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Biomedical subjects

Sue Buckley

Publications and source records attributed to Sue Buckley.

11 recordsLinked to original sources

Evidence that we can change the profile from a study of inclusive education.

This paper discusses the evidence that the specific developmental profile frequently described as being associated with Down syndrome--a profile of communication weaknesses relative to social and daily living skills - can be changed. It is not an inevitable outcome of having Down syndrome. Drawing on data collected to explore the outcomes of fully inclusive education for school-age children with Down syndrome, the authors identify that the profile is seen in teenagers in special education settings but is not evident for teenagers in inclusive education. They argue that this is the result of both the effects of fully inclusive education and teaching approaches which have been adapted to address the cognitive and communication weaknesses of the children from an early age.

Child↗

A comparison of mainstream and special education for teenagers with Down syndrome: implications for parents and teachers.

This article presents data from a research study designed to compare the achievements of teenagers with Down syndrome educated in mainstream classrooms or in special education classrooms throughout their full-time education. Progress is reported for speech and language, literacy, socialisation, daily living skills and behaviour. For all the teenagers, there is evidence of progress with age on all the measures except for communication. Communication continued to improve through teenage years for the included children but not for those in special education classrooms. There were no significant differences in overall outcomes for daily living skills or socialisation. However, there were large significant gains in expressive language and literacy skills for those educated in mainstream classrooms. Teenagers educated in mainstream classrooms showed fewer behavioural difficulties. Further, comparison with data published by these authors in an earlier study, showed no improvements in school achievements in special education over a 13 year period in the UK (1986-1999).

Activities of Daily Living↗

Abnormal mouse lung alveolarization caused by Smad3 deficiency is a developmental antecedent of centrilobular emphysema.

Transforming growth factor-beta (TGF-beta) signaling plays an important regulatory role during lung development and remodeling. Smad3 is a major downstream signal transducer in the TGF-beta pathway from the cell membrane to the nucleus. In Smad3 null mutant mice, we have observed retarded lung alveolarization from postnatal day 7 to day 28, and subsequently centrilobular emphysema starting from day 28, as determined by morphometric analysis. In addition to the morphological changes, peripheral lung cell proliferation in Smad3 knockout mice was reduced compared with the wild-type control between postnatal days 7 and 28. Expression of tropoelastin at the mRNA level was also dramatically decreased in Smad3 knockout lungs from postnatal day 28 through adulthood. Furthermore, increased matrix metalloproteinase-9 protein expression and activity were detected in the Smad3 knockout mouse lung tissue and the bronchoalveolar lavage fluid at postnatal day 28 when the centrilobular emphysema pathology was just beginning to appear. Therefore, these results indicate that Smad3 not only has a positive regulatory impact on neonatal lung alveolarization but also potentially plays a protective role against the occurrence of centrilobular emphysema later on in life.

Animals↗

The matrix metalloproteinase inhibitor prinomastat enhances photodynamic therapy responsiveness in a mouse tumor model.

Photodynamic therapy (PDT) clinical results are promising; however, tumor recurrences can occur and, therefore, methods for improving treatment efficacy are needed. PDT elicits direct tumor cell death and microvascular injury as well as expression of angiogenic, inflammatory, and prosurvival molecules. Preclinical studies combining antiangiogenic drugs or cyclooxygenase-2 inhibitors with PDT show improved treatment responsiveness (A. Ferrario et al., Cancer Res 2000;60:4066-9; A. Ferrario et al., Cancer Res 2002;62:3956-61). In the present study, we evaluated the role of Photofrin-mediated PDT in eliciting expression of matrix metalloproteinases (MMPs) and modulators of MMP activity. We also examined the efficacy of a synthetic MMP inhibitor, Prinomastat, to enhance tumoricidal activity after PDT, using a mouse mammary tumor model. Immunoblot analysis of extracts from PDT-treated tumors demonstrated strong expression of MMPs and extracellular MMP inducer along with a concomitant decrease in expression of tissue inhibitor of metalloproteinase-1. Gelatin zymography and enzyme activity assays performed on protein extracts from treated tumors confirmed the induction of both latent and enzymatically active forms of MMP-9. Immunohistochemical analysis indicated that infiltrating inflammatory cells and endothelial cells were primary sources of MMP-9 expression after PDT, whereas negligible expression was observed in tumor cells. Administration of Prinomastat significantly improved PDT-mediated tumor response (P = 0.02) without affecting normal skin photosensitization. Our results indicate that PDT induces MMPs and that the adjunctive use of an MMP inhibitor can improve PDT tumor responsiveness.

Animals↗

TACE is required for fetal murine cardiac development and modeling.

