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U Baur

Publications and source records attributed to U Baur.

36 records · Page 2Linked to original sources
PubMed1989

Induction of growth-related metabolism in human vascular smooth muscle cells by low density lipoprotein.

Human vascular smooth muscle cells (hVSMC) rendered quiescent by maintenance under serum-free culture conditions for 48 h exhibited several metabolic responses, normally associated with proliferation, following exposure to low density lipoprotein (LDL). LDL induced a time- and dose- (half-maximally effective concentration, ED50 25.0 +/- 8 nM) dependent activation of S6 kinase which could be negated following pretreatment of hVSMC with 12-O-tetradecanoylphorbol-13-acetate (TPA) for 48 h. In myo-[3H]inositol-prelabeled hVSMC, LDL caused a rapid (maximum within 1 min) decrease in phosphatidylinositol 4,5-bisphosphate (35% p less than 0.001) and phosphatidylinositol 4-phosphate (20%, p less than 0.01) with a return to prestimulated levels within 5-10 min. LDL induced a concomitant increase in [3H]inositol phosphates for which the order of generation was inositol-tris greater than -bis greater than -mono phosphate and which reached threshold levels of significance (p less than 0.05) above control values within 1, 2, and 10 min, respectively. The effect of LDL on hVSMC phosphoinositide metabolism was dose-dependent (half-maximally effective concentration, ED50 32.1 +/- 5.0 nM). This concentration, like that for S6 kinase, approximates with the KD (5-21 nM) for high affinity binding of 125I-LDL to specific receptors (1.5 x 10(4) sites/cell) on hVSMC. LDL induced a rapid but transient translocation of protein kinase C from the cytosol to membranes as assessed using both immunoblotting and [3H] 4-beta-phorbol-12-13-dibutyrate-binding procedures. Exposure of quiescent hVSMC to LDL elevated intracellular pH (delta pH 0.30 +/- 0.03, p less than 0.001). Such alkalinization was prevented in the presence of Na+/K+ exchange inhibitors such as amiloride, dimethylamiloride, and ethylisopropylamiloride. In an investigation of the nuclear action of LDL, a time-dependent induction of both c-myc and c-fos was observed. Such LDL-induced expression of these nuclear proto-onco-genes was not detectable in protein kinase C down-regulated hVSMC. Nevertheless, in spite of the cascade of "growth-promotional" responses elicited by LDL in quiescent hVSMC, this lipoprotein alone (under serum-free conditions) was neither mitogenic in nuclear labeling experiments, nor could it support growth of hVSMC in culture. We demonstrate that LDL might function in a complementary/synergistic fashion with other weakly mitogenic (to VSMC) growth factors and suggest that activation of protein kinase C (vis à vis intrinsic tyrosine kinase characteristic of other growth factor receptors) may be crucial to the signal transduction pathway for LDL.

Arterioles↗
PubMed1989

Decreased susceptibility of cultured smooth muscle cells from SHR rats to growth inhibition by heparin.

Smooth muscle cell proliferation is regulated through the coordinated action of growth inhibitors and growth factors/mitogens; a specific heparin-epidermal growth factor (EGF) complementation has been proposed (Reilly et al., 1987, J. Cell. Physiol., 131:149-157). In culture, vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) proliferate more rapidly than VSMC from control Wistar Kyoto rats (WKY). We observed that, compared with WKY-derived VSMC, cells from SHR were markedly less susceptible to growth inhibition both by heparin and its homopolysaccharide analogue pentosan polysulphate (PPS). SHR-derived VSMC exhibited a reduced capacity for binding of [3H]heparin to specific extracellular surface receptors, whereas affinities for heparin were comparable between both VSMC isolates. The early (0-2 hr at 37 degrees C) kinetics of internalization did not differ between SHR- and WKY-derived VSMC, but both internalized equivalent proportions (approximately 10%) of initially surface-bound heparin. VSMC from SHR exhibited a greater capacity, without a changed affinity, for [I125]EGF binding than VSMC from WKY. Pre-exposure of VSMC to heparin or PPS decreased, in a time-dependent manner, the EGF binding capacity for both SHR and WKY (by 40-50% after 72 hr). However, in absolute terms, the EGF-binding capacity of VSMC from SHR exposed to heparinoids was similar to that of nonexposed VSMC from WKY.

Animals↗
PubMed1989

Atrial natriuretic peptide: binding and cyclic GMP response in cultured vascular smooth muscle cells from spontaneously hypertensive rats.

