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Biomedical subjects

G B Ellis

Publications and source records attributed to G B Ellis.

18 recordsLinked to original sources
PubMed1998

Human subject protections in the United States: perspectives from the Office for Protection from Research Risks.

The U.S. Department of Health and Human Services (DHHS) regulations require that all human subjects research supported by DHHS be reviewed and approved by a local institutional review board (IRB). With few exceptions, investigators may not involve human subjects in research without their informed consent, and additional safeguards are required when subjects are likely to be vulnerable to coercion or undue influence. Institutions that receive DHHS funding must enter into an "Assurance" of compliance with the Office for Protection from Research Risks (OPPR), which has the authority for oversight and implementation of the human subjects regulations. As discussed more fully below, Assurances are of a contract nature in that they formally commit the institutions to adherence to the regulations and the ethics standards relevant to research on human subjects. This article addresses the application of human subject protections in biomedical research.

Ethics Committees, Research↗
PubMed1995

No news here.

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Female↗
PubMed1984

Orchidectomy unleashes pulsatile luteinizing hormone secretion in the rat.

We charted the development of pulsatile luteinizing hormone (LH) secretion as a function of the time elapsed after removal of the testes. On seven occasions between the moment of castration and 80 days afterwards, we obtained consecutive blood samples at frequent (2.5- to 5-min) intervals from cannulated male rats. Orchidectomy increased both the amplitude and frequency of LH release within 1 day after surgery. Amplitude: From 19 h through 80 days postcastration, peak LH levels rose steadily, and LH pulses grew progressively more pronounced in nadir-to-peak amplitude. Frequency: Our findings offer new evidence establishing an increase in LH pulse frequency from less than 1 per h to 2-3 per h within 1 day after orchidectomy. Once deprived of testicular influences, the frequency of pulsatile LH discharges remained static through 80 days. The sudden onset (less than 1 day after castration) and temporal uniformity of high-frequency LH pulses demonstrate that LH release is governed by an intrinsic, 20- to 30-min neural periodicity in castrate rats. Most important, these findings imply that the testes mask or modulate the expression of an intrinsic, 20- to 30-min neural generator directing the periodic discharge of LH in the intact male rat.

Animals↗
PubMed1984

Mapping episodic fluctuations in plasma LH in orchidectomized rats.

Reports of the frequency of pulsatile LH release in orchidectomized rats are surprisingly variable. Estimates of the period between LH pulses vary from 18.5 to 250 min in nine reports from six laboratories, published in 1981-1983. In these studies, blood samples were drawn at intervals ranging from 2.5 to 60 min. We examined the relationship between estimated LH pulse frequency and blood-sampling interval. Six castrated male rats were cannulated, and blood samples were drawn at 2.5-min intervals through 4 h. Plasma LH levels were determined by radioimmunoassay. Using the data obtained at 2.5-min intervals, we simulated blood-sampling intervals of 5, 7.5, 10, 12.5, and 15 min by sequentially deleting data points. The original and simulated data sets were analyzed by both the PULSAR and Cycle Detector computer programs. The results show that as the sampling interval increased from 2.5 to 15 min, the apparent period of pulsatile LH release rose steadily from about 20 min to about 100 min. We found a high, positive correlation between blood-sampling interval and the apparent period of LH pulses. Estimates of LH pulse frequency in castrated male rats vary directly with the frequency at which blood samples are taken. Sampling intervals greater than 5 min in orchidectomized rats yield an LH pulse period that is most likely exaggerated.

Animals↗
PubMed1983

Testosterone and photoperiod interact to regulate locomotor activity in male hamsters.

