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Biomedical subjects

E Karlsson

Publications and source records attributed to E Karlsson.

At least 91 records · Page 5Linked to original sources

IgG from cows with parturient paresis changes the thermodynamic behaviour of bovine erythrocyte acetylcholinesterase.

Parturient paresis affects about 10% of all cows. The most common treatment is injection of various Ca-salts and MgCl2 and about 80% recover after repeated injections. The effect of IgG on the Arrhenius plot of bovine erythrocyte AChE was studied. The plot was normal, i.e. biphasic (a broken line) in the presence of IgG from healthy cows. The highest concentration tested was 10 mg/ml. Before one injection of the Ca-Mg solution 5 mg/ml IgG from sera of paretic cows (n = 10) changed the Arrhenius plots to monophasic (linear). Thus, paretic cows have antibodies against AChE. After injection the change to linear plots was observed already with 1 mg/ml IgG. Apparently, the level of antibodies in serum affecting AChE increased about 5-fold. This is considered to be due to dissociation of bound antibodies from various AChEs. All cows recovered after one injection and release of AChE antibodies might be important for the recovery. Incubation of blood from paretic cows (n = 3) with Ca-salts and MgCl2 increased the amount of free AChE-antibodies about twofold; the Arrhenius plots became linear at 2.5 mg/ml IgG compared with 5 mg/ml before the incubation. This should be due to release from AChEs on blood corpuscles as erythrocytes and lymphocytes. But the increase of antibodies after incubation of blood does not account for the whole increase following the treatment of paretic cows. AChE antibodies are probably also dissociated from other sites, such as neuromuscular junctions.

Acetylcholinesterase↗

The value of exercise test, Holter monitoring, and programmed electrical stimulation in detection of ventricular arrhythmias in patients with hypertrophic cardiomyopathy.

To determine the best way to detect serious ventricular arrhythmia in patients with hypertrophic cardiomyopathy (HCM), 15 patients with HCM performed an exercise test, had Holter monitoring during 24 hours, and programmed electrical stimulation (PES) in a randomized order, and the presence and type of ventricular arrhythmia was noted. During exercise testing, only one patient demonstrated ventricular tachycardia (VT) just prior to the test. By Holter monitoring, four patients had short episodes of asymptomatic VT. PES, using up to three extrastimuli induced VT or ventricular fibrillation (VF) in ten patients including those with VT during exercise testing and Holter monitoring. There were no differences between patients with and without ventricular arrhythmia during PES regarding age, left ventricular outflow obstruction, thickness of interventricular septum, interventricular septum/posterior wall thickness ratio, corrected QT interval, or the amplitude of the R wave in lead aVR in electrocardiography. Our results indicate that inducible VT/VF during PES is a common finding in patients with HCM. Twenty-four hour Holter monitoring was superior to exercise testing in revealing serious ventricular arrhythmia in those patients.

Cardiac Pacing, Artificial↗

Immunoglobulin-mediated activity against red blood cells in the saliva of amyotrophic lateral sclerosis (ALS) patients.

Immunoglobulin (Ig)-mediated activity in plasma directed towards normal blood type matched red blood cells (RBC) inducing haemolysis in vitro has earlier been demonstrated to be a characteristic feature in ALS-patients. In this study, saliva of ALS-patients, normal and diseased controls was tested with the same in vitro test. An increased degree of haemolysis was induced by the ALS-patient as compared with control samples. The activity thus found in saliva had the same basic characteristics as that earlier described for plasma; it reacted similarly to serial dilution and was retained in salivary Ig. The effect on red blood cells of saliva from patients with bulbar paralysis was larger than that of saliva from ALS-patients lacking bulbar symptoms. It is discussed whether cytotoxic Ig in saliva could be pathophysiologically active in bulbar paralysis by means of passage through the oral mucosa and local action on motor end plates in perioral muscles.

Adult↗

Neuroendocrine response in acute heart failure and the influence of treatment.

Vasoactive humoral factors were measured in 27 patients before and during the first week of conventional treatment of acute heart failure. On admission, all patients were given frusemide intravenously, followed by oral digoxin and diuretic therapy. Before drug treatment, plasma renin activity and plasma angiotensin II concentrations were within normal ranges in the group of patients without previous diuretic treatment, but were significantly higher in those 16 patients already on diuretic drugs when admitted to hospital. After diuretic treatment, however, even the former group revealed activation of the renin-angiotensin system. Plasma concentrations of catecholamines were increased initially but normalized within 1 day. A majority of the patients initially had very high plasma concentrations of atrial natriuretic peptide (mean 276.9 +/- 39.0 pg ml-1) which decreased but did not normalize during the study period. High plasma levels of arginine vasopressin (mean 56.8 +/- 14.6 pg ml-1) were found, but tended to be reduced during treatment. Thus, patients with acute heart failure displayed increased plasma concentrations of atrial natriuretic peptide, arginine vasopressin and catecholamines, but these vasoactive hormones decreased in parallel to clinical improvement during diuretic therapy. In contrast, the renin-angiotensin system became clearly activated.

