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Biomedical subjects

E Unger

Publications and source records attributed to E Unger.

At least 73 records · Page 4Linked to original sources
PubMed1994

Toluene abuse: physical basis for hypointensity of the basal ganglia on T2-weighted MR images.

PURPOSE: To explain the hypointensity in the basal ganglia on T2-weighted magnetic resonance (MR) images of brains of toluene abusers. MATERIALS AND METHODS: Eight patients with histories of toluene abuse underwent MR imaging. A bilayered model of dipalmitoylphosphatidylcholine (DPPC; 100 mmol/L concentration) and varying concentrations of toluene was formed. The DPPC control and toluene-mixed bilayers underwent MR imaging. T1 and T2 were measured as a function of toluene and lipid concentrations. RESULTS: T2-weighted images of patients who had abused toluene showed marked hypointensity in the thalami and moderate hypointensity in the basal ganglia. Measurements of the DPPC-toluene phantom indicated that toluene-tainted lipid bilayers dramatically shortened T2 and had little effect on T1. By comparison, DPPC itself had little discernible effect on either T1 or T2. CONCLUSION: This model suggests that partitioning of toluene into the lipid membranes of cells in cerebral tissue may be responsible for the hypointensity of basal ganglia noted on T2-weighted MR images of brains of toluene abusers.

Adult↗
PubMed1993

Effects of the fluorescence dye DAPI on microtubule structure in vitro: formation of novel types of tubulin assembly products.

It has been found that the DNA fluorescence dye 4',6-diamidino-2-phenylindole (DAPI) is able to stain also microtubules. However, electron microscopy revealed that DAPI changed microtubule structure and induced the formation of a broad spectrum of polymorphic tubulin assembly products. Upon addition of DAPI to microtubules assembled from 10 to 15 mumol tubulin (molar DAPI/tubulin ratios of 10 to 40) in the presence of microtubule-associated proteins, most of the microtubules were decorated with additional protofilaments usually running parallel to the protofilaments of the microtubule wall (microtubule-protofilament complexes). When DAPI was already present during assembly, curved C- and S-shaped protofilament ribbons and microtubule-ribbon complexes with 6-shaped profiles were the most prominent products, beside microtubules. Additionally, protofilament bundles, some flat sheets, and hoops occurred. Electrophoresis revealed that DAPI lowered the amount of associated proteins, especially of tau-proteins, bound to the assembly products. Nevertheless, DAPI stimulated the assembly, enabled pure tubulin to assemble even at concentrations as low as 10 mumol, and stabilized the assembly products against cold. The microtubule-protofilament complexes, observed for the first time, are interpreted as the result of DAPI-induced protofilament linking as well as of activation of an additional tubulin-tubulin binding site which is possibly identical to that involved in the formation of microtubule doublets.

Animals↗
PubMed1993

Manganese-based liposomes. Comparative approaches.

RATIONALE AND OBJECTIVES: The purpose of this study was to further develop and compare manganese-based liposomes prepared by two different approaches wherein a manganese ion was entrapped within the internal aqueous space of the vesicles or into the bilayer surface via membrane bound complexes. METHODS: Small unilamellar liposomes (SUVs) were prepared entrapping manganese chloride. Alkylated complexes of manganese were prepared and also incorporated into SUVs. The two different manganese-based liposomes were compared for in-vitro relaxivity, stability, toxicity, and in-vivo imaging in rats with liver tumors. RESULTS: Liposomes entrapping manganese had a concentration-dependent change in relaxivity that was maximal at a several-fold molar excess of phospholipid relative to manganese ion. Liposomes bearing membrane-bound complexes showed relaxivity inversely proportional to vesicle size. In-vivo imaging showed greater and more specific hepatic enhancement with manganese liposomes bearing alkylated complexes than those entrapping manganese ion. CONCLUSIONS: Correlation effects likely explain the increased relaxivity of manganese entrapped in phospholipid vesicles. Greater efficacy, however, is afforded by liposomes bearing alkylated complexes.

Animals↗
PubMed1993

Gas-filled liposomes as echocardiographic contrast agents in rabbits with myocardial infarcts.

