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Biomedical subjects

M Møller

Publications and source records attributed to M Møller.

At least 109 records · Page 6Linked to original sources
PubMed1994

Diverse roles for nitric oxide in synaptic signalling after activation of NMDA release-regulating receptors.

NMDA receptors regulating transmitter release were studied in three model systems to investigate whether their activation involves the NO transduction system. In superfused slices of rat brain, the release of [3H]D-aspartate, [3H]noradrenaline and [3H]GABA evoked by NMDA could be modulated by nitrergic drugs. Tetrodotoxin (0.1 microM) exerted differential effects in the three systems indicative of the NMDA receptors (and hence sites of NO generation) being pre- or extra-synaptic, or a combination of both types of localization. L-Arginine (100 microM) enhanced NMDA-evoked release of [3H]GABA (110%), [3H]NA (120%) and [3H]D-ASP (700%). Exogenous NO donors could increase NMDA-induced release of [3H]NA and [3H]D-ASP from hippocampal slices, although differential effects were noted, whilst inhibitors of NO synthase (NG-nitro- and NG-amino-L-arginine, both 100 microM) attenuated (60-85%) the release. NMDA-evoked release of [3H]GABA from striatal slices were insensitive to exogenous NO donors, but NG-nitro- and NG-amino-L-arginine produced 100% increases. In all cases, the NMDA receptors regulating release are linked to a NO system, although the link to the receptors modulating release of [3H]GABA appeared different. The actions of the nitrergic drugs may depend upon the redox state and/or cellular milieu of the individual NMDA receptors involved.

Amino Acid Oxidoreductases↗
PubMed1994

The diurnal expression of genes encoding vasopressin and vasoactive intestinal peptide within the rat suprachiasmatic nucleus is influenced by circulating glucocorticoids.

The mammalian suprachiasmatic nucleus (SCN) is the endogenous pacemaker generating the diurnal rhythm of the stress hormones ACTH and glucocorticoid secretion. In the present study, we have employed male rats entrained to a 12:12 h (light:dark) photoperiod to investigate the effects of chronic and acute administration of exogenous glucocorticoids upon the diurnal expression of vasopressin and vasoactive intestinal peptide (VIP) mRNA in the SCN by semiquantitative in situ hybridization histochemistry. Chronic administration of exogenous glucocorticoids significantly enhanced vasopressin mRNA expression only at zeitgeber time (ZT) 5, while the otherwise rhythmic expression of vasopressin mRNA was unaffected at ZT11, ZT17 and ZT23. In contrast, the same treatment abolished the rhythmic expression of VIP mRNA resulting in constantly elevated mRNA levels. In adrenalectomized rats given an overnight supplement of dexamethasone in their drinking water, the expression of both vasopressin and VIP mRNA in the SCN was elevated the following morning at ZT6 when compared to adrenalectomised rats kept on 0.9% saline. These results suggest that glucocorticoids influence the expression of vasopressin during a narrow window of time in the diurnal cycle coinciding with the time where entrainment of the circadian pacemaker with non-photic cues is possible. Constantly elevated levels of glucocorticoids may also interfere with the suprachiasmatic expression of VIP mRNA which is thought to be driven by photic cues.

Animals↗
PubMed1994

The presence of nerve fibers immunoreactive for vasoactive intestinal peptide (VIP), peptide histidine isoleucine (PHI), and preproVIP(111-122) in the mouse pineal gland.

A low to moderate number of vasoactive intestinal peptide (VIP) and peptide histidine isoleucine (PHI)-immunoreactive nerve fibers with prominent boutons-en-passage were demonstrated in the pineal gland of the mouse. The two peptides, which are parts of the same precursor molecule, were distributed identically in the gland. Positive fibers were present in the connective tissue septae in the gland, in the pineal capsule, and in the pineal parenchyma. No VIP-PHI-immunoreactive elements were found in the deep pineal gland, in the pineal stalk, or in habenular and posterior commissures. This morphological distribution of immunoreactive nerve fibers, which is similar to the distribution in other mammals, indicates that the VIP/PHI fibers of the mouse pineal gland originate exclusively from perikarya in a peripheral ganglion, presumably one of the cholinergic ganglia of the head. No evidence for a VIPergic central innervation was found. VIP and PHI are connected via a bridging peptide equivalent to amino acids 111-122 of the precursor (preproVIP(111-122)). In order to demonstrate the possible existence of this peptide in intra-pineal nerve fibers, antisera directed against a synthetic sequence identical to preproVIP(111-122) and immunohistochemistry were applied. PreproVIP(111-122)-immunoreactive nerve fibers were observed in the mouse pineal gland, with the same distribution pattern and morphology as those immunoreactive for VIP and PHI. To quantify the peptide-immunoreactivities, 50 mice pineals were pooled, extracted, and the concentrations were measured radioimmunologically. The concentrations of the VIP and preproVIP(111-122) immunoreactivities were 1.7 and 2.0 pmol/g, respectively, whereas the concentration of PHI was 0.9 pmol/g.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Effect of thrombolytic therapy on postinfarction myocardial ischemia.

