Search PubMed⌕ Search

Biomedical subjects

L E Scheving

Publications and source records attributed to L E Scheving.

At least 37 records · Page 2Linked to original sources
PubMed1990

Reference values for circadian rhythms of 98 variables in clinically healthy men in the fifth decade of life.

Nine clinically healthy men, 41-47 yr of age, served as subjects in a 24-hr study conducted at the Edward Hines Jr Veterans Administration Hospital in the Chicago area in May 1988. Physiologic measurements, and blood and urine samples were collected at 3-hr intervals over a single 24-hr period beginning at 1900. The number of variables measured or calculated (total = 98) included: 6 vital signs (oral temperature, pulse, blood- and intraocular pressures); 16 in whole blood (counts and differentials); 50 in serum (SMAC-24, lipids, hormones, electrophoresis of LDH and proteins); and 26 in urine (solids, proteins, creatinine, catecholamines, melatonin, cortisol, electrolytes and metals). Data were analyzed for time effect by analysis of variance (ANOVA) and for circadian rhythm by single cosinor. Individual rhythm characteristics for each variable were summarized for the group by population mean cosinor. The vast majority of variables revealed statistically significant within-day changes in values as validated by one-way ANOVA. All vital signs (except for intraocular pressures) and all serum hormones displayed a prominent circadian rhythm for the group, as did most variables in whole blood, while only about half of the variables in urine demonstrated a significant group rhythm. The results obtained are meant to: (a) document the circadian time structure; and (b) serve as reference values for circadian rhythm characteristics (range of change, mesor, amplitude and acrophase) for a defined group of individuals: clinically-healthy adult men in the prime of life.

Adult↗
PubMed1990

A preliminary report of circadian effects of interleukin-2 (IL-2) on the activity of enzymes of intermediary metabolism of mice.

Since it previously has been reported that IL-2 has profound circadian dependent effects upon DNA synthesis in the liver of mice (Scheving et al., 1988; Tsai et al., 1988) the effects of IL-2 on enzyme activities were studied. The objective was to determine the effect of IL-2 when administered at different times to mice who were fed ad libitum, and standardized to 12 h of light alternating with 12 h of dark. Three groups were injected intraperitoneally with either 1 or 4 mg/kg of IL-2, one group was given the vehicle only. The treatment time for each dose and the vehicle was a 2 h into the light for one group and the other was at 2 h into the dark span. Subgroups of 5 mice were killed 4, 8, 12, 16, 20, 24, and 30 h after each treatment, livers were taken and frozen to await preparation and analysis of enzyme activities by our standard procedures. When treatment was in the light span IL-2 had no statistically significant effect on enzymes of lipid, carbohydrate or amino acid metabolism. On the contrary when treatment was given in the dark span IL-2 produced statistically significant increases in enzymes of glycolysis, and lipid synthesis beginning 8 h after treatment (changes ranged from 20 to 43%) with both the higher and lower doses (higher doses always yielded higher activities), and these activities continued to increase through the 24 h post-treatment span (changes ranged from 42 to 64%). At 30 h, activities were returning to normal levels. Amino acid metabolism, on the other hand, was decreased during these post-treatment times (the range of decrease was from 18 to 44%). Thus, we report for the first time that the duration of time, pathway affected, as well as the magnitude of the effect seen and the dosage of IL-2 were all circadian-stage dependent even with two time point samplings. We believe, however, that these two time points represent different critical extremes in liver metabolism, but studies with denser sampling are planned. Interleukin-2 was generously supplied by Cetus Corp. of Emeryville, CA.

Alanine Transaminase↗
PubMed1990

Circadian reference data for men in fifth decade of life.

These results are meant to serve as chrono-biologically-defined reference values for healthy adult men in their fifth decade of life. A thorough statistical analysis of these data is being prepared for presentation elsewhere. A rigorous comparison with results obtained when these same men were in their 20's and again in their 30's may help us to document the kinds and extent of changes in circadian rhythm characteristics (MESOR, amplitude and/or acrophase) which may occur with aging.

Adult↗
PubMed1990

Effect of chronic caloric restriction on hepatic enzymes of intermediary metabolism in aged B6C3F1 female mice.

