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Biomedical subjects

E Theodorsson

Publications and source records attributed to E Theodorsson.

At least 217 records · Page 12Linked to original sources
PubMed1990

Raised plasma concentrations of atrial natriuretic peptide are independent of left atrial dimensions in patients with chronic atrial fibrillation.

The aim of the present study was to determine whether left atrial size--a likely indicator of atrial stretching--correlates with the plasma concentration of atrial natriuretic peptide and whether this relation is different in patients in sinus rhythm and in those with atrial fibrillation. Arterial plasma concentrations of immunoreactive atrial natriuretic peptide (ir-ANP), adrenaline, noradrenaline, aldosterone, and vasopressin were measured in 13 patients in sinus rhythm without apparent heart failure and in 13 patients in atrial fibrillation. The two groups were matched for left atrial diameter and the ratio of the left atrial diameter to the diameter of the aortic root (assessed by echocardiography). There were no significant differences in age, heart rate, blood pressure, or left ventricular end diastolic diameter between the two groups. Left atrial diameters varied from 33 to 60 mm. The mean (SD) plasma concentration of ir-ANP was significantly higher (35 (21) pmol/l) in the patients with atrial fibrillation than in those in sinus rhythm (12 (11) pmol/l). The concentration of plasma aldosterone was also higher in patients with atrial fibrillation (831 (366) v 523 (211) pmol/l). Concentrations of adrenaline, noradrenaline, and vasopressin were similar in both groups. None of the hormone concentrations correlated with left atrial dimensions. These results indicate that plasma concentrations of ir-ANP and aldosterone are highly sensitive indicators of changes in haemodynamic function during atrial fibrillation. They also underscore the difficulties of correlating echocardiographic assessment of patients with plasma concentrations of a vasoactive hormone.

Aldosterone↗
PubMed1990

Renal responses to lower body negative pressure in humans.

Renal blood flow, renal sympathetic nerve activity, assessed by the renal overflows of norepinephrine (NE), dopamine (DA), and neuropeptide Y-like immunoreactivity (NPY-LI), as well as plasma renin activity and angiotensin II (ANG II) were evaluated during stepwise increases in lower body negative pressure (LBNP) in 10 healthy volunteers. The fractional extraction of epinephrine (Epi) was used to assess renal catecholamine removal (approximately 50%) from arterial plasma. Renal NE, DA, and NPY-LI overflows at rest were 235 +/- 31, 30 +/- 5, and 0.6 +/- 0.2 pmol/min, respectively. LBNP increased renal vascular resistance (RVR) by 52% and renal NE overflow by 31%. Renin release increased by 330% (from 64 +/- 12 units/min) and arterial ANG II levels by 119%, without altering the renal ANG II extraction (which was approximately 50%). Renal DA and NPY-LI overflows were unaffected. A "vaso-vagal" reaction in one subject was associated with cessation of renal NE overflow and marked elevations of arterial Epi, renal renin release, and arterial ANG II. Selective unloading of cardiopulmonary baroreceptors by low-level LBNP did not affect RVR, whereas higher levels of LBNP caused renal vasoconstriction probably mediated in part by increased renal sympathetic nerve activity and in part by ANG II.

Adult↗
PubMed1990

Neuropeptide Y as a marker in pediatric neuroblastoma.

Neuropeptide Y (NPY) was investigated as a possible tumor marker in pediatric patients with tumors of the sympathetic nervous system. Seven patients with neuroblastoma, 3 patients with ganglioneuroblastoma, and 2 with ganglioneuroma, were compared with 12 matched healthy controls and 34 tumor controls. NPY-like immunoreactivity (NPYLI) was analyzed in extracted plasma using a competitive radioimmunoassay. At diagnosis, plasma NPYLI was significantly increased (p less than .001) in the neuroblastoma patients (352 +/- 99 pM; mean +/- SEM) when compared with healthy controls (36 +/- 4 pM) and tumor controls (30 +/- 2 pM). Ganglioneuroblastoma and ganglioneuroma patients had lower levels (57 +/- 8 pM) than neuroblastoma patients but still significantly higher than the controls. In all patients with sympathetic tumors, the NPYLI level was decreased after treatment. Five neuroblastoma patients relapsed; all had increasing NPYLI levels. In 3 of these patients, incresing NPYLI was the first sign of relapse. Plasma NPYLI correlated well to urinary levels of homovanillic acid. NPY in plasma (NPYLI) may be a clinically useful marker of pediatric neuroblastoma for diagnosis and differential diagnosis. NPYLI correlates well with the clinical course and can be the first sign of relapse. Plasma determinations of NPYLI make it possible to monitor rapid alterations of disease.

