The parental origin and the meiotic stage of non-disjunction have been determined in 139 Down syndrome patients with regular trisomy 21 and in their parents through the analysis of DNA polymorphism. The meiotic error is maternal in 91.60% cases and paternal in 8.39% of cases. Of the maternal cases, 72.41% were due to meiosis I errors (MMI) and 27.58% were due to meiosis II errors (MMII). Of the paternal cases, 45.45% were due to meiosis I (PMI) and 54.54% were due to meiosis II (PMII). The mean maternal ages were 31.6 +/- 5.3 (+/- SD) years in errors from MMI, 32.3 +/- 6.4 years in errors from MMII, 31.4 +/- 4.6 years in errors from PMI and 29.5 +/- 2.7 years in errors from PMII. No significant statistical differences were observed between maternal and paternal errors, further supporting the presence of a constant chromosome 21 non-disjunction error type.
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Neurology
August 2015
From Janssen Alzheimer Immunotherapy Research & Development, LLC (E.L., R.M., P.C., K.M.G., J.D., Y.L., I.C.T., S.B., E.Y., H.R.B.), South San Francisco, CA; Janssen Pharmaceutical (M.E.S.), Beerse, NV; Brigham & Women's Hospital (R.S.), Boston, MA; University of Michigan (R.K.), Ann Arbor; University of Pittsburgh (N.S.M., W.E.K., C.A.M.), PA; Butler Hospital (S.S.), Providence, RI; UCL Institute of Neurology (N.C.F.), London, UK; IXICO plc (D.L.H., A.S.L.), London, UK; Pfizer Inc. (B.T.W.), Groton, CT; Pfizer Inc. (K.B.), Collegeville, PA; Global R&D Partners, LLC (M.G.), San Diego, CA; and University of California (M.G.), San Diego.
Objective: To evaluate the effects of bapineuzumab on brain β-amyloid (Aβ) burden using (11)C-Pittsburgh compound B ((11)C-PiB)-PET.
Methods: Two phase 3 clinical trials, 1 each in apolipoprotein APOE ε4 carriers and noncarriers, were conducted in patients with mild to moderate Alzheimer disease dementia. Bapineuzumab, an anti-Aβ monoclonal antibody, or placebo, was administered by IV infusion every 13 weeks for 78 weeks.
N Engl J Med
January 2014
From Butler Hospital, Providence, RI (S.S.); Brigham and Women's Hospital, Boston (R.S.); University College London, Institute of Neurology, London (N.C.F.); University of Göteborg, Sahlgrenska University Hospital, Mölndal, Sweden (K.B.); University of Pittsburgh, Pittsburgh (W.K.); Veterans Affairs Medical Center, Seattle (M.R.); Cleo Roberts Center for Clinical Research/Sun Health Research Institute, Sun City, AZ (M.S.); Columbia University (L.S.H.) and New York University Langone Medical Center (S.F.), New York; University of Rochester School of Medicine and Dentistry, Rochester, NY (A.P.P.); Janssen Alzheimer Immunotherapy Research and Development, South San Francisco, CA (M.R., N.K., B.N., V.G., M.M., D.W., Y.L., I.C.T., E.L., E.Y., H.R.B.); Janssen Research and Development, Titusville, NJ (J.L.); Global R&D Partners and the University of California, San Diego - both in San Diego (M.G.); and Pfizer, Collegeville, PA (R.B.).
Background: Bapineuzumab, a humanized anti-amyloid-beta monoclonal antibody, is in clinical development for the treatment of Alzheimer's disease.
Methods: We conducted two double-blind, randomized, placebo-controlled, phase 3 trials involving patients with mild-to-moderate Alzheimer's disease--one involving 1121 carriers of the apolipoprotein E (APOE) ε4 allele and the other involving 1331 noncarriers. Bapineuzumab or placebo, with doses varying by study, was administered by intravenous infusion every 13 weeks for 78 weeks.
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