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Biomedical subjects

A Monnier

Publications and source records attributed to A Monnier.

At least 19 recordsLinked to original sources
PubMed2006

Complete hormonal blockade versus epirubicin-based chemotherapy in premenopausal, one to three node-positive, and hormone-receptor positive, early breast cancer patients: 7-year follow-up results of French Adjuvant Study Group 06 randomised trial.

BACKGROUND: The purpose of this study was to determine optimal adjuvant therapy between complete hormonal blockade in premenopausal patients with hormone receptor positive breast cancer and one to three positive nodes. PATIENTS AND METHODS: We randomised 333 patients to receive either LHRH agonist (triptorelin 3.75 mg i.m., monthly) plus tamoxifen 30 mg/day for 3 years (TAM-LHRHa, n=164), or fluorouracil 500 mg/m2, epirubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 every 21 days for six cycles, without any hormonal treatment (FEC50, n=169). RESULTS: The 7-year disease-free survival (DFS) was 76% with TAM-LHRHa, and 72% with FEC50 (P=0.13). The 7-year overall survival (OS) was 91% and 88%, respectively (P=0.20). The multivariate analysis confirmed that both treatments were not different for DFS and OS (P=0.83 and P=0.41, respectively). Amenorrhoea occurred in 64% of patients treated with FEC50; it was temporary in 58% of cases after hormonotherapy and in 31% after chemotherapy. CONCLUSION: In intermediate-risk breast cancer, complete hormonal blockade and chemotherapy provided similar outcomes. Hormonal treatment is an alternative to chemotherapy in hormone-sensitive patients, considering the preference of patients in terms of quality of life.

Adult↗
PubMed2006

Multicenter randomized phase III study of the cardioprotective effect of dexrazoxane (Cardioxane) in advanced/metastatic breast cancer patients treated with anthracycline-based chemotherapy.

BACKGROUND: Anthracycline-induced cardiotoxicity has led to the adoption of empirical dose limits that may restrict continued use of anthracyclines among patients who might benefit. Dexrazoxane, a cardioprotective agent, has been shown to reduce the risk of anthracycline-associated cardiotoxicity when given from first dose of anthracycline. This study sought to confirm the benefit of dexrazoxane in patients at high risk of cardiotoxicity due to prior anthracycline use. PATIENTS AND METHODS: A total of 164 female breast cancer patients, previously treated with anthracyclines, received anthracycline-based chemotherapy either with (n = 85) or without (n = 79) dexrazoxane for a maximum of six cycles. RESULTS: Compared with those receiving anthracycline alone, patients treated with dexrazoxane experienced significantly fewer cardiac events (39% versus 13%, P < 0.001) and a lower and less severe incidence of congestive heart failure (11% versus 1%, P < 0.05). Tumor response rate was unaffected by dexrazoxane therapy. The frequency of adverse events was similar between groups and there were no significant between-group differences in the number of dose modifications/interruptions. CONCLUSION: Dexrazoxane significantly reduced the occurrence and severity of anthracycline-induced cardiotoxicity in patients at increased risk of cardiac dysfunction due to previous anthracycline treatment without compromising the antitumor efficacy of the chemotherapeutic regimen.

Adult↗
PubMed2006

The evolving role of letrozole in the adjuvant setting: first results from the large, phase III, randomized trial BIG 1-98.

Tamoxifen has been a standard adjuvant therapy, despite its limited 5-year efficacy window and risk of thromboembolism and endometrial malignancy. The potent aromatase inhibitor letrozole (Femara) has emerged as a viable alternative to tamoxifen for the treatment of advanced, metastatic breast cancer, as well as in the neoadjuvant and extended adjuvant settings. Here we describe the first efficacy and safety analysis of BIG 1-98, a large, randomized, independently conducted clinical trial designed specifically to assess and compare the efficacy of sequential or up-front use of letrozole and/or tamoxifen as adjuvant therapy for patients with early breast cancer. The analysis reported here combined the monotherapy arms of letrozole and tamoxifen with the truncated sequential arms. Patients randomized to letrozole had a 19% reduction in the risk of a disease-free survival event (hazard ratio 0.81; P=0.003), especially reducing distant metastases (hazard ratio 0.73; P=0.0012). These results establish letrozole as part of standard adjuvant therapy for postmenopausal women with endocrine-responsive breast cancer.

