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Biomedical subjects

J Philipp

Publications and source records attributed to J Philipp.

17 recordsLinked to original sources
PubMed2001

The effects of digital anaesthesia on predictive grip force adjustments during vertical movements of a grasped object.

Grip force adjustments to fluctuations of inertial loads induced by vertical arm movements with a grasped object were analysed during normal and impaired finger sensibility. Normally grip force is modulated in a highly economical way in parallel with fluctuations of load force. Two subjects performed vertical up and down movements of a grasped object, both with normal finger sensibility and then cutaneously anaesthetized finger sensibility. Short breaks were taken in between single movements, during which the object was held stationary. After digital anaesthesia was applied to the grasping fingers, both subjects substantially increased the grip force. The grip force amplitude and timing still anticipated changes in load force, although the established grip force had already overcome movement-induced load force peaks. This implies that the increase of grip force and consequently the elevated force ratio between maximum grip and maximum load force are not processed to alter the feedforward system of grip force control. Cutaneous afferent information from the grasping digits appears to be necessary for economic scaling of the grip force level, but it plays a subordinate role in the precise anticipatory temporal coupling of grip and load forces during voluntary object manipulation.

Adult↗
PubMed2001

Effects of changing gravity on anticipatory grip force control during point-to-point movements of a hand-held object.

We investigated the quality of predictive grip force control during gravity changes induced by parabolic flight maneuvers. During these maneuvers gravity varied: There were 2 periods of hypergravity, in which terrestrial gravity nearly doubled, and a 20-s period of microgravity, during which a manipulated object was virtually weightless. We determined grip and load forces during vertical point-to-point movements of an instrumented object. Point-to-point movements were a combination of static (stationary holding) and dynamic (continuous movements) task conditions, which were separately analyzed in our previous studies. Analysis of the produced grip forces revealed that grip adjustments were closely linked to load force fluctuations under each gravity condition. In particular, grip force maxima coincided closely in time with load force peaks, although these occurred at different phases of the movement depending on the gravity level. However, quantitative analysis of the ratio of maximum grip force to the corresponding load force peak revealed an increased force ratio during microgravity when compared to that during normal and hypergravity. We hypothesize that the impaired precision of force coupling with respect to force magnitude during microgravity results from reduced feedback information about the object's mass during the stationary holding of the object in between each movement. The results indicate that the temporal grip force regulation is highly automatized and stable, whereas economical planning of force magnitude is more flexible and might reflect changes of the external loading condition.

Adaptation, Physiological↗
PubMed2000

A system for the study of visuomotor coordination during reaching for moving targets.

Prehensile behavior is a popular task in current research on human motor control. Most studies on reaching used stationary target objects and, therefore, most models do not address the challenges the motor system must respond to when reaching for moving objects. The machines used in earlier studies to produce object motion offered a limited range of trajectories and restricted control over various movement parameters. We have developed a device that allows a great variety of object trajectories along a flat-table surface and gives the experimenter full control over all movement parameters. A linear positioning system is used to move a sled beneath the table surface. Magnetic coupling transfers the sled's movement to the target object on the tabletop. This arrangement allows fast movements of the object (up to 5 m/s) and at the same time protects subjects from any harm due to the moving parts. The system is connected to LC shutter glasses, a 3-D movement registration device, and a switch that detects the onset of hand motion. This allows the selective withdrawal of vision during the reaching task or the introduction of changes in the object motion depending on the subject's reactions.

Electronic Data Processing↗
PubMed2000

Moving weightless objects. Grip force control during microgravity.

