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L E Scheving

Publications and source records attributed to L E Scheving.

At least 55 records · Page 3Linked to original sources
PubMed1986

The effects of various lighting schedules upon the circadian rhythms of 23 liver or brain enzymes of C57BL/6J mice.

The activities of 23 brain or liver enzymes were studied in 5-6 week old C57BL/6JNctr male and female mice that had been fed ad libitum and standardized for 2 weeks to either (1) 12 hr of light (0600-1800) alternating with 12 hr of darkness (1800-0600) (LD 12:12), (2) staggered sequences of 12 hr of light and 12 hr of dark (SLD 12:12) or (3) continuous illumination (LL 12:12) for 2 weeks. Mice in the LD 12:12 and LL 12:12 experiments were killed at 4 hr intervals along a 24-hr span in order to sample at six different circadian stages. Lighting schedules for mice in the SLD 12:12 experiment were organized such that six different circadian stages were sampled when all mice were killed at one time of day. All 23 enzymes demonstrated a prominent circadian rhythm in at least one of the experiments. Moreover, about two-thirds of the enzymes in LD and SLD 12:12 had a statistically significant fit to a 24-hr cosine curve, while only one-third of the enzymes in LL 12:12 had significant fits to cosine curves. Peak activities of enzymes from mice in LD 12:12 were clustered at the time of transition from light to dark. This was also the trend for the activities of enzymes from mice in SLD 12:12, but resynchronization did not appear completed within the 2-week span. This, along with the observation that mesors (mean 24-hr activity) were reduced and amplitudes altered, indicated that the 2-week standardization period was not sufficient for some enzymes. Times of peak activities, mesors and amplitudes were affected for most enzymes from mice in the LL 12:12 environment. This suggests that individual mice became desynchronized from one another with respect to the original light-dark schedule and that rhythms were altered or lost because individual mice were free running with frequencies different from 24 hr.

Animals↗
PubMed1986

Effect of thioacetamide on the incorporation of [3H]-thymidine into DNA of 13 tissues and on the mitotic index of the corneal epithelium of BD2F1 in male mice while taking into consideration circadian variation.

An investigation was done to assess the effect of a single intraperitoneal (ip) injection of thioacetamide on the incorporation of [3H]TdR into DNA of 13 different tissues and on the mitotic index of the corneal epithelium of mice. Seven-week-old CD2F1 mice, who had been standardized to 12 hours (hr) of light alternating with 12 hr of darkness, and fed ad libitum were used. The experimental design took into consideration the circadian variation that characterizes cell proliferation in all of the tissues studied. This was done by killing subgroups of seven animals every 6 hr for 96 hr. Thirty minutes prior to killing all mice were injected ip with 25 mu Ci of [3H]-thymidine and its incorporation into DNA was determined. The tissues of all thioacetamide and saline treated mice showed marked circadian variation in DNA synthesis. Thioacetamide treatment brought about significant (P less than 0.05) stimulation of DNA synthesis in the liver and kidney thus confirming, but extending an earlier finding. Moreover, the data showed for the first time that DNA synthesis in the bone marrow and spleen and colon were markedly statistically significantly stimulated at specific times after treatment. Synthesis of DNA in the thymus, lung, testes, tongue, esophagus, duodenum, rectum and the mitotic index in the corneal epithelium were not statistically significantly altered by thioacetamide treatment. A preliminary study also was carried out to explore what effect multiple treatment with epidermal growth factor (EGF) had on DNA synthesis in thioacetamide treated mice. Mice were killed 36 hr after thioacetamide treatment, but were treated with EGF which began 15 hr after the thioacetamide was administered and this was repeated at 18, 21 and 24 hr (50 micrograms/mouse/treatment). Under the conditions of this study EGF significantly (P less than 0.05) depressed DNA synthesis 76% in the liver, 64% in the thymus, 22% in the spleen, 30% in the duodenum and 24% in the esophagus. A histological analysis of the livers of four EGF treated and four non-EGF treated mice was done, but no consistent differences in terms of necrosis, inflammation or regeneration were observed between the two groups.

