Barbara J. Collins

Non-rapid eye movement sleep is suppressed in transgenic mice with a deficiency in the somatotropic system

Sleep-wake activity was studied in a transgenic mouse model (TH-hGH) with a deficiency in the somatotropic axis (growth hormone (GH)-releasing hormone (GHRH)-GH-insulin-like growth factor-I (IGF-I)). This dwarf transgenic mouse strain expresses a human GH (hGH) reporter gene linked to 4.8 kb of the rat tyrosine hydroxylase flanking sequence, targeting the production of hGH to sites of tyrosine hydroxylase synthesis in the brain. Endogenous GH and IGF-I are suppressed in these mice, as well as GHRH. Sleep-wake activity (EEG and EMG) was recorded for 2 to 3 days in nine transgenic mice and nine wild-type littermates. Non-rapid eye movement sleep (NREMS) was significantly suppressed during both the light and the dark period in the transgenic mice; rapid eye movement sleep (REMS) was not altered. The results provide evidence that the somatotropic axis contributes to normal sleep regulation.

Long term inhibition of intake by mannitol

Abstract The addition of mannitol, a slightly sweet carbohydrate which retards absorption, to a palatable glucose-saccharin solution results in the retention of fluid in the intestine for up to 4 hr after intake of the fluid in a 15 min drinking bout. When given access for 4 hr to glucose-saccharin solutions to which mannitol is added, intake is reduced in proportion to the concentration of mannitol (0, 0.05, 0.1, 0.2 M) present. Since rats with access to a 0.2 M mannitol solution consume most of their total intakes in the first 15 or 30 min exposure, and this is sufficient to cause prolonged retention of fluid in the intestine, it was hypothesized that initial exposure to mannitol would suppress intake of a glucose saccharin solution subsequently offered. Intake of a glucose-saccharin solution was diminished for only 1.5 hr when rats were switched from a mannitol-glucose-saccharin solution, indicating that the effect of mannitol was mitigated but not abolished. The suppression of intake by mannitol does not appear to involve a conditioned taste aversion, but may activate a mechanism which is normally involved in limitation of meal size.

Clinical Behavior of Radiation-Induced Thyroid Cancer: Factors Related to Recurrence

BACKGROUND Whether thyroid cancer is more aggressive in radiation-exposed patients is not resolved. The frequency of aggressive features in post-Chernobyl patients suggests this may be the case. Our aim was to address this question by re-examining the pattern of risk factors for recurrence of thyroid cancers found in a cohort exposed to external radiation. METHODS The study population was drawn from a cohort of 4296 people, followed since 1974, who were treated before the age of 16 with conventional external radiation for benign conditions of the head and neck between 1939 and the early 1960s. The study group consisted of 390 patients who had surgically verified thyroid cancer. Potential risk factors for recurrence were evaluated by proportional hazards analysis. RESULTS Fifty patients had recurrences an average of 8.7 years after diagnosis while the other 340 patients were followed for an average of 19.7 years. The sooner after radiation exposure the cancer occurred, the more likely it was to recur (hazard ratio, 0.96/year; 95% confidence interval [CI] 0.91-0.99). Taking into account the effect of the onset of screening in 1974, the features predictive of recurrence were younger age at the initial diagnosis (hazard ratio, 0.95/year; 95% CI, 0.91-0.99) and the size of the thyroid cancer (hazard ratio, 1.2/cm; 95% CI, 1.0-1.6). CONCLUSION Although not based on a direct comparison, we conclude that thyroid cancers following external radiation exposure are not, on average, more aggressive than other thyroid cancers. The similarity of risk factors for recurrence suggests that they should be treated and followed in the same way as non-radiation-induced thyroid cancers.

