and simultaneously the enzyme activity regenerates, the change of the Soret absorption during heating can be regarded as the result of both reversible and irreversible denaturation processes.

Apoenzymes↗

Subunits of IgM and IgD on the surface of murine B-lymphocytes.

Immunoglobulin isolated from 125I-labelled cell surface proteins of murine B-lymphocytes was analyzed by a sensitive two-dimensional polyacrylamide gel electrophoresis technique (2D-SDS-PAGE). Uncleaved Ig molecules were electrophoresed in the first dimension in an SDS-polyacrylamide gel, and after subsequent reduction of the disulphide bonds by mercaptoethanol, the cleaved polypeptides were separated in the second dimension using again an SDS-polyacrylamide gel. This technique enables the identification of unreduced Ig molecules and their corresponding subunit components. In the case of IgM as well as IgD the four chain structure (H2L2), half molecules (HL), and disulphide-linked heavy chains (HH) could be identified. Since all Ig subunits were isolated by an anti-IgG antiserum by virtue of its L-chain specificity we conclude that L-chains are noncovalently associated with the disulphide-linked heavy chains (HH). Free noncovalently bound L-chains could actually be identified by 2D-SDS-PAGE. However, this technique does not determine whether half Ig molecules (HL) are noncovalently associated with each other. In addition to free L-chains noncovalently linked mu and delta-chains were found. Control experiments showed that the identified Ig subunits are not artefacts of the isolation procedure or reduction moieties of H2L2 molecules (e.g. incubation of isolated mu 2L2 and delta 2L2 with detergent extracts of spleen cells does not result in the formation of subunits). On the basis of 125I-radioactivity incorporated into the Ig subunits it was estimated that besides mu 2L2 and delta 2L2, delta L (40-50% of total IgD) is the main Ig structure on B-lymphocytes. The other Ig subunits (mu L, delta 2, structures (ca. 10(4) molecules/B-cell) are sufficient to act as antigen recognition structures and to be involved in B-lymphocyte triggering and tolerance induction.

Animals↗

Computerised planning of maxillo-facial osteotomies: the program and its clinical applications.

A totally computerised program has been developed which undertakes the 2-dimensional planning of a complete maxillo-facial reconstruction using Le Fort I, II & III, Wassmund, Schuchardt, Küfner, Köle, Dingman, Obwegeser and VSS osteotomies with augmentation or reduction genioplasty and rhinoplasty. The program incorporates the calibration of the equipment, initialization of new discs, a filing system for osteotomy patients, unlimited expansion facilities for storage of files and an automatic cephalometric analysis which is updated at each stage. A suggested operation, which may be altered for aesthetics, is generated spontaneously by the computer. The surgeon or the patient is free to accept or reject the computer's suggestion in part or whole.

Cephalometry↗

[Comparative study and clinical implementation of two breathing-adapted radiotherapy techniques: dosimetric benefits for lung cancer treatment].

Breathing can lead to organ motions up to several centimeters. For radiotherapy of lung, these motions are generally taken into account by adding a specific margin around the target. Thus, treated volumes are often too large to allow for the high-dose values requested for local control. To manage respiratory motion, deep-inspiration breath-hold technique (DIBH) and gated radiotherapy are starting being used clinically. DIBH consists in asking the patient to perform breath-hold during the treatment and the image acquisition, DIBH level being measured by a spirometer. Gated radiotherapy consists in treating the patient at a certain phase of the free breathing. Linac is synchronized with the motion of a marker located on the patient chest. Planning images are obtained by a four-dimensional CT (4D-CT) using the same marker. We have assessed the value of these two methods. For lung treatment, compared to a standard treatment, toxicity reduction was mainly due to the lung total volume increase. It is therefore more significant for breath-hold approach. It is also due to the reduction of safety margins, which is similar for both methods. These two techniques, which have specific advantages and drawbacks, are used routinely at Curie Institute for a large proportion of lung patients, but also for some breast, liver or even Hodgkin disease treatments.

Adenocarcinoma↗

Interglycosidic acetals. Part 3. Synthesis and structure determination of cyclic monobenzylidene acetals of cyclodextrin derivatives bridging between two contiguous D-glucopyranosyl residues.

