HIV infection affects the central nervous system (CNS), frequently causing cognitive impairment. ... more HIV infection affects the central nervous system (CNS), frequently causing cognitive impairment. Hippocampal injury impedes the ability to transfer information into memory. Therefore, we aimed to examine neuronal injury and repair in the hippocampal formation in HIV encephalopathy. We compared neuropathological findings in 14 autopsy cases after death from systemic complications of HIV infection and in 15 age-matched HIV-negative control cases after sudden death from nonneurological causes using immunohistochemistry. The density of apoptotic granule cells in the dentate gyrus was higher in HIV-infected than in control cases (P = 0.048). Proliferation of neural progenitor cells in the dentate gyrus was increased in HIV infection (P = 0.028), whereas the density of recently generated TUC-4 [TOAD (turned on after division)/Ulip/CRMP family 4]-expressing neurons in this region was not significantly elevated in HIV-infected cases (P = 0.13). HIV infection caused microglial activation and astrocytosis in the neocortex and hippocampal formation. Conversely, we were unable to detect more pronounced axonal injury in HIV-infected than in control cases. As in other infections involving the CNS, apoptosis of hippocampal neurons accompanied by microglial activation and astrocytosis is a prominent feature of HIV encephalopathy. The regenerative potential, assessed using the density of young neurons in the hippocampal dentate gyrus, in HIV infection appears to be lower than in acute bacterial meningitis and septic encephalitis.
62 intracranial meningiomas in 60 patients were studied with 18FDG-PET prior to neurosurgery in o... more 62 intracranial meningiomas in 60 patients were studied with 18FDG-PET prior to neurosurgery in order to evaluate the relationship between 18FDG uptake and biological aggressiveness of the tumors. Histopathological grading, cellular density, Ki-67 proliferation index and evidence of chromosomal aberrations were used to assess tumor aggressiveness. Significantly elevated 18FDG uptake was found in grade 2- and 3- compared to grade 1-meningiomas, in tumors of high cellularity compared with those of low cellularity, and in meningiomas with an elevated Ki-67 proliferation index (above 2%). The two meningiomas with the most pronounced chromosomal aberrations revealed the highest 18FDG uptake of all cytogenetically studied meningiomas. We conclude that 18FDG-PET is useful for estimating the biological aggressiveness of intracranial meningiomas.
A renal transplant recipient with isolated cerebral aspergilloma 4 months after allograft transpl... more A renal transplant recipient with isolated cerebral aspergilloma 4 months after allograft transplantation is reported. On admission cerebral computed tomography showed a ring-enhancing mass in the left frontal hemisphere and aspirated purulent material revealed A. fumigatus hyphae. He was cured by short-term antifungal therapy and neurosurgical removal of the well demarcated lesion. He is still alive more than two years later and the renal transplant is well functioning. This is the first report of a renal transplant recipient with isolated cerebral aspergillosis without any relapse and only the third patient who has survived longer than 3 months. Early diagnostic procedures with rapid confirmation of aspergillus infection are pivotal for a benign clinical course.
Psychotherapie, Psychosomatik, medizinische Psychologie, Jan 22, 2015
Psychosocial cancer counseling centers represent an increasingly important part of comprehensive ... more Psychosocial cancer counseling centers represent an increasingly important part of comprehensive psychosocial cancer care. Research on the services provided by those centers is sparse, however, as is research on person-, disease-, and treatment-related characteristics of their clients. Therefore, the present study analyzes the services provided by 26 psychosocial cancer counseling centers temporarily being funded by the German Cancer Aid as well as selected characteristics of their clients. Analyses are based on data collected during 2011 by means of a documentation system specifically designed for the purposes of psychosocial cancer counseling. Testing focuses on whether cancer patients and cancer patients' relatives differ with respect to various characteristics and the services used. The results show that psychosocial and benefit counseling represent a major part of counseling services, followed by giving information and employing relaxation techniques. Clients seek counselin...
