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Biomedical subjects

G Bauer

Publications and source records attributed to G Bauer.

At least 19 recordsLinked to original sources

Risk of dying after a free fall from height.

Falls from height are predominantly an urban phenomenon and represent an important form of blunt trauma. Disagreement predominates regarding the height at which death results. The aim of this study was to investigate the risk of dying after a free fall from height in relation to the distance fallen. Therefore, medical records of victims of a fall from height treated in 1989 at Viennese emergency units were analysed. In addition, post-mortem reports of deaths due to falls from height, examined in the same year at the Institute of Forensic Medicine in Vienna, were studied. For the purpose of an homogenous investigation sample in regard to physical condition, only people aged from 20 to 50 years were taken into account. A total of 11 females and 30 males suffered an accidental fall from buildings, seven men from scaffolding and two men from a tree. A total of 18 females and 18 males jumped from residential buildings. One woman and nine men intentionally fell from other buildings. All victims landed on concrete or pavement. Suicidal jumps occurred from significantly higher places than accidental falls. The results of this analysis suggest that death usually occurs when distance is more than five storeys.

Accidental Falls

Common subtypes of idiopathic generalized epilepsies: lack of linkage to D20S19 close to candidate loci (EBN1, EEGV1) on chromosome 20.

Hereditary factors play a major role in the etiology of idiopathic generalized epilepsies (IGEs). A trait locus (EBN1) for a rare subtype of IGEs, the benign neonatal familial convulsions, and a susceptibility gene (EEGV1) for the common human low-voltage electroencephalogram have been mapped close together with D20S19 to the chromosomal region 20q13.2. Both loci are potential candidates for the susceptibility to IGE spectra with age-related onset beyond the neonatal period. The present study tested the hypothesis that a putative susceptibility locus linked to D20S19 predisposes to spectra of IGEs with age-related onset from childhood to adolescence. Linkage analyses were conducted in 60 families ascertained through IGE patients with juvenile myoclonic epilepsy, juvenile absence epilepsy or childhood absence epilepsy. Our results provide evidence against linkage of a putative susceptibility gene for four hierarchically broadened IGE spectra with D20S19 assuming tentative single-locus genetic models. The extent of an "exclusion region" (lod scores below-2) varied from 0.5 cM up to 22 cM on either side of D20S19 depending on the trait assumed. These results are contrary to the expectation that a susceptibility gene in vicinity to D20S19 confers a common major gene effect to the expression of IGE spectra with age-related onset from childhood to adolescence.

Chromosome Mapping

Reactive oxygen species act at both TGF-beta-dependent and -independent steps during induction of apoptosis of transformed cells by normal cells.

We have recently shown that TGF-beta-treated normal fibroblasts can induce apoptosis of transformed cells. The overall process was inhibited by antioxidants and radical scavengers, pointing to a role of reactive oxygen species (ROS). To define the ROS-dependent steps precisely, our experimental system was dissected into three phases. During phase I, TGF-beta 1 induced production and release of apoptosis-inducing signal molecules by normal cells. In phase II, these signal molecules were transferred between normal and transformed cells. During phase III, transformed cells went into apoptosis. The use of antibody directed against TGF-beta revealed that TGF-beta was required only during phase I. Application of radical scavengers and antioxidants at defined phases revealed that reactive oxygen species are involved specifically with biochemical processes induced by TGF-beta in normal cells and early in signal transfer between normal cells and transformed cells. These data therefore point to a functional role of reactive oxygen species both for the TGF-beta 1-induced signal pathway in normal cells and for the induction of apoptosis in transformed cells.

Acetylcysteine

Exclusion of linkage between idiopathic generalized epilepsies and the GABAA receptor alpha 1 and gamma 2 subunit gene cluster on chromosome 5.

Hereditary factors play a major role in the etiology of idiopathic generalized epilepsies (IGEs). The pivotal function of ionotropic gamma-aminobutyric acid type A receptors (GABRs) in inhibitory neurotransmission in the mammalian central nervous system suggests that they may be involved in epileptogenesis and genetic predisposition to IGEs. Dinucleotide repeat polymorphisms associated with the human GABAA receptor alpha 1 (GABRA1) and gamma 2 subunit (GABRG2) gene cluster on chromosome 5q32-q35 offer the opportunity to test whether these candidate genes confer susceptibility to IGEs. Our linkage analyses in 63 families ascertained through IGE patients with either juvenile myoclonic epilepsy, juvenile absence epilepsy or childhood absence epilepsy do not support the hypothesis that variants within the GABRA1 and GABRG2 gene cluster contribute a frequent major gene effect to the expression of the common familial IGEs.

