Kathrin Chamaon | Otto-von-Guericke-University Magdeburg (original) (raw)
Papers by Kathrin Chamaon
Pathology Research and Practice, 2007
Expression of the transforming growth factor-β (TGF-β) protein family in the peripheral nervous s... more Expression of the transforming growth factor-β (TGF-β) protein family in the peripheral nervous system is well established, but the role of their cognate receptors TGF-β receptor type 1 (R1) and type 2 (R2) has been less well studied. TGF-β plays an essential role in Schwann cell proliferation and differentiation, and is involved in neurotrophic effects of several neurotrophic substances. TGF-β
Journal of Neurochemistry, Jan 18, 2002
ABSTRACT Although neuronal nicotinic acetylcholine receptors from insects have been reconstituted... more ABSTRACT Although neuronal nicotinic acetylcholine receptors from insects have been reconstituted in vitro more than a decade ago, our knowledge about the subunit composition of native receptors as well as their functional properties still remains limited. Immunohistochemical evidence has suggested that two α subunits, α-like subunit (ALS) and Drosophilaα2 subunit (Dα2), are colocalized in the synaptic neuropil of the Drosophila CNS and therefore may be subunits of the same receptor complex. To gain further understanding of the composition of these nicotinic receptors, we have examined the possibility that a receptor may imbed more than one α subunit using immunoprecipitations and electrophysiological investigations. Immunoprecipitation experiments of fly head extracts revealed that ALS-specific antibodies coprecipitate Dα2, and vice versa, and thereby suggest that these two α subunits must be contained within the same receptor complex, a result that is supported by investigations of reconstituted receptors in Xenopus oocytes. Discrimination between binary (ALS/β2 or Dα2/β2) and ternary (ALS/Dα2/β2) receptor complexes was made on the basis of their dose-response curve to acetylcholine as well as their sensitivity to α-bungarotoxin or dihydro-β-erythroidine. These data demonstrate that the presence of the two α subunits within a single receptor complex confers new receptor properties that cannot be predicted from knowledge of the binary receptor’s properties.
Osteoarthritis and Cartilage, 2016
Purpose: Obesity is known to be a risk factor for the development of osteoarthritis (OA). Obesity... more Purpose: Obesity is known to be a risk factor for the development of osteoarthritis (OA). Obesity is accompanied by adipocyte hypertrophy and elevated inflammation in subcutaneous and visceral adipose tissue. The infrapatellar fat pad (IPFP) is an adipose tissue that contains adipocytes. The IPFP is believed to be influential in determining the Abstracts / Osteoarthritis and Cartilage 24 (2016) S63eS534 S334
Journal of biomedical materials research. Part B, Applied biomaterials, Jan 27, 2018
Total joint replacement is one of the most successful procedures in orthopedic surgery today. How... more Total joint replacement is one of the most successful procedures in orthopedic surgery today. However, metal implant materials undergo wear and corrosion processes. Generated particles and ions can cause a variety of cellular reactions. Cobalt-containing alloys are used frequently in implant materials. Some studies suggest that cobalt exhibits potential cytotoxic effects, for example, via generation of reactive oxygen species (ROS). To further elucidate the effects of cobalt on human cells, we determined cell viability and cytosolic and mitochondrial superoxide formation after incubation of either ions or particles with different cells. MM-6 and Jurkat cell lines were treated for 24, 48 and 72 h with either CoCrMo particles or cobalt ions (supplied as CoCl ). A total of 24 h exposure of both forms of cobalt did not induce cell death using terminal deoxynucleotidyl transferase (TUNEL) and trypan blue assay. Interestingly, the formation of superoxide (O ) is evoked mainly by ionic CoC...
Clinical neuropathology
We investigated the effects of 2-methoxyestradiol (2-ME), a promising new antitumor agent, on via... more We investigated the effects of 2-methoxyestradiol (2-ME), a promising new antitumor agent, on viable cell number and nuclear morphology of malignant glioma cells (three human and one rat glioma cell lines) and analyzed the controversial role of death recepor 5 (DR5) upregulation in 2-ME induced apoptosis. Microtiter-tetrazolium (MTT) assays showed a significant reduction of viable cells after incubation with 2 microM and 20 microM 2-ME for 48 and 72 hours in all cultures. In the 20 microM concentration, there were even significant effects in the majority of shorter incubation periods. Hoechst 33258 stains showed a substantial amount of cells with nuclear fragmentation indicating a late stage of apoptosis after 20 microM 2-ME treatments of 24 hours and more. The role of the DR5-mediated extrinsic apoptotic pathway was further studied in the three human glioma cell lines; 50 ng/ml of the DR5 ligand TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) and 2 microM 2-ME showe...
