Purification and characterization of a kinase specific for the serine- and arginine-rich pre-mRNA splicing factors.

Members of the SR family of pre-mRNA splicing factors are phosphoproteins that share a phosphoepitope specifically recognized by monoclonal antibody (mAb) 104. Recent studies have indicated that phosphorylation may regulate the activity and the intracellular localization of these splicing factors. Here, we report the purification and kinetic properties of SR protein kinase 1 (SRPK1), a kinase specific for SR family members. We demonstrate that the kinase specifically recognizes the SR domain, which contains serine/arginine repeats. Previous studies have shown that dephosphorylated SR proteins did not react with mAb 104 and migrated faster in SDS gels than SR proteins from mammalian cells. We show that SRPK1 restores both mobility and mAB 104 reactivity to a SR protein SF2/ASF (splicing factor 2/alternative splicing factor) produced in bacteria, suggesting that SRPK1 is responsible for the generation of the mAb 104-specific phosphoepitope in vivo. Finally, we have correlated the effects of mutagenesis in the SR domain of SF2/ASF on splicing with those on phosphorylation of the protein by SRPK1, suggesting that phosphorylation of SR proteins is required for splicing.     

Evidence for a direct stimulatory effect of cibenzoline on insulin secretion in rats.

The effect of cibenzoline succinate, a new antiarrhythmic agent, was studied on insulin secretion in rats. Experiments were performed both in vivo and in vitro using two preparations: the isolated perfused pancreas and isolated islets. In anaesthetized rats, cibenzoline was able to increase plasma insulin levels and to reduce glycaemia. These effects were observed at 1 mg/kg i.v. in fed rats and at 3 mg/kg i.v. in fasted rats. In the isolated pancreas perfused in the presence of a slightly stimulating glucose concentration (8.3 mM), cibenzoline (2 and 6 microM) elicited a progressive and sustained insulin response in a concentration-dependent manner. In the presence of a non-stimulating glucose concentration (4.2 mM), cibenzoline was ineffective at 2 microM and slightly increased basal insulin release at 6 microM. In isolated islets incubated with 8.3 mM glucose, cibenzoline (6 and 20 microM) caused a concentration-dependent stimulation of insulin release. It is concluded that cibenzoline stimulates insulin secretion by a direct action on pancreatic B cells in rats.     

La prothèse totale du coude GUEPAR

Résumé Un grand nombre de prothèses du coude sont actuellement disponibles, beaucoup de critères les opposent les unes aux autres. Après les premières prothèses à charnière contrainte, les prothèses semicontraintes et plus récemment les prothèses à glissement se sont imposées. La prothèse à glissement GUEPAR se situe dans l'évolution récente des implants du coude. Nous rapportons ici les résultats des trente-neuf premières arthroplasties réalisées au sein du Guepar de 1986 à 1991, sur 33 coudes rhumato?des, 4 destructions post-traumatiques, 1 spondylarthrite ankylosante et 1 arthrose sur chondrocalcinose.

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The Guepar total elbow arthroplasty

Summary The Guepar total elbow replacement is a low friction, minimally constrained gliding prosthesis. The humeral and ulnar components are of metal with intramedullary stems, which are cemented. There is a sigmoid shaped, high density polyethylene interposition bearing. The authors have used the prosthesis in 33 patients with rheumatoid arthritis, 4 with post-traumatic problems, one with chondrocalcinosis and another with degenerative changes of uncertain aetiology. In the patients with rheumatoid arthritis, one sustaine a posterior dislocation and two suffered deep infection. In the remaining 30, the overall results were good at an average review of 32 months. The mean range of movement had increased by 31° and pain was absent in 28 elbows. In the management of rheumatoid arthritis total elbow arthroplasty must be part of an overall plan of treatment. Severe involvement of the wrist and shoulder must be dealt with before elbow replacement is considered.

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Nous remercions Mr J. H. Aubriot, M. Condamine, A Deburge, B Lassale, T Le Balc'h, J. Y. Nordin et J Witvoet, membres du GUEPAR (Groupe pour l'utilisation et l'étude des prothèses articulaires) de nous avoir donné leurs observations     

A contribution to the comparison of the efficacy of radiotherapeutic procedures in cervical carcinoma.

This paper presents a new method in which the regression velocity of cervical carcinoma is measured by computer tomography and the results evaluated by two statistical methods: non-linear regression analysis and survival analysis. By means of this approach it was possible to compare the early effect of therapy in patients treated with intracavitary application of 226Ra plus external radiotherapy with those treated with 252Cf, 226Ra and extended radiotherapy. In the latter group a higher efficacy of the therapy was demonstrated by both statistical methods. As the timing between external and intracavitary radiotherapy was different in the two groups and as 252Cf contributed to a rather small part of the total radiation dose it could not be concluded that the difference in efficacy really was due to 252Cf. Of essential interest was, however, that an obvious difference in efficacy could be found between two slightly different treatment techniques. The statistical procedure called survival analysis, used here parallelly with weighed regression analysis seemed to give better results than a classical regression analysis and can thus be recommended for processing of clinical data of the type which is discussed in this paper.     

