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Biomedical subjects

L E Scheving

Publications and source records attributed to L E Scheving.

At least 73 records · Page 4Linked to original sources
PubMed1981

Circadian organization of thirteen liver and six brain enzymes of the mouse.

The activities of 13 liver and 6 brain enzymes were studied in 7-12 week old CD2F1 male mice that had been fed ad libitum and standardized either to 12 hours of light (0600-1800) alternating with 12 hours of darkness (1800-0600) (LD12:12); or to a reversed light-dark cycle (darkness 0600-1800; light 1800-0600) (DL12:12). Three separate studies were performed on two different days; in each experiment, subgroups of 14 animals were sacrificed at 3-hour intervals. Livers were assayed for: isocitrate dehydrogenase, glutamate dehydrogenase, lactate dehydrogenase, alcohol dehydrogenase, glutathione reductase, glyoxylate reductase, L-alanine aminotransferase, glutamate oxalacetate transaminase, pyruvate decarboxylase, fructose-1-phosphate aldolase, fructose diphosphate aldolase, fructose 1,6-diphosphatase, and fatty acid synthetase. Brains were assayed for phosphoglucose isomerase, adenosine triphosphatase, creatine phosphokinase, pyruvate kinase, adenylate kinase, and malate dehydrogenase. All 19 enzymes demonstrated a prominent circadian rhythm in at least one experiment. Moreover, each rhythmic variable showed a statistically significant fit to a 24-hour cosine (sine) curve by the method of least squares. In general, peak activities of the liver enzymes analyzed were associated with the beginning of the dark cycle and initiation of the animal's activity, while the group of brain enzymes had peak activities which occurred at the beginning of the animals' rest span and were near the beginning of the light cycle. The phasing of each of the rhythms could be reversed within a two-week span after reversing the environmental light-dark cycle 180 degrees.

Animals↗
PubMed1981

Circadian stage-dependent effects of epidermal growth factor on deoxyribonucleic acid synthesis in ten different organs of the adult male mouse.

Epidermal growth factor (EGF) previously isolated from the submandibular gland of mice was injected ip at different circadian stages into separate subgroups of adult male CD2F1 mice. Subsequent to each of the five time points of injection (0900, 1500, 1800, 2100, and 0300 h for animals standardized to 12 h of light alternating with 12 h of darkness: light, 0600-1800 h; dark, 1800-0600 h), five animals were killed at 4, 8, and 12 h after the EGF injection; comparable control groups were injected only with the carrier substance. Thirty minutes before sacrifice, each mouse was injected ip with 24 muCi [3H]thymidine. Incorporation of [3H]thymidine into the DNA of the aorta, lung, liver, cornea, testes, kidney, parotid, thymus, spleen, and bone marrow as well as the mitotic index of the corneal epithelium was determined. The results indicate that EGF may play a role in the positive control of growth of many of these tissues, especially the aorta, lung, liver, and cornea. EGF may also play a role in inhibiting growth of the thymus, spleen, and bone marrow. Moreover, the stimulatory effect of EGF on the growth of the various tissues appears to be especially enhanced in mice injected at 1500 h and killed 4 h later at 1900 h.

Animals↗
PubMed1981

Chronobiologic aspects of blood cortisol levels and decay slopes following ethanol administration to adult human subjects.

When single oral doses of ethanol were given to human subjects at different circadian stages on different days, the blood cortisol levels displayed the expected circadian variation and were not significantly affected by the ethanol challenges. When the ethanol was administered repeatedly in a single 24-h experiment, the cortisol levels were variably elevated by these challenges, primarily in the afternoon hours; however, the circadian excursions did not appear to be blocked or markedly phase-shifted. The phase relationships of circadian blood cortisol levels and previously reported blood ethanol decay rates showed individual subject variation. They tended to occur in phase in two of five subjects and out of phase in the remaining three. It is concluded that cortisol clearance rates following ethanol doses are not independent of the circadian stage but are not necessarily synchronous with those for ethanol clearance.