Testicular size, plasma testosterone levels, copulatory behavior, and daily locomotor activity are reduced in male hamsters after 10 weeks of exposure to short days. The role of testosterone in the short day-induced decline in locomotor activity was investigated, determining whether or not photoperiod could alter the effect of testosterone on activity. Castrated adult hamsters were allowed to acclimate to running wheels (wired to digital counters) and then were kept on either long (L:D 14:10) or short (L:D 6:18) days for 60 days. On Day 60, half of the animals on each light cycle were implanted with 12-mm-long testosterone-filled Silastic capsules; half received empty capsules. Digital counting of wheel-running activity continued for another 140 days. Blood samples taken on Day 200 confirmed L:D 14:10 and L:D 6:18 testosterone-treated hamsters had equivalent plasma testosterone levels. After an initial decline in activity, L:D 14:10 animals exhibited a progressive rise in mean running activity (from approximately 2000 to approximately 5000 wheel revolutions per day) through 100 days after the initiation of testosterone treatment. In contrast, activity levels in testosterone-treated L:D 6:18 animals remained uniform (approximately 2000 wheel revolutions per day) during this time, indicating exposure to short days rendered the hamsters less sensitive to the stimulatory effect of testosterone on activity. Of further interest was a marked increase in activity after 160-200 short days in animals treated with either testosterone-filled or empty capsules. It appears the total amount of daily locomotor activity in the hamster is modulated by circulating testosterone levels in a manner which is dependent upon the environmental photoperiod.

Animals↗
PubMed1983

Pinealectomy and lesions of the suprachiasmatic nucleus affect the castration response in hamsters exposed to short photoperiods.

Castration of male hamsters that have been exposed to a nonstimulatory photoperiod (e.g., LD 6:18) results in an attenuated increase in serum LH and FSH levels when compared to the increase observed following castration of hamsters exposed to a stimulatory photoperiod (e.g., LD 14:10). The short-day-induced inhibition of pituitary gonadotropin release, which is not dependent on the negative feedback effects of gonadal steroid hormones, is abolished if (1) the animals are transferred to LD 14:10; (2) the suprachiasmatic nuclei are lesioned at the time of castration; or (3) pinealectomy accompanies castration. These results indicate that both the pineal gland and the SCN mediate the steroid-independent inhibition of pituitary gonadotropin release that occurs during exposure to short days.

Animals↗
PubMed1983

Control of pulsatile LH release in male rats.

Distinct, short-term pulses of pituitary luteinizing hormone (LH) release are a characteristic feature of tonic LH secretion in normal rats. LH pulses are more pronounced, more frequent, and more regular in castrated rats. Using castrated rats, we sought to identify the basis of the pulsatile discharge of LH by the pituitary gland. Indwelling atrial cannulae were used to obtain frequent blood samples through 3-4 h from three cohorts of conscious, freely moving, orchidectomized male rats. Rats were (1) untreated castrates, (2) infused with ovine antiserum to LHRH or control serum, or (3) infused with a luteinizing hormone releasing hormone (LH-RH) analog, [D-pGlu1,D-Phe2, D-Trp3,6]-LH-RH. Castrates exhibited a pulsatile pattern of circulating LH levels; the mean (+/- SE) peak level of LH pulses was 640 +/- 15 ng/ml, with a mean (+/- SE) pulse period of 18.5 +/- 0.8 min. LH-RH antiserum arrested pulsatile LH secretion immediately, leaving plasma LH levels at 80-120 ng/ml. The LH-RH analog caused a similar suppression of LH release, although this effect was of a shorter duration than the suppression of LH pulses induced by LH-RH antiserum. The obliteration of LH pulses by anti-LH-RH and suppression of LH release by an LH-RH antagonist indicate that the pulsatile secretion of LH is due to corresponding stimulation of the pituitary gland by hypothalamic LH-RH. Anti-LH-RH and an LH-RH antagonist are identified as valuable probes for the experimental dissection of blood-borne signals within the rat hypothalamic-pituitary-testicular axis.

Animals↗
PubMed1982

Dark pulses affect the circadian rhythm of activity in hamsters kept in constant light.

