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Biomedical subjects

E Pontén

Publications and source records attributed to E Pontén.

6 recordsLinked to original sources

Perfluorosulfonated ionomer-modified polyethylene. A material for simultaneous solid-phase enrichment and enhanced precolumn dansylation of C-21 ketosteroids in human serum.

A new derivatization procedure has been developed where solid-phase catalysis is utilized to facilitate the formation of hydrazones in precolumn labeling of keto-containing compounds. This procedure has been implemented on a solid-phase enrichment and enhanced derivatization (SPEED) device, prepared from porous polyethylene that has been coated with Nafion and dansylhydrazine. The SPEED devices have been optimized using experimental design and characterized for dansylation of C-21 ketosteroids by multivariate data analysis, using progesterone as the model compound. The reaction temperature and the molar ratio between the steroid and the derivatization reagent were found to be the factors most strongly affecting the reaction. Faster reaction kinetics were achieved when the molar ratio between dansylhydrazine and the steroid was increased. Mass spectroscopic analysis showed that the four derivative peaks eluting when derivatized progesterone was separated on an octadecyl silica stationary phase were due to the syn and anti mono- and bis(hydrazones) formed in the reaction. Using optimal reaction conditions, the derivatives mainly constitute the syn and anti conformers of bis-derivatives. In contrast to solution-based acid catalysis, the SPEED device was remarkably insensitive to water in the reaction mixture. A sample volume of 400 microL was found to be the maximum, enabling sample enrichment prior derivatization. Using optimal experimental conditions, picomole amounts of ketosteroids could be derivatized in 10 min at room temperature. Analysis of spiked serum samples containing 0.4-2.0 nmol of progesterone showed overall recoveries of 52-63%. The corresponding 3delta detection limit was 1.3 pmol (n = 4, 100 microL injected), as estimated from calibration curve data.

Dansyl Compounds↗

Effect of muscle tension during tendon transfer on sarcomerogenesis in a rabbit model.

Sarcomere number change was investigated in an animal model of tendon transfer. In 9 adult New Zealand white rabbits, the flexor digitorum longus muscle was cut distally and transferred and woven into the tibialis anterior tendon. Ankles were then immobilized for 3 weeks in 75 degrees flexion. Transferred flexor digitorum longus muscles were harvested and complete architectural analysis was performed. Sarcomere lengths were measured using laser diffraction. Serial sarcomere number in transferred flexor digitorum longus fibers was a strong function of the sarcomere length at the time of transfer. A highly significant negative correlation between these 2 parameters was approximated by a linear relationship. Based on this finding, we conclude that serial sarcomere number is significantly affected by the degree of stretch during the transfer itself. This could easily compromise the purpose of surgical tendon transfer by reducing the procedure to little more than a tenodesis. (J Hand Surg 2000; 25A:138-143.

Analysis of Variance↗

Phosphorylation of Shc by Src family kinases is necessary for stem cell factor receptor/c-kit mediated activation of the Ras/MAP kinase pathway and c-fos induction.

In this report we show that Tyr568 and Tyr570 are phosphorylated in vivo in the Kit/stem cell factor receptor (Kit/SCFR) following ligand-stimulation. By mutation of Tyr568 and Tyr570 to phenylalanine residues and expression of the mutated receptors in porcine aortic endothelial (PAE) cells, we could demonstrate a loss of activation of members of the Src family of tyrosine kinases when Tyr568 was mutated, while mutation of Tyr570 only led to a minor decrease in activation of Src family members. Mutation of both tyrosine residues led to a complete loss of Src family kinase activation. Phosphorylation of the adapter protein Shc by growth factor receptors provides association sites for Grb2-Sos, thereby activating the Ras/MAP kinase pathway. A much lowered degree of Shc phosphorylation, Ras and Erk2 activation and c-fos induction was seen in the Y568F mutant, while in the Y570F mutant these responses were less affected. In contrast, the mitogenic response was only slightly reduced. In a mutant receptor with both Tyr568 and Tyr570 mutated to phenylalanine residues, no phosphorylation of Shc and no activation of Ras and Erk2 was seen in response to stem cell factor stimulation, very weak induction of c-fos was seen and the mitogenic response was severely depressed. These data show that Ras/MAP kinase activation and c-fos induction by Kit/SCFR are mediated by members of the Src family kinases. However, the mitogenic response is only to a minor extent dependent on Src kinase activity.