Caloric restriction (CR) extends maximum life span and significantly retards the rate of occurrence of most age-associated degenerative diseases. The effect of CR in female mice on several hepatic enzymes was examined after 33 month old mice were killed at either the onset of dark, the onset of light or the mid-dark span. Animals had been singly caged with 12 hr of light followed by 12 hr of dark. All feeding was in the early dark span. CR mice were given 60% of the caloric intake of ad libitum fed mice throughout their lives (CR was initiated at 14 weeks of age). Livers were frozen to await preparation and then analysis for 14 enzymes of intermediary metabolism by our standard procedures. Enzymes of gluconeogenesis and amino acid metabolism were increased at all times due to CR. Enzymes of glycolysis and lipid metabolism were decreased at all times. However, maximum differences between ad libitum and CR mice occurred during the mid-dark span (this is the time of normal acrophase in younger mice). Circadian variation was lost and mesors changed for nearly all enzymes measured from mice that had been fed ad libitum. CR mice were found to maintain circadian variation of activities and activity profiles were similar to those seen in younger ad libitum fed mice. These observations suggest that the mechanism through which CR elicits its effects may involve a circadian component.

Aging↗
PubMed1990

Chronobiology of exercise: the influence of scheduling upon glycemic responses of control and of subjects with diabetes mellitus.

Exercise programs contribute significantly to: a) improve cardiovascular fitness; b) lower blood pressure in hypertension; and c) facilitate glycemic control in subjects with Diabetes Mellitus (DM). The mechanisms involved in promoting the above responses remain undetermined. Circadian phases at which exercise is applied could play a major role in optimizing the individual's physiological responses to exercise. In a pilot study, controls and a subject with Insulin Dependent Diabetes Mellitus (IDDM) were exercised at 0800 and 2000 hours: pedaling on an exercycle for 30 minutes at rates that maintained tachycardia at 70% of maximum reserve heart rates (Karvomen et al., 1957). All subjects were on "standard" rest-activity schedules (rest 2300-2400 to 0600-0700) and were allowed a single 360 ml Sustacal meal either at 2400 hours or at 1200 hours; i.e., 8 hours preceding the exercise program. Blood samples were obtained for determinations of glucose (finger tip) just before exercise (0 time) and at 10, 20, 30, 40 and 60 minutes of exercise/post exercise periods. The results suggest that non-diabetics experience a rapid decrease in blood glucose levels which does not recover during the 60 minute sampling time when exercise was in the morning. However, when these individuals exercised during the evening, glucose levels did not fall as much on a percentage basis and full recovery was obtained within 40-60 minutes. In the case of the diabetic patient, after morning exercise, glucose levels did not decline and after 40 minutes had risen above resting glucose levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗
PubMed1989

Circadian variation of epidermal growth factor receptor in mouse liver.

The liver undergoes a biochemical and morphological circadian transformation. In this paper, we document circadian variation in the binding parameters of the hepatic epidermal growth factor receptor (EGFR). Liver membranes were prepared from ad libitum fed or fasted male CD2F1 mice killed at different circadian phases at 4 h intervals. Bmax (maximum binding) and Kd (dissociation constant) varied in a rhythmic fashion. The range of change for Bmax along the 24 h time scale was 423%. For Kd, it was 162%. Both peaked late in the dark span, and decreased late in the light span. Fasting and EGF treatment reduced Bmax and the amplitude of circadian variation.

Animal Nutritional Physiological Phenomena↗
PubMed1989

Circaseptan (about 7-day) modulation of circadian rhythm in corneal mitoses of Holtzman rats.

An infradian modulation with a 168 h or circaseptan period characterizes epithelial corneal mitoses in adult female and male Holtzman rats, standardized at 24 +/- 1 degree C and approximately 50% relative humidity on six different sequences of light (L) alternating every 12 h with darkness (D). To approximate sampling over a 24 h LD span by convenient sampling within a single hour, the LD 12:12 regimen was staggered by 4 h in the six environments. Bedding was changed 3 days before each day of killing. During each of eight or 12 consecutive days, male and female rats, respectively, were killed and the eyeballs were removed. Mitotic indices in the cornea were determined separately for each eye and the data were analyzed by linear and nonlinear least-squares rhythmometry. For a prominent circadian component of mitotic activity, the 95% confidence interval (CI) of the period extends from 23.6 to 24.3 h for the data from males and from 23.7 to 24.2 h for those from female rats. The circadian amplitude is larger in males as compared to females. The peaks in the 24 h cosine functions best approximating the data, the circadian acrophases, are at -64 degrees or -48 degrees, i.e., 4 h 16 min or 3 h 12 min from lights-on in male and female rats, respectively. In the data from the two genders, the 24 h synchronized circadian acrophases are thus only 16 degrees, i.e., 1 h and 4 min apart. A test for an anticipated circaseptan (7-day) period shows that this particular infradian periodicity is superimposed upon the circadian one in data from both genders.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Ten-year-replicated circadian profiles for 36 physiological, serological and urinary variables in healthy men.

