Effects of repeated maternal separations on the adrenocortical response to stress of preweanling rats.

Previous data indicate that the infant rat shows a marked increase in adrenocortical responsiveness to stress immediately following prolonged maternal separation. In Experiment 1 we studied the immediate effects of repeated maternal deprivation. Our results indicate that the increase in basal as well as stress-induced corticosterone levels is a direct function of the length of the deprivation period immediately preceding testing, and is not cumulative. In Experiment 2 we examined the long-term consequences of maternal deprivation on adrenal responsivity. Four days following a single 24-h period of maternal deprivation, pups remained hyperresponsive to stress, although their basal levels of corticosterone had returned to control values. Shorter periods of deprivation (which did result in increased responsivity immediately following deprivation) did not have persistent effects. Our data suggest: 1) short periods of deprivation do not have a cumulative effect, and 2) there is a critical length of deprivation beyond which persistent changes in adrenocortical responsivity ensue.     

Noxious stimulus-induced increase in spinal prostaglandin E2 is noradrenergic terminal-dependent

Prostaglandins (PGs) were measured in perfusate from the lumbar intrathecal (IT) space of pentobarbital anaesthetized rats. The level of PGE2, but not of PGF2 alpha or 6-keto PGF1 alpha, was increased by immersion of a hindpaw in water at a noxious temperature (50 degrees C). No increase in PGE2 was produced by non-noxious thermal stimulation (35 degrees C water). The noxious stimulus-evoked increase in PGE2, and increases in PGE2 during norepinephrine infusion (10 micrograms/ml), were significantly decreased in rats pretreated with intrathecal 6-hydroxydopamine. These data suggest that noxious stimuli induce an increase in the production of spinal PGE2 and that this production derives from, or requires the presence of noradrenergic terminals in the spinal cord.     

The social worker's interview in chronic urticaria.

Ten patients with chronic urticaria were interviewed by a psychiatric social worker as part of the clinical examination. The information obtained was evaluated in comparison with the allergist-internist's history by the allergist-internist, psychiatrist and social workers. The social worker's interview offered relatively little help to the managing physician or patient in this setting.     

Development of circadian periodicity in base and stress levels of corticosterone.

Base and stress levels of corticosterone were assessed at 4-h intervals over a 24-h period in male and female rats at age 18, 22, and 26 days. A significant periodicity in base levels of corticosterone is present at 22 days of age; however, a rhythm in stress values does not appear until age 26 days. At age 26 days the pattern of the circadian periodicity in both base and stress concentrations of corticosterone resembles that of the mature rhythm.     

Postnatal development of neurogenic inflammation in the rat.

We have studied the development in the rat of neurogenic inflammatory mechanisms that mediate cutaneous plasma extravasation. At birth and at postnatal day 10, intradermal injection of substance P, histamine, and bradykinin produced no significant plasma extravasation. At day 13 through adulthood (days 42-49), all test agents produced significant plasma extravasation which increased with increasing age. In the adult rat, pretreatment with 6-hydroxydopamine, to eliminate sympathetic postganglionic nerve terminals, attenuated the plasma extravasation elicited by substance P, histamine and bradykinin. The possible role of the sympathetic postganglionic neuron in the age-dependent changes in neurogenic inflammation is discussed.     

Characterization of proteins encoded by the Epstein-Barr virus transactivator gene BMLF1

Epstein-Barr virus (EBV) encodes a gene product in the BamHI-M leftward reading frame 1 (BMLF1) that functions as a promiscuous transactivator acting upon many other enhancer-promoter combinations. This protein has been studied by producing a polyclonal rabbit antiserum directed against a LacZ-BMLF1 fusion protein that was synthesized in Escherichia coli. Western blotting was employed to demonstrate that this antiserum specifically detected the BMLF1 proteins in E. coli, monkey, mouse, or B cells transfected with this gene, and in EBV-positive B cells chemically induced to produce this protein. In these induced B cells, two major proteins of 50 and 60 kDa and several minor antigens were detected by these antibodies. Transfection of an expression vector containing the BMLF1 coding sequence resulted in the synthesis of only the 50 kDa proteins. These major products were phosphorylated in vivo and were localized to the cell nucleus. Only the larger 60-kDa antigen was specifically induced to be synthesized by a different EBV encoded transactivator, the BZLF1 gene product. Chemical induction of lymphocytes latently infected with EBV resulted in the synthesis of both the 60- and 50-kDa forms of the BMLF1 transactivator. Two major forms of this EBV-encoded transactivator have been detected. The 60-kDa form is presumably derived from the BSLF2-BMLF1 open reading frame while the smaller antigens, 50 kDa size, appear to be made only by the BMLF1 open reading frame. These two forms of the transactivator are differently regulated and the functional significance of this remains to be explored.     

