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Biomedical subjects

A Eriksson

Publications and source records attributed to A Eriksson.

At least 19 recordsLinked to original sources

PDGF alpha- and beta-receptors activate unique and common signal transduction pathways.

We have examined the signal transduction pathways of the PDGF alpha- and beta-receptors, in order to characterize the specificity of each receptor type in the signaling. Porcine aortic endothelial cell lines expressing equal levels of either PDGF alpha- or beta-receptors were established. The alpha- and beta-receptor cells responded mitogenically to stimulation with the proper PDGF isoforms. Three aspects of actin reorganization were examined after ligand stimulation: loss of stress fibres, appearance of edge ruffles and formation of circular membrane ruffles. The beta-receptor cells showed a response to ligand stimulation which included all three features. The alpha-receptor cells exhibited edge ruffles and loss of stress fibres, but circular ruffles could not be found in several independent alpha-receptor cell lines. The beta-receptor cells, but not the alpha-receptor cells, were able to migrate chemotactically towards a concentration gradient of ligand. The molecular basis for the differences in signalling were explored by comparing the pattern of increased phosphorylation of potential substrates for the alpha- and beta-receptors in [32P]orthophosphate labelled intact cells and using an in vitro kinase assay. Certain of the observed substrates were common for the two receptors, whereas others were specific for either one. We conclude that certain of the known PDGF induced cellular effects are transduced only by the beta-receptor; the presence of alpha-receptor-specific substrates suggests that there are also alpha-receptor-specific signals, which have yet to be identified.

Actins

Identification of two C-terminal autophosphorylation sites in the PDGF beta-receptor: involvement in the interaction with phospholipase C-gamma.

Two novel sites of autophosphorylation were localized to the C-terminal tail of the PDGF beta-receptor. To evaluate the importance of these phosphorylation sites, receptor mutants in which Tyr1009, Tyr1021 or both were replaced with phenylalanine residues, were expressed in porcine aortic endothelial (PAE) cells. These mutants were similar to the wild type receptor with regard to protein tyrosine kinase activity and ability to induce mitogenicity in response to PDGF-BB. However, both the Y1009F and Y1021F mutants showed a decreased ability to mediate association with and the tyrosine phosphorylation of phospholipase C-gamma (PLC-gamma) compared to the wild type PDGF beta-receptor; in the case of the Y1009F/Y1021F double mutant, no association or phosphorylation of PLC-gamma could be detected. These data show that tyrosine phosphorylation of PLC-gamma is dependent on autophosphorylation of the PDGF beta-receptor at Tyr1009 and Tyr1021.

Amino Acid Sequence

Enzyme and immunohistochemical assessment of myocardial damage after ischaemia and reperfusion in a closed-chest pig model.

The usefulness of different enzyme and immunohistochemical stains to distinguish reversible and irreversible myocardial cell injury after experimental coronary artery occlusion of varying duration and reperfusion with or without superoxide dismutase as adjunct was investigated. Biopsies or parts of the infarcted and non-infarcted area were rapidly frozen and sectioned in series for enzyme and immunohistochemical evaluation. Sections were stained for the demonstration of phosphorylase, myofibrillar ATPase and mitochondrial oxidative enzymes and also with periodic acid-Schiff, alizarin red S and routine histological stains. Other sections in series were stained with antibodies against fibronectin and the intermediate filament proteins desmin and vimentin. In 49 biopsies a blind quantitative estimation of the area stained for fibronectin, phosphorylase and alizarin red S was performed and evaluated statistically. Phosphorylase, periodic acid-Schiff, fibronectin and alizarin red S allowed delineation of affected myocardium after 30 min of ischaemia followed by reperfusion whereas with the other stains, affected myocardium was readily detectable only after 60 or 90 min of ischaemia followed by reperfusion as well as after 24 h of ischaemia without reperfusion. The immunostaining for fibronectin was very distinct and inversely related to the phosphorylase activity. We show that fibronectin is an excellent marker for damaged cells and that these positively stained myocytes are necrotic as confirmed ultrastructurally. Using alizarin red S as a marker of calcium accumulation in myocytes, a marked discrepancy was observed between the area of fibronectin-containing myocytes and that of myocytes stained by alizarin red S. Calcium accumulation in mitochondria is thus not a prerequisite for myocyte necrosis but does occur only in some of the irreversibly damaged cells. Of special interest is the finding that there was a significant reduction of intracellular calcium in pigs where superoxide dismutase had been used as an adjunct at reperfusion, thus supporting the theory that free radicals do play a role during reperfusion of ischaemic myocardium.

Adenosine Triphosphatases

Some biases in the alcohol investigative process in traffic fatalities.