Acetamides↗
PubMed1985

Effect of an adrenocorticotropin analogue, ACTH 1-17, on DNA synthesis in murine metaphyseal bone.

The effects of injections of a synthetic adrenocorticotropin (ACTH 1-17, Synchrodyn) on the rate of DNA labeling in the metaphyseal bone of CD2F1 mice were tested on a chronopharmacological dosing schedule. Groups of mice that had been conditioned to a 12-hr light/12-hr dark schedule were injected at one of six different timepoints, 4 hr apart, during a single 24-hr span with either a low (0.02 I.U./kg) or a high (20 I.U./kg) dose of ACTH 1-17. Control groups received injections of a placebo at corresponding timepoints. Subgroups of mice were injected with [3H]thymidine ([3H]Tdr) to follow the changes in DNA labeling in the proximal tibial metaphysis at 15 min and 2, 4, 8, 12 and 24 hr after ACTH 1-17 or placebo treatment. All mice were injected with the isotope 30 min before killing, except for those killed 15 min after Rx administration where the isotope had been injected 14 min before killing. The data were analyzed both by analysis of variance and by the cosinor method, the latter of which tests the fit of a 24-hr cosine curve to the data. The effect of ACTH 1-17 on the target cell population was dependent not only upon the dose but upon the time of administration. Both doses exerted time-dependent action, ranging from stimulation to inhibition of DNA labeling. Inhibition was noted when the ACTH 1-17 was administered at 2 hr after the beginning of the daily dark span when nocturnal animals become active. When administered at this circadian stage, the larger dose in particular was associated with an inhibition of DNA labeling lasting for 24 hr. The inhibitory effect was much shorter when the same dose was injected 4 hr earlier. Moreover, the large ACTH 1-17 dose had a stimulatory effect lasting for 24 hr when it was administered 2 hr after the onset of the daily light span, with a much shorter stimulation following administration of the large dose at 6 hr after the beginning of the daily dark span. A circadian stage-dependent stimulation or inhibition of DNA labeling at 2 or 14 hr after light onset, respectively, was thus complemented by an initial inhibition followed by stimulation and vice versa at 10 and 18 hr after light onset respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenocorticotropic Hormone↗
PubMed1985

Sex differences in circadian rhythms of several variables in lymphoreticular organs, liver, kidney, and corneal epithelium in adult CD2F1 mice.

In this paper data resulting from an investigation into the influence of sex on selected circadian rhythms in lymphoreticular organs, liver, kidney, and corneal epithelium of adult CD2F1 mice are reported. Increased organ weight, total DNA and RNA in the spleen, total DNA and [3H thymidine [( 3H]TdR) incorporation into DNA in the thymus, and [3H]TdR incorporation into DNA in the liver and bone marrow in female mice compared to male littermates is demonstrated. In contrast, kidney weight and [3H]TdR incorporation into DNA as well as the corneal epithelium mitotic index are greater in male mice. Except for the corneal epithelium mitotic index and total splenic RNA and DNA, circadian rhythmicity in the variables studied is validated using the cosinor method of rhythmometric analysis in male but not in female mice. The lack of sinusoidal rhythmicity in female mice is presumed to be due to asynchrony of estrous cycling between mice within this group. Moreover, a differential organ response to exogenous testosterone enthanate is reported. The administration of this hormone suppresses [3H]TdR incorporation into DNA in the thymus and liver but not in the spleen or bone marrow at 18, 42, or 72 hr after injection.

Androgens↗
PubMed1985

The effect of age on the circadian rhythms of 23 liver or brain enzymes from C57BL/6J mice.

