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Biomedical subjects

A Lehmann

Publications and source records attributed to A Lehmann.

At least 127 records · Page 7Linked to original sources
PubMed1987

Evidence for a direct action of N-methylaspartate on non-neuronal cells.

The effects of N-methylaspartate (NMA) on extracellular amino acids and purine catabolites in the hippocampus were studied with brain dialysis in rats with unilateral hippocampal NMA lesions. In the lesioned side, an increased basal output of glutamine was observed while glutamate was significantly decreased. NMA evoked a drop in extracellular glutamine. The effect was not observed in the lesioned hippocampus. NMA markedly enhanced the release of taurine and phosphoethanolamine (PEA). This response was unchanged in NMA-lesioned hippocampus. Analysis of the tissue content of endogenous amino acids revealed decrements in glutamate and GABA whereas other amino acids were not significantly altered. The resting and NMA-stimulated efflux of inosine was higher in the intact hippocampus. However, the extracellular concentrations of the inosine break-down products hypoxanthine and xanthine were not influenced by a prior NMA lesion, neither before nor after NMA administration. The present findings indicate that NMA releases amino acids (mainly taurine and PEA) from non-neuronal cells. The depression of extracellular glutamine elicited by NMA is probably a neuronal event. A direct stimulation of the energy metabolism of non-neuronal cells by NMA appears to exist as measured by the efflux of purine catabolites. I propose that non-neuronal cells, possibly glia, possess NMA receptors which, upon stimulation, initiate biochemical changes. The physiological significance of these responses remains to be elucidated.

Amino Acids↗
PubMed1987

Effects of Ca2+ entry blockers on kainate-induced changes in extracellular amino acids and Ca2+ in vivo.

The effect of organic Ca2+ channel blockers and Co2+ on kainate-induced changes in 45Ca2+ efflux and amino acid release was studied in the rabbit hippocampus with the dialysis-perfusion technique. Administration of 1 mM kainate caused a transient, 50% drop of extracellular Ca2+. This effect was insensitive to 100 microM flunarizine or verapamil, 10 microM nimodipine, and 6 mM CoCl2. The organic Ca2+ entry blockers did not significantly influence kainate-induced changes in extracellular amino acids, whereas Co2+ affected both basal and kainic acid stimulated release of amino acids. These results indicate that kainate-regulated Ca2+ ionophores differ from Ca2+ channels in peripheral tissues in terms of sensitivity to Ca2+ entry inhibitors.

Amino Acids↗
PubMed1987

Phosphoethanolamine transiently enhances excitability of rat hippocampal neurons in vitro.

Application of phosphoethanolamine (PEA; more than 1 mM) to rat hippocampal neurons leads to a change in excitability in two phases: a) A transient increase of EPSP amplitude and membrane input resistance (Ri) in the order of minutes that can be observed after local as well as bath application. b) Decrease of EPSP and IPSP amplitude and of Ri are caused by exposure to PEA (over 1 mM; bath application) for more than 20 min. Membrane potential and action potential are not changed by 10 mM PEA for up to half an hour. Depolarizations evoked by N-methyl-D,L-aspartate (NMA) given locally are transiently enhanced and then reduced by PEA following a time course similar to the effects a) and b) observed on EPSPs. PEA produces an apparent decrease of calcium activity due to its electrochemical properties. A local application into the soma layer results in a complex calcium signal. A shortlasting drop in calcium activity is followed by a large positive signal indicating an increase of calcium activity. It is concluded that liberation of PEA exacerbates rather than mitigates the harmful consequences of strong excitation and/or excitotoxins.

Animals↗
PubMed1987

Amino acid content in astroglial primary cultures from different brain regions during cultivation.

