Biomedical subjects

D Theisen

Publications and source records attributed to D Theisen.

12 recordsLinked to original sources

PubMed2005

Regulation of mTOR by amino acids and resistance exercise in skeletal muscle.

Resistance exercise disturbs skeletal muscle homeostasis leading to activation of catabolic and anabolic processes within the muscle cell. A current challenge of exercise biology is to describe the molecular mechanisms of regulation by which contractile activity stimulates net protein breakdown during exercise and net protein synthesis during recovery. Muscle growth is optimized by combining exercise and appropriate nutritional strategies, such as amino acid (AA) and carbohydrate ingestion. The effects are integrated at the level of one central regulatory protein, mTOR (mammalian target of rapamycin). mTOR is a complex protein integrating signals of the energetic status of the cell and environmental stimuli to control protein synthesis, protein breakdown and therefore cell growth. mTOR is known to be activated by insulin, and the mechanisms involved are well documented. The ways by which exercise and AA lead to mTOR activation remain partially unclear. Exercise and AA use different signalling pathways upstream of mTOR. Exercise seems to recruit partially the same pathway as insulin, whereas AA could act more directly on mTOR. During resistance exercise, the activity of mTOR could be acutely blunted by AMP-activated protein kinase (AMPK), thus inhibiting protein synthesis and enhancing AA availability for energy metabolism. During recovery, the inhibition of mTOR by AMPK is suppressed, and its activation is maximized by the presence of AA. There appears to be a requirement for a minimal concentration of plasma insulin to stimulate muscle protein synthesis in response to resistance exercise and AA ingestion.

Adaptation, Physiological↗

PubMed2002

External power output changes during prolonged cycling with electrical stimulation.

This study analysed external power output and physiologic responses in 5 individuals with paraplegia during 40 minutes of electrical stimulation leg cycle exercise. Cycling was performed on a motor-driven isokinetic ergometer that enabled precise determinations of power output. Electrical stimulation was increased to 120-140 mA within the first 5 minutes and remained constant thereafter. Power output increased to 10.7 +/- 3.0 W after 2 minutes, dropped to 5.3 +/- 1.8 W after 6 minutes and subsequently recovered to 8.2 +/- 2.2 and 6.1 +/- 2.3 W after 19.5 and 40 minutes, respectively. Oxygen consumption increased to 0.47 +/- 0.09 l/min after 6 minutes and declined during the second half of the exercise bout. Gross mechanical efficiency after 19.5 minutes was elevated compared with the value after 6 minutes. Heart rate was significantly increased at the end of the trial. The time-dependent variability of power output and physiological responses question the concept of steady state for this form of exercise.

Adult↗

PubMed2001

Cutaneous vascular response and thermoregulation in individuals with paraplegia during sustained arm-cranking exercise.

This study investigated whether a 60-minute arm-cranking exercise at 50% of the individual maximal power output would increase lower limb skin blood flow (laser Doppler flowmetry) in individuals with high-level (T5-T9; n = 6) and low-level paraplegia (T10-T12; n = 6), compared to 6 able-bodied controls. Significant (P < 0.05) group by time interactions (two-way repeated measures ANOVA) were found for leg cutaneous vascular conductance, leg skin temperature and esophageal temperature. Cutaneous vascular conductance increased to a peak of approximately 180% of pre-exercise rest in both paraplegic groups and to -436% in the control group, with differences after 15, 30, 45 and 60 minutes of exercise. Leg skin temperature increased by approximately 0.3 C in individuals with paraplegia and decreased by approximately 2.0 C in able-bodied. Esophageal temperature increases at the end of exercise were higher in individuals with paraplegia (approximately 0.9 C) than in able-bodied subjects (approximately 0.5 C). Heart rate was higher in the paraplegic groups than in able-bodied, whilst stroke volume and cardiac output were not different (impedance cardiography). The data suggest that lesion level had no influence on the results. These findings indicate that there is no excessive shunting of blood to the skin of the lower limbs of individuals with paraplegia during sustained exercise.

Adult↗

PubMed2001

Central and peripheral haemodynamics in individuals with paraplegia during light and heavy exercise.