RATIONALE AND OBJECTIVES: The authors evaluated gas-filled liposomes as echocardiographic contrast agents in rabbits with myocardial infarcts. METHODS: Ten rabbits underwent ligation of the left anterior descending coronary artery. Five animals underwent echocardiography before and after production of myocardial infarct (MI) and four animals had post-MI imaging only. In either case, images were obtained before and after injection of a single dose of 1 mL of gas-filed liposomes. Three radiologists blinded to clinical information reviewed the pre- and postcontrast images and assessed endomyocardial border definition, wall motion, confidence levels for normal versus abnormal wall motion and visualization of papillary muscle and mitral valve. RESULTS: Postcontrast scans showed significant improvement (P < .05) in endomyocardial border definition, visualization of wall motion, papillary muscle and mitral valve as well as increased reader confidence level. CONCLUSIONS: These results are encouraging and suggest that gas-filled liposomes may be a useful contrast agent for echocardiography.

Animals↗
PubMed1993

Tissue thermometry during ultrasound exposure.

In order to quantify ultrasound therapy it is important to measure the tissue temperature during the treatment. Invasive probes induce several artifacts in ultrasound fields. The magnitude of these artifacts is probe dependent. Several different probes were evaluated for hyperthermia purposes in this study. An alternative noninvasive method to evaluate the temperature elevations and tissue damage is to use magnetic resonance imaging. The fast imaging sequences used in this study are marginally useful for monitoring hyperthermia. However, these imaging sequences can be utilized to guide and monitor ultrasound surgery.

Animals↗
PubMed1992

Permeability of liposomal membranes to water: results from the magnetic field dependence of T1 of solvent protons in suspensions of vesicles with entrapped paramagnetic ions.

The diffusive permeability to water molecules, Pd, of lipid vesicles with entrapped paramagnetic solute ions can be determined rapidly from analysis of the magnetic field dependence (nuclear magnetic relaxation dispersion, or NMRD profile) of T1 of exterior solvent water protons. Such data yield tau, the mean lifetime of solvent molecules inside the vesicles, from tau = (fT1Para) - T1Ves, where f is the volume fraction of entrapped water, T1Para is the observed T1 corrected for buffer background, and T1Ves is the relaxation time of water protons in the entrapped solution. For small spherical unilamellar vesicles of inner radius R, Pd = R/3 tau, f can be obtained accurately from knowledge of both the concentration of Gd(DTPA)2- in the solution in which the vesicles were formed and the average concentration of ions in the final sample. At low temperatures, in the limit of slow exchange, T1Para becomes independent of field and tau = fT1Para; the observation of a field-independent profile is a control that confirms that no paramagnetic material is external to the vesicles. We have measured T1Para, using a field-cycling relaxometer, for suspensions of POPC (1-palmitoyl-2-oleoyl-lecithin) vesicles with 100-500 mM entrapped Gd(DTPA)2- and membrane concentrations of cholesterol ranging from 0 to 40 mol %. These profiles, which span the field range 0.01-50 MHz proton Larmor frequency, were taken at 5, 15, 25, and 35 degrees C. Concentrations of Gd(DTPA)2- were determined independently by both ICP analyses and NMRD methods. Values for Pd for vesicles with 100 mM Gd(DTPA)2- and outer diameters 100 nm +/- 20%, as determined by quasielastic light scattering, are 63, 47, 24, 16, and 8.7 x 10(-4) cm s-1, at 25 degrees C, for cholesterol concentrations of 0, 10, 20, 30, and 40%, respectively. The corresponding activation enthalpies are 14, 14, 14, 17, and 17 kcal/M. Comparison with 2H NMR studies of deuterated POPC vesicles with no cholesterol at 20 degrees C, and with 10% at 40 degrees C, which yielded the same order parameter for the palmitoyl acyl chains, gives no indication of a correlation between order parameter and permeability.

Contrast Media↗
PubMed1992

Regionally disturbed production of cartilage proteoglycans in malformed fetuses from diabetic rats.