PLoS ONE, 2012
Efficient adaptive immune responses require the localization of T lymphocytes in secondary lympho... more Efficient adaptive immune responses require the localization of T lymphocytes in secondary lymphoid organs and inflamed tissues. To achieve correct localization of T lymphocytes, the migration of these cells is initiated and directed by adhesion molecules and chemokines. It has recently been shown that the inhibitory surface molecule CD152 (CTLA-4) initiates Th cell migration, but the molecular mechanism underlying this effect remains to be elucidated. Using CD4 T lymphocytes derived from OVA-specific TCR transgenic CD152-deficient and CD152-competent mice, we demonstrate that chemokine-triggered signal transduction is differentially regulated by CD152 via phosphoinositide 3-kinase (PI3K)-dependent activation of protein kinase B (PKB/Akt). In the presence of CD152 signaling, the chemoattractant CCL4 selectively induces the full activation of Akt via phosphorylation at threonine 308 and serine 473 in pro-inflammatory Th lymphocytes expressing the cognate chemokine receptor CCR5. Akt signals lead to cytoskeleton rearrangements, which are indispensable for migration. Therefore, this novel Akt-modulating function of CD152 signals affecting T cell migration demonstrates that boosting CD152 or its downstream signal transduction could aid therapies aimed at sensitizing T lymphocytes for optimal migration, thus contributing to a precise and effective immune response.
Pathology - Research and Practice, 2007
Expression of the transforming growth factor-β (TGF-β) protein family in the peripheral nervous s... more Expression of the transforming growth factor-β (TGF-β) protein family in the peripheral nervous system is well established, but the role of their cognate receptors TGF-β receptor type 1 (R1) and type 2 (R2) has been less well studied. TGF-β plays an essential role in Schwann cell proliferation and differentiation, and is involved in neurotrophic effects of several neurotrophic substances. TGF-β
Experimental and Clinical Endocrinology & Diabetes, 2010
The reasons for the increase of pituitary tumor-transforming gene (PTTG) transcripts in about 90%... more The reasons for the increase of pituitary tumor-transforming gene (PTTG) transcripts in about 90% of pituitary adenomas are still not fully understood, although upregulation by basic fibroblast growth factor (bFGF) has been discussed as a potential cause. A possible influence of the Insulin like Growth Factor 1 (IGF-1) might be of interest, since this protein is also synthesized in most pituitary adenomas. Moreover, the principal regulation of the PTTG gene by IGF-1 and Insulin has been demonstrated in astrocytoma and breast cancer cells. We analyzed a large group (103 patients) of unselected clinical pituitary adenoma samples. From total RNA of frozen tumor samples (all subtypes) cDNA ( COMPLEMENTARY DNA) was synthesized and transcripts of PTTG, bFGF, IGF-1 were measured by Real-Time-PCR. Not only mRNA ( MESSENGER RNA) levels of bFGF, but also of IGF-1, correlated strongly with PTTG transcripts. This result was obtained, when all pituitary adenoma samples were included in the statistical calculations, irrespective of their subclassification. Our study suggests a connection between PTTG and IGF-1 in pituitary adenomas.
Biochemical and Biophysical Research Communications, 2005
J Neurochem, 2002
Although neuronal nicotinic acetylcholine receptors from insects have been reconstituted in vitro... more Although neuronal nicotinic acetylcholine receptors from insects have been reconstituted in vitro more than a decade ago, our knowledge about the subunit composition of native receptors as well as their functional properties still remains limited. Immunohistochemical evidence has suggested that two ␣ subunits, ␣-like subunit (ALS) and Drosophila ␣2 subunit (D␣2), are colocalized in the synaptic neuropil of the Drosophila CNS and therefore may be subunits of the same receptor complex. To gain further understanding of the composition of these nicotinic receptors, we have examined the possibility that a receptor may imbed more than one ␣ subunit using immunoprecipitations and electrophysiological investigations. Immunoprecipitation experiments of fly head extracts revealed that ALS-specific antibodies coprecipitate D␣2, and vice versa, and thereby suggest that these two ␣ subunits must be contained within the same receptor complex, a result that is supported by investigations of reconstituted receptors in Xenopus oocytes. Discrimination between binary (ALS/2 or D␣2/2) and ternary (ALS/D␣2/2) receptor complexes was made on the basis of their dose -response curve to acetylcholine as well as their sensitivity to ␣-bungarotoxin or dihydro--erythroidine. These data demonstrate that the presence of the two ␣ subunits within a single receptor complex confers new receptor properties that cannot be predicted from knowledge of the binary receptor's properties.
