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Biomedical subjects

O Bock

Publications and source records attributed to O Bock.

At least 19 recordsLinked to original sources

On the distribution of attention in a visuo-manual adaptation task.

We have observed in a previous study that adaptation to reversed visual feedback in a tracking task is better when subjects are instructed to look at the cursor providing feedback (group C) rather than at the target (group T). Since both groups actually looked at the target, irrespective of their instructions, we suggested that the advantage of group C is not related to their eye movements, but rather to their allocation of spatial attention. The present study scrutinized this view by combining the same adaptation task with a concurrent reaction-time task, designed to spread subjects' attention across the whole display area. Again, subjects were instructed to look at the cursor or at the target, and again, both groups actually looked at the target. Adaptation was similar to group T, and poorer than group C of the previous study. We therefore concluded that adaptation indeed depends on the subjects' allocation of attention: focussing attention mainly on the target, or spreading it across the whole display area, is not as good as distributing attention between target and cursor.

Adaptation, Physiological↗

Sensorimotor adaptation to inertial forces in a multi-force environment does not depend on the number of targets: indirect validation of the altered-proprioception hypothesis.

The ability of our sensorimotor system to adapt to changing and complex environmental demands has been under experimental scrutiny for more than a century. Previous works have shown that aimed arm movements adapt quickly and completely to Coriolis force, but incompletely to the combination of Coriolis and centrifugal forces without visual cues. Two hypotheses may be advanced to explain this discrepancy: the workspace-exploration hypothesis, and the degraded-proprioception hypothesis. The aim of this study was to distinguish between the above two alternatives by comparing adaptive improvement during off-axis rotation in subjects pointing at one, three or seven different targets in complete darkness. Two main results emerge: (a) off-axis rotation led initially to errors in the direction of Coriolis force and in the opposite direction of the centrifugal force; (b) the size of the visited workspace has no effect on the way the subjects adapt to a multi-force environment. The lack of a target-number effect and the persistence of lateral errors in the pointing movements performed during rotation of the platform, support the degraded-proprioception rather than the workspace-exploration hypothesis of adaptation to a multi-force environment.

Acclimatization↗

Beta cell death in hyperglycaemic Psammomys obesus is not cytokine-mediated.

AIMS/HYPOTHESIS: It has recently been proposed that IL-1beta may be responsible for beta cell death in type 2 diabetes mellitus. Major support for this assumption was derived from experiments in the gerbil Psammomys obesus (sand rat), a model for nutritionally induced non-insulin-dependent type 2 diabetes. Using gerbil-specific primers for the analysis of gene expression, we investigated the validity of this hypothesis. METHODS: Gene expression was analysed by real-time RT-PCR of isolated and laser-microdissected islets and by in situ RT-PCR, both in beta cells and in immune cells, as well as in lymph nodes and spleen. RESULTS: We were unable to detect Il-1beta and the IL-1beta-inducible enzyme inducible nitric oxide synthase (iNos) by in situ RT-PCR, either in the pancreatic beta cells, or in the small number of non-activated immune cells of healthy and diabetic Psammomys obesus after 1 and 3 weeks on a high-energy diet. Very low levels of Il-1beta and iNos mRNA were detectable in collagenase-isolated and laser-microdissected islets of normoglycaemic gerbils by real-time RT-PCR without any increase of these mRNAs in islets from diabetic animals. These results were confirmed by electron microscopy with immunogold staining for IL-1beta and insulin. CONCLUSIONS/INTERPRETATION: The diabetic syndrome induced in Psammomys obesus by high-energy diet is a classical type 2 diabetes model, which does not show any evidence of an involvement of the proinflammatory cytokine IL-1beta or of activated immune cells in its pathogenesis. This is clearly at variance with the situation in type 1 diabetes.

Animals↗

The role of eye movements in visuo-manual adaptation.

The present study evaluated the role of eye movements for manual adaptation to reversed vision. Subjects tracked a visual target using a mouse-driven cursor. In Experiment A, they were instructed to look at the target, look at the cursor, fixate straight ahead, or received no instructions regarding eye movements (Groups T, C, F, and N, respectively). Experiment B involved Groups T and C only. In accordance with literature, baseline manual tracking was more accurate when subjects were instructed to move their eyes rather than to fixate straight ahead. In contrast, no such benefit was observed for the adaptive improvement of tracking. We therefore concluded that transfer of information from the oculomotor to the hand motor system enhances the ongoing control of hand movements but not their adaptive modification; probably because the large computational demand of adaptation does not allow an additional processing of supplementary oculomotor signals. We further found adaptation to be worse in T than in any other group. In particular, adaptation was worse in T than in C although eye movements were the same: subjects in both groups moved their eyes in close relationship with the target rather than the cursor, Group C thus disobeying our instructions. The deficient performance of Group T is therefore not related to eye movements per se, but rather to our instructions. We conclude that an independently moving target strongly attracts eye movements independent of instruction (i.e. Groups T and C), but instructions may redirect spatially selective attention (i.e. Group T vs C), and thus influence adaptation.