Fetuses from normal and manifestly diabetic rats were obtained on pregnancy day 20. The fetuses from the diabetic rats were of normal or malformed morphology. Three tissue groups were dissected free; costal cartilage, the hard tissue of the rear, and of the frontal portion of the mandible. These tissues were maintained in vitro for 24 h during which time they were labelled with [35S]sulphate. After the culture period the tissues were extracted with guanidine HCl and the resulting residues were further extracted with alkali. The culture medium was saved and its macromolecular content was compared to that of the extracts. The proteoglycans recovered in all extracts eluted at two distinct positions after chromatography on a Sepharose CL-2B column (peak I: Kav approximately 0.4, and peak II: Kav approximately 0.8), but the elution patterns were markedly different in extracts from various tissues. Thus, in rib cartilage, the majority of the labelled proteoglycans were located in peak I (approximately 90%) with no difference between extracts of fetuses from normal and diabetic pregnancies. In extracts of mandibular cartilaginous tissue from normal rat offspring the peak I percentage (60-80%) was lower than in the rib cartilage extracts. In the extracts from the frontal portion of malformed mandibles of fetuses of diabetic rats, the peak I percentage (35 +/- 21%) was the lowest of all recorded and the only one to significantly differ from the other percentages in its (the frontal mandible) group. The results show an association between a congenital malformation, micrognathia, and a disturbance in the production of chondroitin sulphate proteoglycans in the malformed region.

Analysis of Variance↗
PubMed1992

Fluorenone-azomethines, a novel class of microtubule inhibitors that specifically affect cell proliferation.

The effects of various azomethine derivatives on microtubule (MT) assembly in vitro as well as on cell proliferation, cell shape, and the cytoskeleton of some cultured murine cell lines were studied. 3 of them, the alpha-diphenylene-N-(p-[bis-(beta-hydroxyethyl)-amino]-phenyl)-nit rone (DHPN), alpha-diphenylene-N-(p-[N-(hydroxyethyl)-N-(gamma-hydroxypropyl)- amino]-phenyl)-nitrone, and alpha-diphenylene-N-(p-diethylaminophenyl)-nitrone, strongly inhibit the assembly of microtubules (MTs) in vitro (50% inhibition at 4 to 7 mumol/l). The same compounds are also able to disrupt preformed microtubules. Moreover, they were found to inhibit proliferation of leukaemia L 1210, melanoma B16 K, fibroblast L 929, and embryo fibroblast cells down to 1 to 10 mumol/l, completely. Immunofluorescence microscopy revealed that DHPN, used as a representative of the active azomethines, causes a reversible destruction of the microtubule part of the cytoskeleton. Apparently resulting from microtubule disruption, the intermediate filament system collapsed whereas the microfilament system remained unaffected. The results indicate that the antiproliferative action of the azomethines is based, at least partially, on their ability to attack microtubules.

Animals↗
PubMed1992

Lymphatic imaging in experimental filariasis using magnetic resonance.

RATIONALE AND OBJECTIVES: To evaluate acquired lymphatic abnormalities caused by filariasis, the authors examined the peripheral lymphatic system in normal ferrets and those chronically infected with Brugia malayi using magnetic resonance imaging (MRI). The findings were compared with previously obtained lymphangioscintigraphic (LAS) images in ferrets both with and without experimental filariasis. METHODS: Fifteen ferrets (11 infected with B. malayi and four noninfected controls) underwent whole body coronal MRI using a quadrature transmission-receive head coil at 0.5 Tesla operating at a resonant frequency of 21.5 mHz for protons with a 25-cm field of view. RESULTS: In contrast to normal animals, infected ferrets showed dilated hindlimb dermal lymphatic collaterals, enlarged high-signal intensity groin lymph nodes with punctate low-signal intensity centers and separate low-signal intensity spots with irregular thin channels, suggestive of nests of viable adult nematodes within tortuous lymphatics and nodes. MRI correlated with the LAS findings, and the interpretations were supported by light, scanning electron, and video microscopy. CONCLUSIONS: T2-weighted MRI in conjunction with LAS accurately depicts the peripheral lymphatic system in filarial-infected ferrets. These two modalities are useful complementary techniques to examine disorders characterized by lymphatic insufficiency.

Animals↗
PubMed1992

MR lymphography with iron oxide compound AMI-227: studies in ferrets with filariasis.