Amyotrophic lateral sclerosis (ALS) is characterized by the degeneration of motoneurons in the ce... more Amyotrophic lateral sclerosis (ALS) is characterized by the degeneration of motoneurons in the cerebral cortex, brainstem and spinal cord. Neuroinflammation plays an important role in the pathogenesis of ALS and involves the activation of microglia and astrocytes. Intracellular inflammasome complexes are part of the innate immunity as they sense and execute host inflammatory responses. The best characterized component is the NLRP3 inflammasome comprised of the NLR protein NLRP3, the adaptor ASC and pro-caspase 1. The NLRP3 inflammasome is critical for the activation of caspase 1 and the processing and release of IL1β and IL18. In this study, we investigated the expression, activation and co-localization of the NLRP3 inflammasome in the spinal cord of male SOD1(G93A) mice carrying a mutant human superoxide dismutase 1 (SOD1) variant and regarded as an animal model for ALS as well as in post-mortem tissue of ALS patients. NLRP3 and its molecular components as well as IL1β were already...
The European journal of neuroscience, Jan 22, 2015
Many bioartificial nerve guides have been investigated pre-clinically for their nerve regeneratio... more Many bioartificial nerve guides have been investigated pre-clinically for their nerve regeneration supporting function, often in comparison to the autologous nerve transplantation, which is still regarded as the current clinical gold standard. Enrichment of these scaffolds with cells intended to support axonal regeneration has been explored as a strategy to boost axonal regeneration across these nerve guides (Ansellin et al., 1999). In the present study, 20 mm rat sciatic nerve defects were implanted with a cell-seeded microstructured collagen nerve guide (Perimaix) or an autologous nerve graft. Under the influence of seeded, pre-differentiated mesenchymal stromal cells, axons regenerated well into the Perimaix nerve guide. Myelination-related parameters, like myelin sheath thickness, benefit from an additional seeding with pre-differentiated mesenchymal stromal cells. Furthermore, both the number of retrogradely labeled sensory neurons and the axon density within the implant were e...
We investigated the use of PET with 2[18F]fluoro-2-deoxy-D-glucose (FDG) to discriminate between ... more We investigated the use of PET with 2[18F]fluoro-2-deoxy-D-glucose (FDG) to discriminate between atypical or malignant and grade 1 meningiomas. The influence of fasting state and high-dose corticosteroid medication was analyzed retrospectively. Preoperative PET scans of 75 patients with suspected diagnosis of intracranial meningioma were evaluated using standardized uptake values (SUV) and tumor-to-contralateral gray matter ratios (TGR) of FDG uptake. Fifty-one of 75 patients fasted before the PET scan, and 27 of 75 patients were studied under high-dose corticosteroid medication. Eighteen tumors had recurred. PET results were compared to histopathological grading. PET correctly identified 8/9 atypical or malignant meningiomas and 58/66 grade 1 meningiomas using TGR and a threshold of 1.05 in primary meningioma and 0.85 in tumor recurrence. This corresponds to a specificity of 0.88 for the detection of higher tumor grading. Specificity was significantly higher in fasting compared to ...
The generation of complex three-dimensional bioengineered scaffolds that are capable of mimicking... more The generation of complex three-dimensional bioengineered scaffolds that are capable of mimicking the molecular and topographical cues of the extracellular matrix found in native tissues is a field of expanding research. The systematic development of such scaffolds requires the characterisation of cell behaviour in response to the individual components of the scaffold. In the present investigation, we studied cell-substrate interactions between purified populations of Schwann cells and three-dimensional fibrin hydrogel scaffolds, in the presence or absence of multiple layers of highly orientated electrospun polycaprolactone nanofibres. Embedded Schwann cells remained viable within the fibrin hydrogel for up to 7 days (the longest time studied); however, cell behaviour in the hydrogel was somewhat different to that observed on the two-dimensional fibrin substrate: Schwann cells failed to proliferate in the fibrin hydrogel, whereas cell numbers increased steadily on the two-dimensional fibrin substrate. Schwann cells within the fibrin hydrogel developed complex process branching patterns, but, when presented with orientated nanofibres, showed a strong tendency to redistribute themselves onto the nanofibres, where they extended long processes that followed the longitudinal orientation of the nanofibres. The process length along nanofibre-containing fibrin hydrogel reached near-maximal levels (for the present experimental conditions) as early as 1 day after culturing. The ability of this three-dimensional, extracellular matrix-mimicking scaffold to support Schwann cell survival and provide topographical cues for rapid process extension suggest that it may be an appropriate device design for the bridging of experimental lesions of the peripheral nervous system.
