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J Aasly

Publications and source records attributed to J Aasly.

At least 37 records · Page 2Linked to original sources
PubMed1997

Lactate formation from [U-13C]aspartate in cultured astrocytes: compartmentation of pyruvate metabolism.

Metabolism of [U-13C]aspartate in cultured astrocytes and the effects of inhibitors of malic enzyme and phosphoenolpyruvate carboxykinase (hydroxymalonate and 3-mercaptopicolinic acid, respectively) were studied using 13C nuclear magnetic resonance (NMR) spectroscopy. The labelling of glutamate and glutamine showed entry of aspartate into the tricarboxylic acid (TCA) cycle after conversion to oxaloacetate. Production of [U-13C]pyruvate from [U-13C]aspartate was revealed by the presence of [U-13C]lactate in incubation media. Furthermore, labelling patterns in C-2 and C-3 in intracellular aspartate showed entry of [1,2-13C]acetyl-CoA into the TCA cycle; evidence for pyruvate-recycling. No reduction in [U-13C]lactate was observed in the presence of either enzyme inhibitor. However, 3-mercaptopicolinic acid reduced incorporation of labelled acetyl-CoA into TCA cycle intermediates, indicating compartmentation of pyruvate production in astrocytes.

Animals↗
PubMed1997

Nuclear magnetic resonance spectroscopy of cerebrospinal fluid from patients with low back pain and sciatica.

STUDY DESIGN: This study was carried out to assess the metabolic differences between pain-free control subjects and patients with low back pain, either with or without disc protrusion or herniation. OBJECTIVES: To analyze various metabolites in human cerebrospinal fluid using proton nuclear magnetic resonance spectroscopy. The potential use of this technique as an additional tool for diagnostic assessment was also evaluated. SUMMARY OF BACKGROUND DATA: Inflammation is thought to play a major role in the generation of lumbar spine pain, a theory supported both by animal and in vitro studies. The effect of the inflammation in terms of increased metabolism has not yet been studied. METHODS: Cerebrospinal fluid was obtained from patients by lumbar puncture, frozen, redissolved, and analyzed for metabolites by proton nuclear magnetic resonance spectroscopy. RESULTS: Significantly lower values for several key metabolites were found in patients with low back pain or sciatica, with the lowest values in the subgroup of patients with myelographic signs of disc protrusion or herniation. CONCLUSIONS: The results indicate a higher level of metabolic activity in patients with low back pain or sciatica compared with pain-free control subjects, with this difference being most pronounced in the subgroup of patients with myelographic evidence of disc protrusion or herniation.

Adult↗
PubMed1997

NMR spectroscopy study of the effect of 3-nitropropionic acid on glutamate metabolism in cultured astrocytes.

3-Nitropropionic acid (3-NPA) is a selective and irreversible inhibitor of succinate dehydrogenase. The effect of this compound on the metabolism of [U-13C]glutamate was studied in astrocytes using 13C nuclear magnetic resonance spectroscopy. The appearance of [1,2,3-13C]glutamate in cell extracts and [1,2,3-13C]glutamine and [U-13C]lactate in cell media demonstrated the metabolism of labeled glutamate via the tricarboxylic acid cycle. Such labeling was observed in the control situation and also in cells treated with 3 mM 3-NPA. In the cells treated with 3 mM 3-NPA, however, the labeling was significantly reduced, and with 10 mM 3-NPA no such labeling was observed. Labeled aspartate was observed in untreated cells only. Labeled succinate was not detectable under control conditions, but increased dose dependently in the presence of 3-NPA. Glutamate uptake and conversion of [U-13C]glutamate to [U-13C]glutamine was largely unaffected by 3-NPA, and ATP content was unchanged. In a previous study using cerebellar neurons, tricarboxylic acid cycle metabolism was blocked with 3 mM 3-NPA. The present results show that astrocyte metabolism is more adaptable to blockade of the tricarboxylic acid cycle by 3-NPA than neuronal metabolism.

Animals↗
PubMed1997

Cerebrospinal fluid lactate and glutamine are reduced in multiple sclerosis.

