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Biomedical subjects

L Johannsen

Publications and source records attributed to L Johannsen.

35 records · Page 2Linked to original sources

Interleukin 1 alpha and an interleukin 1 beta fragment are somnogenic.

The somnogenic activity of interleukin 1 beta (IL-1 beta) has previously been established. Interleukin 1 alpha (IL-1 alpha) is a distinct gene product that possesses similar biological activities. We report here that IL-1 alpha, like IL-1 beta, has the capacity in rabbits to enhance non-rapid-eye-movement sleep, electroencephalographic slow-wave (0.5-3.5 Hz) voltages, and body temperatures and to inhibit rapid-eye-movement sleep. After IL-1 alpha, sleep remained episodic, and at the doses used no abnormal behavior was observed. Several synthetic IL-1 alpha and IL-1 beta peptides were also tested in vivo for somnogenic and pyrogenic activity and in vitro for their ability to stimulate prostaglandin E2 (PGE2) production by fibroblasts and proliferation of T-cells. Only IL-1 beta-(208-240) enhanced non-rapid-eye-movement sleep and body temperature, although both IL-1 beta-(208-240) and IL-1 alpha-(223-250) stimulated PGE2 production; both of these peptides failed to stimulate T-cell production. In contrast, four other IL-1 peptides were nonpyrogenic and somnogenically inactive yet stimulated T-cell proliferation. We conclude that the components of IL-1 required for sleep and temperature activities are different from those required for T-cell proliferation.

Animals↗

Prolactin, vasoactive intestinal peptide, and peptide histidine methionine elicit selective increases in REM sleep in rabbits.

The purpose of these experiments was to determine whether (1) vasoactive intestinal peptide (VIP) produces effects on rabbit sleep similar to those reported for rats and cats; (2) peptide histidine methionine (PHM), a peptide closely related to VIP, mimics the sleep effects of VIP; and (3) pituitary prolactin (PRL), a pituitary hormone that has a sleep-related secretory pattern and for which VIP and PHM act as releasing factors, has similar effects on sleep. VIP or PHM (0.01, 0.1 and 1.0 nmol/kg) was intracerebroventricularly (i.c.v.) injected; PRL (ovine PRL, 45 and 200 IU/kg) was subcutaneously (s.c.) administered. Sleep-wake activity and brain temperature were recorded for 6 h. For controls, rabbits received artificial cerebrospinal fluid i.c.v. or PRL-vehicle s.c. VIP and PHM promoted rapid eye movement sleep (REMS), although these effects were not dose-dependent. In addition, the high dose of VIP and PHM transiently increased wakefulness. Increases in REMS occurred only during hours 2-6 after i.c.v. injection of VIP and peptide histidine leucine (PHI). After s.c. injection of PRL, REMS started to increase in postinjection hour 3. The effect of the high dose was significantly more pronounced than that of the small dose. Each substance enhanced the frequency of REMS episodes, and the high dose of PRL also increased the duration of REMS bouts. These results are consistent with the hypothesis that VIP is involved in physiological regulation of REMS, and that the VIP- and PHM-induced increases in REMS may be mediated via release of PRL.

Animals↗

Interleukin-6 is pyrogenic but not somnogenic.

Interleukin-6 (IL6) induces acute phase protein production and is hypothesized to mediate systemic and central effects of IL1. To determine whether IL6 possesses somnogenic properties, rabbits were injected intracerebroventricularly with IL6; sleep-wake activity was determined and brain temperatures recorded for 6 hr. IL6 induced fever in a dose-related manner with no effect on sleep-wake activity. IL6, therefore, is the first cytokine reported to elicit fever without promoting sleep. We conclude that the somnogenic action of IL1 is not mediated through IL6.

Acute-Phase Proteins↗

Interleukin-1-induced sleep and febrile responses differentially altered by a muramyl dipeptide derivative.

Muramyl dipeptide (N-acetylmuramyl-L-alanyl-D-isoglutamine; AcMur-L-Ala-D-iGln; MDP) is a somnogenic, pyrogenic, and immunoadjuvant component of bacterial cell wall peptidoglycan. It enhances the production of the cytokine interleukin 1 (IL-1) in vivo and in vitro; IL-1 itself is somnogenic and pyrogenic. The pyrogenic effects of IL-1 may be separated from its somnogenicity by the use of antipyretics. A methyl ester derivative of MDP (murametide; AcMur-L-Ala-D-Gln-alpha-methyl ester) blocks IL-1-induced fever, but induces IL-1 production/release. Therefore, the effects of murametide on IL-1-induced sleep and fever responses were determined. Rabbits were pretreated with intravenous injections of murametide 0, 30 or 60 min before intravenous injection of a pyrogenic/somnogenic dose of recombinant IL-1 beta (rIL-1 beta). Murametide alone produced no effects on sleep or brain temperatures. Murametide given simultaneously with rIL-1 beta potentiated increases of brain temperatures, whereas when there was a 60 min delay between the injection of murametide and rIL-1 beta, responses were similar to those induced by rIL-1 beta alone. Murametide given 30 min before rIL-1 beta, blocked the expected IL-1-induced fevers but not the rIL-1 beta-mediated increases of slow-wave sleep and decreases of rapid-eye-movements sleep. These results reinforce the conclusion that, in part, independent brain mechanisms are involved in the somnogenic and pyrogenic actions of IL-1.