Transacetalation of fully 6-O-pivaloylated alpha-, beta-, and gamma-cyclodextrins with benzaldehyde dimethylacetal in the presence of (+)-10-camphorsulfonic acid gave monobenzylidene acetals (4, 5, 6) in moderately good yields. Benzylation of the beta-cyclodextrin derivative 5 followed by acid-catalyzed hydrolysis of the benzylidene group and acetylation afforded a di-O-acetyl-non-adeca-O-benzyl derivative 9. NMR spectroscopic analysis of 9, including two-dimensional HOHAHA and 1H-(13)C correlation experiments revealed that the benzylidene group bridged the O-2 and O-3 positions of contiguous D-glucopyranosyl residues. Reductive ring-opening of the benzylidene acetal with lithium aluminum hydride/aluminum chloride afforded predominantly a 2(1)-O-unprotected derivative 10 in good yield.

Acetals↗

Computer applications in analysis, mapping and cataloging of proteins separated by two dimensional electrophoresis.

Two dimensional electrophoretic separation of complex mixtures of proteins can only be exploited to its fullest potential using sophisticated computerized spot detection, quantification, pattern recognition, pattern normalization, data reduction and data storage. We present a discussion of some of the technical problems and of the options available which will ultimately lead toward full computerization of the data.

Computers↗

Reversal of iatrogenic myocardial edema and related abnormalities of diastolic properties in the pig left ventricle.

OBJECTIVE: This study examines the resolution of iatrogenic edema and related changes in systolic and diastolic properties in the intact pig left ventricle. METHODS: The coronary arteries were perfused for 50 to 60 seconds with diluted blood (hematocrit value 10% +/- 1%, edema group, n = 5) or whole blood (hematocrit value 28% +/- 1%, control group, n = 6) infused into the aortic root during aortic crossclamping in conditioned, anesthetized pigs. After whole blood reperfusion, preload reduction by vena caval occlusion was used to define systolic and diastolic properties at 15-minute intervals. Left ventricular pressure and conductance, aortic flow, and two-dimensional echocardiography were recorded. RESULTS: Left ventricular mass (wall volume) in the edema group increased significantly compared with that in control pigs after crossclamp removal. Mass returned to preperfusion levels after 45 minutes. The ventricular stiffness constant (beta) increased significantly in the edema group versus the control group, returning to baseline by 30 minutes. The diastolic relaxation constant (tau) and base constant (alpha) did not differ between groups. There was no significant change in contractility. CONCLUSION: Increases in left ventricular mass and diastolic stiffness induced by coronary perfusion with hemodiluted blood resolve after 45 minutes of whole blood perfusion in pigs. This study defines physiologic effects of edema in the normal heart while eliminating most common confounding experimental errors.

Animals↗

Computed tomographic simulation of craniospinal fields in pediatric patients: improved treatment accuracy and patient comfort.

PURPOSE: To reduce the time required for planning and simulating craniospinal fields through the use of a computed tomography (CT) simulator and virtual simulation, and to improve the accuracy of field and shielding placement. METHODS AND MATERIALS: A CT simulation planning technique was developed. Localization of critical anatomic features such as the eyes, cribriform plate region, and caudal extent of the thecal sac are enhanced by this technique. Over a 2-month period, nine consecutive pediatric patients were simulated and planned for craniospinal irradiation. Four patients underwent both conventional simulation and CT simulation. Five were planned using CT simulation only. The accuracy of CT simulation was assessed by comparing digitally reconstructed radiographs (DRRs) to portal films for all patients and to conventional simulation films as well in the first four patients. RESULTS: Time spent by patients in the CT simulation suite was 20 min on average and 40 min maximally for those who were noncompliant. Image acquisition time was <10 min in all cases. In the absence of the patient, virtual simulation of all fields took 20 min. The DRRs were in agreement with portal and/or simulation films to within 5 mm in five of the eight cases. Discrepancies of > or =5 mm in the positioning of the inferior border of the cranial fields in the first three patients were due to a systematic error in CT scan acquisition and marker contouring which was corrected by modifying the technique after the fourth patient. In one patient, the facial shield had to be moved 0.75 cm inferiorly owing to an error in shield construction. CONCLUSIONS: Our analysis showed that CT simulation of craniospinal fields was accurate. It resulted in a significant reduction in the time the patient must be immobilized during the planning process. This technique can improve accuracy in field placement and shielding by using three-dimensional CT-aided localization of critical and target structures. Overall, it has improved staff efficiency and resource utilization.

Adolescent↗

An index to quantify normality of gait in young children.