Base Sequence

Early, full weightbearing with flexible fixation delays fracture healing.

Secondary fracture healing is known to be accelerated by the process of periosteal callus formation that can be induced by flexible fracture fixation in connection with loading of the injured extremity. The purpose of this study was to compare the healing of experimental fractures of long bones in sheep under early weightbearing with that of fractures under delayed, steadily increasing weightbearing. Differences in the quality of fracture healing were described by biomechanical (rigidity of fracture, indentation stiffness of callus) and histologic methods. Prevention from early, full weightbearing resulted in a higher flexural rigidity of the fracture, an increased mechanical stiffness of the callus tissue, and an enhanced bone formation at the healing front. Although early loading of a fresh fracture initiated an enormous amount of periosteal callus, the healing of the osteotomy was significantly delayed, and the quality of the newly formed tissue was reduced as compared with fractures with a reduced loading situation. A reduction of load transfer by delaying full weightbearing is advantageous for the healing of fractures stabilized with flexible fixation systems.

Animals

[Foot stress simulator for biomechanical in vitro studies of lower leg segments].

In this paper we describe a foot-loading simulator that permits in vitro studies on human lower leg and foot specimens. The specimens are fixed in a jig and loaded axially with the aid of a pneumatic cylinder. The resulting transfer of forces through the ankle joint complex and Chopart's articulation (line) can be demonstrated on a pressure-sensitive film. Plantar pressure measurements obtained in patients or normal subjects can be used to ensure the comparability of in vivo and in vitro measurements. The supporting platform can be tilted in such a manner as to provide a range of foot positions up to 20 degrees in plantar- or dorsiflexion, eversion or inversion. The system is used for investigating the effects on the intra-articular pressures and plantar pressure patterns of physiological muscle activity and pathological conditions following fracture of the calcaneum or damage to the lateral ligament. By way of an example, the effects of muscle forces on plantar pressure distribution are presented.

Ankle Joint

[Arthrodesis of the ankle joint].

Arthrodesis of the ankle joint is still an important operation in the treatment of painful arthrosis, chronic infection, and malalignment instability when these cases have been treated unsuccessfully with other therapeutic procedures. To date, prosthetic replacement of the ankle joint has been an alternative only in rheumatoid patients. Concerning the long-term results, ankle arthrodesis is much better than alloarthroplasty. Because of the good functional results achievable by arthrodesis when done in the right position, there is less often a need for prosthetic replacement than in the hip or knee joint. A patient with a fused ankle joint is only limited when running. Compression arthrodesis is possible at present with various operative techniques utilizing external fixators, ring fixators and open reduction internal fixation with plates and screws. The last procedure can be carried out arthroscopically. With these techniques, fusion of the ankle joint in the correct position is possible in nearly all situations, e.g., infection, malalignment, osteoporosis, soft tissue damage. The main complication of ankle arthrodesis is pseudarthrosis (up to 35%) and postoperative infection (3%-25%). An important late sequela is arthrosis in the joints adjacent to the fused ankle joint (10-60%).

Ankle Joint

Elimination of transformed cells by normal cells: a novel concept for the control of carcinogenesis.

Control of transformed cells by neighbouring normal cells is known since the beginning of transformation studies in vitro. The classical explanation for this phenomenon is based on proliferation inhibition of transformed cells by normal cells. We extend this model by presenting data that show that TGF-beta-treated normal cells can eliminate transformed cells by induction of apoptosis. Both the TGF-beta-induced signal pathway in normal cells, leading to the production of a short-lived apoptosis-inducing factor, as well as the specific interaction of this factor with transformed cells depend on the action of reactive oxygen species. Sensitivity to induction of apoptosis seems to be a common feature associated with the transformed state, independent of the originally transforming principle. Therefore, tumor development should require either interference with the process of elimination or acquisition of resistance against it. We discuss experimental evidence for interfering substances, such as antioxidants, as well as for genetic systems that protect transformed cells from the negative effects of their cellular environment, such as Bcl-2 or papilloma viruses. These findings, as well as the general resistance of exvivo tumor cells against induction of apoptosis are in line with the novel model of control of tumor progression presented by us in this review.