Atrial natriuretic peptide (ANP) is vasodilatory and natriuretic, but whereas increased plasma ANP levels occur in spontaneously hypertensive rats, their elevated vascular resistance suggests inappropriate target tissue responsiveness to ANP. This study examines ANP-receptor binding properties (at 25 degrees C and 4 degrees C) in cultured vascular aortic smooth muscle cells from spontaneously hypertensive (SHR) and control Wistar-Kyoto (WKY) rats. [I125]-human ANP saturation (0.0625-12.0 nmol) profiles were analyzed using nonlinear regression (LIGAND). Vascular smooth muscle cells from WKY possessed both high affinity (KD1 0.3 nmol; R1 33 fmol/10(5) cells) and low affinity (KD2 15 nmol; R2 400 fmol/10(5) cells) binding sites for ANP. In contrast, for smooth muscle cells from SHR, two receptor forms could not be resolved using identical analytical protocols. Parameter estimates at 25 degrees C and 4 degrees C were not different for either SHR or WKY. The number of receptors for SHR (Bmax approximately 100 fmol/10(5) cells) was lower than the total number of receptors for WKY (high plus low affinity approximately 430 fmol/10(5) cells). The intermediary KD value (approximately 1.0 nmol) for ANP binding in SHR suggests an ANP-receptor interconversion from high affinity to low affinity in smooth muscle cells from SHR. Competition-binding experiments also revealed a decreased affinity for ANP in SHR-derived smooth muscle cells. The cyclic GMP response (intracellular accumulation and extracellular levels) was decreased in SHR smooth muscle cells compared to WKY, although this difference was evident only after prolonged (one hour) stimulation with ANP. Our data indicate a reduced sustained vascular responsiveness to ANP in hypertension.

Animals↗
PubMed1989

Epidermal growth factor responsiveness in smooth muscle cells from hypertensive and normotensive rats.

Aortic smooth muscle cells from spontaneously hypertensive rats (SHR) exhibit inappropriate proliferation characteristics in culture that suggest a modified response to serum mitogens or growth factors. The present study compares vascular smooth muscle cells from SHR and normotensive Wistar-Kyoto (WKY) rats with respect to their proliferative and functional response to growth factors. Specific attention was focused on the interaction of these vascular smooth muscle cells with epidermal growth factor. An increased growth rate of vascular smooth muscle cells from SHR (vs. WKY rats) was observed when cells were cultured in the presence of serum (10% and 0.5%), but not under serum-free conditions. The additional presence of low serum concentrations (0.5%) was required for epidermal growth factor to elicit a proliferative response, whereupon smooth muscle cells from SHR displayed an increased (vs. WKY rats) growth rate. Saturation binding of [125I]epidermal growth factor to intact smooth muscle cells indicated a twofold increase in receptor density in SHR-derived cells (p less than 0.001 vs. WKY rats) without an alteration in affinity for the growth factor. Cells derived from SHR also exhibited greater functional responsiveness to epidermal growth factor when compared with smooth muscle cells from WKY rats as evidenced by amplifications of both S6 kinase activation, phosphoinositide catabolism, elevation of intracellular pH, and DNA synthesis (nuclear labeling). We conclude that increased responsiveness of SHR-derived smooth muscle cells to epidermal growth factor could contribute to alterations in vascular smooth muscle growth and tone that may be fundamental to the pathogenesis of hypertension and atherosclerosis.

Animals↗
PubMed1989

Enhanced responsiveness to angiotensin II in vascular smooth muscle cells from spontaneously hypertensive rats is not associated with alterations in protein kinase C.

This study compares vascular smooth muscle cells from spontaneously hypertensive and normotensive Wistar-Kyoto rats with respect to protein kinase C and intracellular responses to angiotensin II (Ang II). Ang II-induced degradation of polyphosphoinositides and accumulation of inositol di- and tris-phosphates was enhanced (approximately twofold) in hypertensive-derived cells, without a change (vs. normotensive-derived cells) in half-maximally effective concentrations of Ang II. Intracellular pH (approximately 6.6) was comparable between both cell isolates at quiescence, but alkalinization induced by Ang II, serum, or phorbol ester was greater (delta 0.1-0.2 pH units) for hypertensive-derived cells. For both cell types, the intracellular pH response to these agonists was prevented in the presence of Na+-H+ exchange inhibitors. S6 kinase activation induced by Ang II was enhanced (approximately twofold) in hypertensive-derived cells, whereas activation in response to serum or 12-O-tetradecanoylphorbol 13-acetate did not differ significantly between the two cell types. Quantitation of protein kinase C by immunoblotting and [3H]phorbol dibutyrate binding procedures revealed no differences between the two smooth muscle cell isolates (at quiescence or in the presence of serum) with respect to either total amounts or subcellular distribution. Sensitivity of protein kinase C to phorbol ester was apparently also not different between the two cell types, as assessed from dose-dependent (phorbol ester) S6 kinase activation profiles. Phorbol ester caused a similar subcellular redistribution of [3H]phorbol dibutyrate binding in the two cell isolates, but for both, minimal (10%) translocation occurred in response to Ang II. The data suggest that enhanced agonist responsiveness in vascular smooth muscle cells is unlikely to involve alterations in protein kinase C.

