Metabolic Alterations in Preneoplastic Development Revealed by Untargeted Metabolomic Analysis

Metabolic rewiring is a critical hallmark of tumorigenesis and is essential for the development of cancer. Although many key features of metabolic alteration that are crucial for tumor cell survival, proliferation and progression have been identified, these are obtained from studies with established tumors and cancer cell lines. However, information on the essential metabolic changes that occur during pre-neoplastic cell (PNC) development that enables its progression to full blown tumor is still lacking. Here, we present an untargeted metabolomics analysis of human oncogene HRASG12V induced PNC development, using a transgenic inducible zebrafish larval skin development model. By comparison with normal sibling controls, we identified six metabolic pathways that are significantly altered during PNC development in the skin. Amongst these altered pathways are pyrimidine, purine and amino acid metabolism that are common to the cancer metabolic changes that support rapid cell proliferation and growth. Our data also suggest alterations in post transcriptional modification of RNAs that might play a role in PNC development. Our study provides a proof of principle work flow for identifying metabolic alterations during PNC development driven by an oncogenic mutation. In the future, this approach could be combined with transcriptomic or proteomic approaches to establish the detailed interaction between signaling networks and cellular metabolic pathways that occur at the onset of tumor progression.

Sibling Relationships in Adoptive Families That Disrupted or Were in Crisis

Purpose: The study investigated whether sibling relationships influenced the outcomes of a sample of adoptive placements in England and Wales that had broken down postorder or were in crisis. Method: The study used secondary analysis drawing on in-depth interviews with 41 families who had experienced an adoption disruption and 42 families who described the adoptive placement as being in crisis in England and in Wales. The families contained 214 adopted and birth children. Results: Siblings placed together were statistically more likely to disrupt in comparison with sequential placements. Only 18 of the 83 families described normal sibling relationships. Placements intended to maintain sibling relationships had not done so. Conclusion: Assessments need to pay more attention to sibling dynamics. Children’s relationships might be better supported by separate placements with planned contact. Interventions are needed to improve sibling relationships.

Discordance of Congenital Bilateral Anorchia in Uniovular Twins: 17 Years of Observations on Growth and Development

We have reported observations of growth and development made over a 16-year period on a subject who suffered bilateral congenital anorchia and his uniovular twin brother. The anorchic individual was treated with oxandrolone for a period of 3.6 years prior to the testosterone replacement therapy. The oxandrolone therapy produced a significant increment in the height age without excessive gain in bone age. At the age of 20.9 years the anorchic twin is 5.4 cm taller than his normal twin. Other differences observed between the twins reported here include the following: the anorchic subject had longer extremities, greater biacromial and biiliac distances and a smaller penis than his normal sibling. Oxandrolone therapy does appear to modify the ultimate height in children.

Canine Hemophilia and Hemopoietic Grafting

Two hemophilic beagles were given 1200 R whole-body irradiation followed by a successful marrow graft from a normal sibling. During observation periods of 7 and 24 mo, there was no evidence of factor VIII synthesis.

CARBOXYHEMOGLOBIN LEVELS AS AN INDEX OF HEMOLYSIS

Carbon monoxide (CO) and bilirubin are formed in equimolar amounts during the catabolism of heme. In demonstrating increased endogenous CO formation from accelerated hemolysis it is important to separate out the effect of variable exogenous CO exposure. The carboxyhemoglobin level in 229 normal children ranged from 0.6 to 3.9% saturation, with a mean of 1.30% (S.D. = 0.47%). Forty children with hemolytic diseases had from 0.8 to 4.0% of their circulating hemoglobin saturated with CO with a mean of 1.95% (S.D. = 0.88%). The sixfold range observed in normal children is largely due to variable ambient CO exposure, since 574 comparisons between nonsmoking adults who were breathing the same gas mixture for over 18 hours, always gave carboxyhemoglobin values which differed by less than 0.35% saturation. By comparing the blood CO content of a suspect hemolytic patient with a normal sibling or another control individual who has been exposed to the same exogenous CO level for several hours, it is possible to obtain a qualitative index of increased endogenous CO formation. Thirty-seven children with known hemolytic disease always had carboxyhemoglobin levels which were higher than their matched environmental controls.

Studies in the muscles of meat animals. IV. Comparative composition of muscles from ‘doppelender’ and normal sibling heifers

1. Fourteen muscles from a normal 46-week-old Friesian heifer and from its 40-week-old half-sister, which showed the pronounced muscle hypertrophy of ‘doppelender’ cattle, were analysed for moisture, hydroxyproline, sodium, potassium, total nitrogen, and intramuscular fat: the iodine number of the latter was determined. In four of the muscles sarcoplasmic, myofibrillar and stroma nitrogens were also estimated.2. Hypertrophy was associated with a mean increase in the percentage of total nitrogen, with markedly lower percentages of hydroxyproline and of intramuscular fat, and with a decreased K/Na ratio.