Gait patterns are often described by recording the changes in angular rotation of such joints as the hip, knee and ankle, during a complete cycle. Each joint exhibits distinctive behavior throughout the gait cycle, and abnormal gait can be described by measuring departure from a typical (mean) joint rotation curve. Standard techniques for observation of gait patterns produce large sets of data. Data reduction is achieved in this work by locating primary directions of variation from mean behavior. Variation from the mean can then be summarized with a one-dimensional statistic, thought of as a squared distance from the population mean. Percentiles of this one-dimensional index can be calculated, enabling classification of a child as normal, unusual or abnormal. A key feature of this analysis is that it is applied across multiple joint angle curves and their derivatives, thus providing a measure that takes account of the interactions between the curves as well as their individual characteristics. A data base of 348 gait cycles, collected from normal children, aged 3-7, were analyzed. Data on each child were stored in a 36-dimensional vector. Most information on patterns of variation among normal children can be stored in a smaller 11-dimensional vector, which can be used for diagnostic purposes. Performance of the one-dimensional index of gait is demonstrated on data from very young children, and on children, up to age 7, who were born prematurely.

Ankle Joint↗

Influence of friction at articular surfaces of the temporomandibular joint on stresses in the articular disk: a theoretical approach with the finite element method.

The present study was designed to assess stress and displacement of the temporomandibular joint (TMJ) disk during jaw opening with different frictional coefficients (micro) from 0.0001 to 0.5 at the TMJ disk and bony component interfaces using three-dimensional finite element (FE) models of individual TMJs based on magnetic resonance (MR) images. An asymptomatic female volunteer and a female patient with anterior disk displacement without reduction were selected, and serial sagittal and frontal slices of their MR images were used for the TMJ reconstruction procedure. The condylar movement was recorded during jaw opening by a Gnatho-hexagraph and used as the loading condition for the subsequent stress analysis of the model. In the asymptomatic subject, relatively high von Mises stresses were observed in the anterior and lateral regions of the disk during jaw opening, and the superior boundary, contacting with the glenoid fossa, exhibited lower stresses than those on the inferior boundary facing the condyle. In the symptomatic subject, although the stress value in the disk was relatively low, the posterior connective tissue exhibited high stress throughout jaw opening. Additional increments in stress values and disk displacement were observed as the coefficient of friction increased, especially in the asymptomatic subject. It is concluded that an augmentation in the friction between the disk, glenoid fossa, and condyle produces an increment in stress and displacement of the disk.

Adult↗

Site-directed mutagenesis of the nitrogenase MoFe protein of Azotobacter vinelandii.

A strategy has been formulated for the site-directed mutagenesis of the Azotobacter vinelandii nifDK genes. These genes encode the alpha and beta subunits of the MoFe protein of nitrogenase, respectively. Six mutant strains, which produce MoFe proteins altered in their alpha subunit by known single amino acid substitutions, have been produced. Three of these transversion mutations involve cysteine-to-serine changes (at residues 154, 183, and 275), two involve glutamine-to-glutamic acid changes (at residues 151 and 191), and one involves an aspartic acid-to-glutamic acid change (at residue 161). All three possible phenotypic responses are observed within this group- i.e., normal, slow, and no growth in the absence of a fixed-nitrogen source. Two-dimensional gel electrophoresis indicates that all mutants accumulate normal levels of the subunits of both nitrogenase component proteins. Whole-cell and crude-extract acetylene-reduction activities indicate substantial levels of Fe protein activity in all strains. In contrast, MoFe protein activities do not parallel the diazotrophic growth capability for all strains. Two strains appear to exhibit altered substrate discrimination. Such analyses should aid in the identification of metallocluster-binding sites and subunit-subunit interaction domains of the MoFe protein and also provide insight into the mechanistic roles of the various prosthetic groups in catalysis.

Journal Article↗

A new, brief questionnaire (PEQ) developed in primary health care for measuring patients' experience of interaction, emotion and consultation outcome.