OBJECTIVE: The purpose of this study was to assess the MR lymphographic potential of AMI-227 to reduce the signal intensity of hyperplastic inflammatory lymph nodes by using ferrets with filariasis as the animal model. Both interstitial and IV modes of administration were studied. MATERIALS AND METHODS: Twelve ferrets were infected with the filaria Brugia malayi and six control ferrets were injected with super-paramagnetic iron oxide AMI-227, either interstitially or IV. Signal intensities of the left popliteal lymph node, left hamstring muscle, and left inguinal fat were measured before, 48 hr after, and up to 138 days after contrast injection with the use of both spin-echo and gradient-echo techniques. The signal intensity data were statistically analyzed. The lymph nodes, liver, spleen, and lungs were studied with light and electron microscopy. RESULTS: Forty-eight hours after the interstitial injection of AMI-227, the signal intensities of the ipsilateral popliteal nodes of the infected and control ferrets were significantly reduced (p less than .0005) without significant changes in the signal intensities of the surrounding tissues on both spin-echo and gradient-echo MR images. No nodal signal reduction occurred with the IV route of injection in ferrets. Light microscopy revealed iron to be localized within nodal marginal zones exclusively. Lymphatic trunks were visualized after interstitial injection. Signal reduction persisted to our end point at 138 days. CONCLUSION: AMI-227 shows regional specificity with significant enhancement of nodal structures and demonstrates potential as an interstitial MR lymphographic agent.

Animals↗
PubMed1991

Decreased activity of the heparan sulfate-modifying enzyme glucosaminyl N-deacetylase in hepatocytes from streptozotocin-diabetic rats.

N-Deacetylation is the initial polymer modification step in heparan sulfate biosynthesis and a prerequisite to subsequent N- and O-sulfation. It has previously been shown that the sulfation of liver heparan sulfate is lowered in diabetes (Kjellén, L., Bielefeld, D., and Höök, M. (1983) Diabetes 32, 337-342). To investigate whether the reduced sulfation is the result of a lowered N-deacetylase activity, we have assayed this enzyme in hepatocytes from streptozotocin-diabetic rats. In addition, the activity of the glucuronosyl C5-epimerase, which catalyzes a modification reaction subsequent to N-sulfation, was measured. The deacetylase activity, expressed per microgram of cell protein, was about 40% lower in diabetic hepatocytes as compared with control cells, whereas the epimerase activity was unaffected. Recently, a approximately 110-kDa glycoprotein that carries N-sulfotransferase activity was identified as one of at least two protein components required for N-deacetylation in mouse mastocytoma tissue (Pettersson, I., Kusche, M., Unger, E., Wlad, H., Nylund, L., Lindahl, U., and Kjellén, L. (1991) J. Biol. Chem. 266, 8044-8049). We therefore investigated if the lowered N-deacetylase activity in diabetes could be ascribed to a deficiency in either one of the corresponding rat components. The results indicated that (i) the glycoprotein component is present in limiting amounts in both control and diabetic cells, (ii) diabetes results in a lowered activity of this component, and (iii) excess amounts of the additional protein(s) needed for N-deacetylase activity are present in both control and diabetic cells.

Amidohydrolases↗
PubMed1991

Biosynthesis of heparin. Purification of a 110-kDa mouse mastocytoma protein required for both glucosaminyl N-deacetylation and N-sulfation.

The polymer modification process in the biosynthesis of heparin/heparan sulfate is initiated by N-deacetylation, followed by N-sulfation, of N-acetylglucosamine units. Chromatography of a detergent extract from mouse mastocytoma on wheat germ agglutinin-Sepharose yielded a protein fraction, eluted with 0.3 M N-acetylglucosamine, that expressed N-deacetylase activity, but only after recombination with proteins that did not bind to the lectin column. In subsequent purification of the active lectin-bound component, all assays were performed following addition of the unbound protein fraction. After two additional chromatography steps, on blue Sepharose and 3',5'-ADP-agarose, the lectin-binding N-deacetylase component had been purified about 4300-fold with an 11% yield and showed essentially a single band, corresponding to an apparent molecular weight of approximately 110,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Analysis of the purified 110-kDa protein showed that it contained, in addition to the N-deacetylase, N-sulfotransferase activity; however, the expression of N-sulfotransferase activity was independent of additional proteins. Backtracking the N-sulfotransferase through the purification scheme previously applied to the N-deacetylase showed the two enzyme activities to the N-deacetylase showed the two enzyme activities to be cofractionated in each separation step. It is proposed that the expression of glucosaminyl N-deacetylase activity depends on the concerted action of (at least) two protein components, one of which also possesses glucosaminyl N-sulfotransferase activity.

