Search PubMed⌕ Search

Biomedical subjects

F Halberg

Publications and source records attributed to F Halberg.

At least 109 records · Page 6Linked to original sources

[Blood levels of dehydroepiandrosterone sulfate (DHEA-S) and the risk of breast cancer].

In North American women at low or high risk of developing breast cancer, as assessed by an epidemiologic questionnaire, the plasma concentration of dehydroepiandrosterone sulfate shows a statistically significant circannual variation. In adolescents, in all seasons, circulating dehydroepiandrosterone sulfate is a classifier of the risk of developing breast cancer, a relatively low concentration of this hormone being associated with an increased risk.

Adolescent↗

Neuro-steroids: 3 beta-hydroxy-delta 5-derivatives in rat and monkey brain.

The rat brain accumulates pregnenolone (P) as the unconjugated steroid, the sulfate ester (S) and fatty acid esters (L). P + PS do not disappear from rat brain after combined adrenalectomy (adx) and castration (orx). PL does not serve a source of P after adx + orx. P is metabolized by several rat brain regions to progesterone and to PL. Brain microsomes contain the acyl-transferase which converts P to PL using endogenous substrates. Brain P and dehydroepiandrosterone (D) undergo a prominent circadian variation with their acrophases at the beginning of the dark span. The circadian variation of brain D persists after adx + orx. The monkey brain (Macaca fascicularis) also accumulates P and D. Adrenal suppression with dexamethasone for 4 days does not decrease the concentrations of brain P and 3rd ventricle CSFP and D. The concentrations of brain D are decreased to a much smaller extent than plasma D. D inhibits the aggressive behavior of castrated male mice exposed to lactating female intruders. This is not the case for DS or androst-5-ene-3 beta, 17 beta-diol. The D analog 3 beta-methyl-androst-5-en-17-one, which is not estrogenic and cannot be metabolized to testosterone or estradiol, is as active as D in inhibiting the aggressive behavior of castrated mice.

Adrenal Glands↗

Circadian rhythm of gastric acid secretion in active duodenal ulcer: chronobiological statistical characteristics and comparison of acid secretory and plasma gastrin patterns with healthy subjects and postvagotomy and pyloroplasty patients.

Twenty-one male patients with active duodenal ulcer underwent hourly 24-hr gastric acid collections under controlled, calorically deprived conditions. The 24-hr hourly acid secretory output for the group displayed a statistically significant (p less than 0.001) rhythm, with peak rates occurring during the evening hours and low rates during the early morning hours, by population-mean cosinor statistical analysis. Population-mean cosinor analysis also verified the occurrence of a significant (p = 0.034) circadian rhythm in unstimulated acid secretion in a group (N = 14) of healthy male subjects similarly studied and reported previously. In contrast, population-mean cosinor analysis confirmed the absence of any detectable circadian rhythm in unstimulated acid secretion in a group (N = 17) of postvagotomy and pyloroplasty patients studied 2-11 years after surgery. Population-mean cosinor analysis of 4-hr plasma gastrin determinations, obtained in all groups during the 24-hr gastric acid collection, revealed an absence of any detectable circadian rhythm in plasma gastrin. This latter finding is compatible with the interpretation that the circadian rhythm of unstimulated gastric acid secretion, observed in the clinically healthy and active ulcer groups, is unrelated to changes in plasma gastrin levels. The employment of quantitative chronobiological inferential statistical techniques is important to the analysis of any time-dependent measurement in gastrointestinal function, of which gastric acidity is one example.

Adult↗

The gerontological decline of the renin-aldosterone system: a chronobiological approach extended to essential hypertension.

The circadian (about 24-hr) oscillating function of the renin-angiotensin-aldosterone system (RAAS) was investigated as a function of age in clinically healthy participants and in essential hypertensive patients. A peculiar age-related decline in the RAAS circadian mesor (rhythm-adjusted mean) and amplitude (variability from mesor) was found in the essential hypertensive patients. This finding suggests a nonphysiologic evolution in the tonic (24-hr mean level) as well as phasic (oscillating amplitude) circadian activity of the RAAS with increasing age. A relative hyperreninemic aldosteronism characterized the aged essential hypertensive patients.

Adolescent↗

Effects of a mild and prolonged restriction in sodium or food intake on the circadian rhythm of aldosterone and related variables.

