Nitroimidazole conjugates of bis(thiosemicarbazonato)Cu(II) - Potential combination agents for the PET imaging of hypoxia

Combination agents comprising two different pharmacophores with the same biological target have the potential to show additive or synergistic activity. Bis(thiosemicarbazonato)copper(II) complexes (e.g. ⁶⁴Cu-ATSM) and nitroimidazoles (e.g. ¹⁸F-MISO) are classes of tracer used for the delineation of tumor hypoxia by positron emission tomography (PET). Three nitroimidazole-bis(thiosemicarbazonato)copper(II) conjugates were produced in order to investigate their potential as combination hypoxia imaging agents. Two were derived from the known bifunctional bis(thiosemicarbazone) H₂ATSM/A and the third from the new precursor diacetyl-2-(4-N-methyl-3-thiosemicarbazone)-3-(4-N-ethylamino-3-thiosemicarbazone) - H₂ATSM/en. Oxygen-dependent uptake studies were performed using the ⁶⁴Cu radiolabelled complexes in EMT6 carcinoma cells. All the complexes displayed appreciable hypoxia selectivity, with the nitroimidazole conjugates displaying greater selectivity than a simple propyl derivative used as a control. Participation of the nitroimidazole group in the trapping mechanism is indicated by the increased hypoxic uptake of the 2- vs. the 4-substituted ⁶⁴Cu-ATSM/A derivatives. The 2-nitroimidazole derivative of ⁶⁴Cu-ATSM/en demonstrated superior hypoxia selectivity to ⁶⁴Cu-ATSM over the range of oxygen concentrations tested. Biodistribution of the radiolabelled 2-nitroimidazole conjugates was carried out in EMT6 tumor-bearing mice. The complexes showed significantly different uptake trends in comparison to each other and previously studied Cu-ATSM derivatives. Uptake of the Cu-ATSM/en conjugate in non-target organs was considerably lower than for derivatives based on Cu-ATSM/A.     

Range of the antigenic specificity of peptidoglycan in Staphylococcus aureus compared to other representatives of the Staphylococcus genus

In investigations based on the use of a highly sensitive test system permitting the detection of normal human antibodies to S. aureus peptidoglycan, the antigenic relationships between the peptidoglycans of S. aureus and other representatives of the genus Staphylococcus have been studied. Among other staphylococcal species, S. simulans, S. xylosus, S. hyicus, S. cohnii, S. hyicus s. s. chromogenes have been found to possess peptidoglycans most closely related to S. aureus peptidoglycans, while S. warneri and S. epidermidis peptidoglycans have proved to be least closely related to it.     

Antigen-specific T helper clones in a nonresponder strain require augmentation for expression of helper activity. Evidence for a possible antigen presentation defect in B cells

Hen egg-white lysozyme (HEL)-specific Thy-1+, Lyt-1+2- T cell lines and clones were derived from the nonresponder C57BL/6 strain. Although the antigen-specific proliferative response of these T cells in the presence of syngeneic irradiated spleen cells as a source of antigen-presenting cells (APC) was normal, the same cells were incapable of stimulating B cells to secrete antibody in vitro. This deficiency could, however, be corrected by the addition of an excess of normal T cells or a supernatant from concanavalin A-stimulated rat spleen cells. Alternatively, the use of highly cross-reactive ring-necked pheasant lysozyme in the cultures allowed expression of efficient help, ruling out any inherent deficiency in the T cells. The antibody response was specific and required MHC compatibility between the T lines and responding B cells. By using (H-2b X H-2d)F1 B cells and another H-2d-restricted HEL-specific T line, it was shown that only the H-2b-restricted T-B collaboration required exogenous factors, and the H-2d-restricted collaboration did not. Because both proliferative and helper responses are dependent upon MHC-restricted antigen presentation by macrophage-APC and B cells, respectively, these results suggest that the defect in the nonresponder H-2b-restricted T-B collaborative pathway may relate to the inability of B cells to adequately process and present HEL to clonal T cells.     

Propagation of Zea mays L. by Shoot Tip Culture: A Feasibility Study

A procedure for the stimulation of axillary bud developmentfrom young shoots of maize, their subculture to root-inducingmedia and transfer as rooted plants to soil is described. Axillarybud development was enhanced by the addition of kinetin andauxin to the culture medium. Root initiation on explanted axillarybuds, while successful with some cultivars, was variable. Anumber of mature plants with normal tassels and ears were producedfrom the lowermost buds of an original stem explant. Buds fromhigher positions on the explant exhibited different potentialitieswith some, those normally from cob producing nodes, producingshort-stalked plants with terminal female influorescences. Agradient of bud potentiality along the stem appears to be establishedextremely early after each is initiated. Zea mays., corn, maize, shoot tip culture, clone, vegetative propagation     

Cystic fibrosis gene mutations and linked RFLPs in the Slovenian population.

The authors used polymerase chain reaction to analyse 56 Slovenian cystic fibrosis (CF) chromosomes for the presence of delta F508 and eight other most frequent mutations located in exons 7,11 and 20 (R347P, R334W, G551D, R553X, S549RA, S549RT, S549I and S1255X) of the CF gene. We also determined the frequency of haplotypes associated with CF for six linked RFLP markers (MetD/TaqI, MetH/TaqI, XV-2c/TaqI, KM-19/PstI, MP6d9/MspI and J3.11/MspI) in 27 Slovenian CF families. delta F508 mutation was present in 55.4 percent of the CF chromosomes. No case of the other mutations were detected in the sample of tested CF chromosomes. A very high degree of association (0.88) has been found between DNA marker MetH and CF (as measured by the Yule's association coefficient) in our population. Using the RFLP markers XV-2c and KM-19, we found that 85% of delta F508 mutated chromosomes have a single 1 2 (B) haplotype, and that this haplotype is present on only 15.4 percent of CF chromosomes without this deletion.