Biomedical subjects

M Møller

Publications and source records attributed to M Møller.

At least 19 recordsLinked to original sources

PubMed2007

Dynamic changes in corticospinal tracts after stroke detected by fibretracking.

BACKGROUND AND AIMS: The integrity of motor pathways and functional connectivity patterns are important in assessing plastic changes related to successful recovery, to obtain prognostic information and to monitor future therapeutic strategies of stroke patients. We tested the following hypotheses: (1) that changes in axonal integrity along the corticospinal tract after stroke can be detected as a reduction in fractional anisotropy; and (2) that sustained low fractional anisotropy is indicative of axonal loss and therefore is correlated with poor motor outcome, as measured by specific neurological motor scores. METHODS: We developed a segmentation tool based on magnetic resonance diffusion tensor imaging in conjunction with three dimensional fibretracking for longitudinal studies of the corticospinal tract, and used specific neurological motor scores to test the hypotheses in five stroke patients within the first week and 30 and 90 days after the stroke. RESULTS: Reduction in fractional anisotropy within the first weeks after stroke reflected a decline in axonal integrity, leading to Wallerian degeneration, and demonstrated a correlation between the temporal evolution of fractional anisotropy and motor function in patients with poor motor outcome. CONCLUSION: The study demonstrated the feasibility of fibretracking as a segmentation tool for mapping distal parts of the corticospinal motor pathways and showed that fractional anisotropy in the segmented corticospinal tract is a sensitive measure of structural changes after stroke.

Aged↗

PubMed2006

Telomerase peptide vaccination of patients with non-resectable pancreatic cancer: A dose escalating phase I/II study.

Patients with inoperable pancreatic cancer have a dismal prognosis with a mean life expectancy of 3-6 months. New treatment modalities are thus urgently needed. Telomerase is expressed in 85-90% of pancreas cancer, and immunogenic telomerase peptides have been characterised. A phase I/II study was conducted to investigate the safety, tolerability, and immunogenecity of telomerase peptide vaccination. Survival of the patients was also recorded. Forty-eight patients with non-resectable pancreatic cancer received intradermal injections of the telomerase peptide GV1001 at three dose levels, in combination with granulocyte-macrophage colony-stimulating factor. The treatment period was 10 weeks. Monthly booster vaccinations were offered as follow-up treatment. Immune responses were measured as delayed-type hypersensitivity skin reaction and in vitro T-cell proliferation. GV1001 was well tolerated. Immune responses were observed in 24 of 38 evaluable patients, with the highest ratio (75%) in the intermediate dose group. Twenty-seven evaluable patients completed the study. Median survival for the intermediate dose-group was 8.6 months, significantly longer for the low- (P = 0.006) and high-dose groups (P = 0.05). One-year survival for the evaluable patients in the intermediate dose group was 25%. The results demonstrate that GV1001 is immunogenic and safe to use. The survival data indicate that induction of an immune response is correlated with prolonged survival, and the vaccine may offer a new treatment option for pancreatic cancer patients, encouraging further clinical studies.

Adenocarcinoma↗

PubMed2005

Deformation of the mandible due to neonatal moulding: a 10-year follow-up.

A 3-day-old infant with paralysis of the marginal mandibular branch of the facial nerve and asymmetry of the mandible due to neonatal moulding is presented. Ten years after the initial presentation, the asymmetry and paralysis was still present. Orthodontic treatment has been instituted because of malocclusion. Surgical correction of the mandibular asymmetry after adulthood seems not to be necessary.

Facial Asymmetry↗

PubMed2005

Tachykinins and tachykinin-receptors in the rat pineal gland.

High-pressure liquid chromatography of extracts of rat pineal glands, followed by radio immunological analysis with antibodies against tachykinins, demonstrated the presence of substance P, neurokinin A and neurokinin B in the superficial rat pineal gland. Immunohistochemistry on perfusion-fixed rat brain sections showed substance P and neurokinin A to be present in nerve fibers located both in the perivascular spaces as well as intraparenchymally between the pinealocytes. After extracting total RNA, followed by reverse transcription and polymerase chain reaction amplification with primers specific for NK1-, NK2- and NK3-receptors, agarose gel analysis of the reaction products showed the presence of mRNA encoding all three neurokinin receptors. Immunohistochemical analysis showed NK1 receptor to be located in the interstitial cells of the gland. This location was confirmed by use of in situ hybridization using radioactively labeled antisense oligonucleotide probes. Double immunohistochemical stainings showed that the NK1-immunoreactive cells were not a part of the macrophages or antigen-presenting cells of the gland. Our study suggests that tachykinins, after release from intrapineal nerve fibers, are involved in an up to now unknown function, different from that of melatonin synthesis.