In patients with acute myocardial infarction a substantial reduction in mortality can be achieved by early intravenous thrombolytic therapy. The beneficial effect of thrombolysis on left ventricular function is relatively small, and it seems unlikely that this minor improvement alone can be responsible for the reduction in cardiac death. So far it has not been clearly established how thrombolytic therapy affects postinfarction myocardial ischemia. From studies evaluating ST segment changes on exercise testing or ambulatory monitoring it is concluded that thrombolysis probably results in a reduction of residual ischemia. The reduced ischemic burden is proposed to be one important pathophysiological mechanism underlying the frequently observed improvement in hemodynamic stress test variables following thrombolytic treatment.

Exercise Test↗
PubMed1994

Histamine stimulates c-fos expression in hypothalamic vasopressin-, oxytocin-, and corticotropin-releasing hormone-containing neurons.

The stimulatory action of centrally administered histamine (HA) on secretion of the anterior pituitary hormones ACTH, beta-endorphin, and PRL is indirect, and previous studies have suggested that hypothalamic neurons containing CRH, arginine vasopressin (AVP), and oxytocin (OT) are involved in this response. We studied the effect of HA on neuronal activation in the hypothalamus by investigating the expression of c-fos, which is a protooncogene activated early when neurons are stimulated. The expression of c-fos was evaluated by detection of c-fos immunoreactivity (c-fos-IR) using immunohistochemistry and by measurement of c-fos mRNA using in situ hybridization techniques. In addition, the identity of the HA-stimulated neurons was investigated by dual antigen immunohistochemistry visualizing AVP-, OT-, or CRH-IR in the neurons showing increased c-fos expression. HA (270 nmol) infused intracerebroventricularly increased c-fos-IR in the hypothalamus, especially in the periventricular hypothalamic areas and certain hypothalamic nuclei, including the paraventricular nucleus (PVN) and supraoptic nucleus (SON). c-fos-immunoreactive nuclei were observed throughout the SON, whereas in the PVN, c-fos-IR was particularly pronounced in the subnuclei known to contain AVP, OT, and CRH neurons. Double labeling experiments confirmed that c-fos was expressed in AVP-, OT-, and CRH-immunoreactive as well as other neurons. In addition, HA intracerebroventricularly induced a moderate expression of c-fos-IR in the arcuate nucleus. In situ hybridization showed increased levels of c-fos mRNA in both the PVN and SON after HA infusion. We conclude that HA-induced secretion of ACTH, beta-endorphin, and PRL may be mediated via activation of hypothalamic AVP, OT, and CRH neurons.

Animals↗
PubMed1994

A carnivore species (Canis familiaris) expresses circadian melatonin rhythm in the peripheral blood and melatonin receptors in the brain.

Dogs kept under controlled photoperiodic conditions of 12 h light and 12 h dark expressed a clear diurnal melatonin rhythm in the peripheral blood, with a swift peak restricted to the late part of the scotophase. The highest density of high-affinity, G-protein-linked 2-[125I]iodomelatonin binding sites was found in the pars tuberalis of the pituitary gland. Binding sites were found also in the pars distalis, and light microscopy/high-resolution autoradiography showed that binding was located exclusively over the chromophobe and basophilic cells forming the adenopituitary zona tuberalis, well developed in this species, and extending into the gland as a continuation of pars tuberalis. Cords of basophilic cells located in the pars distalis proper also expressed high receptor density. The eosinophils in the adenohypophysis and the neural lobe were devoid of binding. Heavily labeled were the external laminar and the mitral cell layers of the olfactory bulbs, but no binding was detected in the filae nervi olfactorii or tractus olfactorius. The hypothalamic suprachiasmatic nuclei were discernible clearly. Quantitative autoradiography inhibition experiments revealed that the apparent melatonin inhibitory constant (IC50) in all those areas was around 0.1 nmol/l, which is a physiologically appropriate value considering the peripheral blood melatonin levels. Co-incubation with guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) led to a consequential decrease in the binding density. The specific binding observed in other areas (hippocampus, frontal, parietal, occipital cortex and cerebellum) was rather weak, diffuse and could not be attributed to a particular layer; the apparent IC50 for melatonin was about 1 mumol/l, and co-incubation with GTP gamma S did not modify the binding density. Collectively, these data show that the dog possess all the prerequisites for an efficient network adapted to photoperiodic time measurements. A circadian melatonin signal in the peripheral blood and an apparently functional readout receptor system located in key positions within the brain are both present in this species.

