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Biomedical subjects

R B Sothern

Publications and source records attributed to R B Sothern.

At least 19 recordsLinked to original sources
PubMed2002

Non-linear relation of heart rate variability during exercise recovery with local geomagnetic activity.

Heart rate variability (HRV) during 30 minute's recovery from a 30-minute exercise was established for 6 healthy men 23-30 years old. The exercise-recovery schedule was performed at 8 circadian stages over 11 days for each subject and analyzed over consecutive 5-minute segments. The local K index for the time of the recovery was recorded as a variable for geomagnetic activity. Pooling all HRV values across the different times into recovery, the relation of HRV to local K is found to be non-linear. A quadratic model fitted to the pooled HRV values is statistically significant. The present study indicates that during recovery from exercise, the effect of geomagnetic disturbances on HRV is non-linear. A non-linear relation of HRV with respect to geomagnetic activity deserves further work to determine whether it can account for discrepant findings of an effect of magnetic storms on the incidence of myocardial infarctions, for which a decreased HRV is a predictor.

Adult↗
PubMed2002

Rhythmic variations in pain, stiffness, and manual dexterity in hand osteoarthritis.

OBJECTIVE: To explore circadian variation in pain, stiffness, and manual dexterity in patients with hand osteoarthritis (OA). METHODS: Twenty one patients with hand OA, as defined by ACR criteria (17 women, four men, mean age 62.2 years, range 52-74 years) self rated pain and stiffness on separate 10 cm horizontal visual analogue scales and performed bead intubation coordinometry (BIC) six times each day (on waking up, at bedtime, and every four hours in between) for 10 consecutive days. Each series (using data with the trend removed if there was a significant trend) was analysed for circadian rhythmicity by a cosine vector technique (single cosinor). With individual data expressed as the percentage of the mean, group rhythm characteristics at period 24 hours were summarised for each variable by population mean cosinor analysis. RESULTS: Individual analyses identified significant circadian rhythms at p<or=0.05 for pain (n=15/21), stiffness (n=16/20), and dexterity (n=18/21), and a significant circadian rhythm on a group basis was identified for pain (p=0.013), stiffness (p<0.001), and dexterity (p<0.001). Pain was least at 1610 and stiffness at 1618. Peak dexterity occurred in mid-afternoon at 1548 and occurred within the 95% confidence interval of least pain (1312-1800) and stiffness (1520-1732). CONCLUSIONS: Dexterity was influenced by the patient's level of pain or stiffness, which changed systematically throughout the day. Similar results have been previously reported in 14 patients with rheumatoid arthritis where peak dexterity occurred at 1544 and at 1528 in 14 age and sex matched healthy controls. The predictability of rhythmic variation in pain, stiffness, and dexterity has implications for scheduling activities of daily living and for timing antirheumatic drug treatment.

Aged↗
PubMed2001

Circadian expression of clock genes in human oral mucosa and skin: association with specific cell-cycle phases.

We studied the relative RNA expression of clock genes throughout one 24-hour period in biopsies obtained from the oral mucosa and skin from eight healthy diurnally active male study participants. We found that the human clock genes hClock, hTim, hPer1, hCry1, and hBmal1 are expressed in oral mucosa and skin, with a circadian profile consistent with that found in the suprachiasmatic nuclei and the peripheral tissues of rodents. hPer1, hCry1, and hBmal1 have a rhythmic expression, peaking early in the morning, in late afternoon, and at night, respectively, whereas hClock and hTim are not rhythmic. This is the first human study to show a circadian profile of expression for all five clock genes as documented in rodents, suggesting their functional importance in man. In concurrent oral mucosa biopsies, thymidylate synthase enzyme activity, a marker for DNA synthesis, had a circadian variation with peak activity in early afternoon, coinciding with the timing of S phase in our previous study on cell-cycle timing in human oral mucosa. The major peak in hPer1 expression occurs at the same time of day as the peak in G(1) phase in oral mucosa, suggesting a possible link between the circadian clock and the mammalian cell cycle.

ARNTL Transcription Factors↗
PubMed2001

Geomagnetic activity influences the melatonin secretion at latitude 70 degrees N.