Mice were standardized to 12 h of light exposure alternating with 12 h of darkness and were fed ad libitum. The mice in the first group were 8 weeks old and in the other 104-116 weeks old. Subgroups of 7 animals from each age group were killed at 6 circadian stages. Enzyme activities of 23 enzymes from liver or brain were measured by an analysis of variance for each age group. All but 1 enzyme from young mice, and all but 9 from older mice showed significant changes over time (p less than 0.01). The data from the 22 enzymes from young mice and the 14 enzymes from old mice were fit to the cosinor regression model to further characterize the rhythm. 15 enzymes from the young and 8 from the aged mice showed a significant regression to a 24-hour cosine curve (p less than 0.01); of the 8, 7 were the same enzymes in both groups. Amplitude changes, where they could be compared from the cosinor data (7 enzymes), were not statistically different. When total variance was compared, 12 enzymes showed unequal variance. Of these, old mice had the larger variance in 9 enzymes. Another difference between the young and the old was changes in mean enzyme activities. 12 enzymes from aged mice had decreased mesors, 2 had increased mesors, and 9 were unchanged. In general, our data suggest that some enzyme activity rhythms were lost, others were altered and a few were not affected by aging. In the case of many enzymes, older mice have a diminished ability to synchronize to the light signals.

Animals↗
PubMed1985

Epidermal growth factor enhances guanylate cyclase activity in vivo and in vitro.

Epidermal growth factor (EGF) increases DNA synthesis and cell division both in vivo and in vitro. The mechanism by which EGF increases growth and DNA synthesis is unknown. Since the intracellular messenger cGMP stimulates DNA synthesis, the present investigation was designed to determine if EGF might have part of its mechanism of action through activating guanylate cyclase [EC 4.6.1.2], the enzyme that catalyzes the formation of cGMP. EGF enhanced soluble and particulate guanylate cyclase activities as well as cGMP levels 2- to 3-fold in hypophysectomized and nonhypophysectomized tissues both in vivo and in vitro. EGF increased guanylate cyclase activity 0.5 h after ip injection in mice, and this increased activity was still present 12 h later. Guanylate cyclase activity was increased to a greater extent secondary to EGF in hypophysectomized cecum compared to nonhypophysectomized cecum. Dose-response curves revealed that maximal stimulation of guanylate cyclase by EGF occurred at 1 nM. There was no augmented guanylate cyclase activity when the concentration of EGF was decreased to 0.01 nM. The data in this investigation suggest that guanylate cyclase may play a role in the mechanism of action of EGF.

Animals↗
PubMed1984

Effect of fasting on circadian rhythmicity in deoxyribonucleic acid synthesis of several murine tissues.

These studies were done with CD2F1 adult mice that had been standardized to 12 hours of light alternating with 12 hours of darkness to determine what effect a 24-hour fast had on circadian rhythms in DNA synthesis of 10 different regions of the gut, as well as in the pancreas, liver, thymus, spleen, bone marrow, lung and testis. The mitotic index of the corneal epithelium also was studied. The overall responses varied rather dramatically. For example, in the different regions of the gut the response ranged from no statistically significant change in the colon to a strong statistically significant decrease in DNA synthesis in the cecum. In short, one cannot generalize about the effect of short-term fasting on the entire gut, but when there was any statistically significant effect, it always was a decrease. The spleen was the only tissue that showed no statistically significant response in DNA synthesis. In the bone marrow, however, a statistically significant increase in DNA synthesis was recorded at 8 and 24 hours after fasting began. In the lung there was a rather dramatic increase in DNA synthesis at 8 hours, but this was followed by decreases of 37 and 55% at 16 and 24 hours, respectively. There was a statistically significant increase of 83% in the mitotic index 24 hours after the fasting began. The data clearly demonstrate the necessity of considering circadian variation when evaluating the effects of fasting on cell proliferation.

Animals↗
PubMed1984

Circadian-stage dependent ACTH 1-17 effect on DNA synthesis in murine duodenum, colon and rectum.

The objective was to determine the effect of adrenocorticotropin (ACTH 1-17) on the incorporation of [3H]TdR into DNA (DNA synthesis) in the duodenum, colon and rectum of CD2F1 mice standardised to 12 hr of light alternating with 12 hr of darkness. A question asked was whether the difference in times of administration along the 24-hr time scale influenced any response found. The response was complex as ACTH 1-17 was capable of bringing about statistically significant increases in the incorporation of [3H]TdR into DNA at certain times, decreases at other times, or no response at still another time. A generalization that can be made from all these tissues is that ACTH 1-17 had a greater influence in bringing about a decrease in DNA synthesis when it was administered around the time of transition from dark to light. A similar finding was made earlier for the ACTH 1-17 effect upon the tongue, esophagus and stomach. A 2- and 3-way analysis of variance supports our conclusion that the kind-of-treatment, time-of-treatment and the interval-to-kill (Sampling time) as well as their interactions are important factors when determining any response of ACTH 1-17 or placebo.

