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P Richaud

Publications and source records attributed to P Richaud.

At least 19 recordsLinked to original sources
PubMed1996

Evidence for a proximal histidine interaction in the structure of cytochromes c in solution: a resonance Raman study.

Soret-excited resonance Raman (RR) spectra of oxidized and reduced cytochromes ć from Rhodospirillum molischianum and Rhodobacter sphaeroides, in solution, are reported. The spectra of the type I ferricytochromes ć in both species contain different extents of two forms. One of these is readily assignable to a "normal" five-coordinated high-spin heme. The second species with v3 and v10 modes at 1502 and 1635 cm-1, respectively, is attributed to a five-coordinated intermediate-spin heme. The RR data show that the equilibrium between these two forms is species-dependent at neutral pH and 20 degrees C. The v(Fe-His) mode of the a form of reduced cytochromes ć is assigned to a band at 228-231 cm-1, indicating that the proximal His has a strong electronegative character. X-ray crystallographic data on R. molischianum ferricyt ć show that the proximal His has no interaction with either the protein or water molecules [Finzel, B.C., Weber, P.C., Hardman, K.D., & Salemme, F.R.(1985) J. Mol. Biol. 186, 627-643]. Considering that the absence of H bonding at the coordinated histidine corresponds to a low frequency for the v(Fe-His) mode (195-205 cm-1), the structure and/or environment of the proximal histidine appears different for cyt ć (III) in the crystal and cyt ć (II) in aqueous solution. To account for the elevated frequency of the v(Fe-His) mode of cyt ć (II), several possibilities have been examined. Among these, we propose that a conserved Lys residue, located in the protein sequence three residues before the His ligand, can form an electrostatic interaction with the (His)N1 atom, directly or through a water molecule. It is further suggested that this electrostatic interaction could also play a role in the high-spin <--> intermediate-spin equilibrium of oxidized cytochromes ć.

Amino Acid Sequence↗
PubMed1996

Characterisation of the mcpA and mcpB genes capable of encoding methyl-accepting type chemoreceptors in Rhodobacter capsulatus.

Two contiguous mcp genes, mcpA and mcpB, transcribed from the same DNA strand and capable of encoding methyl-accepting chemotaxis proteins (Mcp) have been isolated from Rhodobacter capsulatus (Rc), sequences and overexpressed in Escherichia coli (Ec). The deduced proteins (McpA, 69 171 Da; McpB, 81 629 Da) show a structure similar to that of Ec Mcp. The products of mcpA and mcpB, overproduced in Ec, were recognized by anti-Ec Mcp (Trg) antibodies.

Amino Acid Sequence↗
PubMed1995

In vivo participation of a high potential iron-sulfur protein as electron donor to the photochemical reaction center of Rubrivivax gelatinosus.

We have found that the only high redox potential electron transfer component in the soluble fraction of Rubrivivax gelatinosus TG-9 is a high-potential iron-sulfur protein (HiPIP). We demonstrated the participation of this HiPIP in the photoinduced electron transfer both in vivo and in vitro. First, the addition of HiPIP to purified membranes enhanced the rate of re-reduction of the photooxidized reaction center. Second, the photooxidation of HiPIP was observed in intact cells of Ru. gelatinosus TG-9 under anaerobic conditions by EPR and absorption spectroscopies. Analysis of flash-induced absorption changes showed that the equilibration of positive equivalents between the reaction center and HiPIP occurs in less than 1 ms after flash excitation. The complete re-reduction of the photooxidized reaction center is achieved in tens of milliseconds. The turnover of a cyt bc1 is also involved in this reaction, as shown by a slow electrogenic phase of the membrane potential linked to this process.

Electron Spin Resonance Spectroscopy↗
PubMed1995

Radiotherapy and chemotherapy for invasive thymomas: a multicentric retrospective review of 90 cases. The FNCLCC trialists. Fédération Nationale des Centres de Lutte Contre le Cancer.