Adult↗
PubMed1980

Amplitude-reduction and acrophase-advance of circadian mitotic rhythm in corneal epithelium of mice with bilaterally lesioned suprachiasmatic nuclei.

Lesions of the suprachiasmatic nuclei (SCN) have been reported to disrupt or abolish circadian rhythms of motor activity and body temperature as well as of several neuroendocrine functions. This study was undertaken to determine any effect the SCN may have on the prominent circadian rhythm characteristic of the mitotic index of the corneal epithelium. Singly caged adult mice of both sexes were fed ad libitum and standardized to 12 hours of light alternating with 12 hours of darkness. Animals were divided into experimental and control groups. Later they were killed in subgroups at the time intervals of 0800, 1200, 1000, 0000, 0400 hour. Mitotic counts were determined on both right and left corneas of all mice. The data were plotted separately for both groups and reflect colony variation. We conclude that major lesioning of the SCN or tis efferent projections disturbed but did not abolish the rhythm. In animals with unilateral lesions of the SCN, the mitotic index was consistently lower in the ipsilateral cornea. The mitotic index for animals with lesions which missed the SCN or its efferent projections did not differ from controls. The nuclei appear to function as pace-resetters and amplifiers of the rhythm studied.

Animals↗
PubMed1980

Circadian phase-dependent stimulatory effects of epidermal growth factor on deoxyribonucleic acid synthesis in the duodenum, jejunum, ileum, caecum, colon, and rectum of the adult male mouse.

Epidermal growth factor (EGF) previously isolated from the submandibular salivary glands of mice was injected ip at five different circadian phases into separate sub-groups of adult male CD2F1 mice that had been standardized to 12 h of light alternating with 12 h of darkness. Comparable control groups were injected only with the carrier substance. Four, 8, and 12 h after each of the five injection times, subgroups of five mice were killed. Thirty minutes before sacrifice, each mouse was injected ip with 24 mu Ci tritiated thymidine ([3H]-TdR). Incorporation of [3H]TdR into the DNA of the duodenum, jejunum, ileum, cecum, colon, and rectum was determined. The results demonstrate for the first time that EGF has a stimulatory effect on DNA synthesis in these tissues, particularly in the colon and rectum. Under the conditions of this study, the stimulatory effects of EGF on DNA synthesis in the cecum, colon, and rectum were more dramatic than those in the three regions of the small intestine; in fact, DNA synthesis in the latter was occasionally statistically significantly decreased, particularly for mice killed during the dark phase. Stimulatory effects of EGF on DNA synthesis in the cecum, colon, and rectum were noticed as early as 4 h after injection; however, maximal stimulation occurred 8 and 12 h post injection.

Animals↗
PubMed1979

Circadian phase-dependent stimulatory effects of epidermal growth factor on deoxyribonucleic acid synthesis in the tongue, esophagus, and stomach of the adult male mouse.

Epidermal growth factor (EGF) previously isolated from the submandibular gland of mice was injected ip at different circadian phases into separate subgroups of adult male CD2F1 mice. Subsequent to each of the five time points of injection (0900, 1500, 1800, 2100, and 0300 h for animals standardized to 12 h of light alternating with 12 h of darkness), five animals were killed, 4, 8, and 12 h after the injection of EGF; comparable control groups were injected only with the carrier substance. Thirty minutes before sacrifice, each mouse was injected ip with 24 muCi [3H]thymidine. Incorporation of [3H]-thymidine into the DNA of the tongue, esophagus, and stomach was determined. The results demonstrate for the first time that EGF has a strong in vivo stimulatory effect on DNA synthesis in the tongue, esophagus, and stomach (studies on other areas of the gut have not yet been completed). Under the conditions of the study, stimulatory effects occurred as soon as 4 h subsequent to injection; however, maximal stimulation occurred for all three tissues 8 h after injection. Twelve hours after injection, the levels of DNA synthesis in all tissues were generally returning to normal levels found in the control animals. The results suggest circadian variation in susceptibility to EGF in the different tissues.

