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Biomedical subjects

L E Scheving

Publications and source records attributed to L E Scheving.

At least 91 records · Page 5Linked to original sources

Circadian influence on the frequency of labeled mitoses method in the stratified squamous epithelium of the mouse esophagus and tongue.

The frequency of labeled mitoses method (FLM) was used to study the cell kinetics in the stratified squamous epithelium of the mouse esophagus and tongue. FLMs were generated by injecting tritiated thymidine (TdR) at two different phases of the mouse circadian system: TdR was injected into one group of mice at 0900 and into a different, second group of mice at 2100. Three variables were monitored for each group; (1) the FLM, (2) the mitotic index and (3) the grain count over the labeled mitotic figures. In both the esophagus and the tongue there was a circadian rhythm in the mitotic index with the peak occurring during the first half of the diurnal phase and the trough occurring during the first half of the nocturnal phase. The FLM curves from each group revealed the following data.

Animals↗

Circadian rhythm in DNA synthesis in mouse thymus: effect of altered lighting regimens, restricted feeding and presence of Ehrlich ascites tumor.

A circadian rhythm in the incorporation of tritiated thymidine into DNA of the mouse thymus has been described. This same rhythm in animals bearing an 8-day Ehrlich ascites tumor (EAT) was altered in its phasing, wave-form and over-all 24-hour mean; the most striking alteration seen in four out of five studies was a reduction in the over-all DNA synthesis rate in tumor-bearing animals. Mice subjected to an altered light-dark cycle did not show a complete phase shift in their thymus DNA rhythm within two weeks, but during this time the rhythm in the mitotic index of their corneal epithelium completely phase shifted; the presence of the tumor had no effect on this latter rhythm. In mice subjected to a daily 4-hour restricted feeding schedule, the rhythm in DNA synthesis in the thymus became synchronized in that the peak occurred toward the end of the 4-hour restricted feeding span in both tumor and non-tumor-bearing animals. The rhythm in the mitotic index in the cornea was not phase shifted or altered by the restricted meal timing. The DNA synthesis rhythm in the normal thymus demonstrated a phasing similar to (1) the rhythm in the length of survival time in untreated mice challenged with EAT and (2) the rhythm in DNA synthesis in the normal spleen.

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Chronopharmacokinetics of ethanol. II. Circadian rhythm in rate of blood level decline in a single subject.

A male human subject administered single, oral doses of ethanol was examined repeatedly for venous ethanol levels. Four separate trials, begun at 03.00, 09.00, 15.00, and 21.00 h, on different days yielded four different estimates of the slope of the apparently linear ethanol disappearance curve. The slopes appeared to exhibit circadian rhythmicity. In a second study of the same subject, the slope was estimated 7 times over a period of 26 h following repeated oral doses. These slopes also appeared to vary in a daily fashion. These preliminary results suggest that pharmacokinetic parameters may not be invariable with time of day.

Adult↗

Close reproduction by different laboratories of characteristics of circadian rhythm in 1-beta-D-arabinofuranosylcytosine tolerance by mice.

The tolerance of BALB/c X DBA/2 F1 mice to the popular cytostatic drug 1-beta-D-arabinofuranosylcytosine (ara-C) was tested in two laboratories about 1000 km apart. According to the same plan and on the same days in Little Rock, Ark., and Minneapolis, Minn., nine groups of 20 mice each received four courses of ara-C treatment, with 4-day intervals between them beginning February 7, 1973. In each course, a total dose of 240 mg/kg was divided among eight separate injections administered at 3-hr intervals. One group of mice received equal doses of ara-C every 3 hr (the homeostatic schedule). The eight other groups in each location received the same total dose per course but in gradually increasing and decreasing doses (the sinusoidal schedule). The timing of the highest doses on the latter schedule differed among the eight groups (by integer multiples of 3 hr). As predicted from earlier work, survival times after treatment with ara-C on different sinusoidal schedules differed drastically. However, the timing of the sinusoidal schedules yielding the longest survival was similar in the two locations. The survival times from all sinusoidal treatments from a given location were fitted by a 24-hr cosine curve. The timing of the rhythm in tolerance as a whole as thereby computed as the lag from local midnight of the peak in the cosine curve best fitting all data. The timing of this tolerance rhythm (briefly, circadian chronotolerance), computed separately for data from Arkansas and Minnesota, agreed within 1 hr. There also was close agreement in the results obtained by the 2 laboratories in mean survival time; the percentage of survivors when mice were treated according to certain of the selected sinusoidal schedules was much greater than for mice treated on the homeostatic schedule. This large and reproducible difference in tolerance and the similar timing of the overall fitted function describing chronotolerance in the hands of different investigators underlines the urgency of testing potential benefits from timed clinical treatment.