OBJECTIVES: To analyse various metabolites in human cerebrospinal fluid from healthy controls and patients with multiple sclerosis. PATIENTS AND METHODS: Cerebrospinal fluid was obtained from patients by lumbar puncture, frozen, redissolved, and analysed for metabolites by proton nuclear magnetic resonance spectroscopy. RESULTS: Significantly lower values for lactate and glutamine were found in patients with multiple sclerosis in comparison with controls. No significant differences were found between patients with the relapsing-remitting and chronic progressive forms of the disease for any of the metabolites measured. CONCLUSION: There is a concomitant reduction in both lactate and glutamine in the cerebrospinal fluid of patients with multiple sclerosis compared to controls. This may be related to altered astrocytic metabolism during the disease. The results clearly show the diagnostic potential of magnetic resonance spectroscopy in diseases such as multiple sclerosis.

Adolescent↗
PubMed1996

MRS study of glutamate metabolism in cultured neurons/glia.

[U-13C]Glutamate metabolism was studied in primary brain cell cultures. Cell extracts as well as redissolved lyophilized media were subjected to nuclear magnetic resonance spectroscopy in order to identify 13C labeled metabolites. Both neurons and astrocytes metabolized glutamate extensively with 13C label appearing in aspartate in all cultures. Additionally, GABA is synthesized in the GABAergic cortical neurons. Labeling of lactate and glutamine was prominent in medium from astrocytes, but not detectable in cerebral cortical neurons. Cerebellar granule neurons showed some labeling of lactate. Glutamate derived from the first turn of the tricarboxylic acid cycle (1,2,3-13C3-isotopomer) is present in all cell types analyzed. However, glutamate derived from the second turn of the cycle was only detected in granule neurons. In astrocytes, the transaminase inhibitor aminooxyacetic acid not only abolished the appearance of aspartate, but also of the 1,2,3-13C3-isotopomer of glutamate, thus showing that transamination is necessary for the conversion of 2-oxoglutarate to glutamate. The entry of glutamate into the tricarboxylic acid cycle was, however, not seriously impaired. 3-nitropropionic acid abolished the appearance of aspartate, the 1,2,3-13C3-isotopomer of glutamate and lactate in cerebellar granule neurons.

Animals↗
PubMed1996

Relaxation of human temporal artery by endothelin ETB receptors.

Endothelin receptors have been characterized in human temporal artery by molecular biological methods and in vitro pharmacology. Reverse transcriptase-polymerase chain reaction was used to detect mRNA encoding ETA and ETB receptors in normal and endothelium-denuded arteries. Vasomotor response experiments with a specific ETA antagonist (FR 139317) suggested the presence of ETA subtypes. Marked ETB-mediated relaxation was obtained with ET-3 when ETA activity was blocked in precontracted arteries. Relaxation was significantly reduced by bosentan, indomethacin, and a nitric oxide synthase inhibitor. It may be speculated that the relaxant activity is mediated through ETB1 receptors.

Azepines↗
PubMed1995

SUNCT syndrome: cerebral SPECT images during attacks.

Two patients with SUNCT syndrome (short-lasting, unilateral, neuralgiform headache attacks with conjunctival injection and tearing) were investigated. Blood flow velocity in the middle cerebral artery was monitored before, during, and outside four spontaneous attacks. An interhemispheric asymmetry was observed. In the second case, velocity decreased significantly on both sides during attacks in comparison with preattack values. Cerebral SPECT (single photon emission computed tomography) images were obtained during a bout and between attacks in one patient. The radiocompound was injected 5 to 10 seconds after the start of an attack. In both patients, normal tracer uptake and symmetric perfusion was observed during headache periods.

Aged↗
PubMed1994

[Peptide modulation in vascular headache].

This article reviews recent developments in the field of vasoactive peptides in relation to certain types of headache. The equilibrium existing in the brain between contraction and dilatation of blood vessels is controlled by, among other factors, vasoactive peptides. Several of these have been discovered only recently and constitute a rapidly expanding field of research with exciting perspectives. Cranial blood vessels are innervated by sympathetic, parasympathetic and sensory nerve fibres, all of which contain certain vasoactive peptides as co-transmitters. Others, like endothelin, can be produced by the endothelium. There is evidence to suggest that vasoactive peptides of the trigeminovascular system are liberated in response to abnormal constriction of cranial blood vessels and contribute to headache. New drug therapies based on the activity of such substances are now being developed.

