Disease relevance of DHDDS

• Features of Down syndrome (DS) caused by three copies of these genes should not be present in mice trisomic for MMU 16 that have been proposed as animal models for DS [1].
• Down syndrome (DS) children with acute myeloid leukemia (AML) have significantly higher event-free survival (EFS) rates compared with non-DS children when treated with protocols containing 1-beta-D-arabinofuranosylcytosine (ara-C) [2].
• Sensitivity and metabolism of ara-C was examined in myeloblasts from DS and non-DS patients with AML, DS infants with the transient myeloproliferative disorder, and Epstein-Barr Virus (EBV) transformed lymphoblastoid cell lines with and without trisomy 21 [2].
• RESEARCH DESIGN AND METHODS--The subjects were 76 patients with well-controlled non-insulin-dependent diabetes mellitus (NIDDM) treated with diet therapy only (diet, n = 17), oral hypoglycemic agents (OHA, n = 28), conventional insulin therapy (CIT, n = 16), or multiple insulin injection therapy (MIT, n = 15) [3].
• The purpose of our study was to prospectively evaluate the striatal uptake of 123I-labeled N-(3-fluoropropyl)-2beta-carbomethoxy-3beta-(4-iodophenyl)nortropane (FP-CIT) and the response to l-dopa therapy in patients with cerebrovascular disease (CVD) who develop clinical symptoms of vascular parkinsonism (VP) [4].

Psychiatry related information on DHDDS

• With the dopaminergic presynaptic ligand FP-CIT and single photon emission tomography we have shown a severe dopaminergic degeneration in a patient with a necropsy confirmed diagnosis of dementia with Lewy bodies (DLB) [5].
• Down syndrome (DS) is the most common human chromosomal abnormality caused by an extra copy of chromosome 21 and characterized by somatic anomalies and mental retardation [6].
• A neuropsychological test (Hasegawa's dementia scale, HDS) was done pre- and postoperatively [7].

High impact information on DHDDS

• The gene for cystathionine beta-synthase (CBS) is located on chromosome 21 and is overexpressed in children with Down syndrome (DS), or trisomy 21 [8].
• The increased activity of CBS in children with DS significantly alters homocysteine metabolism such that the folate-dependent resynthesis of methionine is compromised [8].
• The dual purpose of the present study was to evaluate the impact of overexpression of the CBS gene on homocysteine metabolism in children with DS and to determine whether the supplementation of trisomy 21 lymphoblasts in vitro with selected nutrients would shift the genetically induced metabolic imbalance [8].
• The results indicated that plasma levels of homocysteine, methionine, S-adenosylhomocysteine, and S-adenosylmethionine were all significantly decreased in children with DS and that their lymphocyte DNA was hypermethylated relative to that in normal siblings [8].
• Plasma glutathione levels were significantly reduced in the children with DS and may reflect an increase in oxidative stress due to the overexpression of the superoxide dismutase gene, also located on chromosome 21 [8].

Chemical compound and disease context of DHDDS

• However, significant primary and secondary salivary IgA and serum IgG antibody responses to HDS were induced in all rats when cholera holotoxin (CT) or a detoxified mutant Escherichia coli heat-labile enterotoxin (R192G LT) were intranasally administered with HDS peptide constructs in PLGA [9].
• DYRK1A, dual-specificity tyrosine-regulated kinase 1A, maps to human chromosome 21 within the Down syndrome (DS) critical region [10].
• Decreased striatal dopamine transporter binding assessed with [123I] FP-CIT in first-episode schizophrenic patients with and without short-term antipsychotic-induced parkinsonism [11].
• The aim of the present study was to retrospectively evaluate whether a high-dose sequential chemotherapy programme (HDS: cyclophosphamide, methotrexate, etoposide) administered prior to autologous transplantation could optimize the salvage of patients with refractory or relapsed aggressive non-Hodgkin's lymphoma [12].
• We studied clinical and serological features of five patients with polyneuropathy and serum immunoglobulin M (IgM) binding to the trisulfated disaccharide IdoA2S-GlcNS-6S (TS-HDS), the most abundant disaccharide component of heparin oligosaccharides [13].

