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Biomedical subjects

H Emanuelsson

Publications and source records attributed to H Emanuelsson.

At least 127 records · Page 7Linked to original sources
PubMed1985

Changes in polyamine synthesis and concentrations during chick embryo development.

We have measured the activities of the two rate controlling enzymes in polyamine synthesis, L-ornithine decarboxylase (ODC) and S-adenosyl-L-methionine decarboxylase (SAMDC), and the concentrations of the polyamines, putrescine, spermidine and spermine, in the developing chick embryo from laying to hatching. The embryo exhibited major peaks in the ODC and SAMDC activities as well as in the concentrations of all three polyamines at 15 h (gastrulation), 23-30 h (early organogenesis), days 4-5 (mid-organogenesis), and days 12-17 (organ growth and maturation). In the 4 and a half-day-old embryo, ODC activity and polyamine concentrations were about twice as high in the head region as compared to the trunk region. In the 14-day-old embryo, the highest ODC and SAMDC activities were found in lung, intestine and kidney, and there was a positive correlation between the enzyme activities and the growth rates of most organs/tissues.

Adenosylmethionine Decarboxylase↗
PubMed1985

The endoplasmic reticulum in regenerating liver cells.

Light-microscopic analysis of mouse liver homogenates six days after partial hepatectomy, showed a higher percentage of nuclei with adherent cytoplasm than homogenates from normal liver. This observation was true for animals with either a slow or rapid recovery of body weight after the operation. The phenomenon was not a function of the changes in the proportions of parenchymal and non-parenchymal tissue in the regenerating liver. Electron-microscopic analysis of random samples from normal and regenerating livers indicated an increase in the perinuclear rough endoplasmic reticulum, and a displacement of the glycogen depots within the regenerating cells six days after partial hepatectomy. The marked resistance towards homogenization, shown by the cytoplasm of the regenerating cells, may have been due to the observed increase of perinuclear membranes. However, qualitative changes of the cell membranes and a general decrease of proteolytic activity connected with liver regeneration may also have contributed.

Animals↗
PubMed1985

Acute haemodynamic effects of felodipine in congestive heart failure.

The haemodynamic effects of felodipine 0.1 mg/kg p.o., a new arteriolar dilator, were studied in 7 patients with severe congestive heart failure of NYHA Class IV (Group A) and in 3 patients in Class II-III (Group B). In Group A, measurements were made before and 1 and 4 h after felodipine administration. There was a substantial fall in systemic arterial pressure, which was not associated with a compensatory tachycardia. In fact, there was a fall in heart rate from 92 to 82 beats/min 1 h after drug administration. The pulmonary capillary wedge pressure was reduced from 22 to 14 mm Hg and the cardiac index and stroke volume index rose significantly. Consequently, there was a marked reduction in systemic vascular resistance. In Group B measurements were performed at rest and during exercise before and 1 h after felodipine. The pulmonary wedge capillary pressure during exercise was lower than in the control situation. Coronary sinus flow was increased and there was a pronounced fall in coronary vascular resistance. The results would suggest that felodipine, by virtue of its ventricular unloading potency, might be a valuable drug in the treatment of congestive heart failure.

Adult↗
PubMed1985

Intercellular voltage gradient between oocyte and nurse cell in a polychaete.

In the polychaete Ophryotrocha labronica the oocyte is supported during vitellogenesis by a single nurse cell, which is cytoplasmically contiguous with the oocyte through an intercellular bridge. Our electrical measurements demonstrate a marked potential difference (22-32 mV) between the oocyte and the nurse cell in mid-vitellogenesis, suggesting an electrophoretically caused migration of nurse cell constituents into the oocyte. Possibly this potential gradient helps to create a developmental prepattern in the oocyte, a role postulated for similar gradients within the oocyte-nurse cell complex of the Cecropia moth.

Animals↗
PubMed1985

The effects of transcutaneous electrical nerve stimulation in patients with severe angina pectoris.