Biochemical and Biophysical Research Communications
VAPB is a highly conserved integral membrane protein that is ubiquitously expressed in all eukary... more VAPB is a highly conserved integral membrane protein that is ubiquitously expressed in all eukaryotic organisms and located within the membranes of the endoplasmic reticulum (ER). The P56S missense mutation of the VAPB protein is linked to a hereditary form of amyotrophic lateral sclerosis (ALS8), and the pathogenesis of ALS8 has remained enigmatic. We report the cloning of five novel splice variants of the human VAPB gene, all of which are expressed at the mRNA level in the human nervous system. When transfected into human HEK293 or SH-SY5Y cells, two of these variants (VAPB-2 and VAPB-4,5) were readily detectable by immunoblotting whereas two variants (VAPB-3 and VAPB-3,4) became detectable after proteasomal inhibition, a condition commonly found in neurodegenerative diseases. Interestingly, one of these novel VAPB variants, VAPB-2, co-immunoprecipitated with wt-VAPB. However, so far none of these splice variants could be detected by immunoblotting of lysates from selected human t...
The endoplasmic reticulum (ER) is the largest intracellular endomembrane system, enabling protein... more The endoplasmic reticulum (ER) is the largest intracellular endomembrane system, enabling protein and lipid synthesis, ion homeostasis, quality control of newly synthesized proteins and organelle communication 1 . Constant ER turnover and modulation is needed to meet different cellular requirements and autophagy has an important role in this process 2-8 . However, its underlying regulatory mechanisms remain unexplained. Here we show that members of the FAM134 reticulon protein family are ER-resident receptors that bind to autophagy modifiers LC3 and GABARAP, and facilitate ER degradation by autophagy ('ER-phagy'). Downregulation of FAM134B protein in human cells causes an expansion of the ER, while FAM134B overexpression results in ER fragmentation and lysosomal degradation. Mutant FAM134B proteins that cause sensory neuropathy in humans 9 are unable to act as ER-phagy receptors. Consistently, disruption of Fam134b in mice causes expansion of the ER, inhibits ER turnover, sensitizes cells to stress-induced apoptotic cell death and leads to degeneration of sensory neurons. Therefore, selective ER-phagy via FAM134 proteins is indispensable for mammalian cell homeostasis and controls ER morphology and turnover in mice and humans.
Pain perception has evolved as a warning mechanism to alert organisms to tissue damage and danger... more Pain perception has evolved as a warning mechanism to alert organisms to tissue damage and dangerous environments. In humans, however, undesirable, excessive or chronic pain is a common and major societal burden for which available medical treatments are currently suboptimal. New therapeutic options have recently been derived from studies of individuals with congenital insensitivity to pain (CIP). Here we identified 10 different homozygous mutations in PRDM12 (encoding PRDI-BF1 and RIZ homology domain-containing protein 12) in subjects with CIP from 11 families. Prdm proteins are a family of epigenetic regulators that control neural specification and neurogenesis. We determined that Prdm12 is expressed in nociceptors and their progenitors and participates in the development of sensory neurons in Xenopus embryos. Moreover, CIP-associated mutants abrogate the histone-modifying potential associated with wild-type Prdm12. Prdm12 emerges as a key factor in the orchestration of sensory ne...
