Biomedical subjects

R Gilbertson

Publications and source records attributed to R Gilbertson.

8 recordsLinked to original sources

PubMed2002

Genetic abnormalities detected in ependymomas by comparative genomic hybridisation.

Using comparative genomic hybridisation, we have analysed genetic imbalance in a series of 86 ependymomas from children and adults. Tumours were derived from intracranial and spinal sites, and classified histologically as classic, anaplastic or myxopapillary. Ependymomas showing a balanced profile were significantly (P<0.0005) more frequent in children than adults. Profiles suggesting intermediate ploidy were common (44% of all tumours), and found more often (P<0.0005) in tumours from adults and the spinal region. Loss of 22q was the most common specific abnormality, occurring in 50% of spinal (medullary) ependymomas and 26% of tumours overall. Genetic profiles combining loss of 22q with other specific abnormalities--gain of 1q, loss of 6q, loss of 10q/10, loss of 13, loss of 14q/14--varied according to site and histology. In particular, we showed that classic ependymomas from within the cranium and spine have distinct genetic profiles. Classic and anaplastic ependymomas with gain of 1q tended to occur in the posterior fossa of children and to behave aggressively. Our extensive data on ependymomas demonstrate significant associations between genetic aberrations and clinicopathological variables, and represent a starting point for further biological and clinical studies.

Adolescent↗

PubMed2002

Paediatric embryonic brain tumours. biological and clinical relevance of molecular genetic abnormalities.

Embryonal tumours constitute the largest group of malignant paediatric brain tumours. Their origin and histological classification remain somewhat controversial. However, in recent years real progress has been made in our understanding of the molecular genetic abnormalities that govern the initiation and/or progression of these tumours. A number of these abnormalities appear to involve alterations in signalling systems that control normal cerebellar development. Increasing our understanding of both the biology and clinical relevance of these molecular defects is a major challenge to the field of paediatric neuro-oncology. However, it likely represents the only means by which we will advance the management of these tumours, significantly reducing disease-related morbidity and mortality. This review focuses on the principal molecular genetic abnormalities so far identified in embryonal brain tumours and discusses their biological and clinical relevance.

Brain Neoplasms↗

PubMed2001

Clinical and molecular stratification of disease risk in medulloblastoma.

The accurate assessment of disease risk among children with medulloblastoma remains a major challenge to the field of paediatric neuro-oncology. In the current study we investigated the capacity of molecular abnormalities to increase the accuracy of disease risk stratification above that afforded by clinical staging alone. 41 primary medulloblastoma tumour samples were analysed for ErbB2 receptor expression using immunohistochemistry, and for aberrations of chromosome 17 and amplification of the MYC oncogene using fluorescence in situ hybridisation. The ErbB2 receptor and deletion of 17p were detected in 80% and 49% of tumours, respectively. 17p loss occurred either in isolation (20%), or in association with gain of 17q (29%), compatible with an isochromosome of 17q. Amplification of MYC was detected in only 2 tumours. Significant prognostic factors included, 'metastatic disease' (P = 0.0006), 'sub-total tumour resection' (P = 0.007), 'high ErbB2 receptor expression' (P = 0.003) and 'isolated 17p loss' (P = 0.003). Combined analysis of clinical and molecular factors enabled greater resolution of disease risk than clinical factors alone, identifying a sub-population of patients with particularly favourable disease outcome. These data support the hypothesis that a combination of clinical and molecular factors may afford a more reliable means of assigning disease risk in patients with medulloblastoma, thereby providing a more accurate basis for targeting therapy in children with this disease.

Adolescent↗

PubMed2001

Novel ERBB4 juxtamembrane splice variants are frequently expressed in childhood medulloblastoma.

We recently reported a significant relationship between tumor cell expression of the ERBB4 receptor, the most recently described member of the epidermal growth factor receptor family, and aggressive tumor phenotype in childhood medulloblastoma. Two alternative juxtamembrane (JM) isoforms of the ERBB4 receptor have been described. Termed JMa and JMb, these variants possess different receptor processing and ligand-binding characteristics. In the current study, we employed an RT-PCR and sequencing strategy to determine the pattern of ERBB4 JM isoform expression in a large (n = 78) series of pediatric medulloblastomas. JMa and JMb transcript expression was detected in 53% and 28% of tumor samples, respectively. In addition, two novel ERBB4 JM isoforms, which we have termed JMc and JMd, were isolated from 10% and 36% of tumors, respectively. Sequence analysis revealed the JMc transcript to contain a deletion of the entire JM region. In contrast, JMd includes an extended coding region, retaining both the JMa and JMb sequences. Neither of these novel isoforms was detected in normal human adult cerebellum, but expression of JMd was observed in developing fetal cerebellum, suggesting that this later isoform may represent an ERBB4 transcript restricted to primitive neuroectoderm-derived tissue. To confirm that the four ERBB4 JM isoforms arise by alternative RNA splicing, we sequenced the intron-exon junctions of the human ERBB4 gene within the JM region. This demonstrated the four ERBB4 JM variants to be encoded by two short exons containing the JMb and JMa sequences positioned in the order 5' to 3' and separated by a 121 bp intron.

Alternative Splicing↗

PubMed1999

The drinker's children.

There is no doubt that growing up in a home where one or both parents misuse alcohol is undesirable. However, it is far less certain that this predicament is responsible for psychological damage to the child in the long term. This paper reviews the literature on the psychological effects on children of parental alcohol misuse and concludes that research needs to move beyond crude comparisons between alcohol-affected and nonalcohol-affected homes to a search for the precise mechanism(s) responsible for mediating any statistical associations between parental drinking and psychological deficits in children.

Adolescent↗

PubMed1998

The relative importance of factors which influence order of injecting with a shared needle and syringe.

Injecting drug users (IDUs) in Adelaide, South Australia, rated the likelihood of first use of a shared needle and syringe by persons who have characteristics which have previously been suggested as influencing order of injecting. This enabled the relative importance of these factors to be assessed. It was found that those who supply their own drug and injecting equipment have the greatest likelihood of using first, but it is also somewhat advantageous if one is able to promote one's needs, has recently been tested for HIV or is at home when the opportunity to inject arises. Older IDUs and regular users may be slightly advantaged, as may those who inject others and those who were denied first use the last time sharing occurred. A model for predicting order of use is proposed.

Adolescent↗

PubMed1997

Unilateral interventions for women living with heavy drinkers.

Despite the fact that unilateral therapy is often the only treatment option for women living with heavy drinkers, very few structured programs have been developed for this client group. Moreover, the programs that do exist lack empirical support (as in the case of Al-Anon) or have as their highest priority promoting change in the drinker. This article looks at unilateral therapy for women partners of heavy drinkers and concludes that although a number of promising developments have occurred in recent years, more research is needed on the benefits to the women themselves.

Alcoholics Anonymous↗

PubMed1997

Coping with a partner who drinks too much: does anything work?

This paper reports on a multiple regression study in which the efficacy of positive and negative coping responses adopted by the partners of "heavy drinkers" were compared under conditions of drinker intoxication and sobriety. Results indicated that only one combination of response type and drinker state was associated with higher levels of partner well-being: positive responses when the drinker is sober. Moreover, even this coping pattern accounted for relatively little variance in partner well-being scores. It is concluded that programs which aim to improve the quality of partner's lives should not generalize about desirable coping behaviours but should take account of situational and individual difference variables.

Adaptation, Psychological↗