ABSTRACT
A series of N6,2-disubstituted adenosine analogues have been synthesized and their functional activity measured against A2a and A1 receptors. Examples of compounds with both a lipophilic N6-substituent and amino-functionalized 2-position were highly active at the A2a receptor on the human neutrophil.
Subject(s)
Adenosine/chemistry , Adenosine/pharmacology , Purinergic P1 Receptor Agonists , Adenosine/analogs & derivatives , Anti-Inflammatory Agents/chemistry , GTP-Binding Proteins , Solubility , Structure-Activity RelationshipABSTRACT
Exciting new techniques in molecular cytogenetics--namely, spectral karyotyping, multiplex fluorescence in situ hybridization (M-FISH), and cross species color banding--have been recently developed. An increasing number of reports demonstrate the success of these procedures in providing additional cytogenetic information--identifying marker chromosomes and revealing the presence of previously undetected chromosomal changes. However, these procedures have their limitations, and their absolute sensitivity in the accurate identification of subtle chromosomal abnormalities remains to be established. M-FISH and color banding have been applied to a case of chronic myeloid leukemia with a complex Philadelphia translocation involving chromosomes 9, 17, and 22, which had initially been identified from G-banded chromosome analysis. The abnormalities were confirmed by chromosome "painting" and specific probes. Although M-FISH and color banding revealed no additional cryptic chromosomal changes, this study has clearly demonstrated the success of these multiple color FISH approaches in the accurate characterization of a complex rearrangement with subtle abnormalities.
Subject(s)
Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Philadelphia Chromosome , Adolescent , Chromosome Banding , Chromosome Painting/methods , Chromosomes, Human, Pair 17 , Fluorescent Dyes , Fusion Proteins, bcr-abl/genetics , Humans , Karyotyping , MaleSubject(s)
Aggression , Gender Identity , Social Perception , Adult , Aggression/classification , Aggression/psychology , Child , Female , Humans , Male , Sex FactorsABSTRACT
Systematic modification of the presumed P1 side chain in a series of (carboxyalkyl)amino-based inhibitors of matrix metalloproteinases enabled identification of the 2-(1,3-dihydro-1,3-dioxo-2H-benz[f]isoindol-2-yl)ethyl group as a preferred substituent imparting potent inhibition of the enzymes collagenase and gelatinase. It was subsequently found that the P2'-P3' residues in this series could be replaced by small non-peptide residues, while maintaining inhibitory potency. The imide group in this series of compounds can undergo autocatalytic hydrolysis under neutral conditions.
Subject(s)
Dipeptides/chemistry , Extracellular Matrix/enzymology , Indoles/chemistry , Metalloendopeptidases/antagonists & inhibitors , Zinc , Amino Acid Sequence , Chromogenic Compounds/metabolism , Dipeptides/chemical synthesis , Dipeptides/pharmacology , Drug Stability , Fluorescent Dyes , Gelatinases/antagonists & inhibitors , Half-Life , Humans , Hydrogen-Ion Concentration , Indoles/chemical synthesis , Indoles/pharmacology , Isoindoles , Matrix Metalloproteinase 3 , Matrix Metalloproteinase Inhibitors , Molecular Sequence Data , Molecular Structure , Structure-Activity RelationshipABSTRACT
Thallium sulphate has been given to young rats at 4 and 7 days of age and the mitotic activity of the hair follicles has been assessed quantitatively. It has been found that there is a marked decline in mitotic rate over 48 hr in the thallium-treated animals, which is followed by variable amounts of cell death in the matrix zone. No specific mitotic lesion was found or change in cell cycle indices. A failure of energy metabolism is suggested as a possible cause of the inhibition of hair follicle mitosis by thallium.