The pain-relieving effects of transcutaneous electrical nerve stimulation (TENS) were investigated in patients with severe angina pectoris first with respect to systemic and coronary hemodynamics and myocardial metabolism during pacing-induced angina and second in a controlled long-term study. Two series of patients with severe angina pectoris (NYHA class III to IV) were studied (13 patients in the pacing study and 23 in the long-term study). In the pacing-induced angina study there was increased tolerance to pacing (142 +/- 23 compared with 124 +/- 20 beats/min tolerated, p less than .001), improved lactate metabolism (2 +/- 36% compared with -18 +/- 43%, p less than .01), and less pronounced ST segment depression (2.3 +/- 1.1 compared with 2.9 +/- 2.6 mm, p less than 0.05) with TENS. In the long study the effects of TENS were measured by means of repeated bicycle ergometer test, frequency of anginal attacks, and consumption of short-acting nitroglycerin. TENS was used regularly for 1 hr three times per day. The TENS treatment group had increased work capacity (637 +/- 308 vs 555 +/- 277 W . min, p greater than .001), decreased ST segment depression (2.3 +/- 1.1 vs 3.6 +/- 1.6 mm, p less than .001), reduced frequency of anginal attacks (p less than .05), and reduced consumption of short-acting nitroglycerin per week (p less than .05) compared with the control group. The observed effects were mainly due to decreased afterload resulting from systemic vascular dilatation.

Adult↗
PubMed1985

Factors that modify the flow response to intracoronary injections.

Coronary sinus flow (CSF) was measured in seven patients with normal coronary arteries (group A) during intracoronary injections of 6 ml arterial blood, 6 ml blood from the coronary sinus, 3 and 6 ml isotonic saline, 3 and 6 ml hypertonic glucose, and 6 ml of a contrast agent (sodium metrizoate). In 10 patients with coronary artery disease (group B), CSF was measured after administration of 6 ml isotonic saline, 6 ml sodium metrizoate, and 6 ml of another contrast medium (iohexol). In group A, arterial blood did not affect CSF, while coronary sinus blood induced a 33% increase. After 6 ml isotonic saline, there was a 35% increase in flow and after hypertonic glucose an increase of 70%. Metrizoate induced a rise in flow of 109%. In group B, the increase in CSF after intracoronary injection of saline, metrizoate, and iohexol was 30%, 83%, and 67%, respectively. Blood from the coronary sinus, in contrast to arterial blood, induced a marked rise in peak flow, suggesting a role for reactive hyperemia secondary to myocardial hypoxia in this response. A similar mechanism might have been operative after injection of isotonic saline, as well as after the hyperosmolar contrast agents. However, additional mechanisms mediated by the high osmotic pressure of these substances, such as induction of the Bezold-Jarisch reflex, which will induce coronary vasodilation, may have played a role. Finally, when hyperosmolar agents are used, the possibility of some direct vasodilating properties of the agents cannot be excluded.

Adult↗
PubMed1985

Autoradiographic analysis of RNA synthesis in the oocyte-nurse cell complex of the polychaete Ophryotrocha labronica.

Females of the polychaete Ophryotrocha labronica have been pulse labelled with [5-3H] uridine, and the incorporation of label into the RNA of the oocyte-nurse cell complex was followed by light and electron microscope autoradiography. Up to its regression the polyploid nurse cell displays an intense synthesis of rRNA and mRNA, which sustains an extensive production of electron-dense protein granules in it. Concomitantly rRNA and mRNA are synthesized also in the oocyte. Short-term treatment (7h) of polychaete females with alpha-amanitin provokes serious disturbances of oogenesis and subsequent embryonic development, irrespective of when it is applied during oogenesis. In contrast actinomycin gives such effects only when it is applied at the onset of oogenesis. A previous investigation has demonstrated that nurse cell granules are gradually exported through an intercellular canal to the oocyte, where a fraction of them is incorporated into the typical yolk granules. The present labelling experiments indicate that nurse cell RNA is associated with the exported yolk precursor material. From inhibition experiments with alpha-amanitin and from in situ hybridizations with a poly(U)probe it appears that mRNA is particularly involved. At the final collapse of the nurse cell practically all its contents are transferred to the oocyte. From that time the ooplasm is found to contain nuage-like RNA aggregates, which in contrast to other [5-3H]uridine-labelled ooplasmic structures (yolk granules, and minor granules and aggregates) have a non-uniform distribution. The possible origin and function of these aggregates is discussed. The investigation indicates that the nurse cell has a significant export of RNA essentially similar to that from insect nurse cells.