Acute Disease↗

Toxins from the venom of the green mamba Dendroaspis angusticeps that inhibit the binding of quinuclidinyl benzilate to muscarinic acetylcholine receptors.

Two protein toxins that displace the muscarinic antagonist quinuclidinyl benzilate from rat cortex synaptosomal membranes have been isolated from the green mamba (Dendroaspis angusticeps) venom by gel filtration on sephadex G-50, chromatography on the ion-exchangers Bio-Rex 70 and Sulphopropyl-Sephadex C-25 and reversed-phase HPLC. Toxin 1 has 64 amino acids and four disulfides and a formula weight of 7200 and the corresponding values for toxin 2 are 63, 4 and 6840, respectively. Ultracentrifugation gave a molecular weight of 6900 for toxin 1 and 6700 for toxin 2, Quinuclidinyl benzilate that binds to all types of muscarinic cholinergic receptor was displaced to about 50% by both toxins. This partial displacement indicates that the toxins might be specific for one subtype of receptor.

Amino Acids↗

The antianginal efficacy and tolerability of controlled-release metoprolol once daily: a comparison with conventional metoprolol tablets twice daily.

In a randomized, double-blind, cross-over study treatment with a new controlled-release (CR) preparation of metoprolol, given once daily, was compared with treatment with conventional metoprolol tablets, given twice daily, in 115 patients with stable effort angina pectoris. The patients were treated with 100 mg/day or 200 mg/day, depending on their previous beta-blocker dose. Antianginal efficacy was estimated by counting the number of anginal attacks, by noting the consumption of nitroglycerin tablets, and by exercise tolerance testing. Adverse effects were recorded by a standardized questionnaire. When all patients were analysed together there were no differences in antianginal efficacy between the two treatment regimens. However, when the group taking 200 mg daily was analysed separately better exercise tolerance was found during metoprolol CR therapy, as measured by onset of chest pain and ST-segment change, compared with conventional metoprolol therapy. The two formulations were well tolerated. When given once daily in a total daily dose of 100 mg, the CR preparation induced less adverse effects than the conventional tablets, 50 mg twice daily. It was concluded that the new metoprolol CR preparation, given once daily, possesses the same antianginal efficacy as conventional metoprolol tablets, given twice daily, and may be better tolerated in patients susceptible to side-effects. The antianginal effect of metoprolol CR, 200 mg/day, may be greater over 24 h than that produced by conventional metoprolol tablets, 100 mg twice daily.

Adult↗

Immunoglobulins from patients with amyotrophic lateral sclerosis affect human erythrocyte acetylcholinesterase.

Human erythrocyte acetylcholinesterase (AChE) solubilized with Triton X-100 and obtained as a complex with micelles containing Triton and membrane phospholipids was incubated with immunoglobulins (Igs) from patients with amyotrophic lateral sclerosis (ALS) and from normal individuals. The temperature dependence of the AChE activity was determined. Biphasic (broken) Arrhenius plots were obtained with control Igs with the break point at 32.8 +/- 0.3 degrees C (SD, n = 18) indicating that the enzyme changes its conformation at this temperature. With ALS-Igs monophasic (linear) plots were observed in 14 cases and a biphasic in one case. ALS-Igs prevent the conformational change occurring at the break point temperature. The activation energy at physiological temperature increased by 60% from 2.4 to 3.8 kcal/mol (10.0-15.9 kJ/mol) which implies that ALS-Igs inhibit AChE. Thus, ALS-patients have autoantibodies that change the normal behaviour of erythrocyte AChE and which bind to the enzyme molecule or/and to phospholipids associated with the enzyme. At least part of the autoantibodies should be directed against the enzyme molecule, since a change in the Arrhenius plot was also observed in a control experiment with AChE which probably had micelles without any phospholipids. This enzyme was isolated by affinity chromatography and was washed with a buffer containing Triton X-100 before desorption from the affinity column, a treatment known to remove all phospholipids from erythrocyte AChE.

Acetylcholinesterase↗

Nature and properties of cytotoxic plasma activity in amyotrophic lateral sclerosis.