Magdeburg, Universiẗat, Diss., 2001. Computerdatei im Fernzugriff.
Journal of Biomedical Materials Research Part A, 2015
In the present work we characterize integrin CD11c (αXß2) expression in periprosthetic tissues of... more In the present work we characterize integrin CD11c (αXß2) expression in periprosthetic tissues of 45 hip revisions. Tissues were retrieved from 23 ceramic-on-ultra-high molecular weight polyethylene (UHMWPE), 20 metal-on-UHMWPE, and 2 metal-on-metal total hip arthroplasties (THAs). Capsular tissue retrieved during primary THA from 19 patients served as controls. We identified a system to identify important immunohistochemical markers that are expressed in aseptic loosening. We focused on CD11c, CD68 and CD14. We observed that the CD11c molecule possesses four different cellular patterns in the periprosthetic tissues. Three of them are associated with the occurrence of UHMWPE abrasive material. Double staining with CD14 and CD68 was used for a more detailed analysis of the CD11c expressing cells. We observed that all forms of CD11c positive cells are CD68 positive however, only two forms of CD11c expressing cells are positive for CD14. Providing cellular diversity of CD11c expression in periprosthetic tissue, our results provide a contribution towards the further understanding of different cellular mechanisms to foreign body material. This article is protected by copyright. All rights reserved.
Neurobiology of Disease, 2007
The mechanism of retinal ganglion cell loss in Leber's hereditary optic neuropathy (LHON) is stil... more The mechanism of retinal ganglion cell loss in Leber's hereditary optic neuropathy (LHON) is still uncertain, and a role of enhanced superoxide production by the mutant mitochondrial complex I has been hypothesized. In the present study, it was shown that LHON cybrids, carrying the np11778 mutation, became selectively more H 2 O 2 sensitive compared with the parental cell line only following short-term retinoic acid differentiation. They contained a decreased cellular glutathione pool (49%, p ≤ 0.05), despite 1.5-fold enhanced expression of the regulatory subunit of γ-glutamylcysteine synthetase (p ≤ 0.05). This points to a reduction of the capacity to detoxify H 2 O 2 and to changes in thiol redox potential. The activity of the H 2 O 2 degrading enzyme glutathione peroxidase (GPx) and the activities of glutathione reductase (GR) and superoxide dismutase (SOD) were unaffected.
Journal of Neuro-Oncology, 2005
The purpose of this study was to investigate the potential effects of 2-methoxyestradiol, a natur... more The purpose of this study was to investigate the potential effects of 2-methoxyestradiol, a natural mammalian steroid, in glioma cells, since antiproliferative effects of this compound had been shown earlier in several leukemia and carcinoma cell lines. The effects of 0.2, 2 and 20 lM concentrations of 2-methoxyestradiol were measured in three malignant human glioma cell lines (U87MG, U138MG, LN405) and one malignant rat glioma cell line (RG-2) using a microtiter-tetrazolium (MTT) assay. In all cell lines, a significant reduction of the viable cell number by more then 75% occurred (P < 0.05) for concentrations of 2 and 20 lM 2-methoxyestradiol after 6 days. A concentration of 0.2 lM had smaller effects (10-40% cell reduction), which were significant in two of the cell lines tested. The apoptotic nature of cell death was further analyzed in U87MG and RG-2 cells. Caspase-3 activity was significantly induced to levels between 3.4-and 23-fold after 4 days for the two higher 2-methoxyestradiol concentrations (P < 0.05). In the cell line RG-2 nuclear fragmentation was visible in many nuclei, following stains with Hoechst H33258. A round cell morphology occurred in most treated cells, which was not accompanied by a complete destruction of the microtubule network, as it can be observed with other microtubule targeting drugs. * These authors contributed equally to the work.