Acoustic neuromas following childhood radiation treatment for benign conditions of the head and neck

Childhood radiation exposure has been associated with an increased risk for developing several neoplasms, particularly benign and malignant thyroid tumors, but little is known about the risk of developing acoustic neuromas. The aim of this study was to confirm whether there is a risk for acoustic neuromas and, if so, to determine its magnitude and duration. We investigated the time trend and dose-response relationships for acoustic neuroma incidence in a cohort of 3,112 individuals who were irradiated as children between 1939 and 1962. Most of the patients were treated to reduce the size of their tonsils and adenoids and received substantial radiation exposure to the cerebellopontine angle, the site of acoustic neuromas. Forty-three patients developed benign acoustic neuromas, forty of them surgically resected, far in excess of what might be expected from data derived from brain tumor registries. The mean dose (+/-SD) to the cerebellopontine angle was 4.6 +/- 1.9 Gy. The relative risk per Gy was 1.14 (95% confidence interval 1.0-1.3). The earliest case occurred 20.4 years after exposure and the latest 55 years after exposure (mean 38.3 +/- 10.1 years). Our study provides support for an association between acoustic neuromas and childhood radiation exposure. Although acoustic neuromas are usually benign and often asymptomatic, many cause significant morbidity. Following childhood radiation exposure, they appear after a long latency and continue to occur many decades afterward. Any symptoms of an acoustic neuroma in a patient with a history of radiation to the head and neck area should be investigated carefully, and the threshold for employing imaging should be lowered.

Coordinate enrichment of cranin (dystroglycan) subunits in synaptic membranes of sheep brain.

Cranin (dystroglycan), a mucin-like extracellular matrix receptor comprised of two subunits (alpha and beta), is involved in regulating cell-matrix interactions in a variety of tissues, including brain. A basic issue remains unresolved concerning the distribution of cranin in brain: are the alpha and beta subunits coordinately expressed at the synapse? We report here that cranin is indeed enriched progressively in synaptosomes and synaptic membranes of sheep brain, as assessed by immunoblotting and laminin-blotting assays, and that the extent of enrichment is similar for both alpha and beta subunits. These findings support the hypothesis that cranin (dystroglycan) contributes to synaptic function in the CNS.

Distention of the small intestine, satiety, and the control of food intake

The studies reported here investigated the role that filling of the small intestine plays in the control of ingestion. Adding mannitol, a nonabsorbable carbohydrate, to a palatable solution reduced meal size in rats in proportion to its concentration. Intake is suppressed for the duration of time that the small intestine remains full. If dietary fiber, which sequesters water and swells, fills the small intestine sufficiently, it may act to suppress meal size and prolong the length of intermeal intervals.

Differential desensitization response of the neonatal and adult rat somatotroph to growth hormone-releasing hormone and phorbol ester

Elevated levels of circulating growth hormone (GH) in the perinatal animal may be caused in part by relative resistance to the desensitizing effects of GH secretagogues. We compared the effects of 4-day exposure of primary pituitary cell cultures from adult male and 2-day-old rats to GH-releasing hormone (GHRH; 10 nM) or 12-O-tetradecanoyl-phorbol-13-acetate (TPA; 1 microM) on subsequent acute GH response to these secretagogues. Prolonged exposure to GHRH reduced subsequent GHRH-induced GH release from pituitary cells of both age groups, but the reduction in GH response was significantly less in neonates than adults. In addition, GH secretion from neonatal pituitaries rose progressively during each day of GHRH exposure, to reach levels almost 7 times basal; by contrast, GH secretion from adult pituitaries increased only transiently and then declined. Prolonged exposure to TPA reduced the subsequent GH response to TPA equally in neonates and adults, but differentially affected the GH response to GHRH; TPA exposure reduced the GH response to GHRH in neonates, but not in adults. These data suggest a fundamental difference between the GH regulatory processes of neonatal and adult pituitaries. The ability of the somatotroph to exhibit attenuated GH response on exposure to secretagogue is developmentally regulated, and relative resistance of the immature somatotroph to homologous desensitization by GHRH may contribute to elevated serum GH levels during the perinatal period.