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Clemens Sommer

Publications and source records attributed to Clemens Sommer.

29 records · Page 2Linked to original sources
PubMed2003

Characterization of gene expression profiles associated with glioma progression using oligonucleotide-based microarray analysis and real-time reverse transcription-polymerase chain reaction.

Diffuse astrocytoma of World Health Organization (WHO) grade II has an inherent tendency to spontaneously progress to anaplastic astrocytoma (WHO grade III) and/or glioblastoma (WHO grade IV). The molecular basis of astrocytoma progression is still poorly understood, in particular with respect to the progression-associated changes at the mRNA level. Therefore, we compared the transcriptional profile of approximately 6800 genes in primary WHO grade II gliomas and corresponding recurrent high-grade (WHO grade III or IV) gliomas from eight patients using oligonucleotide-based microarray analysis. We identified 66 genes whose mRNA levels differed significantly (P < 0.01, > or =2-fold change) between the primary and recurrent tumors. The microarray data were corroborated by real-time reverse transcription-polymerase chain reaction analysis of 12 selected genes, including 7 genes with increased expression and 5 genes with reduced expression on progression. In addition, the expression of these 12 genes was determined in an independent series of 43 astrocytic gliomas (9 diffuse astrocytomas, 10 anaplastic astrocytomas, 17 primary, and 7 secondary glioblastomas). These analyses confirmed that the transcript levels of nine of the selected genes (COL4A2, FOXM1, MGP, TOP2A, CENPF, IGFBP4, VEGFA, ADD3, and CAMK2G) differed significantly in WHO grade II astrocytomas as compared to anaplastic astrocytomas and/or glioblastomas. Thus, we identified and validated a set of interesting candidate genes whose differential expression likely plays a role in astrocytoma progression.

Adult↗
PubMed2003

Delayed manifestation of spinal metastasis: a special feature of hemangiopericytoma.

Metastatic hemangiopericytoma to the spine is rare, and operative management of these highly vascularized tumors is challenging. Review of the literature identified only seven previously reported cases. Metastases of hemangiopericytomas to the spine are diagnosed often only after a long delay following resection of the primary tumors. To emphasize the clinical and histopathological features of metastatic hemangiopericytoma to the spine and to review treatment options, a case of a delayed metastatic hemangiopericytoma to the cervicothoracic spine is reported: a 48-year-old woman presented with a large metastatic hemangiopericytoma to the cervicothoracic spine causing left-sided cervicobrachialgias and gait disturbance. Magnetic resonance imaging studies revealed a large left-sided dumbbell-shaped intraspinal and extraspinal tumor from C6 to T2. The patient underwent two-staged total removal of the cervicothoracic mass with posterior stabilization and subsequent radiotherapy. Histopathological findings revealed a malignant hemangiopericytoma which had identical features to the primary cranial meningeal tumor removed 8 years earlier. The radicular symptoms and the gait ataxia disappeared, postoperatively. One year later, however, new metastases were present. Patients with hemangiopericytoma should be controlled regularly for local recurrence and systemic tumor spread. The best available treatment for delayed metastasis to the spinal column is complete tumor removal followed by postoperative radiotherapy.

Brachial Plexus Neuritis↗
PubMed2002

Postischemic neuroprotection in the ischemia-tolerant state gerbil hippocampus is associated with increased ligand binding to inhibitory GABA(A) receptors.

Excitotoxic activation of glutamate receptors is thought to play a key role in delayed neuronal death (DND) of highly vulnerable hippocampal CA1 neurons after transient global ischemia. DND can be prevented by a short sublethal preconditioning (PC) stimulus. Recently, we demonstrated that ischemic PC, but not a single period of 5-min ischemia elicits a transient up-regulation of hippocampal [(3)H]muscimol binding to GABA(A) receptors. This indicates that activation of the GABAergic system may participate in the acquisition of neuroprotection. The present study was designed to test whether postischemic modulation of receptor binding also occurs in the ischemia-tolerant state, i.e., after a PC stimulus of 2.5-min ischemia and a subsequent normally lethal period of 5-min ischemia 4 days apart. Using receptor autoradiography, [(3)H]AMPA and [(3)H]muscimol binding to excitatory AMPA and inhibitory GABA(A) receptors was analyzed in hippocampal subfields CA1, CA3 and dentate gyrus at recirculation intervals of 30 min, 8, 24, 48, 96 h and 3 weeks. Postischemic hippocampal ligand binding to AMPA receptors remained unchanged at any time point investigated, but [(3)H]muscimol binding to GABA(A) receptors in CA1 neurons rendered tolerant to ischemia was up-regulated between 30 min and 48 h of recirculation. Our data suggest that a relative shift between excitatory and inhibitory neurotransmission may promote postischemic survival of CA1 neurons.

Animals↗
PubMed2002

Isolated sarcoid myopathy.

