Biomedical subjects

M Thier

Publications and source records attributed to M Thier.

7 recordsLinked to original sources

PubMed1995

Human ciliary neurotrophic factor: a structure-function analysis.

Ciliary neurotrophic factor (CNTF) promotes survival in vitro and in vivo of several neuronal cell types including sensory and motor neurons. The primary structure of CNTF suggests it to be a cytosolic protein with strong similarity to the alpha-helical cytokine family which is characterized by a bundle of four anti-parallel helices. CNTF exerts its activity via complexation with CNTF receptor (CNTF-R). This complex consists of a CNTF-binding protein (CNTF-R) and two proteins important for signal transduction [gp130 and leukaemia inhibitory factor receptor (LIF-R)]. We have shortened the cDNA coding for CNTF at both the 5' and the 3' end and expressed the truncated proteins in bacteria. Biological activities of the protein preparations were determined by their ability to induce proliferation of BAF/3 cells that were stably transfected with CNTF-R, gp130 and LIF-R cDNAs. CNTF proteins with 14 amino acid residues removed from the N-terminus were biologically active whereas the removal of 23 amino acids resulted in an inactive protein. In addition, 18 amino acid residues could be removed from the C-terminus of the CNTF protein without apparent loss of bioactivity, but further truncation at the C-terminus yielded biologically inactive proteins. The introduction of two point mutations into the CNTF protein at a site that presumably interacts with one of the two signal-transducing proteins resulted in a CNTF mutant with no measurable bioactivity. In addition, a model of the three-dimensional structure of human CNTF was constructed using the recently established structural co-ordinates of the related cytokine, granulocyte colony-stimulating factor. CD spectra of CNTF together with our mutational analysis and our three-dimensional model fully support the view that CNTF belongs to the family of alpha-helical cytokines. It is expected that our results will facilitate the rational design of CNTF mutants with agonistic or antagonistic properties.

Amino Acid Sequence↗

PubMed1995

Site-directed mutagenesis of human CNTF: functional analysis of recombinant variants.

Ciliary neurotrophic factor (CNTF), interleukin-6 (IL-6), leukemia inhibitory factor (LIF), and oncostatin M (OSM) share functional properties, a predicted common helical framework, and partially identical receptor components. CNTF is a survival promoting factor for various types of neurons in vitro and in vivo. In the present study, structural features essential for the biological function of human CNTF were investigated. Several recombinant CNTF variants were constructed by PCR and expressed in E. coli. Their survival promoting activities were determined using cultures of embryonic chick and newborn rat dorsal root ganglion cells. Deletion of 14 N-terminal and 18 C-terminal amino acids significantly increased bioactivity compared to wild-type (wt) CNTF. Further truncation of the CNTF molecule at the N- or C-terminus resulted in a significant reduction or complete loss of activity. Substitution of two amino acids (Lys154Glu and Trp157Pro) abolished the survival promoting effect. Recently described analogous substitutions in IL-6 had resulted in a partial IL-6 receptor antagonist. However, the double substitution variant had no significant inhibitory effect on wtCNTF activity in assays with both wt and mutant factor. The CNTF variants constructed had almost identical effects on both chick and rat neurons indicating a close similarity of the avian and the mammalian CNTF receptor complex. The present results also demonstrate that a core segment of the CNTF molecule is indispensable for biological function. Analogous segments important for activity have already been identified in the related molecules IL-6, LIF, and OSM. Thus, our data confirm the close structural relationship of CNTF to these "neuropoietic" cytokines. In addition, they demonstrate that site-directed mutagenesis of recombinant human CNTF can yield molecules which show increased survival promoting activity on mammalian neurons.

Animals↗

PubMed1992

[A pseudoelastic NiTi uprighting spring for the molars--its design, biomechanical testing and clinical use].

Uprighting inclined molars is one of the most common problems encountered in pre-restorative orthodontics. To prevent occlusal trauma, an intrusive force has to be applied to the molar in addition to the uprighting moment. Owing to their construction, current mechanical devices for uprighting either to not meet this requirement, or are difficult to adjust when in place. For this reason, an improved uprighting spring is described which utilizes the properties specific to super-elastic (pseudo-elastic) NiTi alloys. The most important property of super-elastic wires is the fact that they produce constant forces or moments within a specific deformation range. In order to utilize this useful property, certain design criteria have to be met. Recent measurements have shown that a super-elastic wire (Sentalloy, 0.016'' x 0.022'') having a length of 10 mm generates a constant moment of 7 to 8 Nmm within a bending angle of 50 degrees to 180 degrees. On the basis of these results, a table that permits the determination of the proper wire length needed to provide a constant moment within a given range of bending angles is proposed. The superelastic uprighting spring described here comprises an NiTi wire segment having a length of 7 mm and a mesial and distal steel wire segment. In the active state, the spring generates an uprighting moment of 8 Nmm and an intrusive force of 0.6 N. Numerical analysis using the finite element program, SOLF/MESY, and biomechanical testing with the orthodontic measuring and simulation system (OMSS) have shown that this force system remains stable throughout the entire uprighting process. The clinical application of the spring is demonstrated in a specific case.

