Search PubMed⌕ Search

Biomedical subjects

J Schramm

Publications and source records attributed to J Schramm.

At least 73 records · Page 4Linked to original sources
PubMed2000

Localizing value of epileptic visual auras.

It is difficult to differentiate between seizures of occipital or temporal lobe origin in patients with focal epileptic seizures associated with visual aura. These are often suspected to originate from the visual cortex, which causes reluctance to propose resection as treatment for the affected patient. To determine the value of localizing different types of visual auras, we report on 20 patients experiencing visual aura from a series of 878 surgically treated patients suffering from intractable focal seizures. In all of these patients, a morphological abnormality was identified on MRI (n = 18) or cranial CT (n = 2). These abnormalities were shown to represent the morphological correlate of the epileptogenic zone in each case, as demonstrated by intracranial ictal EEG recordings and/or seizure freedom after focal resective surgery. Elementary hallucinations, illusions and visual loss were reported not only by all patients with occipital lobe epilepsy, but also by patients with occipitotemporal and anteromedial temporal seizure onset. Complex hallucinations never occurred in occipital lobe seizures but were present in the two other groups. The same correlation was found for concentric changes of visual field (tunnel vision), a newly described ictal phenomenon. We conclude that elementary hallucinations, illusions and visual loss, although typical for occipital lobe epilepsy, can also occur in anteromedial temporal or occipitotemporal seizures and are therefore not a discordant feature in presurgical evaluation of patients with suspected temporal lobe epilepsy. Complex hallucinations and tunnel vision, however, should be considered concordant only with the assumption of an anteromedial temporal or occipitotemporal seizure onset.

Adolescent↗
PubMed2000

Subregional pathology of the amygdala complex and entorhinal region in surgical specimens from patients with pharmacoresistant temporal lobe epilepsy.

The hippocampus, amygdala complex, and entorhinal region represent anatomically linked limbic structures of the mesiotemporal lobe. Chronic seizures and mnestic deficits in patients with pharmacoresistant mesial temporal lobe epilepsy (TLE) appear to correlate with distinct patterns of histopathological alterations in these areas. The complex anatomical organization of the amygdala and entorhinal region, however, render a detailed neuropathological evaluation of surgical specimens difficult. In this study, we present a combined cytoarchitectonical, pigmentarchitectonical, myelinarchitectonical, and immunohistochemical reconstruction of the amygdala, entorhinal region, and hippocampus from surgical TLE specimens (n = 20) in order to analyze their regional and cellular patterns of pathology. Anterior mesiotemporal lobes dissected in different spatial planes were obtained from 4 autopsy control patients and used for the characterization of neuroanatomical landmarks. Lateral, basal, and granular subnuclei of the amygdala were consistently identified in the surgical specimens. Major histopathological alterations included neuronal cell loss as revealed by extracellular lipofuscin accumulation, glial satellitosis, as well as cellular and fibrillary gliosis. The regional distribution of neuropathological changes varied considerably between different subnuclei but the lateral nucleus was more often involved than basal and granular nuclei. These amygdala nuclei appeared to be more severely affected compared to the adjacent entorhinal region. In addition, patients presenting with secondary generalized tonic-clonic seizures showed significantly more damage in mesiotemporal structures. Pathological alterations in the amygdala and entorhinal region were found to be associated with Ammon's horn sclerosis in most but not all cases. Our findings reveal the amygdala as a major target for epilepsy-associated neuronal cell damage. Significant variations in the lesional pattern among patients with chronic TLE would also be compatible with different spreading pathways of epileptogenic activity within the mesial temporal lobe.

Adolescent↗
PubMed2000

Expression of 5alpha-reductase and 3alpha-hydroxisteroid oxidoreductase in the hippocampus of patients with chronic temporal lobe epilepsy.

