Biomedical subjects

A Charlesworth

Publications and source records attributed to A Charlesworth.

At least 19 recordsLinked to original sources

PubMed2002

Multidose flurbiprofen 8.75 mg lozenges in the treatment of sore throat: a randomised, double-blind, placebo-controlled study in UK general practice centres.

The flurbiprofen 8.75 mg lozenge is a novel formulation that combines a demulcent effect with the analgesic activity of a non-steroidal anti-inflammatory drug. Previous controlled clinical studies have demonstrated the single- and multi-dose efficacy of these lozenges over placebo. The current study reflected the treatment of sore throat in general practice, investigating multiple dose efficacy where patients also had access to concomitant antibiotics and rescue medication. The efficacy of flurbiprofen 8.75 mg lozenge over placebo was confirmed: there was a significant difference in pain relief obtained from flurbiprofen 8.75 mg versus placebo, along with a significant reduction of difficulty in swallowing from the time of first assessment and significantly greater reductions in throat soreness and difficulty in swallowing throughout the study period. Additionally, significant benefit over placebo was demonstrated where concomitant antibiotic use was introduced, indicating that flurbiprofen 8.75 mg lozenges can be co-administered when antibiotic therapy is appropriate. No significant safety issues were identified.

Adult↗

PubMed2001

A simple risk index for rapid initial triage of patients with ST-elevation myocardial infarction: an InTIME II substudy.

BACKGROUND: Rapid, effective triage is integral to emergency cardiac care of patients with ST-elevation myocardial infarction (STEMI). Available models for predicting mortality in STEMI include up to 45 variables, but have consistently shown advanced age, increased heart rate, and decreased blood pressure to be among the strongest predictors. METHODS: On the basis of observed risk relations among 13,253 patients with STEMI from the InTIME II trial, we developed and assessed a simple risk index using age, heart rate, and systolic blood pressure (SBP) for predicting mortality over 30 days: (heart rate x [age/10](2))/SBP. FINDINGS: The risk index was a strong (c statistic=0.78) and independent predictor of mortality risk (p<0.0001). When the risk index was categorised into quintiles for convenient clinical use, it revealed a more than 20-fold gradient of increasing mortality from 0.8 to 17.4%, p<0.0001. The risk index was also a robust predictor of very early events, including death by 24 h (c statistic=0.81). External validation in patients with STEMI from the TIMI 9 trials (n=3659) showed both a high discriminatory capacity (c statistic=0.79), and excellent concordance between the observed 30-day mortality in each of the five risk groups and the predictions based on InTIME II (goodness-of-fit, p=0.7). INTERPRETATION: A simple risk index based on characteristics easily assessed by any paramedical or clinical personnel captures most of the information from more complex tools, and is likely to be useful in the rapid triage of patients with STEMI outside hospital or on first arrival in the hospital.

Age Factors↗

PubMed2001

Identification and characterization of the gene encoding human cytoplasmic polyadenylation element binding protein.

The maturation of human oocytes occurs in the absence of gene transcription. In model organisms, such as Drosophila, Xenopus, and the mouse, oocyte maturation and early pattern formation is mediated through the regulated translation of maternally derived mRNAs. The maturation-dependent stimulation of maternal mRNA translation is correlated with increases in poly(A) tail length, controlled through a process termed cytoplasmic polyadenylation. However, this mechanism of mRNA translational control has not been characterized in humans. In this study we report the cloning of a human cytoplasmic polyadenylation element binding (hCPEB) protein with sequence-specific RNA binding activity. Our data demonstrate that alternative splicing generates hCPEB mRNAs that encode proteins with a conserved C-terminal RNA binding domain but with different N-terminal regulatory domains. The hCPEB mRNA is expressed in the brain and heart as well as in immature oocytes, consistent with the hypothesis that cytoplasmic polyadenylation may regulate the translation of human mRNAs in both oocytes and somatic cells.

Adult↗

PubMed2001

Compensation between Vav-1 and Vav-2 in B cell development and antigen receptor signaling.

Vav-1 and Vav-2 are closely related Dbl-homology GTP exchange factors (GEFs) for Rho GTPases. Mutation of Vav-1 disrupts T cell development and T cell antigen receptor-induced activation, but has comparatively little effect on B cells. We found that combined deletion of both Vav-1 and Vav-2 in mice resulted in a marked reduction in mature B lymphocyte numbers. Vav-1(-/-)Vav-2(-/-) B cells were unresponsive to B cell antigen receptor (BCR)-driven proliferation in vitro and to thymus-independent antigen in vivo. BCR-stimulated intracellular calcium mobilization was greatly impaired in Vav-1(-/-)Vav-2(-/-) B cells. These findings establish a role for Vav-2 in BCR calcium signaling and reveal that the Vav family of GEFs is critical to B cell development and function.

