Search PubMed⌕ Search

Biomedical subjects

E Unger

Publications and source records attributed to E Unger.

At least 91 records · Page 5Linked to original sources
PubMed1991

Detailed toxicity studies of liposomal gadolinium-DTPA.

Acute, subacute, and delayed toxicity testing was assessed in mice for liposomal gadolinium-DTPA (Gd-DTPA), blank liposomes, and nonliposomal Gd-DTPA. In the subacute experiments mice were injected intravenously (IV) with 0.3 mmol/kg Gd-DTPA per day for 30 days in the form of either free Gd-DTPA, liposomal Gd-DTPA, or an equivalent amount of lipid in blank liposomes without Gd-DTPA. The interpolated acute LD50 of liposomal and nonliposomal Gd-DTPA, estimated as a means of identifying the approximate level, was similar (LD50 = 5.7 mmol/kg Gd-DTPA). In subacute toxicity testing, prolonged high doses of liposomal Gd-DTPA caused splenomegaly, cardiomegaly, lymphocytopenia and hypergammaglobulinemia (P less than .05). Nonliposomal Gd-DTPA caused mild cardiomegaly and altered liver enzymes (P less than .05). Blank liposomes caused relatively mild splenomegaly (P less than .05) but few other changes. Delayed testing three months after the subacute testing showed that most of the changes caused by the liposomal Gd-DTPA were reversible.

Animals↗
PubMed1991

The microtubule system and the reduplication of microtubule organizing centres in Dictyostelium discoideum.

The microtubule system of normal and microtubule-poisoned amoebae of Dictyostelium discoideum has been investigated both by indirect immunofluorescence with antibodies to microtubule proteins and electron microscopy. Nocodazole, like some other microtubule poisons, destroys most of the microtubules in both interphase and dividing cells resulting in an inhibition of nuclear and cell division. The microtubule organizing centres, however, continue to duplicate once or twice. The daughter organizing centres segregate, they seem to be connected with nuclear material, that splits partly, too, forming more or less extended nuclear clefts. This segregation, at least over short distances, takes place without intranuclear microtubules. Duplication of microtubule organizing centres is not strictly correlated with nuclear division and cytokinesis. Microtubule poisons are able to uncouple these events. Different levels of regulation should be responsible for microtubule organizing centre, nuclear, and cell division.

Animals↗
PubMed1991

Can coated vesicles bind directly to microtubules?

Using an ultrathin-sectioning electron microscopic procedure, no efficient binding of coated vesicles to microtubules (both purified from brain tissue) could be achieved, independently of the presence of microtubule-associated proteins. Addition of the ATP analogue AMP-PNP or the inorganic tripolyphosphate, known to cause tight associations of (uncoated) vesicles to microtubules by means of specific motor proteins, could not enhance the binding efficiency. Moreover, crude preparations of clathrin, the major protein of the coat, did not affect the turbidity course of microtubule assembly. These results were confirmed by electrophoresis indicating that within the preparations of microtubule protein, obtained by temperature-dependent cycles of disassembly/reassembly, constituents of coated vesicles were not present. Beside this, coated vesicles have never been found among microtubules reconstituted in vitro. Vice versa, preparations of coated vesicles were completely free of microtubules. Our results suggest that further proteins should be involved in the binding of coated vesicles to microtubules, if there is indeed a biologically relevant interaction.

Animals↗
PubMed1990

Inhibition of microtubule assembly in vitro by anti-tubulin monoclonal antibodies.

Five monoclonal antibodies against N-terminal domains of alpha- or beta-tubulin were tested for their ability to interfere with the in vitro formation of microtubules. Although all the antibodies exhibited similar association constants for immobilized tubulin, they differed in their inhibitory effect on microtubule assembly. For the most potent antibody, TU-13, the antibody/tubulin molar ratio of about 1:320 was sufficient for a 50% inhibition. The data indicate that the surface regions of N-terminal domains of tubulin are involved in the formation of microtubules.

Animals↗
PubMed1990

The effect of lipid composition on the relaxivity of Gd-DTPA entrapped in lipid vesicles of defined size.

The effects of lipid composition on the relaxivity of gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) entrapped in lipid vesicles has been examined for vesicles of different sizes composed of egg phosphatidylcholine and cholesterol in various molar ratios, as well as the stability of those same vesicles in human serum at 37 degrees C. It is found that the incorporation of cholesterol decreases the apparent relaxivity of the entrapped Gd-DTPA, concomitant with an increase in vesicle stability in serum. Cholesterol has little effect on relaxivity when incorporated at ratios up to 20 mole percent, but has an increasing effect at higher mole percentages. These results correlate with the known effects of cholesterol on the osmotic water permeability coefficients of various model membrane systems and suggest that it is the water flux across the vesicle bilayer that is limiting to the T1 relaxivity of the entrapped Gd-DTPA. The incorporation of up to 20 mole percent cholesterol has little effect on the stability of the vesicles in serum, whereas vesicles containing more than 20 mole percent cholesterol show greater increases in stability. It was also found that the stability of vesicles depends upon the size of the vesicles; smaller vesicles are less stable in human serum at 37 degrees C than larger vesicles.