Adrenocorticotropic Hormone↗
PubMed1984

Circadian dependent effect of epidermal growth factor, insulin and glucagon on hepatic pyruvate kinase and malic enzyme of mice.

The influence of epidermal growth factor (EGF), 0.75 micrograms g1; insulin, 1.5 micrograms g-1; glucagon, 1.25 micrograms g-1 and their combinations on the activities of hepatic pyruvate kinase (PK) and malic enzymes (ME) was monitored. Male CD2F1 mice were treated toward the end of the light or dark periods, 9 or 23 hours after lights on (9 or 23 HALO), and subgroups of six mice were killed at 4, 8 or 12 hr post-treatment. PK and ME activities from control mice were well characterized by cosine curves. The PK activity was maximal when ME activity was minimal at the transition from light to dark (9 HALO plus 4 hr) and PK was at a minimum when ME was highest (23 HALO plus 4 hr). Both enzymes were influenced by at least one peptide hormone, and the effects were strongly circadian-stage dependent. The only effect attributed to EGF was an increase of PK activity (23%) 12 hr after injection at 23 HALO. PK activity was increased by insulin (23%) at 23 HALO (4 hr after injection), but not at 9 HALO, and decreased (17%) by glucagon 12 hr after injection at 9 HALO. Several reductions in PK activity in response to various combinations of peptides were observed, and appeared to be caused by glucagon but influenced by insulin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Circadian variation in the urinary excretion of electrolytes and trace elements in men.

Three-hour urine specimens were collected over a period of 27 hours from 11 healthy adult male subjects. Each specimen was analyzed for Na, K, Ca, Mg, and Zn using atomic absorption spectrophotometry. Each sample was also dialyzed, pH 7.35, and subsequently analyzed for Na, K, P, Ca, Mg, Zn, Fe, Pb, Al, Ni, Cu, Mo, Hg, Cr, Cd, and Mn using a multielemental argon-plasma emission system. The data were evaluated on conventional time plots (chronograms) and as computer-determined "cosinor" plots. A population circadian rhythm with a statistical significance was detected for total Na, K, Ca, and Mg, and for nondialyzable Na, K, P, Ca, Zn, and Mo. For almost every element studied the increase from lowest to highest 3-hour group mean along the 24-hour time scale was more than 100%. The 24-hour excretion of Na, K, Ca, Mg, and Zn appeared in good agreement with the so-called "normals." The nondialyzable levels of Fe, Pb, Al, Ni, Cu, Mo, Hg, Cr, Cd, and Mn were similar to the total urinary excretions reported in the literature.

Adult↗
PubMed1983

Several cytokinetic methods for showing circadian variation in normal murine tissue and in a tumor.

Circadian rhythmicity in cell proliferation was studied by several cytokinetic techniques in 8-week-old CD2F1 and Swiss male mice. In separate experiments on four different dates, subgroups of six or seven mice (fed ad libitum and standardized to 8 hours light alternating with 16 hours of darkness) were killed at 3-hour intervals over a period of 24-48 hours. Cosinor analyses were used to determine the parameters of circadian periodicity in the data. Flow cytometric (FCM) analyses of DNA synthesis in tongue and stomach were compared with estimates of tritiated thymidine (3HTdR) incorporation into the DNA in these tissues. Circadian variation in tongue epithelium was reproducible in phasing and in range-of-change (100-140%) in seven 24-hour studies. The proportion of cells in G1 and G2 in tongue epithelium also demonstrated a circadian periodicity. When DNA synthesis in stomach was analyzed by the two methods, the results were entirely different and thus not comparable. The circadian rhythms in 3HTdR uptake agreed with those reported previously, but results of analyses by FCM were less certain, since epithelium of this organ could not be analyzed separately. Circadian rhythms were detected by FCM in G2, S, and G2M in Ehrlich ascites carcinoma (EAC). The mitotic index of this tumor varied with a circadian periodicity similar to that of the FCM-derived rhythm in G2M. This study validates the reliability of older techniques, such as 3HTdR uptake and mitotic indices, and suggests that circadian rhythms can be important in studies of cellular properties using FCM.