Animals↗

PubMed2001

Geographic variation in patient and hospital characteristics, management, and clinical outcomes in ST-elevation myocardial infarction treated with fibrinolysis. Results from InTIME-II.

AIMS: We examined the geographic variations in InTIME-II, a randomized double-blind trial comparing alteplase with lanoteplase for myocardial infarction. METHODS AND RESULTS: We compared baseline characteristics, management, and outcomes in four regions (Western Europe, Eastern Europe, North America, and Latin America) and in countries with historically different management approaches (Germany vs the U.K., the U.S. vs Canada). Thirty-day mortality in Western Europe, Eastern Europe, North America and Latin America was 6.7%, 7.3%, 5.7%, 10.1%, P<0.0001. Adjusted mortality for Europe was intermediate between North America and Latin America (odds ratios (OR) [95% confidence intervals (CI)] compared to Western Europe: North America 0.84 [0.67-1.0], Eastern Europe 1.2 [1.0-1.4], and Latin America 1.8 [1.3-2.7]). Revascularization rates varied 10-fold but did not explain regional mortality differences. Germany and the U.K. had similar adjusted 1-year mortality (OR for the U.K. 1.16 [0.92-1.5]), although invasive procedures were four- to 10-fold more common in Germany. Similarly the U.S. and Canada had equal adjusted 1-year mortality (OR for Canada 0.85 [0.61-1.17]) despite three-fold higher use of invasive procedures in the U.S. CONCLUSIONS: Significant geographic variations in practice and adjusted mortality following fibrinolysis persist despite recent guidelines. These findings have important implications in the design and interpretation of international studies, identify under- and over-utilized therapies, and support further study of treatments with marked worldwide variations.

Adult↗

PubMed2001

Availability of on-site catheterization and clinical outcomes in patients receiving fibrinolysis for ST-elevation myocardial infarction.

AIMS: To compare management and clinical outcomes in hospitals stratified by the availability of on-site catheterization in InTIME-II, a multicentre trial comparing alteplase with lanoteplase for acute myocardial infarction. METHODS AND RESULTS: We studied 15,078 patients enrolled in 35 countries and 855 hospitals. Thirty-one percent of hospitals had 24-h, 25% day-only, and 44% no on-site catheterization facilities. Rates of cardiac angiography (57%, 38%, 26%) and revascularization (37%, 21%, 17%) were higher in hospitals with increasing access to on-site facilities(P<0.0001). The presence of a 24-h on-site facility was the strongest predictor of angiography during the index admission (odds ratio 4.17, 95% CI 3.85-4.54). There were no major differences in patient outcomes at 30 days when hospitals were stratified by availability of on-site catheterization. Adjusted 1-year mortality was similar between groups of hospitals (odds ratio for day-only 0.94 [0.80-1.09] and odds ratio for no availability 0.95 [0.83-1.10] compared to hospitals with 24-h facilities). CONCLUSIONS: There is a marked variation in procedure use by the availability of on-site catheterization with no major differences in patient outcomes. There is a need for additional randomized trials in the current era to address both the appropriate selection of patients and timing of invasive procedures in ST-elevation acute myocardial infarction.

Adolescent↗

PubMed2001

Print media coverage of California's smokefree bar law.

OBJECTIVE: To assess the print media coverage of California's smokefree bar law in the state of California. DESIGN: Content analysis of newspaper, trade journal, and magazine items. SUBJECTS: Items regarding the smokefree bar law published seven months before and one year following the implementation of the smokefree bar law (June 1997 to December 1998). Items consisted of news articles (n = 446), opinion editorials (n = 31), editorials (n = 104), letters to the editor (n = 240), and cartoons (n = 10). MAIN OUTCOME MEASURES: Number and timing of publication of items, presence of tobacco industry arguments or public health arguments regarding law, positive, negative, and neutral views of opinion items published. RESULTS: 53% of items published concerning the smokefree bar law were news articles, 47% were opinion items. 45% of items regarding the smokefree bar law were published during the first month of implementation. The tobacco industry dominated coverage in most categories (economics, choice, enforcement, ventilation, legislation, individual quotes), except for categories public health used the most frequently (government role, tactics, organisational quotes). Anti-law editorials and letters to the editor were published more than pro-law editorials and letters. Region of the state, paper size, presence of local clean indoor air legislation, and voting on tobacco related ballot initiatives did not have an impact on the presence of opinion items. CONCLUSIONS: The tobacco industry succeeded in obtaining more coverage of the smokefree bar law, both in news items and opinion items. The tobacco industry used historical arguments of restricting freedom of choice and economic ramifications in fighting the smokefree bar law, while public health groups focused on the worker protection issue, and exposed tobacco industry tactics. Despite the skewed coverage, public health groups obtained adequate attention to their arguments to keep the law in effect.

