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Biomedical subjects

E Haus

Publications and source records attributed to E Haus.

At least 73 records · Page 4Linked to original sources

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↗

Influence of minor thermal injury on expression of complement receptor CR3 on human neutrophils.

Thermal injury is well known to inhibit functions of the circulating neutrophil related to its role in host defense against infection, but the mechanism(s) of this phenomenon are not fully understood. To gain further clues to these mechanisms, the authors have studied patients with thermal injury in terms of altered expression of neutrophil cell membrane receptors for the opsonic complement-derived ligand C3bi--complement receptor Type 3, or CR3. CR3 expression was selected for study because an increase in the number of receptors on the cell surface can be stimulated by products of complement activation known to accumulate after thermal injury and because of the role of CR3 in phagocytic and adherence functions of the neutrophil. Expression of CR3 was monitored semiquantitatively by flow cytometry with the use of a murine monoclonal antibody (OKM1) specific for an antigen (CD11) associated with this receptor. Patients evaluated were limited in this study to those with minor degrees of thermal injury (second-degree burn involving less than 20% of total body surface area) so that possible confounding effects of major injury and its complications could be eliminated. It was observed that patient neutrophil CR3 becomes significantly up-regulated during the first week, as early as 1 day after injury. The maximum level of expression of CR3 averaged greater than 150% (range, 70-314%) of the respective minimum level observed for each patient. The minimum levels of expression of CR3 on patient neutrophils, reached 11-37 days after injury for 7 of 8 patients, were comparable to the level of expression of CR3 on unstimulated control neutrophils. Such temporal up-regulation of patient neutrophil CR3 suggests the early generation of stimuli of CR3 mobilization in response to thermal injury. Increased numbers of CR3 on patient neutrophils may augment microbicidal function and enhance or inhibit delivery of cells to the burn site.

Adult↗

Circadian endocrine time structure in humans above 80 years of age.

The circadian rhythms in blood hormone concentrations of 17 pituitary, adrenal, pancreatic, testicular, and thyroid hormones were determined in 9 women and 5 men 81 to 91 years of age. Six samples over a 24-hr span were studied for each hormone. Even with the small sample available, 9 of the 17 hormones determined showed a statistically significant circadian rhythm as a group phenomenon (prolactin, estradiol, 17-hydroxyprogesterone, insulin, C-peptide, thyroid stimulating hormone, aldosterone, cortisol, dehydroepiandrosterone sulfate). No rhythm detection by population mean cosinor analysis at the .05 level was obtained in this relatively small group of subjects for adrenocorticotropic hormone, follicle stimulating hormone, growth hormone, luteinizing hormone, triiodothyronine, thyroxine, progesterone (determined in women only) and testosterone (determined in men only).

Adrenocorticotropic Hormone↗

Circannual variation of intestinal cell proliferation in BDF1 male mice on three lighting regimens.

BDF1 male mice were studied over a 24-hr span in winter, spring, summer and fall. For three weeks prior to study, one-third of the animals were kept under a lighting regimen of 8 hr light alternating with 16 hr of darkness (LD 8:16), one-third on a lighting regimen of LD 12:12 and a remainder on a lighting regimen of LD 16:8. During each study, subgroups of animals on all three lighting regimens were killed at 4-hr intervals over a 24-hr span. Twenty minutes prior to being killed, the animals received 5 microCi of [3H]-thymidine/0.2 ml/20 gm of body weight intraperitoneally. The thymidine uptake in the DNA of the colon and of the small intestine were studied as an index of cell proliferation. A circadian rhythm in [3H]-thymidine uptake in the colon was found and validated by cosinor analysis. This rhythm was similar in acrophase and amplitude in the animals kept on LD 8:16 and LD 12:12. Also in the mice on LD 16:8, there was a statistically significant circadian rhythm of [3H]-thymidine uptake in the DNA of the colon during all four seasons. The acrophases of this rhythm, however, varied widely suggesting free running. A circadian rhythm of [3H]-thymidine uptake in small intestine was less consistent. In animals on all three lighting regimens, however, a circannual variation of [3H]-thymidine uptake in DNA in colon and small intestine was found with the highest uptake during summer. This study indicates that a lighting regimen of LD 16:8 does not reliably synchronize the circadian rhythm of [3H]-thymidine uptake in the colon. It further shows a circannual rhythm of this function in the colon and in the small intestine which persists under three lighting regimens (LD 8:16, 12:12 and 16:8) maintained for three to four weeks prior to being killed.