Animals↗
PubMed1994

Protective effect of oxygen and heliox breathing during development of spinal decompression sickness.

A rat model of spinal decompression sickness (DCS) allows study of spinal cord function for at least 3 h after decompression to 1 atm abs (101 kPa) after an exposure to air at 3.8 atm abs (385 kPa) for 1 h. During these 3 h, spinal evoked potentials (SEPs) elicited by peroneal nerve stimulation may be reduced or disappear, and histologic lesions in the spinal cord are observed. Three groups of animals were given either air, oxygen, or heliox (80/20) to breathe at 1 atm abs for 3 h after decompression. Both oxygen and heliox breathing impeded the development of DCS significantly as judged by the mortality of the animals and disappearance of the SEPs. The effect of heliox seemed to be superior to that of oxygen. The latency time from stimulation to the first SEP peak increased significantly during both air and oxygen breathing, whereas no significant increase was seen during heliox breathing. Histologic examination of the spinal cords of animals breathing air, oxygen, or heliox (80/20) showed focal lesions in the white and gray matter. In the white matter, degenerated myelin sheaths as well as expanded extracellular spaces compatible with bubble formation were seen. In the gray matter, perikaryal degeneration was observed. The extracellular space in the white matter was increased in all decompressed animals compared with controls (P < 0.01). Oxygen and heliox breathing caused a smaller increase in extracellular space as compared with air-breathing animals (P < 0.05) and (0.10 > P > 0.05), respectively. It is concluded that breathing of oxygen or heliox (80/20) at 1 atm abs has a preventive effect on the development of DCS when compared with air breathing; the effect of heliox seems to be superior to that of oxygen.

Air↗
PubMed1993

Indications for a central innervation of the bovine pineal gland with substance P-immunoreactive nerve fibers.

An antiserum, raised in rabbits, against substance P was used in an immunohistochemical investigation of the bovine pineal gland. A moderate innervation of all parts of the bovine pineal gland with substance P-immunoreactive nerve fibers was demonstrated. The immunoreactive nerve fibers were located throughout the pineal gland, both perivascularly, intraparenchymally, and with few fibers in the pineal capsule. Within the habenular nucleus, a large number of substance substance P-immunoreactive perikarya were present. From these perikarya processes extended towards the pineal stalk and gland. Some substance P-immunoreactive nerve fibers were located in the stria medullaris and in the posterior commissure. The anatomical location of the substance P-immunoreactive nerve fibers in the pineal gland and stalk strongly indicates that, in this species, substance P-immunoreactive pinealopetal nerve fibers originate from perikarya in the brain, probably from the medial habenular nucleus.

Animals↗
PubMed1993

[Physiopathologic mechanisms behind eye symptoms in primary tumors of the pineal body].

Primary tumors of the pineal body can produce dyscoordinative movements of the eye, pupillary dilatation, paralysis of adduction during convergence and nystagmus. Obstruction of the aqueduct can cause hydrocephalus, increased intracranial pressure and papilledema. Diabetes insipidus may be a presenting symptom. Pinealocytes and the photoreceptors of the eye contain several autoantigens. In man, the best known is the S-antigen. This antigen can be detected in the cerebrospinal fluid of patients with primary tumors of the pineal body. The S-antigen, and possibly other related autoantigens, can elicit an autoimmune mediated reaction causing inflammatory eye symptoms. This recently described paraneoplastic neurologic syndrome shares properties in common with other known cancer-associated ophthalmologic syndromes characterised by rapid development of eye symptoms, rapid loss of sight and by eye manifestations prior to evident appearance of symptoms related to primary tumor growth. A primary tumor of the pineal body should be considered in patients where a monosymptomatic uveoretinitis presents without associated provoking factors. Furthermore, analyses of S-antigen in the spinal fluid can be useful in the clinical diagnosis of the same primary tumors.

Autoimmunity↗
PubMed1993

Transient myocardial ischemia after a first acute myocardial infarction and its relation to clinical characteristics, predischarge exercise testing and cardiac events at one-year follow-up.