A 75-year-old housewife presented with a 5-year history of slowly progressive, painless limb weakness with wasting particularly of the pretibial muscles and without sensory involvement. She was otherwise healthy, but had a history of mild pulmonary sarcoidosis 20 years earlier. Abnormal laboratory findings included serum calcium (3.2 mmol/L; normal 2.15-2.6 mmol/L) and serum angiotensin-converting enzyme (ACE; 38.2 U/L; normal <22.5 U/L). All other laboratory investigations, including antibody studies and diagnostic work-up for systemic sarcoidosis, were negative. Muscle biopsy revealed noncaseating epitheloid granulomas, multinuclear giant cells, and lymphoplasmacellular infiltration. The patient was started on methylprednisolone and recovered to some extent. These findings represent a rare case of isolated sarcoid myopathy without concurrent systemic sarcoidosis.

Aged↗
PubMed2002

Intravascular lymphomatosis presenting with a conus medullaris syndrome mimicking disseminated encephalomyelitis.

We describe the clinical, radiologic, and postmortem findings of a 42-year-old man with intravascular lymphomatosis. The patient presented with a conus medullaris syndrome followed by progressive, disseminated spinal and cerebral symptoms. Disseminated encephalomyelitis was suspected due to the clinical, radiologic, and cerebrospinal fluid findings and the results of a stereotactic brain biopsy, all of which were compatible with inflammatory CNS disease. Treatment with methylprednisolone and cyclophosphamide led to a temporary remission of symptoms. The patient died 13 months after onset of symptoms. The diagnosis of disseminated intravascular lymphomatosis was established after death.

Adult↗
PubMed2002

Ischemia and ischemic tolerance induction differentially regulate protein expression of GluR1, GluR2, and AMPA receptor binding protein in the gerbil hippocampus: GluR2 (GluR-B) reduction does not predict neuronal death.

BACKGROUND AND PURPOSE: Postischemic delayed neuronal death (DND) of hippocampal CA1 neurons has been suggested to occur as a result of formation of calcium-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors lacking the GluR2 subunit (GluR2 hypothesis). DND can be prevented by a short tolerance-inducing ischemic period. The present study was designed to assess whether postischemic protein levels of GluR2 predict neuronal death. Additionally, the role of AMPA receptor binding protein (ABP) was investigated with respect to neuronal death or survival. METHODS: Postischemic protein expression of GluR1, GluR2, and ABP was analyzed in 3 experimental paradigms of transient global ischemia with the use of subunit-specific antisera and semiquantitative densitometric evaluation. Gerbils were subjected (1) to a 5-minute ischemic period resulting in DND of CA1 neurons; (2) to a 2.5-minute period of ischemia mediating tolerance induction; and (3) to 5 minutes of ischemia in the ischemia-tolerant state (2.5+5 minutes of ischemia 4 days apart). RESULTS: The major finding was that GluR2 protein levels were significantly downregulated in neuronal subpopulations destined to survive, ie, in CA1 principal neurons after ischemic tolerance induction and in the ischemia-tolerant state, as well as in CA3 neurons after a 5-minute period of ischemia. ABP expression remained unaffected. CONCLUSIONS: Our results modify the GluR2 hypothesis in that postischemic GluR2 reduction also occurs in hippocampal CA1 and CA3 principal neurons without subsequent neuronal death. ABP is obviously not involved in mechanisms of DND or ischemic tolerance induction.

Animals↗
PubMed2002

[3H]muscimol binding to gamma-aminobutyric acid(A) receptors is upregulated in CA1 neurons of the gerbil hippocampus in the ischemia-tolerant state.

BACKGROUND AND PURPOSE: Excitotoxic activation of glutamate receptors is currently thought to play a pivotal role in delayed neuronal death (DND) of highly vulnerable CA1 neurons in the gerbil hippocampus after transient global ischemia. Postischemic degeneration of these neurons can be prevented by "preconditioning" with a short sublethal ischemic stimulus. The present study was designed to test whether ischemic preconditioning is associated with specific alterations of ligand binding to excitatory glutamate and/or inhibitory gamma-aminobutyric acid (GABA)A receptors compared with ischemia severe enough to induce DND. METHODS: With the use of quantitative receptor autoradiography, postischemic ligand binding of [3H]MK-801 and [3H]alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) to excitatory N-methyl-D-aspartate (NMDA) and AMPA receptors as well as [3H]muscimol to inhibitory GABA(A) receptors in hippocampal subfields CA1, CA3, and the dentate gyrus were analyzed in 2 experimental paradigms. Gerbils were subjected to (1) a 5-minute ischemic period resulting in DND of CA1 neurons and (2) a 2.5-minute period of ischemia mediating tolerance induction. RESULTS: [3H]MK-801 and [3H]AMPA binding values to excitatory NMDA and AMPA receptors showed a delayed decrease in relatively ischemia-resistant CA3 and dentate gyrus despite maintained neuronal cell density. [3H]Muscimol binding to GABA(A) receptors in CA1 neurons was transiently but significantly increased after preconditioning but not after global ischemia with consecutive neuronal death. CONCLUSIONS: Downregulation of ligand binding to glutamate receptors in relatively ischemia-resistant CA3 and dentate gyrus neurons destined to survive suggests marked synaptic reorganization processes despite maintained structural integrity. More importantly, upregulation of binding to inhibitory GABA(A) receptors in the hippocampus indicates a relative shift between inhibitory and excitatory neurotransmission that we suggest may participate in endogenous postischemic neuroprotection.

