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Biomedical subjects

O B Tysnes

Publications and source records attributed to O B Tysnes.

At least 37 records · Page 2Linked to original sources

Anti-cardiac ryanodine receptor antibodies in thymoma-associated myasthenia gravis.

Sera from myasthenia gravis (MG) patients with thymoma were examined in Western blot for the presence of antibodies to proteins in the sarcoplasmic reticulum (SR) of cardiac muscle. Fourteen of 30 MG thymoma sera had IgG antibodies to a protein with the same electrophoretic mobility as cardiac muscle ryanodine receptor (RyR). Anti-cardiac RyR antibodies were not detected in any of the 45 sera from MG patients without thymoma. The same 14 MG thymoma sera, but none of the others, bound to RyR from skeletal muscle as well. Neutralization experiments showed that the anti-RyR antibodies in MG patient cross-reacted with cardiac and skeletal muscle RyR. Since skeletal and cardiac muscle RyRs are antigenically different, our findings may indicate that autoantibodies to RyR in MG originate by sensitization to a peptide shared by cardiac and skeletal muscle RyR, rather than to the complete native RyR.

Autoantibodies↗

[The significance of radiologically diagnosed brain concussion for the outcome after head injury].

The early and late outcome was evaluated in head injury patients who presented brain contusion(s) on the cranial CT scan and in patients hospitalized for concussion. There was a high degree of concurrence between mortality and CT findings. Late complaints were common among cases of concussion of the brain. However, the frequency of impaired memory and concentration, speech problems, paresis and epileptic seizures was increased in cases where the CT scan showed brain contusion. Adaptive and social functioning was most impaired in cases with multifocal contusions in both hemispheres.

Adolescent↗

IgG subclass distribution of ryanodine receptor autoantibodies in patients with myasthenia gravis and thymoma.

Patients with myasthenia gravis (MG) and thymoma often have autoantibodies to the ryanodine receptor (RyR), a ligand-gated Ca(2+)-release channel in the sarcoplasmic reticulum of striated muscle. Using an ELISA, we studied the Ig isotype and IgG subclass distribution of RyR autoantibodies in sera from 30 MG patients with thymoma. RyR IgG antibodies were detected in 16/30 sera. 14/30 sera had IgG1 RyR antibodies, and 15/30 sera had IgG3 RyR antibodies. All sera with IgG1 RyR antibodies also contained IgG3 antibodies. A small number of sera had low amounts of IgG2, IgG4, IgA or IgM RyR antibodies. The RyR autoantibodies are therefore mainly expressed in the IgG1 and IgG3 subclasses. The RyR autoantibodies may be of pathogenic significance by interfering with the mechanism of excitation-contraction coupling in striated muscle.

Autoantibodies↗

[Peripheral facial paresis as a symptom of Borrelia burgdorferi infection].

Infection with the tick-borne Borrelia burgdorferi can lead to a variety of neurologic symptoms, the most frequent being a radicular pain syndrome due to meningitis. General symptoms such as asthenia or headache are also frequent, however, and serious neurologic complications such as dementia or spastic paresis may occur. At an early stage, Borrelia infections can be easily treated with antibiotics, which makes it important to recognize the symptoms and make the correct diagnosis. A common feature of borreliosis is facial palsy, and in the article is described the case of a 14 year-old boy with borreliosis and bilateral facial palsy. The frequency of facial palsy from borreliosis is probably high. The authors discuss the indications for performing lumber puncture in patients with apparent idiopathic facial palsy (Bell's palsy).

Adolescent↗

Ryanodine receptor autoantibodies in myasthenia gravis patients with a thymoma.

Sera from patients with myasthenia gravis were examined by Western blot for the presence of antibodies to proteins of the sarcoplasmic reticulum from rabbit skeletal muscle. Fourteen of 30 patients with myasthenia gravis and a thymoma had IgG autoantibodies to the calcium release channel of the sarcoplasmic reticulum (the ryanodine receptor), which plays a crucial role in the mechanism of excitation-contraction coupling in striated muscle. Ryanodine receptor autoantibodies were not detected in any of the 45 sera from patients with myasthenia gravis without a thymoma. Ryanodine receptor autoantibodies may have pathogenetic relevance in thymoma-associated myasthenia gravis.