Tumor necrosis factor-alpha converting enzyme (TACE) is a membrane-anchored, Zn-dependent metalloprotease, which belongs to the ADAM (a disintegrin and metalloprotease) family. TACE functions as a membrane sheddase to release the ectodomain portions of many transmembrane proteins, including the precursors of TNFalpha, TGFalpha, several other cytokines, as well as the receptors for TNFalpha, and neuregulin (ErbB4). Mice with TACE(DeltaZn/DeltaZn) null mutation die at birth with phenotypic changes, including failure of eyelid fusion, hair and skin defects, and abnormalities of lung development. Abnormal fetal heart development was not previously described. Herein, we report that TACE(DeltaZn/DeltaZn) null mutant mice by late gestation exhibit markedly enlarged fetal hearts with increased myocardial trabeculation and reduced cell compaction, mimicking the pathological changes of noncompaction of ventricular myocardium. In addition, larger cardiomyocyte cell size and increased cell proliferation were observed in ventricles of TACE(DeltaZn/DeltaZn) knockout mouse hearts. At the molecular level, reduced expression of epidermal growth factor receptor, attenuated protein cleavage of ErbB4, and changes in MAPK activation were also detected in TACE(DeltaZn/DeltaZn) knockout heart tissues. The data suggest that TACE-mediated cell surface protein ectodomain shedding plays an essential and a novel regulatory role during cardiac development and modeling.

ADAM Proteins↗

Isolation of a putative progenitor subpopulation of alveolar epithelial type 2 cells.

Alveolar epithelial type 2 cells (AEC2) isolated from hyperoxia-treated animals exhibit increases in both proliferation and DNA damage in response to culture. AEC2 express the zonula adherens proteins E-cadherin, -, - and -catenin, desmoglein, and pp120, as demonstrated by Western blotting. Immunohistochemical analysis of cultured AEC2 showed expression of E-cadherin on cytoplasmic membranes varying from strongly to weakly staining. When cultured AEC2 placed in suspension were labeled with fluorescent-tagged antibodies to E-cadherin, cells could be sorted into at least two subpopulations, either dim or brightly staining for this marker. With the use of antibody to E-cadherin bound to magnetic beads, cells were physically separated into E-cadherin-positive and -negative subpopulations, which were then analyzed for differences in proliferation and DNA damage. The E-cadherin-positive subpopulation contained the majority of damaged cells, was quiescent, and expressed low levels of telomerase activity, whereas the E-cadherin-negative subpopulation was undamaged, proliferative, and expressed high levels of telomerase activity.

Adherens Junctions↗

Reading, language and memory skills: a comparative longitudinal study of children with Down syndrome and their mainstream peers.

BACKGROUND: Many of today's young adults with Down syndrome never had the opportunity to learn to read. However, an increasing number of children with Down syndrome are currently attending mainstream schools and being taught to read. As a consequence, it is now possible to systematically study reading development in children with Down syndrome. AIMS: The aim of this study was to chart the development of reading, language, and memory skills in children with Down syndrome and to investigate the relationships between these abilities. SAMPLE: Twenty-four children with Down syndrome aged between 4 and 12 were followed over two years and compared to 31 children matched for reading age, and 42 children of average reading ability, selected from the same mainstream classes as the children with Down syndrome. METHOD: Standardised assessments were administered annually to obtain measures of reading, spelling, language, memory, and general intelligence. RESULTS: The children with Down syndrome had relatively advanced single word reading ability compared to their other cognitive skills. The reading progress of the children with Down syndrome did not differ significantly from that of the reading matched group even after two years. Different cognitive abilities were highly correlated with one another in all groups. However, after controlling for age, many of the partial correlations between reading and the other measures were reduced to non-significant levels. CONCLUSIONS: Most children with Down syndrome are capable of learning to read single words. However, there was no evidence over this two-year period to support the hypothesis that learning to read will help to enhance language and memory development in children with Down syndrome.

Analysis of Variance↗

Phonological awareness in children with Down syndrome.

Research in the area of phonological awareness has mainly focused on the nature of the relationship between reading ability and awareness of phonemes. However, a recent study of phonological awareness in children with Down syndrome questioned the existence of any necessary relationship (Cossu, Rossini & Marshall, 1993). This paper describes a study of phonological awareness in children with Down syndrome with varying levels of reading ability. The sample consisted of 10 male and 7 female children with Down syndrome (aged 9 years 2 months to 14 years 5 months). All children received a battery of tests which consisted of assessments of: 1) phonological awareness, 2) reading and spelling competence, 3) non-word reading and spelling ability, and 4) non-verbal measures. Children with Down syndrome demonstrated measurable levels of phonological awareness. Significant positive correlations were found between phonological awareness and: reading and spelling competence, ability to spell non-words and non-verbal measures.

Adolescent↗