Biomarkers, Tumor↗
PubMed1990

Acute bronchoconstriction is not a stimulus for sympatho-adrenal activation in asthmatic or healthy subjects.

Bronchoconstriction has been found to cause little sympathoadrenal activation in asthmatic patients. It has been questioned whether this is due to blunted sympatho-adrenal reactivity in asthmatics or if bronchoconstriction is a stimulus for sympatho-adrenal activation at all. We therefore compared sympatho-adrenal responses in eight asthmatic patients and 12 healthy subjects by measurements of plasma adrenaline and noradrenaline concentrations before, during and after methacholine-induced bronchoconstriction. Significant bronchoconstriction was obtained in eight of the healthy subjects and in all of the asthmatics. Considerably higher concentrations of methacholine were required to evoke bronchoconstriction in the healthy subjects but the relative magnitudes of bronchoconstriction were similar in the two groups: peak expiratory flow (PEF) decreased by approximately 24 and approximately 28% and specific airway conductance (sGaw) decreased by approximately 68 and approximately 70% in asthmatics and controls, respectively). Methacholine-induced bronchoconstriction did not alter plasma catecholamine levels significantly in either group. In addition, plasma concentrations of catecholamines and neuropeptide Y-like immunoreactivity (NPY-LI) were measured before and during bronchoconstriction induced by histamine or allergen in 8 and 5 asthmatic subjects, respectively. Plasma noradrenaline, adrenaline and NPY-LI remained unchanged up to 30 min after bronchoconstriction induced by histamine or allergen. We, therefore, conclude that bronchoconstriction is not a stimulus for sympatho-adrenal activation and that the lack of an adrenaline response to bronchoconstriction is not likely to be related to NPY release.

Acute Disease↗
PubMed1989

Immunoreactive tachykinins, calcitonin gene-related peptide and neuropeptide Y in human synovial fluid from inflamed knee joints.

We have analysed the concentrations of substance P (SP), neurokinin A (NKA), calcitonin gene-related peptide (CGRP) and neuropeptide Y (NPY) in the synovial fluid from 5 patients suffering from arthritis with inflamed knee joints as well as from 5 healthy control subjects with an earlier traumatic meniscal or cruciate ligament injury. Competitive radioimmunoassay was done using antisera SP2 (SP), K12 (NKA), R8 (CGRP), and NPY1 (NPY). No SP-like immunoreactivity (-LI) was detected in any patient. NKA-LI was found in all control patients but in none of the arthritis patients. CGRP-LI was seen in all arthritis patients as well as in 3/5 control patients, a non-significant difference. NPY-LI was found in a significantly higher concentration in the arthritis group vs the control patients. The results support an involvement of neuropeptides in human joint inflammation.

Adult↗
PubMed1989

Presence of nerve growth factor-like immunoreactivity in carcinoid tumour cells and induction of a neuronal phenotype in long-term culture.

