Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
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Target Concepts:
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Query: UMLS:C0026986 (
myelodysplastic syndrome
)
14,926
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
One of the first known effects of the endogenous peptide N-acetyl-Ser-Asp-Lys-Pro (AcSDKP) is to inhibit entry into DNA synthesis of pluripotent haematopoietic stem cells (CFU-S) in mice. A specific anti-AcSDKP polyclonal antibody allows the level of the tetrapeptide by to be determined by enzyme immunoassay with good sensitivity and specificity. We present results demonstrating the presence of AcSDKP in humans: serum levels of 34 healthy controls were found to be between 0.7 and 2.5 pm/ml, regardless of age and sex. High levels were found in 44% of asymptomatic controls but only in 8% of AIDS patients out of a total of 37 patients with HIV. Subsequently, studies of serum levels were performed before treatment in 121 subjects with disorders of the nonlymphoid and the lymphoid lineages. Our results did not demonstrate any decrease in serum levels, however a moderate or marked increase was noted in one-third of the subjects, which was greater in disorders of the non-lymphoid lineages (48% of 72 patients) than the lymphoid lineage (21% of 50 patients). The most significant differences were observed between controls versus patients with myeloproliferative disorders (MPD, 24 patients: p < 0.001), controls versus patients with acute myelogenous leukaemia (AML, 15 patients: p < 0.02), as well as patients with AML versus patients with primary
myelodysplastic syndromes
(
PMDS
, 10 patients: p < 0.05). The pathophysiology of these abnormalities is discussed.
...
PMID:Serum levels of a negative regulator of cell proliferation (AcSDKP) are increased in certain human haemopathies. 850 76
Cationic micelles self-assembled from a biodegradable amphiphilic copolymer, poly{(N-methyldietheneamine sebacate)-co-[(cholesteryl oxocarbonylamido ethyl) methyl bis(ethylene) ammonium bromide] sebacate} (P(
MDS
-co-CES)) have recently been reported for efficient gene delivery and co-delivery of drug and nucleic acid. In this study, poly(ethylene glycol) (PEG) of various molecular weights (Mn=550, 1100 and 2000) was conjugated to P(
MDS
-co-CES) having different cholesterol grafting degrees to improve the stability of micelle/DNA complexes in the blood for systemic in vivo gene delivery. DNA binding ability, gene transfection efficiency and cytotoxicity of P(
MDS
-co-CES),
PMDS
, PEGylated
PMDS
and PEGylated P(
MDS
-co-CES) micelles were studied and compared. As with P(
MDS
-co-CES), PEG-P(
MDS
-co-CES) polymers could also self-assemble into stable micelles of small size. However,
PMDS
and PEG-
PMDS
without cholesterol could not form stable micelles but formed large particles. PEGylation of polymers significantly decreased their gene transfection efficiency in HEK293, HepG2, HeLa, MDA-MB-231 and 4T1 cells. However, increasing N/P ratio promoted gene transfection. An increased cholesterol grafting degree led to greater gene expression level possibly because of the more stable core-shell structure of the micelles. PEG550-P(
MDS
-co-CES) micelles induced high gene transfection level, comparable to that provided by P(
MDS
-co-CES) micelles. PEGylated polymers were much less cytotoxic than P(
MDS
-co-CES). PEGylated P(
MDS
-co-CES) micelles may provide a promising non-viral vector for systemic in vivo gene delivery.
...
PMID:The self-assembly of biodegradable cationic polymer micelles as vectors for gene transfection. 1776 36