PURPOSE: The hippocampus is one of the principal target areas for neurosteroidal action, and the major neuroendocrine conversion of progesterone appears to be 5alpha-reduction and 3alpha-hydroxysteroid oxidoreduction, leading to the potent neurosteroid 3alpha,5alpha-tetrahydroxyprogesterone. To investigate whether the human hippocampus is equipped with the enzymes 5alpha-reductase and 3alpha-hydroxysteroid oxidoreductase (3alpha-HSOR), we studied the expression of 5alpha-reductase types 1 and 2 and 3alpha-HSOR types 1 and 2 in the resected hippocampi of patients with medically intractable chronic temporal lobe epilepsy. METHODS: We studied tissue specimens from the hippocampi of 13 women, 25 men, and four children. Quantification of different mRNAs was achieved by competitive reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: 5Alpha-reductase 1 mRNA and 3alpha-HSOR 2 mRNA were expressed in hippocampi of children and adults, whereas 5alpha-reductase 2 mRNA and 3alpha-HSOR 1 mRNA were not expressed. Neither 5alpha-reductase 1 mRNA nor 3alpha-HSOR 2 mRNA concentrations in hippocampal tissue showed any statistically significant differences between women and men or between children and adults. CONCLUSIONS: This study demonstrates for the first time mRNA expression of the type 1 isozyme of 5alpha-reductase and the type 2 isozyme of 3alpha-HSOR in the human hippocampus. The finding that both 5alpha-reductase and 3alpha-HSOR are present in the hippocampus leads us to assume the synthesis of neuroactive steroids in this human brain area.

3-Hydroxysteroid Dehydrogenases↗
PubMed2000

Loss of hilar mossy cells in Ammon's horn sclerosis.

PURPOSE: Hilar mossy cells represent an important excitatory subpopulation of the hippocampal formation. Several studies have identified this cell type as particularly vulnerable to seizure activity in rat models of limbic epilepsy. Here we have subjected hilar mossy cell loss in the hippocampus of patients with chronic temporal lobe epilepsy (TLE) to a systematic morphological and immunohistochemical analysis. METHODS: Hippocampal specimens from 30 TLE patients were included; 21 patients presented with segmental neuronal cell loss [Ammon's horns clerosis (AHS)] and 8 with focal lesions (tumors, scars, malformations) not involving the hippocampus proper. In one additional TLE patient, no histopathological alteration could be observed. Surgical specimens from tumor patients without epilepsy (n = 2) and nonepileptic autopsy brains (n = 8) were used as controls. Hilar mossy cells in the human hippocampus were visualized using a novel polycloncal antiserum directed against the metabotropic glutamate receptor subtype mGluR7b or by intracellular Lucifer Yellow injection, confocal laser scanning microscopy, and three-dimensional morphological reconstruction. RESULTS: Compared with controls, a significant loss of mGluR7 immunoreactive mossy cells was observed in patients with AHS (p < 0.05). In contrast, TLE patients with focal lesions but structurally intact hippocampus demonstrated only a discrete, nonsignificant reduction of this neuronal subpopulation. This observation was confirmed by analysis of 62 randomly injected hilar neurons from AHS patients, in which we were unable to detect neurons with a morphology like that of hilar mossy cells. CONCLUSION: Our present data indicate significant hilar mossy cell loss in TLE patients with AHS. In contrast, hilar mossy cells appear to be less vulnerable in patients with lesion-associated TLE. Although the significance of mGluR7 immunoreactivity in mossy cells remains to be studied, loss of this cell population is compatible with alterations in hippocampal networks and regional hyperexcitability as pathogenic mechanism of AHS and TLE.

Adult↗
PubMed2000

Functional and molecular properties of human astrocytes in acute hippocampal slices obtained from patients with temporal lobe epilepsy.