Animals

Direct transforming activity of TGF-beta on rat fibroblasts.

Treatment of NRK 536 fibroblasts with EGF and transforming growth factor type beta (TGF-beta) is known to lead to the reversible induction of the transformed phenotype in a large percentage of cells. Maintenance of the transformed state is dependent on the continuous presence of the cytokines. Here we show that treatment of these cells with TGF-beta alone leads to the formation of a small percentage of colonies, the majority of which stably retain the transformed phenotype after removal of the cytokine. Colony induction is dependent on the concentration of TGF-beta originally present. Stably transformed cells grow in soft agar without further addition of exogenous TGF-beta, and exhibit criss-cross morphology in monolayer culture and a diffuse actin pattern. Transformation of NRK 536 cells can be demonstrated only for individualized cells treated with TGF-beta in soft agar, as treatment in monolayer leads to the induction of apoptosis in newly transformed cells by neighboring normal cells. Transformation of NRK 536 fibroblasts by TGF-beta is not due to the induction of point mutations by TGF-beta.

Agar

Catechol interferes with TGF-beta-induced elimination of transformed cells by normal cells: implications for the survival of transformed cells during carcinogenesis.

We have recently shown that TGF-beta-treated normal fibroblasts are able to induce apoptosis of transformed fibroblasts, leading to their elimination. Here we describe a test system that allows the quantitative analysis of the elimination of G418-resistant transformed cells by TGF-beta-treated normal cells. This assay system was used to screen for substances that interfere with the elimination of transformed cells. Catechol and hydroquinone, but not resorcinol, were found to represent potent antagonists of TGF-beta-induced elimination of transformed cells by normal cells. Protection of transformed cells from negative effects derived from their cellular environment defines a hitherto unrecognized crucial mechanism for the survival of transformed cells. The protective effect of catechol as seen in this experimental system may act in concert with its co-carcinogenic and promoting activities during carcinogenesis.

Animals

The phenotypic spectrum related to the human epilepsy susceptibility gene "EJM1".

Linkage studies of families ascertained through patients with juvenile myoclonic epilepsy (JME) suggest that an HLA-linked susceptibility gene on chromosome 6, designated "EJM1," predisposes to a group of idiopathic generalized epilepsies (IGEs) comprising JME, juvenile absence epilepsy (JAE), childhood absence epilepsies (CAE), and epilepsies with generalized tonic-clonic seizures (GTCS). To explore the EJM1-related phenotypic spectrum, we conducted linkage studies with HLA-DQ alpha restriction fragment length polymorphisms in 44 families ascertained through patients with CAE or JAE. Our results for the entire group of families provide evidence against a major susceptibility locus for idiopathic absence epilepsies and broader spectra of IGEs in the HLA region. Lod scores less than -2 were obtained for a region from 10 cM up to 23 cM on either side of the HLA-DQ alpha locus, depending on the assumed trait model. Suggestive evidence for linkage was found only for a subgroup of families with JME patients assuming an autosomal dominant mode of inheritance with 70% penetrance. A maximum lod score was obtained when family members with JME, JAE, CAE, and idiopathic GTCS were included into the affection status. Our results demonstrate that (1) the genetic susceptibility to idiopathic absence epilepsies and broader spectra of IGEs is heterogeneous, (2) the gene effect of EJM1 depends on the familial genetic background, and (3) EJM1 confers genetic susceptibility to idiopathic absence epilepsies and broader spectra of IGEs in the presence of family members with JME.

Disease Susceptibility

Clonal analysis of the effect of TGF-beta on the apoptosis-inducing activity of normal cells.

