Biomedical subjects

B Tillmann

Publications and source records attributed to B Tillmann.

At least 19 recordsLinked to original sources

PubMed2006

Effects of pleiotrophin, a heparin-binding growth factor, on human primary and immortalized chondrocytes.

OBJECTIVE: Pleiotrophin (PTN) is a secreted heparin-binding peptide expressed in mesodermal and neuroectodermal cells during development, but rarely in adult tissues. In fetal and juvenile, but not in mature cartilage, PTN is abundant. Furthermore, PTN is re-expressed in chondrocytes in early stages of osteoarthritis (OA). Since little is known about the functions of PTN in cartilage, we investigated the occurrence of PTN receptors in human articular cartilage in situ and PTN effects on human primary and immortalized chondrocytes in vitro. METHODS: Receptor expression and regulation was monitored by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry. PTN effects and signal transduction were studied by electrophoretic mobility shift, Boyden chamber cell migration and proliferation assays, effects on gene expression by real time RT-PCR and that on nitric oxide (NO) by the Griess reaction. RESULTS: Of the putative PTN signaling receptors, immortalized and primary chondrocytes (pc) expressed the anaplastic lymphoma kinase (ALK), less the receptor-type protein tyrosine phosphatase zeta/beta (PTPzeta). ALK expression was upregulated upon ligand exposure. PTN stimulation activated the AP-1 (activator protein-1) transcription factor and altered gene expression. Prolonged stimulation induced PTN mRNA expression slightly, reduced vascular endothelial growth factor (VEGF) mRNA as well as NO production. Whereas mRNA expression of matrix metalloproteinases (MMPs) MMP-1 and MMP-13 was reduced, their inhibitors TIMP-1 and TIMP-2 were induced. Furthermore, PTN stimulated chondrocyte migration and proliferation. CONCLUSIONS: These results show that PTN is an autocrine growth factor in cartilage. We suggest that PTN may be involved in the clustering and proliferation of chondrocytes observed in the early stages of OA.

Animals↗

PubMed2006

Cognitive priming in sung and instrumental music: activation of inferior frontal cortex.

Neural correlates of the processing of musical syntax-like structures have been investigated via expectancy violation due to musically unrelated (i.e., unexpected) events in musical contexts. Previous studies reported the implication of inferior frontal cortex in musical structure processing. However - due to the strong musical manipulations - activations might be explained by sensory deviance detection or repetition priming. Our present study investigated neural correlates of musical structure processing with subtle musical violations in a musical priming paradigm. Instrumental and sung sequences ended on related and less-related musical targets. The material controlled sensory priming components, and differences in target processing required listeners' knowledge on musical structures. Participants were scanned with functional Magnetic Resonance Imaging (fMRI) while performing speeded phoneme and timbre identification judgments on the targets. Behavioral results acquired in the scanner replicated the facilitation effect of related over less-related targets. The blood oxygen level-dependent (BOLD) signal linked to target processing revealed activation of right inferior frontal areas (i.e., inferior frontal gyrus, frontal operculum, anterior insula) that was stronger for less-related than for related targets, and this was independent of the material carrying the musical structures. This outcome points to the implication of inferior frontal cortex in the processing of syntactic relations also for musical material and to its role in the processing and integration of sequential information over time. In addition to inferior frontal activation, increased activation was observed in orbital gyrus, temporal areas (anterior superior temporal gyrus, posterior superior temporal gyrus and sulcus, posterior middle temporal gyrus) and supramarginal gyrus.

Adult↗

PubMed2005

[Rupture of the quadriceps tendon. Diagnosis and treatment of a rare injury].

Rupture of the quadriceps tendon is a rare knee injury. In most cases the tendon ruptures spontaneously without adequate trauma in patients older than 40 years with degenerative changes of the tendon. Suture repair is the only treatment option for acute complete, older ruptures and partial ruptures that do not heal after nonoperative treatment. The type of repair depends on the time of diagnosis and localisation of the rupture. The functional outcome depends on timely repair and early initiation of knee movement and strengthening therapy.