Animals↗

PubMed2004

Safe inoculation of blood and bone marrow for liquid culture detection of mycobacteria.

BACKGROUND: Needlestick injuries confer an unnecessary risk of occupational bloodborne infections such as human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. After an accidental needlestick injury, procedures for inoculation of liquid culture media for rapid detection of Mycobacterium tuberculosis complex and other mycobacteria from blood and bone marrow specimens were reviewed. AIM: To identify a safer transfer device, which could replace the ordinary syringe in inoculation of liquid culture vials. METHODS: We identified a transfer device to transfer blood or bone marrow specimens from bedside tubes into liquid culture vials. CONCLUSION: The changed procedure will reduce the risk of needlestick accidents and be of benefit to other microbiological laboratories using the same or similar inoculation techniques.

Adult↗

PubMed2003

PACAP-containing intrapineal nerve fibers originate predominantly in the trigeminal ganglion: a combined retrograde tracing- and immunohistochemical study of the rat.

Pituitary adenylate-cyclase activating polypeptide (PACAP) is a neuropeptide originally isolated from the hypothalamus and located in many neuronal systems in both the central and peripheral nervous system. PACAP is also found in nerve fibers innervating the pineal gland, where it stimulates the secretion of the pineal hormone, melatonin, by binding to specific PACAP-receptors located on the cell membrane of the pinealocyte. In this study we have investigated the origin of PACAP-containing nerve fibers innervating the rat pineal gland by combined retrograde tracing with Fluorogold and immunohistochemistry for PACAP. A solution of 2% Fluorogold was injected iontophoretically into the superficial pineal gland of Wistar rats, and the animals were allowed to survive for 1 week. After perfusion fixation of the rats, the location of the tracer was investigated in the brain and the sphenopalatine, otic, and trigeminal ganglia. The tracer was found in all the investigated ganglia. However, colocalization with PACAP was predominantly found in the trigeminal ganglion and only occasionally in the sphenopalatine and otic ganglia. Due to the stimulatory function of PACAP on pineal melatonin secretion, the PACAP-containing neurons of this ganglion could be considered a subset of the parasympathetic nervous system. The presence of neurons with a parasympathetic function in a ganglion that has been considered a purely sensory ganglion, is a new concept in neuroanatomy.

Animals↗

PubMed2003

Molecular and behavioral analysis of the R6/1 Huntington's disease transgenic mouse.

Transgenic mice expressing exon 1 of the human Huntington's disease (HD) gene carrying a 115 CAG repeat (line R6/1) are characterized by a neurologic phenotype involving molecular, behavioral and motor disturbances. We have characterized the R6/1 to establish a set of biomarkers, which could be semi-quantitatively compared. We have measured motor fore- and hindlimb coordination, fore- and hindpaw footprinting, general activity and anxiety, feetclasping, developmental instability. Molecular investigations involved measurements of cannabinoid receptor 1 mRNA, met-enkephalin peptide, dopamine and cyclic AMP-regulated phosphoroprotein 32 kDa and neuronal inclusions. Molecular and behavioral testing was performed on female hemizygotic R6/1 transgenic mice and female wildtype littermates between 6 and 36 weeks of age. We show that the cannabinoid receptor 1 receptor is severely and rapidly downregulated in the R6/1 mouse between the 8(th) to the 10(th) week of age. At 14 weeks of age the first transgenic mice showed a behavioral phenotype measured by feetclasping. However, there was great variation between the individual animals. At 11 weeks of age the mice demonstrated progressively increasing developmental instability as measured by fluctuating asymmetry. Weight differences were evident by 22 weeks of age. Mice tested at 23 and 24 weeks of age showed significant impairments in open field and plus-maze analysis respectively. We observed no significant abnormalities in stride length of the R6/1 mouse model. As the analyzed parameters are easily detected and measured, the R6/1 mouse appears to be a good model for evaluating new drugs or types of therapy for HD.

Animals↗

PubMed2003

Serotonin stimulates hypothalamic mRNA expression and local release of neurohypophysial peptides.