Factors other than light may affect variations in melatonin, including disturbances in the geomagnetic field. Such a possibility was tested in Alta, Norway, located at latitude 70 degrees N, where the aurora borealis is a result of large changes in the horizontal component (H) of the geomagnetic field. Geomagnetic disturbances are felt more strongly closer to the pole than at lower latitudes. Also noteworthy in Alta is the fact that the sun does not rise above the horizon for several weeks during the winter. To examine whether changes in geomagnetic activity influence the secretion of melatonin, saliva was collected from 25 healthy subjects in Alta several times during the day-night and at different times of the year. Single cosinor analyses yielded individual estimates of.the circadian amplitude and MESOR of melatonin. A 3-hour mean value for the local geomagnetic activity index, K, was used for approximately the same 24-hour span. A circadian rhythm was found to characterize both melatonin and K, the peak in K (23:24) preceding that of melatonin (06:08). During the span of investigation, a circannual variation also characterized both variables. Correlation analyses suggest that changes in geomagnetic activity had to be of a certain magnitude to affect the circadian amplitude of melatonin. If large enough (> 80 nT/3 h), changes in geomagnetic activity also significantly decreased salivary melatonin concentration.

Adolescent↗
PubMed2001

Circadian characteristics of corticosterone secretion in red-backed voles (Clethrionomys gapperi).

To provide necessary background for study of stress response in red-backed voles (Clethrionomys gapperi), the circadian and ultradian rhythm in corticosterone release was characterized. Animals were maintained under a 16h light, 8h dark cycle. A total of 55 males and 46 females provided 101 independent blood samples over a 6-month span. Samples were obtained at 1h to 2h intervals during the light and at 2h intervals during the dark. Using edited data (5 values beyond the upper 95% limit were removed), a significant time effect was found by analysis of variance (ANOVA) for both sexes at P < .001. The composite single cosine best describing the circadian wave-form for each sex consisted of three components (24h, 12h, and 6h), each significant at P < .05 (overall model P < .001). The 24h mean (mesor) was about 60% higher in females than males (646 ng/mL vs. 412 ng/mL, P = .01), with amplitudes of 429 and 298 ng/mL being proportional (66% vs. 72%) to the respective mesor. The predictable range of change within a 24h span (determined by the double amplitude of a 24h + 12h + 6h cosine model) was large: It was more than 1600 ng/mL for females and more than 900 ng/ mL for males. Highest values were found during the dark phase, with the 24h acrophase located at 2h into the dark span for both sexes. With the caveat of fewer samples obtained during dark than during light, the actual peak values for females occurred at 2h and for males at 6h into the 8h dark span. These results provide baseline information about the circadian time structure for serum corticosterone in red-backed voles under normal light-dark, low-stress conditions.

Activity Cycles↗
PubMed2001

Near 10-year and longer periods modulate circadians: intersecting anti-aging and chronoastrobiological research.

Biological cycles with relatively long and some unusual periods in the range of the half-week, the half-year, years, or decades are being discovered. Their prior neglect constituted a confounder in aging and much other research, which then"flew blind" concerning the uncertainties associated with these cycles when they are not assessed. The resolution of more about 10-year and other cycles, some reported herein, replaces the admission of complete unpredictability, implied by using the label "secularity." Heretofore unaccounted-for variability becomes predictable insofar as it proves to be rhythmic and is mapped systematically to serve as a battery of useful reference values. About 10-year cycles in urinary 17-ketosteroid excretion and in heart rate and its variability, among others, are aligned with cycles of similar length in mortality from myocardial infarction. Associations accumulate between cycles of natural physical time structures, chronomes such as the 10.5-year (circadecennian) Schwabe and the 21-year (circavigintunennian) Hale cycles of solar activity, and chronomes in biota. There are about 50-year (circasemicentennian) cycles in mortality from stroke in Minnesota and in the Czech Republic and also in human morphology at birth, the latter result reducing the likelihood that these cycles are purely human made. Associations among large populations warrant long-term systematic coordinated sampling of natural physical and biological variables of interest for the design of countermeasures against already documented elevated risks of stroke, myocardial infarction, and other catastrophic diseases, notably in elderly adults. New findings will be introduced against the background of the documented value of mapping rhythms in medicine and gerontology. In both these fields, rhythms promise the seeming paradox of better care for less.