Bibliometrics↗

PubMed2000

Comparison of a 60- versus 90-minute determination of ST-segment resolution after thrombolytic therapy for acute myocardial infarction. In TIME-II Investigators. Intravenous nPA for Treatment of Infarcting Myocardium Early-II.

Determination of ST-segment resolution 60 minutes after the administration of thrombolytic therapy allows accurate risk stratification for mortality and congestive heart failure. Patients with complete ST resolution at 60 minutes tended to be at lower risk for 30-day mortality than patients with complete ST resolution at 90 minutes.

Aspirin↗

PubMed2000

The temporal control of Wee1 mRNA translation during Xenopus oocyte maturation is regulated by cytoplasmic polyadenylation elements within the 3'-untranslated region.

The Wee1 protein tyrosine kinase is a key regulator of cell cycle progression. Wee1 activity is necessary for the control of the first embryonic cell cycle following the fertilization of meiotically mature Xenopus oocytes. Wee1 mRNA is present in immature oocytes, but Wee1 protein does not accumulate in immature oocytes or during the early stages of progesterone-stimulated maturation. This delay in Wee1 translation is critical since premature Wee1 protein accumulation has been shown to inhibit oocyte maturation. In this study we provide evidence that Wee1 protein accumulation is regulated at the level of mRNA translation. This translational control is directed by sequences within the Wee1 mRNA 3'-untranslated region (3' UTR). Specifically, cytoplasmic polyadenylation element (CPE) sequences within the Wee1 3' UTR are necessary for full translational repression in immature oocytes. Our data further indicate that while CPE-independent mechanisms may regulate the levels of Wee1 protein accumulation during progesterone-stimulated oocyte maturation, the timing of Wee1 mRNA translational induction is directed through a CPE-dependent mechanism.

3' Untranslated Regions↗

PubMed2000

TIMI risk score for ST-elevation myocardial infarction: A convenient, bedside, clinical score for risk assessment at presentation: An intravenous nPA for treatment of infarcting myocardium early II trial substudy.

BACKGROUND: Considerable variability in mortality risk exists among patients with ST-elevation myocardial infarction (STEMI). Complex multivariable models identify independent predictors and quantify their relative contribution to mortality risk but are too cumbersome to be readily applied in clinical practice. METHODS AND RESULTS: We developed and evaluated a convenient bedside clinical risk score for predicting 30-day mortality at presentation of fibrinolytic-eligible patients with STEMI. The Thrombolysis in Myocardial Infarction (TIMI) risk score for STEMI was created as the simple arithmetic sum of independent predictors of mortality weighted according to the adjusted odds ratios from logistic regression analysis in the Intravenous nPA for Treatment of Infarcting Myocardium Early II trial (n=14 114). Mean 30-day mortality was 6.7%. Ten baseline variables, accounting for 97% of the predictive capacity of the multivariate model, constituted the TIMI risk score. The risk score showed a >40-fold graded increase in mortality, with scores ranging from 0 to >8 (P:<0.0001); mortality was <1% among patients with a score of 0. The prognostic discriminatory capacity of the TIMI risk score was comparable to the full multivariable model (c statistic 0. 779 versus 0.784). The prognostic performance of the risk score was stable over multiple time points (1 to 365 days). External validation in the TIMI 9 trial showed similar prognostic capacity (c statistic 0.746). CONCLUSIONS: The TIMI risk score for STEMI captures the majority of prognostic information offered by a full logistic regression model but is more readily used at the bedside. This risk assessment tool is likely to be clinically useful in the triage and management of fibrinolytic-eligible patients with STEMI.

Aged↗

PubMed2000

Oral glycoprotein IIb/IIIa inhibition with orbofiban in patients with unstable coronary syndromes (OPUS-TIMI 16) trial.

