64 research outputs found
Cytotoxic lymphocytes in B-cell chronic lymphocytic leukemia
No full textThe occurrence of cytotoxic lymphocyte subpopulations (i.e., CD 16+, CD57+ and cytotoxic CD 8+) was studied in the peripheral blood of 18 B-cell chronic lymphocytic leukemia (B-CLL) patients. The absolute numbers of CD 57+, CD 16+ and cytotoxic CD 8+ lymphocytes were increased in the peripheral blood of untreated patients as compared with healthy donors, suggesting a causal relation with the accumulation of malignant B-cells. For 5 B-CLL patients and 5 hematological normal donors, the lymphocyte subpopulations in peripheral blood, lymph nodes and bone marrow were determined. A significant immune response was observed in the lymph nodes of the patients, as reflected by the CD 3+ lymphocytes, which were 1.7–27 times larger in the patients lymph nodes than in their peripheral blood and bone marrow. In contrast, with peripheral blood this was mainly caused by an increase in CD 4+ lymphocytes. The CD 57 lymphocytes in the lymph nodes of the patients had abnormal orthogonal light-scattering signals and an abnormal density of CD 57+ receptors in comparison with their peripheral blood CD 57+ lymphocytes or the CD57+ lymphocytes in the peripheral blood, bone marrow and tonsils of the hematological normal donors. This study shows that although a significant increase of cytotoxic lymphocytes in the peripheral blood of B-CLL patients is observed, the actual distributions of the non-malignant lymphocytes can be quite different at the actual tumor sites, i.e., bone marrow and lymph node
The effects of splenic irradiation on lymphocyte subpopulations in chronic B-lymphocytic leukemia
No full textWe describe the effect of splenic irradiation (SI) (0,5–1 Gy weekly) on lymphocyte subpopulations for 7 patients with progressive B chronic B-lymphocytic leukemia (B-CLL). Using specific cellular characteristics we could distinguish normal from abnormal cells. The irradiation resulted in a decrease of lymph node size, reduction in spleen volume and decrease in peripheral blood lymphocytes. The one exception was a patient with a prolymphocytoid transformation of B-CLL. For 3 patients SI had to be interrupted or stopped because of severe cytopenia. Quantitation of malignant B cells and normal T lymphocytes revealed that the total irradiation dose which resulted in a specific decrease of malignant lymphocytes varied from patient to patient. Normal T-cell subpopulations, which were increased before SI, decreased to normal or abnormally low values during SI. In previously untreated patients, natural killer (NK) cell numbers decreased more rapidly than T-cell subpopulations. For 2 patients refractory to chemotherapy an increase of NK cells was observed upon SI
Two-armed molecular receptors : peptide recognition and vesicle formation driven by selective non-covalent interactions
No full textThis thesis presents examples for applying encoded combinatorial chemistry to trace molecular interactions between two-armed receptors and peptidic substrates that could have not been predicted by conventional means. Starting from these selective non-covalent interactions, applications, like supramolecular self-assembly, were investigated in organic and aqueous media. In the first part the synthesis of macrocyclic diketopiperazine receptors and their binding properties towards peptides is described. Combinatorial on-bead studies showed that both macrocyclization of the receptor and choice of the linker-type lead to significant changes in the binding properties compared to their flexible open-chain parent diketopiperazine receptors. Macrocyclization rigidifies the receptor and should induce a higher preorganisation. Thus, the conformations of the macrocyclic receptors were expected to differ from the open-chain diketopiperazine receptor prototype. Binding studies revealed that macrocyclization led not only to lower binding selectivities but also lower affinities toward peptidic guest compared to the open-chain parent receptors. Thus, the flexibility of the open-chain receptor allows the arms to better adjust to a peptidic guest and can be beneficial for selective and higher binding. The second part describes the development of a new class of two-armed receptors consisting of a rigid carbazole backbone and peptidic side-chains which allow for structural as well as functional variations. Compared to the diketopiperazine template, a third functionality is present and allows for attachment of a dye, polymer chain or resin, at the opposite site of the recognition modules. Combinatorial binding studies and solid phase binding assays showed that these carbazole receptors interact with certain tripeptides, in organic solvents, with sequence selectivities and binding affinities that are comparable to
those of diketopiperazine receptors. These two-armed receptors have been the basis for the
design of receptor libraries to identify selective receptors for interesting peptidic and nonpeptidic
substrates.
In the third part, selective non-covalent interactions between a diketopiperazine
receptor and peptide-PEG conjugates were used to induce the assembly of vesicles in
aqueous solution. The vesicles were analysed by a combination of light scattering, electron
transmission and atomic force microscopy as well as surface pressure measurements. Vesicle
formation was found to be independent of the ratio of receptor to ligand and relies upon
selective receptor-peptide interactions. Other peptide-PEG conjugates did not assemble into
vesicular structures when mixed with the receptor
Experimental and model investigations of bleaching and saturation of fluorescence in flow cytometry
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Visual perception of colourful petals reminds us of classical fragments
No full textColour has attracted the interest and attention of many of the most gifted intellects of all time. Ideas of early thinkers were not -and could not have been- grasped on a scientific level without knowledge of a kind that lay far in the future. One character that is being considered is the colourful surfaces of living tissues, which could hardly have been visualized without a corresponding reference to the microscale parallel. Millions of years before man made manipulated synthetic structures, biological systems were using nanoscale architecture to produce striking optical effects. Here we show the microsculpture of the adaxial surface of flower petals from the asphodel, the Stork's-bill and the common poppy by using optical, scanning electron and atomic force microscopy. Microsculpture has been studied in leaves and pollen grains of higher plants. To the best of our knowledge imaging and nanoscale morphometry of petals has not been reported hitherto. Our findings on flower petals' microsculpture may be linked with aspects on colour revealed from ancient literature
Molecular mechanisms and kinetics between DNA and DNA binding ligands
No full textSischka A, Tönsing K, Eckel R, et al. Molecular mechanisms and kinetics between DNA and DNA binding ligands. Biophysical Journal. 2005;88(1):404-411.Mechanical properties of single double-stranded DNA (dsDNA) in the presence of different binding ligands were analyzed in optical-tweezers experiments with subpiconewton force resolution. The binding of ligands to DNA changes the overall mechanic response of the dsDNA molecule. This fundamental property can be used for discrimination and identification of different binding modes and, furthermore, may be relevant for various processes like nucleosome packing or applications like cancer therapy. We compared the effects of the minor groove binder distamycin-A, a major groove binding [alpha]-helical peptide, the intercalators ethidium bromide, YO-1, and daunomycin as well as the bisintercalator YOYO-1 on [lambda]-DNA. Binding of molecules to the minor and major groove of dsDNA induces distinct changes in the molecular elasticity compared to the free dsDNA detectable as a shift of the overstretching transition to higher forces. Intercalating molecules affect the molecular mechanics by a complete disappearance of the B-S transition and an associated increase in molecular contour length. Significant force hysteresis effects occurring during stretching/relaxation cycles with velocities >10 nm/s for YOYO-1 and >1000 nm/s for daunomycin. These indicate structural changes in the timescale of minutes for the YOYO-DNA and of seconds for the daunomycin-DNA complexes, respectively
Dynamic regulation of activated leukocyte cell adhesion molecule-mediated homotypic cell adhesion through the actin cytoskeleton
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Multiple wavelength illumination in flow cytometry using a single arc lamp and a dispersing element
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