At 3-hr intervals over a 24-hr span, 36 systemic, serologic and urinary variables were examined in 7 men in their mid 20's in the Spring of 1969, and again in the same 7 men in the Spring of 1979 under a similar chronobiologic protocol, using the same chemical and numerical analytical procedures. The variables examined for rhythms by cosinor were: vital signs--blood pressure (systolic, diastolic, pulse pressure and mean arterial pressure), heart rate, intraocular pressure (left and right), oral temperature; serum components--albumin, albumin/globulin ratio, total bilirubin, calcium, carbon dioxide, chlorides, bilirubin, cholesterol, globulin, glucose, potassium, sodium, sodium/potassium ratio, transaminase, triglycerides, total protein, urea nitrogen; and urine components--calcium, calcium/magnesium ratio, creatinine, magnesium, pH, potassium, sodium, sodium/potassium ratio, urea clearance, urea nitrogen, volume and zinc. Although all subjects appeared clinically healthy in 1969 and in 1979, certain inter-study differences were observed in a number of rhythm parameters of different variables. Statistically significant increases in mesor for the group as a whole were observed for serum Ca, cholesterol, Cl, CO2, K, Na, and while statistically significant mesor decreases for a group as a whole were noted in serum glucose and transaminase. Statistically significant increases in amplitude for the group as a whole were observed in serum chloride and urinary Na/K ratio, while statistically significant decreases were observed in amplitude for blood pressure, heart rate, serum albumin, A/G ratio, globulin, glucose, protein, sodium and transaminase.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Circadian variations in eleven radioimmunoassay variables in the serum of clinically healthy men.

Radioimmunoassay studies were conducted on 13 clinically healthy male subjects. Ten ranged in age between 23 and 44 years, two were age 51, and one was age 58. Blood samples were collected at 3-hr intervals over a period of 27 hr. Each serum sample was analyzed for the following hormones: insulin, gastrin, melatonin, prolactin, triiodothyronine (uptake), thyroid-stimulating hormone, triiodothyronine, thyroxine, luteinizing hormone, growth hormone, and follicle-stimulating hormone. Group data for each hormone were fitted to a 24-hr cosine curve. A statistically significant fit to this curve was evident in the six italicized variables. Those that did not yield a statistically significant fit frequently revealed a statistically significant variation along the 27-hr span. Chronogram and cosinor plots are presented.

Adult↗
PubMed1987

Circadian-dependent response in DNA synthesis to epidermal growth factor in spleen, bone marrow, and lung and in mitotic index of corneal epithelium in ad libitum-fed and fasted CD2F1 mice.

The effect of epidermal growth factor (EGF) on DNA synthesis in the spleen, bone marrow, and lung and on the mitotic index in the corneal epithelium was investigated in CD2F1 mice that were standardized on an LD 12:12 cycle and either fed ad libitum or fasted for 24-34 hr. EGF brought about decreases in DNA synthesis in both the bone marrow and spleen in ad libitum-fed male mice. Moreover, the degree of response and the duration of time it took for the decreases to become statistically significant were circadian-stage dependent. The response brought about by EGF on DNA synthesis in the lung also was circadian-stage dependent, but it was an increase and occurred much later than in the spleen or bone marrow. The maximum decreases brought about by EGF in spleen and bone marrow occurred at 13 hr after EGF treatment, being 37% and 28%, respectively. The maximum increase in DNA synthesis in the lung was 116% and was recorded 33 hr after treatment, but the first statistically significant increase (35%) was recorded 28 hr after treatment. Under the conditions of this study, fasting diminished the overall level of DNA synthesis in the bone marrow, spleen, and lung. We conclude, however, that sampling was too limited to draw definitive conclusions regarding the persistence of a DNA synthesis rhythm in fasting and the effect that EGF has on the fasting rhythm. There was no apparent effect on fasting on the mitotic index of the corneal epithelium.

Animals↗
PubMed1987

Circadian-infradian intermodulation of corneal epithelial mitoses in adult female rats.

