Biomedical subjects

Andrew Kaye

Publications and source records attributed to Andrew Kaye.

7 recordsLinked to original sources

PubMed2006

ADAM22, expressed in normal brain but not in high-grade gliomas, inhibits cellular proliferation via the disintegrin domain.

OBJECTIVE: To study the expression and function of the brain-specific proteinase deficient disintegrins, ADAM11 and ADAM22 (a disintegrin and metalloproteinase). METHODS: Specimens of low- and high-grade gliomas and normal brain were analyzed for ADAM11 and ADAM22 expression using Western blotting. The effects of overexpression of ADAM11 and ADAM22 in glioma cells on growth were analyzed using bromodeoxyuridine incorporation linked to immunocytochemistry. Similarly analyzed were the effects on cell proliferation of bacterially expressed glutathione S-transferase fusion proteins with the disintegrin domain of ADAM11 and ADAM22. RESULTS: ADAM22 is expressed in normal brain and some low-grade gliomas, but not in high-grade gliomas, whereas ADAM11 is expressed in all low- and high-grade gliomas. In vitro, ADAM22 inhibits cellular proliferation of glioma derived astrocytes. The growth inhibition appears to be mediated by interactions between the disintegrin domain of ADAM22 and specific integrins expressed on the cell surface. This growth inhibition can be avoided by over-expression of integrin linked kinase. CONCLUSION: ADAM22, a brain-specific cell surface protein, mediates growth inhibition using an integrin dependent pathway. It is expressed in normal brain but not in high-grade gliomas. A related protein, ADAM11, has only a minor effect on cell growth, and its expression is unchanged in low- and high-grade gliomas.

ADAM Proteins↗

PubMed2004

Epilepsy surgery for pathologically proven hippocampal sclerosis provides long-term seizure control and improved quality of life.

PURPOSE: To examine long-term seizure and quality-of-life outcome in a homogeneous group of patients after temporal lobectomy with pathologically proven hippocampal sclerosis (HS). Previous research has had limited follow-up (generally <2 years) and has grouped patients across multiple pathologies. METHODS: Fifty consecutive patients were identified as having had a temporal lobectomy for the treatment of temporal lobe epilepsy at Royal Melbourne Hospital with pathologically proven HS and >or=2 years' follow-up. All patients were sent a postal survey concerning seizure activity, quality of life (QOLIE-89), and antiepileptic drug (AED) use. The mean follow-up was 5.8 years (range, 2-9.2). RESULTS: The rate of complete postoperative seizure freedom was 82% at 12 months, 76% at 24 months, and 64% at 63 months (no further seizure recurrences observed after this time). A class I seizure outcome was achieved by 83.3% of patients. Patients with better seizure outcome had significantly better quality of life (Kendall's tau =-234, p < 0.01). Seizure recurrence was associated with a reduction in AED intake or absorption in five (29%) of 17 cases, including three of the five patients with a first seizure recurrence after 24 months after surgery. CONCLUSIONS: Temporal lobectomy provides continued long-term seizure control in the majority of patients with HS. However, patients remain at risk of seizure recurrence >or=2 years after surgery. Long-term quality of life is dependent on seizure outcome.

Adolescent↗

PubMed2003

Preoperative evaluation for temporal lobe surgery.

Temporal lobe epilepsy (TLE), the most common form of partial epilepsy in adults is often refractory to medical treatment and in these patients epilepsy surgery is considered. Successful surgery is dependent on accurate localisation and lateralisation of the epileptogenic zone. The preoperative evaluation involves a series of assessments and investigations including detailed clinical history, interictal EEG, video-EEG monitoring, MRI, PET, SPECT, and neuropsychology and neuropsychiatric assessment. The role of each of these investigations and assessments in the preoperative evaluation is discussed. Advanced MR techniques including magnetic resonance spectroscopy, MR diffusion and MR perfusion have recently been assessed and are likely to enhance the pre-surgical evaluation of patients with TLE.The surgical outcome and preoperative investigations performed of 80 consecutive patients who underwent temporal lobe surgery between 1993 and 2002 at Royal Melbourne Hospital were reviewed. All patients had MRI, video-EEG monitoring and neuropsychology assessment and 56% a PET scan. During a mean follow-up of 5.9 years 75% had Class 1 outcome, 22% non-Class 1 outcome and 3% were lost to follow-up. The results of preoperative investigations were correlated with outcome. For interictal EEG, seizure semiology, ictal EEG, PET and neuropsychology assessment the surgical outcome of patients in whom results were concordant to side of surgery was compared with those discordant or non-lateralising. There was no significant difference. In 78 of 80 patients MRI revealed mesial temporal sclerosis or a foreign tissue lesion. The outcome was no different between these two groups. Results suggest that in patients with unilateral temporal lobe lesion on MRI and where ictal EEG is either concordant or non-lateralising, other investigations including PET, provide little additional prognostic information.

Electroencephalography↗

PubMed2003

Emotional and social dysfunction in patients following surgical treatment for brain tumour.