The effect of a mild reduction in dietary sodium intake (-30 mEq/24 hr) and body weight (-2 kg/2 months) on circadian rhythms of urinary aldosterone (UA), sodium (UNa), potassium (UK), creatinine (UC) and volume (UV) have been investigated in nine clinically healthy subjects. The mild reduction in dietary sodium is associated with: (1) a decrease in the 24-hr excretion rate of UNa, UK and UV, and an increased mesor of UA and UC; (2) a lowered extent of the circadian variation for UNa, UK, UV and a greater amplitude for UA and UC (3) a later crest in the temporal phase for UK, UA, UC, an earlier phasic wave for UNa. The mild reduction in calorie intake resulting in a body weight loss is associated with a more pronounced decrease in the 24-hr excretion rate of UNa and UK, and in the extent of circadian fluctuation for UNa. Peculiar events are: (1) the decreased 24-hr excretion rate for UA, and the increased mesor for UV; (2) the extent variability increased for UV, decreased for UC. Such effect may have a practical resonance for heuristic physiology since the role of dietary sodium and food intake has been better clarified. Dietary sodium and food can be regarded as 'chronomodulatory agents' for the adrenal cortex since their adrenotropic influence is extended to the tonic as well as phasic secretion of aldosterone.

Adult↗

Autometrically and automatically monitored, iatrogenous, inhalant-decongestant-associated high blood pressure quantified by rhythmometry.

Blood pressure and heart rate were oscillometrically monitored with an automatic Nippon Colin instrument (Komaki, Japan) and were also self-measured by a 20-year-old man treated with an inhalant-decongestant containing an adrenergic and a corticosteroid analog. The subject also collected 24-hr urines for aldosterone determination. An elevation of urinary aldosterone excretion was observed compared to the usual value range of a peer group. After removal of the drug, urinary aldosterone dropped as did urinary potassium, whereas plasma potassium rose. Chronobiologic serial sections, carried out to follow the time course of blood pressure and heart rate, showed decreasing trends in MESOR after discontinuance of treatment. A decrease in the hyperbaric index, a measure of blood pressure excess over 24 hr, was also observed. Another subject treated with the same and a third treated with a similar inhalant-decongestant, who also monitored their blood pressures automatically and/or with self-measurements, showed similar effects: a decrease in blood pressure after removal of treatment and an increase in blood pressure when (for testing only) treatment was briefly resumed.

Adult↗

Chronobiologic dynamics of delta 5-3 beta-hydroxysteroids and glucocorticoids in rat brain and plasma and human plasma.

While a different timing of circadian rhythms does not necessarily demonstrate the operation of independent mechanisms, it is one step in the isolation of separate interacting rhythmic factors underlying the dynamics of all life. With this step in mind, circadian rhythms are quantified in rat plasma and brain for corticosterone (B), pregnenolone (P), and dehydroepiandrosterone (D) by the rejection of the zero-amplitude assumption with the single cosinor method, from data obtained every 3 hr for 24 hr on groups of three male Sprague-Dawley rats, 11-12 weeks of age. The rats were killed; steroids were extracted from brain and plasma and were radioimmunoassayed. In relation to the acrophase (phi) of B, the phi of P in brain (P = 0.035) and of D in plasma (P = 0.0012) preceded the phi of B. By contrast, in clinically healthy women, the phi of plasma dehydroepiandrosterone sulfate (DHEA-S) lags behind that of cortisol (F), on the average by 6 hr 28 min. Such a lag is also seen in men. A species difference in the time relations of delta 5-3 beta-hydroxysteroids vs. glucocorticoids in plasma is obvious (P less than 0.01). A difference in time relations of human circulating D, DHEA-S, and F between schizophrenic and clinically healthy men renders the time relations of glucocorticosteroids and delta 5-3 beta-hydroxysteroids in brain particularly interesting, as do relations of an egocentric and expansive personality to the rhythm characteristics of DHEA-S. The fact that the acrophases for some of the steroids investigated in brain and plasma, respectively, are differently timed is in keeping with the assumption that they involve partly different mechanisms, even if differences in the metabolic handling of different steroids also remain to be investigated.

Animals↗

Circatrigintan hormonal and skin surface temperature rhythms following hysterectomy.

Starting 2.5 weeks after removal of her uterus, but not of her ovaries, a 34-year-old, clinically healthy woman contributed a daily blood sample at 0900 and measured her skin surface temperature on her right breast above the nipple and just below the right breast daily for the ensuing 2 months. In aliquots of serum stored frozen, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were determined in the United States; these hormones and prolactin, estradiol (E2), progesterone, testosterone, dehydroepiandrosterone-sulfate (DHEA-S), cortisol, triiodothyronine (T3), free thyroxine (T4), and free testosterone were determined in Italy. Hormonal data were analyzed by least-squares rhythmometry with and without the data obtained around the FSH-LH surge, to assess any circatrigintan variation. Technically, there is good agreement between the rhythm characteristics of the series of determinations made in Italy and the United States. A circatrigintan rhythm is thus quantified for LH, FSH, prolactin, E2, progesterone, and testosterone. Analyses of the differential skin surface temperature (DST) between the two sites were carried out to examine the usefulness of this variable as a marker rhythm for a noninvasive assessment of the time of ovulation. Features as prominent as the LH and FSH surge, which would render the noninvasive assessment of ovulation time more reliable, were not found in the DST of the subject under the conditions examined, even if a circatrigintan component is demonstrable for DST and some of the hormones examined after hysterectomy.