Cytotoxic activity of plasma towards normal red blood cells in patients with amyotrophic lateral sclerosis (ALS) has been studied as a function of progressive plasma dilution and compared with plasma from patients with Charcot-Marie-Tooth's disease (CMT). At progressive dilution the hemolysis by ALS-plasma showed a specific pattern that differed qualitatively and quantitatively from that of normal plasma as well as CMT and persisted up to a dilution of 1:6561. Differences in dilution pattern were found when comparing different clinical types of ALS. There was evidence for a partial complement dependency of the reaction that brings about the hemolysis provoked by ALS plasma. Experiments with plasma fractionated by gel filtration and with isolated immunoglobulins produced evidence for cytotoxic properties of IgA and IgG from ALS plasma. The observations speak in favor of a consistency between the observations of plasma cytotoxicity in ALS and earlier observations on immunological abnormalities in the disease.

Adult↗

Severe aortic stenosis in elderly patients.

Clinical and non-invasive findings were compared with catheterisation data in 91 elderly patients (mean 65 years, range 52-78) with suspected severe aortic stenosis requiring operation. Heart catheterisation showed that forty nine patients had a valve area of less than or equal to 0.6 cm2, 36 had a valve area of 0.7 - 1.0 cm2, and six an area of greater than or equal to 1.1 cm2. Coexistent aortic regurgitation was found in 85% of the cases, but severe regurgitation was found in only one patient (1%). Seventy seven per cent of patients had chest pain, 74% had dyspnoea, and 46% had exertional vertigo or syncope. Coronary angiography, which was performed in 77 patients, showed coronary artery disease in 24% of those with a history of angina pectoris and in none of those without. All patients had echodense valves; aortic valve calcification was shown by x ray in 76% and in all but one by cineradiography. The peak of the systolic murmur was delayed in 98% of the patients. Although a prolonged left ventricular ejection time was characteristic of severe aortic stenosis, a normal value did not exclude this diagnosis. Most patients (84%) had increased QRS amplitude on the electrocardiogram. Echocardiography showed an increased left ventricular wall thickness in 90% of the patients in whom it was possible to define the myocardial borders. There was an inadequate blood pressure increase in response to exercise in 82%. In about 25% of the patients the exercise test was at variance with the New York Heart Association classification. Findings suggesting severe aortic stenosis resembled those reported for younger age groups. When most findings point to severe aortic stenosis, the absence of a single symptom or non-invasive sign does not exclude severe aortic stenosis.

Aged↗

Prenalterol as long-term therapy for chronic congestive heart failure. A randomized cross-over trial.

Ten patients with severe chronic congestive heart failure (CHF) due to ischaemic heart disease treated with digitalis and diuretics were randomly allocated to oral treatment with prenalterol (100-200 mg daily in addition to their basal treatment) or to intensified treatment with diuretics in a cross-over trial. A wash-out period of 1-4 weeks was allowed between the two modes of treatment. Most of the patients demonstrated subjective improvement during prenalterol therapy, but this improvement could not be verified objectively by exercise test, echocardiography, chest X-ray or weight measurements. No serious side-effects of either mode of treatment were observed. Heart rate was significantly lower during exercise when the patients were treated with prenalterol than during the control periods or during intensified conventional treatment, indicating that prenalterol acts as a beta-adrenergic receptor blocker during exercise in this patient group. The results indicate that prenalterol is a partial beta-receptor agonist without superior beneficial effects compared to those of intensified conventional treatment in patients with chronic, severe CHF.

Adrenergic beta-Agonists↗

Facilitation of transmitter release by neurotoxins from snake venoms.

Toxins C13S1C3 and C13S2C3 from green mamba venom (Dendroaspis angusticeps) acted like dendrotoxin to increase acetylcholine release in response to nerve stimulation in the chick biventer cervicis preparation. Proteins B and E from black mamba venom (Dendroaspis polylepis) had no prejunctional facilitatory activity. All four proteins are trypsin inhibitor homologues. Binding of a prejunctional facilitatory toxin (Polylepis toxin I) to motor nerves was rapid and did not require the presence of Ca2+ or nerve stimulation. Binding was not prevented by protease inhibitors that lacked facilitatory actions. Prejunctional facilitatory toxins also augmented transmitter release in the chick oesophagus and the mouse vas deferens preparations. The effects were rapid in onset and could wane spontaneously. 125I-labelled dendrotoxin bound specifically to rat brain synaptosomes with a KD of about 3 nM. Binding was prevented by native dendrotoxin but not by beta-bungarotoxin or atropine. It is concluded that prejunctional facilitatory toxins affect transmitter release at many types of nerve endings in addition to motor nerve terminals. From consideration of the structures of active and inactive molecules, it is thought that binding of the active toxins may involve several exposed lysine residues.