An infradian modulation with a 5-day period characterizes corneal mitoses in adult female inbred Lewis rats. The animals had been standardized, two per cage, with Purina Chow and deionized water freely available at 24 +/- 1 degree C and approximately 50% relative humidity, on six different sequences of light (L) alternating every 12 hr with darkness (D). The LD 12:12 regimen was staggered by approximately 4hr in the six environments to approximate, by sampling within 1 hr, sampling over a 24-hr LD span. Bedding was changed 3 days before each day of killing. During each of 8 consecutive days, one rat from each environment was anesthetized with ether and the eyeballs were removed. Mitotic indices, computed separately for each eye, were analyzed by linear and nonlinear least-squares analyses. For a prominent circadian component of mitotic activity, the 95% confidence interval (CI) extended from 23.84 to 24.85 hr, with a point estimate of 24.32 hr; for a second component of 117 hr, the Cl extended from 90 to 163 hr. Whether the approximate 5-day infradian rhythm is of ovarian or other origin is a problem for further study.

Animals↗
PubMed1987

Regulation of the circadian rhythm of hepatic pyruvate kinase in mice.

We have previously demonstrated circadian variation of pyruvate kinase (PK) activity. PK is a key enzyme of glycolysis, whose activity has been shown to be regulated at the level of enzyme concentration and catalytic activity. To investigate the mechanism of regulation and the components of the circadian rhythm of PK activity, Michaelis-Menten kinetic values were determined. C57BL/6J male mice that had been standardized for over 2 weeks to 12 hr light followed by 12 hr dark (lights on at 0600 hr CST), were killed at 3-hr intervals (six mice/circadian stage) over a 24-hr span. Vmax values, which are a measure of enzyme concentration, were found to be characterized by circadian variation (P = 0.01 by ANOVA, but P = 0.38 by cosinor analysis). The time of highest observed Vmax occurred at the early dark and continued through the entire dark and early light spans. An abrupt decrease in Vmax (-40%) was observed at the end of the light span. PK catalytic activity is regulated by covalent modification (phosphorylation/dephosphorylation) of the enzyme, and the phosphorylated, inactive form of the enzyme has a high Km for its major substrate (1.41 mM phosphoenol pyruvate; PEP). Km values were found to be characterized by a circadian rhythm (P less than 0.001 by cosinor analysis) whose acrophase (1117 hr) was at the beginning of the light cycle (high Km indicates low catalytic activity at subsaturating PEP concentrations). These results indicate that the circadian rhythm for PK activity is composed of at least two components. Enzyme concentration is high during the dark and early light phases but decreases at the end of the light phase. Concentration recovers rapidly within 3 hr after the lights are turned off. Catalytic activity is maximal at a time just after enzyme concentration becomes maximal in the dark phase. Maximal efficiency of the enzyme is thus achieved at the time when animals are eating and glycolysis is operating at high levels.

Animals↗
PubMed1987

Circadian and other variation in epinephrine and norepinephrine among several human populations, including healthy blinded and sighted subjects and patients with leprosy.

Urinary levels of epinephrine and norepinephrine were studied in three populations: presumably healthy young men who were studied twice, 8 years apart, and in the same month to avoid seasonal influences; blinded but otherwise healthy males and females; and patients with leprosy. Determinations of epinephrine and norepinephrine were done on urine samples collected at 3-hr intervals for 72 hr from the first two groups and for 10 days from patients with leprosy. The same chemist, method, and protocol were used in all studies. In one study of the group of healthy young men, the effect of meal timing and fasting on the rhythms was investigated. From these studies several generalizations can be made. Highly statistically significant population circadian rhythms characterize both epinephrine and norepinephrine in all three groups. In general, the rhythm in norepinephrine was "noisier" than that in epinephrine; in the blind subjects, both variables were characterized by noisier rhythms than in the sighted. The overall levels of epinephrine were much higher in blind than in sighted subjects. The overall levels of norepinephrine were much higher in blind males than in blind females. In the studies done with the group of healthy young men, the overall levels of epinephrine and norepinephrine increased significantly over a 10-year period. The amplitude of the rhythm also increased significantly with time. The average age of the group was 27 years at the time of the first study and 40 years at the time of the second. The patients with leprosy also showed strong circadian variation in both epinephrine and norepinephrine, but, because many of the subjects were on medication, comparisons with the other groups are questionable. In general the data raise some questions about, but do not refute, the commonly held view that the amplitude and mesor of the circadian rhythm in epinephrine decrease with age. Additional work is needed to resolve this question completely.

Adult↗