Journal of Neurochemistry, 2002
The second beta-like subunit (SBD) is a putative structural subunit of Drosophila melanogaster ni... more The second beta-like subunit (SBD) is a putative structural subunit of Drosophila melanogaster nicotinic acetylcholine receptors (nAChRs). Here we have produced specific antibodies against SBD to study, which other nAChR subunits can co-assemble with SBD in receptor complexes of the Drosophila nervous system. Immunohistochemical studies in the adult optic lobe revealed that SBD has a distribution similar to that of the alpha-subunit ALS in the synaptic neuropil. The subunits ALS, D(alpha)2 and SBD can be co-purified by alpha-bungarotoxin affinity chromatography. Moreover, anti-SBD antibodies co-precipitate ALS and D(alpha)2 and, vice versa, ALS and D(alpha)2 antibodies co-immunoprecipitate SBD protein. Two-step immunoaffinity chromatography with immobilized antibodies against ALS and D(alpha)2 revealed the existence of nAChR complexes that include ALS, D(alpha)2 and SBD as integral components. Interestingly, the genes encoding these three subunits appear to be directly linked in the Drosophila genome at region 96 A of the third chromosome. In addition, SBD appears to be a component of a different receptor complex, which includes the ARD protein as an additional beta-subunit, but neither ALS nor D(alpha)2 nor the third alpha-subunit D(alpha)3. These findings suggest a considerable complexity of the Drosophila nicotinic receptor system.
Journal of Biomedical Materials Research Part A, 2013
Large-diameter metal-on-metal (MoM) bearings evolved from the success of hip resurfacing. These i... more Large-diameter metal-on-metal (MoM) bearings evolved from the success of hip resurfacing. These implants were used in revision surgery in cases with well-fixed acetabular cups but loose or failed femoral stems, to avoid cup revision. Early data showed low rates of dislocation and potentially low wear profiles due to better fluid film lubrication. The risk of impingement was also thought to be low due to the increased head-neck ratio. Subsequently large-diameter MoM heads gained popularity in primary hip replacement. Recent data has emerged on the unacceptably high revision rates among patients with large-diameter MoM total hip arthroplasties (THAs), high blood levels of metal ions, and adverse tissue reactions. The head-neck (cone-taper) modular interface probably represents the weak link in large metal heads that have been used on conventional tapers. Increased torque of the large head, micromotion, and instability at the cone-taper interface, synergistic interactions between corrosion and wear, edge loading, low clearance, and psoas impingement are the likely causes for early failure of these prostheses.
International Journal of Legal Medicine, 2008
Intron 40 of the von Willebrand factor (vWF) gene exhibits a highly variable region of about 0.65... more Intron 40 of the von Willebrand factor (vWF) gene exhibits a highly variable region of about 0.65 kb, which contains 5 juxtaposed STRs. We sequenced 0.65 kb amplicons from 68 chromosomes and found 2 frequent indel polymorphisms and 5 SNPs. The 68 chromosomes investigated here presented a total of 47 different haplotypes. Regarding the SNP allele distribution in our sample, we arranged our results of the vWF intron 40 into a system of 3 haplotypes, i.e. haplotypes a, b and c. Our review may be valuable in further optimising vWF typing in forensic applications and in avoiding pitfalls. Further attempts to develop sophisticated techniques may soon enable haplotyping using autosomale STR clusters.
Clinical Orthopaedics and Related Research®, 2012
Metal-on-metal (MoM) THAs have reduced wear rates compared with metal-on-polyethylene. However, e... more Metal-on-metal (MoM) THAs have reduced wear rates compared with metal-on-polyethylene. However, elevated serum metal ion levels and pseudotumors have been reported in large MoM articulations. We therefore determined (1) if corrosion occurred at the cone/taper interface leading to instability in patients with large-diameter THAs; (2) how patients presented clinically and radiographically; (3) if adverse periprosthetic tissue reactions occurred; (4) whether metal was released from the implants into the periprosthetic tissues; and (5) if head size correlated with metal release. We reviewed 114 patients who had revisions of large-diameter head MoM articulations. Mean time of implantation was 46 months. To identify adverse reactions and particle load, tissues were stained by hematoxylin and eosin and CD3/CD20/CD68 antibodies. Periprosthetic tissues were analyzed for metal content and distribution in different regions. Electrochemical reactions between the stem and adapter were investigated by a minicell electrode. Electrochemical studies on the stem and the head adapter showed a risk for galvanic corrosion. Ninety-four percent of patients had instability at the cone/taper interface. All patients presented with early clinical symptoms; 59 patients had radiographic signs of loosening. One hundred four patients had foreign body reactions and necrosis. The largest amounts of metal released were titanium or iron. We found no correlation between head size and metal ion release. These findings suggest that in modular cone/taper connections, friction of the MoM articulations may cause failure of the cone/taper interface leading to galvanic corrosion and loosening. It is unclear whether the design of this MoM system provides sufficient stability at the taper.
