Effect of different doses of ionizing radiation on the binding of prostaglandin E2 in mouse tissues

The effect of various radiation doses on membrane reception of prostaglandin E2(PGE2) of spleen, small intestine, brain, and liver cells of mice was studied in dynamics. Irradiation of the animals with doses producing bone marrow, intestinal and cerebral forms of radiation sickness was shown to change specific binding of PGE2 to cell membranes of both radiosensitive tissues and a relatively radioresistant organ, the liver.     

Construction of a BAC library for Haplochromis chilotes,a cichlid fish from Lake Victoria

Cichlid fishes in Lake Victoria are model organisms for studying rapid radiation and speciation. On the way to examine the molecular basis of how these cichlid fishes achieved such a remarkable morphological diversification, we constructed a bacterial artificial chromosome (BAC) library derived from a cichlid species, Haplochromis chilotes, from Lake Victoria. The library includes 157,056 clones with the average insert size of 128 kb, corresponding to a 10-fold coverage of the H. chilotes genome. Given that the cichlid fishes endemic to Lake Victoria are closely related to one another phylogenetically and their genomes are nearly identical, this BAC library can be utilized to isolate genes from the more than 200 Haplochromine cichlid species in Lake Victoria.     

Analysis of the modifying effect of liver injury on the course and outcome of acute radiation sickness

In studying the aggravating effect of liver injury on the development of radiation sickness in irradiated rats it was found that the death rate increased within the range of minimal and median lethal doses and was not associated with the aggravation of both the haematologic and the hemorrhagic syndromes; it was not related to infectious complications as well. The data are presented on auto-intoxication as a factor aggravating the outcome of the combined radiation injury.     

NMR spectroscopy based metabolic profiling of urine and serum for investigation of physiological perturbations during radiation sickness

Radiation accidents are rare events that induce radiation syndrome, a complex pathology which is difficult to treat. In medical management of radiation victims, life threatening damage to different physiological systems should be taken into consideration. The present study was proposed to identify metabolic and physiological perturbations in biofluids of mice during different phases of radiation sickness using ¹H nuclear magnetic resonance (¹H NMR) spectroscopy and pattern recognition (PR) technique. The ¹H NMR spectra of the biofluids collected from mice irradiated with 5 Gray (Gy) at different time points during radiation sickness were analysed visually and by principal components analysis. Urine and serum spectral profile clearly showed altered metabolic profiles during different phases of radiation sickness. Increased concentration of urine metabolites viz. citrate, α ketoglutarate, succinate, hippurate, and trimethylamine during prodromal and clinical manifestation phase of radiation sickness shows altered gut microflora and energy metabolism. On the other hand, serum nuclear magnetic resonance (NMR) spectra reflected changes associated with lipid, energy and membrane metabolism during radiation sickness. The metabonomic time trajectory based on PR analysis of ¹H NMR spectra of urine illustrates clear separation of irradiated mice group at different time points from pre dose. The difference in NMR spectral profiles depicts the pathophysiological changes and metabolic disturbances observed during different phases of radiation sickness, that in turn, demonstrate involvement of multiple organ dysfunction. This could further be useful in development of multiparametric approach for better evaluation of radiation damage as well as for medical management during radiation sickness.     

Chronic radiation damage by uranium and plutonium nuclear fission products

Chronical radiation sickness is a special form of the radiation damage. It occurs when doses of chronical irradiation exceed their values established for professionals. The sickness is well studied in clinical observations. It may take place also if uranium and plutonium nuclear fission products (NFP) enter the organism. In the last case the chronical radiation sickness practically is not investigated. In the article we present the results of the experimental studies on dogs of the damage caused by NFP.     

Utilization of a zebra finch BAC library to determine the structure of an avian androgen receptor genomic region

The zebra finch (Taeniopygia guttata) is an important model organism for studying behavior, neuroscience, avian biology, and evolution. To support the study of its genome, we constructed a BAC library (TG__Ba) using DNA from livers of females. The BAC library consists of 147,456 clones with 98% containing inserts of an average size of 134 kb and represents 15.5 haploid genome equivalents. By sequencing a whole BAC, a full-length androgen receptor open reading frame was identified, the first in an avian species. Comparison of BAC end sequences and the whole BAC sequence with the chicken genome draft sequence showed a high degree of conserved synteny between the zebra finch and the chicken genome.     