We compared the effects of light pulses in constant darkness (DD) and dark pulses in constant light (LL) on the free-running rhythm of locomotor activity in male golden hamsters. Light pulses yielded advances, delays, or no change in the rhythm of activity. These data conform to a typical phase-response curve; this curve was unaffected by pinealectomy. Dark pulses occurring either late in the subjective night or early in the subjective day had little effect. In contrast, dark pulses occurring either late in the subjective day or early in the subjective night altered the rhythm in one of three ways: advance of the rhythm; splitting into two components; or induction of a new component, in phase with the pulse. Because dark pulses in LL perturb the circadian system in a different manner than do light pulses in DD, they may have value in identifying heretofore unknown aspects of circadian systems. As such, the use of dark pulses to perturb circadian rhythmicity will be a useful tool in examining the formal properties of circadian systems.

Animals↗
PubMed1982

Male rats secrete luteinizing hormone and testosterone episodically.

We studied the temporal aspects of endocrine signaling between the pituitary gland and testes by measuring moment to moment changes in blood LH and testosterone levels in individual male rats. Each rat was fitted with an indwelling vascular cannula, and blood was withdrawn every 5 min for 8-12 h. Rats were maintained throughout the intensive blood-sampling period with an isotonic blood replacement mixture containing rat red blood cells and a human plasma protein preparation. LH and testosterone measurements were made in plasma volumes of 50 and 60 microliters. Most rats released LH in well defined pulses, characterized by a rapid increase in plasma LH within 5-10 min and a gradual decline lasting for the next 50-70 min. LH pulses occurred singly or in trains of two to four. Episodes of testosterone secretion spanned 3-6 h and were marked by a slowly graded rise and fall of plasma testosterone. In several instances, testosterone episodes were preceded (1-2 h) by a train of closely coupled LH pulses. Within a particular animal on different days, hormone episodes varied in number, amplitude, and timing. A particular hormone profile did not serve as a reliable hormone signature for an individual rat. Many rats displayed a characteristic sequence of 1) multiple LH pulses, 2) a sustained testosterone episode, and 3) a period of no LH pulses. This tripartite sequence of events is viewed as the essence of pituitary-testicular stimulation, and testicular negative feedback. Intermittent, short term fluctuations in peripheral levels of LH and testosterone represent the blood-borne, gland to gland signals controlling hypothalamic-pituitary-testicular function in the normal rat.

Animals↗
PubMed1980

Photoperiod-induced change in responsiveness of the hypothalamic-pituitary axis to exogenous 5 alpha-dihydrotestosterone and 17 beta-estradiol in castrated male hamsters.

Exposure to short day lengths for 9 weeks renders the hypothalamic-putuitary axis of the castrate hamster extremely responsive to the negative feedback effect of exogenous testosterone. The systemic and/or local conversion of testosterone to 5 alpha-dihydrotestosterone (5 alpha-DHT) or 17 beta-estradiol (E2) is considered to be an important step in its action on target tissues. The present study was designed to determine if the photoperiod can induce changes in the sensitivity of the hypothalamic-pituitary axis to the inhibitory effects of 5 alpha-DHT or E2. 5 alpha-DHT-filled Silastic capsules that were 2, 4, or 8 mm long greatly reduced serum LH and FSH levels in castrates that were exposed to a nonstimulatory LD 8:16 light cycle, but not in animals exposed to a stimulatory LD 14:10 light cycle. E2 capsules that were 1, 2, 4, or 8 mm long greatly reduced serum LH and FSH levels in castrates exposed to LD 8:16, but not in animals exposed to LD 14:10. Serum gonadotropin levels were reduced in all of the animals receiving the larger 5 alpha-DHT (20 or 50 mm long) or E2 (20 mm long) capsules, irrespective of photoperiod. Thus, the photoperiod can alter the sensitivity of the gonadotropin control center to the negative feedback effect of both the 5 alpha-reduced derivative of testosterone, 5 alpha-DHT, and the aromatized metabolite of testosterone, E2. These results suggest that testicular secretions besides testosterone and/or extratesticular conversion of testosterone to its metabolites may be involved in the photoperiodic inhibition of the hamster reproductive system.

Animals↗