ISSN:0002-9106    

DOI:10.1002/aja.1001680402

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1983

数据来源: WILEY

摘要:

AbstractChronobiology is that branch of science that objectively explos and quantifies mechanisms of biological time structure, including the important rhythmic manifestations of life. It is the study of biological rhythms. This paper introduces chronobiology and some of its vocabulary, principles, and techniques.A circadian rhythm is a regularly repetitive, quantitative physiological change with a period of about 24 hr (20–28), but the spectrum of rhythms includes those with periods less than 20 hr (ultradian) and longer than 28 hr (infradian). These rhythms are ubiquitous among the eukaryotes, innate and endogenous; their periods are precisely controlled by synchronizers in the environment. Rhythms can be manipulated by altering their synchronizers or by introducing more dominant ones. When organisms are removed from their environment and placed in constant conditions, rhythms revert to their natural frequencies and free‐run. All of an organism's rhythms operate simultaneously, but their peaks and troughs do not necessarily occur at the same time.There are rhythms in susceptibility to drugs; a fixed dose may have a therapeutic effect at one point along the 24 hr time scale and a harmful one at another. Knowledge of these rhythms can be important when designing experimental or treatment protocols and interpreting results. Examples are provided to show that single‐time‐point sampling can lead to erroneous results, unless biological periodicity is taken into consid

ISSN:0002-9106    

DOI:10.1002/aja.1001680403

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1983

数据来源: WILEY

摘要:

AbstractThis review considers cellular chronobiology and examines, at least in a superficial way, several classes of models and mechanisms that have been proposed for circadian rhythmicity and some of the experimental approaches that have appeared to be most productive. After a brief discussion of temporal organization and the metabolic, epigenetic, and circadian time domains, the general properties of circadian rhythms are enumerated. A survey of independent oscillations in isolated organs, tissues, and cells is followed by a review of selected circadian rhythms in eukaryotic microorganisms, with particular emphasis placed on the rhythm of cell division in the algal flagellateEuglenaas a model system illustrating temporal differentiation. In the ensuing section, experimental approaches to circadian clock mechanisms are considered. The dissection of the clock by the use of chemical inhibitors is illustrated for the rhythm of bioluminescence in the marine dinoflagellateGonyaulaxand for the rhythm of photosynthetic capacity in the unicellular green algaAcetabularia. Alternatively, genetic analysis of circadian oscillators is considered in the green algaChlamydomonasand in the bread moldNeurospora, both of which have yielded clock mutants and mutants having biochemical lesions that exhibit altered clock properties. On the basis of the evidence generated by these experimental approaches, several classes of biochemical and molecular models for circadian clocks have been proposed. These include strictly molecular models, feedback loop (network) models, transcriptional (tape‐reading) models, and membrane models; some of their key elements and predictions are discussed. Finally, a number of general unsolved problems at the cellular level are briefly mentioned: cell cycle interfaces, the evolution of circadian rhythmicity, the possibility of multiple cellular oscillators, chrono‐pharmacology and chronotherapy, and cell‐cycle clocks in development and

ISSN:0002-9106    

DOI:10.1002/aja.1001680404

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1983

数据来源: WILEY

摘要:

AbstractThis paper summarizes recent and continuing work on circadian rhythms in the alimentary tract of rodents; these include: (1) cell proliferation, (2) activities of intestinal enzymes, and (3) behavioral aspects of spontaneous feeding and drinking. All regions of the intestinal tract show marked circadian behavior in cell proliferation. The roles of the light‐dark cycle and meal timing in synchronizing such rhythms are discussed as well as the influence of epidermal growth factor, insulin, glucagon., and ACTH 1‐17. Attention is called to the potential importance of these rhythms to basic research and medicine. Other circadian rhythms in the alimentary tract are reviewed briefly, such as those characterizing a host of intestinal enzymes, monosaccharide transport, and the height and width of the villi. Many of these have been shown to be cued to a feeding schedule; however, a number of the enzyme rhythms persist for one or two cycles in fasting animals, and this also is the case for the cell‐proliferation rhythms.After having been acclimated to a circadian feeding schedule (within a range of 23–30 hr), rodents can on subsequent days anticipate the food an hour or more prior to its arrival. Some enzymes behave in a similar manner in that their activities increase prior to the expected intake of the daily food. These anticipatory response rhythms are under endogenous control, since both will persist in the fasted animal and both will free run when a mouse is placed under constant conditions. Somehow these animals are able to measure circadian intervals of time. This challenges the concept that the oscillations seen in enzyme activities are simply a passive consequence of feeding and fasting, respe

