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R Simon

Publications and source records attributed to R Simon.

At least 181 records · Page 10Linked to original sources
PubMed1996

Cytoplasmic polyadenylation of activin receptor mRNA and the control of pattern formation in Xenopus development.

The activin receptor, a transmembrane serine-threonine kinase, is a key component necessary for pattern formation in early Xenopus development. This protein interacts with members of the transforming growth factor beta family and stimulates cells of the marginal zone to differentiate along the mesodermal pathway. In large part, this function of the activin receptor has been inferred from observations of phenotypes induced by injected mRNA encoding wild-type or mutant forms of the protein. Naturally occurring activin receptor mRNA is maternally inherited and contains within its 3' untranslated region an embryonic-type cytoplasmic polyadenylation element (CPE), an oligouridylic acid sequence that promotes cytoplasmic polyadenylation and resultant translational activation. Based on the presence of this element, we predicted in a previous report that activin receptor mRNA expression in embryos might be regulated by cytoplasmic polyadenylation (Simon and Richter, Mol. Cell. Biol. 14, 7867-7875, 1994). In this study, we have tested this hypothesis and show that not only do endogenous and injected activin receptor mRNAs undergo cytoplasmic polyadenylation during embryogenesis, but also that this process is necessary for stimulating translation and inducing the morphological defects observed by mRNA overexpression. The activin receptor CPE is bound by a Mr 36 x 10(3) protein in vitro, and competition for this factor between mRNAs in vivo inhibits activin receptor mRNA polyadenylation. This competition may be responsible for the lack of mesoderm formation observed in such injected embryos. These data suggest that cytoplasmic polyadenylation controls differentiation and pattern formation in early Xenopus development.

Activin Receptors↗
PubMed1996

Herbage density of third-stage larvae of goat strongyles during the dry season in Guadeloupe.

The objective of this study was to determine the main sources of variation in herbage densities of infective third stage larvae of goat strongyles during the marked dry season of 1994 in Guadeloupe (FWI). Herbage samples were collected for L3 density (LD) determination by an accurate method, 4 times at 4-week intervals in 58 paddocks of 21 farms spread out in five regions of the archipel of Guadeloupe. At the same time, FEC of each grazing animal and fecal culture for parasite genus determination according to sex and age were carried out. Stocking rate, dry matter content of soil, and daily climatic data were also recorded. An index of egg development in larvae (IEDL) was calculated as the ratio of LD to the eggs deposed during the 4th, 3rd, and 2nd weeks before sampling. Medians of LD in herbage were 3397, 1853, 1410, and 324 L3/kg DM for all parasites, Haemonchus, Trichostrongylus, and Oesophagostomum, respectively. Date of sampling, region, and irrigation practice in the northern windward region were the main sources of variation in LD and in frequency of each parasite. LD decreased as the dryness lasted, but it remained important (500 L3/kg DM) despite the drought. LD in windward regions were higher than in other regions. The region, the farm, and the paddock were the main sources of variation of IEDL. LD of each parasites were inversely correlated to global radiation recorded 1 to 3 weeks before herbage sampling, but no relation was found with rainfall data. Trichostrongylus frequency in L3 population increased as the dryness lasted. A dryness axis was extracted from environmental variables (climatic data, dry matter of soil, duration of dryness) by a multiple factorial procedure. LD and Haemonchus frequency in L3 population were inversely correlated to dryness axis (p < 0.01). In contrast, Trichostrongylus frequency was positively correlated to the dryness component.

Animal Feed↗
PubMed1996

Microbiological contamination of drinking water in a commercial household water filter system.

The microbiological quality of filtered water in a commercial water filter system (Brita) was tested in households and in two laboratories. In 24 of 34 filters used in households, bacterial counts increased in the filtered water up to 6,000 cfu/ml. In 4 of 6 filters tested in the laboratory, bacterial counts in the fresh filtrate were higher than in tap water after approximately one week of use both at room temperature and at 4 degrees C, suggesting growth or biofilm formation in the filter material. In some cases colony counts in the filtered water were 10,000 times those in tap water. The filter material of 5 of 13 new commercial filters was contaminated with bacteria or moulds. National or international regulatory agencies should ensure that water filters marketed for domestic use do not allow deterioration in the microbiological quality of drinking water.

Bacteria↗
PubMed1996

[Comparative genomic hybridization in pathology. A new molecular cytogenetic method].