Adaptation, Physiological↗

Genetic susceptibility to keloid disease: mutation screening of the TGFbeta3 gene.

Keloid disease (KD) is a fibroproliferative dermal tumour of unknown aetiology. The increased familial clustering in KD, its increased prevalence in certain races and its presence in identical twins suggest a strong genetic predisposition to keloid formation. Transforming growth factor beta isoforms (TGFbeta) play a central role in wound healing and fibrosis and have been implicated in KD pathogenesis. Recent data has suggested that TGFbeta(3) has an important role in scar formation. There is little known about the genetic variation present within the TGFbeta(3) gene, which contains seven exons and six introns spanning 43,000 base pairs of the human genome. Exons one to seven and the promoter region (1000 bp upstream from exon 1 in the 5'-flanking regions) were screened in 95 Caucasian KD cases and 95 Caucasian controls for the presence of novel mutations using a high throughput DHPLC mutation detection technology. There were no mutations identified in any of the exonic regions, however, multiple nondisease associated mutations were found in the promoter region of the TGFbeta(3) gene. These data demonstrate that there is no association between the exonic and promoter regions of TGFbeta(3) gene and keloid scarring in our cohort of Caucasian patients.

Adolescent↗

Compartment-specific quantitative gene expression analysis after laser microdissection from archival renal allograft biopsies.

BACKGROUND: Various immunological and non-immunological pathomechanisms are responsible for the cellular damage in renal allografts. Since the kidney is an anatomically complex organ with functional and morphological heterogeneous compartments (interstitium, tubuli, vessels, glomeruli), the local response to injury maybe variable, therefore, the identification of local pathomechanisms is important. AIM: To elucidate any discrepancies in quantitative mRNA expression profiles between a total specimen analysis and a cell-specific evaluation after laser microdissection. METHODS: Real-time RT-PCR was performed for complement component C3 and heme oxygenase-1 (HO-1) genes compared to the housekeeping gene beta-actin using whole section RNA extracted from formalin-fixed and paraffin-embedded archival material of 16 explanted, rejected renal allografts. Ten non-transplant nephrectomies served as controls. For five cases from each group, five different compartments of the organs (interstitium, proximal tubuli, distal tubuli, vessels, glomeruli) were microdissected and quantitative analysis for C3 and HO-1 was performed identically. RESULTS: Whole section mRNA expression analysis: the data showed a constant expression of the housekeeping gene beta-actin, a 7-fold increased expression of C3 and a 3-fold decreased expression of HO-1 in the allograft group as compared to the control group. mRNA expression results from microdissected compartments: in the control group, C3 and HO-1 expression could only be detected in the proximal tubuli of all cases whereas all five compartments analyzed from the rejecting kidneys showed expression of the two genes. In the allografts, expression levels of the investigated genes varied considerably not only among the different compartments but between individual cases as well. CONCLUSION: Laser microdissection combined with real-time RT-PCR is a feasible approach for retrospective quantitative gene expression analysis in formalin-fixed and paraffin-embedded renal allograft specimens. As shown for C3 and HO-1, cell-specific expression patterns ofpathogenetically relevant genes vary considerably between individual cases. A close correlation of morphology and cell-specific gene expression analysis will contribute to the elucidation of the complex pathogenesis of chronic renal allograft nephropathy.

Actins↗

Validity of the speed-accuracy tradeoff for prehension movements.

Subjects (n=12) grasped mirror-viewed visual targets with thumb and index finger, while prescribed movement time differed between blocks of trials. The variability of both final grip aperture (i.e. distance between thumb and index finger) and of final wrist position increased with decreasing movement time, indicating the existence of a speed-accuracy tradeoff both in the grasp and in the transport component of prehension. This tradeoff was limited to relatively short movement times (<400 ms) for the grasp component, but it extended to longer movement times for the transport component, which supports the view that the two components are controlled by separate mechanisms.

Adult↗

Genetic susceptibility to keloid disease: transforming growth factor beta receptor gene polymorphisms are not associated with keloid disease.