The purpose of this study was to analyse lower leg skin blood flow (laser Doppler flowmetry) in five individuals with high-level paraplegia (T5-T9), six participants with low-level paraplegia (T10-T12) and six able-bodied controls during 3-minute light and heavy arm-cranking exercises (approximately 15% and 80% peak power output, respectively). Throughout light exercise, cutaneous vasoconstriction was shown for the control group (-20%), but not the low-level (+62%) or the high-level paraplegic group (+33%). During heavy exercise, vasoconstriction was initially found for controls followed by an increase in skin blood flow during the last 2 minutes, whereas the participants with paraplegia demonstrated skin blood flow increases. Skin blood flow responses were not related to lesion level. Metabolic parameters were not different among the three groups, but heart rates for participants with paraplegia were higher during heavy exercise than in controls. These results suggest impaired sympathetic vasoconstriction in individuals with paraplegia during exercise.

Adult↗

PubMed2001

Wheelchair propulsion biomechanics: implications for wheelchair sports.

The aim of this article is to provide the reader with a state-of-the-art review on biomechanics in hand rim wheelchair propulsion, with special attention to sport-specific implications. Biomechanical studies in wheelchair sports mainly aim at optimising sport performance or preventing sport injuries. The sports performance optimisation question has been approached from an ergonomic, as well as a skill proficiency perspective. Sports medical issues have been addressed in wheelchair sports mainly because of the extremely high prevalence of repetitive strain injuries such as shoulder impingement and carpal tunnel syndrome. Sports performance as well as sports medical reflections are made throughout the review. Insight in the underlying musculoskeletal mechanisms of hand rim wheelchair propulsion has been achieved through a combination of experimental data collection under realistic conditions, with a more fundamental mathematical modelling approach. Through a synchronised analysis of the movement pattern, force generation pattern and muscular activity pattern, insight has been gained in the hand rim wheelchair propulsion dynamics of people with a disability, varying in level of physical activity and functional potential. The limiting environment of a laboratory, however, has hampered the drawing of sound conclusions. Through mathematical modelling, simulation and optimisation (minimising injury and maximising performance), insight in the underlying musculoskeletal mechanisms during wheelchair propulsion is sought. The surplus value of inverse and forward dynamic simulation of hand rim stroke dynamics is addressed. Implications for hand rim wheelchair sports are discussed. Wheelchair racing, basketball and rugby were chosen because of the significance and differences in sport-specific movement dynamics. Conclusions can easily be transferred to other wheelchair sports where movement dynamics are fundamental.

Arm↗

PubMed2000

Cutaneous vasomotor adjustments during arm-cranking in individuals with paraplegia.

difference, P<0.05). The paraplegics developed a higher esophageal and leg skin temperature, which was attributed to the lack of active vasodilation and evaporative cooling over the legs. The results indicate that individuals with paraplegia suffer from impaired cutaneous vasoconstriction at the onset of arm exercise, and possess only a limited vasodilatory capability in the paralyzed regions. During intense exercise, thermoregulation depends critically on active cutaneous vasodilation and skin cooling.

Adult↗

PubMed2000

Blood distribution adaptations in paraplegics during posture changes: peripheral and central reflex responses.

The veno-arteriolar reflex (VAR) in spinal-cord-injured subjects (SCI) has been attributed little interest, although it might contribute substantially to their blood redistribution. This peripheral reflex response, which is based on an axon reflex, consists of a reduction in limb blood flow following an increase in venal transmural pressure. The purpose of the present investigation was to assess the peripheral and central cardiovascular adaptations of paraplegics with high (HP) and low (LP) spinal lesions to subsequent, passive posture changes involving leg dependency and upright sitting, and to compare them to able-bodied (AB) subjects. Lower-limb cutaneous vascular conductance (CVC) was evaluated from skin blood flow measurements (laser Doppler flowmetry) taken from the dorsal foot, and from ankle blood pressure. Cardiac stroke volume, heart rate and myocardial performance were assessed using impedance cardiography and brachial blood pressure. During leg dependency, a significant vasoconstriction was noted in all three groups. The initial decrease in CVC was higher in HP (-76.82%) than in AB (-45.82%), the values for LP (-67.08%) lying in between these two (significant group x time interaction: F = 2.832; P = 0.042). There were no differences for parameters of central hemodynamics. No between-group differences were noted in any parameter tested during upright sitting. CVC remained at a similar low level as compared to leg dependency, stroke volume decreased, heart rate and blood pressure increased, and myocardial performance remained constant. The present results suggest that paraplegics have a peripheral VAR in their paralyzed lower limbs, and that this contributes to their cardiovascular stability.