Sialic acids (Sia) are widely expressed as terminal monosaccharides on eukaryotic glycoconjugates... more Sialic acids (Sia) are widely expressed as terminal monosaccharides on eukaryotic glycoconjugates. They are involved in many cellular functions, such as cell-cell interaction and signal recognition. The key enzyme of sialic acid biosynthesis is the bifunctional UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (GNE), which catalyses the first two steps of Sia biosynthesis in the cytosol. In this study we analysed sialylation of muscles in wild type (C57Bl/6 GNE +/+ ) and heterozygous GNE-deficient (C57Bl/6 GNE +/2 ) mice. We measured a significantly lower performance in the initial weeks of a treadmill exercise in C57Bl/6 GNE +/2 mice compared to wild type C57Bl/6 GNE +/+ animals. Membrane bound Sia of C57Bl/6 GNE +/2 mice were reduced by 33-53% at week 24 and by 12-15% at week 80 in comparison to C57Bl/6 GNE +/+ mice. Interestingly, membrane bound Sia concentration increased with age of the mice by 16-46% in C57Bl/6 GNE +/+ , but by 87-207% in C57Bl/6 GNE +/2 . Furthermore we could identify specific morphological changes in aged muscles. Here we propose that increased Sia concentrations in muscles are a characteristic feature of ageing and could be used as a marker for agerelated changes in muscle.
Obstetric brachial plexus palsy is rare, but the limb impairments are manifold and often long-las... more Obstetric brachial plexus palsy is rare, but the limb impairments are manifold and often long-lasting. Physiotherapy, microsurgical nerve reconstruction, secondary joint corrections, and muscle transpositions are employed with success. The role of conservative and operative treatment options should be regularly reviewed. Selective literature review (evidence levels 3 and 4) and analysis of personal clinical operative and scientific experience over the past 15 years. Children with upper and total plexus palsy displaying nerve root avulsions and/or -ruptures are treated today by early primary nerve reconstruction in the first few months of life followed by secondary corrections, with good functional results. The late complications, with muscle weakness, impaired motion patterns, and joint dysplasia, are often underrated. The potential for scientific analysis is limited, due to the rarity and interindividual variability of the lesions and the varying effects on function and growth. Exp...
HIV infection affects the central nervous system (CNS), frequently causing cognitive impairment. ... more HIV infection affects the central nervous system (CNS), frequently causing cognitive impairment. Hippocampal injury impedes the ability to transfer information into memory. Therefore, we aimed to examine neuronal injury and repair in the hippocampal formation in HIV encephalopathy. We compared neuropathological findings in 14 autopsy cases after death from systemic complications of HIV infection and in 15 age-matched HIV-negative control cases after sudden death from nonneurological causes using immunohistochemistry. The density of apoptotic granule cells in the dentate gyrus was higher in HIV-infected than in control cases (P = 0.048). Proliferation of neural progenitor cells in the dentate gyrus was increased in HIV infection (P = 0.028), whereas the density of recently generated TUC-4 [TOAD (turned on after division)/Ulip/CRMP family 4]-expressing neurons in this region was not significantly elevated in HIV-infected cases (P = 0.13). HIV infection caused microglial activation and astrocytosis in the neocortex and hippocampal formation. Conversely, we were unable to detect more pronounced axonal injury in HIV-infected than in control cases. As in other infections involving the CNS, apoptosis of hippocampal neurons accompanied by microglial activation and astrocytosis is a prominent feature of HIV encephalopathy. The regenerative potential, assessed using the density of young neurons in the hippocampal dentate gyrus, in HIV infection appears to be lower than in acute bacterial meningitis and septic encephalitis.
62 intracranial meningiomas in 60 patients were studied with 18FDG-PET prior to neurosurgery in o... more 62 intracranial meningiomas in 60 patients were studied with 18FDG-PET prior to neurosurgery in order to evaluate the relationship between 18FDG uptake and biological aggressiveness of the tumors. Histopathological grading, cellular density, Ki-67 proliferation index and evidence of chromosomal aberrations were used to assess tumor aggressiveness. Significantly elevated 18FDG uptake was found in grade 2- and 3- compared to grade 1-meningiomas, in tumors of high cellularity compared with those of low cellularity, and in meningiomas with an elevated Ki-67 proliferation index (above 2%). The two meningiomas with the most pronounced chromosomal aberrations revealed the highest 18FDG uptake of all cytogenetically studied meningiomas. We conclude that 18FDG-PET is useful for estimating the biological aggressiveness of intracranial meningiomas.