Adult↗

Rhythmic pineal-hypophyseal-adrenal intermodulations ex vivo.

To assess circadian and circaseptan rhythmic intermodulation, female mice, kept on regimens of 12 hr light (L) alternating with 12 hr of darkness (D) (LD 12:12) were sampled for 1-13 days at six circadian stages. Pineals were removed and homogenized with 0.9% NaCl. Adenohypophyses were bisected and incubated in Krebs-Ringer buffer (KRb) and/or with 10(-7) M melatonin (Mt). Adrenals were bisected and incubated with KRb, with 10(-7) M Mt, with 0.05 IU of ACTH 1-17 (Sy; Hoechst, Italy), or with Sy + 0.025 ml of the aqueous pineal homogenate (APH). ACTH and prolactin (PRL) in adenohypophysis incubation fluid were determined by radioimmunoassay (RIA), and corticosterone in adrenal incubation fluid was determined by RIA or by a fluorometric method. By this chronobiologic approach, time series were collected systematically in the search for predictable variability. Once these series reveal an algorithmically formulatable pattern, with a waveform validated by inferential statistical means, they are graded in terms of complexity as alpha, beta, gamma, and delta rhythms. Spontaneously (alpha-) rhythmic along the 24-h scale is the corticosterone produced by bisected adrenal glands incubated with KRb only, and the Mt content of the APH, in keeping with earlier work. Reactively (beta-) rhythmic is the response, again along the 24-hr scale, of the adrenal to Sy or Mt and the response of the anterior pituitary to Mt at different circadian times. Modulatory (gamma and delta) rhythms characterize the Mt effect on the (beta-rhythmic) adrenal stimulation by Sy. Chronomodulations thus emerge as more or less complete sequences of a decrease, no effect and/or increase; or, rather, as an attenuation, no effect and/or amplification by the pineal, of the pituitary effect upon the adrenal. Linear least-squares rhythmometry, mostly single cosinors, describes and quantifies circadian (alpha, beta, and gamma) and infradian (delta) rhythms in the original series and in the differences in responses [beta - alpha] and [gamma - beta] (P less than 0.001 in each case). These spontaneous alpha, response beta, modulatory gamma, and frequency-divided delta rhythms reveal a collateral neuroendocrine hierarchy, characterized by the pineal feedsideward phenomenon, as a feature of interactions recurring with circadian and infradian frequencies.

Adrenocorticotropic Hormone↗

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↗

Temperature-compensated ultradian variation in cellular protein content of Acanthamoeba castellanii revisited.

Synchronous cultures of the soil amoeba Acanthamoeba castellanii, established in the laboratory by selection procedures, show oscillations of total cell protein, as well as respiration. Previously, time series analysis by Aspect, a University of Warwick Computer Unit Program, showed an average period of 76 min. A reanalysis by least-squares rhythmometry revealed that, in general, the analyses accompanying the original paper and those in this replication agree very well. The periods extracted by the two approaches differ by only 1 to 5 min. In one case, when the original analysis did not detect a statistically significant period, however, the analysis used here does so. While the incubation temperatures used varied from 20 to 30 degrees C and cell division time increased from 7.8 hr at 30 degrees C to 16 hr at 20 degrees C, the metabolic bioperiodicity appeared to be temperature compensated. Decimation studies indicate that the sampling interval of 5 to 15 min must not be further reduced. It is promising to incorporate the study of ultradian metabolic rhythms into a broad spectral approach, i.e., for a concomitant assessment of ultradian, circadian, and infradian rhythms.

Activity Cycles↗

Rhythms of isolated platelet glutathione, aging, and the internal evolution of species.