PURPOSE: Thymoma is a rare disease. The treatment of patients with invasive thymoma remains controversial. The prognosis of such patients is poor, even with the use of postoperative radiation therapy and chemotherapy. We retrospectively reviewed the outcome and prognostic factors in a series of 90 patients presenting with an invasive thymoma treated by partial resection or biopsy and radiation therapy. METHODS AND MATERIALS: From 1979-1990, 163 patients with the diagnosis of lymphoepithelial thymoma were treated in 10 French cancer centers. Patients were staged using the postoperative "GETT" classification derived from that of Masaoka. Ninety patients who presented with an invasive thymoma, 58 Stage III (21 IIIA: partial resection and 37 IIIB: biopsy) and 32 Stage IVA (intrathoracic thymoma spread), are the subject of this report. Treatment combined surgery and radiation therapy (+/- chemotherapy), with curative intent. Surgery consisted of partial resection in 31 patients (21 Stage III), and biopsy in 55 patients (37 Stage III). The median radiation dose to the tumor was 50 Gy (30-70 Gy). Supraclavicular radiation was performed in 59 patients (median dose 40 Gy). Chemotherapy, combined with radiation in 59 patients, consisted of multidrug regimens, mainly platinum based. RESULTS: The median follow-up is 105 months (20-165 months). The 5- and 10-year overall survival rates are 51 and 39%, respectively. There is a great impact of the extent of surgery on survival: the 5- and 10-year survival rates were 64% and 43%, respectively, after partial resection, compared to 39% and 31% after biopsy (p < 0.02). Local control at 8.5 years was obtained in 59 of 90 patients (66%): 40 Stage III, 19 Stage IVA. There is a significant relationship between the extent of surgery and the local control (16% of relapse after partial resection vs. 45% after biopsy, p < 0.05). Seven patients developed significant (grades 3-4 WHO grading system) treatment-induced side effects. Stage, histologic type, and chemotherapy were not prognostic factors. CONCLUSION: In this large multicentric retrospective study of invasive thymomas (Stage III-IVA) treated by surgery and radiation, results show the importance of loco-regional treatments, such as surgery and radiation therapy. There is also a great impact of radiation on local control. However, the rate of local recurrence (34%) justifies recommending a higher dose of radiation (> 50 Gy) than doses used in this study, for incompletely resected patients. The role of chemotherapy needs to be further assessed.

Adolescent↗
PubMed1995

Phase I-II study of the somatostatin analogue lanreotide in hormone-refractory prostate cancer.

Lanreotide (BIM 32014), a somatulin analogue, was found to be as effective as castration in a rat prostate tumor model. Therapeutic benefit was also demonstrated in the hormone-resistant phase of this tumor model. The activity of lanreotide may be due to a reduction in the levels of growth factors such as insulin growth factor 1 (IGF1). A total of 30 patients with hormone-refractory prostate cancer were treated with a slow-release formulation of lanreotide. The mean age was 71 years. Patients were treated with one intramuscular injection of 30 mg BIM 23014 once a week and were followed for prostate-specific antigen (PSA) level evolution until disease progression or WHO grade 3 or 4 toxicity and for survival. The patients were treated for a mean duration of 12 weeks (range, 2-60 weeks). The performance status and bone pain were improved in 40% and 35% of patients respectively. In all, 20% of the patients had a decrease of > or = 50% in PSA levels and 16% showed a stabilization. The biological response was correlated with clinical improvement. The 1-year global survival rate was 72%, with the rate being 89% in the group of patients who were responders on PSA plasma level and 64% in patients with progressive disease. The response duration ranged from 16 to 60 weeks. Toxicity was minor, with transient grade I digestive side effects being noted in a few patients. Lanreotide given at 30 mg once a week to patients with metastatic hormone-refractory prostate cancer was well tolerated. The response rate was higher than that reported in recent published series. Higher doses of lanreotide should be evaluated.

Aged↗
PubMed1995

Thymoma: results of a multicentric retrospective series of 149 non-metastatic irradiated patients and review of the literature. FNCLCC trialists. Fédération Nationale des Centres de Lutte Contre le Cancer.