Biological context of DHDDS

• There were no significant differences in the cell cycle distributions of DS and non-DS cells [2].
• DS cell lines also generated higher levels of ara-CTP compared with cell lines with diploid chromosome numbers (66.5 v 13.6 pmol/mg protein and 137.6 v 41.7 pmol/mg protein at 1 and 5 micromol/L ara-C, respectively) [2].
• In the CIT group, vibratory perception threshold (VPT) of the great toe and the medial malleolus deteriorated, as did heart rate variation (HRV) at rest, at deep breathing (.05 less than P less than .06), and at standing [14].
• These studies provided evidence for distinct binding sites coordinating SERT antagonists and revealed a close interaction between TM1 and TM3 differentially targeted by stereoisomers of CIT [15].
• The C-28/I2 cells were cultured under flow shear at 1-20 dyn/cm2, and the role of CIT-ED2 in regulation of MMPs was examined using the plasmids encoding sense and antisense CITED2 DNA sequences [16].

Anatomical context of DHDDS

• 8-fold higher in DS compared with non-DS myeloblasts (P <.0001 and P <.0001, respectively) [17].
• The present study examines Dyrk1A in the cerebral cortex of sporadic AD, adult DS with associated AD, and PiD [10].
• Increased Dyrk1A immunoreactivity has been found in the cytoplasm and nuclei of scattered neurons of the neocortex, entorhinal cortex, and hippocampus in AD, DS, and PiD [10].
• Between 1985 and 1999, 103 patients (median age 43 years, range 16-65) from eight Italian centres and one Swiss centre, with refractory (n = 38) or relapsed (n = 65) diffuse large B-cell and T-cell lymphoma, were treated using HDS followed by high-dose regimens with autologous haematopoietic stem cell transplantation [12].
• The percentage of sperm DNA fragmentation index (%DFI) and the percentage of sperm with abnormally high DNA stainability (HDS; immature spermatozoa) were determined by SCSA using the metachromatic properties of acridine orange [18].

Associations of DHDDS with chemical compounds

• In vivo interaction between the human dehydrodolichyl diphosphate synthase and the Niemann-Pick C2 protein revealed by a yeast two-hybrid system [19].
• Elevated ara-CTP levels in the DS cells were accompanied by slightly lower levels of endogenous deoxycytidine triphosphate (dCTP) pools, slightly greater extent of ara-C incorporation into DNA, and increased relative numbers of double strand DNA strand breaks [2].
• IL-10 rats after 24 hr of CIT showed higher PaO2 levels (260 +/- 29 mmHg) than empty vector (96 +/- 24 mmHg) or diluent (133 +/- 10 mmHg) lungs (p < 0.05) [20].
• Several methods of facilitation of the immune response were studied: the incorporation of peptides in bioadhesive poly(D,L-lactide-coglycolide) (PLGA) microparticles, the use of monoepitopic (HDS) or diepitopic (HDS-GLU) peptide constructs, or the use of mucosal adjuvants [9].
• Autograft was the final part of a hd-sequential (HDS) chemotherapy program, including a debulkying phase (1-2 APO +/- 2 DHAP courses) and then sequential administration of hd-cyclophosphamide, methotrexate (or Ara-C) and etoposide, at 10 to 30 day intervals [21].

Analytical, diagnostic and therapeutic context of DHDDS

• The further identification of the molecular mechanisms of chemotherapy sensitivity of DS AML patients may lead to significant improvements in the treatment and cure of AML [17].
• TUNEL (terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling) assays demonstrate that gammaH2AX formation in late S and G2 cells following CPT treatment corresponds to DNA breaks [22].
• Serotonergic transporter binding can be assessed with 11C-DASB PET and 123I-beta CIT SPECT, whereas HT1A binding can be measured with 11C-WAY100635 PET [23].
• After 24 hr of in vivo transfection, lungs were stored at 4 degrees C (cold ischemic time, CIT) for 6 hr (groups 1-3) or 24 hr (groups 4-6) before transplantation [20].
• Serum IgG antibody, which was induced to the HDS peptide construct by coadministration with these adjuvants, also bound intact mutans streptococcal GTF in an enzyme-linked immunosorbent assay and inhibited its enzymatic activity [9].

References