Biomedical subjects

C Hopf

Publications and source records attributed to C Hopf.

At least 19 recordsLinked to original sources

PubMed2003

Calcium-dependent maintenance of agrin-induced postsynaptic specializations.

Although much progress has been made in understanding synapse formation, little is known about the mechanisms underlying synaptic maintenance and loss. The formation of agrin-induced AChR clusters on cultured myotubes requires both activation of the receptor tyrosine kinase MuSK and intracellular calcium fluxes. Here, we provide evidence that such AChR clusters are maintained by agrin/MuSK-induced intracellular calcium fluxes. Clamping intracellular calcium fluxes after AChR clusters have formed leads to rapid MuSK and AChR tyrosine dephosphorylation and cluster dispersal, even in the continued presence of agrin. Both the dephosphorylation and the dispersal are inhibited by the tyrosine phosphatase inhibitor pervanadate. In contrast, clamping intracellular calcium at the time of initial agrin stimulation has no effect on agrin-induced MuSK or AChR phosphorylation, but blocks AChR cluster formation. These findings suggest an avenue by which postsynaptic stability can be regulated by modification of intracellular signaling pathways that are distinct from those used during synapse formation.

Acetylcholine↗

PubMed2001

[Principles of surgical treatment of upper thoracic and cervicothoracic kyphosis].

Idiopathic upper thoracic and cervicothoracic kyphoses are rare. More frequently they are the consequence of spinal instability as in neurofibromatosis (von Recklinghausen's disease), after laminectomies, in tumors, congenital disorders, spondylodiscitis, and fractures. Neurologic problems with severe pareses complicate these deformities. Anterior bone loss (fracture, tumor, spondylodiscitis), posterior instability (post-laminectomy kyphosis) or a combination of both are responsible for the deformity. The operative treatment of the anatomically unfavorable localization requires great experience in spinal surgery; the procedures often are salvage surgeries. In the absence of a successful conservative treatment, early posterior/anterior or anterior/posterior reconstruction of the sagittal profile with primary stable implants is necessary to minimize the risk of renewed surgery. Transplantation of stable bone grafts such as the fibula is a precondition for postoperative treatment without external support. The indication is restrictive in the presence of malignant primary and secondary tumors with poor prognosis. Restitution of existing neurologic deficits is unpredictable.

Adolescent↗

PubMed2001

[Kyphotic deformation in fractures of the thoracic and lumbar spine].

Kyphosis is the typical deformity of untreated spine fractures. In the majority of all injuries, destruction of the anterior part of the spine occurs. Biomechanical aspects require reconstruction of the anterior column. In 112 patients with a traumatic fracture of the thoracolumbar spine, a loss of correction in the sagittal plane exceeded the intraoperative correction. The cause of deterioration was in the main part the destruction of the intervertebral disk. The results of different surgical techniques are reviewed and discussed based on the literature. The dorsal instrumentation with or without autogenous bone grafting is not sufficient for spinal stabilization and kyphosis is the result. The golden standard for prevention of kyphosis is the combined approach with anterior cortical bone graft and posterior transpedicular screwing. In the case of anterior cage implantation, the risk of graft failure can be avoided. With anterior minimally invasive approaches, traumatization can be reduced by using the same biomechanical principles. In the case of a type A fracture with intact posterior elements, use of an anterior primary stable implant with bone graft represents an alternative method.

Adolescent↗

PubMed2000

Nitric oxide synthase (NOS-1) coclustered with agrin-induced AChR-specializations on cultured skeletal myotubes.

Previously we reported that neuronal nitric oxide synthase type-1 (NOS-1) is expressed in skeletal myotubes in vitro. In the present paper we sought to determine whether agrin-induced membrane specializations known to include the nicotinic acetylcholine receptor (AChR) on cultured myotubes may also contain NOS-1 and related molecules. After treatment with various agrin constructs containing the full C-terminally AChR-clustering domain (fragments N2, N4), but not with fragment C2 (truncated), NOS-1 expressed in the cytosol of mouse C2C12 skeletal myotubes coclustered with AChR, 43K rapsyn, MuSK, and the dystrophin/utrophin glycoprotein-complex (DUGC). Agrin-induced specializations also included coaggregates of N-methyl-d-aspartic acid (NMDA)-receptor, alpha-sodium (NaCh), or Shaker-type K+ channel (KCh)/PSD-95 complexes, and NOS-1. We conclude that agrin is crucial for recruitment of preassembled multimolecular membrane clusters, including AChR, NMDAR, and ion channels linked to NOS-1. Coassembly of NOS-1 to postsynaptic molecules may reflect site-specific NO-signaling pathways in neuromuscular junction formation and functions.

