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Biomedical subjects

Michael Fitzgerald

Publications and source records attributed to Michael Fitzgerald.

25 records · Page 2Linked to original sources
PubMed2002

Synthesis and biological evaluation of 2-indolyloxazolines as a new class of tubulin polymerization inhibitors. Discovery of A-289099 as an orally active antitumor agent.

A series of indole containing oxazolines has been discovered as a result of structural modifications of the lead compound A-105972. The compounds exert their anticancer activity through inhibition of tubulin polymerization by binding at the colchicine site. A-289099 was identified as an orally active antimitotic agent active against various cancer cell lines including those that express the MDR phenotype. The anticancer activity, pharmacokinetics, and an efficient and enantioselective synthesis of A-289099 are described.

Animals↗
PubMed2002

Symptom domains in autism and related conditions: evidence for familiality.

Heterogeneity in autism impairs efforts to localize and identify the genes underlying this disorder. As autism comprises severe but variable deficits and traits in three symptom domains (social interaction, communication, and repetitive behaviors) and shows variability in the presence and emergence of useful phrase speech, different genetic factors may be associated with each. The affected cases (n=457) in multiply affected siblingships (n=212), including a proband with autism and one or more siblings with either autism or marked deficits in autism symptom domains, were assessed using the Autism Diagnostic Interview, Revised. Symptom domain scores and language features were examined to determine their similarity within siblingships. The variance within siblingships was reduced for the repetitive behavior domain and for delays in and the presence of useful phrase speech. These features and the nonverbal communication subdomain provided evidence of familiality when we considered only the diagnosis of autism to define multiply affected siblingships (cases: n=289; siblingships: n=136). In addition, the same familial features identified also appeared familial for those with autism-related conditions. Finally, the level of severity of almost all of the familial features varied within multiplex siblingships independently. The features identified as familial replicate the combined set suggested in earlier, smaller studies. Furthermore, the familiality of these features extend to related conditions of milder severity than autism and appear to be independent. Making distinctions among families by the severity of these features may be useful for identifying more genetically homogeneous subgroups in studies targeted at genes for specific autism-related symptom domains.

Autistic Disorder↗
PubMed2002

Dopaminergic system genes in ADHD: toward a biological hypothesis.

Converging evidence has implicated abnormalities of dopamine neurotransmission to the pathology of attention deficit hyperactivity disorder (ADHD). Several genetic association studies have been published, but so far, no DNA variants have been unequivocally demonstrated as contributing to ADHD susceptibility. Four dopamine related gene loci have been implicated, however: DAT 1, DRD 4, DBH, and DRD 5. Each of these may influence the liability of ADHD to a small degree. Notably, all are involved in signal transduction at the neuronal synapse. In this article, we investigate as candidate genes for ADHD, DNA polymorphisms at dopamine receptors, the dopamine transporter, and genes known to be involved in dopamine synthesis and metabolism. In a recent article, we confirmed the previously reported association of DAT 1 (480 bp allele) with ADHD and identified polymorphisms at two additional loci showing preferential transmission to ADHD children of alleles at DRD 5 (148 bp allele) and at DBH (allele 2, Taq I polymorphism). Increased transmission of the 4 bp deletion in the untranslated exon 1 of the DOPA decarboxylase gene was also observed but was of marginal significance. Nonsignificant trends of association were found for TH (allele 2) and DRD2 (Ser-311). No preferential transmission of alleles to ADHD children was observed for polymorphisms at DRD 1, DRD 2 (Taq I), DRD 3, DRD 4, and COMT. Analyzing the data by sex of transmitting parent showed significant preferential paternal transmission of alleles at TH (allele 2) and a nonsignificant trend for paternal transmission for DRD 2 (Ser-311). We attempt to put these findings together with what is known of the function of the particular proteins, and suggest working hypotheses.

Adolescent↗
PubMed2002

European adolescent substance use: the roles of family structure, function and gender.

OBJECTIVES: The aim of this study was, first, to explore family structure and measures of family functioning in relation to adolescent substance use and secondly, to establish if these relationships differed according to gender or according to the city of origin of the sample. DESIGN, SETTING, PARTICIPANTS: The study surveyed pupils aged 14-15 years in representative samples drawn from five European cities: Newcastle upon Tyne, Dublin, Rome, Bremen and Groningen. Data were obtained on 3984 participants in relation to their substance use, living with both biological parents, confiding in parents and grandparents. and supervision, as well as other variables representing delinquency, social class and drug availability. RESULTS: Living with both parents was associated with reduced levels of drug use in four cities but not in Dublin, due perhaps to the high availability from peers in that city. It was not associated with reduced levels of regular drinking. The effect of confiding in mother was evident in all cities and in relation to substance use in general. However, when a delinquency variable was added to the logistic regressions, its significance in relation to polydrug use disappeared. Supervision was somewhat more important in relation to male than female drug use. CONCLUSION: Living with both parents is a less robust barrier to substance use than qualitative aspects of family life, particularly attachment to mothers. The latter is a robust inhibitor of substance use irrespective of regional differences in drug availability, weakening only in the face of more generally problematic behaviour. Perhaps because of their greater tendency to risk-taking or rule breaking, supervision appears more important for male than female drug use. These findings underscore the role of families, but especially that of mothers, in regulating the substance-related behaviour of young people.

Adolescent↗