Dipeptidyl peptidase IV in the human lung and spinocellular lung cancer.

The isoelectric point and proportions of soluble and membrane bound dipeptidyl peptidase IV (DPP-IV) in human lung and spinocellular lung cancer tissue were tested. It was found that soluble DPP-IV is relatively less frequent in the cancer than in normal lung tissue. We demonstrated multiple molecular forms of DPP-IV in normal and cancer lung tissues, differing probably not only in the degree of sialylation. DPP-IV from lung cancer tissue consists of more basic molecular forms than that from normal lung tissue. These results suggest that the molecular properties of DPP-IV in normal and cancerous lung tissues may be different.     

Sound transmission in the lung as a function of lung volume.

We were interested in how the transmission of sound through the lung was affected by varying air content in intact humans as a method of monitoring tissue properties noninvasively. To study this, we developed a method of measuring transthoracic sound transit time accurately. We introduced a "coded" sound at the mouth and measured the transit time at multiple microphones placed over the chest wall by using a 16-channel lung sound analyzer (Stethographics). We used a microphone placed over the neck near the trachea as our reference and utilized cross-correlation analysis to calculate the transit times. The use of the coded sound, composed of a mix of frequencies from 130 to 150 Hz, greatly reduced the ambiguity of the cross-correlation function. The measured transit time varied from 1 ms at the central locations to 5 ms at the lung bases. Our results also indicated that transit time at all locations decreased with increasing lung volume. We found that these results can be described in terms of a model in which sound transmission through the lung is treated as a combination of free-space propagation through the trachea and a propagation through a two-phase system in the parenchyma.     

Microgravity and the lung.

Although environmental physiologists are readily able to alter many aspects of the environment, it is not possible to remove the effects of gravity on Earth. During the past decade, a series of space flights were conducted in which comprehensive studies of the lung in microgravity (weightlessness) were performed. Stroke volume increases on initial exposure to microgravity and then decreases as circulating blood volume is reduced. Diffusing capacity increases markedly, due to increases in both pulmonary capillary blood volume and membrane diffusing capacity, likely due to more uniform pulmonary perfusion. Both ventilation and perfusion become more uniform throughout the lung, although much residual inhomogeneity remains. Despite the improvement in the distribution of both ventilation and perfusion, the range of the ventilation-to-perfusion ratio seen during a normal breath remains unaltered, possibly because of a spatial mismatch between ventilation and perfusion on a small scale. There are unexpected changes in the mixing of gas in the periphery of the lung, and evidence suggests that the intrinsic inhomogeneity of the lung exists at a scale of an acinus or a few acini. In addition, aerosol deposition in the alveolar region is unexpectedly high compared with existing models.     

Local control of pulmonary resistance and lung compliance in the canine lung.

Local control of pulmonary resistance and lung compliance was studied in the in situ left lower lobe of the canine lung. Recirculation of blood through the lobe while the Pco2 of the ventilatory gas was varied resulted in an increase in resistance and a decrease in compliance only when the pulmonary venous pH was greater than 7.42. Alternating sodium bicarbonate and lactic acid infusion while alveolar Pco2 was maintained below 5 mmHg demonstrated the dependence of the hypocapnic response on the acid-base status of the blood perfusing the respiratory airways. The increase in resistance and decrease in compliance observed at a pulmonary venous pH of 7.64 was comparable to that observed after lobar pulmonary artery occlusion. Varying degrees of hypoxia did not significantly affect bronchomotor tone, nor was the bronchoconstriction following lobar pulmonary artery occlusion affected by the hypoxia. Vagal stimulation superimposed on a stepwise increase in pulmonary venous pH from 7.32 to 7.62 resulted in an increase in resistance which paralleled the increase in resistance when pulmonary venous pH alone was increased. Compliance was not significantly affected by vagal stimulation at any level of pulmonary venous pH.     

Vascular remodeling in the circulations of the lung.

The lung is unique in its double sources of perfusion from the pulmonary and systemic circulations. One striking difference between the two circulations is the capacity for angiogenesis. The bronchial circulation has a capacity that seems quite similar to all systemic arteries, whereas the pulmonary circulation seems relatively inert in this regard. Extra-alveolar pulmonary arteries can grow somewhat in length, and septal capillaries seem to have the capability of reforming, but these processes do not seem to occur with nearly the same intensity associated with the bronchial arteries. In this review, we emphasize these differences between the two circulations of the lung, anticipating that future research will allow more focused probing into the molecular signaling that regulates the novel mechanistic and pathological pathways of each.     