17-Ketosteroids↗
PubMed2000

Relation between circadian patterns in levels of circulating lipoprotein(a), fibrinogen, platelets, and related lipid variables in men.

BACKGROUND: A correlation has been reported between lipoprotein(a) [Lp(a)] concentration and risk for coronary artery disease. High concentrations of Lp(a) might be markers for vascular or tissue injury or might be associated with other genetic or environmental factors that can cause acute myocardial infarction. METHODS: We measured the circadian characteristics of circulating Lp(a), fibrinogen, platelets, cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol for a group of adult male volunteers who had no clinical symptoms. We obtained samples every 3 hours around the clock to assess the normal degree of variation within a 24-hour period and to test for similarities in circadian patterns and correlations with level of Lp(a). RESULTS: Each variable displayed a highly significant circadian rhythm. Lp(a), fibrinogen, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol peaked in the morning. Cholesterol and platelets peaked in the late afternoon, and triglycerides peaked in the evening. CONCLUSIONS: Although peak levels of Lp(a) and fibrinogen coincide with reported morning peak frequencies of myocardial infarction and stroke, the platelet peak appears to coincide with late afternoon peak frequencies of sudden cardiac death and fatal stroke. The data suggest that proper timing of single samples may improve the usefulness and accuracy of diagnosis, risk assessment, and therapy.

Aged↗
PubMed1999

Circadian variation in the expression of cell-cycle proteins in human oral epithelium.

At the tissue level, there is experimental and clinical data to suggest a cytokinetic coordination of the cell cycle with a greater proportion of cycling cells entering S-phase and mitosis at specific times of the day. The association of certain cell-cycle proteins with defined events in the cell cycle is well established and may be used to study the timing of cell-cycle phases over 24 hours. In this study oral mucosal biopsies were obtained from six normal human volunteers at 4-hour intervals, six times over 24 hours. Using immunohistochemistry, the number of positive cells expressing the proteins p53, cyclin-E, cyclin-A, cyclin-B1, and Ki-67 was determined for each biopsy and expressed as the number of positive cells per mm of basement membrane. We found a statistically significant circadian variation in the nuclear expression of all of these proteins with the high point of expression for p53 at 10:56 hours, cyclin-E at 14:59 hours, cyclin-A at 16:09 hours, cyclin-B1 at 21:13 hours, and Ki-67 at 02:50 hours. The circadian variation in the nuclear expression of cyclins-E (G1/S phase), -A (G2-phase), and -B1 (M-phase) with a normal physiological progression over time suggests a statistically significant circadian variation in oral epithelial cell proliferation. The finding of a circadian variation in the nuclear expression of p53 protein corresponding to late G1 is novel. This information has clinical implications regarding the timing of chemotherapy and radiotherapy.

Adult↗
PubMed1999

Circadian interrelationships among levels of plasma fibrinogen, blood platelets, and serum interleukin-6.

Circadian (24 h) rhythms of fibrinogen, interleukin-6 (IL-6), and platelet levels were studied in 11 males ages 46 to 72 years. Since there is a known circadian rhythm for fibrinogen and IL-6, we postulated that the peak level (acrophase) of fibrinogen would follow the acrophase of IL-6, based on the fact that IL-6 is the stimulus for fibrinogen production in the liver. Platelet levels were measured to show whether there was any correlation with the IL-6 acrophase because it has been reported that IL-6 affects megakaryocytes and platelets in dogs. We found that the acrophase for IL-6 occurred at 02:03 h and the acrophase for fibrinogen occurred at 09:16 h. Platelet counts peaked at 16:56 h. Thus, there was a positive correlation between IL-6 and fibrinogen acrophases and a negative correlation of each with the acrophase for platelets. The positive linkage of IL-6 with fibrinogen in this study suggests that suppression of IL-6 production would lower those peak fibrinogen levels that occur in the morning in association with arterial ischemic events. This could result in fewer arterial ischemic events, especially in the morning.

Aged↗
PubMed1999

Immunomodulatory screening test of corn oil administered orally to female mice: effect of timing of dosing within 24 hours.

