Search PubMed⌕ Search

Biomedical subjects

S Jung

Publications and source records attributed to S Jung.

At least 127 records · Page 7Linked to original sources
PubMed1997

Diffusion characteristics of placental preparations affect the digoxin passage across the isolated placental lobule.

Our aim was to evaluate the isolated placental lobule to study maternofetal transplacental digoxin transfer and accumulation in placental tissue in vitro. Digoxin passage across the isolated lobule of 10 human placentas was calculated from repeated fetal and maternal perfusate samples, and placental tissue digoxin concentrations were measured at the end of the experiments. To determine the degree of overlap of the fetal and the maternal circulation, the antipyrine clearance was used. Digoxin disappearance from the maternal circuit was not significantly affected by the degree of overlap. In contrast, the increase of digoxin in the fetal compartment was significantly higher in "well-perfused" placentas (antipyrine clearance > 1.60 ml/min; n = 5) than in "malperfused" placentas (antipyrine clearance < 1.50 ml/min; n = 5) (end-feto to initial maternal digoxin ratio 0.44 +/- 0.08 vs. 0.30 +/- 0.08; p < 0.05), whilst the accumulation in placental tissue was higher in the latter group (0.45 +/- 0.07 vs. 0.62 +/- 0.10 ng/mg protein; p < 0.05). We conclude that the isolated placental lobule is suitable to quantify transplacental digoxin transfer in vitro, but the diffusion characteristics of each preparation have to be considered.

Anti-Arrhythmia Agents↗
PubMed1997

Slow AV nodal pathway ablation utilizing a unique temperature controlled radiofrequency energy system.

Thirty-nine consecutive patients with symptomatic AV nodal reentrant tachycardia (AVNRT) underwent temperature guided slow AV nodal pathway ablation (group 1). Forty-three consecutive patients undergoing nontemperature guided slow AV nodal pathway ablation late in our experience compose the control population (group 2). Slow pathway ablation was achieved in all patients of both groups. The mean fluoroscopy and ablation times for group 1 were significantly shorter than for group 2 (26.1 +/- 14.9 vs 33.9 +/- 18.9 min, P < 0.05; 19.9 +/- 12.1 vs 30.9 +/- 23.3 min, P < or = 0.02). There were no episodes of coagulum formation in group 1, while there were 15 episodes (7.1% of energy applications) in group 2 (P = 0.0006) despite a significantly higher applied power in group 1 (53.4 +/- 25.1 vs 35.6 +/- 9.5W, P = 0.0001). Successful energy applications were associated with significantly higher temperatures than unsuccessful applications in group 1 (55.6 degrees +/- 5.8 degrees C vs. 52.9 degrees +/- 6.8 degrees C, P < or = 0.03). The minimum temperature required for successful ablation was 48 degrees C for two patients (5%) and was > or = 50 degrees C for the remainder of patients (37/39 [95%]). The catheter ablation system used in this study was safe, effective, and prevented coagulum formation while delivering relatively high power. In addition, shorter ablation times and radiation exposure were seen with this system. Although successful energy applications and the production of junctional rhythm were associated with higher achieved temperatures, temperature alone did not predict either endpoint. Future prospective, randomized trials are needed to confirm these findings and further evaluate the value of temperature monitoring.

Atrioventricular Node↗
PubMed1997

Hinge and amino-terminal sequences contribute to solution dimerization of human progesterone receptor.

We and others have shown previously that progesterone receptors (PR) form homodimers in solution in the absence of DNA and that dimers are the preferential form of receptor that binds with high affinity to target DNA. To determine the sequence regions involved in solution homodimerization, wild type PR and truncated PR proteins were expressed in an insect baculovirus system. The expression constructs included the ligand-binding domain [LBD, amino acids (aa) 688-933], the LBD plus hinge (hLBD, aa 634-933), the hLBD plus the DNA-binding domain (DhLBD, aa 538-933), and the full- length A and B isoforms of PR. PR-PR interactions were detected by three methods, coimmunoprecipitation of the PR fragments with full-length PR-A, pull-down of PR-polypeptides with polyhistidine-tagged versions of the same polypeptides immobilized to metal affinity columns and cooperative ligand-binding assays (Hill coefficient, n(H) > 1 indicating PR-PR interaction). By all three assays, the LBD alone was not sufficient to mediate protein-protein interaction. However, the LBD did exhibit other properties ascribed to this domain, including binding to steroids with a relatively good affinity and specificity, ligand-induced conformational changes at the carboxyl terminus tail and binding of heat shock protein 90 and its dissociation in response to hormone. Thus, failure of the expressed LBD to mediate dimerization does not appear to be due to an extensively misfolded or unstable polypeptide. The minimal carboxyl-terminal fragment capable of mediating PR-PR interaction was the hLBD construct. However, by immobilized metal affinity chromatography assay, self-association of PR-A was 3.5-fold more efficient than that of either the DhLBD or hLBD constructs. An expressed amino-terminal domain (aa 165-535) lacking the DNA-binding domain, hinge, and LBD was found to physically associate with PR-A or with another amino-terminal fragment lacking the LBD, but retaining the DNA-binding domain. These results provide evidence for direct amino-terminal interactions in the more efficient PR-PR interaction exhibited by wild-type PR-A, as compared with DhLBD and hLBD constructs. The overall results of this paper are consistent with the conclusion that the carboxyl-terminal LBD is not sufficient for mediating PR dimerization and that multiple regions, including the hinge and amino-terminal sequences, contribute either directly or indirectly to homodimerization of PR.