This study compares data regarding alcohol involvement from police records and from chemical analyses of body fluids taken prior to or after death of 121 traffic fatalities in Washtenaw County, Michigan. Differences regarding the choice of who will or will not be screened for alcohol were found. The police and emergency room personnel were more likely to focus on males and drivers, while medical examiners were less biased. The police documented whether or not drinking took place in only 36% of the cases and suspected drinking in only half of these cases. Males and at-fault drivers were most likely to be investigated. Blood alcohol level was measured before death in 11 of 29 emergency room treated victims, with 10 (91%) positive samples. All but two of those tested before death were drivers, and all but one were males. After death, blood alcohol was measured in 47% of the 121 cases, with a higher proportion of males and motor-vehicle occupants tested, compared to females and pedestrians. Alcohol was detected in 63% of the samples. A lower mean blood alcohol concentration was found in victims who received intravenous treatment, and a higher proportion of positive samples was found in victims who died immediately in the crash. Thus, the frequency of alcohol-related traffic fatalities varied between the different data sources. The police records revealed 51%, the emergency records 91%, and the medical examiner records 63% with alcohol involvement. This wide discrepancy has the potential of leading to erroneous results here and possibly in studies done elsewhere.(ABSTRACT TRUNCATED AT 250 WORDS)

Accidents, Traffic

Head and face injuries in bicyclists--with special reference to possible effects of helmet use.

Fatal and nonfatal head and face injuries to unhelmeted bicyclists were analyzed to assess the injury-reducing potential of bicycle helmet use. Of the fatally injured, 64% (median age, 55 years) had fatal head and face injuries compared with 38% (median age, 18 years) with head and face injuries in the nonfatal injury group. The fatally injured often had multiple impact points, mostly to the occipital and temporal regions. Brain contusions, most often to the frontal and temporal lobes, were the most common cause of fatal injury, followed by subdural hematomas. In the nonfatal injury group abrasions/lacerations were most common type of injury, followed by cerebral concussions/contusions and superficial contusions. If all types of injuries to bicyclists are taken into account a helmet might have had an injury-reducing effect in two of every five fatal cases and in one of every five nonfatal cases. To increase the helmet use among bicyclists, a law, as in Australia, would be an excellent instrument.

Adolescent

Gamma-aminobutyric acid-B (GABAB) binding sites in postmortem suicide brains.

Gamma-aminobutyric acid-B (GABAB) binding sites labelled with [3H]GABA were determined in postmortem frontal cortex samples of 20 control subjects and 16 suicides. The suicide group was further subdivided according to the method of suicide and the existence of depressive symptoms prior to death. No significant differences in GABAB binding were found either between overall suicide and control groups or between the control group and the other subgroups (violent suicide, nonviolent suicide, nondepressed and depressed suicide victims). A significant increase in GABAB binding was observed in those individuals dying from carbon monoxide poisoning. It is concluded that although GABAB binding sites are not altered in our suicide group, a presynaptic dysfunction might account for the increased GABAB binding found in the carbon monoxide subgroup.

Adult

Ligand-induced homo- and hetero-dimerization of platelet-derived growth factor alpha- and beta-receptors in intact cells.

Porcine aortic endothelial cells expressing platelet-derived growth factor (PDGF) alpha- or beta-receptors after transfection of the corresponding cDNAs, were used to investigate whether PDGF receptor dimerization occurs in intact cells after ligand binding. Using three different methods--covalent cross-linking of 125I-labeled ligand, cross-linking of metabolically labeled cells after ligand-binding followed by immunoprecipitation, and immunoblotting of cells after ligand binding and cross-linking--it was demonstrated that alpha- as well as beta-receptors form ligand-induced dimeric complexes. Dimerization correlated with induction of receptor kinase activity, measured as receptor autophosphorylation. Heterodimeric complexes could furthermore be induced by PDGF-AB, when added to a mixture of lysates from the alpha- and beta-receptor expressing cell lines, or when added to human fibroblasts which express both receptor types.

Animals

[The reality behind the bruises--clinical picture and documentation in abuse of women].

Most battered women consult for their injuries at the community health centre or the emergency room--often without disclosing the fact that they are the victims of battery. Beyond venturing to inquire, lending a sympathetic ear and being supportive, with a view to any future criminal proceedings it is particularly important that the attending physician meticulously documents all injuries manifested by a battered woman--even if at that juncture she does not intend to bring charges. If necessary the forensic pathologist can assist the clinician in drawing up a report of the injuries and in assessing their origin.

Adolescent

Induction of platelet-derived growth factor alpha- and beta-receptor mRNA and protein by platelet-derived growth factor BB.