The effect of varying the dose-delivery time within a 24 h period (12:12 light-dark cycle) on the immunomodulatory properties of corn oil administered by gavage to 120 B6C3F1 female mice was investigated. Mice, housed in six separate boxes equipped with timers to regulate light onset and offset (staggered by 4 h increments), were treated for 5 consecutive days by intragastric (i.g.), administration of 5 mL/kg corn oil. Negative and positive control mice were given sham injections (needle inserted, but no injection). Sheep red blood cells (SRBCs) were injected intraperitoneally (i.p.) on the fifth day. Three days later, positive control mice were given cyclophosphamide intraperitoneally (80 mg/kg). Four days after SRBC injection, mice were weighed and killed, and spleens and thymuses were removed and weighed. Spleens were brought to single-cell suspensions and tested for an antibody response to the SRBC. Plaque-forming cells (PFCs), as measured per spleen, per 10(6) viable spleen cells or per 10(6) total spleen cells, exhibited significant circadian rhythms for mice given corn oil, but not for sham-gavage- and cyclophosphamide-treated mice. The peak response (acrophase, phi) occurred at 21 h, 22 h, and 23 h after lights on (HALO), respectively, with PFC values significantly different between the different time points. Corn oil and sham gavage affected the circadian pattern of antibody production; there was a high-amplitude (21-27%) rhythm observed when mice were treated with corn oil and no rhythm when mice received the sham-gavage treatment. In addition to testing mice near the end of the daily dark span and/or early light span to obtain a maximum immune response, this finding points to the importance of including as controls a group of animals that are not treated at all and a group given vehicle alone, rather than only sham-treated animals, for comparison with experimentally treated animals.

Adjuvants, Immunologic↗
PubMed1998

Seasonal variations in the presentation and growth of thyroid cancer.

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.

Female↗
PubMed1998

Variation in cell yield and proliferative activity of positive selected human CD34+ bone marrow cells along the circadian time scale.

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.

Adult↗
PubMed1998

7-year (circaseptennian) patterns in psychology and biology? Comment on Verhulst and Onghena.

Nonlinear rhythmometry confirms a pattern of about 7 years, describing the number of births by birth year of quantum fathers reported by Verhulst and Onghena in 1996 and estimates the period to be 6.53 years with a 95% confidence interval overlapping 7 years. Other patterns of about 7 years are found in biology, as shown herein for the mean gonadal weight of an echinoderm (the purple sea urchin) and a mollusk (the black chiton). A number of periodic components with different frequencies, some shown to be genetically anchored, await applications in psychology as well as in other fields of medicine and biology.

Animals↗
PubMed1998

Reanalysis of filter-feeding behavior of caddis fly (Brachycentrus) larvae reveals masking and circadian rhythmicity.

Data published on the subjectively determined presence or absence of circadian periodicity in feeding of Brachycentrus occidentalis Banks, an aquatic insect belonging to the order Trichoptera, were reanalyzed by statistical methods based on the cosine model. The 4h data for 5 days of synchronized environmental conditions followed by 5 days of constant conditions (using original values and purified values after removal of an 8h component attributed to the feeding schedule) were quantified for rhythm characteristics by the least-squares fit of cosines. A circadian rhythm was highly significant during synchronized conditions (light-dark and cycling water temperature) and in continuous light when water temperature continued to cycle. A circadian rhythm in the percentage of larvae feeding during continuous light and constant water temperature, which had not been observed by visual inspection in the original data, was detected in the unmasked data with a "free-running" period not overlapping 24.0h (95% confidence limits from 18.95h to 21.66h). Effects of masking brought about by manually feeding the larvae every 8h were statistically significant under both synchronized and constant environmental conditions.

Animals↗
PubMed1998

Ultradian movements of shoots of two species of soybeans Glycine soja (Sieb. and Zucc.) and Glycine max (L.) Merr.