Combined effect of normobaric hyperoxia and vibration on the radiosensitivity of animals

In experiments with hybrid mice (CBA X C57B1)F1 and F2(CBWA), a study was made of the combined effect of normobaric hyperoxia and vibration on sensitivity of the organism to gamma-radiation. A single and protracted (for 5 days, daily) vibration before irradiation aggravated acute radiation sickness. A modifying effect of hyperoxia on the development of the intestinal form of radiation sickness was the same as that observed under the effect of vibration. In the experiments with tetrahybrids, the combined effect of the two factors aggravated drastically the intestinal syndrome of acute radiation sickness (DMF = 1.24).     

Proteinase inhibitors of the blood plasma in the early period of the development of acute radiation sickness in monkeys

A study was made of the postirradiation kinetics of blood antiproteinase activity in monkeys (Macaca nemestrina). Whole-body uniform gamma-irradiation (LD100/45) was shown to induce a significant decrease in the activity of alpha 2-macroglobulin during the first 24 h following irradiation: the decreased activity level was retained throughout the entire latent period of radiation sickness. At the height of radiation sickness (the 7th-10th day) up to the animals' death, a sharp increase was registered in the activity of alpha 1-inhibitor of blood plasma proteinases. The authors discuss a pathogenetic role of the diminution of the inhibitory potential of blood in the course of radiation sickness.     

Mechanisms of the protective action of sulfur-containing radioprotectors on the intestinal epithelium

In studying the influence of cystamine and gammaphos on the recovery of mouse jejunum epithelium after irradiation with doses inducing intestinal form of acute radiation sickness, it was shown that the radioprotective agents did not influence D0 value for intestinal epithelium stem cells, but in crypts the number of DNA-synthesizing enterocytes that entered mitosis increased after the preventive administration of the radioprotectors. All this caused the number of cells per villus to increase and intestinal mucosa to recover more readily.     

Effect of ionizing radiation on the functional state of the vascular-thrombocytic component of the hemostasis system

The influence of ionizing radiation (gamma-rays 60Co) on aggregation activity of the vascular wall and functional (aggregation) platelet activity was studied in the course of the development of acute radiation sickness. The decrease in the aggregation properties of the vascular wall and high functional activity of platelets were inversely proportional, correlating with the periods of acute radiation sickness development and depending on the radiation dose. It is suggested that the changes detected may play a role in the pathogenesis of the development of the postirradiation thrombohemorrhagic syndrome.     

Delayed effects of acute radiation injuries by radioactive carbon (14C-glycine)

A study was made of late biological effects of radioactive carbon (14C-glycine) applied in acute doses. The course of radiation sickness, at its acute stage, is similar to that of acute radiation sickness caused by external gamma-irradiation. The recovery is slow, and the disease becomes chronic exhibiting metabolism disturbances and early death of animals. Radioactive carbon has a pronounced blastomogenic action.     

Functional analysis of bacterial artificial chromosomes in mammalian cells: mouse Cdc6 is associated with the mitotic spindle apparatus

Bacterial artificial chromosomes (BACs) provide a well-characterized resource for studying the functional organization of genes and other large chromosomal domains. To facilitate functional studies in cell cultures, we have developed a simple approach for generating stable cell lines with variable copy numbers of any BAC. Here we describe hamster cell lines with BAC transgenes that express mouse Cdc6 at levels that correlate with BAC copy number; show that mouse Cdc6 is regulated normally during the cell cycle, binds chromatin, and is degraded during apoptosis; and report a novel fraction of Cdc6 that associates with the spindle apparatus during mitosis. With RNA interference to assess genetic complementation by BAC alleles, this system will facilitate functional studies on large chromosomal domains at variable copy number in mammalian cell models.     

Simple, fast, tissue-specific bacterial artificial chromosome transgenesis in Xenopus

We have developed a method of injecting bacterial artificial chromosome (BAC) DNA into Xenopus embryos that is simple and efficient, and results in consistent and tissue-specific expression of transgenes cloned into BAC vectors. Working with large pieces of DNA, as can be accommodated by BACs, is necessary when studying large or complex genes and conducive to studying the function of long-range regulatory elements that act to control developmentally restricted gene expression. We recombineered fluorescent reporters into three Xenopus tropicalis BAC clones targeting three different genes and report that up to 60% of injected embryos express the reporter in a manner consistent with endogenous expression. The behavior of these BACs, which are replicated after injection, contrasts with that of smaller plasmids, which degrade relatively quickly when injected as circular molecules and generally fail to recapitulate endogenous expression when not integrated into the Xenopus genome.     

