American Journal of AnatomyVolume 192, Issue 4 p. 325-328 Article American journal of anatomy: 1901–1991 Dr. John E. Pauly, Corresponding Author Dr. John E. Pauly Office of the Vice-Chancellor for Academic Affairs, University of Arkansas for Medical Sciences, Little Rock, AR 72205Office of the Vice Chancellor, Slot 541, University of Arkansas for Medical Sciences, 4301 West Markham, Little Rock, AR 72205Search for more papers by this author Dr. John E. Pauly, Corresponding Author Dr. John E. Pauly Office of the Vice-Chancellor for Academic Affairs, University of Arkansas for Medical Sciences, Little Rock, AR 72205Office of the Vice Chancellor, Slot 541, University of Arkansas for Medical Sciences, 4301 West Markham, Little Rock, AR 72205Search for more papers by this author First published: December 1991 https://doi.org/10.1002/aja.1001920402Citations: 85AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Citing Literature Volume192, Issue4December 1991Pages 325-328 RelatedInformation

The activities of 23 brain or liver enzymes were studied in 5-6 week old C57BL/6JNctr male and female mice that had been fed ad libitum and standardized for 2 weeks to either (1) 12 hr of light (0600-1800) alternating with 12 hr of darkness (1800-0600) (LD 12:12), (2) staggered sequences of 12 hr of light and 12 hr of dark (SLD 12:12) or (3) continuous illumination (LL 12:12) for 2 weeks. Mice in the LD 12:12 and LL 12:12 experiments were killed at 4 hr intervals along a 24-hr span in order to sample at six different circadian stages. Lighting schedules for mice in the SLD 12:12 experiment were organized such that six different circadian stages were sampled when all mice were killed at one time of day. All 23 enzymes demonstrated a prominent circadian rhythm in at least one of the experiments. Moreover, about two-thirds of the enzymes in LD and SLD 12:12 had a statistically significant fit to a 24-hr cosine curve, while only one-third of the enzymes in LL 12:12 had significant fits to cosine curves. Peak activities of enzymes from mice in LD 12:12 were clustered at the time of transition from light to dark. This was also the trend for the activities of enzymes from mice in SLD 12:12, but resynchronization did not appear completed within the 2-week span. This, along with the observation that mesors (mean 24-hr activity) were reduced and amplitudes altered, indicated that the 2-week standardization period was not sufficient for some enzymes. Times of peak activities, mesors and amplitudes were affected for most enzymes from mice in the LL 12:12 environment. This suggests that individual mice became desynchronized from one another with respect to the original light-dark schedule and that rhythms were altered or lost because individual mice were free running with frequencies different from 24 hr.

American Journal of AnatomyVolume 169, Issue 1 p. 59-59 PrefaceFree Access On bones for beginners John E. Pauly, John E. Pauly EditorSearch for more papers by this author John E. Pauly, John E. Pauly EditorSearch for more papers by this author First published: January 1984 https://doi.org/10.1002/aja.1001690105Citations: 1AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume169, Issue1January 1984Pages 59-59 RelatedInformation

Chronobiology is that branch of science that objectively explores 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 consideration.

Oscillation is a fundamental property of all animal and plant life: it also characterizes all levels of organization from the molecular to that of the whole organism. This chapter focuses on the circadian rhythms or those with a frequency of about a day. It should be kept in mind that rhythms of higher (ultradian) or lower (infradian) frequency may be superimposed on the circadian frequency. The frequency spectrum of rhythms is broad, ranging from fractions of a minute to days or months or even a year. The chapter describes some generalizations about mammalian chronobiology, then introduces several descriptive terms and cites examples of biological rhythms. The attention then gets focused on chronopharmacological implications. Because the biological system is rhythmically changing, it follows that the organism is biochemically a different entity at different circadian phases; therefore it reacts differently to an identical stimulus at different times. Researchers have been exploring rhythms in various organs in both the tumor-bearing and normal animal. High-amplitude circadian rhythms have been reported for the DNA synthesis in liver, bone marrow, gut, thymus, and spleen of normal rodents; the presence of a tumor may dramatically alter the rhythm.

The Anatomical RecordVolume 183, Issue 1 p. 101-227 American Association of AnatomistsFree Access Proccedings of the American association of anatomists. Eighty-eighth meeting. University of California, Los Angeles schools of medicine and dentistry March 24, 25, 26, 27, 1975 with list of officers and members, and constitution First published: September 1975 https://doi.org/10.1002/ar.1091830111AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Volume183, Issue1September 1975Pages 101-227 RelatedInformation

Adult guinea pigs were carefully standardized for at least seven days prior to each experiment; this included an artificial light-dark cycle with light extending from 0600 to 1800. On three experimental days, eight animals were injected subcutaneously with 300 μg of histamine at six-hour intervals over a 24-hour period; each animal received four injections during one day. The size of the erythema produced each time was measured. In all three experiments a prominent group rhythm was demonstrated with maximum response occurring during the dark phase; minimum response always occurred during the latter part of the light phase. Such results indicate a strong synchronization among the animals of the group. Two additional, similar studies were performed on animals standardized in one case for 21 days and in the second for 35 days under continuous illumination. The group rhythms of histamine response under these conditions, when compared to the light-dark adapted group rhythm, were greatly modified in phasing and profile. The circadian rhythm in response to histamine persisted in each individual animal. The change in the phasing and profile of the group rhythm was due to a partial desynchronization among the individual animals subjected to continuous illumination.