Circumnutation movements of shoot tips of two species of soybean were studied. Shoot tips of Glycine soja (Sieb. and Zucc.) moved in a counterclockwise direction with a mean period (+/- SD) of 108 +/- 9 minutes when the shoots were not handled prior to monitoring (n = 17). Effects of mechanical stress or stimulation (thigmomorphogenesis) resulted in the lengthening of the mean period by 15% when shoot lengths were measured (handled) prior to monitoring movements (124 +/- 18 minutes, n = 49) or handled and restaked prior to monitoring movements (124 +/- 14 minutes, n = 11). Shoot tips of G. max cultivars moved counterclockwise, and, depending on the cultivar, periods ranged from 112 minutes to 133 minutes, with an overall average period of 124 +/- 21 minutes (n = 21). This period was identical to the mean period of comparably handled G. soja shoot tips. Amplitudes for the four G. max cultivars were much smaller (0.12 cm to 1.43 cm) than for G. soja (2.9-8.7 cm). Factors that may have contributed to differences in rhythm characteristics between species and among cultivars included the presence of a distinguishable bending zone in G. soja, but not in G. max, and morphological features associated with shoot development.

Activity Cycles↗
PubMed1998

Rhythmic patterns in incidence of peptic ulcer perforation over 5.5 decades in Norway.

The incidence of ulcer perforation in 1480 patients treated in the Bergen area of Norway between 1935 and 1990 was analyzed for daily (circadian), weekly (circaseptan), and yearly (circannual) time effects. A circadian rhythm was found overall that was reproducible and fairly stable across seasons, decades, and days of the week. After subgrouping, a circadian rhythm was found in younger patients, males, and duodenal perforations, while a 12 h (circasemidian) rhythm characterized ulcer perforation for women and for gastric ulcers. Duodenal perforations showed highest incidence in the afternoon, while gastric perforations showed a major peak around noon and a secondary peak near midnight. For duodenal ulcer perforation, the circannual pattern was characterized by a 6-month rhythm, with significantly higher incidence in May-June-July and in November-December in most subgroups. A circaseptan rhythm was not found, but there was a significantly higher incidence on Thursday-Friday as compared to Sunday-Monday. The pathophysiological mechanisms underlying the perforation of an ulcer thus seemed to show pronounced circadian and 6-month rhythmic variations, much less so circaseptan or circannual rhythms. While it is likely that exogenous environmental and/or societal factors play a significant role, variations in ulcer perforation may be related to endogenous biological rhythms in pathophysiological factors since the circadian pattern of duodenal perforation follows that for gastric acidity. Knowledge of the temporal patterns in peptic ulcer perforation and associated pathophysiologic factors should prove useful in optimizing the chronotherapeutic management of ulcer disease.

Adolescent↗
PubMed1997

The influence of vehicle gavage on seasonality of immune system parameters in the B6C3F1 mouse.

Seasonal hyporesponsiveness and other immune system variations were observed in female B6C3F1 mice during routine screening tests for immunomodulation. In a retrospective assessment, 4 years of data from over 1200 naive, vehicle, and immunosuppressed (cyclophosphamide-treated) control mice were compiled and analyzed for uniformity and significant circannual pattern of immune response. Endpoints included body, spleen, and thymus weights and an immunotoxicity assessment which enumerates specific antibody plaque-forming cells (PFC) in the spleen following immunization with sheep red blood cells. Dosing vehicles were water, corn oil, or 1% methyl cellulose instilled by oral gavage in a 5-20 ml/kg volume once daily for 5 days. Four days later, terminal organ and body weights were recorded and PFC were quantitated. Upon analysis, individual datapoints were arrayed in consistent circannual and seasonal patterns. In naive mice, the yearly peak response in circannual rhythm (acrophase) for body weight and PFC parameters occurred in the summer, with acrophases for spleen and thymus weights located in the spring. Vehicle gavage modulated the circannual/seasonal means and acrophases of all measured endpoints in distinct patterns which varied by vehicle. Body weight was the endpoint least affected by vehicle treatment. Corn oil was the vehicle resulting in the most dramatic effects on natural rhythm. As expected, the naive mice receiving an ip injection of cyclophosphamide exhibited significant decreases (p </= 0.05) in circannual mean values for PFC response and relative organ weights when compared to naive controls and the elimination of significant expression of rhythm for PFC parameters. Our results indicate that dosing vehicles alter normal seasonal patterns of biological responses in the mouse. These effects on natural rhythms should be considered in toxicity evaluations, especially when comparing datapoints collected at different times of the year.

Animals↗