Mortality among male anaesthetists in the United Kingdom, 1957-83.

A cohort of 3769 male anaesthetists resident in the United Kingdom between 1957 and 1983 was followed up for a total of 51,431 person years of observation. All subjects were fellows of the Faculty of Anaesthetists and held full registration with the General Medical Council. With all men in social class I being taken as the standard, the standardised mortality ratio among anaesthetists for all causes of death was 68 (95% confidence interval 59 to 77) and the standardised mortality ratio for all cancers was 50 (95% confidence interval 36 to 67). There was no significant excess mortality from lymphomas or leukaemias, but 16 of the 221 deaths in anaesthetists were due to suicide, giving a standardised mortality ratio of 202 (95% confidence interval 115 to 328). When anaesthetists were compared with all doctors the standardised mortality ratio for suicide was only 114, a nonsignificant excess. These findings confirm that the risk of suicide among anaesthetists is twice as high as among other men in social class I but suggest that the risk does not differ significantly from that among doctors as a whole. There was no evidence of a significant excess risk of cancer, and, in particular, the small excess of cancer of the pancreas reported previously could not be confirmed.     

Studies on direct and indirect effects of DNA damage on mutagenesis in monkey cells using an SV40-based shuttle vector

We are using an SV40-based shuttle vector, pZ189, to study mechanisms of mutagenesis in mammalian cells. The vector can be treated with mutagens in vitro and replicated in animal cells; resulting mutants can be selected and amplified in bacteria for DNA sequencing. This versatile vector system has allowed us to explore several different questions relating to the mutagenic process. We have studied the direct effects of template damage caused by UV or benzo[a]pyrene diolepoxide by treating vector DNA with these agents and then replicating the damaged DNA in monkey cells. Mutational mechanisms were deduced from the spectrum of mutations induced in the supF target gene of the vector DNA. To study the role of indirect effects of DNA damage on mutagenesis in mammalian cells, we have treated the cells and the vector DNA separately with DNA-damaging agents. We find that pretreatment of cells with DNA-damaging agents, or with conditioned medium from damaged cells, causes an enhancement of mutagenesis of a UV-damaged vector. Thus, DNA damage can act indirectly to enhance the mutagenic process. We also have preliminary evidence that pZ189 can be used in an in vitro DNA replication system to study the process of mutation fixation on the biochemical level. We believe that the pZ189 vector will prove to be as useful for in vitro studies of mutational mechanisms as it has been for in vivo studies.     

Water relations of the parasite: host relationship between the mistletoe Amyema linophyllum (Fenzl) Tieghem and Casuarina obesa Miq

Summary Seasonal and diurnal gas exchange and water relations of Amyema linophyllum and its host Casuarina obesa were studied at Gingin Western Australia. As recorded elsewhere for other species of mistletoe, stomatal conductances and transpiration rates were consistently higher in parasite than host, but assimilation rates did not differ significantly between partners, and water use efficiency was accordingly substantially lower in the parasite. Parallel responses of the species to environmental conditions suggested closely coordinated stomatal behaviour. However, sunlit and artifically shaded clumps of Amyema maintained high leaf conductances even when foliage fell below turgor loss point, yet their tissue capacitance values indicated maintenance of greater tissue water reserves during stress than in the host. Pressure-volume relationships indicated that differences in tissue water relations were unlikely to contribute significantly to the observed gradient in leaf water potential between partners. An experiment measuring changes in water potential of freshly detached host: parasite systems cut with the host shoot end immersed in water indicated that the haustorial junction was the principal site of resistance to transpiration-driven water flow into the parasite. A parallel experiment on intact attached shoots with mistletoe clumps enclosed and darkened just before dawn, demonstrated that, once the host commenced rapid transpiration, the water potential gradient between partners became reversed.     

Zeatin Glycosylation Enzymes in Phaseolus: Isolation of O-Glucosyltransferase from P. lunatus and Comparison to O-Xylosyltransferase from P. vulgaris

An enzyme catalyzing the formation of O-glucosylzeatin in immature embryos of Phaseolus lunatus was purified 2500-fold using ammonium sulfate precipitation followed by affinity and anion exchange chromatography. The enzyme uses trans-zeatin as substrate (K_m 28 micromolar) but not cis-zeatin, ribosylzeatin, or dihydrozeatin. Both UDP-glucose and UDP-xylose can serve as glycosyl donors, with K_ms of 0.2 and 2.7 millimolar, respectively, for the formation of O-glucosylzeatin and O-xylosylzeatin. In comparison, the UDPxylose-zeatin:O-xylosyltransferase (JE Turner, DWS Mok, MC Mok, G Shaw [1987] Proc Natl Acad Sci USA 84: 3714-3717) isolated by the same procedures from P. vulgaris embryos uses only UDP-xylose as donor substrate and the K_ms for both zeatin and UDP-xylose are much lower (2 and 3 micromolar, respectively). The chromatographic behavior on affinity columns and molecular weights (approximate M_r 44,000 daltons) of the two enzymes are similar. Results from substrate competition experiments and enzyme separation by anion exchange HPLC indicate a single, distinct, zeatin O-glycosylation enzyme occurs in embryos of each of these Phaseolus species.     

Infection with the human T-lymphotropic virus type I. A review for clinicians.

The human T-cell lymphotropic virus type I (HTLV-I) is the first retrovirus identified in humans. It has been responsible for a number of clinical syndromes, most notably adult T-cell leukemia or lymphoma and tropical spastic paraparesis. In the United States, infection with this virus is most frequently found in specific subsets of our population, particularly in those who live in the southeastern states, have southern Japanese ancestry, or share intravenous drug paraphernalia. Understanding the epidemiology and clinical manifestations of this virus is necessary to properly diagnose and care for patients with HTLV-I infection.     

Application of the synthetic method to other amines.

Taurine and 2-aminoethylphosphonic acid were synthesized by the method of the main paper [Geoghegan & Dixon (1989) Biochem. J. 260, 295-296], i.e. by treating the corresponding halo compound with 2-aminoethanol and then with periodate.     

A C-terminal domain of GAP is sufficient to stimulate ras p21 GTPase activity.

The cDNA for bovine ras p21 GTPase activating protein (GAP) has been cloned and the 1044 amino acid polypeptide encoded by the clone has been shown to bind the GTP complexes of both normal and oncogenic Harvey (Ha) ras p21. To identify the regions of GAP critical for the catalytic stimulation of ras p21 GTPase activity, a series of truncated forms of GAP protein were expressed in Escherichia coli. The C-terminal 343 amino acids of GAP (residues 702-1044) were observed to bind Ha ras p21-GTP and stimulate Ha ras p21 GTPase activity with the same efficiency (kcat/KM congruent to 1 x 10(6) M-1 s-1 at 24 degrees C) as GAP purified from bovine brain or full-length GAP expressed in E. coli. Deletion of the final 61 amino acid residues of GAP (residues 986-1044) rendered the protein insoluble upon expression in E. coli. These results define a distinct catalytic domain at the C terminus of GAP. In addition, GAP contains amino acid similarity with the B and C box domains conserved among phospholipase C-II, the crk oncogene product, and the non-receptor tyrosine kinase oncogene products. This homologous region is located in the N-terminal half of GAP outside of the catalytic domain that stimulates ras p21 GTPase activity and may constitute a distinct structural or functional domain within the GAP protein.