High- and low-LET induced chromosome damage in human lymphocytes: a time-course of aberrations in metaphase and interphase.

PURPOSE: To investigate how cell-cycle delays in human peripheral lymphocytes affect the expression of complex chromosome damage in metaphase following high- and low-LET radiation exposure. MATERIALS AND METHODS: Whole blood was irradiated in vitro with a low and a high dose of 1 GeV u(-1) iron particles, 400MeV u(-1) neon particles or y-rays. Lymphocytes were cultured and metaphase cells were collected at different time points after 48-84h in culture. Interphase chromosomes were prematurely condensed using calyculin-A, either 48 or 72 h after exposure to iron particles or gamma-rays. Cells in first division were analysed using a combination of FISH whole-chromosome painting and DAPI/ Hoechst 33258 harlequin staining. RESULTS: There was a delay in expression of chromosome damage in metaphase that was LET- and dose-dependant. This delay was mostly related to the late emergence of complex-type damage into metaphase. Yields of damage in PCC collected 48 h after irradiation with iron particles were similar to values obtained from cells undergoing mitosis after prolonged incubation. CONCLUSION: The yield of high-LET radiation-induced complex chromosome damage could be underestimated when analysing metaphase cells collected at one time point after irradiation. Chemically induced PCC is a more accurate technique since problems with complicated cell-cycle delays are avoided.

Low-power laser irradiation induces leukocyte priming.

Laser radiation (LR) of various spectral composition has been broadly used in clinical practice. However, the mechanism of the stimulating effects of LR remains obscure. The effect of He-Ne LR (633 nm) on human blood leukocytes was investigated both in the absence and presence of 8.65 nmol/l phthalocyanine (PhC). Irradiation of non-stimulated leukocytes with 0.025 to 0.5 J/cm2 did not lead to any activation of their luminol-dependent chemiluminescence (LCL). On the other hand, LR increased in most cases the subsequent CL response of the cells to opsonized zymosan (priming action of He-Ne-laser light). The effect of LR on the leukocytes was not standard. In irradiated leukocytes isolated from patients with severe acute or chronic pneumonia, or chronic bronchitis, the maximal LCL exceeded that for non-irradiated cells by 80% (0.05 J/cm2), 20-25% (0.15 J/cm2), and 0%, respectively (doses are shown in parentheses). Further increase of the exposure brought about a dose-dependent inhibition of LCL in cells from patients with severe acute and chronic pneumonia. There was an intriguing relationship between maximal CL responses of leukocytes subjected to laser irradiation in the presence and without PhC. When the priming effect of LR on isolated cells was small, it increased in the presence of exogenous photosensitizer, phthalocyanine; in cells of severely ill patients where the initial effect of LR was strong, Pc inhibited the priming action of LR. Apparently, different cells contained different amounts of endogenous photosensitizer(s); the addition of exogenous sensitizer increased the priming action of LR at low concentrations and decreased it at higher concentrations of the endogenous photosensitizer.

[Gaseous dispersion in the central airways of the human lung. In vivo study]. / Dispersion gazeuse dans les voies aériennes centrales du poumon humain. Etude in vivo.

In order to estimate the contribution of either laminar or turbulent dispersion in the central airways during spontaneous breathing, the results of the computer simulation of a mathematical model were compared with those of an appropriate in vivo test performed on normal subjects. The model takes into account, along with the summed cross-section of Weibel lung model [31], both axial convection and longitudinal dispersion of helium and sulphur hexafluoride in air. The simulations were carried out by incorporating two dispersion coefficients corresponding to laminar and turbulent flow into the mathematical model. The experiments were performed on five normal subjects by injection of 10 ml bolus of helium and sulphur hexafluoride into the later part of the inspired airstream in such a way that the whole bolus entered the inspiratory flow and was recovered during the following expiration. When the experiment is simulated using the laminar dispersion coefficient, no concordance could be seen between computed and experimental data; however, there is a good concordance when the simulation is performed with the turbulent dispersion coefficient. It is concluded that Taylor laminar dispersion [24] cannot play a significant role in the human airways; however, it seems that convective gas mixing with turbulent dispersion [21] can account for most gas transport during spontaneous ventilation.

Radiation absorbed dose estimates for positron emission tomography (PET): inert gases 19Ne and 77Kr.

Detailed estimates of radiation absorbed dose based on solubility data and the distribution of body water and fat are presented for 19Ne and 77Kr, useful PET rCBF imaging agents. The steady-state inhalation of 75 mCi of 19Ne and the bolus inhalation of 18 mCi of 77Kr should result in comparable imaging statistics for typical protocols and lung radiation absorbed doses less than approx. 0.5 rad. A model for both steady-state and bolus inhalation techniques for soluble gases used for these radiation absorbed dose calculations is also presented.

Vertical distributions of pulmonary diffusing capacity and capillary blood flow in man.

In six normal upright subjects, a 100 mol bolus-composed of equal parts of neon, carbon monoxide, and acetylene (Ne, CO, and C(2)H(2))-was inspired from either residual volume (RV) or functional residual capacity (FRC) during a slow inspiration from RV to total lung capacity (TLC). After breath holding and subsequent collection of the exhalate, diffusing capacity and pulmonary capillary blood flow per liter of lung volume (D(L)/V(A) and Q(C)/V(A)) were calculated from the rates of CO and C(2)H(2) disappearances relative to Ne. The means: D(L)/V(A) = 5.26 ml/min x mm Hg per liter (bolus at RV), 6.54 ml/min x mm Hg per liter (at FRC); Q(C)/V(A) 0.537 liters/minute per liter (bolus at RV), 0.992 liters/minute per liter (at FRC). Similar maneuvers using Xenon-133 confirmed that, during inspiration, more of the bolus goes to the upper zone if introduced at RV and more to the lower, if at FRC. A lung model has been constructed which describes how D(L)/V(A) and Q(C)/V(A) must be distributed to satisfy the experimental data. According to this model, there is a steep gradient of Q(C)/V(A), increasing from apex to base, similar to that previously determined by other techniques-and also a gradient in the same direction, although not as steep, for D(L)/V(A). This more uniform distribution of D(L)/V(A) compared with Q(C)/V(A) indicates a vertical unevenness of diffusing capacity with respect to blood flow (D(L)/Q(C)). However, the relative degree of vertical unevenness of D(L)/V(A) compared with Q(C)/V(A) can account only in part for previous observations attributed to the inhomogeneity of D(L)/V(A) and Q(C)/V(A). Thus, a more generalized unevennes of these ratios must exist throughout the lung, independent of gravitation.