Agrin↗

PubMed2000

[Criteria for treatment of idiopathic scoliosis between 40 degrees and 50 degrees. Surgical vs. conservative therapy].

The treatment of idiopathic scoliosis over 40 degrees (Cobb) during the growth period is under discussion concerning the indication for conservative or surgical treatment. Curve progression depends on the degree of the frontal and sagittal deformity, vertebral rotation, rigidity of the curve, the skeletal age, the age and sex of the patient, the familial frequency of scoliosis and the location of the curve. In scoliosis over 40 degrees progression is fast and the possibilities for successful conservative brace treatment are reduced during the growth period. Progression occurs more frequently in thoracic and double major scolioses, especially in young patients (Risser sign 0 and 1). Predictive factors of a successful brace treatment are the correction of scoliosis and rotation; deterioration of both during the brace treatment leads to poor results. Evaluating the flexibility of the sagittal profile is important, as is primary correction of 30-50% in the brace during the 3 months. Operative correction of small primary curves reduces the fusion length, operation time, and blood loss and is followed by a reduction in loading on the adjacent vertebral segments in comparison to the long fusions necessary in more structural and double major scolioses. So far it is not possible to make an equivalent judgment of the frequency of the "crankshaft" phenomenon and the treatment necessary in young patients (Rissersign 0 and 1) treated by dorsal instrumentation alone, but temporary brace treatment may be considered in those cases.

Adolescent↗

PubMed1999

Shock-wave therapy for tennis and golfer's elbow--1 year follow-up.

Thirty patients with chronic medial epicondylitis were treated with low-energy shock waves. They received 500 impulses of 0.08 mJ/mm2 three times at weekly intervals. At 1 year follow-up examinations were performed. According to the Verhaar criteria, only seven patients reached excellent or good results. In eight cases a fair outcome was recorded, and in 14 patients the outcome was poor. Only six patients were satisfied with the treatment. The average relief of pain was 32%. These data were significantly worse than for identically treated patients with chronic tennis elbow. Thus, the question arises as to whether extracorporal shock-wave therapy is indicated in medial epicondylitis.

Adult↗

PubMed1999

Sagittal static imbalance in myelomeningocele patients: improvement in sitting ability by partial and total gibbus resection.

The progression of kyphosis in myelomeningocele is independent of skeletal growth and requires early operative correction and stabilization to prevent a loss of sitting ability. In severe cases, only vertebrectomy makes it possible to achieve correction, stability and skin-closure without tension. In 14 patients with myelomeningocele gibbus, kyphectomy was performed, removing two vertebral bodies on average. The average kyphosis angle decreased from 128 degrees to 81 degrees, enabling most of the patients to participate again in social life by restoring wheelchair mobility. Nevertheless, a significantly higher complication rate was found compared to other correctional operations, lengthening the average hospital stay to 41 days. Special problems arose from trophic disorders of the skin and soft tissue and from the dystrophic muscles below the level of neural malfunction. In three cases, kyphosis reappeared cranial to the fused segments, requiring ventral stabilization. With respect to increasing kyphosis angle, an early intervention should be aimed at. A secondary operation can be necessary, if surgery is performed without taking care of the growth potential.

Child↗

PubMed1999

Orthopedic and neurosurgical treatment of severe kyphosis in myelomeningocele.

Kyphosis in myelomeningocele is characterized by a complex pattern of problems during development and therapy. On the one hand, decompensation of upright posture leads to loss of sitting ability and social integration; on the other hand, accompanying malformations and trophic alterations threaten the physical integrity and performance. Neurologic function, cerebrospinal fluid (CSF) circulation, skeletal deformity and the urinary transport system need to be kept in mind and need to be treated with cooperation between the different specialties. Especially during serious surgical interventions such as spinal surgery, neither the nervous system nor the kidneys must be ignored. Sixteen patients underwent kyphectomy in the Orthopedic Department of the University of Mainz between 1993 and 1997, all of them supervised by the Neurosurgical Department. In 13 cases, transversal myelotomy was performed. No insufficiency of CSF circulation was seen; neither were there any CSF fistulae. Particular problems arose from the skin and soft tissue above the gibbus, the lack of muscles and the regeneration deficiency caused by trophic disorders. Therefore, a significantly higher complication rate was found than with other correctional operations.