BACKGROUND: A deepened understanding of patients' perspectives is essential in order to improve medical communication. By changing focus from patient satisfaction to patient experiences, more immediate, personal and affective responses may be captured. OBJECTIVE: Our aim was to develop a new consultation-specific questionnaire on patient experiences. METHODS: The questionnaire was developed in Norwegian primary care in three main phases. Phase 1: focus groups with patients in order to identify important aspects of patients' experiences, and their words and language when describing such experiences. Phase 2: a questionnaire survey with 110 items including 660 patients. Extensive testing resulted in a reduction to 25 items on six dimensions. Phase 3: a questionnaire survey with 25 items including 1092 patients. Psychometric analyses and feedback from patients and physicians involved dimensionality and tests of validity and reliability. RESULTS: A final questionnaire was produced with 18 items on five dimensions: communication; emotions; short-term outcome; barriers; and relations with the auxiliary staff. The validity and reliability estimates were highly satisfactory. Three scales were skewed while two were more equally distributed. Forty-eight per cent of the patients described less than optimal communication experiences; some communication barriers were detected in 70% of the visits and less helpful experiences with the staff were reported in 55% of the visits. Twenty-four per cent of patients left with no positive feelings, and 48% scored low on the outcome scale (knowledge, perceived result). CONCLUSIONS: The patient experience questionnaire (PEQ) emphasizes what patients value the most, i.e. interaction, emotions and outcome, and may represent a valuable tool for doctors who want feedback from their patients on the function of their doctor-patient relationships.

Adolescent↗

Consistent theory of turbulent transport in two-dimensional magnetohydrodynamics.

A theory of turbulent transport is presented in two-dimensional magnetohydrodynamics with background shear and magnetic fields. We provide theoretical predictions for the transport of magnetic flux, momentum, and particles and turbulent intensities, which show stronger reduction compared with the hydrodynamic case, with different dependences on shearing rate, magnetic field, and values of viscosity, Ohmic diffusion, and particle diffusivity. In particular, particle transport is more severely suppressed than momentum transport, effectively leading to a more efficient momentum transport. The role of magnetic fields in quenching transport without altering the amplitude of flow velocity and in inhibiting the generation of shear flows is elucidated. Implications of the results are discussed.

Journal Article↗

Polyphase antialiasing in resampling of images.

Changing resolution of images is a common operation. It is also common to use simple, i.e., small, interpolation kernels satisfying some "smoothness" qualities that are determined in the spatial domain. Typical applications use linear interpolation or piecewise cubic interpolation. These are popular since the interpolation kernels are small and the results are acceptable. However, since the interpolation kernel, i.e., impulse response, has a finite and small length, the frequency domain characteristics are not good. Therefore, when we enlarge the image by a rational factor of (L/M), two effects usually appear and cause a noticeable degradation in the quality of the image. The first is jagged edges and the second is low-frequency modulation of high-frequency components, such as sampling noise. Both effects result from aliasing. Enlarging an image by a factor of (L/M) is represented by first interpolating the image on a grid L times finer than the original sampling grid, and then resampling it every M grid points. While the usual treatment of the aliasing created by the resampling operation is aimed toward improving the interpolation filter in the frequency domain, this paper suggests reducing the aliasing effects using a polyphase representation of the interpolation process and treating the polyphase filters separately. The suggested procedure is simple. A considerable reduction in the aliasing effects is obtained for a small interpolation kernel size. We discuss separable interpolation and so the analysis is conducted for the one-dimensional case.

Algorithms↗

Clinical and endosonographic effect of ciprofloxacin on the treatment of perianal fistulae in Crohn's disease with infliximab: a double-blind placebo-controlled study.

BACKGROUND: Ciprofloxacin is effective in perianal Crohn's disease but after treatment discontinuation symptoms reoccur. Infliximab is effective but requires maintenance therapy. AIM: To evaluate the effect of combined ciprofloxacin and infliximab in perianal Crohn's disease. METHODS: A double-blind placebo-controlled study was conducted. Patients were randomly assigned to receive 500-mg ciprofloxacin twice daily or a placebo for 12 weeks. All patients received 5-mg/kg infliximab in week 6, 8 and 12 and were followed for 18 weeks. Primary end-point was clinical response, defined as a 50% or greater reduction from baseline in the number of draining fistulae. Secondary end-points were the change in Perianal Disease Activity Index and hydrogen peroxide enhanced three-dimensional endoanal ultrasonography findings. Analysis was by intention-to-treat. RESULTS: Twenty-four patients were included but two discontinued treatment. At week 18, response was 73% (eight of 11) in the ciprofloxacin group and 39% (five of 13) in the placebo group (P = 0.12). Using logistic regression analysis patients treated with ciprofloxacin tended to respond better (OR = 2.37, CI: 0.94-5.98, P = 0.07). The Perianal Disease Activity Index score only improved (P = 0.008) in the ciprofloxacin group. Three-dimensional endoanal ultrasonography improved in three patients with a clinical response. CONCLUSIONS: A combination of ciprofloxacin and infliximab tended to be more effective than infliximab alone.