Mid-gut carcinoid tumour cells expressed a neuronal phenotype, observed and characterized immunocytochemically in long-term culture. Initially the culture contained a main population of spherical tumour cells with granules immunopositive for serotonin (5-HT) and tachykinins (TK). Production and secretion of these substances into media was verified biochemically. Cytoplasmic granules with 5-HT-like immunoreactivity (5-HT-LI) were markedly reduced during culture, while granules with TK-LI were unchanged in number, corresponding to the biochemical findings. After a few days in culture, tumour cells were flattened and fine neurite-like processes extended. After 2-3 weeks many endocrine tumour cells had converted to neuron-like cells with slender cell processes containing granules with TK-LI. Varicose enlargements and apparent growth cones were observed. When neurites were extended, 50-80% of the neuron-like cells were positive with antisera against the neurofilament triplet. Cells of both endocrine and neuronal phenotypes were positive with antisera against tetanustoxin, Thy 1-antigen, neuron-specific enolase, synapsin and a synaptic vesicle protein (p 38) supporting the concept of these tumour cells as para-neurons. Intermediate filaments, studied with monoclonal anti-vimentin, were found in all cells. Filaments were also observed ultrastructurally. Initially, nerve growth factor (NGF)-LI was found in granules of all spherical tumour cells. When neuritic processes were extended, the cells appeared to lose these granules. After 40 days in culture, NGF-LI was absent or very sparse. The studies indicate autocrine secretion of a growth factor, reacting with the NGF antiserum, by cultured mid-gut carcinoid tumour cells inducing a neuronal phenotype with enhanced NF and TK synthesis and suppressed 5-HT synthesis. In bioassay systems the culture media caused a delayed neurite reaction on PC12 cells, but no reaction on chick ciliary ganglion cells, indicating that the factor is not authentic NGF.

Carcinoid Tumor↗
PubMed1989

Plasma atrial natriuretic peptide in carcinoid heart disease.

Plasma atrial natriuretic peptide (ANP) concentration was determined and cardiac ultrasound studies were performed in 50 patients with malignant mid-gut carcinoid tumors. The extent of carcinoid-related heart disease varied among the patients. The patients with the most severe right-sided heart disease, who often had signs of right ventricular failure, had significantly (p less than 0.001) higher plasma ANP concentrations than either patients with less or no abnormal ultrasound findings or age- and sex-matched healthy control subjects. ANP levels were serially determined for 0.5 to 4 years (median 2.1) in 12 patients. The levels increased above the reference range in patients with clinical findings of right ventricular failure. In patients without cardiac decompensation the levels remained within the reference range. In 3 patients who had successful tricuspid and pulmonary valve replacements, signs and symptoms of right ventricular failure disappeared and plasma ANP levels declined and normalized. Five patients with progressive right ventricular failure and increasing plasma ANP levels during follow-up eventually died from cardiac decompensation. This study demonstrates the predictive value of serial determinations of plasma ANP in carcinoid heart disease. Such measurements can be an additional guide in the clinical management of these patients.

Adult↗
PubMed1989

Treatment of malignant carcinoid tumors with recombinant interferon alfa-2b: development of neutralizing interferon antibodies and possible loss of antitumor activity.

Twenty patients with malignant carcinoid tumors were treated for 6 months with recombinant interferon alfa-2b (IFN alpha-2b; Intron-A; Schering Corp., Bloomfield, NJ) at a mean dose of 5.9 megaunits three times per week. Eleven of the 20 patients (55%) had a greater than 50% reduction of tumor markers (urinary 5-hydroxyindoleacetic acid or plasma neuropeptide K), showing objective tumor response. Six patients (30%) had stable disease with no significant change in tumor markers or tumor size, and three (15%) had progressive disease with an increase in tumor markers and size. These results are similar to those reported earlier for treatment with natural leukocyte IFN in patients with carcinoid tumors. Only two patients (35%) had a slight reduction of tumor size after 6 months of treatment. Three patients developed neutralizing antibodies to IFN alpha-2b. Two of these patients initially showed an objective response, which lasted until IFN antibodies developed. In one of these patients, a change to human leukocyte IFN resulted in normalization of antibody titers within 3 months, and the patient had a second objective clinical response. There was no correlation between development of IFN antibodies and development of autoimmune phenomena such as increased titers of antinuclear antibodies or thyroid autoantibodies. IFN alpha-2b seems to be as potent as human leukocyte IFN in the treatment of patients with malignant carcinoid tumors, but it is important to recognize that antibodies neutralizing IFN may develop in some patients, with concomitant loss of antitumor effects. A change to natural leukocyte IFN might be beneficial in these patients.