Adolescent↗

PubMed1998

[Results of extracorporeal shock-wave application in lateral elbow tendopathy].

AIM: This review article focuses on a possible pain-alleviating effect of shock-wave application in persistent lateral epicondylopathy of the elbow and compares the effects with data on other non-operative and operative procedures. METHODS: Patients who suffered from chronic tennis elbow for more than 12 months and were therefore referred for a surgical procedure were assigned at random to two groups of low-energy shock-wave therapy. Group I received a total of 3000 (3 x 1000) impulses of 0.08 mJ/mm(2), while group II (control group) received a total of 30 (3 x 10) impulses of 0.08 mJ/mm(2). Follow-up examinations were carried out after 3, 6, and 24 and 52 weeks. RESULTS: There was a significant improvement of pain and function in group I, with a good or excellent outcome in 52% of cases compared to 6% in group II at the last evaluation. CONCLUSION: Extracorporeal shock-wave application has a dose-dependent pain-relieving effect on chronic tendopathy of the lateral elbow.

Clinical Trial↗

PubMed1998

Tyrosine phosphorylation of the muscle-specific kinase is exclusively induced by acetylcholine receptor-aggregating agrin fragments.

During formation of the neuromuscular junction, the basal membrane protein agrin initiates the aggregation of acetylcholine receptors (AChR) on the surface of myotubes. A muscle-specific kinase (MuSK) becomes phosphorylated upon incubation with agrin, although it does not bind to agrin on its own. Utilizing MuSK-specific antibodies, we demonstrate that the ability of different splicing variants and truncation fragments of agrin to trigger MuSK phosphorylation and AChR aggregation are correlated. Only agrin forms which are potent inducers of AChR-clustering are able to trigger the phosphorylation of MuSK. Picomolar concentrations of agrin are already sufficient to induce MuSK phosphorylation. Similar amounts are necessary for the aggregation of AChRs as well as their phosphorylation on a tyrosine residue. The complete overlap of specificities for MuSK phosphorylation and AChR aggregation suggests that only binding of agrin to a MuSK-containing receptor complex is responsible for the initiation of AChR aggregation. In contrast, interactions of agrin with binding proteins on the muscle surface harbouring different specificities such as alpha-dystroglycan do not seem to be necessary for this process.

Agrin↗

PubMed1998

Formation of postsynaptic-like membranes during differentiation of embryonic stem cells in vitro.

To analyze the formation of neuromuscular junctions, mouse pluripotent embryonic stem (ES) cells were differentiated via embryoid bodies into skeletal muscle and neuronal cells. The developmentally controlled expression of skeletal muscle-specific genes coding for myf5, myogenin, myoD and myf6, alpha 1 subunit of the L-type calcium channel, cell adhesion molecule M-cadherin, and neuron-specific genes encoding the 68-, 160-, and 200-kDa neurofilament proteins, synaptic vesicle protein synaptophysin, brain-specific proteoglycan neurocan, and microtubule-associated protein tau was demonstrated by RT-PCR analysis. In addition, genes specifically expressed at neuromuscular junctions, the gamma- and epsilon-subunits of the nicotinic acetylcholine receptor (AChR) and the extracellular matrix protein S-laminin, were found. At the terminal differentiation stage characterized by the formation of multinucleated spontaneously contracting myotubes, the myogenic regulatory gene myf6 and the AChR epsilon-subunit gene, both specifically expressed in mature adult skeletal muscle, were found to be coexpressed. Only the terminally differentiated myotubes showed a clustering of nicotinic acetylcholine receptors (AChR) and a colocalization with agrin and synaptophysin. The formation of AChRs was also demonstrated on a functional level by using the patch clamp technique. Taken together, our results showed that during ES cell differentiation in vitro neuron- and muscle-specific genes are expressed in a developmentally controlled manner, resulting in the formation of postsynaptic-like membranes. Thus, the embryonic stem cell differentiation model will be helpful for studying cellular interactions at neuromuscular junctions by "loss of function" analysis in vitro.

Agrin↗

PubMed1998

Dimerization of the muscle-specific kinase induces tyrosine phosphorylation of acetylcholine receptors and their aggregation on the surface of myotubes.