Keloid disease (KD) is an abnormal form of scarring with a familial predisposition. Genetic studies have yet to identify the genes involved in KD. Transforming growth factor beta (TGF-beta) has multiple cellular activities including cellular proliferation, differentiation and extracellular matrix production. TGF-beta family members such as TGF-beta(1) and TGF-beta(2) are known to be involved in KD formation. However, we previously demonstrated a lack of association between common TGF-beta(1) and TGF-beta(2) polymorphisms and KD. Other studies have implicated TGF-beta receptors in KD pathogenesis. TGF-beta receptors were therefore selected as candidate-susceptibility genes for this condition. Single-nucleotide polymorphisms (SNPs) in TGF-beta receptors I, II and III (TGF-betaRI, TGF-betaRII and TGF-betaRIII) were identified and investigated for association with the risk of developing KD. A polymerase chain reaction-restriction fragment length polymorphism method was used for genotyping novel and known TGF-beta receptor polymorphisms. DNA samples from 92 KD cases and 181 controls were examined. There were no statistically significant differences in genotype or allele frequency distributions between cases and controls for the TGF-beta receptor SNPs. Therefore, these TGF-beta receptor polymorphisms are unlikely to be associated with keloid scarring. It is possible that other SNPs in other TGF-beta family members are associated with KD. To our knowledge, this is the first report of a case-control association study with KD and TGF-beta receptor gene polymorphisms.

Case-Control Studies↗

Production of isometric forces during sustained acceleration.

BACKGROUND: The operation of high-performance aircraft requires pilots to apply finely graded forces on controls. Since they are often exposed to high levels of acceleration in flight, we investigated to what extent this ability is degraded in such an environment. METHODS: Twelve healthy non-pilot volunteers were seated in the gondola of a centrifuge and their performance was tested at normal gravity (1 G) and while exposed to sustained forces of 1.5 G and 3 G oriented from head to foot (+Gz). Using an isometric joystick, they attempted to produce force vectors with specific lengths and directions commanded in random order by a visual display. RESULTS: Acceleration had substantial effects on the magnitude of produced force. Compared with 1 G, maximum produced force was about 2 N higher at 1.5 G and about 10 N higher at 3 G. The size of this effect was constant across the different magnitudes, but varied with the direction of the prescribed force. CONCLUSIONS: Acceleration degrades control of force production. This finding may indicate that the motor system misinterprets the unusual gravitoinertial environment and/or that proprioceptive feedback is degraded due to increased muscle tone. The production of excessive isometric force could affect the safe operation of high-performance aircraft.

Acceleration↗

Transdermal fentanyl for the treatment of back pain caused by vertebral osteoporosis.

Pain relief for patients with osteoporosis is important to maintain mobility and facilitate physical therapy. Transdermal fentanyl may be useful but has not been studied systematically. Patients with at least one osteoporotic vertebral fracture requiring strong opioids were enrolled and received transdermal fentanyl. Treatment history, pain, ease of physical therapy, and quality of life were recorded at baseline and after 4 weeks. Of 64 patients enrolled, 49 completed the study; 12 withdrew because of adverse events, most commonly nausea, vomiting, or dizziness. Pain at rest and on movement decreased significantly from baseline to final assessment (mean scores 7.84 and 8.55, respectively, at baseline, falling to 3.56 and 4.50 after 4 weeks). Quality of life improved significantly, and 61% of patients were satisfied with the treatment. Ability to undergo physical therapy improved significantly. Transdermal fentanyl is useful for the treatment of severe back pain caused by osteoporosis.

Administration, Cutaneous↗

The coordination of hand transport and grasp formation during single- and double-perturbed human prehension movements.

We investigated the mechanisms underlying human prehension movements, by perturbing the size and position of virtual targets. Subjects grasped virtual target discs with thumb and index finger. In 25% of trials, target size or position (single perturbation), or both (double perturbation) were changed 300 ms after target appearance. The experiments were designed such that the kinematic profiles of grasp formation and hand transport had a similar shape, and were analysed by the same algorithm. We found that grasp kinematics were influenced by changes of target position, and transport kinematics by changes of target size; we also found that the kinematics of double-perturbation trials could not be explained as a linear combination of single-perturbation effects. These findings confirm and expand previous evidence against the view that grasp and transport are controlled by fully independent channels. Most importantly, we found that the time of correction onset was not the same for grasp and transport, neither in single- nor in double-perturbation trials. This outcome argues against a holistic (single-channel) model of prehension; instead, our data are consistent with the notion of two mutually coupled channels.

Adult↗

[Keloids. A fibroproliferative disorder of unknown etiology].