Free amino acids in astroglial primary cultures obtained from newborn rat cerebral cortex, striatum and hippocampus were analyzed and compared during cultivation. Glutamate and taurine exhibited the highest concentrations. Aspartate and glutamate showed the highest values after 1 and 3 weeks of cultivation with lower values after 2 weeks in culture, while taurine, beta-alanine/hypotaurine and phosphoethanolamine showed the highest value after 2 weeks in culture. The non-neuroactive amino acids and gamma-aminobutyric acid were present at a low level and the former showed the lowest concentration at 2 weeks of cultivation. Astrocytes from the different regions did generally not differ with respect to amino acid content. We conclude that the morphological and biochemical maturation of glia in culture is accompanied with marked quantitative changes in amino acid pattern.

Amino Acids↗
PubMed1987

Pharmacological protection against the toxicity of N-methyl-D-aspartate in immature rat cerebellar slices.

In order to delineate the pharmacological characteristics of the toxicity of N-methyl-D-aspartate (NMDA), slices of cerebellum from 7-day old rats were incubated with NMDA, together with various putative protective agents. These comprised three different groups: (i) a competitive receptor antagonist (kynurenic acid), (ii) direct (cobalt ions, flunarizine) and indirect (taurine) calcium entry blockers, (iii) cyclo-oxygenase inhibitors (indomethacin and acetylsalicylic acid) and a blocker of calcium-activated, neutral proteases (leupeptin). When the slices were incubated for 30 min in medium containing 100 microM NMDA, postmigratory granule cell nuclei were rounded and swollen. After 90 min of recovery in normal medium, the nuclei were pyknotic and the cells were irreversibly injured. As expected, these changes were completely blocked by kynurenate, indicating that NMDA receptors mediate the cell death. Cobalt ions abolished the acute toxicity of NMDA, but after recovery, some granule cell nuclei were swollen. This effect could be attributed to the toxicity of cobalt ions and not to delayed toxicity of NMDA. The other inhibitors of the uptake of calcium, flunarizine and taurine, did neither affect acute nor persistent toxicity of NMDA. These results support the previous finding that the toxicity of NMDA is calcium-dependent and that organic calcium channel blockers are ineffective against NMDA-induced uptake of calcium. Leupeptin had no effect on the toxicity of NMDA, suggesting that calcium-activated proteolysis was not the crucial event in excitotoxic necrosis. Indomethacin, but not acetylsalicylic acid, prevented neuronal degeneration provoked by NMDA, but only in very large concentrations (greater than or equal to 100 microM).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Alterations in hippocampal extracellular amino acids and purine catabolites during limbic seizures induced by folate injections into the rabbit amygdala.

The effects on hippocampal extra- and intracellular amino acids of focal injection of folic acid into the amygdala in the rabbit were studied with brain dialysis. Folate seizures were accompanied by pronounced elevations of extracellular alanine and phosphoethanolamine. The increase of extracellular alanine was related to an enhanced level of this amino acid in total hippocampal tissue, whereas phosphoethanolamine was unaltered in tissue biopsies. Folate seizures did not significantly affect extracellular aspartate and extracellular glutamate was only slightly elevated (50-75% over baseline values). The tissue concentration of glutamate remained at control levels during the seizures and tissue aspartate was decreased by 28%. Extracellular glutamine decreased rapidly after folate injection with a concomitant increase of total hippocampal glutamine. Neither extra- nor intracellular taurine was affected by folate epilepsy. The experiments also encompassed measurements of the extracellular purine catabolites inosine, hypoxanthine and xanthine. Folic acid-induced epilepsy produced changes in these compounds indicative of moderately accelerated degradation of adenosine 5'-triphosphate. The findings support the view of glutamate as a mediator of epilepsy-related brain damage. It is, however, questionable if the small enhancement of extracellular glutamate is enough to provoke neuronal necrosis associated with folate epilepsy.

Amino Acids↗
PubMed1987

Pentylenetetrazol seizure threshold and extracellular levels of cortical amino acids in taurine-deficient kittens.