Angiotensin II↗
PubMed1988

Atrial natriuretic peptide induces breakdown of phosphatidylinositol phosphates in cultured vascular smooth-muscle cells.

Discrepancies exist between extent of guanylate cyclase activation by atrial natriuretic peptide (ANP) in cell-free systems and ANP-stimulated levels of cyclic GMP in whole cells, and also between receptor affinity and dose effectiveness of ANP. Therefore, we have investigated whether, in addition to receptor-coupled guanylate cyclase activation, other second-messenger cascade systems may be involved in mediating both an increase in cyclic GMP and the physiological response to ANP. Equilibrium 125I-ANP binding studies on cultured thoracic aorta smooth muscle cells revealed the existence of low-affinity (approximately 10(-8) M, 84.5 fmol/10(5) cells) and high-affinity (approximately 10(-10) M, 12.5 fmol/10(5) cells) binding sites. We confirm that ANP elevates intracellular cyclic GMP (EC50 approximately 10(-8) M) and inhibits agonist-(isoproterenol and forskolin)-induced increases in intracellular cyclic AMP (IC50 approximately 10(-9) M). ANP also stimulated breakdown of phosphatidylinositol phosphates and generation of inositol phosphates with a half-maximally effective concentration of approximately 10(-10) M. The extent of phosphatidylinositol polyphosphate hydrolysis was small (120%) in comparison to that of phosphatidylinositol (Ptd-Ins) (200%). Ptd-Ins hydrolysis was paralleled by the appearance of glycerophosphoinositol, and there was also a close temporal relationship between these processes and the accumulation of intracellular cyclic GMP. Smooth muscle cells released [3H]arachidonic acid label in response to ANP (EC50 approximately 10(-10) M). Taken together, the data suggest that the vasorelaxant hormone ANP has stimulatory effects on phosphoinositol lipid metabolism via both phospholipase C (generation of inositol phosphates) and phospholipase A2 (generation of releasable [3H]arachidonic acid and indirectly glycerophosphoinositol). In contrast, stimulation of phosphatidylinositol phosphate breakdown by the vasoconstrictive hormone angiotensin II is not associated with glycerophosphoinositol formation, and neither cyclic GMP nor cyclic AMP levels were influenced by this hormone.

Angiotensin II↗
PubMed1988

Amiloride sensitive activation of S6 kinase by angiotensin II in cultured vascular smooth muscle cells.

Angiotensin II was shown to activate S6-kinase in cultured vascular smooth muscle cells (VSMC) in a dose- (10(-9)-10(-6) M) and time-dependent manner. Pretreatment of quiescent cells with 12-O-Tetradecanoylphorbol-13-acetate had no effect on the activation levels of the kinase at the hormone levels used. However, stimulation of S6-kinase activity by angiotensin II was markedly inhibited by the inclusion of amiloride hydrochloride in serum-free medium during activation procedures. Angiotensin was not mitogenic for VSMC at even the highest doses used (10(-6) M). These findings support the notion that raised intracellular pH results in the activation of protein synthesis in quiescent cells.

Amiloride↗
PubMed1988

Activation of S6 kinase in cultured vascular smooth muscle cells by submitogenic levels of thrombospondin.

Purified human platelet thrombospondin was shown to activate S6 kinase in cultured vascular smooth muscle cells in a dose- (1-9 micrograms/ml) and time-dependent manner. Down regulation of epidermal growth factor and somatomedin C receptors by prior treatment of cells with their respective growth factors did not reduce this effect. Kinase activation by thrombospondin was only marginally reduced in the presence of platelet-derived growth factor specific antibody at levels that totally inhibited platelet-derived growth factor (5 ng/ml) induced activation. Additionally, thrombospondin elicits a rapid dose-dependent phosphoinositide turnover response analogous to that of platelet-derived growth factor, epidermal growth factor and somatomedin C. Prior treatment of cells with phorbol ester for 48 hrs in serum-free culture medium resulted in a small enhancement of S6 kinase activation by thrombospondin and the above mentioned growth factors but a complete loss in the ability of phorbol ester to activate this enzyme. These findings with cultured smooth muscle cells suggest a growth factor-like role for thrombospondin.

