Search PubMed⌕ Search

Biomedical subjects

J Lehmann

Publications and source records attributed to J Lehmann.

At least 253 records · Page 14Linked to original sources
PubMed1986

[Age-related changes in peripheral nerves].

Semi-thin sections of the sural nerve from 200 autopsy specimens taken from individuals of both sexes, ages 10 to 91 were morphologically examined. Thickness of the endoneurial capillary walls, and of the perineurium, number of endoneurial capillaries, myelinated fiber density and distribution of myelinated fibers were determined. An additional ultrastructural examination of selected nerves with characteristic values was performed. The analysis revealed a statistically significant age dependence for the investigated features. Increasing age was associated with decreased myelinated fiber density and decreased number of endoneurial capillaries. There was an age dependent increase in the thickness of capillary walls and the perineurium as well as increasing loss of large myelinated fibers. The findings were discussed and compared with similar results from the literature. Age related changes in peripheral nerves have to be interpreted as the result of the cumulative, life-long effect of various pathogenic factors, modified by genetic determinants and by a gradual decrease in regenerative capacity.

Adolescent↗
PubMed1986

Vitamin E in foods from high and low linoleic acid diets.

As part of a human diet study, vitamin E activity was estimated in foods used in seven daily menus. Each menu was designed to contain 35% fat calories with either 10 or 30 gm/day of linoleic acid (18:2) and 500 mg/day of cholesterol. To estimate vitamin E activity, each food used in the menus was analyzed for alpha and gamma tocopherol content by high-pressure liquid chromatography with fluorescence detection. This article reports the alpha and gamma tocopherol contents of those foods, tocopherol contributions from each food in one sample 2,400-kcal menu, and the mean daily vitamin E activity (milligram alpha tocopherol equivalents) of all seven menus at five caloric levels. Major sources of alpha tocopherol (greater than 10% of the RDA) common to both diets (10 and 30 gm linoleic acid) were olive oil and a few fruits and vegetables. Additional major sources in the 30-gm linoleic acid diets were polyunsaturated fatty acid (PUFA) vegetable oils and margarine. Contrary to a common assumption, increasing the level of PUFA in the menus did not necessarily result in higher milligram equivalents of alpha tocopherol because soybean oil, with a tocopherol composition that is predominantly gamma tocopherol, was the major source of linoleic acid in the diets. Thus, vitamin E activity was not necessarily increased when soybean oil was substituted for a less saturated fat such as olive oil, which has mostly alpha tocopherol.

Chromatography, High Pressure Liquid↗
PubMed1985

Comparative stability of 1-alkoxyalkyl alpha-D-glucosides in the presence of acid or alpha-D-glucosidase from yeast.

The aminated 1-alkoxyalkyl glycosides [(S)-2-amino-1-methoxyethyl] 6-amino-6-deoxy-alpha-D-glucopyranoside (3) and [(R,S)-1-ethoxyethyl] 6-amino-6-deoxy-alpha-D-glucopyranoside (4) have been synthesised and characterised. These compounds as well as [(R)-2-amino-1-methoxyethyl] alpha-D-glucopyranoside (1) prepared earlier are resistant against alpha-D-glucosidase (maltase, alpha-D-glucoside glucohydrolase, E.C. 3.2.1.20) from yeast, yet undergo hydrolysis under relatively mild acidic conditions. The kinetic parameters of the interaction with alpha-D-glucosidase and with acid were determined. The relative rates of acid hydrolysis of aminated 1-alkoxyalkyl glycosides compared with aminated ordinary glycosides suggest essential differences in the mechanism of acid-catalysed hydrolysis.

Drug Stability↗
PubMed1985

Dissociation between the excitatory and "excitotoxic" effects of quinolinic acid analogs on the striatal cholinergic interneuron.

