Biomedical subjects

A de Haan

Publications and source records attributed to A de Haan.

At least 55 records · Page 3Linked to original sources

PubMed2001

High-frequency initial pulses do not affect efficiency in rat fast skeletal muscle.

This study investigated the effects of high-frequency initial pulses on the efficiency (=total work output/high-energy phosphate consumption) of rat fast skeletal muscle. In situ rat medial gastrocnemius muscles performed 15 repeated shortening contractions (2 s(-1); velocity 50 mm s(-1)) with occluded blood flow while activated with triplets of 400 Hz followed by 60 Hz trains (T400;60) or with constant-frequency trains of either 60 or 91 Hz. All stimulation patterns consisted of six pulses. After the last contraction, the muscles were quickly freeze-clamped and analysed for metabolite levels. The calculated efficiencies were 20.4+/-3.0 mJ micromol(-1 )P (N=7), 19.4+/-1.8 mJ micromol(-1 )P (N=8) and 19.6+/-2.5 mJ micromol(-1 )P (N=7; means +/- s.d.) for T400;60, 60 and 91 Hz stimulation respectively (P>0.05). It is concluded that, although high-frequency initial pulses can enhance muscle performance, the efficiency of rat fast skeletal muscle did not differ from that for submaximal constant-frequency stimulation patterns.

Animals↗

PubMed2000

Adenylate kinase 1 gene deletion disrupts muscle energetic economy despite metabolic rearrangement.

Efficient cellular energy homeostasis is a critical determinant of muscle performance, providing evolutionary advantages responsible for species survival. Phosphotransfer reactions, which couple ATP production and utilization, are thought to play a central role in this process. Here, we provide evidence that genetic disruption of AK1-catalyzed ss-phosphoryl transfer in mice decreases the potential of myofibers to sustain nucleotide ratios despite up-regulation of high-energy phosphoryl flux through glycolytic, guanylate and creatine kinase phosphotransfer pathways. A maintained contractile performance of AK1-deficient muscles was associated with higher ATP turnover rate and larger amounts of ATP consumed per contraction. Metabolic stress further aggravated the energetic cost in AK1(-/-) muscles. Thus, AK1-catalyzed phosphotransfer is essential in the maintenance of cellular energetic economy, enabling skeletal muscle to perform at the lowest metabolic cost.

Adenine↗

PubMed2000

Activation of alloreactive T cells by allogeneic nonprofessional antigen-presenting cells and interleukin-12 from bystander autologous professional antigen-presenting cells.

BACKGROUND: After solid organ transplantation most alloantigens are presented to the recipient's immune system by normal tissue cells, which can be considered to act as nonprofessional antigen-presenting cells (APC). It is well accepted that such nonprofessional APC fail to activate recipient resting T cells due to their inability to deliver costimulatory activity. In our study, we tested a hypothesis that such costimulatory activity may be provided by "bystander" recipient professional APC. METHODS: We set up mixed lymphocyte cultures (MLC) of purified T cell responders and T cell stimulator cells, the latter as nonprofessional APC carrying allogeneic MHC class I and II, and tested if responder-type autologous APC could facilitate responder T cell proliferation. In this assay also the effects of anti-CD28 antibody and interleukin- (IL) 1beta, IL-6, or IL-12 mediated costimulation on responder T cell proliferation and IL-2 production were investigated. RESULTS: Autologous APC, i.e., monocytes, were found to facilitate the proliferative response of resting T cells stimulated by allogeneic nonprofessional APC. IL-12 was identified as the most important costimulatory factor for induction of proliferation. IL-1beta enhanced IL-2 production and proliferation of allostimulated resting T cells but its presence was not essential. Although CD28 triggering alone was ineffective, this costimulatory pathway enhanced IL-2 production and proliferation when combined with IL-12 or IL-1beta. CONCLUSIONS: We conclude that costimulatory activity for activation of resting human T cells by nonprofessional donor APC can be delivered through activity of bystander recipient-type autologous APC. This mechanism of allostimulation may contribute to the induction and perpetuation of alloreactivity "in vivo" in a time frame when intragraft professional donor-type APC have been replaced with professional recipient-type APC.