Animals↗
PubMed1987

Increased proliferation fate and phosphoinositide turnover in cultured smooth muscle cells from spontaneously hypertensive rats.

We cultured smooth muscle cells from matched sections of thoracic aortas of 20-week-old, male, spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats and compared their rates of proliferation and phosphoinositide metabolism. After seeding at initially identical densities, smooth muscle cells from SHR grow at significantly faster (P less than 0.001) rates than those from WKY rats, so that after 10 days in culture, the cell density of SHR-derived cells (3.10 +/- 0.32 x 10(5) cells/cm2) was double that of WKY-derived cells (1.59 +/- 0.28 x 10(5) cells/cm2). Following prolonged steady-state labelling in culture, incorporation of [3H]-myo-inositol into phosphatidylinositolbiphosphate (PIP2) was greater (P less than 0.01) in SHR smooth muscle cells (10.3 +/- 1.4%) than in those from WKY (6.9 +/- 1.4%). Incorporation of [3H]-myo-inositol into inositol triphosphate was also increased (P less than 0.01) in SHR (20.2 +/- 7.3%) relative to WKY cells (11.5 +/- 5.2%), while that into glycerophosphoinositol was lower (P less than 0.01) in SHR (46.5 +/- 8.0%) than in WKY (51.3 +/- 7.8%). Enhanced smooth muscle cell growth and altered phosphoinositide metabolism may be causally or consequentially involved in enhanced vasoconstriction and vascular hypertrophy in SHR.

Animals↗
PubMed1979

[Value of the oral TRH test for the evaluation of thyroid function in impaired TSH reserve. Preliminary report].

Oral TRH (40 mg) exerts a marked and protracted stimulatory effect on TSH release. The potency of oral TRH in stimulating TSH and T3 was evaluated in 26 euthyroid patients with absent or impaired TSH response in the i.v. TRH test (200 micrograms). All were given i.v. and oral TRH at an interval of at least 3 days. Based on the response to i.v. TRH, they were divided into "non-responders" (TSH increment less than 1.0 microU/ml) and "low-responders" (TSH increment 1.0--3.7 microU/ml). The results were compared with those in 11 patients with overt hyperthyroidism. 10 "non-responders" were additionally tested with 400 micrograms TRH i.v. to study the effect of a supramaximal dose. Most patients unresponsive to i.v. TRH had a pronounced response to oral TRH (TSH increment 0.1 +/- 0.1 and 4.0 +/- 0.9 microU/ml (mean +/- SEM) respectively, p less than 0.005). The "low-responders" in the i.v. test had a significantly enhanced response to the oral dose (2.4 +/- 0.3 and 7.6 +/- 1.6 respectively, p less than 0.005). The euthyroid patients with treated Graves' disease with a weak response to i.v. TRH showed a distinct response to the oral dose. On the other hand, plasma TSH in patients with overt hyperthyroidism failed to increase either after intravenous or after oral TRH. In contrast to oral TRH, the supramaximal dose of 400 micrograms i.v. TRH did not enhance the TSH-response in the "non-responders". In most patients with absent or impaired response to i.v. TRH, a marked increase in T3 could be demonstrated (0.5 +/- 0.1 ng/ml and 0.6 +/- 0.1 ng/ml in "non-responders" and "low-responders" respectively, p less than 0.01); thus, oral administration allows simultaneous stimulation of TSH and triiodothyronine. Oral TRH can be considered the test of choice for the investigation of patients with diminished TSH reserve.

Administration, Oral↗
PubMedDate not supplied

Extending a teleradiology system by tools for visualization and volumetric analysis through a plug-in mechanism.

This paper describes ongoing research concerning interactive volume visualization coupled with tools for volumetric analysis. To establish an easy to use application, the three-dimensional-visualization has been embedded in a state of the art teleradiology system, where additional functionality is often desired beyond basic image transfer and management. Major clinical requirements for deriving spatial measures are covered by the tools, in order to realize extended diagnosis support and therapy planning. Introducing a general plug-in mechanism, this work exemplarily describes the useful extension of an approved application. Interactive visualization was achieved by a hybrid approach taking advantage of both the precise volume visualization based on the Heidelberg ray-tracing model and the graphics acceleration capabilities of modern workstations. Several tools for volumetric analysis extend the three-dimensional-viewing. They are controlled by adequate input devices to select locations in the data volume, measure anatomical structures or initiate a segmentation process. Moreover, a haptic interface can be connected to provide a more realistic feedback while navigating within the three-dimensional-reconstruction. The work is closely related to research in the field of heart, liver and head surgery. In cooperation with our medical partners the development of tools as presented facilitates the integration of image analysis into the clinical routine.

Humans↗