Comparative genomic hybridisation (CGH) is a new cytogenetic method, which is based on a combination of fluorescence microscopy and digital image analysis. The molecular genetic basis is the hybridization of a mixture of fluorescein labeled test-DNA and reference-DNA on normal metaphase chromosomes. Comparative analysis allows the identification of all unbalanced chromosomal aberrations of the test-DNA in a single experimental step. The resulting DNA gains or DNA losses on the chromosomal or subchromosomal level mirror possible amplifications of oncogenes or losses of suppress orgenes. As CGH can be performed with genomic DNA of formalin-fixed and fresh-frozen tissue or cells, this new method is a very effective tool for pathologists and cytologists in the extended genomic screening of tumors and genetically altered tissues. Despite CGH analysis at present is restricted to research applications; its widespread dissemination as a routine method in diagnostic pathology can be expected in the near future.

Animals↗
PubMed1996

[Synopsis of unbalanced chromosome aberrations in neuroblastoma by comparative genomic hybridization].

Neuroblastoma is the most frequent extracranial solid tumor of early childhood. Histologically and genetically, neuroblastoma represents a heterogeneous group of tumors with significant differences in clinical behavior. In the past, several different characteristic chromosomal aberrations of neuroblastoma have been described, of which a deletion on chromosome 1p and N-myc amplification have been shown to be of major prognostic significance. However, the role of various other nonrandom DNA imbalances in tumor development and progression needs to be clarified. Taking advantage of the recently established comparative genomic hybridization (CGH), we show that this method is able to accurately detect chromosomal imbalances of known prognostic impact. As CGH gives a comprehensive picture of genetic imbalances in just one experiment, it additionally sheds light on other abnormalities of possible prognostic relevance. We therefore recommend further use of this method not only in the field of research but also for the purpose of genetic routine diagnostics in neuroblastoma.

Child↗
PubMed1996

A novel class of 5-HT2A receptor antagonists: aryl aminoguanidines.

Local delivery of serotonin (5-HT) produces a rapid edematous response in soft tissues via increased fluid extravasation which is prevented by 5-HT2 antagonists such as ketanserin or mianserin. Here we report the effects of a new class of aminoguanidine 5-HT2 antagonists, with relative selectivity for 5-HT2A receptors which are potent inhibitors of 5-HT-induced paw edema in the rat. Radioligand binding studies with 125I DOI on human 5-HT2A and 5-HT2C receptors and with 3H-5-HT on human 5-HT2B receptors demonstrated that, LY314228, and LY320954 displayed some selectivity for the 5-HT2A receptor. When compared to binding at other 5-HT2 receptor subtypes, LY314228 had an 18.6-fold greater affinity for the 5-HT2A site over the 5-HT2B site, and 2.6 fold greater at the 5-HT2C site. LY320954 displayed similar preference for 5-HT2A sites. Both compounds also inhibited 5-HT-induced paw swelling in rats, with ED50's of 6.4 and 4.8 mg/kg (for LY314228 and LY320954, respectively). These studies offer evidence for a novel class of pharmacophores for the 5-HT2 receptor family which show greater relative affinities for the 5-HT2A receptor subclass.

Animals↗
PubMed1996

Comparison of methods for counting third stage larvae of gastrointestinal nematodes of small ruminants in tropical pastures.

The accuracy and the precision of a simple and reliable technique for the extraction and the counting of third stage larvae densities of gastro-intestinal strongyles of ruminants from pasture samples are assessed in tropical conditions, i.e. for pangola pastures and for the genera of Haemonchus and Trichostrongylus. To separate the larvae from herbage samples, water washings obtained by a centrifuge spin-dryer were put to sediment in disposable plastic bags. The extraction and counting of larvae from sediments were achieved by exhaustion of sediments with repeated sucrose/water interface procedures. The recovery rate of third stage infective larvae (L3) added to the sediment was 79.1% (+/- 9.49%). The accuracy, estimated as recovery rate of L3 added to herbage samples, was 76.5 (+/- 11.31%). The recovery by the sedimentation method was 3.5 times higher than that of a filtering method through a 20 microns sieve. The detection limit was estimated to be 130 L3 kg-1 dry matter. Precision, estimated as the residual standard deviation of duplicate assays, was 1857 L3 kg-1 dry matter (mean 9164 L3 kg-1 dry matter). Results obtained in routine epidemiological surveys of gastro-intestinal strongylosis of small ruminants in West Africa and in the West Indies demonstrated the usefulness of the technique.