A renal transplant recipient with isolated cerebral aspergilloma 4 months after allograft transpl... more A renal transplant recipient with isolated cerebral aspergilloma 4 months after allograft transplantation is reported. On admission cerebral computed tomography showed a ring-enhancing mass in the left frontal hemisphere and aspirated purulent material revealed A. fumigatus hyphae. He was cured by short-term antifungal therapy and neurosurgical removal of the well demarcated lesion. He is still alive more than two years later and the renal transplant is well functioning. This is the first report of a renal transplant recipient with isolated cerebral aspergillosis without any relapse and only the third patient who has survived longer than 3 months. Early diagnostic procedures with rapid confirmation of aspergillus infection are pivotal for a benign clinical course.
Psychotherapie, Psychosomatik, medizinische Psychologie, Jan 22, 2015
Psychosocial cancer counseling centers represent an increasingly important part of comprehensive ... more Psychosocial cancer counseling centers represent an increasingly important part of comprehensive psychosocial cancer care. Research on the services provided by those centers is sparse, however, as is research on person-, disease-, and treatment-related characteristics of their clients. Therefore, the present study analyzes the services provided by 26 psychosocial cancer counseling centers temporarily being funded by the German Cancer Aid as well as selected characteristics of their clients. Analyses are based on data collected during 2011 by means of a documentation system specifically designed for the purposes of psychosocial cancer counseling. Testing focuses on whether cancer patients and cancer patients' relatives differ with respect to various characteristics and the services used. The results show that psychosocial and benefit counseling represent a major part of counseling services, followed by giving information and employing relaxation techniques. Clients seek counselin...
Amyotrophic lateral sclerosis (ALS) is characterized by the degeneration of motoneurons in the ce... more Amyotrophic lateral sclerosis (ALS) is characterized by the degeneration of motoneurons in the cerebral cortex, brainstem and spinal cord. Neuroinflammation plays an important role in the pathogenesis of ALS and involves the activation of microglia and astrocytes. Intracellular inflammasome complexes are part of the innate immunity as they sense and execute host inflammatory responses. The best characterized component is the NLRP3 inflammasome comprised of the NLR protein NLRP3, the adaptor ASC and pro-caspase 1. The NLRP3 inflammasome is critical for the activation of caspase 1 and the processing and release of IL1β and IL18. In this study, we investigated the expression, activation and co-localization of the NLRP3 inflammasome in the spinal cord of male SOD1(G93A) mice carrying a mutant human superoxide dismutase 1 (SOD1) variant and regarded as an animal model for ALS as well as in post-mortem tissue of ALS patients. NLRP3 and its molecular components as well as IL1β were already...
The European journal of neuroscience, Jan 22, 2015
Many bioartificial nerve guides have been investigated pre-clinically for their nerve regeneratio... more Many bioartificial nerve guides have been investigated pre-clinically for their nerve regeneration supporting function, often in comparison to the autologous nerve transplantation, which is still regarded as the current clinical gold standard. Enrichment of these scaffolds with cells intended to support axonal regeneration has been explored as a strategy to boost axonal regeneration across these nerve guides (Ansellin et al., 1999). In the present study, 20 mm rat sciatic nerve defects were implanted with a cell-seeded microstructured collagen nerve guide (Perimaix) or an autologous nerve graft. Under the influence of seeded, pre-differentiated mesenchymal stromal cells, axons regenerated well into the Perimaix nerve guide. Myelination-related parameters, like myelin sheath thickness, benefit from an additional seeding with pre-differentiated mesenchymal stromal cells. Furthermore, both the number of retrogradely labeled sensory neurons and the axon density within the implant were e...