Animals↗

[NMR study of the spatial structure of the Naja naja siamensis toxin 3].

The 300 and 500 MHz 1H NMR spectra of a long-chain neurotoxin, toxin 3 Naja naja siamensis (S-T3), its derivatives and close homolog, toxin 3 Naja naja naja (N-T3), have been analyzed. A combination of double resonance, difference spectroscopy and usage of a series of toxin S-T3 derivatives acetylated or trifluoroacetylated at lysine residues allowed to assign the signals from all aromatic protons and a number of signals in the aliphatic region, and to elucidate the microenvironment of certain functionally important residues. Analysis of chemical shifts pH-dependences in the 1H and 19F NMR spectra of toxin S-T3 and its trifluoroacetylated congeners delineated a considerable region of the neurotoxin molecule affected by the conformational transition, with the midpoint at pH 5,4, between two states. This conformational transition is induced by protonation of His22 and is accompanied by a change in the accessibility of its imidazole ring for the solvent, along with the alteration of the distance between the side chains of functionally important Lys27 and Lys53 residues. According to EPR data (-196 degrees) for the respective S-T3 derivative having spin labels at Lys27 and Lys53 epsilon-amino groups, the inter-label distance increases from 18 A at pH 7,5 to 23 A at pH 3,5. Notwithstanding this conformational change, the totality of the obtained results evidences in favor of considerable similarity of the toxin S-T3 spatial structure in the solution and crystalline state.

Acetylation↗

[Relative localization of the bound acetylcholine receptor subunits and neurotoxin].

A series of neurotoxin II (Naja naja oxiana) derivatives, each containing one p-azido-[14C]benzoyl group, have been prepared. Those labeled at Leu1, Lys15, Lys25, Lys26, or Lys46 associate specifically with the acetylcholine receptor from the Torpedo marmorata electric organs and form the crosslinks with it as a result of irradiation. Electrophoresis in polyacrylamide gel and gel chromatography revealed the contacts between the neurotoxins and alpha, beta, gamma and delta subunits of the receptor, modification of a particular subunit being governed by the photoactivable group position in the neurotoxin molecule. The differences of the two neurotoxin binding sites in the receptor were demonstrated by analysis of the photoinduced crosslinks under the conditions of one site being blocked by hexa (trifluoroacetyl) neurotoxin II. The mutual arrangement of the two bound neurotoxin molecules was established. On the basis of data obtained, two models for the acetylcholine receptor subunit topography were proposed.

Animals↗

Fasciculins, anticholinesterase toxins from the venom of the green mamba Dendroaspis angusticeps.

Two toxins that are potent inhibitors of acetylcholinesterase have been isolated from the venom of the green mamba, Dendroaspis angusticeps. The toxins have been called fasciculins since after injection into mice (i.p. 0.5-3 micrograms/g body weight) they cause severe, generalized and long-lasting (5-7 h) fasciculations. Homogenates of diaphragm, tibialis anterior and gastrocnemius muscles from mice injected with fasciculins showed a decrease in acetylcholinesterase activity by 45-60% compared to muscles from control animals. Histochemical staining revealed a greatly reduced acetylcholinesterase activity at neuromuscular junctions. Fasciculins have 61 amino acid residues and four disulfides. The molecular weights are 6765 (fasciculin 1) and 6735 (fasciculin 2). The sequences of the two toxins differ probably only at one position by a replacement of Tyr with Asp/Asn. 1 g of venom contained about 40 mg of fasciculins, 2/3 of which was fasciculin 2. A similar inhibitor has also been isolated from D. polylepis (black mamba) venom. The sequence of fasciculin 2 is known. Most of the positive charges are concentrated in a small section of the central part of the molecule, and most of the negative charges are in the C-terminal region. Fasciculins appear to have a pronounced dipole character. Fasciculin binds to the peripheral anionic site, since it can displace propidium, a probe for that site, from acetylcholinesterase. In vitro, in Krebs-Henseleit solution containing 2 mM NaH2PO4 (pH 7.4), fasciculin 2 inhibits acetylcholinesterase from human erythrocytes (Ki = 1.1 X 10(-10) M, 37 degrees C), rat muscle (Ki = 1.2 X 10(-10) M, 37 degrees C) and Electrophorus electricus (Ki = 3.0 X 10(-10) M, 22 degrees C).(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