Humans↗

PubMed2005

[Overload damage to the Achilles tendon: the importance of vascularization and angiogenesis].

In the Achilles tendon, degenerative changes mostly occur in regions that are hypo- or avascular. Angiogenesis is mediated by angiogenic factors and recent studies have shown that vascular endothelial growth factor (VEGF) is highly expressed in degenerative Achilles tendons, whereas VEGF expression is nearly completely downregulated in healthy tendons. VEGF expression in tendon fibroblasts is regulated by the transcription factor hypoxia inducible factor 1 (HIF-1). Several factors are able to upregulate VEGF expression in tenocytes: hypoxia, inflammatory cytokines and mechanical load. Angiogenesis plays an important role in the tendinotic process. The neovessels are accompanied by small glutamate positive neural structures. This finding suggests that angiogenesis plays an important role in the pain experienced during the degenerative tendon disease. On the other hand, there is some evidence that HIF-1/VEGF induced angiogenesis has an effect on the material properties of the tendinotic tendon tissue. Since VEGF has the potential to stimulate the expression of matrix metalloproteinases and inhibits the expression of tissue inhibitors of matrix metalloproteinases (TIMP) in various cell types this cytokine might play a significant role in the pathogenetic processes during degenerative tendon disease. These experimental findings are in accordance with clinical results which show that eccentric training leads to a regression of neovessels and decrease of pain. Another strategy is the local administration of a sclerosing agent (Polidocanol) to destroy neovessles. Preliminary results show that both strategies are effective in reducing vascular density and pain.

Achilles Tendon↗

PubMed2005

Repetition priming: Is music special?

Using short and long contexts, the present study investigated musical priming effects that are based on chord repetition and harmonic relatedness. A musical target (a chord) was preceded by either an identical prime or a different but harmonically related prime. In contrast to words, pictures, and environmental sounds, chord processing was not facilitated by repetition. Experiments 1 and 2 using single-chord primes showed either no significant difference between chord repetition and harmonic relatedness or facilitated processing for harmonically related targets. Experiment 3 using longer prime contexts showed that musical priming depended more on the musical function of the target in the preceding context than on target repetition. The effect of musical function was decreased, but not qualitatively changed, by chord repetition. The outcome of this study challenges predictions of sensory approaches and supports a cognitive approach of musical priming.

Association Learning↗

PubMed2004

Further investigation of harmonic priming in long contexts using musical timbre as surface marker to control for temporal effects.

Harmonic priming studies have reported facilitated processing for chords that are harmonically related to the prime context. Responses to the target (the last chord of an 8-chord sequence) were faster and more accurate when the target was strongly related, i.e., a tonic chord, to the preceding prime context than when it was less related, i.e., a subdominant chord. Results have been interpreted in terms of musical expectations and processing speed: the prime allows listeners to develop expectations for future events which lead to facilitated processing of the most strongly expected event. The present experiment investigated an alternative hypothesis suggesting that the harmonic structure of the prime context might create an ambiguity about "when" to respond that is stronger in contexts ending on less related targets than in contexts ending on strongly related targets. A change of musical timbre was used as surface marker indicating without ambiguity the temporal occurrence of the target. Participants made speeded intonation judgments of the target, i.e., judging whether targets are acoustically consonant or dissonant. The findings replicate the previously reported priming effect and rule out that processing differences are solely due to ambiguities about when in time the target will occur.

Humans↗

PubMed2003

Pleiotrophin, an embryonic differentiation and growth factor, is expressed in osteoarthritis.