Animals↗
PubMed1978

Circadian variation in cell division of the mouse alimentary tract, bone marrow and corneal epithelium.

Circadian rhythms in DNA synthesis are described for the tongue epithelium, five different regions of the alimentary canal (gut)--esophagus, stomach, duodenum, jejunum and rectum--and bone marrow in a group of BDF1 male mice. A circadian rhythm is also described for the mitotic index in the corneal epithelium in the same mice. The data document for the first time in the same animals the dramatic variation in cell division encountered from one region of the gut to another. This variation is seen in the amplitudes of the rhythms as well as in the over-all 24-hour means. On the contrary, the phasings of the rhythms in the different regions of the gut are remarkably similar. In this study, where the mice were standardized to 12 hours of light (0600-1800) alternating with 12 hours of darkness, the peak of the DNA-synthesis rhythm occurred around the time of transition from dark to light, and the trough around the time of transition from light to dark. The implications of these findings, and those of others, to the study of cell kinetics and to cancer chemotherapy are discussed.

Animals↗
PubMed1978

Chronopharmacokinetics of ethanol. III. Variation in rate of ethanolemia decay in human subjects.

Five male human subjects were administered repeated oral doses of ethanol approximately four hours apart and were examined for venous ethanol levels during the third and fourth hours after each dose. Estimates of the slopes of the apparently linear ethanol disappearance curves exhibited statistically significant variation along a 24-hour time scale within 4 of the 5 subjects, as well as among individuals. Prior findings on one of the subjects were confirmed. It is proposed in general that pharmacokinetic parameters may vary in accord with the physiologic circadian phase at the time of drug challenge.

Adult↗
PubMed1977

Effects of the scheduling of meal-feeding at different phases of the circadian system in rats.

This study was designed to determine whether or not a number of diverse rhythmic variables in the rat could be synchronized to meal timing. This was tested by restricting the availability of food; once during each 24-hour period an unrestricted quantity of food was made available for a 4-hour period to four different groups at different phases of the light-dark cycle, and the rhythms of the variables studied in the different groups were compared. Liver glycogen and serum glucose did synchronize to or were strongly influenced by feeding schedules; corticosterone and the several enzymes measured seemed to reflect an interaction of both the restricted feeding schedule and the light-dark cycle. The mitotic index in the corneal epithelium in all groups remained remarkably synchronized to the light-dark cycle and was altered only minimally by restricted meal timing. All groups on restricted feeding schedules gained less weight than the group fed ad libitum and maintained on a light-dark cycle. These studies caution against assuming that all body functions react in the same manner to different synchronizers; and they emphasize that one must not generalize about the synchronizing effect of meal-timing or even the light-dark cycle.

Animals↗
PubMed1977

Survival and cure of leukemic mice after circadian optimization of treatment with cyclophosphamide and 1-beta-D-arabinofuranosylcytosine.

When cyclophosphamide and 1-beta-D-arabinofuranosylcytosine were administered to mice previously given injections of L1210 leukemia cells, the combination was more effective than either drug given alone. The effectiveness of the 2 drugs in combination was strongly influenced by the stage of the circadian system at which the drugs were administered. With the use of a chronobiological (sinusoidal) approach, in comparison with one or two conventional treatment schedules, it was possible to demonstrate an overall lower toxicity as monitored by death or weight loss. In general, mean survival times and cures (when obtained) were circadian stage dependent; for example, in 1 study the cure rate was 94% in mice treated at 1 circadian stage, but only 44% in those treated at another stage. It cannot be overemphasized, however, that just as the "right" timing can enhance (with statistical significance) both the tolerance to chemotherapeutic agents and the rate of cure in leukemic mice, so can the "wrongly" timed (wrongly placed) ara-C sinusoid or "wrongly" timed cyclophosphamide enhance toxicity and host death rate.

Animals↗