ISSN:0002-9106    

DOI:10.1002/aja.1001680405

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1983

数据来源: WILEY

摘要:

AbstractThe 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 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. Low‐frequency rhythms in cell production and in the number of circulating leukemic cells have been found in some patients with chronic myelogenous leukemia. Circannual variations of several hematologic parameters have been described. Among those are cell proliferation of granulocytic bone marrow in soft agar cultures (CFU‐C) in mice and circannual variations in lymphocyte subtypes and functions.Chronobiologic considerations are essential in the design of animal experiments and human studies. High‐amplitude rhythms of a number of parameters may have diagnostic implications and should be evaluated against time‐qualified reference ranges. Low‐amplitude rhythms may not be of diagnostic importance at this time but do indicate functional changes in the cell systems studied and may be related to changes in susceptibility and responsiveness to a wide variety of stimuli. Quantitative rhythm parameters obtained by statistical methods of rhythmometry lend themselves as new endpoints in the study of the hematopoietic and immune systems. The multifrequency time structure of the mammalian organism is an essential part of its function and, as a morphology in time, complements its anatomy in space and in many aspects may be instrumental in maintaining th

ISSN:0002-9106    

DOI:10.1002/aja.1001680406

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1983

数据来源: WILEY

摘要:

AbstractThe introduction to medical practice of chemical agents for fighting human cancer some 30 years ago brought hope to a field of medicine previously shrouded in despair and impeded by superstition. Gradually more and better agents have become available to the physician and to the patient suffering from cancer. The physician‐scientist has, in turn, learned a great deal about normal and abnormal cellular biology by using these drugs as probes. The observations that certain tissues and certain tumors share patterns of drug toxicity have led to a broadening of biologic understanding and to the use of combinations of drugs with shared antitumor activity and unshared toxicities. This empiric art of cancer chemotherapy has resulted in great progress in the treatment of a large number of advanced cancers. As important, however, is that this experience has resulted in knowledge which is leading to the development of rationally designed therapeutic regimens; to drug analogues seeking greater therapeutic‐toxic ratios; to the development of methods for chemically interfering with toxic drug effects while allowing or enhancing antitumor effect; and to work defining effects of drug timing. Drug timing research considers drug dosage in respect to the timing of a drug relative to the timing of other drugs (drug‐time‐drug interactions) or to other doses of that same drug (drug‐drug interval); the order of drugs (drug‐drug sequence); and the timing of drugs relative to an internal organismic time structure (time‐drug interactions). Data in this brief review clearly show that drug timing needs to be considered when designing rational chemotherapy for a living organism suffering from a cancer. The beautiful spatiotemporal complexity of life is not to be ignored or avoided, but should be considered as a golden opportunity to use what few imprecise chemical weapons we have a little mor

ISSN:0002-9106    

DOI:10.1002/aja.1001680407

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1983

数据来源: WILEY

摘要:

AbstractChronobiology is the eminently interdisciplinary science of interactions in time among metabolic, hormonal, and neuronal networks. It involves anatomy, biochemistry, microbiology, physiology, and pharmacology, at the molecular, intracellular, intercellular, and still higher levels of organization. The compounds coordinating a time structure‐–proteins, steroids, and amino‐acid derivatives–provide for the scheduling of interactions among membrane, cytoplasmic, and nuclear events in a network involving rhythmic enzyme reactions and other intracellular mechanisms. The integrated temporal features of the processes of induction, repression, transcription, and translation of gene expression remain to be mapped in relation to the available framework, consisting of the sequences of phospholipid and RNA labeling, DNA formation, and mitosis, to delineate a circadian cell cycle upon which further hormonal and neural coordination acts (Halberg et al., 1959a,b, 1979a). There is a need for communication over temporal as well as spatial distances among different specialized structures devoted, in individuals, to metabolism, growth, reproduction, and the ability to adjust, and, in species, to the capacity to adapt. For a better understanding at all levels of behavior in its broader sense of organization in time, chronobiology requires familiarity with temporal aspects of metabolism, hormones, and neurons. In other words, broadly trained, full‐time “general practitioners” of a chronobiology in its own rig

ISSN:0002-9106    

DOI:10.1002/aja.1001680408

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1983

数据来源: WILEY

ISSN:0002-9106    

DOI:10.1002/aja.1001680401

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1983

数据来源: WILEY