Animals↗
PubMed1983

Chronobiology of the intestinal tract of the mouse.

This paper summarizes recent and continuing work on circadian rhythms in the alimentary tract of rodents; these include: (1) cell proliferation, (2) activities of intestinal enzymes, and (3) behavioral aspects of spontaneous feeding and drinking. All regions of the intestinal tract show marked circadian behavior in cell proliferation. The roles of the light-dark cycle and meal timing in synchronizing such rhythms are discussed as well as the influence of epidermal growth factor, insulin, glucagon, and ACTH 1-17. Attention is called to the potential importance of these rhythms to basic research and medicine. Other circadian rhythms in the alimentary tract are reviewed briefly, such as those characterizing a host of intestinal enzymes, monosaccharide transport, and the height and width of the villi. Many of these have been shown to be cued to a feeding schedule; however, a number of the enzyme rhythms persist for one or two cycles in fasting animals, and this also is the case for the cell-proliferation rhythms. After having been acclimated to a circadian feeding schedule (within a range of 23-30 hr), rodents can on subsequent days anticipate the food an hour or more prior to its arrival. Some enzymes behave in a similar manner in that their activities increase prior to the expected intake of the daily food. These anticipatory response rhythms are under endogenous control, since both will persist in the fasted animal and both will free run when a mouse is placed under constant conditions. Somehow these animals are able to measure circadian intervals of time. This challenges the concept that the oscillations seen in enzyme activities are simply a passive consequence of feeding and fasting, respectively.

Adrenocorticotropic Hormone↗
PubMed1983

Bilateral lesions of suprachiasmatic nuclei affect circadian rhythms in [3H]-thymidine incorporation into deoxyribonucleic acid in mouse intestinal tract, mitotic index of corneal epithelium, and serum corticosterone.

Investigations into the role of the suprachiasmatic nuclei (SCN) in the coordination of circadian rhythms have presented differing results. Several reports have shown that ablation of the suprachiasmatic nuclei (SCNA) alters the phase and amplitude of rhythms but does not abolish them. The present study investigates the effect of SCNA on the rhythms in cell proliferation in various regions of the intestinal tract as measured by the incorporation of [3H]-thymidine into deoxyribonucleic acid, in the mitotic activity of the corneal epithelium, and in serum corticosterone levels. The study involved mice with verified lesions of the SCN (six to 13 mice per time point) and control groups of both sham-operated and unoperated mice (seven of each per time point). The mice were killed in groups that represented seven time points over a single 24 hr span (3 hr intervals with the 0800 hr sampled both at start and end of the series). The tissues examined were the tongue, esophagus, gastric stomach, and colon for DNA synthesis, the corneal epithelium for mitotic index, and blood serum for corticosterone level. The most consistent result of SCNA was a phase advance in the rhythms in cell proliferation in the tongue, esophagus, gastric stomach, colon, and corneal epithelium. A reduction in rhythm amplitude occurred in the tongue, esophagus, and corneal epithelium; however, there was an amplitude increase for the stomach, colon, and serum corticosterone. The mesor (rhythm-adjusted mean) was increased by SCNA in all tissues except the corneal epithelium. These findings further support the role of the suprachiasmatic nuclear area in the control of rhythms in cell proliferation and corticosterone production, by acting as a "phase-resetter" and as a modulator of rhythm amplitude.

Animals↗
PubMed1983

Pineal modulation of ACTH 1-17 effect upon murine corticosterone production.