Antibodies↗

PubMed2000

Decreased donor-specific cytotoxic T cell precursor frequencies one year after clinical lung transplantation do not reflect transplantation tolerance: a comparison of lung transplant recipients with or without bronchiolitis obliterans syndrome.

BACKGROUND: Decreased in vitro T cell alloreactivity, demonstrated by decreased frequencies of peripheral blood donor-specific T cell precursors, may reflect a tolerant state after transplantation and lower the risk for development of chronic graft dysfunction. It is unknown whether a decrease in donor-specific T cell frequencies also occurs after clinical lung transplantation and if such a decrease lowers the risk for bronchiolitis obliterans syndrome (BOS), a hallmark of chronic graft dysfunction. Therefore, we compared changes in posttransplant donor-specific cytotoxic T lymphocyte (CTLp) and helper T lymphocyte precursor (HTLp) frequencies in lung allograft recipients with good graft function and in recipients with BOS. METHODS: Donor and third party specific CTLp and HTLp frequencies were determined by limiting dilution assay in pre- and posttransplant (1 year) peripheral blood samples of lung allograft recipients with good graft function (n = 13) and BOS (n = 10). RESULTS: In recipients with good graft function, mean donor-specific CTLp frequencies decreased after transplantation (183 vs. 16 precursors before and after transplantation, respectively). Additionally, HTLp frequencies decreased but this was not specific for donor alloantigens because third party-specific HTLp frequencies decreased also. Surprisingly, recipients with BOS also showed a decrease in mean donor-specific CTLp frequencies after transplantation (332 vs. 49 precursors before and after transplantation, respectively). Again, HTLp frequencies decreased nonspecifically. CONCLUSIONS: We conclude that donor-specific CTLp frequencies decrease after lung transplantation, but that this does not result in transplantation tolerance protecting the lung against the development of chronic graft dysfunction.

Acute Disease↗

PubMed2000

No acute effects of short-term creatine supplementation on muscle properties and sprint performance.

In a double-blind, placebo, controlled study, we investigated the acute effects of short-term oral creatine supplementation (20 g.day-1 for 6 days) on muscle activation, fatigue and recovery of the m. quadriceps femoris during electrical stimulation, and on maximal performance during sprint cycling. The quadriceps muscles of 23 well-trained rowers were stimulated at different frequencies (10, 20, 50, 100, 150 and 200 Hz). Furthermore, 40 repetitive, electrically stimulated (duration 220 ms, stimulation frequency 150 Hz) concentric contractions were imposed at a constant angular velocity of 180 degrees.s-1 over a range of 50 degrees (from 90 to 140 degrees knee angle), each extension/flexion cycle lasting 1200 ms. To determine recovery, torque was measured at 20, 50, 80, 120, 180 and 300 s after the last contraction. In addition, two maximal 30-s sprints were performed on a cycle ergometer with 4 min rest in between. Following short-term creatine supplementation, body mass [mean (SEM)] increased (P < 0.05) from 85.7 (2.7) kg to 87.3 (2.9) kg. Creatine supplementation had no effect on maximal voluntary isometric torque and muscle activation, or on fatigue and recovery of dynamic exercise. There was also no significant effect on peak power, time to peak power and work to peak power, or total work during both sprints on the cycle ergometer. It was concluded that short-term oral creatine supplementation resulted in increased body mass, but did not enhance muscle performance or maximal output during sprint cycling.

Adult↗

PubMed2000

Ultrasonographic assessment of congestion of the choroid plexus in relation to carbon dioxide pressure.

Routine cerebral ultrasound examinations of the neonatal brain often show the choroid plexus to be enlarged, without revealing any other structural pathology. This enlargement might be due to congestion of the choroid plexus as a result of increased cerebral blood flow, due to increased partial pressure of carbon dioxide, amongst other factors. In this exploratory study, 76 cerebral ultrasound examinations, performed on 42 newborn infants within the first 10 days after birth, were analysed retrospectively. The ultrasonograms were classified into three diagnostic groups: normal, congestion of the choroid plexus and haemorrhage. The relationship between the diagnostic groups and the estimated mean arterial partial pressure of carbon dioxide (P(a)CO(2)) was investigated. In the first three postnatal days, the estimated mean P(a)CO(2) in the normal group was significantly lower than in the congestion group (P<0.001). No significant differences were found between the P(a)CO(2) in the congestion and the haemorrhage groups. The findings might support a relation between a high P(a)CO(2) and congestion of the choroid plexus in the first three postnatal days and might be a sign of increased risk for a periventricular haemorrhage.

