Search PubMed⌕ Search

Biomedical subjects

E Morgenstern

Publications and source records attributed to E Morgenstern.

At least 37 records · Page 2Linked to original sources
PubMed1991

Aldehyde fixation causes membrane vesiculation during platelet exocytosis: a freeze-substitution study.

Despite a plethora of reports on the ultrastructure of secretory granule release by exocytosis, the release of coagulant activity from stimulated platelets is still being attributed to membrane vesiculation. Membrane vesiculation and the formation of myelin figures have been shown to be artifacts of glutaraldehyde GA fixation. Cells fixed by direct osmium or rapid freezing are free of such structures. Yet there is still doubt that rapid freezing interferes with vesiculation process. This study has addressed this issue by examining: (1) whether freezing and freeze-substitution affects membrane vesiculation, (2) whether paraformaldehyde-fixation also induces the phenomenon, and (3) whether the aldehyde concentration is of influence. Aldehyde fixation was carried out prior to impact freezing and freeze-substitution. In thrombin-stimulated platelets, membrane vesiculation and myelin figures were found. Glutaraldehyde induced multivesicular structures, paraformaldehyde or low aldehyde concentrations only blebs on the platelet surface. The membrane vesicles were in continuity with the cytoplasmic matrix. Unstimulated platelets did not show vesiculation or myelin figures. Control samples, without aldehyde fixation, showed instead of membrane vesiculation, granule fusion with the plasmalemma, or, instead of myelin figures, compound granules. This confirms that membrane vesiculation and the formation of myelin figures are artifacts induced by the failure of aldehydes to arrest lipid mobility within membranes undergoing rapid changes in structure. Although the presence of membrane vesiculation and myelin figures in platelets indicates that exocytotic processes were occurring at the moment of aldehyde fixation, the finding of membrane vesiculation in aldehyde-fixed platelets does not indicate a separate type of exocytosis.

Aldehydes↗
PubMed1991

Rapid determination of the elevated Na(+)-H+ exchange in platelets of patients with essential hypertension using an optical swelling assay.

Accumulating evidence suggests an increased activity of the Na(+)-H+ exchanger in essential hypertension. The present investigation aimed at developing a test for routine measurements. Platelet-rich plasma was added directly to a cuvette placed into an aggregometer containing 140 mmol/l sodium propionate medium (pH 6.7, 37 degrees C). The accumulation of intracellular sodium due to activation of Na(+)-H+ exchange results in an osmotic cell swelling, which is detectable as a decrease in optical density (OD). This reaction reflects activation of the Na(+)-H+ exchanger since we observed (1) a dose-dependent inhibition by amiloride (inhibition constant, Ki = 10 mumol/l) and ethylisopropylamiloride (Ki = 0.07 mumol/l) and (2) a dependence on extracellular sodium of the OD changes. Electron microscopy of sodium propionate-treated platelets revealed a general swelling and a distinct decrease in electron density of the cytosol without other significant alterations. Quantification of Na(+)-H+ exchange activities was accomplished by calculating rate constants of the recorded changes in OD. Application of this assay to 20 essential hypertensives and 32 normotensives demonstrated an increased activity of the Na(+)-H+ exchanger in essential hypertensives (rate constants 29.8 x 10(-3) per s versus 21.7 x 10(-3) per s).

Adult↗
PubMed1990

The origin of the membrane convolute in degranulating platelets. A comparative study of normal and "gray" platelets.

Thrombin-stimulated normal platelets contain a membrane system of dilated channels with openings to the exterior. Whether these membranes originate from the surface connected system (SCS), the alpha-granules or internalized portions of the plasmalemma has not yet been defined. The present study traces in series of ultrathin sections the rearrangement of these membranes during shape change, degranulation and internalization of surface membranes in washed normal and "gray" platelets upon the stimulation with thrombin (1 IU/ml). Cationized ferritin (CF) was used as a surface marker in order to recognize internalized portions of the plasmalemma. Within the first seconds after stimulation, both normal and gray platelets changed their shape by extrusion of the SCS membranes. Simultaneously they started to internalize surface membrane and formed surface membrane invaginations closely attached to the outer rim of the cytoskeletal sphere which developed during the internal contraction. CF was internalized in these invaginations. CF was not observed within the system of dilated channels of stimulated platelets, however. Thrombin-stimulated gray platelets showed a markedly reduced number of dilated channels or none at all. This observation may be due to the fact "gray" platelets are deficient in alpha-granules. It is concluded that the dilated system of membranes in degranulated normal platelets originates from membranes of the alpha-granules which have performed compound exocytosis.