Animals↗
PubMed1997

Perfluoro-15-crown-5-ether labelled macrophages in adoptive transfer experimental allergic encephalomyelitis.

In this serial in vivo study, macrophages labelled with perfluoro-15-crown-5-ether (15C5) were monitored in rats after inducing adoptive transfer experimental allergic encephalomyelitis (AT-EAE). AT-EAE is an animal model of multiple sclerosis and is characterized by inflammatory infiltrates in the central nervous system (CNS) and breakdown of the blood-brain-barrier. A particular feature of AT-EAE are macrophage infiltrates. Purpose of this study was to monitor the invasive and evasive phase of the macrophages in AT-EAE by using 3-dimensional 19F magnetic resonance imaging (3D 19F-MRI). In the early stage of the disease, a much stronger 19F-signal intensity was observed in AT-EAE-rats than in healthy control rats in the tissue adjacent to CNS regions severely affected by inflammatory infiltrates, and thereafter the 19F-signal intensity was decreasing over the time. However, no 19F-signal could be observed in the CNS itself neither in AT-EAE-rats nor in control rats. According to these findings it is assumed that we monitored the evasion of the macrophages from the region of inflammation.

Animals↗
PubMed1997

Role of glial filaments in cells and tumors of glial origin: a review.

In the adult human brain, normal astrocytes constitute nearly 40% of the total central nervous system (CNS) cell population and may assume a star-shaped configuration resembling epithelial cells insofar as the astrocytes remain intimately associated, through their cytoplasmic extensions, with the basement membrane of the capillary endothelial cells and the basal lamina of the glial limitans externa. Although their exact function remains unknown, in the past, astrocytes were thought to subserve an important supportive role for neurons, providing a favorable ionic environment, modulating extracellular levels of neurotransmitters, and serving as spacers that organize neurons. In immunohistochemical preparations, normal, reactive, and neoplastic astrocytes may be positively identified and distinguished from other CNS cell types by the expression of the astrocyte-specific intermediate filament glial fibrillary acidic protein (GFAP). Glial fibrillary acidic protein is a 50-kD intracytoplasmic filamentous protein that constitutes a portion of, and is specific for, the cytoskeleton of the astrocyte. This protein has proved to be the most specific marker for cells of astrocytic origin under normal and pathological conditions. Interestingly, with increasing astrocytic malignancy, there is progressive loss of GFAP production. As the human gene for GFAP has now been cloned and sequenced, this review begins with a summary of the molecular biology of GFAP including the proven utility of the GFAP promoter in targeting genes of interest to the CNS in transgenic animals. Based on the data provided the authors argue cogently for an expanded role of GFAP in complex cellular events such as cytoskeletal reorganization, maintenance of myelination, cell adhesion, and signaling pathways. As such, GFAP may not represent a mere mechanical integrator of cellular space, as has been previously thought. Rather, GFAP may provide docking sites for important kinases that recognize key cellular substrates that enable GFAP to form a dynamic continuum with microfilaments, integrin receptors, and the extracellular matrix.

Animals↗
PubMed1997

[Modification of transplacental digoxin transfer in the isolated placental lobule].