Autoantibodies↗

Myasthenia gravis patients with a thymoma have antibodies against a high molecular weight protein in sarcoplasmic reticulum.

Our purpose was to investigate whether components of the sarcoplasmic reticulum (SR) are relevant antigens in myasthenia gravis (MG). Using enzyme-linked immunosorbent assay (ELISA), 75 MG sera and 120 control sera were examined for IgG antibodies against SR prepared from rabbit skeletal muscle. 16/30 thymoma MG patients had IgG antibodies that reacted with SR. 1/30 MG patients with thymic hyperplasia and 3/15 MG patients with thymic atrophy had SR antibodies in low concentrations. Control sera were negative. Using immunoblot, SR antibodies were detected in the thymoma group only. 14/30 sera from thymoma patients reacted with a protein of 320 kDa relative molecular weight. The only reported SR protein with similar electrophoretic mobility is the subunit of the spanning protein which links junctional SR to sarcolemma and functions as a calcium-release channel.

Adult↗

Early and late outcome in head injury patients with radiological evidence of brain damage.

This study examined the early and late outcome in head injury patients with focal or multifocal (unilateral or bilateral) brain contusions revealed by computerized tomography (CT) scanning. The outcome was also evaluated in patients hospitalized due to brain concussion. Three months after the injury (the early outcome) 43% of the 86 cases with multifocal contusions on the CT scan were dead. As evaluated by the Glasgow Outcome Scale, all the 57 patients with a focal brain contusion, as well as the 117 cases with brain concussion, made a good recovery or were moderately disabled. The late outcome (1 to 5 years after injury) was evaluated in 78 cases with brain contusion and in 85 cases with brain concussion, and revealed that complaints and impaired adaptive functioning were frequent in both the contusion and concussion group. The occurrence of headache, dizziness and sleep problems did not significantly differ among the various head injury groups. However, focal or multifocal brain contusions on the CT scan increased the frequency of impaired memory, impaired concentration, speech problems, weakness in arms or legs and seizures with loss of consciousness. Cognitive deficits and speech problems were particularly common in patients with a focal contusion in the temporal lobe. The late adaptive and social functioning were most markedly impaired in cases with multifocal bilateral contusions.

Adolescent↗

Activation of blood platelets in workers exposed to organic solvents.

Organic solvents probably exert their clinical effects through distortion of cellular membrane structure and function. Blood platelets represent an easily available membrane system. This study describes an evaluation of mean platelet volume (MPV) and total platelet count (TPC) in a group of workers exposed to a mixture of organic solvents in paint factories. We have found a correlation between decreased MPV and present exposure. The reduction was reversed within an exposure-free interval of 3 weeks. The intracellular adenosine triphosphate/adenosine diphosphate (ATP/ADP) ratio was significantly increased in exposed workers, compatible with dense granule secretion. A quantitative study of the phosphoinositide cycle in the platelets revealed an increased concentration of the phosphatidic acid, indicating an increased turnover. These findings are consistent with a solvent-induced activation of circulating platelets.

Adenosine Diphosphate↗

[Amyotrophic lateral sclerosis. Occurrence and prognosis].

The epidemiology of amyotrophic lateral sclerosis in Hordaland county, western Norway, was studied during the period 1979 through 1988. Average annual incidence was 1.60 per 100,000 habitants and the male/female ratio was 1:26. The maximal age-adjusted annual incidence was 8.12 and occurred in the age-group 61-65 years. The mean age at start of symptoms was 60.9 years. The prevalence of amyotrophic lateral sclerosis in Hordaland as per 1 January 1989 was 3.67 per 100,000. The mean survival from onset of disease was 28 months, distributed as 24 months in patients with bulbar onset of symptoms and 40 months in patients with spinal onset symptoms.