Acetylmuramyl-Alanyl-Isoglutamine↗

Elevated serum levels of calcitonin gene-related peptide (CGRP) but no evidence for CGRP gene expression in non-small cell lung carcinomas.

Calcitonin gene-related peptide (CGRP) is a hormone formed by alternative post-transcriptional processing of the calcitonin gene. It is a neuropeptide localized to discrete regions of the central nervous system (CNS) and in nerve fibres associated with blood vessels. It is also expressed in medullary carcinomas of the thyroid and lung carcinoma cell lines. The latter finding suggests a possible value for CGRP as tumour marker in lung carcinomas. In this investigation of 22 patients undergoing operation for lung tumours, pre and post-operative levels of serum CGRP were measured. Preoperative as well as postoperative serum CGRP levels were significantly elevated when compared to age-matched normals. However, no evidence could be found for CGRP gene expression in tumour tissue from the same patients as judged by immunocytochemistry or in-situ hybridization using CGRP cRNA probes. CGRP has been localized to nerve fibres in relation to pulmonary blood vessels and has been shown to be a potent vasodilator. These findings, and the absence of evidence for synthesis in tumours, as opposed to cell lines derived from lung carcinomas, suggests that the lack of post-operative normalization of serum CGRP concentrations may be related to physiological changes in cardiovascular haemodynamics following surgery. Elevated pre-operative serum CGRP levels may also reflect a consequence of the lung carcinoma leading to increased release of CGRP from sites in the vasculature yet to be determined, but does not indicate synthesis de novo and secretion of CGRP by the tumours.

Biomarkers, Tumor↗

Somnogenic activity of O-acetylated and dimeric muramyl peptides.

Slow-wave sleep-promoting factors in brain and urine were identified as muramyl peptides (MPs), the building blocks of bacterial cell wall peptidoglycan. In this study, structural variations of MPs that occur naturally in bacterial peptidoglycan were investigated for somnogenic activity. Monomeric and dimeric MPs were isolated and purified from Neisseria gonorrhoeae and Actinomadura sp. strain R39. The structures of these MPs were verified by fast atom bombardment mass spectroscopy and tandem mass spectroscopy. After intracerebroventricular administration of MPs, electroencephalograms and brain temperatures of rabbits were recorded for 6 h and were analyzed to determine durations of slow-wave sleep, rapid-eye-movement sleep, and wakefulness. The 6-O acetylation of muramic acid enhanced the somnogenic effects of certain monomeric MPs relative to their non-O-acetylated (but otherwise identical) counterparts. Two monomeric MPs containing an unsubstituted amide (i.e., Iso-Gln) were inactive, thus confirming previous results showing that amidation of a variety of MPs can block somnogenic activity. Two peptide-cross-linked MP dimers tested had no effect on slow-wave sleep, although a third peptide-cross-linked MP containing a 1,6-anhydro muramyl end on one of its monomeric subunits, a structure that enhances somnogenic potency of un-cross-linked monomers, was somnogenic. Two dimers connected by glycosidic bonds and containing an Iso-Gln moiety were inactive. Two other glycosidically linked dimers that also contained an Iso-Gln moiety, but were of lower molecular weight, were somnogenic. In summary, 6-O acetylation of muramic acid in somnogenic MPs enhances activity, and as a class, peptide-linked dimeric MPs tend to be less active than their constituent monomers.

Acetylation↗

Onset of penicillin-induced bacteriolysis in staphylococci is cell cycle dependent.

Synchronously growing staphylococci were treated with "lytic" concentrations of penicillin at different stages of their division cycle. Coulter Counter measurements and light microscopy were used to determine the onset of bacteriolysis. Independent of the stage of the division cycle at which penicillin was added, (i) the cells were always able to perform the next cell division; (ii) the following division, however, did not take place; and (iii) instead, at this time, when the onset of the subsequent cell separation was observed in control cultures, lysis of the penicillin-treated cells occurred. These results support a recent model (P. Giesbrecht, H. Labischinski, and J. Wecke, Arch. Microbiol. 141:315-324, 1985) explaining penicillin-induced bacteriolysis of staphylococci as the result of a special morphogenetic mistake during cross wall formation.