Patients following brain surgery for tumour were assessed using the Emotional and Social Dysfunction questionnaire on a self-rating and partner version of the questionnaire. Analyses were performed on those patients who had self-ratings following surgery for astrocytoma (n=13), meningioma (n=26), neuroma (n=13) and pituitary adenoma (n=17). Patients with astrocytoma were rated highest when compared to the other tumour groups, although all groups of patients performed more poorly on some of the individual scales compared to a matched control group of extra-cerebral neurosurgery patients and terminally ill cancer patients. A malignant (n=48) and benign (n=33) classification similarly showed a higher partner and self-rating of malignant tumour patients. Both diagnosis and location of lesion determined outcome independently. Some differences in profile and severity between patient self-ratings and partner ratings indicate the need to survey both perspectives. This study shows a broader based emotional dysfunction in these patients which includes such prominent features such as anger, helplessness, fatigue, emotional dyscontrol, indifference, and maladaptive behaviour. These results are discussed in terms of follow-up therapeutic care and the need to further explore the relationship between lesion location and emotional profile.

Adenoma↗

PubMed2003

The ESDQ: a new method of assessing emotional and social dysfunction in patients following brain surgery.

The Emotional and Social Dysfunction Questionnaire (ESDQ) has been designed to overcome some of the difficulties of inappropriately applying psychiatric based questionnaires to brain-damaged populations. Two-hundred and twenty-five patients were assessed following brain surgery (BS) using a self-rating patient version of the ESDQ and 211 of these patients were rated by their partner. A factor analysis using a varimax rotation and principal components analysis found the partner results to show eight factors including, Anger, Helplessness, Emotional Dyscontrol, Indifference, Inappropriateness, Fatigue, Maladaptive behaviour, and Insight. The analysis of the Self-rating questions revealed a similar profile, Anger, Emotional Dyscontrol, Helplessness, Inertia, Fatigue, Indifference, Inappropriate, and Euphoria. The scales based on the factors were subjected to discriminant analysis in which the BS patients were compared with a combination control group of neurosurgical outpatients and terminally-ill cancer patients, all of which were without cerebral complaints. The brain surgery results for the partner-rated and the Self-rated version of the ESDQ were compared with control ratings of 42 partners and 54 self-ratings, respectively. The analysis showed a significant discrimination for the Partner-rated version on each of the eight scales individually with an overall significant overall separation (Wilks Lambda=.903, chi=21.1, df=8, p=<.005). The Self-rated version showed less separation on an individual scale basis the Emotional Dyscontrol scale failing to show a significant separation. The overall difference on the Self-rating version was significant [Wilks Lambda=.908, chi=26.2, df=8, p=<.001). The levels of internal consistency of the questionnaire scales were found to be satisfactory (Alpha,.78 -.94). Also the relationship between ESDQ scales and standardised measures of aggression, anxiety, depression, and vigour (STAXI, HADS, and POMS) gave an indication of acceptable levels of concurrent validity.

Adult↗

PubMed2002

Imaging and quantitation of the hypoxic cell fraction of viable tumor in an animal model of intracerebral high grade glioma using [18F]fluoromisonidazole (FMISO).

We have demonstrated that FMISO uptake is significantly higher in tumor tissue in the C6 intracerebral glioma rat model compared to normal brain, and that there is persisting hypoxia in gliomas independent of tumor size. FMISO uptake was observed homogeneously throughout viable glioma tissue in tumor sizes ranging from 2mm to almost 1cm. Quantitation of uptake of FMISO showed a tumor/brain ratio of 1.9 and a tumor/blood ratio of 2.6 at 2 hours post injection.

Animals↗

PubMed2002

EGF receptor modifies cellular responses to hyaluronan in glioblastoma cell lines.

Cell contact with the extracellular matrix component, hyaluronan, plays a pivotal role in glioma cell invasion and proliferation. Although it is well established that glioma cells can bind hyaluronan to their surface via the expression of CD44, the cellular responses following ligand-receptor interaction remain poorly understood. Given that a large proportion of human high grade gliomas over express the epidermal growth factor receptor (EGFR) and ErbB2, this study aimed to investigate whether an interaction exists between CD44 and these receptor tyrosine kinases. Here we present evidence that CD44 co-immunoprecipitates with EGFR and ErbB2 in the glioma cell lines U87MG and SMA560. Hyaluronan treatment mediated the rapid and transient phosphorylation of extracellular signal regulated kinases 1 and 2 (ERK1 and ERK2) in glioma cell lines. This response to hyaluronan was augmented by the co-expression of EGFR. EGFR also differentially modified the hyaluronan induced expression of a number of genes associated with cellular invasion and proliferation. Northern blot analysis demonstrated that genes encoding urokinase type plasminogen activator (uPA), urokinase type plasminogen activator receptor (uPAR), plasminogen activator inhibitor-1 (PAI-1), tissue inhibitor of metalloproteinases (TIMP-1) and c- myc were up-regulated in response to hyaluronan. Furthermore, zymographic analysis revealed increased levels of uPA in the conditioned medium of hyaluronan stimulated cells. These results indicate a novel functional relationship between CD44 and EGFR in glioma cell lines. The capacity of CD44 to form stable complexes with receptor tyrosine kinases may provide a versatile system for the regulation of cellular invasion and proliferation that allows hyaluronan to activate signal transduction pathways and modulate gene expression via an EGFR-dependent manner. These findings provide new insights into the mode by which hyaluronan regulates the malignant phenotype and also suggest a role for EGFR-CD44 interactions in glial tumorigenesis.

Cell Division↗