scholarly journals A year of unprecedented progress in Down syndrome basic research

2007 ◽  
Vol 13 (3) ◽  
pp. 215-220 ◽  
Author(s):  
Roger H. Reeves ◽  
Craig C. Garner
Keyword(s):  
Down Syndrome ◽  
Basic Research

scholarly journals CHROMOSOMAL DISEASES IN THE HUMAN PATHOLOGY

2020 ◽  
Vol 6 (1) ◽  
pp. 50-60
Author(s):  
T.V. Bihunyak ◽  
Yu. I. Bondarenko ◽  
O. O. Кulyanda ◽  
S. M. Charnosh ◽  
A. S. Sverstiuk ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Trisomy 21 ◽  
Dna Analysis ◽  
Klinefelter Syndrome ◽  
Basic Research ◽  
Multiple Birth ◽  
X Chromosomes ◽  
Screening Programs ◽  
Human Pathology ◽  
Chromosomal Diseases

Background. Chromosomal diseases are the cause of 45-50 % of multiple birth defects. Basic research on mutations is performed using genomic technologies to identify a correlation between genotype and phenotype in aneuploidies and to understand its pathogenesis. Objective. The aim of the research is to study the etiology, pathogenesis of symptoms and diagnostics for patients with Down, Klinefelter, Turner syndromes and double aneuploidies by 21 and sex chromosomes. Methods. A literature review by the keywords “Down syndrome”, “Klinefelter syndrome”, “Turner syndrome”, “double aneuploidy” for the period of 2000-2020 was carried out. Results. Down, Klinefelter and Turner syndromes are the most common aneuploidy among viable newborns. Frequency of meiotic non-disjunction events causing these aneuploidies increases with the age of a woman. Identified genes are responsible for pathogenesis of symptoms in trisomy 21, Turner and Klinefelter syndromes. Diagnostics of chromosomal diseases includes prenatal screening programs and postnatal testing. Conclusions. Cytogenetic variants of Down syndrome are simple complete trisomy 21, translocation form and mosaicism. Trisomy 21 is associated with advanced maternal age. Phenotypic manifestations of Down syndrome are associated with the locus 21q22. The maternal and parental nondisjunction of X-chromosomes in meiosis causes Klinefelter and Turner syndromes. These chromosomal diseases are variants of intersexualism with intermediate chromosomal sex. Down-Klinefelter and Down-Turner syndromes are double aneuploidies. Patients have a Down syndrome phenotype at birth, and signs of Klinefelter and Turner syndromes occur during puberty. Diagnosis of aneuploidy is based on the cytogenetic investigation (karyotyping), DNA analysis, ultrasonography and biochemical markers of chromosomal pathology.

scholarly journals The first transchromosomic rat model with human chromosome 21 shows robust Down syndrome features

2021 ◽  
Author(s):  
Yasuhiro Kazuki ◽  
Feng J Gao ◽  
Miho Yamakawa ◽  
Masumi Hirabayashi ◽  
Kanako Kazuki ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Human Chromosome ◽  
Mouse Models ◽  
Rat Model ◽  
Heart Development ◽  
Basic Research ◽  
Craniofacial Morphology ◽  
Chromosome 21 ◽  
Brain Morphology ◽  
Human Chromosome 21

Progress in earlier detection and symptom management has increased life expectancy and quality of life in people with Down syndrome (DS). However, no drug has been approved to help individuals with DS live independently and fully. Although rat models could support more robust physiological, behavioral, and toxicology analysis than mouse models during preclinical validation, no DS rat model is available due to technical challenges. We developed the first transchromosomic rat model of DS, TcHSA21rat, which contains a freely segregating, EGFP-inserted, human chromosome 21 (HSA21) with >93% of its protein coding genes. RNA-Seq of neonatal forebrains demonstrates that TcHSA21rat not only expresses HSA21 genes but also has an imbalance in global gene expression. Using EGFP as a marker for trisomic cells, flow cytometry analyses of peripheral blood cells from 361 adult TcHSA21rat animals show that 81% of animals retain HSA21 in >80% of cells, the criterion for a "Down syndrome karyotype" in people. TcHSA21rat exhibits learning and memory deficits and shows increased anxiety and hyperactivity. TcHSA21rat recapitulates well-characterized DS brain morphology, including smaller brain volume and reduced cerebellar size. In addition, the rat model shows reduced cerebellar foliation, a prominent feature of DS that is not observed in DS mouse models. Moreover, TcHSA21rat exhibits anomalies in craniofacial morphology, heart development, husbandry, and stature. TcHSA21rat is a robust DS animal model that can facilitate DS basic research and provide a unique tool for preclinical validation to accelerate DS drug development.

scholarly journals MRD-Based Strategy without Myeloablative Transplantation for AML in Children