Physiological and behavioral effects of prior aversive stimulation (preshock) in the rat

Physiological and behavioral measures were assessed in rats that had been previously exposed to unsignaled inescapable intense shock (preshock). Animals subjected to such prior aversive stimulation exhibited greater adrenocortical steroid response compared to nonpreshocked controls when subsequently tested in the open field. An increment in defecation was also observed, with ambulation and rearing behavior being markedly inhibited in the preshocked rat during these sessions.     

Tales of tails: regulation of telomere length and telomerase activity during lymphocyte development, differentiation, activation, and aging

Summary: Telomerase activity and the regulation of telomere length are factors which have been implicated in the control of cellular replication. These variables have been examined during human lymphocyte development, differentiation, activation, and aging. It was found that telomere length of peripheral blood CD4⁺ T cells decreases with age as well as with differentiation from naive to memory cells in vivo , and decreases with cell division in vitro. These results provide evidence that telomere length correlates with lymphocyte replicative history and residual replicative potential. In contrast, telomere length appears to increase during tonsil B-cell differentiation and germinal center (GC) formation in vivo. It was also found that telomerase activity is highly regulated during T-cell development and B-cell differentiation in vivo , with high levels of telomerase activity expressed in thymocytes and GC B cells, and low levels of telomerase activity in resting mature peripheral blood lymphocytes. Finally, resting lymphocytes retain the ability to upregulate telomerase activity upon activation, and this capacity does not appear to decline with age. Although the precise role of telomerase in lymphocyte function remains to be elucidated, telomerase may contribute to protection from telomere shortening in T and B lymphocytes, and may thus play a critical role in lymphocyte development, differentiation and activation. The future study of study telomerase and its regulation of telomere length may enhance our understanding of bow the replicative lifespan is regulated in lymphocytes.     

Orexin A mediation of time spent moving in rats: Neural mechanisms

The brain regulates energy balance and spontaneous physical activity, including both small- and large-motor activities. Neural mediators of spontaneous physical activity are currently undefined, although the amount of time spent in sedentary positions versus standing and ambulating may be important in the energetics of human obesity. Orexin A, a neuropeptide produced in caudal hypothalamic areas and projecting throughout the neuraxis, enhances arousal and spontaneous physical activity. To test the hypothesis that orexin A affects the amount of time spent moving, we injected orexin A (0–1000 pmol) into three orexin projection sites in male Sprague–Dawley rats: hypothalamic paraventricular nucleus, rostral lateral hypothalamic area and substantia nigra pars compacta, and measured spontaneous physical activity. Orexin A affects local GABA release and we co-injected orexin A with a GABA agonist, muscimol, in each brain site. Dopamine signaling is important to substantia nigra function and so we also co-injected a dopamine 1 receptor antagonist (SCH 23390) in the substantia nigra pars compacta. In all brain sites orexin A significantly increased time spent vertical and ambulating. Muscimol significantly and dose-dependently inhibited orexin A effects on time spent moving only when administered to the rostral lateral hypothalamic area. In the substantia nigra pars compacta, SCH 23390 completely blocked orexin A–induced ambulation. These data indicate that orexin A influences time spent moving, in three brain sites utilizing separate signaling mechanisms. That orexin A modulation of spontaneous physical activity occurs in brain areas with multiple roles indicates generalization across brain site, and may reflect a fundamental mechanism for enhancing activity levels. This potential for conferring physical activity stimulation may be useful for inducing shifts in time spent moving, which has important implications for obesity.