Adaptation, Physiological↗

PubMed1999

A hemagglutinin-derived peptide-vaccine ignored by virus-neutralizing passive antibodies, protects against murine measles encephalitis.

The neutralizing and protective monoclonal antibody BH47 defines the sequential epitope H236-255 of the measles virus hemagglutinin protein (MV-H). The objective of this study was to design peptides combining this B cell epitope (BCE) with different T cell epitopes (TCE) to obtain protective immunity. Most TTB peptides based on the 15mer BCE H236-250 induced MV-crossreactive antibodies, but only certain TCE induced virus neutralizing antibodies. The shortest BCE required for MV-reactivity and -neutralization was the 8mer H243-250 containing residue R243 implicated in CD46 down-regulation. Sera obtained after immunization with the TTB peptide containing the MV-derived TCE F421-435 protected mice against a lethal challenge with a neuro-adapted MV strain. Our results further demonstrate that this TTB peptide is fully immunogenic, even in the presence of protective levels of pre-existing MV-specific antibodies, suggesting that subunit vaccines based on such peptides could potentially be used to immunize infants in the presence of persisting maternal antibodies. It is therefore interesting that neutralizing antibodies were also obtained with a TTB peptide comprising a human promiscuous TCE (tt830). However, our results also emphasize the need to test sera induced with epitope-based vaccines against different virus strains, in particular if the epitope is not fully conserved.

Animals↗

PubMed1998

Enhanced antigenicity of a four-contact-residue epitope of the measles virus hemagglutinin protein by phage display libraries: evidence of a helical structure in the putative active site.

Antigenicity and conformational propensities of synthetic peptides corresponding to the sequential epitope H236-255 of the measles virus hemagglutinin protein were investigated. This epitope corresponds to the neutralising and protective monoclonal antibody BH129 and includes Arg243, implicated in CD46-down-regulation and Arg253 that has been mapped to the putative enzymatic site. Fine mapping with truncation-, elongation-, Gly- and Ala-substitution analogues defined EL-QL as the critical residues of the minimal epitope S244ELSQL249. CD spectra of peptides, comparison with the 3D-structure of homologous sequences, and prediction algorithms suggested a helical structure with the contact residues E245L-QL249 located on the protein surface. Mimotopes obtained with a 6-mer phage display library contained a consensus Pro (important for binding) instead of Ser247 of the wild-type sequence (irrelevant for binding). The kink induced by Pro seemed to be essential to bring the 4 contact-residues in the mimotopes and in the corresponding short peptides together. CD analysis and prediction algorithms suggested that non-helical conformations of the phage insert and of the peptides may favourably mimic the antigenic helical turns of the wild-type sequence, resulting in an up to 135 times higher antigenicity of the mAb towards the mimotope peptides.

Animals↗

PubMed1998

The molecular basis of virus crossreactivity and neutralisation after immunisation with optimised chimeric peptides mimicking a putative helical epitope of the measles virus hemagglutinin protein.

