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B Sommer

Publications and source records attributed to B Sommer.

At least 19 recordsLinked to original sources
PubMed1999

Cerebral amyloid induces aberrant axonal sprouting and ectopic terminal formation in amyloid precursor protein transgenic mice.

A characteristic feature of Alzheimer's disease (AD) is the formation of amyloid plaques in the brain. Although this hallmark pathology has been well described, the biological effects of plaques are poorly understood. To study the effect of amyloid plaques on axons and neuronal connectivity, we have examined the axonal projections from the entorhinal cortex in aged amyloid precursor protein (APP) transgenic mice that exhibit cerebral amyloid deposition in plaques and vessels (APP23 mice). Here we report that entorhinal axons form dystrophic boutons around amyloid plaques in the entorhinal termination zone of the hippocampus. More importantly, entorhinal boutons were found associated with amyloid in ectopic locations within the hippocampus, the thalamus, white matter tracts, as well as surrounding vascular amyloid. Many of these ectopic entorhinal boutons were immunopositive for the growth-associated protein GAP-43 and showed light and electron microscopic characteristics of axonal terminals. Our findings suggest that (1) cerebral amyloid deposition has neurotropic effects and is the main cause of aberrant sprouting in AD brain; (2) the magnitude and significance of sprouting in AD have been underestimated; and (3) cerebral amyloid leads to the disruption of neuronal connectivity which, in turn, may significantly contribute to AD dementia.

Amyloid beta-Protein Precursor↗
PubMed1999

Importance of AMPA receptors for hippocampal synaptic plasticity but not for spatial learning.

Gene-targeted mice lacking the L-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor subunit GluR-A exhibited normal development, life expectancy, and fine structure of neuronal dendrites and synapses. In hippocampal CA1 pyramidal neurons, GluR-A-/- mice showed a reduction in functional AMPA receptors, with the remaining receptors preferentially targeted to synapses. Thus, the CA1 soma-patch currents were strongly reduced, but glutamatergic synaptic currents were unaltered; and evoked dendritic and spinous Ca2+ transients, Ca2+-dependent gene activation, and hippocampal field potentials were as in the wild type. In adult GluR-A-/- mice, associative long-term potentiation (LTP) was absent in CA3 to CA1 synapses, but spatial learning in the water maze was not impaired. The results suggest that CA1 hippocampal LTP is controlled by the number or subunit composition of AMPA receptors and show a dichotomy between LTP in CA1 and acquisition of spatial memory.

Action Potentials↗
PubMed1999

NGD 94-1 as an agonist at human recombinant dopamine D4.4 receptors expressed in HEK293 cells.

The atypical antipsychotic, clozapine has some selectivity for dopamine D4 receptors and is a silent antagonist at these receptors. NGD 94-1 (2-phenyl-4(5)-[4-(2-pyrimidinyl)-piperazin-1-yl-methyl]-imidazole ) is a highly selective dopamine D4 receptor ligand recently introduced as a putative antipsychotic mimicking the dopamine D4 receptor antagonist effects of clozapine. We show that NGD 94-1 is not silent. It behaved as an agonist in human embryonic kidney 293 cells expressing human recombinant dopamine D4.4 receptors. This questions the clinical use of NGD 94-1.

Cells, Cultured↗
PubMed1999

[Tumescent technique for local anesthesia. Use and prospectives of aa new anesthetic method].

The tumescent technique for local anesthesia (TLA) involves the infiltration of the subcutaneous fatty tissue with a large volume of a diluted local anesthetic. This large added volume increases the tension in the tissue, creating more favorable conditions for the action of the analgesic and for dermatological operative measures. Originally developed for use in the area of liposuction, TLA has since proved to have advantages over other forms of analgesia in numerous other dermatological indications. Overall, TLA is an effective and practical analgesic technique associated with comparatively few side effects that has been shown to be very useful in surgery of the skin.

Adipose Tissue↗
PubMed1999

Efficient gene transfer into normal human skeletal cells using recombinant adenovirus and conjugated adenovirus-DNA complexes.