Cerebral Arteries↗
PubMed1993

Minor structural brain changes in young drug abusers. A magnetic resonance study.

Twenty-three drug abusers and seventeen controls underwent clinical neurological examinations and magnetic resonance imaging (MRI) of the brain. The drug abuse encompassed cannabis, inhalants, opiates, psychedelics, amphetamines, and cocaine but not necessarily all drugs in all persons. The drug abuse was always combined with heavy alcohol consumption. One drug abuser had abnormal neurological findings which consisted of lower limb ataxia and 3 others had mild imbalance. MRI examinations did not show differences in width of the third, fourth or lateral ventricles nor the diameter of the cerebral aqueduct but the drug abusers had significantly smaller vermes cerebelli compared to controls. White matter changes also occurred more often in the drug abuser group. These findings are not consistent with known side-effects of the narcotic drugs but more probably a result of very high alcohol consumptions in parallel with drug abuse. Alcohol is clearly a much more potent brain toxic agent than are the most commonly abused narcotic drugs.

Adult↗
PubMed1992

A new hereditary syndrome with a bleeding tendency, extreme miosis, spasms, dyslexia, thrombocytopathia etc. Pupillometric, evaporimetric, and ophthalmological observations.

A recently described familiar syndrome consists of the following components: A bleeding tendency with thrombocytopathia, miosis, muscular weakness and spasms, ichthyosis, asplenia, dyslexia, and headache. Four definite and 2 probable patients have been identified in 4 generations. In the present study, the pupillary behaviour was scrutinized in two 'definite' cases with the infrared, binocular pupillometer. The forehead sweating pattern was also investigated with an Evaporimeter. The basal pupillary widths were: 1.25-1.75 mm. Only minor responses were noted upon topical stimulation with an indirectly acting pupillodilating agent (OH-amphetamine). A directly acting sympathicomimetic drug (phenylephrine) exerted a more marked influence on the pupil, indicating a relative supersensitivity. The evaporimetric pattern in the forehead seemed to be within reference limits, at variance with what is the case in Horner's syndrome. Further findings were: the orbit seemed to be smaller than normal; a bilateral VI. cranial nerve palsy was identified, and a marked upward gaze palsy coexisted with pupils with Argyll Robertson's traits. There is no readily acceptable explanation for the ocular abnormalities. The disorder underlying the pupillary abnormality may possibly be located in the upper mesencephalon.

Adult↗
PubMed1992

Segregation and manifestations of the mtDNA tRNA(Lys) A-->G(8344) mutation of myoclonus epilepsy and ragged-red fibers (MERRF) syndrome.

We have studied the segregation and manifestations of the tRNA(Lys) A-->G(8344) mutation of mtDNA. Three unrelated patients with myoclonus epilepsy and ragged-red fibers (MERRF) syndrome were investigated, along with 30 of their maternal relatives. Mutated mtDNA was not always found in the offspring of women carrying the tRNA(Lys) mutation. Four women had 10%-33% of mutated mtDNA in lymphocytes, and no mutated mtDNA was found in 7 of their 14 investigated children. The presence of mutated mtDNA was excluded at a level of 3:1,000. Five women had a proportion of 43%-73% mutated mtDNA in lymphocytes, and mutated mtDNA was found in all their 12 investigated children. This suggests that the risk for transmission of mutated mtDNA to the offspring increases if high levels are present in the mother and that, above a threshold level of 35%-40%, it is very likely that transmission will occur to all children. The three patients with MERRF syndrome had, in muscle, both 94%-96% mutated mtDNA and biochemical and histochemical evidence of a respiratory-chain dysfunction. Four relatives had a proportion of 61%-92% mutated mtDNA in muscle, and biochemical measurements showed a normal respiratory-chain function in muscle in all cases. These findings suggest that > 92% of mtDNA with the tRNA(Lys) mutation in muscle is required to cause a respiratory-chain dysfunction that can be detected by biochemical methods. There was a positive correlation between the levels of mtDNA with the tRNA(Lys) mutation in lymphocytes and the levels in muscle, in all nine investigated cases. The levels of mutated mtDNA were higher in muscle than in lymphocytes in all cases. In two of the patients with MERRF syndrome, muscle specimens were obtained at different times. In both cases, biochemical measurements revealed a deteriorating respiratory-chain function, and in one case a progressive increase in the amount of cytochrome c oxidase-deficient muscle fibers was found.