Aged↗

Neomycin does not interfere with the inositol phospholipid metabolism, but blocks binding of alpha-thrombin to intact human platelets.

Neomycin was demonstrated to inhibit the binding of thrombin to intact human platelets. The effects of neomycin on both thrombin binding and thrombin-induced changes in inositol phospholipid metabolism could be reproduced by the thrombin antagonist hirudin. We propose that neomycin inhibits thrombin-induced platelet activation by interference with the cellular receptor.

Blood Platelets↗

Stimulation of human platelets with low concentrations of thrombin: evidence for equimolar accumulation of inositol trisphosphates and phosphatidic acid.

1. Gel-filtered human platelets prelabeled with [32P]Pi or [3H]glycerol were exposed to 0-0.3 U/ml of thrombin and analyzed for radioactivities and masses in the phosphoinositides, inositol trisphosphates (IP3), phosphatidic acid (PA) and diacylglycerol (DAG) at 15 and 180 sec of stimulation. 2. At thrombin concentrations below 0.1 U/ml, PA and IP3 accumulated in equimolar amounts. 3. The production and disappearance of the metabolites of the polyphosphoinositide cycle was balanced during 180 sec of stimulation with 0.03-0.1 U/ml of thrombin. 4. Under these conditions no increase in [3H]DAG or [3H]monoacylglycerol could be detected. 5. The data indicate that all DAG is converted to PA and support our conclusion that phosphatidylinositol 4,5-bisphosphate represents the major source for production of DAG upon stimulation of human platelets with low concentrations of thrombin.

Blood Platelets↗

Epidemiology of amyotrophic lateral sclerosis in Hordaland county, western Norway.

The incidence, prevalence and prognosis of amyotrophic lateral sclerosis (ALS) in the county of Hordaland, western Norway were determined for the years 1978 through 1988. The average annual incidence rate was 1.60 per 100,000 population with a male to female ratio of 1.26 (95% confidence interval: 0.76-2.09). The maximal age-specific annual incidence was 8.12 per 100,000 and occurred in the age-group between 61 and 65 years. The prevalence of ALS was 3.67 per 100,000 on December 31, 1988. The average age at the onset of the disease was 60.9 years ranging from 34 to 82 years of age. Survival was studied with life table techniques. Median survival from the onset of symptoms was 28.0 months overall. In patients with bulbar onset the median survival was 24.0 months whereas it was 40 months in patients with spinal onset of disease (log rank test, P = 0.0004). The difference in survival between ALS with bulbar or spinal onset was not explained by age or sex differences in the two groups.

Aged↗

Evidence that chlorpromazine and prostaglandin E1 but not neomycin interfere with the inositol phospholipid metabolism in intact human platelets.

Human platelets that had been prelabelled with [32P]Pi were stimulated with trombin in the presence or absence of neomycin, prostaglandin E1 (PGE1) or chlorpromazine. The content of [32P]Pi in phosphatidylinositol 4-phosphate, phosphatidylinositol 4,5-bisphosphate and phosphatidic acid (PA) were determined. The data demonstrate that PGE1 and chlorpromazine but not neomycin interfere with the tight metabolic relationship that exists between the inositol phospholipids and PA in thrombin-stimulated platelets [(1989) Biochem. J. 263, 621-624]. Our results therefore indicate that neomycin does not inhibit signal transduction in intact platelets at the level of the inositol phospholipid metabolism.

Alprostadil↗

Evidence for tight metabolic control of the receptor-activated polyphosphoinositide cycle in human platelets.

The [32P]PIP2/[32P]PA and the [32P]PIP/[32P]PA relationships were demonstrated to be remarkably similar after stimulation of [32P]Pi-prelabelled platelets for 90 s with various combinations and concentrations of agonists and inhibitors. Thus the activity of the PI and PIP kinases with the corresponding phosphomonoesterases may be tightly controlled during receptor-mediated platelet stimulation involving phospholipase C activation.