In order to assess efficient DNA gene transfer into human primary cell cultures derived from the skeleton we tested two viral-based procedures. First, replication-deficient recombinant adenoviruses (ADV) were used to infect post-confluent human marrow stromal fibroblasts (HMSF) and human trabecular bone (HTB) cells. Both cell types were readily infected by modified adenoviral vectors carrying a reporter gene making this virus an attractive candidate to facilitate DNA gene transfer. In a second approach we coincubated DNA with ADV that had polylysine (PLL) covalently attached. With this ADV/PLL/DNA complex, very efficient gene transfer into multilayered HMSF and HTB cell cultures was observed, and DNA coincubated with unmodified ADV failed to be effectively transferred. These data imply that the covalently bound PLL more effectively binds exogenous DNA, resulting in a highly efficient internalization event in both cell types. Thus, this latter method has many advantages over conventional ADV gene transfer procedures. It is simple, rapid, and it does not require engineering of DNA into the viral genome, thereby allowing transfer of large fragments of DNA.

Adenoviridae↗
PubMed1999

Association of microglia with amyloid plaques in brains of APP23 transgenic mice.

Microglia are a key component of the inflammatory response in the brain and are associated with senile plaques in Alzheimer's disease (AD). Although there is evidence that microglial activation is important for the pathogenesis of AD, the role of microglia in cerebral amyloidosis remains obscure. The present study was undertaken to investigate the relationship between beta-amyloid deposition and microglia activation in APP23 transgenic mice which express human mutated amyloid-beta precursor protein (betaPP) under the control of a neuron-specific promoter element. Light microscopic analysis revealed that the majority of the amyloid plaques in neocortex and hippocampus of 14- to 18- month-old APP23 mice are congophilic and associated with clusters of hypertrophic microglia with intensely stained Mac-1- and phosphotyrosine-positive processes. No association of such activated microglia was observed with diffuse plaques. In young APP23 mice, early amyloid deposits were already of dense core nature and were associated with a strong microglial response. Ultrastructurally, bundles of amyloid fibrils, sometimes surrounded by an incomplete membrane, were observed within the microglial cytoplasm. However, microglia with the typical characteristics of phagocytosis were associated more frequently with dystrophic neurites than with amyloid fibrils. Although the present observations cannot unequivocally determine whether microglia are causal, contributory, or consequential to cerebral amyloidosis, our results suggest that microglia are involved in cerebral amyloidosis either by participating in the processing of neuron-derived betaPP into amyloid fibrils and/or by ingesting amyloid fibrils via an uncommon phagocytotic mechanism. In any case, our observations demonstrate that neuron-derived betaPP is sufficient to induce not only amyloid plaque formation but also amyloid-associated microglial activation similar to that reported in AD. Moreover, our results are consistent with the idea that microglia activation may be important for the amyloid-associated neuron loss previously reported in these mice.

Animals↗
PubMed1999

Receptor density as a factor governing the efficacy of the dopamine D4 receptor ligands, L-745,870 and U-101958 at human recombinant D4.4 receptors expressed in CHO cells.

1. The relationships between the density of dopamine D4.4 receptors and the agonist efficacies of L-745,870 (3-(4-[4-chlorophhenyl]piperazin-1-yl)-methyl-1H-pyrrolo [2, 3-b]pyridine) and U-101958 ((1-benzyl-piperidin-4-yl)-(3-isopropoxy-pyridin-2-yl)-methyl-a min e) were investigated in Chinese hamster ovary (CHO) cells, after treatment with the gene expression enhancer, sodium butyrate. 2. In CHO cells expressing D4.4 receptors (CHO/D4 cells), dopamine inhibited forskolin-stimulated cyclic AMP accumulation (Emax 56+/-1% inhibition, pEC50 7.4+/-0.1, n=10). U-101958 behaved as a partial agonist (39+/-7% the efficacy of dopamine, pEC50 8.1+/-0.3, n=4), whereas L-745,870 had no detectable agonist effect. 3. Receptor density, as estimated by [3H]-spiperone saturation binding was 240+/-30 fmol mg-1 protein (n=8) in CHO/D4 cell homogenates. It reached 560+/-150 (n=6), 1000+/-190 (n=4) and 840+/-120 (n=4) fmol mg-1 protein after treatment with sodium butyrate (5 mM) for 6, 18 and 48 h, respectively. 4. The increase in receptor density was associated with a gradual enhancement of the agonist effects (increased Emax and pEC50 values) of dopamine. The efficacy of U-101958 (relative to dopamine) doubled and L-745,870 was turned into a partial agonist (efficacy 49% relative to dopamine, pEC50 8. 6+/-0.2, n=6, after 48 h treatment with sodium butyrate). These agonist effects of U-101958 and L-745,870 could be antagonized by spiperone (0.1 microM) but not by raclopride (10 microM). 5. The results show that U-101958 and L-745,870 are partial agonists at human dopamine D4.4 receptors expressed in CHO cells. Their efficacy is governed by receptor density. Agonist effects of these two compounds in vivo cannot be excluded under circumstances of increased receptor levels.