We describe that stimulation of human fibroblasts with platelet-derived growth factor BB (PDGF-BB) induces a transient up-regulation of the PDGF alpha- and beta-receptor transcript and protein levels. The effect of PDGF-BB on the receptor transcript levels was more pronounced than those seen when other cytokines were used. Regulation of transcript levels by PDGF-BB was mediated through post-transcriptional mechanisms. No induction could be observed in a nuclear run-on analysis, but cycloheximide treatment attenuated the accumulation of both alpha- and beta-receptor transcripts induced by PDGF-BB. An increase in receptor protein levels was observed using two different experimental approaches. Increased amounts of receptor precursor forms could be immunoprecipitated from metabolically labeled cells, stimulated with PDGF-BB. In a second approach, cells were exposed to different concentrations of PDGF-BB, and, in a subsequent step, ligand binding analysis was performed. In this experiment, an initial down-regulation of receptors was followed by increased levels of the cell surface forms of the receptors. In conclusion, PDGF-BB, but not PDGF-AA, induces increased synthesis of both PDGF alpha- and beta-receptor protein; this constitutes a positive feed-back mechanism, which, for example, could serve to potentiate autocrine stimulation of growth.

Amino Acid Sequence

Differential expression of platelet-derived growth factor receptors in human malignant glioma cell lines.

Glioma cells in culture express platelet-derived growth factor (PDGF) A- and B-chains and secrete PDGF-like activity that is mainly PDGF-AA. In this work, we show that the PDGF alpha- and beta-receptors are independently expressed in human malignant glioma cells. We also define three different receptor phenotypes that are related to the morphology of glioma cells: cells with only alpha-receptors, only beta-receptors, or with both types of receptors. By the help of Northern blot analyses, 125I-PDGF-binding experiments, and immunoprecipitations the receptors are shown to be structurally normal PDGF receptors, except for minor variations in size that probably are due to differences in glycosylation. PDGF-BB induces DNA synthesis in cells of all three receptor phenotypes, whereas PDGF-AA or PDGF-AB has this effect only on cells with alpha- or with alpha- and beta-receptors. 125I-PDGF-AB binds with high affinity and down-regulates beta-receptors only in cells where alpha-receptors are present in addition to beta-receptors. Thus, the different functional capacities of PDGF isoforms on glioma cells fit with their known receptor-binding specificities and are compatible with the hypothesis that the isoforms act by inducing dimeric receptor complexes. When data on PDGF A- and B-chains, as well as alpha- and beta-receptor expression are compiled and the pattern of receptor binding specificity is taken into account, the majority of glioma cell lines are found to have a phenotype that makes autocrine stimulation possible.

DNA

Fiber type composition of the human female trapezius muscle: enzyme-histochemical characteristics.

Tne anatomy of the human trapezius muscle is complex, with an extensive origin and fibers running in different directions. The muscle is commonly divided into three different muscle portions according to the fiber direction: the descending, transverse, and ascending portions. In a previous study in males, the structure of the muscle differed between different portions with respect to the enzyme-histochemical fiber-type profile. The lower regions of the descending portion and the transverse and the ascending portions had a predominance of type I fibers. The type II fibers were more frequent in the upper regions of the descending portion, and the cross-sectional fiber area in this region of the muscle was smaller. In this study, we have investigated the trapezius muscle in females and compared the results with those from males. The different portions of the female muscle had a relatively even fiber-type composition. However, there tended to be fewer type I fibers and more type IIB fibers in the descending portion of the muscle, and the fibers of the lower regions of the descending portion were somewhat larger. The fiber-type distribution pattern was similar to that of the male trapezius muscle, but the mean cross-sectional area of the fibers in the female muscle was considerably smaller. Thus, our conclusion is that the trapezius muscle of females has a similar activity pattern as that of males. The significantly smaller cross-sectional fiber area, however, may indicate a lower functional capacity which may be of importance in the development of neck and shoulder dysfunction in females.

Adolescent

Autopsy-verified pulmonary embolism in a surgical department: analysis of the period from 1951 to 1988.

A retrospective analysis was undertaken of all surgical patients in Malmö, Sweden, during the period from 1951 to 1988 in whom pulmonary emboli were found at autopsy. The analysis included a comparison with the earlier analysed and reported time period from 1951 to 1980. A continued high frequency of pulmonary embolism at autopsy was seen during the 1980s (20.3 per cent of deaths, 31.7 per cent of autopsies). Of the 391 autopsy-verified pulmonary emboli found between 1981 and 1988, 113 (28.9 per cent) were considered fatal, 104 (26.6 per cent) contributed to death and 174 (44.5 per cent) were incidental. Few patients had symptomatic deep vein thrombosis or pulmonary embolism before death. The overall frequency of major pulmonary embolism in surgical patients remained unchanged (0.3 per cent). The frequency of major postoperative pulmonary embolism showed an increase during the 1950s and 1960s (maximum 0.4 per cent) but a decrease in the last 5-year period of the 1970s (0.3 per cent), which has earlier been reported upon. This decrease continued during the 1980s (0.2 per cent) (P less than 0.05). An increase was found in the number of patients operated on who had autopsy-proven pulmonary embolism and who received thromboprophylaxis. Pulmonary embolism continues to be a major cause of death in surgical patients; however, postoperative major pulmonary embolism has shown a reduction in the last 15-year period.

