Biomedical subjects

D Troost

Publications and source records attributed to D Troost.

At least 19 recordsLinked to original sources

PubMed2007

Differential expression patterns of chloride transporters, Na+-K+-2Cl--cotransporter and K+-Cl--cotransporter, in epilepsy-associated malformations of cortical development.

Malformations of cortical development are recognized causes of chronic medically intractable epilepsy. An increasing number of observations suggests an important role for cation-chloride co-transporters (CCTs) in controlling neuronal function. Deregulation of their expression may contribute to the mechanisms of hyperexcitability that lead to seizures. In the present study the expression and cell-specific distribution of Na+-K+-2Cl--cotransporter (NKCC1) and K+-Cl--cotransporter (KCC2) were studied immunocytochemically in different developmental lesions, including focal cortical dysplasia (FCD) type IIB (n=9), hemimegalencephaly (HMEG, n=6) and ganglioglioma (GG, n=9) from patients with medically intractable epilepsy and in age-matched controls. In normal control adult cortex, NKCC1 displayed low neuronal and glial expression levels. In contrast KCC2 showed strong and diffuse neuropil staining. Notable glial immunoreactivity (IR) was not found for KCC2. NKCC1 was highly expressed in the majority of FCD, HMEG and GG specimens. NKCC1 IR was observed in neurons of different size, including large dysplastic neurons, in balloon cells (in FCD and HMEG cases) and in glial cells with astrocytic morphology. The immunoreactivity pattern of KCC2 in FCD, HMEG and GG specimens was characterized by less neuropil staining and more intrasomatic IR compared with control. KCC2 IR was observed in neurons of different size, including large dysplastic neurons, but not in balloon cells or in glial cells with astrocytic morphology. Double-labeling experiments confirmed the differential cellular distribution of the two CCTs and their expression in GABA(A) receptor (alpha1 subunit)-positive dysplastic neurons. The cellular distribution of CCTs, with high expression of NKCC1 in dysplastic neurons and altered subcellular distribution of KCC2 resembles that of immature cortex and suggests a possible contribution of CCTs to the high epileptogenicity of malformations of cortical development.

Adolescent↗

PubMed2006

Local recurrence and distant metastasis of supratentorial primitive neuro-ectodermal tumor in an adult patient successfully treated with intensive induction chemotherapy and maintenance temozolomide.

Supratentorial primitive neuro-ectodermal tumors (PNET) in adults are very rare. Extraneural metastasis are unusual and the optimal palliative chemotherapy regimen is not established. We present a 26-year-old patient with local recurrence and distant metastasis of supratentorial PNET successfully treated with intensive induction chemotherapy and maintenance temozolomide.

Adult↗

PubMed2006

The IL-1beta system in epilepsy-associated malformations of cortical development.

Focal cortical dysplasia (FCD) and glioneuronal tumors (GNT) are recognized causes of chronic intractable epilepsy. The cellular mechanism(s) underlying their epileptogenicity remain largely unknown. Compelling evidence in experimental models of seizures indicates an important role of interleukin (IL)-1beta in the mechanisms of hyperexcitability leading to the occurrence of seizures. We immunocytochemically investigated the brain expression and cellular distribution pattern of IL-1beta, IL-1 receptor (IL-1R) types I and II and IL-1R antagonist (IL-1Ra) in FCD and GNT specimens, and we correlate these parameters with the clinical history of epilepsy in patients with medically intractable seizures. In normal control cortex, and in perilesional regions with histologically normal cortex, IL-1beta, IL-1Rs and IL-1Ra expression was undetectable. In all FCD and GNT specimens, IL-1beta and its signalling receptor IL-1RI were highly expressed by more than 30% of neurons and glia whereas the decoy receptor IL-RII and IL-Ra were expressed to a lesser extent by approximately 10% and 20% of cells, respectively. These findings show a high expression of IL-1beta and its functional receptor (IL-1RI) in FCD and GNT specimens together with a relative paucity of mechanisms (IL-1RII and IL-1Ra) apt to inactivate IL-1beta actions. Moreover, the number of IL-1beta- and IL-1RI-positive neurons was positively correlated with the frequency of seizures, whereas the number of IL-1Ra-positive neurons and astroglial cells was negatively correlated with the duration of epilepsy prior to surgery. The expression of IL-1beta family members in these developmental lesions may contribute to their intrinsic and high epileptogenicity, thus possibly representing a novel target for antiepileptic strategies.