Fluorometric measurements were made of 5-hydroxytryptamine levels in spleens obtained from separate subgroups of adult male rats killed at two-hourly intervals over four separate 24-hour time spans. For three weeks prior to obtaining tissue, all rats were standardized carefully and were subjected to 12 hours of light (0600–1800) followed by 12 hours of darkness. Analyses showed in each study very significant fluctuation over the 24-hour time scale; the range of change over this period was as great as 131%. The phasing of the rhythms, in spite of the rigid environmental synchronization, was not similar in any of the four studies. Possible explanations for this unexpected desynchronization are discussed. Spleen weights also fluctuated with a significant 24-hour circadian frequency. In addition, the rhythm characterizing this amine was described in female rats as well as the effect of different stimuli on the same rhythm. These stimuli were ether, immobilization and a ‘novelty’ situation; and all three significantly increased the levels of 5-HT in spleen when the overall 24-hour mean values of each experimental group were compared with controls. However, in all cases there were discrete time points when significant differences in 5-HT levels could not be obtained with any of the stimuli. This study demonstrates that the effect of the stimuli used depends on the phase of the rat's circadian system during which it was applied. The necessity of considering the natural rhythmic fluctuation in any investigation evaluating this biogenic amine in spleen is demonstrated.

Circadian rhythms are demonstrated in the tongue of adult rats for both the mitotic index of the basal epithelium and the uptake rate of injected 3H‐thymidine by the tongue tip. The animals were entrained to a light‐dark cycle for four weeks prior to the experiments with the light phase extending from 0600 to 1800 hours (CST). The daily fluctuation is approximately 300% for the mitotic index and 185% for the uptake rate of 3H‐thymi‐dine. The highest mitotic index occurs at 1100, and the highest uptake of 3H‐thymidine occurs four hours earlier at 0700. The least activity for both parameters occurs during the first part of the dark span of the light‐dark cycle. Estimates of several other rhythmic parameters are determined by a computerized method.

Mitotic activity in the duodenum of the rat and mouse exhibits a circadian periodicity with a peak in the rat between 1200 and 1500 hours and a sustained trough between 1800 and 0600. Scintillation counts revealed a similar rhythm in the total uptake of 3 H-thymidine by the rat duodenum with a sustained but fluctuating crest occurring between 0800 and 1800 and a trough between 1900 and 0100. In the mouse the peak mitotic activity occurred at 0900 and the trough at 1700. Isoproterenol completely abolishes the rhythm in mitosis in mouse duodenum, when injected exactly 28 hours previous to sacrifice. The results are discussed in relation to reports that deny a circadian rhythm in mitotic activity in the duodenum.

A colony of adult rats was maintained on a standardized regimen with artifical photoperiods extending from 0600 to 1800 alternating with 12 hours of darkness. Every hour during a 24-hour period separate subgroups of rats were injected with 35 mg/kg of pentobarbital sodium, and the duration of time each animal remained under anesthesia was recorded. The rats remained anesthetized for longer periods of time between the hours of 1600 and 2200 than at other times of the day; this indicates that the response to the drug is dependent on he circadian phase system of the animal. When the results were plotted along the 24-hour time scale, the difference between the crest and trough of the curve was about 100%. A second colony of rats was maintained in a similar fashion except that the animals were subjected to continuous illumination. The rhythm of their susceptibility to pentobarbital sodium persisted for at least four weeks in a form highly modified from the animals synchronized to a light-dark cycle. In a third colony of animals, the rhythm still was present four months after they had been blinded; but it was modified and different from either the light-dark synchronized animals or from rats subjected to continuous illumination. The importance of recognizing the time structure of the living organism is discussed.

SEVERAL daily drug-susceptibility rhythms have been reported in rodents1–12. This report demonstrates the daily pattern in susceptibility to D-amphetamine sulphate as measured by percentage of mortality for normal rats housed in a light-dark (LD) environment, for rats maintained in continuous illumination (LL) and for blinded rats kept in continuous darkness (DD).