Aromatase Inhibitors↗
PubMed2006

Improved disease-free survival with epirubicin-based chemoendocrine adjuvant therapy compared with tamoxifen alone in one to three node-positive, estrogen-receptor-positive, postmenopausal breast cancer patients: results of French Adjuvant Study Group 02 and 07 trials.

BACKGROUND: The purpose was to compare disease-free survival (DFS) between epirubicin-based chemoendocrine therapy and tamoxifen alone in one to three node-positive (N1-3), estrogen-receptor-positive (ER+), postmenopausal early breast cancer (EBC) patients. PATIENTS AND METHODS: We analyzed, retrospectively, 457 patients randomized in FASG 02 and 07 trials who received: tamoxifen alone (30 mg/day, 3 years); or FEC50 (fluorouracil 500 mg/m2, epirubicin 50 mg/m2, cyclophosphamide 500 mg/m2, six cycles every 21 days) plus tamoxifen started concurrently. Radiotherapy was delivered after the third cycle in FASG 02 trial, and after the sixth in FASG 07 trial. RESULTS: The 9-year DFS rates were 72% with tamoxifen and 84% with FEC50-tamoxifen (P = 0.008). The multivariate analysis showed that pathological tumor size >2 cm was an independent prognostic factor (P = 0.002), and treatment effects remained significantly in favor of chemoendocrine therapy (P = 0.0008). The 9-year overall survival rates were 78% and 86%, respectively (P = 0.11). In the multivariate model, there was a trend in favor of chemoendocrine therapy (P = 0.07). CONCLUSION: The addition of FEC50 adjuvant chemotherapy to tamoxifen significantly improves long-term DFS in N1-3, ER+ and postmenopausal women. Chemoendocrine therapy seems to be more effective than tamoxifen in terms of long-term survival.

Adult↗
PubMed2005

Long-term cardiac toxicity after adjuvant epirubicin-based chemotherapy in early breast cancer: French Adjuvant Study Group results.

BACKGROUND: The aim of the study was to evaluate and compare incidence and risk factors of left ventricular dysfunction (LVD) in early breast cancer patients receiving (E+) or not (E-) epirubicin-based adjuvant chemotherapy. PATIENTS AND METHODS: Among eight FASG trials, 3577 assessable patients were analyzed retrospectively: 2553 received epirubicin, 662 received hormonotherapy alone and 362 had no systemic treatment. Chemotherapy was FEC regimen in 86% of cases (fluorouracil, epirubicin, cyclophosphamide). Epirubicin cumulative dose was < 300 mg/m2 in 1040 patients, 300-600 in 1155, > or = 600 in 279, followed by radiotherapy in 96% of cases. RESULTS: Twenty delayed LVD occurred: two in E- patients and 18 in E+ patients. In E+ patients, 14 patients normalized their cardiac function or did not require further investigations, one patient was stabilized with specific treatment, two patients worsened their functions and one died of congestive heart failure. The 7-year risk of LVD was 1.36% (95% CI 0.85-1.87) in E+ patients and 0.21% (95%CI: 0.00-0.52) in E- patients (P = 0.004). Two significant risk factors were identified: age > or = 65 years and body mass index > 27 kg/m2. CONCLUSION: After a long-term follow-up, epirubicin-related LVD risk was acceptable (1.36%) with one toxic death (0.04%). In 78% of cases, LVD were transient or well controlled.

Adult↗
PubMed2005

Secondary leukemia after epirubicin-based adjuvant chemotherapy in operable breast cancer patients: 16 years experience of the French Adjuvant Study Group.