PURPOSE: The specific role of glial cells in epilepsy is still elusive. In this study, functional properties of astrocytes were investigated in acute hippocampal brain slices obtained from surgical specimens of patients with drug-resistant temporal lobe epilepsy (TLE). METHODS: The patch-clamp technique together with a single-cell reverse transcription-polymerase chain reaction approach were used to combine functional and molecular analysis in the same individual cell in situ. RESULTS: In patients with Ammon's horn sclerosis, the glial current patterns resembled properties of immature astrocytes in rodent hippocampus. Depolarizing voltage steps activated delayed rectifier and transient K+ currents as well as tetrodotoxin-sensitive Na+ currents. Hyperpolarizing voltages elicited inward rectifier K+ currents. Comparative recordings were made in astrocytes from patients with lesion-associated TLE that lacked significant histopathological hippocampal alterations. The inward rectifier K+ current density was significantly smaller in astrocytes from the sclerotic group compared with lesion-associated TLE patients. CONCLUSIONS: During normal development of rodent brain, astroglial inward rectification gradually increases. It thus appears that astrocytes in human sclerotic tissue reexpress an immature current pattern. Reduced astroglial inward rectification in conjunction with seizure-induced shrinkage of the extracellular space may lead to impaired spatial K+ buffering. This will result in stronger and prolonged depolarization of glial cells and neurons in response to activity-dependent K+ release and may thus contribute to seizure generation and spread in this particular condition of human TLE.

Action Potentials↗
PubMed2000

Modulation of calcium channels by group I and group II metabotropic glutamate receptors in dentate gyrus neurons from patients with temporal lobe epilepsy.

PURPOSE: Metabotropic glutamate receptors (mGluRs) might be promising new drug targets for the treatment of epilepsy because the expression of certain mGluRs is regulated in epilepsy and because activation of mGluRs results in distinctive anti- and proconvulsant effects. Therefore, we examined how mGluR activation modulates high-voltage-activated (HVA) Ca2+ channels. METHODS: Whole-cell patch-clamp recordings were obtained from granule cells and interneuron-like cells acutely isolated from the dentate gyrus of patients with pharmacoresistent temporal lobe epilepsy. RESULTS: Agonists selective for either group I or group II mGluRs rapidly and reversibly reduced HVA currents in most dentate gyrus cells. These modulatory effects were inhibited by the respective group I and group II mGluR antagonists. The specific Ca2+ channel antagonists nifedipine and omega-conotoxin GVIA potently occluded the effects of group I and II mGluR agonists, respectively, indicating that group I mGluRs acted on L-type channels and group II mGluRs affected N-type channels. About two thirds of the responsive neurons were sensitive either to group I or group II mGluRs, whereas a minority of cells showed effects to agonists of both groups, indicating a variable mGluR expression pattern. CONCLUSIONS: Group I and group II mGluRs are expressed in human dentate gyrus neurons and modulate L- and N-type HVA channels, respectively. The data shed light on the possible cellular sequelae of the mGluR1 upregulation observed in human epileptic dentate gyrus as well as on possible mGluR-mediated anticonvulsant mechanisms.

Anticonvulsants↗
PubMed2000

Behavioural disorders in children with epilepsy: early improvement after surgery.

OBJECTIVES: Epilepsy surgery has proved to be a successful intervention method to achieve freedom from seizures or seizure relief in children with pharmacoresistant epilepsy. Long term studies on operated children suggest that behavioural disorders, which are often seen before surgery, improve after surgery. However, the early postoperative development of behavioural problems has not been systematically evaluated. METHODS: Parents of 28 children with pharmacoresistant focal epilepsies completed the child behaviour checklist (CBCL) preoperatively and 3 months after surgery. Surgeries comprised 24 focal resections (13 temporal, 11 extratemporal), two hemispherectomies, and two callosotomies. Twenty eight conservatively treated children with comparable CBCL scores served as a control group. A repeated measurement multivariate analysis of variance (MANOVA) and a regression analysis were computed to compare the development of behaviour between both groups and to identify predictors of postoperative changes in behaviour. RESULTS: Preoperatively 39% of the children exhibited significant behavioural problems, a further 11% were within the borderline range. The MANOVA disclosed a significant interaction between time of examination and group (F=2.23, p<0.05). The surgery group showed significant improvements on the scales "internalising problems", "externalising problems", "attention problems", and "thought problems". Behavioural problems in the control group, however, remained unchanged. No changes were seen in social problems in both groups. The significant predictor of total behavioural improvement was a good seizure outcome (R(2)=0.11, p<0.05). Age, sex, onset, and duration of epilepsy, the site of the focus, and changes in antiepileptic drug regimen did not influence changes in behaviour. CONCLUSIONS: The data demonstrate an early improvement of behavioural problems after epilepsy surgery in children. The behavioural improvements can be assumed to result directly from the removal of the epileptic focus. They are not predictable on the basis of information available preoperatively, but depend on the seizure outcome.