Between 1979 and 1990, 149 patients with non-metastatic thymomas were treated in ten French cancer centers. Patients were staged according to the 'GETT' classification, derived from that of Masaoka. There were 13 stage I patients, 46 stage II, 58 stage III and 32 stage IVA. Gross total resections were performed in 63 cases, subtotal resections in 31 cases and in 55 cases a biopsy alone was performed. All patients received radiotherapy and 74 were given post-operative chemotherapy. Median follow-up was 7.7 years. Local control was achieved in 117 cases (78.5%) and was influenced by the stage of the disease (p < 0.01) and the extent of surgery (p < 0.01). Twenty-six patients developed metastatis after a median period of 9 months. Five- and ten-year disease-free survival rates were 59.5% (51-67%) and 49.5% (39-60%), respectively, and were influenced by the stage of the disease (p < 0.01), the extent of surgery (p < 0.001) and a mediastinal compression on presentation (p = 5 x 10(-6)). Four factors could predict a worse overall survival in the multivariate analysis: mediastinal compression on presentation (p < 0.001), absence of chemotherapy (p < 0.001), biopsy alone (p = 0.003), and young age (p = 0.013). A worse DFS was predicted by mediastinal compression on presentation (p < 0.001), absence of chemotherapy (p < 0.001), young age (p = 0.006), and stages III-IVA (p = 0.04). Future therapeutic strategies are discussed and the literature is reviewed.

Adolescent↗
PubMed1995

[Radiotherapy of thymoma. Study of the literature apropos of a retrospective and multicenter series of 149 cases].

Thymomas is a rare disease. Staging systems and surgical adjuvant treatments remain controversial. We retrospectively reviewed the outcome and the prognostic factors in a series of 149 patients with non metastatic thymomas treated in ten French cancer centers between 1979 and 1990. Patients were staged according to the "GETT" classification derived from that of Masaoka. There were 13 stage I patients, 46 stage II, 58 stage III and 32 stage IV. Surgery consisted of complete resection in 63 patients, partial resection in 31 patients and biopsy alone in 55 patients. All patients received postoperative radiation therapy and 74 were given postoperative chemotherapy. Median follow-up was 7.7 years. Local control was obtained in 117 patients (78.5%) and was influenced by the extent of surgery (p < 0.0001). Metastases occurred in 26 patients. Seven patients developed grade 3-4 pulmonary and heart complications. One patient developed a malignant lymphoma after 24 cycles of chemotherapy. Disease-free survival (DFS) rates were of five years 92%, 75%, 60%, 39% and 48% in stage I, II, IIIA, IIIB and IVA patients, respectively. After complete resection, partial resection and biopsy alone, these rates were 74%, 60% and 38%, respectively. With a multivariate analysis, DFS rates were influenced by the extent of surgery (p < 0.001) and by chemotherapy (p < 0.001). Three other factors could predict a worse DFS: young age (p < 0.006), stages III-IV (p < 0.04) and mediastinal symptoms (p < 0.001), "GETT" staging correlated well with local control and survival. After complete resection, a 50 Gy postoperative radiation therapy can be recommended in patients with invasive thymomas. Despite a 65% local control rate after partial resection or biopsy alone in this series, a higher dose of radiation (> 60 Gy) must be evaluated. Despite the benefit of the chemotherapy in this retrospective and multicentric study, the role of this treatment remains to be assessed.

Adolescent↗
PubMed1994

Radiobiological features of acute myeloblastic leukemia: comparison of self-renewal versus terminally differentiated populations.

PURPOSE: To evaluate the radiosensitivity of self-renewing progenitor cells in acute myeloblastic leukemia (AML), we have compared the radiosensitivity of the cells grown either in methylcellulose alone for 7 days, or first in suspension culture for 7 days before being plated in methylcellulose. Methylcellulose selects for terminal-dividing cells and suspension cultures have been developed because they allow self-renewal to occur: The exponential growth of the progenitors of AML cultured in suspension is due to self-renewal. METHODS AND MATERIALS: Cells were harvested from previously untreated leukemic human bone marrows. The myeloblastic lineage of the colonies was assessed by morphological, cytochemical, and immunophenotypic analysis, and by the use of growth factors that did not stimulate the growth of T-lymphocytes. The cell-cycle distribution of the blasts was analyzed by flow cytometry and was comparable for all samples. The irradiation was performed with gamma-photons at a dose-rate of 0.05 Gy/min, similar to the clinical conditions used in our institution for total body irradiation (TBI). RESULTS: The culture methods selected aggressive leukemias. There were large variations of the individual radiosensitivity whatever culture method was used. The progenitor cells capable of self-renewal were more radiosensitive than terminal dividing cells. In two cases, a shoulder was found in the initial part of the cell-survival curves of cells capable of self-renewal. In these two cases, the best fit for the data was the linear quadratic model (survival = e-alpha D-beta D2) with alpha/beta values of 1.49 Gy and 3.12 Gy, respectively. CONCLUSION: The very low values of alpha/beta suggest a reduced antileukemic effect in case of fractionated TBI, and may lead to more reliable screening methods to determine the most appropriate technique for radiation ablation of bone marrow prior to bone marrow transplantation (BMT).

