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Biomedical subjects

A Eriksson

Publications and source records attributed to A Eriksson.

At least 109 records · Page 6Linked to original sources

Role of alcohol in traffic crashes involving women: passenger car fatalities in northern Sweden.

OBJECTIVE: Since increased alcohol consumption and increased driving among women may lead to a growing mortality due to drunken driving among women, the study analyzed gender differences among traffic fatalities. METHOD: Traffic fatalities (597 victims, 159 women) in northern Sweden were investigated, using autopsy and police reports, for a 10-year period, 1980-1989. RESULTS: The incidence of inebriated female driver fatalities was 0.51 per 100 million km (men, 0.66). Eighty-six percent of the female inebriated drivers (98% of men) and 68% of female sober drivers (78% of men) initiated the crash. Blood alcohol was detected in 10% of the women (men, 32%) with a mean blood alcohol concentration of 1.1 g/kg (men, 1.9 g/kg). Of the women, 13% had liver steatosis (men, 28%). The proportion of victims with liver steatosis increased with increasing blood alcohol concentration. Only one case of liver cirrhosis was found (a man). The majority of the inebriated victims were killed from May through October (women, 73%; men, 76%), and from Fridays through Sundays (women, 87%; men, 70%). Only 27% of the inebriated women crashed between 9 PM and 6 AM, compared to 62% of the men. The body location of fatal trauma was similar in men and women and was not influenced by alcohol. CONCLUSIONS: Female traffic fatalities differ from those of men in several respects. No evidence was found for an increase in the number of women in alcohol-related traffic fatalities in Sweden over the 10-year period studied. Drunken driving and alcohol abuse in traffic is still mainly a male problem.

Accidents, Traffic↗

Bifunctional role of the bc1 complex in plants. Mitochondrial bc1 complex catalyses both electron transport and protein processing.

Nuclear encoded mitochondrial precursor proteins are cleaved to mature size products by the general mitochondrial processing peptidase (MPP). In contrast to non-plant sources where MPP is a matrix enzyme, the plant mitochondrial MPP is localised in the inner membrane and constitutes an integral part of the bc1 complex of the respiratory chain. Core proteins of the complex are immunologically related and show high sequence similarity to the MPP subunits from non-plant sources. The bc1 complex in plants is thus bifunctional, being involved both in respiration and in protein processing.

Catalysis↗

Brain 5-HT1A, 5-HT1D, and 5-HT2 receptors in suicide victims.

We report on 5-HT1A, 5-HT1D, and 5-HT2 binding sites in 23 control subjects and 18 suicide victims subdivided according to the method of death and the previous existence of depressive symptoms. No difference in maximum binding (Bmax) or binding affinity (Kd) was found between the control and overall suicide groups for the binding sites studied. The drug overdose subgroup showed, however, a significant decrease in the 5-HT1A binding affinity, probably explained by the higher sensitivity of this binding site to the acute administration of tricyclic antidepressants. A significant decrease in 5-HT1D binding affinity was also found in the depressed suicides, together with a significant decrease in the number of 5-HT1D binding sites in the nondepressed suicides. Further studies should be carried out on the 5-HT1D binding site as it might represent a new tool in the understanding of the depressive illness.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Adenylyl cyclase activity and G-protein subunit levels in postmortem frontal cortex of suicide victims.

Basal and stimulated adenylyl cyclase activities and Gs and Gi protein alpha-subunit levels (Gs alpha and Gi alpha) were compared in postmortem frontal cortex from 18 suicide cases and 22 matched controls. Basal, guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) stimulated and forskolin stimulated enzyme activities were significantly lower in the suicide cases, compared to controls. These effects were most apparent in those suicides that had died from violent means or that had had a history of depression and appeared to reflect the lowered basal activity rather than a reduced ability of either GTP gamma S or forskolin to activate the enzyme. No significant correlations were found between adenylyl cyclase activity and either subject age or postmortem delay. Western blotting revealed no significant differences in Gs alpha and Gi alpha levels between control and suicide cases. However, levels of the smaller Gs alpha isoform (Gs alpha-S) showed a tendency to be increased in the violent death suicide and depressed suicide subgroups, compared to controls. Levels of the larger Gs alpha isoform (Gs alpha-L) showed a significant positive correlation with subject age. Gi alpha levels showed a significant negative correlation with subject age and a positive correlation with postmortem delay. These results support the hypothesis that suicidal behaviour and depressive illness may be associated with an altered regulation of adenylyl cyclase.

Adenylyl Cyclases↗

Interleukin-1-induced activation of a protein kinase co-precipitating with the type I interleukin-1 receptor in T cells.