Animals↗

Circadian and circannual rhythms of hormonal variables in elderly men and women.

A group of fourteen men (73 +/- 5 yr of age), and eighteen women (77 +/- 7 yr of age) institutionalized at the Berceni Clinical Hospital, Bucharest, Romania, were studied over a 24-hr span once during each season (winter, spring, summer and fall). All subjects followed a diurnal activity pattern with rest at night and ate three meals per day with breakfast at about 0830, lunch at about 1300 and dinner at about 1830. The meals were similar, although not identical for all subjects during all seasons. On each day of sampling blood was collected at 4-hr intervals over a 24-hr span. Seventeen hormonal variables were determined by radioimmunoassay. Statistically significant circadian rhythms were detected and quantitated by population mean cosinor analysis in pooled data from all four seasons in both sexes for ACTH, aldosterone, cortisol, C-peptide, dehydroepiandrosterone-sulfate (DHEA-S), immunoreactive insulin, prolactin, 17-OH progesterone, testosterone, total T4 and TSH. In women, estradiol and progesterone also were determined and showed a circadian rhythm during all seasons. Total T3 and FSH showed circadian rhythm detection by cosinor analysis in the men only; LH showed no consistent circadian rhythm as group phenomenon in men or women. A circannual rhythm was detected using the circadian means of each subject at each season as input for the population mean cosinor in the women for ACTH, C-peptide, DHEA-S, FSH, LH, progesterone, 17-OH progesterone and TSH. In the men, a circannual rhythm was detected for ACTH, FSH, insulin, LH, testosterone and T3. There were phase differences between men and women in ACTH, FSH and LH. In those functions in which both the circadian and circannual rhythms were statistically significant, a comparison of the amplitudes showed in the women a higher circannual rather than circadian amplitude for DHEA-S. In 17-OH progesterone, TSH and C-peptide, the circadian amplitude in women was larger. In men, the circannual amplitude of T3 was larger than the circadian amplitude and in insulin the circadian amplitude was larger than the circannual amplitude. There was no statistically significant difference between the circadian and circannual amplitudes in the women in ACTH and progesterone and in the men in ACTH and testosterone.

Aged↗

Chronobiology in hematology and immunology.

The hematopoietic and the immune systems in all their components are characterized by a multifrequency time structure with prominent rhythms in cell proliferation and cell function in the circadian, infradian, and rhythms in cell proliferation and cell function in the circadian, infradian, and circannual frequency ranges. The circulating formed elements in the peripheral blood show highly reproducible circadian rhythms. The timing and the extent of these rhythms were established in a clinically healthy human population and are shown as chronograms, cosinor summaries and, for some high-amplitude rhythms, as time-qualified reference ranges (chronodesms). Not only the number but also the reactivity of circulating blood cells varies predictably as a function of time as shown for the circadian rhythm in responsiveness of human and murine lymphocytes in vitro to lectin mitogens (phytohemagglutinin and pokeweed mitogen). Some circadian rhythms of hematologic functions appear to be innate and are presumably genetically determined but are modulated and adjusted in their timing by environmental factors, so-called synchronizers. Phase alterations in the circadian rhythms of hematologic parameters of human subjects and of mice by manipulation of the activity-rest or light-dark schedule and/or of the time of food uptake are presented. Characteristically these functions do not change their timing immediately after a shift in synchronizer phase but adapt over several and in some instances over many transient cycles. The circadian rhythm of cell proliferation in the mammalian bone marrow and lymphoid system as shown in mice in vivo and in vitro may lend itself to timed treatment with cell-cycle-specific and nonspecific agents in an attempt to maximize the desired and to minimize the undesired treatment effects upon the marrow. Differences in response, and susceptibility of cells and tissues at different stages of their circadian and circaseptan (about 7-day) rhythms and presumably of cyclic variations in other frequencies are expected to lead to the development of a chronopharmacology of the hematopoietic and immune system. Infradian rhythms of several frequencies have been described for numerous hematologic and immune functions. Some of these, i.e., in the circaseptan frequency range, seem to be of importance for humoral and for cell mediated immune functions including allograft rejection. Infradian rhythms with periods of 19 to 22 days seem to occur in some hematologic functions and are very prominent in cyclic neutropenia and (with shorter periods) in its animal model, the grey collie syndrome.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Circadian as well as circannual rhythms of circulating aldosterone have decreased amplitude in aging women.