Adolescent↗
PubMed1994

Structure and function of the tetraheme cytochrome associated to the reaction center of Roseobacter denitrificans.

We have characterized the tetrahemic RC bound cytochrome isolated from the quasi-photosynthetic bacterium Roseobacter denitrificans in terms of absorption spectrum, redox property and orientation with respect to the membrane plane. The heme, designated H1, which possesses the highest redox midpoint potential (+290 mV), absorbs at 555 nm. Its plane makes an angle of 40 degrees with the membrane plane. The second high potential heme, H2 (+240 mV), peaks at 554 nm and makes a tilt of 55 degrees with the membrane. The two low potential hemes, L1 and L2, present a similar and rather high redox midpoint potential (+90 mV). They absorb at 553 nm and 550 nm. One of these hemes is oriented at 40 degrees while the other makes an angle of 90 degrees with the membrane plane. The soluble cytochrome c551 completes the cyclic electron transfer between the RC and the bc1 complex. Both the oxidation and the re-reduction of cytochrome c551 are diffusible processes. Under semi-aerobic conditions, one of the low potential hemes is photo-oxidized under illumination but only extremely slowly re-reduced. This explains the requirement of high aerobic conditions for growth of Roseobacter denitrificans cells in the light.

Bacteria↗
PubMed1993

Ethmoidal cancers: a retrospective study of 22 cases.

From April 1978 to June 1990, 22 patients with ethmoidal cancer were treated at Fondation Bergonié by a combination of surgery and radiation therapy. The mean age was 59.6 years (range 34-79 years) and the sex ratio is 2.7 (16 males/6 females). Histologic types were: adenocarcinoma, 13 cases; squamous carcinoma, 4 cases; undifferentiated carcinoma, 3 cases and esthesioneuroblastoma, 2 cases. Exposure to wood dust was encountered in 11 patients, especially in cases of adenocarcinoma: 10/13 (77%). Staging according to the classification of the University of Florida was: Stage I, 10 patients; Stage II, 5 patients and Stage III, 7 patients. Resection was considered as complete in 16 cases and only one orbital exenteration was performed. The postoperative radiation therapy delivered a mean given dose of 55.7 Gy (range 50-70 Gy) expressed to the hot spot using a technique adapted to tumor location and extension. Complete remission was achieved in 20 cases. Median follow-up is 28 months. The 5-year overall and disease-free survival are 44% and 38%, respectively. Analysis of recurrences according to staging gives: 5/10 Stage I, 2/5 Stage II and 5/7 Stage III. Recurrence is pejorative since death occurs in all cases within an average of 6 months following salvage treatment, except for three patients still alive within less than 6 months and in second remission. Prognosis of ethmoidal cancer depends on staging and local control.

Adenocarcinoma↗
PubMed1993

Organization of the genes necessary for hydrogenase expression in Rhodobacter capsulatus. Sequence analysis and identification of two hyp regulatory mutants.

A 25 kbp DNA fragment from the chromosome of Rhodobacter capsulatus B10 carrying hydrogenase (hup) determinants was completely sequenced. Coding regions corresponding to 20 open reading frames were identified. The R. capsulatus hydrogenase-specific gene (hup and hyp) products bear significant structural identity to hydrogenase gene products from Escherichia coli (13), from Rhizobium leguminosarum (16), from Azotobacter vinelandii (10) and from Alcaligenes eutrophus (11). The sequential arrangement of the R. capsulatus genes is: hupR2-hupU-hypF-hupS-hupL-hupM-hu pD-hupF-hupG-hupH-hupJ-hupK-hypA- hypB-hupR1- hypC-hypD-hypE-ORF19-ORF20, all contiguous and transcribed from the same DNA strand. The last two potential genes do not encode products that are related to identified hydrogenase-specific gene products in other species. The sequence of the 12 R. capsulatus genes underlined above is presented. The mutation site in two of the Hup- mutants used in this study, RS13 and RCC12, was identified in the hypF gene (deletion of one G) and in the hypD gene (deletion of 54 bp), respectively. The hypF gene product shares 45% identity with the product of hydA from E. coli and the product of hypF from R. leguminosarum. Those products present at their N-terminus a Cys arrangement typical of zinc-finger proteins. The G deletion in the C-terminal region of hypF in the RS13 mutant prevented the expression of a hupS::lacZ translational fusion from being stimulated by H2 as it is observed in the wild-type strain B10. It is inferred that the HypF protein is a factor involved in H2 stimulation of hydrogenase expression.