BACKGROUND: Although intravenous glycoprotein IIb/IIIa inhibitors are beneficial in patients with acute coronary syndromes, prolonged oral IIb/IIIa inhibition might provide an additional reduction in recurrent events. METHODS AND RESULTS: Investigators at 888 hospitals in 29 countries enrolled 10 288 patients with acute coronary syndromes, which was defined as ischemic pain at rest within 72 hours of randomization, associated with positive cardiac markers, electrocardiographic changes, or prior cardiovascular disease. Patients received aspirin and were randomized to receive, for the duration of the trial, (1) 50 mg of orbofiban twice daily (50/50 group), (2) 50 mg of orbofiban twice daily for 30 days followed by 30 mg of orbofiban twice daily (50/30 group), or (3) a placebo. The primary composite end point was death, myocardial infarction, recurrent ischemia requiring rehospitalization, urgent revascularization, or stroke. The trial was terminated prematurely because of an unexpected increase in 30-day mortality in the 50/30 orbofiban group. Mortality through 10 months was 3.7% for the placebo group versus 5.1% in the 50/30 group (P=0.008) and 4.5% in the 50/50 group (P=0.11). There were no differences in the primary end point (22.9%, 23.1%, and 22.8%, for the placebo, 50/30, and 50/50 groups, respectively). Major or severe bleeding (but not intracranial hemorrhage) was higher with orbofiban; it occurred in 2. 0%, 3.7% (P=0.0004), and 4.5% (P<0.0001) of patients, respectively. Exploratory subgroup analyses found that patients who underwent percutaneous coronary intervention had a lower mortality and a significant reduction in the composite end point (P=0.001) with orbofiban. CONCLUSIONS: -Fixed-dose orbofiban failed to reduce major cardiovascular events and was associated with increased mortality in this broad population of patients with acute coronary syndromes; however, a benefit was observed among patients who underwent percutaneous coronary intervention.

Administration, Oral↗

PubMed2000

Renal function, neurohormonal activation, and survival in patients with chronic heart failure.

BACKGROUND: Because renal function is affected by chronic heart failure (CHF) and it relates to both cardiovascular and hemodynamic properties, it should have additional prognostic value. We studied whether renal function is a predictor for mortality in advanced CHF, and we assessed its relative contribution compared with other established risk factors. In addition, we studied the relation between renal function and neurohormonal activation. METHODS AND RESULTS: The study population consisted of 1906 patients with CHF who were enrolled in a recent survival trial (Second Prospective Randomized study of Ibopamine on Mortality and Efficacy). In a subgroup of 372 patients, plasma neurohormones were determined. The baseline glomerular filtration rate (GFR(c)) was calculated using the Cockroft Gault equation. GFR(c) was the most powerful predictor of mortality; it was followed by New York Heart Association functional class and the use of angiotensin-converting enzyme inhibitors. Patients in the lowest quartile of GFR(c) values (<44 mL/min) had almost 3 times the risk of mortality (relative risk, 2. 85; P<0.001) of patients in the highest quartile (>76 mL/min). Impaired left ventricular ejection fraction (LVEF) was only modestly predictive (P=0.053). GFR(c) was inversely related with N-terminal atrial natriuretic peptide (ANP; r=-0.53) and, to a lesser extent, with ANP itself (r=-0.35; both P<0.001). CONCLUSIONS: Impaired renal function (GFR(c)) is a stronger predictor of mortality than impaired cardiac function (LVEF and New York Heart Association class) in advanced CHF, and it is associated with increased levels of N-terminal ANP. Moreover, impaired renal function was not related to LVEF, which suggests that factors other than reduced cardiac output are causally involved.

Aged↗

PubMed2000

Very early risk stratification after thrombolytic therapy with a bedside myoglobin assay and the 12-lead electrocardiogram.

