tritiated water as a diffusible indicator. This method requires extensive arterial sampling and time-consuming laboratory procedures for liquid scintillation counting. Besides, it does not provide information on the regional content of ELW. Regional information can be obtained by using gamma emitting tracers. Using the cyclotron produced 1 5 0 labelled water we demonstrated the feasibility of estimating ELW by external counting in the dog. The technique has now been extended to man. It is relatively non-invasive, requiring only central venous injection of isotopes (Il3In as a non-diffusible intravascular indicator and Hz 150 as a diffusible indicator) and external recording by means of. probes collimated over the chest. The total absorbed radiation dose is 0-3 rads. With this technique, information on regional blood flow, blood volume, and extravascular water volume in the lung can be readily obtained. In particular, regional ELW can be obtained expressed either in ml/ml of blood volume or in ml/ml of tissue volume.Normal subjects and patients with chronically raised left atrial pressure have been studied in the supine position. ELW was elevated above the normal range in all patients, although some of them had no radiological evidence of interstitial oedema. This increase in patients was more marked at the lung base, in contrast to normal subjects where the distribution of ELW in the supine position was uniform from apex to base. This technique is suitable to follow the sequence of regional accumulation of ELW as well as its relationship with regional blood flow and volume in patients with acute. left heart failure.
32.
ts 2 BalB/C-3T3 mouse fibroblasts are cdc mutants, which arrest late in G1, at or near the G1/S traverse, upon full expression of the heat-sensitive lesion. The kinetics of temperature inhibition of DNA synthesis in logarithmically growing cultures reveal three stages of heat inactivation. During the first generation time equivalent, normal semiconservative, semidiscontinuous replication proceeds but is reduced as cells exit and do not reenter S phase. During a second such period, a minimal rate of normal DNA synthesis is maintained. Thereafter, as the cells move into a third aborted cell division cycle, the rate of DNA synthesis increases. However, all semiconservative synthesis is then replaced by DNA repair replication. Temperature inactivation of the ts 2 protein results in shutdown of nuclear DNA synthesis. In contrast, normal replication of mitochondrial DNA proceeds at control rate throughout the first stage of temperature inactivation. Synthesis of this organellar genome is quantitatively reduced as the cells move into the second phase of heat inhibition. Titration of chromatin-bound DNA with ethidium bromide revealed that wild-type cells exhibit a changing DNA topology as the temperature is raised. Temperature-inactivated ts 2 cells behave as though their DNA has been topologically frozen in the configuration of control cells at or near entry into S phase.
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