BACKGROUND: The purpose of this study was to evaluate incidence and risk factors of secondary leukemia after adjuvant epirubicin-based chemotherapy in breast cancer patients. PATIENTS AND METHODS: Among eight French Adjuvant Study Group trials, 3653 patients were assessable: 2603 received epirubicin; 682 received hormonotherapy; and 368 had no systemic treatment. Chemotherapy was FEC regimen in 85% of cases (fluorouracil 500 mg/m2, epirubicin 50, 75 or 100 mg/m2, cyclophosphamide 500 mg/m2, three or six cycles). Epirubicin cumulative dose was <300 mg/m2 in 1045 patients; 300-600 mg/m2 in 1187; and > or =600 mg/m2 in 286, followed by radiotherapy in 96% of cases. The median follow-up was 104 months. RESULTS: Eight cases of leukemia occurred in epirubicin-exposed patients and one in non-exposed patients. After 9 years, the risk of developing a leukemia was 0.34% (95% confidence interval 0.11-0.57) in epirubicin-exposed patients. In patients receiving chemotherapy, leukemia subtypes were: AML2 (two), AML3 (one), AML4 (three) and ALL (two). None of the classically recognized risk factors was significantly correlated with the occurrence of a leukemia. CONCLUSION: Irrespective of the dose, the incidence of secondary leukemia after adjuvant epirubicin-based chemotherapy was low. After a long follow-up, the benefit/risk ratio for early breast cancer patients remained in favor of epirubicin-based adjuvant chemotherapy: eight cases (0.31%) occurred, and in some of them, treatment causality could be debatable.

Adult↗
PubMed2005

Sequential two-line strategy for stage IV non-small-cell lung cancer: docetaxel-cisplatin versus vinorelbine-cisplatin followed by cross-over to single-agent docetaxel or vinorelbine at progression: final results of a randomised phase II study.

BACKGROUND: This phase II trial compared docetaxel-cisplatin (DC) with vinorelbine-cisplatin (VC), both as first-line therapy followed by cross-over at progression to single-agent vinorelbine or docetaxel in advanced non-small-cell lung cancer (NSCLC). METHODS: Overall, 115 patients received DC (docetaxel 75 mg/m(2) and cisplatin 100 mg/m(2) both on day 1, every 3 weeks, arm A1) and 118 VC (vinorelbine 30 mg/m(2)/week on days 1 and 8 and cisplatin 100 mg/m(2) on day 1, every 3 weeks, arm B1) for six cycles, and subsequently maintained by monotherapy with docetaxel (A1) or vinorelbine (B1) with cross-over on disease progression to vinorelbine 30 mg/m(2) days 1 and 8 (A2), or docetaxel 100 mg/m(2), day 1, both every 3 weeks (B2). The primary end point was overall response rate (ORR). RESULTS: Patient characteristics were balanced; median follow-up was 8.8 months. First-line response rate was 33.9% with DC and 26.3% with VC (P=0.20). In arms A1 and B1, respectively: duration of response was similar (8.2 versus 8.4 months); median time to progression was 5 months in both; median survival was 8 versus 9 months (P=0.38); 1-, 2- and 3-year survival was 36% versus 35%, 17% versus 10% and 13% versus 6% (P not significant). However, with a low number of long-term survivors, statistical significance was not reached. Overall, almost half of the patients crossed over to second-line therapy; there were no response with vinorelbine and 6 (11.2%) partial responses with docetaxel. Considering the safety profile, the occurrence of febrile neutropenia was 9.6% with DC and 26.3% with VC. Treatment-related mortality was 2.5% with DC and 8.5% with VC. CONCLUSIONS: The trend in favour of the DC arm in ORR, even though statistical significance was not reached, is consistent with previous reports. This study suggests an activity of first-line DC in advanced NSCLC, and that second-line vinorelbine does not provide additional clinical benefit. As already shown in other studies, the use of DC in first-line should provide a better percentage of long-term survivors, despite the absence of efficacy of the second-line in our study.