Amino Acid Sequence↗
PubMed1993

Sequence analysis and interposon mutagenesis of the hupT gene, which encodes a sensor protein involved in repression of hydrogenase synthesis in Rhodobacter capsulatus.

The hupT gene, which represses hydrogenase gene expression in the purple photosynthetic bacterium Rhodobacter capsulatus, has been identified and sequenced. The nucleotide sequence of hupT and of the contiguous downstream open reading frame, hupU, is reported. The HupT protein of 456 amino acids (48,414 Da) has sequence similarity with the FixL, DctB, NtrB, and ArcB proteins and is predicted to be a soluble sensor kinase. Insertional inactivation of the hupT gene led to deregulation of transcriptional control, so that the hydrogenase structural operon hupSLC became overexpressed in cells grown anaerobically or aerobically. The HupT- mutants were complemented in trans by a plasmid containing an intact copy of the hupT gene. The hupU open reading frame, capable of encoding a protein of 84,879 Da, shared identity with [NiFe]hydrogenase subunits; the strongest similarity was observed with the periplasmic hydrogenase of Desulfovibrio baculatus.

Amino Acid Sequence↗
PubMed1993

[ORL cancers in patients under the age of 45 years. Epidemiology, prognosis and treatment: apropos of 106 cases].

106 ENT localized carcinomas (97 men and 9 women) in adults under 45 years old are reviewed. The mean age was 40.0 years old and most suffered from an alcoholic and/or nicotine addiction. 89.6% expressed an epidermoid carcinoma and buccal cavity and larynx lesions represented the most frequent locations, followed by the pharynx. Overall survival does not differ from that of an older population but some locations seem to have a very poor prognosis: mobile tongue, vallecula, piriform sinus and amygdala. On the other hand, the laryngeal locations confirm their favorable prognosis.

Adult↗
PubMed1992

Intra-operative electron beam radiotherapy and abdomino-pelvic surgery for cancer: influence on immunological parameters.

Evolution of some immunological parameters was observed during the first month in 20 patients with different abdomino-pelvic cancers who underwent surgery with intra-operative radiation therapy (IORT) (mean dose of 19.44 Gy, range 15, 25). Observed parameters before (DO-) and after procedure (DO+), on seventh (D7) and fourteenth (D14) days and fifth week (D30) were: lymphocyte count, lymphocyte subsets (CD19, CD3, CD4, CD8, CD56), natural killer (NK) activity, immunoglobulins, C3 and C4b fractions of complement, soluble receptor for interleukin 2 (sIL2-R). Results showed a decrease of circulating lymphocytes (DO-: 1189 +/- 168 cells/mm3; D7: 889 +/- 91; P = 0.011), of absolute number of CD3 lymphocytes (DO-: 785 +/- 114 cells/mm3; D7: 563 +/- 86; P = 0.025), of CD4 lymphocytes (DO-: 441 +/- 70 cells/mm3; DO+: 299 +/- 43; P = 0.013) and of CD8 lymphocytes (DO-:361 +/- 50 cells/mm3, D7:250 +/- 44; P = 0.006). All values returned towards preoperative levels by D30. Absolute number of NK cells was unchanged but NK activity was significantly diminished (effector target ratio 5:1 DO-:33 +/- 5%; DO+:44 +/- 7%; D7:18 +/- 3%; D14:21 +/- 4%; D30:25 +/- 4%). sIL2-R was significantly enhanced from D7 to D30. All these impairments are moderate and these observations provide some evidence of satisfactory tolerance to IORT for abdomino-pelvic cancers during the immediate postoperative period.