Animals↗
PubMed2000

Long-term TGFbeta2 protein expression in heterotopic cortical grafts located in the rat striatum.

Purpose: Transforming growth factor beta 2 (TGFbeta2) is a multifunctional cytokine thought to play a crucial role in neuronal growth, differ-entiation and survival. In the cortex of adult rats, TGFbeta2 is constitutively expressed in a subset of neurons and astrocytes. In the present study we analyzed whether TGFbeta2 is also present in intrastriatal transplants of cortical anlage. In addition we investigated the temporo-spatial expression pattern of TGFbeta2 in the surrounding host striatum. Methods: Cortical primordia of rat fetuses (E14) were stereotactically grafted into the rostral striatum of adult recipient rats. Grafts were allowed to differentiate for 1, 2, 3, 4, 8 weeks or one year, respectively, followed by morphological and immunohistochemical analysis. Results: From week 2 on, TGFbeta2-immunoreactivity (IR) was detectable in transplanted neurons. Within the graft, GFAP-IR was already present one week after transplantation, whereas TGFbeta2-immunostained astrocytes were first seen after 2 weeks. One year after transplanta-tion, TGFbeta2 positive neurons and astrocytes were still present. In the host striatum and at the graft-host interface an increase of TGFbeta2-immu-noreactive astrocytes first occured after one week both in grafted animals and in sham-operated (lesioning without grafting) rats. Conclusions: Our data suggest that at least a subpopulation of transplanted neurons develops a phenotype as cortical neurons in situ with respect to TGFbeta2 expression. Upregulation of astrocytic TGFbeta2 expression within the graft, however, is due to the trauma imposed by the transplantation procedure rather than an intrinsic differentiation program of co-grafted astrocytes.

Journal Article↗
PubMed1998

Lymphocytic Hypophysitis: Light and Electron Microscopic Findings and Correlation to Clinical Appearance.

Light and electron microscopic findings of six cases of lymphocytic hypophysitis of a collective of 2500 surgical specimens are presented. Five cases were obtained by surgery, one case was obtained from autopsy. Light microscopy revealed an infiltration of mature lymphocytes and plasma cells in the interstitium, partly in the acini, as well as in the posterior lobe and the capsule. The structure of the remaining anterior lobe was normal. The final stage of lymphocytic hypophysitis is fibrosis, which was seen in all cases to varying degrees. The infiltrate consisted mainly of Tiymphocytes, being positive for CK 45 RO and CD 43. Immunocytochemical staining revealed different proportions of residual adenohypophyseal cells. Mainly prolactin reactive cells were observed as were growth hormone reactive cells. By electron microscopy some ruptured acini and damaged adenohypophyseal cells could be seen. Few pituitary cells contained enlarged lysosomal bodies or oncocytic changes. lnflammation causing enlargement of the pituitary leads to patients often being operated under the preoperative diagnosis of a tumor of the sellar region. It is important to identify this special type of hypophysitis, as a different course of treatment is required.

Journal Article↗
PubMedDate not supplied

Does permanent carotid artery occlusion produce a 'preconditioning-like' effect towards more severe hypotension in energy metabolites? Role of cerebral adenosine.

1. The aim of the present study was to investigate the potential energy preserving effect of permanent bilateral common carotid artery occlusion (BCCAO) towards additional systemic hypotension of severe duration (30 min). In addition, the role of adenosine A1 receptors in cerebral ischaemic preconditioning was investigated in male Wistar rats. Thus, oligaemic rats were assigned randomly to continuous treatment with the adenosine A1 receptor agonist 2-chloro-N6-cyclopentyladenosine (CCPA) or the adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dimethylxanthine (CPT), receiving daily intraperitoneal infusions of 0.1 mg/kg bodyweight CCPA or CPT or placebo (200 microL aqueous 2-hydropropyl-beta-cyclodextrin) at a delivery rate of 0.5 microL/h over 14 days. 2. Haemodynamic parameters and arterial blood gases were monitored. Rat cortical energy metabolites ATP, ADP, AMP, phosphocreatine and adenosine were measured using HPLC techniques. Adenosine A1 receptor expression was determined by immunhistochemistry and quantified by western blotting. 3. Two weeks of permanent BCCAO induced an 'energy saving' effect in rat cortical ATP concentrations. Under subchronic conditions, significant increases were detected in ADP and AMP concentrations after CCPA compared with placebo. Because similar changes were also seen after CPT, this adenosine A1 receptor-mediated effect does not seems to be specific. Furthermore, no differences in adenosine A1 receptor expression could be detected. 4. Adenosine was not specifically involved in the 'preconditioning-like' effect via the modulation of the adenosine A1 receptor in the present oligaemia model. Obviously, adenosine A1 receptor-specific effects after delayed cerebral ischaemic preconditioning do not seem to play an essential role if BCCAO is followed by a prolonged additional severe ischaemic event.

Adenine Nucleotides↗