Age differences in the characteristics of the circadian rhythm in circulating radioimmunoassayable aldosterone were studied on nine 20 to 26 year-old and ten 70 to 78 year-old women and ten 23 to 26 year old and ten 70 to 80 year old men in Würzburg, West Germany. These diurnally active-nocturnally resting subjects were sampled every 3 hours for 15 hours. A classical analysis of variance and a multivariate analysis of rhythm characteristics revealed major effects of age exerted on the circadian aldosterone amplitude in women (p = 0.003) but not in concomitantly sampled men. These observations complement the study of circadian and circannual rhythms in 8 young adults (15-21 years), 10 mature adults (29-36 years) and 10 post-menopausal (44-59 years) North American women, sampled at 100 minute intervals for 24 hours, once in each season, and document that the adrenocortical aldosterone-producing system remains rhythmic with at least two frequencies up to the late decades of human life, although in women it may be characterized by a reduction in the extent of spectral change after 70 years of age.

Adult↗

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↗

Comparison of circadian rhythms of the renin-angiotensin-aldosterone system and electrolytes in clinically healthy young women in Fukuoka (Japan) and Minnesota (USA).

Circadian rhythms of the renin-angiotensin-aldosterone (R-A-A) system and electrolytes were evaluated in young healthy Fukuokan (Japan) and Minnesotan (USA) women. A similar protocol was used and each group remained on its usual diet. Blood was taken for 24 h at 4 h intervals from 8 a.m. during which time urine samples were also collected. The determinations in both groups were made in a laboratory in Japan. Plasma renin activity, plasma aldosterone concentration and aldosterone excretion rate showed similar circadian rhythms in both groups. However, those values at each sampling time and each span were always significantly higher in the Americans while the urinary Na and Cl excretions and blood pressure were higher in Japanese. The significant differences in the R-A-A system and blood pressure levels between these two groups may be due to the large amount of salt consumed by the Japanese.

Adult↗

Change in phase relations of circadian rhythms in cell proliferation induced by time-limited feeding in BALB/c X DBA/2F1 mice bearing a transplantable Harding-Passey tumor.

The synchronization of the circadian rhythms of [3H]thymidine uptake (as gauge of DNA synthesis and presumably of cell proliferation) in colon, thymus, and Harding-Passey melanoma were studied in 456 male BALB/c X DBA/2F1 mice under a 12-hr-light, 12-hr-dark regimen. In two groups of animals, the feeding time was restricted to 4 hr/day (either at the beginning of the light span or at the beginning of the dark span). The circadian rhythms in body temperature and [3H]thymidine uptake in the colon were determined in their timing primarily by the time of food intake. In contrast, the circadian rhythm of [3H]thymidine uptake in the thymus and in the transplanted melanoma remained synchronized with the lighting regimen, and under the conditions of this study, was not altered in its timing by the change in feeding time. It thus appears feasible to alter the phase relations between certain circadian rhythms of host and tumor. If applicable to the human situation, this observation might be of interest for the scheduling of chemo- and radiotherapy, in an attempt to obtain maximal effects upon the tumor with minimal undesired side effects upon vital functions of the host.

Animals↗

Lethal nephrotoxicity and hematologic toxicity of cis-diamminedichloroplatinum ameliorated by optimal circadian timing and hydration.

Three hundred and forty-one female F344 (Fischer) rats were kept in light for 8 hr alternating with darkness for 16 hr; some were observed for survival for 21 days, while others were killed for blood sampling 4.5 days after a single intraperitoneal (i.p.) injection of 11 mg/kg cis-diamminedichloroplatinum (cis-DDP). cis-DDP was administered with or without concomitant i.p. saline load at one of six equispaced circadian stages. This high dose of cis-DDP resulted in marked lethal and renal toxicity, but in a moderate bone marrow suppression. Blood urea nitrogen (BUN), circulating total white blood cell counts (WBC) and survival times revealed statistically significant circadian rhythms of drug toxicity (P less than 0.03). Optimal tolerance for cis-DDP gauged by these three variables resulted from drug administration in the second half of the dark span. Renal tolerance for cis-DDP guaged by BUN was improved two-fold by appropriate drug timing. This benefit from drug timing alone was further improved two-fold if hydration and cis-DDP were given at the optimal circadian stage. Hydration-induced ameloriation of cis-DDP nephrotoxicity requires time qualification of both hydration and cis-DDP.