Adult

Evidence of fibre hyperplasia in human skeletal muscles from healthy young men? A left-right comparison of the fibre number in whole anterior tibialis muscles.

Cross-sections (thickness 10 microns) of whole autopsied left and right anterior tibialis muscles of seven young previously healthy right-handed men (mean age 23 years, range 18-32 years) were prepared for light-microscope enzyme histochemistry. Muscle cross-sectional area and total number of fibres, mean fibre size (indirectly determined) and proportion of the different fibre types (type 1 and type 2 on basis of myofibrillar adenosine triphosphatase characteristics), in each muscle cross-section were determined. The analysis showed that the cross-sectional area of the left muscle was significantly larger (P less than 0.05), and the total number of fibres was significantly higher (P less than 0.05), than for the corresponding right muscle. There was no significant difference for the mean fibre size or the proportion of the two fibre types. The results imply that long-term asymmetrical low-level daily demands on muscles of the left and the right lower leg in right-handed individuals provide enough stimuli to induce an enlargement of the muscles on the left side, and that this enlargement is due to an increase in the number of muscle fibres (fibre hyperplasia). Calculations based on the data also explain why the underlying process of hyperplasia is difficult, or even impossible, to detect in standard muscle biopsies.

Adaptation, Physiological

Human fatalities caused by wasp and bee stings in Sweden.

Bee and wasp stings represent an uncommon cause of death. In a retrospective study of all fatalities due to venomous animals in Sweden during a 10-year-period, we found 19 fatalities due to wasps, 1 due to bees but none due to snake bite. This gives an annual incidence of 0.2 per million inhabitants. Most of the deceased were older than 50 years and had an underlying cardiovascular disease while previous severe reactions after insect stings were uncommon. The number of stings was not a factor of importance. Symptoms and death occurred within minutes after the sting. The autopsy findings were in most cases non-specific. Although uncommon, the possibility of a fatal insect sting should be considered in unwitnessed deaths occurring outdoors in summertime.

Adult

Monoaminergic dysfunction in Sjögren-Larsson syndrome.

The anteroposterior distribution of monoamine and monoamine metabolite concentrations was determined in subcortical brain nuclei of two cases of Sjögren-Larsson syndrome (SLS) and was compared to two control cases. The brains were divided into halves and sectioned coronally. For biochemical analyses, caudate nucleus, putamen, globus pallidus, substantia nigra, nucleus accumbens, amygdala, and hippocampus were dissected macroscopically. Monoamine and its metabolites were determined by reverse-phase liquid chromatography with electrochemical detection. The other hemisphere was studied neuropathologically. The SLS cases revealed cell loss in substantia nigra and putamen and a widespread white-matter destruction. Biochemically, most pronounced alterations were seen in the dopamine system in putamen with severely reduced concentrations of dopamine (DA; 14% of control values) and the catabolic metabolites 3-methoxytyramine (3-MT; 9% of control values) and homovanillic acid (HVA; 20% of control values). In substantia nigra and the other striatal regions studied, a general decrease of 3-MT and HVA concentrations was observed in the SLS subjects compared to the controls, although the decrease was less pronounced than in putamen. Generally, somewhat reduced noradrenaline and 3-methoxy-4-hydroxyphenylglycol (MHPG) concentrations were seen in the SLS cases, whereas serotonin and 5-hydroxyindoleacetic acid (5-HIAA) concentrations were increased compared to the controls in most regions studied. These data suggest a specific monoaminergic dysfunction in patients with SLS. The severe decline in the dopaminergic system in putamen suggests that supplementation of dopamine agonists may ameliorate the symptoms of SLS patients.

Biogenic Monoamines

Injuries caused by animals.

Injuries caused by animals and treated at the University Hospital of Umeå were analysed. Dogs caused nearly one-half of the injuries, while horses caused one-third of the injuries and the highest number of fractures. The 'cost' of treatment and sickness benefit was fairly evenly distributed between horse-, cattle-, and dog-related injuries. The average 'cost' per injured person was, however, highest in those injured in cattle accidents and moose-car collisions. The impact of animal-related injuries on the health care and social security systems was similar to occupational accidents and car accidents in several respects.

Acute Disease