Front Cover: Highly hydrophilic cationic gold nanorods stabilized by novel quaternary ammonium surfactant with negligible cytotoxicity (J. Biophotonics 12/2019)

Cationic gold nanorods stabilized by quaternary ammonium salts (QAS) are a promising tool for photothermal destruction of cancer cells. However, cytotoxicity of the alkanethiol‐QAS limits their medical applications. A novel design of cationic surfactant composed of the quaternary ammonium group and ethylene glycol chain significantly reduces the compound cytotoxicity in the free state while allowing the preparation of stable nanorods with high cellular uptake and lysosomal localization. Further details can be found in the article by Sarka Salajkova, Michal Sramek, David Malinak, et al. ( e201900024 ).

     

Modification of yttrium alkoxides: β-Ketoesterate-substituted yttrium alkoxo/hydroxo/oxo clusters

Reaction of Y₅O(OiPr)₁₃ (“yttrium iso-propoxide”) with one molar equivalent of isopropyl acetoacetate (iprac) per Y resulted in the formation of Y₉O(OH)₉(OiPr)₈(iprac)₈, a rare example of an yttrium alkoxo/hydroxo/oxo cluster. Reaction in a 1:3 molar ratio gave Y₄(OH)₂(iprac)₁₀ and Y₆(OH)₆(iprac)₁₂ instead. A fourth cluster, Y₉O(OH)₉(iprac)₁₆, structurally closely related to Y₉O(OH)₉(OiPr)₈(iprac)₈, was obtained upon recrystallization of Y₄(OH)₂(iprac)₁₀ from CDCl₃.     

Effect of Body Size on Toxicity of Zinc in Neonates of Four Differently Sized <Emphasis Type="Italic">Daphnia</Emphasis> Species

The sensitivity of neonates of four Daphnia species to zinc was tested in relation to their mean body size. These mean sizes of these four Daphnia spp were: D. magna, 0.813 ± 0.055 mm, D.␣pulicaria, 0.745 ± 0.063 mm, D. pulex, 0.645 ± 0.044 mm and D. galeata, 0.611 ± 0.058 mm. A positive relationship between EC₅₀ (24, 48) values and neonates size was found. The smaller the size of the daphnid the higher was the sensitivity to heavy metal toxicity. For all tested species did the EC₅₀ values decrease with time; the decrease was most marked for D. magna and the least for D. galeata. The EC₅₀ values of D. magna were higher than would be expected on basis of its body size.     

Sites in Myelin Basic Protein that React with Monoclonal Antibodies

The epitopes (antigenic sites) for seven monoclonal antibodies (MAbs) evoked in rats or mice by guinea pig or monkey myelin basic protein (BP) have been located in four different sequences of the BPs extracted from various species. Six of the MAbs were evoked by guinea pig BP. (1) One epitope, possibly a pair, is included within residues 1-14 of all BPs tested and reacts with two rat IgG MAbs. (2) A definite pair of overlapping epitopes includes the central Phe91-Phe92 sequence. One epitope is contained entirely within sequence 90-99 and reacts with a rat IgG MAb. The substitution of Ser in chicken BP for Thr97 destroys this epitope. The other epitope appears to include residues on the amino side of Phe44 and even of His32 and suggests some tertiary structure in BP. This epitope reacts with a mouse IgM MAb that does not recognize the chicken substitution. (3) The third epitope lies within residues 114-121, specifically including Trp118, and reacts with a rat IgG MAb. A cross-reacting epitope probably includes residues 44-45 in certain species (guinea pig and bovine but not rabbit). (4) Another pair of epitopes is located within residues 131-140 but is severely species-restricted. This region in guinea pig BP evoked a species-specific mouse IgM MAb. The same region in monkey BP evoked the seventh MAb, a mouse IgG, which reacts with human, chimpanzee, monkey, bovine, and rat-18.5 kDa BPs and to a lesser extent rabbit BP but not with guinea pig, pig, or chicken BPs. Some tertiary structure in guinea pig BP is also suggested by the reactivities with the IgM MAb. All of the MAbs react with myelin in histologic preparations, but the optimum method of preparation of the tissue varies with each.     