We investigated the use of PET with 2[18F]fluoro-2-deoxy-D-glucose (FDG) to discriminate between ... more We investigated the use of PET with 2[18F]fluoro-2-deoxy-D-glucose (FDG) to discriminate between atypical or malignant and grade 1 meningiomas. The influence of fasting state and high-dose corticosteroid medication was analyzed retrospectively. Preoperative PET scans of 75 patients with suspected diagnosis of intracranial meningioma were evaluated using standardized uptake values (SUV) and tumor-to-contralateral gray matter ratios (TGR) of FDG uptake. Fifty-one of 75 patients fasted before the PET scan, and 27 of 75 patients were studied under high-dose corticosteroid medication. Eighteen tumors had recurred. PET results were compared to histopathological grading. PET correctly identified 8/9 atypical or malignant meningiomas and 58/66 grade 1 meningiomas using TGR and a threshold of 1.05 in primary meningioma and 0.85 in tumor recurrence. This corresponds to a specificity of 0.88 for the detection of higher tumor grading. Specificity was significantly higher in fasting compared to ...
The generation of complex three-dimensional bioengineered scaffolds that are capable of mimicking... more The generation of complex three-dimensional bioengineered scaffolds that are capable of mimicking the molecular and topographical cues of the extracellular matrix found in native tissues is a field of expanding research. The systematic development of such scaffolds requires the characterisation of cell behaviour in response to the individual components of the scaffold. In the present investigation, we studied cell-substrate interactions between purified populations of Schwann cells and three-dimensional fibrin hydrogel scaffolds, in the presence or absence of multiple layers of highly orientated electrospun polycaprolactone nanofibres. Embedded Schwann cells remained viable within the fibrin hydrogel for up to 7 days (the longest time studied); however, cell behaviour in the hydrogel was somewhat different to that observed on the two-dimensional fibrin substrate: Schwann cells failed to proliferate in the fibrin hydrogel, whereas cell numbers increased steadily on the two-dimensional fibrin substrate. Schwann cells within the fibrin hydrogel developed complex process branching patterns, but, when presented with orientated nanofibres, showed a strong tendency to redistribute themselves onto the nanofibres, where they extended long processes that followed the longitudinal orientation of the nanofibres. The process length along nanofibre-containing fibrin hydrogel reached near-maximal levels (for the present experimental conditions) as early as 1 day after culturing. The ability of this three-dimensional, extracellular matrix-mimicking scaffold to support Schwann cell survival and provide topographical cues for rapid process extension suggest that it may be an appropriate device design for the bridging of experimental lesions of the peripheral nervous system.
Biochemical and Biophysical Research Communications
VAPB is a highly conserved integral membrane protein that is ubiquitously expressed in all eukary... more VAPB is a highly conserved integral membrane protein that is ubiquitously expressed in all eukaryotic organisms and located within the membranes of the endoplasmic reticulum (ER). The P56S missense mutation of the VAPB protein is linked to a hereditary form of amyotrophic lateral sclerosis (ALS8), and the pathogenesis of ALS8 has remained enigmatic. We report the cloning of five novel splice variants of the human VAPB gene, all of which are expressed at the mRNA level in the human nervous system. When transfected into human HEK293 or SH-SY5Y cells, two of these variants (VAPB-2 and VAPB-4,5) were readily detectable by immunoblotting whereas two variants (VAPB-3 and VAPB-3,4) became detectable after proteasomal inhibition, a condition commonly found in neurodegenerative diseases. Interestingly, one of these novel VAPB variants, VAPB-2, co-immunoprecipitated with wt-VAPB. However, so far none of these splice variants could be detected by immunoblotting of lysates from selected human t...