During development of the neuromuscular junction, neuronal splice variants of agrin initiate the aggregation of acetylcholine receptors on the myotube surface. The muscle-specific kinase is thought to be part of an agrin receptor complex, although the recombinant protein does not bind agrin with high affinity. To specify its function, we induced phosphorylation and activation of this kinase in the absence of agrin by incubating myotubes with antibodies directed against its N-terminal sequence. Antibody-induced dimerization of the muscle-specific kinase but not treatment with Fab fragments was sufficient to trigger two key events of early postsynaptic development: acetylcholine receptors accumulated into aggregates, and their beta-subunits became phosphorylated on tyrosine residues. Heparin partially inhibited receptor aggregation induced by both agrin and anti-muscle-specific kinase antibodies. In contrast, it did not affect kinase or acetylcholine receptor phosphorylation. These data indicate that agrin induces postsynaptic differentiation by dimerizing the muscle-specific kinase. They also suggest that activation of the kinase domain can account for only part of agrin's effects. Dimerization of this molecule appears to activate an additional signal, most likely by organizing a scaffold for other postsynaptic proteins.

Agrin↗

PubMed1998

Preoperative estimation of screw fixation strength in vertebral bodies.

STUDY DESIGN: Bone mineral density and bone cross-sectional area of human cadaveric vertebral bodies were investigated radiologically and histologically, respectively. After ventral instrumentation with ventral derotation spondylodesis screws, axial pullout force was measured and compared with radiologic and histologic data. OBJECTIVES: To elucidate how well ventral derotation spondylodesis screw fixation strength can be estimated before surgery by specified applications of dual-energy x-ray absorptiometry, quantitative computed tomography, T2*-relaxation time in magnetic resonance imaging, and histomorphometry. SUMMARY OF BACKGROUND DATA: It is postulated that bone quality plays a crucial role in initial strength of the instrumented spine. Bone quality is even more important in anterior fixation because of the prevalence of spongy bone in the vertebral body. METHODS: Bone mineral density of human cadaveric lumbar-vertebral bodies was assessed by dual-energy x-ray absorptiometry and quantitative computed tomography (cancellous and cortical bone separately). Cancellous bone was also characterized by T2*-relaxation time, measured by magnetic resonance imaging and histomorphometric study. Vertebral bodies were instrumented ventrally with VDS screws, and screw axial pullout force was measured and correlated with each of the nonmechanical measures. Patients with manifest osteoporosis, osteomalacia and tumors were excluded. For statistical analysis, the Mann-Whitney rank sum test was used with a significance value of P < 0.05. RESULTS: The highest correlation with pullout force was for density of cancellous bone determined by quantitative computed tomography (r = 0.72; P < 0.001), immediately followed that determined by dual-energy x-ray absorptiometry (r = 0.70; P < 0.001). Results of measurement of T2*-relaxation time and those of histomorphometric study correlated moderately (r = 0.55; r = 0.50), whereas cortical bone density determined by quantitative computed tomography showed negligible correlation (r = 0.2). CONCLUSIONS: The absorptiometric techniques, quantitative computed tomographic scan of cancellous bone and dual-energy x-ray absorptiometric study, provide more accurate readings for preoperative estimation of initial VDS screw fixation strength than do the other methods studied.

Absorptiometry, Photon↗

PubMed1998

Operative treatment of spondylodiscitis--what is the most effective approach?

In a study the results recorded in 34 surgically treated patients with specific or unspecific spondylodiscitis after dorsoventral one-stage instrumentation with CDI and anterior grafting (group 1) were compared with those obtained in a group of 38 patients treated with anterior CDH instrumentation in combination with anterior grafting (group 2). The mean observation periods were 48.4 (19-82) months in group 1 and 29.0 (8-54) months in group 2. In both groups the infection healed after fusion without a secondary operation. In group 1 the mean values for blood loss, operating time, length of hospital stay and fusion length (3.5 segments) were significant higher than those in group 2; in particular, the fusion length was shorter (1.3 segments) in group 2. Only 8 patients in group 1 were treated with postoperative external support. The mean preoperative segmental angle of 18.2 degrees (group 1) was corrected by a mean of 11.9 degrees, and the reposition loss during follow-up amounted to an average of 2.7 degrees. Group 2 showed a mean preoperative segmental deformity angle of 13.4 degrees, which was corrected by 11.6 degrees, and the loss of reposition was 2.9 degrees on average. Even in florid spondylodiscitis a short-range anterior fusion of the affected spinal segment can be performed with a primary stable implant, avoiding a second operation without an increased risk of infection-related dislocation. In the authors' own experience a secondary dorsal operation can be avoided except in the case segment L-5/S-1, the fast mobilization without external support allows a up-to-date treatment in this severe spinal disease.