Abdominal Neoplasms↗
PubMed1992

Regimen-related toxicity in patients undergoing BMT with total body irradiation using a sweeping beam technique.

In our institution, total body irradiation (TBI) is performed by means of a sweeping beam technique. Toxicity of the procedure was evaluated according to the only grading system designed for high dose chemoradiotherapy. One hundred patients undergoing TBI and conditioned with a standard cyclophosphamide regimen before BMT were evaluated. Regimen-related toxicity was graded according to the Seattle transplantation toxicity system, from 0 to IV (fatal toxicity), in eight organs on days 0, 7, 14, 28 and 100 for lungs. Eighteen patients did not develop any toxicity. Grades III, IV toxicities were uncommon (9%) and were not influenced by dose of TBI, GVHD prophylaxis, disease status and allogenicity although no grade IV toxicity was observed among autologous marrow recipients. However, grade II toxicity was more common in patients receiving allogeneic vs autologous grafts (p < 0.01) because of increased mucosal (p = 0.002) and liver (p = 0.12) toxicities. Renal toxicity was unevaluable. When cumulative toxicity was equal or higher than 4, day 100 survival was worse (p = 0.05). These data confirm the safety of our TBI procedure and the validity of the grading system except for renal toxicity. We suggest that a more aggressive conditioning regimen may be tolerated by patients receiving autologous grafts.

Adolescent↗
PubMed1991

A mutation in a Rhodobacter capsulatus gene encoding an integration host factor-like protein impairs in vivo hydrogenase expression.

A gene capable of encoding a protein sharing 45% identical amino acids with the alpha subunit of the integration host factor (IHF) of Escherichia coli was isolated from the photosynthetic bacterium Rhodobacter capsulatus strain B10 by complementation of a hydrogenase-deficient (Hup-) mutant, IR4. A DNA fragment of 274 base pairs containing an IHF binding consensus sequence, isolated from the promoter region of the hydrogenase structural genes (hupSL), was shown by gel retardation assays to bind the IHF protein from E. coli. The product of the R. capsulatus gene was shown to bind specifically to the 274-base-pair DNA fragment from the hupSL promoter. By analogy to the E. coli himA gene, which encodes the alpha subunit of IHF, the gene complementing the IR4 mutant was named himA of R. capsulatus. The wild-type himA gene, cloned in plasmid pBO2, was introduced into the IR4 strain and shown to restore, in trans, hydrogenase activity and autotrophic growth in the mutant. In IR4, a C----T transition mutation had replaced Arg-8 by Cys-8. Gel mobility shifts of the 274-base-pair DNA fragment, not observed with the himA gene product of IR4, were restored with extracts from IR4(pBO2) cells, containing the himA gene on the recombinant plasmid pBO2.

Amino Acid Sequence↗
PubMed1991

Low-grade follicular lymphomas: analysis of prognosis in a series of 281 patients.

From 1963 to 1988, 281 patients with newly diagnosed follicular lymphomas were treated and followed at the Foundation Bergonié. Distribution of stages was: 72 I, 61 II, 83 III and 65 IV. Within stage III, two subgroups were retrospectively defined: stages III1 (32 cases) included patients with less than 8 involved sites, only 1 or 2 above diaphragm, and no spleen or mediastinal enlargement. Stage III2 (51 cases) included the remaining stage III cases. Median follow-up was 9 years. Complete remission (CR) rate was 82%. 10-year overall survival (OS) and time to treatment failure (TTF) rates were, respectively 38% and 29.5%. 10-year time to relapse (TTR) rate was 36%. Statistical analyses showed concordant results with two main prognostic factors: age (less than 60/greater than 60) and stage (I to III1/III2 and IV). Age was the most important factor for OS analysis and stage for CR and TTR analysis. This leads to only three prognostic groups with different outcome. The first includes younger patients (less than 60 years) with limited stages (less than or equal to III1); the second, patients either older than 60 or with advanced stages; the last, elderly patients with advanced stages. CR rates of these three groups were, respectively 97%, 75% and 57%. 10-year OS were, respectively 73.5%, 27% and 0%; 10-year TTR were 54%, 22% and 0%. These results have lead to data which are easy to handle and which can help to establish a rationale for further prospective trials.

Adult↗