Adolescent↗

PubMed2006

Evidence of activated microglia in focal cortical dysplasia.

Focal cortical dysplasia (FCD), which is caused by malformations of cortical development, is known to be a major cause of intractable epilepsy. Cortical laminar disorganization and the presence of abnormal neuronal and astroglial cell types are histological characteristics of FCD. Though, little information is known about the microglia/macrophage cell system in FCD and its possible contribution to the high epileptogenesis of this disorder. In the present study, the distribution of cells of the microglia/macrophage lineage was studied in 20 specimens of FCD (type II) by immunocytochemistry for CD68 and human HLA-DR. A significant number of microglial cells and macrophages were observed within the dysplastic cortex. The mean number of CD68- and HLA-DR-positive cells was significantly higher in FCD specimens than in normal-appearing control cortex obtained at autopsy. HLA-DR-positive cells, which represent activated microglia, were localized around blood vessels and also clustered around dysplastic neuronal cells. The density of these activated HLA-DR-positive microglial cells correlated with the duration of epilepsy, as well as with the frequency of seizures prior to surgical resection. CD68-positive macrophages were mainly located around vessels and the number of these cells did not correlate with seizure frequency, neither with the duration of symptoms prior to surgical resection. In conclusion, our findings demonstrate a specific and persistent increase in the numerical density of HLA-DR-positive activated microglia within the dysplastic region, supporting the contribution of the inflammatory response and proinflammatory molecules to the epileptogenicity of FCD.

Adolescent↗

PubMed2005

Congenital disorder of glycosylation type Ia: a clinicopathological report of a newborn infant with cerebellar pathology.

Congenital disorders of glycosylation (CDG) represent a newly delineated group of inherited multisystem disorders characterized by defective glycoprotein biosynthesis. In the present study we report and discuss the clinical and neuropathological findings in a newborn with CDG type Ia (CDG-Ia). The patient presented mild dysmorphic facial features, inverted nipples, progressive generalized edema, hypertrophic cardiomyopathy, hepatosplenomegaly, muscular hypotonia and had severe hypoalbuminemia. Deficiency of phosphomannomutase (PMM)-2 activity was detected. Molecular analysis showed V231M/T237R mutations of the PMM2 gene. Muscular biopsy, disclosed myopathic alterations with myofibrillar disarray by electron microscopy. The patient died at 1 month of age of circulatory and respiratory failure. Autopsy showed liver fibrosis and renal abnormalities. Neuropathological abnormalities were mainly confined to the cerebellum. Histological and immunocytochemical examination of cerebellar tissue showed partial atrophy of cerebellar folia with severe loss of Purkinje cells, granular cell depletion and various morphological changes in the remaining Purkinje cells and their dendritic arborization. Autopsy findings confirm the complexity of the CDG-Ia syndrome, and indicate that CDG-Ia is a distinct disease entity, which can be differentiated from other neurological disorders and other types of CDG, not only clinically, but also based on unique pathological findings. The data proved useful in determining the underlying disease process associated with a defective N-glycosylation pathway.

Arginine↗

PubMed2005

Expression patterns of Group III metabotropic glutamate receptors mGluR4 and mGluR8 in multiple sclerosis lesions.

Recent evidence supports a role for metabotropic glutamate receptors (mGluRs) in neuroinflammatory diseases. In the present study, we have investigated whether the group III mGluR subtypes mGluR4 and mGluR8 are expressed in MS lesions at various stages of evolution. In control patient tissue and in normal-appearing MS white matter (NAWM), no microglial or astrocyte staining was detected. In contrast, in active lesions, mGluR8 immunoreactivity (IR) was detected in cells of the microglia/macrophage lineage. Fewer macrophage-like cells were positive for mGluR8 in chronic active and inactive lesions. No mGluR4 IR was detected in cells of the microglia/macrophage lineage in the MS lesions studied. In chronic active lesions, however, a population of reactive astrocytes localized in the rim of the lesions expressed both mGluR4 and mGluR8. Our results suggest a role for these receptor subtypes in the inflammatory response in MS that involves both astrocytes and cells of the microglia/macrophage lineage.

Brain↗

PubMed2005

Activation of metabotropic glutamate receptor 3 enhances interleukin (IL)-1beta-stimulated release of IL-6 in cultured human astrocytes.