Extravascular lung water in the exercising horse.

Seven Standardbred horses were exercised on a treadmill at speeds (approximately 12 m/s) producing maximal heart rate, hypoxemia, and a mean pulmonary arterial pressure of approximately 75 mmHg. Extravascular lung water was measured by using transients in temperature and electrical impedance of the blood caused by a bolus injection of cold saline solution. Lung water was approximately 3 ml/kg body wt when standing but did not increase significantly with exertion. We conclude that any increase in fluid extravasation from the pulmonary hypertension accumulates in the lung at a level that is less than that detectable by this method. At maximal exertion, the volume of blood measured between the jugular vein and the carotid artery increased by approximately 8 ml/kg, and the actively circulating component of the systemic blood volume increased by approximately 17 ml/kg with respect to corresponding values obtained when walking before exertion. These volume increases, reflecting recruitment and dilatation of capillaries, increase the area for respiratory gas exchange and offset the reduced transit times that would otherwise be imposed by the approximately eightfold increase in cardiac output at maximal exertion.     

Postnatal lung function in the developing rat.

Little is known about lung function during early stages of postnatal maturation, although the complex structural changes associated with developing rat lung are well studied. We therefore analyzed corresponding functional (lung volume, respiratory mechanics, intrapulmonary gas mixing, and gas exchange) and structural (alveolar surface area, mean linear intercept length, and alveolar septal thickness) changes of the developing rat lung at 7-90 days. Total lung capacity (TLC) increased from 1.54 +/- 0.07 to 16.7 +/- 2.46 (SD) ml in proportion to body weight, but an increase in body weight exceeded an increase in lung volume by almost twofold. Series dead space volume increased from 0.21 +/- 0.03 to 1.38 +/- 0.08 ml but decreased relative to TLC from 14% to 8%, indicating that parenchymal growth exceeded growth of conducting airways. Diffusing capacity of CO (D(CO)) increased from 8.1 +/- 0.8 to 214.1 +/- 23.5 micromol min(-1) hPa(-1), corresponding to a substantial increase in surface area from 744 +/- 20 to 6,536 +/- 488 cm(2). D(CO) per unit of lung volume is considerably lower in the immature lung, inasmuch as D(CO)/TLC in 7-day-old rats was only 42% of that in adult (90 day-old) rats. In humans, however, infants and adults show comparable specific D(CO). Our functional and structural analysis shows that gas exchange is limited in the immature rat lung. The pivotal step for improvement of gas exchange occurs with the transition from bulk alveolarization to the phase of expansion of air spaces with septal reconstruction and microvascular maturation.     

Cerebroside sulfotransferase activity in human lung tissues. An elevated level in lung adenocarcinoma.

Cerebroside sulfotransferase activity was demonstrated in particulate fractions from human lung and its carcinoma tissues. The activity in human lung adenocarcinoma was significantly higher than those in a different histological type of carcinoma (squamous cell carcinoma) and in normal tissue from which each carcinoma was derived.     

Oxygen-dependent reperfusion injury in the isolated rat lung.

To further define the relationship between oxygen dependence of lung injury during ischemia and ischemia-reperfusion, we used the isolated, perfused, and ventilated rat lung model, so that oxygenation and perfusion could be separated. During ischemia, lungs were ventilated with various oxygen concentrations and then ventilated with 95% oxygen during the 60-min reperfusion period. Other lungs were ventilated with 0% oxygen (nitrogen) during ischemia, and the reperfusion phase oxygen concentration was varied. Tissue and perfusate lipid peroxidation products (thiobarbituric acid-reactive substances and conjugated dienes), dry-to-wet weight ratio, and lactate dehydrogenase were measured as indexes of lung damage. In addition, electron microscopy of some lungs was performed. Results demonstrate an oxygen dependence of lipid peroxidation in both the ischemic and reperfusion phases, but lipid peroxidation is severalfold greater in the reperfusion than in the ischemic phase. Products of lipid peroxidation closely correlate with indexes of lung injury (dry-to-wet weight ratio, lactate dehydrogenase, and electron microscopy).