Calculation of the Biological Efficiency of the Proton Component from 14.8 MeV Neutron Irradiation in Computational Biology with Help of Video Cards

Bulletin of Experimental Biology and Medicine - Fast neutron therapy, which previously has demonstrated effective results, but along with a large number of complications, can again be considered a...     

Regenerative medicine of pancreatic islets

The pancreas became one of the first objects of regenerative medicine,since other possibilities of dealing with the pancreatic endocrine insufficiency were clearly exhausted.The number of people living with diabetes mellitus is currently approaching half a billion,hence the crucial relevance of new methods to stimulate regeneration of the insulin-secreting β-cells of the islets of Langerhans.Natural restrictions on the islet regeneration are very tight;nevertheless,the islets are capable of physiological regeneration via β-cell self-replication,direct differentiation of multipotent progenitor cells and spontaneous α-to or δ-to β-cell conversion(trans-differentiation).The existing preclinical models of β-cell dysfunction or ablation(induced surgically,chemically or genetically) have significantly expanded our understanding of reparative regeneration of the islets and possible ways of its stimulation The ultimate goal,sufficient level of functional activity of β-cells or their substitutes can be achieved by two prospective broad strategies β-cell replacement and β-cell regeneration.The "regeneration" strategy aims to maintain a preserved population of β-cells through in situ exposure to biologically active substances that improve β-cell survival,replication and insulin secretion,or to evoke the intrinsic adaptive mechanisms triggering the spontaneous non-β-to β-cell conversion.The "replacement" strategy implies transplantation of β-cells(as non-disintegrated pancreatic material or isolated donor islets) or β-like cells obtained ex vivo from progenitors or mature somatic cells(for example,hepatocytes or a-cells) under the action of small-molecule inducers or by genetic modification.We believe that the huge volume of experimental and clinical studies will finally allow a safe and effective solution to a seemingly simple goal-restoration of the functionally activeβ-cells, the innermost hope of millions of people globally.     

Extracellular portions of HLA antigens are not compact globulae

Membranes of human spleen cells were hydrolyzed by papain and the extracellular portions of HLA antigen molecules isolated by monoclonal antibodies fixed on Sepharose. The isolated proteins were spin-labeled by TEMPO-dichlorotriazine. The values of rotational correlation times (tau) of spin-labeled proteins were calculated using dependencies of magnetic parameters found from ESR spectra vs viscosity at constant temperature. The tau-values were equal to 8 nsec for class I molecules and 14 nsec for class II molecules. These values were significantly lower than those predicted for a rigid sphere with dimensions equal to the extracellular portions of HLA molecules (20 nsec). This fact suggests the existence of flexibility in poly-functional HLA molecules, which seems to be important for their biological activity. In this respect, extracellular portions of HLA molecules resemble flexible Fc fragments (tau = 12 nsec) and differ from rigid Fab fragments (tau = 20 nsec) of immunoglobulins G. The rotation of the oligosaccharide chains attached to HLA molecules is restricted.     

Comet-FISH using peptide nucleic acid probes detects telomeric repeats in DNA damaged by bleomycin and mitomycin C proportional to general DNA damage

For the optimal use of anticancer drugs a knowledge of the whole spectrum of side-effects is required. A potential hazard, so far only scarcely investigated, is uncontrolled effects of drugs such as bleomycin (BLM) and mitomycin C (MMC) on telomere shortening in non-cancerous tissues of the treated person. For the first time, directly labelled telomere-specific peptide nucleic acid (PNA) hybridization probes were applied in comet-FISH to detect DNA fragmentation on an intermediate scale. The effects of BLM and MMC were measured in peripheral blood cells of three human volunteers, following ex vivo incubation. Fragmentation of telomeres and subtelomeric regions was highly specifically detected by the comet-FISH assay, a combination of the comet assay and fluorescence in situ hybridization. As a technical detail, the effects of the hybridization procedure have been studied on the level of single comets. Image analysis before and after the hybridization process reveals a small decrease in the detected fragmented DNA, probably due to diffusion of small fragments. It could not only be shown that both drugs actually induce breaks in telomere-associated DNA, but also that the comet-FISH technique, as a quantitative approach, is a useful tool for the detection and evaluation of the role of sequence-specific DNA damage after mutagenic action. The breakage frequency for DNA of or adjacent to telomeric repeats was found to be proportional to that of the total DNA, which hints at random induction of DNA breaks by BLM and MMC. In terms of therapy, the results indicate that no over- or under-proportional effects on telomeres of BLM or MMC need be expected.