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Biomedical subjects

M Møller

Publications and source records attributed to M Møller.

At least 73 records · Page 4Linked to original sources

Serial Holter ST-segment monitoring after first acute myocardial infarction. Prevalence, variability, and long-term prognostic importance of transient myocardial ischemia.

Based on serial Holter monitoring performed 7 times within 3 years after a first acute myocardial infarction, we assessed the prevalence, variability and long-term clinical importance of transient myocardial ischemia (TMI) defined as episodes of ambulatory ST-segment depression. In all, 121 consecutive male patients <70 years old were studied. The prevalence of TMI on different Holter recordings varied around 20% ranging between 18 and 27%. Fifty-five of the patients (46%) had TMI on at least 1 of the 7 Holter recordings. Considerable variability was found within and between patients for the presence of TMI. No high-risk group for cardiac death, nonfatal reinfarction or coronary revascularization during up to 10 years of follow-up could be identified by the detection of TMI. From these results we conclude that a routine search for TMI on serial Holter monitoring cannot be recommended in male survivors of an uncomplicated first acute myocardial infarction.

Aged↗

Development of selective antibodies against the human somatostatin receptor subtypes sst1-sst5.

Antisera selective for five somatostatin receptor subtypes, human sst1-sst5, were raised in rabbits. C-terminal parts of human sst1-sst5 receptors were expressed as fusion proteins with glutathione S-transferase. Fusion proteins were affinity-purified and used for raising polyclonal antibodies. In Western blot analysis, all five antisera were tested on preparations of mammalian cell lines transfected with human sst1-sst5, respectively. sst1 antiserum reacted with a broad band of 53-72 kDa. A band of 71-95 kDa was detected with the antiserum raised against sst2, 65-85 kDa with sst3 antiserum, 45 kDa with sst4 antiserum and 52-66 kDa with sst5 antiserum. No cross-reactivity could be detected to any of the other four somatostatin receptor subtypes. Enzymatical deglycosylation of the receptors revealed that sst1, sst2, sst5 and possibly sst3 in this system are subjected to N-linked glycosylation, whereas sst4 is not. Two of the antisera (sst2 and sst5) were used for immunohistochemical localization of the receptors. sst2 and sst5 antisera labeled neurons in e.g. the amygdaloid complex, hippocampus, fascia dentata and the neocortex in rat and monkey tissue. This is the first report on antisera against all five somatostatin receptor subtypes and the first immunohistochemical visualization of sst5 receptors in the mammalian brain.

Amygdala↗

[Melatonin].

Explore the source record for details and available documents.

Humans↗

Demonstration of nerve fibers containing the C-terminal flanking peptide of neuropeptide Y (CPON) in the pig pineal gland (Sus domesticus): an immunocytochemical study by light and electron microscopy.

BACKGROUND: The pineal gland is richly innervated by the neuropeptide Y (NPY)-positive nerves that mostly exibit immunoreactivity for the enzyme tyrosine hydroxylase, a marker of sympathetic nerve fibers. NPY is synthesized as a part of larger prepromolecule. The present study was undertaken to demonstrate that the posttranslational processing of preproNPY resulted in the presence of C-terminal flanking peptide of NPY (CPON) in nerve fibers of the pig pineal gland. METHODS: An immunohistochemical anti-CPON technique was done over mounted sections of perfusion-paraformaldehyde-fixed material. An immunocytochemical preembedding technique was done to study the CPON-positive nerve terminals under electron microscopy. RESULTS: The pig pineal gland is densely innervated by CPON-immunoreactive nerve fibers. These nerve fibers follow from the pineal capsule into the connective tissue septa and farther into the pineal parenchyma, where the varicose branches terminate between the pinealocytes. The fiber density was the highest in the peripheral and ventral parts of the gland. At the ultrastructural level, the CPON-immunoreactive nerve terminals were found in the perivascular spaces and in the parenchyma. The terminals contained small vesicles (30-40 nm in diameter), some of which showed an eccentrically located dense core. In addition, large clear vesicles (80-100 nm in diameter) were present. Some of the CPON-immunoreactive nerve terminals were found in close apposition to the pinealocyte cell membrane, making a synapticlike contact with the pinealocytes. CONCLUSIONS: Our results show the presence of dense CPON-IR innervation in the pig pineal gland. The ultrastructural localization of CPON-IR nerve terminals shows that the peptide can be released to both perivascular and intercellular spaces. The functional role for this peptide in pig pineal gland is still an open question.