We review recent advances in keloid research and treatment. Keloids are benign tumours of the skin. They tend to occur in younger patients after different kinds of injuries, infections or they may develop spontaneously. In contrast to hypertrophic scars, keloids are not confined to the original wound, but grow into the corresponding healthy skin. They rarely recede within time. Most patients complain of itching and suffer from impairment of their quality of life. Only little is known about the pathogenesis of keloids, although they have been clinically well characterized for a long time. New results point towards a disruption in the signaling pathway of TGFbeta. In addition there seems to be evidence of an increased familiar incidence and therefore the genetic background should be screened. Successful treatment of keloids is difficult. As contact cryotherapy and intralesional corticosteroid injections are in most cases not successful, the pulsed dye-laser seems to be a promising alternative. In addition topical treatment with extracts of onions, occlusive silicone sheets and pressure improves the clinical appearance of keloids.

Cell Division↗

Genetic susceptibility to keloid disease and transforming growth factor beta 2 polymorphisms.

Keloid disease (KD) is a benign fibroproliferative scarring condition of unknown aetiopathogenesis. There is a familial predisposition to keloid scarring. The genes involved in the pathogenesis of abnormal dermal scarring have yet to be identified. Transforming growth factor beta (TGF beta) is a family of multifunctional cytokines, which play a central role in wound healing and fibrosis. The TGF beta 2 isoform is a member of this cytokine family and has previously been implicated in KD pathogenesis. We tested for an association between KD and two novel polymorphisms within the TGF beta 2 gene: an insertion polymorphism within the 59-untranslated region, 109 base pairs away from the initiation codon, and a single nucleotide polymorphism in exon one. We examined DNA samples from 101 patients with KD and 187 ethnically matched controls. No statistically significant differences in TGF beta 2 genotype or allele frequency distribution were observed between the patients and the controls. We believe this to be the first report of a case-control association study in KD and TGF beta 2 polymorphisms.

Cicatrix, Hypertrophic↗

Speed-accuracy trade-off of grasping movements during microgravity.

BACKGROUND: Earthbound studies have shown that for pointing movements there is a specific relationship between movement speed, amplitude, and accuracy that is known as Fitts' law. We investigated the validity of Fitts' law for grasping movements in normal and microgravity. METHOD: Subjects performed grasping movements toward virtual targets under three different time constraint conditions before and during exposure to microgravity in parabolic flights. RESULTS: The "speed-accuracy trade-off" phenomenon was observed for the grasp component of prehension movements. The results were quantitatively similar in normal and microgravity such that increasing the speed resulted in a diminished accuracy. CONCLUSIONS: Fitts' law is partially valid for grasping movements toward virtual targets without visual feedback of the hand in normal gravity. In a microgravity environment, performance of grasping movements also follows some of the predictions of Fitts' law.

Adult↗

Development of a new method of analysing chemotactic deactivation of human neutrophil granulocytes.

Measurement of chemotactic migration of human neutrophil granulocytes (PMN) induced by chemotaxins serves as a simple and reliable method for assessing the expression of chemotaxin receptors. Incubation of PMN with a certain chemotaxin leads to a diminished chemotactic migration towards this chemotaxin. This is called chemotactic deactivation. We developed a new deactivation chamber to determine chemotaxis and chemotactic deactivation of human PMN. This novel chamber is a modification of the commercially available acrylic 48-well microchemotaxis chamber consisting of an upper block with wells drilled all the way through the block and a blind-well lower block. Both blocks are separated by a polycarbonate membrane. PMN from the wells in the upper block migrate through the pores of the membrane into the wells of the lower block containing the chemoattractants. Migrated PMN on the lower side of the PC membrane were quantified after staining by measuring specific light absorbance. The chemotactic activity is quantified as a ratio of stimulated migration and random migration (chemotactic index=CI). For our novel chamber, only the upper blocks of this commercial chamber were connected like a sandwich, including a polyvinylpyrrolidone-free polycarbonate membrane with a pore size of 3 microm. The wells in the upper compartment were filled with 5 x 10(4) PMN and deactivating chemotaxin. The lower block was then filled with the chemotactic stimulus and the chamber was then incubated in humidified air with 5% CO2 atmosphere at 37 degrees C. The influence of cell concentration, incubation time, chemotactic factor concentration, pore size and alkaline treatment of polycarbonate membranes on migrational activity of PMN have been investigated. The technique was rigorously standardized in order to optimize the assay conditions. The method is relatively simple, sensitive and fast. The determination of chemotaxis and deactivation are performed in the same chamber, thus avoiding cell loss due to nonspecific adherence in other incubation tubes. The chamber can be used to characterize the chemotactic activity of chemoattractants of unknown structure via known and unknown receptors. This new chamber can be very helpful in detecting unknown chemotactic stimuli, which are not detectable by, for example, antibodies.

Cell Culture Techniques↗