The neurotransmitter serotonin (5-HT) stimulates the secretion of vasopressin and oxytocin, and 5-HT is involved in the mediation of the vasopressin and oxytocin response to stress. In male Wistar rats, we investigated the 5-HT receptors involved in the 5-HT-induced increase of mRNA expression of vasopressin and oxytocin in the hypothalamic paraventricular nucleus (PVN) and supraoptic nucleus (SON). The 5-HT precursor, 5-hydroxytryptophan, injected in combination with the 5-HT reuptake inhibitor, fluoxetine, increased oxytocin mRNA expression in the PVN, and the concentration of vasopressin and oxytocin in plasma, whereas mRNA in the SON was not affected. Intracerebroventricular infusion of 5-HT agonists selective for the 5-HT1A, 5-HT1B, 5-HT2A and 5-HT2C receptor increased oxytocin mRNA in the SON and PVN. Infusion of agonists selective for the 5-HT2A + 2C receptor increased vasopressin mRNA in the PVN, whereas none of the 5-HT agonists affected vasopressin mRNA in the SON. All the 5-HT agonists infused increased peripheral oxytocin concentration and vasopressin was increased by stimulation of the 5-HT2A, 5-HT2C and 5-HT3 receptor. Intracerebroventricular infusion of 100 nmol 5-HT increased the extracellular hypothalamic concentration of vasopressin as measured by microdialysis in the PVN. To evaluate the involvement of hypothalamic-pituitary system in the 5-hydroxytryptophan and fluoxetine-induced vasopressin secretion, rats were immunoneutralized with a specific anti-corticotropin-releasing hormone antiserum. This treatment reduced plasma vasopressin and oxytocin responses. We conclude that stimulation with 5-hydroxytryptophan or 5-HT agonists increases mRNA expression of oxytocin in the PVN and the SON via stimulation of at least 5-HT1A, 5-HT1B, 5-HT2A and 5-HT2C receptors. Vasopressin mRNA in the PVN was increased only via the 5-HT2 receptor, whereas vasopressin mRNA in the SON does not seem to be affected by 5-HT stimulation. Corticotropin-releasing hormone appears to be partly involved in the mediation of 5-HT induced vasopressin and oxytocin secretion.

Animals↗

PubMed2003

Origin of cerebrospinal fluid melatonin and possible function in the integration of photoperiod.

Melatonin, which is synthesized at night by the pineal gland, is present in the cerebrospinal fluid (CSF), but its entry site and its role in this compartment are not known. Using several approaches, we tested the hypothesis that melatonin enters the CSF through the pineal recess, an evagination of the third ventricle. CSF melatonin concentrations are higher near the pineal gland than in the anterior part of the third ventricle, and decrease markedly (80%) after sealing off the pineal recess. Moreover, ultrastructure and permeability analyses of the pineal-CSF interface showed that melatonin could reach the CSF either via delivery in situ by protruding pinealocytes that make direct contact with the CSF or via extracellular secretion and interstitial fluid draining into the ventricular lumen. These data indicate that melatonin in the CSF probably originates from a few pinealocytes of the basal part of the pineal gland neighbouring the pineal recess. Melatonin carried to the brain by the blood appears to be able to mediate the effects of photoperiod on reproduction, but it is unclear whether melatonin in CSF may fine-tune this response both in terms of timing and amplitude. It is critical to determine which pathway, blood or CSF, allows melatonin to reach its central targets more efficiently.

Animals↗

PubMed2002

Serotonergic stimulation of corticotropin-releasing hormone and pro-opiomelanocortin gene expression.

The neurotransmitter serotonin (5-HT) stimulates adrenocorticotropic hormone (ACTH) secretion from the anterior pituitary gland via activation of central 5-HT1 and 5-HT2 receptors. The effect of 5-HT is predominantly indirect and may be mediated via release of hypothalamic corticotropin-releasing hormone (CRH). We therefore investigated the possible involvement of CRH in the serotonergic stimulation of ACTH secretion in male rats. Increased neuronal 5-HT content induced by systemic administration of the precursor 5-hydroxytryptophan (5-HTP) in combination with the 5-HT reuptake inhibitor fluoxetine raised CRH mRNA expression in the paraventricular nucleus (PVN) by 64%, increased pro-opiomelanocortin (POMC) mRNA in the anterior pituitary lobe by 17% and stimulated ACTH secretion five-fold. Central administration of 5-HT agonists specific to 5-HT1A, 5-HT1B, 5-HT2A or 5-HT2C receptors increased CRH mRNA in the PVN by 15-50%, POMC mRNA in the anterior pituitary by 15-27% and ACTH secretion three- to five-fold, whereas a specific 5-HT3 agonist had no effect. Systemic administration of a specific anti-CRH antiserum inhibited the ACTH response to 5-HTP and fluoxetine and prevented the 5-HTP and fluoxetine-induced POMC mRNA response in the anterior pituitary lobe. Central or systemic infusion of 5-HT increased ACTH secretion seven- and eight-fold, respectively. Systemic pretreatment with the anti-CRH antiserum reduced the ACTH responses to 5-HT by 80% and 64%, respectively. It is concluded that 5-HT via activation of 5-HT1A, 5-HT2A, 5-HT2C and possibly also 5-HT1B receptors increases the synthesis of CRH in the PVN and POMC in the anterior pituitary lobe, which results in increased ACTH secretion. Furthermore, the results indicate that CRH is an important mediator of the ACTH response to 5-HT.