The endoplasmic reticulum (ER) is the largest intracellular endomembrane system, enabling protein... more The endoplasmic reticulum (ER) is the largest intracellular endomembrane system, enabling protein and lipid synthesis, ion homeostasis, quality control of newly synthesized proteins and organelle communication 1 . Constant ER turnover and modulation is needed to meet different cellular requirements and autophagy has an important role in this process 2-8 . However, its underlying regulatory mechanisms remain unexplained. Here we show that members of the FAM134 reticulon protein family are ER-resident receptors that bind to autophagy modifiers LC3 and GABARAP, and facilitate ER degradation by autophagy ('ER-phagy'). Downregulation of FAM134B protein in human cells causes an expansion of the ER, while FAM134B overexpression results in ER fragmentation and lysosomal degradation. Mutant FAM134B proteins that cause sensory neuropathy in humans 9 are unable to act as ER-phagy receptors. Consistently, disruption of Fam134b in mice causes expansion of the ER, inhibits ER turnover, sensitizes cells to stress-induced apoptotic cell death and leads to degeneration of sensory neurons. Therefore, selective ER-phagy via FAM134 proteins is indispensable for mammalian cell homeostasis and controls ER morphology and turnover in mice and humans.
Pain perception has evolved as a warning mechanism to alert organisms to tissue damage and danger... more Pain perception has evolved as a warning mechanism to alert organisms to tissue damage and dangerous environments. In humans, however, undesirable, excessive or chronic pain is a common and major societal burden for which available medical treatments are currently suboptimal. New therapeutic options have recently been derived from studies of individuals with congenital insensitivity to pain (CIP). Here we identified 10 different homozygous mutations in PRDM12 (encoding PRDI-BF1 and RIZ homology domain-containing protein 12) in subjects with CIP from 11 families. Prdm proteins are a family of epigenetic regulators that control neural specification and neurogenesis. We determined that Prdm12 is expressed in nociceptors and their progenitors and participates in the development of sensory neurons in Xenopus embryos. Moreover, CIP-associated mutants abrogate the histone-modifying potential associated with wild-type Prdm12. Prdm12 emerges as a key factor in the orchestration of sensory ne...
Sialic acids (Sia) are widely expressed as terminal monosaccharides on eukaryotic glycoconjugates... more Sialic acids (Sia) are widely expressed as terminal monosaccharides on eukaryotic glycoconjugates. They are involved in many cellular functions, such as cell-cell interaction and signal recognition. The key enzyme of sialic acid biosynthesis is the bifunctional UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (GNE), which catalyses the first two steps of Sia biosynthesis in the cytosol. In this study we analysed sialylation of muscles in wild type (C57Bl/6 GNE +/+ ) and heterozygous GNE-deficient (C57Bl/6 GNE +/2 ) mice. We measured a significantly lower performance in the initial weeks of a treadmill exercise in C57Bl/6 GNE +/2 mice compared to wild type C57Bl/6 GNE +/+ animals. Membrane bound Sia of C57Bl/6 GNE +/2 mice were reduced by 33-53% at week 24 and by 12-15% at week 80 in comparison to C57Bl/6 GNE +/+ mice. Interestingly, membrane bound Sia concentration increased with age of the mice by 16-46% in C57Bl/6 GNE +/+ , but by 87-207% in C57Bl/6 GNE +/2 . Furthermore we could identify specific morphological changes in aged muscles. Here we propose that increased Sia concentrations in muscles are a characteristic feature of ageing and could be used as a marker for agerelated changes in muscle.
Obstetric brachial plexus palsy is rare, but the limb impairments are manifold and often long-las... more Obstetric brachial plexus palsy is rare, but the limb impairments are manifold and often long-lasting. Physiotherapy, microsurgical nerve reconstruction, secondary joint corrections, and muscle transpositions are employed with success. The role of conservative and operative treatment options should be regularly reviewed. Selective literature review (evidence levels 3 and 4) and analysis of personal clinical operative and scientific experience over the past 15 years. Children with upper and total plexus palsy displaying nerve root avulsions and/or -ruptures are treated today by early primary nerve reconstruction in the first few months of life followed by secondary corrections, with good functional results. The late complications, with muscle weakness, impaired motion patterns, and joint dysplasia, are often underrated. The potential for scientific analysis is limited, due to the rarity and interindividual variability of the lesions and the varying effects on function and growth. Exp...
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Papers by Joachim Weis