BACKGROUND: Available clinical criteria to estimate prognosis in patients with evolving ST-segment elevation myocardial infarction do not consider the impact of reperfusion therapy and do not incorporate measurement of baseline levels of cardiac serum markers. We evaluated the combination of a baseline myoglobin assay and early (60- to 90-minute) ST resolution for risk stratification after ST-segment elevation myocardial infarction. METHODS: In a prospective substudy of the Intravenous nPA for Treatment of Infarcting Myocardium Early-II (InTIME-II) trial carried out in 2079 patients, a rapid qualitative assay for myoglobin was performed immediately before thrombolysis. Serial 12-lead electrocardiograms were performed at baseline and 60 to 90 minutes after thrombolysis. ST resolution was categorized as complete (>/=70%), partial (30% to <70%), or none (<30%). RESULTS: Mortality rate at 30 days was 3.3% in the 905 patients with a negative baseline myoglobin assay versus 8.9% in the 527 patients with a positive assay (P <.0001). Mortality rate was lowest (2.4%) among the 614 patients with complete ST resolution, intermediate (4.9%) among the 512 patients with partial ST resolution, and highest (8.1%) among the 540 patients with no ST resolution (P <.0001 for trend). In a logistic regression model incorporating other baseline predictors of 30-day mortality rate, both a positive myoglobin assay (relative risk 1.98, 95% confidence interval 1.00-3.90) and ST resolution <70% (relative risk 2.86, 95% confidence interval 1.22-6.69) were independently associated with increased mortality rate. At 30 days, mortality rate was 0.4% among patients with a negative myoglobin assay and complete ST resolution, 4.8% among patients with either a positive myoglobin assay or ST resolution <70%, and 9.6% among those with both a positive myoglobin ratio and ST resolution <70% (P <.001 for trend). CONCLUSIONS: Within 90 minutes after administering thrombolytic therapy for acute myocardial infarction, clinicians can determine the risk for death at the patient's bedside with a hand-held myoglobin assay and 2 serial 12-lead electrocardiograms. A strategy using these 2 simple, rapid, and inexpensive tests may facilitate triage after thrombolytic therapy.

Adult↗

PubMed2000

Relief of sore throat with the anti-inflammatory throat lozenge flurbiprofen 8.75 mg: a randomised, double-blind, placebo-controlled study of efficacy and safety.

In this double-blind study, 301 patients with subjective and objective signs of sore throat were randomly assigned to flurbiprofen 8.75 mg (n = 129), flurbiprofen 12.5 mg (n = 43) or placebo (demulcent lozenge without active drug [n = 129]). Efficacy was assessed by changes in subjective rating scales primarily after a single dose and also over a 4-day period. Flurbiprofen 8.75 mg was superior to placebo in a number of efficacy parameters, notably throat soreness. Throat soreness was significantly reduced after 15 minutes (p < 0.05), with effects sustained for at least 2 hours (p < 0.05). Multiple dosing with flurbiprofen 8.75 mg lozenges continued to provide effective symptomatic relief over the 4-day treatment period. The small sample size was considered contributory to the variable results obtained with flurbiprofen 12.5 mg lozenges, but overall these were not inconsistent with previous trials. Both treatments were tolerated well. Flurbiprofen 8.75 mg lozenges provide an effective and well tolerated treatment for sore throat.

Adolescent↗

PubMed1999

Tourism and hotel revenues before and after passage of smoke-free restaurant ordinances.

CONTEXT: Claims that ordinances requiring smoke-free restaurants will adversely affect tourism have been used to argue against passing such ordinances. Data exist regarding the validity of these claims. OBJECTIVE: To determine the changes in hotel revenues and international tourism after passage of smoke-free restaurant ordinances in locales where the effect has been debated. DESIGN: Comparison of hotel revenues and tourism rates before and after passage of 100% smoke-free restaurant ordinances and comparison with US hotel revenue overall. SETTING: Three states (California, Utah, and Vermont) and 6 cities (Boulder, Colo; Flagstaff, Ariz; Los Angeles, Calif; Mesa, Ariz; New York, NY; and San Francisco, Calif) in which the effect on tourism of smoke-free restaurant ordinances had been debated. MAIN OUTCOME MEASURES: Hotel room revenues and hotel revenues as a fraction of total retail sales compared with preordinance revenues and overall US revenues. RESULTS: In constant 1997 dollars, passage of the smoke-free restaurant ordinance was associated with a statistically significant increase in the rate of change of hotel revenues in 4 localities, no significant change in 4 localities, and a significant slowing in the rate of increase (but not a decrease) in 1 locality. There was no significant change in the rate of change of hotel revenues as a fraction of total retail sales (P=.16) or total US hotel revenues associated with the ordinances when pooled across all localities (P = .93). International tourism was either unaffected or increased following implementation of the smoke-free ordinances. CONCLUSION: Smoke-free ordinances do not appear to adversely affect, and may increase, tourist business.

Commerce↗

PubMed1999

Achieving appropriate endpoints in heart failure trials: the PRIME-II protocol. The Second Perspective Randomised study of Ibopamine on Mortality and Efficacy.

