Jinyi Wu

Surgical Influence on Murine Immunity and Tumor Growth: Relationship of Body Temperature and Hormones with Splenocytes

Abstract Adrenalectomy predisposed the C3HeB/FeJ Mouse to tumor from a low dose of tumor cells, derived from a C3H spontaneous mammary adenocarcinoma. Sham surgery had a similar effect. In contrast, ovariectomized females, intact females, and male mice did not allow the low dose of cells to develop into a tumor. In order to better understand the role of hormones on the immune system controlling tumor growth, normal C3HeB/FeJ mice were studied for the effect of corticosterone or estradiol on splenic lymphocyte surface antigen expression. Adrenalectomy and ovariectomy caused a decrease in the percentage of all T cell subclasses and an increase in absolute numbers of immunoglobulin-bearing cells. Reconstitution of ovariectomized mice with estradiol did not significantly alter lymphocyte cell surface antigen expression. In contrast, injection of corticosterone into adrenalectomized mice brought these values to normal. Further study on normal mice placed on a 12:12-hr light:dark schedule showed that the hours after lights on (HALO) had a significant effect (analysis of variance) on body temperature, percentage of splenic B cells, T pan, T helper and T suppressor cells, and absolute numbers of T pan cells. Brain dehydroepiandrosterone sulfate correlated positively with T pan lymphocytes, but showed no significant effect on HALO. In contrast, body temperature showed a strong circadian rhythm (P < 0.001). In addition, the presentation of estrus was circadian rhythmic (P = 0.003) with 58% of mice in estrus at 16 HALO and only 8% at 4 HALO. Multiple regression analysis revealed body temperature was strongly associated with absolute numbers of splenic T lymphocytes and their subsets, as well as percentage of B lymphocytes, Thy 1.2-, and Lyt-2-bearing cells. Similarly, HALO and estrous cycle stage were associated with percentage of T helper cells.

Chronopharmacologic individualized and group assessment of outcomes in antihypertensive drug trials

Chronobiologic methods are illustrated for the individualized assessment of the patients response to antihypertensive medication. In addition to the 24-h mean from blood pressure profiles obtained by ambulatory monitoring, specific endpoints serve as gauges of treatment efficacy. These endpoints include the circadian amplitude, a measure of predictable extent of change within 24 h, and hyperbaric (or hypertensive) indices of excess or load. The latter indices assess the duration and amount of blood pressure excess by comparison to critical thresholds. In view of the large circadian variation characterizing blood pressure, the usual time-invariant limits of 140/90 mm Hg (systolic/diastolic) are replaced by time-specific 90% prediction limits derived from data of clinically healthy peers.<<ETX>>

Circadian and circaseptan (about-7-day) free-running physiologic rhythms of a woman in social isolation

An investigation into the time structure of rhythms in the absence of a clock during prolonged human social isolation is presented. A clinically healthy woman lived underground and her systolic, mean arterial, and diastolic blood pressure and her heart rate were automatically monitored most of the time during 14 weeks. She also self-measured, several times during wakefulness, her oral and axillary temperature. A circadian period slightly longer than 24 h came to the fore for all variables investigated, both by linear-nonlinear rhythmometry and by chronobiologic serial sections on the data obtained from the middle of the second week of isolation for the ensuing 97 days. In heart rate, an about-seven-day (circaseptan) rhythm was also found, with a confidence interval that did not overlap the precise seven-day trial period, notably during the first seven weeks. Some loose coupling of rhythms in metabolism gauged by core temperature and the heart rate is demonstrated for two components of the physiologic rhythm spectrum, the circadian of several variables and the circaseptan of heart rate.<<ETX>>

Circadian variation of human circulating cholesterol components on vegetarian and omnivorous diets in healthy Indians

Circadian periodicity of human circulating total (T), high-density lipoprotein (HDL) and low-density lipoprotein (LDL + VLDL; briefly LDL) cholesterol (C) was studied in 30 clinically healthy, diurnally active, norturnally resting young volunteers divided into two groups of 15 each (10 men; 5 women) taking vegetarian and non-vegetarian diets. A marked circadian variation in T-C, HDL-C and LDL-C was recorded in all volunteers irrespective of the diety habits. However, total mean values and the acrophase differed between the two groups. Lower MESOR of studied variables for the vegetarians and higher MESOR for the omnivores in both the sexes exhibited endogeneous rhythmic changes as well as lower values of cholesterol components in vegetarians as compared to omnivores. Fasting unmasks a presumably endogeneous change around a lower MESOR with a smaller circadian amplitude both of HDL and LDL cholecterol metabolism. The recognition that the human circulating cholesterol components oscillate physiologically, in the peripheral blood with a shift of acrophase according to a circadian rhtyhm in two dietry schedules may prove to be of significance in the clinical interpretation of the laboratory result under tropical conditions.

Chronobiologic approach to beat-to-beat variations of cultured murine myocardial cells

An earlier demonstration of a circadian rhythm in rat atria by others is complemented herein by observations in culture: A single murine myocardial cell and two sets of grouped cells beating in culture for several days reveal several features of an anticipated, presumably built-in spectrum of multifrequency rhythms and trends, the chronome. Circadian and about 12-h (circasemidian) components are modulated by an approximately 84-h (circasemiseptan) component, which cannot be separated from trends in view of the brevity of the series. The circumstance under which the culture is aging and in which fibroblasts proliferate is a further complication that limits the findings to a single cycle reproduced in three separate cultures. Whether it is a rhythm that repeats itself or a response to placement into culture, an approximately 3.5-d component in the beating of myocardial cells in culture is to be aligned with a very prominent similar component found in the incidence of 85,819 human myocardial infarctions.

Cardiovascular rhythms, their adjustment to schedule change and shift work

With illustrative chronobiologic methodology, the rules of rhythm shifting by work schedule manipulation are reviewed with reference to self-measured or ambulatory blood pressure and heart rate. The literature on the cardiovascular performance of shift workers studied with miniaturized devices or by self-measurement is reviewed and the systolic blood pressure status of 36 police officers presented. 53% of these officers had blood pressure excess. The cosinor approach defines blood pressure characteristics and their deviation with respect to those of healthy peers by fitting cosine curves for assessing static and dynamic parameters. Some of these chronobiologic endpoints are introduced in the minicourse to stimulate their use in particular for individuals under a burden such as police work on shifting schedules.<<ETX>>

Representations of feed-sideward modulation

To account for phenomena that occur when three or more rhythmic entities interact, called feedsidewards, models from engineering are considered as a possibly useful scaffolding from which to formulate tests of the mechanisms underlying such observations. Rhythms at different organizational levels and cephaloadrenal interactions are discussed. A description of an experiment involving the effects of light on mice is presented. Models for biological and biochemical rhythms are also discussed.<<ETX>>