Directly after weaning, kittens were raised on a semisynthetic diet supplemented with 0.4% taurine or devoid of this amino acid. Eight to twelve weeks later the blood plasma concentration of taurine was decreased by 98-99% in kittens fed a taurine-free regimen. Parietal cortex dialysis, performed in anaesthetized kittens, revealed a selective, but less marked, reduction of extracellular taurine. When kainic acid was included in the dialysis buffer, taurine was doubled in taurine-supplemented kittens, but it was only slightly affected in deficient animals. The animals were also used for determination of the threshold of pentylenetetrazol-induced epilepsy 3 days after the dialysis experiment. This was not significantly different between the groups. The present work shows that taurine deficiency in its own right does not elevate interstitial glutamate, an effect previously observed in the 2-guanidino-ethane sulphonic acid model for taurine deficiency. The results further suggest that taurine is better retained in neural cells in the taurine-deficient state. Moreover, the findings argue against a role for endogenous taurine in the control of epileptiform discharge initiation and/or spread.

Amino Acids↗
PubMed1987

Nucleotide sequence and linkage map position of the secX gene in maize chloroplast and evidence that it encodes a protein belonging to the 50S ribosomal subunit.

The nucleotide sequence of the segment of maize chloroplast DNA lying between the map coordinate positions 32.59 and 32.98 Kb and containing the secX gene has been determined. The derived amino acid sequence of maize chloroplast secX is 95%, 87% and 62% identical to the corresponding derived amino acid sequences from two plant chloroplasts and Escherichia coli, respectively. It is also 70% identical to the experimentally determined amino acid sequence of a protein isolated from Bacillus stearothermophilus ribosomes. Separation of the 50S ribosomal subunit proteins of E. coli by reversed phase HPLC gave a peak which contained pure secX protein, as determined by N-terminal amino acid sequencing. Spinach chloroplast 50S subunit proteins separated by HPLC also gave a peak corresponding to pure secX protein. From these results we conclude that the secX gene in E. coli and in plant chloroplasts encodes a small (37-38 amino acid residues) ribosomal protein belonging to the 50S subunit. The same conclusion has been reached recently by A. Wada with respect to E. coli secX. In agreement with Wada, we name the secX protein L36. Its chloroplast gene is designated rpL36.

Base Sequence↗
PubMed1987

Breast reconstruction without implant: experience of 52 cases.

Reconstruction of the breast (BR) after mastectomy without using a prosthetic implant has always presented a challenge for plastic surgeons, allowing them to avoid complications due to foreign body and to provide a more natural reconstructed breast. Out of 66 women who underwent BR using the rectus abdominis musculocutaneous flap, 52 received no implant. Ten upper rectus (ERF) and 42 lower rectus (TRAM) were the two procedures applied. The ERF has been abandoned due to the 9% rate of complete necrosis encountered among the total series of rectus flap regardless of the implant inclusion. Partial necrosis was also the most frequent complication of the TRAM (28% among those not having received an implant), but the reconstruction was nevertheless possible in all the cases. The TRAM technique produced abdominal sequelae in 45% of the no-implant cases, though it also improved the cosmetic aspect of the abdomen in an equal number of cases, particularly in obese women. Overall cosmetic results were also better for the TRAM without implant than for the ERF (72% good vs. 51%). Moreover the BR without implant could be performed in only 48% of the total ERF, as compared to 93% of the total TRAM. The major advantage of such BR without implant is that it provides a reconstructed breast which appears more symmetrical to the contralateral breast and which remains even after several years of follow-up.

Breast↗
PubMed1986

Blockade of N-methyl-D-aspartate-sensitive acidic amino acid receptors inhibits ischemia-induced accumulation of purine catabolites in the rat striatum.