Adolescent↗
PubMed2000

Telomerase activity and expression of the telomerase catalytic subunit, hTERT, in meningioma progression.

OBJECT: In recent reports, 6 to 19% of meningiomas have been classified as atypical or anaplastic/malignant. Some atypical and anaplastic meningiomas appear to arise from benign tumors by progression. Telomerase activation has recently been associated with malignant progression of human tumors. The authors have investigated a series of benign, atypical, and anaplastic/malignant meningiomas for telomerase activity and expression of the telomerase catalytic subunit human telomerase reverse transcriptase (hTERT). METHODS: A quantitative telomeric repeat amplification protocol was used to detect telomerase enzyme activity in seven (21%) of 34 benign, but in nine (75%) of 12 atypical and in seven (100%) of seven anaplastic/malignant meningiomas. Very high levels of telomerase activity were observed only in highly aggressive tumors. Messenger (m)RNA expression of the catalytic subunit hTERT was found in 11 (33%) of 33 benign, 12 (92%) of 13 atypical, and all seven anaplastic/malignant tumors. All telomerase-positive lesions were also positive for hTERT mRNA, whereas no telomerase activity was detected in six (21%) of 29 hTERT-positive tumors. This indicates that upregulation of hTERT is the rate-limiting step for telomerase activation in the majority of meningiomas. Expression of telomerase and hTERT was seen in all four tumors with gross brain invasion. All recurrent tumors or meningiomas recurring during follow up expressed hTERT. CONCLUSIONS: The results are consistent with a role for telomerase activation during the development of malignancy in meningiomas. Hence, expression of telomerase activity and hTERT might prove to be potentially useful markers for the evaluation of these tumors.

Adult↗
PubMed2000

Up-regulation of the metabotropic glutamate receptor mGluR4 in hippocampal neurons with reduced seizure vulnerability.

Selective hippocampal cell loss and altered neurotransmitter receptor expression have been proposed as pathogenic mechanisms in the development of chronic mesial temporal lobe epilepsy (TLE). Studies in animal models point to metabotropic glutamate receptors (mGluRs) as modulators of hippocampal epileptogenesis. In addition, mGluRs may constitute specific targets for the development of novel anticonvulsive drugs. As mGluR4 represents an inhibitory class III mGluR associated with the reduction of intracellular cyclic AMP levels and calcium influx, we have analyzed the regional and cellular expression of mGluR4 in surgical hippocampal specimens obtained from patients with TLE by using immunohistochemistry and in situ hybridization. Although the hippocampi of control specimens (n = 11) were almost devoid of mGluR4 immunolabeling, all TLE specimens (n = 35) showed a striking up-regulation of mGluR4 immunoreactivity, in particular within the dentate gyrus. Immunoelectron microscopy localized the receptor protein to the periphery of presynaptic and postsynaptic membranes. In situ hybridization revealed increased transcript levels of mGluR4 in dentate granule cells and residual CA4 neurons of TLE specimens compared with controls. Our results suggest a potential role of mGluR4 in counteracting excitatory hippocampal activity and in modulating seizure-associated vulnerability of hippocampal neurons. These data may also provide a basis for pharmacological studies of mGluR4 agonists as potential novel drugs in the treatment of TLE.

Adult↗
PubMed2000

Mitochondrial complex I deficiency in the epileptic focus of patients with temporal lobe epilepsy.