Adaptor Proteins, Signal Transducing↗

Sarcomere length changes after flexor carpi ulnaris to extensor digitorum communis tendon transfer.

Sarcomere length was measured intraoperatively on five patients undergoing tendon transfer of the flexor carpi ulnaris (FCU) to the extensor digitorum communis (EDC) for radial nerve palsy. The most significant result was that the absolute sarcomere length and sarcomere length operating range of the FCU increased after transfer into the EDC (p < .001). Preoperatively, with the wrist fully extended and fingers flexed, FCU sarcomere length was 4.22 +/- .24 microns and decreased to 3.19 +/- .05 microns as the wrist was fully flexed. This represented an overall sarcomere length range of 1.03 microns. After the tendon transfer using standard recommended techniques, all sarcomere lengths were significantly longer (p < .001). Specifically, sarcomeres were 0.74 +/- .14 microns longer with the muscle in its fully lengthened position (4.96 +/- .43 microns with the wrist and digits flexed) and 0.31 +/- .16 microns longer with the FCU in the fully shortened position (3.50 +/- .06 microns with the wrist and digits extended). At these sarcomere lengths, the FCU muscle was predicted to develop relatively high force only during movement involving synergistic wrist flexion and finger extension. Under the conditions of the procedures performed, the transferred FCU muscle was predicted to produce maximum force over the range of about 30 degrees of wrist flexion and 0 degree of finger flexion to 70 degrees of wrist extension and 90 degrees of finger flexion. While this is acceptable, a more desirable result was predicted to occur if the muscle was transferred at a longer length. In this latter case, greater stretch of the FCU during transfer (increasing sarcomere length to about 5 microns) was predicted to improve the transfer. The more highly stretched FCU was predicted to result in maximum force as the wrist and fingers progressed from about 60 degrees of wrist extension and 0 degree of finger flexion to 80 degrees of wrist extension and 70 degrees of finger flexion. These results quantify the relationship between the passive tension chosen for transfer, sarcomere length, and the estimated active tension that can be generated by the muscle. The results also demonstrate the feasibility of using intraoperative laser diffraction during tendon transfer as a guide for optimal placement of the transferred muscle.

Adolescent↗

Hemodynamic effects of prenalterol, a beta1-adrenoreceptor agonist, in hypotension induced by high thoracic epidural block in man.

The hemodynamic effects of prenalterol, a new beta1-adrenoreceptor agonist, on hypotension induced by a thoracic epidural block extending between T1 and T12 and thereby blocking the cardiac sympathetic supply have been studied in eight patients scheduled for abdominal aortic aneurysm resection. The thoracic epidural block induced a drop in blood pressure, due to a reduction in cardiac output and systemic vascular resistance. Intravenous infusion of 10 mg of prenalterol rapidly and effectively reversed the hypotension by an increase in cardiac output without any effects on systemic vascular resistance or heart rate. The results indicate that prenalterol is a pure beta1 agonist with a marked inotropic but no chronotropic property.

Adrenergic beta-Agonists↗

Effects of thoracic epidural block and the beta-1-adrenoreceptor agonist prenalterol on the cardiovascular response to infrarenal aortic cross-clamping in man.

Sixteen patients scheduled for abdominal aortic resection and grafting were randomly assigned to two groups to study the cardiovascular effects of infrarenal aortic cross-clamping. The patients in the first group had received a thoracic epidural block followed by intravenous administration of the selective beta-1-adrenoreceptor agonist prenalterol prior to induction of general anaesthesia. The patients in the second group served as controls and received no specific treatment prior to general anaesthesia. In both groups, aortic cross-clamping was followed by an equal rise in pulmonary artery diastolic pressure and mean systemic arterial pressure. There was a significant difference in systemic vascular resistance, as the control group had a 46% increase 30 s after cross-clamping, while the pretreated patients had only a 7% increase at the same time. Moreover, the patients given the thoracic epidural block followed by prenalterol increased their stroke volume and cardiac indices, as compared to the patients in the control group who showed a significant decrease in these parameters. Possible mechanisms for the mode of action of the combined thoracic epidural block and beta-1-adrenoreceptor agonist pretreatment are discussed.

Adrenergic beta-Agonists↗