We have recently described induction of apoptosis in transformed fibroblasts by transforming growth factor type beta (TGF-beta)-treated normal fibroblasts, which leads to the specific elimination of transformed cells. Here we investigate whether the ability to eliminate transformed cells is the property of a specialized subpopulation of normal fibroblasts or whether all cells within the population are able to respond to exogenous TGF-beta by induction of elimination of transformed cells. Clonal analysis of the eliminative capacity of normal fibroblasts showed that all cells are able to induce elimination after addition of optimal concentrations of exogenous TGF-beta. In the absence of exogenously added TGF-beta, a minority of clones exhibited complete eliminative activity. Neither the ability nor the inability to perform elimination in the absence of exogenous TGF-beta was a stable characteristic of the respective cell clones. The number of cell clones with the ability to respond to suboptimal concentrations of TGF-beta increased with the passage number of the normal cells, whereas the number of clones inducing apoptosis in the absence of exogenous TGF-beta remained constant.

3T3 Cells

Displaced scapular fractures: indication and long-term results of open reduction and internal fixation.

Displaced scapular fractures are often found in polytraumatized patients. In emergency treatment they assume a minor role. Advances in dealing with severely injured patients in most instances allow us to perform an operation on the fractured scapula within the first 2 weeks after injury. A differentiated approach is necessary as exclusively conservative treatment does not always bring about good results. From 1981-1991 we performed open reduction and internal fixation (ORIF) in 25 patients with displaced fractures of the scapula. The long-term results could be assessed in 20 patients after an average of 6.1 years. The different types of fractures were classified according to Habermeyer/Ideberg, and the Constant score was used in the evaluation of results. Some 64% of patients were involved in road accidents, and 64% suffered concomitant injuries. Articular fractures (n = 6) were the most common ones, followed by fractures of the coracoid process (n = 5) and the neck of the scapula (n = 2). There was no early postoperative complication, and follow-up showed a breakage of K-wires in one patient (fracture of the acromion). Thirteen patients obtained a very good, two patients a good, four a fair and one a poor result (according to the Constant score). Fractures of the scapular neck had the best results in terms of pain, daily activity, range of motion, and strength) as compared with fractures of the glenoid and apophyseal fractures.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Refinement of map position of the human GluR6 kainate receptor gene (GRIK2) and lack of association and linkage with idiopathic generalized epilepsies.

Hereditary factors play a major role in the etiology of idiopathic generalized epilepsies (IGEs). The pivotal function of glutamate receptors (GluRs) in excitatory neurotransmission implicates their involvement in epileptogenesis and genetic susceptibility to IGEs. A trinucleotide repeat polymorphism detected in the 3' untranslated region of the kainate-selective GluR6 receptor gene (GRIK2) on chromosome 6 makes it possible to perform linkage and association studies with this high-ranking candidate gene. The present study tested the hypothesis that allelic variants of GRIK2 contribute to the genetic susceptibility to the common IGEs. Linkage and association analyses were conducted in 63 families ascertained through IGE patients with juvenile myoclonic epilepsy, juvenile absence epilepsy, or childhood absence epilepsy. Our linkage and association results suggest that allelic variants of GRIK2 are not involved in the expression of the common familial IGEs, and radiation hybrid mapping assigns GRIK2 to the chromosomal region 6q16.3-q21. This localization excludes GRIK2 as a candidate for the putative IGE susceptibility locus "EJM1" on the short arm of chromosome 6.

Chromosome Mapping

Reconstitution of complete SV40 DNA replication with purified replication factors.

The identification and purification of human cell proteins required for the production of form I DNA following DNA replication from the simian virus 40 (SV40) origin is described. Using these proteins, complete SV40 DNA replication was reconstituted with only purified DNA replication factors: SV40 large tumor antigen (TAg), replication protein A (RPA), DNA topoisomerases I and II, DNA polymerase alpha-primase, replication factor C (RFC), the proliferating cell nuclear antigen (PCNA), DNA polymerase delta, maturation factor 1 (MF1), and DNA ligase I. MF1, a 5' to 3' exonuclease and DNA ligase I were both identified as essential components for production of covalently closed circular relaxed (form I) DNA. MF1 is probably the same exonuclease previously shown by others to function during DNA synthesis on artificial DNA templates or in conjunction with DNA polymerase alpha from the SV40 origin. Combined with these previous studies, our results suggest that MF1 functions to remove an RNA primer attached to every Okazaki fragment during lagging strand DNA synthesis. Interestingly, whereas mammalian DNA ligase I functioned in the reconstituted replication system, mammalian DNA ligase III did not substitute and the phage T4 DNA ligase functioned inefficiently, suggesting that DNA ligase I has a specific role as a replicative DNA ligase in eukaryotic cells.