Adult↗
PubMed1991

[Mitochondrial diseases. Diagnostic light and electron microscopic changes in muscle biopsies from patients with mitochondrial myopathy].

Mitochondrial myopathy can be caused by several metabolic defects in the mitochondria. Cells with high levels of oxidative metabolism, such as skeletal muscle, myocardium and brain cells, are particularly vulnerable to these defects. We describe the structural changes in muscle biopsies from 49 patients with mitochondrial myopathy. The younger patients were often symptom-free, but the possibility of a genetic defect was suggested by the family history. "Ragged-red fibres" were found in 10% of the biopsies. Typical paracrystalline inclusions were seen in the mitochondria of the oldest patients. Electron-lucent matrix and increased thickness of the inner membranes of the mitochondria in particular were found in the younger patients. Disorganization of cristae, with cristolysis and unfolding of the cristae was also found. We suggest that structural mitochondrial changes in mitochondrial myopathy constitute a stepwise process and that the mitochondrial alterations of the cristae may represent an early stage in the morphogenesis of mitochondrial disease.

Age Factors↗
PubMed1991

Mitochondrial myopathy in Marinesco-Sjögren syndrome.

Myopathy represents one of the major features of Marinesco-Sjögren syndrome (MSS). Seven patients with MSS from three different families were studied with morphological and neurophysiological methods. In two patients ragged-red fibres were found after Gomori trichrome staining. Transmission electron microscopy (EM) showed that subsarcolemmal accumulation of abnormal mitochondria regularly occurred and in one patient paracrystalline inclusion bodies were found. The EMG showed myopathic changes while the nerve condition velocities were normal. A delayed normalization of exercised-induced hyperlactatemia was noted. These findings show that mitochondrial myopathic changes are present in MSS.

Adolescent↗
PubMed1991

Myopathy in Marinesco-Sjögren syndrome: an electrophysiological study.

Electrophysiological studies were performed in 7 patients with Marinesco-Sjögren syndrome in order to search for neuromuscular involvement in this multiorgan disorder. In 6 patients muscle biopsies were also obtained. Light microscopic examinations of the biopsies showed extensive myopathic changes, and in two patients ragged red fibers were found. Electron microscopy showed subsarcolemmal accumulation of abnormal mitochondria in all. Concentric needle EMG revealed unequivocal myopathic changes, more extensive in the anterior tibial than in the biceps brachii muscle. Motor and sensory conduction velocities in the peripheral nerves were normal. There were remarkably high amplitudes of sensory responses. Macro EMG studies in the biceps brachii muscle in four patients showed increased amplitude and area of the macro MUPs. This may be due to abnormal membrane function. Both electrophysiological and morphological findings confirm myopathic features of Marinesco-Sjögren syndrome.

Adolescent↗
PubMed1991

Epilepsy in a mitochondrial disorder.

In a large family with maternally inherited mitochondrial disease, a mild defect in the NADH-ubiquinone oxidoreductase step (complex 1) in the respiratory chain was found. Epilepsy was seen in nine (22%) of the 37 family members. Five of them, belonging to one branch of the family, had myoclonus epilepsy and EEG abnormalities consistent with this. The remaining four patients, belonging to other branches of the family tree, had partial epilepsy. Neurological symptoms also varied in different parts of the family. Possible explanations for the differences in phenotypic expressions are discussed.

Adolescent↗
PubMed1990

Brain perfusion with intracarotid injection of 99mTc-HM-PAO in partial epilepsy during amobarbital testing.

Technetium (99mTc) hexamethyl propylene amine oxime (HM-PAO) was injected into the internal carotid artery in ten epileptic patients after the end of amobarbital speech-memory tests. The cerebral perfusion as visualized from SPET was compared to cerebral angiographies, which showed unilateral filling of intracranial vessels in seven patients. SPET revealed cross-flow between the hemispheres in four of these seven patients. In three patients in whom the angiograms had shown bilateral contrast filling, SPET showed cross-flow in only two. It is concluded that 99mTc-HM-PAO SPET examinations provide valuable information for correct interpretation of amobarbital tests on cognitive hemisphere functions. The SPET technique may help to explain atypical speech and memory responses caused by unusual intracranial vascularization.

Adult↗