Many clinical trials unintentionally include patients with a low risk of the trial endpoints. PRIME II (The Second Perspective Randomised study of Ibopamine on Mortality and Efficacy) was a large international randomised double blind trial comparing the addition of ibopamine or placebo to the therapy of patients with advanced heart failure. The trial was stopped prematurely because ibopamine was associated with an increased fatality rate, but the protocol achieved its objective of including high-risk patients. Here we describe the protocol details that enabled patients with the desired degree of risk to be included. We also amplify our definition of mode of death. The PRIME II protocol was designed with the intention that patients in the placebo group would have an annual fatality rate of 20%. Since the study was to be conducted in some 200 centres in 13 European countries, the inclusion criteria had to be simple and flexible, allowing for different clinical practice. The inclusion criteria, together with the use of simple investigations (which did not have to include angiographic or radionuclide ventriculography) are described. The annual fatality rate in the placebo group was just over 20%. Six categories of mode of death were used, but while they were reasonably easy to apply they did not reveal the reason for the unexpected adverse effect of ibopamine. The inclusion and exclusion criteria used for PRIME II, and the definitions of mode of death, were effective. The PRIME II protocol can be used as a model for future heart failure studies.

Clinical Protocols↗

PubMed1999

Differences in drug treatment of chronic heart failure between European countries.

AIMS: A large number of drugs are currently used for the treatment of chronic heart failure. Treatment for other cardiovascular disorders has been shown to differ between countries. In this study we examined whether this would also be true in heart failure. METHODS AND RESULTS: We studied patients with moderate to severe heart failure, who were enrolled in an international survival study, and compared patterns of drug use between the nine countries that each included >50 patients in the study. The results were analysed to determine whether observed differences between countries could be explained by differences in the patients recruited. 1825 patients were studied (range 81-427 per country). By trial protocol, most patients were treated with angiotensin converting enzyme (ACE) inhibitors (92%) and all with diuretics, but the proportion of patients taking high doses of these drugs was markedly different between countries. Large differences were also observed in the use of digoxin (overall 64%, 39% in the U.K. to 87% in Germany) and antiarrhythmics (overall 25%, with the highest use 44% in France). The use of beta-blockers and calcium antagonists was low (overall 6% and 8%, respectively), but also different between countries. Anticoagulants (overall 43%) were used in many patients in the Netherlands and Switzerland (around 70%), while antiplatelets (overall use 30%) were most often prescribed in Denmark (51%). CONCLUSIONS: Large differences in drug use and dosing for patients with advanced heart failure are observed between (European) countries. None of these differences could be explained by differences in patient characteristics, and whether they are related to factors such as tradition, economic circumstances and national guidelines, etc. is unknown.

Adolescent↗

PubMed1999

The mitogen-activated protein kinase signaling pathway stimulates mos mRNA cytoplasmic polyadenylation during Xenopus oocyte maturation.

The Mos protein kinase is a key regulator of vertebrate oocyte maturation. Oocyte-specific Mos protein expression is subject to translational control. In the frog Xenopus, the translation of Mos protein requires the progesterone-induced polyadenylation of the maternal Mos mRNA, which is present in the oocyte cytoplasm. Both the Xenopus p42 mitogen-activated protein kinase (MAPK) and maturation-promoting factor (MPF) signaling pathways have been proposed to mediate progesterone-stimulated oocyte maturation. In this study, we have determined the relative contributions of the MAPK and MPF signaling pathways to Mos mRNA polyadenylation. We report that progesterone-induced Mos mRNA polyadenylation was attenuated in oocytes expressing the MAPK phosphatase rVH6. Moreover, inhibition of MAPK signaling blocked progesterone-induced Mos protein accumulation. Activation of the MAPK pathway by injection of RNA encoding Mos was sufficient to induce both the polyadenylation of synthetic Mos mRNA substrates and the accumulation of endogenous Mos protein in the absence of MPF signaling. Activation of MPF, by injection of cyclin B1 RNA or purified cyclin B1 protein, also induced both Mos protein accumulation and Mos mRNA polyadenylation. However, this action of MPF required MAPK activity. By contrast, the cytoplasmic polyadenylation of maternal cyclin B1 mRNA was stimulated by MPF in a MAPK-independent manner, thus revealing a differential regulation of maternal mRNA polyadenylation by the MAPK and MPF signaling pathways. We propose that MAPK-stimulated Mos mRNA cytoplasmic polyadenylation is a key component of the positive-feedback loop, which contributes to the all-or-none process of oocyte maturation.

Animals↗