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3738-3738
Author(s):  
Akihisa Sawada ◽  
Sadao Tokimasa ◽  
Masahiro Yasui ◽  
Maho Koyama-Sato ◽  
Mariko Shimizu ◽  
...  
Keyword(s):  
Down Syndrome ◽  
De Novo ◽  
Conflicts Of Interest ◽  
Residual Disease ◽  
Basic Research ◽  
High Risk Group ◽  
Rank Test ◽  
Eligibility Criteria ◽  
Period Range ◽  
Hematopoietic Stem

Abstract Background. For the purpose of increasing survival rate and minimizing early and late toxicities, we conducted a clinical study of an individualized treatment of AML in children between Jun/2002 and September/2014. Minimal residual disease (MRD)-based stratification was employed in this study, and patients in the high-risk group underwent allogeneic hematopoietic stem cell transplantation (HSCT) following reduced-intensity conditioning (RIC). This study was following our previous studies of a basic research on MRD in 1990s, and an early multi-center study between Feb/1999 and May/2002 [Miyamura T, et al. IJH 79: 243-249, 2004]. Methods. The main eligibility criteria were as follows: children with newly diagnosed de novo AML (excluding FAB M3), and with written informed consent obtained by the patients' guardians and the patients if aged 16 years or more. The main exclusion criteria were children with organ failure, and with uncontrolled infections. The treatment consisted of one induction chemotherapy and 5 courses of consolidation chemotherapy originating from the AML99 protocol [Tsukimoto I, et al. JCO 27: 4007-4013, 2009]. Patients with Down syndrome were treated with a dose-reduced protocol. WT1 mRNA in PB, WT1 mRNA in BM, and chimeric-gene mRNA in BM were measured as MRD markers by quantitative RT-PCR. MRD was assessed at every hematopoietic recovery after course of chemotherapy. Patients were categorized into 5 groups: (a) non-complete remission (non-CR; blast cells >= 5% in BM) after the induction therapy, (b) MRD positive after 1st consolidation therapy, (c, d) MRD negative after 1st consolidation, and (e) patients without any MRD markers available. The patients whose MRD became negative after the 1st consolidation were divided into two: (c) reemerging MRD after 2nd consolidation or later, and (d) continuously negative for MRD. Patients in categories (a), (b) and (c) underwent allogeneic RIC-HSCT (with one exception of myeloablative conditioning (MAC)). HLA-haploidentical HSCT was performed for the patients in (a). MRD monitoring was finished with a negative result for MRD after the last course of consolidation in the group of (d). Results. Enrolled patient number was 35. A median age at diagnosis was 2 years old (range; 2 months - 20 years old). Three patients were stratified in the group of (a), 12 in (b), 4 in (c), 10 in (d), and 6 in (e). Eighteen patients (51.4%) underwent allogeneic HSCT. Five-year EFS (5y-EFS) was 77.9+/-7.4%, and 5y-OS was 86.0+/-6.6%, with 7.0 years of an median observation period (range; 0.7-12.6 years). Among non-Down syndrome patients (n = 29), 5y-EFS was 77.7+/-8.1%, and 5y-OS was 87.5+/-6.9%. RIC seemed to work, as resulted in a 5y-EFS 75.4+/-12.6% (2 relapses and 1 non-relapse mortality) and a 5y-OS 77.9+/-14.1% in all patients who underwent HSCT (excluding group (a)). Discussion. It has already reported that the AML99 protocol, which did not employ MRD-based stratification, resulted in a 5y-EFS 61.6% and a 5y-OS 75.6%. Although direct comparison of our presenting strategy and the AML99 protocol cannot be carried out mainly because ours was conducted one decade later and time-event data was missing in the AML99 report for log-rank test, our strategy may contribute to shortening the treatment period and increasing the 1st continuous CR rate. In addition, RIC potentially contributes to reducing late complications [Shimizu M, et al. BMT 47: 141-142, 2012]. In the AML99 study 18.1% (41/227) received allogeneic MAC-HSCT in 1st CR, and 32.2% relapsed in total [2]. Therefore, RIC-HSCT in the present study seems to be comparable with those of MAC-HSCT. Conclusion. Our strategy of MRD-based stratification and RIC-HSCT for childhood AML may provide a promising platform for further study. Disclosures No relevant conflicts of interest to declare.