When we move grasped objects, our grip force precisely anticipates gravitational and inertial loads. We analysed the control of grip forces during very substantial load changes induced by parabolic flights. During these flight manoeuvres, the gravity varies between hypergravity associated with a doubling of normal terrestrial gravity and a 20-s period of microgravity. Accordingly, the contribution of the object's weight to the load changed from being twice the normal value to being absent. Two subjects continuously performed vertical and horizontal movements of an object equipped with grip force and acceleration sensors. Whereas, during vertical movements performed under normal and hypergravity, a load force maximum occurred at the lower turning point and a minimum at the upper turning point, the load force pattern was completely changed under microgravity. In particular, the upper turning point was also associated with a load force maximum. Analysis of the grip forces produced by the two subjects revealed that the grip forces underwent the same characteristic changes as the load forces. Thus, subjects were able to adjust grip forces in anticipation of arm movement-induced fluctuations in load force under different and novel load conditions. Adaptation to changing levels of gravity was also obvious when the vertical and horizontal movements were compared: grip forces depended heavily on movement direction during normal and hypergravity but not during microgravity. The predictive coupling of grip force and load force was observed even during transitions between gravity levels, indicating rapid adaptation to changing load conditions. To account for the striking preservation of the normal characteristics of grip force control, we suggest that a highly automatized, extremely flexible sensorimotor mechanism firmly implemented within the central nervous system can cope with even massive changes in the environmental conditions.

Adaptation, Physiological↗
PubMed1999

Tumor suppression by p27Kip1 and p21Cip1 during chemically induced skin carcinogenesis.

p27Kip1 and p21Cip1 are cyclin dependent kinase inhibitors which can arrest cell proliferation and p27 is a tumor suppressor gene. To address the mechanism of tumor suppression by p27 and to determine if p21 has a tumor suppressor phenotype, we utilized the two stage skin carcinogenesis model on p27 and p21 knockout mice. In this model, initiation, which involves mutation of H-ras induced by DMBA, can be distinguished from promotion induced by TPA, and progression to carcinoma. The mean number of papillomas did not differ between p27-/- and control littermates, but papilloma growth rate was increased and carcinomas developed earlier. Thus, p27 deficiency did not enhance initiation, but resulted in more rapid clonal expansion of initiated cells during promotion. TPA treatment reduced p27 expression in keratinocytes also supporting a role for p27 during promotion. Tumors from p27-/- mice contained mutant H-ras indicating that p27 deficiency did not substitute for mutant ras and further, that during ras driven tumor growth, p27 is partially antagonistic since its removal led to faster growth. The treated p27-/- mice also developed intestinal adenomas. p21-/- mice did not display a significant increase in tumor numbers, growth rate or progression to carcinomas and these tumors also had mutated H-ras. Carcinomas from p21-/- mice were more poorly differentiated with a high frequency of anaplastic spindle cell carcinomas. Thus p21 deficiency mainly resulted in higher grade undifferentiated tumors.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1999

Grip forces exerted against stationary held objects during gravity changes.

In the present study, grip forces exerted against a stationary held object were recorded during parabolic flights. Such flight maneuvers induce changes of gravity with two periods of hypergravity, associated with a doubling of normal terrestrial gravity, and a 20 s period of microgravity. Accordingly, the object's weight changed from being twice as heavy as normally experienced and weightless. Grip-force recordings demonstrated that force control was seriously disturbed only during the first experience of hyper- and microgravity, with the grip forces being exceedingly high and yielding irregular fluctuations. Thereafter, however, grip force traces were smooth, the force level was scaled to the object's weight under normal and high-G conditions, and the grip force changed in parallel with the weight during the transitions between hyper- and microgravity. In addition, during weightlessness, when virtually no force was necessary to stabilize the object, a low force was established, which obviously represented a reasonable safety margin for preventing possible perturbations. Thus, all relevant aspects of grip-force control observed under normal gravity conditions were preserved during gravity changes induced by parabolic flights. Hence, grip-force control mechanisms were able to cope with hyper- and microgravity, either by incorporating relevant receptor signals, such as those originating from cutaneous mechanoreceptors, or by adequately including perceived gravity signals into control programs. However, the adaptation to the uncommon gravity conditions was not complete following the first experience; finer tuning of the control system to both hyper- and microgravity continued over the measurement interval, presumably with a longer observation period being necessary before a stable performance can be reached.

