Prediction of individual response to chemotherapy in patients with acute myeloid leukaemia using the chemosensitivity index Ci.

As the response to chemotherapy in patients with acute myeloid leukaemia (AML) may still not be accurately determined by known prognostic factors, such as karyotype, the ex vivo chemosensitivity profile may help to predict the individual response. The predictive accuracy of an ex vivo assay should be assessed by correlation of assay results with both response rate and survival. We prospectively investigated the prognostic relevance of pre-therapeutic ex vivo chemosensitivity testing in primary cell cultures from adult AML patients by applying a new evaluation methodology, designated the chemosensitivity index, C(i).

E. coli derived human granulocyte-macrophage colony-stimulating factor (rh GM-CSF) available for clinical trials.

Recombinant human GM-CSF has been expressed as a fusion protein in E. coli in the form of inclusion bodies. Using denaturing agents, acid cleavage and sulfitolysis, the biologically inactive GM-CSF protein could be highly purified and additionally renaturated under suitable reoxidizing conditions.

Carbon-13 and phosphorus-31 nuclear magnetic resonance studies of myocardial metabolism in live guinea pigs.

Myocardial metabolism in live guinea pigs was investigated by 13C and 31P nuclear magnetic resonance (NMR) at 20.18 and 32.5 MHz, respectively.

Carbon-13 nuclear magnetic resonance studies of myocardial glycogen metabolism in live guinea pigs.

Myocardial glycogen metabolism was studied in live guinea pigs by 13C NMR at 20.19 MHz. Open-chest surgery was used to expose the heart, which was then positioned within a solenoidal radio frequency coil for NMR measurements.

In vivo 31P-NMR studies of myocardial high energy phosphate metabolism during anoxia and recovery.

31P NMR spectra of heart in-situ in live guinea pigs were obtained continuously in 20.5 s time blocks during 3 min of anoxia, during subsequent reoxygenation and, in separate animals, during terminal anoxia. Reversible anoxia resulted in rapid degradation of phosphocreatine (t 1/2 = 54.

In vivo carbon-13 nuclear magnetic resonance studies of heart metabolism.

Guinea pig heart metabolism was studied in vivo by 13C NMR at 20.18 MHz. High-quality proton-decoupled 13C NMR spectra with excellent signal-to-noise ratios and resolution could be obtained in 6 min.

Binding of disaccharides by peanut agglutinin as studied by ultraviolet difference spectroscopy.

The binding of the disaccharides methyl beta-D-lactoside and 2-acetamido-2-deoxy-3-O-(beta-D-galactopyranosyl)-beta-D-galactopyranose [beta-D-Gal-(l leads to 3)-D-GalNAc] to peanut agglutinin was studied by ultraviolet difference spectroscopy. The magnitude of the difference spectra varied with the concentration of the carbohydrates; association constants and thermodynamic parameters were determined from titration experiments at different temperatures. The enthalpy and entropy changes for binding of methyl beta-D-lactoside were found to be delta H degree = -65 +/- 4 kJ mol-1, delta S degree = -156 +/- 14 J mol-1 K-1.

Kinetics of binding of methyl alpha- and beta-D-galactopyranoside to peanut agglutinin: a carbon-13 nuclear magnetic resonance study.

The binding kinetics of methyl alpha- and methyl beta-D-galactopyranoside to the anti-T lectin from peanuts were studied by 13C NMR, employing methyl galactopyranosides specifically enriched in 13C at C-1. Association and dissociation rate constants, as well as their activation parameters, are reported. The association rate constants, 4.

Molecular dynamics of sugars bound to wheat germ agglutinin, as studied by deuterium nuclear magnetic resonance.

Deuterium nuclear magnetic resonance is used to delineate the molecular dynamics of sugars bound to a lectin. 2H spin-spin relaxation times (from linewidth measurements) and reorientational correlation times are determined for N-acetylglucosamine specifically-labeled with 2H in the N-acetyl group and at carbon-3 of the pyranoside ring, in the presence and absence of wheat germ agglutinin. The correlation time for the 2H-label of N-acetylglucosamine-3-2H in the bound state is the same as that of the protein (3 X 10(-8)S), indicating that the six-membered ring has negligible motional freedom relative to the protein.

Determination of the carbohydrate-binding properties of peanut agglutinin by ultraviolet difference spectroscopy.

The anti-T lectin from peanuts was purified on a new affinity matrix, and the number of carbohydrate binding sites was determined by equilibrium dialysis with [14C]lactose to be four per tetramer. Methyl-alpha- and methyl-beta-D-galactopyranoside and lactose were found to perturb the UV spectrum of the lectin in the aromatic region and their association constants were determined by UV difference spectroscopy to be 1.8, 1.

Complex formation of carnosine with purine nucleotides in aqueous solution.

This 1H-NMR study provides experimental evidence for an intermolecular interaction between the dipeptide carnosine (beta-alanyl-L-histidine) and the purine nucleoside 5'-monophosphates 5'-AMP, 5'-GMP. From the observed upfield shifts of the purine nucleotide and imidazole proton resonances it is concluded that the interaction is of the stacking type and that it involves the purine base of the nucleotide and the histidine moiety of carnosine. Apparent microscopic equilibrium constants and complex shifts are obtained with a microscopic model which considers the formation of both 1:1 and 1:2 complexes.