Pathology Research and Practice, 2007
Expression of the transforming growth factor-β (TGF-β) protein family in the peripheral nervous s... more Expression of the transforming growth factor-β (TGF-β) protein family in the peripheral nervous system is well established, but the role of their cognate receptors TGF-β receptor type 1 (R1) and type 2 (R2) has been less well studied. TGF-β plays an essential role in Schwann cell proliferation and differentiation, and is involved in neurotrophic effects of several neurotrophic substances. TGF-β
Journal of Neurochemistry, Jan 18, 2002
ABSTRACT Although neuronal nicotinic acetylcholine receptors from insects have been reconstituted... more ABSTRACT Although neuronal nicotinic acetylcholine receptors from insects have been reconstituted in vitro more than a decade ago, our knowledge about the subunit composition of native receptors as well as their functional properties still remains limited. Immunohistochemical evidence has suggested that two α subunits, α-like subunit (ALS) and Drosophilaα2 subunit (Dα2), are colocalized in the synaptic neuropil of the Drosophila CNS and therefore may be subunits of the same receptor complex. To gain further understanding of the composition of these nicotinic receptors, we have examined the possibility that a receptor may imbed more than one α subunit using immunoprecipitations and electrophysiological investigations. Immunoprecipitation experiments of fly head extracts revealed that ALS-specific antibodies coprecipitate Dα2, and vice versa, and thereby suggest that these two α subunits must be contained within the same receptor complex, a result that is supported by investigations of reconstituted receptors in Xenopus oocytes. Discrimination between binary (ALS/β2 or Dα2/β2) and ternary (ALS/Dα2/β2) receptor complexes was made on the basis of their dose-response curve to acetylcholine as well as their sensitivity to α-bungarotoxin or dihydro-β-erythroidine. These data demonstrate that the presence of the two α subunits within a single receptor complex confers new receptor properties that cannot be predicted from knowledge of the binary receptor’s properties.
Osteoarthritis and Cartilage, 2016
Purpose: Obesity is known to be a risk factor for the development of osteoarthritis (OA). Obesity... more Purpose: Obesity is known to be a risk factor for the development of osteoarthritis (OA). Obesity is accompanied by adipocyte hypertrophy and elevated inflammation in subcutaneous and visceral adipose tissue. The infrapatellar fat pad (IPFP) is an adipose tissue that contains adipocytes. The IPFP is believed to be influential in determining the Abstracts / Osteoarthritis and Cartilage 24 (2016) S63eS534 S334
Journal of biomedical materials research. Part B, Applied biomaterials, Jan 27, 2018
Total joint replacement is one of the most successful procedures in orthopedic surgery today. How... more Total joint replacement is one of the most successful procedures in orthopedic surgery today. However, metal implant materials undergo wear and corrosion processes. Generated particles and ions can cause a variety of cellular reactions. Cobalt-containing alloys are used frequently in implant materials. Some studies suggest that cobalt exhibits potential cytotoxic effects, for example, via generation of reactive oxygen species (ROS). To further elucidate the effects of cobalt on human cells, we determined cell viability and cytosolic and mitochondrial superoxide formation after incubation of either ions or particles with different cells. MM-6 and Jurkat cell lines were treated for 24, 48 and 72 h with either CoCrMo particles or cobalt ions (supplied as CoCl ). A total of 24 h exposure of both forms of cobalt did not induce cell death using terminal deoxynucleotidyl transferase (TUNEL) and trypan blue assay. Interestingly, the formation of superoxide (O ) is evoked mainly by ionic CoC...
Clinical neuropathology
We investigated the effects of 2-methoxyestradiol (2-ME), a promising new antitumor agent, on via... more We investigated the effects of 2-methoxyestradiol (2-ME), a promising new antitumor agent, on viable cell number and nuclear morphology of malignant glioma cells (three human and one rat glioma cell lines) and analyzed the controversial role of death recepor 5 (DR5) upregulation in 2-ME induced apoptosis. Microtiter-tetrazolium (MTT) assays showed a significant reduction of viable cells after incubation with 2 microM and 20 microM 2-ME for 48 and 72 hours in all cultures. In the 20 microM concentration, there were even significant effects in the majority of shorter incubation periods. Hoechst 33258 stains showed a substantial amount of cells with nuclear fragmentation indicating a late stage of apoptosis after 20 microM 2-ME treatments of 24 hours and more. The role of the DR5-mediated extrinsic apoptotic pathway was further studied in the three human glioma cell lines; 50 ng/ml of the DR5 ligand TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) and 2 microM 2-ME showe...