Adrenocorticotropic Hormone↗

PubMed2002

Quality assessment of pacemaker implantations in Denmark.

AIMS: Quality assessment of therapeutic procedures is essential to insure a cost-effective health care system. Pacemaker implantation is a common procedure with more than 500,000 implantations world-wide per year, but the general complication rate is not well described. We studied procedure related complications for all implantations performed in an entire nation over a 3-year period. METHODS AND RESULTS: A prospective study of complications related to 99% of the 5648 primary pacemaker implantations performed in the 12 Danish pacemaker centres in 1997-1999 was carried out. Overall 76% of the patients received a physiological pacemaker system and 91% received the optimal pacing mode according to international guidelines. Perioperative complications requiring reoperation were: haematoma 0.3%, atrial lead related 1.9%, ventricular lead related 1.7%. Late complications requiring reoperation were: infection 02%, atrial lead related 13%, ventricular lead related 1.2%. The complication rate decreased over the study period, but overall the complication rate was higher than expected and showed considerable variation between centres. CONCLUSIONS: Our results demonstrate that sensitive data such as complications related to pacemaker implantations can be collected on a national basis. We suggest that a reoperation rate higher than 3% for atrial as well as ventricular pacing electrodes in the individual implanting centre should cause the centre to evaluate carefully the procedure as well as the performance of the individual implanter.

Adolescent↗

PubMed2001

Frameshift-mutation-derived peptides as tumor-specific antigens in inherited and spontaneous colorectal cancer.

The functional role and specificity of tumor infiltrating lymphocytes (TIL) is generally not well characterized. Prominent lymphocyte infiltration is the hallmark of the most common form of hereditary colon cancer, hereditary nonpolyposis colon cancer (HNPCC) and the corresponding spontaneous colon cancers with the microsatellite instability (MSI) phenotype. These cancers are caused by inherited or acquired defects in the DNA mismatch-repair machinery. The molecular mechanism behind the MSI phenotype provides a clue to understanding the lymphocyte reaction by allowing reliable prediction of potential T cell epitopes created by frameshift mutations in candidate genes carrying nucleotide repeat sequences, such as TGF beta RII and BAX. These tumors therefore represent an interesting human system for studying TIL and characterizing tumor-specific T cells. We here describe T cell reactivity against several T helper cell epitopes, representing a common frameshift mutation in TGF beta RII, in TIL and peripheral blood lymphocytes from patients with MSI(+) tumors. The peptide SLVRLSSCVPVALMSAMTTSSSQ was recognized by T cells from two of three patients with spontaneous MSI(+) colon cancers and from all three patients with HNPCC. Because such mutations are present in 90% of cancers within this patient group, these newly characterized epitopes provide attractive targets for cancer vaccines, including a prophylactic vaccine for individuals carrying a genetic disposition for developing HNPCC.

Adenocarcinoma↗

PubMed2001

Inhibitory effect of neuropeptide Y on morphine withdrawal is accompanied by reduced c-fos expression in specific brain regions.

