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Biomedical subjects

M Ericsson

Publications and source records attributed to M Ericsson.

At least 19 recordsLinked to original sources
PubMed1992

Reptilian alcohol dehydrogenase. Heterogeneity relevant to class multiplicity of the mammalian enzyme.

Liver alcohol dehydrogenase of the ethanol-active type ('class I enzyme') from the lizard, Uromastix hardwickii, was purified and screened for relationships with other vertebrate forms of the enzyme. Two different acetylated N-termini (acetyl-Gly and acetyl-Ser) and further positional differences already in the N-terminal segments establish the presence of two types of protein chain. The multiplicity is different from that hitherto detected within vertebrate class I alcohol dehydrogenase isozymes but typical of that which would be expected for subunits of different classes. In particular, relationships to class II or to class II-related forms appear likely. This may indicate yet further vertebrate alcohol dehydrogenase multiplicity or discovery of a class II non-mammalian enzyme. The results give prospects of defining gene duplications corresponding to more than one alcohol dehydrogenase class split to at an early vertebrate stage.

Alcohol Dehydrogenase↗
PubMed1991

Analogues of parathyroid hormone modified at positions 3 and 6. Effects on receptor binding and activation of adenylyl cyclase in kidney and bone.

Predictive and spectroscopic methods were used to develop a model of the structures of the 1-34 peptides of parathyroid hormone (PTH) and the PTH-related protein (PTHrP). Circular dichroism (CD) studies of bovine PTH-(1-34) and human PTHrP-(1-34)amide in the presence of trifluoroethanol suggest the presence of 24-26 alpha-helical residues. For both peptides, interactions between amino- and carboxyl-region alpha-helices are predicted to result in a hydrophobic core with externally facing hydrophilic residues that include probable determinants of receptor binding and activation. Two such residues, Ser3 and Gln6, are conserved in all known members of the PTH/PTHrP family. We have synthesized 13 novel analogues of bovine PTH-(1-34) monosubstituted at positions 3 and 6 and have determined their biological activities in renal and bone cell radioreceptor and adenylyl cyclase assays. Position 3 analogues displayed biological activity that was reduced in direct proportion to the volume of the substituent side-chain. Position 6 analogues also displayed reduced biological activity, but no simple correlation with side-chain volume or hydrophobicity was evident. The analogues fully displaced labeled PTH from binding sites in renal membranes and bone cells, but [Phe3]bPTH-(1-34), [Tyr3]bPTH-(1-34), [Phe6] bPTH-(1-34), and [Ser6]bPTH-(1-34) were only partial agonists in one or both adenylyl cyclase assays. Of these, [Phe3]bPTH-(1-34) and [Phe6]bPTH-(1-34) were tested for antagonist activity and were found to inhibit the activation of adenylyl cyclase in response to bPTH-(1-34) or hPTHrP-(1-34)amide. These results indicate that positions 3 and 6 contribute important determinants of PTH receptor binding and activation. Modification at these positions represents a novel approach to the development of antagonists of PTH action.

Adenylyl Cyclases↗
PubMed1991

Behavioural profile of partial D2 dopamine receptor agonists. 1. Atypical inhibition of d-amphetamine-induced locomotor hyperactivity and stereotypy.

The effects of partial D2 dopamine (DA) receptor agonists on the behavioural activation produced by 1.5 and 8.0 mg/kg d-amphetamine were compared with the changes produced by the classical DA antagonist haloperidol. Alterations in behaviour were assessed in standard activity monitoring cages by direct observation of the rats using a rapid time sampling procedure. Haloperidol blocked d-amphetamine (1.5 mg/kg)-induced increases in photocell counts, ambulation, rearing and sniffing up, and after the highest dose of the DA antagonist the animals were mainly inactive. The partial D2 DA agonist SDZ 208-911 was equipotent to haloperidol in blocking the increase in photocell counts and rearing produced by d-amphetamine. However, even high doses of the drug did not reduce the incidence of sniffing or induce inactivity, but qualitative changes in the form of sniffing did occur. Although considerably less potent, preclamol exerted similar effects to SDZ 208-911. The profiles of SDZ 208-912 and terguride were intermediary to those of SDZ 208-911 and haloperidol. All compounds blocked the repetitive sniffing down produced by 8.0 mg/kg d-amphetamine. After a low dose of haloperidol, these stereotyped behaviours were replaced by a behavioural syndrome similar to that observed with low dose d-amphetamine, but inactivity was observed following a further small increase in antagonist dose. The blockade of stereotypy by SDZ 208-911, preclamol and terguride was accompanied only by the low dose d-amphetamine behavioural syndrome; no inhibition of sniffing or induction of inactivity occurred. SDZ 208-912 exhibited a profile with features very similar to that noted with haloperidol. These findings suggest that partial D2 agonists exert similar, but not identical, behavioural effects to classical DA antagonists when dopaminergic function in increased by d-amphetamine. The differences in behavioural profile are discussed in relation to variations in the intrinsic efficacy of the dopaminergic compounds and to differences in the response capability of D2 receptor populations underlying the different behaviours produced by d-amphetamine.

