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Biomedical subjects

F Halberg

Publications and source records attributed to F Halberg.

At least 109 records · Page 6Linked to original sources

Circatrigintan rectal temperature and endocrine rhythms of clinically healthy, menstrually cycling women.

Rectal temperatures were measured automatically every 10 min for part or most of two menstrual cycles in ten clinically healthy young women, 20-30 years of age, with a wearable instrument, the Polychronor. Occasional malfunction of the instrumentation resulted in corresponding gaps in the series. Data were examined by chronograms, plexograms, and chronobiologic serial sections computed with the fit of a 24-hr period, population-mean cosinor, and linear-nonlinear least-squares analyses. Single cosinor-derived circadian parameters were next fitted with a cosine curve of a period equal to the number of days of the corresponding intermenstruum. Second-order infradian inferential statistics were calculated next; the first day of menstruation was used as acrophase reference. A population-mean cosinor at the intermenstrual period yields a temperature acrophase of -279 degrees, with the 95% confidence interval extending from -254 degrees to -312 degrees. Since the intermenstruum differs in different subjects and/or in different menstrual cycles of a given woman, this acrophase corresponds to different time intervals from the first day of menstruation in different cases. This acrophase thus indicates the relative timing within the menstrual cycle of overall high rectal temperatures. On four subjects in four stages of their menstrual cycle, plasma was also obtained at 2-hr intervals around the clock. Ten hormones were determined. The sparse endocrine sampling along the menstrual cycle notwithstanding, a circatrigintan rhythm in all hormones investigated was demonstrated for a woman 26 years of age. At the period corresponding to the intermenstrual interval, the acrophases for T3, cortisol, FSH, testosterone, DHEA-S, T4, and LH occurred before the circatrigintan rectal temperature acrophase, whereas the acrophases for prolactin, estradiol, and progesterone occurred near or shortly after the rectal temperature acrophase. Whereas earlier circatrigintan mapping of adult women had been summarized on a group basis, this study allows individualized circatrigintan rhythm assessment. Circatrigintan, like circadian and circannual, acrophase and amplitude relations do not necessarily imply causal relations, yet they are an indispensable quantitative reference standard for the study of basic mechanisms and for diagnosis and intervention, including endeavors in planned parenthood that might take into account the organism's dynamics with multiple frequencies.

Adult

Bootstrapped potential circadian harbingers if not determinants of cardiovascular risk.

Among 12 endocrine variables in blood from clinically healthy adult women sampled systematically around the clock and the year, discriminant analysis methods have singled out certain hormones in certain seasons as classifiers for a high or low risk of developing diseases associated with a high circadian rhythm-adjusted mean (midline estimating statistic of rhythm, MESOR, M) of blood pressure, i.e., risk of M-hypertension (RMH). Before extending the labor intensive, costly data base, showing circadian changes with RMH, we reanalyzed available data by circadian bootstrapping, complementing earlier circannual bootstrapping. Differences in circadian M for aldosterone in all four seasons and for TSH in spring and summer (the only seasons checked), but not for the cortisol M checked in spring and summer, are validated, as are differences in circadian amplitude for TSH in spring and summer and aldosterone in spring. Identification of classifiers provides cost-effective, time-specified endocrine checks complementing the targeted automatic monitoring of blood pressure as part of a system of chronobioengineering for health maintenance.

Adolescent

Ultradian rhythmometry by adaptive line enhancer.

Widrow's adaptive line enhancer (ALE) was applied to human rectal temperatures at 12-min intervals for 9 days. Changes along the scale of 9 days in circadian pattern suggested the occurrence of infradian variation, resolved by analyses of the entire series by linear-nonlinear rhythmometry. Once the original signal is filtered to extract the circadian component, ultradian components appear. A wide peak with a period of about 100 min, seen each day, may reflect a consistent ultradian component. Other peaks at lower ultradian frequencies (around a period of approximately 8 hr) are unsteady and may correspond to harmonics of the partially extracted circadian oscillation. Ultradian components with periods of approximately 131 and approximately 68 min were also suggested independently by population-mean cosinor summarizing data collected over a total of 158 days. Results show the ability of ALE to detect and reconstruct periodic components in noise and to track their changes in frequency, notably when other methods are also used to assess separately the components and the corresponding uncertainties involved.