Adolescent↗

Dynamics of circus movement re-entry across canine Purkinje fibre-muscle junctions.

1. To determine the cellular electrophysiological mechanisms for unidirectional conduction block and re-entrant excitation, single cycles of circus movement re-entry were induced in canine Purkinje fibre-papillary muscle preparations containing two Purkinje fibre-muscle junctions (PMJs). The preparations were mounted in a partitioned tissue bath that permitted independent superfusion of each PMJ. The pre-existing dispersion of refractoriness between PMJs was accentuated by superfusing PMJ1 with normal Tyrode solution or Tyrode solution containing 6-8 mM KCl and superfusing PMJ2 with Tyrode solution containing 0.5 mM heptanol and 4-10 mM KCl. 2. Premature stimuli delivered to the Purkinje fibre induced unidirectional anterograde conduction block at PMJ2. Conduction proceeded from Purkinje cells to papillary muscle at PMJ1 and from papillary muscle retrogradely across the previously blocked PMJ2. 3. The difference in refractory periods between the two PMJs defined a range of premature coupling intervals within which re-entry was inducible. Conduction block at the PMJ occurred in papillary muscle at short coupling intervals and in the Purkinje fibre at longer intervals. 4. Once initiated, re-entry could be reset or annihilated by properly timed subthreshold current pulses delivered to cells at the PMJ. 5. To define better the mechanisms for conduction block and re-entry, an analytical model was developed using non-linear regression analysis to derive equations from the experimental results. Varying parameters within the constraints of the model reproduced the key features of the rate-dependent conduction block observed experimentally. Critical elements of the model included the induction of significant activation delays at short diastolic intervals and a reduction in the rate of action potential duration restitution after exposure to heptanol. 6. These results help to establish the conditions necessary for induction of one-dimensional circus movement re-entry and to define the roles of non-linearities of activation delay and excitability in the dynamics of conduction block at the PMJ.

Animals↗

Analysis of crack growth in a 3D Voronoi structure: a model for fatigue in low density trabecular bone.

Both creep and crack growth contribute to the reduction in modulus associated with fatigue loading in bone. Here we simulate crack growth and subsequent strut failure in fatigue in an open-cell, three-dimensional Voronoi structure which is similar to that of low density, osteoporotic bone. The model indicates that sequential failure of struts leads to a precipitous drop in modulus: the failure of 1% of the struts leads to about a 10% decrease in modulus. A parametric study is performed to assess the influence of normalized stress range, relative density, initial crack size, crack shape and cell geometry on the fatigue life. The fatigue life is most sensitive to the relative density and the initial crack length. The results lead to a quantitative expression for the fatigue life associated with crack growth. Data for the fatigue life of trabecular bone are compared with the crack growth model described in this paper as well as with a previous model for creep of a three-dimensional Voronoi structure. In our models, creep dominates the fatigue behavior in low cycle fatigue while crack growth dominates in high cycle fatigue, consistent with previous observations on cortical bone. The large scatter in the trabecular bone fatigue data make it impossible to identify a transition between creep dominated fatigue and crack growth dominated fatigue. The parametric study of the crack growth model indicates that variations in relative density among specimens, initial crack size within trabeculae and crack shape could easily produce such variability in the test results.

Bone Density↗

Two-dimensional magnetic particles

Single two-dimensional (2D) atomically thick magnetic particles of cobalt and iron with variable size and shape were fabricated by combining a mask technique with standard molecular beam epitaxy. Reduction of the lateral size of in-plane magnetized 2D cobalt films down to about 100 nanometers did not essentially modify their magnetic properties; although the separation of boundaries decreased greatly, neither domain penetrated the particle, nor was any sizable shape anisotropy observed. The mutual interaction of 2D cobalt particles was negligible, and the magnetic state of a single particle could be switched without modifying the state of the neighbors. Perpendicularly magnetized iron particles did not exhibit such responses. These results suggest that only a few atoms forming a 2D in-plane magnetized dot may provide a stable elementary bit for nanorecording.

Journal Article↗

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