Neuropeptide Y (NPY) was previously shown in our laboratory to attenuate behavioral signs of morphine withdrawal. To further characterize the anti-withdrawal effect of NPY, the present study attempted to identify specific brain regions where NPY inhibits neuronal activity during withdrawal. Morphine dependence was induced in male Wistar rats by two daily subcutaneous injections of morphine at increasing doses, and the withdrawal syndrome was precipitated acutely by intraperitoneal administration of naloxone. Rats were pre-treated with an intracerebroventricular (icv) injection of NPY (12 nmol) or vehicle 30 min before the naloxone challenge. Withdrawal behavior was quantified using a point scoring technique based on motor- and non-motor-related signs. Brain areas involved in the attenuation of morphine withdrawal were delineated by radioactive in situ hybridization for the immediate early gene c-fos, which is a marker for neuronal activity. The present study confirmed the inhibitory effect of NPY on withdrawal behavior. Inhibition of behavioral signs of naloxone-precipitated morphine withdrawal was accompanied by significantly reduced c-fos expression in the locus coeruleus, lateral septal nucleus, ventral part of the periaqueductal grey, cingulate and frontal cortices, and septohippocampal nucleus. Our data suggest that neo- and allo-cortical areas as well as specific brainstem nuclei are involved in the anti-withdrawal effects of NPY.

Animals↗

PubMed2001

Intradermal ras peptide vaccination with granulocyte-macrophage colony-stimulating factor as adjuvant: Clinical and immunological responses in patients with pancreatic adenocarcinoma.

K-RAS mutations are frequently found in adenocarcinomas of the pancreas, and induction of immunity against mutant ras can therefore be of possible clinical benefit in patients with pancreatic cancer. We present data from a clinical phase I/II trial involving patients with adenocarcinoma of the pancreas vaccinated by i.d. injection of synthetic mutant ras peptides in combination with granulocyte-macrophage colony-stimulating factor. Forty-eight patients (10 surgically resected and 38 with advanced disease) were treated on an outpatient basis. Peptide-specific immunity was induced in 25 of 43 (58%) evaluable patients, indicating that the protocol used is very potent and capable of eliciting immune responses even in patients with end-stage disease. Patients followed-up for longer periods showed evidence of induction of long-lived immunological memory against the ras mutations. CD4(+) T cells reactive with an Arg12 mutation also present in the tumor could be isolated from a tumor biopsy, demonstrating that activated, ras-specific T cells were able to selectively accumulate in the tumor. Vaccination was well tolerated in all patients. Patients with advanced cancer demonstrating an immune response to the peptide vaccine showed prolonged survival from the start of treatment compared to non-responders (median survival 148 days vs. 61 days, respectively; p = 0.0002). Although a limited number of patients were included in our study, the association between prolonged survival and an immune response against the vaccine suggests that a clinical benefit of ras peptide vaccination may be obtained for this group of patients.

Adenocarcinoma↗

PubMed2001

Identification and distribution of CCK-related peptides and mRNAs in the rainbow trout, Oncorhynchus mykiss.

Peptides homologous to mammalian cholecystokinin (CCK), and their corresponding cDNAs, have been isolated and sequenced from the rainbow trout, Oncorhynchus mykiss. Three cDNAs encoding CCK-like preprohormones were identified from the brain. The cDNAs encode three different putative CCK-8 peptides containing Asn, Leu or Thr, in position 6 (counting from the C-terminus). Hence, the trout CCKs are named CCK-N, CCK-L and CCK-T respectively. RT-PCR showed differential expression of the three mRNAs although all were detected in the brain and intestine, similar to the expression pattern of CCK in tetrapods. In situ hybridization on trout brain sections using (35)S-labeled gene-specific antisense oligonucleotides showed that the three mRNAs were present in different parts, suggesting that the three CCK peptides may have different functions in the brain. Purification of CCK-immunoreactive material from the trout brain resulted in two CCK octapeptides: DYNGWMDF(.)NH2 (CCK-N) and DYLGWMDF(.)NH2 (CCK-L) present in equal amounts. In the pyloric caeca, three forms of CCK-L were identified, consisting of 7, 8 and 21 residues, respectively. The last was dominating and had the sequence ASGPGPSHKIKDRDYLGWMDF(.)NH2. All isolated peptides were fully sulfated. The trout is the first species in which three different CCK-like cDNAs have been identified.

Amino Acid Sequence↗

PubMed2001

Fractal analysis and time- and frequency-domain measures of heart rate variability as predictors of mortality in patients with heart failure.