The relation between early out-of-hospital ambulatory ST-segment monitoring, clinical characteristics, predischarge maximal exercise testing and cardiac events was determined in 123 consecutive men (age 55 +/- 8 years) with a first acute myocardial infarction (AMI). During 36 hours of ambulatory recording 11 +/- 5 days after AMI 23 patients (19%) had 123 ischemic episodes (group 1), whereas 100 patients demonstrated no ischemia (group 2). Exercise-induced ST-segment depression was more prevalent in group 1 (83%) than in group 2 (47%) (p < 0.005). Group 1 patients also had more severe ischemia as judged from a shorter exercise duration before significant ST-segment depression (5.5 +/- 2.4 vs 7.7 +/- 4.1 minutes; p < 0.03) and more pronounced ST-segment depression on exercise testing (4.1 +/- 2.6 vs 2.6 +/- 1.6 mm; p < 0.03). Furthermore, exercise test results revealed an impaired hemodynamic response in group 1 compared with group 2: systolic blood pressure at maximal work load 160 +/- 31 vs 176 +/- 28 mm Hg (p < 0.025) and systolic blood pressure increase during exercise 41 +/- 24 vs 56 +/- 22 mm Hg (p < 0.01). With-in 368 +/- 8 days of follow-up the frequency of cardiac events (cardiac death, nonfatal reinfarction, and severe angina including the need of revascularization) was 52% in group 1 compared with 22% in group 2 (p < 0.01). Exercise-induced ischemia did not predict an adverse outcome: event rate 30 vs 25% in patients without residual ischemia (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Echocardiography↗
PubMed1993

Isolation of chromaffin cell thapsigargin-sensitive Ca2+ store in light microsomes from bovine adrenal medulla.

1. A subcellular fractionation procedure for bovine adrenal glands was designed with the aim to study the biochemical properties of Ca2+ stores in chromaffin cells. 2. The thapsigargin-sensitive compartment of Ca2+ stores was found to be highly enriched in a light microsomal fraction (LMF) on a 15-30% linear sucrose gradient, and was found to be essentially devoid of contamination by plasma, mitochondrial or secretory granule membranes. 3. A Ca(2+)-pumping ATPase was identified in this LMF as a 97 kDa protein forming an acid-stable, Ca(2+)-dependent, thapsigargin-sensitive phosphorylated intermediate upon incubation with [gamma-32P]ATP, suggesting this protein to represent a SERCA-3 isoform of Ca2+ ATPases. 4. A major 162 kDa protein, previously demonstrated in the isolated chromaffin cells, was enriched in the LMF, distributing on sucrose gradients in parallel with the thapsigargin-sensitive Ca2+ uptake. 5. LMF appears to represent a part of the thapsigargin-sensitive Ca2+ store of chromaffin cells, and should be useful for further studies of the store properties at the subcellular and molecular level.

Adrenal Medulla↗
PubMed1993

Residual myocardial ischaemia in first non-Q versus Q wave infarction: maximal exercise testing and ambulatory ST-segment monitoring.

In a prospective study of 123 consecutive survivors of a first myocardial infarction (43 non-Q wave, 80 Q wave), we determined the total residual ischaemic burden by use of pre-discharge maximal exercise testing and post-discharge 36 h ambulatory ST-segment monitoring initiated 11 +/- 5 days after the infarction. The prevalence of exercise-induced ischaemic manifestations in the infarct types was similar: chest pain 14% vs 16% and ST-segment depression 54% vs 54%. The ischaemic threshold did not differ either (heart rate at 1 mm of ST-segment depression 120 +/- 27 vs 119 +/- 25 beats.min-1). During early post-discharge daily activities, more patients with non-Q wave infarction demonstrated transient episodes of ST-segment depression: 28% vs 14% (ns). Furthermore, ischaemic episodes were significantly longer (42.5 +/- 50.1 vs 22.0 +/- 20.6 min; P < 0.001), and the ischaemic threshold was significantly lower in non-Q wave infarction (heart rate at onset of ST-segment depression 84 +/- 11 vs 88 +/- 9 beats.min-1; P < 0.05). During 3.5 +/- 0.9 years of follow-up the proportion of patients with > or = 1 ischaemic event (non-fatal reinfarction, angina pectoris, revascularization) was significantly higher in non-Q wave infarction (51%) as compared to Q wave infarction (31%) (P < 0.05). In both infarct types the presence of ST-segment depression on ambulatory recording and exercise testing significantly predicted the development of future angina pectoris, whereas patients at increased risk for subsequent non-fatal reinfarction or cardiac death were not identified.

Activities of Daily Living↗
PubMed1993

An immunohistochemical study of neuropeptide Y in the bovine pineal gland.

