Risk of iron overload is decreased in beating heart coronary artery surgery compared to conventional bypass.

Conventional cardiopulmonary bypass surgery (CCPB) increases the iron loading of plasma transferrin often to a state of plasma iron overload, with the presence of low molecular mass iron. Such iron is a potential risk factor for oxidative stress and microbial virulence. Here we assess 'off-pump' coronary artery surgery on the beating heart for changes in plasma iron chemistry. Seventeen patients undergoing cardiac surgery using the 'Octopus' myocardial wall stabilisation device were monitored at five time points for changes in plasma iron chemistry. This group was further divided into those (n=9) who had one- or two- (n=8) vessel grafts, and compared with eight patients undergoing conventional coronary artery surgery. Patients undergoing beating heart surgery had significantly lower levels of total plasma non-haem iron, and a decreased percentage saturation of their transferrin at all time points compared to conventional bypass patients. Plasma iron overload occurred in only one patient undergoing CCPB. Beating heart surgery appears to decrease red blood cell haemolysis, and tissue damage during the operative procedures and thereby significantly decreases the risk of plasma iron overload associated with conventional bypass.     

Characterization of indolinones which preferentially inhibit VEGF-C- and VEGF-D-induced activation of VEGFR-3 rather than VEGFR-2.

VEGF-C and VEGF-D are lymphangiogenic factors that bind to and activate VEGFR-3, a fms-like tyrosine kinase receptor whose expression is limited almost exclusively to lymphatic endothelium in the adult. Processed forms of VEGF-C and VEGF-D can also activate VEGFR-2, a key player in the regulation of angiogenesis. There is increasing evidence to show that these receptor-ligand interactions play a pivotal role in a number of pathological situations. Inhibition of receptor activation by VEGF-C and VEGF-D could therefore be pharmaceutically useful. Furthermore, to understand the different roles of VEGF-C, VEGF-D, VEGFR-2 and VEGFR-3 in pathological situations it will be necessary to dissect the complex interactions of these ligands and their receptors. To facilitate such studies we cloned, sequenced and characterized the expression of rat VEGF-C and VEGF-D. We showed that Cys152-->Ser mutants of processed rat VEGF-C can activate VEGFR-3 but not VEGFR-2, while the corresponding mutation in rat VEGF-D inhibits its ability to activate both VEGFR-2 and VEGFR-3. We also synthesized and characterized indolinones that differentially block VEGF-C- and VEGF-D-induced VEGFR-3 kinase activity compared to that of VEGFR-2. These tools should be useful in analysing the different activities and roles of VEGF-C, VEGF-D and their ligands, and in blocking VEGFR-3-mediated lymphangiogenesis.     

Perspectives on establishing a public cord blood inventory in South Africa

The South African population is highly diverse, both ethnically and genetically. This diversity is particularly true for the African ancestry and various mixed ancestry population groups. These groups are under-represented in national and international bone marrow and peripheral blood donor registries, making it challenging to identify HLA-matched and mismatched unrelated donors when patients from these groups require allogeneic hematopoietic stem and progenitor cell transplantation. In most high-income countries, banked cord blood (CB) units provide an attractive source of hematopoietic progenitor cells for genetically diverse populations. SA does not have a public CB inventory, leaving many patients without access to this important treatment modality. Haploidentical transplantation provides an alternative. In recent years, the use of post-transplant cyclophosphamide has significantly reduced the incidence of graft-versus-host disease after haploidentical transplantation and has improved transplantation outcomes. However, it is difficult to identify suitable haploidentical donors in SA because of family disruption and a high prevalence of HIV. Here the authors provide a brief historical overview of the ethnic and genetic diversity of the country and region. The authors provide a southern African perspective on HLA diversity, consider the allogeneic hematopoietic stem and progenitor cell transplantation landscape and explore the need to establish a public CB bank (CBB) in SA. The health policy and regulatory frameworks that will impact on a CBB in the country SA are also explored. Finally, the authors discuss several matters we believe require attention when considering the establishment of a sustainable public CBB in the South African context.     

Plant root distributions and nitrogen uptake predicted by a hypothesis of optimal root foraging

CO(2)-enrichment experiments consistently show that rooting depth increases when trees are grown at elevated CO(2) (eCO(2)), leading in some experiments to increased capture of available soil nitrogen (N) from deeper soil. However, the link between N uptake and root distributions remains poorly represented in forest ecosystem and global land-surface models. Here, this link is modeled and analyzed using a new optimization hypothesis (MaxNup) for root foraging in relation to the spatial variability of soil N, according to which a given total root mass is distributed vertically in order to maximize annual N uptake. MaxNup leads to analytical predictions for the optimal vertical profile of root biomass, maximum rooting depth, and N-uptake fraction (i.e., the proportion of plant-available soil N taken up annually by roots). We use these predictions to gain new insight into the behavior of the N-uptake fraction in trees growing at the Oak Ridge National Laboratory free-air CO(2)-enrichment experiment. We also compare MaxNup with empirical equations previously fitted to root-distribution data from all the world's plant biomes, and find that the empirical equations underestimate the capacity of root systems to take up N.     

Heterogeneity of chromosomal genes encoding chloramphenicol resistance in streptococci

The DNA of 21 chloramphenicol-resistant plasmid-free streptococci was tested for sequence homology with the genes encoding chloramphenicol acetyltransferase (cat) of the staphylococcal plasmids pC194 and pC221. Homology to the cat gene of pC194 was detected in 11 strains, including the 8 strains of Streptococcus pneumoniae examined, and homology to cat of pC221 was found in 3 strains. The DNA of 7 strains did not detectably hybridize with either probe.     

Localization of tubulin in the mitotic apparatus of mammalian cells by immunofluorescence and immunoelectron microscopy

Antitubulin antibody was used as an immunofluorescent and immunoelectron microscopic probe to localize tubulin in components of the mitotic apparatus of rat kangaroo (strain PtK₁) cells in vitro. In addition to the detection of tubulin in the spindle microtubules and centrioles, other structures were found to display specific staining including kinetochores, amorphous pericentriolar material and small virus-like particles associated with the centrioles. The kinetochores consisted of a densely stained outer layer about 400 Å thick which is separated from an inner layer of the same dimension by a lightly staining middle layer. Microtubules were primarily associated with the outermost plate of the kinetochore but tubulin was uniformly distributed in both outer and inner plates. Colcemid treatment prevented the assembly of spindle microtubules and resulted in specific alterations of the kinetochore but failed to diminish the staining of the kinetochores. These observations suggest that tubulin molecules may comprise an important structural component of the kinetochore.     

Export of extracellular levansucrase by Bacillus subtilis: inhibition by cerulenin and quinacrine.

Bacillus subtilis B secretes an inducible, extracellular enzyme, levansucrase. Inhibition studies were undertaken to investigate the possible mechanism of release of this enzyme. The antibiotic cerulenin, at a concentration of 10 micrograms/ml, totally inhibited de novo lipid synthesis in B. subtilis B for at least 1 h, while only slightly reducing protein and RNA synthesis. At this concentration cerulenin, added concomitantly with the inducer sucrose, prevented the release of levansucrase for at least 150 min. This was not due to the prevention of inducer uptake by the cells. The release of the enzyme was also independent of cell division. In B. subtilis 1007 the induction of beta-galactosidase by 5 mM lactose was not prevented by cerulenin. Preliminary evidence indicated the association of a lipid moiety with the enzyme as it passes through the cytoplasmic membrane. Quinacrine (0.2 mM), which inhibits the penicillinase-releasing protease of Bacillus licheniformis, inhibited levansucrase release from B. subtilis B, but had no effect on lipid synthesis.