Aminopyridines↗
PubMed1999

Brain-derived neurotrophic factor exerts opposing effects on beta2-adrenergic receptor according to depolarization status of cerebellar neurons.

To investigate the molecular mechanisms underlying brain-derived neurotrophic factor (BDNF)-controlled synaptic plasticity, we studied beta2-adrenergic receptor (beta2-AR) expression in cultured cerebellar granule cells. We show that, depending on the state of depolarization, BDNF exerts opposite effects on beta2-AR expression. In neurons maintained in low K+ medium (5 mM K+) that will enter apoptosis, BDNF increases beta2-AR and beta2-AR transcripts. In contrast, in depolarized neurons (high K+ medium, 25 mM K+) BDNF represses beta2-AR expression. The use of reporter genes (driven by the beta2-AR promoter or restricted regulatory elements) revealed that BDNF exerts its opposite effects at the transcriptional level by recruiting a cyclic AMP response element (CRE) and the trans-acting factor CRE binding protein. These results provide the first evidence that a neurotrophin, e.g., BDNF, may exert an opposite effect on receptor expression and function (beta2-AR) according to the depolarization status of the neuron. Based on this finding, we propose that BDNF not only mediates neuronal survival, but is also involved in the modulation of the general sensitivity of the neuron to external signals, thus maintaining its optimal functional integration within the neuronal network.

Animals↗
PubMed1999

Expression and signaling of group I metabotropic glutamate receptors in astrocytes and microglia.

Stimulation of astrocytes with the excitatory neurotransmitter glutamate leads to the formation of inositol 1,4,5-trisphosphate and the subsequent increase of intracellular calcium content. Astrocytes express both ionotropic receptors and metabotropic glutamate (mGlu) receptors, of which mGlu5 receptors are probably involved in glutamate-induced calcium signaling. The mGlu5 receptor occurs as two splice variants, mGlu5a and mGlu5b, but it was hitherto unknown which splice variant is responsible for the glutamate-induced effects in astrocytes. We report here that both mRNAs encoding mGlu5 receptor splice variants are expressed by cultured astrocytes. The expression of mGlu5a receptor mRNA is much stronger than that of mGlu5b receptor mRNA in these cells. In situ hybridization experiments reveal neuronal expression of mGlu5b receptor mRNA in adult rat forebrain but a strong neuronal expression of mGlu5a mRNA only in olfactory bulb. Signals for mGlu5a receptor mRNA in the rest of the brain were diffuse and weak but consistently above background. Activation of mGlu5 receptors in astrocytes yields increases in inositol phosphate production and transient calcium responses. It is surprising that the rank order of agonist potency [quisqualate > (2S,1 'S,2'S)-2-(carboxycyclopropyl)glycine = trans-(1S,3R)-1-amino-1,3-cyclopentanedicarboxylic acid (1S,3R-ACPD) > glutamate] differs from that reported for recombinantly expressed mGlu5a receptors. The expression of mGlu5a receptor mRNA and the occurrence of 1S,3R-ACPD-induced calcium signaling were found also in cultured microglia, indicating for the first time expression of mGlu5a receptors in these macrophage-like cells.

Animals↗
PubMed1999

Tumescent liposuction in Germany: history and new trends and techniques.

Due to the developments and changes of tumescent solution, infiltration technique, and cannulas, we perform tumescent liposuction today using up to 6-8 l tumescent solution. Total aspirate measures up to 9 l, pure fat aspired up to 5 l. Tumescent liposuction of extended areas can still be done as an outpatient procedure. The condition of patients intra- and postoperatively as well as results has improved and the predictability of outcome is more certain.

Germany↗
PubMed1999

Sociodemographic profile and satisfaction with treatment of patients undergoing liposuction in tumescent local anesthesia.