Adolescent↗

PubMed1998

Gait analysis in idiopathic scoliosis before and after surgery: a comparison of the pre- and postoperative muscle activation pattern.

In a prospective experimental study the level gait activity scores of the iliocostalis lumborum, glutaeus medius, tensor fasciae latae, vastus lateralis and peronaeus longus muscles of both body sides were examined by computerized electromyography in 23 patients with idiopathic scoliosis before and after CD instrumentation. The pre- and postoperative findings were examined as to asymmetric patterns in muscle requisition during gait and the respective changes induced by the spinal correction. These results were compared with the corresponding results obtained in healthy subjects in two independent sessions with identical experimental conditions. A muscle activity asymmetry coefficient was defined to quantify the degree of left/right muscle activation asymmetry observed. Postoperatively a statistically significant reduction (P < 0.05) of a preoperatively strongly increased activity was found in the lumbar muscles of the convex side of double major scolioses as well as in the glutaeus medius and tensor fascia lata muscles of the concave side of thoracic curvatures. Both the casuistic and statistical analysis of the results of our study support the hypothesis that activity asymmetries observed in the paravertebral musculature in idiopathic scoliosis patients are the result of the scoliotic body deformities, with consequent asymmetries in the biomechanical force patterns of body postures and body motions, rather than an aetiological factor of scoliotic curvatures.

Adult↗

PubMed1998

Invasion of human cartilage by cultured multicellular spheroids of rheumatoid synovial cells--a novel in vitro model system for rheumatoid arthritis.

OBJECTIVE: A new 3-dimensional cell culture system was established to examine the invasion of rheumatoid synovial cells into cartilage. METHODS: Synovial cells from 20 patients with rheumatoid arthritis (RA) and 15 patients with osteoarthritis (OA) were co-cultured as multicellular spheroids with cartilage fragments. RESULTS: After 4 weeks the rheumatoid spheroids eroded the cartilage. The destruction of cartilage was supported by a high expression level of cathepsin D and matrix metalloproteinases. In contrast, the OA tissue showed attachment to the cartilage only. CONCLUSION: Our results indicate that spheroid/cartilage co-cultures seem to be a suitable in vitro model for the study of destructive cellular mechanisms that occur in RA.

Arthritis, Rheumatoid↗

PubMed1997

[Extracorporeal shockwave therapy in orthopedics. Positive results in tennis elbow and tendinosis calcarea of the shoulder].

Since the beginning of the 1990s scientific investigations on the use of extracorporeal shock wave therapy (ESWT) in the field of orthopedics have been carried out at the Orthopedic Department of the University of Mainz. Prospective studies demonstrated beneficial effects in chronic lateral humeral epicondylitis (tennis elbow), and in calcifying tendinitis of the shoulder in more than 50% of the cases. Additional indications for which positive results of prospective studies have been published during the past 2 years are plantar calcaneodynea and pseudoarthrosis. On the basis of the results achieved, it may be concluded that, for specific indications, extracorporeal shock wave therapy may now be taken out of the clinical testing stage and introduced into routine practice.

Calcinosis↗

PubMed1997

Application of extracorporeal shock-waves in the treatment of pseudarthrosis of the lower extremity. Preliminary results.

Between January 1991 and January 1996, pseudarthroses of the legs were treated prospectively in 48 patients by application of high-energy extracorporeal shock waves with an experimental device. The mean duration of pseudarthrosis was 12 months. On average, 2.4 surgical interventions had previously been performed. A total of 3000 impulses with an energy density of 0.6 mJ/mm2 was applied to the pseudarthrosis. Bony union was achieved in 60.4% of our patients after an average of 3.4 months. Failures were found especially in the atrophic types of pseudarthrosis as well as in congenital bone disorders like fibrous dysplasia or osteogenesis imperfecta. No serious complications were observed. Even after numerous surgical interventions high-energy extracorporeal shock-wave therapy showed a fair success rate. A higher success rate of this non-invasive method for the treatment of bony non-unions may be expected by applying strict selection criteria.

Adolescent↗