Amanitins↗
PubMed1985

Development in vitro of the female germ cells of the polychaete Ophryotrocha labronica.

In the polychaete Ophryotrocha labronica each oocyte is during its growth period associated with a single nurse cell. The fact that the oocyte-nurse cell pairs occur isolated in the female coelom makes them easily removable for analysis of their developmental ability in vitro. Using Dulbecco's modified Eagle medium supplemented with amino acids, nucleosides, foetal calf serum and sea water, we have managed to support development in vitro of germ cell pairs from early and mid-oogenesis until maturation of the oocyte, when the nurse cell degenerates and the oocyte enters meiotic metaphase. Radiolabelling of germ cells in mid-oogenesis with tritiated amino acids and uridine during the first day of incubation indicates normal development with synthesis of RNA and protein, and pulses two days later verify a continued normal protein synthesis and yolk formation. The investigation confirms autosynthesis of yolk proteins in the germ cells of this species and indicates a leading role of the nurse cell in the process.

Animals↗
PubMed1984

Göteborg Metoprolol Trial: enzyme-estimated infarct size.

In 1,375 patients serum activity of heat-stable lactate dehydrogenase (LD; E.C.1.1.1.27.) was analyzed every twelfth hour for 48 to 108 hours. The mean maximum LD activity was 11.1 +/- 0.4 mu kat X 1(-1) in the metoprolol group vs 12.4 +/- 0.5 mu kat X 1(-1) in the placebo group (p = 0.054). In patients in whom treatment was started 12 hours or less after the onset of pain, a 17% reduction in LD activity was observed (p = 0.009) and similar results were found in patients randomized 8 hours or less. Groups in which the effect after metoprolol treatment was more pronounced were those with an initially higher heart rate and also those with anterior myocardial infarction.

Aged↗
PubMed1984

Hemodynamic and clinical findings after combined therapy with metoprolol and nifedipine in acute myocardial infarction.

In a double-blind trial, 30 patients with suspected acute myocardial infarction with onset of symptoms within the previous 24 h were randomized to treatment with 10 mg nifedipine/placebo orally 4 times a day during hospitalization. All patients were given 15 mg metoprolol intravenously 20 min after the initial administration of nifedipine/placebo, and thereafter, 50 mg 4 times a day. The combined therapy resulted only in moderate changes in systolic blood pressure and heart rate compared with metoprolol alone. Three of the 15 patients in the nifedipine group versus 2 of the 15 in the placebo group were withdrawn because of hypotension and/or bradycardia. None was withdrawn because of congestive heart failure or A-V block. It is concluded that the combination of nifedipine and metoprolol seems to be a relatively well-tolerated combination in acute myocardial infarction.

Adult↗
PubMed1984

Comparison of atrial pacing and the cold pressor test in patients with angina pectoris.

A haemodynamic and myocardial metabolic study was performed to compare effects of maximal atrial pacing and the cold pressor test (CPT) in patients with angina pectoris. Twelve patients (group I) had angiographically severe coronary artery disease, while 16 patients (group II) had normal coronary angiograms. At maximal pacing, angina developed in all patients in group I, and myocardial lactate production was found in eight of 12 patients. In group II, 12 out of 16 patients experienced chest pain, but only two patients had myocardial lactate production. Neither angina nor myocardial lactate production was present in any patient in either group during CPT. Coronary sinus flow increased and coronary vascular resistance decreased significantly in both groups at maximal pacing (P less than 0.001). At CPT, coronary flow decreased (P less than 0.05) and coronary resistance increased (P less than 0.001) in group I, while individual response was more variable in group II. In conclusion, maximal pacing was a more effective method of provocation of angina pectoris than CPT. The reactions of coronary sinus flow and coronary vascular resistance were different in group I than in group II. However, because of the variability of response in patients with normal coronary arteries, CPT cannot be used to distinguish patients with coronary artery disease from patients with no such disease.