We have investigated the possibility of a protein kinase participating in the signal transduction mechanisms of the interleukin-1 (IL-1) type I receptor (IL-1RI). Our data show that a protein kinase was co-precipitated with the IL-1RI from the two murine T helper cell lines D10N and EL-4. The kinase activity was detected in an in vitro kinase assay performed with the immuno beads in the presence of exogenous substrates. IL-1 treatment of the cells resulted in a rapid activation of this protein kinase in a concentration-dependent manner. Both forms of IL-1, IL-1 alpha and IL-1 beta, induced this kinase activity, whereas the IL-1 receptor antagonist (IL-1ra) was inactive. In excess IL-1ra competitively antagonized IL-1 stimulation. In the in vitro kinase assay the exogenous substrates myelin basic protein and histone H1 were phosphorylated, whereas casein or heat-shock protein HSP27 were not accepted, reflecting a certain selectivity of this protein kinase. The IL-1RI co-precipitable protein kinase showed a serine/threonine specificity and was inhibited by staurosporine, but not by inhibitors specific for protein tyrosine kinase or protein kinase C. These results show that a serine/threonine protein kinase directly interacts with the IL-1RI at the plasma membrane level of T helper cells forming a novel type of IL-1 inducible signaling complex. This protein kinase may resemble the link coupling the plasma membrane IL-1 receptor to cytosolic downstream elements in the IL-1 signaling pathway.

Animals↗

The genomes of the animal papillomaviruses European elk papillomavirus, deer papillomavirus, and reindeer papillomavirus contain a novel transforming gene (E9) near the early polyadenylation site.

We report that the genomes of reindeer papillomavirus (RPV), European elk papillomavirus (EEPV), and deer papillomavirus (DPV) contain a short conserved translational open reading frame (ORF), E9, which is located between the E5 ORF and the early polyadenylation site. In RPV, DPV, and EEPV, E9 ORFs have the potential to encode extremely hydrophobic polypeptides of approximately 40 amino acids. In mouse C127 cells transformed by EEPV and RPV, there exists a unique, abundant mRNA species of approximately 700 nucleotides which has the capacity to encode an E9 polypeptide. This mRNA is transcribed from a previously unrecognized promoter at position 4030 in the EEPV genome. The EEPV E9 ORF exhibits weak transforming activity in C127 cells and primary rat embryo fibroblasts. We also show that EEPV E5 is the major oncogene in the EEPV genome when assayed in C127 cells, although it is less efficient in transformation than the E5 genes of bovine papillomavirus type 1, DPV, and RPV.

Amino Acid Sequence↗

Would a helmet law for snowmobile riders reduce head injuries?

Swedish authorities have discussed making the use of helmets for snowmobile riders compulsory. To evaluate the possible injury-reducing potential of such a law, 245 non-fatally injured riders and 104 fatalities were analyzed. Non-minor (AIS > 1) head injuries were far less common than in motorcycling, and many fast driving young snowmobile riders seem to use helmets regardless of a law. The persons with head injuries who had not used helmets, or whose helmet use was unknown, had violated other laws, most often the Traffic Temperance Law, or the law forbidding driving on public roads. A helmet law for snowmobile riders will probably not increase the helmet use in this group and consequently have a negligible injury-reducing effect. Helmets are, however, strongly recommended, especially for riders who favour fast driving.

Adolescent↗

Effect of aging in human cortical pre- and postsynaptic serotonin binding sites.

5-HT1A, 5-HT1D, 5-HT2 binding sites and affinity and 5-HT uptake sites were simultaneously determined in frontal cortex samples from 23 control subjects, aged 16-75 years. A significant reduction in the number of 5-HT1D and 5-HT2 binding sites was found with regard to age, together with a significant decrease in the 5-HT2 binding affinity. It is suggested that the total 5-HT1 age-related loss described in previous studies could be ascribed to the 5-HT2 subtype. Furthermore, aging does not seem to be associated with a reduced cortical serotonergic innervation, as indicated by the stability of the [3H]paroxetine-labeled 5-HT uptake sites.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Pool of ligand-bound platelet-derived growth factor beta-receptors remain activated and tyrosine phosphorylated after internalization.

