Tracheobronchial epithelial multinucleation, viral inclusion bodies and malignant disease.

Patients with malignant disease are known to have an increased incidence of multinucleation in their tracheobronchial ciliated epithelial cells as compared with controls matched by age, sex and smoking habit. A seasonal relationship of viral inclusion bodies in the cilated epithelium of asymptomatic subjects has also been shown and is not related to age, sex and smoking habit. We have conducted an epidemiologic study to determine the possible relationships between these factors. Smears from 4,150 patients with a wide variety of pathologic conditions were examined for the presence of viral inclusions and multinucleated, ciliated epithelial cells. High degress of multinucleation were observed least frequenctly in the summer both in patients with and without known malignancy. Cytoplasmic inclusion bodies were also seen least frequently in the summer and autumn both in patients with and without know malignancy. In the presence of cancer, multinucleated epithelial cells and inclusion bodies were seen more frequently regardless of the season. When the seasonal incidence of multinucleated cells in 155 smears containing viral inclusion bodies was analyzed, it was found that patients without cancer had the lowest levels of multinucleation in the summer, whereas cancer patients had a depressed incidence of multinucleation in the winter and spring. Respiratory viruses may have a specific effect on the ciliated epithelium of cancer patients.

Th control of isocitrate oxidation by rat liver mitochondria.

1. The factors capable of affecting the rate of isocitrate oxidation in intact mitochondria include the rate of isocitrate penetration, the activity of the NAD-specific and NADP-specific isocitrate dehydrogenases, the activity of the transhydrogenase acting from NADPH to NAD(+), the rate of NADPH oxidation by the reductive synthesis of glutamate and the activity of the respiratory chain. A quantitative assessment of these factors was made in intact mitochondria. 2. The kinetic properties of the NAD-specific and NADP-specific isocitrate dehydrogenases extracted from rat liver mitochondria were examined. 3. The rate of isocitrate oxidation through the respiratory chain in mitochondria with coupled phosphorylation is approximately equal to the maximal of the NAD-specific isocitrate dehydrogenase but at least ten times as great as the transhydrogenase activity from NADPH to NAD(+). 4. It is concluded that the energy-dependent inhibition of isocitrate oxidation by palmitoylcarnitine oxidation is due to an inhibition of the NAD-specific isocitrate dehydrogenase. 5. Kinetic studies of NAD-specific isocitrate dehydrogenase demonstrated that its activity could be inhibited by one or more of the following: an increased reduction of mitochondrial NAD, an increased phosphorylation of mitochondrial adenine nucleotides or a fall in the mitochondrial isocitrate concentration. 6. Uncoupling agents stimulate isocitrate oxidation by an extent equal to the associated stimulation of transhydrogenation from NADPH to NAD(+). 7. A technique is described for continuously measuring with a carbon dioxide electrode the synthesis of glutamate from isocitrate and ammonia.