Animals↗

Circadian rhythm in urinary N-acetyl-beta-glucosaminidase (NAG) of clinically healthy subjects. Timing and phase relation to other urinary circadian rhythms.

Urinary N-acetyl-beta-glucosaminidase (NAG), a lysosomal enzyme of renal tubular origin, has been shown to be a sensitive indicator of renal tubular function. This study documents a circadian rhythm in the urinary activity of NAG, statistically validated and quantified by the cosinor method, in 19 female and 15 male human subjects. The acrophase of the circadian rhythm in urinary NAG activity occurs at 09(40) with 95% confidence limits between 08(40) and 12(08) and is similar to the timing of the circadian rhythm in urinary free cortisol. The circadian acrophase of urinary NAG activity lags in timing the circadian rhythms in urine volume, Na and K excretion, and urinary free adrenalin and noradrenalin, by about five to ten hours and the circadian rhythm in creatinine excretion by about 11 hours. These functions with their characteristic phase relations are part of the internal circadian time structure of the human organism, and may provide internal phase references, independent of the "time of day." This study also documents a sex difference in mesor of the circadian rhythms in urinary NAG activity, with female subjects having a higher mesor and amplitude than the male subjects, and in the excretion of creatinine and potassium, with male subjects having a higher mesor and amplitude than the female subjects.

Acetylglucosaminidase↗

Lithium delays biochemical circadian rhythms in rats.

Recent evidence has indicated that a fast circadian oscillator or pacemaker might contribute to affective illnesses, particularly manic depressive disease. In order to test the hypothesis that lithium exerts its therapeutic effect by slowing or delaying overly fast circadian rhythms, 95 rats were fed a lithium-containing diet for a period of 3-4 weeks, and 91 rats were fed a control diet. The animals were sacrificed at times around the clock. Eight of the eleven substances measured (plasma prolactin, PTH, corticosterone, and aldosterone, serum calcium and magnesium, and cerebellar calcium and magnesium) showed large delays in their circadian rhythms in the lithium-fed rats. This supports the hypothesis that lithium's therapeutic action is to delay overly fast circadian rhythms.

Animals↗

Toward chronobiologic pattern discrimination of the risk of developing breast cancer and other diseases.

With a view of the prevention as well as treatment of cancer and other diseases, it is important to quantify health positively and on an individual basis by chronobiologic methods. These include the assessment of the characteristics of certain circadian, circannual and other endocrine rhythms and trends, for the recognition of risk (prior to the occurrence of a given disease) by an alteration of the same rhythm characteristics and even by a time-specified single sample. With this aim in mind, a small number of selected (rather than randomly picked) women of 3 age groups was extensively sampled for 12 plasma hormones around the clock and the calendar, in 2 geographic locations. Such data revealed correlations of the familial risk of developing breast cancer with the circannual amplitudes of circulating prolactin and TSH. The risk of several other conditions was also correlated with hormonal rhythm characteristics; for example, the risk of developing diseases associated with a high blood pressure was correlated with the circannual amplitude of plasma aldosterone. The mapping of circannual characteristics, however, is time-consuming and costly and may not be warranted as a first step, for example when a physician is not in a position to wait for a year to make a diagnosis. With the possibility in mind that sampling requirements may be reduced to one or at most two samples, a chronobiologic pattern discrimination analysis was undertaken on the original data from young adults. The results are presented to indicate the method and to suggest the singling-out of certain variables for further testing on a larger, properly stratified and randomized sample, rather than as definitive results. Different classifiers and different corresponding reference values from variables that undergo circadian and circannual rhythms may perhaps withstand the test (and, with Vergil, the tooth) of time. If so, reference values that are time-specified may well prove to be a sine qua non in the assessment of certain neuroendocrine aspects of developing certain diseases, including breast cancer.

Adolescent↗

Reduction of cis-diamminedichloroplatinum nephrotoxicity in rats by optimal circadian drug timing.

