Induction of cAMP receptors by disaggregation of the multicellular complexes of Dictyostelium discoideum.
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The hypoxia-induced increase of spectrophotometrically measured light absorption at 560 nm, considered as reduced cytochrome b, in HepG2 cells is diminished after exposure to cobalt chloride (50 or 100 microM) for 18-36 h. The redox state of cytochrome c and cytochrome aa3, however, remains stable, indicating a particular affinity of cytochrome b for cobalt. Erythropoietin production of HepG2 cells increases after application of cobalt chloride, whereas H2O2 production, as measured by the dihydrorhodamine technique, decreases. It is concluded that cobalt stimulates a signal cascade with cytochrome b as receptor and H2O2 as second messenger for regulating erythropoietin production.
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We extend the development of a quantitative phenomenological theory of aging rooted in order theory. An organism is represented abstractly by a chain with a finite number of links. Each link corresponds to a possible rate-limiting event or process in senescence. A link is said to break when the corresponding event occurs or the corresponding process goes to completion. The chain is said to break, and the organism subsequently to perish, when the first link breaks, whichever link that might be. Two models are introduced to describe the failure of an arbitrary link. The first requires that a link break only after sustaining a fixed amount of deterioration; the second associates a non-zero probability of failure with each level of wear. The net deterioration of an intact chain is taken, crudely, to correspond to the decline in physiological vitality sustained by an organism during senescence. Failure of an arbitrary link is described in both models by a Markov process. The corresponding mortality rate derived in each instance describes aspects of available empirical data which cannot be accounted for by either the Gompertz or power-law relations. The decline in vitality is shown in both cases to be linear over time intervals of practical interest. The influence of temperature on the senescence of poikilotherms is briefly examined. We describe the effect of temperature both on longevity and the decline in vitality; indicate how substantial discrepancies can arise in the calculation of a macroscopic, effective, activation enthalpy; and lend theoretical support to the existence of temperature--memory effects in senescence.
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Following urethane inhalation exposure, clear dose--response relationships were apparent in all cell types examined in hepatectomized and intact mice. At concentrations of 0.1 mg/l and higher, induced SCE frequencies were linearly related to log urethane concentrations. No significant differences in SCE response between like cell types of hepatectomized and intact mice were apparent. In hepatectomized mice, there was no significant difference in the SCE response of regenerating liver and alveolar macrophage cells. However, bone-marrow response was significantly lower (p = 0.01). Likewise, in intact mice bone marrow response was significantly lower than in alveolar macrophages (p = 0.01). Inhalation and intravenous infusions of the same total dose of urethane (193 mg/kg) administered over a 4-h period produced comparable SCE responses in all cell types. However, a single intraperitoneal injection of 193 mg/kg just prior to BrdU infusion produced significantly higher SCE frequencies in bone marrow (alpha = 0.01), and alveolar macrophages (alpha = 0.05) of intact mice than did the equivalent inhalation dose. Intraperitoneal injections produced similar results in 2-month-old mice as in 4-month-old mice. However, regardless of the route of administration SCE frequencies in regenerating liver and/or alveolar macrophages were significantly higher than in bone marrow.
Survival of exponentially growing V79 monolayer cells was measured after irradiation at low dose-rate (up to 1.1 Gy/h) and at high dose-rate (2.5 Gy/min) and compared to corresponding survival data of V79 spheroid cells. The so-called contact effect, the increased radioresistance of cells irradiated in spheroids, was expressed to a greater extent with low dose-rate exposure. Lesion fixation by hypertonic treatment was more pronounced in spheroid versus monolayer cells and abolished the contact effect. The reduced radiosensitivity of V79 spheroid cells could not be related to a reduced number of initial DNA lesions or a higher capacity to rejoin DNA breaks (measured by neutral elution). These findings suggest that the ratio of lesion repair to fixation/misrepair may differ between cells from spheroids and monolayer culture thus influencing the response of cells to dose-rate changes differentially.
The importance of signal transduction pathways in regulating developmental processes in a number of organisms has become evident in recent years. This is exceptionally clear for Dictyostelium, which uses soluble factors to regulate morphogenesis and cellular differentiation. It is now known that many of these processes are controlled by signal transduction pathways mediated by cyclic AMP through cell surface receptors coupled to G proteins, and that others are mediated by the morphogen DIF.
This article offers algorithms and an algebra for estimating effects of bone turnover, remodelling space, undermineralized bone and trabecular surface-to-volume ratio effects on trabecular bone mass estimation by photon absorptiometry. From published histomorphometric data and other evidence the algorithms suggest the amount of mineral in a given bone sample can suggest to absorptiometry an amount of bone that differs from the truth by over 40% in the extreme, and more commonly by 5-15%. They suggest that by reducing a bone's global mineral content high bone turnover causes underestimation of true bone mass. They suggest that by letting mineral return to the remodelling space and undermineralized bone, reduced bone turnover causes apparent gains in bone mass. The commonly suggested 5-15% magnitude of such errors exceeds those assumed in the past. The algorithms suggest that after a challenge to remodelling those bone mineral changes can take from 6 months to over 3 years to reach steady states. Those features could explain why many osteoporosis treatments judged effective from initial absorptiometric evidence failed when used for long periods in patients. Finally the algorithms suggest that a real increase in ideal bone volume can even appear to absorptiometry as no gain or an initial loss, which has already happened in two human experiments.