A New 1,000 kV Electron Microscope

1967 ◽  
Vol 25 ◽  
pp. 260-261
Author(s):  
M. Nishigaki ◽  
S. Katagiri ◽  
H. Kimura ◽  
B. Tadano
Keyword(s):  
Electron Microscope ◽  
High Voltage ◽  
Basic Research ◽  
Chromatic Aberration ◽  
High Accuracy ◽  
Biological Specimen ◽  
Voltage Electron ◽  
High Voltage Electron Microscope ◽  
High Voltage Electron

The high voltage electron microscope has many advantageous features in comparison with the ordinary electron microscope. They are a higher penetrating efficiency of the electron, low chromatic aberration, high accuracy of the selected area diffraction and so on. Thus, the high voltage electron microscope becomes an indispensable instrument for the metallurgical, polymer and biological specimen studies. The application of the instrument involves today not only basic research but routine survey in the various fields. Particularly for the latter purpose, the performance, maintenance and reliability of the microscope should be same as those of commercial ones. The authors completed a 500 kV electron microscope in 1964 and a 1,000 kV one in 1966 taking these points into consideration. The construction of our 1,000 kV electron microscope is described below.

An emerging technology: Nuclear magnetic resonance microscopy

1988 ◽  
Vol 46 ◽  
pp. 1000-1001
Author(s):  
M.J. Hennessy ◽  
E. Kwok
Keyword(s):  
Nuclear Magnetic Resonance ◽  
Magnetic Resonance ◽  
Relaxation Times ◽  
Basic Research ◽  
Local Environment ◽  
Magnetic Resonance Images ◽  
Nmr Microscopy ◽  
Mri Scans ◽  
Temperature Relaxation ◽  
Nuclear Magnetic

Much progress in nuclear magnetic resonance microscope has been made in the last few years as a result of improved instrumentation and techniques being made available through basic research in magnetic resonance imaging (MRI) technologies for medicine. Nuclear magnetic resonance (NMR) was first observed in the hydrogen nucleus in water by Bloch, Purcell and Pound over 40 years ago. Today, in medicine, virtually all commercial MRI scans are made of water bound in tissue. This is also true for NMR microscopy, which has focussed mainly on biological applications. The reason water is the favored molecule for NMR is because water is,the most abundant molecule in biology. It is also the most NMR sensitive having the largest nuclear magnetic moment and having reasonable room temperature relaxation times (from 10 ms to 3 sec). The contrast seen in magnetic resonance images is due mostly to distribution of water relaxation times in sample which are extremely sensitive to the local environment.

Alopecia areata and Down syndrome

1976 ◽  
Vol 112 (10) ◽  
pp. 1397-1399 ◽  
Author(s):  
D. M. Carter
Keyword(s):  
Down Syndrome ◽  
Alopecia Areata

Mother-to-child transmission of HIV: developing integration of healthcare programmes with clinical, social and basic research studies

2003 ◽  
Vol 92 (11) ◽  
pp. 1343-1348
Author(s):  
Menu E ◽  
Scarlatti G ◽  
Barré-Sinoussi F ◽  
Gray G ◽  
Bollinger B ◽  
...  
Keyword(s):  
Basic Research ◽  
Mother To Child Transmission ◽  
Child Transmission ◽  
Mother To Child ◽  
Research Studies

The Multiple Faces of Risk-Taking

2016 ◽  
Vol 32 (1) ◽  
pp. 17-38 ◽  
Author(s):  
Florian Schmitz ◽  
Karsten Manske ◽  
Franzis Preckel ◽  
Oliver Wilhelm
Keyword(s):  
Risk Taking ◽  
Basic Research ◽  
Formal Models ◽  
Experimental Paradigm ◽  
Nomological Network ◽  
Balloon Analogue Risk Task ◽  
Parameter Recovery ◽  
Task Specificity ◽  
Available Information ◽  
Criterion Variables

Abstract. The Balloon-Analogue Risk Task (BART; Lejuez et al., 2002 ) is one of the most popular behavioral tasks suggested to assess risk-taking in the laboratory. Previous research has shown that the conventionally computed score is predictive, but neglects available information in the data. We suggest a number of alternative scores that are motivated by theories of risk-taking and that exploit more of the available data. These scores can be grouped around (1) risk-taking, (2) task performance, (3) impulsive decision making, and (4) reinforcement sequence modulation. Their theoretical rationale is detailed and their validity is tested within the nomological network of risk-taking, deviance, and scholastic achievement. Two multivariate studies were conducted with youths (n = 435) and with adolescents/young adults (n = 316). Additionally, we tested formal models suggested for the BART that decompose observed behavior into a set of meaningful parameters. A simulation study with parameter recovery was conducted, and the data from the two studies were reanalyzed using the models. Most scores were reliable and differentially predictive of criterion variables and may be used in basic research. However, task specificity and the generally moderate validity do not warrant use of the experimental paradigm for diagnostic purposes.

NIMH and Basic Research

1972 ◽  
Vol 17 (3) ◽  
pp. 146-147
Author(s):  
THOMAS S. HYDE
Keyword(s):  
Basic Research
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