Aged↗
PubMed1989

Effect of repeated electroconvulsive treatment on regional concentrations of tachykinins, neurotensin, vasoactive intestinal polypeptide, neuropeptide Y, and galanin in rat brain.

The effects of single and repeated electroconvulsive treatments (ECTs) on brain regional distribution of substance P (SP), neurokinin A (NKA), neurotensin (NT), neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), and galanin (GAL) were studied in the rat. Rats were divided into four groups receiving one of the following treatments: one ECT, one sham ECT, six ECTs, or six sham ECTs. After sacrifice by focused microwave irradiation, brains were dissected into frontal cortex, striatum, occipital cortex, hippocampus, hypothalamus, and pituitary sections. Peptides were extracted by boiling the tissues in 1 mol/l acetic acid and measured in extract aliquots by specific radioimmunoassays. Marked regional differences (P = .0005) were found for each of the peptides measured. The highest concentrations of SP and NKA were found in the hypothalamus and, in descending order, in striatum, pituitary, frontal cortex, occipital cortex, and hippocampus. For NT, the highest level was found in the hypothalamus and, in descending order, in pituitary, striatum, hippocampus, frontal cortex, and occipital cortex. The highest VIP concentrations were measured in frontal and occipital cortex, followed by pituitary, hypothalamus, striatum, and hippocampus. The highest NPY and GAL concentrations were found in the hypothalamus and the pituitary; in frontal and occipital cortex, as well as in the striatum and hippocampus, the peptides levels were rather evenly distributed. Repeated handling (stress?) decreased both NT and GAL in frontal (P = .05 and .04) and occipital cortex (P = .09 and .07). ECT, one or six treatments, had no effect on SP, NKA, NT, VIP, or GAL concentrations in different brain regions. However, an increase in NPY concentrations in hippocampus (six sham ECTs vs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Neurotransmitters, neuropeptides and binding sites in the rat mediobasal hypothalamus: effects of monosodium glutamate (MSG) lesions.

Indirect immunofluorescence histochemistry and receptor autoradiography were used to study the localization of transmitter-/peptide-containing neurons and peptide binding sites in the mediobasal hypothalamus in normal rats and in rats treated neonatally with repeated doses of the neurotoxin monosodium-glutamate (MSG). In the arcuate nucleus, the results showed a virtually complete loss of cell bodies containing immunoreactivity for growth hormone-releasing factor (GRF), galanin (GAL), dynorphin (DYN), enkephalin (ENK), corticotropin-like intermediate peptide (CLIP), neuropeptide Y (NPY), and neuropeptide K (NPK). Tyrosine hydroxylase(TH)-glutamic acid decarboxylase(GAD)-, neurotensin(NT)- and somatostatin(SOM)-immunoreactive (IR) cells were, however, always detected in the ventrally dislocated, dorsomedial division of the arcuate nucleus. In the median eminence, marked decreases in numbers of GAD-, NT-, GAL-, GRF-, DYN-, and ENK-IR fibers were observed. The numbers of TH-, SOM- and NPY-IR fibers were in contrast not or only affected to a very small extent, as revealed with the immunofluorescence technique. Biochemical analysis showed a tendency for MSG to reduce dopamine levels in the median eminence of female rats, whereas no effect was observed in male rats. Autoradiographic studies showed high to moderate NT binding sites, including strong binding over presumably dorsomedial dopamine cells. In MSG-treated rats, there was a marked reduction in GAL binding in the ventromedial nucleus. The findings implicate that most neurons in the ventrolateral and ventromedial arcuate nucleus are sensitive to the toxic effects of MSG, whereas a subpopulation of cells in the dorsomedial division of the arcuate nucleus, including dopamine neurons, are not susceptible to MSG-neurotoxicity. The results indicate, moreover that the very dense TH-IR fiber network in the median eminence predominantly arises from the dorsomedial TH-IR arcuate cells, whereas the GAD-, NT-, GAL-, GRF- and DYN-IR fibers in the median eminence to a large extent arise from the ventrolateral arcuate nucleus. Some ENK- and NPK-positive cells in the arcuate nucleus seem to project to the lateral palisade zone of the median eminence, but most of the ENK-IR fibers in the median eminence, located in the medial palisade zone, seem to primarily originate from an area(s) located outside the arcuate nucleus, presumably the paraventricular nucleus.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Distribution of galanin-binding sites in the monkey and human telencephalon: preliminary observations.

