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Down Syndrome Patients (down + syndrome_patient)
Selected AbstractsCharacterization of the cardiac phenotype in neonatal Ts65Dn miceDEVELOPMENTAL DYNAMICS, Issue 2 2008Austin D. Williams Abstract The Ts65Dn mouse is the most-studied of murine models for Down syndrome. Homology between the triplicated murine genes and those on human chromosome 21 correlates with shared anomalies of Ts65Dn mice and Down syndrome patients, including congenital heart defects. Lethality is associated with inheritance of the T65Dn chromosome, and anomalies such as right aortic arch with Kommerell's diverticulum and interrupted aortic arch were found in trisomic neonates. The incidence of gross vascular abnormalities was 17% in the trisomic population. Histological analyses revealed interventricular septal defects and broad foramen ovale, while immunohistochemistry showed abnormal muscle composition in the cardiac valves of trisomic neonates. These findings confirm that the gene imbalance present in Ts65Dn disrupts crucial pathways during cardiac development. The candidate genes for congenital heart defects that are among the 104 triplicated genes in Ts65Dn mice are, therefore, implicated in the dysregulation of normal cardiogenic pathways in this model. Developmental Dynamics 237:426,435, 2008. © 2007 Wiley-Liss, Inc. [source] Characterization of a mouse model overexpressing beta-site APP-cleaving enzyme 2 reveals a new role for BACE2GENES, BRAIN AND BEHAVIOR, Issue 2 2010G. Azkona BACE2 is homologous to BACE1, a ,-secretase that is involved in the amyloidogenic pathway of amyloid precursor protein (APP), and maps to the Down syndrome critical region of chromosome 21. Alzheimer disease neuropathology is common in Down syndrome patients at relatively early ages, and it has thus been speculated that BACE2 co-overexpression with APP would promote the early neurodegenerative phenotype. However, the in vivo function of BACE2 has not yet been elucidated. The aim of the present work has been to analyse the impact of in vivo BACE2 overexpression using a transgenic mouse model. Our results suggest that BACE2 is not involved in the amyloidogenic pathway, cognitive dysfunction or cholinergic degeneration. However, TgBACE2 animals showed increased anxiety-like behaviour along with increased numbers of noradrenergic neurones in locus coeruleus, thus suggesting an unexpected role of BACE2 overexpression. [source] Treatment-related death in childhood acute lymphoblastic leukaemia in the Nordic countries: 1992,2001BRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2005Merete Stubkjaer Christensen Summary Despite continuously more successful treatment of childhood acute lymphoblastic leukaemia (ALL), 2,5% of children still die of other causes than relapse. The Nordic Society of Paediatric Haematology and Oncology-ALL92 protocol included 1652 patients ,15 years of age with precursor B- and T-cell ALL diagnosed between 1992 and 2001. Induction deaths and deaths in first complete remission (CR1) were included in the study. A total of 56 deaths (3%) were identified: 19 died during induction (1%) and 37 in CR1 (2%). Infection was the major cause of death in 38 cases. Five patients died of early death before initiation of cytotoxic therapy. Five patients died because of toxicity of inner organs and one of accidental procedure failures. Seven patients died of complications following allogenic haematopoietic stem cell transplantation (HSCT) in CR1. Girls were at higher risk of treatment-related death (TRD) [relative risk (RR) = 2·2; 95% confidence interval (CI95%): 1·2,4·0, P < 0·01], mostly because of infections. Risk of TRD was also higher in children with Down syndrome (RR = 4·5; CI95%: 2·0,10·2, P < 0·00). In conclusion, 3% of children with ALL died of TRD, with bacterial infections as the most common cause of death. Girls and Down syndrome patients had a higher risk of TRD. Infections still remain a major challenge in childhood ALL. [source] Analysis of matrix metalloproteinase (MMP-8 and MMP-2) activity in gingival crevicular fluid from children with Down's syndromeJOURNAL OF PERIODONTAL RESEARCH, Issue 2 2010T. Yamazaki-Kubota Yamazaki-Kubota T, Miyamoto M, Sano Y, Kusumoto M, Yonezu T, Sugita K, Okuda K, Yakushiji M, Ishihara K. Analysis of matrix metalloproteinase (MMP-8 and MMP-2) activity in gingival crevicular fluid from children with Down's syndrome. J Periodont Res 2010; doi: 10.1111/j.1600-0765.2009.01214.x. © 2009 John Wiley & Sons A/S Background and Objective:, High levels of colonization by periodontopathic bacteria and a high prevalence of chronic inflammatory periodontal disease have been reported in children with Down's syndrome. Matrix metalloproteinases (MMPs) are mediators of extracellular matrix degradation and remodelling, and are deeply involved in the course of periodontal disease. To clarify the relationship between Down's syndrome and periodontitis, we investigated levels of MMP-2 and MMP-8 in gingival crevicular fluid (GCF) and detection of periodontopathic bacteria from subgingival plaque. Material and Methods:, Samples of GCF and plaque were isolated from central incisors. Levels of MMPs were evaluated by enzyme-linked immunosorbent assay, and periodontopathic bacteria were detected by polymerase chain reaction. Results:, Levels of MMP-2 and MMP-8 in Down's syndrome patients were higher than those in healthy control subjects. In the Down's syndrome group, increases in these MMPs were observed in GCF from patients with an oral hygiene index score of < 2 and in GCF from sites that were negative for bleeding on probing. The detection rate of periodontopathic bacteria in Down's syndrome patients was higher than that in the control subjects. Matrix metalloproteinase-2 levels in sites harbouring Porphyromonas gingivalis or Aggregatibacter (Actinobacillus) actinomycetemcomitans were lower than in those without these microorganisms. Conclusion:, These results suggest an increase in MMP-2 and MMP-8 in Down's syndrome patients, regardless of whether inflammation of periodontal tissue is present or not. [source] Enhancement of matrix metalloproteinase (MMP)-2 activity in gingival tissue and cultured fibroblasts from Down's syndrome patientsORAL DISEASES, Issue 1 2001T Komatsu OBJECTIVES: To identify one of the possible factors responsible for periodontal disease in Down's syndrome (trisomy 21) patients, we studied the enzyme activity and the mRNA expression pattern of matrix metalloproteinases (MMPs) of cultured gingival fibroblasts (GF) and fresh gingival tissues. MATERIALS AND METHODS: Gingival tissue was used as the cell source and was biopsied at the time of dental treatment from nine patients with Down's syndrome and nine non-Down's controls. GF were cultivated in serum-free media for analyses of their MMP activities at the transcription or the protein level. The MMP activities in the supernates were measured by gelatin impregnated zymography. Relative levels of MMP mRNA from the cultured GF or freshly isolated gingival tissues were determined using the reverse transcription polymerase chain reaction (RT-PCR). RESULT AND CONCLUSIONS: The production of the active type of MMP-2 in GF from Down's syndrome patients (D-GF) was found to be significantly higher (P < 0.05) than that of the control GF (C-GF) at the protein level. The mRNA expressions of membrane-type1 MMP (MT1-MMP) and MMP-2 in D-GF were constitutively augmented when compared with those of C-GF. These findings suggest that specific increase of the active form of MMP-2 in D-GF may possibly be due to the concomitant expression of MT1-MMP in the cultured cells, and this could be related to the pathogenesis of gingivitis/periodontitis associated with Down's syndrome patients. [source] |