Previous studies have demonstrated that human astrocytes express mRNA and receptor protein for group I and II metabotropic glutamate receptors (mGluRs). Whether these receptors can influence the inflammatory and immune response and can modulate the capacity of astrocytes to produce inflammatory cytokines is still unclear. Inflammatory cytokines can be produced by activated glial cells and play a critical role in several neurological disorders. Astrocyte-enriched human cell cultures growing in a serum-free chemically defined medium were used to study the regulation of IL (interleukin)-1beta and IL-6 in response to mGluR activation. Astrocytes cultured in the absence or in the presence of epidermal growth factor (EGF), did not secrete significant IL-1beta and IL-6, as determined by specific enzyme-linked immunosorbent assay (ELISA). Activation of mGluRs using (S)-3,5-dihydroxyphenylglycine (DHPG; selective group I agonist) or DCG-IV (selective group II agonist) did not affect the production of interleukins under both growth conditions. On exposure to IL-1beta high levels of IL-6 were detected. Activation of mGluR3 with DCG-IV (but not of mGluR5 with DHPG) enhanced, in the presence of IL-1beta, the release of IL-6 in a dose dependent manner in astrocytes cultured under conditions (+EGF) in which the mGluR expression is known to be upregulated. The effect of mGluR3 activation on IL-1beta stimulated release of IL-6 was prevented by selective group II mGluR antagonists. The capacity of mGluR3 to modulate the release of IL-6 in the presence of IL-1beta supports the possible involvement of this receptor subtype in the regulation of the inflammatory and immune response under pathological conditions associated with glial cell activation.

Adult↗

PubMed2005

Neuropathological findings after continuous intrathecal administration of S(+)-ketamine for the management of neuropathic cancer pain.

Questions have been raised about the potential neurotoxicity of the neuraxial use of ketamine although ketamine and its active enantiomer S(+)-ketamine have been used intrathecally and epidurally (caudally) for the management of perioperative pain and in a variety of chronic pain syndromes. Clinical experience following neuraxial administration of S(+)-ketamine has been documented without reference to local central nervous system toxicity following this approach. In addition, there are no preclinical safety data regarding stability, compatibility, and neurotoxicity on intrathecal use of single S(+)-ketamine or combinations of S(+)-ketamine, morphine, bupivacaine, and clonidine. In the present case, the continuous intrathecal administration of S(+)-ketamine, in combination with morphine, bupivacaine, and clonidine resulted in adequate pain relief in a patient suffering from intractable neuropathic cancer pain. However, postmortem observation of the spinal cord and nerve roots revealed severe histological abnormalities including central chromatolysis, nerve cell shrinkage, neuronophagia, microglial upregulation, and gliosis. Based on our results, neuraxial administration of S (+)-ketamine cannot be recommended for clinical practise before a systematic study of toxicology of neuraxial S(+)-ketamine in animals or humans has been performed.

Analgesics↗

PubMed2005

Neonatal lactic acidosis, complex I/IV deficiency, and fetal cerebral disruption.

Cerebral developmental abnormalities occur in various inborn errors of metabolism including peroxisomal deficiencies, pyruvate dehydrogenase complex deficiency and others. Associations with abnormalities of the respiratory chain are rare. Here we report male and female siblings with microcephaly, a complex neuromigrational disorder including ependymal cysts, leptomeningeal and subcortical heterotopia, polymicrogyria, multifocal cerebral calcifications, agenesis of the corpus callosum, and spongiform changes in brainstem and cerebellum. Intractable lactic acidosis, causing death on the first day of life, was associated with severely reduced activities of complex I and complex IV. The neuropathological and biochemical findings are closely similar to those reported previously. The findings confirm a distinct genetic syndrome of disrupted brain development with TORCH-like calcifications, and a complex neuronal migration disorder associated with a multicomplex disorder of the respiratory chain.

Acidosis, Lactic↗

PubMed2005

Distribution, characterization and clinical significance of microglia in glioneuronal tumours from patients with chronic intractable epilepsy.