Mitochondria are cellular organelles crucial for energy supply and calcium homeostasis in neuronal cells, and their dysfunction causes seizure activity in some rare human epilepsies. To directly test whether mitochondrial respiratory chain enzymes are abnormal in the most common form of chronic epilepsy, temporal lobe epilepsy (TLE), living human brain specimens from 57 epileptic patients and 2 nonepileptic controls were investigated. In TLE patients with a hippocampal epileptic focus, we demonstrated a specific deficiency of complex I of the mitochondrial respiratory chain in the hippocampal CA3 region. In contrast, TLE patients with a parahippocampal epileptic focus showed reduced complex I activity only in parahippocampal tissue. Inhibitor titrations of the maximal respiration rate of intact human brain slices revealed that the observed reduction in complex I activity is sufficient to affect the adenosine triphosphate production rate. The abnormal complex I activity in the hippocampal CA3 region was paralleled by increased succinate dehydrogenase staining of neurons and marked ultrastructural abnormalities of mitochondria. Therefore, mitochondrial dysfunction is suggested to be specific for the epileptic focus and may constitute a pathomechanism contributing to altered excitability and selective neuronal vulnerability in TLE.

Adolescent↗
PubMed2000

Is there a benefit of preoperative meningioma embolization?

OBJECTIVE: To evaluate the effect of preoperative embolization of meningiomas on surgery and outcomes. METHODS: In a prospective study, 60 consecutive patients with intracranial meningiomas who were treated in two neurosurgical centers were included. In Center A, embolization was performed for none of the patients (n = 30). In Center B, 30 consecutive patients with embolized meningiomas were treated. Preoperatively, tumor size and location, neurological status, and Barthel scale score were recorded. In Center B, the extent of tumor devascularization was evaluated using angiography and postembolization magnetic resonance imaging. Intraoperatively, blood loss, the numbers of blood units transfused, and the observations of the neurosurgeon concerning hemostasis, tumor consistency, and intratumoral necrosis were recorded. Postoperatively, the neurological status and duration of hospitalization were recorded. Six months after surgery, the outcomes were assessed using the Barthel scale and neurological examinations. RESULTS: The mean tumor sizes were 22.9 cc in Center A and 29.6 cc in Center B (P > 0.1). The mean blood losses did not differ significantly (646 ml in Center A versus 636 ml in Center B; P > 0.5). However, for a subgroup of patients with subtotal devascularization (>90% of the tumor) on postembolization magnetic resonance imaging scans in Center B, blood loss was less, compared with the entire group in Center A (P < 0.05). The observations of the neurosurgeon regarding hemostasis, tumor consistency, and intratumoral necrosis did not differ significantly. There were no surgery-related deaths in either center. The rates of surgical morbidity, with permanent neurological worsening, were 20% (n = 6) in Center A and 16% (n = 5) in Center B. There was one permanent neurological deficit (3%) caused by embolization. CONCLUSION: In this preliminary study, only complete embolization had an effect on blood loss. The value of preoperative embolization for all meningiomas must be reconsidered, especially in view of the high costs and risks of embolization.

Adult↗
PubMed1999

Cellular pathology of hilar neurons in Ammon's horn sclerosis.

In addition to functionally affected neuronal signaling pathways, altered axonal, dendritic, and synaptic morphology may contribute to hippocampal hyperexcitability in chronic mesial temporal lobe epilepsies (MTLE). The sclerotic hippocampus in Ammon's horn sclerosis (AHS)-associated MTLE, which shows segmental neuronal cell loss, axonal reorganization, and astrogliosis, would appear particularly susceptible to such changes. To characterize the cellular hippocampal pathology in MTLE, we have analyzed hilar neurons in surgical hippocampus specimens from patients with MTLE. Anatomically well-preserved hippocampal specimens from patients with AHS (n = 44) and from patients with focal temporal lesions (non-AHS; n = 20) were studied using confocal laser scanning microscopy (CFLSM) and electron microscopy (EM). Hippocampal samples from three tumor patients without chronic epilepsies and autopsy samples were used as controls. Using intracellular Lucifer Yellow injection and CFLSM, spiny pyramidal, multipolar, and mossy cells as well as non-spiny multipolar neurons have been identified as major hilar cell types in controls and lesion-associated MTLE specimens. In contrast, none of the hilar neurons from AHS specimens displayed a morphology reminiscent of mossy cells. In AHS, a major portion of the pyramidal and multipolar neurons showed extensive dendritic ramification and periodic nodular swellings of dendritic shafts. EM analysis confirmed the altered cellular morphology, with an accumulation of cytoskeletal filaments and increased numbers of mitochondria as the most prominent findings. To characterize cytoskeletal alterations in hilar neurons further, immunohistochemical reactions for neurofilament proteins (NFP), microtubule-associated proteins, and tau were performed. This analysis specifically identified large and atypical hilar neurons with an accumulation of low weight NFP. Our data demonstrate striking structural alterations in hilar neurons of patients with AHS compared with controls and non-sclerotic MTLE specimens. Such changes may develop during cellular reorganization in the epileptogenic hippocampus and are likely to contribute to the pathogenesis or maintenance of temporal lobe epilepsy.