OBJECTIVE: To assess patient satisfaction with liposuction in tumescent local anesthesia (TLA) and to define a patient profile regarding sociodemographic data. METHODS: Three hundred randomly selected patients were asked by mail to complete a standardized questionnaire on aesthetic dermatology and cosmetic surgery 3-25 months after liposuction. The 64 items addressed treatment satisfaction, treatment effects on body, social, and professional life as well as self-confidence, body feeling, and social contacts. RESULTS: One hundred fifty-nine (53.0%) of 300 patients returned complete questionnaires. Ninety-two percent of the patients were female and the mean age was 45.3 +/- 11.8 years. The mean body mass index (BMI) was 24.5 +/- 3.7, and 61.7% of the patients had a normal BMI. Satisfaction with the liposuction was high (about 85% mostly or completely satisfied). The procedure was regarded by most patients as a nonstressful event (>80%). About 40% reported positive effects on social life, about 91% on body feeling, 57% on attractiveness, and 20% on their profession. CONCLUSION: Liposuction in TLA is a satisfying and well-tolerated treatment for most patients.

Adult↗
PubMed1999

Transgenic animals in Alzheimer's disease research.

Alzheimer's disease (AD) is a neurodegenerative disorder of the brain accounting for about 50-70% of the typical late onset cases of dementia. The pathological and diagnostic hallmarks of the disease are principally the presence of extracellular deposits called neuritic amyloid plaques and the intracellular aggregation of neurofibrillary tangles. In addition selective neuronal cell loss accompanied by cerebrovascular amyloidosis is detectable. In the case of familial AD, defects in at least three different genes (APP, PS1, PS2) leading to indistinguishable pathology are now well defined. There is as yet no real treatment for AD. Therefore the availability of an easily manipulable animal model is crucial for the development of new drugs, which could slow down or, even better, stop the progression of the disease. The development and originality of such experimental models that could greatly facilitate the investigation of the aetiology and pathogenesis of AD are described and discussed in this review. They are based mainly on the attempt to reproduce the neurofibrillary tangles or the amyloid deposits and plaque formation.

Alzheimer Disease↗
PubMed1999

(R,S)-4-phosphonophenylglycine, a potent and selective group III metabotropic glutamate receptor agonist, is anticonvulsive and neuroprotective in vivo.

Group III metabotropic glutamate receptors (mGluRs) are thought to modulate neurotoxicity of excitatory amino acids, via mechanisms of presynaptic inhibition, such as regulation of neurotransmitter release. Here, we describe (R,S)-4-phosphonophenylglycine (PPG) as a novel, potent, and selective agonist for group III mGluRs. In recombinant cell lines expressing the human receptors hmGluR4a, hmGluR6, hmGluR7b, or hmGluR8a, EC50 values for (R,S)-PPG of 5.2 +/- 0.7 microM, 4.7 +/- 0.9 microM, 185 +/- 42 microM, and 0.2 +/- 0.1 microM, respectively, were measured. The compound showed EC50 and IC50 values of >/=200 microM at group I and II hmGluRs and was inactive at cloned human N-methyl-D-aspartate, alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate, and kainate receptors (>300 microM). On the other hand, it showed micromolar affinity for a Ca2+/Cl--dependent L-glutamate binding site in rat brain, similar to other phosphono-substituted amino acids like L-2-amino-4-phosphonobutyrate. In cultured cortical neurons, (R, S)-PPG provided protection against a toxic pulse of N-methyl-D-aspartate (EC50 = 12 microM), which was reversed by the group III mGluR antagonist (R,S)-alpha-methylserine-O-phosphate but not by the group II antagonist (2S)-alpha-ethylglutamate. Moreover, (R,S)-PPG protected against N-methyl-D-aspartate- and quinolinic acid-induced striatal lesions in rats and was anticonvulsive in the maximal electroshock model in mice. In contrast to the group III mGluR agonists L-2-amino-4-phosphonobutyrate and L-serine-O-phosphate, (R,S)-PPG showed no proconvulsive effects (2200 nmol i.c.v.). These data provide novel in vivo evidence for group III mGluRs as attractive targets for neuroprotective and anticonvulsive therapy. Also, (R,S)-PPG represents an attractive tool to analyze the roles of group III mGluRs in nervous system physiology and pathology.

Animals↗
PubMed1998

Destabilization of beta-catenin by mutations in presenilin-1 potentiates neuronal apoptosis.