Analogs of quinolinic acid were tested for excitatory properties in evoking neurotransmitter release from striatal cholinergic interneurons and for their ability to lesion these same neurons in vivo (excitotoxin activity). The ability of these analogs to inhibit the specific binding of several ligands thought to label excitatory amino acid receptors was also investigated. Dipicolinic acid (2,6-pyridine dicarboxylic acid) was found to be as potent and as efficacious as quinolinic acid (2,3-pyridine dicarboxylic acid) at N-methyl-D-aspartate (NMDA)-type receptors mediating [3H]acetylcholine release from striatal slices. However, unlike quinolinate, the structure of NMDA is not superimposable upon that of dipicolinic acid. Moreover, unlike quinolinic acid, dipicolinic acid injected intrastriatally did not produce detectable excitotoxic lesions. Most unexpectedly, phthalic acid (1,2-benzene dicarboxylic acid), which lacks a nitrogen, also evoked [3H]acetylcholine release from striatal slices, apparently by acting at NMDA-type receptors. Phthalic acid was equipotent to quinolinic acid and dipicolinic acid but possessed less intrinsic activity than these compounds in evoking [3H]acetylcholine release. Despite its lack of a nitrogen and low intrinsic activity, intrastriatal injection of phthalic acid produced axon-sparing lesions of intrinsic cell bodies, like quinolinic acid as assessed by neurochemical and histologic methods. Quinolinic acid, dipicolinic acid and phthalic acid were moderately potent inhibitors (Kl = approximately equal to 100 microM) of the specific binding of 2-[3H]amino-7-phosphonoheptanoic acid a compound thought to be a competitive antagonist of NMDA-type receptors. In contrast, these three compounds failed to inhibit the chloride-dependent or chloride-independent binding of L-[3H]glutamate or [3H]kainic acid. The present results suggest a major dissociation between the structure-activity relationships for "excitotoxicity" vis-à-vis excitation as reflected in the [3H]acetylcholine release model, for compounds acting at NMDA-type receptors.

Animals↗
PubMed1985

[The role of endoneural edema in the pathogenesis of diabetic neuropathy].

Average endoneurial area was correlated with measurements of myelinated fiber density in sural nerves from diabetics and controls. Although, in general, myelinated fiber density decreased with increasing endoneurial area, this relationship was not significant for diabetic nerves. The increase in endoneurial area was attributed to expansion of the endoneurial space as a result of endoneurial edema. A possible role for such edema in the pathogenesis of diabetic neuropathy is considered.

Diabetic Neuropathies↗
PubMed1985

Production of human interferon-beta in mouse L-cells.

A mouse fibroblast cell-constructed by genetic engineering--expresses glycosylated human interferon-beta constitutively. The cells were cultivated on microcarriers in special bioreactors. Under these conditions they produce a maximum yield of 6 000 units interferon-beta/ml/day at cell densities of about 2,2 X 10(6) cells/ml. The production stage of interferon-beta is longer than one month.

Animals↗
PubMed1985

Morphology, organelles and susceptibility to viruses of cultured ferret cells.

Cells explanted from a normal 6-week-old ferret's brain have been subcultured over 100 times, have undergone over 400 population doublings, possess ferret-specific antigens and are referred to as Mpf cells. Low passage-level Mpf cells formed diffuse colonies with ill-defined borders which had a swirling 'finger-print' pattern whereas the colonies formed by high passage-level cells were more densely populated and had distinct borders. Mpf cells at their 100th passage level appeared as a loose monolayer with ill-defined cytoplasmic borders and contained microfilaments, ovoid nuclei, granular endoplasmic reticula with large dilated cisternae filled with an amorphous medium electron-dense product, abundant free ribosomes, irregular and hypertrophic Golgi bodies, mitochondria, and lipid inclusions associated with lipofuscin deposits. Chains of vesicles, 120-150 nm in diameter, some opening to the exterior, were aligned at the cytoplasmic border. The Mpf cells exhibited cytopathology and synthesized progeny virus when exposed to representatives of the Arboviruses, Arenoviruses, Paramyxoviruses, Poxviruses, Retroviruses and Rhabdoviruses.

Animals↗
PubMed1984

Methyl 4-O-(4-alpha-D-glucopyranosyloxy-4-methoxybutyl)-alpha-D-+ ++glucopyranosi de, a modified oligosaccharide for studying interactions of carbohydrates with multisite proteins.

Methyl 4-O-(4-alpha-D-glucopyranosyloxy-4-methoxybutyl)-alpha-D-glu copyranoside (9) was synthesised by transacetalation from methyl 2,3,6-tri-O-acetyl-4-O-(4,4-dimethoxybutyl)-alpha-D-glucopyranosid e and trimethylsilyl 2,3,4,6-tetra-O-acetyl-alpha-D-glucopyranoside followed by removal of the blocking groups. Compound 9, which is methyl alpha-maltotrioside modified by replacing the middle D-glucosyl residue with an acyclic spacer, competitively inhibits the hydrolysis of p-nitrophenyl alpha-maltotrioside by porcine alpha-amylase.