PLoS ONE, 2012
Efficient adaptive immune responses require the localization of T lymphocytes in secondary lympho... more Efficient adaptive immune responses require the localization of T lymphocytes in secondary lymphoid organs and inflamed tissues. To achieve correct localization of T lymphocytes, the migration of these cells is initiated and directed by adhesion molecules and chemokines. It has recently been shown that the inhibitory surface molecule CD152 (CTLA-4) initiates Th cell migration, but the molecular mechanism underlying this effect remains to be elucidated. Using CD4 T lymphocytes derived from OVA-specific TCR transgenic CD152-deficient and CD152-competent mice, we demonstrate that chemokine-triggered signal transduction is differentially regulated by CD152 via phosphoinositide 3-kinase (PI3K)-dependent activation of protein kinase B (PKB/Akt). In the presence of CD152 signaling, the chemoattractant CCL4 selectively induces the full activation of Akt via phosphorylation at threonine 308 and serine 473 in pro-inflammatory Th lymphocytes expressing the cognate chemokine receptor CCR5. Akt signals lead to cytoskeleton rearrangements, which are indispensable for migration. Therefore, this novel Akt-modulating function of CD152 signals affecting T cell migration demonstrates that boosting CD152 or its downstream signal transduction could aid therapies aimed at sensitizing T lymphocytes for optimal migration, thus contributing to a precise and effective immune response.
Pathology - Research and Practice, 2007
Expression of the transforming growth factor-β (TGF-β) protein family in the peripheral nervous s... more Expression of the transforming growth factor-β (TGF-β) protein family in the peripheral nervous system is well established, but the role of their cognate receptors TGF-β receptor type 1 (R1) and type 2 (R2) has been less well studied. TGF-β plays an essential role in Schwann cell proliferation and differentiation, and is involved in neurotrophic effects of several neurotrophic substances. TGF-β
Experimental and Clinical Endocrinology & Diabetes, 2010
The reasons for the increase of pituitary tumor-transforming gene (PTTG) transcripts in about 90%... more The reasons for the increase of pituitary tumor-transforming gene (PTTG) transcripts in about 90% of pituitary adenomas are still not fully understood, although upregulation by basic fibroblast growth factor (bFGF) has been discussed as a potential cause. A possible influence of the Insulin like Growth Factor 1 (IGF-1) might be of interest, since this protein is also synthesized in most pituitary adenomas. Moreover, the principal regulation of the PTTG gene by IGF-1 and Insulin has been demonstrated in astrocytoma and breast cancer cells. We analyzed a large group (103 patients) of unselected clinical pituitary adenoma samples. From total RNA of frozen tumor samples (all subtypes) cDNA ( COMPLEMENTARY DNA) was synthesized and transcripts of PTTG, bFGF, IGF-1 were measured by Real-Time-PCR. Not only mRNA ( MESSENGER RNA) levels of bFGF, but also of IGF-1, correlated strongly with PTTG transcripts. This result was obtained, when all pituitary adenoma samples were included in the statistical calculations, irrespective of their subclassification. Our study suggests a connection between PTTG and IGF-1 in pituitary adenomas.
Biochemical and Biophysical Research Communications, 2005
J Neurochem, 2002
Although neuronal nicotinic acetylcholine receptors from insects have been reconstituted in vitro... more Although neuronal nicotinic acetylcholine receptors from insects have been reconstituted in vitro more than a decade ago, our knowledge about the subunit composition of native receptors as well as their functional properties still remains limited. Immunohistochemical evidence has suggested that two ␣ subunits, ␣-like subunit (ALS) and Drosophila ␣2 subunit (D␣2), are colocalized in the synaptic neuropil of the Drosophila CNS and therefore may be subunits of the same receptor complex. To gain further understanding of the composition of these nicotinic receptors, we have examined the possibility that a receptor may imbed more than one ␣ subunit using immunoprecipitations and electrophysiological investigations. Immunoprecipitation experiments of fly head extracts revealed that ALS-specific antibodies coprecipitate D␣2, and vice versa, and thereby suggest that these two ␣ subunits must be contained within the same receptor complex, a result that is supported by investigations of reconstituted receptors in Xenopus oocytes. Discrimination between binary (ALS/2 or D␣2/2) and ternary (ALS/D␣2/2) receptor complexes was made on the basis of their dose -response curve to acetylcholine as well as their sensitivity to ␣-bungarotoxin or dihydro--erythroidine. These data demonstrate that the presence of the two ␣ subunits within a single receptor complex confers new receptor properties that cannot be predicted from knowledge of the binary receptor's properties.