Digoxin is widely used in the transplacental therapy of fetal tachyarrhythmia. Unfortunately, in cases with severe cardiac insufficiency and hydrops fetalis, transplacental passage of digoxin is often hampered and therapy therefore ineffective. The present study was designed to establish the isolated placental lobule to quantify transplacental digoxin passage under different experimental conditions. Ten human placentas were obtained immediately after delivery, and a lobule was dually perfused after cannulating a small artery and vein of the chorionic plate and piercing four catheters through the corresponding basal plate. Flow rates were 12 ml/min in the maternal circuit and 6 (I) respectively 3 ml/min (II) in the fetal circuit. The maternal circuit was spiked with digoxin to 6.18 +/- 0.40 ng/ml, and transplacental passage was calculated from repeated fetal and maternal perfusate samples (Fluorescence-Polarization-Immunoassay; TDx, Abbott Laboratories). Within three hours of recirculating perfusion with a fetal flow rate of 6 ml/min (I), digoxin concentrations in the maternal circuit (400 ml) declined to 3.56 +/- 0.09 ng/ml, whereas digoxin levels in the fetal compartment (200 ml) increased to 2.58 +/- 0.37 ng/ml. With a fetal perfusion rate of 3 ml/min (II), the efflux of digoxin out of the maternal circuit was lower (p < 0.05) and the influx in the total compartment was reduced (fetal digoxin concentrations reached only 26.9 +/- 10.6% vs. 39.1 +/- 5.5% of the initial maternal digoxin concentrations). These data suggest that severe fetal cardiac insufficiency with reduced placental perfusion may be in part responsible for the decrease of transplacental digoxin passage in fetuses with hydrops.

Anti-Arrhythmia Agents↗
PubMed1996

Cicutoxin from Cicuta virosa--a new and potent potassium channel blocker in T lymphocytes.

The effect of cicutoxin, the poisonous principle of the genus Cicuta, on K+ currents of activated T lymphocytes was investigated using the patch clamp technique. Cicutoxin produced a dose-dependent [5 x 10(-6) to 7 x 10(-5) mol/l] and completely reversible block of K+ currents with an EC50 of 1.8 x 10(-5) mol/l. A maximum block of 71% was achieved with cicutoxin at a concentration of 7 x 10(-5) mol/l. Since previous studies have shown that T lymphocyte proliferation is associated with K+ currents, the effect of cicutoxin on T lymphocyte proliferation was studied by means of 3H-thymidine uptake assays. At noncytotoxic concentrations [10(-7) to 5 x 10(-5) mol/l] cicutoxin reduced the 3H-thymidine incorporation dose-dependently. In conclusion, cicutoxin is a potent K+ current blocker which inhibits K+ channel-dependent proliferation of naive and memory T lymphocytes.

Alkynes↗
PubMed1996

Preventive but not therapeutic application of Rolipram ameliorates experimental autoimmune encephalomyelitis in Lewis rats.

Experimental autoimmune encephalomyelitis (EAE) in Lewis rats, an animal model mimicking some aspects of multiple sclerosis, was treated with the type IV-specific phosphodiesterase inhibitor Rolipram. Actively induced EAE evoked by immunization with myelin basic protein (MBP) in complete Freund's adjuvant was delayed but only slightly ameliorated in its maximal severity by preventive treatment with Rolipram (2 x 3 mg/kg per day) starting on the day of immunization. Therapeutic administration of Rolipram (2 x 5 mg/kg per day) was begun within hours after onset of first clinical signs of EAE but could not modify the further course of the disease. Both doses had significant side effects. Injection of 5 mg Rolipram/kg provoked transient slackening and unsteady gait while chronic application of 6 mg/kg/day strongly accelerated the weight gain in adolescent rats. EAE adoptively transferred by injection of encephalitogenic T line blasts was shortened and significantly suppressed in its severity by application of Rolipram (2 x 5 mg/kg per day) starting on the day of cell transfer. In corresponding lumbar spinal cord sections density of inflammatory infiltration by T cells and macrophages was reduced. Rolipram did not prevent generation of an antigen-specific immune response in vivo. In vitro the drug inconsistently inhibited MBP-induced activation of encephalitogenic T cells. TNF-alpha secretion by encephalitogenic T cells was limited only when T cell proliferation was also affected. In contrast, TNF-alpha production by LPS-activated macrophages was consistently and markedly suppressed by Rolipram. However, since the encephalitogenic T line cells produced at least 100 times more TNF-alpha than the same number of Rolipram-sensitive macrophages, the impact of Rolipram on the total amount of TNF-alpha synthesized in EAE may be limited. Together with our histological findings, the data suggest that relevant immunosuppressive mechanisms of Rolipram may be the inhibition of migration of leukocytes into the central nervous system and to some extent its inhibitory effect on T cell proliferation and macrophage activity. The downregulatory effects of Rolipram may be partially counteracted by its augmenting impact on the production of nitric oxide by macrophages.

Animals↗
PubMed1996

Partial inhibition of AT-EAE by an antibody to ICAM-1: clinico-histological and MRI studies.