Animal Feed↗
PubMed1996

Continued benefit of coronary stenting versus balloon angioplasty: one-year clinical follow-up of Benestent trial. Benestent Study Group.

OBJECTIVES: This study sought to determine the 1-year clinical follow-up of patients included in the Benestent trial. BACKGROUND: The Benestent trial is a randomized study comparing elective Palmaz-Schatz stent implantation with balloon angioplasty in patients with stable angina and a de novo coronary artery lesion. Seven-month follow-up data have shown a decreased rate of restenosis and fewer clinical events in the stent group. It is not established whether this favorable clinical outcome is maintained for longer periods or whether coronary stenting defers restenosis and its subsequent clinical manifestations. METHODS: To clarify this uncertainty, we updated clinical information on all but 1 of 516 patients enrolled in the Benestent trial (257 in balloon group, 259 in stent group) at least 12 months after the intervention. Major clinical events (primary clinical end point) were tabulated according to the intention to treat principle and included death, the occurrence of a cerebrovascular accident, myocardial infarction, the need for bypass surgery or a further percutaneous intervention in the previously treated lesion. RESULTS: After 1 year, no significant differences in mortality (1.2% vs. 0.8%), stroke (0.0% vs. 0.8%), myocardial infarction (5.0% vs. 4.2%) or coronary bypass graft surgery (6.9% vs. 5.1%) were found between the stent and balloon angioplasty groups, respectively. However, the requirement for a repeat angioplasty procedure was significantly lower in the stent group (10%) than the balloon angioplasty group (21%, relative risk [RR] 0.49, 95% confidence interval [CI] 0.31 to 0.75, p = 0.001), and overall primary end points were less frequently reached by stent group patients (23.2%) than those in the balloon group (31.5%, RR 0.74, 95% CI 0.55 to 0.98, p = 0.04). No differences were found between groups with respect to functional class angina and prescribed medication at the time of follow-up. CONCLUSIONS: These clinical follow-up data show that the benefit of elective native coronary artery stenting in patients with stable angina is maintained to at least 1 year after the procedure and results in a significantly reduced requirement for repeat intervention.

Angina Pectoris↗
PubMed1996

Data monitoring committees and problems of lower-than-expected accrual or events rates.

Data monitoring committees for randomized clinical trials must frequently decide what action, if any, is required for trials whose accrual has been slower than expected, or whose event rates have been less than expected. We discuss in this article some of the practical issues concerning modifying or closing such trials, including what data and analyses could be helpful to the data monitoring committee in their deliberations.

Decision Making↗
PubMed1996

Uniform approach to risk classification and treatment assignment for children with acute lymphoblastic leukemia.

PURPOSE: To define more uniform criteria for risk-based treatment assignment for children with acute lymphoblastic leukemia (ALL), the Cancer Therapy Evaluation Program (CTEP) of the National Cancer Institute (NCI) sponsored a workshop in September 1993. Participants included representatives from the Childrens Cancer Group (CCG), Pediatric Oncology Group (POG), Dana-Farber Cancer Institute (DFCI), St Jude Children's Research Hospital (SJCRH), and the CTEP. METHODS: Workshop participants presented and reviewed data from ALL clinical trials, using weighted averages to combine outcome data from different groups. RESULTS: For patients with B-precursor (ie, non-T, non-B) ALL, the standard-risk category (4-year event-free survival [EFS] rate, approximately 80%) will include patients 1 to 9 years of age with a WBC count at diagnosis less than 50,000/microL. The remaining patients will be classified as having high-risk ALL (4-year EFS rate, approximately 65%). For patients with T-cell ALL, different treatment strategies have yielded different conclusions concerning the prognostic significance of T-cell immunophenotype. Therefore, some groups/institutions will classify patients with T-cell ALL as high risk, while others will assign risk for patients with T-cell ALL based on the uniform age/WBC count criteria. Workshop participants agreed that the risk category of a patient may be modified by prognostic factors in addition to age and WBC count criteria, and that a common set of prognostic factors should be uniformly obtained, including DNA index (DI), cytogenetics, early response to treatment (eg, day-14 bone marrow), immunophenotype, and CNS status. CONCLUSIONS: The more uniform approach to risk-based treatment assignment and to collection of specific prognostic factors should increase the efficiency of future ALL clinical research.