Adenosine Diphosphate↗

Potentiation by adrenaline of thrombin-induced elevation of pHi is not essential for synergistic activation of human platelets.

Gel-filtrated human platelets were stimulated with thrombin in the absence and presence of adrenaline. Adrenaline markedly enhanced the thrombin-induced increase in cytoplasmic pH (pHi) in BCECF-loaded platelets. This rise in pHi was strongly inhibited by the Na+/H+ exchange blocker EIPA. The potentiation by adrenaline of thrombin-induced PLC activation measured as [32P]PA formation and final platelet responses was, however, not blocked by EIPA, even at low concentrations of thrombin. These results indicate that the enhancement by adrenaline of thrombin-induced cytoplasmic alkalinization may be a secondary effect which is not essential for the potentiation by adrenaline of platelet activation by thrombin.

Amiloride↗

Neomycin inhibits platelet functions and inositol phospholipid metabolism upon stimulation with thrombin, but not with ionomycin or 12-O-tetradecanoyl-phorbol 13-acetate.

Gel-filtered human platelets that had been pre-labelled with [32P]Pi were stimulated with thrombin, ionomycin or the phorbol ester 12-O-tetradecanoyl-phorbol 13-acetate (TPA). The effect of the hexacationic aminoglycoside antibiotic, neomycin, on platelet physiological responses, such as aggregation and secretion, as well as changes in phosphoinositide metabolism was studied. Neomycin strongly inhibited thrombin-induced aggregation and secretion whereas the antibiotic had no effect on ionomycin- or TPA-induced platelet functions. The thrombin-induced enhancement of inositol phospholipid metabolism was strongly inhibited by the presence of neomycin whereas the TPA- or ionomycin-induced increase in inositol [32P]polyphospholipids remained unaffected. The inhibitory effect of some other aminoglycoside antibiotics was compared to that of neomycin and the data demonstrate that the inhibition of platelet secretion and phosphatidic acid production was dependent on the cationic charge of the antibiotic. It is suggested that neomycin inhibits signal transduction in platelets at a level prior to the inositol-phospholipid-specific phosphodiesterase.

Blood Platelets↗

Synergism between thrombin and adrenaline (epinephrine) in human platelets. Marked potentiation of inositol phospholipid metabolism.

We have studied synergism between adrenaline (epinephrine) and low concentrations of thrombin in gel-filtered human platelets prelabelled with [32P]Pi. Suspensions of platelets, which did not contain added fibrinogen, were incubated at 37 degrees C to measure changes in the levels of 32P-labelled phosphatidylinositol 4,5-bisphosphate (PIP2), phosphatidylinositol 4-phosphate (PIP) and phosphatidate (PA), aggregation and dense-granule secretion after stimulation. Adrenaline alone (3.5-4.0 microM) did not cause a change in any parameter (phosphoinositide metabolism, aggregation and dense-granule secretion), but markedly enhanced the thrombin-induced responses over a narrow range of thrombin concentrations (0.03-0.08 units/ml). The thrombin-induced hydrolysis of inositol phospholipids by phospholipase C, which was measured as the formation of [32P]PA, was potentiated by adrenaline, as was the increase in the levels of [32P]PIP2 and [32P]PIP. The presence of adrenaline caused a shift to the left for the thrombin-induced changes in the phosphoinositide metabolism, without affecting the maximal levels of 32P-labelled compounds obtained. A similar shift by adrenaline in the dose-response relationship was previously demonstrated for thrombin-induced aggregation and dense-granule secretion. Also, the narrow range of concentrations of thrombin over which adrenaline potentiates thrombin-induced platelet responses is the same for changes in phosphoinositide metabolism and physiological responses (aggregation and dense-granule secretion). Our observations clearly indicate that adrenaline directly or indirectly influences thrombin-induced changes in phosphoinositide metabolism.

Blood Platelets↗