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R Houben

Publications and source records attributed to R Houben.

7 recordsLinked to original sources

High uniformity of left and right ventricular repolarization dynamics induced by an abrupt decrease in pacing cycle length in a dog is not affected by left ventricular ischemia.

INTRODUCTION: After an abrupt increase in heart rate, action potential duration (APD) will shorten. To assess the effect of ischemia on APD shortening dynamics, we compared right ventricular (RV) and left ventricular (LV) APD shortening induced by an abrupt decrease in pacing cycle length (PCL) during control and LV ischemia. METHODS AND RESULTS: In eight anesthetized AV block dogs, endocardial LV and RV APD were determined simultaneously after an abrupt PCL decrease from 800 to 350 msec. Measurements were repeated during left anterior descending coronary artery (LAD) occlusion. During control, LV and RV APD shortened 97 +/- 27 and 71 +/- 14 msec, respectively (P < 0.05). Shortening was pronounced in a short initial phase and gradual in the longer secondary phase. Linear regression analysis revealed very high uniformity of LV and RV APD shortening dynamics (r2 = 0.96 +/- 0.01). During repeated LAD occlusion, ischemia induced a gradual LV APD shortening from 314 +/- 25 msec to a new steady-state value of 251 +/- 23 msec, whereas RV APD remained stable at 289 +/- 28 msec. The additional PCL decrease resulted in LV and RV APD shortening of 72 +/- 8 and 68 +/- 15 msec, respectively, with the same high uniformity of shortening dynamics as seen during control (r2 = 0.94 +/- 0.03). CONCLUSION: There is a pronounced difference in APD shortening dynamics induced by an abrupt decrease in PCL compared with ischemia. LV shortening dynamics induced by a decrease in PCL are not affected by LV ischemia, preserving a high interventricular uniformity of repolarization dynamics.

Action Potentials↗

Regulation of c-myc expression by Ras/Raf signalling.

The c-myc gene is induced upon growth factor stimulation of arrested cells. The interaction of a mitogen with a transmembrane receptor triggers a variety of parallel signal transduction cascades. In order to analyse the role of the Ras/Raf cascade in the regulation of c-myc expression we have established fibroblast cell lines harboring conditional systems activating or inhibiting this pathway. Fusion of the c-Raf-1 kinase domain with the hormone binding domain of the estrogen receptor (c-Raf-1-BxB-ER) provides a 4-hydroxytamoxifen regulated form of the oncogenic c-Raf-1 kinase. We have generated NIH3T3 cells stably expressing the chimeric Raf protein (N-BxB-ER). 4-hydroxytamoxifen mediated activation of the fusion protein in serum starved N-BxB-ER induces the expression of the c-myc gene within 2-6 h. Deletion of the c-Raf-1 kinase domain generates a mutant c-Raf-1 protein (c-Raf-1-C4B), which can directly interact with the effector domain of the Ras protein and thereby block Ras mediated signalling. We have established a NIH3T3 based cell line expressing the c-Raf-1-C4B protein under the control of a tetracycline responsive promoter (N-C4B-tet). Serum starved cells expressing the c-Raf-1-C4B protein exhibit a significantly reduced induction of c-myc expression following serum stimulation compared to the same cells not expressing the Ras inhibitor. The induction of c-myc mRNA following the activation of the isolated Raf/Mek/Erk cascade in addition to the partial inhibition of serum mediated induction of c-myc expression in the presence of the Ras inactivating c-Raf-1-C4B mutant strongly indicates an involvement of the Ras/Raf pathway in the regulation of c-myc expression.

3T3 Cells↗

Strategies for developing human osteocalcin standards: a critical evaluation.

Osteocalcin is a small protein uniquely produced by osteoblasts and odontoblasts. Since about 30% of the de novo synthesized osteocalcin is set free in the blood stream, it is widely used as a marker for bone formation. However, circulating immunoreactive osteocalcin (irOC) consists of several fractions, which may differ from each other with respect to size and calcium binding properties. Whereas it is generally assumed that the fraction with high affinity for hydroxyapatite reflects bone formation, we have found a high correlation between bone mass and irOC with low affinity for hydroxyapatite. Since the antibodies used in various commercial test kits for osteocalcin have different affinities for the various irOC fractions, well-defined homogenous standards have to be prepared which may be used for standardization of the detection techniques used in various laboratories. In this paper we give a critical evaluation of the strategies which may be followed.

Amino Acid Sequence↗

Production of purified alginates suitable for use in immunoisolated transplantation.

Alginate is used as a matrix for immunoisolation of cells and tissues in vivo. We have demonstrated previously that commercial alginates contain various fractions of mitogenic impurities and that they can be removed by free flow electrophoresis. The use of purified material is a necessity in order to reveal the parameters that control biocompatibility of the implanted material (such as stability, size, surface charge and curvature, etc.). In this study, we present a protocol for the chemical purification of alginates on a large-scale. Beads made from alginates purified by this multi-step chemical extraction procedure did not induce a significant foreign body reaction when implanted for 3 weeks either intraperitoneally or beneath the kidney capsule of Lewis or non-diabetic BB/Gi rats.

Alginates↗

[Immunologic isolation of transplanted islets of Langerhans: microcapsules with defined molecular limits].

Immunoisolated transplantation of islets of Langerhans in barium alginate microcapsules is a promising therapeutic approach to cure diabetes. An improved membrane for the coating of barium alginate microcapsules has been developed. Chemically stable barium alginate microcapsules with a controlled molecular weight cutoff between 9400 and 40,500 D were obtained after coating of barium alginate capsules in Polybrene solutions. Microcapsules prepared by this new method were still freely permeable to low molecular weight substances.

Alginates↗