Aged↗
PubMed1999

Expression of cytochrome P450scc mRNA in the hippocampus of patients with temporal lobe epilepsy.

The hippocampus is one of the target areas of neurosteroidal action. Expression of cytochrome P450scc (P450scc, CYP11A1), one of the key enzymes in steroid metabolism, results in de novo synthesis of the neurosteroid pregnenolone. We used a competitive RT-PCR assay to quantify the amount of P450scc mRNA in hippocampal tissue specimens obtained at neurosurgery from patients with temporal lobe epilepsy (TLE). P450scc mRNA is expressed approximately 200 times lower in the hippocampus than in adrenal tissue known for high P450scc expression. P450scc mRNA concentrations were significantly higher in the hippocampus of women (1.72 +/- 0.36 aU, arbitrary units; mean +/- s.e.m.) than of men (0.92 +/- 0.15 aU, p < 0.004). Our data show for the first time the sex-dependent expression of P450scc mRNA in the hippocampus of patients with TLE.

Adrenal Glands↗
PubMed1999

Corrosion on an internal spinal fixator system.

STUDY DESIGN: Thirteen spinal fixators with 26 stabilization bridges and 52 pedicle screws and a mean length of implantation of 10 months were prospectively examined for corrosion. OBJECTIVES: To determine the type of corrosion and the correlation between the construction of the spinal fixator and the type of corrosion. SUMMARY OF BACKGROUND DATA: Evidence of fretting and crevice corrosion is seen in many stainless steel implants in retrieval studies. Such reactions have not been described in the literature on spinal fixator systems. METHODS: Macroscopic and microscopic alterations in the adjacent tissue were examined, and the corrosive alterations were documented photographically using stereoscopic optical light microscopy. The chemical composition of the implants was determined spectrographically. Microradiography and x-ray fluorescence analysis of the soft tissue were performed. RESULTS: At surgery, tissue discoloration was found in four cases. Histologic examination showed extensive fibrosis, foreign body reaction and inflammation associated with a small number of metal particles, indicating metallosis in five cases. Corresponding particles were detected by microradiography. Corrosion was found on 13 telescopic rods and on two pedicle screws. The alterations on the telescopic rods could be interpreted as crevice corrosion and the alterations in the pedicle screws as fretting corrosion. The two monobloc fixator bridges did not show signs of corrosion. In these implants, the neighboring tissue was macroscopically inconspicuous, and histologic examination showed minimal fibrosis or presence of metal particles. Spectrographic examination of the spinal fixators showed no structural imperfection. CONCLUSIONS: The construction constraints of a spinal fixator make it prone to corrosion. New spinal implants should be examined not only in vitro but also in vivo to ascertain whether corrosion and adjacent tissue reaction occur. Corrosion is one reason to explant the internal fixation system after fusion of the spinal fracture.

Adult↗
PubMed1999

Amobarbital effects on the posterior hippocampus during the intracarotid amobarbital test.