Blood Platelet Disorders↗
PubMed1990

Ultrastructure of the interaction between human platelets and polymerizing fibrin within the first minutes of clot formation.

In the presence of fibrinogen, thrombin induces the aggregation of platelets, the formation of fibrin, and the retraction of the fibrin network. Since these phenomena are initiated in the first minutes after stimulation, the platelet-fibrin interaction in the early stages of clot formation was investigated. To avoid the formation of high fibrin masses, which may obstruct the morphological evaluation, suspensions of washed platelets were diluted with homologous platelet-poor plasma and stimulated with thrombin. The incubation was stopped by fixation after different times and the clots were studied in series of ultra-thin sections. Between 30 and 60 s after stimulation, polymerizing fibrin was found to be situated predominantly within the contact spaces in aggregates of degranulating platelets. Assembling fibres were seen also in plasmalemmal invaginations located in the close vicinity of the constricting contractile cytoskeleton. Between 5 and 10 min after stimulation, fibres with increasing thickness were observed between the platelets and were internalized into deep-surface invaginations, which remained attached to the outer rim of the contractile cytoskeleton. Surface areas without connection to the cytoskeleton revealed no binding or internalization of fibres. Clots obtained after addition of cytochalasin (36 microM) showed no retraction. Fibrin was found to be bound on the whole surface of discoid and degranulated platelets but no internalization occurred. These results suggest that the association of the clustered fibrin(ogen)-receptor complexes to the contractile cytoskeleton and the formation of a constricting sphere leads to the retraction of the clot by internalization of the fibres.

Adenosine Diphosphate↗
PubMed1990

[Synthesis and pharmacologic testing of 1-oxo-pyridazine and 1-oxo-phthalazine-2-acetic acid derivatives].

The title compounds, starting from variously substituted beta-benzoylpropionic or beta-benzoylbenzoic acids, were prepared by cyclocondensation with alpha-ethylhydrazinoacetate monohydrochloride and subsequent alcaline hydrolysis or aminolysis of the 2-carbethoxymethyl-1,2,5,6-tetrahydro-1-oxo-pyridazines or 1,2-dihydro-1-oxo-phthalazines respectively. The 1-oxo-phthalazines 42 and 34 have a weak anticonvulsive effect. Like a large number of the other synthezized compounds, they show a central sedative component and are relatively nontoxic.

Acetates↗
PubMed1990

Pentylenetetrazole kindling impairs learning in mice.

Repeated administration of 35 mg/kg body weight pentylenetetrazole (PTZ) induced a kindling phenomenon and an impairment of inhibitory avoidance learning. In contrast, a single administration of the same dose PTZ had no effect on learning. Kindled mice showed impaired habituation of exploratory activity. The results may be of relevance for antiepileptic drug testing.

Animals↗
PubMed1989

Novel O-linked carbohydrate chains in the cellulase complex (cellulosome) of Clostridium thermocellum. 3-O-Methyl-N-acetylglucosamine as a constituent of a glycoprotein.

Alkaline borohydride treatment of the cellulosome of Clostridium thermocellum yielded two major oligosaccharide-alditols, namely D-Galp-beta(1----4)-D-GalOH and (formula; see text) The compounds, isolated via gel permeation chromatography and high performance liquid chromatography, were analyzed by monosaccharide analysis, methylation analysis, gas-liquid chromatography/mass spectrometry, fast atom bombardment/mass spectrometry, and one- and two-dimensional 500-MHz (COSY, HOHAHA, ROESY) 1H NMR spectroscopy. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis combined with blotting technology indicated that the tetrasaccharide is mainly associated with one of the cellulosome subunits.

Acetylglucosamine↗
PubMed1989

Antihypoxic effects of AWD 23-15 in mice and rats.

AWD 23-15 (6-Methyl-1,2,3,4-tetrahydro-pyrimidin-2,4 dion) which is known to improve learning and memory processes in laboratory animals, was investigated in several hypoxia models. The following results were obtained: 1. Increase of survival rate, 2. change in hypoxia-induced decrease of cerebral post-mortem adenylic energy charge and in concentrations of metabolic products in the brain and 3. antagonism of the hypoxia-induced decrease of dopamine release. However in the general behavioral test the drug was ineffective. These results support the idea that AWD 23-15 is a potential nootropic drug.

Adenine Nucleotides↗
PubMed1987

Specialized cell surface structures in cellulolytic bacteria.