With other environmental factors rigidly standardized, normal Sprague-Dawley rats were maintained under the following lighting schedules: (1) LD 12:12, artificial light from 6:00 A.M. to 6:00 P.M. alternating with 12 hours of darkness; (2) DL 12:12, reversal of the first schedule; (3) DD, constant darkness; and (4) LL. constant illumination. During each lighting regimen, blood glucose levels were determined on separate subgroups of 11 to 18 animals at bi-hourly intervals during a 24-hour period. Significant circadian fluctuations or rhythms under all lighting conditions were found when the mean blood glucose values for each bi-hourly group were plotted as a function of time. Rats maintained under LD 12:12 conditions showed approximately a 25% difference between the maximum and minimum values. When the phasing of the peaks and troughs of blood glucose rhythm in Sprague-Dawley rats was compared with that of a separate colony of Wistar rats, it was noted that they were similar. Starvation of the LD rats for 66 hours did not abolish the characteristic rhythm, although a lower level of blood glucose resulted. The LD 12:12 blood glucose pattern was reversed by reversing the LD cycle 180 degrees. Under LL and DD the troughs and crests seen in the glucose curves were out of phase with those of LD and with each other; this suggested that under LL or DD the rhythm had become free-running because of the absence of the light-dark synchronizer. Hypophysectomy modified the phasing of the normal LD pattern but did not abolish its fluctuating nature; this suggested that the LD cycle of light no longer was an effective entraining agent. Adrenal medullectomy caused an overall 13% decrease in the 24-hour mean but did not alter the phasing of the LD pattern. The significance of periodicity analysis in relation to bioassay is discussed.

The Anatomical RecordVolume 128, Issue 4 p. 733-746 Article Further electromyographic studies on muscles of costal respiration in man David S. Jones, David S. Jones Departments of Anatomy, The Stritch School of Medicine, Loyola University, The Chicago Medical School, Chicago, IllinoisSearch for more papers by this authorJohn E. Pauly, John E. Pauly Departments of Anatomy, The Stritch School of Medicine, Loyola University, The Chicago Medical School, Chicago, IllinoisSearch for more papers by this author David S. Jones, David S. Jones Departments of Anatomy, The Stritch School of Medicine, Loyola University, The Chicago Medical School, Chicago, IllinoisSearch for more papers by this authorJohn E. Pauly, John E. Pauly Departments of Anatomy, The Stritch School of Medicine, Loyola University, The Chicago Medical School, Chicago, IllinoisSearch for more papers by this author First published: August 1957 https://doi.org/10.1002/ar.1091280407Citations: 11AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat Literature Cited Campbell, E. J. M. 1955a An electromyographic examination of the role of the intercostal muscles in breathing in man. J. Physiol., 129: 12–26. Campbell, E. J. M. 1955b The role of the scalene and sternomastoid muscles in breathing in normal subjects. J. Anat., 89: 378–386. Campbell, E. J. M. 1955c The functions of the abdominal muscles in relation to the intra-abdominal pressure and the respiration. Arch. Middlesex Hosp., 5: 87–94. Campbell, E. J. M., and J. H. Green 1955 The behaviour of the abdominal muscles and the intra-abdominal pressure during quiet breathing and increased pulmonary ventilation. A study in man. J. Physiol., 127: 423–426. Jones, D. S., R. J., Beargie and J. E. Pauly 1953 An electromyographic study of some muscles of costal respiration in man. Anat. Rec., 117: 17–24. Koepke, G. H., A. J., Murphy, J. W. Rae and D. G. Dickinson 1955 An electromyographic study of some of the muscles used in respiration. Arch. Physical Med. and Rehabilitation. April: 217–222. Pauly, J. E., D. S., Jones, A. Jarach and J. E. P. Toman 1957 A vectorelectromyographic study of the intercostal muscles in human respiration. Federation Proceedings, 16: No. 1, 430. Citing Literature Volume128, Issue4August 1957Pages 733-746 ReferencesRelatedInformation

SUMMARY The tolerance of BALB/c x DBA/2 F, mice to the popular cytostatic drug 1-@-D-anabinofunanosylcytosine (ara-C) was tested in two laboratories about 1000 km apart. According to the same plan and on the same days in Little Rock, Ark., and Minneapolis, Minn., nine groups of 20 mice each ne ceived four courses of ara-C treatment, with 4-day intervals between them beginning February 7, 1973. In each course, a total dose of 240 mg/kg was divided among eight separate injectionsadministered at3-hr intervals.One group of mice received equal doses of ara-C every 3 hr (the homeostatic schedule). The eight other groups in each location received the same total dose pen course but in gradually increasing and decreasing doses (the sinusoidal schedule). The timing of the highest doses @n the latter schedule differed among theeightgroups(byinteger multiples of3 hr).Aspredicted from earlier work, survival times after treatment with ara-C on different sinusoidal schedules differed drastically. How ever, the timing of the sinusoidal schedules yielding the longest survival was similar in the two locations. The sun vival times from all sinusoidal treatments from a given loca tion were fitted by a 24-hr cosine curve. The timing of the rhythm in tolerance as a whole was thereby computed as the lag from local midnight of the peak in the cosine curve best fitting all data. The timing of this tolerance rhythm (briefly, circadian chronotolenance), computed separately for data from Arkansas and Minnesota, agreed within 1 hr. There also was close agreement in the results obtained by the 2 laboratories in mean survival time; the percentage of survivors when mice were treated according to certain of the selected sinusoidal schedules was much greater than for mice treated on the homeostatic schedule. This large and reproducible difference in tolerance and the similar timing of the overallfittedfunction describing chronotolen ance in the hands of different investigators underlines the urgency of testing potential benefits from timed clinical treatment.