Using X-ray film autoradiography the distribution of 125I-galanin binding sites was studied in the forebrain of monkey and man. In the monkey a high density was found in all areas of the neocortex, especially layer 4, and in certain subfields in the hippocampal region. Also in the human brain high activity was seen in neocortex, mainly layer 6 and in hippocampal areas, as well as in amygdala, piriform cortex and hypothalamus. These results suggest that the 29-amino acid peptide galanin may be involved in the regulation of higher cortical functions in primates.

Amygdala↗
PubMed1989

Effects of cholera toxin, Escherichia coli heat stable toxin and sodium deoxycholate on neurotensin release from the ileum in vivo.

Neurotensin (NT) is a biologically active peptide found in specialized epithelial cells (N-cells) in the distal small intestine. In this study we tested the hypothesis that NT may be released by luminal secretagogues, i.e., cholera toxin, Escherichia coli heat-stable toxin and sodium deoxycholate. Cholera toxin elicited net fluid secretion in anesthetized cats. This secretion was accompanied by an increased release of NT-like immunoreactivity (NTLI) into the mesenteric vein when NTLI was measured with either a C-terminally or a N-terminally directed antibody. An increasing plasma NTLI concentration (N-terminally directed antibody) was recorded in the mesenteric vein and femoral artery in cholera experiments. These results indicate that cholera toxin releases NT from the small intestine. Since neurotensin causes intestinal fluid secretion at least in part via an activation of enteric nerves we propose that the N-cell functions as a 'receptor cell' which activates an intramural secretory reflex upon luminal stimulation by cholera toxin. This study does not support a similar role for NT in the secretion elicited by the heat stable toxin of Escherichia coli or by sodium deoxycholate since we were unable to demonstrate any intestinal release of NTLI after exposing the intestine to these secretory agents.

Animals↗
PubMed1989

Intraocular transplants of a human gastrinoma in immuno-suppressed rats: morphological, chromatographic and functional studies.

Tissue pieces of a metastatic human gastrinoma (ultrastructural Type II) were successfully transplanted to the anterior eye-chamber of rats immunosuppressed with Cyclosporin A. Immunocytochemical investigation of the transplants showed evidence for preserved endocrine activity of tumour cells with immunoreactivity towards the C-terminal of the gastrin/cholecystokinin molecule. Studies of gastric acid secretion in tumour-bearing rats and sham-operated controls with chronic gastric fistulas showed that the basal acid output did not differ between the groups during 3 weeks of study. However, the stimulated gastric acid secretion decreased after 5 days in both groups to remain significantly depressed throughout the study, an effect probably due to Cyclosporin A treatment of the groups. The concentration of immunoreactive gastrin in plasma from rats with tumours in oculo was 5 times higher than in sham-operated rats. Gastrin-34 was the major immunoreactive component in both patient serum and rat plasma. An immunoreactive fraction corresponding to component I was found in the patient serum, but not in the rat plasma, although present in the chamber fluid. Components corresponding to gastrin-17 were found both in the patient serum and in the rat plasma. The chromatographic pattern of the tumour was similar to that in rat chamber fluid. The dominating component corresponded to gastrin-17, while gastrin-34 represented the quantitatively smaller component. Gastrin-34 was, however, relatively more abundant in the tumour extract than in the chamber fluid. The study also indicates that a gastrin-producing tumour transplanted in oculo in immunosuppressed rats may increase the rat plasma concentration of the same molecular forms of gastrin as seen in the clinical situation.