Adult↗
PubMed1995

Alternative mRNAs encode multiple isoforms of transcription factor AP-2 during murine embryogenesis.

Transcription factor AP-2 has been implicated as an important regulator of gene expression during vertebrate embryogenesis. We report here the cDNA cloning and analysis of mouse embryonic mRNA splice variants encoding four AP-2 isoforms. Isoform 1 is the homolog of the previously known human (HeLa) AP-2. The three new AP-2 isoforms all share the same DNA binding/dimerization domain as isoform 1 but either lack the proline-rich transcriptional activation domain encoded by exon 2 (isoform 2) or have different amino-termini encoded by two previously unknown alternative first coding exons for AP-2 (isoforms 3 and 4). All four AP-2 mRNA variants are present at significant levels between Days 11.5 and 17.5 of mouse embryogenesis. Variants 1, 3, and 4 show qualitatively but not quantitatively similar restricted expression patterns in 8.5-12.5 dpc embryos examined by in situ hybridization. At mid-embryogenesis, variant 3 is the major AP-2 mRNA species in the nervous system and in total embryo RNA but is less prevalent than variants 1 and 4 in the epidermis. The four mRNAs are all induced, although unequally, during differentiation of P19 cells into neural cell types and by cAMP stimulation of primary astrocytes. Variants 1-3 are coexpressed in different ratios in HeLa cells and in three human glioblastoma cell lines. These findings reveal that transcriptional regulation by AP-2 is likely to be more complex than previously assumed given the potential for multiple AP-2 homo- and heterodimeric DNA binding forms.

Alternative Splicing↗
PubMed1995

[Surgical results of per- and subtrochanteric femoral fractures. An overview of 15 years].

During the last 15 years, new methods for the surgical approach to pertrochanteric and subtrochanteric fractures were developed (eg. the dynamic hip screw (DHS) and the gamma-nail (GN)). Reviewing the results of this change in methods, we report on 450 patients with pertrochanteric fractures and 102 patients after subtrochanteric fractures of the femur. According to different surgical techniques, the patients were allocated into three periods (1980-1984, period I: 1986-1989, period II; 1991-1993, period III). During period I. 65% of the pertrochanteric fractures were stabilized using Ender-rods, during period III nearly 60% were operated using the DHS and 22% using the gamma-nail. The total hospital stay (department of surgery as well as the geriatric hospital) decreased from 80.4 +/- 31.7 days to 66.6 +/- 24 days (p < 0.001). Serious complications decreased by 80% during this time. During period I, 86.2% of patients with pertrochanteric fractures could be discharged at home, but in 89% in period II and 94.7% during period III. During period I, 74% of the subtrochanteric fractures were stabilized using an angle plate. During period III, more than 30% were operated by using the DHS and nearly 50% by using the gamma-nail. The total hospital stay (department of surgery as well as the geriatric hospital) decreased from 107.5 +/- 46.5 to 78.9 +/- 24.3 days (p < 0.001). During period I, 86.2% of patients with subtrochanteric fractures could be discharged at home, but 100% during period III. Serious complication as well as discharges to nursing home decreased during these 15 years.

Aged↗
PubMed1994

Cell type-specific regulation of expression of transcription factor AP-2 in neuroectodermal cells.

AP-2 is a cell type-specific DNA-binding transcription factor that regulates selected target genes in vertebrate organisms. Here we investigated cell type-specific expression and regulation of AP-2 in neuroectodermal cell lineages. During retinoic acid (RA)-mediated differentiation of P19 embryonal carcinoma cells into neuroectodermal cell types that include immunohistochemically defined neurons and astrocytes, we observed a strong induction of AP-2 transcripts and protein. In contrast, AP-2 mRNA was not induced in P19 cells which undergo mesoendodermal differentiation in response to 1% dimethylsulfoxide or low concentrations of RA, respectively. The potential of both neurons and astrocytes to express AP-2 was ascertained by using cerebellar neurons and astrocytes derived from newborn mice. Unlike these types of cells, microglial cells do not express AP-2. Dibutyryl cyclic AMP further enhanced levels of AP-2 transcripts in both P19 astrocytes and primary astrocytes which also respond to agents elevating intracellular cAMP (noradrenaline, isoproterenol, forskolin). The cAMP-dependent induction of AP-2 could be blocked by inhibitors of protein kinase A. In contrast to its action in P19 cells, RA had no effect on AP-2 mRNA levels in primary astrocytes. Our results indicate that AP-2 may play a role as a retinoic acid-sensitive regulator during differentiation of neurons and glia from an embryonic neural precursor. Furthermore, AP-2 may be involved in gene transcription in both mature neurons and astrocytes.

