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Besides vobtusine and vobtusine-lactone, deoxyvobtusine was isolated from the leaves of Voacanga grandifolia (Miq. Rolfe. Spectral and chemical evi  相似文献   
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The frequency of cytokine-producing CD4-/CD8- mononuclear cells was assessed in patients of different age groups (29 infants, aged 1-5 years; 30 schoolchildren, aged 6-14 years, 26 adults, aged > 15 years) with acute Plasmodium falciparum malaria, from Gabon. Fifteen patients were followed up before antimalarial treatment (day 0), during parasite clearance (day 3) and after resolution of parasitemia (day 10). By using flow cytometry for intracellular detection of cytokines, a striking expansion of CD4-/CD8- cells producing the type 1 cytokines interleukin (IL)-2-/interferon (IFN)-gamma+, IL-2+/IFN-gamma+ and IL-2+/IFN-gamma- was observed in adults as compared with children. Type 2 cytokine expression (IL-4+/IFN-gamma-, IL-13+/IFN-gamma-) and type 0 cells (IL-4+/IFN-gamma+, IL-13+/IFN-gamma+) were not significantly different between the three age groups. Patients with severe malaria had a significantly increased frequency of type 2 cytokine-producing CD4-/CD8- cells. Drug-induced clearance of parasitemia was characterized by a decrease of IL-2+/IFN-gamma- and type 2 cytokine expressing CD4-/CD8- cells and by a gradual increase of IL-10+/IFN-gamma- expression. The type 1/type 2 dichotomy observed within the CD4-/CD8- cell population is likely to be of significance in the host response against P. falciparum malaria.  相似文献   
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We have previously shown that replacing the P1-site residue (Ala) of chicken ovomucoid domain 3 (OMCHI3) with a Met or Lys results in the acquisition of inhibitory activity toward chymotrypsin or trypsin, respectively. However, the inhibitory activities thus induced are not strong. In the present study, we introduced additional amino acid replacements around the reactive site to try to make the P1-site mutants more effective inhibitors of chymotrypsin or trypsin. The amino acid replacement Asp-->Tyr at the P2' site of OMCHI3(P1Met) resulted in conversion to a 35000-fold more effective inhibitor of chymotrypsin with an inhibitor constant (K(i)) of 1. 17x10(-11) M. The K(i) value of OMCHI3(P1Met, P2'Ala) indicated that the effect on the interaction with chymotrypsin of removing a negative charge from the P2' site was greater than that of introducing an aromatic ring. Similarly, enhanced inhibition of trypsin was observed when the Asp-->Tyr replacement was introduced into the P2' site of OMCHI3(P1Lys). Two additional replacements, Asp-->Ala at the P4 site and Arg-->Ala at the P3' site, made the mutant a more effective inhibitor of trypsin with a K(i) value of 1. 44x10(-9) M. By contrast, Arg-->Ala replacement at the P3' site of OMCHI3(P1Met, P2'Tyr) resulted in a greatly reduced inhibition of chymotrypsin, and Asp-->Ala replacement at the P4 site produced only a small change when compared with a natural variant of OMCHI3. These results clearly indicate that not only the P1-site residue but also the characteristics, particularly the electrostatic properties, of the amino acid residues around the reactive site of the protease inhibitor determine the strength of its interactions with proteases. Furthermore, amino acids with different characteristics are required around the reactive site for strong inhibition of chymotrypsin and trypsin.  相似文献   
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Binding of the cationic tetra(tributylammoniomethyl)-substituted hydroxoaluminum phthalocyanine (AlPcN4) to bilayer lipid membranes was studied by fluorescence correlation spectroscopy (FCS) and intramembrane field compensation (IFC) methods. With neutral phosphatidylcholine membranes, AlPcN4 appeared to bind more effectively than the negatively charged tetrasulfonated aluminum phthalocyanine (AlPcS4), which was attributed to the enhancement of the coordination interaction of aluminum with the phosphate moiety of phosphatidylcholine by the electric field created by positively charged groups of AlPcN4. The inhibitory effect of fluoride ions on the membrane binding of both AlPcN4 and AlPcS4 supported the essential role of aluminum-phosphate coordination in the interaction of these phthalocyanines with phospholipids. The presence of negative or positive charges on the surface of lipid membranes modulated the binding of AlPcN4 and AlPcS4 in accord with the character (attraction or repulsion) of the electrostatic interaction, thus showing the significant contribution of the latter to the phthalocyanine adsorption on lipid bilayers. The data on the photodynamic activity of AlPcN4 and AlPcS4 as measured by sensitized photoinactivation of gramicidin channels in bilayer lipid membranes correlated well with the binding data obtained by FCS and IFC techniques. The reduced photodynamic activity of AlPcN4 with neutral membranes violating this correlation was attributed to the concentration quenching of singlet excited states as proved by the data on the AlPcN4 fluorescence quenching.  相似文献   
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Expression of the glycoprotein clusterin is markedly increased following tissue injury. One function of clusterin is to promote cell interactions which are perturbed in these pathologic settings. Clusterin causes cell aggregation and adhesion in vitro yet the molecular mechanism for this effect is not known. In order to identify the active site(s) of clusterin, 34 peptides, each 15 amino acid residues in length, were synthesized from hydrophilic regions of human clusterin. When studied individually, none of the peptides caused aggregation of LLC-PK1 cells, a porcine renal epithelial cell line. However, two out of the 34 peptides inhibited clusterin-induced cell aggregation in a dose-dependent manner. Scrambled versions of these two 'active' peptides did not inhibit cell aggregation. Seven peptides promoted cell adhesion. In conclusion, these findings provide evidence for novel amino acid sequences mediating clusterin-induced renal cell interactions.  相似文献   
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