Time-domain measures of heart rate (HR) variability provide prognostic information among patients with congestive heart failure (CHF). The prognostic power of spectral and fractal analytic methods of HR variability has not been studied in the patients with chronic CHF. The aim of this study was to assess whether traditional and fractal analytic methods of HR variability predict mortality among a population of patients with CHF. The standard deviation of RR intervals, HR variability index, frequency-domain indexes, and the short-term fractal scaling exponent of RR intervals were studied from 24-hour Holter recordings in 499 patients with CHF and left ventricular ejection fraction < or =35%. During a mean follow-up of 665 +/- 374 days, 210 deaths (42%) occurred in this population. Conventional and fractal HR variability indexes predicted mortality by univariate analysis. For example, a short-term fractal scaling exponent <0.90 had a risk ratio (RR) of 1.9 (95% confidence interval [CI] 1.4 to 2.5) and the SD of all RR intervals <80 ms had an RR of 1.7 (95% CI 1.2 to 2.1). After adjusting for age, functional class, medication, and left ventricular ejection fraction in the multivariate proportional-hazards analysis, the reduced short-term fractal exponent remained the independent predictor of mortality, RR 1.4 (95% CI 1.0 to 1.9; p <0.05). All HR variability indexes were more significant univariate predictors of mortality in functional class II than in class III or IV. Among patients with moderate heart failure, HR variability measurements provide prognostic information, but all HR variability indexes fail to provide independent prognostic information in patients with the most severe functional impairment.

Aged↗

PubMed2001

Smoking, sex of the offspring, and risk of placental abruption, placenta previa, and preeclampsia: a population-based cohort study.

BACKGROUND: : Placental abruption, placenta previa, and preeclampsia are serious pregnancy complications with an increased risk of perinatal death. Smoking during pregnancy is associated with increased risk of abruption and placenta previa, and it reduces the risk of preeclampsia. We examined the association between mothers' smoking habits during pregnancy, taking the sex of the offspring into consideration, and the risk and prognosis of placental abruption, placenta previa, and preeclampsia METHODS: : We conducted the study in the County of North Jutland, Denmark. Using the 10-digit personal identification number given to every Danish citizen at birth, we linked data from the Danish Medical Birth Registry, including information on mother and child, to data from the Pharmaco-Epidemiological Prescription Database with data on all reimbursed prescriptions to use selected drugs as a proxy measure for some maternal diseases, and data from the Regional Hospital Discharge Registry, including the discharge diagnoses. Among 47,932 singleton births we included only births for which we had information about the mothers' smoking habits, leaving 46,313 births for analysis. RESULTS: : Smoking was associated with the risk of placental abruption (OR=1.99 (95% CI 1.72-2.30)) and placenta previa (OR=1.88 (95% CI 1.15-3.07)). Smoking was inversely associated with the risk of preeclampsia (OR=0.55 (95% CI 0.48-0.62)). After stratification for the sex of the offspring the risk estimate of smoking as risk factor for placenta previa decreased for male fetuses (OR=1.63 (95% CI 0.75-3.51)) and increased for female fetuses (OR=4.82 (95% CI 1.69-13.75)). CONCLUSION: : Female fetuses are more vulnerable than male to the negative effect of maternal smoking on placenta previa.

Abruptio Placentae↗

PubMed2001

The effects of adrenergic agonists on c-fos, jun-B and nitric oxide synthase-like immunoreactivities in cultured rat pinealocytes.

Pineal melatonin synthesis is enhanced by the activation of adrenergic and opioid receptors. The precise mechanism of how signal transduction is affected by the activation of these receptors, leading to an increase in melatonin synthesis, is not clear. An attempt has been made to investigate the effects of the activation of these two types of receptors that might lead to the induction of immediate early genes (IEGs) and nitric oxide synthase (NOS) expressions. The present study shows that the stimulation of cultured pinealocytes by 1 microM epinephrine (an alpha- and beta-adrenergic agonist) for 2 h increased the number of c-fos immunoreactive (IR) cells, and that this stimulatory effect was abolished by adding 10 microM prazosin (an alpha-adrenergic antagonist) to the culture medium. No significant change of c-fos-IR cells was found when cells were treated with either 1 microM isoproterenol (a beta-adrenergic agonist) or 100 microM morphine (an opioid agonist). Neither epinephrine (1 microM), isoproterenol (1 microM) nor morphine (100 microM) altered jun-B-IR cells in the culture. With regard to NOS, the number of IR cells was slightly increased after 2 h of incubation by 10 microM isoproterenol, whereas morphine (100 microM) and epinephrine (10 microM) did not change the number of IR cells. The results of this experiment have demonstrated that c-fos expression is induced by alpha-adrenergic but not beta-adrenergic agonists, nor by opioid agonists. Neither alpha-, beta-adrenergic nor opioid agonists had any significant effect on jun-B, whereas NOS was slightly increased by isoproterenol.

Adrenergic Agonists↗