Biometry

Circadian rhythm of gastric acid secretion in men with active duodenal ulcer.

Twenty-one men with active duodenal ulcer underwent hourly gastric acid and 4-hourly plasma collections under fasting conditions. A statistically significant circadian rhythm was demonstrated for the group by population-mean cosinor analysis, a statistical technique designed for time-dependent measurements, for the 24-hr acid secretory output but not for plasma gastrin concentration. These findings are compatible with the interpretation that the circadian rhythm of unstimulated gastric acid secretion, here observed in most patients of the active ulcer group and previously reported for a group of healthy subjects, does not depend critically upon a circadian-rhythm change in plasma gastrin. Chronobiologic statistical techniques add an important quantitative element to the time-dependent measurement of gastrointestinal function of which one example is gastric acidity, with high rates occurring during the evening and low ones in early morning.

Adult

Does Gonyaulax polyedra measure a week?

Cell communication was investigated in Gonyaulax polyedra by mixing two cultures grown on opposite lighting regimens, as reported in a companion paper. Herein, using the same data, 7-d (circaseptan) rhythms are also shown to characterize the luminescence of this cellular organism. A fraction of a culture of G. polyedra, grown in 12 h of light (L), alternating with 12 h of darkness (D), was exposed for 3 d to an LD-shift by 11 h. The circadian glow rhythm was compared under free-running conditions (LL) for cultures previously kept on the two differing LD regimens and for mixed cultures. A circaseptan modulation of the circadian amplitude is detected in cultures that had not undergone an LD shift and in some of the mixed cultures, but not in the shifted cultures. A statistically significantly lower circaseptan amplitude (less than 50%) and acrophase advance of over 120 degrees or 56 h (p less than 0.001) characterizes the mixed cultures, as compared to the original unshifted cultures, a finding that could mean that G. polyedra communicates along a circaseptan frequency. Whether a prior phase-shift known to affect circaseptan behavior in another unicell, Acetabularia mediterranea, led to an alteration of the time structure of G. polyedra remains an interesting subject for further study in this model, a model attractive to students of unicellular rhythms and underlying mechanisms that henceforth should be studied at multiple circadian and circaseptan frequencies. Circadian and circaseptan interrelations can both serve as markers for mechanisms of intercellular communication.

Animals

Circadian rhythm and diurnal excursion of plasma cortisol in diabetic pregnant women.

The effect of type I and II diabetes in pregnancy on the circadian rhythm and diurnal excursion of plasma cortisol was studied in the second and third trimesters and post partum. Cosignor analysis demonstrated persistence during gestation of the significant circadian rhythm of the nonpregnant state. As previously reported in control pregnancies, plasma cortisol levels (24-hour mean, nadir, peak, and nadir-peak excursion) increased during gestation while the relative excursion of cortisol (expressed as the percent deviation from the 24-hour mean) was blunted. No significant difference was found between diabetic groups or when diabetic groups were compared with control subjects. Nocturnal hypoglycemia was common among diabetic women during pregnancy and post partum. Although these episodes were usually asymptomatic, the mean concomitant cortisol levels were increased over the corresponding cortisol levels of nonhypoglycemic diabetic and control subjects. We conclude that differences between control and type I and II diabetic subjects in carbohydrate tolerance or glycemic excursion are not explained by differences in cortisol levels or rhythm. The pregnancy-associated blunting of the excursion of cortisol is consistent with an autonomous source of adrenocorticotropin. Asymptomatic nocturnal hypoglycemia is common in insulin-requiring diabetic women and is associated with increased cortisol secretion.

Circadian Rhythm

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

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

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

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

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

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

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

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

[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