The cell surface topology of various gram-negative and -positive, anaerobic and aerobic, mesophilic and thermophilic, cellulolytic and noncellulolytic bacteria was investigated by scanning electron microscopic visualization using cationized ferritin. Characteristic protuberant structures were observed on cells of all cellulolytic strains. These structures appeared to be directly related to the previously described exocellular cellulase-containing polycellulosomes of Clostridium thermocellum YS (E. A. Bayer and R. Lamed, J. Bacteriol. 167:828-836, 1986). Immunochemical evidence and lectin-binding studies suggested a further correlation on the molecular level among cellulolytic bacteria. The results indicate that such cell surface cellulase-containing structures may be of general consequence to the bacterial interaction with and degradation of cellulose.

Bacteria↗
PubMed1987

The exocytosis of human blood platelets. A fast freezing and freeze-substitution analysis.

Human platelets were stimulated with thrombin or collagen in order to induce the release of alpha-granules and dense bodies. The platelets were cryofixed in various stages of exocytosis and subsequently cryosubstituted in acetone containing 4% osmium tetroxide. The platelets embedded in araldite were analyzed in serial sections. The initial changes of the alpha-granules were characterized by an impressive swelling and a dispersal of the granular matrix. Swollen alpha-granules in different stages of exocytosis formed contacts. Between the attached membranes of the alpha-granules electron-dense connections were sometimes observed. In a later stage, the membranes formed a pentalaminar structure (apposition), typical for the prefusion state. After apposition, sequential fusion of single alpha-granules took place and fusions of single or of compound granules with the plasmalemma were observed. The formation of a pore on the platelet surface allowed the passage of granular constituents to the exterior. The dense bodies extruded their electron-dense contents in a similar way after fusion with the plasmalemma but, compared with the alpha-granules, after less extensive swelling. These findings suggest that swelling of the secretory organelles plays an important role for granule fusion and platelet exocytosis. There is some evidence that the characteristic "internal contraction" of cytoskeletal structures in stimulated platelets is not the driving force of the platelet release reaction. An involvement of membranes of the surface connected system in the secretory pathway could not be ascertained.

Blood Platelets↗
PubMed1986

Morphology of the interaction of collagen fibrils with normal human platelets and thrombasthenic platelets.

The ultrastructure of the platelet contacts with collagen fibrils (CF) as well as the course taken by CF on the platelet surface were studied on ultrathin sections of platelets and CF. Platelets from normal donors and from a patient with thrombasthenia were incubated in citrated plasma with collagen. For electron microscopy a protein-stabilizing fixation procedure was applied. Platelet-collagen contacts (PCC) are characterized by a distance of 7 +/- 3 nm between the platelet membrane and the CF; the gap contains electron-dense bridges. The PCC of normal and thrombasthenic platelets are morphologically identical. Hence, it is unlikely that the glycoproteins IIb/IIIa-complex, which is absent in thrombasthenic platelets, plays a significant role in the platelet collagen interaction. The CF induce random movements of the platelets and their pseudopods, whereby the fibrils, which often show multisite attachment, coil up around the platelet surface; they become bent and often display drastic directional changes. CF are found inside invaginations of the platelet membrane as well as in depressions of the platelet surface. These processes require an involvement of the platelet's contractile system, which appears to interact reversibly with the platelet plasma membrane.

Blood Platelet Disorders↗
PubMed1986

[Spectrum of the adverse effects of Cordemcura].

Side-effects of Cordemcura were verified in a relatively extensive repertoire of methods. Investigations of blood pressure activity, effect on heart frequency as well as PQ and QT times after continuous infusion, influence on diuresis and antidiuresis and behaviour to achieve results of a possible activity of the central nerve system were given priority. The proved vasodilatory qualities of Cordemcura become also evident in the rat blood pressure reduction due to higher dose as a result of i.v. injection. No hypotensive effect could be observed after oral administration of the drug. Heart frequency as well as PQ and QT times after i.v. infusion of 1 X 10(-4) mol/kg/min Cordemcura over a period of 15 min remained unchanged. Doses going far beyond therapeutically applied doses indicate a reduction of diuresis after oral administration of Cordemcura for rats. Only due to these high doses unspecific changes in the behaviour of rats and mice occurred. No specific central nerve system activity could be observed.

Aminopyridines↗
PubMed1986

[Effect of piracetam on passive avoidance learning in ethanol-treated mice].

Mice received pre- and postnatal drinking water containing 20% ethanol. Ethanol treatment significantly impaired learning, reflected by shorter latency to enter the dark compartment of the apparatus. This effect could be antagonized by the administration of twice daily 100 mg/kg piracetam for ten days. The ethanol treatment and the administration of piracetam did not affect the step-through latencies in the training situation.

Animals↗