Animals

Transforming growth factor beta-treated normal fibroblasts eliminate transformed fibroblasts by induction of apoptosis.

Transforming growth factor beta (TGF-beta) induces normal fibroblasts to perform an inhibitory effect directed against transformed cells (P. Höfler, I. Wehrle, and G. Bauer, Int. J. Cancer, 54: 125-130, 1993). Coculture of normal fibroblasts with transformed cells, either resistant to G 418 or expressing Mx antigen detectable by specific immunofluorescence, allowed discrimination between three theoretical mechanisms of inhibition: irreversible inhibition of proliferation; reversion to the nontransformed phenotype; or elimination of transformed cells. Our data demonstrate that normal fibroblasts treated with TGF-beta are able to eliminate transformed cells by induction of apoptosis. Sensitivity against TGF-beta-induced elimination seems to be a general feature of in vitro-transformed cell lines. TGF-beta-induced elimination of transformed fibroblasts by their untransformed counterparts is proposed as a potential potent control point in carcinogenesis, which may lead to the suppression of transformed cells.

3T3 Cells

IgA directed against early antigen of Epstein-Barr virus is no specific marker for the diagnosis of nasopharyngeal carcinoma.

The aim of this study was to evaluate the significance and specificity of IgA directed against Epstein-Barr virus (EBV)-specific early antigens (EA) for the unequivocal diagnosis of nasopharyngeal carcinoma (NPC). Therefore, sera from patients with diseases other than NPC, selected on the basis of elevated antibody titres against EBV antigens, were compared to sera from NPC patients with regard to the presence of IgA directed against EBV viral capsid antigen (VCA-IgA) and IgA directed against EA (EA-IgA). Four hundred forty-seven out of 7,508 non-NPC sera tested showed high titres (> 512) of IgG directed against Epstein Barr viral capsid antigen (VCA-IgG) and positive VCA-IgA (> or = 32). Two hundred twenty-seven of these sera were compared to 51 VCA-IgA-positive sera from NPC patients regarding the titre of EA-IgA. 60.7% of VCA-IgA-positive NPC sera showed positive EA-IgA, however 33% of VCA-IgA-positive non-NPC patients also exhibited EA-IgA. This result demonstrates that EA-IgA is not specific for NPC and does not allow an unequivocal serological diagnosis of NPC in individual cases. It seems therefore to be of questionable use for screening programs in NPC low-risk areas. The data do not contradict the usefulness of this marker for monitoring of patients treated for NPC and for screening programmes in high-risk areas.

Adult

Avidities of IgG directed against viral capsid antigen or early antigen: useful markers for significant Epstein-Barr virus serology.

Classical Epstein-Barr virus (EBV) serology can be misleading in some cases due to the variability of the viral capsid antigen (VCA)-IgM response, persistent or reactivated VCA-IgM, or loss of anti-EBNA-1 during suppression of the cellular immune system. Therefore, we studied the usefulness and significance of avidity determinations of VCA-IgG and EA-IgG to achieve unequivocal interpretation of serological results. Avidities of EBV capsid antigen-specific IgG (VCA-IgG) and early antigen-specific IgG (EA-IgG) were determined by indirect immunofluorescence during and after acute EBV infection. Low-avidity antibodies were removed from antigen-antibody complexes by incubation with 6 M urea for 3 minutes. The analysis of 105 sera taken at defined time spans with regard to the onset of clinical symptoms allowed us to determine the kinetics of maturation of avidity of VCA-IgG. All sera had low-avidity antibodies at the onset of disease. More than 90% of the sera showed an avidity index below 0.25 during the first 10 days after the onset of disease. Fifty percent of the sera exhibited an avidity index of 0.25 or above 20-30 days after the onset of clinical symptoms. Sera from past infections uniformly exhibited avidity indices of 0.5 or 1. Avidity of EA-IgG may still be low when avidity of VCA-IgG is already borderline or high, thus allowing further differentiation of acute and recent infections. Avidity determination represents an important additional marker of serology in classical cases and allows diagnosis in aberrant cases, such as acute infections with low or undetectable VCA-IgM.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease