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Biomedical subjects

F Halberg

Publications and source records attributed to F Halberg.

At least 127 records · Page 7Linked to original sources
PubMed1986

Schedule-shifts, circadian rhythms and lifespan of freely-feeding and meal-fed mice.

Mice feeding ad lib were subjected to weekly 12-hr shifts of the daily light-dark (LD) schedule beginning at either 7, 20 or 52 weeks of age and continuing until death. Other mice were meal-fed and, from 7 weeks of age until death, experienced weekly 12-hr shifts of the LD schedule alone (with mealtime fixed) or of both the LD schedule and mealtime. Telemetered core temperature data indicated marked differences in response to the different shift conditions and suggested, in the case of meal-fed animals, involvement of a food-anticipatory rhythm. Shifting of the LD schedule had no statistically significant effect on the mean survival time of mice feeding ad lib, regardless of when shifting began. While meal-feeding in itself prolonged life, the added imposition of schedule-shifting had no statistically significant effect on mean survival time, regardless of whether the meal schedule reinforced or opposed shifts of the LD schedule. In the latter case, tenth-decile survival time may have been increased.

Aging↗
PubMed1986

The manpower crisis facing radiation oncology.

Data from several sources document that the number of radiation oncologists being trained is substantially above the number projected as recently as 1983. This paper addresses the manpower crisis facing radiation oncology and includes information on the supply of and need for specialists, as well as possible courses of action given current circumstances.

Internship and Residency↗
PubMed1986

Evidence for a circaseptan and a circasemiseptan growth response to light/dark cycle shifts in nucleated and enucleated Acetabularia cells, respectively.

Nucleated as well as enucleated Acetabularia mediterranea cells were subjected to 14 different patterns of shifts in a regimen of 12 hr of light alternating with 12 hr of darkness in four 30-day long experiments. With one exception, which might be due to a circannual modulation, these experiments showed that nucleated cells had maximal growth rates when a shift was performed every 7th or 15th day. In enucleated cells, maxima were observed on shift schedules that were about 3-4 days rather than about 7 days apart. The results indicate that in the unicellular green alga Acetabularia a rhythm of about 7 days (circaseptan) exists and that removal of the nucleus results in a circaseptan frequency multiplication.

Acetabularia↗
PubMed1986

Meal-timing, circadian rhythms and life span of mice.

The possibility that circadian rhythm alteration may contribute to the life-prolonging effect of food restriction was investigated in female CD2F1 mice housed in a room with a 12-h span of fluorescent lighting daily. A control group was allowed to feed ad libitum throughout life while three other groups began lifelong restriction to about 75% of ad libitum intake when 6 wk old. The daily schedule of food accessibility differed among these three groups: a single meal during early darkness; a single meal during early light; six smaller meals at about 2-h intervals during darkness. Food restriction as such clearly prolonged life, but there were no statistically significant differences in overall mean life span or in 10th-decile life span among the three restricted groups. Telemetered body temperature data confirmed marked differences in the effects of these different restricted feeding schedules on circadian rhythms. The effect of food restriction on survival is probably not due to altered relations among circadian rhythmic variables. Possible contributing factors suggested by the results are a lower body temperature, a reduced overall metabolic rate and an increased circadian amplitude.

Animals↗
PubMed1986

Circadian characteristics of urinary melatonin from clinically healthy young women at different civilization disease risks.

Rhythm characteristics in the about-daily (circadian) and about-yearly (circannual) frequency ranges were assessed for urinary melatonin. Clinically healthy women in Minnesota, USA, and Kyushu, Japan, were sampled around the clock once in 1-4 seasons. Possible differences that could reflect the large difference in breast cancer incidence in these two geographic locations were investigated. Each subject's risk of developing breast cancer, cardiovascular diseases resulting from an elevated blood pressure, and emotional conditions was numerically evaluated according to epidemiologic questionnaires. A prominent circadian rhythm characterizes urinary melatonin in both populations, peaking in the middle of the night. The American women exhibit a larger circadian rhythm-adjusted mean (mesor) than do the Japanese women. A circannual rhythm is also apparent in the North American women, but not in the Japanese women. The circadian mesor of urinary melatonin correlates negatively with the risk score of emotional depression and positively with that of developing cardiovascular diseases.

Adolescent↗
PubMed1986

Circadian stage-dependent prolongation by cyclosporine of segmental pancreatic allograft function in the rat.

While the toxicity of many drugs has been reduced by their administration at certain circadian rhythm stages (if not at certain times of day), as shown herein, direct therapeutic benefit from the improvement of the desired effect can be obtained by the circadian timing of intraperitoneal cyclosporine (Cs) for Lewis rats bearing an ACI segmental pancreas allograft. Under conditions of light (L) and darkness (D) alternating at 12-hour intervals, staggered by 8 h in 3 rooms kept at 24 degrees C, the effect of Cs in delaying graft rejection was improved by timing. When the mean time to rejection during the L span is equated to 100%, graft function is prolonged by 40% at the right time (injection daily during the D span) as compared to the wrong time (injection daily during the L span).

Animals↗
PubMed1986

Circadian characteristics of urinary epinephrine and norepinephrine from healthy young women in Japan and U.S.A.

Clinically healthy diurnally active young adult women were studied during the same season (March) at the Universities of Kyushu (Fukuoka City, Japan) and of Minnesota (Minneapolis, U.S.A.), under comparable conditions, except that the habitual diets were not changed. The subjects (20 Japanese and 16 Americans of mixed Caucasian background) were studied over a single 24-hr span. Urine was collected at 4-hr intervals. A circadian rhythm in total urinary norepinephrine excretion showed similar characteristics in Japanese and Americans. In epinephrine excretion, the Japanese women showed a statistically significantly higher amplitude with higher peak values, but no statistically significant difference in the rhythm-adjusted mean. This intergroup difference is strictly time dependent; it does not come to the fore in urine samples covering the nocturnal rest span of the subjects.

Adult↗
PubMed1986

Circadian rhythm in mammary cytoplasmic estrogen receptor content of Balb/C female mice with and without pituitary isografts.

Cytoplasmic estrogen receptors were determined by the dextran-coated charcoal method in inguinal breast tissue of three groups of Balb/C female mice 6-8 weeks following subcutaneous implantation into the intact animals of three pituitary glands and three pieces of skeletal muscle (group I), three pituitary glands and three segments of hypothalamic tissue (group II), or three pieces of skeletal muscle (group III) obtained from animals of the same inbred strain as control. A circadian rhythm in estrogen receptor content was statistically quantified by cosinor analysis in the muscle implanted control and the pituitary and hypothalamic implant groups. In the pituitary and muscle implant group the circadian rhythm is of borderline significance with a P-value between 0.05 and 0.10. The timing (acrophase) and extent of change (amplitude) are similar in all three treatment groups. The average receptor content (MESOR) in the two pituitary-implanted groups, which in previous studies were shown to have an increased breast cancer incidence is about twice that of the control group. The reduction in the pituitary induced breast cancer rate by hypothalamic tissue addition to a cancer incidence between the animals with pituitary and muscle isograft and the mice carrying no pituitary at all has also been shown previously in this strain of mice and is not reflected in receptor content.

Animals↗
PubMed1986

[Persistence of the circadian rhythm of dehydroepiandrosterone in the brain, but not in the plasma, of castrated and adrenalectomized rats].

In adrenalectomized and orchidectomized rats, the removal of the steroidogenic endocrine glands is associated with a near-disappearance of corticosterone (B) from plasma and brain; circadian variations of B and of plasma dehydroepiandrosterone (D), characteristic of the intact rat, are no more detected. By contrast, analyses of brain D measurements by the cosinor method demonstrate a persisting circadian rhythm of large amplitude.

Adrenalectomy↗
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

Circadian toxicology of cyclosporin.

Cyclosporin (Cs), a cyclic nonpolar undecapeptide of fungal origin, has potent immunosuppressive and antiparasitic activities, and renal and hepatic toxicities, the mechanisms of which are not worked out. Many nephrotoxins and hepatotoxins are predictably more or less harmful, depending upon the circadian stage at which they are administered. In order to find treatment schedules that might damage the animal least, the toxicity of 20 mg kg-1 day-1 of Cs given intraperitoneally was studied at six different circadian stages in adult male Lewis rats. Cs toxicity was gauged by body temperature decline, body weight loss, and survival time. Rectal temperatures over a 24-hr span during the 2 days prior to the first death revealed that rats treated during darkness were 1.6 +/- 0.3 degree C cooler than vehicle-treated controls, whereas rats treated during the light span were only 0.4 +/- 0.2 degree C cooler than controls (p less than 0.01). Rats treated in darkness lost twice as much weight compared to those treated in light (20 +/- 2 versus 10 +/- 2%, p less than 0.01). Rats receiving daily Cs in the dark span lived an average of 28 +/- 5 days compared with 44 +/- 4 days for animals getting Cs during the light span (p less than 0.05). Three separate nonspecific measures of drug toxicity confirmed that there was substantial circadian stage dependence to Cs toxicity. The safest time for the drug in rats was 2 to 10 hr after lighting onset, a time when rats are usually beginning their diurnal rest and/or sleep span.

Animals↗
PubMed1985

Temporal correlation of some endocrine circadian rhythms in elderly subjects.