Adult↗
PubMed1984

Effects of felodipine on systemic and coronary haemodynamics in patients with angina pectoris.

In order to study the systemic and coronary haemodynamic effects of felodipine, a new dihydropyridine derivative, 10 patients with coronary artery disease were studied during cardiac catheterization. Measurements were performed at rest and during pacing-induced angina pectoris. At rest, the heart rate rose from 70 +/- 20 to 78 +/- 20 (P less than 0.05), the systemic arterial pressure decreased by about 20% (P less than 0.01) and the cardiac index rose from 2.9 +/- 1.2 to 4.0 +/- 1.0 (P less than 0.05). The coronary sinus flow (CSF) increased about 50% (P less than 0.01). During pacing to the same heart rate as in the control measurements, felodipine induced similar changes in systemic haemodynamic values as in the resting position. Myocardial lactate extraction and ST segment depression were not significantly altered. After felodipine, the pacing rate could be further increased in 7 patients as compared with the control value. Both systemic and coronary effects were then very similar compared with those during the lower pacing rate. In conclusion, felodipine is a very potent systemic and coronary vasodilator with potential value in the treatment of hypertension and cardiac failure. The drug may also be of value in the treatment of ischaemic heart disease, but further studies with titration of optimal doses are needed in that respect.

Adult↗
PubMed1984

Localization of ornithine decarboxylase in mutant CHO cells that overproduce the enzyme. Differences between the intracellular distribution of monospecific ornithine decarboxylase antibodies and radiolabeled alpha-difluoromethylornithine.

The intracellular localization of ornithine decarboxylase (ODC), a key enzyme in polyamine synthesis and cell growth, is a matter of present debate. Using two independent methods of analysis, we have attempted to determine the actual distribution of ODC in a mammalian cell. To overcome the problem of a normally very low cellular ODC content, we have used ODC overproducing mutant CHO cells. These mutant cells exhibit a 10-fold higher ODC activity than do the wild type cells. The localization of ODC protein in exponentially growing cells, was determined by indirect immunofluorescence microscopy (permeabilized whole-cell preparations and 1 micron sections), using a monospecific ODC antibody. The intracellular localization of catalytically active ODC was determined by light and electron microscope autoradiography following pulselabeling of cells with alpha-difluoromethyl(5-3H)ornithine (3H-DFMO) at the time of peak ODC activity. alpha-Difluoromethylornithine (DFMO) is an enzyme-activated irreversible inhibitor of ODC and binds covalently to the active enzyme. The specificity of this reaction in the cell was ascertained by immunoprecipitation of 3H-DFMO-labeled ODC. ODC (as determined by both methods) was present in all the cells of a serum-stimulated monolayer culture. The highest concentration of ODC protein and of catalytically active ODC was observed in the smallest and most rapidly proliferating cells. Polyploid and multinuclear cells always exhibited the lowest concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Suppression of ribosomal gene expression in oocytes and nurse cells of a polychaete as a result of polyamine synthesis inhibition.

The role of the polyamines in ribosomal gene expression was evaluated in the polychaete Ophryotrocha labronica by analyzing the effects of polyamine synthesis inhibition on RNA synthesis during oogenesis, a period characterized by intense nucleolar activity. At various stages of oogenesis adult polychaete females were blocked in their polyamine synthesis by the addition of 10 mM DL-alpha-difluoromethylornithine (DFMO) to the sea water in which they were cultivated. To monitor RNA synthesis during DFMO treatment the animals were pulse-labeled with [5-3H]uridine and processed for autoradiography. Light and electron microscope autoradiographs demonstrate that DFMO treatment suppresses incorporation of label into nucleolar RNA (rRNA) both in the oocytes and their associated nurse cells. The ultrastructural appearance of both cell types reveals interference with nucleolar and ribosomal activity; the endoplasmic reticulum is deprived of ribosomes, and the production of protein granules (vitellogenesis) is reduced. The high specificity of DFMO for polyamine synthesis and the fact that the effects of DFMO were counteracted by addition of a low concentration (10 microM) of putrescine shows that the observed interference with ribosomal gene expression is indeed due to polyamine deficiency.