Cells of the microglia/macrophage lineage represent an important component of different brain tumours. However, there is little information about the microglia/macrophage cell system in glioneuronal tumours and its possible contribution to the high epileptogenecity of these lesions. In the present study, the distribution of cells of the microglia/macrophage lineage was studied by immunocytochemistry for CD68 and human leucocyte antigen (HLA)-DR in a group of glioneuronal tumours, including gangliogliomas (GG, n = 30), and dysembryoplastic neuroepithelial tumours (DNT, n = 17), from patients with chronic intractable epilepsy. A significant number of microglia/macrophage cells were observed in the large majority of glioneuronal tumours, both within the tumour and in the peritumoral region. Activated microglial cells positive for HLA-DR were localized around blood vessels and clustered around tumour neuronal cells. The density of activated microglial cells correlated with the duration of epilepsy, as well as with the frequency of seizures prior to surgical resection. These observations indicate that the presence of cells of the microglial/macrophage cell system is a feature of glioneuronal tumours and is functionally related to epilepsy, either directly in epileptogenesis or through activation following seizure activity.

Adolescent↗

PubMed2004

Immunohistochemical localization of vascular endothelial growth factor receptors-1, -2 and -3 in human spinal cord: altered expression in amyotrophic lateral sclerosis.

Vascular endothelial growth factor (VEGF) has recently been implicated in several neurological disorders. Apart from its prominent role in angiogenesis, VEGF has been shown to have direct effects on neuronal and glial cells through activation of different VEGF receptor (VEGFR) types. In the present study the expression patterns of VEGFR-1, -2 and -3 were investigated in the spinal cord of control and both sporadic and familial amyotrophic lateral sclerosis (ALS) patients. Immunocytochemical analysis of control human spinal cord demonstrated that VEGFR-1, but not VEGFR-2 or -3 was found to be present in blood vessels of both white and grey matter. All three VGEFRs were not detectable in resting glial cells of control tissue. Diffuse neuropil staining was observed in the control spinal cord grey matter for VEGFR-3. Regional differences in VEGFRs immunoreactivity (IR) were apparent in ALS compared to controls. In particular, VEGFR-1 expression was increased in reactive astroglial cells in both grey (ventral horn) and white matter of ALS spinal cord. In addition to the astroglial labelling, increased expression of VEGFR-1 and, to a less extent also of VEGFR-2, was observed in blood vessels of the ALS spinal cord. No changes in VEGFR-3 IR were detected in blood vessels or reactive astroglial cells, whereas VEGFR-3 neuropil expression was reduced and paralleled the distribution of neuronal loss in the ventral horn of ALS spinal cord. These findings indicate that VEGFRs have specific distribution patterns, suggesting different physiological functions in human spinal cord. Moreover, the altered expression observed in ALS supports a role for these receptors in the complex reactive processes that are associated with the progression of spinal cord damage.

Adult↗

PubMed2004

Neurotrophin receptor immunoreactivity in the hippocampus of patients with mesial temporal lobe epilepsy.

Recent evidence supports a critical role of neurotrophins in the regulation of both neuronal survival and synaptic transmission during epileptogenesis. We have examined the immunohistochemical expression of high- (tyrosine kinase receptors, trk) and low-affinity (p75) neurotrophin receptors (NTRs) in the hippocampal specimens from 18 patients with chronic temporal lobe epilepsy [TLE; 14 patients with hippocampal sclerosis (HS) and four with focal lesions (tumours) not involving the hippocampus proper]. Nonepileptic autopsy brains (n = 6) and surgical specimens from tumour patients without epilepsy (n = 3) were used as controls. Immunoreactivity (IR) for the trk receptors (trkA, trkB, trkC) was detected in normal human brain within the pyramidal neurones of hippocampal cornus ammoni (CA) regions and in the dentate gyrus. There were no detectable differences in the neuronal trk IR patterns in the hippocampus between control and TLE cases with HS, except for a decrease in neuronal density in regions where cell death had occurred (CA1, CA3 and CA4). In contrast, a consistent increase in trkA IR was observed in reactive astrocytes in CA1 and dentate gyrus. The low-affinity p75 neurotrophin receptor (p75(NTR)) was expressed in low levels in postnatal normal hippocampus. In contrast, neuronal p75(NTR) IR was detected in 10/14 cases of HS in spared neurones within the CA and hilar regions of the hippocampus. Double labelling revealed that p75(NTR)-positive neurones also contain trk receptor IR. In six cases with prominent glial activation strong p75(NTR) IR was observed in microglial cells within the sclerotic hippocampus. The present results indicate that changes in NTR expression are still detectable in the hippocampus of patients with chronic TLE and involve both glial and neuronal cells. Reactive astrocytes were immunoreactive for trkA, whereas activated microglia cells were reactive for p75(NTR), suggesting different functions for specific NTRs in the development of reactive gliosis. Moreover, the increased expression of p75(NTR) in hippocampal neurones of TLE patients may critically influence the neuronal survival during the epileptogenic process.