Animals↗
PubMed1984

Excitatory amino acid receptor interactions of a novel alpha-phosphinic acid analogue of alpha-methylaspartic acid.

An alpha-phosphino analogue of alpha-methylaspartate has been synthesized. The compound may not interact with excitatory amino acid receptors directly, as assessed by direct in vitro radioreceptor binding methods; however, it possesses weak anticonvulsant activity and exhibits an excitant action in vitro that is apparently not mediated by a N-methyl-D-aspartate receptor.

Acetylcholine↗
PubMed1984

Production of five human lymphokines (granulocyte-macrophage colony stimulating factor, interferon-gamma, interleukin 2, macrophage cytotoxicity factor and macrophage migration inhibitory factor) from Con A stimulated lymphocyte cultures in bioreactors.

Cultivation parameters for the production of five lymphokines, granulocyte-macrophage colony stimulating factor (GM-CSF), interferon-gamma (IFN-gamma), interleukin 2 (IL-2), macrophage cytotoxicity factor (MCF), and macrophage migration inhibitory factor (MIF) from human spleen cells or peripheral blood lymphocytes were optimized. Cultivation was done in bioreactors containing up to 200 ml of medium, usually serum-free. The reactors were equipped with surface aeration facilities, stirrers and oxygen electrodes. Whereas stirring speed alone did not influence the yields of lymphokines, good aeration was especially beneficial for high IL-2 yields. However, all lymphokines were also produced under anaerobic conditions. The concentration of the mitogen concanavalin A was mainly critical for optimal IL-2 release. Optimal cell concentrations varied from 5 X 10(6)/ml (for GM-GSF and MCF) to 10 X 10(6)/ml (for IL-2 and IFN-gamma). It was possible to increase the yields of individual lymphokines 3 to 10-fold per batch of lymphocytes by a reinduction procedure which involved a change of medium and mitogen every 24 hrs. Reinduction was possible up to 4 times, especially when serum was present in the culture media.

Cells, Cultured↗
PubMed1984

Presynaptic nicotinic cholinergic receptors labeled by [3H]acetylcholine on catecholamine and serotonin axons in brain.

Nicotinic cholinergic receptor binding sites labeled by [3H]acetylcholine were measured in the cerebral cortices, thalami, striata, and hypothalami of rats lesioned by intraventricular injection of either 6-hydroxydopamine or 5, 7-dihydroxytryptamine. In addition, [3H]acetylcholine binding sites were measured in the cerebral cortices of rats lesioned by injection of ibotenic acid into the nucleus basalis magnocellularis. [3H]Acetylcholine binding was significantly decreased in the striata and hypothalami of both 6-hydroxydopamine- and 5,7-dihydroxytryptamine-lesioned rats. There was no change in binding in the cortex or thalamus by either lesion. Ibotenic acid lesions of the nucleus basalis magnocellularis, which projects cholinergic axons to the cortex, did not alter [3H]acetylcholine binding. These results provide evidence for a presynaptic location of nicotinic cholinergic binding sites on catecholamine and serotonin axons in the striatum and hypothalamus.

Acetylcholine↗
PubMed1983

Quinolinic acid evokes [3H]acetylcholine release in striatal slices: mediation by NMDA-type excitatory amino acid receptors.

Quinolinic acid evoked the release of [3H]acetylcholine from striatal slices with an EC50 of approximately 2 mM and an efficacy similar to that of N-methyl-D,L-aspartic acid. (+/-)-2-Amino-5-phosphonopentanoic acid and (-)-2-amino-7-phosphonoheptanoic acid antagonized quinolinic acid-evoked release, while glutamate diethylester and 2-amino-4-phosphonobutyric acid were ineffective as antagonists. Release of [3H]acetylcholine evoked by quinolinic acid was strongly attenuated by the presence of magnesium (1.2 mM) in the medium. The results are consistent with the interaction of quinolinic acid with NMDA-type excitatory amino acid receptors on the striatal cholinergic interneurons.

2-Amino-5-phosphonovalerate↗
PubMed1983

Dopamine receptors modulating [3H]acetylcholine release in slices of the cat caudate: effects of (-)-N-(2-chloroethyl)-norapomorphine.