Magdeburg, Universiẗat, Diss., 2001. Computerdatei im Fernzugriff.
Journal of Biomedical Materials Research Part A, 2015
In the present work we characterize integrin CD11c (αXß2) expression in periprosthetic tissues of... more In the present work we characterize integrin CD11c (αXß2) expression in periprosthetic tissues of 45 hip revisions. Tissues were retrieved from 23 ceramic-on-ultra-high molecular weight polyethylene (UHMWPE), 20 metal-on-UHMWPE, and 2 metal-on-metal total hip arthroplasties (THAs). Capsular tissue retrieved during primary THA from 19 patients served as controls. We identified a system to identify important immunohistochemical markers that are expressed in aseptic loosening. We focused on CD11c, CD68 and CD14. We observed that the CD11c molecule possesses four different cellular patterns in the periprosthetic tissues. Three of them are associated with the occurrence of UHMWPE abrasive material. Double staining with CD14 and CD68 was used for a more detailed analysis of the CD11c expressing cells. We observed that all forms of CD11c positive cells are CD68 positive however, only two forms of CD11c expressing cells are positive for CD14. Providing cellular diversity of CD11c expression in periprosthetic tissue, our results provide a contribution towards the further understanding of different cellular mechanisms to foreign body material. This article is protected by copyright. All rights reserved.
Neurobiology of Disease, 2007
The mechanism of retinal ganglion cell loss in Leber's hereditary optic neuropathy (LHON) is stil... more The mechanism of retinal ganglion cell loss in Leber's hereditary optic neuropathy (LHON) is still uncertain, and a role of enhanced superoxide production by the mutant mitochondrial complex I has been hypothesized. In the present study, it was shown that LHON cybrids, carrying the np11778 mutation, became selectively more H 2 O 2 sensitive compared with the parental cell line only following short-term retinoic acid differentiation. They contained a decreased cellular glutathione pool (49%, p ≤ 0.05), despite 1.5-fold enhanced expression of the regulatory subunit of γ-glutamylcysteine synthetase (p ≤ 0.05). This points to a reduction of the capacity to detoxify H 2 O 2 and to changes in thiol redox potential. The activity of the H 2 O 2 degrading enzyme glutathione peroxidase (GPx) and the activities of glutathione reductase (GR) and superoxide dismutase (SOD) were unaffected.
Journal of Neuro-Oncology, 2005
The purpose of this study was to investigate the potential effects of 2-methoxyestradiol, a natur... more The purpose of this study was to investigate the potential effects of 2-methoxyestradiol, a natural mammalian steroid, in glioma cells, since antiproliferative effects of this compound had been shown earlier in several leukemia and carcinoma cell lines. The effects of 0.2, 2 and 20 lM concentrations of 2-methoxyestradiol were measured in three malignant human glioma cell lines (U87MG, U138MG, LN405) and one malignant rat glioma cell line (RG-2) using a microtiter-tetrazolium (MTT) assay. In all cell lines, a significant reduction of the viable cell number by more then 75% occurred (P < 0.05) for concentrations of 2 and 20 lM 2-methoxyestradiol after 6 days. A concentration of 0.2 lM had smaller effects (10-40% cell reduction), which were significant in two of the cell lines tested. The apoptotic nature of cell death was further analyzed in U87MG and RG-2 cells. Caspase-3 activity was significantly induced to levels between 3.4-and 23-fold after 4 days for the two higher 2-methoxyestradiol concentrations (P < 0.05). In the cell line RG-2 nuclear fragmentation was visible in many nuclei, following stains with Hoechst H33258. A round cell morphology occurred in most treated cells, which was not accompanied by a complete destruction of the microtubule network, as it can be observed with other microtubule targeting drugs. * These authors contributed equally to the work.