An immunohistochemical study of the bovine pineal gland was performed using rabbit polyclonal antibodies raised against neuropeptide Y (NPY) or against the C-terminal flanking peptide of proNPY (CPON). A large number of NPY/CPON-immunoreactive (IR) nerve fibers were demonstrated throughout bovine pineal gland. The IR-fibers were located in the capsule of the gland, usually piercing into the gland together with blood vessels. In the gland itself, the fibers were also located intraparenchymally between the pinealocytes. Within the rostral and caudal areas of the pineal stalk, NPY-IR fibers were also observed, and these fibers could be followed not only into the gland but also to the habenular and posterior commissures. The morphological localization of the NPY-IR nerve fibers in the bovine pineal gland indicate that the majority of fibers originate from the superior cervical ganglion. However, some fibers probably originate from the brain itself.

Animals↗
PubMed1993

Supervised learning on large redundant training sets.

Efficient supervised learning on large redundant training sets requires algorithms where the amount of computation involved in preparing each weight update is independent of the training set size. Offline algorithms like the standard conjugate gradient algorithms do not have this property while on-line algorithms like the stochastic backpropagation algorithm do. A new algorithm combining the good properties of off-line and on-line algorithms is introduced.

Algorithms↗
PubMed1992

Histamine-immunoreactive nerve fibers in the rat pineal gland: evidence for a histaminergic central innervation.

An immunohistochemical method that utilizes carbodiimide as a fixative and antisera directed against histamine was applied to investigate the location of histamine in the rat pineal complex. Numerous histamine-immunoreactive cell bodies were observed in different subdivisions of the tuberomammillary nucleus of the posterior hypothalamus, and a few cell bodies were present in the posterior and dorsal part of the periventricular hypothalamic nucleus. Histamine-immunoreactive fibers were observed to leave the posterior hypothalamus in various directions of which one dorsally projecting tract was followed in the periventricular area of the caudal diencephalon to the epithalamus. Several histamine-immunoreactive nerve fibers of this tract continued through the posterior commissure directly into the deep pineal gland. A few immunoreactive fibers were also observed in the habenular commissure. In midsagittal sections, histamine-immunoreactive nerve fibers were observed to enter the pineal stalk from the deep pineal gland. Most of histamine-immunoreactive fibers in the stalk continued towards the superficial pineal gland, but their number decreased in more distal locations of the stalk, indicating that some fibers terminate in the stalk as well. A few fibers were found to terminate in the most rostral part of the superficial pineal gland. The immunoreactive nerve fibers in the epithalamus and pineal complex were endowed with prominent varicosities. Taken together, these results indicate that histaminergic nerve fibers, originating from the posterior hypothalamus, project to the pineal complex of the rat. Histamine must therefore be considered a putative neurotransmitter contained in the central innervation of the pineal gland, but its function in pineal physiology has so far not been elucidated.

Animals↗
PubMed1992

Monoaminergic systems in the brainstem and spinal cord of the turtle Pseudemys scripta elegans as revealed by antibodies against serotonin and tyrosine hydroxylase.

With the aim of gaining more insight into the monoaminergic regulation of spinal motor systems in the turtle, we have studied the distribution of 5-HT (5-HTir) and tyrosine hydroxylase immunoreactivity (THir) in the brainstem and spinal cord of Pseudemys scripta elegans. 5-HTir cell bodies were located in the midline in nucleus raphe inferior, nucleus raphe superior, and laterally in nuclei reticularis superior and inferior and nucleus reticularis isthmi. THir cell bodies were located in the commissural nucleus, nucleus tractus solitarii, the locus coeruleus-subcoeruleus complex, nuclei reticularis superior and inferior, the pretectal area, and substantia nigra. 5-HTir and THir tracts were found in lateral and ventral bundles superficially in the brainstem. 5-HTir fibers in the spinal cord were located in a large dorsolateral and a smaller ventrolateral tract. In the gray matter, a high concentration of 5-HTir fibers were observed in areas I-IV and in the lateral motor column of cervical and lumbar enlargements. Areas V-VIII and area X were less intensively innervated, with the lowest fibre concentration in areas VII-VIII and area X. Throughout the spinal cord, THir nerve fibres were located in the same areas but with a lower density. Small bipolar 5-HTir and THir cell bodies were found ventromedially to the central canal especially in cervical and lumbosacral segments. Large THir cells were found in area IX in the caudal sacral and coccygeal spinal cord. THir cerebrospinal fluid-contacting cells were also found in the most caudal part of the brainstem and the upper cervical spinal cord. The well developed spinal 5-HT system and the less developed THir system provides an anatomical explanation for the monoaminergic modulation of turtle motoneuron membrane properties, which has been observed in electrophysiological experiments.

Animals↗