Platelet integrity upon reinfusion after storage for varying periods of time constitutes a clinical problem requiring chronobiologic study. For such a study, total glutathione (GSH) served as an index. Blood from healthy volunteers drawn at 0800 was mixed with citrate-citric acid-dextrose (CCD) and centrifuged at 100g to obtain platelet-rich plasma (PRP), transferred to sterile containers, and maintained under ordinary laboratory conditions at room temperature in casually alternating light (L) and darkness (D), in LD 16.8, in continuous light (LL), or in continuous darkness (DD). In 5-ml aliquots of PRP mixed with 500 microliter of 0.34 M EDTA and recentrifuged for 15 min at 200g, a circadian rhythm of GSH per 10(9) platelets was found. The fit to 4-hr data of a linear trend and a 24-hr cosine yields similar acrophases (phi) under the various conditions investigated. With 360 degrees = 24 hr and with 95% limits in parentheses, the acrophases for PRP from a male donor stored in LD, LL, or DD are -64 degrees (-20 degrees, -107 degrees), -67 degrees (-28 degrees, -106 degrees), and -74 degrees (-35 degrees, -112 degrees), respectively. The corresponding values for platelets from a female donor in LD, LL, and DD are -49 degrees (-17 degrees, -80 degrees), -82 degrees (-50 degrees, -113 degrees), and -68 degrees (-29 degrees, -107 degrees), respectively. Six of six best-fitting circadian periods are longer than 24 hr, a result in keeping with a possibly free-running circadian rhythm.(ABSTRACT TRUNCATED AT 250 WORDS)

Biological Evolution↗

Consistent synchronization and circaseptennian (about-7-yearly) modulation of circannual gonadal index rhythm of three marine invertebrates.

A circannual rhythm in mean gonadal weight, expressed as percentage of overall body weight, is quantified by cosinor and linear-nonlinear least-squares rhythmometry in three marine invertebrates. Data series from the purple sea urchin (Strongylocentrotus purpuratus), a mollusk, the black chiton (Katharina tunicata), and the ochre sea star (Pisaster ochraceus), exhibiting circannual periods of 368, 361, and 365 days, have relatively tight 95% limits of 356-387, 356-367, and 359-371 days, respectively, when scrutinized by nonlinear least-squares rhythmometry. These limits overlap a precise year (365.25 days). This findings supports the occurrence of a 1 year-synchronized circannual rhythm in these marine invertebrates. For the ochre sea star, the about-yearly timing of greatest gonadal weight in relation to body mass, analyzed for a circannual rhythm by the fitting of a 1-year cosine to the data, remains virtually identical within 30 years. The 95% confidence intervals of the acrophase for mean gonadal weight (as percentage of body weight), range from March 3 to April 12 in the 1950s and from March 8 to April 12 in the 1980s. A MESOR (midline-estimating statistic of rhythm) difference may relate to geographic factors (Pacific Grove, California, from January 1954 to December 1958 vs. Terrace Point near Santa Cruz, California, from December 1978 to June 1985) that in turn may reflect a different food supply and/or temporal factors, e.g., it may result from changes in the ecology of the sea. A possible circaseptennian rhythm is only suspected in the data from the ochre star (P = 0.14); it is rigorously described for the purple sea urchin (P less than 0.001) and also detected in the black chiton (P = 0.029) in time series covering 9.5 years, from September 1953 to April 1963 for the purple sea urchin and from January 1957 to September 1966 for the black chiton. Least-squares rhythmometry (with trial periods between 1 and 15 years in 6-month increments) resolves the two (circannual and circaseptennian) components concomitantly below the 3% level of statistical significance. Nonlinear least-squares rhythmometry validates a period of 7.01 years for the purple sea urchin, although within broad 95% limits (ranging from 5.58 to 10.41 years). The life span of these marine invertebrates is not determined. One deals with a population rhythm sampled with serial independence.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Chronobiologic view of molt and longevity of Folsomia candida (Collembola) at different ambient temperatures.

A reanalysis of data published earlier indicates that the springtail, Folsomia candida, kept in continuous darkness, lengthens its intermolt interval (stadia) with age. At an environmental temperature of 21 degrees or 26 degrees C, the early stadia show an about-half-weekly or circasemiseptan interval and later stadia an about-weekly or circaseptan intermolt interval. At 15 degrees C, early stadia are about circaseptan, lengthening to nearly circadiseptan with aging. Our own studies of Folsomia candida at 23 degrees C show that the incidence of molting in 24 springtails observed at 3-hr intervals for 17 days is characterized by a prominent circadian rhythmicity and an infradian periodicity with a period of about 3 days. Both components are statistically highly significant (P = 0.001) when assessed concomitantly by least-squares rhythmometry.

Aging↗

Life span of springtail on 12-hr shifts at varying intervals of 12-hr alternation in ambient temperature.

The effect of shifts at different intervals of a regimen of quasioptimal and nonoptimal ambient temperatures alternating at 12-hr intervals was tested on the springtail, Folsomia candida. Life span data demonstrate that shifts of the temperature regimen can be optimized to prolong life rather than to shorten it or to leave it unaffected. Optimal shift intervals are 7 days apart, in keeping with the results on effects of shifts of a regimen of alternating light and darkness in a giant alga, Acetabularia mediterranea, and in the face fly, Musca autumnalis.

Acetabularia↗