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Biomedical subjects

J Videler

Publications and source records attributed to J Videler.

6 recordsLinked to original sources

Interference of PR3-ANCA with the enzymatic activity of PR3: differences in patients during active disease or remission of Wegener's granulomatosis.

Anti-neutrophil cytoplasmic antibodies (ANCA) against proteinase 3 (PR3) are strongly associated with Wegener's granulomatosis (WG) and are thought to be involved in its pathogenesis. Levels of PR3-ANCA do not always correspond to clinical disease activity. To investigate the relationship between functional effects of PR3-ANCA and disease activity, we tested the effect of IgG samples from sera of 43 WG patients, taken during active disease or remission, for their capacity to interfere with the proteolytic activity of PR3. Furthermore, longitudinal sera of seven WG patients were included. The enzymatic activity of PR3 was determined (1) with casein or with a small synthetic substrate and (2) by complexation of PR3 with alpha1-antitrypsin (alpha1-AT). With a fixed concentration (100 microg/ml) of IgG, PR3-ANCA from patients during an active phase of WG had a higher inhibitory capacity towards the proteolytic activity of PR3 and complexation of PR3 with alpha1-AT than did PR3-ANCA from WG patients during remission. However, the number of PR3-ANCA units that gave 50% inhibition of the PR3 enzymatic activity and its complexation with alpha1-AT was lower for patients during remission than for patients during an active phase of WG, indicating a stronger inhibitory capacity at a molar base. In conclusion, PR3-ANCA from patients during remission had a relatively higher inhibitory capacity towards the enzymatic activity of PR3 than PR3-ANCA from patients during an active phase. This may indicate that during active disease the ANCA titre is increased, but the number of active ANCA molecules that recognize the enzyme-inhibiting epitopes is not increased.

Adult↗

Fish foot prints: morphology and energetics of the wake behind a continuously swimming mullet (Chelon labrosus Risso).

The structure of the wake behind a continuously swimming mullet was analysed qualitatively and quantitatively by applying two-dimensional particle image velocimetry. A detailed analysis of the flow pattern and of the swimming movements of the fish allowed us to derive a kinematic explanation of the flow pattern as well as an estimate of the relative contributions of the body and the tail to thrust production. During active propulsion, the undulatory swimming fish shed a wake consisting in the medio-frontal plane of a rearward, zigzagging jet flow between alternating vortices. The fish shed one vortex per half tailbeat when the tail reached its most lateral position. Part of the circulation shed in the vortices had been generated previously on the body by the transverse body wave travelling down the body. This undulatory pump mechanism accounted for less than half of the energy shed in the wake. The remainder was generated by the tail. The vortex spacing matched the tailbeat amplitude and the stride length.

Journal Article↗

Quantitative flow analysis around aquatic animals using laser sheet particle image velocimetry

Two alternative particle image velocimetry (PIV) methods have been developed, applying laser light sheet illumination of particle-seeded flows around marine organisms. Successive video images, recorded perpendicular to a light sheet parallel to the main stream, were digitized and processed to map the flow velocity in two-dimensional planes. In particle tracking velocimetry (PTV), displacements of single particles in two subsequent images were determined semi-automatically, resulting in flow diagrams consisting of non-uniformly distributed velocity vectors. Application of grid-cell averaging resulted in flow field diagrams with uniform vector distribution. In sub-image correlation PIV (SCPIV), repetitive convolution filtering of small sub-areas of two subsequent images resulted in automatic determination of cross-correlation peaks, yielding flow field diagrams with regularly spaced velocity vectors. In both PTV and SCPIV, missing values, caused by incomplete particle displacement information in some areas of the images or due to rejection of some erroneous vectors by the vector validation procedure, were interpolated using a two-dimensional spline interpolation technique. The resultant vector flow fields were used to study the spatial distribution of velocity, spatial acceleration, vorticity, strain and shear. These flow fields could also be used to test for flow in the third dimension by studying the divergence, and to detect the presence and location of vortices. The results offer detailed quantitative descriptions of the flow morphology and can be used to assess dissipated energy. The versatile character of the technique makes it applicable to a wide range of fluid mechanical subjects within biological research. So far it has been successfully applied to map the flow around swimming copepods, fish larvae and juvenile fish and the ventilation current of a tube-living shrimp.