Carbon Dioxide↗

PubMed2000

Mitochondrial minicircles in the free-living bodonid Bodo saltans contain two gRNA gene cassettes and are not found in large networks.

In trypanosomatids, the majority of the guide (g) RNAs that provide the information for U-insertion/deletion RNA editing are encoded by minicircles that are catenated into large networks. In contrast, in the distantly related cryptobiid Trypanoplasma borreli, gRNA genes appear to reside in large 180-kb noncatenated DNA circles. To shed light on the evolutionary history and function of the minicircle network, we have analyzed minicircle organization in the free-living bodonid Bodo saltans, which is more closely related to trypanosomatids than T. borreli. We identified 1.4-kb circular DNAs as the B. saltans equivalent of minicircles via sequence analysis of 4 complete minicircles, 14 minicircle fragments, and 14 gRNAs. We show that each minicircle harbors two gRNA gene cassettes of opposite polarity residing in variable regions of about 200 nt in otherwise highly conserved molecules. In the conserved region, B. saltans minicircles contain a putative bent helix sequence and a degenerate dodecamer motif (CSB-3). Electron microscopy, sedimentation, and gel electrophoresis analyses showed no evidence for the existence of large minicircle networks in B. saltans, the large majority of the minicircles being present as circular and linear monomers (85-90%) with small amounts of catenated dimers and trimers. Our results provide the first example of a kinetoplastid species with noncatenated, gRNA gene-containing minicircles, which implies that the creation of minicircles and minicircle networks are separate evolutionary events.

Amino Acid Sequence↗

PubMed2000

Altered contractile properties of the quadriceps muscle in people with spinal cord injury following functional electrical stimulated cycle training.

STUDY DESIGN: A longitudinal training study. OBJECTIVES: To assess if contractile speed and fatigability of paralysed quadriceps muscles in individuals with spinal cord injury (SCI) can be altered by functional electrical stimulation leg cycle ergometry (FES-LCE) training. SETTINGS: The Sint Maartenskliniek rehabilitation centre and the University of Nijmegen, Nijmegen, the Netherlands. METHODS: Contractile properties of the quadriceps muscle were studied in seven people with motor-complete SCI who participated in a FES-LCE training program. Subjects trained for 30 min, three times per week for 6 weeks. Contractile speed and fatigue characteristics of electrically stimulated isometric contractions were compared before and after 6 weeks of FES-LCE. RESULTS: Fatigue resistance improved following FES-LCE training as indicated by the higher forces maintained in response to repetitive electrical stimulation. In contrast with an improved fatigue resistance, the maximal rate of force rise was unaffected, the speed of relaxation increased and the fusion of a 10 Hz force signal decreased. Furthermore, the force-frequency relationship shifted to the right at low stimulation frequencies, indicated by a decline in the ratio of 1 and 100 Hz force responses as well as the ratio of 10 and 100 Hz force responses. CONCLUSION: FES-LCE training can change the physiological properties of the quadriceps muscle in people with SCI. Even after a short period of training, the stimulated muscles become more resistant to fatigue. Furthermore, the increased speed of relaxation and associated decreased fusion and altered force-frequency relationship following training may be related to adaptations in the calcium handling processes, which reflect an early response of long-term disused muscles.

Adult↗

PubMed2000

Effects of high-frequency initial pulses and posttetanic potentiation on power output of skeletal muscle.

The effects of high-frequency initial pulses (HFIP) and posttetanic potentiation on mechanical power output during concentric contractions were examined in the in situ medial gastrocnemius of the rat with an intact origin on the femur and blood supply. Stimulation of the muscle was performed via the severed sciatic nerve. In the experiments, HFIP or the potentiating tetanus was followed by a stimulation of 80, 120, or 200 Hz. The results showed that both HFIP and the tetanus increased power output at high contraction velocities (>75 mm/s) when followed by a train of 80 or 120 Hz (200 Hz resulted in no effects). Mechanical power output was increased maximally by HFIP to 120 and 168% by the tetanus. Furthermore, when HFIP or the tetanus were followed by a train of 80 Hz, the peak power in the power-velocity curve tended to be shifted to a higher velocity.