Blood↗
PubMed1990

Structural diversity and dynamics of microtubules and polymorphic tubulin assemblies.

Tubulin, the main protein of microtubules (MTs), has the potency of forming a variety of other assembly products in vitro: rings, ring-crystals, C- and S-shaped ribbons, 10 nm fibres, hoops, sheets, heaped sheets, MT doublets, MT triplets, double-wall MTs, microtubules, curled ribbons, and paracrystals. The supramolecular subunits of all of them are the protofilaments which might be arranged either parallel to the axis (e.g., in MTs, ribbons) or curved (e.g., in hoops, microtubules). There is strong evidence that in the second case the protofilaments have an inside-out orientation compared to MTs. All assembly products mentioned are described structurally and their relevance to the in vivo situation is considered. Moreover, MTs and the other assemblies undergo permanent changes. These dynamics occurring in both individual assemblies and assembly populations are discussed from the structural point of view.

Animals↗
PubMed1990

Biodistribution and clearance of liposomal gadolinium-DTPA.

Gadolinium-DTPA (Gd-DTPA) liposomes have been studied previously as liver contrast agents and have been shown to improve the detection of hepatic metastases in rats. We synthesized 100-nm and 50-nm liposomes that encapsulated Gd-DTPA and did biodistribution and clearance studies in rats. Parallel magnetic resonance imaging (MRI) studies were also done. Biodistribution showed a prolonged blood pool phase for Gd-DTPA liposomes with a blood pool half-life of approximately 4 hours for the 100-nm liposomes. The highest uptake per gram of tissue was achieved by the spleen. Clearance of gadolinium from the liver and spleen showed a half-life of 3 to 4 days. The smaller 50-nm Gd-DTPA liposomes resulted in a longer blood pool phase and a higher delivery of gadolinium to the liver, bone marrow, and spleen. Imaging studies after intravenous (IV) administration of liposomal Gd-DTPA showed organ enhancement that paralleled the data on biodistribution studies, with appreciable hepatic enhancement at doses as low as 0.025 mm/kg of liposomal Gd-DTPA.

Animals↗
PubMed1990

Metabolism in vitro of cartilage proteoglycans in rat (pre)chondrocytes from different embryonic regions.

Diabetes in the mother may cause disturbances in the chondrocyte development in the embryo. A rat model was used to investigate whether this was reflected in the production of proteoglycans by cells from two embryonic regions. One of these regions is resistant (limb bud) and the other susceptible (mandibular arch) to malformation in diabetic pregnancy. Chondroitin sulphate proteoglycans from cultures of day-12 rat embryo limb bud and mandibular arch chondrocytes were extracted with guanidine-HCl and analyzed by gel chromatography after in vitro 35S-sulphate-labeling. Two sizes of proteoglycans (Kav 0.26 and 0.66 on CL-2B Sepharose) were found in both types of chondrocytes and in all media. The polysaccharide chain length was the same (Kav 0.36 on CL-6B Sepharose) for both proteoglycans. Elevated levels of D-glucose or beta-hydroxybutyric acid had no effect on either proteoglycan size or proportion, nor on polysaccharide chain length. However, there were differences (in all culture conditions) between limb bud and mandibular arch cultures in that the larger proteoglycan accounted for 80% of total radioactivity in the limb bud cultures, 53% in the mandibular arch cultures, and only 25-29% in the media from both types of cultures. Furthermore, different ratios between radioactive proteoglycans in medium and matrix suggested markedly different efficiencies for matrix formation in the two cell types. These findings indicate differences in the metabolism of the proteoglycans in these two cell types which may be related to the induction of mandibular malformation in diabetic pregnancy.

Animals↗
PubMed1990

Structural comparison of assemblies from brain microtubule proteins of different vertebrates.

Formerly, we reported for microtubule protein (MTP), i.e. tubulin plus microtubule-associated proteins (MAPs), from porcine brain that the protofilament number of microtubules and the percentage of aberrant assemblies depend on taxol and MAP activity (Böhm et al., BBA 800, 119, 1984). Now, it is demonstrated that these effects can be also observed when MTPs from other higher vertebrate brains (Guinea pig, mouse chicken) were used. Comparing the structural features of assemblies formed from these kinds of MTP with each other no significant differences were found, excepted chicken MTP which produces more aberrant assemblies in the presence of taxol.

Actin Cytoskeleton↗
PubMed1990

Determination of the protofilament number in microtubules by templates.

We have used microtubules (MTs) and double-walled microtubules (dwMTs), both fragmented, as templates for MT formation from phosphocellulose-purified tubulin. In both cases the mean protofilament number of the nucleated MTs corresponds to that of the templates. The results confirm the observations of Scheele et al. (J. Mol. Biol. 154, 485, 1982) that templates determine the protofilament number of nucleated MTs.

Actin Cytoskeleton↗
PubMed1990

Effect of sodium chloride on the structure of tubulin assemblies.