OBJECTIVE: Pleiotrophin (PTN) is a 15.3 kDa heparin-binding peptide, which is expressed in mesodermal and neuroectodermal cells during development, but rarely in adult tissues. In fetal or juvenile cartilage, PTN is an abundant protein and appears to be involved in chondrocyte differentiation. Since developmentally regulated factors often re-appear in the disease state, we examined PTN expression in cartilage and synovial fluid of patients with osteoarthritis (OA). METHODS: PTN mRNA and protein expression was assayed by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot, the protein was localized by immunohistochemistry and quantified by enzyme-linked immunoassay (ELISA). RESULTS: PTN was undetectable in normal adult cartilage, but PTN mRNA and protein were found in OA. In cartilage from the tibial plateaus of OA patients, PTN could be immunostained in clusters of superficial chondrocytes. In the synovial fluids of OA patients, PTN concentrations were elevated in earlier OA stages, but rarely in late OA stages. Chondrosarcomas were PTN-immunonegative. CONCLUSIONS: In addition to certain types of cancer, the embryonic growth and differentiation factor PTN is found also in adults in inflammatory diseases. In OA, PTN is especially expressed in early stages, and PTN concentrations in the synovial fluid could serve as a marker for the progress of the disease. PTN might be involved in cartilage repair in OA, in particular, in earlier stages.

Adult↗

PubMed2002

[Anatomy and function of the anterior cruciate ligament].

The anterior cruciate ligament originates at the medial wall of the lateral femoral condyle and inserts into the middle of the intercondylar area. It contributes significantly to the stabilization and kinematics of the knee joint. The femoral origin is oval and is located in the posterior aspect of the lateral femoral condyle. Therefore, it is difficult to visualize the femoral origin arthroscopically. This might be one reason for anterior malpositioning of the femoral bone tunnel during anterior cruciate ligament reconstruction. The position of the femoral origin is behind the center of rotation of the knee joint; therefore, it becomes tense when the knee is extended. The tibial insertion is oval and its center is nearly in the middle of the tibial plateau. Definite landmarks for tibial tunnel placement in anterior cruciate ligament reconstruction are the distance between the central insertion point at the intercondylar floor and the posterior cruciate ligament (7-8 mm) and the anterior horn of the lateral meniscus. The anterior cruciate ligament consists of multiple small fiber bundles. From a functional point of view, one can differentiate the anteromedial and posterolateral fiber bundles. The anteromedial fibers are tense during a greater range of motion than the posterolateral fibers. The main part of the anterior cruciate ligament consists of type I collagen-positive dense connective tissue. The longitudinal fibrils of type I collagen are divided into small bundles by thin type III collagen-positive fibrils. In the distal third, the structure of the tissue varies from the typical structure of a ligament. In this region, the structure of the tissue resembles fibrocartilage. Oval-shaped cells surrounded by a metachromatic extracellular matrix lie between the longitudinal collagen fibrils. The femoral origin and the tibial insertion have the structure of a chondral apophyseal enthesis. Near the anchoring region at the femur and tibia, there should be various mechanoreceptors, which might have an important function for the kinematics of the knee joint. The blood supply of the anterior cruciate ligament arises from the middle geniculate artery. The ligament is covered by a synovial fold where the terminal branches of the middle and the inferior geniculate artery form a periligamentous network. From the synovial sheath, the blood vessels penetrate the ligament in a horizontal direction and anastomose with a longitudinally orientated intraligamentous network. The distribution of blood vessels within the anterior cruciate ligament is not homogeneous. We detected three avascular areas within the ligament: Both fibrocartilaginous entheses of the anterior cruciate ligament are devoid of blood vessels. A third avascular zone is located in the distal zone of fibrocartilage adjacent to the roof of the intercondylar fossa.

Anterior Cruciate Ligament↗

PubMed2002

The blood supply of the posterior tibial tendon.