Animals↗
PubMed1991

Targeting of frog prodermorphin to the regulated secretory pathway by fusion to proenkephalin.

We have investigated the sorting and processing of the amphibian precursor prepro-dermorphin in mammalian cells. Dermorphin, a D-alanine-containing peptide with potent opioid activity, has been isolated from the skin of the frog Phyllomedusa sauvagei. The maturation of this peptide from the precursor involves several posttranslational steps. Recombinant vaccinia viruses were used to infect AtT-20, PC12, and HeLa cells to study the sorting and processing of prepro-dermorphin. While this precursor was not processed in any of the examined cell lines, AtT-20 cells were able to process approximately 40% of a chimeric precursor consisting of the first 241 amino acids of prepro-enkephalin fused to a carboxy-terminal part of pro-dermorphin. By immunogold-EM, we could show that the chimeric protein, but not pro-dermorphin, was sorted to dense-core secretion granules. The processing products could be released upon stimulation by 8-Br-cAMP. We conclude that the pro-enkephalin part of the fusion protein contains the information for targeting to the regulated pathway of secretion, while this sorting information is missing in pro-dermorphin. This indicates that sorting mechanisms may differ between amphibian and mammalian cells.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1990

Detection of doubly stained fluorescent specimens using confocal microscopy.

Studies of doubly stained specimens were performed with a confocal scanning microscope. The instrument used provides the possibility of making separate detections of the fluorescent dyes. The optimal choice of excitation wavelengths and optical filters are discussed. The fluorphores that were used are Lucifer Yellow, Texas Red, fluorescein isothiocyanate and tetramethylrhodamine isothiocyanate.

Animals↗
PubMed1990

Spinal epidural abscesses in adults: review and report of iatrogenic cases.

A retrospective review of the medical records of adults with diagnosed spinal epidural abscess (SEA) admitted to the Departments of Neurosurgery and Infectious Diseases at the University Hospital of Umeå, Sweden, during a 10-year-period (1978-1987) is presented. 10 patients were diagnosed as having SEA during the study period. An iatrogenic origin was suspected in 5. Spondylitis was the most common source of infection. Bacteriological aetiology was confirmed in 8 cases and Staphylococcus aureus was the most common aetiological agent. Trauma and degenerative diseases of the spine, were underlying conditions in 6 cases. Laminectomy was performed in 7 cases. 5/6 patients operated within 48 h after onset of neurological symptoms improved. The remaining case with therapy resistant tuberculous spondylitis died. One patient with surgery after 96 h became paretic. 2/3 conservatively treated patients had a successful outcome while the third patient had a permanent paraparesis due to missed diagnosis. Early diagnosis and early laminectomy are still the most important prognostic factors. Recommended initial antibiotic therapy is the combination of a cephalosporin with extended spectrum and metronidazole.

Abscess↗
PubMed1989

The quadriceps femoris muscle in 20-70-year-old subjects: relationship between knee extension torque, electrophysiological parameters, and muscle fiber characteristics.

Comparisons have been made between torque (isometric and isokinetic), electrophysiological (SFEMG, Macro EMG), and muscle fiber characteristics in the vastus lateralis muscle of both legs in healthy subjects aged between 20 and 70 years. Torque was greater in males and decreased with age in both sexes. Multifactorial analysis showed a positive correlation between torque, body surface area, and mean fiber area. These variables explained only about 30-40% of the torque changes. The electrophysiological parameters (Marco EMG amplitudes and fiber density) revealed evidence of reinnervation, indicating preceeding denervation and therefore loss of motor units. It was concluded that this fall out of motor units also contributes to the reduction in torque, when compensatory reinnervation begins to fall. Other factors, such as reduction in muscle fiber contractility, metabolic factors, and central factors, may also play a role in age-related reduction in torque.