By use of a taxol-containing assembly medium, it has been demonstrated that the mean protofilament number of microtubule populations is significantly lower at elevated NaCl concentrations. Assembly of microtubule protein, i.e. tubulin plus microtubule-associated proteins (MAPs), at 80 and 580 mM NaCl results in microtubule populations with mainly 13 and 10 protofilaments whereas microtubules formed from tubulin alone have 12 and 10 protofilaments, respectively. Moreover, when MAPs are prevented from assembly, the formation of taxol-induced aberrant assemblies (C- and S-shaped protofilament ribbons) is suppressed at high NaCl concentrations in favour of microtubules. The described effects are obviously caused by both weakening of MAP binding to tubulin and alterations in tubulin-tubulin association.

Actin Cytoskeleton↗
PubMed1990

Structural changes within mixed populations of microtubules and protofilament ribbons caused by dilution and cold incubation.

By means of electron microscopy we have investigated the influence of dilution and cold incubation (0 degree C) on mixed populations of tubulin assemblies consisting of microtubules (MTs) and protofilament ribbons with C- and S-shaped profiles formed in the presence of glycerol. Dilution results in a partial disappearance of ribbons, whereas cold incubation causes a decrease of the percentage of MTs in favour of C-ribbons, probably produced by splitting of MT ends. In the case of dilution, we assume a lower dynamic stability of ribbons compared with MTs, which was already observed during long-time incubation of mixed population (Böhm et al., Biochem. Biophys. Acta 929, 154, 1987), whereas the splitting effect in the cold should be caused by the deficiency of MT-bound microtubule-associated proteins (MAPs), which is observed in the presence of glycerol.

Actin Cytoskeleton↗
PubMed1990

[Effect of alloxans on pancreatic B-cells with special regard to the alloxan-metal-complex theory. I. Effects of alloxan, alloxan-zinc chelates, dilauric acid and colchicine on blood sugar and rate of mitosis of B-cell Langerhans islets].

Alloxan, alloxan-zinc-chelate, sodium salt of dialuric acid, and colchicine significantly raised the blood sugar level under the previously mentioned experimental conditions 28 h after the application. The typical three-phase blood sugar curve development after alloxan (initial hyperglycemia, hypoglycemia, permanent hyperglycemia) was only approximately reached by dialuric acid which initiated, however, instead of the initial hyperglycemia a more pronounced hypoglycemic phase within the first 6 h. Alloxan-zinc-chelate protractedly and significantly made the blood sugar's increase up to the 7th d post injectionem, without being able to maintain a permanent hyperglycemia with half-normal dosage in comparison with alloxan. Non-diabetogenic alloxan doses (19 mg/kg i. v.) and the appropriate alloxan-zinc-chelate dosage (35 mg/kg) led to a significant increase of the blood sugar only in the chelate group with the long-term test up to 10 d, suggesting an increased and prolonged effect of the metal-chelates by stabilization of alloxan. The tested substances differently acted on the mitotic frequency of B-cells. The mitosis did not increase in the alloxan-zinc- and dialuric acid treated animals and was similar to normal animals far below the fractions of 1/10(6). A 4- and 5-fold increase of the mitotic frequency in the colchicine or alloxan treated animals as well as an accumulation of delayed metaphases suggest an impeded transition to the anaphase and include alloxan among the mitotic poisons.

Alloxan↗
PubMed1990

[Mechanism of action of alloxan on pancreatic B-cells with special regard to the alloxan-metal-complex theory. II. Actions of alloxan, alloxanic acid, Zn2+ and ethyleneglycol-bis-(beta-aminoethylether)-N,N'tetraacetic acid (EGTA) on the assembly of microtubule proteins (MTP) into microtubules or MPT sheets in vitro].

Analyses of the cell structures in the islets of Langerhans revealed the presence of 2 predominant cations, calcium (beta-granules and saccules, mitochondria, sac membranes, and cell membranes) and zinc (secretory granules, encasing membraneous sacs) in association with organelles which involve directional secretion. Both elements are known to interact with microtubules influencing their structural and functional properties, e.g. movement of secretory granules. Influences of Zn2+ on microtubules are investigated with a view to interactions in vitro with and without diabetogenic substances. Turbidimetry and electron microscopic investigations showed that under the conditions mentioned above, alloxan of a concentration of 2 x 10(-5) mol/l (alloxan/tubulin 1:1) inhibits the formation of microtubules and increases the portion of microtubules stabilized of 4 degrees C. The Zn2(+)-induced formation of MTP sheets is not influenced by alloxan and the metal complex forming agent EGTA, if the molar concentrations of the substance and Zn2+ are equally high. With a molar proportion of 2:1 (EGTA:Zn2+), the formation of sheets does not longer occur and only microtubules are formed, whereas neither sheets nor microtubules were assembled by alloxan with this molar proportion. However, neither the assembly of microtubules nor the formation of Zn2(+)-induced sheets are influenced by alloxanic acid in both molar proportions. It is shown that the diabetogenic alloxan influences the formation of microtubules and that performed microtubules are destroyed. This result of alloxan corresponds to its antimitotic activity analogously to the wellknown effect of colchicine (s. Schmidt et al. 1990).(ABSTRACT TRUNCATED AT 250 WORDS)

Alloxan↗