The aim of this chronobiological study was to investigate temporal correlations in the circadian patterns of 6 hormones, namely somatotrophic hormone (STH), prolactin (PRL), cortisol (F), aldosterone (ALD), insulin (IRI) and C-peptide (CP), assayed in systemic blood serum drawn at 07:00, 10:00, 13:00, 16:00, 19:00 and 22:00 h from an antecubital vein in 19 young subjects (aged 20-29 yr, comprising 10 males and 9 females; and 20 elderly subjects (aged 70-81 yr, comprising 10 males and 10 females). All subjects were sampled on a normal dietary sodium intake (120-140 mEq/24h) while following a social routine of diurnal activity (07:00-23:00) and nocturnal rest (23:00-07:00). Time-qualified data were analyzed by lead-lag correlation and by cosinor analysis. According to the lead-lag correlation findings, it would appear that the correlation which exists between several time-qualified series in young subjects is no longer present in elderly subjects. The circadian rhythms which were found to have lost their temporal correlations with advancing age were those between STH and IRI, STH and ALD, PRL and IRI, PRL and CP, and ALD and CP. It should be noted that the correlation between hormonal rhythms breaks down mainly on account of a peculiar age-related change in the magnitude of the circadian fluctuation. This chronological decline in amplitude led to the conclusion that the senescence of endocrine rhythmic functions is a biological phenomenon characterized by altered circadian variability.

Adult↗
PubMed1985

Circadian rhythms of plasma renin activity and aldosterone: changes related to age, sex, recumbency and sodium restriction. Chronobiologic specification for reference values.

Plasma renin activity (PRA) and aldosterone (PA) levels are characterized by a circadian rhythmicity (CR). The present study revealed that this rhythmicity is influenced by several factors including posture, sodium intake and age. Time-qualified PRA and PA reference intervals can reduce the incidence of false positives and false negatives in a diagnostic work-up. The circadian rhythmicity of PRA and PA have been quantified in relation to posture, sodium intake and age. The cosinor procedure has been applied to quantify the properties of the circadian rhythmicity under these conditions. Chronograms and circadian parameters can be used to optimize the use of PRA and PA measurements in clinical practice. The chronobiological specification of reference values for PRA and PA is of valuable importance since the assessment of PRA and PA circadian rhythmicity has a diagnostic interest for a certain type of clinical disorder. It should be noted that several studies have described circannual variations for renin and aldosterone. The next step in the optimation of laboratory time-qualified reference values is the assessment of changes induced by the deterministic factors on a circannual domain.

Adult↗
PubMed1985

[Circadian course of delta 5,3 beta-hydroxysteroids and glucocorticosteroids in the plasma and brain of rats].

Corticosterone (B), pregnenolone (P) and dehydroepiandrosterone (D) undergo circadian variations in the rat plasma and brain. When the data are interpreted by the Cosinor method, the acrophases of P in brain and of D in plasma significantly precede the acrophase of B. The asynchrony of delta 5-3 beta-hydroxysteroid and glucocorticosteroid rhythms brings an additional argument in favor of separate regulatory mechanisms.

Animals↗
PubMed1984

Toward a chronophysiology of circulating aldosterone.

The physiology of aldosterone secretion has been prominently investigated by homeostatic studies on the levels of the steroid in plasma and/or urine. Aldosterone secretion is, however, arranged in a rhythmic fashion along the 24-hr cycle. The dynamics of aldosterone should thus be reanalyzed chronobiologically in order to gain further insight into the physiology of the hormone. Such a revisitation has been performed in the present study on four groups of clinically healthy volunteers categorized according to sex and age. Aldosterone has been assayed in the plasma of systemic venous blood six times a day (0600, 0800, 1200, 1800, 2000, 0000) in different conditions of physical activity and sodium intake. Time-qualified data have been analyzed by the single-cosinor method and then summarized by the population-mean cosinor procedure to quantify the circadian rhythms in their properties (mesor, amplitude, acrophase). Differences in rhythmometric parameters have been tested by a multivariate analysis for vectorial units. (Hotelling's T2 test). Cosinor analysis indicates that the dynamics of circulating aldosterone substantially changes in relation to posture. The habit of having a routine of diurnal activity leads the circadian rhythm of aldosterone to delay its acrophase from morning to afternoon. The postural shift of acrophase is essentially accompanied by an elevation in the 24-hr mean level. The restriction of salt intake is associated with an increase in mesor; the temporal localization of the circadian crest shows, however, a very high stability. Sex is not characterized by significant differences in the 24-hr patterns of aldosterone in the sense that young males and females show substantially identical time-qualified curves and circadian parameters. Increasing age until the seventh decade in life is responsible for changes mainly in 24-hr mean levels with a slight modification in amplitude. Such a chronophysiology for circulating aldosterone related to the motor-rest schedule, sodium intake, sex, and age, is of interest not only to heuristic but also to practical approaches in clinical medicine.

Adolescent↗