We studied the vascular pattern of human posterior tibial tendons by injection techniques and immunohistochemically using antibodies against laminin. The intravascular volume of the posterior tibial tendon was determined using a new method of injection of a solution of 99mTc and gelatin ink into the lower legs of cadavers. Three segments of 1 cm length from different regions of the human posterior tibial tendon were measured using a gamma well counter. The main blood supply arises from the posterior tibial artery. Blood vessels enter the paratenon of the posterior tibial tendon via a mesotenon from the posterior aspect. From the paratenon, the blood vessels penetrate the posterior tibial tendon and anastomose with a longitudinally orientated intratendinous network. The number of vessels in the substance of the tendon is consistently less than that in the surrounding paratenon. The distribution of blood vessels within the posterior tibial tendon is not homogeneous. In the retromalleolar region the intravascular volume was significantly reduced with a mean value of 15 microl/g of tendon tissue. There was no significant difference between the mean intravascular volumes of the proximal and distal areas (distal, 27.7 microl/g tendon tissue; proximal, 30 microl/g tendon tissue). The immunohistochemical investigation showed that there was no immunostaining for laminin in the anterior part of the tendon in the region where it passes behind the medial malleolus. This region is avascular. The most frequent site of rupture of the posterior tibial tendon is in the region behind the medial malleolus. A potential endogenous risk factor may be the limited healing potential of avascular tissue.

Aged↗

PubMed2001

The splice variants VEGF121 and VEGF189 of the angiogenic peptide vascular endothelial growth factor are expressed in osteoarthritic cartilage.

OBJECTIVE: Vascular endothelial growth factor (VEGF) has recently been shown to play an important role during endochondral bone formation in hypertrophic cartilage remodeling, ossification, and angiogenesis, but it is not expressed in normal adult cartilage. Since genes expressed during development often reappear in the disease state, we investigated whether VEGF and its receptors (VEGFRs) are expressed in osteoarthritic (OA) cartilage. METHODS: VEGF production in OA cartilage from the tibial plateau was measured by enzyme-linked immunosorbent assay. Deposition of VEGF and VEGFR was determined by immunohistochemistry. Expression of messenger RNA for the different VEGF splice forms and for VEGFR was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: Increased VEGF concentrations were measured in OA cartilage from the tibial plateau, while VEGF was almost undetectable in normal cartilage but could be immunostained within the intracellular and pericellular matrices of OA chondrocytes. In analyses of cartilage samples from all 10 OA patients evaluated, VEGF121 and VEGF189 were identified as the only VEGF splice forms expressed. RT-PCR and immunohistochemistry for VEGF in normal hyaline cartilage yielded negative findings. In addition to VEGF, VEGFR-2 (kinase domain region/fetal liver kinase 1), but not VEGFR-1 (fms-like tyrosine kinase 1), could be detected by RT-PCR in OA cartilage and immunostained on OA chondrocytes. CONCLUSION: Apart from its production in hypertrophic chondrocytes, VEGF is also produced in chondrocytes of OA cartilage. While the splice variant VEGF189 binds to extracellular matrix proteoglycans, VEGF121 is diffused freely. Both proteins should contribute to the inflammatory process by autocrine/paracrine stimulation of chondrocytes, chemotaxis of macrophages, and promotion of angiogenesis.

Alternative Splicing↗

PubMed2001

[The efferent lacrimal ducts of the human. Morphological and biochemical studies].

PURPOSE: Infections occur frequently in the region of the efferent tear ducts. Exact knowledge of the anatomical structure and of cellular defense mechanisms is necessary to understand the pathological processes. This study analyzed the efferent tear ducts with regard to physiological function and possible defense mechanism against infections. MATERIALS AND METHODS: We used histological, immunohistochemical and electronmicroscopic techniques to investigate the lacrimal systems from 31 body donors aged 54-88 years. RESULTS: The efferent tear ducts are lined by a double-layered epithelium resting on a broad basement membrane. These cells contain many lipid droplets and secretory vacuoles in their apical part. Inside the epithelium cells are arranged partly in cell groups forming mucous glands, which morphologically resemble goblet cells of the tarsus palpebrae. The secretory products of these cells contain various carbohydrates including sialic acid. Lymphocytes and macrophages are found in the submucosa partly penetrating the epithelium. CONCLUSIONS: Lipids and mucins of epithelial and goblet cells form a specialized protective layer on the epithelium of the tear ducts which enables easy drainage of tear fluid into the inferior meatus of the nose. Together with immunocompetent cells the protective layer prevents invasion of pathogenetic agents.