Adult↗
PubMed1988

Three-dimensional reconstruction of transmitter-identified central neurons by "en bloc" immunofluorescence histochemistry and confocal scanning microscopy.

A new method for three-dimensional reconstruction of transmitter-identified neurons is presented which involves "en bloc" immunofluorescence histochemistry and confocal scanning microscopy. The technique was applied to different types of neurons in the rat brain and lamprey spinal cord. Thick sections or tissue "blocs" (50-200 micron thick) were incubated with antisera against neuropeptides or monoaminergic markers, followed by fluorescent secondary antibodies. Three-dimensional reconstructions were obtained by scanning the preparations in sequential focal planes with a thin laser beam, while sampling the emitted light in each focal plane. The method is convenient and can be applied to a wide variety of neuron types. The reconstructions obtained are accurate since the "optical serial sections" of the specimen are perfectly aligned, and optic disturbances such as "halo" phenomena do not occur.

Animals↗
PubMed1988

Myocardial turnover of plasma free fatty acids during angina pectoris induced by atrial pacing.

Myocardial extraction of free fatty acids (FFA), together with glucose, lactate, pyruvate, glycerol and oxygen was determined by simultaneous sampling of blood from an artery (a) and the coronary sinus (cs) at rest and during chest pains induced by atrial pacing in seven fasting male patients with ischaemic heart disease. Results were compared to those, at rest and during pacing at heart rate 140 beats min-1, in ten healthy men of similar age. A continuous i.v. infusion of 14C oleate and 3H palmitate enabled the calculation of simultaneous myocardial uptake and release of FFA as well as of the fraction of extracted FFA which underwent direct oxidation. During chest pain lactate net extraction decreased to become, in some patients, negative. FFA extraction, as estimated from the fractional extraction of labelled fatty acid was likewise decreased, while the a-cs O2 difference was not significantly altered. The fractional oxidation of extracted FFA was increased, whereas the calculated fatty acid release from the heart was unaltered. The increase in fractional oxidation was quantitatively correlated with the decrease in lactate extraction suggesting that it was related to the degree or extent of ischaemia. It was also proportional to the decrease in FFA extraction. Thus, in patients with angina pectoris the ischaemic myocardium may be subjected to a limitation not only with regard to oxygen but also substrate flux into the myocardial cells.

Angina Pectoris↗
PubMed1985

Clearance of triglycerides from the circulation and its relationship to serum lipoproteins: influence of age and sex.

In this study of a randomly selected population from 20 to 70 years of age, the clearance of triglycerides from the blood was studied after i.v. injection of an artificial triglyceride emulsion Intralipid. In women, the triglyceride clearance from the blood decreases with increasing age, but for men there was no change with age. Women had faster fractional removal rates of i.v. injected triglycerides than men in all age-groups. The triglyceride clearance showed a negative correlation to Broca index (obesity), serum triglyceride, serum cholesterol, triglycerides in very low density lipoproteins, and to cholesterol in very low density lipoproteins and in low density lipoproteins, but showed a strong positive correlation to cholesterol in high density lipoproteins.

Adult↗
PubMed1984

Pancreatic polypeptide-producing tumors. Report on two cases.

Histochemical, chemical and clinical features of two malignant endocrine pancreatic tumors were studied. Both tumors contained pancreatic polypeptide (PP)-immunoreactivity in the majority of tumor cells. In addition, one tumor contained a few scattered serotonin-fluorescent cells and the other scattered gastrin-immunoreactive cells. Pancreatic polypeptide hypersecretion was established from both tumors. Serotonin was produced by one tumor and gastrin was secreted by the other. No PP-associated endocrine symptoms were present, whereas the hypergastrinemia may have caused a bleeding duodenal ulcer in one patient. Although both tumors were highly malignant the clinical courses in the two patients were very different; one patient died within a few months whereas the other is alive 2 years after the diagnosis.

Adult↗
PubMed1984

Decreased removal of triglycerides from the blood--a mechanism for the hypertriglyceridemia in male patients with coronary artery disease.