In tests of corticosterone production in vitro, aqueous pineal homogenate (APH) modulates the effect of a short-chain ACTH analogue, ACTH 1-17, added to adrenals from different circadian stages. Adrenal and pineal glands from female B6D2F1 mice, standardized on staggered LD 12:12 regimens, were obtained at the same clock-hour from each room, in order to cover 6 different circadian stages. Adrenals from each circadian stage were bisected and incubated with APH from the same circadian stage (isophasic incubation) or from one of the other 5 circadian stages (heterophasic incubation). ACTH 1-17 (0.05 IU) was added to each incubation medium. After 4 hours of incubation at 37 degrees C with 95% O2 and 5% CO2, the media were stored at -20 degrees C until corticosterone RIA were done. APH was found to have a statistically significant modulatory effect upon the stimulation by ACTH 1-17 of adrenal corticosterone production in vitro. This APH effect changed rhythmically as a function of circadian stage from amplification over no effect to attenuation, as a so-called feed-sideward.

Adrenal Glands↗
PubMed1983

Circadian pineal modulation of pituitary effect on murine corticosterone in vitro.

An old controversy is resolved as a novel effect: In a rhythmic fashion, aqueous pineal homogenate (APH) enhances, attenuates or leaves unaffected the production of corticosterone by mouse adrenals incubated with pituitary media. All glands stem from the same circadian stage in these (isophasic) studies on 72 female CD2F1 mice, standardized for two weeks in L 0600-1800 and D 1800-0600. Every 4 hours during a 24-hour span, 12 mice were killed. Pineals were removed for the preparation of APH and stored at 4 degrees C. Hypothalami, pituitaries and adrenals were removed, bisected and placed in wells containing 1 ml Krebs-Ringer buffer (K), at 4 degrees C, until incubation. At each circadian stage, bisected adrenals were incubated with 95% O2 and 5% CO2 at 37 +/- 1 degree C for 5 hours, with K only or with the addition of 0.05 IU ACTH 1-17 or APH or with isophasic pituitary or hypothalamic preincubation media with and without APH or muscle. Media were stored at -20 degrees C until corticosterone RIA. A circadian rhythm (p less than 0.05) characterized corticosterone production after stimulation by the pituitary alone or with APH. The overall modulatory effect of APH is an increased circadian amplitude of adrenal corticosterone production, in response to the isophasic pituitary.

Adrenal Glands↗
PubMed1983

Circadian rhythm.

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Cell Division↗
PubMed1982

Circadian stage-dependent effects of insulin and glucagon on incorporation of [3H]thymidine into deoxyribonucleic acid in the esophagus, stomach, duodenum, jejunum, ileum, caecum, colon, rectum, and spleen of the adult female mouse.

Insulin and glucagon were injected ip at four different circadian states into separate subgroups of female adult BALB/Cann mice that had been standardized to 12 h of light alternating with 12 h of darkness. Comparable control subgroups were injected with saline. Four, 8, 12, and 18 h after each of the four injections, subgroups of seven mice that had been injected 30 min earlier with tritiated thymidine ([4H]TdR) were killed; a total of 336 mice were used. The incorporation of [3H]TdR into DNA of the esophagus, stomach, duodenum, jejunum, caecum, colon, rectum, and spleen was subsequently determined. The results demonstrate for the first time that both hormones affect the incorporation of [3H]TdR into DNA in all of the examined organs but in different ways and at different circadian stages. The effects of these hormones were complex, but several generalizations emerged. 1) Insulin tended to increase the incorporation of [3H]TdR into DNA in the examined organs, whereas glucagon tended to decrease it. 2) Insulin was more effective in stimulating the incorporation of [3H]TdR into DNA when injected either at the end of the dark span or the beginning of the light span, as opposed to the end of the light span or the beginning of the dark span. 3) Insulin had its greatest effect on [3H]TdR incorporation into DNA in the glandular stomach and rectum, whereas glucagon had its greatest effect on the colon and spleen. 4) The effects of both insulin and glucagon were different from those of epidermal growth factor, as revealed in a similar study done by us. Our results suggest that insulin, glucagon, and epidermal growth factor play important roles in the control of growth of various endodermally derived organs.

Animals↗