Animals↗
PubMed1992

Differential expression of transforming growth factor-beta 1, -beta 2, and -beta 3 by glioblastoma cells, astrocytes, and microglia.

The type beta transforming growth factors (TGF) are potent regulators of the growth and functions of lymphocytes and macrophages. Recently the human glioblastoma cell line 308 was shown to produce TGF-beta 2. The relevance of this finding was evaluated further by comparing human glioblastoma cells with their nontransformed animal counterpart, astrocytes, with regard to the production of the three TGF-beta isoforms observed so far in mammals. In this report astrocytes are demonstrated to secrete also TGF-beta 2 and to express TGF-beta 1, -beta 2, and -beta 3 mRNA in vitro. In contrast, cultured murine brain macrophages release TGF-beta 1 and are positive for TGF-beta 1 mRNA only. Glia cell-derived TGF-beta 1 and -beta 2 are detected in latent form whereas both latent and active TGF-beta are identified in the supernatant of three human glioblastoma cell lines tested. These cell lines, however, show heterogeneity in regard to the isoform of TGF-beta expressed but share with astrocytes the inability to release TGF-beta 3. Provided production and activation of latent TGF-beta occur in vivo, astrocytes and microglia may then be expected to exert regulatory influences on immune mediated diseases of the central nervous system.

Animals↗
PubMed1992

Protease inhibitors interfere with the transforming growth factor-beta-dependent but not the transforming growth factor-beta-independent pathway of tumor cell-mediated immunosuppression.

Tumor cells have been reported to exert inhibitory effects on the activation of T lymphocytes in vitro. We show that the IL-2-stimulated proliferation of a Th cell line is suppressed when the T cells are cocultured with human glioblastoma and melanoma cell lines. The use of two Th cell clones that differ in their responsiveness to growth-inhibition by transforming growth factor-beta (TGF-beta) and the analysis of tumor cell-derived supernatants as well as of TGF-beta 1/TGF-beta 2 gene expression allowed to distinguish two pathways of tumor-induced immunosuppression. Glioblastoma cells exert their immunosuppressive effects by producing biologically active TGF-beta 2, whereas the immunosuppressive state induced by melanoma cells is TGF-beta-independent and requires direct contact between tumor cell and T cell. The TGF-beta-dependent immunosuppression is down-regulated by various protease inhibitors and up-regulated by estradiol via modulation of the production of biologically active TGF-beta 2 by glioblastoma cells leaving total activatable TGF-beta 2 unaffected. No such modulation is functional for the TGF-beta-independent pathway of immunosuppression. We conclude that the production of active TGF-beta by tumor cells is regulated at a posttranslational level by the coordinated action of several proteolytic enzymes.

Animals↗
PubMed1991

Stented laser-welded vasovasostomy in the rat: comparison of Nd:YAG and CO2 lasers.

In 54 male Sprague-Dawley rats, 108 vasovasostomies were performed. Sutureless laser welding with the assistance of a removable stent was done using a CO2- and an Nd:YAG-laser system. Conventional two-layer microsurgical anastomoses served as controls. The Nd:YAG laser resulted in significantly lower patency rates, with a higher percentage of sperm granulomas; the CO2 laser produced results equivalent to conventional suturing. Sutureless laser welding utilizing a removable stent proved to be a time- and cost-saving procedure for vasovasostomies in the rat.

Animals↗