Search PubMed⌕ Search

Biomedical subjects

R M Shymko

Publications and source records attributed to R M Shymko.

28 records · Page 2Linked to original sources
PubMed1985

Field size dependence of radiation sensitivity and dose fractionation response in skin.

Four sets of data from the literature were analyzed to assess the effects of field size on dose tolerance and dose fraction size dependence in irradiated skin. The data consisted of combinations of total dose and dose per exposure (or number of fractions) required to yield a given degree of visible damage to the skin, for fields of different sizes. Putative cell survival curves were constructed, under the assumptions that the isoeffect represents a fixed cell survival, and that each exposure during a course of fractionated irradiation has equal effect on cell survival. The analysis showed that overall sensitivity to radiation, and dependence on dose per exposure, both increase with field size. To account for these results we describe a model that can be qualitatively related to the geometric properties of the dermal vascular network. First, vascular function after irradiation should depend on the length of the vessels exposed to the radiation. This directly predicts an increasing sensitivity in large irradiated fields. Furthermore, if vascular function determines radiation response, the shape of the shoulder (low-dose) region of the effective survival curve will depend on the average number of vessels nourishing each cell, with a more pronounced shoulder for a high multiplicity of vessels. The model predicts a greater fractionation sensitivity in large than in small fields, in agreement with our analysis of the isoeffect data. It is therefore possible that the advantages of hyperfractionation in reducing late effects in normal tissues may be related to vascular architecture, and not to inherent differences between late and acutely responding cell populations.

Animals↗
PubMed1985

Quasi-exponential generation time distributions from a limit cycle oscillator.

In spite of the apparently random behaviour and the often exponential distribution of generation times expressed in cell populations, there is evidence for rather precise timekeeping in the cell cycle. In experiments using time-lapse video-tape microscopy, we have noted that cell generation times are often not distributed smoothly but in many cases seem to cluster at roughly 4 hr intervals. Phase shift responses following application of heat shock, ionizing radiation or serum pulses in each case show a pattern which is repeated twice in cells with an 8-9 hr modal generation time. We describe here a cell cycle model with an independent cellular clock controlling cell cycle events which accounts for the phase response data, while also reconciling the stochastic and periodic behaviour characteristic of animal cells.

Animals↗
PubMed1984

Lack of correlation between basal cell survival and gross response in irradiated swine skin.

The relationship between basal cell survival and gross response in irradiated swine skin was tested by comparing dose survival curves derived from time-dose isoeffect data with curves obtained directly from basal cell counts in histological sections. Assuming equal effect per exposure and constant cell survival at isoeffect, best-fitting single-hit multi-target and linear-quadratic response curves were determined for time-dose schedules resulting in non-healing of 50% of irradiated fields. Basal cell survivals for single doses of 970, 1649, 2231, and 2619 rad were estimated 1) by counting regenerating islands and 2) by monitoring total basal cell counts through time. The dose survival curve derived from the isoeffect data was steeper than the curve obtained from direct basal cell counts. Furthermore, the direct basal cell survival curve extrapolates to less than 100% at zero dose, indicating the presence of a resistant basal cell subpopulation. The data show that the isoeffect in this case is not strongly coupled to basal cell survival. Rather, the probability of healing of an irradiated field is more sensitive to the dose per fraction than is basal cell survival, implying a contribution to non-healing from damage to stromal elements such as the capillary endothelium.

Animals↗
PubMed1982

Mitotic delay following inhibition by 5'-fluorodeoxyuridine of S-phase in Physarum is not due to delay in termination of S-phase.

It has been known for several years that inhibition by 5'-fluorodeoxyuridine (FdUrd) of DNA synthesis in plasmodia of Physarum polycephalum delays subsequent nuclear mitosis. To test whether this delay is due to delay in the termination of S-phase, we blocked DNA synthesis with FdUrd + uridine for 3 h at different stages of S-phase, and in plasmodia with different cycle times. The results show that in short-cycling plasmodia the delay in mitosis can be as long as 9 h, despite little delay in termination of S-phase, and is longest when plasmodia are blocked in early S-phase. In plasmodia with long cycle times, no mitotic delay following 3 h inhibition by FdUrd of S-phase is observed. Our results suggest that mitotic delay after pulses of FdUrd is not due to delay in termination of S-phase, which therefore does not appear to 'gate' entry into a G2 period of fixed length. The fact that delay is longest after FdUrd blocks in early S-phase suggests that normal progress through S-phase, not its termination, is critical for the timing of the subsequent mitosis. This may reflect an obligate coupling between replication and transcription of specific genes needed for progress toward mitosis. The lack of mitotic delay in long-cycling plasmodia shows that S-phase-coupled processes need not act as 'timers' if other processes become rate-limiting.

Cell Cycle↗
PubMed1980

Mapping the mitotic clock by phase perturbation.

In synchronized V79 cells perturbed by serum, heat shock, or ionizing radiation at half-hour intervals through a modal 8.5-hour cell cycle, phase-response curves show a characteristic biphasic pattern of advances and delays in subsequent cell divisions. These observations, together with previous observations of quantizement of generation times in this an other cell lines have led us to consider a model incorporating, in the simplest case, a two-component oscillator with two threshold crossings required per cell cycle. By assuming that oscillator variables respond in a simple way to the experimental perturbations, for example, by first order destruction due to heat shock, a map of the qualitative features of the oscillator can be obtained by matching simulated with experimental phase response curves. Random fluctuations in oscillator variables about a fixed trajectory lead to subthreshold oscillations and result in a distribution of generation times which is roughly a negative exponential, but quantized within this exponential envelope. The extent of the random fluctuations can be determined from comparison with data on desynchronization of a cell population after mitotic selection. The same parameters which correctly simulate phase response and the desynchronization data also give good agreement with generation time distribution data.

Animals↗
PubMed1978

Control of sequential compartment formation in Drosophila.

During development of Drosophila melanogaster, sequential commitment to alternative development programs occurs in neighboring groups of cells. These commitments appear to be reflected by lines of clonal restriction, called compartmental boundaries, which progressively subdivide the early embryo, and later the imaginal discs, which give rise to different adult appendages. We propose that a reaction-diffusion system acts throughout development and generates a sequence of differently shaped chemical patterns. These patterns account for the sequence and geometries of compartmental boundaries, and predict that each terminal compartment is specifiied by a unique combination of binary choices made during its formation. This binary "code" interprets coherently the patterned metaplasia seen in transdetermination and homeotic mutations.

Animals↗