Successful childbirth in a patient with chronic myelogenous leukemia treated with imatinib mesylate during early pregnancy

Aims: To report a case of successful pregnancy in a patient with chronic myelogenous leukemia treated with imatinib mesylate for the first 4 months of pregnancy. Results: Imatinib mesylate is potentially teratogenic and its use during pregnancy in humans can lead to abortion or development of fetal abnormalities in nearly 40% of fully reported cases. We report a case of a 28-year-old woman who delivered a healthy child of normal weight after having been treated with imatinib for Ph1-positive CML during the first four months of her pregnancy. She refused advocated interruption and for the rest of the pregnancy was treated with interferon. The treatment was associated with a rapid 2-log increase in the leukemia clone measured by the real-time polymerase chain reaction. Reintroduction of imatinib after delivery resulted in achievement of the complete cytogenetic response again. Conclusions: We discuss possible strategies for successful management of pregnancy in CML patients treated with imatinib.     

Prime/boost immunotherapy of HPV16-induced tumors with E7 protein delivered by Bordetella adenylate cyclase and modified vaccinia virus Ankara

The Bordetella adenylate cyclase toxoid (CyaA) targets cells expressing the α_Mβ₂ integrin receptor CD11b/CD18 (CR3 or Mac-1) and can penetrate into cytosol of professional antigen-presenting cells, such as dendritic cells. This allows us to use CyaA for delivery of passenger antigens into the cytosolic pathway of processing and MHC class I-restricted presentation, which can promote induction of antigen-specific CD8⁺ cytotoxic T-lymphocyte immune responses. We show here that vaccination with a genetically detoxified CyaA336/E7 protein, carrying the full-length oncoprotein E7 of the human papilloma virus 16 inserted at position 336 of the cell-invasive AC domain of CyaA, induces an E7-specific CD8⁺ T-cell immune response and confers on mice protective, as well as therapeutic immunity against challenge with TC-1 tumor cells expressing the E7 oncoprotein. The therapeutic efficacy of priming with the CyaA336/E7 vaccine could further be enhanced by a heterologous booster immunization with a highly attenuated modified vaccinia virus Ankara (MVA) expressing the E7 protein fused to the lysosome-associated membrane protein (LAMP1). These results establish the potential of CyaA as a new antigen delivery tool for prime/boost immunotherapy of tumors. This paper won the poster prize at the conference “Progress in Vaccination against Cancer 4”, PIVAC 4, held in Freudenstadt-Lauterbad, Black Forest, Germany, from 22 to 25 September 2004. For further material on this conference, please see the series of Symposium Papers, published     

Two new methods monitoring kinetics of hydrolysis of acetylcholine and acetylthiocholine

Hydroxylamine and HPLC methods, measuring in vitro kinetics of enzymatic hydrolysis of acetylcholine or acetylthiocholine by cholinesterases, are described. The hydroxylamine method determines the dependence of substrate concentration vs. time, the HPLC method is able to measure simultaneously the time dependences of substrate and both primary products, choline or thiocholine, and acetic acid. Practical determinations are shown, comparison with known (above all Ellman's and pH-stat) methods, advantages and disadvantages are discussed.     

Array comparative genome hybridization in patients with developmental delay: two example cases

Developmental delay is often a predictor of mental retardation (MR) or autism, two relatively frequent developmental disorders severely affecting intellectual and social functioning. The causes of these conditions remain unknown in most patients. They have a strong genetic component, but the specific genetic defects can only be identified in a fraction of patients. Recent developments in genomics supported the establishment of the causal link between copy number variants in the genomes of some patients and their affection. One of the techniques suitable for this analysis is array comparative genome hybridization, which can be used both for detailed mapping of chromosome rearrangements identified by classical cytogenetics and for the identification of novel submicroscopic gains or losses of genetic material. We illustrate the power of this approach in two patients. Patient 1 had a cytogenetically visible deletion of chromosome X and the molecular analysis was used to specify the gene content of the deletion and the prognosis of the child. Patient 2 had a seemingly normal karyotype and the analysis revealed a small recurrent deletion of chromosome 1 likely to be responsible for his phenotype. However, the genetic dissection of MR and autism is complicated by high heterogeneity of the genetic aberrations among patients and by broad variability of phenotypic effects of individual genetic defects.