(-)-N-(2-Chloroethyl)-norapomorphine [-)-NCA) inhibited in a concentration-dependent manner the electrically evoked [3H]acetylcholine release in slices of cat caudate. The inhibition by (-)-NCA was reversible and antagonized by the benzamide neuroleptic S-sulpiride. Although (-)-NCA is an irreversible antagonist at some behaviorally relevant postsynaptic dopamine receptors, its effect as an agonist on dopamine receptors modulating [3H]acetylcholine release strongly resembles its action on presynaptic dopamine autoreceptors modulating [3H]dopamine release. Our results suggest that the dopamine receptor modulating [3H]acetylcholine release may not be an appropriate in vitro model for those behaviorally relevant postsynaptic dopamine receptors which are antagonized by (-)-NCA. It is more likely that it conforms to the characteristics of presynaptic release-modulating dopamine autoreceptors. The agonistic action of (-)-NCA at presynaptic dopamine receptors, in contrast to the irreversible antagonism of some postsynaptic dopamine receptors by (-)-NCA, should be interpreted with caution. Evidence is presented which suggests that (-)-NCA breaks down in solution into (-)-N-(2-hydroxylethyl)-norapomorphine [-)-NHA). Since (-)-NHA is an agonist at presynaptic dopamine receptors, this physicochemical breakdown product may be partly responsible for the apparent agonistic properties of (-)-NCA under our in vitro conditions.

Acetylcholine↗
PubMed1983

Characterization of dopamine autoreceptor and [3H]spiperone binding sites in vitro with classical and novel dopamine receptor agonists.

The specific D2 receptor agonist, LY 141865, but not the specific D1-receptor agonist, SK&F 38393, potently inhibited electrically evoked [3H]dopamine release from slices of the cat caudate. Similarly, LY 141865, but not SK&F 38393, inhibited [3H]spiperone binding to membranes of the cat caudate. The inhibition by dopamine receptor agonists of electrically evoked [3H]dopamine release was antagonized by the specific D2-receptor antagonist S-sulpiride. The inhibition of the electrically evoked release of [3H]dopamine by apomorphine was not, however, antagonized by the specific D1-receptor antagonist, bulbocapnine. Similarly, S-sulpiride but not bulbocapnine potently inhibited [3H]spiperone binding to membranes of the cat caudate. These results suggest that the dopamine autoreceptor modulating the depolarization-evoked release of [3H]dopamine, and the binding site of [3H]spiperone, are valid in vitro models for D2-dopamine receptors. Contrary to some previous reports, DPI was inactive in both in vitro dopamine receptor models. The IC50 values of a series of dopamine receptor agonists correlated very well in the two in vitro dopamine receptor models. One exception to this correlation was bromocriptine, which was more potent at [3H]spiperone binding sites than at the dopamine autoreceptor. With the exception of bromocriptine, all dopamine receptor agonists had one-hundred fold higher potency at the dopamine autoreceptor than at [3H]spiperone binding sites. [3H]Spiperone binding sites are localized primarily postsynaptic to dopamine terminals. Possible differences between the pharmacological properties of pre- and postsynaptic dopamine receptors should become apparent in the comparison of the two in vitro dopamine receptor models. However, the order of potency of dopamine receptor agonists with both in vitro models, dopamine autoreceptor and [3H]spiperone binding, was the same: N-n-propylnorapomorphine greater than TL-99 = 7-HAT greater than M-7 greater than Apomorphine greater than LY 141865.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1983

Stereoisomers of apomorphine differ in affinity and intrinsic activity at presynaptic dopamine receptors modulating [3H]dopamine and [3H]acetylcholine release in slices of cat caudate.

We investigated the effects of R(-)-apomorphine and S(+)-apomorphine on dopamine receptors modulating electrically evoked [3H]dopamine and [3H]acetylcholine release from slices of cat caudate nucleus. R(-)-Apomorphine inhibited the release of both [3H]dopamine and [3H]acetylcholine with an IC50 of 20 nM, while S(+)-apomorphine was without inhibitory action on the electrically evoked release of either neurotransmitter at concentrations up to 1 microM. At a concentration of 1 microM, however, S(+)-apomorphine antagonized the inhibition by R(-)-apomorphine, producing a parallel five-fold shift to the right in the concentration-response curve to R(-)-apomorphine. These results indicate that S(+)-apomorphine is devoid of intrinsic activity to stimulate presynaptic dopamine receptors modulating the electrically evoked release of dopamine and acetylcholine. In addition, S(+)-apomorphine has an approximately ten-fold lower affinity for presynaptic dopamine receptors compared to R(-)-apomorphine.

Acetylcholine↗