Adolescent↗

PubMed2004

Molecular-genetic characterisation of gliomas that recur as same grade or higher grade tumours.

BACKGROUND: Due to their invasive growth, gliomas usually cannot be removed completely and almost always recur as same grade or higher grade malignancies. OBJECTIVE: To determine whether there were differences in the accumulation of genetic changes between the two types of glioma recurrence. METHODS: We genetically characterised 14 cases of lower grade glioma with a same grade recurrence, 12 cases of glioblastoma recurrence, and 14 cases of lower grade glioma with a higher grade recurrence. We investigated LOH (loss of heterozygosity) at 1p36, 10p15, the PTEN region in 10q23, the DMBT1 region in 10q25, 19q13, 22q13, LOH and mutation of TP53, and EGFR amplification. RESULTS: Genetic heterogeneity in the primary tumour was inferred in 3 cases of lower grade glioma with a higher grade recurrence. The cases of lower grade glioma with a higher grade recurrence displayed increased genetic instability in the recurrence (mean of 2.0 additional genetic changes per case) compared to cases with a same lower grade recurrence or those with a glioblastoma recurrence (mean of 0.6 and 0.8 additional changes per case, respectively). Compared to unselected primary glioblastomas, the glioblastomas that recurred as an operable tumour had infrequent EGFR amplification (8% v 30-40% of cases). CONCLUSIONS: Gliomas recurring as higher grade lesions might be genetically heterogeneous and accumulate more genetic changes than gliomas recurring as same grade lesions (whether originally low or high grade). Primary glioblastomas from patients for which the recurrence is operated because of prognostically more favourable clinical indices have infrequent EGFR amplification.

Adolescent↗

PubMed2003

Altered expression patterns of group I and II metabotropic glutamate receptors in multiple sclerosis.

Recent evidence supports a role for glutamate receptors in the pathophysiology of multiple sclerosis. In the present study, we have focused specifically on the expression of metabotropic glutamate receptors (mGluRs) in multiple sclerosis brain tissue. The expression of group I (mGluR1alpha and mGluR5) and group II (mGluR2/3) mGluRs was studied using immunohistochemistry in tissue from 12 multiple sclerosis cases and seven non-neurological controls. The expression patterns of both group I and II mGluRs in multiple sclerosis tissue differed significantly from those in control tissue. Strong mGluR1alpha immunoreactivity was observed in axons of the subcortical white matter, particularly in the centre of actively demyelinating lesions and in the borders of chronic active lesions. mGluR1alpha axonal immunopositivity was also found in normal appearing multiple sclerosis white matter, but axons in control white matter were generally negative. mGluR1alpha axonal labelling was associated with the presence of non-phosphorylated neurofilaments and beta-amyloid precursor protein, which are sensitive markers for axonal injury and disturbed axonal transport. Changes in mGluR immunoreactivity were also observed in glia. A diffuse increase in the expression of mGluR5 and mGluR2/3 was detected in reactive astrocytes in multiple sclerosis lesions. However, only a subpopulation of reactive astroglial cells expressed mGluR1alpha. In addition, labelling with antibodies to mGluR2/3 and, to a lesser extent labelling with antibodies to mGluR1alpha, was detected in a population of cells of the microglial/macrophage lineage that displayed a macrophage-like morphology. Our data suggest that mGluRs, like ionotropic glutamate receptors, play a role in the complex processes that are associated with the progressive brain damage in multiple sclerosis, including both glial activation and pathological changes in axons.

Adult↗

PubMed2003

Expression and cellular distribution of multidrug transporter proteins in two major causes of medically intractable epilepsy: focal cortical dysplasia and glioneuronal tumors.