Adult↗
PubMed2003

Phase II multicentre study of docetaxel plus 5-fluorouracil in patients with anthracycline-pretreated metastatic breast cancer.

The purpose of the study was to determine the efficacy and safety of docetaxel plus continuous infusion of 5-fluorouracil (5-FU) in patients with metastatic breast cancer previously treated with anthracyclines. A total of 41 patients with histologically proven metastatic breast cancer and performance status 0-2, who had received at least one anthracycline-containing regimen, received docetaxel 85 mg m(-2) followed by continuous infusion of 5-FU 750 mg m(-2) day(-1) for 5 days every 3 weeks for up to eight cycles. All patients received corticosteroid premedication, but there was no prophylactic colony-stimulating factor support. The most frequent metastatic sites were the liver (61%), bone (29%), and lung (29%). All 41 patients were assessable for toxicity and 30 were eligible and assessable for efficacy. The objective response rate was 70.0% (95% CI: 53.6-86.4%) for the per protocol group and 53.7% (95% CI: 38.4-68.9%) for the intent-to-treat (ITT) population. For the ITT population, median duration of response was 8.4 months (95% CI: 6.7-12.2 months), median time to progression was 6.7 months (95% CI 5.5-8.6 months), and median survival was 17 months (95% CI: 12.3-not recorded months). Grade 3/4 neutropenia occurred in 54% of patients, with febrile neutropenia in 24% of patients and 5% of cycles, but infections were rare. Stomatitis was frequent, grade 3 in 24% of patients and grade 4 in one patient (2%), but manageable. Diarrhoea was rare, grade 3 in 7% of patients and 1% of cycles. Other grade 3/4 nonhaematological toxicities were infrequent. In conclusion, this docetaxel/5-FU regimen is highly active and well tolerated in patients with anthracycline-pretreated metastatic breast cancer. The efficacy is particularly promising, as one-third of patients were either second-line and/or anthracycline-resistant/refractory.

Adenocarcinoma↗
PubMed2003

Defining ventral medullary respiratory compartments with a glutamate receptor agonist in the rat.

The regional organization of the ventral respiratory group (VRG) was examined with respect to generation of respiratory rhythm (breathing frequency) versus control of the respiratory motor pattern on individual nerves. In urethane-anaesthetized, neuromuscularly blocked and vagotomized Sprague-Dawley rats, arterial blood pressure (ABP) and respiratory motor outputs (phrenic, pharyngeal branch of the vagus, or superior laryngeal nerves) were recorded. The VRG organization was mapped systematically using injections of the excitatory amino acid DL-homocysteic acid (DLH; 5-20 mM, 2-6 nl) from single- or double-barrel pipettes at 100-200 microm intervals between the facial nucleus and the calamus scriptorius. Recording of respiratory neurons through the injection pipette ensured that the pipette was located within the VRG. At the end of each experiment, the injection pipette was used to make an electrical lesion, thereby marking the electrode position for subsequent histological reconstruction of injection sites. Four rostrocaudal regions were identified: (1) a rostral bradypnoea area, at the level of the Bötzinger complex, in which respiratory rhythm slowed and ABP increased, (2) a tachypnoea/dysrhythmia area, at the level of the preBötzinger complex, in which breathing rate either increased or became irregular, with little or no change in ABP, (3) a caudal bradypnoea area at the level of the anterior part of the rostral VRG in which ABP decreased and (4) a caudal 'no effect' region in the posterior part of the rostral VRG. The peak amplitude of phrenic nerve activity decreased with injections into all three rostral regions. Changes in respiratory rhythm were associated with opposite changes in inspiratory (TI) and expiratory (TE) durations after injections into either the Bötzinger complex or anterior rostral VRG, while both TI and TE decreased after injections into the preBötzinger complex. Effects on selected cranial nerves were similar to those on the phrenic nerve except that tonic activity was elicited on the superior larygneal nerve ipsilateral to injections in the Bötzinger complex and on the pharyngeal branch of the vagus ipsilateral to injections in the preBötzinger complex. These data reinforce the subdivision of the VRG into functionally distinct compartments and suggest that a further subdivision of the rostral VRG is warranted. They also suggest that region-specific influences, especially on the pattern of cranial motor discharge, can be used to assist the identification of recording sites within the VRG. However, the postulated clear functional separation of rhythm- versus pattern-generating regions was not supported.