The role of quantitative proton magnetic resonance imaging (MRI) for the evaluation of immunopathological lesions in the CNS was studied in adoptively transferred experimental allergic encephalomyelitis (AT-EAE). We utilized a recently established treatment model, inhibition of the cell adhesion molecule ICAM-1 by the monoclonal antibody 1A-29. The animals were scanned on days 3, 5 and 7 after injection of encephalitogenic T-cells, before and after bolus injection of Gd-DTPA by performing T1-measurements to assess the integrity of the blood-brain barrier (BBB). On day 7, immunohistochemistry was performed looking for T-cells, activated macrophages, and albumin staining. There was clinical evidence of partial inhibition of AT-EAE in rats treated with antibodies against ICAM-1. This finding was in line with a significantly reduced number of T-cells in the medulla. However, the number of activated macrophages and the distribution of albumin did not differ from untreated AT-EAE animals. The histological findings are in agreement with the MRI data before and after Gd-DTPA injection which were similar in treated and untreated AT-EAE rats on day 3 and 5. On day 7 after Gd-DTPA injection there was evidence of a delayed breakdown of the BBB in the treated rats. The observation of a dissociation of clinical and MRI findings, especially evidence of Gd-enhancement despite clinical improvement, may be important in the context of interpreting MRI studies in MS patients in treatment trials.

Animals↗
PubMed1996

Digoxin transfer across the isolated placenta is influenced by maternal and fetal albumin concentrations.

The aim of this study was to evaluate the influence of different maternal and fetal albumin concentrations on the transplacental transfer and the placental tissue accumulation of digoxin. Digoxin passage across the isolated lobules of 15 human placentae was calculated from repeated fetal and maternal perfusate samples, and placental tissue digoxin concentrations were measured at the end of the experiments. Metildigoxin (Lanitop) was added to the maternal medium at a concentration of 5.70 +/- 0.73 ng mL-1, and maternal and fetal perfusate albumin (BSA) concentrations were kept equal either at a high concentration of 21 g L-1 (Group I; n = 5) or at a low concentration of 3 g L-1 (Group III; n = 5), or differed with a materno-fetal gradient of 21:3 g L-1 (Group II; n = 5). In the experiments with low maternal albumin concentrations (Group III), digoxin concentrations in the maternal circuit decreased to 3.56 ng mL-1, whereas digoxin concentrations in the fetal circuit reached 2.59 ng mL-1 over a 3-h period. With maternal BSA concentrations of 21 g L-1 (Group I and Group II), the decrease in digoxin concentration in the maternal circuit was lower (P < 0.05), and digoxin tissue concentrations at the end of the experiments were smaller (0.45 +/- 0.07 and 0.42 +/- 0.03 v. 0.82 +/- 0.32 ng mg-1 protein, Group I and Group II v. Group III respectively; P < 0.05). Comparing only those lobules with similar high concentrations of maternal protein, fetal BSA concentrations of 21 g L-1 resulted in a greater increase in digoxin concentrations in the fetal circuit (end-feto to initial-maternal digoxin concentrations of 0.44 +/- 0.08 v. 0.37 +/- 0.04 ng mg-1 protein (Group I v. Group II respectively), although this was not significant. The data suggest that maternal and fetal serum albumin concentrations may have an influence on transplacental digoxin transfer, and this should be considered when treating fetuses with cardiac disease transplacentally with glycosides.

Anti-Arrhythmia Agents↗
PubMed1996

In vivo MRI and its histological correlates in acute adoptive transfer experimental allergic encephalomyelitis. Quantification of inflammation and oedema.

In vivo proton MRI was carried out on a 7 Tesla system at 2-3 day intervals over 10 days in rats with adoptive transfer experimental allergic encephalomyelitis (AT-EAE), an animal model of some aspects of multiple sclerosis. In order to assess the integrity of the blood-brain barrier (BBB), MRI was performed by acquiring quantitative MR-relaxation time T1 images of the AT-EAE rat brain before and after i.v. injection gadolinium-diethylene triaminepentaacetic acid (Gd-DTPA) using an ultrafast MRI technique. The MRI findings were compared with the immunohistochemical stain of T cells, macrophages and albumin and, in addition, apoptosis of T cells was assessed using in situ nick translation (ISNT). Prior to injection of Gd-DTPA, an increase of T1 times in the brain of the AT-EAE rats was observed, which paralleled the time course of albumin in histological sections. These were MRI findings observed well before the onset of major cellular infiltration and before the onset of clinical signs. After i.v. injection of Gd-DTPA the observed decrease of T1 times paralleled macrophage activation, and less closely T-cell infiltration. Our results provide evidence that using MRI, it is possible to assess quantitatively the breach of the BBB and to distinguish in vivo between two components of the early phase of the lesion, inflammatory infiltrates and vasogenic oedema.