The cell-specific distribution of multidrug resistance extrusion pumps was studied in developmental glioneuronal lesions, including focal cortical dysplasia (15 cases) and ganglioglioma (15 cases) from patients with medically intractable epilepsy. Lesional, perilesional, as well as normal brain regions were examined for the expression of the multidrug resistance gene 1 encoded P-glycoprotein (P-gp) and the multidrug resistance-associated protein 1 (MRP1) by immunocytochemistry. In normal brain MRP1 expression was below detection, whereas P-gp staining was present only in blood vessels. MRP1 and P-gp immunoreactivity was observed in dysplastic neurons of 11/15 cases of focal cortical dysplasia, as well as in the neuronal component of 14/15 ganglioglioma. Glial cells with astrocytic morphology within the lesion showed multidrug-resistant protein immunoreactivity (P-gp>MRP1). Moderate to strong MRP1 and P-gp immunoreactivity was observed in a population of large ballooned neuroglial cells. P-gp appeared to be most frequently expressed in glial fibrillary acidic protein-positive balloon cells (glial type), whereas MRP1 was more frequently expressed in microtubule-associated protein 2-positive balloon cells (neuronal type). In both types of lesions strong P-gp immunoreactivity was found in lesional vessels. Perilesional regions did not show increased staining in vessels or in neuronal cells compared with normal cortex. The predominant intralesional cell-specific distribution of multidrug transporter proteins supports the hypothesis of a constitutive overexpression as common mechanism underlying the intrinsic pharmaco-resistance to antiepileptic drugs of both malformative and neoplastic glioneuronal developmental lesions.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2002

Elevated levels of neurotrophins in human biceps brachii tissue of amyotrophic lateral sclerosis.

Previous studies suggest that neurotrophins support regeneration and survival of injured motoneurons. Based on these findings, brain-derived neurotrophic factor (BDNF) has been clinically investigated for its therapeutic potential in amyotrophic lateral sclerosis (ALS), a rapidly progressing and fatal motoneuronal disease. We questioned whether imbalances of neurotrophic levels are indeed involved in the pathology of ALS. Therefore the expression of nerve growth factor (NGF), BDNF, neurotrophin-3 (NT-3), and neurotrophin-4/5 (NT-4/5) was investigated in postmortem muscle tissue of the biceps from 15 patients with neuropathologically confirmed sporadic ALS and 15 age-matched controls. Using mRNA analysis techniques and quantitative protein measurements, we have demonstrated that both mRNA and protein levels of all four neurotrophins are increased in muscle tissue of ALS patients. The production levels displayed a disease duration dependency and different expression patterns emerged for the four neurotrophins. Whereas the early phase of the disease was characterized by a strong upregulation of BDNF, levels of NGF, NT-3, and NT-4/5 gradually increased in the course of the disorder, peaking at later stages. We conclude that decreased neurotrophic support from muscle tissue is most likely not the cause of motoneuron degeneration in ALS. On the contrary, our results suggest that degenerating motoneurons in ALS are exposed to elevated levels of muscle-derived neurotrophins.

Adult↗

PubMed2002

"Vanishing white matter" and ovarian dysgenesis in an infant with cerebro-oculo-facio-skeletal phenotype.

We describe a girl with intrauterine growth retardation, congenital cataracts, mild dysmorphic features and joint contractures. MRI performed at 1 week and 6 months, demonstrated postnatal cerebral and cerebellar atrophy and loss of white matter. The patient died at 10 months. Post-mortem examination revealed ovarian dysgenesis. There was normal development of neuronal and axonal structures, but lack of myelination in brainstem and cerebellum. Subcortical and deep white matter of the cerebral hemispheres were largely destroyed (cavitated), with preserved, but unmyelinated axons in other brain areas. These findings are compatible with a severe leukodystrophic process of pre- or perinatal onset. The exact pathogenesis is not known.

Abnormalities, Multiple↗

PubMed2001

GOA, a novel gene encoding a ring finger B-box coiled-coil protein, is overexpressed in astrocytoma.

Serial analysis of gene expression (SAGE) was used to identify a gene named GOA (gene overexpressed in astrocytoma), which codes for a novel Ring finger B-box coiled-coil (RBCC) protein. Northern blot hybridization showed overexpression of GOA in 9 of 10 astrocytomas. Except for kidney, in which high expression was found, expression levels in normal tissues were low and comparable to normal brain. Immunohistochemistry demonstrated presence of GOA, with prominent nuclear staining, in astrocytoma tumor cells and astrocytes of fetal brain, but virtual absence in mature astrocytes. Overexpression was not due to amplification, since amplification of GOA was only found in one of 65 astrocytomas. GOA was localized to 17q24-25, a region that is frequently gained or amplified in a number of other tumor types. GOA contains two LXXLL motifs, which are thought to be important for nuclear receptor binding. Our data suggest an important role of GOA in the process of dedifferentiation that is associated with astrocytoma tumorigenesis and possibly with that of other tumor types as well.

Amino Acid Motifs↗