The loop comprising aminoacids H236-256, connects two strands of sheet 1 of the propeller-like hemagglutinin (H) protein of the measles virus (MV) and contains a putative active site residue (R253), a residue implicated in CD46-downregulation (R243) and the minimal epitope E245L-QL249 of the neutralising and protective monoclonal antibody BH129. The objective of this study was to design synthetic peptides which induce neutralising antibodies against this important functional domain. Peptide-design was based on the colinear synthesis of this sequential B cell epitope (BCE) with different T cell epitopes (TCE). Chimeric constructs were systematically optimised with respect to length and copy number of the BCE and the nature and orientation of the TCE. Surprisingly, the induction of MV-crossreactive antibodies did not correlate with the antigenicity of the peptides. The best MV-crossreactive antibodies were obtained with TB oriented constructs containing TCEs of the MV fusion (F) protein and the BCE H236-250 (TB15mer) or H236-255 (TB20mer). In vitro virus-neutralising sera were obtained solely with the latter construct. A glycine scan showed that binding to MV depended on a defined pattern of contact residues compatible with the putative alpha helical nature of this epitope. The contact residues of the neutralising serum (S244EL-QL249) differed from those of the non-neutralising serum (S244EL246) but no unique differences in the immunoglobulin subclasses were detected. Surface plasmon resonance measurements detected a higher affinity for the neutralising serum compared to the TB15mer serum. These results emphasize the need of an optimal design of immunogenic peptides which cannot always be guided by the antigenicity of the peptide constructs. This study demonstrates that neutralising antibodies can be generated with peptides mimicking this helical epitope, provided that the critical contact residues are recognized with high affinity and underlines the potential of the epitope as an element of a future subunit vaccine.

Amino Acid Sequence↗

PubMed1998

Impedance cardiography applied to maximal arm cranking exercise: a matter of sampling and processing strategy.

PURPOSE: A new ensemble-averaging (EA) approach was developed with the goal of investigating central hemodynamics by transthoracic impedance cardiography during maximal arm cranking. This EA procedure of the first time derivative of impedance changes (dZ/dt) over several cardiac cycles differs from previously reported techniques with respect to cycle selection strategy, according to fixed criteria, and processing methods. METHODS: First, the primary elements of the Kubicek stroke volume (SV) formula, as determined by EA, were compared with the values determined by the standard hand-processing (HP) method over a large range of cardiac outputs. RESULTS: Results showed a very high reliability for ventricular ejection time (r = 0.996), (dZ/dt)min (r = 0.995), SV (r = 0.977), and heart rate (r = 0.999). Second, the EA procedure was applied to six subjects performing a continuous, multistage arm cranking test to volitional fatigue. The present technique allowed for an effective filtering of movement and breathing artifacts of the original signal. Thus, interpretation of the dZ/dt wave form was convenient, even at maximal arm cranking power outputs up to 120 W. Stroke volume ranged from 63.83 to 127.18 mL.beat-1, showing no significant variations with oxygen consumption. Cardiac output increased linearly with oxygen uptake, reaching a mean maximal value of 16 L.min-1. CONCLUSION: The present procedure opens a new field of application to impedance cardiography, permitting to measure cardiac output during maximal arm cranking exercise.

Adult↗

PubMed1996

A new procedure to determine external power output during handrim wheelchair propulsion on a roller ergometer: a reliability study.

This study presents a mathematical model by which power output (PO) delivered to the rear wheel during handrim wheelchair propulsion on a roller ergometer can be determined for individual wheelchair-user combinations. PO is calculated from the torque applied to the wheel and its angular velocity. The torque applied is a function of one total internal torque of the wheelchair-ergometer system, the rotational moment of inertia of the rear wheel, the one of the roller and its angular acceleration. The total internal torque reflects all internal friction forces and is determined with a deceleration test. To assess the reliability of this approach, 11 able-bodied subjects underwent progressively increasing exercise tests on two different occasions. PO values ranged from 12 to 63 W and were highly reliable (r2 > 0.95). Peak physiological responses were never different from test 1 and 2 (repeated measures ANOVA; p: N.S.) and correlations were 0.90, 0.72, 0.88, 0.82, 0.70 and 0.85 for PO, oxygen uptake (VO2), heart rate, minute ventilation, carbon dioxide production and blood lactate concentration, respectively. After an initial increase, gross mechanical efficiency dropped at higher velocities, with values ranging from 4.64 to 11.26%. In conclusion, the roller ergometer, the mathematical model to determine PO and the protocol used seem to be adequate to exercise test people in a handrim wheelchair. It is feasible to apply the theoretical procedure to other roller ergometers which would allow for comparisons of exercise intensities and protocols between different devices used in exercise physiology and rehabilitation.

Adult↗