Adolescent↗
PubMed1989

Substance P-, CGRP- and NPY-immunoreactive nerve fibers in rat sciatic nerve-end neuromas.

Substance P (SP)-, calcitonin gene-related peptide (CGRP)- and neuropeptide Y (NPY)-immunoreactive nerve fibers were examined in experimental sciatic nerve-end neuromas in the rat with immunohistochemical techniques. At 1-3 days after nerve ligation and section of the sciatic nerve there was an accumulation of SP-like immunoreactivity (SP-LI). Six days after the lesion there was, however, a marked reduction and the neuromas remained virtually depleted from SP-LI at survival times between 8 days and 3 months. CGRP-LI was strong at 1-5 days post-operatively. By 8 days, CGRP-LI was reduced, but a large number of axons were still immunoreactive, and remained immunolabelled up to 3 months. CGRP-LI nerve fibers formed endbulbs, and appeared to grow in both anterograde and retrograde directions. Fine fibers sprouts were first observed at 8 days, but preterminal branching in neuromas aged less than a month was uncommon. At early stages (1-3 days) after ligation, there was a marked accumulation of NPY-LI proximal to the nerve constriction. NPY-LI was reduced from 5 days and on, but many fibers remained NPY-positive and their growth pattern through proximal and distal neuroma segments could be determined. The present results thus may indicate a differential effect of nerve injury on neuropeptide expression: immunohistochemically detectable SP-LI rapidly disappears from sciatic nerve fibers trapped in nerve-end neuromas, but CGRP-LI and NPY-LI remain and are useful as neuroanatomical markers for two subclasses of sprouting axons. Furthermore, the findings suggest that both CGRP and NPY, but not SP, could be involved in ectopic electrical activity in experimental neuromas.

Animals↗
PubMed1989

Calcitonin gene-related peptide in the rat kidney: occurrence, sensitivity to capsaicin, and stimulation of adenylate cyclase.

The occurrence, effects and sensitivity to capsaicin and stimulation of adenylate cyclase of calcitonin gene-related peptide (CGRP) in the rat kidney have been investigated. CGRP-like immunoreactivity was higher in the medulla than in the papilla and the cortex. Capsaicin pretreatment significantly reduced CGRP-like immunoreactivity in the medulla and papilla while a small reduction was found in the cortex. CGRP-immunoreactive nerve fibres were observed surrounding blood vessels and occasionally in the vicinity of renal tubules and between the collecting ducts in the papilla. Some CGRP-immunoreactive fibres were also seen in kidneys from capsaicin-pretreated rats. Infusion of capsaicin (1 microM) through the renal artery of isolated and perfused rat kidney increased the CGRP-like immunoreactivity outflow from the venous effluent. This effect exhibited desensitization at the second challenge with the drug. Infusion of either capsaicin (1 microM) or CGRP (1 microM) reduced the increase of perfusion pressure induced by norepinephrine in isolated perfused rat kidney. Plasma protein extravasation was studied in the various regions of the rat kidney following infusion of capsaicin. No significant change was observed in the medulla, papilla or cortex after capsaicin administration. Adenylate cyclase activity was studied in membrane preparations from cortex, medulla and papilla of rat kidney. Cortical and medullary adenylate cyclase was stimulated in a concentration-dependent manner by salmon calcitonin, rat calcitonin and rat CGRP. Salmon calcitonin in these two areas showed half-maximal effective concentration approximately 1000 times lower and maximal stimulation only slightly higher than those of rat calcitonin and rat CGRP. However, in the papilla, only rat CGRP was able to induce a 60% increase of enzyme activity (half-maximal effective concentration, 19 +/- 1.6 nM). It is concluded that CGRP contained in capsaicin-sensitive sensory nerve may exert a local function in discrete areas of the rat kidney.

Adenylyl Cyclases↗