Animals↗
PubMed2003

Sea urchin elongation factor 1delta (EF1delta) and evidence for cell cycle-directed localization changes of a sub-fraction of the protein at M phase.

Eukaryotic elongation factor 1 (eEF1) is a translational multimolecular complex reported in higher eukaryotes to be a target of CDK1/cyclin B, the universal regulator of M phase, but whose role in the cell cycle remains to be determined. A specific polyclonal antibody was produced and used to characterize the delta subunit of sea urchin elongation factor 1 (SgEF1delta) in early embryos, a powerful model for investigating cell cycle regulation. The SgEF1delta protein was present in unfertilized eggs as two isoforms of 35 and 37 kDa, issued from two different mRNAs. The two canonical eEF1delta partners, eEF1gamma and eEF1beta, were shown to co-immunoprecipitate with the SgEF1delta isoforms. Both isoforms were associated in a macromolecular complex, which resolved upon gel filtration chromatography at a molecular weight > 400 kDa, suggesting association with other yet unidentified partners. After fertilization, the amount as well as the ratio of both SgEF1delta isoforms remained constant during the first cell division as judged by Western blotting. Immunofluorescence analysis showed that a pool of the protein concentrated as a ring at the embryo nuclear location around the period of nuclear envelope breakdown and was visualized later as two large spheres around the mitotic spindle poles. Thus, the eEF1delta protein shows cell cycle-specific localization changes in sea urchin embryos.

Amino Acid Sequence↗
PubMed2002

Docetaxel vs 5-fluorouracil plus vinorelbine in metastatic breast cancer after anthracycline therapy failure.

This multicentre, randomised phase III study compared docetaxel with 5-fluorouracil+vinorelbine in patients with metastatic breast cancer after failure of neo/adjuvant or one line of palliative anthracycline-based chemotherapy. One hundred and seventy-six metastatic breast cancer patients were randomised to receive docetaxel (100 mg m(-2)) every 3 weeks or 5-fluorouracil+vinorelbine: 5-fluorouracil (750 mg m(-2) per day continuous infusion) D1-5 plus vinorelbine (25 mg m(-2)) D1 and D5 of each 3-week cycle. Eighty-six patients received 516 cycles of docetaxel; 90 patients received 476 cycles of 5-fluorouracil+vinorelbine. Median time to progression (6.5 vs 5.1 months) and overall survival (16.0 vs 15.0 months) did not differ significantly between the docetaxel and 5-fluorouracil+vinorelbine arms, respectively. Six (7%) complete responses and 31 (36%) partial responses occurred with docetaxel (overall response rate 43%, 95% confidence interval: 32-53%), while 4 (4.4%) complete responses and 31 (34.4%) partial responses occurred with 5-fluorouracil+vinorelbine (overall response rate 38.8%, 95% confidence interval: 29-49%). Main grade 3-4 toxicities were (docetaxel vs 5-fluorouracil+vinorelbine): neutropenia 82% vs 67%; stomatitis 5% vs 40%; febrile neutropenia 13% vs 22%; and infection 2% vs 7%. There was one possible treatment-related death in the docetaxel arm and five with 5-fluorouracil+vinorelbine. In anthracycline-pretreated metastatic breast cancer patients, docetaxel showed comparable efficacy to 5-fluorouracil+vinorelbine, but was less toxic.

Adult↗
PubMed2002

[The retromolar area, an alternative for the mandibular symphisis graft in implant surgery: quantitative and qualitative analysis of 52 samples].

