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Biomedical subjects

P Rousseau

Publications and source records attributed to P Rousseau.

At least 37 records · Page 2Linked to original sources
PubMed2000

The X1 box of HLA-G promoter is a target site for RFX and Sp1 factors.

HLA-G gene regulation was investigated with regards to homologies among the pathways regulating both classical MHC class I and MHC class II gene expression. They include four conserved cis-acting regulatory elements located in the proximal promoter region referred to as the W/S/Z box, the X box that is comprised of the X1 and X2 halves, and the Y box with an inverted CCAAT site. The X1 box is the binding site for the ubiquitous RFX complex consisting of three subunits; the X2 box is bound by the X2BP/ATF/CREB family factors. The basic S-X-Y regulatory module interacts with CIITA, which is expressed constitutively in APCs, but may be inducible in others cell types by IFN-gamma. Within HLA-G gene promoter the only conserved motifs are S and X1 boxes. We thus investigated the binding capacity of the HLA-G X box in comparison to that of HLA-DRA and HLA-E. We demonstrate that X2 box mutations in HLA-G promoter affect the binding of ATF/CREB family factors and may privilege the X2 box to access by other shared factors. The X1 box is the target for RFX complex and an additional factor we identified as Sp1. We propose that the X region in the HLA-G gene promoter might participate to the combination of factors which play a role in HLA-G gene activation.

Cell Extracts↗
PubMed2000

The ethical validity and clinical experience of palliative sedation.

The physician's main goal in caring for a dying person is to reduce suffering, including pain, physical symptoms, and emotional, psychosocial, and spiritual distress. In refractory and intractable cases, palliative sedation offers a compassionate and humane alternative to conscious and continual suffering, both for the patient and the patient's family. Without a doubt, further studies are necessary, particularly in cases of cognitive impairment, but palliative sedation offers a valuable and efficacious intervention for interminable suffering at the end of life.

Death↗
PubMed1999

Conformational changes induced by phosphorylation of the FixJ receiver domain.

BACKGROUND: A variety of bacterial adaptative cellular responses to environmental stimuli are mediated by two-component signal transduction pathways. In these phosphorelay cascades, histidine kinases transphosphorylate a conserved aspartate in the receiver domain, a conserved module in the response regulator superfamily. The main effect of this phosphorylation is to alter the conformation of the response regulator in order to modulate its biological function. The response regulator FixJ displays a typical modular arrangement, with a phosphorylatable N-terminal receiver domain and a C-terminal DNA-binding domain. In the symbiotic bacterium Sinorhizobium meliloti, phosphorylation of this response regulator activates transcription of nitrogen-fixation genes. RESULTS: The crystal structures of the phosphorylated and of the unphosphorylated N-terminal receiver domain of FixJ (FixJN) were solved at 2.3 A and 2.4 A resolution, respectively. They reveal the environment of the phosphoaspartate in the active site and the specific conformational changes leading to activation of the response regulator. Phosphorylation of the conserved aspartate induces major structural changes in the beta 4-alpha 4 loop, and in the signaling surface alpha 4-beta 5 that mediates dimerization of the phosphorylated full-length response regulator. A site-directed mutant at this protein-protein interface decreases the affinity of the phosphorylated response regulator for the fixK promoter tenfold. CONCLUSIONS: The cascade of phosphorylation-induced conformational changes in FixJN illustrates the role of conserved residues in stabilizing the phosphoryl group in the active site, triggering the structural transition and achieving the post-phosphorylation signaling events. We propose that these phosphorylation-induced conformational changes underly the activation of response regulators in general.

Amino Acid Sequence↗
PubMed1999

A phase I/II trial of neoadjuvant chemotherapy with cisplatin and vinorelbine followed by accelerated irradiation for patients with inoperable nonsmall cell lung carcinoma.