Journal of Neurochemistry, 2002
The second beta-like subunit (SBD) is a putative structural subunit of Drosophila melanogaster ni... more The second beta-like subunit (SBD) is a putative structural subunit of Drosophila melanogaster nicotinic acetylcholine receptors (nAChRs). Here we have produced specific antibodies against SBD to study, which other nAChR subunits can co-assemble with SBD in receptor complexes of the Drosophila nervous system. Immunohistochemical studies in the adult optic lobe revealed that SBD has a distribution similar to that of the alpha-subunit ALS in the synaptic neuropil. The subunits ALS, D(alpha)2 and SBD can be co-purified by alpha-bungarotoxin affinity chromatography. Moreover, anti-SBD antibodies co-precipitate ALS and D(alpha)2 and, vice versa, ALS and D(alpha)2 antibodies co-immunoprecipitate SBD protein. Two-step immunoaffinity chromatography with immobilized antibodies against ALS and D(alpha)2 revealed the existence of nAChR complexes that include ALS, D(alpha)2 and SBD as integral components. Interestingly, the genes encoding these three subunits appear to be directly linked in the Drosophila genome at region 96 A of the third chromosome. In addition, SBD appears to be a component of a different receptor complex, which includes the ARD protein as an additional beta-subunit, but neither ALS nor D(alpha)2 nor the third alpha-subunit D(alpha)3. These findings suggest a considerable complexity of the Drosophila nicotinic receptor system.
Journal of Biomedical Materials Research Part A, 2013
Large-diameter metal-on-metal (MoM) bearings evolved from the success of hip resurfacing. These i... more Large-diameter metal-on-metal (MoM) bearings evolved from the success of hip resurfacing. These implants were used in revision surgery in cases with well-fixed acetabular cups but loose or failed femoral stems, to avoid cup revision. Early data showed low rates of dislocation and potentially low wear profiles due to better fluid film lubrication. The risk of impingement was also thought to be low due to the increased head-neck ratio. Subsequently large-diameter MoM heads gained popularity in primary hip replacement. Recent data has emerged on the unacceptably high revision rates among patients with large-diameter MoM total hip arthroplasties (THAs), high blood levels of metal ions, and adverse tissue reactions. The head-neck (cone-taper) modular interface probably represents the weak link in large metal heads that have been used on conventional tapers. Increased torque of the large head, micromotion, and instability at the cone-taper interface, synergistic interactions between corrosion and wear, edge loading, low clearance, and psoas impingement are the likely causes for early failure of these prostheses.
International Journal of Legal Medicine, 2008
Intron 40 of the von Willebrand factor (vWF) gene exhibits a highly variable region of about 0.65... more Intron 40 of the von Willebrand factor (vWF) gene exhibits a highly variable region of about 0.65 kb, which contains 5 juxtaposed STRs. We sequenced 0.65 kb amplicons from 68 chromosomes and found 2 frequent indel polymorphisms and 5 SNPs. The 68 chromosomes investigated here presented a total of 47 different haplotypes. Regarding the SNP allele distribution in our sample, we arranged our results of the vWF intron 40 into a system of 3 haplotypes, i.e. haplotypes a, b and c. Our review may be valuable in further optimising vWF typing in forensic applications and in avoiding pitfalls. Further attempts to develop sophisticated techniques may soon enable haplotyping using autosomale STR clusters.
Clinical Orthopaedics and Related Research®, 2012
Metal-on-metal (MoM) THAs have reduced wear rates compared with metal-on-polyethylene. However, e... more Metal-on-metal (MoM) THAs have reduced wear rates compared with metal-on-polyethylene. However, elevated serum metal ion levels and pseudotumors have been reported in large MoM articulations. We therefore determined (1) if corrosion occurred at the cone/taper interface leading to instability in patients with large-diameter THAs; (2) how patients presented clinically and radiographically; (3) if adverse periprosthetic tissue reactions occurred; (4) whether metal was released from the implants into the periprosthetic tissues; and (5) if head size correlated with metal release. We reviewed 114 patients who had revisions of large-diameter head MoM articulations. Mean time of implantation was 46 months. To identify adverse reactions and particle load, tissues were stained by hematoxylin and eosin and CD3/CD20/CD68 antibodies. Periprosthetic tissues were analyzed for metal content and distribution in different regions. Electrochemical reactions between the stem and adapter were investigated by a minicell electrode. Electrochemical studies on the stem and the head adapter showed a risk for galvanic corrosion. Ninety-four percent of patients had instability at the cone/taper interface. All patients presented with early clinical symptoms; 59 patients had radiographic signs of loosening. One hundred four patients had foreign body reactions and necrosis. The largest amounts of metal released were titanium or iron. We found no correlation between head size and metal ion release. These findings suggest that in modular cone/taper connections, friction of the MoM articulations may cause failure of the cone/taper interface leading to galvanic corrosion and loosening. It is unclear whether the design of this MoM system provides sufficient stability at the taper.