Adolescent↗

PubMed1992

An experimental apparatus for the simulation of three-dimensional movements in orthodontics.

An apparatus for the study of three-dimensional force systems and the resulting movements during orthodontic treatment is presented. The instrument consists of two force-torque transducers which are capable of recording both forces and torques simultaneously, in all spatial directions. Each sensor has a measuring range of 15N (450 Nmm) and a resolution of 0.02 N (0.5 Nmm) and is mounted on a set of three translational and three rotational stages driven by stepping motors. Positioning accuracy is in the range of 1 micron and 0.01 degrees respectively. The apparatus is computer controlled and supported by comprehensive software.

Biomechanical Phenomena↗

PubMed1991

[Orthodontic measuring and simulating systems (OMSS) for the static and dynamic analysis of tooth movement].

An orthodontic measurement and simulation system (OMSS) is presented. The major components of this system are two measuring tables each comprising a force/torque sensor and a motor driven, fully three-dimensionally adjustable positioning stage. The force/torque sensors are capable of measuring simultaneously all forces and torques acting on a tooth. Using the computer program "OMSS" which runs on a personal computer, several different measurements can be conducted. On the one hand, the system supports absolute measurements such as the registration of a force/deflection diagram. Furthermore, even multidimensional force/deflection- or torque/distance curves can be measured. On the other hand, simulations of orthodontic tooth movement can be conducted. In such simulations, the force system acting on a tooth is measured and the resulting tooth movements are calculated. By using this "computer typodont", not only the static but the dynamic behaviour of orthodontic appliances can be studied. The application of this system is demonstrated by the analysis of several orthodontic problems.

Computer Simulation↗

PubMed1991

Application of the orthodontic measurement and simulation system (OMSS) in orthodontics.

An orthodontic measurement and simulation system (OMSS) is introduced. The major component of the system consists of two force-moment sensors capable of measuring forces and moments in all three planes of space simultaneously. The two sensors are mounted on motor-driven positioning tables with full three-dimensional mobility. All mechanical components are built in a temperature-controlled chamber. A control programme executed by a personal computer performs various types of measurement which can be classified as absolute measurements (e.g. force-deflection diagrams) and simulations of orthodontic tooth movement. By using the OMSS any orthodontic problem at the level of a two-tooth model can be analysed statically and dynamically. Besides other applications, the study evaluates three mechanical systems available for uprighting molars, namely a straight wire, a conventional uprighting spring, and a modified Burstone uprighting spring. It was found that the force systems produced by the straight wire and by the conventional uprighting spring showed a severe extrusive force component which may lead to occlusal trauma. The uprighting performance of the straight wire was inadequate. The conventional uprighting spring produced a large uprighting moment (17.8 Nmm), but also a strong lingual tipping moment (1.5 Nmm). The modified Burstone loop showed the best static and dynamic performance. It produced a force system with substantial uprighting moments in both the sagittal (11.6 Nmm) and frontal plane (4.2 Nmm). A slight intrusive force (0.09 N) might prevent the development of occlusal trauma during treatment. However, concern should be addressed to the fact that intra-oral adjustment of this uprighting spring is difficult because of its high susceptibility to minor modifications of its geometry.

Biomechanical Phenomena↗

PubMed1990

[The materials engineering characteristics of orthodontic nickel-titanium wires].

Since their introduction in 1971 nickel-titanium wires have been widely used in orthodontics. Today, there is a multitude of new NiTi-alloys, whose properties are described. Beside the memory effect, these alloys have particular elastic properties, which can be characterized by a low modulus of elasticity, excellent springback, and pseudoelasticity (superelasticity). These properties are a consequence of the fact that depending on temperature and mechanical stress NiTi-alloys have two crystalline structures: martensite and austenite. The transition between these two phases, called martensitic transformation, is responsible for the memory effect, where a one way and a two way effect can be distinguished. For orthodontic applications pseudoelasticity is regarded as a highly favourable property. Pseudoelastic behavior is caused by stress induced martensite. Analysing the elastic properties of the available wires two categories can be distinguished: "work hardened martensite" and "pseudoelastic alloy". The biocompatibility of NiTi is sufficient, it can be used as an implant material.

Crystallography↗