Aged↗

PubMed2001

The angiogenic peptide vascular endothelial growth factor is expressed in foetal and ruptured tendons.

The Achilles tendon is one of the most common sites of injury and rupture. Evidence suggests that local vascularisation is involved in this aetiology. We investigated the expression of one important angiogenic factor, the vascular endothelial growth factor (VEGF), in normal and pathologic human Achilles tendons using immunohistochemical, biochemical, molecular and cell biology methods. VEGF could be immunostained in tenocytes of ruptured and foetal Achilles tendons, but not in normal adult ones. In microvessels, the VEGF receptor VEGFR-1 (flt-1) could be visualised as well. High VEGF levels were measured in homogenates from ruptured adult, lower ones in foetal and negligible concentrations in normal adult Achilles tendons using enzyme-linked immunoassay (ELISA) and Western blot experiments. Reverse transcriptase-polymerase chain reaction (RT-PCR) showed that the splice variants VEGF121 and VEGF165 are exclusively expressed. In tenocytes cultivated from newborn rat Achilles tendons, hypoxia or epidermal growth factor (EGF) raised VEGF production moderately whereas their combination resulted in a strong, synergistic induction. These results prove the presence of an angiogenic peptide and vascularisation in ruptured and foetal tendons and support the view that microtrauma or degeneration in the Achilles tendon precedes its rupture.

Achilles Tendon↗

PubMed2001

The effect of harmonic context on phoneme monitoring in vocal music.

The processing of a target chord depends on the previous musical context in which it has appeared. This harmonic priming effect occurs for fine syntactic-like changes in context and is observed irrespective of the extent of participants' musical expertise (Bigand & Pineau, Perception and Psychophysics, 59 (1997) 1098). The present study investigates how the harmonic context influences the processing of phonemes in vocal music. Eight-chord sequences were presented to participants. The four notes of each chord were played with synthetic phonemes and participants were required to quickly decide whether the last chord (the target) was sung on a syllable containing the phoneme /i/ or /u/. The musical relationship of the target chord to the previous context was manipulated so that the target chord acted as a referential tonic chord or as a congruent but less structurally important subdominant chord. Phoneme monitoring was faster for the tonic chord than for the subdominant chord. This finding has several implications for music cognition and speech perception. It also suggests that musical and phonemic processing interact at some stage of processing.

Auditory Perception↗

PubMed2001

Global context effect in normal and scrambled musical sequences.

The processing of chords is facilitated when they are harmonically related to the context in which they appear. The purpose of this study was to assess whether this harmonic priming effect depends on the version (normal vs. scrambled) of the context chord sequences. Normal sequences were scrambled by permuting chords two-by-two (Experiment 1) or four-by-four (Experiments 2 and 3). Normal chord sequences were judged less coherent than scrambled sequences. However, normal chord sequences showed facilitation for harmonically related rather than for unrelated targets, and this effect of relatedness did not diminish for scrambled sequences (Experiments 1-3). The data of musicians and nonmusicians were interpreted with Bharucha's (1987) spreading activation framework. Simulations suggested that harmonic priming results from activation that spreads via schematic knowledge of Western harmony and accumulates in short-term memory over the course of the chord sequence.

Auditory Perception↗

PubMed2001

Expression of natural peptide antibiotics in human articular cartilage and synovial membrane.

In view of frequent present use of invasive procedures on limb joints, it is astonishing that articular joint inflammation is a rare event. We questioned whether antimicrobial peptides play a role in protecting human articular cartilage and synovial membrane against inflammatory agents. Our results implicate defensins in the protection of human articular joints against pathogens.

Anti-Bacterial Agents↗

PubMed2001

Splice variants VEGF121 and VEGF165 of the angiogenic peptide vascular endothelial cell growth factor are expressed in the synovial tissue of patients with rheumatoid arthritis.