BACKGROUND: We conducted an comparative anatomy study of two sites for harvesting bone grafts for implant surgery: the mandibular symphysis and the ramus area. MATERIAL AND METHOD: Fifty-two anatomical specimens were studied (34 from the retormolar region and 18 from the symphysis region. Measurement were: size, weight, bone volume, bone density, cortical/cancellous ratio. RESULTS: Samples from the two sites gave equivalent results. DISCUSSION: We describe the harvesting method and the difficulties encountered at each site. The retromolar site appears to be an attractive alternative to the symphysis region for bone graft harvesting.

Bone Density↗
PubMed2001

Superior efficacy of letrozole versus tamoxifen as first-line therapy for postmenopausal women with advanced breast cancer: results of a phase III study of the International Letrozole Breast Cancer Group.

PURPOSE: To compare the efficacy and tolerability of tamoxifen with that of letrozole, an oral aromatase inhibitor, with tamoxifen as first-line therapy in postmenopausal women with advanced breast cancer. PATIENTS AND METHODS: Nine hundred seven patients were randomly assigned letrozole 2.5 mg once daily (453 patients) or tamoxifen 20 mg once daily (454 patients). Patients had estrogen receptor- and/or progesterone receptor-positive tumors, or both receptors were unknown. Recurrence during adjuvant antiestrogen therapy or within the following 12 months or prior endocrine therapy for advanced disease precluded enrollment. One prior chemotherapy regimen for metastatic disease was allowed. The primary end point was time to progression (TTP). Secondary end points included overall objective response rate (ORR), its duration, rate and duration of clinical benefit, time to treatment failure (TTF), overall survival, and tolerability. RESULTS: TTP was significantly longer for letrozole than for tamoxifen (median, 41 v 26 weeks). Treatment with letrozole reduced the risk of progression by 30% (hazards ratio, 0.70; 95% confidence interval, 0.60 to 0.82, P =.0001). TTP was significantly longer for letrozole irrespective of dominant site of disease, receptor status, or prior adjuvant antiestrogen therapy. Similarly, TTF was significantly longer for letrozole (median, 40 v 25 weeks). ORR was higher for letrozole (30% v 20%; P =.0006), as was the rate of clinical benefit (49% v 38%; P =.001). Survival data are currently immature and not reported here. Both treatments were well tolerated. CONCLUSION: Letrozole was significantly superior to tamoxifen in TTP, TTF, ORR, and clinical benefit rate. Our results support its use as first-line endocrine therapy in postmenopausal women with advanced breast cancer.

Adult↗
PubMed2001

Combined paclitaxel and gemcitabine as first-line treatment in metastatic non-small cell lung cancer: a multicentre phase II study.

The efficacy and toxicity of combined paclitaxel and gemcitabine was evaluated in 54 chemotherapy-naive patients with metastatic non-small cell lung cancer (NSCLC). Gemcitabine i.v. 1000 mg/m(2)was administered on days 1 and 8 and paclitaxel 200 mg/m(2)as a continuous 3-hour infusion on day 1. Treatment was repeated every 21 days. Patients had a median age of 53 years. ECOG performance status was 0 or 1 in 48 patients. 41 patients (75.9%) had initial stage IV disease; histology was mainly adenocarcinoma (46.3%). 2 patients (4.3%) achieved a complete response and 15 (31.9%) achieved a partial response giving an overall response rate of 36.2% (95% CI: 22.4-49.9%); 19 patients (40.4%) had stable disease and 10 (21.3%) had progressive disease. The median survival time was 51 weeks (95% CI: 46.5-59.3), with a 1-year survival probability of 0.48 (95% CI: 0.34-0.63). Grade 3/4 neutropenia and febrile neutropenia occurred in 15.2% and 2.2% of courses, respectively. Grade 3/4 thrombocytopenia was rare (1.8% of courses). Peripheral neurotoxicity developed in 25 patients (47.2%), mostly grade 1/2. Arthalgia/myalgia was observed in 30 patients (56.6%), generally grade 1 or 2. Grade 3 abnormal levels of serum glutamate pyruvate transaminase (SGPT) and serum glutamate oxaloacetate transaminase (SGOT) occurred in 5 patients (9.4%) and 1 patient (1.9%), respectively. Combined paclitaxel and gemcitabine is an active and well-tolerated regimen for the treatment of advanced NSCLC, and warrants further investigation in comparative, randomized trials.