Animals↗

PubMed2000

Influence of muscle temperature on the contractile properties of the quadriceps muscle in humans with spinal cord injury.

Low muscle temperature in paralysed muscles of individuals with spinal cord injury may affect the contractile properties of these muscles. The present study was therefore undertaken to assess the effects of increased muscle temperature on the isometric contractile properties of electrically stimulated paralysed quadriceps muscles. When muscle temperature at a depth of 3 cm was increased from approximately 32 degrees C to approximately 36 degrees C by ultra-short-wave application, the half-relaxation time shortened and low-frequency force responses became less fused, but the maximal rate of increase in force remained unchanged. Heating had no effect upon either force decline or slowing of relaxation during fatiguing contractions. The force-frequency relationship of the paralysed quadriceps muscle was shifted to the right after the muscle was heated. Despite this shift, however, the relationship still resembled that in muscles of non-paralysed individuals, probably due to the unexplained high twitch forces. These results indicate that reduced muscle temperature in spinal-cord-injured individuals may lead to an underestimation of the changes in contractile properties in terms of relaxation rate or the degree of fusion with low-frequency stimulation. In addition, the force-frequency relationship of paralysed muscles does not accurately reflect the magnitude of these changes, even when the muscle is heated, and should therefore be treated with caution.

Adult↗

PubMed1999

Temperature effect on the rates of isometric force development and relaxation in the fresh and fatigued human adductor pollicis muscle.

The purpose of the present study was to investigate the effect of temperature on the rates of isometric force development and relaxation in electrically activated fresh and fatigued human adductor pollicis muscle. Following immersion of the lower arm for 20 min in water baths of four different temperatures, muscle temperatures were approximately 37, 31, 25 and 22 C. Maximal isometric force was reduced by 16.8 +/- 1.5 % at 22 C. The stimulation frequency-force and -rate of force development relationships were shifted to the left at lower temperatures. Q10 values for the maximal rates of force development and relaxation, and the times for 100 to 50 % and 50 to 25 % force relaxation, were about 2.0 between 37 and 25 C and about 3.8 between 25 and 22 C. However, the time for 50 to 25 % force relaxation had a relatively high Q10 value between 25 and 22 C (6.9) and this parameter also appeared to be more sensitive to fatigue compared to the other indices of relaxation. Nevertheless, the effect of fatigue on all parameters decreased with cooling over the entire (37-22 C) temperature range.

Adult↗

PubMed1998

Donor-specific hyporeactivity after liver transplantation: prominent decreases in donor-specific cytotoxic T lymphocyte precursor frequencies independent of changes in helper T lymphocyte precursor frequencies or suppressor cell activity.

BACKGROUND: The development of immunological donor-specific hyporeactivity may account for the low incidence of chronic rejection after clinical liver transplantation. We investigated whether hyporeactivity commonly develops after liver transplantation by analyzing precursor frequencies of donor-reactive cytotoxic (CTLp) and helper (HTLp) T lymphocytes and mixed lymphocyte culture (MLC) reactivity in liver allograft recipients. We further studied whether CTLp hyporeactivity correlated with changes in donor-specific HTLp frequencies or suppressor cell activity. METHODS: CTLp and HTLp frequencies and MLC reactivity against donor and third-party spleen cells were determined in pre- and posttransplantation peripheral blood samples from 18 recipients with good graft function 2 years after transplantation. By mixing posttransplantation samples (with "putative" suppressor cell activity) with pretransplantation samples (in which normal CTL activity with no suppressor cell activity is expected), the presence of suppressor cell activity in peripheral blood was analyzed. RESULTS: Two years after transplantation, all but one (94%) of the recipients had developed CTLp hyporeactivity as evidenced by reduced donor-specific CTLp frequencies. The development of hyporeactivity was not specific for any particular underlying disease. The occurrence of HTL hyporeactivity, however, was less frequent: 38% and 20% of recipients were HTLp and MLC hyporeactive, respectively. Decreases in CTLp frequencies did not correlate with decreased donor-specific HTL function or suppressor cell activity in peripheral blood samples. CONCLUSIONS: Donor-specific CTLp hyporeactivity can develop in the majority of liver allograft recipients, irrespective of underlying disease. Donor-specific HTL hyporeactivity, however, occurs infrequently. A reduction in donor-specific CTLp frequencies was found to be independent of changes in donor-specific HTLp or suppressor cell activity, suggesting that other mechanisms (e.g., clonal deletion) are operative in the reduction of donor-specific CTLp after liver transplantation.