Adolescent↗
PubMed1996

[Differential therapy of cardiogenic shock with dopamine/milrinone in comparison with dopamine/dobutamine].

In cardiogenic shock, combined pharmacotherapy with dopamine/dobutamine was being used as a standard regimen and was compared to dopamine/milrinone in this study. In a total of 20 patients with persistent hemodynamic depression despite mechanical ventilation plus dopamine (10-12 micrograms/kg/min) and nitroglycerin (33 micrograms/min) infusions additional therapy with dobutamine (maximal dose: 9 micrograms/kg/min; n = 10) or milrinone (0.5 microgram/kg/min; n = 10) was started. Dobutamine induced an increase of cardiac index (2.0 +/- 0.1 to 2.9 +/- 0.21/min/m2; p < 0.01; mean +/- SEM) and heart rate (96 +/- 6 to 117 +/- 5 min-1; p < 0.05) while mean arterial pressure (75 +/- 2 to 71 +/- 4 mm Hg) and pulmonary capillary wedge pressure (21 +/- 2 to 19 +/- 2 mm Hg) hardly changed. The rate-pressure product rose from 10790 +/- 684 to 13234 +/- 678 mm Hg/ min (p < 0.05). Milrinone had a comparable effect on cardiac index (2.0 +/- 0.1 to 2.6 +/- 0.1 I/min/m2; p < 0.01) but induced a minor change in heart rate (94 +/- 6 to 104 +/- 8 min-1; p < 0.05) and a more pronounced decrease in mean arterial pressure (77 +/- 2 to 65 +/- 2 mm Hg; p < 0.01) and pulmonary capillary wedge pressure (24 +/- 2 to 17 +/- 1 mm Hg; p < 0.01). The rate-pressure product declined (11033 +/- 711 to 10555 +/- 929 mm Hg/min). In comparison, dopamine/milrinone appeared to be advantageous in terms of pre- and afterload reduction and myocardial oxygen demand. However, the concomitant decline in arterial pressure might impair end-organ perfusion.

Aged↗
PubMed1995

Human CNTF and related cytokines: effects on DRG neurone survival.

Ciliary neurotrophic factor (CNTF), leukaemia inhibitory factor (LIF), oncostatin M (OSM), interleukin-6 (IL-6), and interleukin-11 (IL-11) are structurally and functionally related cytokines. We compared their survival-promoting activities on embryonic chick and newborn rat dorsal root ganglion (DRG) neurones. Human CNTF showed the well known trophic effect on both chick and rat DRG neurones. Human and murine LIF and, at unphysiologically high doses, human OSM were trophic for rat neurones, but failed to promote chick DRG cell survival. Human IL-11, murine IL-6 and human IL-6 did not improve chick or rat DRG neurone survival; soluble human IL-6 receptor alpha did not increase sensitivity to human IL-6. Thus, human CNTF as well as murine and human LIF had special neurotrophic properties compared with other related cytokines.

Animals↗
PubMed1995

A comparison of hirudin with heparin in the prevention of restenosis after coronary angioplasty. Helvetica Investigators.

BACKGROUND: The likelihood of restenosis is a major limitation of coronary angioplasty. We studied whether hirudin, a highly selective inhibitor of thrombin with irreversible effects, would prevent restenosis after angioplasty. We compared two regimens of recombinant hirudin with heparin. METHODS: We randomly assigned 1141 patients with unstable angina who were scheduled for angioplasty to receive one of three treatments: (1) a bolus dose of 10,000 IU of heparin followed by an intravenous infusion of heparin for 24 hours and subcutaneous placebo twice daily for three days (382 patients), (2) a bolus dose of 40 mg of hirudin followed by an intravenous infusion of hirudin for 24 hours and subcutaneous placebo twice daily for three days (381 patients), or (3) the same hirudin regimen except that 40 mg of hirudin was given subcutaneously instead of placebo twice daily for three days (378 patients). The primary end point was event-free survival at seven months. Other end points were early cardiac events (within 96 hours), bleeding and other complications of the study treatment, and angiographic measurements of coronary diameter at six months of follow-up. RESULTS: At seven months, event-free survival was 67.3 percent in the group receiving heparin, 63.5 percent in the group receiving intravenous hirudin, and 68.0 percent in the group receiving both intravenous and subcutaneous hirudin (P = 0.61). However, the administration of hirudin was associated with a significant reduction in early cardiac events, which occurred in 11.0, 7.9, and 5.6 percent of patients in the respective groups (combined relative risk with hirudin, 0.61; 95 percent confidence interval, 0.41 to 0.90; P = 0.023). The mean minimal luminal diameters in the respective groups on follow-up angiography at six months were 1.54, 1.47, and 1.56 mm (P = 0.08). CONCLUSIONS: Although significantly fewer early cardiac events occurred with hirudin than with heparin, hirudin had no apparent benefit with longer-term follow-up.