Adult↗
PubMed2001

Evidence for regulation of protein synthesis at the elongation step by CDK1/cyclin B phosphorylation.

Eukaryotic elongation factor 1 (eEF-1) contains the guanine nucleotide exchange factor eEF-1B that loads the G protein eEF-1A with GTP after each cycle of elongation during protein synthesis. Two features of eEF-1B have not yet been elucidated: (i) the presence of the unique valyl-tRNA synthetase; (ii) the significance of target sites for the cell cycle protein kinase CDK1/cyclin B. The roles of these two features were addressed by elongation measurements in vitro using cell-free extracts. A poly(GUA) template RNA was generated to support both poly(valine) and poly(serine) synthesis and poly(phenylalanine) synthesis was driven by a poly(uridylic acid) template. Elongation rates were in the order phenylalanine > valine > serine. Addition of CDK1/cyclin B decreased the elongation rate for valine whereas the rate for serine and phenylalanine elongation was increased. This effect was correlated with phosphorylation of the eEF-1delta and eEF-1gamma subunits of eEF-1B. Our results demonstrate specific regulation of elongation by CDK1/cyclin B phosphorylation.

Animals↗
PubMed2001

Respiratory rhythm generation: preBötzinger neuron discharge patterns and persistent sodium current.

Considerable evidence from several laboratories (c.f., Rekling and Feldman, Ramirez et al.) is consistent with the concept that the pBc contains the kernel of the central rhythm generating network for breathing. The work summarized in this manuscript is also generally consistent with this notion. Of particular note is the observation that pre-I neurons and E-Dec neurons maintain a consistent phase relationship with phrenic nerve activity and maintain a similar peak discharge rate despite marked changes in the phrenic nerve rhythm and pattern. Other categories of respiratory neurons failed to maintain this relationship. Hence, the findings are consistent with pBc pre-I and E-Dec neurons having a key role in rhythm generation. A persistent sodium current has been postulated to underlie the rhythm generating mechanism of pacemaker neurons within the pBc. In the present study, a substantial persistent sodium current was documented in many neurons from the pBc and adjacent respiratory regions. This finding is not inconsistent with the postulated role in rhythm generation. However, it does suggest that other neuronal properties must act in concert with the persistent current to define a unique population of pacemaker neurons.

Animals↗
PubMed2001

Protein translation during early cell divisions of sea urchin embryos regulated at the level of polypeptide chain elongation and highly sensitive to natural polyamines.

Protein synthesis was analysed following fertilisation in sea urchin. Fluctuations in the accumulation of neo-synthesised proteins were observed during the first cell cycles. Accurate translation analyses were performed from lysates prepared from early embryos. The lysates readily translated endogenous pre-initiated mRNAs allowing the determination of elongation rates in the absence of re-initiation in vitro. The translation capacity of embryo lysates increased 18-fold from 0 to 90 min after fertilisation, reflecting the increase in the amount of pre-initiated mRNAs during early development. Kinetics analysis at a short time interval during the course of early development (240 min) showed an overall increase in the elongation rate (> 10-fold) which is regulated by pauses in synchrony with the cell divisions. Elongation activity in the lysates was highly sensitive to the natural polyamines, spermine (ID50 = 0.2 mM) and spermidine (ID50 = 1.8 mM), indicating high potential regulation by the intracellular level of polyamines in embryos. The regulation in the elongation changes associated with the early embryo cell divisions is discussed in the light of the physiological fluctuations in polyamine concentrations.

Animals↗