BACKGROUND: Both locoregional and distant disease control remains poor in the treatment of Stage III nonsmall cell lung carcinoma (NSCLC). This trial was conducted to evaluate the tolerance and responses of patients with NSCLC given a neoadjuvant regimen of cisplatin and vinorelbine chemotherapy followed by accelerated thoracic radiotherapy. METHODS: Forty-two patients with Stage IIIA and IIIB NSCLC were entered into the study. Treatment consisted of cisplatin 100 mg/m2 given on Days 1 and 29 and vinorelbine 30 mg/m2 given weekly for 5 weeks, with a planned 50% dose reduction to 15 mg/m2 planned for Week 2. This was followed by thoracic irradiation of 60 gray (Gy) in 30 fractions of 2 Gy over 4 weeks (once daily during Weeks 1 and 2 and twice daily during Weeks 3 and 4). RESULTS: With a median follow-up time of 12.2 months (27-65 months for survivors), the median survival was 12.2 months (16.6 months for patients with no prior weight loss and 7.8 months for those with prior weight loss). The response rate after induction chemotherapy was 46.1%, increasing to 74.4% after radiation therapy (8 complete responses and 21 partial responses). The rate of progression was 13 of 18 (72%) for those who responded to chemotherapy (4 distant, 9 local) and 18 of 21 (86%) for those who did not respond to chemotherapy (14 distant, 7 local). The most frequent acute Grade 3 toxicity was nausea (21.4%). CONCLUSIONS: Accelerated thoracic irradiation after induction chemotherapy is well tolerated and yields therapeutic results that compare favorably with those reported for other regimens of chemotherapy and standard fractionated radiotherapy. The data from this study suggest that the responses of patients with clinically apparent disease to induction chemotherapy might indicate a likelihood of controlling microscopic distant metastases.

Adult↗
PubMed1999

Phosphorylation-induced dimerization of the FixJ receiver domain.

The 'two-component' transcriptional activator FixJ controls nitrogen fixation in Sinorhizobium meliloti. Phosphorylation of FixJ induces its dimerization, as evidenced by gel permeation chromatography and equilibrium sedimentation analysis. Phosphorylation-induced dimerization is an intrinsic property of the isolated receiver domain FixJN. Accordingly, chemical phosphorylation of both FixJ and FixJN are second-order reactions with respect to protein concentration. However, the second-order phosphorylation constant is 44-fold higher for FixJN than for FixJ. Therefore, the C-terminal transcriptional activator domain FixJC inhibits the chemical phosphorylation of the receiver domain FixJN. Conversely, FixJN has been shown previously to inhibit FixJC activity approximately 40-fold, reflecting the interaction between FixJN and FixJC. Therefore, we propose that modulation of FixJ activity involves both its dimerization and the disruption of the interface between FixJN and FixJC, resulting in the opening of the protein structure. Alanine scanning mutagenesis of FixJN indicated that the FixJ approximately P dimerization interface involves Val-91 and Lys-95 in helix alpha4. Dimerization was required for high-affinity binding to fixK promoter DNA.

Bacterial Proteins↗
PubMed1999

[Plea for accelerated rehabilitation after ligament plasty of the knee by a bone-patellar tendon-bone graft].

Knee rehabilitation after ACL repair with bone-tendon-bone graft is still controversial. While there was a tendency to protect the graft and the donor site in the eighties, actual tendency is to propose more aggressive, so called accelerated rehabilitation protocol. An extensive analysis of the literature shows that this accelerated rehabilitation is justified because of histologic, biomechanic, surgical and clinical arguments. This accelerated rehabilitation is based on seven reasons, at least: 1) the necrosis of the graft, initially observed in animals, does not seem to be as important in humans as demonstrated by histological studies after in vivo biopsies; 2) the use of solid bone-tendon-bone graft, whose resistance is maximum in the early post-operative period and is superior to the resistance of the ACL; 3) the more precise positioning (more "isometric") because of optic magnification allowed by arthroscopy; 4) the absence of graft impingement, routinely controlled, because of a more posterior tibial placement of the graft and the eventual notch-plasty; 5) the solid and confident fixation of the graft because of interference screws; 6) anterior knee pain are less important when early constraints are applied on the knee; 7) finally, undisciplined and demanding patients who refuse all protection for the graft and the donor site, have good and stable results regarding stability of the knees. Early constraints on the knee after bone-tendon-bone graft and interference fixation give better tolerance on the extension mechanism without compromising integrity of the graft and knee stability. Appropriate level of constraints on the ACL graft and the donor site guides the collagenic reorganisation process. Early restoration of normal hyperextension, decreased knee pain and maintenance of muscular trophicity, allowing patients to go back to sport at 4 months, are the most evident benefits of this accelerated rehabilitation. These considerations cannot be applied to the other grafts (fascia lata, semi-tendinous, allografts ...) and to other ways of fixation (sutures, staples, ...).

Animals↗
PubMed1998

[Ganglioneuroblastoma in the adult].

BACKGROUND: Ganglioneuroblastoma is commonly observed in children but rarely in adults. Therapy and prognosis are not well defined in adults. CASE REPORT: We report the case of a female adult who developed a ganglioneuroblastoma of the left adrenal gland with liver metastasis. Surgical treatment combined with radio and chemotherapy led to complete remission. DISCUSSION: The outcome in our patient and data reported in the literature suggest that a multidisciplinary approach is necessary and that initial surgical resection should be performed whenever possible. Adjuvant radiotherapy or chemotherapy have been shown to be somewhat effective in children but their true impact in adults remains to be ascertained. Follow-up after resection should include physical examination, assay of adrenal derivatives in plasma and urine and imaging.