Amidohydrolases↗
PubMed1991

Liposomes as MR contrast agents: pros and cons.

Liposomes are generally thought of as being useful for entrapping drugs within their internal aqueous space. When used with MR contrast agents, this has the drawback that water flux across the membrane bilayer is limiting to contrast enhancement. This can be partially overcome by making the liposomes very small, such that surface area is relatively great compared to internal volume, thereby facilitating water exchange. Alternatively the membranes can be designed to be permeable to water but this may render the vesicles unstable in serum. Another approach is to incorporate the contrast agents into the lipid bilayer. By designing novel complexes of manganese with the ligands incorporated onto dual acyl chains, we have achieved R1 and R2 values of over 20/mmol sec-1 or more than five times higher than Gd-DTPA. Hepatic metastasis detection is significantly improved in rats at doses of only 10 mumol/kg manganese. Membrane-bound manganese complexes function as highly effective liver imaging agents and merit further study for development as agents to undergo human clinical trials.

Animals↗
PubMed1991

A laryngeal pacemaker for inspiration-controlled, direct electrical stimulation of the denervated posterior cricoarytenoid muscle in sheep.

Bilateral recurrent nerve palsies were induced in four sheep and unilateral nerve palsy in one sheep. Vocal cord abductions were achieved by direct electrical stimulation of the posterior cricoarytenoid muscles (PCMs). By means of the diaphragmatic myogram, respiratory synchronous activation of the glottis opening musculature was shown possible. In all cases an adequate glottis opening for respiratory function was achieved during a maximum period of stimulation of 5-8 h in each animal. Abductor movements of the vocal cords were documented with video laryngoscopy. Using digital image processing, the areas of the open glottis were measured at rest and during bilateral direct electrical stimulation of the PCMs.

Animals↗
PubMed1991

Effect of insulin on the altered production of proteoglycans in rib cartilage of experimentally diabetic rats.

Costal cartilage from experimentally diabetic rats, labeled in vivo or in vitro with [35S]sulfate, was shown to incorporate less label into proteoglycans than cartilage from nondiabetic rats. Analyses of guanidine HCl cartilage extracts by gel chromatography on Sepharose CL-2B showed two major peaks at Kav approximately 0.4 and 0.8 (peaks I and II, respectively). Cartilage extracts from the diabetic rats contained predominantly peak II proteoglycans, while 60 and 55%, respectively, of the total 35S-labeled proteoglycans extracted from control cartilage labeled in vivo and in vitro with [35S]sulfate were present in peak I. After insulin treatment of the diabetic rats, the relative amount of peak I 35S-labeled proteoglycans synthesized in vivo was increased to 70%. The overall in vivo incorporation of [35S]sulfate into proteoglycans was also stimulated in diabetic rats treated with insulin to levels above those found for control rats. Thus, diabetes-induced changes in the biosynthesis of rat costal cartilage proteoglycans may be alleviated by normalization of the diabetic state by insulin treatment. However, addition of insulin (10(-5)-10(-9) M) to the culture medium did not affect the amount of 35S-labeled proteoglycans synthesized in vitro or the relative amounts of peak I proteoglycans produced by control or diabetic cartilage, suggesting that insulin does not have a direct effect on proteoglycan production. Moreover, no decrease in the amount of 35S-labeled proteoglycans produced was found when glucose at high concentrations was present in the culture medium. However, the presence of rat serum resulted in an increase in the amount of 35S-labeled proteoglycans produced by both control and diabetic cartilage, demonstrating that the cartilage explants were metabolically responsive to stimulatory factors.

Animals↗