Acute Disease↗
PubMed1996

T cell directed immunotherapy of inflammatory demyelination in the peripheral nervous system. Potent suppression of the effector phase of experimental autoimmune neuritis by anti-CD2 antibodies.

Experimental autoimmune neuritis (EAN) of Lewis rats, an inflammatory demyelinating neuropathy and model of the human Guillain-Barré syndrome (GBS), was used to evaluate the novel T cell directed immunotherapy with the anti-CD2 monoclonal antibody (mAb) OX34. Clinical signs of EAN actively induced by immunization with bovine peripheral nerve myelin in complete Freund's adjuvant (CFA) were totally prevented or markedly suppressed by preventative injections of OX34 starting 8 days post-immunization (p.i.). Moreover, therapeutic application of the mAb beginning on the day of first clinical signs of EAN markedly inhibited progression of disease. Electrophysiological and histological investigation of sciatic nerves 17 and 18 days p.i. respectively, also revealed an inhibitory effect of OX34 on EAN-associated functional and morphological nerve damage. Similarly, therapeutic injections of OX34 after onset of EAN actively induced by immunization with a neuritogenic peptide of the P2 protein completely halted further deterioration of clinical disease. Finally, clinical, electrophysiological and histological signs of adoptive transfer EAN mediated by injection of neuritogenic T helper line cells were prevented or strongly suppressed by OX34-application on the day of cell transfer and 4 days later, underlying the impact of the mAb on the effector phase of the disease. Since the anti-CD2 mAb did not exert its effect by inhibition of T cell activation, induction of anergy, modulation of CD2 antigens, or by T cell depletion, we assume that it may affect migration of T lymphocytes across the blood-nerve barrier. The immediate and marked suppression of ongoing EAN by the mAb lead to the recommendation of anti-CD2 mAbs as candidates for T cell directed immunotherapy of the GBS.

Animals↗
PubMed1996

Comparison of the substrate specificities of cAMP-dependent protein kinase from bovine heart and Ascaris suum muscle.

The catalytic subunits of cAMP-dependent protein kinases (protein kinase A) from bovine heart and Ascaris suum muscle exhibit only 48% sequence identity and show quantitative differences in substrate specificity. These differences were not obvious at the level of short synthetic substrate peptides but were distinct for some protein substrates. Phosphofructokinase from Ascaris, a physiological substrate, was a better substrate for the protein kinase from the nematode in comparison to the mammalian protein kinase due to a 10-fold lower Michaelis constant. Selective phosphorylation by the two kinases was also observed with some in vitro substrates. In addition, quantitative differences in the interactions between R- and C-subunits from Ascaris and bovine heart were observed. However, several synthetic peptides whose sequence reflected the phosphorylation site of Ascaris suum phosphofructokinase (AKGRSDS*IV), or variations of it, were phosphorylated with the same efficiency by both protein kinases. Based on the data the following are concluded: (1) In agreement with the conservation of structure in the catalytic cleft, the recognition of substrates by protein kinases from phylogenetically distant organisms exhibits similarity. (2) Non-conserved parts of the surface of the protein kinase molecule may contribute to binding of protein substrates and thus to selective recognition.

Amino Acid Sequence↗
PubMed1996

Transforming growth factor-beta 1 in experimental autoimmune neuritis. Cellular localization and time course.

Experimental autoimmune neuritis (EAN) is a monophasic inflammatory disorder of the peripheral nervous system that resolves spontaneously by molecular mechanisms as yet unknown. We have investigated whether the immunosuppressive cytokine transforming growth factor-beta 1 (TGF-beta 1) might be endogenously expressed in the peripheral nervous system of Lewis rats with actively induced and adoptive transfer EAN. TGF-beta 1 mRNA was upregulated to high levels in sensory and motor roots, spinal ganglia, and sciatic nerve as revealed by quantitative Northern blot analysis and in situ hybridization histochemistry, with peak levels just preceding the first signs of clinical recovery. TGF-beta 1 mRNA was localized to scattered round cells and dense cellular infiltrates, but only rarely to Schwann cell profiles. Double labeling studies revealed macrophages and subpopulations of T cells as the major cellular source of TGF-beta 1 mRNA. TGF-beta 1 protein was visualized immunocytochemically and localized to infiltrating mononuclear cells with peak expression around the same time as mRNA, in addition to some constitutive expression in axons and Schwann cells. Our studies suggest that the spontaneous recovery observed in Lewis rat EAN might be mediated by the endogenous elaboration of TGF-beta 1 within the peripheral nerve, and that macrophages might control their own cytotoxicity by expressing TGF-beta 1.

Animals↗