Erythrocyte elastic and mechanical properties and mechanism of their change during irradiation

A decrease in erythrocyte deformation, which was maximum at the height of radiation sickness, was registered as early as 1-3 days following 6 Gy irradiation of rats. The aggregation of erythrocytes increased during the latent period of radiation sickness then sharply decreased. The role of the observed changes in radiation sickness then pathogenesis is discussed. It is established that they are associated with the altered fatty acid composition of the lipid phase of erythrocytic membranes, on the one hand, and with the disturbances in its ionic permeability, on the other.     

BAC及其转基因研究进展

本文综述了细菌人工染色体(BacterialArtificialChromsomes,BAC)的构建、物理图谱制作方法及其靶位精细操作策略的研究进展。同时,简要介绍了BAC转基因在基因功能以及基因表达与调控研究中的应用 。     

A physical map of the 20q12-q13.1 region associated with type 2 diabetes

Several recent genetic studies have suggested linkage of Type 2 diabetes (non-insulin-dependent diabetes mellitus) susceptibility to a region of chromosome 20q12-q13.1. To facilitate the identification and cloning of a diabetes susceptibility gene(s) in this region, we have constructed correlated radiation hybrid and YAC/BAC contig physical maps of the region. A high-resolution radiation hybrid map encompassing 9.5 Mb between the PLC and the CEBPB genes was constructed using 68 markers: 25 polymorphic markers, 15 known genes, 21 ESTs, and 7 random genomic sequences. The physical order of the polymorphic markers within this radiation hybrid map is consistent with published genetic maps. A YAC/BAC contig that gives continuous coverage between PLC and CEBPB was also constructed. This contig was constructed from 24 YACs, 34 BACs, and 1 P1 phage clone onto which 71 markers were mapped: 23 polymorphic markers, 12 genes, 24 ESTs, and 12 random genomic sequences. The radiation hybrid map and YAC/BAC physical map enable precise mapping of newly identified transcribed sequences and polymorphic markers that will aid in linkage and linkage disequilibrium studies and facilitate identification and cloning of candidate Type 2 diabetes susceptibility genes residing in 20q12-q13.1.     

Changes in the dog endocrine system in the hematopoietic form of radiation sickness

The endocrine status of the organism estimated by the cortisol, insulin and triiodothyronine content of blood considerably changes during radiation sickness. The most pronounced changes in the endocrine status occur during the primary response and at the height of radiation sickness. The endocrine status test may be used in the individual radiosensitivity prognosis.     

A possible approach to large-scale laboratory testing for acute radiation sickness after a nuclear detonation

After the detonation of an improvised nuclear device, several key actions will be necessary to save the greatest number of lives possible. Among these tasks, the identification of patients with impending acute radiation sickness is a critical problem that so far has lacked a clear solution in national planning. We present one possible solution: the formation of a public-private partnership to augment the capacity to identify those at risk for acute radiation sickness.     

Defective repair of radiation-induced DNA damage is complemented by a CHORI-230-65K18 BAC clone on rat chromosome 4

The Long Evans cinnamon (LEC) rat is highly susceptible to X-irradiation due to defective DNA repair and is thus a model for hepatocellular carcinogenesis. We constructed a bacterial artificial chromosome (BAC) contig of rat chromosome 4 completely covering the region associated with radiation susceptibility. We used transient and stable transfections to demonstrate that defective DNA repair in LEC cells is fully complemented by a 200-kb BAC, CHORI-230-65K18. Further analysis showed that the region associated with radiation susceptibility is located in a 128,543-bp region of 65K18 that includes the known gene Rpn1. However, neither knockdown nor overexpression of Rpn1 indicated that this gene is associated with radiation susceptibility. We also mapped three ESTs (TC523872, TC533727, and CB607546) in the 128,543-bp region, suggesting that 65K18 contains an unknown gene associated with X-ray susceptibility in the LEC rat.     

Radiation diagnosis of bronchioloalveolar cancer

The paper analyzes the results of examination of 260 patients with bronchioloalveolar cancer (BAC) who were followed up at the Russian Research Center of Radiology and Roentgenology for 30 years. It provides its clinical, X-ray, and morphological manifestations and classification and the methodological aspects of differential diagnosis. An optimum radiation diagnosis programme has been drawn up, which involves currently available procedures, including computed tomography. The morphological forms of BAC are given in detail.