Adrenal Gland Neoplasms↗
PubMed1998

Intestinal infarctions: a reappraisal of the factors predictive of operative mortality.

OBJECTIVE: To assess the factors that predict operative mortality after intestinal infarction, and show what effect referral patterns have on mortality. DESIGN: Retrospective study. SETTING: Two university departments of surgery, France. SUBJECTS: 144 patients with intestinal infarctions operated on between January 1980 and August 1995. INTERVENTIONS: Univariate and multivariate analyses. MAIN OUTCOME MEASURES: Operative mortality and the factors associated with it. RESULTS: Operative mortality was 67% (96/144) during the first 45 days postoperatively. The univariate analysis showed that age over 75 years (p=0.0002), female sex (p=0.007), the presence of shock (p < 0.0001), and referral from cardiovascular medical or surgical unit (p=0.01) were significantly associated with mortality. However, the multivariate analysis reduced these to extent of infarction (p=0.0001), the presence of shock (p=0.0002), age over 75 years (p=0.0001), and recent cardiac or vascular operation (p=0.03). CONCLUSIONS: The influence of referral pattern was related to previous cardiac or vascular operation, and the risk among women to the fact that their age was 10 years older than that of men. This study shows how the type of referral may explain the wide variations in reported mortality. To compare published series, care should be taken to avoid any selection bias.

Adult↗
PubMed1998

Management of malignant bowel obstruction in advanced cancer: a brief review.

Malignant bowel obstruction is an odious complication of numerous malignancies, most notably ovarian and colorectal cancers. It reduces quality of life and promotes considerable physical and emotional suffering, precluding a peaceful and comfortable death and deterring appropriate familial bereavement. Palliative management of bowel obstruction includes operative and nonoperative strategies, with therapeutic selection based on patient preference and anticipated life expectancy. Available therapies include laparotomy, enteral intubation, intravenous and subcutaneous hydration, parenteral nutrition, and pharmacologic agents.

Journal Article↗
PubMed1998

Efficacy and costs of patient-controlled analgesia versus regularly administered intramuscular opioid therapy.

BACKGROUND: Many studies have shown the efficacy of patient-controlled analgesia (PCA). However, it is not clear whether PCA has clinical or economic benefits in addition to efficient analgesia. The current study was designed to evaluate these issues by comparing PCA with regularly administered intramuscular injections of opioids after hysterectomy. METHODS: This prospective study included 126 patients who underwent abdominal hysterectomy and were randomly assigned to receive PCA or regularly timed intramuscular injections of morphine during a period of 48 h. Doses were adjusted to provide satisfactory analgesia in both treatment groups. Pain at rest and with movement, functional recovery, drug side effects, and patient satisfaction were measured using rating scales and questionnaires. The costs of PCA and intramuscular therapy were calculated based on personnel time and drug and material requirements. RESULTS: Comparable analgesia was observed with the two treatment methods, with no significant differences in the incidence of side effects or patient satisfaction. The medication dosage had to be adjusted significantly more frequently in the intramuscular group than in the PCA patients. The PCA did not favor a faster recuperation time compared with intramuscular therapy in terms of times to ambulation, resumption of liquid and solid diet, passage of bowel gas, or hospital discharge. The results of the economic evaluation, which used a cost-minimization model and sensitivity analyses, showed that PCA was more costly than regular intramuscular injections despite the fact that no costs for the pump were included in the analyses. Cost differences in nursing time favoring PCA were offset by drug and material costs associated with this type of treatment. CONCLUSIONS: Compared with regularly scheduled intramuscular dosing, PCA is more costly and does not have clinical advantages for pain management after hysterectomy. Because of the comparable outcomes, the general use of PCA in similar patients should be questioned.

Analgesia↗
PubMed1998

Palliative care in managed Medicare: reasons for hope--and for concern.

Growing numbers of persons age 65 and older are enrolling in managed care plans to obtain benefits that are not available or are more expensive in free-for-service Medicare. The relatively greater prevalence of chronic disease and mortality in this population presents new challenges to managed care to provide cost-effective, yet laudable, palliative care. Certain aspects of managed care have the potential to improve the dying process. These include integrated care, reduced financial incentives for nonessential tests and procedures, portable and computerized medical records, and appropriate accountability for quality. On the other hand, possible barriers to attaining this goal in managed care include divided loyalties, conflicts of interest, the risk of devaluation of dying persons, and cost constraints.

Aged↗