Animals↗

Impact of continuous quality improvement on selection of pacing mode and rate of complications in permanent pacing.

OBJECTIVE: To improve pacing mode selection and to reduce complications of pacing using continuous quality improvement. DESIGN: Criterion standard study. Comparison of implantations from 1992-94 with preset standards. Implementation of corrections in 1994 and re-evaluation in 1995, with one year follow up of all patients. SETTING: Tertiary hospital. PATIENTS: Consecutive patients implanted with a pacemaker from January 1992 to October 1993, 361 patients; October 1993 to June 1994, 115 patients; and January 1995 to October 1995, 140 patients. MAIN OUTCOME MEASURES: Reasons for not choosing physiological pacing and complications of pacemaker implantation. RESULTS: Most frequent reasons for not selecting physiological pacing for patients in sinus node disease were age (12.8%, 5 of 39) and technical problems (12.8%, 5 of 39); and for patients in atrioventricular block, age (31.4%, 16 of 51), and disability due to other diseases (13.7%, 7 of 51). To improve the standards, age as a sole reason for not selecting physiological pacing was disregarded and VDD pacing was introduced. Follow up showed fulfillment of standards. Cost analysis indicated minimally increased expenses of pacing hardware and no additional costs of procedures. A high rate of complications (16.2%, 77 of 476) was found related to atrial lead displacement (10.2%, 19 of 186), and to subclavian puncture from January 92-June 94. To reduce complications use of atrial screw-in leads and cephalic cut down were encouraged. Follow up showed significant reduction of complications from January 92-June 94 (77 of 476) compared with January 95-October 95 (12 of 140) (P = 0.03). CONCLUSIONS: Better compliance with international pacing guidelines was obtained by registration of reasons for deviations followed by corrections of procedures. By using screw-in leads and by using cephalic cut down the set standards were met.

Adolescent↗

Innervation of the sheep pineal gland by nonsympathetic nerve fibers containing NADPH-diaphorase activity.

We used the NADPH-diaphorase histochemical method as a potential marker for nitric oxide synthase (NOS)-containing nerve fibers innervating the pineal gland of the sheep. Nerve fibers containing NADPH-diaphorase activity provide dense innervation of the sheep pineal gland. The nerve fibers were located in the pineal capsule, in the connective tissue septae separating the lobull of the gland, and penetrating between the pinealocytes. The nerve fibers were either smooth or endowed with boutons en passant. After bilateral removal of the superior cervical ganglion, the dense network of NADPH-diaphorase-positive fibers was still present in the gland. Ganglionectomy affected neither the distribution nor the appearance of the NADPH-diaphorase-positive fibers. Most of the NADPH-diaphorase-positive fibers also contained peptide histidine isoleucine and vasoactive intestinal polypeptide, and a comparatively smaller fraction contained neuropeptide Y. Pinealocytes never exhibited NADPH-diaphorase activity. These results demonstrate a major neural input to the sheep pineal gland with NADPH-diaphorase-positive nerve fibers of nonsympathetic origin.

Animals↗

Characterization of the cholecystokinin and gastrin genes from the bullfrog, Rana catesbeiana: evolutionary conservation of primary and secondary sites of gene expression.

The gastrin and cholecystokinin (CCK) genes, and the complementary DNAs they encode, have been isolated and sequenced from the bullfrog, Rana catesbeiana. The CCK gene promoter region possess the same four well characterized transcriptional control elements as the human CCK gene, namely an E-box, AP-1 binding site, Sp1 site, and TATA box. In contrast, no obvious regulatory motifs are conserved in the gastrin gene. Alignment of the bullfrog preprohormone sequences with other members of the CCK/gastrin peptide family showed that preproCCK has been conserved to a greater degree during evolution than preprogastrin. In mammalian species, gastrin gene expression is typically associated with the antrum, and CCK with the small intestine and brain. However numerous secondary sites of CCK/gastrin gene expression have also been found. RT-PCR showed a high degree of conservation of both primary and secondary sites of CCK/gastrin production between mammals and the bullfrog, with gastrin messenger RNA being detected in the antrum, duodenum, colon, pancreas, brain, and testes, whereas CCK mRNA was observed in the brain, lung, testes, and throughout the length of the small intestine. In situ hybridization using radiolabeled gene specific antisense oligonucleotides uncovered CCK and gastrin messenger RNA in distinct areas of the bullfrog central nervous system and pituitary gland. Notably, the gastrin gene was expressed in the pituitary gland and hypothalamus of the bullfrog, as previously seen in mammals. This highly preserved tissue expression pattern suggests that gastrin plays specific roles in the hypothalamus and pituitary gland that are distinct from those of CCK. Our findings show that in spite of the structural resemblance, bullfrog CCK and gastrin constitute independent neuroendocrine peptide systems.