Journal Article↗

Tuning in to fish swimming waves: body form, swimming mode and muscle function

Most fish species swim with lateral body undulations running from head to tail. These waves run more slowly than the waves of muscle activation causing them, reflecting the effect of the interaction between the fish's body and the reactive forces from the water. The coupling between both waves depends on the lateral body shape and on the mechanical properties of the tail. During steady swimming, the length of each myotomal muscle fibre varies cyclically. The phase relationship between the strain (muscle length change) cycle and the active period (when force is generated) determines the work output of the muscle. The muscle power is converted to thrust either directly by the bending body or almost exclusively by the tail, depending upon the body shape of the species and the swimming kinematics. We have compared the kinematics and muscle activity patterns from seven species of fish with different body forms and swimming modes and propose a model which yields a consistent pattern, with at least three extremes. Subtle tuning of the phase relationship between muscle strain and activation cycles can lead to major changes in the way muscles function in different swimming modes.

Journal Article↗

pol mutations conferring zidovudine and didanosine resistance with different effects in vitro yield multiply resistant human immunodeficiency virus type 1 isolates in vivo.

Specific mutations in the human immunodeficiency virus type 1 (HIV-1) pol gene that cause zidovudine (3'-azido-2',3'-dideoxythymidine; AZT) and didanosine (2',3'-dideoxyinosine; ddI) resistance were studied. The 50% inhibitory concentrations (IC50s) of nucleosides for cloned viruses containing these mutations were compared with the IC50s of the corresponding triphosphate analogs for mutant recombinant-expressed reverse transcriptases (RTs). Changes in ddATP inhibition of RNA-dependent DNA polymerase activity fully accounted for the ddI resistance of the virus caused by a Leu-74-->Val substitution in RT, including an augmentation by the AZT-selected substitutions Thr-215-->Tyr and Lys-219-->Gln in RT. In contrast, the AZT-selected substitutions studied did not cause as great a change in the IC50 of AZT-triphosphate (AZT-TP) for polymerase as they did in the IC50 of AZT for mutant virus. In addition, the mutation at codon 74 suppressed AZT resistance in the virus caused by the mutations at codons 215 and 219 but did not suppress the AZT-TP resistance of enzyme containing these same mutations in RT. The mutation at codon 74 was found in clinical isolates whether or not the patient had received AZT prior to starting ddI therapy. AZT resistance coexisted with ddI resistance following acquisition of Leu-74-->Val in three clinical isolates, indicating that the suppressive effect of Val-74 on the AZT resistance of the virus does not occur in all genetic contexts. When this suppression of AZT resistance was seen in the virus, Val-74 did not appear to cause mutually exclusive changes in AZT-TP and ddATP binding to RT in vitro. The results of the in vitro experiments and characterization of clinical isolates suggest that there are differences in the functional effects of these AZT and ddI resistance mutations.

AIDS-Related Complex↗

Differences between upstroke and downstroke in swimming dolphins.

Steady swimming movements of dolphins were recorded in a search for direct evidence of asymmetry between upstrokes and downstrokes. Kinematic swimming and gliding data from frame-by-frame analysis of ciné pictures taken at constant frame rates with a camera in a fixed position are presented. We estimated the propulsive forces generated by the tail blade with a simple hydrodynamic model. Dolphins accelerate during the downstroke and decelerate during the upstroke: the net hydrodynamic force in the animal is always positive during the downstroke and negative during the upstroke. Both parts of the stroke cycle are equally long. The propulsive forces of downstrokes are on average larger than the forces of the upstrokes. Occasionally the average forces within an upstroke are greater than within a downstroke of the same sequence. Our data suggest that the drag on the body during the upstroke exceeds the drag in the course of the downstroke. The specific swimming speed or stride length of dolphins swimming at low speeds is about 0.9 body lengths per tail beat.

Animals↗