We have examined the state of tyrosine phosphorylation of ligand-bound, internalized platelet-derived growth factor (PDGF) beta-receptors. Analysis by immunofluorescence staining of cells stimulated with PDGF-BB at 37 degrees C indicated colocalization of phosphotyrosine, PDGF beta-receptors, and PDGF-BB in endosome-like vesicles. Treatment of cells with an acidic buffer, which removed cell surface-bound PDGF-BB, led to a considerable decrease in phosphorylation and kinase activity of cell surface localized PDGF beta-receptors, but not of internalized receptors. Immunoprecipitations using antisera against phosphotyrosine and the PDGF beta-receptor from metabolically labeled cells showed that a major fraction of the tyrosine-phosphorylated pool of receptors were still accessible to the acid buffer treatment after 10 min of incubation of the cells at 37 degrees C. Under these conditions, about 20-25% of the total pool of tyrosine-phosphorylated receptors were intracellular, since they remained tyrosine phosphorylated after the acid buffer treatment. A considerable pool of tyrosine-phosphorylated, internalized receptors, after 10 min of incubation of the cells at 37 degrees C, could also be detected by immunoblotting analysis, using antisera against the PDGF beta-receptor and phosphotyrosine. Analysis by in vitro kinase assays of immunoprecipitated PDGF beta-receptors, obtained from PDGF-BB-stimulated cells different times after acid wash, showed that the internalized receptors retained kinase activity. These data suggest that a pool of internalized PDGF beta-receptors remain active and may participate in signalling a considerable time after internalization.

Animals↗

Comparison of triphenyltetrazolium chloride (TTC) staining versus detection of fibronectin in experimental myocardial infarction.

Staining with triphenyltetrazolium chloride (TTC), although controversial, has frequently been used for the delineation of myocardial infarction. This study was performed further to explore the reliability of the TTC method. In 24-h experiments pigs were subjected to closed-chest occlusion of the left anterior descending coronary artery for 30, 60 or 90 min followed by reperfusion with or without superoxide dismutase (SOD) as an adjunct. One TTC-stained slice from each heart was stabilized by microwave irradiation, gelatin-embedded, frozen in hexane chilled with dry ice and cryosectioned. Serial sections were stained with antibodies against fibronectin in order to identify irreversibly injured myocytes and with van Gieson histologically to confirm the necrotic tissue. A close correspondence of the infarct size was found between TTC stained slices and anti-fibronectin stained sections. The infarct size in the van Gieson stained sections also showed good correspondence but the area of infarction tended to be larger. In the experimental group subjected to 30 min ischaemia and with SOD as an adjunct, the estimated infarcted area in the TTC stained slices was significantly smaller than the area estimated from the anti-fibronectin stained sections. In sections viewed in the light microscope an inverse pattern of TTC and anti-fibronectin staining was observed. It was confirmed at the light microscopic level that myocytes containing an abundance of TTC deposits lacked fibronectin whereas myocytes stained with antifibronectin in general lacked TTC staining except for a zone approximately 0.5 mm wide which was located at the intersection between damaged and surviving myocytes where small TTC deposits were present. The width of the stained zone did not differ among the experimental groups. Thus, differences in estimated infarct size by the three methods used reflect problems in correctly delineating the border between living and dead myocardium rather than an interference by SOD on TTC staining.

Animals↗

Single-vehicle crashes and alcohol: a retrospective study of passenger car fatalities in northern Sweden.

This retrospective study of fatal passenger car crash victims in northern Sweden compares 396 multiple-vehicle (MV) and 201 single-vehicle (SV) fatalities from 1980 through 1989. Compared to MV fatalities, SV victims were more frequently males, were younger, were more often inebriated, had higher blood alcohol concentrations, had a higher frequency of fatty liver, and were less often restrained. The SV fatalities occurred most often from May through October, from Fridays through Sundays, and from 9 p.m. to 6 a.m. The road surface was usually dry, especially for drunken SV drivers. The SV drivers also more often lacked a valid driver's license. The study confirms that alcohol is one of the most important factors associated with traffic fatalities, particularly in SV crashes. More than half (56%) of the SV victims were inebriated by alcohol (MV, 11%), had a mean blood alcohol concentration of 1.9 g/l (MV, 1.6 g/l), and one-third had a fatty liver (MV, 20%). We also found a relation between fatty liver and increased blood alcohol concentrations, suggesting that studies regarding the role of alcohol in traffic fatalities should also include an evaluation of liver morphology.

Accidents, Traffic↗

Elderly in the traffic environment: analysis of fatal crashes in northern Sweden.