A prominent circadian rhythm in the nephrotoxicity of a therapeutic dose of cis-diamminedichloroplatinum (cisplatin) is demonstrated in female Fischer rats. Rats were randomized to receive two doses of either cisplatin or 0.9% NaCl solution 14 days apart at the times of either high or low values in their circadian rhythm of urinary volume. Toxicity was assessed by measuring changes in body weight and changes in the 24-hr means of urinary volume, blood urea nitrogen, and urinary beta-N-acetylglucosaminidase (NAG) activity. Toxicity was least in rats which received the drug near the circadian maximum of urinary volume. Conversely, rats which received the same dose of drug near the circadian minimum of urinary volume lost more weight and exhibited a 2-fold increase in the 24-hr mean of urinary volume, a 3-fold rise in the 24-hr mean of blood urea nitrogen, and a 5-fold increase in the 24-hr mean of urinary NAG activity. A positive correlation between urinary NAG at the time of cisplatin administration and the extent of cisplatin nephrotoxicity was demonstrated (p less than 0.02). A correlation also was found between tissue NAG concentration and tissue uptake of cisplatin (p less than 0.001). A marked circadian rhythm of NAG activity in proximal tubular cells may contribute to the prominent circadian rhythm in murine renal tolerance for cisplatin.

Acetylglucosaminidase↗

[Plasma cortisol concentrations and circadian rhythm in healthy young Japanese and caucasians (author's transl)].

We report herein a method of solid-phase radioimmunoassay (RIA) for assessment of plasma cortisol concentration using 125I-labeled ligand [CORTCTK-125]. Plasma cortisol concentrations and its circadian rhythm in healthy young Japanese and American whie women were also evaluated using CORTCTK-125. Nineteen Japanese women, of an average age of 20.3 +/- 0.1 years, and 12 Caucasians of mixed ethnic origin (Minnesota), average 20.0 +/- 0.5 years, were studied using a similar protocol. The distribution of the menstrual stage of the two groups was similar. Blood was drawn from each subject into EDTA containers at 4-hour intervals starting at 0800 on one day and was continued for the ensuing 24 hours. The samples were immediately placed in a refrigerated centrifuge at 4 degrees C, and then stored at -20 degrees C until the assay. The samples from Minnesota were packed in dry ice and brought by air to Japan. Determinations of plasma cortisol concentration in samples from both groups were carried out at Kyushu University. Advantages of the solid-phase RIA method are as follows: (1) 0.05 ml of plasma or serum was sufficient for determination of plasma cortisol concentrations, (2) no other solvents or solutions for the extraction or purification were required, (3) the procedure was simple and readily facilitated, and (4) the concentration of cortisol in heparin-plasma was somewhat higher than that in serum or EDTA-plasma, but there was no statistical difference. Plasma cortisol concentrations in the samples from the Japanese (19.73 +/- 1.44 on the first and 18.94 +/- 1.32 microgram/dl on the second day) and that of the American group (17.48 +/- 2.38 and 19.37 +/- 2.16 microgram/dl, respectively) at 0800 was similar. The average value of 7 determinations at 4-hour intervals was 11.01 +/- 2.00 microgram/dl in the Japanese and 10.29 +/- 1.05 microgram/dl in the American group. A remarkable and similar circadian rhythm was observed in both groups with a peak at 0800 and with nadirs at 2000 in the Japanese (4.80 +/- 0.45 microgram/dl) and 2400 in the American group (5.18 +/- 0.83 microgram/dl). There were statistically significant differences between the values at the peak and the nadir. The related subjects were then classified into Group-F (9 subjects) and Group-T (9); the former included high body mass index [BMI: body weight(kg)/body height(m)2] of more than 24.0, and the latter included a relatively lower BMI of less than 21.5. The circadian rhythm of both groups revealed a similar pattern, whereas plasma cortisol concentration was always higher in Group-F than in Group-T, at all 7 determinations. There were no significant differences except for the value at 0400. Furthermore, the average values of plasma cortisol concentration and circadian rhythm were compared; the group with a larger body surface area (BSA) (Group-L) and the group with a smaller BSA (Group-S). No difference was found in the plasma cortisol concentration of Group-L and -S, and the circadian rhythm was similar in both groups...

Adult↗