We determined serum apolipoprotein A I and A II concentrations and triglyceride and cholesterol concentrations in serum lipoprotein density classes in 28 male patients with severe ischaemic heart disease (IHD) and with angiographically verified coronary artery disease (CAD) and in age-matched controls. Both triglyceride and cholesterol concentrations in very low density lipoproteins and in low density lipoproteins were higher in IHD-patients than in the controls. The triglyceride but not the cholesterol concentration in serum was higher in IHD-patients than in the controls. The cholesterol in high density lipoproteins and the serum apolipoprotein A I concentration were lower in IHD-patients than in the controls. At least in part the higher triglyceride concentration in very low density lipoproteins could be attributed to a decreased removal of triglycerides from the blood since the fractional removal rate of an i.v. injected artificial triglyceride emulsion (Intralipid) was slower in IHD-patients than in the controls.

Adult↗
PubMed1983

Peroperative studies of S-calcitonin in thyroid and peripheral venous samples from patients with normal C-cells, C-cell hyperplasia, and medullary carcinoma on the thyroid.

The calcitonin (Ct) secretion was studied during surgery in 11 patients with benign thyroid and/or parathyroid disorders and in six patients with familial medullary carcinoma of the thyroid (MCT) and C-cell hyperplasia (CCH). The preoperative diagnosis of MCT and CCH was established by S-Ct determinations before and after pentagastrin provocation. During surgery blood samples were collected from thyroid and peripheral veins before and after injection of 0.6 micrograms pentagastrin . kg-1 in the inferior thyroid artery. In the control group the thyroid venous concentration of S-Ct increased from 395 +/- 42 pmol . l-1 to 2,692 +/- pmol . l-1 after intra-arterial (i.a) pentagastrin. The basal value for S-Ct in thyroid venous samples from patients with MCT and CCH was distinctly elevated in five of six patients. After pentagastrin stimulation a very prompt and striking S-Ct peak in thyroid venous samples was demonstrated (range 11,500-2,700,000 pmol . l-1), which in all cases widely exceeded that in the control group. Varying responses were registered in peripheral vein samples. S-Ct values obtained in the present investigation constitute valuable information for the interpretation of S-Ct values obtained in thyroid venous catheterization studies.

Adult↗
PubMed1983

Automatic analysis of the EMG interference pattern.

A method is described for the automatic analysis of EMG interference patterns obtained at optional non-controlled force levels. It is a modification of Willison's method of measuring turns and amplitude of the signal. In the method, the mean amplitude is plotted against turns obtained during 300 msec for each of 20 recording sites. Different voluntary strengths are used and a scatter of points is obtained. Confidence limits enclosing these points are constructed for healthy subjects for 4 different muscles with concentric and monopolar electrodes. The normal values differ with age, muscle, sex and electrode. The method is tested on patients with myopathic or neurogenic EMG and a high diagnostic yield is obtained. The method is objective, reproducible, fast and needs relatively small computer facilities.

Adolescent↗
PubMed1983

Circulation, respiration and serotonin levels in carcinoid patients during neurolept anaesthesia.

Release of hormones peri-operatively in patients with metastatic carcinoids may lead to severe circulatory and respiratory disturbances. Fourteen patients with liver metastases were studied during 16 operations with a modified neurolept anaesthesia in order to evaluate the central haemodynamic and respiratory functions as well as plasma serotonin levels. The premedication in five patients was supplemented with levopromazine. During the 11 operations performed on patients not pretreated with levopromazine, no major significant fluctuations in circulatory or respiratory functions were recorded although big variations in serotonin plasma levels were measured. In the patients treated with levopromazine, however, significant changes were observed in heart rate, mean pulmonary artery pressure, cardiac index, and left and right ventricular stroke work especially during flushing episodes. However, these changes did not correlate with the changes in plasma serotonin levels. Modified neurolept anaesthesia without levopromazine pretreatment combined with careful monitoring seems to be a safe procedure for carcinoid patients. Using this type of anaesthetic procedure only one major complication occurred in connexion with 16 major operations and then in the postoperative period.

Adult↗
PubMed1983

Failure of exogenous secretin to induce secretion of calcitonin in man.

The effect of secretin on calcitonin secretion from the human thyroid gland was studied in 15 patients undergoing thyroid and parathyroid surgery. Secretin was administered into the inferior thyroid artery at two different doses (0.75 and 7.5 CU) and into a peripheral vein at a dose of 75 CU. Blood samples for measurements of calcitonin and calcium were collected from thyroid or peripheral veins. However, neither intraarterially nor iv administered secretin was able to evoke any significant calcitonin response as measured in thyroid or peripheral venous blood. The calcium level was unaffected by secretin. The results demonstrate that secretin does not act as a calcitonin secretagogue in man.

Adult↗