Variations in cell yield and proliferative activity of human bone marrow (BM) progenitor cells were determined with flow cytometry along the 24‐h (circadian) time scale. Equal volumes of BM were aspirated every 5 h, altogether 5 times in 5 healthy men. An average 6‐fold higher yield of positive selected CD34+ cells occurred in each subject when BM was aspirated during the daytime and late afternoon, while a lower yield occurred during the night. Using all CD34+ cell yield data normalized to percentage of mean, a significant time–effect was found by ANOVA (p=0.02) and a significant circadian rhythm was detected by the least‐squares fit of a 24 h cosine (p=0.02). The 95% confidence limits of the acrophase (time of highest values) were computed to be at midday between 10:24 and 14:48 h. A highly significant correlation (p=0.001) was found between proliferation of positive selected CD34+ cells and the more mature myeloid precursor cells from the same BM aspirates, suggesting a common temporal pattern along the circadian time scale. However, no correlation was demonstrated between proliferation and cell yield of CD34+ selected cells, suggesting that mechanisms other than variation in proliferation may cause the circadian rhythm in stem cell yield. These circadian variations in stem cell yield and proliferation suggest that proper timing within 24 h may potentially be important regarding outcome from progenitor cell harvesting and treatment with haematopoietic growth factors.

Summary Seasonal variation has been described in the presentation and growth of several malignant tumours, including cancers of the breast, uterus, uterine cervix, urinary bladder, liver, lymphatic system and skin, although the mechanisms are not known. We herein describe a circannual rhythm for thyroid cancer (total = 2627), with significantly more cases presenting during the late autumn and winter. In a subset of these cases (127 papillary carcinomas), significant seasonal variations with highest values in autumn-winter were found for tumour diameter and proliferation indicators (S-and G2M-phase fractions). These results indicate the likelihood of a seasonal factor (or factors) of importance for the regulation and modification of tumour cell proliferation. When further clarified, this might be of relevance for the planning of diagnostic and therapeutic strategies.Keywords: thyroid cancer; season; tumour diameter; proliferation; %S-phase-%G2M-phase Biological rhythms, especially circadian (24 h) and circannual (12 months), have been found in a wide range of physiological parameters and normal tissues (Aschoff, 1981; Shifrine et al, 1982;Halberg et al, 1983;Lerum et al, 1988;Sothem et al, 1995). Regarding seasonal variations, higher incidence of female breast cancer has been reported for the spring and summer (Cohen et al, 1983;Mason et al, 1985), and circannual contrasts have also been found for other tumours (Newell et al, 1985;Swerdlow, 1985; Hermida and Ayala, 1996). As for the thyroid, some studies have reported seasonal variations in endocrine parameters, with variables such as T3, T4 and thyroid-stimulating hormone (TSH) being higher in the autumn or winter (Halberg et al, 1981;Nicolau et al, 1987;Haus et al, 1988). As seasonal variations might be of potential interest for the detection and management of thyroid carcinomas, we wanted to review this group of tumours, most of which are slowly growing and have a good prognosis. MATERIALS AND METHODS PatientsDuring the period 1970-85, 2627 patients with thyroid cancer were reported to the Cancer Registry of Norway. Of these, 10% (n = 263) were surgically treated at the Department of Surgery, Haukeland University Hospital, in the period 1971-85. There were no major differences in the distribution of sex, age and histological types between our hospital cases and cases in the population-based Cancer Registry (Akslen and Myking, 1992 subtyping of malignant tumours according to the 1988 WHO criteria, 127 of these cases were found to represent papillary thyroid carcinomas with a diameter greater than 10 mm (microcarcinomas < 10 mm were excluded). These 127 cases were included for further studies of seasonal variations with reference to time (month) of diagnosis, largest diameter of the primary tumour and proliferation indicators (S-phase and G2M-phase fractions). Most of these patients (93%) were treated with total or near-total thyroidectomy. Regarding time of diagnosis, the date of initial histological/cytological diagnosis was used for both the registry (n = 26...

In order to confirm the presence of an acrophase difference based upon genotype in the seasonal expression of an immune competence end point, splenic plaque-forming cell (PFC) response to sheep red blood cells (SRBC), female B6C3F1 and CD1 mice were concurrently studied for PFC response during two studies performed in each season for 1 year. Mice were multiply housed, fed ad libitum, and standardized to light (06:00-18:00); dark (18:00-06:00). For each strain and study, subgroups were either naive (n = 10), received a vehicle (n = 10) or Cytoxan (n = 5). Challenge with SRBC occurred in early afternoon 4 days before harvesting of spleens and PFC assay. All other procedures were performed early in the daily light span. Analysis of variance and single cosinor analysis revealed a significant seasonal time effect for PFC in naive mice of both strains. Antibody formation was greatest in spring for CD1 mice and in summer for the B6C3F1 mice. These acrophases were consistent with earlier results for both strains and show the phenomena to be reproducible and genetically based.

Circadian variation in the circulating concentrations of the N-terminal and C-terminal portions of the atrial natriuretic factor prohormone (pro ANF) was evaluated in 8 men, ages 41-47, who have been followed for 19 years with respect to circadian variation in physiological variables including blood pressure and clinical chemistries. The N-terminus of the ANF prohormone contains two peptides consisting of amino acids 1-30 and 31-67 while the C-terminus contains 1 peptide (amino acids 99-126) of this 126 amino acid prohormone which lower blood pressure and have natriuretic properties. To determine if either the N-terminus and/or the C-terminus of the prohormone have a circadian variation in their circulating plasma concentrations these 8 men had blood samples obtained for radiommunoassay every 3 hr during a 24-hr period. Three radiommunoassays which immunologically recognize (1) the whole N-terminus (i.e. amino acids 1-98), (2) the midportion of the N-terminus (amino acids 31-67) and (3) the C-terminus (amino acids 99-126) of the ANF prohormone were utilized. The whole N-terminus, the midportion of the N-terminus which circulates after being proteolytically cleaved from the rest of the N-terminus, and the C-terminus each had a peak circulating concentration between 0400 and 0700 which were significantly (P less than 0.001) higher than their concentrations at any other time throughout the 24-hr period.(ABSTRACT TRUNCATED AT 250 WORDS)

Twenty healthy athletes exercised for 30 min at four different times (beginning at 1130 and 1630) in December (darkness period) and in April (18 h of daylight). Four hours after intake of a standardized meal, a 30-min bike exercise with an intensity of 60% maximal O2 uptake was performed. Blood samples (fingertip) were drawn at 1, 5, 10, and 30 min into exercise and 5, 10, and 30 min after termination of exercise for determination of blood glucose. Glucose values were normalized by reexpressing each as a percentage of the starting value. The total area under the glucose-time curves as well as the area below the starting value was calculated. Areas were tested for the effect of sex, time of day, and season by analysis of variance. For the group as a whole during exercise, a significant effect was found by analysis of variance for sex, time of exercise, and season. During recovery, significant differences were found for sex and time of exercise but not for season. The minimal integrated glucose response to exercise occurred in females, who also showed the most rapid return to baseline values during the recovery period. Exercise in the morning produced the smallest glucose response for both sexes and faster recovery compared with exercise in the afternoon. This was also the case overall for exercise in December compared with April. This finding implies that the glycemic response may be influenced by season and timing of exercise, which may be of importance for athletes involved in vigorous training and patients with diabetes mellitus.