Amino Acid Sequence↗

Peptidergic cells in the mammalian pineal gland. Morphological indications for a paracrine regulation of the pinealocyte.

Several neuropeptides are present in the mammalian pineal gland. Most of these peptides, e.g. neuropeptide Y, vasoactive intestinal peptide, and peptide histidine isoleucine, are located in nerve fibres innervating the gland. In some mammalian species, neuropeptides are also found in cells scattered in the pineal parenchyma. In the rat, bipolar cells immunoreactive for somatostatin are present, just as cells containing mRNA encoding somatostatin can be detected in the gland by in situ hybridisation. In the pineal gland of the European hamster, many cells are immunoreactive for enkephalin. Ultrastructural cytochemical analysis of these cells reveals a pinealocyte morphology. Processes from the opioidergic pinealocytes terminate in the parenchyma between the non-immunoreactive pinealocytes. Some of the processes contain small clear and large dense core vesicles and end in club shaped swellings which make synapse-like contacts with other pinealocytes. The ultrastructural morphology suggests that the opioidergic cells exert a paracrine regulation on other pinealocytes.

Animals↗

[The Danish Pacemaker Registry. A database for quality assurance].

The Danish Pacemaker Register was established in 1982 and since then all Danish pacemaker and lead implantations have been registered on a prospective basis by use of the European Pacemaker Patient Identification Card. The Register contains data on 17,002 patients with an implanted pacemaker. In 1994 the implantation rate was 314 per million inhabitants. The ECG indication was atrioventricular conduction disturbances in 46%, sick sinus syndrome in 37% and atrial fibrillation with bradycardia in 13%. Fifteen percent received a single atrial system and 41%, a dual chamber system. In 62% a rate adaptive pacemaker was used. Overall, the international recommendations for choice of pacing mode were met in 64% of the implantations. As the 11 implanting centres in Denmark report to the Register with a few days delay from the intervention, the Register is able to detect any irregularity in pacemaker or lead function within a very short period of time.

Aged↗

The chemical neuroanatomy of the mammalian pineal gland: neuropeptides.

The mammalian pineal gland contains multiple afferent peptidergic nerve fibres. Sympathetic nerve fibres, with their origin in the superior cervical ganglia, contain neuropeptide Y colocalized with norepinephrine. Other pinealopetal nerve fibres, probably originating in the pterygopalatine ganglion, contain vasoactive intestinal peptide and peptide histidine isoleucine. Fibres containing substance P and calcitonin gene-related peptide have also been demonstrated in pinealopetal nerve fibres. These fibres might originate in the trigeminal ganglion. The neurotransmitter content of the fibres of the central innervation, innervating the gland from the brain via the pineal stalk, has not been elucidated. However, strong indications for the presence of neuropeptide Y, substance P, somatostatin, and vasopressin in these fibres have been presented. Recent immunohistochemical studies have further shown the presence of subtypes of pinealocytes containing neuropeptides. Thus, pinealocytes containing beta-endorphin, leu-enkephalin, and somatostatin have been demonstrated in the gland. Immunohistochemistry at the electron microscopical level has shown, that in some species, leu-enkephalin containing pinealocytes make synaptic contacts with other pinealocytes indicating of paracrine regulation of the pineal gland. It must however be emphasized that large interspecies variations exist with regard to the peptidergic pineal innervation and its content of peptidergic cells.

Animals↗

Appraisal of pacing lead performance from the Danish Pacemaker Register.