Mutations of the presenilin-1 gene are a major cause of familial early-onset Alzheimer's disease. Presenilin-1 can associate with members of the catenin family of signalling proteins, but the significance of this association is unknown. Here we show that presenilin-1 forms a complex with beta-catenin in vivo that increases beta-catenin stability. Pathogenic mutations in the presenilin-1 gene reduce the ability of presenilin-1 to stabilize beta-catenin, and lead to increased degradation of beta-catenin in the brains of transgenic mice. Moreover, beta-catenin levels are markedly reduced in the brains of Alzheimer's disease patients with presenilin-1 mutations. Loss of beta-catenin signalling increases neuronal vulnerability to apoptosis induced by amyloid-beta protein. Thus, mutations in presenilin-1 may increase neuronal apoptosis by altering the stability of beta-catenin, predisposing individuals to early-onset Alzheimer's disease.

Adenomatous Polyposis Coli Protein↗
PubMed1998

[Calculation accuracy of volumes for evaluating dose-volume histograms. Comparison of various radiation planning systems].

BACKGROUND: Modern 3-dimensional treatment planning systems on the basis of sectional imaging allow the calculation of volumes for organs of interest. The aim of this study is to investigate systematically the accuracy of calculations of volumes by the use of a phantom for 4 different treatment planning systems. MATERIAL AND METHOD: The tests were done with a phantom with 5 cylindrical structures and 6 spherical shaped structures. After performing a CT-scan and reading the data into the planning systems the structures were contoured and the volumes were calculated in order to compare these values with the values calculated by mathematical equations. This was systematically done as a function of different parameters. RESULTS: Comparing different methods of contouring showed notable influence on the result. Parameters as number of calculation points or length of cylinders showed no significant differences. In summary, the mean deviations for cylinders were +7% for system A, -2% for B, -17% for C, and 0% for D. For larger spheres (radii between 5 and 2.5 cm) the mean deviations were -5% for A, +3% for B, +1% for C, and +5% for D. For smaller spheres (radii between 1.75 and 1.25 cm) the mean deviations were -14% for A, -2% for B, -10% for C, and -4% for D. CONCLUSION: Verifying results of planning systems is important for the daily routine, but it has to be taken into account, that small changes of the radius of a cylinder or sphere cause substantial volume changes. The differences are also caused by inaccuracies of the whole procedure, e.g., the CT study, the shape and dimensions of the cylinders and the spheres and the CT information and the delineariation of the structures.

Dose-Response Relationship, Radiation↗
PubMed1998

Involvement of different Ca2+ pools during the canine bronchial sustained contraction in Ca2+-free medium: lack of effect of PKC inhibition.

We evaluated the role of protein kinase C (PKC) in the sustained bronchial contraction (SBC) induced by carbachol (Cch) or histamine in a Ca2+-free medium and the possibility that each agonist uses a different Ca2+ store for this response. We studied third-order bronchi and airway smooth muscle (ASM) from first-order bronchi dissected free of cartilage and epithelium. Bronchial and ASM responsiveness to Cch or histamine were evaluated in Krebs solution (2.5 mM Ca2+) and in Ca2+-free medium. Cch and histamine induced an SBC in bronchial tissues in Ca2+-free medium. In ASM each agonist produced a transient contraction, but the response to histamine was much smaller. Cch induced a concentration-dependent accumulation of inositol phosphates (IPs) in both bronchi and ASM; however, histamine did not induce significant accumulation of IPs. Repeated exposure to histamine in bronchial rings abolished contractile responses in Ca2+-free media, but Cch added afterwards still produced a sustained contraction. This response was blocked when bronchial tissues were preincubated with 10 microM cyclopiazonic acid (CPA). Brief incubation of these preparations with a high EGTA concentration (1 mM) abolished the histamine-induced SBC. The SBC induced by Cch or histamine in Ca2+-free medium was not affected by the preincubation of the tissues with calphostin C, chelerythrine or staurosporine. We concluded that Cch mobilizes Ca2+ from two different sources during the SBC in Ca2+-free medium: from a CPA-sensitive one from sarcoplasmic reticulum (SR) and from a putative extracellular membrane Ca2+ pool sensitive to 1 mM EGTA, and neither process involved PKC activation. Histamine appeared to utilize the extracellular membrane pool only.

Animals↗