OBJECTIVE: To determine the expression of the angiogenic peptide vascular endothelial growth factor (VEGF, also known as vascular permeability factor, VPF) in the synovium of patients with rheumatoid arthritis (RA). METHODS: Expression of VEGF protein from the synovial tissue of 10 patients with RA was monitored by ELISA and visualized by immunocytochemistry, and by double-staining with the VEGFR-1/flt-1. VEGF mRNA and its splice variants were determined by reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: VEGF protein was strongly increased in rheumatoid synovium and localized at the synovial surface, whereas the VEGF receptor flt-1 (VEGFR-1) was visualized on microvessels in close vicinity. In synovial tissues from all 10 patients with RA, VEGF121 and VEGF165 were identified at the mRNA level as the only VEGF splice forms expressed. CONCLUSION: Since VEGF165 and VEGF121 are differently diffusible due to their opposite heparan sulfate-binding properties, they act at different distances. The presence of VEGF121 may explain induction of the VEGFR-1 on infiltrating blood vessels near the synovial surface.

Alternative Splicing↗

PubMed2000

Tendon entheses of the human masticatory muscles.

Tendons attach to the limb skeleton via chondral-apophysary or periosteal-diaphysary entheses. It was the aim of the present study to investigate the tendon entheses of the temporal, the masseter, as well as the medial and lateral pterygoid muscles, considering the biomechanics and the mode of osteogenesis at the attachment sites. The origin and insertion zones of the four masticatory muscles were studied histologically and by polarization light microscopy in six halves of human heads. Contrary to the limb skeleton no causal relationship between the histological structure of the tendon entheses and the osteogenic mode of the bone areas involved was observed in the masticatory muscles that were studied. Based on the histological findings, a purely structural classification of the tendon attachments irrespective of the osteogenesis is therefore proposed that is applicable to the entire skeleton. It is possible to distinguish between tendon entheses inserting into periosteum, into bone or into fibrocartilage. Tendon attachments with periosteal insertion are found at the temporal plane, the retromolar triangle, zygomatic arch, lateral pterygoid plate, in the caudal zone of the pterygoid fovea of the neck of mandible as well as major portions of the ramus and angle of the mandible. The attachment zones in which collagen fibrils of tendons insert into the bone via the periosteum correspond in their structure to plane periosteal-diaphysary insertions into the diaphyses of long bones. Attachment zones to the bone are present at the inferior temporal line, the base of the coronoid process, the caudal surface of the zygomatic arch, the cranial zones of the pterygoid fovea of the neck of the mandible as well as at circumscribed areas of the ramus and angle of the mandible. In these zones the collagen fibers of the tendon insert immediately into the bone without any mediation of other tissues. The entheses resemble those of circumscribed periosteal-diaphysary attachments to long bones. Fibrocartilaginous entheses occur at the coronoid process, the cranialmost portions of the pterygoid fovea of the neck of the mandible as well as in circumscribed areas of the medial and lateral facets of the angle of the mandible. The structures of these attachment sites are comparable to chondral-apophysary tendon attachments. As for masticatory muscles, the described forms of tendon entheses occur at the same time in the majority of the attachment sites. From the structure of the three types of tendon entheses it is possible to conclude that they fulfill a biomechanical function similar to that of the limb skeleton, namely adapting the different elasticity moduli of bone and tendon tissues. From a technical perspective they can be considered to act as an "angle and stretching brake".

Aged↗

PubMed2000

Implicit learning of tonality: a self-organizing approach.

Tonal music is a highly structured system that is ubiquitous in our cultural environment. We demonstrate the acquisition of implicit knowledge of tonal structure through neural self-organization resulting from mere exposure to simultaneous and sequential combinations of tones. In the process of learning, a network with fundamental neural constraints comes to internalize the essential correlational structure of tonal music. After learning, the network was run through a range of experiments from the literature. The model provides a parsimonious account of a variety of empirical findings dealing with the processing of tone, chord, and key relationships, including relatedness judgments, memory judgments, and expectancies. It also illustrates the plausibility of activation being a unifying mechanism underlying a range of cognitive tasks.

Algorithms↗