Fatal crashes of the elderly (> or = 60 years; N = 379) in northern Sweden in the traffic environment, between 1977 and 1986, were investigated using autopsy and police reports. Males had double the death rate of females. The car occupants made up the largest category (43%) followed by pedestrians, pedalcyclists, and two-wheel-motorvehicle (TWMV) riders, but the risk of fatal injury per unit distance travelled was highest for pedestrians and pedalcyclists. Most car occupants were killed in vehicle-vehicle crashes, mostly in the daylight and at intersections or straight roads. Ice and/or snow (31%) was the major precrash factor. In two-thirds of single car crashes, roadside hazards such as trees were involved. Most elderly fatally injured car drivers were responsible for the crash, and they were commonly involved in collisions with oncoming vehicles. Only 4% of the fatally injured car drivers were driving under the influence of alcohol. Head injuries appeared to be more common in side impact than in frontal impacts. Serious chest injuries were more common than head injuries in car crashes. One-quarter of the pedestrians were injured at pedestrian crossings and about half during darkness. One in six pedestrians were under the influence of alcohol. All pedalcyclists were injured in collisions with motor vehicles and most were injured at intersections. Pedestrians, pedalcyclists, and TWMV riders had more serious head injuries than chest injuries.

Abbreviated Injury Scale↗

Pedal cycling fatalities in northern Sweden.

The aim of the study was to elucidate the crash and injury mechanisms in bicycle fatalities in the northern half of Sweden. All available autopsy protocols, hospital records and police reports were scrutinized. In 11 years, 146 bicyclists were fatally injured. The majority of the victims were males (66%) and the median age was 60 years. Most of the crashes (81%) occurred from May through October, during weekdays (84%), and during daylight (86%). Almost all victims (88%) died in a motor vehicle collision, in 21% with a truck. None was wearing a helmet. Poor hearing and cerebral arterosclerosis were probable risk factors among the elderly. Of the victims tested, 10% were under the influence of alcohol, half of whom were involved in single-bicycle crashes. In an additional five cases, the motor vehicle driver was impaired by alcohol. All injuries were due to blunt trauma and 69% of the victims died from head injuries. In 91% of all cases, there was an Abbreviated Injury Scale (AIS) score of the head region of > or = 3. The results indicate that separation of bicyclists from motor vehicle traffic by separate cycling tracks and protection of the head by a helmet would be beneficial.

Accidents, Traffic↗

Unique binding characteristics of antipsychotic agents interacting with human dopamine D2A, D2B, and D3 receptors.

In the present study we have compared the pharmacological properties of human dopamine (DA) D2A, D2B, and D3 receptors expressed in mammalian cell lines, using [3H]raclopride as a radioligand. Most of the compounds tested had about equal affinity for D2A and D3 receptors, with the exception of remoxipride, which displayed a 10-fold D2 selectivity, and the aminotetralin (+)-UH 232, which displayed a 5-fold D3 selectivity. Several antipsychotic agents, including clozapine and substituted benzamides, bound with 2-3-fold higher to the D2B (short) than to the D2A (long) isoform, whereas others failed to differentiate between the two isoforms. The atypical antipsychotic agent clozapine bound in a biphasic manner and with unexpectedly high affinity (35 nM) to the D2B receptor, suggesting that clozapine may not be as D4 selective as reported previously. In addition, remoxipride, a new antipsychotic agent with low potential to produce extrapyramidal side effects, displayed 2-3-fold higher affinity for the D2B receptor than for the D2A receptor. Furthermore, sodium differently regulated clozapine and benzamide binding to the various DA receptor subtypes. Thus, sodium decreased the affinity of clozapine for D2A and D2B receptors about 3-fold, whereas the affinity for D3 receptors was unaltered. In contrast, the affinity of raclopride for the three DA receptor subtypes was increased by sodium. Whether the unique characteristics of the binding of clozapine and benzamides to cloned DA receptors demonstrated in the present study are related to the favorable clinical properties of these compounds remains to be elucidated.

Animals↗

Accidental deaths from asphyxia. A 10-year retrospective study from Sweden.

Accidental mechanical asphyxia is an unusual cause of death. In reviewing 73 cases occurring during a 10-year-period in Sweden, young boys and elderly women seemed to be most prone to this type of fatality. A striking number of victims had deliberately put a noose-like structure around the neck, and yet another group became entangled in some part of their clothing. Thoracic immobilization was seen in a number of cases, also involving work-related accidents. Hospitalized patients, asphyxiophilics and inebriated victims represent other risk groups. A case involving the use of a helmet is reported in view of the growing frequency with which Swedish children use bicycle helmets. The material contains only a few cases where the victim was not alone at the time of the accident, and it seems plausible that supervision could have prevented many of the reported fatalities. Public knowledge of accident mechanisms may increase the awareness of hazardous situations and activities. Spreading of the medical examiner's knowledge may thus form a basis for accident prevention.

Accidents↗

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↗