Humans↗

PubMed1998

RNA editing in the free-living bodonid Bodo saltans.

In parasitic kinetoplastid protozoa, mitochondrial (mt) mRNAs are post-transcriptionally edited by insertion and deletion of uridylate residues, the information being provided by guide (g) RNAs. In order to further explore the role and evolutionary history of this process, we searched for editing in mt RNAs of the free-living bodonid Bodo saltans. We found extensive editing in the transcript for NADH dehydrogenase (ND) subunit 5, which is unedited in trypanosomatids. In contrast, B.saltans cytochrome c oxidase (cox) subunit 2 and maxicircle unidentified reading frame (MURF) 2 RNAs display limited editing in the same regions as their trypanosomatid counterparts. A putative intramolecular cox2 gRNA and the gene for gMURF2-I directing the insertion of only one U in the 5' editing domain of MURF2 RNA, are conserved in B.saltans. This lends (further) evolutionary support to the proposed role of these sequences as gRNAs. Phylogenetic analysis showed that B.saltans is more closely related to trypanosomatids than the cryptobiids Trypanoplasma borreli and Cryptobia helicis, in line with the trypanosomatid-like cox2 and MURF2 RNA editing patterns. Nevertheless, other features like the apparent absence of a catenated mtDNA network, are shared with bodonid and cryptobiid species. ND5 RNA editing may represent yet another example of editing 'on the way out' during kinetoplastid evolution, but in view of the fact that cox2 RNA is unedited in T. borreli and C.helicis, we infer that the editing of this RNA may have arisen relatively recently. Our results provide the first examples of RNA editing in a free-living kinetoplastid, indicating that there is no direct link between U-insertion/deletion editing and a parasitic lifestyle.

Amino Acid Sequence↗

PubMed1998

Donor-specific immunological non-responsiveness after liver transplantation.

Since the rate of immunological losses of liver allograft after the immediate posttransplant period is much lower than in other organs, we studied the immune responses against donor HLA antigens in 18 patients with a good long-term outcome to determine whether the development of a state of immunological non-responsiveness to donor antigens might account for this favorable outcome. The reactivity against donor spleen cells was measured before and 2 years after transplantation. The reactivity in mixed lymphocyte culture (MLC) and the frequencies of cytotoxic T cell precursors (CTLp) were determined. Responses against third-party spleen cells were determined concurrently to exclude a generalized reduction of immunocompetence due to chronic immunosuppressive treatment. Before orthotopic liver transplantation, the majority of patients had normal T cell responses against donor antigens that were comparable to those against third-party antigens. Two years after transplantation, donor-specific MLC non-reactivity had developed in 10 of the 18 (56%) patients. In addition, 15 of 18 (83%) patients had developed donor-specific cytotoxic T cell (CTL) non-responsiveness; 2 had reduced numbers of CTLp against both donor and third-party cells, while the remaining patient had maintained reactivity against donor antigens. In conclusion, donor-specific non-responsiveness is present in the majority of patients 2 years after successful liver transplantation, but occurs predominantly at the CTL level.

Humans↗

PubMed1998

The influence of stimulation frequency on force-velocity characteristics of in situ rat medial gastrocnemius muscle.

Force (and power)-velocity characteristics were determined at different stimulation frequencies in th situ rat muscle with nerve stimulation at 36 degrees C. In isometric contractions (duration, 150 ms), maximal force is generated at approximately 120 Hz. In contrast, in the high velocity (250 mm s-1) shortening contractions, frequencies of approximately 400 Hz were needed to obtain maximal dynamic force, while 120 Hz elicited only approximately 26% of the maximum. At the highest velocity measured, power production was significantly different (P < 0.05) among frequencies of 80, 120, 200 and 400 Hz, suggesting that maximal shortening velocity should be assessed using very high stimulation frequencies. However, the results further indicate that lower frequencies may be adequate in exercise studies that investigate fatigue and changes in power output during series of repetitive contractions.