OBJECTIVE: To relate functional effects on the hippocampus during the intracarotid amobarbital test (IAT) to its direct perfusion with amobarbital. METHODS: In 17 patients with intractable temporal lobe epilepsy, 28 hemispheres were perfused with 2.3 mL of 10% solution of 200 mg amobarbital and 37 MBq 99mTc-hexamethylpropylene amine oxime (HMPAO). For evaluation of amobarbital effects, data were combined from stereo-EEG (S-EEG) recordings from intrahippocampal depth electrodes and high-resolution SPECT after intracarotid injection of HMPAO. RESULTS: Perfusion of the entire hippocampus was observed only in hemispheres with a fetal origin of the posterior cerebral artery (PCA). In 10 hemispheres, S-EEG recordings could not unequivocally be assigned to either the anterior or the posterior part of the hippocampus. In the remaining 18 hemispheres, only the two with a fetal type of PCA showed perfusion of the entire hippocampus. In both, hippocampal electrical activity changed under the influence of amobarbital but did not differ in anterior and posterior contacts. In 15 of 16 hemispheres in which SPECT demonstrated perfusion of the anterior hippocampus only, amobarbital injection resulted in significant S-EEG activity change in both the anterior and the posterior parts of the hippocampus. CONCLUSION: S-EEG effects on the posterior hippocampus during the IAT can occur without direct perfusion of those brain areas.

Adolescent↗
PubMed1999

Analysing metabotropic glutamate group III receptor mediated modulation of synaptic transmission in the amygdala-kindled dentate gyrus of the rat.

Metabotropic glutamate receptors (mGluRs) provide a powerful control of synaptic transmission in the hippocampus and may serve as a target for drug development in human temporal lobe epilepsies. Agonists and antagonists at these receptors influence the development and propagation of seizures in some animal models of epilepsy. Experimental seizures can change the level of expression of mGluRs in the rat hippocampus. In the human dentate gyrus of patients suffering from temporal lobe epilepsy (TLE), group III mGluR mediated inhibition of synaptic transmission is almost lost in the sub-group with Ammon's horn sclerosis. We tested the modulation of synaptic transmission by the group III mGluR specific agonist L(+)-2-amino-4-phosphonobutyric acid (L-AP4) in the dentate gyrus outer molecular layer in control and amygdala-kindled rats, a common model for TLE. Extracellular field potential recordings upon subthreshold stimulation of lateral perforant path fibers were measured simultaneously in the outer molecular layer and granule cell layer. Analysis of 'paired-pulse' characteristics in the absence and presence of L-AP4 and group III mGluR mediated inhibition of synaptic transmission in the lateral perforant path revealed no significant alterations in fully kindled rats. Since there is no evidence of altered L-AP4 responses, a loss of group III mGluR function, particularly that of subtype mGluR8, seems not necessary for the kindling epilepsy.

Amygdala↗
PubMed1999

Analysis of the MEN1 gene in sporadic pituitary adenomas.

The MEN1 gene on chromosome 11q13 is mutated in patients afflicted with multiple endocrine neoplasia syndrome type 1 (MEN1). These patients develop endocrine tumours of the pancreas, the parathyroid, and the anterior pituitary. In order to determine the role of MEN1 in sporadic pituitary adenomas, 61 pituitary adenomas were analysed from patients without evidence of a familial tumour syndrome. Single strand conformation polymorphism (SSCP) analysis was performed for the entire coding sequence of MEN1. Fragments with aberrant migration patterns were sequenced bidirectionally. Only a single somatic mutation was detected in this series. In addition, several previously reported and three novel polymorphisms were observed. Loss of heterozygosity analysis with 12 polymorphic markers, however, identified 13 pituitary adenomas with allelic deletions on chromosome 11. Allelic losses occurred significantly more often in pituitary adenomas with hormone secretion than in non-functioning adenomas. These data suggest that MEN1 mutations are rare events in sporadic pituitary adenomas. However, the discrepancy of only 1/61 adenomas with MEN1 mutation but 13/61 (22 per cent) with allelic loss on chromosome 11 may suggest the presence of a yet unknown tumour suppressor gene, relevant to the pathogenesis of sporadic pituitary adenomas.

Adenoma↗