The effect of blocking N-methyl-D-aspartate (NMDA)-sensitive excitatory amino acid (EAA) receptors during brain ischemia was studied in order to test a link between EAAs and neuronal energy metabolism. The receptors were blocked unilaterally in the rat striatum before, during and after an ischemic insult. The receptor blocker, D-2-amino-5-phosphonovalerate (D-APV) was administered by dialysis perfusion, which also allowed continuous sampling for analysis of adenosine triphosphate degradation products, i.e. purine catabolites, in control and D-APV-treated striata. Purine catabolites were analysed with reversed-phase liquid chromatography. Hypoxanthine, xanthine, inosine and adenosine increased dramatically in the striatum during ischemia and reached maximum levels during early reperfusion. D-APV reduced the extracellular accumulation of all measured purine catabolites during ischemia/reflow and improved to some extent the recovery of the striatal electroencephalographic activity in the majority of the animals. The results suggest that NMDA receptor blockade attenuates acute changes in energy metabolism during ischemia.

2-Amino-5-phosphonovalerate↗
PubMed1986

Effects of kainic acid on brain calcium fluxes studied in vivo and in vitro.

The effect of in vivo administration of kainic acid into the rabbit hippocampus was studied with brain dialysis and subsequent determination of the Ca2+ concentration in the dialysate. When included in the perfusing medium, kainic acid as well as veratridine induced a decrease in extracellular Ca2+. The effect of kainic acid (but not of veratridine) was insensitive to tetrodotoxin. In vitro studies revealed no effect of kainic acid on 45Ca2+ uptake by isolated astrocytes, but showed an enhancement of synaptosomal 45Ca2+ accumulation. This was, however, only 25% of the stimulatory effect of high K+ depolarization. Glutamate activated synaptosomal Ca2+ uptake, whereas dihydrokainate had no effect. The uptake evoked by kainate and glutamate was independent of the K+ level in the medium which indicates the involvement of other than voltage-sensitive Ca2+ channels. The results confirm previous finding that kainic acid promotes the uptake of Ca2+ in brain cells. Kainate affects Ca2+ fluxes pre- and postsynaptically. Presynaptic Ca2+ influx may be mediated by chemically gated mechanisms.

Animals↗
PubMed1985

Effects of status epilepticus on extracellular amino acids in the hippocampus.

Extracellular amino acids were followed in the hippocampus during sustained seizures induced by systemic administration of kainic acid (KA) or bicuculline (BC). KA epilepsy was associated with marked increases in phosphoethanolamine (PEA) and taurine. Alanine and ethanolamine were moderately raised while other amino acids were unaffected. BC seizures encompassed a slightly different pattern of alterations. In contrast to KA seizures, BC epilepsy had no effect on taurine. Significant increments were observed for PEA and alanine while elevations of ethanolamine were subtle. In both types of seizures, glutamate and GABA remained unaffected extracellularly, probably due to efficient recapture mechanisms.

Amino Acids↗
PubMed1985

Ischemia-induced shift of inhibitory and excitatory amino acids from intra- to extracellular compartments.

Brain ischemia was induced for 10 or 30 min by clamping the common carotid arteries in rabbits whose vertebral arteries had previously been electrocauterized. EEG and tissue content of high energy phosphates were used to verify the ischemic state and to evaluate the degree of postischemic recovery. Extracellular levels and total contents of amino acids were followed in the hippocampus during ischemia and 4 h of recirculation. At the end of a 30-min ischemic period, GABA had increased 250 times, glutamate 160 times, and aspartate and taurine 30 times in the extracellular phase. The levels returned to normal within 30 min of reflow. A delayed increase of extracellular phosphoethanolamine and ethanolamine peaked after 1-2 h of reflow. Ten minutes of ischemia elicited considerably smaller but similar effects. With respect to total amino acids in the hippocampus, glutamate and aspartate decreased to 30-50% of control while GABA appeared unaffected after 4 h of reflow. Alanine, valine, phenylalanine, leucine, and isoleucine increased severalfold. The importance of toxic extracellular levels of excitatory amino acids, as well as of high extracellular levels of inhibitory amino acids, are considered in relation to the pathophysiology of neuronal cell loss during cerebral ischemia.

Amino Acids↗