Cell Cycle↗

Bacterial products, cytokines and sleep.

Sleep deprivation, infection and administration of muramyl peptides or certain other immune response modifiers all alter sleep. Sleep, temperature and hematologic effects observed after bacterial infection are also elicited after administration of isolated bacterial cell walls. Macrophages have the capability to digest bacterial peptidoglycan and in the process produce pyrogenic and somnogenic substances of low molecular weight. Activated macrophages also produce cytokines and some of these, e.g., interleukin-1 (IL-1), are somnogenic. Our results emphasize the close connection of the infection process, fever and sleep. Muramyl peptides and/or IL-1 may also be involved in daily regulation of sleep.

Animals↗

Growth hormone-releasing factor enhances sleep in rats and rabbits.

Previously, it was suggested that a hypothalamic mechanism links somatotropin [growth hormone (GH)] secretion to sleep regulation, and this may explain the temporal correlation between GH release and nonrapid eye movement sleep (NREMS) on sleep onset. The purpose of these experiments was to study whether growth hormone-releasing factor (GRF), a hypothalamic peptide responsible for stimulation of GH secretion, also has the capacity to promote sleep in rats and rabbits. Artificial cerebrospinal fluid or GRF (human GRF-[1-40], 0.01, 0.1, and 1 nmol/kg) was intracerebroventricularly injected to rats at dark onset, and the electroencephalogram (EEG), brain temperature (Tbr), and motor activity were recorded for 24 h. Rabbits received the same doses of GRF during the light period, and sleep-wake activity was monitored for 6 h. GRF promoted NREMS and rapid eye movement sleep (REMS) and increased EEG slow-wave activity in both rats and rabbits. NREMS increased in postinjection hour 1 after low doses of GRF, whereas the effect was more prolonged after higher doses. REMS increased in response to the low and middle doses of GRF in postinjection hour 1 in rats and in hour 2 after each dose in rabbits. The diurnal rhythms of sleep-wake activity, motor activity, and Tbr were not affected in rats. Because GRF promotes sleep and also stimulates GH secretion, it is a likely candidate for linking GH secretion and sleep regulation.

Animals↗

Demonstration of S-100 protein in sustentacular cells of phaeochromocytomas and paragangliomas.

Eighteen phaeochromocytomas, including both sporadic and familial cases, four cervical paragangliomas, two jugular paragangliomas, and one abdominal paraganglioma were examined immunohistochemically for the presence of S-100 protein. Positive staining in cells morphologically similar to the sustentacular cells of normal paraganglia and adrenal medulla were found in all paragangliomas and in the benign and aggressively growing phaeochromocytomas. In the two malignant tumours no positive reaction was demonstrated. In one tumour the sustentacular cells were shown to contain glial fibrillary acidic protein further supporting their Schwann cell relationship. The number of S-100 positive cells varied considerably. They demonstrated a spindle celled or elongated configuration with long slender processes. The nature of the sustentacular cell proliferation, neoplastic versus reactive, is discussed.

Adolescent↗

Somnogenic cytokines and models concerning their effects on sleep.

All the sleep-promoting substances currently identified also have other biological activities. Despite years of effort, a single specific central nervous system sleep center has not been described. These observations led us to propose a biochemical model of a sleep activational system in which the effects of several sleep factors are integrated into a regulatory scheme. These sleep factors interact by altering the metabolism, production, or activity of each other and thereby result in multiple feedback loops. This web of interactions leads to sleep stability in that minor challenges to the system will not greatly alter sleep. The system, however, is responsive to strong perturbations, such as sleep deprivation and infectious disease. The sleep-promoting effects of cytokines and their interactions with prostaglandins and the neuroendocrine system are used to illustrate the functioning of a part of the sleep activational system under normal conditions and during infectious disease. Although the actions of individuals sleep factors are not specific to sleep, their interactions at various levels of the neuraxis can mediate a specific sleep response. Such a system would also be responsive to the autonomic and environmental parameters that alter sleep.

Animals↗

Adolescent abortion and mandated parental involvement.

Laws mandating parental involvement in adolescent abortion decisions are in contrast to laws governing other aspects of adolescent health care. Studies support that adolescents are often capable of making mature, informed health care decisions. Nurses encountering these adolescents have a unique opportunity to support them through the system and enhance the decision-making process.

Abortion, Legal↗