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Effect of altered lighting regimens, time-limited feeding, and presence of Ehrlich ascites carcinoma on the circadian rhythm in DNA synthesis of mouse spleen.

The objectives of the series of experiments described were (a) to determine whether there was a circadian rhythm in the incorporation of tritiated thymidine into DNA of the spleen in mice kept on a conventional light-dark cycle and fed ad libitum, (b) to study the effect that different light-dark cycles and a time-limited feeding schedule had on this circadian rhythm, (c) to ascertain what effect the presence of an 8-day Ehrlich ascites carcinoma (EAC) had on the rhythm in DNA synthesis in the spleen and what effect the EAC had on the circadian rhythm in the mitotic index in the corneal epithelium, and (d) to determine whether there was a circadian rhythm in the duration of life-span in mice bearing the EAC. A circadian rhythm in the incorporation of tritiated thymidine into DNA of the mouse spleen consistently was characterized by a peak during the nocturnal phase and a trough during the diurnal phase of the 12-hr light-12-hr dark cycle. In animals bearing an 8-day EAC, the rhythm in DNA synthesis in the spleen was phase-shifted, its wave form was changed, and the overall 24-hr mean was increased significantly. The phasing of the rhythm in EAC-bearing mice was not reproducible. This finding demonstrated that the presence of the EAC severely altered the natural rhythm in DNA synthesis in the spleen and resulted in a rhythmic pattern which was constantly changing. The presence of an 8-day EAC, however, had no effect on the amplitude, overall level, or the phasing of the circadian rhythm in the mitotic index in the cornea. A staggered light-dark cycle of 2 weeks duration did not completely phase-shift the DNA synthesis rhythm in the spleen but did completely phase-shift the rhythm in the mitotic index in the corneal epithelium. In mice subjected to a daily feeding period limited to 4 hr, the rhythm in DNA synthesis in the spleen, in both EAC-bearing and non-EAC bearing mice, was phase-shifted such that the peak occurred during the time of feeding and the trough occurred prior to the feeding period. The rhythm in the mitotic index in the cornea was not phase-shifted or altered in any way by the feeding schedule and thus remained fixed to the light-dark cycle. The DNA synthesis rhythm in the normal spleen demonstrated a phasing very similar to the circadian rhythm in the length of survival in mice challenged with EAC and the circadian rhythm in DNA synthesis in the normal thymus.

Animals↗

Meal timing dominates the lighting regimen as a synchronizer of the eosinophil rhythm in mice.

Mouse eosinophils undergo circadian fluctuation, and the phasing of the rhythm normally is synchronized to the environmental light-dark cycle if food always is available. This study was undertaken to determine whether or not the same rhythm could be synchronized to restricted feeding schedules. It was found that if food is available ad libitum for only short spans (in this case, 4 h during each 24 h period), the rhythm becomes synchronized to the feeding schedule. In addition, restricting food to certain 4 h spans causes the amplitude of the eosinophil rhythm to increase significantly over that of normal, light-dark synchronized animals. Not all rhythmic variables synchronize to restricted feeding schedules. Some remain synchronized to the light-dark cycle; the phasing of others seems to be the result of an interaction between both the light-dark cycle and the feeding schedule. These studies help dispel the popular misconception that all body functions react in the same manner to different synchronizers and emphasize that one must not generalize about the synchronizing effect of feeding or lighting.

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