Potassium transfer from brain to blood during sustained hyponatraemia in the newborn calf

Summary The effect of dilutional hyponatraemia on cerebral blood flow and oxygen consumption, and net transfer of K⁺ to the circulation from brain tissue drained by the sagittal sinus was investigated in anaesthetized calves. Cerebral blood flow decreased, and net transfer of K⁺ to the circulation increased during hyponatraemia.Acknowledgments. The expert assistance of Miss B.N. O'Connor, Miss D. McNaughton and Mr P.M.M. Bircham is gratefully acknowledged.     

The DNA sequence of human chromosome 21

Chromosome 21 is the smallest human autosome. An extra copy of chromosome 21 causes Down syndrome, the most frequent genetic cause of significant mental retardation, which affects up to 1 in 700 live births. Several anonymous loci for monogenic disorders and predispositions for common complex disorders have also been mapped to this chromosome, and loss of heterozygosity has been observed in regions associated with solid tumours. Here we report the sequence and gene catalogue of the long arm of chromosome 21. We have sequenced 33,546,361 base pairs (bp) of DNA with very high accuracy, the largest contig being 25,491,867 bp. Only three small clone gaps and seven sequencing gaps remain, comprising about 100 kilobases. Thus, we achieved 99.7% coverage of 21q. We also sequenced 281,116 bp from the short arm. The structural features identified include duplications that are probably involved in chromosomal abnormalities and repeat structures in the telomeric and pericentromeric regions. Analysis of the chromosome revealed 127 known genes, 98 predicted genes and 59 pseudogenes.     

Cerebral ammonia production during hypoglycaemia in the newborn calf

Summary The effect of insulin hypoglycaemia on cerebral blood flow, and cerebral metabolic rates of glucose, oxygen and ammonia was investigated in the unanaesthetized newborn calf. A net loss of ammonia from the brain occurred during hypoglycaemia, and was greater in convulsing than in comatose animals.Acknowledgments. The expert assistance of Mr P.M.M. Bircham and Miss B.N. O'Connor is gratefully acknowledged. This work was supported by the Medical Research Council.     

Seven prostate cancer susceptibility loci identified by a multi-stage genome-wide association study

Prostate cancer (PrCa) is the most frequently diagnosed male cancer in developed countries. We conducted a multi-stage genome-wide association study for PrCa and previously reported the results of the first two stages, which identified 16 PrCa susceptibility loci. We report here the results of stage 3, in which we evaluated 1,536 SNPs in 4,574 individuals with prostate cancer (cases) and 4,164 controls. We followed up ten new association signals through genotyping in 51,311 samples in 30 studies from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. In addition to replicating previously reported loci, we identified seven new prostate cancer susceptibility loci on chromosomes 2p11, 3q23, 3q26, 5p12, 6p21, 12q13 and Xq12 (P = 4.0 × 10(-8) to P = 2.7 × 10(-24)). We also identified a SNP in TERT more strongly associated with PrCa than that previously reported. More than 40 PrCa susceptibility loci, explaining ～25% of the familial risk in this disease, have now been identified.     

Cerebral ammonia production during hypoglycemia in the newborn calf.

The effect of insulin hypoglycaemia on cerebral blood flow, and cerebral metabolic rates of glucose, oxygen and ammonia was investigated in the unanaesthetized newborn calf. A net loss of ammonia from the brain occurred during hypoglycaemia, and was greater in convulsing than in comatose animals.