Cognitive processes involved in the appraisal of stress

Four experiments were organized around a central question: What is the form of relationship between estimated stress level on the one hand and situation strain, personal resources and social support, on the other? The first experiment examined the form of the relationship between estimated level of stress, situation strain and personal resources. The participants were students. They integrated situation strain and personal resources information in a non‐additive way. In particular, the effect of personal resources on the estimated level of stress varied as a function of the level of situation strain considered. When the situation strain was low, the stress level related with this circumstance largely depended on the personal resources of the individual. When the situation strain was high, the stress level related with this circumstance was much less dependent on the personal resources of the individual. The second experiment replicated these results among first‐aid workers, fire‐fighters and persons that had recently been injured. The third and fourth experiments replicated these results in various conditions differing as regards the level of social support. Copyright © 2002 John Wiley & Sons, Ltd.     

Preliminary evaluation of a fuzzy logic-based automatic quantitative analysis in myocardial SPECT.

This study validates a new quantitative myocardial perfusion SPECT software. METHODS: The processing starts with the extraction of the morphologic skeleton of the left ventricular myocardium from reconstructed transverse sections. Fuzzy logic is used to decide whether a pixel belongs to the myocardium and any perfusion defect is filled according to a truncated bullet model. The resulting image is partitioned in 18 isovolumetric sectors. Sex-matched normal limits, criteria of abnormality for rest (201)Tl and (99m)Tc-labeled perfusion tracers, reproducibility studies, and detection of coronary artery disease were developed and validated in an overall population of 343 patients. The sex- and tracer-matched means and SDs of a normal response were calculated in 93 male and 93 female patients with a <5% likelihood of coronary artery disease. Reproducibility measurements and assignment of different sectors of the myocardium to a specific coronary were performed from data collected in 49 and 60 patients, respectively. The accuracy of the detection of a coronary artery occlusion was assessed in 48 patients who also underwent coronary angiography. RESULTS: The intra- and interoperator reproducibility of the sectorial activity was high with a linear regression coefficient of 0.97 and a SD of the difference measurement at 4.4% and 3.8%, respectively. Overall sensitivity and specificity for the detection of occluded coronary artery were 90% and 80%, respectively. For the detection of left anterior descending, left circumflex, and right artery coronary occlusion, sensitivity was 92%, 75%, and 92.5%, respectively, and specificity was 75%, 78%, and 90%, respectively. CONCLUSION: The new quantitative myocardial perfusion SPECT software appears to be a very helpful program for the objective analysis of perfusion tracer distribution in myocardial SPECT and a very accurate tool in the detection and localization of coronary artery occlusion.     

Genetic polymorphisms and heart failure.

Heart failure is a complex clinical syndrome. There is evidence for a genetic contribution to the pathophysiology of heart failure. Considering the fundamental role of neurohormonal factors in the pathophysiology and progression of cardiac dysfunction and hypertrophy, variants of genes involved in this system are logical candidate genes in heart failure. In this report, genetic polymorphisms of the major neurohormonal systems in heart failure will be discussed. Studies on polymorphisms of the renin-angiotensin-aldosterone system (RAAS), adrenergic receptor polymorphisms, endothelin (receptor) polymorphisms, and a group of miscellaneous polymorphisms that may be involved in the development or phenotypic expression of heart failure will be reviewed. Research on left ventricular hypertrophy is also included. The majority of genetic association studies focused on the ACE I/D polymorphism. Initial genetic associations have often been difficult to replicate, mainly due to problems in study design and lack of power. Promising results have been obtained with genetic polymorphisms of the RAAS and sympathetic system. Considering the evidence so far, a modifying role for these polymorphisms seems more likely than a role of these variants as susceptibility genes. Besides the need for larger studies to examine the effects of single nucleotide polymorphisms and haplotypes, future studies also need to focus on the complexity of these systems and study gene-gene interactions and gene-environment interactions.     

Hypointense transcerebral veins at T2*-weighted MRI: a marker of hemorrhagic transformation risk in patients treated with intravenous tissue plasminogen activator.

Prediction of hemorrhagic transformation (HT) in patients treated by intravenous recombinant tissue-type plasminogen activator (rt-PA) is a challenging issue in acute stroke management. HT may be correlated with severe hypoperfusion. Signal changes may be observed at susceptibility-weighted magnetic resonance imaging (MRI) within large perfusion defects. A signal drop within cerebral veins at T2*-weighted gradient-echo MRI may be expected in severe ischemia, and may indicate subsequent risk of HT. The authors prospectively searched for an abnormal visibility of transcerebral veins (AVV) within the ischemic area in patients with hemispheric ischemic stroke, before they were treated with intravenous rt-PA therapy. Any correlation between AVV and baseline clinical or MRI findings, or further HT, was noted. An AVV was present in 23 of 49 patients (obvious, n = 8; moderate, n = 15), and was supported by severe hemodynamic changes at baseline MRI. The AVV was correlated with the occurrence of parenchymal hematoma type 2 at computed tomography during the first week (r = 0.44, P = 0.002). Five of six type 2 parenchymal hematomas occurred in association with obvious AVV. At multiple regression analysis, two baseline MRI factors had an independent predictive value for HT risk during the first week: the AVV and the cerebral blood volume ratio (Nagelkerke R2 = 0.48).