Age Factors↗
PubMed1983

Effects of polyamine limitation on nucleolar development and morphology in early chick embryos.

Inhibition of polyamine synthesis in early chick embryos by in ovo treatment with DL-alpha-difluoromethylornithine (DFMO), injected beneath the blastoderm after 5 h of incubation, permanently blocks post-gastrular development. After the first day of polyamine limitation, the embryos possess a thickened primitive streak. Further morphogenesis is blocked and the ectoderm and mesoderm are condensed around the streak. There is obvious suppression of nucleolar formation in 24 h DFMO-treated embryos. In the mesoderm obliquely in front of Hensen's node the frequency of nucleolus-possessing cells is only a few percent lower in DFMO-treated than in control embryos. However, in the same area the frequency of mesoderm cells possessing multiple nucleoli is about 50% lower in the polyamine-depleted embryos. At the ultrastructural level, mesoderm cells from 24 h DFMO-treated embryos show a reduction of the fibrillar component of the nucleolus with a resulting segregation of the nucleolar material. Our data indicate that stimulation of polyamine synthesis is an obligatory step in the differentiation of epiblast cells into mesoderm cells.

Animals↗
PubMed1983

Mechanisms of angina relief after nifedipine: a hemodynamic and myocardial metabolic study.

To elucidate the mechanisms of action of nifedipine in angina pectoris, 14 patients were studied before and after sublingual administration of 10 mg nifedipine. Systemic and coronary hemodynamic and myocardial metabolic measurements were taken at rest and during pacing. At the pacing rate that induced pain in the control situation, no patient experienced angina after nifedipine administration. Lactate production during control turned into extraction after nifedipine administration (p less than .05), and the double product was reduced (p less than .001). Systemic and coronary vascular resistance were reduced by 26% (p less than .001) and 19% (p less than .005), respectively. Systolic blood pressure fell from 160 +/- 29 to 127 +/- 25 mm Hg (p less than .001) and diastolic from 100 +/- 14 to 79 +/- 11 mm Hg (p less than .001). Pulmonary artery diastolic blood pressure fell from 14 +/- 4 to 10 +/- 3 mm Hg (p less than .01). When the pacing rate was further increased after nifedipine administration until pain developed, the double product and the degree of lactate production were the same as during pain before nifedipine was administered. The pacing rate was 131 +/- 12 compared with 119 +/- 13 during control (p less than .001). Both the systolic and diastolic blood pressures were still significantly reduced compared with control pacing values, 131 +/- 26 mm Hg (p less than .01) and 84 +/- 13 mm Hg (p less than .01), respectively. Our data demonstrate that the antianginal efficiency can be partly explained by afterload reduction, which decreases myocardial oxygen consumption. The data also suggest additional mechanisms, possibly an increase in collateral flow, direct dilatation of stenotic parts of epicardial arteries, or a decrease in myocardial back pressure secondary to reduced left ventricular filling pressure.

Adult↗
PubMed1983

Nuclear ornithine decarboxylase. Electron microscope autoradiographic identification of the active enzyme using alpha-[5-3H]difluoromethylornithine.

alpha-Difluoromethylornithine (DFMO) is an enzyme-activated irreversible inhibitor of ornithine decarboxylase, that forms a covalent bond with the active enzyme. The highly selective binding of tritium-labeled DFMO to ornithine decarboxylase in vivo, as identified by electron microscope autoradiography, was used to determine the intracellular distribution of the enzyme in the germ cells of a polychaete (Ophryotrocha labronica). In mid-oogenesis ornithine decarboxylase was predominantly located in the nurse cells, which are actively supporting growth of the oocytes. On the basis of biochemical analyses ornithine decarboxylase has been considered mainly cytoplasmic in its distribution. However, in metabolically active polychaete cells (oocytes, nurse cells, intestinal and body wall cells), binding sites for tritiated DMFO, indicating the presence of active ornithine decarboxylase, were as abundant in the nucleus. The nucleolus was the most densely labeled organelle in nurse cells and oocytes.

Animals↗