Angina, Unstable↗
PubMed1995

Investigating a sequence of randomized phase II trials to discover promising treatments.

We consider clinical trial strategies to study diseases in which there is rapidly developing technology. We assume the availability of a limited number of patients for screening treatments over a time horizon, and that availability of new treatments for test is staggered over time. We assume further that patient response is binary and rapidly observable. We consider the strategy of conducting a sequence of two-armed randomized clinical trials. We carry over the treatment with the larger number of observed successes on the current trial to the next trial for comparison with a new treatment, with this process repeated at each step. For a fixed total number of patients (N), the number of trials one may conduct in sequence (k) is inversely related to the sample size per trial (2n), N = 2nk. We investigate how k and n influence (a) the expected success probability for the treatment selected at the end, and (b) the expected number of total successes for the N patients. The ultimate objective is to select one treatment, the winner at stage k, to test against a standard regimen in a randomized comparative phase III trial.

Clinical Trials, Phase II as Topic↗
PubMed1995

Human ciliary neurotrophic factor: a structure-function analysis.

Ciliary neurotrophic factor (CNTF) promotes survival in vitro and in vivo of several neuronal cell types including sensory and motor neurons. The primary structure of CNTF suggests it to be a cytosolic protein with strong similarity to the alpha-helical cytokine family which is characterized by a bundle of four anti-parallel helices. CNTF exerts its activity via complexation with CNTF receptor (CNTF-R). This complex consists of a CNTF-binding protein (CNTF-R) and two proteins important for signal transduction [gp130 and leukaemia inhibitory factor receptor (LIF-R)]. We have shortened the cDNA coding for CNTF at both the 5' and the 3' end and expressed the truncated proteins in bacteria. Biological activities of the protein preparations were determined by their ability to induce proliferation of BAF/3 cells that were stably transfected with CNTF-R, gp130 and LIF-R cDNAs. CNTF proteins with 14 amino acid residues removed from the N-terminus were biologically active whereas the removal of 23 amino acids resulted in an inactive protein. In addition, 18 amino acid residues could be removed from the C-terminus of the CNTF protein without apparent loss of bioactivity, but further truncation at the C-terminus yielded biologically inactive proteins. The introduction of two point mutations into the CNTF protein at a site that presumably interacts with one of the two signal-transducing proteins resulted in a CNTF mutant with no measurable bioactivity. In addition, a model of the three-dimensional structure of human CNTF was constructed using the recently established structural co-ordinates of the related cytokine, granulocyte colony-stimulating factor. CD spectra of CNTF together with our mutational analysis and our three-dimensional model fully support the view that CNTF belongs to the family of alpha-helical cytokines. It is expected that our results will facilitate the rational design of CNTF mutants with agonistic or antagonistic properties.

Amino Acid Sequence↗
PubMed1995

[Fatal Aspergillus sepsis following orthotopic heart transplantation].

In a 64-year-old man heart transplantation had been performed for ischaemic heart disease. 7 months later severe vascular disease in the transplant necessitated a second transplantation. Both procedures had been performed under immunosuppression (cyclosporine, azathioprine, prednisolone, antithymocyte globulin), with a subsequent prednisolone maintenance dose of 10 mg daily. At first there were no complications, but 31 days after the re-transplantation atrial flutter developed. Although this was quickly terminated by drugs, circulatory failure set in. Because of signs of infection (white blood cell count 29,800/microliters, 17% stab cells, C-reactive protein 24 mg/l) broad-spectrum antibiotics were administered, but without response. As a trial anti-rejection treatment was started (prednisolone 250 mg daily: antithymocyte globulin 100 mg daily for 4 days). When cytomegalovirus (CMV) infection was demonstrated, ganciclovir and CMV hyperimmunoglobulin were administered and slow improvement was noted. The finding of Aspergillus in tracheal secretion was interpreted as apathogenic colonization. The patient died from cardiorespiratory failure 57 days after the second transplantation. Autopsy revealed Aspergillus sepsis.

Aspergillosis↗