The Danish Pacemaker Register was established in January 1982, and the 11 implanting centers in Denmark report to the Register on a continuous basis by use of the European Pacemaker Patient Identification Card proposed by the European Working Group on Cardiac Pacing. As of May 1994, the Register contained data on 18,053 lead implants performed in Denmark, i.e., 1,253 (7%) lead implants before 1982, and all the 16,800 initial lead implants since 1982 on 17,020 generators in 15,366 patients for a total of 12,188 (67.5%) ventricular unipolar, 3,178 (17.6%) ventricular bipolar, 1,316 (7.3%) atrial unipolar, and 1,371 (7.6%) atrial bipolar leads. Preformed J shaped leads were used in 3.5% of the atrial implants and active fixation in < 8%. Lead failure was defined as need for replacement or abandonment of the lead due to pacing or sensing problems with the exception of lead displacement. The 10-year survival rate for unipolar atrial and ventricular leads was 95.8% +/- 2.1% (2 standard errors) and 97.1% +/- 0.6%, respectively, as compared to a 4-year survival rate of 91.5% +/- 4.6% and 91.6% +/- 1.7% for bipolar atrial and ventricular leads, and an 8-year survival rate for bipolar ventricular leads of 75.1% +/- 5.0%. The 5-year survival rate for the bipolar Medtronic model 4012 lead was 85.8% +/- 8.1% and 67.4% +/- 7.3% for the bipolar Siemens model 1010T lead, indicating a poor performance. The Siemens lead models 105T and 1050T seem to be performing like the model 1010T. The 5-year survival rate for the bipolar Telectronics model 284 lead was 88.4% +/- 6.2%. The data from the Danish Pacemaker Register confirm the previous reported good survival of unipolar pacing leads irrespective of the chamber paced, and demonstrate that the bipolar Medtronic 4012 lead, the bipolar Telectronics 284 lead, and especially the bipolar Siemens 1010T, 105T, and 1050T models are unreliable leads that need careful monitoring and appropriate replacement.

Aged↗

Localization of NADPH-diaphorase in the rat pineal gland: an experimental enzyme histochemical study.

We have used the NADPH-diaphorase enzyme histochemical technique to localize the enzyme nitric oxide synthase in the rat pineal gland. Some scattered NADPH-diaphorase positive pineal cells were present, mostly in the rostral part of the gland close to the pineal stalk. In addition, NADPH-diaphorase positive nerve fibers were located in the pineal capsule, in the connective tissue septae of the gland, and also intraparenchymally between the pinealocytes. Most nerve fibers were endowed with boutons en passage. These nerve fibers remained in the gland after bilateral removal of the superior cervical ganglia verifying a non-sympathetic nature of the NADPH-diaphorase positive nerve fibers. Pineal blood vessels also exhibited NADPH-diaphorase activity. The number and distribution of NADPH-diaphorase containing cells and nerve fibers were not affected by bilateral superior cervical ganglionectomy. Furthermore, animals sacrificed during day or night exhibited the same NADPH-diaphorase pattern. The present investigation provides the first morphological evidence for the presence of NADPH-diaphorase activity in rat pineal cells, suggesting an influence of nitric oxide on pineal metabolism. Furthermore, the presence of NADPH-diaphorase activity in the pineal blood vessels as well as in the perivascular nerve fiber suggests an influence of nitric oxide on the blood flow to the gland and/or the metabolism of the pineal cells adjacent to the blood vessels.

Animals↗

Central administration of GLP-1-(7-36) amide inhibits food and water intake in rats.

Glucagon-like peptide (GLP)-1-(7-36) amide and its pancreatic receptors are important for control of blood glucose levels. However, rat GLP-1 receptors are also localized in the brain, in hypothalamus, and in areas without a blood-brain barrier. When rats were kept on a food restriction schedule, intracerebroventricular injection of GLP-1 just before food was offered inhibited food intake. However, peripheral GLP-1 administration by intraperitoneal injection had little effect. GLP-1 effects on water intake and output were also investigated. Intracerebroventricular GLP-1 profoundly inhibited angiotensin II-induced drinking behavior in rats, and water intake was suppressed by exogenous GLP-1 in rats habituated to a water restriction schedule. These effects were reproduced by intraperitoneal administration of GLP-1. Furthermore, intracerebroventricular GLP-1 stimulated urinary excretion of water and sodium. The centrally elicited effects were blocked by the GLP-1 antagonist exendin-(9-39) amide, whereas the N-terminally extended and inactive GLP-1-(1-36) amide had no effect on feeding and drinking. GLP-1 had no effect in behavioral assays measuring exploratory locomotor activity and conditioned taste aversion. In conclusion, GLP-1 may play a physiological role in regulation of both ingestion and the water and salt homeostasis.