Animals↗

PubMed1998

Manual dexterity and keyboard use in spastic hemiparesis: a comparison between the impaired hand and the 'good' hand on a number of performance measures.

OBJECTIVE: To assess the functional deficits in tapping performance of subjects with spastic hemiparesis. DESIGN: In a pilot study, typing performance on a computer keyboard was examined on a number of performance measures. SETTING: Department of Research and Development at the Werkenrode Institute. SUBJECTS: Four subjects (mean age 16.4 years, standard deviation 1.8 years) with cerebral palsy and diagnosed as having spastic hemiparesis. INTERVENTIONS: Subjects had to type a sequence of one or more keys as quickly as possible within an 8 second period with the fingers of both hands separately. MAIN OUTCOME MEASURES: The average number of good and false responses were calculated. Within the false response category, four, mutually exclusive, types of errors were distinguished; wrong key, repetition, registrations under 75 ms and holding. Speed and regularity of the typing responses were also established. RESULTS: The 'good' hand outperformed the impaired hand on all performance measures except on the amount of repetition errors made. The holding error was only present for the impaired hand, and there was an increase in holding errors from the index to the little finger in this hand. In addition, the impaired hand performed the task with a slower speed and in a more irregular fashion. CONCLUSIONS: The results are discussed with reference to keyboard design. It is concluded that the standard 'QWERTY' keyboard hampers typing performance extensively, especially for subjects with left spastic hemiparesis. A learning method is presented in which the role of an external pacer (e.g. metronome) is discussed. This device can initially be used to decrease movement variability and, eventually, for increasing movement speed.

Adolescent↗

PubMed1998

Cytoarchitectural and metabolic adaptations in muscles with mitochondrial and cytosolic creatine kinase deficiencies.

We have blocked creatine kinase (CK) mediated phosphocreatine (PCr) <==> ATP transphosphorylation in mitochondria and cytosol of skeletal muscle by knocking out the genes for the mitochondrial (ScCKmit) and the cytosolic (M-CK) CK isoforms in mice. Animals which carry single or double mutations, if kept and tested under standard laboratory conditions, have surprisingly mild changes in muscle physiology. Strenuous ex vivo conditions were necessary to reveal that MM-CK absence in single and double mutants leads to a partial loss of tetanic force output. Single ScCKmit deficiency has no noticeable effects but in combination the mutations cause slowing of the relaxation rate. Importantly, our studies revealed that there is metabolic and cytoarchitectural adaptation to CK defects in energy metabolism. The effects involve mutation type-dependent alterations in the levels of AMP, IMP, glycogen and phosphomonoesters, changes in activity of metabolic enzymes like AMP-deaminase, alterations in mitochondrial volume and contractile protein (MHC isoform) profiles, and a hyperproliferation of the terminal cysternae of the SR (in tubular aggregates). This suggests that there is a compensatory resiliency of loss-of-function and redirection of flux distributions in the metabolic network for cellular energy in our mutants.

Animals↗

PubMed1997

Altered Ca2+ responses in muscles with combined mitochondrial and cytosolic creatine kinase deficiencies.

We have blocked creatine kinase (CK)-mediated phosphocreatine (PCr) -->/<-- ATP transphosphorylation in skeletal muscle by combining targeted mutations in the genes encoding mitochondrial and cytosolic CK in mice. Contrary to expectation, the PCr level was only marginally affected, but the compound was rendered metabolically inert. Mutant muscles in vivo showed significantly impaired tetanic force output, increased relaxation times, altered mitochondrial volume and location, and conspicuous tubular aggregates of sarcoplasmic reticulum membranes, as seen in myopathies with electrolyte disturbances. In depolarized myotubes cultured in vitro, CK absence influenced both the release and sequestration of Ca2+. Our data point to a direct link between the CK-PCr system and Ca2+-flux regulation during the excitation and relaxation phases of muscle contraction.

Adenosine Triphosphate↗