Animals↗

Presence of nitric oxide synthase in the sheep pineal gland: an experimental immunohistochemical study.

By use of immunohistochemistry, a dense network of nerve fibres immunoreactive to the neuronal form of nitric oxide synthase (NOS, subtype I) was demonstrated in the pineal gland of sheep. The NOS-immunoreactive fibres were located in the pineal capsule and the connective tissue septae of the gland, but fibres were also present intraparenchymally between the pinealocytes. NOS-immunoreactive nerve fibres were still present in the gland 1 month after bilateral removal of the superior cervical ganglia. By use of an antibody directed against endothelial NOS (subtype III), only pineal blood vessels were stained. This staining was still present in the ganglionectomized animals. No difference was found in the staining between the control animals and the ganglionectomized ones. The pinealocytes were not stained, neither by the antibody against neuronal NOS nor by the antibody against endothelial NOS. By use of double immunohistochemical stainings, NOS was in many nerve fibres colocalized with vasoactive intestinal peptide. Western blot analysis of supernatant fractions of sheep pineal homogenates showed the presence of a band corresponding to the neuronal NOS. Thus, the present data show a prominent innervation of the sheep pineal gland with NOS-immunoreactive nerve fibres with their origin outside the sympathetic nervous system, indicating an influence of NO on the pinealocyte metabolism from non-sympathetic nerve fibres in this species. The presence of NOS in both perivascular nerve fibres and the endothelium of the blood vessels of the gland suggests a role of NO in the regulation of the circulation of the sheep pineal gland.

Animals↗

Glucagon-like peptide I receptors in the subfornical organ and the area postrema are accessible to circulating glucagon-like peptide I.

The intestinal incretin hormone glucagon-like peptide I (GLP-I) inhibits gastric motility and secretion in normal, but not in vagotomized subjects, pointing to a centrally mediated effect. Therefore, our aim was to study the availability of rat brain GLP-I receptors to peripherally injected 125I-labeled GLP-I. The specificity of the binding was tested by co-injection of excess amounts of unlabeled GLP-I. Using light microscopical autoradiography of rat brain sections, we found specific 125I-GLP-I binding exclusively in the subfornical organ and the area postrema. This binding was abolished when an excess amount of unlabeled GLP-I was co-injected with the labeled GLP-I. We conclude that cells in the subfornical organ and the area postrema could be responsive to blood-borne GLP-I. The observed binding of peripherally administered GLP-I to the subfornical organ and the area postrema, which both have close neuroanatomical connections with hypothalamic areas involved in water and appetite homeostasis, is consistent with the potential roles of circulating GLP-I in the central regulation of appetite and autonomic functions.

Animals↗

Nitric oxide synthase in the pineal gland.

The recent discovery of nitric oxide (NO) as a biological messenger molecule with unique characteristics has opened a new field in pineal research. This free radical gas is synthesized by the enzyme nitric oxide synthase (NOS) from L-arginine. The activation of adrenoreceptors in the membrane of the pinealocytes mediates the increase in NO through a mechanism that involves G proteins. In the pinealocyte, NO stimulates guanylyl cyclase resulting in an increased intracellular content of cGMP. The role of cGMP in pineal metabolism, however, is still enigmatic. Using enzyme histochemistry and immunohistochemistry, the presence of NOS has been confirmed in the pineal gland of some species. In the rat and especially in the sheep, NOS is located in nerve fibres innervating the gland. These nerve fibres also contain the neuropeptides vasoactive intestinal peptide (VIP) and peptide histidine isoleucine (PHI), and are probably of parasympathetic origin. In cell cultures and tissue sections NOS immunoreactivity has been shown to be present in pinealocytes of the rat and bovine but not in the sheep. Finally, NOS is also present in the endothelial cells of the blood vessels of the pineal gland. Accordingly, in the mammalian pineal gland, NO is synthesized in both presynaptic nerve fibers and pinealocytes, as well as in blood vessels. However, the anatomical location of NO synthesis varies considerably among species. NO released in the pineal gland, might influence both the pineal metabolism and the blood flow of the gland.

Animals↗